Markell Voges Medical Parasitology Ebook - 10th SEA Ed

10th South-East Asian edition
Markell and Voge’s
Medical
Parasitology
DAVID T. JOHN, MSPH, PHD
Professor of Microbiology/Parasitology
Associate Dean for Basic Sciences and Graduate Studies
Oklahoma State University
Center for Health Sciences
College of Osteopathic Medicine
Tulsa, Oklahoma
WILLIAM A. PETRI, JR., MD, PHD

Wade Hampton Frost Professor of Epidemiology
Professor of Medicine, Microbiology and Pathology
Chief of the Division of Infectious Diseases and International Health
Department of Internal Medicine
University of Virginia School of Medicine
Charlottesville,Virginia
Adapting editor
GREGORIO L. MARTIN I, RMT, MSMT, MPH, PHD
Assistant Professor
Faculty of Pharmacy, Department of Medical Technology
University of Santo Tomas
Manila, Philippines
Elsevier (Singapore) Pte Ltd
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Markell and Voge’s Medical Parasitology
Copyright © 2006, Elsevier Inc. All rights reserved.
Previous editions copyrighted 1958, 1965, 1971, 1976, 1981, 1986, 1992, 1999
ISBN: 978-0-721-64793-7
This adaptation of Markell and Voge’s Medical Parasitology, 9e, by David T. John and William A. Petri, was undertaken by Elsevier
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Markell and Voge’s Medical Parasitology 10th South-East Asian edition
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Printed in the Philippines

Edward K. Markell, 1918-1998
Marietta Voge, 1918-1984

Preface
The first edition of Markell and Voge’s Medical Parasitolo- his MD and PhD degrees from the University of Vir-
gy was published 48 years ago in 1958 under the title of ginia, Charlottesville, where currently he is Professor
Diagnostic Medical Parasitology. The name was abbrevi- and Chief of the Division of Infectious Diseases and
ated to Medical Parasitology with the second edition and International Health. Dr. Petri is a past president of the
remained as such until the eighth edition, at which time American Society of Tropical Medicine and Hygiene and his
the current title was adopted.Marietta Voge passed away research has been with Entamoeba histolytica and am-
in 1984 at the age of 66 and Edward Markell in 1998 ebiasis. His research has taken him around the world
at the age of 80.The present edition is the first revision as an invited lecturer to Australia, Japan, Thailand,
that one or both of them have not been involved with. Bangladesh, India, Turkey, Israel, France, Germany,
By way of historical note, Dr. Markell received his Argentina,Mexico, Canada, and throughout the United
PhD in zoology from the University of California, States.
Berkeley in 1942 and his MD from Stanford University Ed Markell was born in Brooklyn, New York, but he
in 1951. Dr.Voge received her PhD also from the Uni- had a knack for recruiting “non-natives” to work with
versity of California, Berkeley in 1950.They were both him on the book. Marietta Voge was born in Yugosla-
assistant professors at the University of California, Los via, Al Krotoski in Latvia, and I was born in Nigeria. Bill
Angeles, School of Medicine when they published the Petri was born in Washington, DC, so we have come
first edition of Medical Parasitology. full circle.A good sign,I believe.
I became co-author with the sixth edition and Al This book is intended primarily for the medical stu-
Krotoski with the eighth edition. Dr. Krotoski and I dent and the physician, but it is equally useful to the
both received our introduction to the field of parasi- medical technologist and others who are concerned
tology through the first edition of Medical Parasitology. with the laboratory identification of the parasites of
Dr.Krotoski retired from active professional work in 1995 humans.All the chapters have been thoroughly updat-
and has decided not to participate in further editions of ed and give current information on the life cycles of
the book. My collaboration with Al Krotoski has been the human parasites and on the epidemiology, immu-
most enjoyable and productive and it was with regret that nology, diagnosis, and treatment of the diseases they
I accepted his decision to withdraw from authorship. cause.
With the ninth edition, I am indeed fortunate to
have William Petri become co-author. Dr. Petri earned David T. John, MSPH, PhD
Acknowledgments
We are indebted to the people who contributed in vari- was undergoing revision.The staff of Saunders, an im-
ous ways to this edition. Our special thanks to Terry print of Elsevier, as usual, has been most considerate
Drenner, Joni Finfrock, Sheila Pete, and Marianna Wil- and helpful. Our special appreciation to Ellen Wurm,
son.We are grateful to our wives, Rebecca John and Developmental Editor, and Mindy Hutchinson, Manag-
Mary Ann Petri, for their understanding, encourage- ing Editor, and the other members of their team,Missy
ment, and assistance during the months while the book Boyle,Heather Fogt,Alaina Webster,and Rich Barber.
v
South-East Asian edition Contributors
and Reviewers
CONTRIBUTORS REVIEWERS
Sheila Grace Alarilla-Martin, RMT, MS Mary Jane Cruz-Flores, PhD
Microbiology President (2017-2019)
College of Medical Technology Philippine Society of Parasitology (PSP)
Manila Central University Philippines
Manila, Philippines
Lydia R. Leonardo, MS, DrPH
Diana Leah M. Mendoza, RMT Professor Emeritus, University of the Philippines Manila
Faculty of Pharmacy, Department of Medical President, PSP (2019 - present)
Technology Institute of Biology, College of Science,
University of Santo Tomas University of the Philippines Diliman
Manila, Philippines Philippines
Rolter Lorenz M. Lee, RMT Haily Liduin Koyou, MLT, MSc

University of Santo Tomas Faculty of Health Sciences
Manila, Philippines Faculty of Engineering & Life Sciences
Universiti Selangor
Joven Francis F. Morales, RMT Shah Alam, Malaysia
Manila, Philippines
Noe Raphael D. Tarrosa, RMT

Manila, Philippines
Jeremie Faye B. Umali, RMT

Manila, Philippines
Patricia Alyanna Marie P. Madrigal

Manila, Philippines
Kyle Patrick R. Magistrado

Manila, Philippines
Kharam B. Molbog
Manila, Philippines
vi
Contents
Preface iv 7 Phylum Platyhelminthes: Class

Acknowledgments v Cestoda 211
South-East Asian edition Contributors Patricia Alyanna Marie P. Madrigal
and Reviewers vi
8 Introduction to Medical
1 Introduction to Medical Parasitology Entomology 241
and Basic Terminologies 1 Sheila Grace Alarilla-Martin
Sheila Grace Alarilla-Martin
9 Pseudoparasites: A Parasite Look
2 Protozoa: Phylum Sarcomastigophora Alike 247
(Amoebae and Flagellates) 23 Sheila Grace Alarilla-Martin
Diana Leah M. Mendoza
10 Diagnostic Parasitology 253
3 Miscellaneous Lumen-Dwelling Noe Raphael D. Tarrosa
Protozoa 93
Joven Francis F. Morales 11 Therapy Against Parasitic
Infections 285
4 Protozoa: Phylum Apicomplexa Noe Raphael D. Tarrosa
(Malaria, Coccidian, Babesia) 103
Rolter Lorenz M. Lee, Kharam B. Molbog Glossary: Signs and Symptoms
of Parasitic Disease 315
5 Phylum Nemathelminthes: Atlas of Medically Important
Roundworms 135 Parasites 331
Kyle Patrick R. Magistrado
Answers to Chapter Questions 343
6 Phylum Platyhelminthes: Class Index 345
Trematoda 171
Jeremie Faye B. Umali
vii
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CHAPTER 1
Introduction to Medical Parasitology

and Basic Terminologies
SHEILA GRACE ALARILLA-MARTIN
Parasitic infections represent more than 50% of those the chapters dealing with technical methods, the prob-
listed in the WHO list of neglected tropical diseases. lems of technologists are discussed; physicians will be
Research shows that helminths and protozoans are better able to utilize laboratory services if they under-
among the common agents of infections that affect stand them. The manner in which parasitic organisms
ASEAN countries that include these ten member states: are acquired and how they produce disease in humans
Brunei Darussalam, Cambodia, Indonesia, Lao Peo- are perhaps of no direct importance to technologists.
ple’s Democratic Republic (PDR), Malaysia, Myanmar, Yet a basic understanding of these matters should not
the Philippines, Singapore, Thailand, and Vietnam. only make technologists’ work more interesting but en-
These NTDs draw attentions among health clusters pri- able them to do it better and more efficiently.
marily because of their public health impact especially • Parasites, parasitism, and host relations
in many marginalized areas. NTDs and poverty are in- • Many terms have been devised to describe the
terconnected ideas that should be given utmost atten- relationships that exist between different kinds
tion by health workers and policy making bodies of the of plants and animals at the fundamental food-
government. Extensive efforts were already made at the seeking or food-supplying level.
community level however despite the several control • Organism may at different times exhibit differ-
measures that were instituted the problems still exist ent nutritional habits or at a given time obtain its
and continually affecting one’s productivity. nutriment in more than one way.
Studying the basic concepts of parasitology will en- • Fundamentally, there are two ways in which an
lighten us to the issues arising from existence of para- animal may obtain food at the expense of other
sites and their effects to the general population. More animals.
so, understanding the biology of the parasites and their Predation: It may attack another living animal, con-
unique interaction with their host will provide clear suming part or all of its body for nourishment.
evidence about their life cycle. Laboratory tests are rele- The attacker is the predator, and the victim is called
vant for parasite diagnosis and require skills for proper the prey. In predator-prey relationship, the prey is
processing and recognition. Misidentification of the usually killed because it is eaten by the predator.
parasite may lead to serious consequence thereby af- Scavenging: An animal deriving its nutrition from
fecting correct diagnosis. already dead animals, either devouring those
The primary purpose of this book is to serve as a dead of natural causes or taking the leavings of a
guide both to the clinical diagnosis and treatment and predator. Animals that subsist in this manner are
to the laboratory diagnosis of the protozoan and hel- known as scavengers.
minthic diseases of medical importance, and to a lesser • Some animals are pure predators, others pure
extent to the arthropods in relation to disease. While it scavengers, but many predators are not averse an
is intended primarily for medical students and physi- occasional bit of scavenging.
cians, it is hoped that this book will prove equally useful • Some animals always seek their food by their
to medical technologists and all others concerned with own efforts or in association with others of their
laboratory identification of the animal parasites of hu- own species.
mans. The success of the cooperative diagnostic efforts • This is the most conspicuous and perhaps the
of the physician and laboratory technologist depends most common way in which animals go about
on a mutual appreciation of their several problems. In obtaining food.
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2 Markell & Voge's Medical Parasitology
• Symbiosis (“living together”): This refers to associa- • Intermediate host

tion of two species for food and shelter. Different • Harbors the larval stages or asexual forms of
forms of symbiosis may be distinguished on the the parasites.
basis of whether or not the association is detri- • First intermediate host (1st IH): harbors the
mental to one of the two partners. early larval stage of the parasites.
Commensalism: Latin for “eating at the same table,” Example: Snail is an intermediate of all the
denotes an association that is beneficial to one trematodes.
partner and at least not disadvantageous to the Blood–feeding arthropods: mosquitoes,
other. tsetse flies, sandflies, triatomid bugs.
Example: Entamoeba coli lives in the lumen of the
intestine, subsists there on the bacterial flora of Vector is a blood feeding arthropod. The
the gut, and does its host no appreciable harm. term mechanical vector is used to describe
Mutualism: A specialized type of symbiosis that oc- a vector which assist in the transfer of a
curs when associations are beneficial to both or- parasitic form between hosts but is not
ganisms. essential in the life cycle of parasite. This
Parasitism: Symbiotic relationship in which one ani- means that no parasitic development oc-
mal, the parasite, lives at the expense of the other curs in the vector. A good example of a me-
animal, the host. chanical vector is a fly that transfers amoe-
Parasitism, like other forms of symbiosis, necessar- bic cysts from infected feces to food/drink
ily involves an intimate relationship between the that is consumed by humans. Non-arthro-
two species, and it is this close and prolonged pods mechanical vector is called transport
contact that differentiates parasitism from the or paratenic host. In such a host, a parasite
predatory activities of many nonparasites. remains viable but does not develop.
Parasitism as a way of life may be the only possibil-
ity for a given organism, or it may be but one • Second intermediate host (2nd IH): harbors
alternative. the infective larval stage of the parasite.
Example: snail, fish, vegetable, crabs, ants.
• Paratenic host
DEFINITION OF MEDICAL PARASITOLOGY • Harbors the parasite in an underdeveloped or
Medical Parasitology is a branch of biology that is fo- in arrested state of development.
cused on the animal parasites of human and their med- • It will only continue the life cycle of parasite
ical significance and public health impact. It also covers only if this paratenic host carrying the parasite
phenomena of dependence among living organisms. is consumed by a susceptible definitive host.
Parasitology is the scientific study of a parasite, an Example: In Paragonimus westermani, fresh
organism that depends, and a host, an organism that water prawn/crab acts as its second interme-
provides shelter and nourishment. diate host while wild boar acts as its paratenic
host. Both of these carries the infective meta-
cercariae.
HOST • Reservoir host
• Host is known as the organism that provides physi- • Alternative host to a parasite that is harbored
cal protection and nourishment to the parasite. normally by humans.
• Different types of hosts: • Host the continues the life cycle of the parasite
• Definitive or final host and acts as an additional source of infection.
• Harbors the adult or sexually mature stage of • Must be considered in parasite control mea-
parasite. sures.
Example: Example: Pigs are known reservoir host of Bal-
• Human is definitive host for lymphatic fi- antidium coli.
larial worms that cause elephantiasis and • A parasitic infection in which the normal host is an
trypanosomes that cause African trypano- animal but can produce disease in human if they be-
somiasis. come infected accidentally is known as zoonosis. Ex-
• Anopheles mosquito is the definitive host amples of this include the following parasitic diseas-
for Plasmodium spp. that causes malaria. es: leishmaniasis, South American trypanosomiasis,
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CHAPTER 1 Introduction to Medical Parasitology and Basic Terminologies 3
African trypanosomiasis, schistosomiasis (S. japoni- • Only groups of protozoans that contain nothing but
cum), trichinellosis, echinococcosis. Lack of adapta- parasitic forms: Phylum Apicomplexa and Microsporidia.
tion to human host may cause serious infection in • Members of these phyla have no locomotor organ-
the person infected. elles, although the structures are present in one form
or another in all other phyla of protozoa, even in
their parasitic representatives.
PARASITE • Most of the free-living turbellarian flatworms are pro-
These are organisms that depend on the host for sur- vided with a ciliated epidermis in the adult stage.
vival. • Cilia are not found on the parasitic members of this
group or on the related but strictly parasitic trema-
Types of Parasites todes and cestodes.
According to relationship between host and a • A digestive tract, moderately complex in the turbel-
parasite larians, is generally reduced in the trematodes and is
Obligate parasite: Organism that cannot survive in absent in the cestodes.
any other manner in the absence of a host. • The reproductive system is highly developed in the
Facultative parasite: Organism that may exist in a two latter groups; this seems a reflection of the dif-
free-living state or as a commensal and that, if opportu- ficulties inherent in transfer of these organisms to
nity presents itself, may become parasitic. new hosts.
Temporary parasite: Parasites that are obligatory at • Specialized attachment organs in the form of suck-
one or more stages of their life cycles but free living at ers and hooks have been developed by the parasitic
others. flatworms.
Intermittent parasite: Small organisms, such as mos- • Body size may be greatly affected by the parasitic
quitoes, which must periodically seek out other and state.
larger forms on which to nourish themselves. These are • The majority of free-living turbellarians are less
parasites that visit their host during feeding time. than a half centimeter in length, and while some
land planarians may reach a half meter, none
According to habitat approaches the length of 10 m or more seen in
Endoparasite: Parasites living within the host. some tapeworms.
Ectoparasite: Parasites that are found on the surface • Most free-living nematodes barely attain naked-
of the body. eye visibility as adults, but Ascaris can reach
• The essence of the parasitic relationship, which sep- 35 cm and Dracunculus as much as 1 m.
arates it from predation, is the protracted and inti- • The parasitic mode of existence may result in pro-
mate association between parasite and host. found biochemical changes.
• Streamlining
Adaptations to Parasitism • Loss of certain metabolic pathways common
• The parasitic relationship probably evolved early in to free-living organisms.
the history of living organisms. • The parasite, no longer able to synthesize cer-
• The possibility of the adaptation of a parasitic mode tain necessary cellular components, obtains
of existence may depend on what is known as pread- them instead from its host.
aptation, or evolutionary changes that make possible • Profound differences between metabolic
existence in an unfavorable environment. pathways in parasite and host characterize:
• Preadaptive changes is due to increased resistance to Kinetoplastida (Leishmania and Trypanosoma)
the enzymatic activities of the host. species in humans.
• Physiologic adaptations to parasitism might involve Entamoeba histolytica
the loss of enzymes or enzyme systems, which are Giardia duodenalis (formerly Giardia lamblia)
then supplied by the host. Trichomonas vaginalis
• Profound morphologic adaptations modifications Helminth parasites
are more striking in those groups that are wholly • Specialized mechanisms for effecting entrance
parasitic than in those that contain both free-living into the body or tissues.
and parasitic species. • E. histolytica (pathogenic intestinal amoeba)
• Organs not necessary to a parasitic existence are fre- elaborates a proteolytic enzyme that aids its
quently lost. penetration of the intestinal mucosa.
• Schistosoma sp. (blood fluke) in its cercarial • Immune system of the host may also be affected.
stage has penetration glands which produce • The most widespread type of injury is that brought
enzyme capable of digesting the skin. about by interference with the vital processes of the
• Hymenolepis nana (dwarf tapeworm) during host through the action of secretions, excretions, or
its embryonic stage prior to developing into a other products of the parasite.
cysticercoid larva, penetrates an intestinal vil- • Mechanisms of parasite infection
lus with the help of the six hooklets it bears. • Fasciolopsis buski (Giant intestinal fluke) when
• Once within the host’s body, the parasite is present toxic symptoms in large numbers but
subject to those defense mechanisms mobi- the precise cause is unknown. It may produce
lized in the immune response. severe local damage to the intestinal wall by
• Continuation of a parasitic relationship de- means of its powerful suckers. In high intensity
pends on how successfully the immune reinfection when there is a significant number of
sponse of the host is overcome. adult flukes, intestinal obstruction may likely
• Many different defense mechanisms have evolved. occur.
• Immune evasion may involve the following • Entamoeba histolytica erodes the intestinal wall,
factors: destroying the tissues locally by means of a pro-
• Location of the parasite in relatively proteolytic enzyme.
tected sites. • Plasmodium falciparum (pathogenic species of
• Changes in the parasite surface antigenic malarial parasite) invade and multiply in red
structure. blood cells, which are destroyed in the process
• Active modification of the host immune re- and may also attach to the walls of smaller blood
sponse by products of parasite metabolism. vessels in the brain, occluding them to produce
• Increased reproductive capacity localized ischemia.
• Most metazoan parasites exhibit such an • The helminth parasites, by virtue of their size,
increase, which in some cases involves lar- may damage the host in other ways impossible
val stages as well as adults. for the smaller parasites.
• The chances that a particular egg will • Ascaris lumbricoides (Giant intestinal round-
successfully infect a new host are usually worm) may perforate the bowel wall, cause intes-
very small, and if more than one host tinal obstruction if present in large numbers, and
species is involved, the chance of suc- ectopically may invade the appendix, bile duct,
cessful completion of the cycle becomes or other organs.
still smaller. • Some parasites exert their effects by depriving the
• If a parasite is successful in infecting an host of essential substances.
intermediate host, it is obviously advanta- • Human Hookworms, like Ancylostoma duode-
geous if the larval stage that develops there nale and Necator americanus, suck blood de-
can multiply to produce many additional prive the host of more iron than is replaced
organisms capable of infecting the defini- by diet and therefore leading to a case of mi-
tive or a second intermediate host. crocytic hypochromic anemia.
• Such a modification is seen in the trema- • The broad fish tapeworm Dibothriocephalus
todes and many of the cestodes, where in latus (formerly Diphyllobothrium latum) selec-
the intermediate host a single egg develops tively removes vitamin B12 from the alimen-
into a larva, which in turn produces many tary tract, producing a megaloblastic anemia in
larvae of a more advanced kind. some infected persons.
PATHOLOGY: SIGNS AND SYMPTOMS Effects of the Host on the Parasite

Effects of the Parasite on the Host • Genetic constitution of the host influences the host-
• A parasite, by definition, is an organism that lives at parasite relationship.
the expense of its host. • Duffy null phenotype: Fy (a - b -): demonstrates
• Overt symptoms of infection with this parasite may resistance to Plasmodium vivax infection.
depend on the number of worms present, the nutri- • Sickle cell trait is associated with increased resis-
tional status of the host, or both. tance to Plasmodium falciparum infection.
• Diet or nutritional status of the host • Infants born in such areas to a semi-immune
• A high-protein diet is unfavorable for the devel- parent are at birth, and for some time thereaf-
opment of many intestinal protozoa. ter, partially protected by maternal antibodies
• A low-protein diet favors the appearance of acquired transplacentally.
symptoms of amoebiasis. • If infection with one such parasite takes
• A rich-carbohydrate diet favors the development place during the first few months of life, it
of certain tapeworms. is likely not to be as severe as it would oth-
• Effects on the immune mechanisms of the host erwise have been, and repeated infections
• Every species of animal is naturally resistant to over the years keep the acquired immunity
infection by many organisms that parasitize dif- at a high level and symptoms correspond-
ferent species. ingly mild.
• In the case of certain strains of malaria, resistance • If, on the other hand, such a person leaves
may also be a racial phenomenon. the endemic area for a protracted period, the
• In some cases, it has been possible to adapt par- acquired immunity wanes, and on returning
asites to hosts that they normally infect poorly to the endemic area that person may fare no
or not at all. This does not necessarily involve better than someone becoming infected after
changes in the host’s natural resistance but rather entering the endemic area for the first time.
changes in the parasite.
• Acquired immunity can be demonstrated in Parasites and the Compromised Host
many parasitic diseases, and it is generally found Natural defenses of a patient may be compromised and
to be at a lower level than that produced by bac- poses him to be at risk of parasitic infection:
teria and viruses.
• Issues arising to immunity to parasitic infec-
tion: Risk factor Parasitic infection
• Occurs rarely following protozoal infec- Patient undergoing aggressive Toxoplasmosis
tions. treatment for leukemia
• Probably never with helminth infections of Corticosteroids Acute amoebic colitis
humans. State of malignancy: Primary gastric amoebiasis
• As yet, no useful vaccines have been devel- Reticulum cell carcinoma
oped against protozoal or helminthic infec-
Immunologically compromised Strongyloidiasis and
tions. hosts trichinosis
• Although malaria is a likely candidate for a
Acquired Immunodeficiency Toxoplasmosis
vaccine, recent field trials of potential ma-
Syndrome (AIDS) Cyclosporiasis
laria vaccines have failed to meet expecta- Cryptosporidiosis
tions. Cystoisosporiasis
• Primary infection with Leishmania seems to Strongyloidiasis
confer a degree of immunity to reinfection. (disseminated form)
• While many protozoal and helminthic in-
fections confer no long-lasting immunity
to reinfection, they do seem to stimulate
resistance while the parasites are still in the LIFE CYCLE: INFECTIVE AND DIAGNOSTIC
body. STAGES, MODE OF TRANSMISSION
• This resistance to hyperinfection, known as Life Cycles of Protozoa and Helminths
premunition, may be of great importance in • Many parasitic organisms have but a single host,
endemic areas in limiting the extent of infec- being transferred from one individual to another
tion with plasmodia, hookworms, and other of the same species either through direct physical
parasites. contact or by means of resistant or semi-resistant
• Acquired immunity may be very important in forms that are able to survive a period outside or
modifying the severity of disease in endemic away from the host.
areas, particularly diseases such as vector- Encysting protozoans: Infective stage is called the cyst.
borne malaria and filariasis and snail-borne, Non-encysting protozoans: Infective stage is called
schistosomiasis. the trophozoite.
Examples: • In certain cases, like among the coccidians, a cer-

• Entamoeba gingivalis, a commensal organism that tain host may act both as an intermediate and
inhabits the mouth, has no cyst stage or other definitive host.
means of survival outside of the host, and it • All parasites undergo the different developmen-
probably is transferred by direct contact. tal stages before it reaches its mature state and
• Trichomonas spp. (T. tenax, T. hominis, T. vagina- reproduction. This life cycle can be classified into
lis) likewise is unable to form cysts, but it prob- the following based on the number of intermedi-
ably can survive for short periods outside the ate hosts required.
body. • Monoxenous: involves only one intermediate
Egg laying nematodes: Infective stage is called the host.
embryonated egg. • Heteroxenous: involves more than one inter-
Examples: mediate hosts.
• Ascaris lumbricoides and Trichuris trichiura are ex- • Life Cycle refers to the development of a parasite in
amples of soil-transmitted helminthes that infect its earliest form and its survival and development in
host through ingestion of embryonated egg. the outside environment and within the host. The
• Enterobius vermicularis is a contact-transmitted life cycle of parasite may simple or complex. This
parasite whose embryonated eggs can be either cycle divided in three groups.
ingested or inhaled.
• Vector-transmitted parasites
• A vector may also be a host if development of the Parasite Definitive Intermediate
parasite takes place within its body. Group cycle involved host host
• If the arthropod is simply an instrument of Those with Ascaris Man/ Pig None
passive transfer, we refer to it as mechanical vec- definitive sp.
tor. If a fly, feeding on fecal matter containing host but does
cysts of E. histolytica, becomes contaminated not require
with some of these cysts, which it then trans- intermediate
fers to food, it is acting as a mechanical vector host.
of the amoeba. Those with Echinococcus Dog and Sheep, Goat,
• When an Anopheline mosquito sucks blood definitive granulosus other Swine,
from a malaria patient, the parasites must devel- host with one canidae Cattle,
intermediate Horse,
op in the mosquito before she is able to transmit
host required. Herbivores
the infection. In this instance the mosquito is Human
both acting as a host and biologic vector.
Those with Fasciola Water 1st IH: Snail
• Some protozoa and many helminths have complex
definitive hepatica1 buffalo/ 2nd IH:
life cycles, with not one but two, and sometimes host and with Man Aquatic
more, hosts. two or more plants or
When more than one host species is necessary to the intermediate vegetation
development of the parasite, that host in which sex- host required.
ual reproduction occurs is called the definitive host 1Nowadays, Fasciola hepatica may encyst in water and therefore
(DH). transmission happens even in the absence of second intermediate
The species in which larval (or asexual if both sexual host. (Tolan, 2011)
and asexual forms occur) stages of the parasites de-
velop are called intermediate hosts (IH); they are usu-
ally designated first and second intermediate hosts CONTROL, PREVENTION, AND TREATMENT
if there is more than one. • Preventive and control measures may be taken against
• Disconcerting as it may be to those with a strictly every parasite that is infective to human. These are de-
anthropocentric point of view, humans are but the signed to break the transmission cycle are therefore
intermediate host of the malarial parasite Plasmo- crucial for successful parasite eradication. Therefore,
dium, which undergoes sexual reproduction in mos- preventing the infections to happen is to intervene in
quitoes of the genus Anopheles. [IH – human; DH the life cycle of the parasite and prevent the successful
– female Anopheles mosquito). entry of the infective stage to the host.
How to break the chain of Infection

Parasite cluster Mode of transmission Infective stage Representative parasite Preventive measure
Soil-transmitted Ingestion Embryonated Ascaris lumbricoides • Hand washing
helminths (STH) egg Trichuris trichiura • Proper disposal of excreta
• Provision of clean toilet
Skin penetration Filariform Hookworm • Personal Protective Equipment:
larva (L3 gloves
larva) • Use of slippers
Food and water- Ingestion cyst Balantidium coli • Handwashing
borne • Proper disposal of excreta
metacercaria Paragonimus westermani • Proper cooking of crab
Skin penetration cercaria Schistosoma spp. • Avoid contact with water
• Provision of clean water and toilet
• Snail control
Drinking contaminated cyst Giardia duodenalis • Water purification system
water • Iodine treatment
Vector-borne Bite of an infected sporozoite Plasmodium sp. • Protective clothing
vector • Mosquito net
• Insect repellent
• Integrated vector control
Contact transmitted Direct contact Embryonated Enterobius vermicularis Proper hygiene:
- Inhalation egg • Handwashing
- Ingestion • Clean clothing
- Autoinfection
Sexually transmitted Direct contact Trophozoite Trichomonas vaginalis • Avoid unprotected sexual contact
- Sexual intercourse or multiple sexual partners
• Use of condom
(Beaver et al., 1984; Belizario and De Leon, 2015)
• Parasitic treatment options include the following: • Popularity of the tropics and subtropics as vaca-
1. Antiparasitic medication tion areas.
Representative • Modifications of the environment.
Parasite group anti-parasitic drugs • Flooding of vast areas creating new habitats for
Protozoan Metronidazole the snail hosts (i.e., schistosomiasis).
Nematode Mebendazole • Global warming as a reason for the eventual
Platyhelminthes: Praziquantel spread of diseases now seen primarily in the
trematodes and cestodes tropics to more temperature climates.
• Parasitic infections among immunosuppressed
2. Therapies option and immunocompromised.
a. Change in diet • Therapy for parasitic infections
b. Vitamin supplements • Differential toxicity: antiparasitic agent is more
c. Fluid replacement toxic to the parasite than to the host.
d. Blood transfusion • Individual variation in host resistance.
e. Bed rest • Toxic side effects.
• Risk factors for transmission of parasitic infections • Treatment of certain parasitic diseases is changing
• Modifications of host resistance resulting in the which necessitates every physician to keep abreast of
appearance of numbers of organisms in unfamil- the advances in this field.
iar pathogenic roles. • The Medical Letter on Drugs and Therapeutics.
• Failure of chemical treatment to eliminate the • The Tropical Diseases Bulletin:
vector-transmitted parasitic infections like ma- • A monthly abstracting journal published in
laria and filariasis. England, lists the worldwide literature in trop-
• Increased mobility of large segments of the pop- ical medicine.
ulation.
• Drug Information for the Health Care Profes- • Mastigophora: flagellates: equipped with flagellum,
sional: a whip-like structure.
• Published yearly, originally by the U. S. Phar-
macopeia but, since January 2004, now main- Phylum Ciliophora
tained by Thomson Healthcare, Inc., in which • Ciliata: ciliates: equipped with cilia, hair-like struc-
the USP-approved drugs are listed by disease. tures.
• Some ciliates are multinucleate, while others
contain but two nuclei, a large macronucleus and
EXCITING NEW AREAS OF RESEARCH a small micronucleus.
• Role of eosinophils in killing young schistosomes • The only ciliate parasite of humans is Balantidium
and microfilariae. coli, found in the intestinal tract. Although rare, it
• Ability of older schistosomes to induce immuno- is important, as it may produce severe intestinal
suppression in the host. symptoms.
• Discovery of host-like antigens on the surface of
some parasites. Phylum Apicomplexa
• Phenomenon of antigenic variation in trypano- • Parasites that are not equipped with definite loco-
somes. motor apparatus.
• Role of cytokines, tumor necrosis factor (TNF) or ca- • Demonstrates asexual cycle called schizogony and a
chectin. sexual cycle called sporogony.
• Cachectin, a major secretory product of activated • Contains apical complex that is composed of the
macrophages, in low doses is protective against following: micronemes, subpellicular tubules, polar
experimental malaria in mice, stimulates the kill- rings, conoids, rhoptries.
ing of schistosomules by eosinophils in vitro, but Example: Plasmodium spp.: causative agent of malaria
paradoxically is thought to bring about the state Babesia microti: causative agent of Nantucket fever
of cachexia seen in trypanosomiasis. Toxoplasma gondii: causative agent of Toxoplasmosis
• Side effects of administration of TNF to cancer
patients are almost identical to the various signs Phylum Platyhelminthes
and symptoms seen in severe falciparum malaria. • The Platyhelminthes, or flatworms, are multicellular
• Importance of the “secretions and excretions” of animals characterized by a flat, bilaterally symmetri-
protozoa and helminths as antigenic substances cal body.
stimulating host resistance. • Most flatworms are hermaphroditic, having both
• In Trypanosoma lewisi infections in rats, the meta- male and female reproductive organs in the same
bolic products of the parasites are more effective individual except schistosomes that have separate
in producing immunity than are the dead try- sexes.
panosomes themselves. • Adults may be less than 1 mm long or they may
• Immunologic tests on the ability of the serum of an reach a length of many meters.
infected host to precipitate the secretions or excre- • Most members of the phylum are parasites, living
tions of eggs, larvae, or adults of a number of differ- on or in the body of their hosts.
ent helminths. • 3 classes are recognized:
Class Turbellaria (Roberts and Janovy, 2013)
• Mostly existing as free-living forms inhabiting
IMPORTANT GROUPS OF ANIMAL terrestrial, freshwater and marine environments.
PARASITES • Ciliated epithelium envelops the body of the
Protozoan adult worm.
• Exist as motile trophozoite stage and the nonmotile • With or without suckers.
infective cyst. • Direct development without metamorphosis.
• Locomotor apparatus serves as one of the bases of • These hermaphrodites are commensals or para-
classification. sites of invertebrates especially of echinoderms
and molluscs.
Phylum Sarcomastigophora Class Trematoda: “flukes”
• Sarcodina: amoebae: equipped with pseudopods • Leaf-shaped or elongate, slender organisms.
(“false feet”).
• Possess attachment organs in the form of cup- • The life cycle requires an arthropod intermediate
shaped muscular depressions called suckers. host: beetle, cockroach.
• An incomplete digestive tract is present. • While thorny-headed worms are widely distributed
• Of the three orders of the Trematoda, the order among wild and domestic animals, only three gen-
Digenea contains all the species that are parasitic era have been reported in human beings: Monilifor-
in humans. mis, Macracanthorhynchus, Bulbosoma.
• Members of this order have complex life histo-
ries, with at least one intermediate molluscan Phylum Arthropoda
host. • Arthropods are segmented and bilaterally symmetri-
• Included in the digenetic trematodes of humans cal animals with a body enclosed in a stiff, chitinous
are forms that inhabit: small intestine, liver, covering or exoskeleton and bearing paired, jointed
lungs, pancreas and blood vessels. appendages.
Class Cestoda: “tapeworm” • The digestive system is well developed.
• Elongate, ribbon-like, segmented body that bears • Sexes are separate.
a specialized anterior attachment organ called • The phylum is subdivided into a number of classes,
the scolex. many of which are of medical importance.
• A digestive tract is absent.
• Adult cestodes or tapeworms inhabit the small Class Crustacea
intestine. • Primarily aquatic forms, which breathe by means of
• Cestode larvae require an intermediate host for gills.
development. However, Hymenolepis nana or the • Crabs, shrimps, crayfish, and copepods.
dwarf tapeworm, may or may not require an in- • Serve as intermediate hosts of human parasites.
termediate host. Autoinfection is also observed • Freshwater crab: Paragonimus westermani: oriental
in its life cycle. lung fluke.
• Humans may be host to either adult or larval • Copepods: Dibothriocephalus latus (formerly
stages, depending on the species of cestode. Diphyllobothrium latum): broad fish tapeworm.
Class Chilopoda
Phylum Nemathelminthes
• Centipedes are characterized by the possession of
• The nematodes, or roundworms, are elongate, cylin-
one pair of legs on each body segment.
drical worms, frequently attenuated at both ends.
• First pair of appendages is modified as poison claws.
• They possess a stiff cuticle, which may be smooth
or may be extended to form a variety of structures, Class Arachnida
particularly at the anterior and posterior ends. • Spiderlike animals, possess a body divided into two
• The sexes are separate, the male frequently being parts, the cephalothorax and the abdomen.
considerably smaller than the female and posses • Adults have four pairs of legs.
copulatory structures like spicule or bursa. • Scorpions, the spiders, and the ticks and mites.
• A complete digestive tract is present. • Scorpions and spiders produce venom, which in
• While most nematodes are free living, a large number some species may be extremely toxic.
of species parasitize humans, animals, and plants. • Ticks and mites may act as intermediate host for cer-
• Intermediate hosts are necessary for the larval devel- tain parasitic infection.Ixodes tick: Babesia sp.
opment of some forms.
• Parasites of humans include intestinal and tissue- Class Insecta
inhabiting species. • From a medical or economic point of view, the most
important of the arthropods.
Phylum Acanthocephala • Three pairs of legs and a body divided into three dis-
• The thorny-headed worms are all endoparasitic or- tinct parts: head, thorax, and abdomen.
ganisms, the anterior end of which is modified into • Several orders of insects are worthy of special mention.
a hook-bearing, retractable proboscis that serves in
attachment. Order Anoplura
• A digestive tract is absent. • Sucking lice
• Sexes are separate, and males are usually smaller • Wingless, dorsoventrally compressed insects
than females. • Human lice
Order Hemiptera • Derived from their body shape, which is elongate,

• True bugs, wingless bedbugs. and in some species tonguelike.
• Two pairs of wings, first pair has thickened membra- • Other species have a ringed or annulated body.
nous bases. • Lack external appendages and possess two pairs of
• Cone-nosed bugs, or reduviids: vectors of Trypano- hooks near the mouth.
soma cruzi that causes American trypanosomiasis or • Adults live in the respiratory tract of vertebrates.
Chaga’s disease. • Encysted larval stages may occur in the lungs and
other internal organs of humans, and they are found
Order Coleoptera principally in tropical areas.
• Beetles
• Two pairs of wings, but the anterior pair is thickened Phylum Microsporidia
throughout. • Formerly classified with the Sporozoa
• Beetles are intermediate hosts of tapeworms: • Minute intracellular parasites of many kinds of ver-
• Grain beetle - Hymenolepis nana tebrates and invertebrates
• Flour beetle – Hymenolepis diminuta • Differ significantly in structure from the Apicom-
plexa
Order Hymenoptera • Rarely cause disease in immunocompetent persons,
• Ants, bees, wasps but may do so with greater frequency in immuno-
• Medically important source of venom suppressed persons
• Ants serve as intermediate hosts for flukes: Fasciola • Fungi-related organisms (Metenier and Vivares,2004)
lanceolata, Eurytrema pancreaticum. • Most human infections are caused by the following
genera: Enterocytozoon and Encephalitozoon
Order Siphonaptera
• Fleas
• Wingless and laterally compressed EPIDEMIOLOGY
• Fleas act as intermediate hosts of tapeworm: Dypi- • Epidemiology is the body of knowledge that concerns
lidium caninum. with occurrence and distribution of disease in hu-
man population and communities. It may include
Order Diptera the study to the manifestation of any time. Even
• One pair of true wings. though treatment, prevention, and control measure
• Mosquitoes, flies, and gnats. are available, parasitic infection still occurs and thus
• Some larval flies are parasitic in humans and ani- it is important to study and monitor their trends.
mals. • Prevalence is a statistical study referring to the num-
• Acts as vectors of parasites. ber of cases of a disease that are present in a particu-
lar population at a given time.
Mosquito : Plasmodium sp. : Malaria • Incidence refers to the number of new cases that de-
: Wuchereria bancrofti : Lymphatic filariasis velop in a given period of time
Tse-tse fly : Trypanosoma brucei : Sleeping sickness
• Distribution of disease (Belizario and De Leon, 2015).
gambiense
: Trypanosoma brucei 1. Endemic When a disease in human population
rhodesiense maintains a relatively steady, moderate
Sand fly : Leishmania donovani : Kala-azar level
Deer fly : Loa loa : Calabar swelling 2. Epidemic If there is a sharp rise in the incidence or
an outbreak of considerable intensity
Black fly : Onchocerca volvulus : River blindness
occurs
Gnats : Mansonella sp. : Commensal filarial
3. Hyperendemic If the prevalence of a disease in a
worms
community is high
4. Sporadic If it appears only occasionally in one or at
Phylum Pentastomida most few members of the community
• All are endoparasitic forms. 5. Pandemics The disease covers extensive area of the
• Known as tongue worms, or linguatulids. world
• Prevalence of parasitic infections • Heterophydiasis: 1.6% prevalence in 2004

• Estimates of the prevalence of parasitic diseases but increased to 10% in 2005 (Philippines)
are at best extremely rough, as reporting of mor- (Montejo and Yumang, 2008).
bidity is essentially nonexistent in many of the
areas in which these diseases occur. WORLD DISTRIBUTION OF PARASITIC
• The following estimates are based on those of DISEASES
the World Health Organization (WHO) through
Figs. 1.1 through 1.12 show in rough outline the world
2002, the Centers for Disease Control and Pre-
distribution of many of the important parasitic diseas-
vention (CDC) through 2004, and others:
es. Those with a restricted distribution are omitted, as
• Amoebiasis: approximately 1% of world popula-
are those that occur essentially worldwide.
tion infected; annual deaths, to 100,000; 2nd
leading cause of death due to parasitic disease.
NEWS UPDATE
• Giardiasis: worldwide, G. duodenalis (formerly
G. lamblia) approximately >300 million cases 60 TO 80% OF POPULATION AT HIGH RISK FROM
are reported annually; Giardiasis is 20% to PARASITES
40% of infection is highest among children Cebu City – As many as 80% of the Philippines’
<5 years of age. population is at risk from parasites, according to the
• Malaria: population currently infected, more Department of Health (DOH) in Central Visayas. Dr.
than 500 million; annual deaths, 2.5 million. Van Philip Baton, DOH regional medical officer, said
• Leishmaniasis: estimated 700,000 to 1 million new at Tuesday’s AGIO Forum that every January and
June DOH goes on a nationwide deworming program
cases; 26,000 to 65,000 deaths occur annually.
to rid the country’s youth of parasites. Baton said the
• African trypanosomiasis: new cases per year,
“Ascaris” parasite thrives in dirty environments, “mostly
100,000; annual deaths, 50,000. in rural mountain and coastal areas or even in some
• American trypanosomiasis: population current- urban/slums where people do not have toilets and open
ly infected, 16 million to 18 million; annual defecation is almost a norm among children.” The lack
deaths, 50,000. of clean water supply is another factor why parasites
• Schistosomiasis: approximately 200 million in- thrive, he said. Children are the targets for mass
fected (includes combined cases):Schistosoma deworming because they are more prone to getting
haematobium, approximately 100 million in- parasites. DOH has a two-pronged approach to fight
fected Schistosoma mansoni, approximately parasitism, Baton said. Community-based deworming
targets children ages 1 to 4, 5 to 12, and 13 to 18 years,
80 million infected Schistosoma japonicum,
while school-based deworming is for children ages 5
approximately 1.5 million infected; annual
to 12 and 13 to 15 years. Baton said that in July 2017
deaths, 500,000 to 1 million. DOH dewormed 925,543 of the over 1.045 million
• Clonorchiasis and opisthorchiasis: 13.5 million children in Central Visayas ages 5 to 12, and 500,994
infected. children ages 13 to 15. Baton said community-based
• Paragonimiasis: 20 million infected. deworming is not as successful because some villages
• Fasciolopsiasis: 10 million infected. are too remote, and not all parents bring their children
• Lymphatic filariasis: 128 million infected. to health centers for deworming. For community-based
• Onchocerciasis: 17.7 million infected with ap- deworming, of 766,670 children ages 1 to 4, only
proximately 270,000 blinds. 604,503 were dewormed. Of the 437,418 children ages
5 to 12 years, only 15,574 or 30.99% were dewormed.
• Dracunculiasis: <75,000 infected in sub-Saha-
Of 481,967 children 13–18 years old only 58,937 or
ran Africa.
12.23% had been dewormed, Baton said. Overall, “65%
• Ascariasis: 1.3 billion infected: annual deaths, of the eligible population of 1 to 18 years old have been
approximately 60,000. dewormed based on our July 2017 data,” Baton said.
• Hookworm: at least 1 billion infected. DOH has various programs to eradicate parasitism
• Trichuriasis: 900 million infected. infection in the country. Baton advised the public
• Strongyloidiasis: 35 million infected. to have toilets at home and in schools with available
• Trichostrongyliasis: 5.5 million infected. water to clean the toilets and for washing hands.
• Cestodiases: 65 million infected. “Hygiene and environmental sanitation and cleanliness
• Fascioliasis: estimated 91.1 million at risk for are still the best protection against parasites,” he said.
Reference: Manila Bulletin, Philippines, February 7,
infection worldwide and as many as 17 mil-
2018, by Minerva BC Newma
lion maybe infected.
(Continued on page 18)
FIG. 1.1 Distribution of cutaneous leishmaniasis.
FIG. 1.2 Distribution of mucocutaneous leishmaniasis.
FIG. 1.3 Distribution of visceral leishmaniasis.
FIG. 1.4 Distribution of trypanosomiasis.
FIG. 1.5 Distribution of malaria; distribution of chloroquine resistance (2004).
FIG. 1.6 Distribution of schistosomiasis.
FIG. 1.7 Distribution of Echinococcus granulosus.
FIG. 1.8 Distribution of Echinococcus multilocularis and Echinococcus vogeli.
FIG. 1.9 Distribution of hookworm infection.
FIG. 1.10 Distribution of clinically important whipworm disease.
FIG. 1.11 Distribution of lymphatic filarial diseases.
FIG. 1.12 Distribution of onchocerciasis and loiasis.
NEWS UPDATE ( Cont. ) Insights from the News Article:

The battle against malaria is still on-going. Researches
Insights from the News Article: have been made on effective control of this deadly parasitic
Children are most vulnerable victims of soil-transmitted infection. Efforts have been done on vector control but
helminthiasis (STH). Key elements in its existence include still too far to be actually effective. Vaccines are still on
unsanitary disposal of stool due to absence of toilets trials. As drug resistance becomes more evident among
and supply of clean water. In this context, a strong health Plasmodia, research on this aspect must be intensified.
policy on environmental sanitation and provision of clean
water supply must be advocated. Moreover, mass drug
administration in the area with high prevalence is highly
encouraged. Health education and promotion can also SUMMARY
be a good approach in reducing the number of cases in
a highly endemic area. • Medical parasitology involves the study of parasites
that establish human infections and cause harm.
• Parasitism refers to a unique relationship that exists
between a parasite and its host.
• Parasites may pose public health problems and
Experts Sound Alarm Over Drug-resistant should be addressed in both veterinary and human
Malaria Strain perspectives.
Multidrug-resistant forms of malaria-causing parasites • Life cycle of every parasite should be well understood
are spreading across Southeast Asia leading to to be able to propose the most appropriate control
“alarmingly high” treatment failure rates of widely used measures.
frontline medication, researchers warned Tuesday. • Infective stages of each parasite and their modes of
In twin studies published in The Lancet Infectious transmission vary and therefore preventive measures
Diseases journal, they revealed that in parts of Thailand, may also differ.
Vietnam and Cambodia up to 80% of the most common • Laboratory diagnosis of the parasites using the
malaria parasite were now resistant to the two most appropriate techniques is crucial in establishing
common antimalarial drugs. The Plasmodium falciparum epidemiologic data. Moreover, accurate laboratory
parasites have also acquired resistance linked to diagnosis is necessary for appropriate treatment.
the failure of treatment in half of cases to one of the
• Prevalence of parasitic infections is continually
newest and most potent frontline drug combinations,
increasing and each community must be alerted on
they said. “These worrying findings indicate that the
the reemerging ones.
problem of multidrug resistance in P. falciparum has
substantially worsened in southeast Asia since 2015,”
said Olivo Miotto from the Wellcome Sanger Institute
and University of Oxford, who co-led the study. “This
REVIEW QUESTIONS
highly successful resistant parasite strain is capable A. Crossword challenge: Learning basic concepts in Para-
of invading new territories and acquiring new genetic sitology! Direction: Read the questions carefully and
properties.” He warned of the “terrifying prospect” of the spell out your answers on the boxes provided in the
parasite spreading to Africa, where most malaria cases crossword puzzle.
occur. A similar resistance to a long-time frontline 1. Refers to a close association that exist between
malaria drug, chloroquine, contributed to millions of two organisms demonstrating dependency to
deaths across Africa in the 1980s. More than 200 million each other.
people are infected with the P. falciparum parasite,
2. Genus to where the most pathogenic intestinal
which is responsible for 9 out of 10 malaria deaths
globally. A drug combination known as DHA-PPQ was
amoeba belongs.
initially effective against the parasite before doctors 3. Majority of this group of helminths are described
noticed signs of resistance in 2013. The most recent as “leaf-like” flattened worms.
study into DHA-PPQ failure rates showed they have now 4. Parasites that do not solely depend on their hosts
reached 53% in southwest Vietnam, and as high as 87% because they can live in their absence.
in northeastern Thailand. 5. A group of soil-transmitted helminths that can
Reference: Manila Bulletin, Philippines, July 23, 2019, cause anemia and are transmitted through skin
by Agence France-Presse penetration of filariform larvae.
6. Insect vector for the transmission of Chaga dis-
ease or American trypanosomiasis.
7. Mechanical or Biological agents of transmission 17. Represent the head of every tapeworm with ros-
of parasitic infections. tellum that either be armed or unarmed.
8. Parasites belonging to the Class Cestode are com- 18. An organism to whom a parasite is dependent to
monly referred to as _____: for food and shelter.
9. Scientific study of a parasite and its unique rela- 19. Genus of tapeworm that requires rodents in its
tionship to its host. life cycle.
10. Resistant forms of most of the protozoans which 20. An example of white blood cell that provides
serve as their infective stages. protection against parasitic infection.
11. Hair-like structures found in the ectoplasm that
B. Multiple choice (20 items). Choose the best answer
aid protozoans in their locomotion
from the given choices.
12. Mosquito-borne parasitic infection that is caused
1. Which among the following amoebae is capable
by Plasmodium sp.
of destroying tissues locally by means of its pro-
13. Group of parasites (Plasmodia and coccidians)
teolytic enzymes?
that have sexual and asexual life cycles.
a. Entamoeba coli
14. Known infective stage of schistosomes that appears
b. Entamoeba histolytica
fork-tailed and is transmitted by skin infection.
c. Dientamoeba fragilis
15. Generally regarded as roundworm.
d. Entamoeba polecki
16. Parasites that thrive outside the body of the host.
Examples include tick and lice.
2. All of the following are considered vector-borne 9. Dientamoeba fragilis in its new taxonomic classifi-
parasitic infection, except: cation is a/an _____.
a. Leishmaniasis a. amoeba
b. Filariasis b. flagellate
c. Malaria c. ciliate
d. Schistosomiasis d. coccidian
3. Entamoeba coli is an example of _____: 10. Resistance to malarial infection caused by

a. Commensal parasite Plasmodiun vivax may be related to _____.
b. Ectoparasite a. Duffy null phenotype
c. Facultative parasite b. Inability of the mosquito to bite
d. Oviparous parasite c. Abnormal red cell morphology
d. Actions of TNF
4. Which among the following parasite depletes vi-
tamin B12 and causes megaloblastic anemia? 11. Which among the following has been associated
a. Fasciolopsis buski to fungi and may cause disease among immuno-
b. Hymenolepis nana suppressed individuals?
c. Dibothriocephalus latus a. Toxoplasma
d. Plasmodium falciparum b. Entamoeba
c. Microsporidia
5. Which among the following may act as a me- d. Acanthocephala
chanical vector passively transferring infective
cyst of Entamoeba histolytica to food? 12. The following insects all belong to the order
a. Mosquito Diptera, except:
b. Tick a. flea
c. Fly b. mosquito
d. Bug c. fly
d. gnat
6. All of the following are true for a trematode, except:
a. They are otherwise called flukes or fluke worm. 13. These are free-living platyhelminths.
b. It requires an intermediate molluscan host. a. trematode
c. Digenetic flukes are parasitic to humans. b. turbellarian
d. Adults appear elongate and ribbon-like. c. tapeworm
d. flukes
7. Which among the following group of parasites
demonstrates antigenic variation? 14. Which among the following parasitic conditions
a. Trypanosomes have been noted in immunocompromised pa-
b. Schistosomes tients?
c. Entamoeba a. strongyloidiasis
d. Ascaris b. schistosomiasis
c. malaria
8. Humans in malarial parasite life cycle act as d. fascioliasis
_____.
a. Definitive Host 15. Pseudopodia are locomotor apparatus used
b. Intermediate Host by _____.
c. Paratenic Host a. Giardia duodenalis
d. Reservoir Host b. Balantidium coli
c. Trypanosoma cuzi
d. Entamoeba histolytica
For items 16 to 20. To which group of parasites would Belizario V, De Leon W. Medical parasitology in the
the following belong to: Philippines. Diliman, Quezon city: The University of the
16. Toxoplasma gondii a. Sarcomastigophora Philippines Press, 2015;5:228–268.
17. Giardia duodenalis b. Ciliophora Metenier G, Vivares CP. Genomics of microbial parasites: The
microsporidial paradigm, pp 207–236, 2004. In: Hirt RP,
18. Balantidium coli c. Apicomplexa
Homer DS (eds.). Organelles, genomes and eukaryote
19. Hymenolepis nana d. Nemathelminthes phylogeny: an evolutionary synthesis in the age of
20. Ascaris lumbricoides e Platyhelminthes genomics. Boca Raton, FL: CRC Press; 2004.
Motejo RD, Yumang AP, Sabay BV. Heterophyidiasis: a
Answers to review questions are available at the end of this re-emerging disease in Davao region. Epidemiology.
book. 2008;19(6). S165–S166.
Robert LS, Janovy J. Foundations of parasitology. 8th ed. New
York: Mc. Graw Hill International ed; 2013.
REFERENCES Tolan RW. Fascioliasis due to Fasciola hepatica and Faciola
Beaver PC, Jung RC, Cupp EW. Clinical parasitology. 9th ed. gigantica infection: an update of this neglected Tropical
USA: Lea and Febiger; 1984. Disease. Lab Med. 2011;42(2):107–116.
CHAPTER 2
Protozoa: Phylum Sarcomastigophora

(Amoebae and Flagellates)
DIANA LEAH M. MENDOZA
INTRODUCTION • Entamoeba polecki, is a zoonotic protozoan of pigs

This chapter outlines the discussion of medically impor- and monkeys. Known to be commensals in humans,
tant Protozoans under the phylum Sarcomastigophora, E. polecki infections are asymptomatic and seldom
their life cycle, morphological characteristics, epidemi- may cause diarrhea.
ology, and clinical diagnosis and treatment. The chap- • Other commensals are Endolimax nana, Blastocystis
ter includes the protozoans classified as intestinal or hominis, and Iodamoeba bütschlii.
lumen-dwelling amoebae, free-living amoebae, atrial • Naegleria and Acanthamoeba are free-living protozo-
flagellates, and the hemoflagellates. It also contains a ans found mainly in freshwater (Table 2.1).
number of commensals and some species of question-
The genus Entamoeba
able pathogenicity. These organisms are generally of
• It is frequently affecting invertebrate and vertebrate
worldwide distribution; the prevalence of the intestinal
organisms.
protozoa in the population correlates roughly with the
• Characterized by a vesicular nucleus with a compar-
level of sanitation.
atively small karyosome located at or near its center
and with varying characteristics of the peripheral
chromatin attached to the nuclear membrane.
PHYLUM SARCOMASTIGOPHORA
• All species are distinguishable from each other
• Organisms from the phylum Sarcomastigophora,
except E. histolytica, E. dispar, E. moshkovskii, and
are amoeboid and flagellated parasites classified
E. hartmanni.
under the Kingdom Protozoa known to cause infec-
• E. histolytica, E. dispar, and E. moshkovskii are mor-
tions in humans.
phologically similar and can only be differenti-
• Amoebae are classified under the sub-phylum Sar-
ated by isoenzyme analysis, restriction fragment
codina. They are characterized by the presence of
length polymorphism, typing with monoclonal
foot-like projections in the cytoplasm known as
antibodies, and polymerase chain reaction.
pseudopodia.
• E. hartmanni is considered to be the “small race”
• Flagellates are classified under the sub-phylum Mas-
of E. histolytica because of its small size.
tigophora, and are organisms characterized by the
• Generalities:
presence of whip-like flagella.
• All entamoeba are lumen-dwelling protozoans ex-
cept E. gingivalis.
The Amoeba
• All are non-pathogenic except E. histolytica.
• Amoeba are known for its ameboid characteristic,
• Cystic stage is the infective stage except E. gingiva-
a cortical zone of undifferentiated ectoplasm, the
lis (Table 2.2).
presence of pseudopodia as a locomotory structure.
• Entamoeba, Naegleria, and Acanthamoeba represent Entamoeba histolytica
the important amoeba in humans. • First described by a young Russian peasant named
• Six species of the genus Entamoeba capable of infect- Losch, from a patient with diarrheic stool.
ing man. • A species-complex amoeba considered to cause
• The commensals, Entamoeba coli, Entamoeba hart- amoebic dysentery and liver abscess worldwide.
manni, Entamoeba dispar, Entamoeba moshkovskii, • Found mostly in tropical and subtropical areas with
and Entamoeba gingivalis. highest prevalence in areas with poor sanitation and
• The pathogenic Entamoeba histolytica. overcrowding.
http://radiologyebook.vn/http://radiologyebook.vn/23
TABLE 2.1
Review of free-living protozoan infections of humans.
Means of human Location of Clinical Laboratory
Disease Parasite infection parasites in humans features diagnosis
Primary amoebic Naegleria Intranasal Brain tissue, menin- Severe frontal Trophozoites in
meningoencephalitis fowleri instillation of ges headache, CSF
(PAM) (free-living amoeba fever, nausea,
amoeba) vomiting, stiff
neck
Granulomatous Acanthamoeba Through lungs or Lungs, s in, Altered Trophozoites in
amoebic meningo- spp. and skin ulcers hematogenous mental state, CSF, trophozoites
encephalitis (GAM) Balamuthia spread to brain headache, or cysts in brain
mandrillaris (disseminated in AIDS seizures, stiff tissue
(free-living patients) neck
amoebae)
Acanthamoeba Acanthamoeba Eye trauma, Cornea Severe ocular Trophozoites or
keratitis spp. (free-living contaminated pain, corneal cysts in corneal
amoebae) contact lenses ulceration, scraping or
CNS abscess biopsy
TABLE 2.2
Review of lumen-dwelling protozoan infections of humans.
Location of
Means of parasites in Other sites Laboratory
Disease Parasite infection humans of infections Clinical features diagnosis
Amoebiasis Entamoeba Ingestion of Large intestine Liver, lungs, Diarrhea, Trophozoites
histolytica cysts (causing ulcers) etc. (causing dysentery, or cysts in
(amoeba) abscesses) abdominal pain feces or tissue
and cramping, aspirate,
tenesmus serologic tests
Giardiasis Giardia Ingestion of Small intestine Common Diarrhea, Cysts or
duodenalis cysts (attached) bile duct, abdominal cramps, trophozoites in
(flagellate) gallbladder flatulence, feces, duodenal
steatorrhea, aspirate, or
malabsorption string test
Trichomoniasis Trichomonas Sexual Vagina, urethra Prostate, Vaginal or urethral Trophozoites
vaginalis intercourse seminal discharge, burning, in vaginal
(flagellate) vesicles itching, dysuria or urethral
discharge
• Distinguished genetically from the commensal E. • Portion of the ectoplasm which is glass-like,
dispar and E. moshkovskii. “hyaline-like” projections.
Morphological characteristics • Cytoplasmic protrusions that may be formed
• Trophozoite at any point on the surface of the organism.
• Size: 12 to 60 µm in diameter (invasive forms • Vary in form: short, blunt, or broad to long
may be more than 20 µm). and finger-like.
• Motility: active and rapid; progressive and unidi- • Motility is seen in freshly passed specimens;
rectional. enhanced by warming of slide by means of
• Move by means of pseudopodia. thermostatically controlled warm stages or by
CHAPTER 2 Protozoa: Phylum Sarcomastigophora (Amoebae and Flagellates) 25
means of a copper coin heated in the flame of cytoplasm—a “Swiss cheese” appearance—
a Bunsen burner and placed on the glass slide. and such degenerate forms can never be iden-
• Warming will not revive amoeba kept too tified with any accuracy.
long in room temperature. • Even without such gross degenerative chang-
• Motility is rarely used to confirm cases of E. es, if the amoebae are kept too long at room
histolytica infection. temperature before being fixed, the finer
• Examination using permanent stains such as tri- structures of the nucleus undergo change.
chrome or iron hematoxylin. These structures are of great importance in
• Mononucleated specific identification of the amoebae.
• Nucleus: the nuclear membrane appears as • Examination using electron microscopy.
delicate but distinct line, on the inner surface • Researchers have described phagocytic stoma-
of which is seen the peripheral chromatin. ta or endocytic food cups on trophozoites of
• A layer of granules, characteristically uniform E. histolytica.
and small. • Present on the surface of amoebae, phagocytic
• Karyosome, is a small mass of chromatin; lo- stomata are used in engulfment.
cated centrally at the nucleus. • Small endocytic stomata are used in pinocyto-
• Between the karyosome and the peripheral sis, the engulfment of liquids, whereas larger
chromatin, the faintly stained fibrils of the li- stomata are involved in phagocytosis of bac-
nin network are occasionally seen. teria and epithelial cells.
• Typical nuclear structure previously described, • Cyst
is depicted in most of the organisms. • Recognized by the presence of a hyaline cyst wall.
• Cytoplasm: finely granular with few bacterial • Highly refractile in unstained preparations.
inclusions and debris. • Yellow-stained glycogen mass (reddish brown
• With iron hematoxylin stain the cytoplasm is with iodine stain) and highly refractile chromatoi-
grayish, nuclear structures are intense bluish dal bars with smoothened and rounded edges are
black, and freshly ingested erythrocytes stain typically seen in immature cysts (precystic stage).
similarly; the red blood cells become progres- • Mature cyst:
sively paler as they are digested. • Size: 10 to 20 µm in diameter.
• With trichrome stain, the cytoplasm is typi- • Usually spherical but may be ovoid or irregu-
cally green, occasionally light pink; nuclear lar in shape.
structures are dark red; and freshly ingested • Nuclei: quadrinucleated mature cyst
erythrocytes may be cherry-red or green. • Cysts contain from one to four (or, rarely,
• Presence of red blood cell inclusion from patient more) nuclei.
with dysentery is diagnostic for E. histolytica. • May appear as small, refractile spheres
• Trophozoites with ingested RBCs are properly within the cytoplasm of the unstained cyst,
termed as “hematophagous” trophozoites. but more often they are not visible.
• In preparation for formation of the resistant • Peripheral chromatin ring may appear
cyst stage, trophozoites extrude all ingested thicker and less uniform in size.
material and assume a rounded form. This • Karyosomes appear small and compact;
stage, referred to as the precyst, may be distin- centrally located, but usually eccentric.
guished by its single rounded nucleus, absence • Cytoplasm:
of ingested material, and lack of a cyst wall; • Glycogen mass disappears.
however, nuclear morphology is often confus- • Chromatoidal bars stain with hematoxylin
ing at this stage, and it is best to rely on either like the chromatin of the nucleus. Elongat-
trophozoites or cysts for specific identification. ed, with rounded or squared ends but may be
• The nucleus of the unstained trophozoite usually ovoid or cigar shaped.
is not visible. • Chromatoidals are more frequently en-
• Bacteria may at times be ingested by this countered in the mono- and binucleate
amoeba. They may also be seen in the cyto- cysts, and a large proportion of mature
plasm if the amoeba is degenerating. quadrinucleate cysts do not possess them.
• Death or degeneration of the parasites leads • With hematoxylin, the chromatoidals
quickly to the formation of vacuoles in the take the same bluish black stain as the
chromatin material of the nucleus, and • Encystation

with trichrome they stain bright red. • Formation of non-labile, non-motile protozoan.
The following characteristics are valuable in the • Cyst formation is possible when the gut is dehy-
identification of the E. histolytica/E. dispar/E. mosh- drated.
kovskii species complex: • Happens only in the intestinal tract; once passed
in stool, cyst formation will no longer possible.
• When hypermotility in the intestinal tract happens,
I. Trophozoites, Suggestive: progressive motility; hyaline
unstained pseudopodia; no ingested bacteria; the amoeba in the lumen may be passed out in liq-
nuclei not visible uid or semi-formed stool as trophozoites. If the mo-
Diagnostic: ingestion of red blood cells tility is normal, they will be “round up” and will be
II. Trophozoites, Suggestive: clear differentiation of differentiated and developed into the four nucleated
stained ectoplasm and endoplasm; no resistant cyst stages.
ingested bacteria • The life cycle of E. histolytica is illustrated in Fig. 2.1.
Diagnostic: fine, uniform granules of Symptoms and pathogenesis (Figs. 2.2–2.9)
peripheral chromatin and small • The symptoms of amoebiasis are far from clear cut and
central karyosome in nucleus; depend in large measure on the extent of tissue inva-
ingested red blood cells; average size sion and on whether the infection is confined to the
over 12 µm intestinal tract or has spread to involve other organs.
III. Cysts, unstained Suggestive: four nuclei; rodlike • Intestinal amoebiasis is the most common form of
chromatoidals infection and may be asymptomatic.
IV. Cysts, stained Suggestive: maximum of four nuclei • Other patients may have more definite symptoms,
having both karyosome and such as diarrhea or dysentery, abdominal pain and
peripheral chromatin; diameter over cramping, flatulence, anorexia, weight loss, and
10 µm
chronic fatigue.
Diagnostic: typical nuclear structure;
• All patients with symptomatic intestinal amoebiasis
chromatoidal bars with rounded or
squared ends; diameter over 10 µm are spoken of as having amoebic dysentery with pre-
sentation of blood and mucus in their stools.
Differentiation of E. histolytica from the commensals E. dispar • Amoebic colitis is a term that can be used to denote
and E. moshkovskii is not possible by morphology but any symptomatic intestinal infection.
requires the use of species-specific monoclonal antibodies or
• The susceptibility of humans to E. histolytica infec-
highly sensitive and specific PCR techniques (Tanyuksel and
tion is associated with specific alleles of the HLA
Petri, 2003; Garcia, 2017).
complex.
Life cycle • The number of ingested cysts, the pathogenic capac-
• Infective E. histolytica cyst is ingested by the host. ity of the strain, host immunity, and the presence of
• Excystation happens in the small intestine. enteric bacteria are determining factors of the degree
• Requires neutral pH levels or slightly alkaline en- of invasion.
vironment. • Patients supplemented with corticosteroid and
• No excystation occurs in an acidic environment. those severely burned patients may provoke severe
• Once activated, the ingested cyst will separate into amoebic colitis.
four trophozoites. • Mortality cases are high among pregnant women in
• E. histolytica trophozoites inhabit and undergo bi- relation with the amoebic severity and maternal stress.
nary fission in the large intestines. • Proposed mechanism for E. histolytica virulence:
• Trophozoites invade the intestinal lumen some • Production of enzymes and cytotoxic substances.
may invade the mucosal crypts of the intestine • Cysteine proteinase - degrades of host proteins;
where they feed on red blood cells and form ul- enables attachment to the gut by degrading
cers. mucus and debris; stimulates host cell proteo-
• Ulceration of the intestinal wall may give rise lytic cascades.
to amoebic dysentery. • Contact-dependent cell killing.
• Invading amoeba may find their way into the • Gal/GalNAc-binding lectin - responsible for cel-
capillaries to be transported via the blood- lular adherence, contact-dependent toxicity,
stream to the liver or other organs where ab- resistance to host complement, and cell endo-
scess formation may occur. cytosis.
FIG. 2.1 Life cycle of Entamoeba histolytica.
FIG. 2.2 Trophozotie of Entamoeba histolytica stained

with iron hematoxylin. ote the presence of harcot-
Leyden crystals and clumped red blood cells. (Hunter ,
Swartzwelder JC, Clyde DF. Tropical Medicine, 5th ed. FIG. 2.3 Trophozoite of Entamoeba histolytica stained with
Philadelphia: Saunders; 1976.) trichrome. Note the ingested red blood cells (trichrome stain).
FIG. 2.4 Cysts of Entamoeba histolytica, showing nuclei and chromatoidal bars (Photomicrographs by
Zane Price.)
FIG. 2.5 Entamoeba histolytica: 1, trophozoite with hyaline pseudopodium; 4, trophozoite containing
red blood cells; 5, early cyst containing glycogen mass and chromatoidals; 8, mature quadrinucleate cyst
without chromatoidals. Entamoeba hartmanni: 2, 3, trophozoites; 6, 7, mononucleate cysts (2, 4, 6, 7, and 8
show diagnostic features only).
FIG. 2.6 Entamoeba histolytica. Variations in nuclear structure (some original, others adapted from various
sources).
FIG. 2.7 Entamoeba coli. Variations in nuclear structure (some original, others adapted from various
sources).
• Although complement is amoebicidal, patho- • Asymptomatic infection

genic strains of E. histolytica may be resistant • Passing cysts are present in stool among patients
to complement-mediated lysis via inhibition with negative or weak antibody titer.
of membrane attack complex formation. • Occurs in patients infected with pathogenic or
• Amebapore - forms ion channels in the phago- nonpathogenic species.
cytized bacteria and eukaryotic cells. • E. histolytica / E. dispar trophozoites may be re-
• Cytophagocytosis covered in stool; however, phagocytized red
• Trophozoites of a virulent strain of E. histo- blood cells are absent in the cytoplasm.
lytica are able to kill normal human poly- • Results of isoenzyme analysis may be particular
morphonuclear neutrophils, monocytes, and for the nonpathogenic isolates –E. dispar.
macrophages in vitro; however, activated • Symptomatic infections
macrophages are able to kill the same viru- • Symptoms are accompanied by little local reac-
lent amoebae through a contact-dependent, tion and often no recognizable symptoms, dif-
antibody-independent mechanism. fuse inflammation, indistinguishable from the
The following clinical classification is adapted from nonspecific inflammatory lesion of other types
the World Health Organization (WHO) Report on Am- of colitis.
oebiasis (1969). • May provoke mild diarrhea with only a few loose
I. Asymptomatic infections stools daily, perhaps alternating with periods of
II. Symptomatic infections constipation.
A. Intestinal amoebiasis • In normal stools, careful examination of the fe-
1. Dysenteric ces may reveal flecks of blood-tinged mucus, of-
2. Nondysenteric colitis ten containing numbers of motile E. histolytica.
B. Extraintestinal amoebiasis • Patients with more acute illness may have a doz-
1. Hepatic en or more explosive liquid stools daily, contain-
a. Acute nonsuppurative ing much blood and mucus and perhaps accom-
b. Liver abscess panied by abdominal cramps.
2. Pulmonary • Tenesmus, painful spasms of the anal sphincter, is
3. Other extraintestinal foci (very rare) a sign of rectal ulceration.
FIG. 2.8 Entamoeba coli: 1, trophozoite with ingested bacteria and granular pseudopodium; 2, 3,
trophozoites; 4, early cyst with nucleus undergoing division and containing glycogen mass; 5, octonucleate
cyst with chromatoidals; 6, octonucleate cyst; 7, quadrinucleate cyst (2, 3, 5, 6, and 7 show diagnostic
features only).
• Intestinal infections: • After attachment, the parasite kills the host

• The attachment of E. histolytica trophozoites to cell in an extracellular process that involves
the colonic mucosa is mediated by an amoe- activation of host cell Caspase-3, leading to
bal galactose-inhibitable adherence lectin. apoptotic death and engulfment of the host
• Intestinal secretory IgA against the parasite cell.
Gal / GalNAc lectin is associated with im- • Fever is not characteristic of uncomplicated
munity to reinfection. amoebic colitis.
FIG. 2.9 1, 2, Early cysts of Entamoeba histolytica and Entamoeba coli, respectively; both contain nuclei
undergoing division; 3, binucleate cyst of Entamoeba hartmanni with resting nuclei; 4, quadrinucleate
cyst of E. hartmanni; 5, harcot-Leyden crystals 6, Entamoeba polecki cyst with inclusion mass and
chromatoidals with angular and pointed ends (3 and 4 show diagnostic features only).
• Mild leukocytosis may be seen, which is prob- • Abdominal palpation may reveal tenderness
ably a response to the secondary bacterial in- of the cecum, transverse colon, or sigmoid.
fection so frequently present. • Amoebae penetration
• The white blood cell count seldom rises • Penetration of muscularis mucosae into
above 12,000 per microliter; in bacillary the submucosa
dysentery the average may be not much • Flask-shaped ulceration
higher, but counts may reach 16,000 to • Intraluminal bleeding
20,000 per microliter. • If large numbers of ulcers are produced,
• Even in moderately severe attacks of diar- they may coalesce by means of intercom-
rhea or dysentery, spontaneous subsidence municating submucosal sinus passages.
or alteration with periods of constipation is • The undermined mucosa may remain fair-
common. ly normal in appearance.
• If the undermining is extensive and there is • Known as a toxic response to intestinal in-
secondary bacterial infection, there may be fection, unrelated to the local presence of
necrosis and sloughing of large portions of amoebae.
the intestinal wall. • A condition known as amoebic hepatitis
• Intestinal casts may appear, but rarely in has been postulated, but if defined as a dif-
the stools. fuse early stage of liver infection, without
• Sigmoidoscopic examination abscess formation, it remains hypothetical.
• Almost normal mucosal pattern or one • Hepatic infection is characterized by liver ten-
that is indistinguishable from those seen derness and enlargement, fever, weight loss,
in ulcerative or granulomatous colitis. and sometimes a cough with evidence of
• Scattered ulceration may range from few pneumonitis involving the right lower lung
millimeters in diameter (10 or 12 mm) field.
with raised edges but with normal-looking • In some cases, hepatomegaly and tender-
mucosa elsewhere. ness may occur in amoebic colitis without
• Used to differentiate amoebic from bacil- any evidence of hepatic infection.
lary dysentery, where the entire mucosa be- • The right leaf of the diaphragm may be el-
ing involved in bacillary dysentery. evated and fixed on position.
• As the amoebic infection progresses, co- • Multiplication of amoebae in the liver
alescence of the ulcers may produce irregu- may lead to the development of single or
larly wandering ulcer trenches, sometimes multiple abscesses, although the majority
with hairlike remnants of the more resis- of amoebae that reach the liver are prob-
tant supportive structures projecting from ably destroyed there and do not produce
their bases (“buffalo skin” or “Dyak hair” abscesses.
ulcers). • Single large abscess may arise from the co-
• Perforation of an amoebic ulcer alescence of multiple smaller ones.
• It is accompanied by the usual signs of • With abscess formation, hepatic pain be-
peritoneal irritation or infection; how- comes more severe and continuous; pain
ever, slow leakage to the abdominal cavity may also be referred to the right or left
through a severely diseased colonic wall shoulder, depending on the position of the
may be more common. abscess.
• It is marked by distention, ileus, and gas in • There is leukocytosis of 1 ,000 to 3 ,000
the peritoneal cavity, but not by the board- per microliter without a characteristic dif-
like abdomen that marks acute perfora- ferential, and also fever and night sweats.
tion. Surgical intervention may be feasible • Fever occurs usually in the afternoon, reach-
in cases of acute perforation but not in the ing a peak of about 102°F, and it is accom-
chronic type or in amoebic appendicitis, as panied or followed by profuse sweating.
the infected gut is quite friable. • Aspiration of an amoebic abscess usually
• Formation of chronic granulomatous lesion yields a thick, reddish brown fluid, which
• Also known as an amoeboma, develops rarely contains amoebae.
most frequently in the cecal or rectosig- • Pleuro-pulmonary amoebiasis
moid region. • Pulmonary amoebiasis occurs in 2 to 3
• It may produce a so-called napkin-ring con- of patients with invasive infections.
striction of the bowel wall indistinguish- • It is the second most common extraint-
able on x-ray examination from an annular estinal infection caused by pathogenic E.
carcinoma, or it may give rise to a charac- histolytica, frequently associated with the
teristic (though nonspecific) conical con- erosion of a hepatic abscess through the
figuration of the cecum. diaphragm into the lung.
• Radiologic findings are similar to those • Pleurisy, with or without effusion or pleural
seen in inflammatory bowel disease, al- rub, or right lower lobe pneumonitis may
though seldom with involvement of the signal a subdiaphragmatic abscess without
terminal ileum. actual rupture into the pleural space.
• Extraintestinal amoebiasis • If the abscess is localized in the left lobe of
• The hepatic enlargement the liver, it may, involve the left lung.
• If hepatic spread of the infection extends • A seroepidemiologic survey of antibody respons-

to involve a bronchus, amoebae may be es to the zymodemes of E. histolytica showed that
found in the sputum. 94% to 100% of persons infected with amoe-
• Primary pulmonary amoebiasis is associ- bae having pathogenic zymodemes were sero-
ated with infection resulted from blood positive, even though some had no symptoms,
leakage from the colon as the primary site whereas only 2% to 4% of persons infected with
rather from the liver. amoebae of nonpathogenic zymodemes were se-
• Other extraintestinal involvement such as the ropositive.
brain, pericardium, and spleen, are uncom- • Molecular diagnosis
mon and when they occur are most often ac- • The polymerase chain reaction (PCR) amplifica-
companied by amoebic liver abscess. tion of genomic DNA, hybridization of cDNA
• Amoebic infection of the skin is rare but clones, and rRNA probes provided additional
may produce extensive gangrenous ulcer- evidence for the separation of the invasive E.
ations of the perineal tissues or affect the histolytica from the noninvasive E. dispar.
skin surrounding a colostomy or draining • Subsequent research using RNA and DNA probes
hepatic abscess. also indicated differences between invasive and
• Vaginal, urethral, and clitoral infections noninvasive strains.
have been reported. • The inability to morphologically distinguish E.
• Amoebiasis of the penis is seen following histolytica from the nonpathogens E. dispar and
intercourse with a partner who has vaginal E. moshkovskii underscores the importance of the
amoebiasis and also as a consequence of modern diagnostic tests.
anal intercourse. • Liver scans
Diagnosis • Reveal areas of nonvisualization, most frequently
• Whenever possible, a laboratory diagnosis of E. single and in the right lobe, less often multiple or
histolytica infection, unless confirmed by visualiza- in other locations.
tion of ingested red blood cells in the trophozoite, • Sonography, magnetic resonance imaging, and
should be substantiated by: computed tomography offer convenient means
1. Presence of red blood cells in the stool for evaluating the development and resolution
2. Serum antibody titer, and when refined imaging techniques lead to early
3. Stool E. histolytica antigen titer. diagnosis and treatment.
• Routine diagnosis • Liver function tests are of little value in the dif-
• For the diagnosis of amoebiasis, microscopic ex- ferential diagnosis of amoebic abscess.
amination of stool is useful, especially in devel- • Organisms are confined to the hepatic tissue of
oping countries with limited sources. the abscess walls. Under these circumstances,
• The traditional stool ova and parasite exam is diagnosis by response to therapy is frequently
not sensitive and it lacks specificity in identi- the only practical approach, although modern
fying the organism. techniques such as real-time PCR are highly
• Antigen and antibody detection sensitive for detecting E. histolytica DNA in the
• The best way to diagnose E. histolytica infection is abscess.
by a combination of stool antigen detection and • Tissue examination
serology. • Processing may include special histological stain-
• Serologic techniques (see Chapter 10) have been ing techniques.
employed for many years in the diagnosis of • Periodic acid-Schiff (PAS) staining is used to lo-
amoebiasis. cate organisms within the tissues.
• Indirect hemagglutination (IHA) and enzyme- • Trophozoites appearance - bright pink in a
linked immunosorbent assay (ELISA) tests are green-blue background
available. • Hematoxylin and eosin staining allows accurate
• Enzyme immunoassays (EIA) are available morphological demonstration of trophozoites.
to detect Entamoeba-specific antigen in fecal Epidemiology
specimens. • Sporadic cases of E. histolytica infections occur
• A monoclonal ELISA kit detects E. histolytica worldwide, but mostly prevalent throughout the
Gal/GalNAc lectin in stool and distinguishes countries in the south-east Asia, south-east and west
it from E. dispar. Africa, and Central and South America.
• The prevalence of amoebic infection, as of most en- Treatment

teric diseases, varies with the level of sanitation and • Treatment varies with the clinical stage of the infec-
is generally higher in the tropics and subtropics than tion.
in temperate climates. • For asymptomatic intestinal amoebiasis, treatment
• Based from the comparisons in the Global Bur- may not be strictly necessary, although it is impru-
den of Disease (GBD compare), enteric infections dent to neglect such infections, which may either
caused by pathogenic amoeba remain one of the become symptomatic or provide a nidus for extrain-
causes of mortality worldwide in 2017. testinal disease or spread to others.
• In the Philippines, amoebiasis has been noted • Methods of treatment of the asymptomatic case and
among children alongside with other diarrheal dis- of amoebic colitis are essentially identical.
ease etiologies such as rotavirus, cholera, shigella, • Treatment for invasive disease.
salmonella, and enterotoxigenic organisms. • Metronidazole or the related drug tinidazole.
• The severity of the disease and the incidence of com- • Treatment of intestinal (luminal) infection.
plications may likewise be greater in the tropics, re- • Paromomycin
flecting the higher incidence of infection. • Diloxanide furoate (Furamide), another luminal
• The severity of the infection is associated greatly amoebicide, is restricted to patients who only
with malnutrition. pass cysts.
• E. histolytica and E. dispar infection is observed in • Metronidazole is effective only against anaerobic or
men who have sex with men. microaerophilic organisms. It is activated by reduc-
• In the United States, amoebiasis is more common in tion by ferredoxin, generating a reactive radical.
immigrants and travelers from developing countries. • Metronidazole or tinidazole is recommended for
• In any region, it is more prevalent under crowded treatment of acute amoebic colitis.
conditions, and may reach epidemic proportions • Side effects of metronidazole treatment include
in orphanages, prisons, and asylums. nausea, diarrhea, metallic taste, and headache.
• In the United States, Canada, and Europe, the • Other side effects are uncommon, and none is
relatively few epidemic outbreaks can usually be usually so severe as to preclude use of the drug.
traced to sewage-contaminated drinking water. • The patient should be warned to abstain from al-
• Of 914 autopsies performed in a general hospital cohol during treatment with metronidazole.
in Mexico in the 1960s, amoebiasis was found to be • It is approved for use during the last two trimes-
the fourth leading cause of death. ters of pregnancy.
• In another report, amoebiasis was identified as the • Tinidazole is in general better tolerated than
third most prevalent infectious disease in Mexico metronidazole and requires a shorter course of
and currently approximately 10% of the popula- treatment.
tion has serologic evidence of prior amoebiasis. • A 14-year study by the Centers for Disease Control
• A study using modern diagnostic techniques dem- and Prevention involving 4371 treatment courses
onstrated E. histolytica dysentery in 2% of children concluded that diloxanide was a safe and effective
per year in Dhaka, Bangladesh. drug for treating asymptomatic cyst passers and that
• From an epidemiologic standpoint, asymptomatic it was particularly well tolerated in children.
patients are of utmost importance in the transmis- • In cases of treatment failures, metronidazole treat-
sion of the disease. ment should be followed with a luminal agent (par-
• Water contamination. omomycin or diloxanide) to eliminate intestinal
• Poor food handling. colonization and prevent relapse.
• Food contamination by flies, and possibly cock- • Emetine was formerly used for treatment of amoe-
roaches. biasis, but cardiac toxicity has precluded its routine
• The use of human feces (night soil) as fertilizer. use.
• Cysts are relatively resistant but are killed by drying, • Metronidazole and tinidazole are first-line agents
by temperatures over 55oC, and by superchlorina- in the treatment of hepatic abscess.
tion or the addition of iodine to drinking water. • Drainage of larger abscesses may be necessary in
• Entamoeba moshkovskii has been isolated from sew- exceptional circumstances.
age plants in many parts of the world and in one Prevention
study was shown to infect a substantial minority of • Most amoebiasis is acquired through fecal con-
children in Bangladesh. tamination of food and water, and prevention of
infection involves measures designed to break the • Regardless of symptoms, the presence of what
chain of transmission. appear to be E. histolytica-like forms in the stool,
• Water can readily be disinfected by boiling and along with a positive serologic response, indi-
treatment with iodine. cates the presence of true E. histolytica.
• Avoid the usage of human feces (night soil) as • A negative serologic test and E. histolytica-like
fertilizers. amoebae in the stool indicates E. dispar.
• In most developing countries, it is best to • Using routine microscopic analysis of stool without
avoid eating food sold in streets and to avoid the use of immunoassay procedures, morphologi-
consumption of salads and fruits from unreli- cally distinguished organism must be reported as
able food handlers. “Entamoeba histolytica/Entamoeba dispar.”
• Food handlers found to have amoebiasis should • Reliable detection procedures for Entamoeba anti-
be treated completely for amoebiasis before re- gens and antibodies are commercially available.
suming to work. • Commercially produced serological test kits that
• Regulations in this regard may vary from one detect a fecal Entamoeba antigen or antibody
area to another, but a minimum criterion for common to both species, various assays are now
cure should be a series of negative results of available (see Chapter 10).
stool examinations (preferably at least three • Molecular studies have been flourished in the past
examinations) taken at least 1 month after decades. Attempts on genetic encoding have identi-
completion of treatment. fied techniques that will differentiate various para-
sitic species.
Entamoeba dispar and E. moshkovskii • Detection rates and specificity have been greatly
• Originally proposed by Emile Brumpt in 192 , that improved by PCR assays.
E. histolytica considered to be a single species is actu- • In one study in Iran (Najafi, 2019), PCR has
ally a species complex in which E. histolytica is the 99% to 100% specificity in targeting the spe-
invasive species, and E. dispar and E. moshkovskii are cific gene among stool samples. They concluded
morphologically identical noninvasive ones. the reliability of the technique in early detec-
• Based on evidence accumulated from numerous tion of asymptomatic and symptomatic cases of
sources, a redescription of E. histolytica has con- amoebiasis.
firmed Brumpt’s hypothesis
• E. dispar (dispar = different) and E. moshkovskii are Entamoeba hartmanni
then synonymous with what was formerly designat- • There are no morphologic differences between E.
ed nonpathogenic E. histolytica. histolytica/E. dispar/E. moshkovskii and E. hartmanni,
• E. dispar seems capable of causing focal intestinal except for size.
lesions in experimental animals such as kittens, ger- • E. hartmanni has now attained general acceptance as
bils, and guinea pigs. the name for the amoebae formerly designated as
• E. dispar does not cause symptomatic disease, nor “small race” E. histolytica.
does it elicit the production of serum antibodies. • Studies of prevalence in which this E. hartmanni
• E. dispar is approximately nine times more preva- has been differentiated from E. histolytica indicate
lent than E. histolytica, and together they infect roughly similar incidence and distribution for the
about 10% of the world’s population. two.
• However, only E. histolytica causes disease, which • Most authorities consider E. hartmanni to be non-
affects some 50 million persons worldwide, with pathogenic and accordingly do not treat this
up to 110,000 deaths yearly. infection.
• The prevalence of E. moshkovskii is not known. General morphology
Diagnosis • Rounded trophozoites of E. hartmanni measure
• Microscopy alone for the unequivocal detection of from 3 to nearly 12 µm in diameter; the cyst size
E. histolytica infection is not reliable as E. histolytica, range is from 4 to 10 µm.
E. dispar, and E. moshkovskii are morphologically in- • Nuclear structure shows the same variations seen in
distinguishable. E. histolytica, and there is no consistent difference be-
• Microscopic identification of E. histolytica can only tween the two species in nuclear-cytoplasmic ratio.
be made if ingested erythrocytes are present in its • The chromatoidal material assumes a similar rod- or
trophozoites. cigarlike form in the two species.
• E. hartmanni organisms ingest bacteria but not red • Granules of chromatin may be seen scattered
blood cells. between the karyosome and the peripheral
The characteristics shown in the following table are chromatin, and sometimes a linin network is
of value in the identification of Entamoeba hartmanni. visible.
• Cytoplasm:
• The cytoplasm is granular, frequently contain-
I. Trophozoites, unstained Not characteristic
ing many vacuoles.
II. Trophozoites, stained Diagnostic: nuclear structure
• Red blood cells are not ingested by this amoeba
similar to that of
E. histolytica; ingested bacteria;
except under the most unusual circumstances.
diameter less than 12 µm • Bacteria are regularly seen in vacuoles in the
cytoplasm.
III. Cysts, unstained Suggestive: four nuclei; rounded
form
• Precystic forms are seen, as in E. histolytica, but
as in that species the morphology is not very dis-
IV. Cysts, stained Diagnostic: typical nuclear
tinctive and identification should never be based
structure; chromatoidal bars
with rounded or squared ends; on examination of these forms alone, whether
diameter less than 10 µm stained or unstained.
• Cyst
Entamoeba coli • The spherical cyst wall is highly refractile and the
• E. coli is a nonpathogenic amoeba that closely resem- cytoplasm granular in appearance.
bles E. histolytica; the two species may be confused, • Food vacuoles are absent.
leading either to superfluous treatment for a non- • Size: 10 to nearly 3 µm in diameter; the average
pathogenic parasite or to omission of appropriate diameter is greater than in cysts of the pathogenic
therapy for pathogens. species.
• Initially considered as pathogenic not later than the • Nuclei:
year 1913, when E. coli was proven to be nonpatho- • The nuclei are usually readily observed; they
genic. vary in number from one to eight.
Morphological characteristics • Mature cyst contains 8 nuclei; hypernucleate
• Trophozoite forms with 16 or 32 nuclei were observed.
• Size: 1 to 0 µm in diameter (average slightly • The eccentric position of the karyosome
more than 20 µm). can frequently be distinguished, even in un-
• Motility: sluggish nondirectional and nonpro- stained amoebae.
gressive. • Cytoplasm
• Move by means of blunt and short pseudopo- • E. coli cyst cytoplasm is very granular; areas oc-
dia; never long and fingerlike as they may be cupied by glycogen before fixation are marked
in E. histolytica. by empty spaces in the cytoplasm of the fixed
• Pseudopodia are extruded slowly and are not and stained cysts.
hyaline, and there is no striking differentia- • While glycogen may occur in the cysts of
tion of the cytoplasm into ectoplasm and en- E. histolytica, the perinuclear disposition
doplasm. of this material is more characteristic of
• Nucleus: E. coli.
• The single nucleus is usually easily discerned. • Chromatoidal bodies are less common than
• Peripheral chromatin in E. coli is irregular in E. histolytica but occasionally may be ob-
both in size and in arrangement on the nucle- served as clear, thin lines or rods of refractile
ar membrane; it is definitely more abundant material in the cytoplasm.
than is usual in E. histolytica. • Less frequently observed than E. histolytica/
• A ring of refractile granules representing the E. dispar.
peripheral chromatin encloses another eccen- • The chromatoidals are seen to be com-
tric refractile mass, the karyosome. posed of splinter-shaped or rarely ribbon-
• The karyosome is large, frequently irregular in or threadlike bodies.
shape, usually eccentric in position, and sur- • Heavier bodies with irregular ends are also
rounded by a halo of nonstaining material. frequently seen.
FIG. 2.10 Trophozoite of Entamoeba gingivalis. There is no cyst stage. Note ingested leukocytes.
• With an iodine stain, glycogen may be seen in Entamoeba gingivalis

the cysts of E. coli; often masses of this dark- • E. gingivalis (Fig. 2.10) bear a close morphologic re-
staining material completely surround the semblance to E. histolytica.
nuclei, which are not, however, entirely ob- • Isolates are often found in pyorrheal pockets be-
scured. tween the teeth and gums and in the tonsillar crypts.
• It was noted to be the first parasitic amoeba describe
The characteristics shown in the following table are in humans.
of value in the identification of Entamoeba coli. • It has been reported to multiply in bronchial mucus
and to appear in the sputum, where it might be mis-
I. Trophozoites, unstained Suggestive: sluggish, taken for E. histolytica from a pulmonary abscess.
nondirectional • These amoebae are most frequently recovered from
motility; short, granular the mouths of patients suffering from pyorrhea al-
pseudopodia; ingested veolaris.
bacteria; visible nucleus • In a survey made from gingival scrapings, amoebae
II. Trophozoites, stained Suggestive: granular of E. gingivalis were found in 59% of 113 dental pa-
cytoplasm without much tients and in 32% of 96 control subjects with good
differentiation into oral hygiene.
ectoplasm and endoplasm;
• A few cases of Entamoeba infection of the uterus have
bacteria in food vacuoles
Diagnostic: nucleus with
been described in patients with no intestinal infec-
irregular clumps of tion who lived in areas of low endemicity.
peripheral chromatin; General morphology
large, irregular, eccentric • E. gingivalis forms no cysts.
karyosome • Size: to 1 µm in diameter.
III. Cysts, unstained Suggestive: eight nuclei; • The cytoplasm of the E. gingivalis may contain bac-
glycogen mass surrounding teria and occasional red cells but most frequently is
nuclei (iodine stains) filled with portions of ingested leukocytes.
IV. Cysts, stained Suggestive: maximum of • Lobose pseudopodia may seen to be long and blunt.
eight nuclei, having • Nuclear fragments from the leukocytes are usually
karyosome and peripheral recognizable in stained specimens and serve to iden-
chromatin tify the amoeba, as E. gingivalis is the only species
Diagnostic: typical nuclear that ingests these cells.
structure; splinter-shaped • Mononucleated with centrally located small karyo-
or irregular chromatoidals
some.
Entamoeba polecki • Sometimes larger granules are scattered among

• First reported as an intestinal parasite of pigs and the smaller ones, or the peripheral chromatin
monkeys. may be massed at one or both poles.
• E. polecki has been found occasionally in humans. • Cyst
• A few reports describe patients with diarrhea appar- • The cyst state of E. polecki is characterized by a
ently caused by infection with this parasite. single nucleus.
• In parts of Papua New Guinea, it has been noted to • Very rarely, it is binucleate or quadrinucleate.
be most common intestinal amoeba of humans. • Chromatoidal material resembling that seen in
• Although pig-to-human transmission is considered E. histolytica is formed in the cysts and is often
to be the most likely route of human infection, the abundant.
possibility of human-to-human transmission exists • The ends of the chromatoidals are frequently
where the prevalence of infection is high. angular and sometimes pointed, rather than
• In eastern China where pig industry is common, oc- regularly rounded or squared off as in E. histo-
currences were noted. lytica.
• Findings of a study suggest that pigs are potential • Threadlike chromatoidals have also been
sources of zoonotic amoebiasis. reported.
• Entamoeba chattoni, an organism morphologically • Glycogen may be present, and in addition
identical to E. polecki and one that frequently is approximately half of the cysts contain an “in-
found in apes and monkeys, has been identified clusion mass.”
in eight human infections. All but one of the in- • These masses are spherical or ovoid, without
fected individuals had close contact with monkeys. being sharply defined
Trophozoites were isolated in culture and positively • In hematoxylin preparations they are not dis-
identified as E. chattoni by isoenzyme characteriza- solved as is glycogen, and they stain much
tion. more faintly than chromatoidal material.
• Apparently, the organisms cause no clinical dis- • Unstained cysts cannot be differentiated with any
ease in either simians or humans. certainty from mononucleate cysts of the other
Morphological characteristics two species of Entamoeba, though the presence in
• Trophozoite a formed stool of large mononucleate cysts, and
• Most trophozoites of E. polecki resemble those of the near absence of ones with greater numbers of
E. coli in their motility, in the granularity and de- nuclei, is suggestive.
gree of vacuolization of their cytoplasm, and in • Iodine-stained cysts are likewise not distinctive.
the ingestion of bacteria. • The inclusion mass does not take the dark
• Directional motility such as is seen in E. histo- stain characteristic of glycogen and is not seen
lytica occurs only sporadically. clearly.
• Pseudopodia are usually formed slowly but The following characteristics are of value in the
occasionally may be thrust out in the explo- identification of Entamoeba polecki:
sive manner characteristic of E. histolytica.
• The nucleus is occasionally visible in the un- I. Trophozoites, Not characteristic
stained trophozoite. unstained
• In stained preparations the nuclear structure ap- II. Trophozoites, Suggestive: nucleus with minute central
pears somewhat intermediate between those of stained karyosome, with peripheral chromatin
E. histolytica and E. coli. evenly distributed or massed at one or
• The karyosome is small in trophozoites and is both poles; ingested bacteria
usually centrally located. III. Cysts, unstained Suggestive: uniform mononuclear
• In permanently stained preparations, it may condition
be spherical or stellate in shape, or it may con- IV. Cysts, stained Suggestive: mononucleate cysts: large
sist of a group of small granules. central karyosomes with evenly
• The peripheral chromatin is generally seen in the distributed peripheral chromatin or
form of fine granules evenly distributed on the peripheral chromatin massed at one or
nuclear membrane. both poles
• Normally compact, the peripheral chromatin is Diagnostic: inclusion masses, chromatoidal
occasionally dispersed. bars with angular or pointed ends
Diagnosis basis for immediate identification of this genus in

• Routine microscopic analysis of fresh stool remains stained preparations.
the traditional method. However, morphological • Peripheral chromatin forming a distinct layer under
characteristic of E. polecki is difficult to distinguish the nuclear membrane is not regularly seen in the
from other Entamoeba spp. other two genera.
• Molecular techniques including polymerase chain
reaction and nucleotide sequencing are widely uti- Iodamoeba bütschlii (Figs. 2.11 and 2.12)
lized for accurate diagnosis of Entamoeba species • Iodamoeba bütschlii receives its generic name from
and subtypes. the characteristic glycogen vacuoles of the cyst stage
• Some doubt is cast on the validity of this species by which are so prominent that in iodine stains the
isoenzyme studies of a number of isolates showing cysts seem to contain little else.
the morphologic characteristics of E. polecki. • Of historical interest, two fatal infections of the CNS
• In every case, the isoenzyme pattern fell within one were originally attributed to Iodamoeba.
or another of what are now recognized as E. dispar • The first was a case of disseminated amoebiasis
groupings. in a 22-year-old Japanese prisoner of war who
• Further comparison with E. dispar is needed. previously had been treated for malaria and
Treatment dysentery.
• Metronidazole alone has been used successfully to • The second case involved a granuloma of the
treat E. polecki infection in humans (Chacin-Bonilla, brain in a 6-year-old girl in Arizona who had
1980; Gay et al., 1985, Garcia, 2012). fallen from a slide a year earlier and bruised the
Other intestinal amoebae parietooccipital region.
• It is generally not difficult to distinguish amoebae • In both infections the pathogen was identified
belonging to the genus Entamoeba from other amoe- as Iodamoeba because of the large nuclear karyo-
bae occurring in the stool, even before a specific some in the amoebae in tissue sections, a fea-
identification is possible. ture very unlike that of E. histolytica, which at the
• Trophozoites of the various species of Entamoeba, if time was the only known pathogenic amoeba of
we except E. hartmanni, are on average larger than humans.
those of Iodamoeba or Endolimax, but differentiation Morphological characteristics
on this basis alone should not be attempted. • Unlike other amoebae containing glycogen vacuoles
• I. bütschlii and E. nana have prevalence rates rough- in their cyst stages, I. bütschlii glycogen is distinctly
ly equivalent to those of the Entamoeba complex. outlined and is consistent among isolates.
E. nana is usually encountered with about the same • Large, somewhat irregular glycogen masses are
frequency as E. coli; both are somewhat more com- frequently seen in iodine stains of E. coli cysts; in
mon than E. histolytica/E. dispar. mature cysts they often appear to surround the
• Iodamoeba generally has prevalence rates somewhat nuclei. In Iodamoeba cysts the single nucleus is
similar to those of E. histolytica / E. dispar and E. hart- seen at one side of the glycogen vacuole. Rarely,
manni. hypernucleate forms with two or three nuclei are
• Iodamoeba or Endolimax are nonpathogenic and re- reported.
quire no treatment. Their presence in stools is an • Trophozoite
indication of fecal contamination and may sug- • Positive identification of unstained trophozoites
gest the desirability of a more thorough search for is difficult.
pathogens (Table 2.3). • Size: 4 to 20 µm, the majority being within the
range of 9 to 14 µm
General characteristics • Motility: sluggish nonprogressive and has hya-
• Cyst of Entamoeba are usually larger than those of line pseudopodia.
Endolimax or Iodamoeba, although there is somewhat • Nucleus:
more of an overlap in size range. • The nucleus is usually not clearly visible.
• Endolimax may be spherical but tend more often to • Often referred to as “basket nucleus” because
be ovoid, whereas Iodamoeba cysts are frequently ir- of the distinct formation of the nuclear gran-
regular in shape. ules.
• Nuclear structure in Entamoeba is quite different • Permanent stains reveal the characteristic nu-
from that seen in the other genera and affords a clear structure.
TABLE 2.3
40
Comparison of amoebae.
CYST TROPHOZOITE
Nuclear structure
No. of nuclei of cyst and
Markell & Voge's Medical Parasitology

Protozoan Size (µm) and shape in mature cyst Cytoplasm Size (µm) Motility Cytoplasm trophozoite
Entamoeba 10 to 20 Four Glycogen 12 to 60 Active and Finely Small centrally
histolytica Usually Spherical vacuole not rapid granular; located karyosomes;
usually seen Progressive Few Evenly distributed
Chromatoidal and bacterial peripheral chromatin
bars: Rounded unidirectional Inclusions;
or squared RBCs and
ends; other debris
Elongated may be
present
Entamoeba 10 to 35 Eight Glycogen 15 to 50 Sluggish Vacuolated; Large, eccentric

coli Spherical vacuole not Nonprogressive Granular; karyosomes;
seen and With Irregularly distributed
Chromatoidal nondirectional ingested peripheral chromatin
bars: Splinter- bacteria
shaped or and other
irregular; debris.
Elongated
Endolimax 5 to 12 Four Glycogen vacu- 5 to 12 Sluggish Vacuolated; Large, irregularly

nana Oval ole not seen Usually Granular; shaped “blot-like”,
Chromatoidal nonprogressive With eccentric karyosome;
bars: not and ingested No peripheral chro-
present nondirectional bacteria matin
and other
debris.
Iodamoeba 6 to 16 One With large 4 to 20 Sluggish Vacuolated; Large, eccentric

bütschlii Oval, or irregular glycogen mass Usually nonpro- With karyosome containing
Chromatoidal gressive; and ingested achromatic granules;
bars: not nondirectional bacteria No peripheral
present chromatin
Source: Adapted from: Garcia (2016); John et al. (2006); Zeibig (2013); and Mahon et al. (2015).
FIG. 2.11 1,2, Iodamoeba bütschlii trophozoites; 3,4, I. bütschlii cysts containing glycogen vacuoles; 5, 6,
Endolimax nana trophozoites; 7, 8, E. nana cysts (2, 6, 7, and 8 show diagnostic features only).
FIG. 2.12 Iodamoeba bütschlii. Variations in nuclear structure.
• The nuclear membrane is delicate, and if it

does not take the stain the karyosome will ap- • The small chromatin granules may occa-
pear to be contained in a vacuole. sionally form a ring at some distance from
• The karyosome is large, more or less central in the karyosome, between it and the nuclear
position, irregularly rounded, and surround- membrane.
ed by a layer of small granules. • Cytoplasm:
• The granules may lie closely applied to the • Appears to be granular and vacuolated.
karyosome, in which case they are not vis- • Bacteria may be seen scattered throughout
ible unless staining and subsequent differ- the cytoplasm, and red blood cells are never
entiation have been optimal. ingested.
• Cyst Endolimax nana

• Mononucleated • The most common of the smaller intestinal amoebae.
• Instead of having the spherical or ovoid shape of • Endolimax usually encountered with about the same
most amoebic cysts, the majority of cysts of Iod- frequency as is E. coli.
amoeba are irregular in outline, and there is much • The size range for both trophozoites and cysts is
variation in shape. similar to that of E. hartmanni, with which they may
• Size: 6 to 16 µm (average 9 or 10 µm) in diameter be confused in unstained preparations.
• The unstained cyst is surrounded by a refractile Morphological characteristics
wall. • Trophozoites
• Nucleus: • Size: to 12 µm in diameter (average size close
• It is seldom distinct in unstained cysts. to 7 µm).
• The nuclear membrane and karyosome ap- • Motility: sluggish and random.
pear as highly refractile structures within the • Pseudopodia are blunt and hyaline; they are
pale-yellow cytoplasm. extruded rapidly as in E. histolytica but fail to
• The karyosome is usually quite eccentric produce the directional locomotion seen in
and may even be in contact with the nuclear that species.
membrane. • Nucleus
• The chromatin granules, which surrounded • The nuclear structure (Fig. 2.13) becomes
the karyosome in the trophic stage, usu- more visible in stained preparations.
ally form a crescentic aggregate between the • The single nucleus contains large karyosome,
karyosome and the nuclear membrane. which is centrally or eccentrically located and
• In well-stained specimens, linin fibrils may be often irregular in outline.
seen running between the karyosome and the • Smaller extrakaryosomal chromatin granules
chromatin granules. are sometimes present.
• Nuclei exhibiting this structure have been • When the trichrome stain is employed, the
likened to a “basket of flowers”, the karyo- chromatin may at times be seen massed
some forming the basket, the linin fibrils against the nuclear membrane, without for-
the stems, and the granules the blossoms. mation of a distinct karyosome.
• In other cysts the chromatin granules form • Cytoplasm
a compact crescent closely applied to the • The cytoplasm contains food vacuoles with
nuclear membrane, or they are disposed as ingested bacteria.
in the trophozoite. • Cysts
• Cytoplasm • Cysts of Endolimax exhibit about the same size
• Large glycogen vacuole is distinct even in the range as the trophozoites.
unstained cyst because of its refractility. • Most frequently ovoid in shape, but sometimes
• Cyst is prone to collapse because of the they are spherical or subspherical.
large glycogen vacuole.
• When stained with iodine, the glycogen vac-
uole is a dark brown mass, often more than
half the diameter of the cyst.
The following characteristics are of value in identifi-
cation of Iodamoeba bütschlii:
I. Trophozoites, Not characteristic

unstained
II. Trophozoites, Diagnostic: nucleus with large central
stained karyosome surrounded by a ring of small
chromatin granules; or nuclear structure
as in cyst
III. Cysts, Suggestive: large refractile body in
unstained cytoplasm; single nucleus
IV. Cysts, stained Diagnostic: basket nuclei or nuclei as in
trophozoite; large glycogen vacuole FIG. 2.13 Endolimax nana. Variations in nuclear structure.
• A refractile cyst wall is present, which is par- • Occasionally, minute brown masses of
ticularly evident when concentrations are made glycogen may be seen in the cytoplasm of
by the zinc sulfate technique and the cysts are cysts stained with iodine.
stained with iodine. • Although bacteria are, of course, not seen in
• Nucleus: cysts, granules of chromatoidal material that
• When stained with a permanent stain, the resemble them may be present.
cysts are seen to possess one to four nuclei. The following characteristics are of value in the
• Rare hypernucleate forms containing eight identification of Endolimax nana:
nuclei have been reported.
• A large, usually eccentric, karyosome charac-
I. Trophozoites, Not characteristic
terizes the nucleus. unstained
• Other chromatin granules and intranuclear fi-
II. Trophozoites, Diagnostic: a nucleus with large
brils have been reported but are seldom seen stained karyosome, generally with little or no
in routine stains. peripheral chromatin
• Cytoplasm:
III. Cysts, unstained Suggestive: ovoid shape
• inc sulfate concentration results in a shrink-
IV. Cysts, stained Diagnostic: four nuclei with large
age of the cytoplasm of many of the cysts,
karyosomes and little or no
which pull away from the cyst wall, leaving a
peripheral chromatin
clear space on one side of the organisms be-
tween the cytoplasm and the undistorted cyst
wall. The free-living amoeba (Figs. 2.14–2.19)
• In unstained cysts, little detail can be seen and • Known to be thermotolerant organisms, the free-
an iodine stain is seldom more revealing. living amoebae comprise a large group, inhabiting
FIG. 2.14 Life cycle of Naegleria fowleri.
FIG. 2.15 Life cycle of Acanthamoeba spp. and Balamuthia mandrillaris.
fresh, brackish, and salt water, moist soil, and decay- late form while being completely devoid of fla-
ing vegetation; some are coprozoic. gella in the ameboid stage.
• Free-living amoebae have been observed as human • Acanthamoeba organisms, belonging to the family
symbionts. Acanthamoebidae, never produce flagella.
• The association seems to be without pathologic con- • The invasive potential of these normally free-living
sequence; in others it may result in devastating dis- organisms has been recognized since 1959.
ease. • Human infections were first reported in 196 .
• The taxonomy of this large and diverse group is • Mode of transmission:
involved; for convenience, they may be separated • Hematogenous route has been reported apparent-
into two groups on the basis of their ability to un- ly from the infection of the lungs or skin lesions.
dergo transformation from an amoeba to a flagel- (Usually associated with Acanthamoeba spp.).
late stage. • Infections:
• Naegleria belongs to the family Vahlkampfiidae, • Naegleria is known to cause primary amoebic me-
members of which are characterized as amebo- ningoencephalitis (PAM), an acute, fulminant, rap-
flagellates, able temporarily to assume a flagel- idly infection involving the CNS.
• Acanthamoeba organisms are commonly involved • Nucleus:

in granulomatous amoebic encephalitis (GAE) • Mononucleated
or granulomatous amoebic meningoencephalitis • Large and densely stained.
(GAM) which are more chronic and are associated • With large, centrally located karyosome.
among immunodeficient individuals. • Peripheral chromatin is absent.
• Other cases of meningoencephalitis was reportedly • Cytoplasm:
acquired from zoonotic sources: • Granular and vacuolated.
• Vahlkampfia spp. • Trophozoite: flagellated forms
• Balamuthia mandrillaris • Size: to 1 µm in diameter.
• Sappinia diploidea • Motility: 2 flagella at the broad end; spinning or
jerky movements.
Naegleria fowleri • Nucleus:
• Referred to as the “brain-eating amoeba”. • Mononucleated
• It belongs to the family Vahlkampfiidae, members • With large, centrally located karyosome.
of which are characterized as ameboflagellates, able • Cytoplasm:
to temporarily assume a flagellate form while being • Granular and vacuolated.
completely devoid of flagella in the ameboid stage. • The pear shaped flagellated form is maintained
• The forms found in the tissues are ameboid, and at a temperature of 27 to 37oC.
in the tissues they are distinguished with difficulty • In water or in vitro culture.
from the genera; however, in Naegleria infections, • Not capable of dividing except when flagella are
only trophozoites occur in the tissue, whereas with lost back to the ameboid form.
Acanthamoeba and Balamuthia infections both tro- • Cyst
phozoites and cysts are found in the tissues. • Size: to 1 µm in diameter; rounded thick dou-
• Known to cause fatal intracerebral infections, Naegle- ble wall.
ria amoebae were erroneously identified as belong- • Nucleus:
ing to the genus Hartmannella (now Acanthamoeba). • Mononucleated
• N. fowleri was named in honor of Dr. Malcom Fowl- • With large, centrally located karyosome.
er, who first recognized the disease it caused. • Peripheral chromatin is absent.
Life cycle • Cytoplasm:
• N. fowleri has 3 life cycle stages: trophozotie, flagel- • Granular and vacuolated.
lated, and cyst. Symptoms and pathogenesis
• Transition from one stage to another depends on • Infection by N. fowleri presents dramatic clinical
the environmental conditions. course involving the CNS.
• Trophozoites are found in water or in moist soil • PAM is an acute, fulminant, suppurative infection of
where they infect human hosts. the brain and the meninges.
• They access the central nervous system (CNS) of the • A day or so of prodromal symptoms of headache
host by inhalation. and fever is followed by the rapid onset of nausea
• Amoebic form pass through the upper respiratory and vomiting accompanied by the signs and symp-
tract in the nasal cavity followed by the penetra- toms of meningitis with involvement of the olfac-
tion of the nasal mucosa where they get in contact tory, frontal, temporal, and cerebellar areas.
with the olfactory nerves, penetrating the cribri- • Meningeal irritation may be accompanied by stiff
form plate, then to the olfactory bulb, moving to neck, generalized seizures, and Kernig’s sign.
the arachnoid space and finally to the brain. • Olfactory lobe involvement is perhaps most charac-
Morphological characteristics teristic; disturbances in the sense of smell or taste
• Trophozoite: ameboid forms may be noted early in the course of the disease but
• Size: to 3 µm in diameter for the ameboid are not always seen.
forms (only found in humans); 10 to 18 µm in • Patients often become irrational before lapsing into
diameter for rounded forms. coma.
• Elongated with broad anterior and tapered pos- • Death occurs early; the entire clinical course seldom
terior ends. extends beyond 3 to 6 days.
• Motility: sluggish movement is produced by Diagnosis
means of blunt and broad pseudopodia. • Microscopic analysis
• Used to microscopically identify either living or enzymelike substance produced by actively grow-
stained amoebae in patient’s CSF. ing amoebae in the adjacent gray matter.
• Amoebae can be distinguished from other cells Epidemiology
by their “limax” (Latin, sluglike) shape and pro- • PAM is a relatively rare disease with a worldwide dis-
gressive movement. tribution.
• It is not necessary to warm the slide, because these • Compared to protozoan diseases such as malaria,
amoebae are fully active at room temperature. African sleeping sickness, and amoebic dysentery,
• Refrigeration of the spinal fluid is not recommend- infections caused by free-living amoebae seem in-
ed. See Chapter 10 for cultivation procedures. The consequential.
flagellate form of N. fowleri may be induced by • Naegleria infection is seen most often in active,
suspending amoebae in distilled water. At 37 °C, healthy, young persons, the majority of reports com-
maximum enflagellation occurs in 4 to 5 hours. ing from developed rather than developing nations,
• Analysis of spinal puncture probably because of greater awareness and not be-
• Spinal puncture reveals a cloudy to frankly pu- cause of greater incidence.
rulent or sanguinopurulent fluid, usually under • First reports of PAM were recorded in Australia and
increased pressure. America
• The cell count ranges from a few hundred to • A number of similar infections have been docu-
more than 20,000 white blood cells per micro- mented in the United States, Europe, Asia, New ea-
liter, predominantly neutrophils, and the failure land, Africa, Central America, and South America.
to find bacteria in such a purulent spinal fluid • Australia, Czechoslovakia, and the United States
should alert physicians and laboratory technolo- have reported 75% of all cases of PAM. In the United
gists to the possibility of PAM. States, the greatest number of reported cases have
• Spinal fluid protein is generally, though not in- been from the coastal states of Virginia, Florida, and
variably, increased, and glucose levels are low. Texas, accounting for 67% of the U.S. cases.
• Red blood cells are frequently present, and mo- • Most cases have occurred during the hot summer
tile amoebae may be found in unstained prepa- months in young persons who within the preced-
rations of spinal fluid. ing week swam or dived in fresh or brackish water.
• Their activity is characterized by the explosive Lakes, streams, hot springs, and swimming pools
formation of blunt pseudopodia, like those of have been apparent sources of the infection.
E. histolytica, rather than the tapering, spiky • The majority of patients with Naegleria infection
projections (acanthopodia) seen on the pseu- have a history of recent swimming in fresh water
dopodia of Acanthamoeba. during hot summer weather.
• Novel phagocytic structures referred to as amebo- • In Richmond, Virginia, infection in 14 of 16 cas-
stomes have been described for amoebae of N. fowl- es probably was acquired in two artificial lakes
eri. Used for engulfment, their role in pathogenesis located within a few miles of each other.
is unclear. • Over a 3-year period, 16 young people died in
• Red blood cells may be seen within the amoebae. Czechoslovakia after swimming in the same
• Post-mortem analysis heated, chlorinated, indoor swimming pool.
• On autopsy, signs of acute meningoencephalitis • Similar fatal cases have been reported follow-
are seen: an exudate of neutrophils and mono- ing swimming in pools in Belgium, England,
cytes is found in the subarachnoid space, and and New ealand; in hot springs in California
hemorrhage and an inflammatory exudate ex- and New ealand; in lakes in Arkansas, Florida,
tend into the gray matter. Missouri, Nevada, South Carolina, and Texas; in
• Rounded amoebae, 10 or 11 µm in diameter, are streams in Belgium, Mississipi, and New ealand;
seen in the gray matter, ahead of the advanc- and in an irrigation ditch in Mexico.
ing margin of hemorrhage or necrosis. They are Treatment
particularly prominent in the Virchow–Robin • The antibiotics used to treat bacterial meningitis are
spaces. ineffective, as are the antiamoebic drugs.
• Focal demyelination of the white matter of the • The current therapy against PAM involves the use of
brain and spinal cord has been described. Amphotericin B, a drug of considerable toxicity, is
• It has been suggested that demyelination may the anti-Naegleria agent for which there is evidence
have been caused by a phospholytic enzyme or of clinical effectiveness.
• All known survivors of PAM have been treated with prevention and control of Naegleria infection in-
Amphotericin B given intravenously and intrathe- clude public education, awareness in the medical
cally. community.
• Amphotericin B is best known for its antifungal ac- • Because of the swimming-related nature of Nae-
tivity, and has been indicated as an antiviral and an- gleria infection, swimming areas have been sub-
tiprotozoal drug (Bellini et al., 2018). jected to intensive investigation.
• Amphotericin B is a polyene compound that acts on • There are factors that favor the development of
the plasma membrane, disrupting its selective per- N. fowleri in swimming areas: warm temperature,
meability and causing leakage of the cellular com- the presence of an adequate food supply, mini-
ponents. It is administered intravenously in large mal competition from other protozoans, and
doses: 1 to 1.5 mg/kg body weight daily for 3 days, probably optimal pH and oxygen levels.
followed by 1 mg/kg daily for 6 days. Additionally, • Adequate chlorination of public water supplies, in-
amphotericin B may be given intrathecally. cluding swimming facilities.
• Seidel and colleagues (1982) successfully treated • Adequate chlorination is a continuous free
a 9-year-old girl with proven Naegleria infection chlorine residual of 0.5 mg/L water. This level
with the following regimen: of chlorination has effectively controlled the N.
• Amphotericin B intravenously, 0. mg kg twice fowleri problem in the public water supplies of
daily × 3 days, then 1.0 mg/kg daily × 6 days. South Australia.
• Amphotericin B intravenously via lumbar cath- • Water filtration can be done using a filter spe-
eter, 1.5 mg daily × 2 days, then 1.0 mg every cifically designed to remove microbes in the
other day × 8 days. water.
• Miconazole intravenously, 11 mg m2 body sur- • Use distilled and sterile water as much as possible.
face three times daily × 9 days. • Vaccination: Although not thoroughly proven,
• Miconazole intrathecally via lumbar catheter, Bellini et al. (2018) recommended that vaccina-
10 mg daily × 2 days, then 10 mg every other day tion can be used as future strategy in combating
× 8 days. imminent surge of infections worldwide. Practical
• Rifampin by mouth, 3.3 mg kg three times daily application of vaccination needs to be validated by
× 9 days. future studies.
• Its efficacy has been demonstrated to be markedly
potentiated by tetracycline in the delayed treatment Acanthamoeba spp. and Balamuthia mandrillaris
of mice experimentally infected with N. fowleri. • The majority of the infections previously described
Similarly, amphotericin B and rifampin have been were first thought to be caused by amoebae various-
found to be synergistic in mice. ly classified as Hartmannella or Acanthamoeba.
• Goswick and Brenner (2003) have described the ef- • These two genera are similar in appearance to the
fective treatment of experimental PAM in mice with ameboid stage of Naegleria but have no flagellate
azithromycin. Treatment was initiated 72 hours stage.
after infection and was continued for 5 days, with • Acanthamoeba has been reported to be associated
protection being 100% and greater than for the am- with human infection on only two occasions, once
photericin B-treated mice. with a CNS infection and once with a corneal infec-
• Bellini et al. (2018) outlined in their literature re- tion.
view various treatment strategies for PAM. They list • Acanthamoeba organisms infects the CNS when they
current PAM therapies published from the year 2003 are in contact with skin ulcerations or traumatic
to 2017. Therapeutic approaches are the following: penetration. Ulceration of the corneal surface can
• Amphotericin B intravenous, fluconazole, cause keratitis when contaminated saline of a con-
rifampin, azithromycin, miltefosine. tact lenses is used.
• Amphotericin B intravenous intrathecal, flucon- • Acanthamoeba spp. and Balamuthia spp. are caus-
azole, rifampin, azithromycin, miltefosine. ative agents of granulomatous amoebic encephalitis
• Amphotericin B intravenous, fluconazole, ri- (GAE) which are usually associated with immuno-
fampin, azithromycin, miltefosine. compromised hosts.
Prevention Life cycle
• Given the present limited understanding of the • Acanthamoeba spp. and Balamuthia mandrillaris have
ecology of N. fowleri, practical measures for the two life cycle stages: trophozoite and cyst stages.
• These organisms are commonly found in soil, fresh- • Cytoplasm:

brackish water, lakes, swimming pools, sea water, • Granular and vacuolated.
tap water, and in air and ventilating conditioning
systems. Balamuthia spp.
• The infective trophozoite will enter several sites of • It is relatively uncommon unlike Acanthamoeba.
the body such as eyes, nasal passages, and skin le- • Discovered in an animal park in the United States
sions. where number of primates, and other mammals
• Amoebae reach the brain by way of the blood- have died from CNS infection.
stream, most likely from the lower respiratory tract • Known to produce virulence factors that enable the
or through ulcers of the skin or mucosa. organism to enhance its binding and penetrating ca-
• GAE is not associated with swimming, as is Naegle- pacity to the blood brain barrier.
ria infection, and invasion of the CNS is secondary • Human-to-human transmission was noted in 2009
to infection elsewhere in the body. and 2010 through solid organ transplantation.
• When Acanthamoeba enters the eye, severe keratitis • Balamuthia do not have spiky pseudopodia com-
may occur. pared to Acanthamoeba.
Morphological characteristics
Acanthamoeba spp. • Trophozoite
• Acanthamoeba was first noted as a contaminant in • Some may possess more than one nucleoli as this
tissue cultures and subsequently was found to pro- organism is considered as (eukaryotic).
duce lethal meningoencephalitis on nasal instilla- • Size: 12 to 60 µm in diameter.
tion into mice and other animals. • Motility: move by means of broad pseudopodia.
• Commonly described for its characteristic spiky ac- • Nucleus:
anthopodia. • Mononucleated
• Are ubiquitous, free-living organisms found in air, • Cytoplasm:
soil, water, and dust. • Granular and vacuolated.
• Widely attributed to cause GAE and Acanthamoeba • Cyst
keratitis. • 3-layered cyst: outer wrinkled ectocyst, mesocyst,
• CNS infection happens through hematogenous dis- and inner thin endocyst.
semination. • Size: 13 to 30 µm in diameter.
• Ten species of Acanthamoeba have been identified • Rounded shape with wrinkled edges.
from human infections. • Nucleus:
• A. castellanii is the species most often seen in • Mononucleated
cases of GAE and ocular infection, followed by • Cytoplasm:
A. culbertsoni for GAE and A. polyphaga for ocular • Granular and vacuolated.
infection. Symptoms and pathogenesis
Morphological characteristics • Acanthamoeba may produce a chronic CNS infec-
• Trophozoite tion (which is known as granulomatous amoebic
• Size: 1 to 4 µm in diameter. encephalitis [GAE] to distinguish it from the fulmi-
• Motility: move by means of spinelike pseudopodia. nant disease caused by N. fowleri) or a serious eye
• Nucleus: infection referred to as Acanthamoeba keratitis.
• Mononucleated • Other forms of Acanthamoeba infection include
• With large, centrally located karyosome. chronic granulomatous infection of the skin and
• Peripheral chromatin is absent. other tissues and invasion of bone with subsequent
• Cytoplasm: osteomyelitis.
• Granular and vacuolated. • Balamuthia causes a chronic CNS infection similar
• Cyst to that produced by Acanthamoeba, also termed GAE.
• Size: 8 to 2 µm in diameter. Skin lesions are the most commonly reported clini-
• Rounded shape with jagged edges. cal condition caused by Acanthamoeba and Balamu-
• Nucleus: thia in patients with AIDS.
• Mononucleated • Balamuthia causes a chronic CNS infection similar
• With large, centrally located karyosome. to that produced by Acanthamoeba, also termed GAE.
• Peripheral chromatin is absent. Skin lesions are the most commonly reported clini-
cal condition caused by Acanthamoeba and Balamu- • Acanthamoeba keratitis is a serious ocular infec-
thia in patients with AIDS. tion and if not properly managed can lead to loss
• GAE of vision and of the eye.
• It usually occurs in debilitated or chronically ill • Ocular infections are characterized by a chronic
persons, some of whom may be undergoing im- progressive ulcerative keratitis. Corneal ulcer-
munosuppressive therapy, not all victims of GAE ation may progress to perforation. Trophozoites
have been debilitated or immunocompromised; and cysts of Acanthamoeba are found in the in-
some have been otherwise healthy. fected corneal tissue.
• The course of infection is subacute or chronic, Diagnosis
lasting from weeks to months, in some instances • GAE or GAM
perhaps even years, and is characterized by focal • The laboratory diagnosis of GAE is made by iden-
granulomatous lesions of the brain. tifying trophozoites of Acanthamoeba or Balamuth-
• The onset of GAE, unlike that of PAM, is insidi- ia in CSF or trophozoites and cysts in brain tissue.
ous, with a prolonged clinical course. GAE most • Differentiation of the organisms in tissue is
probably occurs by way of the lungs or through made by using the indirect immunofluorescent
skin and mucosal ulcers, with invasion of the antibody technique and antisera to Acanthamoeba
CNS by hematogenous spread. or Balamuthia.
• The incubation period in GAE is not known but • N. fowleri is readily cultured from spinal fluid
probably takes weeks or months, during which or brain tissue, Acanthamoeba and Balamuthia
single or multiple space-occupying lesions de- are not.
velop. • On just a few occasions have Acanthamoeba or Bal-
• An altered mental state is a prominent feature of amuthia been isolated in GAE. In such infections,
GAE. Headache, seizures, and stiff neck occur in characteristic cysts may be found in the tissues.
about half the cases. • Cysts are never seen in the tissues in Naegleria in-
• Nausea and vomiting may also be noted. In con- fections.
trast to Naegleria infection, characterized by dif- • Acanthamoeba keratitis
fuse meningoencephalitis, GAE is focal. • Acanthamoeba keratitis diagnosis has been ex-
• Similar lesions have been described from other tremely challenging as current methods used are
tissues as well, including prostate, kidneys, uterus, invasive.
and pancreas, probably the result of hematoge- • Corneal culture
nous dissemination of amoebae from the primary • Biopsy
focus in skin or lungs, or possibly even from a sec- • It is diagnosed by identifying amoebae cultured
ondary CNS lesion. Cases of disseminated acan- from corneal scrapings or by histologic examina-
thamoebiasis have been described in patients with tion of infected corneal tissue.
AIDS. • Acanthamoeba may be cultivated from corneal
• Acanthamoeba keratitis scrapings on nonnutrient agar spread with gram-
• It is a chronic infection of the cornea caused by negative bacteria and later transferred to liquid
several species of Acanthamoeba. medium with antibiotics for axenic growth.
• Infection is by direct contact of the cornea with • Cultures of corneal material should be incubated
amoebae, which may be introduced through mi- at 30oC rather than 37oC. Species identification
nor corneal trauma or by exposure to contami- is based on indirect immunofluorescent anti-
nated water or to contact lenses that have be- body staining. Calcofluor white staining also has
come contaminated. been used to identify Acanthamoeba cysts in cor-
• Keratitis usually develops over a period of weeks neal scrapings.
or months and is characterized by severe ocular Epidemiology
pain, often out of proportion to the degree of in- • The first cases of Acanthamoeba keratitis were reported
flammation observed, affected vision, and a stro- in the mid-1970s from Great Britain and the United
mal infiltrate that frequently is ring shaped and States and were associated with trauma to the eye.
composed predominantly of neutrophils. • A dramatic increase in the number of cases since 198
• Keratitis in contact lens wearers has also been as- has been linked to the wearing of contact lenses, es-
sociated with infection by amoebae of Hartman- pecially soft ones. Hartmannella and Vahlkampfia have
nella and Vahlkampfia. also been isolated from cases of amoebic keratitis.
• Fewer cases of Acanthamoeba or Balamuthia CNS in- • Persons who wear contact lenses should follow
fection have been reported than of Naegleria infec- closely the manufacturer’s recommendations for
tion, more than half from the United States. wear, care, and disinfection of the lenses.
• Unlike Naegleria infection, GAE is not associated • Homemade saline solutions remain an important
with swimming. Infections often occur in persons risk factor associated with Acanthamoeba keratitis.
who are debilitated or immunosuppressed and fatal
cases have been reported in patients with AIDS. In
one of the AIDS patients, the features of the disease
were more like PAM than GAE, presumably because
The Flagellates
of the immunosuppression. • A large group of protozoans possessing common
• Most cases of Acanthamoeba keratitis have been re- feature: whip-like protoplasmic extrusion/s termed
ported from the United States. as flagella.
• One survey of 208 cases reported that 8 of the • Widespread in nature and multiply by binary fis-
patients wore contact lenses. sion.
Treatment • There are four common species of intestinal flagel-
• Prompt and early diagnosis offer best chance to treat lates:
the disease. • Giardia duodenalis (formerly known as G. lamblia)
• Earlier cases of Acanthamoeba infections required • Chilomastix mesnili
corneal transplants to manage the disease. • Trichomonas hominis
• The first successful medical cure, reported by Wright • Dientamoeba fragilis
and coworkers (1985), involved the use of a com- • Enteromonas hominis and Retortamonas intestinalis, are
bination of dibromopropamide ointment (Otami- sometimes encountered.
dyl), propamide isethionate drops (Brolene), and • There is no evidence that any of these organisms ex-
neomycin drops. cept Giardia and Dientamoeba can cause disease.
• For a thorough discussion of the treatment of the • A pathogenic trichomonad, Trichomonas vaginalis,
diseases caused by the opportunistic amoebae, in- occurs in the urogenital tract, and the commensal
cluding PAM, GAE, and Acanthamoeba keratitis, see Trichomonas tenax is found in the mouth.
the review by Schuster and Visvesvara (2004). • The flagellates other than Dientamoeba are readily
• Two classes of antimicrobial agents are currently uti- recognized by their characteristic rapid motility, and
lized for Acanthamoeba infections (Juárez et al., 2018): the three larger species can usually be identified in
• Biguanides unstained saline mounts.
• Diamidines • Trichrome stain is generally preferable to iron he-
• These antimicrobial agents have amoebicidal ca- matoxylin for staining flagellates.
pacity which may be presented differently among • The intracytoplasmic fibrillar structures of these
different strains. Variations may be due to differ- organisms, often of diagnostic importance, are
ence in the degree of virulence and pathogenicity brought out much better by trichrome than by any
among species and strains of Acanthamoeba. but the most careful hematoxylin staining.
• To date, there are no drugs specifically approved for • Hemoflagellates are characterized by the presence of
Acanthamoeba keratitis by the Food and Drug Ad- kinetoplast, a large mitochondrion which contains
ministration (FDA). the parasite DNA material.
• For a thorough discussion of the treatment of the • Two genera have known importance capable of in-
diseases caused by the opportunistic amoebae, infecting humans: the Trypanosoma and Leishmania.
cluding PAM, GAE, and Acanthamoeba keratitis, see • Both genera require athropod vectors to infect
the reviews by Bellini et al. (2018), Juárez et al. their human hosts.
(2018), and Carrijo-Carvalho et al. (2017).
Prevention Giardia duodenalis
• Factors that have been associated with Acanthamoeba • Also known as Giardia lamblia and Giardia intesti-
keratitis in contact lens wearers include the use of nalis.
nonsterile, homemade saline; disinfection of lenses • Flagellated protozoans known to cause prolonged
less frequently than recommended; and wearing and chronic diarrhea in healthy and immunocom-
lenses while swimming. promised individuals (giardiasis).
FIG. 2.16 Life cycle of Giardia duodenalis.
• Transmitted by the fecal-oral route causing severe

gastroenteritis in vertebrates, including humans,
other mammals, birds, reptiles, and fishes (Koehler
et al., 2014).
• High-risk groups include the children, immigrants,
travelers, and immunocompromised individuals.
• Outbreaks of human giardiasis are associated with
children day-care centers, travelling individuals
accessing contaminated waters, and recreational
swimming pools.
Life cycle
• Two main life cycle stages: the proliferating tropho-
zoite and the infective cyst.
• The infection is initiated by the ingestion of the infec-
tive cyst.
• Excystation FIG. 2.17 Scanning electron micrograph of Giardia,
• The cyst is then stimulated to excyst by the pres- showing sucking disk and flagella; imprints of sucking disks
ence of an acidic environment of the stomach and are seen on surface of intestinal mucosa. (Courtesy of Dr.
the presence of bile and trypsin in the intestines. obert L. Owen, San rancisco, .)
FIG. 2.18 1, Giardia lamblia trophozoite; 2, 3, G. lamblia cysts; 4, 5, 6, 7, Chilomastix mesnili trophozoites
showing variation in structural detail, which may be seen in permanent preparations; 8, 9, 10, 11, C. mesnili
cysts (3, 4, 6, 7, 9, 10, and 11 show diagnostic features only).
• The cyst will quickly emerge as excyzoites that produce a considerable degree of mechanical
will develop into trophozoites. irritation to the tissues.
• Trophozoites are found in the upper part of the • The sucking discs serve as an essential viru-
small intestine, where they live closely applied to lence factor of Giardia.
the mucosa. • Attachment of Giardia to the duodenal mu-
• These trophozoites will attach themselves cosa also may be facilitated by a lectin pro-
to the lining of the intestinal epithelia using duced by the parasite and activated by duo-
their sucking discs. denal secretions.
• The anterior portion of the ventral surface of • They may penetrate down into the secre-
the organism is modified to form a sucking tary tubules of the mucosa and are found at
disk, which serves for attachment of the or- times in the gallbladder and in biliary
ganism and which, in relation to its size, may drainage.
FIG. 2.19 1, 2, Trichomonas hominis; 3, Retortamonas intestinalis trophozoite; 4, 5, R. intestinalis cysts; 6,

Enteromonas hominis trophozoite; 7, 8, 9, E. hominis cysts (2, 4, 5, 7, 8, and 9 show diagnostic features only).
• Encystation • Size: length ranges from 9 to 21 µm and width

• The trophozoites undergo encystation when from 5 to 15 µm.
changes in the environment occur as they are • Motility: erratic, with slow oscillation about the
transported down the small intestines. long axis; likened to the motion of a falling leaf.
• This will allow the formation of cyst cell wall that • Shape: pear-shaped when seen in surface view;
enables the parasite to survive outside the host in having a broad anterior and a very much attenu-
colder environment. ated posterior end.
• Flagella: 4 pairs of flagella; anterior, lateral, ven-
Morphological characteristics tral, and posterior.
• Trophozoite • Nuclei: two nuclei lie in the area of the sucking
• The trophozoite is bilaterally symmetrical, each disk in the anterior portion of the body.
structure being paired. • It possesses two nuclei in the trophic form.
• It resembles an “old man wearing glasses” or “old • The nuclei are spherical or ovoid and contain
man’s face with an eyeglass” or “smiling face with a large, usually central, karyosome.
prominent eyes” (McPherson, and Pincus, 2011) or • There is no peripheral chromatin.
“old man with whiskers”, “a cartoon character”, and/ • Two curved rods are seen posterior to the sucking
or a “monkey’s face” (Zeibig, 2013). disk. These rods are known as median bodies.
• These median bodies are unique to Giardia. They III. Cysts, Suggestive: ovoid body shape, numerous
are termed parabasal bodies, kinetoplast or chro- unstained refractile threads in cytoplasm
matoid bodies by other authors but ultrastructur- IV. Cysts, stained Diagnostic: four nuclei; four median
ally revealed otherwise. (Cheissin, 1964). bodies; jumble of axonemes
• Function of median bodies: Energy metabolism
energy source that help support the posterior end Symptoms and pathogenesis
of the organism (Roberts and Janovy, 2013) . • Long considered nonpathogenic and often found in
• The motile trophozoite is supported by a midline completely asymptomatic persons, there is now abun-
structure called an axostyle made up of two axo- dant evidence of the pathogenic potential of Giardia.
nemes ( eibig, 2013) and this distinct medial line • Trophozoites adhering to the epithelial lining of
confers to the bilateral symmetry of the parasite. the intestines target specific signaling networks such
• Axoneme is the intracellular portion of a flagel- as caspases that can initiate cellular apoptosis. This
lum (core comprising the microtubules) while leads to the following:
axostyle is the axial rod (tubelike organelle) that • Loss of intercellular junctions.
functions as a support in flagellates. (Leventhal • Cytoskeleton rearrangement.
and Cheadle, 2012, Roberts and Janovy, 2013). • Cell barrier dysfunction.
• Unstained trophozoites: the characteristic body • Pathophysiological mechanisms.
shape and motility may be observed, and some • Diarrhea
of the flagella can usually be seen. • Malabsorption
• Stained trophozoites: most readily observable • Electrolyte imbalance.
features are body shape, nuclei, axonemes, and • Giardiasis should be considered in the differential
the median bodies. diagnosis of any “traveler’s diarrhea.”
• Cyst • Children are more frequently affected than adults,
• Size: 8 to 14 µm by 7 to 10 µm. although all ages may exhibit symptoms ranging
• Shape: ovoid. from mild diarrhea, flatulence, anorexia, crampy ab-
• The cyst wall is smooth and colorless and is usu- dominal pains, and epigastric tenderness to steator-
ally well set off from the cytoplasm, owing to rhea and full-blown malabsorption syndrome.
shrinkage of the latter at the time of fixation. • A prepatent period of 10 to 36 days before organisms
• Some of the nuclei or median bodies may occa- could be detected in the stools has been observed in
sionally be detected in living specimens, the ad- groups of students, in whom the mean incubation
dition of D’Antoni’s iodine usually reveals these period before clinical illness was but 8 days.
structures. • Like celiac disease in children and its adult coun-
• In permanent stains, the following are observed terpart, nontropical sprue, severe giardiasis may be
all dispersed in a seemingly helter-skelter fashion: marked by the production of copious light-colored,
• Four prominent nuclei. fatty stools, hypoproteinemia with hypogammaglobu-
• Four median bodies. linemia, folic acid and fat-soluble vitamin deficiencies,
• Intracytoplasmic flagellar structures seen in and changes in the architecture of the intestinal villi.
the trophozoite. • Achlorhydria may predispose to symptomatic giar-
• When stained with trichrome, Giardia cysts may dial infections, as may hypogammaglobulinemia,
appear in varying shades of green or red, or the or a relative deficiency in secretory IgA in the small
internal structures may be reddish brown against bowel, even in the presence of normal serum immu-
a green background. noglobulin levels.
The following characteristics are of value in the • Bacterial colonization of the jejunum (as seen in
identification of Giardia duodenalis: tropical sprue) potentiates the damage done by the
giardias and may be responsible for the develop-
I. Trophozoites, Suggestive: progressive, “falling leaf” ment of symptomatic malabsorption.
unstained motility; pear-shaped body with • Lactose intolerance, apparently precipitated by Giar-
attenuated posterior end dia infection, may persist after eradication of the
II. Trophozoites, Diagnostic: pear shaped; with nuclei in the parasites.
stained area of a sucking disk; the two median • Host response:
bodies posterior to the sucking disk; • The possible role of T-cell activity in this regard
typical arrangement of axonemes
is suggested by the persistence of infection by
Giardia in hypothymic (nude) mice derived from outbreaks from contaminated water supplies in the
strains that initially were characterized by rapid United States.
elimination of this parasite. • It is affected by much the same socioeconomic fac-
• Lymphoid cells have been shown by scanning tors that influence the distribution of E. histolytica.
electron microscopy to migrate into the intestinal • The first recorded waterborne outbreak of giardiasis
lumen and attach to Giardia trophozoites during involved travelers to St. Petersburg, Russia.
clearance from the intestine in normal adult mice. • Numerous less prolonged outbreaks have been re-
• Macrophages isolated from intestinal Peyer’s ported from the United States and elsewhere.
patches were able to ingest trophozoites of Giar- • Giardia has also been found in beavers, muskrats,
dia in vitro, suggesting their role in host defense and water voles from other localities, and these
in giardiasis. observations may provide an explanation for those
• The killing of G. duodenalis trophozoites by the li- infections seen occasionally in backpackers and
pase of milk from nonimmune humans is due to mountain climbers who have drunk from mountain
the release of free fatty acids from milk triglycerides streams in areas where the possibility of a human
by the action of bile salts. Human milk, therefore, source seems remote.
may be instrumental in affording protection against in- • Cross-species transmission studies have demonstrat-
testinal protozoan parasites to breast-fed babies. ed that beavers and muskrats can be infected with
• In some patients, biopsy of the jejunum reveals Giardia cysts obtained from humans.
shortening and blunting of the villi, reduction in • Day care centers have been implicated as a major
height of the columnar epithelial cells of the muco- site of significant endemic giardiasis and transmis-
sa, and hypercellularity of the lamina propria. Even sion.
total villous atrophy has been reported. • A report on severe giardiasis in the United States
• Others have found these changes primarily in pa- by the Centers for Disease Control and Prevention
tients with hypogammaglobulinemia. identified two high-risk groups: children younger
• Giardiasis of the pancreas with reversible pancreatic than 5 years of age and women of childbearing age.
exocrine dysfunction has been reported in an elderly • In the United States, approximately 6 of all
woman with diabetes. women with a child younger than 1 year of age are
in the workforce, and about 60% of these children
Diagnosis
are cared for in day care homes or day care centers.
• Routine stool examination.
• Sexual practices, particularly anal-oral contact, may
• Giardia does not appear consistently in the stools
favor transmission of this parasite. Several reports
of all patients.
document an increased prevalence among homo-
• Three patterns of excretion have been described:
sexual males.
high, with parasites present in nearly all stools;
low, with small numbers of parasites present in
only about 40% of stool specimens; and a mixed Treatment
pattern, with 1 to 3 weeks of a high excretion rate • Anti-giardial drugs which are used widely today are
alternating with a shorter period of low excretion. 5-nitroimidazole compounds such as Metronida-
• Duodenal fluid examination. zole, Nitroimidazole, and Tinidazole. These drugs
• Microscopic analysis of duodenal fluid obtained have treatment success of 80% to 90%. (Abraham
by intubation, or string test (Enterotest), or by et al., 2019).
biopsy. • Metronidazole (Flagyl) and Tinidazole are first-line
• Antigen detection: giardiasis may be diagnosed by agents for treatment.
• ELISA • Nitazoxanide is available in a liquid formulation
• Immunofluorescence suitable for children.
• Counterimmunoelectrophoresis (CIE). • Precaution must be applied for Metronidazole as
• Molecular testing treatment of choice because of its unwanted side ef-
• PCR fects such as nausea, headaches, vomiting, fatigue,
malaise, and potentially carcinogenic (Abraham
Epidemiology et al., 2019; Nagel and Aronoff, 2015).
• Giardiasis is worldwide in distribution. • Resistance to the commonly used drugs for giardia-
• It is the most common parasitic infection, and sis have been reported (Abraham et al., 2019; Nagel
it is considered to be a major cause of diarrheal and Aronoff, 2015).
Prevention • Cysts
• The precautions that were mentioned in connection • Size: 6 to 10 µm long, their width being some-
with the prevention of amoebiasis are applicable to what less.
giardial infection. • Shape: At the anterior pole of the cyst is a nipple-
• Because Giardia has been demonstrated to be able like protuberance that gives this stage a charac-
to withstand filtration and chlorination of the usu- teristic lemon shape not seen in any of the other
al sort, it would desirable (though impractical) to intestinal protozoa (American Lemon shaped
guard against the contamination of municipal wa- with nipple-like protruberance).
tersheds, if not by beavers and other water rodents • In stained preparations, a single, large nucleus
at least by human carriers. may be distinguished, with the chromatin fre-
• For purification of small supplies of drinking water, quently condensed to appear as a large central
a saturated solution of iodine, used double strength, karyosome.
is effective in killing Giardia cysts with a 20-minute • The curved cytostomal fibrils are usually quite
exposure at 20oC (68oF). prominent and may even be apparent in iodine-
• Of the many portable water purification systems stained preparations.
available to campers and backpackers, those that use • In specimens particularly well stained with he-
iodine solutions are the most effective, provided the matoxylin, the recurrent flagellum may be seen
directions are followed precisely. between the cytoplasm and the cyst wall at the
anterior end of the organism.
Chilomastix mesnili The following characteristics are of value in the
• Chilomastix is not pathogenic to humans. identification of Chilomastix mesnili:
• It must be differentiated from Giardia and from the
other flagellates occasionally seen in stool speci-
I. Trophozoites, Diagnostic: anterior flagella; a spiral
mens. unstained groove
II. Trophozoites, Diagnostic: pear shaped; with single
Morphological characteristics stained anterior nucleus; cytostome
• Trophozoites with curved, shepherd’s crook
• Size: 10 to 20 µm in length. fibril; no costa or undulating
• Motility: in fresh specimens one readily distin- membrane (see Trichomonas)
guishes the flagella and a groove running in a III. Cysts, unstained Diagnostic: protuberance at one
spiral along the length of the body. Flagella allow end of cyst (lemon shape)
the trophozoite to move in a stiff, rotary, and di- IV. Cysts, stained Diagnostic: body shape, as above;
rectional manner (corkscrew motion). single large nucleus; curved
• Shape: elongate, tapering toward the posterior cytostomal fibril
end; at the anterior, broad end of the body are
three flagella. Trichomonas hominis
• In stained preparations: • Also known as Pentatrichomonas hominis.
• trophozoites are characterized by a single nu- • There is little evidence that T. hominis is pathogenic
cleus near the origin of the anterior flagella; for humans.
• cytostome, or oral depression, bordered by cy- • It is indicative of direct fecal contamination, as it
tostomal fibrils; and does not form cysts.
• a short flagellum, which is directed posteri-
orly within the cytostomal area. Morphological characteristics
• The most prominent of the cytostomal fibrils, • Trophozoites
curving posteriorly around the cytostome, re- • Size: to 1 µm long.
sembles a shepherd’s crook. • Motility:
• Flagella: 3 anterior, 1 in cytostome. • they move about rapidly, with a jerky and
• Nuclear chromatin may appear in the form of nondirectional motion, and are difficult to
granules; in addition, it may form plaques ap- observe until slowed down.
plied to the nuclear membrane. • T. hominis has four anterior flagella plus a re-
• A small, central or eccentric karyosome may at current flagellum that arises anteriorly and par-
times be observed. allels the body, running to the posterior end.
• It forms the outer edge of the undulating Trichomonas vaginalis

membrane, a thin sheet of protoplasm that • T. vaginalis is closely related to T. hominis, yet mor-
joins the body along a line marked by the phologically and physiologically distinct from each
presence of a curved, thin rod called the costa. other.
• The costa is about the same length as the un- • In general appearance these flagellates are very simi-
dulating membrane and, as it stains well, is an lar to T. hominis, from which they differ in having
important diagnostic characteristic. a short undulating membrane that extends only
• The recurrent flagellum, which forms the out- about half the distance to the posterior end of the
er edge of the undulating membrane, projects body, with no free flagellum.
behind the body as a free flagellum. • While it is possible to distinguish T. vaginalis from T.
• The undulating membrane imparts a rotatory hominis on morphologic grounds, this is not a prac-
motion to the organism, while the anterior tical necessity, because the two organisms are site
flagella serve for propulsion. specific.
• Nucleus: • Numerous attempts have been made to introduce T.
• The single nucleus is situated at the anterior hominis into the vagina, but without success. When
end of the body, close to the origin of the an- T. vaginalis is similarly introduced, a high percentage
terior flagella. of infections results.
• Its chromatin is unevenly distributed, and a • A specific identification may be made on the basis
small karyosome may be observed. of finding a trichomonad in the vaginal secretions.
• A slender rod, the axostyle, extends through the • The life cycle of T. vaginalis is illustrated in Fig. 2.20.
body from the anterior to the posterior end. It is
sharply pointed and protrudes prominently be- Life cycle
yond the posterior end of the body. • Life cycle stages of T. vaginalis are: flagellated tro-
• The activity of the anterior flagella may be distin- phozoites, amoeboid trophozoite, and pseudocyst
guished even if the individual flagella cannot be stages.
seen. • The infective trophozoite is transmitted through
• The posteriorly protruding axostyle, which may sexual intercourse, infant delivery, and use of con-
be seen even when other structures are not dis- taminated clothing from an infected individual.
tinguishable, is diagnostic. • Once they reach the urogenital tract, they will un-
• It is more difficult to identify stained organisms dergo rapid transition from the flagellated tropho-
than living material. zoites to actively dividing and tissue-feeding ame-
• In a routine iron hematoxylin preparation, the boid forms.
flagella and undulating membrane do not stain • They are known as oxygen-adapted parasites causing
well, but the single nucleus at the anterior end cytoskeletal rearrangement and proliferation in hu-
and the costa are diagnostic. No other intestinal man epithelial cells.
protozoan possesses the latter structure. • The life cycle of this parasite has yet to be defined
• The costa stains intensely with iron hematox- completely.
ylin, but careful focusing is needed to demon-
strate it. Morphological characteristics
• The trichrome stain is superior to hematoxylin to • Trophozoites
bring out the flagella and axostyle. • Size: to 1 µm long; some may reach a length
The following characteristics are of value in the of 30 µm.
identification of Trichomonas hominis: • Motility: jerky, rapid, nondirectional.
• Shape: pear shaped.
• Nucleus: mononucleated; visible in stained prep-
I. Trophozoites, unstained Diagnostic: pear shaped; with arations.
an undulating membrane; • Nuclear chromatin is evenly distributed.
an axostyle protruding • Flagella: 3 to anterior, 1 posterior; usually of
through the posterior part flagella, wherein 1 of its flagella is found within
of the body the undulating membrane.
II. Trophozoites, stained Diagnostic: the costa; the • Contains axostyle surrounded by many sidero-
axostyle phile granules.
FIG. 2.20 Life cycle of Trichomonas vaginalis. (Image must be changed. Other than trophozoites,
T. vaginalis has pseudocyst and ameboid stages.)
• Pseudocyst: rounded in shape; non-motile; no true peremic and not infrequently normal in appear-
cyst wall. ance.
• Ameboid forms: flagellated, with some pseudopodia. • Frequency of urination and dysuria are the com-
monest associated symptoms, and urethral involve-
Symptoms and pathogenesis ment is found in a large proportion of cases.
• Trichomoniasis is a common sexually transmit- • Cystitis may occur in a small portion of cases.
ted disease that causes an estimated 2 to 3 million • A relationship between this infection and cervical
symptomatic infections per year among sexually ac- carcinoma has been suggested.
tive women in the United States. • T. vaginalis also may be an important cofactor in am-
• Vaginal discharge is the most common complaint plifying HIV transmission (Sorvillo et al., 2001).
associated with vaginal trichomoniasis. • The pathology induced by T. vaginalis infection
• The discharge is frequently profuse and is often as- in a person co-infected with HIV increases HIV
sociated with burning, itching, or chafing. shedding.
• When viewed through a speculum, the vaginal mu- • Studies in Africa have indicated that T. vaginalis
cosa is sometimes diffusely hyperemic, with bright infection may increase the rate of HIV transmis-
red punctate lesions, sometimes only patchily hy- sion by approximately twofold.
• T. vaginalis has been isolated from the respiratory although they may readily be recognized in Pa-
tract of infants with respiratory disease and from panicolaou smears.
the conjunctivae of several infants with conjuncti- • Examination of urethral discharge in the female
vitis. may yield positive results when no organisms
• Evidence suggests that the infants were infected can be found in the vaginal discharge.
during vaginal delivery of an infected mother. • In the male, the diagnosis is made by examina-
• In males, infection is frequently asymptomatic, but tion of urethral discharge, prostatic secretions, or
more severe symptoms are likely to be seen when centrifuged urine.
the infection involves the prostate and seminal vesi- • Phase-contrast microscopy
cles or higher parts of the urogenital tract. • Used to observe the flagella and undulating
• A thin discharge, frequently containing tricho- membrane of living T. vaginalis.
monads, may be observed, with dysuria and • “Rippling” of the undulating membrane can be
nocturia. seen for several hours after the organisms have
• The prostate may be enlarged and tender, and stopped moving.
there is sometimes associated epididymitis. • Culture methods may be employed and sometimes
• Studies in vitro of T. vaginalis with mammalian cell increase the percentage of positive identifications.
cultures have demonstrated a contact-dependent cy- • Of the various commercial culture media avail-
topathic effect. able, modified Diamond’s medium consistently
• Organisms were able to kill target cells by direct con- supports growth of T. vaginalis.
tact without phagocytosis. • Modified thioglycolate medium, supplemented
• At least four trichomonad surface proteins have with yeast extract, horse serum, and antimicro-
been identified in cell adherence. bial agents, was found to be as efficient as Dia-
• It has been shown to produce a cell-detaching fac- mond’s medium in recovering T. vaginalis from
tor that causes detachment of cultured mammalian clinical specimens and may be used as a readily
cells and likely the sloughing of vaginal epithelial available, low-cost substitute for the standard
cells seen in clinical disease. medium.
• The amount of cell-detaching factor produced by • The combination of wet-mount examination and
the flagellates appeared to correlate with the sever- culture remains the standard approach for detecting
ity of the clinical infection and therefore may be a T. vaginalis in patient samples.
virulence marker in T. vaginalis pathogenesis. • Commercially available kits for the immunodetec-
• Experimental evidence suggests that the symptoms tion of T. vaginalis antigens in clinical specimens in-
of trichomoniasis may be influenced by the vaginal clude the following types of tests: enzyme immuno-
concentration of estrogens; the greater the concentra- assay (EIA), direct fluorescent antibody (DFA), latex
tion the less severe the symptoms. agglutination (LA), and DNA probe.
• β-Estradiol was shown to decrease the activity of
cell-detaching factor and may explain why intravagi- Treatment
nal estradiol pellets ameliorate the clinical symp- • Metronidazole is generally effective in vaginal
toms of Trichomonas vaginitis by providing high trichomoniasis.
local concentrations of estrogens. • As the infection can be transmitted by sexual inter-
course, treatment of the sexual partner should be
Diagnosis considered.
• Specimens for examination may best be obtained • Metronidazole also might be effective in cases of
through a vaginal speculum using a cotton-tipped nonspecific urethritis in which T. vaginalis can be
applicator stick. demonstrated.
• If the applicator is placed for a short time in a tube • Metronidazole is contraindicated during the first
containing a small quantity of 5% glucose in nor- trimester of pregnancy; during the second and
mal saline before examination, the organisms are third trimesters or for nursing mothers it should
less likely to be rounded up and motionless under be employed only when local palliative measures
the microscope. fail.
• Routine microscopic examination • Infants beyond the fourth week of life with symp-
• Diagnosis is by demonstration of the trichomo- tomatic trichomoniasis can be treated with metroni-
nads, most commonly in wet film preparations dazole 10 to 30 mg/kg daily for 5 to 8 days.
Trichomonas tenax Morphological characteristics

• T. tenax, which has also been called Trichomonas bucca- • Trophozoite
lis, resembles T. vaginalis more closely than T. hominis. • Size: diameter from 3 µm to as much as 18 µm
• Like E. gingivalis, it occurs most frequently in pyor- but are generally within the range of 7 to 12 µm.
rheal pockets and tonsillar crypts, and it is some- • Motility: nonprogressive movement due to pseu-
times aspirated to set up a transitory bronchial or dopodia.
pulmonary infection. • Pseudopodia are hyaline, broad, and leaflike in
• Since 1942, 36 cases of pulmonary trichomoniasis appearance, with characteristic serrated margins.
have been reported. • Organisms are quite active in freshly passed
• A survey of 38 dental patients in clinical practice re- stools but round up quickly on cooling.
vealed six (16%) with oral T. tenax. • Shape: ameboid; similar to amoeba.
• T. tenax trophozoite is the infective stage; the para- • Nuclei: 80 of them are seen in the binucleate
site has no cystic stage. form.
• Dientamoeba is identified on the basis of a
Morphological characteristics high percentage of binucleate forms and the
• Trophozoites typical nuclear structure.
• Size: 6 to 10 µm in length. • The nuclear membrane is delicate, and there
• Motility: Jery, rapid, rapid, nondirectional. is no peripheral chromatin. In the center of
• Flagella: 4 anterior, 1 posterior. the nucleus lies a large mass composed of four
• Shape: pear shaped. to eight separate chromatin granules, usually
• Slender axostyle reaches the posterior end. arranged symmetrically.
• Flagellum at the posterior end extends half the • With good iron hematoxylin stains, the sepa-
trophozoite body. rate granules are readily observed.
• Trichrome stain is less likely to reveal the sep-
Dientamoeba fragilis arate granules of chromatin.
• D. fragilis was considered by most parasitologists to
• Vacuoles containing ingested bacteria may be
be an amoeba, albeit unique among the intestinal
seen scattered through the cytoplasm.
amoebae in its binucleate condition and in the ab-
• Mononucleate forms may be confused with E.
sence of a cyst stage.
nana if the individual chromatin granules are
• Despite the lack of flagella, various protozoologists
not obvious, but binucleate forms are recognized
have recognized its flagellate affinities.
without difficulty.
• It remained for electron microscope studies to con-
• Cysts
firm the flagellate relationships of this organism,
• Size: diameter from to 8 µm.
which is classified among the trichomonads.
• Shape: oval to round.
• The parasite is transmitted from person-to-person
• Nuclei: mono- or binucleated.
through ingestion of trophozoites and/or cysts.
• Have distinct inner and less distinct outer cyst
• Flagellated trophozoites of Dientamoeba are known
walls.
to live in mucosal crypts of the large intestine and
• Less observed in routine examination of stool
have been seen rarely to ingest red blood cells; ap-
compared to the trophozoites.
parently, they never invade the tissues.
The following characteristics are of value in the
• In 1940 Dobell, one of the first to recognize Dient-
identification of Dientamoeba fragilis:
amoeba as a flagellate, suggested (by analogy with
the flagellate Histomonas meleagridis, transmitted
I. Trophozoites, Diagnostic: not characteristic
among poultry via the egg of the nematode Heterakis
unstained
gallinae) that transmission might take place by way
II. Trophozoites, Diagnostic: high percentage of binucleate
of the egg of an intestinal nematode.
stained trophozoites; nuclei without peripheral
• Various studies have noted an impressively greater chromatin and with four to eight
frequency of association between infection with Di- chromatin granules in a central mass
entamoeba and infection with Enterobius vermicularis
than would be expected on the basis of chance.
• Structures resembling Dientamoeba have been found Symptoms
in the eggs of Enterobius, but only in those from per- • A number of reports indicate that D. fragilis causes
sons infected with both parasites. symptoms in some infected persons.
• Initially considered as pathogenic, infection with D. Enteromonas hominis

fragilis may cause “irritable-bowel-like” gastrointes- • The small flagellate Enteromonas is encountered but
tinal disease. rarely.
• Patients may experience abdominal pain, acute diar- • A nonpathogenic protozoan.
rhea, and flatulence.
• Estimates of the incidence of symptomatic infection Morphological characteristics
vary from about 15 to as high as 27%. • Trophozoites
• A number of other symptoms were listed, includ- • Size: 4 to 10 µm long.
ing anal pruritus and low-grade eosinophilia (per- • Motility: there are three anterior flagella, by
haps of significance in relation to a current theory means of which the organisms move in a rapid,
about the mode of transmission, discussed below). jerky fashion.
• The fourth flagellum is directed posteriorly.
Epidemiology • Shape: The body is broadly oval anteriorly and
• The reported prevalence of Dientamoeba infection somewhat attenuated posteriorly.
ranges from less than 1.5% to nearly 20%, but it • Mononucleated
may be much higher in some population groups or • In living specimens little can be observed other
among institutionalized persons. than the general body shape, the anterior flagel-
• Prevalence of Dientamoeba was found to be 52.3% lar movement, and the trailing flagellum.
among 220 members of a semicommunal group in • In stained preparations, the single nucleus is seen
Los Angeles and 3.1% among a sample of 415 per- near the anterior end.
sons surveyed as a part of routine health examina- • There is a distinct nuclear membrane and a large
tion in Oakland, California. central karyosome.
• Among a series of more than 600 homosexual men • Cyst
from the latter area, the prevalence was found to be • Cysts are inconspicuous.
about 1%, lending support to the idea that this para- • Size: 6 to 8 µm long.
site is not transmitted by the conventional fecal-oral • In fresh specimens they are likely to be mistaken
route. for yeasts.
• In a study conducted in Spain in 201 , patients • Stained cysts may be seen to possess one to four
diagnosed positive for Dientamoeba were found to nuclei, generally with a predominance of the bi-
have coinfection by E. vermicularis. The role of E. nucleate condition.
vermicularis in the maintenance and transmission • Cyst nuclei have the same structure as those of
of Dientamoeba infections has yet to be determined the trophozoites.
completely. • Cysts of Enteromonas are of about the same shape
as those of E. nana, and the size ranges of cysts of
Diagnosis the two species overlap.
• Routine microscopic examination of stool. • A predominance of binucleate cysts of small size
• Antigen detection: is highly suggestive of Enteromonas.
• Enzyme immunoassays.
The following characteristics are of value in the
• Antibody detection:
identification of Enteromonas hominis:
• Indirect immunofluorescent.
• Molecular testing
• PCR I. Trophozoites, Diagnostic: anterior flagella; trailing
unstained flagellum but no undulating
Treatment membrane
• Iodoquinol, paromomycin, tetracycline, or metroni- II. Trophozoites, Suggestive: absence of costa,
dazole are recommended. stained axostyle, or cytostomal fibrils;
• Paromomycin (Humatin) has been found effective single nucleus with large central
karyosome; small size
in cases refractory to those drugs.
• Paromomycin is an aminoglycoside antibiotic III. Cysts, unstained Not characteristic
that inhibits protein synthesis. IV. Cysts, stained Suggestive: oval shape; one to four
• Gastrointestinal side effects of treatment are not un- nuclei; with predominance of
common; eighth nerve and renal damage are rare. binucleate forms; small size
Retortamonas intestinalis THE HEMOFLAGELLATES

• Retortamonas is not frequently observed in routine • The family Trypanosomatidae contains a number
microscopy. of genera but only two of which parasitize humans
• A nonpathogenic protozoan. and are therefore considered medically important:
Trypanosoma and Leishmania.
Morphological characteristics • Previously under the Phylum Sarcomastigophora
• Trophozoites (Murray, Barron and Pfaller, 1995; Mcpherson & Pin-
• Size: 4 to 10 µm long. cus, 2011) now under Phylum Euglenozoa (Cox, 2015;
• Motility: move rapidly by means of two anterior McPherson & Pincus, 2017; and Bogitsh et al., 2019).
flagella. • The primitive structure in this group is represented
• Shape: trophozoites are ovoid or teardrop by the genus Leptomonas, parasitic in insects. These
shaped. organisms have a fusiform body, with the nucleus
• Mononucleated central in position, and a single anterior flagellum
• In stained preparations a relatively large nucleus arising from a kinetoplast near the anterior end
is seen at the anterior end. (Fig. 2.21, promastigote).
• The nucleus contains a small, compact central • In the genus Trypanosoma, those forms that are seen
karyosome; there is a layer of fine chromatin in human blood have been rather profoundly mod-
granules on the nuclear membrane. A fibril ified from the promastigote form. The kinetoplast
borders the cytostome. has assumed a position near the posterior end of
• A cytostome extends from near the anterior end the body, and the flagellum passes anteriorly, form-
to about half the length of the organism. ing the outer edge of the undulating membrane,
• Note: This fibril of R. intestinalis does not have a thin protoplasmic sheet running along one side
the shepherd’s crook curve characteristic of Chilo- of the organism. Anteriorly in the trypomastigote
mastix. (Fig. 2.21), the flagellum may project free of the un-
• In unstained trophozoites it is sometimes possible dulating membrane. One species of trypanosome
to see the two anterior flagella and cytostome. that parasitizes humans may be found both in the
• Cyst circulating blood and intracellularly in cardiac mus-
• Size: 4 to µm long and up to 5 µm wide. cle. It has the typical trypomastigote form as a blood
• They contain a single relatively large nucleus, fre- parasite, whereas the stages found in cardiac muscle
quently near the center. are more nearly rounded, have lost the undulating
• Two fibrils extend from the nuclear region to the membrane and all trace of an external flagellum,
attenuated end of the cyst. and are known as amastigotes (Fig. 2.21).
• This fibrillar arrangement, suggesting a bird’s • In these minute parasites, the only structures that
beak, is quite characteristic. can be distinguished are the nucleus and the ki-
• Unstained, they are difficult or impossible to netoplast, with sometimes a remaining short intra-
identify. cytoplasmic portion of the flagellum. This type of
The following characteristics are of value in the organization is also seen in members of the genus
identification of Retortamonas intestinalis: Leishmania, which are always intracellular parasites,
principally in cells of the reticuloendothelial system.
• They may at times be present in the bloodstream in
I. Trophozoites, Diagnostic: a cytostome; two anterior large mononuclear cells. The hemoflagellates were
unstained flagella only; small size in all probability originally parasites of insects. As
II. Trophozoites, Diagnostic: large nucleus with small evidence for this, we see that these organisms are
stained central karyosome, fine granules of transmitted by insects, in which they undergo a de-
peripheral chromatin; cytostomal velopmental cycle.
fibril (not in form of a shepherd’s • Some genera are still exclusively insect parasites. The
crook); small size forms of the parasites that occur in the insect host
III. Cysts, unstained Not characteristic are often quite different from those found in the ver-
IV. Cysts, stained Suggestive: pear shape; small size tebrate.
Diagnostic: bird-beak fibrillar • In culture, Leishmania assumes a promastigote form,
arrangement seen in small, pear- whereas trypanosomes also exhibit forms similar to
shaped cysts those that occur naturally in the insect host.
ing sickness, and on the other by Chagas’ disease or

American trypanosomiasis.
• In both the Gambian and Rhodesian forms of
African trypanosomiasis, the parasites occur as try-
pomastigotes in the bloodstream lymphatics, and
cerebrospinal fluid. They also have been reported to
occur as amastigotes in the choroid plexus, and pos-
sibly other organs.
• In Chagas’ disease, trypomastigotes are found in
the bloodstream, and amastigotes occur intracellu-
larly in cardiac muscle and other tissues.
• In Africa, several species of trypanosomes are im-
portant parasites of cattle, horses, and other do-
mestic animals; the effects of these diseases on the
economy of Central Africa can hardly be overesti-
mated.
Trypanosoma cruzi
• Chagas’ disease is caused by T. cruzi, an organism
that differs from other trypanosomes infecting hu-
mans in that it has an intracellular amastigote stage
in cardiac muscle and other tissues, as well as try-
panosome forms in the circulating blood.
Morphological characteristics
• The trypomastigotes average 20 µm in length, rang-
ing in their proportions from rather short and stub-
by to long, slender forms.
• The nucleus is usually positioned centrally and
the large oval kinetoplast is located posteriorly. In
stained blood films they characteristically assume a
C or U shape (Fig. 2.22).
• Presence of delicate undulating membrane.
FIGURE 2.21 Morphologic types seen in various • Intracellular amastigote stage in cardiac muscle and
hemoflagellates of humans. other tissues, as well as trypanosome forms in the
circulating blood.
• The Old World forms of leishmaniasis are transmit-
ted by the bite of various species of sandflies of the
genus Phlebotomus; the South American leishmani-
ases are likewise carried by sandflies.
• African sleeping sickness is transmitted by bites of sev-
eral species of Glossina, or tsetse flies; the American
trypanosomiasis is transmitted by reduviid bugs and
transmission occurs when infective feces of the bug con-
taminate the wound made by the insect’s bite or an
abrasion of the skin.
Trypanosoma
• Two distinctly different forms of the genus Try-
panosoma occur in humans, represented on the one FIGURE 2.22 Trypanosoma cruzi trypomastigote in
hand by the species associated with African sleep- blood film. (Photomicrograph by Zane Price.)
Life cycle • The infection may also be transmitted congenitally.

• Shown in Fig. 2.23. Infective stage: metacyclic trypomastigote found in
• T. cruzi develops successfully in a large number of bug’s excreta
insects, but it is considered that reduviid bugs are Diagnostic stage: C or S shaped trypomastigotes in
the only vectors of importance and only those spe- blood films
cies that invade houses and habitually defecate dur- Mode of transmission: 1. Entry of infective trypomas-
ing the process of feeding or immediately thereafter tigotes in the site of the bite after scratching the
are major vectors of the human disease. area
• The importance of time of defecation lies in the fact 2. Blood transmission, kidney transplantation,
that the trypanosomes develop in the hindgut of the congenital transmission
insect and are carried in the feces, in contrast to T.
rangeli, which is transmitted in the reduviid’s saliva. Laboratory diagnosis
• Unless the insect deposits infective feces near the • Blood examination
bite, it is unlikely that parasites will be introduced • Machado-Guerreiro test is a complement fixation
into the skin through scratching the intensely pru- test using T. cruzi antigen
ritic lesions. • Electrocardiography
FIGURE 2.23 Life cycle of Trypanosoma cruzi.
FIGURE 2.24 Patient with chagasic megacolon undergoing xenodiagnoses. ote pillbox, which contains
the reduviid bugs, attached to the right forearm.
• Serological test: IFA, RIA, ELISA

• Xenodiagnosis using reduviid bug
• PCR
• An ELISA test has been described that detects T. cruzi
antigens in the urine (antigenuria) of patients with
acute of enlarged lymph nodes may reveal parasites
in the amastigote stage
• Lymph node biopsy showing amastigotes in scan-
ning electron microscopy
Pathology and symptoms

• T. cruzi from various areas and hosts are reflected in
the apparent difference in incidence of cardiopathy
(cardiomegaly), megaesophagus, and megacolon
(Figs. 2.24 and 2.25).
• The disease is seen most commonly, and in its
most severe form, in children younger than 5 years,
in which symptoms of central nervous system in-
volvement may predominate. In older children
and adults, the disease usually occurs in a milder,
subacute or chronic form, which generally follows
an acute attack. An outline of the evolution of FIGURE 2.25 Megacolon in chronic Chagas’ disease.
American trypanosomiasis, as compared with that (Courtesy of Dr. Fritz Köberle, Sao Paulo, Brazil.)
of African trypanosomiasis.
• At the site of infection, the organisms proliferate, • The nodes are hard and moderately tender, and they
producing an erythematous indurated area known usually contain amastigote forms. Lesions similar
as a chagoma. This lesion occurs most frequently on to the initial chagoma may appear elsewhere on the
the face but may appear elsewhere on the body. body in the first few weeks of infection, apparently
• Trypomastigotes or amastigotes may be aspirated by hematogenous spread, and localized areas of hard,
from the chagoma in the early stages of the infec- nonpitting edema may develop in various parts of
tion. They spread rapidly to the regional lymph the body.
nodes, which become enlarged and palpable within • Unilateral edema affecting both the upper and the
3 days. lower eyelid, usually with conjunctivitis, is known
as Romaña’s sign. The edema usually spreads to in- • Organisms appear in the blood at about 10 days and
volve the cheek and sometimes the neck of the same persist during the acute stage. Generalized malaise,
side; occasionally, the eyelids of the other side may chills, high fever, which may be continuous, inter-
be involved, and rarely there is bilateral facial edema. mittent, or remittent; muscle aches and pains; and
• Unilateral ocular and facial edema, involving the increasing exhaustion characterize the acute stage.
submaxillary lymph nodes, is also known as the • The high levels of CSF albumin probably correlate
oculoglandular syndrome (ophthalmoganglionary with the presence of amastigotes in meningeal and
complex). neuronal tissues, known to occur in acute chagasic
• Symptoms of generalized infection may appear meningoencephalitis (Figs. 2.26 and 2.27).
from 4 days to 2 weeks or more after the bite.
Pathogenesis
• Upon its entry into the vertebrate host, T. cruzi pro-
duces an acute local inflammatory reaction. Lym-
phatic spread then carries the organisms to regional
lymph nodes, where they transform into amasti-
gotes upon ingestion by histiocytes or other cells.
• Alternatively, trypomastigotes may actively invade
macrophages and other cells. Evidence suggests that
lectin-like carbohydrate interactions are involved in
the binding of trypanosomes to the host cell. A protein
on the surface of the trypomastigote has been shown
to bind to N-acetylglucosamine on the host cell.
• Amastigotes attach to the cell surface, suggesting the
presence of receptors, and, although they are usually
phagocytosed, they may actively penetrate the cell.
• After local multiplication, the organisms may as-
sume the trypomastigote form to invade the blood-
stream, carrying the infection to all parts of the
FIGURE 2.26 Scanning electron micrograph of a cluster
body.
of Trypanosoma cruzi amastigotes from Vero cell culture. • In the amastigote form, parasites can multiply
Bar is 5 µm. (Photomicrograph by Dr. Thomas B. Cole, Jr.) within the cells of virtually every organ and tissue.
FIGURE 2.27 Trypanosoma cruzi amastigotes in heart muscle. (Photomicrograph by Zane Price.)
Cells of the reticuloendothelial system; the cardiac, • Küpffer cells of the liver, the macrophages of the
skeletal, and smooth muscle; and neuroglia cells are spleen, and cardiac muscle are especially prone to
preferentially parasitized. infection. Within the cardiac muscle, the amasti-
• Chagoma consists of an intense inflammatory reac- gotes proliferate to form pseudocysts; loss of muscle
tion, with invasion of histiocytes, adipose cells of substance and a diffuse inflammatory exudate and
the subcutaneous tissue and the adjacent muscle proliferation of interstitial connective tissue are seen
cells by the proliferating amastigotes, and of the area (Fig. 2.28).
by neutrophilic leukocytes and lymphocytes. • Invasion of the CNS is marked by inflammation of
• Eventually, a lipogranuloma forms, but not before the cortex and meninges.
lymphatic spread of the parasites to the regional • Early in the chronic stage of infection, the heart may
nodes has occurred. As the infection spreads beyond be normal in size or only slightly enlarged, although
the regional lymph nodes, trypanosomes appear in later massive cardiomegaly may develop. The heart
the circulating blood, infecting other organs and tis- weight increases, and all chambers, especially the
sues as they are carried throughout the body. right ventricle, become dilated.
FIGURE 2.28 Life cycle of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense.
• Damage to the autonomic nervous system of the • In California, woodrat burrows are frequently very
heart parallels that to Auerbach’s plexus in the walls heavily infested with the local reduviid, Triatoma
of the digestive tract. Hypertrophy of the muscle lay- protracta, an insect that does not ordinarily defecate
ers and diminution in number of the ganglion cells while feeding, and it is known that the animals can
are seen in affected portions of the digestive tract, become infected by eating the insects or licking in-
most frequently in the esophagus and colon. fected feces from their fur.
• The parasites may be mimicking host antigens as a • A developmental cycle of T. cruzi involving the mul-
strategy for survival. tiplication of epimastigotes in the lumen of the anal
• Host resistance to T. cruzi infection involves both glands of opossums has been described. The devel-
humoral and cellular responses. opment of the parasite in the anal glands appears to
• Antibody-mediated immunity has been shown to be similar to that in the intestinal tract of the redu-
be associated mainly with the IgG class of immuno- viid bug. Mice could be infected by feeding them a
globulins. Lysis of trypomastigotes by complement mixture of breadcrumbs moistened with milk and
is related to the complement activation by way of material squeezed from the glands of an infected
the alternative pathway. Cell-mediated resistance opossum. These findings suggest a potential role
includes killing of trypomastigotes by activated for opossums in the direct transmission of T. cruzi
macrophages and by neutrophils and eosinophils without the aid of the insect vector.
through antibody-dependent mechanisms. • Zymodemes are associated with strains involved
• Host intracellular iron pools appear to play a role in the sylvatic transmission cycle: one in arboreal
in protection against T. cruzi. T. cruzi amastigotes mammals, one in terrestrial, one in humans or in
require iron for optimal growth and pathogenic- domestic mammals.
ity. It is suggested that depletion of host intracellu-
lar iron stores may protect against T. cruzi, whereas Treatment
host responses that transfer iron to the intracellular • The current drug of choice in the treatment of
sites of T. cruzi multiplication may enhance parasite Chagas’disease is the nitrofurfurylidine derivative
pathogenicity. nifurtimox (Lampit, also known as Bayer 2502).
• Nifurtimox inhibits intracellular development of
Epidemiology T. cruzi in tissue culture.
• From the southern parts of the United States through • Benznidazole, an imidazole compound, whose
Mexico and Central America, and in South Ameri- mode of action may be similar to that of metronida-
ca as far south as Argentina, various wild rodents, zole on Trichomonas vaginalis, namely inhibition of
opossums, and armadillos may be found infected nucleic acid synthesis.
with a trypanosome that is also capable of produc- • Verapamil was able to reverse the drug resistance to
ing disease in humans. T. cruzi to nifurtimox in vitro.
• The organism was found, first in the reduviid bug • Allopurinol appears to be an effective drug for the
Panstrongylus megistus and later in humans, by the Bra- treatment of T. cruzi infection as well as the leish-
zilian worker Carlos Chagas while he was still a medi- maniases.
cal student; in his honor the disease received its name.
• Molecular techniques have identified T. cruzi DNA Prevention
in 4000-year-old mummies in the Atacama desert • Control of insect vector.
region of coastal southern Peru and northern Chile. • Education and other efforts toward the construction
• The reduviids (also known as cone-nose bugs of reduviid-proof housing are being undertaken in
or triatomids) that carry T. cruzi are widespread areas of high endemicity.
throughout the America. • Periodic spraying programs.
• Dogs and cats are important reservoirs of infection • Antigenic variation does not seem to occur in T. cruzi
in Brazil. as it does in the African trypanosomes, and prospects
• Certain species of reduviids do not ordinarily def- for the eventual development of vaccines seem good.
ecate at the time of feeding, as do the important vec-
tors of Chagas’ disease. Trypanosoma brucei gambiense
• The lack of domiciliary species of reduviids with the • African sleeping sickness occurs in what originally
necessary defecation habits may explain the fact that must have been two distinctly separate geographic
this disease seldom infects humans in North America. areas and in two clinically distinguishable forms.
• The causative agents of the two types of disease are trypanosomes, confronting the immune system
not readily differentiated, and there has been con- with constantly changing antigenic stimuli.
siderable controversy over their taxonomic status.
Symptoms and pathogenesis
Life cycle • Following the bite of an infected tsetse fly, most
• T. b. gambiense causes the Gambian or West African frequently Glossina palpalis, there is an asymptom-
form of the disease. atic incubation period of a few days to several weeks
• It is a highly pleomorphic organism, frequently (symptom-free period of low-grade parasitemia) in
showing in single blood smear a variety of forms, Africans, and an acute onset is usual in non-Africans.
ranging from slender bodied organisms with a long, • Occasionally, there is ulceration in the area of the
free flagellum that reach a length of 30 µm or more, bite, with formation of an indurated, painful “try-
to fatter, stumpier forms without a free flagellum panosomal chancre,” which slowly disappears. This
that average about 15 µm in length. is much more common in non-Africans,
• The same pleomorphism characterizes Trypanosoma • Parasites may invade lymphatic tissues.
brucei rhodesiense, the cause of Rhodesian or East • Macrophages are involved in the elimination of an-
African sleeping sickness, and Trypanosoma brucei tibody-sensitized trypanosomes.
brucei, which produces a relatively mild disease (Na- • Invasion of the lymph nodes is usually accompa-
gana disease) in native game animals and a severe nied by the onset of febrile attacks. Symptoms in-
infection in many domestic animals but apparently clude fever, malaise, headache, anorexia, generalized
does not infect humans. weakness, nausea, vomiting, and night sweats.
• These three organisms, morphologically indistin- • During the fever, trypanosomes may be found in
guishable except under special and somewhat de- large numbers in the circulating blood, but in the
batable circumstances, cannot be differentiated by afebrile periods they are few in number.
serologic means with any certainty. • With the commencement of febrile attacks there is
• As their pathogenicity for humans and laboratory usually some glandular enlargement. Any lymph
animals is the only criterion for separating them, node may be infected, but those of the posterior
some authorities prefer to consider all three as vari- cervical region are most frequently involved. En-
eties of T. brucei. largement of these nodes is known as Winterbot-
tom’s sign (Fig. 2.29).
Laboratory diagnosis • An irregular erythematous rash, suggestive of erythe-
• Blood examination (thick blood smear) ma multiforme, sometimes with underlying edema
• Spinal fluid examination (double centrifugation
technique enhances detection)
• Fluid aspirate from ulcer or enlarged lymph nodes
(Winterbottom sign)
• PCR analysis for mixed infections
• Buffy coat examination
• Cell counts and spinal fluid protein determinations
(response to therapy)
• Inoculation into the usual laboratory animals (rats,
mice, hamsters)
• Serologic tests
• Card indirect agglutination test for trypanosomiasis:
TrypTect CIATT
• Serum and spinal fluid immunoglobulin M (IgM)
measurements are of diagnostic value.
• Immunoelectrophoresis or ultracentrifuga-
tion of the serum of infected persons usually
demonstrates an IgM level greater than 4 times
that found in pooled normal serum. These sus- FIGURE 2.29 Enlargement of posterior cervical lymph
tained IgM elevations are thought to be a result nodes—Winterbottom’s sign. (Courtesy of Dr. James R.
of the antigenic variability characteristic of these Busvine, London School of Hygiene and Tropical Medicine.)
and frequently accompanied by pruritus, may appear

and disappear during attacks of fever.
• Although congenital transmission is uncommon at
any stage of the disease, abortions and stillbirths are
frequent.
• The infection may terminate without overt nervous
system involvement, or this may occur at any time
after the patient develops symptoms of infection.
• The increasing lassitude and apathy common in
the later stages of the glandular phase of the dis-
ease probably point to beginning nervous system
involvement. There is steady progression in devel-
opment of meningoencephalitis, with general dete-
rioration of the patient and increase of apathy, fati-
gability, confusion, and somnolence.
• Neurologic signs develop late. Motor changes may FIGURE 2.30 Trypanosoma brucei gambiense
include fibrillation of the muscles of the face, lips, trypomastigotes in blood film.
and fingers, and incoordination, leading to slurred
speech and an ataxic gait. Sensory changes are fre-
quently less marked; paresthesias and loss of kines-
thetic sense sometimes are observed.
• Kerandel’s sign: Pressure on the palms of the hands
or over the ulnar nerve may be followed by severe
pain a short time after the pressure is removed.
• In the final stages of the disease there may be pro-
found character changes and mental deterioration.
Motor involvement may lead to convulsions, hemi-
plegia or paraplegia, and incontinence of urine and
feces; severe paresthesias often occur.
• The patient is gradually more and more difficult to FIGURE 2.31 Trypanosoma brucei gambiense
arouse and finally becomes comatose. The progres- trypomastigotes in centriguged spinal fluid.
sion of the central nervous systems (CNS) symptoms
is usually continuous, but there may be remissions tissues early in the disease and the CNS in its later
and exacerbations with a course extending over sev- stages.
eral years. • There is generalized lymphoid hyperplasia as the re-
• Until recently, it was believed that trypomastigotes sult of the proliferation of the parasites in the lymph
were the only developmental stages of the T. brucei nodes (Fig. 2.32).
complex found in the mammalian host (Fig. 2.30). • Hematologic examination reveals: anemia, normal
• It is now known that, at least in experimental ani- WBC count, relative lymphocytosis, thrombocyto-
mals, amastigotes of T. brucei are found early in in- penia as a consequence of hypertrophy of the reticu-
fection in the choroid plexus. There they may block loendothelial system and of the presence of dissemi-
capillaries, causing localized edema and obstruc- nated intravascular coagulation (DIC).
tion to the flow of cerebrospinal fluid and possibly • Hypergammaglobulinemia
by this means producing the headache seen early • Mechanism of evasion: Trypanosomes change their
in human infections. Intracellular forms were not surface antigens (glycoproteins) by turning off one
found in the ependymal cells in human infection gene coding for a variant surface glycoprotein (VSG)
(Fig. 2.31). and turning on another. Estimates are that a single
• During the first flush of trypomastigotes in the trypanosome may have as many as 1000 or more
blood, amastigotes disappear from the choroid VSG genes. By constantly changing surface proteins
plexus to become reestablished there later in the (antigens), trypanosomes are able to evade host de-
course of infection. They may also occur in the lung. fense mechanisms. Such an IgM increase, otherwise
Overt infection involves particularly the lymphoid associated with Waldenström’s macroglobulinemia
the surrounding brain parenchyma. Astrocytes, one

of the most numerous cell types in the CNS, appear
to be the primary antigen-presenting cells regulating im-
mune reactivity in the CNS parenchyma and, as such,
would be involved in the production of cytokines,
which enhance the immune response, and prosta-
glandins, which affect immunosuppression.
• The T lymphocyte suppressor prostaglandin D2
is elevated in the spinal fluid of patients with ad-
vanced sleeping sickness and may in part account
for the increased somnolence of these patients.
Epidemiology
• T. b. gambiense is most frequently transmitted to hu-
mans by the bite of the tsetse flies, Glossina palpalis
FIGURE 2.32 Oriental sores in face and forehead (Armed and G. tachinoides.
Forces Institute of Pathology #80,717). • These species dwell on the banks of shaded streams,
generally in proximity to human habitation.
or other dysproteinemias, may, however, be found • Consequently, Gambian sleeping sickness is like-
occasionally in Africans without evidence of these ly to assume an endemic form, affecting persons
diseases or of trypanosomiasis. whose daily activities bring them in contact with
• Absence of an elevated serum IgM level effectively such streams.
rules out trypanosomiasis, whereas a detectable lev- • No animal reservoirs are known or suspected for
el in the cerebrospinal fluid is diagnostic for CNS T. b. gambiense.
trypanosomiasis. Invasion of the CNS is marked
by a progressive leptomeningitis, with perivascu-
Treatment
lar lymphocyte and plasma cell infiltration of the
• Melarsoprol for treatment of all stages of Gambian
Virchow-Robin spaces, an increased spinal fluid pro-
sleeping sickness.
tein level, and a cell count of 15–500 white blood
• Less toxic drugs may be substituted in the early stag-
cells per microliter.
es (no evidence of neurologic involvement).
• Growth of the parasites in this location is reported
• Suramin: enzyme inhibitor that seems to be tak-
to lead to localized antigen-antibody reactions with
en up selectively by trypanosomes (and filariae)
the release of kinin, disruption of collagen fibers,
and not by mammalian cells.
and destruction of fibroblasts.
• Pentamidine: a diamidine that apparently interacts
• Trypanosomes may occur outside the bloodstream
selectively with kinetoplast DNA to kill trypano-
and spinal fluid and in the gray and white matter
somes, is effective in the hemolymphatic stages of
of the brain, and they have been reported to invade
the infection. This drug does not cross the blood-
other organs and tissues as well. The exact mecha-
brain barrier and therefore is ineffective during the
nism by which these parasites cause death of the
later stages of the disease.
host has long been debated and is still uncertain.
• Trivalent arsenical melarsoprol has the trypanocidal
• Both cellular and humoral immunity are depressed
activity of melarsen oxide and also has that drug’s
in patients with Gambian trypanosomiasis, and
ability to penetrate the blood-brain barrier
such immunosuppression may contribute to the in-
• Eflornithine: an inhibitor of ornithine decarboxyl-
creased susceptibility to secondary infection charac-
ase, has been shown to be a highly effective treat-
teristic of the disease.
ment for both early- and late-stage Gambian sleep-
• Exacerbation of a clinically inapparent and unsus-
ing sickness. Eflornithine is not effective against
pected infection (with the production of ascites and
Rhodesian sleeping sickness.
the presence of trypomastigotes in the ascites fluid)
has been noted in a patient treated with steroids for
an unrelated condition. Prevention
• Microglia and astrocytes have been shown to pro- • African trypanosomiasis is in what has been called a
liferate in the areas of perivascular infiltration and state of controlled endemicity.
• Bush clearing along streams to control breeding Pathogenesis

sites of the tsetse flies. • The disease picture is similar to that of Gambian try-
• Application of insecticides by airplane to reduce the panosomiasis but is much more rapidly progressive.
number of flies breeding in inaccessible areas. Rapid course of the Rhodesian type of infection,
• Surveillance, case detection, and treatment of the neurologic involvement may be expected to occur
people. very early, especially in non-Africans.
• Persons visiting endemic areas should wear protec- • Patients frequently die before the full development
tive clothing (long-sleeved shirts and long trousers of the meningoencephalitic signs and symptoms
of reasonably heavy material—flies can bite through seen in the former disease.
thin clothing). • Incubation period is commonly short, and clinical
• Use of screening, bed netting, and insect repellents. symptoms may be ushered in with a rigor and fever.
• Injections of pentamidine for prophylaxis (no lon- • Trypanosomes appear in the blood early in the infec-
ger recommended for individual use because of the tion and often are present in considerable numbers.
possibility that latent CNS infections may develop • There is usually little obvious glandular involve-
in persons so treated). ment and Winterbottom’s sign may not be present.
• Weight loss is rapid, and the CNS is involved early.
Trypanosoma brucei rhodesiense • Untreated persons usually die within 9 months to a
• Causative agent of the East African sleeping sick- year after the onset of disease.
ness (Rhodesian trypanosomiasis), a fatal disease • Features of imported Rhodesian sleeping sickness
that leads to death before demonstration of the ner- as seen in Americans: malaise, confusion, anorexia,
vous symptoms. lethargy, personality changes, headache, fever, and
• Found in eastern and central Africa. chills
• Inhabits the blood, lymph nodes, CSF. • A differential diagnosis can frequently be made on
geographic grounds but there are some areas, such
Morphology
as Uganda, where the two infections coexist.
• Appears similar to T. b. gambiense.
• Rhodesian sleeping sickness
• more acute
Life cycle • trypanosomes are numerous in the peripheral
Appears similar to T. b. gambiense (Fig. 2.28) blood
Infective stage: metacyclic trypomastigote • little lymphadenopathy
Diagnostic stage: trypomastigotes in peripheral blood • CNS invasion takes place relatively early in the
Mode of rransmission: bite of an infected tsetse fly course
• Glomerulonephritis
Laboratory diagnosis
• Hypocomplementemia
• Peripheral blood examination during febrile stages
• Lymph node biopsy (best diagnostic method) Treatment
• Similar treatment regimens as for Gambian sleeping
Epidemiology
sickness
• In Eastern and Central Africa, a more acutely viru-
lent form of trypanosomiasis is seen. It is sporadic Prevention
in occurrence and generally has a discontinuous dis- • Widespread use of insecticides
tribution. • Vector control
• The agent of this type of infection: T. b. rhodesiense,
is carried by Glossina pallidipes, Glossina morsitans, Trypanosoma rangeli
and occasionally other species of game-attacking • Hemoflagellate that is harmless to man and wild
tsetse flies. domestic animals but damaging to a triatomine bug
• Infection tends to be acute rather than chronic; as- (Beaver, 1984).
ymptomatic carriers do not play a role in the trans-
mission of the disease that they do in Gambian try- Morphology
panosomiasis. • Slender trypanosome is about 30 µm in length,
• Unlike T. b. gambiense, the Rhodesian species has a with a nucleus anterior to the middle of the body, a
number of animal reservoirs: bushbuck, hartebeest, small kinetoplast, and a well-developed undulating
and domestic ox. membrane.
Life cycle Brazil, Venezuela, Colombia, Panama, El Salvador,

• Resemblance to the life cycle of Trypanosoma cruzi. Costa Rica, Honduras, and Guatemala.
• It is transmitted directly by the bite of the reduviid • The organism has been known as Trypanosoma ariari
bug Rhodnius prolixus and a few related species. and T. guatemalensis but seems to be correctly named
• The parasites may be isolated from the bloodstream T. rangeli.
for some months after infection or stay in blood • In Panama, T. rangeli is found 6 times more fre-
throughout the course of the infection. quently than T. cruzi, in a population in which the
• Natural infections have been found in dogs, and average combined infection rate is 3.4%.
T. rangeli will multiply in a number of laboratory, • T. rangeli infections are most common in persons
domestic, and wild animals, apparently none of less than 16 years old, being encountered in some
which develop disease. 75% of that age group.
Infective stage: metacyclic trypomastigote found in • An intracellular amastigote state of T. rangeli has
the saliva of the vector been described from the tissues of experimentally
Diagnostic stage: trypomastigote infected suckling mice.
Mode of transmission: through the bite of an in- • In the Amazon basin of Brazil, T. rangeli has been
fected reduviid bug isolated from opossums, anteaters, coati, and the
vectors Rhodnius pictipes and Rhodnius robustus.
Pathogenicity
• No evidence of pathogenicity has been noted in any Treatment
of the natural infections. • Not necessary but patients maybe given Nifurti-
• Harmless in humans. If infected, humans are gener- mox and benzimidazole, which are used for T. cruzi
ally asymptomatic and no evidence of illness is ob- (Zeibig, 2013).
served (Zeibig, 2013). Prevention
• Control of reduviid bugs
• The diagnosis of T. rangeli infection is made by the Leishmania
identification of trypanosomes in stained blood • The genus Leishmania are obligate intracellular para-
films. In contrast to the other American trypano- sites transmitted by the vector—female Phleboto-
some, T. cruzi, in which the kinetoplast is quite large mine sandflies.
that of T. rangeli is small and inconspicuous. • Leishmaniasis is either zoonotic or anthroponotic
• Xenodiagnosis where humans serve as reservoir hosts (Table 2.4).
• Hemoculture • Three species of Leishmania were recognized, corre-
• Serological test sponding to the clinical entities of leishmaniasis in-
• Molecular techniques: PCR cluding the visceral leishmaniasis (VL) (also known
as kala-azar), cutaneous leishmaniasis (CL), and
Epidemiology mucosal leishmaniasis (ML).
• Human cases of an apparently asymptomatic try- • Other criteria have been utilized, such as restric-
panosomal infection have been reported from tion analysis of kinetoplast DNA, also known as
TABLE 2.4
Morphological Forms (Fig. 2.21) and Required Vectors as Observed in the Life Cycle of Trypanosoma
and Leishamania.
MORPHOLOGICAL FORMS
Amastigote Promastigote Epimastigote Trypomastigote Vector for
Hemoflagellate (Leishmanial) (Leptomonad) (Crithidial) (Trypanosomal) transmission
Trypanosoma cruzi + + + + Reduviid bug
Trypanosoma brucei complex − − + + Tsetse fly
Leishmania spp. + + − − Sand fly
Infective stage: Trypanosoma spp.—metacyclic trypomastigotes/Leishmania spp.—promastigote.
• The various species of Leishmania are transmitted by

TABLE 2.5
sandflies.
The Clinical Diseases Caused by Leishmania
• Human infection happens when a female sand fly
Species and Respective Geographic Location.
takes its blood meal introducing the infective meta-
Clinical Leishmania Geographic cyclic promastigote into the skin of the vertebrate.
Disease Species Location The promastigotes are then ingested by the mac-
Cutaneous L. tropica complex Old World rophages and dendritic cells via phagocytosis. Pro-
leishmaniasis L. tropica mastigotes transform into amastigotes in the mac-
L. aethiopica rophages. Amastigotes replicate in cells of various
L. major tissues including macrophages.
L. mexicana complex New World • In sand fly, the infected macrophages contain-
L. mexicana ing amastigotes are ingested by the sand fly dur-
L. pifanoi ing blood meal in a vertebrate with leishmaniasis.
L. amazonensis Amastigotes transform into promastigote in the
L. garnhami midgut of the sand fly. Promastigotes divide in
L. venezuelensis
midgut and migrate into the proboscis of the vector
L. braziliensis complex* New World awaiting for another blood meal to take place (see
L. peruviana Fig. 2.37 for the generalized life cycle).
L. guyanensis
L. panamensis
Cutaneous Leishmaniasis
L. lainsoni
L. colombiensis • It is the most common form of Leishmania infec-
tions characterized with skin lesions and ulcerations
L. infantum Old World
but can be self-healing over a period of months or
L. chagasi New World years.
Mucocutaneous L. braziliensis complex* New World • Multiple Leishmaniasis species cause CL in both chil-
leishmaniasis L. braziliensis dren and adults (Murray et al., 2005), all are trans-
L. guyanensis mitted by sandflies belonging to the genus Phleboto-
L. panamensis mus.
L. mexicana New World • Old world cutaneous leishmaniasis: L. tropica, L.
L. tropica Old World major, and L. aethiopica
• New world cutaneous leishmaniasis: L. mexicana
L. major Old World
complex and L. braziliensis complex
Visceral L. donovani complex • Oriental sore, as seen in the Old World (Fig. 2.32) is
leishmaniasis L. donovani Old World produced by leishmanias belonging to the Leishma-
L. infantum Old World nia tropica complex.
• Most lesions show in papules, nodules, or nodule
L. chagasi New World
ulcers.
L. tropica Old World • Lesihmania tropica produces chronic disease that, if
L. amazonensis New World not treated, lasts for a year or longer; it is character-
ized by the production of dry lesions that ulcerate
*Members of L. braziliensis complex are considered to be a only after several months, are usually single, and oc-
separate subgenus, Viannia, from all other Leismania, which
belong to the subgenus Leishmania. L. braziliensis complex
cur primarily on the face.
organisms develop in the hindgut of the sandfly vector (referred to • It is found in urban areas, widely distributed
as peripylarian development), whereas other Leishmania species around the Mediterranean littoral, in Armenia,
develop in the midgut (suprapylarian development). Azerbaijan, Turkmenistan, and Uzbekistan; it is
seen also in Afghanistan, India, and Kenya.
schizodeme analysis, nuclear DNA hybridization, • Rock hyraxes in the genus Procavia are known res-
isoenzyme patterns (zymodeme analysis, referred to ervoir host of this species (Salah et al., 2020).
as zymotaxonomy), and serologic testing. • Lesihmania major produces an acute infection with a
• For clarity of presentation, we consider these diseas- duration of 3–6 months.
es under clinical rather than under strictly taxonom- • The lesions occur primarily on the lower limbs,
ic groupings. Table 2.5 lists the various Leishmania they are moist and tend to ulcerate very early;
species and the clinical diseases they cause. there may be secondary or satellite lesions.
• L. major occurs in the Kara Kum and Kyzyl Kum • The organisms do not invade the viscera, and the
deserts of Turkmenistan, Uzbekistan, and Ka- patient remains in general good health.
zakhstan; in Iran, Syria, Israel, and Jordan; and • Leishmania amazonensis is found in the Amazon ba-
in Africa in Algeria, Egypt, Tunisia, the Sahara, sin of Brazil and is the cause of cutaneous and dif-
Sudan, Chad, Nigeria, Niger, Burkina Faso, Mali, fuse cutaneous forms of leishmaniasis
Senegal, and Kenya. • Reservoir hosts for this species of the L. mexicana
• Sand rat in the genus Psammomys is the reservoir complex are a number of small forest mammals,
host of L. major (Salah et al., 2020). including rodents, marsupials, and foxes.
• Leishmania aethiopica is known main causative agent • The principal vector is a Lutzomyia sandfly.
of CL (van Henten et al., 2018) but has been one of • Only a small percentage of the cases of cutaneous
the most neglected Leishmania species. leishmaniasis is due to L. amazonensis; however,
• L. aethiopica is seen in the highlands of Ethiopia, in Belém, Brazil, approximately 30% of cutane-
in Kenya, and possibly in south Yemen. ous leishmaniasis cases caused by this parasite
• Sandfly vectors and rock hyraxes are considered have progressed to incurable diffuse cutaneous
main reservoir host of L. aethiopica. leishmaniasis, presumably in persons with defec-
• New World cutaneous leishmaniasis is caused by tive cell-mediated immunity.
species of the Leishmania mexicana complex, of • Two other described species of the L. mexicana com-
which L. mexicana and L. pifanoi are the most impor- plex are L. garnhami, which causes Venezuelan An-
tant. dean cutaneous leishmaniasis, and L. venezuelensis,
• The chiclero ulcer or Bay sore is caused by L. mexi- which causes cutaneous leishmaniasis in a forested
cana. area along the River Turbio, state of Lara, Venezuela.
• It is found in Belize, the Yucatan peninsula, and The identification of these subspecies is based on iso-
Guatemala. Twenty-nine cases of autochthonous enzyme profiles and monoclonal antibody studies.
human cutaneous leishmaniasis have been re- • A species of the Leishmania braziliensis complex, L.
ported from south central Texas. peruviana, is confined to the western Peruvian Andes
• Amastigotes of the L. mexicana complex have and causes a disease in humans known locally as
been isolated from dermal lesions of humans “uta.”
and from woodrats and a cat in the same area of • There may be one or a small number of skin le-
Texas. sions that are self-healing and similar to those of
• Lesions are usually single, and 40% affect the ear, L. tropica; it has, in fact, been suggested that this
where they can be quite destructive of cartilage. species is actually imported L. tropica. However,
Rarely the diffuse cutaneous form is seen, with isoenzyme profiles show it to be distinct from L.
extensive proliferative lesions more or less all tropica.
over the body. • The domestic dog and probably a wild rodent are
• Six cases of diffuse cutaneous leishmaniasis, at- reservoir hosts, and sandflies of the genus Lutzo-
tributed to infection with L. mexicana, have been myia are the vectors.
reported from widely separated geographic re- • Two other species of the L. braziliensis complex, L. guy-
gions in Mexico. Three of the patients had evi- anensis (which occurs in the Guyanas and northern
dence of nasopharyngeal mucosal involvement. Brazil) and L. panamensis (which occurs in Panama,
• A number of forest rodents are reservoir hosts of Costa Rica, and Colombia), also produce single skin
this parasite, and the vector is a sandfly of the ulcers, but with both organisms lymphatic spread
genus Lutzomyia. may occur, resulting in widespread ulceration.
• L. pifanoi occurs in the Amazon basin, in Mato Gros- • The disease caused by L. guyanensis is known local-
so State in Brazil, and in Venezuela. ly as pian bois; reservoir hosts are arboreal sloths
• It has been isolated only from patients with the and anteaters, and Lutzomyia is the sandfly vector.
diffuse cutaneous form of the disease. • L. panamensis has a variety of reservoir hosts, in-
• The initial lesion is a single one, and often a pe- cluding sloths, rodents, monkeys, and procyo-
riod of months or years passes (during which it nids. Lutzomyia and Psychodopygus sandflies are
may ulcerate or even disappear) before the disease vectors.
spreads both locally and to distant skin areas. • L. lainsoni, a species belonging to the L. braziliensis
• The irregularly shaped papules, which bear a re- complex, is another cause of cutaneous lesions.
semblance to the lepromatous lesions of leprosy, • Infections have been reported from Brazil
spread slowly and do not ulcerate or heal. and Peru, where Lutzomyia sandflies are the
natural vector and the agouti is the wild animal • This type of response, known as leishmaniasis
reservoir. recidiva, may be seen with any of the cutaneous
• The subgenus Viannia develop in the hindgut of leishmaniases.
the sandfly vector, whereas organisms of the sub- • Host recovery in cutaneous leishmaniasis depends
genus Leishmania (all non-L. braziliensis complex on the development of cell-mediated immunity.
leishmanias) develop in the midgut of the sandfly. • The course of development of cellular immunity
• The enzyme aconitate hydratase is able to distin- was closely monitored in an accidental laboratory
guish the subgenus Viannia from the other leish- infection with L. tropica.
manias. • In vitro bioassays of cell-mediated immunity showed
• L. colombiensis, also a member of L. braziliensis com- that lymphocyte proliferation and interleukin-2
plex, is closely related to L. lainsonis causes cutane- production, induced by solute L. tropica antigens,
ous lesions, and has been reported to infect human appeared within 5 weeks of infection and reached
in Colombia, Venezuela, and Panama. maximum levels with ulceration of the skin lesion.
• The sandfly vector is Lutzomyia, and the sloth is a • Interleukin-2 production rapidly decreased, where-
natural reservoir. as lymphocyte proliferation declined more slowly.
• L. infantum in north Tunisia and L. chagasi in Healing was complete after 20 weeks.
Honduras are two leishmanias that usually produce
visceral disease have been identified as the cause of Diagnosis
cutaneous lesions in certain areas. • Diagnosis of cutaneous leishmaniasis is usually
made in endemic areas on clinical grounds, but this
Symptoms requires much familiarity with the disease.
• The incubation period may be a couple of months • Currently, there are available standardized and
or as long as 3 years in L. tropica and L. aethiopica sensitive assays that detects serum antileishmanial
infections; in L. major it is much shorter, as little as antibody; however, microscopic identification of
2 weeks. amastigotes in tissue biopsies, lesion scrapings, or
• The first sign of infection is a small red papule, impression smears remains the common practice
which may itch intensely and grows to 2 cm or more (Murray et al., 2005).
in diameter. • The specimen of choice is to be collected from sever-
• In L. major infections, the papule is covered with a al punch biopsy samples taken from areas with most
serous exudate and ulcerates early; papules are dry active lesions (Garcia, 2016).
and ulcerate only after several months in L. tropica • Samples collected are used for cultures and touch
and L. aethiopica infections. preparations.
• Although the usual cutaneous lesions heal sponta- • For histologic testing, slides with samples (impres-
neously. sion smears) shall be subjected to fixation using
• In certain instances, healing does not occur of itself, 100% methanol followed with Giemsa staining
cases as these may be considered to represent the (Garcia, 2016).
two poles of the spectrum of response—anergy and • It is usually possible to demonstrate the rounded
hypersensitivity. or oval organisms, approximately 4.5 × 3.3 µm
• The anergic patient is incapable of mounting a re- in diameter and having a typical amastigote
sponse to infection, which therefore can proliferate structure, within large monocytic cells obtained
indefinitely, forming many lesions teeming with by aspiration of fluid from beneath the ulcer bed,
parasites. especially its active border.
• This type of disease, known as diffuse cutaneous • Scrapings taken from the ulcer surface do not reveal
leishmaniasis, is probably the result not only the organisms, which are destroyed in areas second-
of deficient cell-mediated immunity but also of arily infected with bacteria.
some characteristics of the parasite itself, as it is • Culture on Novy-MacNeal-Nicolle (NNN) medium
seen primarily in infections caused by L. aethi- of material obtained by aspiration or biopsy may
opica and L. pifanoi. demonstrate promastigote forms that can be also
• The hypersensitive patient is capable of excellent an- stained with Giemsa to facilitate tissue observation
tibody and cellular responses but cannot completely (Garcia, 2016).
eliminate the parasites, so as the central lesion heals, • Schneider’s Drosophila medium supplemented
active peripheral ones continue to form. with 30% fetal bovine serum has been useful in
isolating organisms from humans with cutaneous

leishmaniasis.
• Aspirate or biopsy material may be inoculated sub-
cutaneously into the nose of a golden hamster and
the animal watched for nasal inflammation.
• A combination of tissue biopsy microscopy, cul-
ture, and histopathology may be required for op-
timal diagnosis (Garcia, 2016).
• The result of the Montenegro test, involving the
intradermal injection of a suspension of killed pro-
mastigotes, is positive in a high percentage of L. trop-
ica infections and in more than 95% of L. braziliensis
infections.
• Today, microscopic and culture diagnostics ensure
sensitivity to more than 85% (Murray et al., 2005)
in diagnosing cutaneous and ML. FIGURE 2.33 Typically depressed, flattened scar left by
healed oriental sore. (Courtesy of Dr. Roy Leeper, Kaiser-
• Culture or DNA analyses allow species identifica-
Permanente Medical Center, Oakland, CA.)
tion (Murray et al., 2005).
Pathogenesis L. tropica does not confer the same immunity to sub-

• When the bite of an infected sandfly liberates pro- sequent challenge with L. major.
mastigotes into the skin, the parasites proliferate as
amastigotes in the macrophages and the endothe- Epidemiology
lium of the capillaries and other small blood vessels • Although sandflies are the natural vectors of all
of the immediate area. types of leishmaniasis, contact infection is possible,
• Lysis of the amastigotes occurs following activation and vaccination is practiced in certain areas by inoc-
of the macrophages by sensitized lymphocytes. ulating serum from naturally acquired lesions into
• A granulomatous reaction results in the formation an inconspicuous location on the body of a nonim-
of a localized nodule, which ulcerates when the mune person.
blood supply to the area is compromised by para- • Mechanical transmission through the bites of flies
site-induced damage. such as Stomoxys has also been documented.
• A pyogenic infection, generally a trivial one, devel- • Infected monocytes may be a source of transfusion-
ops in the open ulcer bed, and as host immunity associated leishmaniasis.
increases, the ulcer heals. • The infection produced by L. tropica is generally
• Enlarged regional lymph nodes (bubonic leishman- transmitted from one human to another; the other
iasis) have been reported to accompany the cutane- forms of cutaneous leismaniasis are principally zoo-
ous lesions of L. braziliensis. noses.
• A survey in Brazil indicated that 77% of 595 persons • Construction work that involves opening the bur-
with parasitologically confirmed cutaneous leish- rows of infected gerbils has caused serious outbreaks
maniasis reported lymphadenopathy in addition to of L. major infection in humans.
skin lesions. • Current estimates of cutaneous leishmaniasis cases
• L. braziliensis should be considered in cases of unex- are ranging from approximately 700,000 to 1.2 mil-
plained lymphadenopathy in endemic areas. lion or more (CDC, 2020).
• Whereas in humans, infection with L. tropica is • During an 18-month period in 2002–04, 522 cases
confined to the skin and heals spontaneously of cutaneous leishmaniasis were confirmed in mili-
(Fig. 2.33), the hamster is unable to develop any tis- tary personnel deployed to Afghanistan, Iraq, and
sue resistance and is ultimately killed by the infec- Kuwait (CDC, 2004).
tion, which spreads to the viscera. • L. major was the organism identified by isoen-
• Resistance to reinfection with the same species zyme electrophoresis where clinical isolates were
following a primary infection is nearly absolute. cultivated.
Infection with L. major protects the host against • Patients were treated with sodium stibogluconate
subsequent L. tropica infection, but infection with at Walter Reed Army Medical Center.
Treatment • Electrocardiographic (EKG) abnormalities are

• Cutaneous leishmaniasis heals over time by re- rare, but if they occur the drug should be with-
epithelization with signs of scarring (Murray held until the EKG returns to normal, at which
et al., 2005). time the dose is reduced slightly.
• Self-cure or spontaneous healing in old world cu- • Antimony-resistant cutaneous leishmaniasis has
taneous leishmaniasis heals within 2–4 months been successfully treated with suboptimal doses
(L. major) or 6–15 months (L. tropica). of pentavalent antimonials (Glucantime, 10 mg/
• In new world leishmaniasis infections, self- kg body weight daily for 30 days) and intramus-
healing occurs after 3 months. Rapid in L. mexi- cular recombinant human interferon gamma,
cana (>75%), but slow in infections caused 100 µg/m2 of body surface area daily for 30 days
by L. braziliensis (∼10%), and L. panamensis (Falcoff et al., 1994).
(∼35%). • Intradermal injections of interferon gamma
• Treatment is used to accelerate cure to reduce scar- around lesions caused by L. tropica and L. guy-
ring, prevent dissemination (ML), or disease relapse anensis reportedly promote healing of ulcers
(Murray et al., 2005). (Harms et al., 1989).
• Antimonials were the first effective drug against • Apparently, healing was accomplished by cell-
Leishmania (Tiwari et al., 2019). mediated immune responses elicited by the in-
• Currently, there are two pentavalent antimony that terferon gamma.
are commercially available; these are the sodium • Amphotericin B has been used in patients unre-
stibogluconate and meglumine antimoniate (Tiwari sponsive to pentavalent antimonials, administered
et al., 2019). by slow intravenous infusion, gradually increasing
• Sodium stibogluconate (antimony sodium gluco- the dose to 1 mg/kg weight, at which level it should
nate; Pentostam), less toxic than the earlier pentava- be continued on alternate days until a total of 2–3 g
lent antimonials, is the most effective compound has been given.
presently available for treatment of all cutaneous • A less toxic alternative is ketoconazole.
leishmaniasis except the Ethiopian form of diffuse • Oral ketoconazole, 400 mg daily for 4–8 weeks, has
cutaneous leishmaniasis, which is reported to re- been reported to be effective in treating longstand-
spond best to pentamidine. ing cutaneous leishmaniasis (Viallet et al., 1986).
• Pentavalent antimony inhibits glycolytic en- • Itraconazole has been used in India to treat cu-
zymes and fatty acid oxidation in leishmanial taneous lesions. Topical preparations containing
amastigotes. chlorpromazine (2%) or paromomycin (15%),
• Pentostam is administered either intravenously used in clinical studies in Israel, have demon-
or intramuscularly; the dosage is 20 mg/kg body strated considerable potential for the treatment
weight daily for 20 days. of cutaneous leishmaniasis.
• The course may be repeated at 10-day intervals • Clotrimazole (1%) cream was an effective topi-
in resistant cases; a maximum of three courses is cal treatment of cutaneous infection in Saudi
advised. Arabia.
• Pentamidine is administrated as outlined below • Oral dapsone, 200 mg daily for 6 weeks, showed
for the treatment of kala-azar. Coughing, head- an 82% cure rate in a double-blind trial in India.
ache, and vomiting are frequent side effects of • Finally controlled, localized heat, three 30-sec-
antimonial drugs. ond treatments of 50°C at weekly intervals, has
• In areas where sodium stibogluconate is not readily been used to treat cutaneous leishmaniasis in
available (such as Latin America), meglumine anti- Guatemala (Navin et al., 1990).
moniate (Glucantime) may be substituted. • The cure rate with heat treatment was the same as
• The recommended dose is 20 mg/kg per day in- with the pentavalent antimonial, 73%.
travenously or intramuscularly for 20 days. • Steroids may be of value in the initial treatment of
• The course may be repeated or continued, as leishmaniasis recidiva.
some patients may need a longer duration. • The efficacy of a combined vaccine (heat-killed L.
• Meglumine antimoniate is not available in the amazonensis plus viable bacille Calmette-Guérin
United States. [BCG]) in immunotherapy of American cutaneous
• Some authorities recommend continuous ad- leishmaniasis was evaluated in a clinical study in-
ministration until healing is complete. volving 217 patients (Convit et al., 1989).
• Clinical cure was observed in more than 90% of Symptoms

those who received the vaccine; the average time for • ML starts with erythema and ulceration at the na-
healing was 16 to 18 weeks and it was comparable res, leading to the perforation of the nasal septum
to that for meglumine antimoniate (Glucantime). and destructive inflammatory lesions (Murray
et al., 2005).
Prevention • Lesions caused by ML can cause an obstruction in
• Vector control can be done using the residual spray- the pharynx or larynx and may produce a significant
ing method against malaria has been useful in pre- disfigurement (Murray et al., 2005).
venting Leishmaniasis (Garcia, 2016). • The cutaneous lesions develop exactly as does
• Insect repellent application oriental score, but they are more frequently mul-
• No vaccines are currently approved for use, but tiple and may become large.
there are candidates that are now in stages of test- • Secondary infection plays a prominent role in
ing. Live attenuated vaccines show a promising fu- the persistence of these ulcers and in the size that
ture for Leishmania vaccination (Zabala-Peñafiel they may attain.
et al., 2020). • Sometimes ulcerations of adjacent areas extend
• Field trials of a vaccine made from cultured pro- to involve mucosal surfaces, but more frequently,
mastigotes of several strains of leishmanias from the lesions seem to develop by metastasis.
Brazil showed that the use of this vaccine resulted • The cutaneous lesions may be completely healed
in Montenegro skin-test positivity in 78.4% of the at the time mucosal lesions are first seen, or the
experimental group 3 months after inoculation. two types may coexist.
• The proportion of positive results fell to 73.2 in • Mucosal lesions sometimes develop many years
1 year, 54.1 after 2 years, and 30.9 after 3 years. after the patient has left an endemic area, in per-
• Skin test positivity is associated with resistance to sons with no history of cutaneous lesions.
superinfection, and these results must be consid- • If mucosal ulcerations develop, progress of the
ered promising. infection, while slow, is steady. Unless effective
treatment is given, the entire nasal mucosa, and
Mucocutaneous Leishmaniasis that of the hard and soft palates, eventually is af-
• ML has been recorded in Brazil, eastern Peru, Bo- fected (Fig. 2.34).
livia, Paraguay, Ecuador, Colombia, and Venezuela.
• The outstanding feature of this disease, known in
Brazil as espundia, is the development, in a variable
percentage of patients, of ulcers on the oral or nasal
mucosa.
• In some parts of Brazil, such lesions are said to occur
in about one-fifth of cases of the disease.
• A form of tegumentary leishmaniasis, ML is com-
monly associated with L. braziliensis, L. panamensis,
and less frequently with L. amazonensis (Table 2.5).
• Various forest rodents and dogs are naturally
infected.
• Sandflies belonging to the genera Lutzomyia and
Psychodopygus are vectors.
• A clinically similar disease is seen in Ethiopia and
Sudan, characterized by ulceration of the lips and
mucous membranes of the nose and mouth and
sometimes by the destruction of the nasal alae.
• The lesions are not as extensive as those seen in
espundia and are believed to results from direct
extension of primary cutaneous lesions of the
nose or lips. FIGURE 2.34 Patient with mucocutaneous
• The causative agent is believed to be L. tropica leishmaniasis. (Courtesy of Dr. Q. H. Geiman, Stanford
and possibly L. major. University Medical School, Palo Alto, CA.)
• The nasal septum is destroyed, but unlike similar

syphilitic lesions, the process does not involve
the bones.
• Ulceration may result in loss of all the soft parts
of the nose, the lips, the soft palate, and so forth.
• Death usually occurs from secondary infection.
Treatment
• Sodium stibogluconate (Pentostam), administered
as described for cutaneous leishmaniasis (except
that the length of treatment is 28 days rather than FIGURE 2.35 Leishmania donovani amastigotes in
20 days), is also effective in the mucocutaneous Küpffer cells. (Photomicrograph by Zane Price.)
form of disease.
• Cycloguanil pamoate (Camolar), a folic acid inhibi-
tor, is reported effective when administered intra-
muscularly at the rate of 300 mg for adults, 280 mg
for children 1–5 years of age, and 140 mg for infants
in a single dose.
• Amphotericin B (Fungizone) is also reported to
yield good results when given intravenously at the
rate of 0.5–1 mg/kg body weight, daily or every oth-
er day, for periods up to 8 weeks.
• Coughing, headache, and vomiting may be noted
with either antimonials or amphotericin; renal dam-
age and bone marrow depression are frequently seen
when amphotericin is given for extended periods.
Visceral Leishmaniasis
• Widely known by its Indian name of kala-azar, VL.
• It is no longer considered to be caused by a single FIGURE 2.36 Leishmania donovani amastigotes in
agent but by at least three species belonging to the spleen impression preparation from infected hamster.
(Photomicrograph by Zane Price.)
Leishmania donovani complex, but clinically and bio-
chemically distinct and with different geographic
distributions.
• As in cutaneous and ML, the causative organisms are • In the Indian area there seem to be no reservoir
parasites of the reticuloendothelial system. hosts; the same is possibly true of Kenya, but in
• Unlike those discussed previously, the parasites the Sudan, it is found in various rodents.
that cause kala-azar are not confined to the reticu- • Dogs are the principal reservoir in China.
loendothelial cells of the subcutaneous tissues and • Vectors are Phlebotomus sandflies. It has been sug-
mucous membranes but may be found throughout gested that further studies will probably result
the body (Figs. 2.35 and 2.36). The life cycle of the in the separation of one or more African strains
L. donovani complex is illustrated in Fig. 2.37. from those seen in the Indian subcontinent.
• L. donovani occurs in India, Burma, East Pakistan, • L. tropica has been the reported cause of VL in two
Sumatra, and Thailand, and in the Central African patients in Kenya who were unresponsive to treat-
Republic, Chad, Ethiopia, Somali Republic, Djibou- ment with Pentostam, in patients in northeast
ti, Kenya, northern Uganda, Sudan, Gabon, Gam- India, and in veterans returning from the Persian
bia, and Niger. Gulf War.
• Infection caused by L. donovani is commonly re- • Leishmania infantum is found along the whole Medi-
ferred to as “dum dum fever” terranean littoral—in Europe, the near East, and Af-
• Known to affect all ages of human host. rica. Elsewhere in Europe it occurs in Hungary, Ro-
• It formerly occurred in epidemic proportions mania, and the former southern USSR.
in the People’s Republic of China but has been • It has also been reported in northern China and
brought under control. southern Siberia.
FIGURE 2.37 Life cycle of Leishmania donovani complex.
• Human infections are confined almost entirely • VL caused by L. chagasi has been observed pri-
to children. marily in children.
• Humans are considered to be an accidental host, • Foxes and domestic dogs and cats are naturally
with natural infections occurring in dogs, other infected; the vectors are Lutzomyia sandflies.
Canidae, and porcupines. • Also causing VL, L. amazonensis has been isolated
• Transmission is by Phlebotomus sandflies. L. in- from the bone marrow of a patient with typical VL
fantum has been the cause of an increasing num- in Brazil.
ber of cases of VL in HIV-infected patients in Italy
and other Mediterranean countries. Symptoms
• Leishmania chagasi, the common causative agent of • As in the cutaneous and mucocutaneous leishmani-
VL, have been reported in Central and South Amer- ases, the parasites that cause VL are transmitted by
ica—Argentina, Bolivia, Brazil, Surinam, Venezuela, various species of sandflies.
Colombia, Ecuador, El Salvador, Honduras, and • Promastigote forms of the parasite multiply in the
Guatemala—and in Mexico and Guadeloupe in the gut and migrate anteriorly to escape from the pro-
West Indies. boscis when the fly feeds.
• The onset of the disease is gradual, after an incu- • Ascites may occur in advanced stages of the disease.
bation period that may vary between 2 weeks and • Kala-azar means, literally, black fever, having ref-
18 months. erence to a characteristic darkening of the skin,
• Frequently, the patient may present with a com- which has been most often noted in light-skinned
plaint of abdominal swelling, which has taken place Indians and is difficult to distinguish in persons
without any definite illness. with either very dark or very light skin. It is most
• On examination, hepatomegaly and splenomegaly marked on the forehead, over the temples, and
are found. around the mouth.
• Sometimes there is acute onset, which may closely • L. donovani does not in most areas cause skin le-
mimic an attack of malaria, even to the tertian or sions, although an initial papule (presumably at the
quartan periodicity. site of the infecting bite) has rarely been noted.
• There is sometimes diarrhea and an onset resem- • A condition known as dermal leishmanoid
bling typhoid fever. (Fig. 2.38) is sometimes seen in patients who have
• If the onset is insidious, there may be only an been treated for VL and may occur in persons who
indefinite feeling of ill health during the earlier deny any history of disease.
stages of the disease. • The dermal lesions may be erythematous or de-
• Fever may be continuous, intermittent, or remittent, pigmented macules, distributed over the entire
and recur at irregular intervals. body or in patches.
• A double (or “dromedary”) or even triple fever • A butterfly distribution over the nose is not un-
peak daily is characteristic but is not always seen, common.
as the temperature must be taken every 3 hours • Later the lesions tend to become nodular and at
day and night to detect the sometimes transitory this stage may be mistaken for leprosy nodules.
peaks. • Organisms may be found in the dermal lesions, and
• Anemia is generally present. it has been suggested that patients with such lesions
• There is progressive weight loss as the disease pur- represent an important source of infection for the
sues its course. sandfly.
• The body becomes emaciated, with the abdomen • Neurologic changes in VL are rarely reported.
hugely swollen by the enlarged liver and spleen. • However, 46% of 111 patients with VL in
• Both organs are frequently soft and generally not Khartoum, Sudan, had neurologic signs or
tender. symptoms.
FIGURE 2.38 Dermal leishmanoid lesion on buttocks. (Armed Forces Institute of Pathology, #384,447.)
• The most common symptom was a sensation of • Enzyme immunoassay, immunoblot, and indirect
burning feet; followed by deafness, foot drop, fluorescent antibody tests are the serologic tests
and multiple cranial nerve palsies. available.
• L. donovani amastigotes have been recovered • Antileishmanial immunoglobulin G in high ti-
from the cerebrospinal fluid of a 10-year-old boy ter has been used as a standard diagnosis for VL
with kala-azar in India. (Murray et al., 2005).
• Freeze-dried antigen and RK39 strip test (rapid
Diagnosis detection of anti-K39 antibody) using blood
• The clinical picture may be suggestive, but a defini- from fingerstick have been tested using immuno-
tive diagnosis rests on the demonstration of the par- chromatographic strip test (Murray et al., 2005).
asites. • Formol-Gel test can be used to screen patients with
• Splenic puncture is undoubtedly an effective meth- kala azar (Garcia, 2016).
od for securing reticuloendothelial cells for study • Kala azar patients characterized with hypergam-
but is a somewhat risky procedure. maglobulinemia (Garcia, 2016).
• Liver puncture is safer but possibly not as produc- • A drop of formalin is added to a test tube with
tive. 1 mL of patient serum, which is then observed for
• Sternal marrow aspiration may likewise reveal the the presence of opaque and stiff jelly consistency
parasites and is considered by some the diagnostic within 3 minutes to 24 hours (Garcia, 2016).
procedure of choice. • New approach leads to the testing of urine for
• Buffy coat films, prepared from venous blood, are leishmanial antigen and antibody testing as a sub-
sometimes of value. stitute for invasive diagnostic procedures (Murray
• It appears that in certain forms of VL parasites et al., 2005).
frequently are found in the blood. • With excellent specificity and sensitivity, molecular
• For example, parasitemia was detected in 15 of diagnostics using PCR has been used to detect para-
20 patients with Kenyan VL. site DNA (Garcia, 2016).
• Similar results have been reported for VL in In-
dia. Pathogenesis
• Culture of venous blood or of specimens of sternal • The various species that cause VL parasitize cells of
marrow, liver, or spleen may reveal the parasites the reticuloendothelial (RE) system occur through-
when they are scanty in the original material. out the body.
• Three culture media and Giemsa-stained smears • VL is progressive, and the mortality rate in untreated
have been compared for their ability to detect Leish- cases ranges from 75% to 95%; death usually occurs
mania organisms in splenic aspirates from patients within 2 years. In a relatively mild form, the disease
with VL. may persist for many years; spontaneous cures un-
• Microscopy and culture were equally sensitive in de- doubtedly occur.
tecting parasites before treatment. • Proliferation of the RE cells, particularly of the
• During and after treatment, culture on Schneider’s spleen and liver, leads to massive hypertrophy of
Drosophila medium was the most sensitive meth- these organs, which may return essentially to nor-
od for detecting organisms, followed by microsco- mal size after successful treatment.
py and culture on RPMI medium 1640 and NNN • The bone marrow may be involved, resulting in ane-
medium. mia and leukopenia.
• Hamsters are very susceptible to the disease and • The white blood cell count is generally below
can be infected by intraperitoneal inoculation (see 4000 per µL, often ranging from 2000 to 3000,
Fig. 2.36). accompanied by a progressive monocytosis.
• Interestingly, the result of the Montenegro (leish- • In kala-azar and trypanosomiasis, gamma globu-
manin) skin test is negative in active kala-azar, but lins may constitute 60% to 70% of the serum
it becomes positive within 2 months following suc- proteins.
cessful treatment. • Splenomegaly with stasis of blood in the sinusoids
• Presumably, it likewise is positive after sponta- may result in increased destruction of both red and
neous cure; in surveys, a leishmanin-positive rate white blood cells.
of over 5% is considered evidence of endemic • Glomerular involvement, with deposition of sub-
kala-azar. endothelial and mesangial immune complexes
resembling those found in the kidney in human cases and represent healed ulcerations at the site of
of hepatosplenic schistosomiasis, has been described. infection.
• IgA, IgG, IgM, complement, and fibrinogen have • The Montenegro test is often positive in the early
been identified from these glomerular complexes. stages of the disease, a consequence presum-
• Interstitial nephritis, with infiltration of lympho- ably of the dermatotrophic nature of L. donovani
cytes and plasma cells, has been described in human strains in this area.
infection. • The ground squirrel strain of L. donovani isolated in
• Ocular complications of kala-azar are rare. Kenya is apparently not viscerotropic in humans.
• They include retinal hemorrhage, keratitis, • Introduced into the skin, it gives rise to a leish-
central retinal vein thrombosis, papillitis, iritis, manioma but does not extend to produce a vis-
and uveitis. ceral infection.
• Amastigotes have been demonstrated in eye le- • At least a temporary immunity is produced
sions of patients with anterior uveitis in southern against viscerotropic strains of L. donovani by this
Sudan. Death usually is the result of intercurrent means.
infection. • In Tuscany, Italy, where human and canine leish-
• Mechanisms that are involved in recovery from maniases are endemic, rats have been shown to carry
leishmanial infection are generally believed to in- L. infantum, suggesting their role as wild reservoirs
volve interactions between T lymphocytes and mac- of infection.
rophages; however, recent studies have demonstrat- • Clinical VL has been described in foxhounds in
ed a role for humoral factors in human resistance to central Oklahoma.
reinfection with L. donovani. • The dogs, all from the same private kennel, had
• Normal human serum and serum from patients never traveled to areas of known leishmaniasis or
with kala-azar are cytotoxic for amastigotes of associated with known infected animals, suggest-
L. donovani, killing parasites via the alternate path- ing that infection was acquired locally.
way of serum complement. • Ticks have been proposed as possible vectors.
• Cytotoxicity of normal serum was enhanced by fac- • Ultrastructural studies show the organisms to be
tors present in patient serum characterized as para- morphologically similar to L. donovani.
site-specific IgG.
Treatment
Epidemiology • Sodium stibogluconate (Pentostam), administered
• Various clinical forms of VL are characteristic of dif- as described for L. tropica infections, (see Chapter 11)
ferent localities. In general, two different forms of except that the suggested length of treatment is 28
transmission are observed. rather than 20 days, is the drug of choice for initial
• In the urban form, the transmission is primarily therapy in all but Sudanese infections.
from human to human. • Strains acquired in Sudan are generally resistant
• A rural form of transmission, seen in other areas, to antimonials, and treatment should be initi-
is primarily a zoonosis. ated with pentamidine at the rate of 2–4 mg/kg
• The infection is epizootic in rodents or other wild body weight, given in daily intramuscular doses
animals; humans are sporadic and somewhat acci- for 10–15 days.
dental victims. • Resistance to Pentostam has also been reported
• In the semiarid Transcaucasian areas, wild jackals in Kenya. Meglumine antimonate (Glucantime),
serve as a reservoir of infection, which in rural areas not available in the United States, may be used as
occurs primarily in adults. described for cutaneous leishmaniasis, except it
• In Africa a rural form of transmission is generally seen; is administered for 28 days.
rats in Sudan and gerbils and ground squirrels in East • Animal experiments suggest that liposomal en-
Africa carry the infection, which sporadically infects capsulation may be utilized to deliver antimonial
humans. Epidemics have occurred in these areas. drugs to the reticuloendothelial system, allowing
• The African forms of kala-azar differ in several ways treatment with much smaller doses than is now the
from those seen elsewhere. case.
• Primary skin lesions (leishmaniomas) are • Liposomal Amphotericin B has been effective
characteristic; they generally occur on the legs in treating antimony-resistant case of VL in the
Mediterranean, France, India, and Brazil, as has Am- Nonhuman Trypanosmatids

photericin B. • There have been two reports of HIV-positive patients
• Allopurinol, 20 mg/kg 3 times a day, has been used who were infected with nonhuman trypanosoma-
in the treatment of VL in patients with AIDS. tids, members of the family Trypanosomatidae,
• Allopurinol plus sodium stibogluconate has which parasitize a wide variety of plants, insects,
been found effective in treating antimony-resis- and vertebrates.
tant cases of VL in Kenya. • Trypanosomatids that infect plants and insects are
• Patients with VL have also been treated with a referred to as lower trypanosomatids.
combination of interferon gamma and pentava- • The first individual, a male from Martinique, ini-
lent antimony. Interferon gamma may enhance tially was diagnosed as having diffuse cutaneous
the intracellular killing of Leishmania amastigotes. leishmaniasis, but biochemical and transmission
• Miltefosine (Impavido), an alkylphosphocho- electron microscope characterization of skin lesion
line, has been used in India to treat VL (Sundar isolates, amastigotes in the lesions, and promasti-
et al., 2002). gotes in culture showed them to be monoxenous
• The drug was administered orally at a rate of (single host) trypanosomatids of insects.
2.5 mg/kg daily in two doses for 28 days. • The second person, a female living in Spain, was
• The cure rate was 94% for the miltefosine-treated suspected of having VL because of clinical and labo-
group as compared to 97% for the Amphotericin ratory findings.
B-treated standard treatment group. • Organisms were isolated from a bone marrow as-
• The drug appears to be an effective and safe oral pirate, and isoenzyme analysis and DNA hybridiza-
treatment for VL. It is not available in the United tion of the cultured promastigotes failed to identify
States. them as Leishmania.
• All that could be determined was that the isolate
Prevention was of nonhuman origin, possibly a lower trypano-
• A bite of an infected sand fly is the usual route of somatid of insects. It is likely that additional cases
transmission, other ways could be through blood of nonhuman trypanosomatid infection will be de-
transfusion, sexual contact, congenital transmis- scribed from AIDS patients and from other severely
sion, and exposure (Garcia, 2016). immunocompromised persons.
• Humans serve as main reservoir host, therefore • Another isolate was described from the skin le-
treatment of active cases has been used to interrupt sions of a patient also living in Martinique (Noyes
the cycle of transmission (Garcia, 2016). et al., 2002).
• Insecticide spraying was shown to be successful in • Isoenzyme analysis found it to be identical with the
vector control (Garcia, 2016). first Martinique isolate, although the patient in the
• No vaccines are commercially available (Garcia, second case was HIV-negative and immunocompe-
2016). tent (Tables 2.6 and 2.7).
TABLE 2.6
Summary of Vectors for Transmission of Hemoflagellates and Associated Disease.
Hemoflagellate Disease Vector
Trypanosoma cruzi Chaga’s disease (American trypanosomiasis) Reduviid bug: Triatoma spp.
Trypanosoma rangeli None Reduviid bug: Rhodnius prolixus
Trypanosoma brucei West African sleeping sickness Tse-tse fly: Glossina palpalis Glossina
gambiense tachinoides
Trypanosoma brucei East African sleeping sickness Tse-tse fly: Glossina pallidipes Glossina
rhodesiense morsitans
Trypanosoma brucei brucei Nagana disease (Animal trypanosomiasis) Tse-tse fly: Glossina spp.
Leishmania sp. Leishmaniasis Sandfly: Phlebotomus spp.
86
TABLE 2.7
Summary of Blood- and Tissue-Dwelling Protozoan Infections of Humans.
Means of Human Location of Parasites
Disease Parasite Infection in Humans Clinical features Laboratory diagnosis
Markell & Voge's Medical Parasitology

African trypano- Trypansoma brucei “Bite” of infected Blood lymphatics, CNS Winterbottom’s sign, fever, Trypanosomes in blood,
somiasis (sleeping gambiense, T. b. rho- tsetse fly (Glossina) (extracellular) headache, “sleeping sickness,” lymph, CSF; culture,
sickness) desiense (flagellates) increased IgM serologic tests
American trypano- Trypanosoma cruzi Feces of infected redu- Blood (extracellular); Romaña’s sign, fever, hepa- Trypanosomes in blood;
somiasis (Chagas’ (flagellate) viid bug (Triatoma and reticuloendothelial tosplenomegaly, myocarditis, culture, xenodiagnosis,
disease) other) entering “bite” system, heart, brain, meningoencephalitis biopsy, serologic tests
(intracellular)
Cutaneous leishmani- Leishmania tropica, “Bite” of infected Skin (intracellular) Skin ulcers (single or multiple; Parasites in smears and
asis L. mexicana, L. bra- sandfly (Phlebotomus, self-healing to incurable) culture of ulcer aspirate,
ziliensis complexes Lutzomyia) skin test, serologic tests
(flagellates)
Mucocutaneous Leishmania bra- “Bite” of infected Skin and adjacent Ulcers of skin and oral and Parasites in smears and
leishmaniasis ziliensis complex sandfly (Lutzomyia, mucous membranes nasal mucosa culture of ulcer material,
(flagellates) Psychodopygus) (intracellular) skin test, serologic tests
Visceral leishmaniasis Leishmania donovani “Bite” of infected Liver, spleen, lymph Hepatosplenomegaly, anemia, Parasites in smears and
(kala-azar) complex (flagellates) sandfly (Phlebotomus, nodes, bone marrow fever, weight loss culture of bone marrow,
Lutzomyia) (intracellular) hamster inoculation,
serologic tests
Toxoplasmosis Toxoplasma gondii Ingestion of infected Cells of reticuloendo- Lymphadenopathy, fever, Parasites in biopsy or
(apicomplexan) meat or oocysts in thelial system, lungs, pneumonia, eye and brain fluids, serologic tests
cat feces (congenital eye, brain (intracellular) damage
infection)
Babesiosis Babesia microti in “Bite” of infected Erythrocytes (intracel- Chills and fever, headache, Parasites in blood films,
North America, B. Ixodes tick lular) fatigue, anemia hamster inoculation,
divergens in Europe serologic tests
(apicomplexa)
Primary amoebic me- Naegleria fowleri Intranasal instillation of Brain tissue, meninges Severe frontal headache, fever, Trophozoites in CSF
ningoencephalitis (free-living amoeba) amoeba nausea, vomiting, stiff neck
Granulomatous Acanthamoeba spp. Through lungs or skin Lungs, skin, hematog- Altered mental state, head- Trophozoites in CSF,
amoebic encephalitis and Balamuthia ulcers enous spread to brain ache, seizures, stiff neck trophozoites or cysts in
mandrillaris (free- (disseminated in AIDS brain tissue
living amoebae) patients)
Acanthamoeba Acanthamoeba spp. Eye trauma, contami- Cornea Severe ocular pain, corneal Trophozoites or cysts
keratitis (free-living amoebae) nated contact lenses ulceration, CNS abscess in corneal scraping or
biopsy
REVIEW QUESTIONS
SUMMARY
1. Rounded cysts were found in a fresh stool prepara-
• Phylum Sarcomastigophora are single-celled protozoans tion. The mononucleated cysts measured about 5 to
known to cause intestinal infections in humans. 20 µm in diameter and contained a large glycogen
• Fecal-oral route is the mode of transmission of vacuole. What is the most likely identification of
lumen-dwelling protozoans. Cysts are the infective this cyst?
stage while the trophozoites are the motile, feeding a. Endolimax nana
stages of the parasite that cause tissue damage. b. Entamoeba histolytica
• E. histolytica and G. duodenalis are the pathogenic c. Giardia lamblia
lumen-dwelling protozoans. d. Iodamoeba bütschlii
• E. histolytica are morphologically similar but
genetically distinct from the commensals E. dispar 2. Which of the following correctly describe giardiasis?
and E. moshkovskii. a. Attachment to the epithelia is facilitated by pro-
• E. hartmanni is morphologically similar with E. tein secretions
histolytica, except that it is smaller in size. b. Giardia is one of the most common opportunis-
• Specific immunoassays must be performed to tic infection in immunosuppressed patients.
differentiate pathogenic isolates of E. histolytica
c. The infection is initiated by the ingestion of
from the morphologically similar commensals.
oocyst.
• Main virulence factors contributing to the
d. Trophozoites attached to the host is mediated by
pathogenicity of E. histolytica are cysteine proteinase,
Gal/Gal-NAc-binding lectin, and amoebapore.
the ventral disc.
• Extraintestinal infection caused by E. histolytica may
affect mainly the liver, other infections may involve 3. Which of the following is the specimen of choice to
the lungs, pericardium, and spleen. diagnose PAM?
• E. coli is a non-pathogenic amoeba commonly a. Corneal scrapings
mistaken as E. histolytica in routine fecalysis. They b. CSF
can be differentiated microscopically. c. Sputum
• I. butschlii is generally non-pathogenic amoeba that is d. Stool
distinct because of the presence of a large glycogen
vacuole in the cytoplasm of its cystic stages. 4. This virulence factor of Entamoeba histolytica is
• The non-pathogenic E. nana is the most common of known to cause cellular protein degradation in the
the smaller intestinal amoebae. basement membrane of host intestinal mucosa. It is
• N. fowleri, Acanthamoeba spp., and Balamuthia known as:
spp. are the most common free-living amoeba a. Amebapore
infecting man. b. Gal/GalNAc-binding-lectin
• N. fowleri is also referred as the “brain-eating c. Cysteine proteinase
amoeba” is known to cause primary amoebic d. Hyaluronidase
meningoencephalitis, a fatal CNS infection.
• Acanthamoeba spp. is the causative agent of
granulomatous amoebic encephalitis, amoebic 5. Cyst formation of E. histolytica occurs only within
keratitis, and skin infections. which of the following:
• Balamuthia spp. causes similar pathology as with a. Intestines
the Acanthamoeba spp. except that Balamuthia b. Stomach
spp. is consistent among patients with AIDS. c. Lungs
• G. duodenalis and T. vaginalis are flagellated d. Liver
protozoan that are considered as sexually transmitted.
G. duodenalis causes severe gastroenteritis, while 6. Upon examination of stool of a patient, a medical
T. vaginalis causes acute to severe infection to the
technologist observed the following:
reproductive tract of most sexually active women.
i. Trophozoites motility is progressive and rapid
• Vector transmitted flagellates belong to 2 important
ii. With fine, evenly distributed granules in the
genera: Trypanosoma and Leishmania. They are
hemoflagellates which require bugs (T. cruzi), tse-tse peripheral chromatin; darkly stained
fly (T. brucei gambiense and T. brucei rhodesiense) iii. Contains small and compact karyosome central-
and sandflies (Leishmania spp.) in their life cycle. ly locate in the nucleus
iv. ∼8 to 10 µm diameter trophozoites
These are attributed to which of the following protozoans? specimen for ova and parasites, the following data
a. Entamoeba histolytica were obtained:
b. Entamoeba dispar i. Trophozoites of about 25 µm in diameter
c. Entamoeba hartmanni ii. With unidirectional and progressive motility
d. Entamoeba coli iii. Mononucleated with evenly distributed periph-
eral chromatin
7. This commensal has a pear-shaped trophozoite with
iv. Finely granular cytoplasm
three anterior flagella, a nucleus and a prominent
a. Entamoeba histolytica
shepherd’s crook-like cytostome
b. Entamoeba coli
a. Trichomonas vaginalis
c. Iodamoeba bütschlii
b. Giardia lamblia
d. Endolimax nana
c. Chilomastix mesnili
d. Trichomonas hominis 13. A sexually active woman complains of vaginal itching
and purulent vaginal discharge. To verify trichomo-
8. Habitat: Trophozoites in the urogenital system
niasis, which of the following tests should be done?
Infective stage: Trophozoite
a. Direct fecal smear examination
Size: 5 to 18 um
b. Enzyme Linked Immunosorbent Assay (ELISA)
Flagella: 4 anterior
c. Urine analysis
Undulalating membrane: extends half the length of
d. Wet mount examination of vaginal fluid
the body
Axostyle: present 14. Infection of this free-living amoeba typically occurs
in healthy individuals causing CNS, eye, and dis-
The following descriptions are attributed to:
seminated infections:
a. Dientamoeba fragilis
a. Acanthamoeba
b. Trichmonas vaginalis
b. Balamuthia
c. Chilomastix mesnili
c. Naegleria
d. Retortamonas intestinalis
d. Sappinia
9. A student came from a 1-month visit in USA from
15. Cysts of Entamoeba coli typically have:
April to May. She was then hospitalized for she com-
a. A large glycogen vacuole
plained of constant headaches, purulent nasal dis-
b. Centrally located karyosome
charge. She was admitted to the hospital with a di-
c. Ingested RBCs
agnosis of bacterial meningitis and died 5 days later.
d. Splinter shaped chromatoidal bars
Which of the following parasites should have been
considered in the diagnosis? 16. Eye infections with Acanthamoeba spp. have most
a. Balamuthia spp. commonly been traced to:
b. Acanthamoeba spp. a. Use of other’s sunglasses
c. Entamoeba histolytica b. Failure to remove contact lenses while swimming
d. Naegleria fowleri c. Use of contaminated lens care solutions
d. Application of eye make up
10. Fresh stool samples are requested specifically for
the recovery of: Match the following protozoans with the correspond-
a. Cysts ing trophozoite motility
b. Motile trophozoites a. Falling leaf motility
c. Cysts and trophozoites b. Jerky and rapid
d. Degenerated proglottid c. Progressive and rapid
d. Rotary
11. These are known as the energizing structures of
e. Sluggish and nondirectional
flagellates:
a. Flagellum 17. Entamoeba coli
b. Cytostome
18. Entamoeba hartmanni
c. Median bodies
d. Axostyle 19. Giardia lamblia
12. A patient is suspected of having amoebic dysen- 20. Trichomonas vaginalis
tery. Upon microscopic examination of a fresh fecal
Answers to review questions are available at the end of this book.
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CHAPTER 3
Miscellaneous Lumen-Dwelling
Protozoa
JOVEN FRANCIS F. MORALES
PHYLUM CILIOPHORA Cyst

Balantidium coli is the only member of its phylum to • Spherical or ellipsoid
parasitize humans. The organisms inhabit the large in- • About 50 to 75 µm long
testine, cecum, and terminal ileum. They are chiefly lu- • Has a thick, refractile cyst wall
men dwellers that subsist on bacteria. • In some specimens, newly encysted, the cilia are still
present and the organisms may be seen slowly rotating.
General Morphology After a long period of encystment, the cilia disappear.
Trophozoite • In stained specimens, the macronucleus can usu-
• 200 µm in length ally be seen within the cyst wall, but other structures
• Two size ranges are consistently seen usually are not observed.
• Smaller organisms: average 42 to 60 µm long by
30 to 40 µm wide Life Cycle
• Larger organisms: range from 90 to 120 µm by 60 Life cycle is completed in a single host (Fig. 3.2)
to 80 µm • Pig is the natural host
• Conjugation occurs only between “large” and • Man is the accidental host
“small” individuals
Infective stages
• Body shape: ovoid, somewhat flattened on one side
• Cysts are the infective stage and it undergoes excys-
• Cytostome: funnel-shaped, opens on the flattened
tation in the small intestine following ingestion.
side, near the anterior end that represents the mouth
• Cytopyge: serves as an anus of the parasite where Diagnostic stages
waste products are eliminated • Both cysts and trophozoites may be shed in diar-
• Cilia: covers the entire body and are especially long rheal stools.
and stout near the cytostome
• Motility: thrown football or thrown ball/rotary motion
• Unstained: readily recognized due to size, ciliary
covering, and motility
• On stained preparations, the characteristic two nu-
clei of a ciliate may be observed
• The larger nucleus (macronucleus): near the mid-
dle of the body and may be spherical, ellipsoid,
elongate, curved, or kidney-shaped. It is respon-
sible for the daily metabolic activity of the para-
site.
• The micronucleus: involved in genetics and cell di-
vision and is spherical, small and lies quite close
to the macronucleus. It contains the DNA.
• Both nuclei stain intensely with the ordinary stains.
• Food vacuoles and contractile vacuoles may be seen
in the cytoplasm (Fig. 3.1). FIG. 3.1 Balantidium coli trophozoite, stained specimen.
93
FIG. 3.2 Life cycle of Balantidium coli.
Mode of transmission • Demonstration of trophozoites in biopsy specimens

• The host most often acquires the cyst through inges- from lesions obtained through sigmoidoscopy
tion of contaminated food or water. • Bronchoalveolar washings may also contain B. coli
trophozoites in the case of pulmonary infection.
Diagnostic Test
• Microscopic demonstration of trophozoites and Pathogenesis
cysts in feces using direct examination or concentra- • Produces hyaluronidase which facilitates its tissue in-
tion techniques. (Belizario and de Leon, 2004) vasion
The following characteristics are of value in the • This virulence factor allows it to penetrate the in-
identification of B. coli: testinal mucosa to cause ulceration.
• Description of ulcer formed: rounded base and
I. Trophozoites, unstained Diagnostic: ciliary covering
wide neck.
II. Trophozoites, stained Diagnostic: macronucleus
• Secondary bacterial infection may occur following
and micronucleus
III. Cysts, unstained Diagnostic: cyst containing mucosal invasion.
ciliated organism • After bacterial invasion, a striking inflammatory re-
IV. Cysts, stained Diagnostic: macronucleus action may be noted around Balantidium trophozo-
and micronucleus ites present in tissue.
CHAPTER 3 Miscellaneous Lumen-Dwelling Protozoa 95
• Many patients are asymptomatic carriers of the in- the infections have been described in persons infected
fection; clinical balantidiasis may closely simulate with HIV.
severe amebic dysentery, or there may be only mild Six genera of microsporidia have been reported
colitis and diarrhea. in humans: Encephalitozoon, Trachipleistophora (Pleis-
• Extraintestinal spread to the mesenteric nodes, liver, tophora), Nosema, Brachiola, Vittaforma, and Enterocy-
pleura, lungs, and urogenital tract has been reported tozoon.
but is most uncommon. Enterocytozoon bieneusi
• A case of fatal balantidial infection was reported, in • infects the enterocytes of AIDS patients,
which peritonitis followed perforation of the appen- • invades other epithelial cells and has been recovered
dix; pulmonary involvement also occurred. from an immunocompetent patient with diarrhea.
• An additional case of Balantidium appendicitis has Encephalitozoon intestinalis (formerly known as
been reported in the literature. Septata intestinalis)
• enteric and disseminated infections in patients with
Epidemiology AIDS.
• Largest of the protozoa that parasitize humans Encephalitozoon cuniculi
• The worldwide prevalence is estimated at 0.02% • disseminated infections in immunocompetent and
to 1% immunocompromised persons.
• The major factors leading to human balantidiasis Encephalitozoon hellem
include: • causes eye infections and has been exclusively found
• close contact between pigs and humans, in AIDS patients.
• a lack of appropriate waste disposal such that Vittaforma corneae (formerly Nosema corneum) and
swine and human excrement contaminate drink- Nosema ocularum
ing water sources (e.g., wells and streams) and • corneal infections in HIV-negative patients.
food, and Nosema connori
• subtropical and/or tropical climatic conditions • disseminated infection in an athymic infant.
(e.g., warmth and humidity) favoring survival of Pleistophora sp.
cysts • recently renamed Trachipleistophora hominis,
• Rare in most areas, although epidemic outbreaks are • identified in the muscles of AIDS patients with myo-
occasionally seen sitis.
• A morphologically identical organism occurs in Brachiola algerae and Brachiola vesicularum
hogs, and epidemic outbreaks may follow its suc- • cause myositis in immunocompromised patients,
cessful transfer from porcine to human host. This • B. algerae: isolated from the cornea of an immuno-
must not be a common occurrence because attempts competent patient.
to infect humans with the porcine strain have not
been successful. General Morphology
• Reproduction involves the formation of minute
Treatment
spores, ranging in diameter from 1 to 2.5 µm, that
• Oxytetracycline (Terramycin) or iodoquinol, is usu-
have polar tubules, or filaments
ally effective in the treatment of this parasite.
• Tubules: used to inject the infective material
Prevention (sporoplasm) into the host cells.
• Presence of the characteristic polar tubules, or
• Pigs should not be allowed to roam in and around
filaments, of the spores distinguishes the mi-
feeder streams or rivers.
crosporidia from all other intracellular proto-
• Pigs should not have access to areas where crops are
zoans.
being raised.
• Microsporidia are considered to be primitive eu-
karyotic organisms
PHYLUM MICROSPORA • Lack mitochondria, peroxisomes, Golgi mem-
Microsporidia are obligate intracellular parasites, branes, and other typically eukaryotic organelles.
widely distributed in nature, belonging to the phy- • Some microsporidia have been shown to possess
lum Microspora. The first human case of microspo- ribosomes similar to those of prokaryotic cells
ridiosis was reported in 1959, and since then, most of (Figs. 3.3 and 3.4).
FIG. 3.4 Transmission electron micrograph of a

microsporidian spore with an extruded polar tubule inserted
FIG. 3.3 Electron micrograph of an Enterocytozoon
into a eukaryotic cell. The spore injects the infective
bieneusi spore. Arrows indicate the double rows of polar
sporoplasms through its polar tubule. (Courtesy of the CDC
tubule coils in cross section which characterize a mature E.
Public Health Image Library; Massimo Scaglia, Laboratory
bieneusi spore. (Courtesy of the CDC Public Health Image
of Clinical Parasitology, Institute of Infectious Diseases,
Library)
University-IRCCS San Matteo, Pavia, Italy.)
Life Cycle Infective stages

Microsporidia multiply within the cytoplasm of their • The infective form of microsporidia is the resistant
host cells, either in a parasitophorous vacuole as in En- spore, which can persist in the environment for
cephalitozoon spp. or directly in the cytoplasm like E. bi- months.
eneusi undergoing a process of simple binary fission or
multiple fission followed by the production of spores Diagnostic stages
(Figs. 3.5 and 3.6). • Spores in feces and bodily fluids
• Organisms in biopsy
Mode of transmission
• Sources of microsporidia infecting humans and the
modes of transmission are uncertain. However, infec-
tion most likely is acquired by ingestion of spores.
• Inhalation of spores also may be a route of transmis-
sion as may ocular exposure and sexual intercourse.
• Experiments with laboratory animals suggest that
rectal infection, analogous to the sexual transmis-
sion of other intestinal protozoa, may lead to dis-
seminated disease.
Diagnostic Test
Diagnosis is made by identification of organisms in bi-
opsy material or spores in feces, urine, bile, and duode-
nal, bronchial, or nasal fluids.
• Spores are Gram-positive and portions of their inter-
nal structure are acid-fast and periodic acid–Schiff
FIG. 3.5 Transmission electron micrograph of E. intestinalis positive.
depicting developing forms inside a parasitophorous • Giemsa-stained organisms are readily seen in histo-
vacuole (red arrows) with mature spores (black arrows). logic sections and in touch preparations of biopsy
(Courtesy of the CDC Public Health Image Library) material.
FIG. 3.6 Life cycle of microsporidia. Source: https://www.cdc.gov/dpdx/microsporidiosis/index.html
• Because of their small size, which approximates that • Molecular probes are being developed but at the
of bacteria, microsporidial spores in the feces and present are used only in the research laboratory.
bodily fluids may be easily overlooked by routine • Several different mammalian cell lines have been
laboratory procedures. used to grow some of the microsporidia.
• Modified trichrome stains produce a distinct con- The following characteristics are of value in identifi-
trast between the minute spores and the background cation of microsporidia:
debris.
• Ryan’s modified trichrome method uses reduced
phosphotungstic acid and has an aniline blue In stool or bodily fluids, minute spores, pink-red when stained
by modified trichrome stain, with clear polar or central
counterstain (Ryan et al., 1993).
nonstaining zones, giving appearance of bands; average size 1
• Weber’s modification of the trichrome stain in-
to 2.5 mm.
cludes a fast green counterstain (Weber, 1992).
• In both procedures, the spores stain pink-red
with clear vacuole-like polar or central nonstain- Pathogenesis
ing zones, which make the stained portions ap- Clinical manifestations depend on the site of infec-
pear as bands, a feature typical of microsporidial tion, which includes intestinal, ocular, muscular, and
spores. systemic.
• Slides should be examined using oil immersion
magnification. Intestinal infection
• Species identification requires transmission electron • Most common form
microscopy. • Seen in AIDS patients infected with E. bieneusi or E.
• Concentration techniques are reportedly ineffective intestinalis
in concentrating microsporidial spores. • Characterized by prolonged diarrhea and wasting.
• A nonspecific IFA procedure has been described; • About half of the patients report abdominal pain,
however, commercial monoclonal or polyclonal re- and some have nausea and vomiting.
agents are not available. • Malabsorption is common in these patients.
• Infection by E. bieneusi may also spread to other epi- • Approximately 30% of AIDS patients with Cryp-
thelial cells in the biliary tract and nasopharynx and tosporidium are also infected with microsporidia.
cause cholangitis and rhinosinusitis. • From an intestinal infection, microsporidia may
• E. intestinalis, together with the other species of En- disseminate to produce systemic disease.
cephalitozoon, develop in a variety of cells, including
macrophages, causing disseminated infections. Treatment
• Oral albendazole (Dore et al., 1995; Sobottka
et al., 1995) has been effective in treating intestinal
Ocular microsporidiosis
and disseminated infection caused by Encephalito-
• Caused by Nosema ocularum and Vittaforma corneae
zoon intestinalis.
in otherwise healthy persons
• Albendazole, reduced the number of bowel move-
• Infection involves the stroma, with keratitis lead-
ments in intestinal disease caused by Enterocytozoon
ing to corneal ulcers
bieneusi but did not clear the infection (Dieterich
• Caused by E. hellem in HIV-infected patients
et al., 1994).
• Infection is restricted to the superficial epithe-
• Disseminated infection by Encephalitozoon cuniculi
lium of the cornea and conjunctiva
was effectively eliminated by continuous treatment
with albendazole, (De Groote et al., 1995).
Microsporidial myositis • Topical fumagillin has been used successfully in the
• Caused by T. hominis treatment of ocular infection caused by Encephalito-
• Described in patients with severe cellular immuno- zoon hellem (Diesenhouse et al., 1993).
deficiency
• Symptoms include generalized muscle weakness,
myalgia, fever, and weight loss. PHYLUM MYXOZOA
The phylum Myxozoa consists of obligate parasites that
Systemic infections occur in the tissues and organ cavities of lower verte-
• Caused by three species of Encephalitozoon—E. cu- brates, primarily fishes and some invertebrates.
niculi, E. hellem, and E. intestinalis According to Garcia, they are recognized as a sepa-
• Have been found in AIDS patients, especially those rate phylum with two classes:
with CD4 T-cell counts below 50 cells per microliter • Myxosporea, which infect fish, amphibians, and
• In addition to intestinal, biliary, and ocular infec- reptiles
tion, these microsporidia have produced hepatic, • Actinosporea, which infect aquatic invertebrates
renal (with renal failure), and respiratory infections (primarily oligochaetes and sipunculids)
• E. cuniculi and N. connori have caused disseminated General Morphology
infections in HIV-negative, immunocompetent, and
• Myxozoans have valved multicellular teardrop-
immunodeficient persons.
shaped spores
• contain polar capsules with coiled filaments,
Epidemiology similar to those found in microsporidia
• Its extensive host range includes most invertebrates • Contain mitochondria and Golgi bodies (unlike mi-
and all classes of vertebrates. crosporidia)
• Produce significant diseases in commercially im- • Morphology can mimic normal human spermato-
portant animals such as honeybees, silkworms, fish, zoa, causing confusion with possible sexual abuse
laboratory rodents, rabbits and other fur-bearing situations
mammals; and in primates.
• Nearly 1000 species belonging to over 100 genera Life Cycle
have been described in the phylum Microspora. • There are over 1000 species, and new ones are being
• Microsporidia are emerging as opportunistic patho- described each year; however, many of the life cycles
gens in patients with AIDS. have not yet been defined. (Garcia, 2016).
• Most common microsporidial disease is pro- • Alternation between actinosporean stages in oligo-
longed diarrhea with wasting in AIDS patients chaetes and myxosporean stages in fish may occur.
with CD4 T-cell counts below 50 cells per micro- (Garcia, 2016)
liter.
• Reported in up to 39% of AIDS patients with di- Diagnostic Test
arrhea. • Recovery of spores in stool
Pathogenesis
• Myxozoans produce a disease in salmonid fish PHYLUM MICROSPORA
known as whirling disease. • Obligate intracellular parasite
• Organisms developing in the cartilage of the • Most infections have been described in persons
head and spine cause the fish to swim erratically infected with HIV
and whirl, making it difficult for them to feed • Has a distinct polar tubules or filaments used to
and avoid predators. inject infective material to host cell
• Mortality rates can be very high among young fish. • Encephalitozoon spp. multiply in a parasitophorous
• True human infection is still somewhat unclear. vacuole within the cytoplasm of the host cell
• E. bieneusi multiply directly in the cytoplasm
Epidemiology • Infective stage: spores
Myxozoan spores have been identified in the stool spec- • Diagnostic stage: spores in feces and bodily fluids as
imens of seven patients, two whom were infected with well as in biopsies
HIV and five who were not immunocompromised. • Transmission electron microscopy is required in
• The most recent report is that of Moncada et al. speciation
(2001). The patients presented with abdominal pain • Clinical manifestations depend on the site of
and diarrhea, with one patient passing more than 30 infection, which includes intestinal, ocular, muscular,
stools per day. and systemic.
• Three of the patients had eaten freshwater golden • Intestinal infection is the most common form
perch, Plectroplites ambiguus, infected with Myxozoa. • Oral albendazole: effective against intestinal and
• Eating of fish, however, could not be confirmed disseminated infection caused by E. intestinalis
for the other four patients. • Topical fumagillin: for treatment of ocular infection
• Five of the seven patients were also infected with caused by E. hellem
other microorganisms that cause diarrhea.
• Based on morphology, the spores were identified PHYLUM MYXOZOA
as Henneguya salminicola in two of the patients • Consists of obligate parasites that occur in the
and Myxobolus sp. in the other five. tissues and organ cavities of lower vertebrates,
• The proof is not yet there to link the presence of primarily fishes and some invertebrates.
myxozoan spores in the stool to the abdominal pain • Have valved multicellular teardrop-shaped spores
and diarrhea of the seven patients. Nonetheless, fu- • Contain mitochondria and Golgi bodies (unlike
ture studies may in fact reveal such an association, microsporidia)
especially in immunosuppressed patients. • Morphology can mimic normal human spermatozoa
• Spores can be recovered in stool
SUMMARY • Can produce a disease in salmonid fish known as
whirling disease
Balantidium coli • True human infection is still somewhat unclear
• Only member of its phylum to parasitize humans
• Largest protozoa parasitizing human
• Locomotor structure: cilia REVIEW QUESTIONS
• Natural host: pigs 1. Which parasite is the largest protozoa parasitizing
• Accidental host: man human?
• Habitat: large intestine, cecum, and terminal ileum a. Chilomastix mesnili
• Motility of the trophozoite: thrown football b. Entamoeba histolytica
• Infective stage: cyst c. Balantidium coli
• Diagnostic stage: cyst and trophozoite d. Enterocytozoon bieneusi
• MOT: ingestion of contaminated food or water
• Causes balantidiasis
2. Balantidium coli is covered with what organ of loco-
motion?
• Virulence factor hyaluronidase allows penetration
of intestinal mucosa and producing a rounded base
a. Pseudopods
and wide neck ulcer b. Flagella
• Drug of choice: tetracycline
c. Cilia
d. Apical complex
3. What is the natural host of Balantidium coli? c. Myxozoans

a. Pigs d. Coccidians
b. Horse
c. Man True or False: Write T if the statement is TRUE, F if the
d. Sheep statement is FALSE.
1. Cilia maybe observed in the encysted form of Bal-
4. The motility of the Balantidium coli antidium coli.
a. Falling leaf motility 2. The invasive property of Balantidium coli is attrib-
b. Thrown football motility uted to the presence of cysteine proteinase.
c. Progressive and unidirectional motility 3. In balantidiasis, only the trophozoites may be
d. Jerky tumbling motility shed in diarrheal stools.
4. Trophozoite of Balantium coli is binucleated.
5. This factor is responsible for the ulceration caused 5. Balantidium coli is considered the largest protozoan
by Balantidium coli of medical importance.
a. Amoebapores 6. Microsporidium infections are associated with
b. Ventral sucking disk persons with HIV.
c. Cysteine proteases 7. Microsporidia are considered as primitive prokary-
d. Hyaluronidase otic organisms.
8. Parasites in phylum Myxozoa are obligate para-
6. What structure of the phylum Microspora allows it sites of the fish.
to inject infective material to host cell? 9. Whirling disease is caused by Pleistophora sp.
a. Polar tubules 10. Myxozoan parasites transmit infection through
b. Parasitophorous vacuole their infective spores.
c. Peroxisomes
d. Hyaluronidase Answers to review questions are available at the end of this
book.
7. Which laboratory technique is required for species
identification of microsporidia?
a. Modified trichrome stain
b. Biopsy
REFERENCES
Belizario VY, De LWU. Philippine textbook of medical
c. Immunofluorescence assay
parasitology. Manila, Philippines: University of the
d. Electron microscopy Philippines Manila; 2004. 42–45.
De Groote MA, et al. Polymerase chain reaction and culture
8. Which Microspora multiply directly in the cyto- confirmation of disseminated Encephalitozoon cuniculi in
plasm? a patient with AIDS: successful therapy with albendazole. J
a. E. cuniculi Infect Dis. 1995;171:1375–1378.
b. E. hellem Diesenhouse MC, et al. Treatment of microsporidial
c. E. bieneusi keratoconjunctivitis with topical fumagillin. Am J
d. E. intestinalis Ophthalmol. 1993;115:293–298.
Dieterich DT, et al. Treatment with albendazole for intestinal
disease due to Enterocytozoon bieneusi in patients with
9. What is the most common form of Microspora in-
AIDS. J Infect Dis. 1994;169:178–183.
fection? Dore GJ, et al. Disseminated microsporidiosis due to Septata
a. Ocular intestinalis in nine patients infected with the human
b. Intestinal immunodeficiency virus: response to therapy with
c. Muscular albendazole. Clin Infect Dis. 1995;21:70–76.
d. Systemic Garcia LS. Diagnostic medical parasitology. 6th ed. Washington,
DC: ASM Press; 2016. 605, 648, 846, 850.
10. Whirling disease in salmonid fishes is caused by? Moncada LI, et al. Myxobolus sp., another opportunistic
a. Ciliates parasite in immunosuppressed patients? J Clin Microbiol
b. Sporozoans 2001;39:1938–1940.
Ryan NJ, et al. A new trichrome-blue stain for detection of following treatment with albendazole. J Clin Microbiol.
microsporidial species in urine, stool, and nasopharyngeal 1995;33:2948–2952.
specimens. J Clin Microbiol. 1993;31:3264–3269. Weber R. Improved light-microscopical detection of
Sobottka I, et al. Disseminated Encephalitozoon (Septata) microsporidia spores in stool and duodenal aspirates.
intestinalis infection in a patient with AIDS: novel diagnostic N Engl J Med. 1992;326:161–166.
approaches and autopsy-confirmed parasitological cure
CHAPTER 4
Protozoa: Phylum Apicomplexa

(Malaria, Coccidian, Babesia)
ROLTER LORENZ M. LEE, RMT, KHARAM B. MOLBOG
MALARIA TABLE 4.1

Clinical syndromes having malarial-like symptoms Summary of the old and new/alternate names
have already been recorded in the past. These diseases of the malarial diseases and their agents.
were referred to their outstanding clinical feature, the
febrile cycles. The cycles are namely: quotidian, tertian, Old name New name/alternate Agent
sub-tertian and quartan fevers, 24-, 48-, 36-48- and 72- Benign tertian Vivax malaria Plasmodium
hour cycles of fever, respectively. Other names desig- malaria vivax
nated additional clinical features of the disease. The Aestivoautumnal, Falciparum malaria Plasmodium
modern tendency is to refer to the various types of malignant tertian, falciparum
malaria by the name of the agent. (Table 4.1) Malarial subtertian malaria
parasites are from the phylum Apicomplexa, family Plas- Quartan malaria Malarial malaria Plasmodium
modiidae, and genus Plasmodium. These parasites have malariae
an insect vector namely the female Anopheles mosquito, Benign tertian Ovale tertian malaria Plasmodium
although the parasite can be acquired in various ways malaria ovale
as well. The anopheline mosquitoes may be of various
species namely (Fig. 4.1):
1. Anopheles minimus var. flavirostris
2. Anopheles maculates
3. Anopheles litoralis
4. Anopheles balabacencis
5. Anopheles mangyamus
6. Anopheles philippinensis
• Plasmodium knowlesi, a malarial parasite of long-
tailed macaque monkeys (Macaca irus), resembles
P. malariae and originally was described as such by
microscopy in the infected humans.
This is the known causative agent of QUOTIDIAN MA-
LARIA which is characterized by 24-hour cyclic parox-
ysmal attack.
Mode of Infection
• The bite of an infected female anopheline mosquito
Note: There are more than 200 known species of
Anopheles but only about 60 are considered to be
vectors of malaria.
FIG. 4.1 Diagram of adult female
• Blood transfusion from an infected individual anopheline mosquito. (https://www.
• Congenital transmission from an infected mother cdc.gov/malaria/about/biology/
mosquitoes/female_diagram.html.)
103
104 Markell & Voge’s Medical Parasitology
General Life Cycle 3. The zygote becomes elongated and active and is called
• Malarial parasites are generally obligate intracellular an ookinete. The ookinete penetrates cells of the stom-
parasites. ach wall of the mosquito and rounds up just beneath
• They typically involve 2 hosts namely: humans (inter- the outer covering of that organ to become an oocyst.
mediate host) and mosquitoes (definitive host). In the 4. Growth and development of the oocyst result
intermediate host, the parasite has an exo-erythrocytic/ in the production of a large number of slender,
pre-erythrocytic (happens in the liver) and erythrocytic threadlike haploid sporozoites, which break out and
stages (Fig. 4.2). wander throughout the body of the mosquito.
Length of the developmental cycle in the mosquito
Events in the malarial life cycle depends not only on the species of Plasmodium but
1. When the female mosquito bites an infected person, on the particular mosquito host and the ambient tem-
she draws into her stomach blood that may contain perature for example 8 days in P. vivax and 35 days
male and female gametocytes. in P. malariae.
2. In the mosquito, as the blood temperature falls, 5. Those sporozoites that enter the salivary glands of
the male or microgametocyte undergoes maturation the mosquito may be inoculated into the next per-
that results in the production of microgametes. The son bitten. Sporozoites injected into the bloodstream
extrusion of these delicate spindle-shaped gametes leave the blood vascular system within 40 minutes
has been termed exflagellation. At the same time, (30-60 minutes) and subsequently invade the paren-
the female or macrogametocyte matures to become a chymal cells of the liver.
macrogamete, after which it may be fertilized by the 6. Asexual multiplication (schizogony) in the liver results
microgamete, forming a zygote. in the production of thousands of tiny merozoites in
FIG. 4.2 Life history of Plasmodium. 1–4, pre-erythrocytic (or exoerythrocytic) asexual stages undergoing
schizogony in liver; 1a, hypnozoite (only in P. vivax and P. ovale among species infecting humans); 5–11,
erythrocytic asexual cycle; 12–15, microgametocyte development; 16–19, macrogametocyte development;
20, exflagellation to produce microgametes; 21, fertilization of macrogamete; 22, ookinete penetrates cells
(wall) of mosquito stomach; 23–25, production of sporozoites within oocyst (sporogony); 26, release of
sporozoites, most reaching salivary glands of mosquito.
CHAPTER 4 Protozoa: Phylum Apicomplexa (Malaria, Coccidian, Babesia) 105
FIG. 4.3 Pre-erythrocytic schizont of Plasmodium vivax

in liver.
each schizont (Fig. 4.3). Rupture of the infected he-

patic cells releases merozoites into the circulation.
7. In the bloodstream, an asexual cycle takes place
within the red blood cells upon parasitic invasion.
This process, known as erythrocytic schizogony, results,
within a period of 44 to 72 hours, in the formation
of from 4 to 36 new parasites in each infected cell.
8. At the end of the schizogonic cycle, the infected blood
cells rupture, liberating merozoites, which in turn in-
fect new red blood cells. Rupture of the red blood cells
liberates products of metabolism of the parasites and
of the red blood cells thrown into the bloodstream
FIG. 4.4 (A) Hypnozoite of Plasmodium vivax, Chesson
may be sufficient to bring about a malarial paroxysm.
strain (arrow), just below hepatocyte nucleus in
In all four species, asexual multiplication takes
chimpanzee’s liver, ×1430. (B) Hypnozoite of P. cynomolgi
place within the liver cells, but with P. vivax and P. bastianelli in monkey liver (arrow), ×850. Giemsa-
ovale a varying proportion of the infecting sporozo- colophonium-restrained indirect immunofluorescence (IFA)
ites enter a resting stage before undergoing asexual preparations. (From Krotoski WA et al. Am J Trop Med Hyg
multiplication, while others undergo this multiplica- 1982;31:218–225, 1291–1293.)
tion without delay. The resting stage of the parasite is
known as a hypnozoite or cryptozoite (Fig. 4.4). After a
period of weeks or months, reactivation of the hypno- with a different reactivation time. These subpopulations
zoite initiates asexual division. are grouped characteristically within a given strain, with
In relation to malarial diseases, fever, relapse and shorter latency in strains originating from “tropical” ar-
recrudescence are commonly encountered terms. Fever eas, and longer latency in those originating in temperate
may be classified as continuous, remittent, or intermittent. and, especially, colder (“northern”) areas (Fig. 4.3).
A relapse is a recurrence that takes place when there Sometime after the asexual parasites first appear
is reinvasion of the bloodstream by parasites from the in the bloodstream, when the patient develops clini-
dormant pre-erythrocytic stages after the complete ini- cal signs and symptoms, gametocytes appear in the
tial clearing of the erythrocytic infection. A recrudes- red blood cells. These forms, derived from merozo-
cence is a recurrence of symptoms in a patient whose ites similar in appearance to those that continue the
initial bloodstream infection levels are too low to be asexual cycle, grow but do not divide and finally form
demonstrated clinically. the male and female gametocytes. Gametocytes con-
Hypnozoite reactivation brings about the relapse’s tinue to circulate in the bloodstream for some time
characteristic of these species (Fig. 4.5), producing a and, if ingested by a mosquito of the genus Anopheles,
wide variation in time of relapse, due to differences in undergo transformation to gametes (gametogony),
the latency period of hypnozoites produced by distinct sexual fusion, and subsequent development to spo-
subpopulations of sporozoites. Successive relapses in rozoites (sporogony) in the mosquito. However, it is
the same patient are the result of infection by a num- always best to rely on asexual stages of the parasite for
ber of sporozoites, each of which produces hypnozoites identification.
FIG. 4.5 Representation of hypnozoite theory of malarial relapse. Activation (A) of hypnozoites to
schizogony at intervals predetermined by intrinsic capability of individual sporozoites, resulting in release
of merozoites at species- or strain-determined times. (Original figure drawn by Dr. Steve Ayala. Modified
from Trans R Soc Trop Med Hyg 1985; 79, Krotoski WA, Discovery of the hypnozoite and a new theory of
malarial relapse, 1–11 with permission from the Royal Society of Tropical Medicine and Hygiene.)
Specific Malarial Parasite Characteristics • Infected cell becomes noticeably enlarged and pale
Plasmodium vivax contain a number of very fine reddish granules
• P. vivax is the predominant parasite worldwide and known as Schüffner’s dots.
is the only one whose range extends into the tem- • Schüffner’s dots are always seen in a red blood cell
perate regions. infected 15 to 20 hours or longer in properly stained
• In blood smears, a variety of stages in the asexual slides.
cycle of the parasite may be seen: ring forms, devel- • At about 40 hours, the mature trophozoite largely
oping trophozoite, schizont and gametocytes. ceases its ameboid activity and becomes compact,
• Tertian Malaria (every 48 hours): The paroxysm fol- thus sometimes appearing smaller than the actively
lows the somewhat synchronous rupture of the ma- motile stages that preceded it.
jority of infected cells, liberating merozoites, which • The single nucleus divides repeatedly to give rise to
in turn infect new red blood cells (Fig. 4.6). 12 to 24 nuclear masses, with average numbers that
• For the first few hours post-paroxysm, the majority vary, according to the strain, from 14 to 22. Dur-
of infected cells contain very early forms of the para- ing the stages of division, the parasite is known as a
site, known as trophozoites or “rings”. schizont within which are merozoites formed
• In a blood film correctly stained with Giemsa’s or • Once mature, it may rupture along with the red cell
Field’s stain, the parasites appear first as minute blue and initiate paroxysmal attack.
disks with a red nucleus lying within the pink cyto- • Gametocytes are frequently seen after the first few
plasm of the erythrocyte. Merozoites prefer infecting paroxysms which mature more slowly than the asexu-
younger red blood cells. al forms, do not exhibit as much ameboid activity,
• Sometimes the parasites are first seen as crescentic and develop more pigment.
masses at the periphery of the red blood cell—the • The infected cells enlarge, and Schüffner’s granules
so-called accolé (French, joined together) forms. may be seen. Fully mature gametocytes, in contrast
• Shortly thereafter, an apparent vacuole forms in the with trophozoites about to undergo schizogony, fill
blue cytoplasm of the parasite, pushing the nuclear the cell more completely and contain more pigment.
chromatin to a peripheral position. The parasite now • Microgametocytes have pale staining nucleus with loose
resembles a signet ring and has grown to a diameter network of chromatin while macrogametocytes have
about one third that of the infected cell (Fig. 4.7). dense nucleus.
• Very active ameboid motility is exhibited during the • All stages seen in thin films may be found also in
growth period, and the parasite may assume bizarre thick-film preparations but the parasites appear
and irregular forms within the red blood cell. It was somewhat distorted.
this ameboid activity that suggested the specific • Young trophozoites may be seen as typical rings, but
name vivax (Latin, vigorous). more frequently they are collapsed.
FIG. 4.6 Plasmodium vivax stages in Giemsa-stained thin and thick films. (Basic Malaria Microscopy
Learner’s Guide 2nd ed. of the WHO, p. 63.)
• Only 4 to 12 (average of 8) merozoites produced in

schizogony
• 12 to 18 (average of 14–16) merozoites are pro-
duced sometimes
• Infected cells are enlarged, pale, elongated, ovoid, or
irregular in shape with characteristic ragged edges
• Thick films are similar to those of P. vivax. If in such
films schizonts larger than those of P. malariae but
with no more than 12 merozoites are seen to con-
tain distinct Schüffner’s dots, a tentative diagnosis of
P. ovale infection may be made.
• Malarial stipplings: Schuffner’s dots (Jame’s dots in
older terminology) (Fig. 4.8).
FIG. 4.7 Signet ring appearance of P. vivax. Plasmodium malariae

• Occurring primarily in those subtropical and tem-
perate areas where other species of malaria are
found, P. malariae is less frequently seen than P. vivax
or P. falciparum.
• A red dot of nuclear material may have a small wisp • The asexual cycle of P. malariae occupies 72 hours
of blue cytoplasm at one side (comma trophozoite), which is relatively long compared to the others. Ring
or thin lines of cytoplasm may appear on either side forms of P. malariae are not readily distinguished
of the nucleus (swallow trophozoite). from those of P. vivax.
• As the parasites become older, their ameboid activ- • The parasite has the following characteristics:
ity is reflected by the irregular shapes they assume in • Exhibits little ameboid activity
thick film. The ghostlike shadows of lysed infected • Assumes an elongated (band or stab) form, stretch-
cells may be seen surrounding the parasites, and ing partway or entirely across the red blood cell.
usually Schüffner’s dots are visible within them. • Infected cells are not enlarged
• Schizonts, if mature can be recognized by the num- • Cytoplasm of the red blood cells may contain
ber of merozoites. dust-fine, pale pink dots, Ziemann’s stippling,
• Gametocytes of P. vivax, P. ovale, and P. malariae are found in heavy stained slides only
similar in appearance, except those of P. malariae are • 6 to 12 (average of 8) merozoites produced in
smaller and darker than the other two and do not schizogony
contain Schüffner’s dots. • Merozoites arranged in a rosette, symmetrically
around a central mass of pigment but usually
Plasmodium ovale
irregularly displaced. Sometimes described as
• P. ovale has been known only since 1922. It seems to
“daisy-head” or flower-like in appearance.
be rather widely distributed in tropical Africa, and it
• Gametocytes are ovoid, slightly larger, and con-
apparently supplants P. vivax almost entirely on the
tain more pigment than mature trophozoites
West African coast.
• Merozoites infect older red blood cells
• The morphologic feature that originally led to the
• In the thick film, trophozoites of P. malariae
establishment of P. ovale as a separate species, an
do not assume the ameboid, comma, or swal-
ovoid shape of many of the infected red blood cells,
low forms seen in the other species, but because
has been found to be variable.
of their compact nature they usually appear as
• Thin smears that because of excessive humidity have
small dots of nuclear material with rounded or
dried slowly may not show this characteristic at all.
slightly elongate masses of cytoplasm.
These are the characteristics used to distinguish it
• The older trophozoites of P. malariae are also
from P. vivax.
compact, and the predominant color may be that
• Not as ameboid in morphology
of the abundant pigment. The fully developed
• Nuclei in all stages are larger
schizont, containing an average of 8 merozoites,
• Scanty pigment but larger and more distinct if prop-
is readily recognized (Fig. 4.9).
erly stained
FIG. 4.8 Plasmodium ovale stages in Giemsa-stained thin and thick films. (Basic Malaria Microscopy
Learner’s Guide 2nd ed. of the WHO.)
FIG. 4.9 Plasmodium malariae stages in Giemsa-stained thin and thick films. (Basic Malaria Microscopy
Learner’s Guide 2nd ed. of the WHO.)
Plasmodium falciparum comma or swallow shape. Gametocytes are easily

• Falciparum malaria is almost entirely confined to recognizable by their shape, which is much the same
the tropics and subtropics. as in the thin film.
• Clinically and morphologically, falciparum malaria is
quite sharply differentiated from the other malarias. Diagnostic Tests
• The gametocytes of P. falciparum are elongate or sau- Gold standard: thick and thin blood films
sage shaped, in contrast with the spherical or ovoid • Generally, thick films are for parasitic quantification/
gametocytes of the other species. general screening and thin films are for parasitic species
• On the basis of the shape of the gametocytes, P. fal- identification.
ciparum was placed by some workers in a separate • EDTA-blood maybe used provided blood smear
genus, Laverania. must be made within 1 hour because true stipplings
• Schizogony usually does not take place in the pe- of infected immature RBCS may not be retained
ripheral blood in falciparum malaria. (Leventhal and Cheadle, 2012).
• Therefore, the only stages of the parasite ordinarily • Artifacts may appear as malarial parasites in the mi-
seen are young trophozoites (“rings”) and gametocytes. croscopic examination of thin smear of which the
• Double and even triple infections of red blood cells most common are platelets. They may appear singly
are common as P. falciparum attacks all stages of red on top of red cells (resembles ring form), clumped
blood cells, the percentage of cell parasitized may be (appears as schizont) or mass of fused platelets (ap-
very large. The young trophozoites are minute rings pears as gametocytes of P. falciparum).
(Fig. 4.10). • Other artifacts include precipitated stain, bacteria,
• More frequently than in other species, the ring may fungi and microbial structures like spores.
have two small chromatin dots. Occasionally the • It will be appreciated that, depending on the stage
earliest stages do not assume a ring form but lie of the parasite’s developmental cycle at which the
spread out along the periphery of the red blood cell, blood sample is taken, various stages of the parasite
in the accolé form. will appear.
• The parasites may grow somewhat in size and be- • These may include tropozoites (ring form), schizonts
come irregular in outline, although they still retain or gametocytes which may be used for speciation.
the ring form while in the circulating blood. Pig- • Blood specimens ideally are collected just before the
ment is rarely seen in the forms normally found in next anticipated fever spike or at the onset of fever.
the circulating blood. (Mc Pherson and Pincus, 2011)
• The infected red blood cells, which retain their origi- • Immediately after a paroxysm, the merozoite-filled
nal size, may develop a few irregular, dark red, rod- red cells have ruptured and free merozoites are
or wedge-shaped markings, known as Maurer’s dots found in the bloodstream.
or clefts. • These are difficult to locate and virtually impossible
• Gametocytes are characteristic, being crescentic in to identify by species; however, gametocytes may be
outline which may have pointed or bluntly rounded present and readily identifiable.
ends, and the remains of the red blood cell may be • If parasites are not found in the first blood films, it is
seen in the concavity formed by the arched body of advisable to take additional thick and thin films ev-
the parasite. ery 6 to 12 hours, for as long as 48 hours if necessary.
• Gametocytes may continue to circulate after therapy • Negative morning and afternoon thick-stained
for clinical illness has been completed, have no clin- smears for 3 consecutive days during symptoms
ical significance if found, unaccompanied by other indicate ABSENCE OF INFECTION (Leventhal and
stages, following clinical resolution. Cheadle, 2012).
• In heavy infections, generally occurring only in mor- • It should be noted that a first level of diagnosis is the
ibund patients, schizonts may be seen in the periph- presumptive differentiation of P. falciparum from the
eral blood. other species, as the presence of this parasite in a
• The mature schizont forms from 8 to 36 merozoites, non-native (i.e., in a nonimmune patient) consti-
with an average of about 24. P. falciparum produce tutes a medical emergency.
schizont with the most number of merozoites. • A presumptive diagnosis of P. falciparum can be
• In the thick film, one is usually impressed by the made on the basis of finding exclusively “ring”
large number of early trophozoites. As these are forms, with or without characteristic gametocytes, in
delicate, they frequently collapse to assume the a blood film.
FIG. 4.10 Plasmodium falciparum stages in Giemsa-stained thin and thick films. (Basic Malaria
Microscopy Learner’s Guide 2nd ed. of the WHO.)
• Serological tests • Infection with P. falciparum can rapidly build up

• Molecular biologic approaches to the diagnosis of to levels not obtained with the other three species
malaria include the use of recombinant DNA probes and, because of the physiologic characteristics of
and ribosomal RNA probes. red blood cells infected with P. falciparum, may lead
• Rapid Diagnostic Tests (RDT) rely on the detec- to localized capillary obstruction, decreased blood
tion of plasmodial antigens or enzymes (Haditsch, flow, tissue hypoxia, infarction, and death.
2004). • Chronic P. malariae infections in children may result
in immune-complex deposition on the glomerular
Symptoms walls, leading to the nephrotic syndrome
• The incubation period is longest in malarial and short- • Cerebral Malaria: most serious complication of falci-
est in falciparum malaria. parum infection and a frequent cause of death.
• The last few days of the incubation period may be • Anemia: consequence of the heavy parasite load in
marked by prodromal symptoms of a nonspecific falciparum malaria due to the lysis of the red blood
sort: headache, photophobia, muscle aches and cells and the formation of hemozoin
pains, anorexia, nausea, and sometimes vomiting. • Renal disease: common in severe falciparum malaria
• These symptoms may be seen in all types of malaria; and may occur also with repeated P. malariae infec-
they are at times entirely absent in vivax infections and tions, especially in children.
they are generally mild in ovale malaria (Table 4.2). • Acute renal failure may occur as a result of tubu-
lar necrosis resulting from red cell sludging and
Complications renal anoxia
• Vivax, ovale, and quartan malaria are relatively be- • Nephrotic syndrome, due to acute glomerulone-
nign, and complications that arise during the course phritis
of infection with one of these parasites are usually • Proteinuria is common during the period of a
due to preexisting debility or intercurrent disease. clinical attack of quartan malaria
TABLE 4.2
Clinical comparison of the types of malaria.
Feature Vivax Ovale Malariae Falciparum
Incubation period 10–17 days 10–17 days 18–40 days 8–11 days
Sometimes prolonged for months to years
Prodromal symptoms May be influenza-like in all four types
Severity ++ + ++ +
Initial fever pattern Irregular to quotidian Usually regular Continuous, remittent,
every 72 hours or quotidian
Periodicity 44–48 hours 48–50 hours 72 hours 36–48 hours
Initial paroxysm
Usual severity Moderate to severe Mild Moderate to severe Severe
Average duration 10 hours 10 hours 11 hours 16–36 hours
Duration of untreated 3–8 + weeks 2–3 weeks 3–24 weeks 2–3 weeks
primary attack
Duration of untreated 5–8 yearsa 12–20 monthsa 20–50 + yearsb 6–17 months
infection
Anemia ++ + ++ +++ +
CNS involvement ± ± ± +++ +
Nephrotic syndrome ± – +++ +
aIncluding relapses.
bIncluding recrudescences.
• Renal lesions are apparently secondary to de-

position within the glomeruli of circulating an-
tigen-antibody complexes in the antigen-excess
situation that may occur in a chronic low-grade
quartan infection.
• Blackwater fever: a syndrome that results from
massive intravascular hemolysis and the passage of
usually black urine
• Dysenteric malaria: an uncommon but extremely
serious complication of falciparum malaria char-
acterized by abdominal pain, nausea, vomiting,
and upper gastrointestinal bleeding, which may
be related to focal ischemic changes in the intes-
tinal wall capillary bed.
• Algid malaria: a term used for falciparum malaria
attacks characterized by rapid development of hy-
potension and impairment of vascular perfusion.
• Pulmonary edema: may develop rapidly in an
oliguric or anuric patient, secondary to overzeal-
ous parenteral fluid administration, or it may
develop without evidence of fluid retention or
cardiac decompensation, possibly as the result of
disseminated intravascular coagulation (DIC) or
anoxia affecting the pulmonary microcirculation.
• Tropical Splenomegaly Syndrome.
• The spleen normally enlarges during an acute FIG. 4.11 Tropical splenomegaly. (From Crane
attack of malaria but then regresses toward GG. Hyperreactive malarious splenomegaly [tropical
normal, so persistent splenomegaly in adults splenomegaly syndrome]. Parasitol Today 1986;2:4–9.)
is not a normal finding.
• The syndrome is characterized by chronic sple- absence of hyperinsulinemia and unrelated to
nomegaly and marked elevation of the serum im- antimalarial treatment; it may be the result of
munoglobulin M (IgM). impairment of hepatic gluconeogenesis.
• Related to overproduction of immunoglobu- Pathogenesis
lins, especially IgM, and the reduction of T • Cytoadherence is the result of the expression on the
lymphocytes. It has been suggested that the surface of the parasitized red cell of strain- and
underlying defect may be in the suppressor T stage-specific parasite-derived ligands (located on
cells that control B-cell activation (Fig. 4.11). the electron-dense “knobs” that appear at about
• Hyperparasitemia the time the parasite starts to divide), which adhere
• Parasitemias in excess of 10% to 20% of the to a specific receptor complex on the endothelial
red blood cells carry a very high mortality rate cells.
despite prompt and vigorous treatment, and • Glycoprotein thrombospondin may be involved in the
in cerebral malaria the same seems true of specific receptor complex.
parasite levels as low as 5%. Prompt exchange • Small vessels may thus become plugged by masses
blood transfusions may be life saving in these of parasitized red blood cells (Fig. 4.12).
circumstances. • Ischemia consequent to plugging of the vessels pro-
• Hypoglycemia duces symptoms that vary with the organ involved
• Hyperinsulinemia may result from treatment of and the degree of tissue anoxia.
falciparum malaria in adults with quinine and • Counts of parasitized erythrocytes in cerebral and
quinidine, and the subsequent hypoglycemia other vessels have shown that the proportion of
may be an important cause of fetal distress and parasitized red blood cells is consistently higher in
death during the third trimester of pregnancy. the brain than in other organs and even higher in
• In African children, profound hypoglyce- patients with cerebral malaria than in patients who
mia leading to death has been noted in the do not exhibit this form of the disease.
• The interactions of some of the phenomena discussed

earlier, leading to the signs and symptoms character-
istic of malaria, are shown schematically in Fig. 4.13.
The various species of malarial parasites differ in their
ability to infect red blood cells and may account to the
degree of spread and severity:
• Merozoites of P. vivax and P. ovale are able to invade
only reticulocytes (young red cells).
• Merozoites of P. malariae are limited to senescent cells
(old red cells).
• Merozoites of P. falciparum is able to invade all ages
of red blood cells indifferently, and consequently
infections by this parasite result early in consider-
able degrees of anemia.
Thus, a natural limit is placed on these infections: re-
ticulocytes constitute less than 2% of the total number
FIG. 4.12 Plasmodium falciparum. Malarial pigment in of red blood cells, and those suitable for infection by
capillaries of the brain. P. malariae, even less.
Mechanisms of red blood cell invasion:
• There is suggestive evidence that anterior organelles
• Dramatic decrease in deformability of the P. falci- within the merozoite, known as rhoptries, play an
parum-infected red blood cells, once the parasite has active part in the invasion process. The entire se-
matured beyond the ring stage. quence of attachment and penetration takes only
• Sensitization due to repeated attacks leads to the about 30 seconds.
production of autoantibodies to the red blood cell • Initial recognition and attachment may require spe-
during infection or through the binding of soluble cific determinants on the surface of the red blood cell:
malarial antigen or of circulating antigen-antibody • In the case of P. knowlesi and P. vivax, the determinant
complexes to the cell surface. seems related to the Duffy blood group antigen.
FIG. 4.13 Pathogenesis of malaria.

• Glycophorin A and human erythrocyte band 3, a laria infection has been noted and gives evidence
major membrane protein, is apparently involved that this is caused by a complement-mediated
in the attachment process of P. falciparum. immune process.
• Rupture of the infected red blood cells brings on the • Leukopenia is generally noted, especially in falci-
malarial paroxysm. parum malaria, though there may be leukocytosis
• Both infected and uninfected red blood cells during the febrile paroxysms.
show increased osmotic fragility. • The total plasma protein concentration is un-
• Lysis of numerous uninfected cells during the changed or slightly lower than normal during an
paroxysm, plus enhanced phagocytosis of normal attack of malaria; the albumin concentration is
cells in addition to the cell remnants and other generally lower and the globulin concentration
debris produced by schizogony, leads both to ane- is increased.
mia and to enlargement of the spleen and liver. • The globulin increase is in the gamma fraction
• Malarial pigment (hemozoin) collects to give the liver and is associated with the appearance of antibod-
a grayish to dark brown or black color. ies measurable by the indirect immunofluores-
• The liver becomes congested, and the Küpffer cence technique.
cells are packed with hemozoin, which indeed, is • Serum potassium may increase with the lysis of
seen throughout the viscera. red blood cells.
• Hemozoin is derived from the hemoglobin of the
infected red blood cell, and, as it is insoluble in Epidemiology
plasma, its formation depletes the iron stores of • About 3.4 billion people in 92 countries are at risk
the body, thus adding to the anemia. to suffer from malaria. Highest death rates estimat-
• An increased destruction of normal red blood ed at 93% were observed in WHO African regions
cells for several weeks after eradication of a ma- (WHO, 2018) (Fig. 4.14).
FIG. 4.14 Global report on malarial cases (World Malaria Report of the World Health Organization, 2018.).
Online access: https://apps.who.int/iris/bitstream/handle/10665/275867/9789241565653-eng.pdf?ua=1
• Malarial parasites have a distinct pattern of distribu- • First drugs employed to destroy the asexual para-
tion around the globe: sites in the bloodstream.
• Falciparum and ovale malaria are primarily dis-
eases of the tropics; Chloroquine
• Quartan malaria is seen in the subtropics and • The main stay malarial treatment. It is the treatment
temperate zones as well of choice for uncomplicated malarial infections
• Vivax malaria is usually the most common type • Resistance has been reported with the use of this
in all endemic areas. drug
• The transmission of all species of malaria parasites
Arthemeter-Lumefantrine – a combination
depends on the presence both of suitable species of
therapy
Anopheles mosquitoes and of infected (gametocyte-
• Under the brand name, Coartem. It is a WHO
bearing) humans.
recommended drug for Plasmodium falciparum in-
• Congenital transmission is rare. However, pregnant
fections and uncomplicated infections
women are more attractive to Anopheles gambiae
mosquitoes than nonpregnant women, making them
Quinine
more vulnerable to malaria (Ansell et al., 2002).
• Used for severe malarial infections and for in-
• Glucose-6-phosphate dehydrogenase (G-6-PD)–defi-
fected pregnant women
cient cells are from 2 to 80 times more resistant to in-
vasion by P. falciparum than are normal erythrocytes. Artesunate
• Various hemoglobinopathies, especially the pres- • An Artemisinin derivative for severe malarial in-
ence of hemoglobin S, have been found to be relat- fections
ed to increased resistance to P. falciparum infection.
• Southeast Asian ovalocytosis (a form of hereditary Primaquine
elliptocytosis found in Malaysia, Indonesia, Papua • For relapsing Plasmodium vivax and Plasmodium
New Guinea, and the Philippines) is associated with ovale infections
increased resistance to malaria, probably because • Only primaquine is effective against tissue stages,
of a structurally and functionally abnormal band including the hypnozoites of P. vivax and P. ovale.
3 protein.
• African descent people who have Duffy blood group Tetracycline and Doxycycline
characteristic of Fy(a-b-) have resistance to Plasmo- • Antibiotics for malarial prophylaxis
dium vivax and Plasmodium knowlesi infections.
Prevention
Treatment • In actuality, malarial chemoprophylaxis is not a
• Treatment of malarial infections depend on factors form of prevention, as the person so protected may
including the clinical status of the patient, the in- become infected but fails to manifest disease symp-
fecting malaria species, and the drug susceptibility toms while taking the suppressive drugs.
of the infecting parasite. • More lasting preventive efforts must be directed at
• Classification of antimalarial drugs breaking the human-mosquito-human cycle.
1. Quinolone compounds like Chloroquine, Pri- • Well-controlled studies have demonstrated the effi-
maquine, and Quinine cacy of bed nets (mosquito nets) in the prevention
2. Quinoline related compounds like Lumefantrine of malaria in hyperendemic areas, particularly when
3. Artemisinin derivatives like Arthemeter and Arte- impregnated with permethrin.
sunate • Mosquito repellents are essential for persons in un-
4. Artemisinin-based combination therapy like protected areas between the hours of dusk and sun-
Arthemeter-Lumefantrine rise, when anopheline mosquitoes bite.
5. Antibiotics like tetracycline and doxycline • The development of malaria vaccines would be of
immeasurable benefit to the more than 1 billion
Quinine persons now at risk of developing malaria through-
• Only specific antimalarial drugs available prior out the world. Three areas of vulnerability on the
to World War I part of the parasitic life cycle have been focused on
• Isolated from the bark of the South American the sporozoite, the merozoite, and the developmen-
Cinchona tree (“Jesuits’ bark”) tal stages in the mosquito.
OTHER BLOOD- AND TISSUE-DWELLING containing fully developed sporocysts and spo-
PROTOZOA rozoites takes 4 to 5 days.
The Apicomplexa (Sporozoa)—Intestinal 2. Mature oocysts with sporozoites are ingested by
Coccidians the human host. The sporocysts excyst in the small
The coccidians are a group of microscopic, spore-form- intestine. The sporozoites are released, which pen-
ing, single-celled obligate intracellular protozoans. etrate the intestinal wall and undergo schizogony in
The intestinal sporozoa of man include Isospora belli the epithelial cells.
(Cystoisospora belli) two species of Sarcocystis, Crypto- 3. Schizonts containing merozoites rupture after a pe-
sporidium parvum, and Cyclospora cayetanensis. All these riod of development. The merozoites invade new
parasites share the common characteristic of having epithelial cells and continue the cycle of asexual
alternating asexual (schizogonic) and sexual (sporo- multiplication.
gonic) cycles. 4. Some of the merozoites undergo gametogony to
This alternation of sexual and asexual multiplica- produce microgametes and macrogametes
tion is typically characterized by three sequential stag- 5. Fertilization results in the development of unspor-
es, namely: ulated/immature oocysts that are excreted in the
1. Sporogony – the sexual cycle; produces oocysts stool.
2. Schizogony (merogony) – the asexual cycle; produc- • Sporulation usually occurs within 48 hours after
es merozoites (meronts) passage with the stool (Fig. 4.15).
3. Gametogony – results in the development of male Infective stage: Mature (sporulated) oocyst with 2
and female gametocytes, or micro- and macrogame- sporocysts and 4 sporozoites each.
tocytes, respectively. Diagnostic stage: Unsporulated oocyst
Mode of transmission: ingestion of contaminated
Isospora food and water
Isospora is a parasite of epithelial cells of the intestine,
in which it may undergo repeated asexual develop- Symptoms and pathogenesis
ment, with consequent destruction of the surface layer • Infections often are asymptomatic and self-
of considerable portions of the intestine. In addition limited.
to asexual stages, which serve to spread the infection • Some have reported symptoms ranging from mild
within the bowel wall, sexual stages occur, and these gastrointestinal distress to severe dysentery with fa-
culminate in oocysts passed in the feces. tal consequences
Three species have been recognized as human para- • Symptomatic cystoisosporiasis presents with chron-
sites, namely: ic diarrhea, vague or crampy abdominal pain, weight
1. Cystoisospora belli loss, weakness, malaise, and anorexia.
2. I. natalensis, which has been reported only twice • Eosinophilia may be evoked, even in asymptomatic
3. I. hominis, which no longer belongs to the genus infections.
Isospora • Malabsorption syndrome.
• Increased fecal fat resulting in loose, pale yellow,
Cystoisospora belli (formerly known: Isospora and foul-smelling stools.
belli ) • Jejunal biopsy may reveal villous atrophy.
Life cycle (Fig. 4.15) • Oocysts may persist in stools for as long as
1. Immature oocysts are released from the intestinal 120 days.
wall and are passed in feces and undergo develop- • Cystoisosporiasis is predominantly an infection of
ment in stool: people in the developing world and can be a com-
• The spherical mass of undivided protoplasm mon presentation of HIV/AIDS.
contained inside the immature oocyst divides to
form two sporoblasts, which are still within the Laboratory diagnosis
oocyst. • Cystoisospora belli oocysts may be seen in stool through:
• The sporoblasts develop heavy cyst walls and be- • Direct microscopic examination – iodine-stained
come known as sporocysts. Within each sporo- smear (oocysts are transparent and difficult to
cyst, four curved, sausage-shaped sporozoites develop. recognize if smears are unstained).
• This whole process of maturation from the pro- • Concentration techniques (zinc sulfate tech-
toplasm-containing immature oocyst to those nique, Sheather’s sugar flotation).
FIG. 4.15 Life cycle of Cystoisospora belli. (https://www.cdc.gov/dpdx/cystoisosporiasis/index.html.)
• Sporulation happens when unfixed specimen is left • Sheather’s sugar flotation procedure – most sensitive
at room temperature for 1-2 days (Mc Pherson and and accurate method for detecting C. belli oocysts in
Pincus, 2011). feces.
• Immature oocysts are ellipsoidal, or at times spin- • The zinc sulfate method concentrates oocysts well
dle-shaped, with blunt ends. They average 30 µm in but they are so light that they float even in the cus-
length by 12 µm in width. tomary zinc sulfate-iodine mixture and are seen
cyst (with 4 sporozoites) maybe passed out from the

stool of an infected person.
2. The infective sporocyst is ingested by an intermedi-
ate host: cattle (S. hominis) and pig (S. suihominis),
then ruptures to release the sporozoites. Sporozo-
ites invade endothelial cells of the blood vessels
and start the schizogony cycle resulting into FIRST
GENERATION schizont with merozoites (I). Once
released, it invades small capillaries to form SEC-
OND GENERATION schizont with merozoites (II).
Once merozoites (II) are released, they invade mus-
cle cells and transform into SARCOCYST containing
BRADYZOITES which when ingested by a definitive
FIG. 4.16 Cystoisospora belli. Oocyst containing two host, infection happens.
sporocysts with sporozoites. (Photomicrograph by Prof.
3-5. Bradyzoites within a sarcocyst found in an under-
John Gullberg.)
cooked meat are released in the small intestine once
the cyst ruptures.
only if the area directly beneath the coverslip is ex- • They start to invade intestinal epithelial cells and
amined carefully with reduced illumination. differentiate into microgametocyte and microga-
• Stains metocyte then to their corresponding gametes.
• Acid-fast staining (auramine-rhodamine or Kin- • When these gametes unite, they form a zygote
youn) which undergoes oocyst wall formation and spo-
• Modified acid-fast technique – sporoblasts with- rogony (formation of sporocysts and sporozo-
in the oocysts stain a deep red. ites).
• Phenol-auramine • Immature oocyst may sporulate even before pas-
• Iodine sage to the stool.
• The Enterotest (duodenal string test) has also been • Thin-walled oocysts are fragile therefore sporo-
used to recover C. belli oocysts. cysts may also be observed in stool specimen.
• Charcot-Leyden crystals are present in the stool. Infective stage to the:
• Blood examination will reveal peripheral eosinophil- • Intermediate host (cattle and pigs): Thin-walled
ia (Fig. 4.16). sporulated oocyst or sporocyst
• Definitive host (human): Bradyzoites within a
Treatment sarcocyst
• Trimethoprim-sulfamethoxazole combination ther- Diagnostic stage: Thin-walled sporulated oocyst or
apy eliminates chronic infection in immunosup- sporocyst
pressed persons, when given for 3 weeks (Whiteside Mode of transmission: ingestion of undercooked meat
et al., 1984). with bradyzoites
• Combined pyrimethamine and sulfadiazine is also • The organism occurs in striated muscle (or sometimes
an effective treatment. unstriated muscle) as Miescher’s tubules.
• Miescher’s tubules – white, threadlike cysts in
Sarcocystis striated muscles.
Human sarcocystosis remains rare, especially in tem- • Cyst characteristics
perate regions, despite the increasing awareness of hu- • Limiting membrane may show radial striations.
man coccidial infection. Infections are attributed to two • Septa may divide the cyst into compartments.
species, S. suihominis (from pork) or S. hominis (referred • The contained trophozoites (bradyzoites) are con-
to by some as S. bovihominis, from beef). siderably larger than those of Toxoplasma.
Humans serve as the definitive host for both species,
but occasionally, humans can act as intermediate hosts.
• Intestinal sarcocystosis generally does not produce
clinical symptoms.
Life cycle (Fig. 4.17)
• Symptomatic patients experience nausea, stomach
1. Thin-walled sporulated oocyt (with 2 sporocyst
pains, and diarrhea appearing within 3 to 6 hours
each having 4 sporozoites) or an individual sporo-
after ingestion of beef.
FIG. 4.17 Life cycle of Sarcocystis. (https://www.cdc.gov/parasites/sarcocystosis/biology.html.)
• Symptoms are more pronounced in others who Laboratory diagnosis

ingested infected uncooked pork, with stomach • Oocysts are usually passed in the feces fully developed
pains and diarrhea persisting for 2 to 3 weeks. and with the sporocysts ruptured out of the oocyst.
• Symptoms typically continue for 48 hours. • The sporocysts may occur singly or may be seen
• May occasionally be severe or life-threatening. in pairs in the feces, apparently held together by
• A rare invasive form exists, presenting with vasculitis some sort of cement substance.
and myositis. • Sporocysts of S. hominis measure 13.1 to17.0 by
• Occurs in the lymph nodes, muscles, and the larynx 7.7 to 10.8 µm.
• First excreted 14 to 18 days after ingesting Life cycle (Fig. 4.19)

beef. 1-3. Sporulated thick-walled oocyst containing four
• Sporocysts of S. suihominis measure 11.6 to 13.9 sporozoites (but no sporocysts) are readily infective
by 10.1 to 10.8 µm. when passed out in the stool and contaminate di-
• First excreted 11 to 13 days after ingesting rectly food and water which when ingested by the
pork. host, infection sets in.
• Species cannot be distinguished from one another 4: a-c. Once oocyst reaches the intestinal tract, excystation
solely by microscopy happens releasing the sporozoites which invade the en-
• Definitive diagnosis can be made through biopsy of terocyte to become a trophozoite and initiate schizog-
an infected muscle ony or merogony (asexual cycle) in the brush border.
• Sarcocysts of S. hominis are microscopic in mus- d-f. Asexual cycle produces a Type I MERONT which
cles of cattle, whereas those of S. suihominis are release merozoite that will invade another epithelial
macroscopic in muscles of swine. cell or transform to become Type II MERONT.
• Hematoxylin-eosin staining, PAS staining g-i: Merozoites from Type II meronts undergo sexual
• Humans may serve as the intermediate host of an multiplication to become an undifferentiated GAM-
unknown Sarcocystis species, therefore harboring ONT. A fertilized zygote is formed after the union of
intramuscular cysts. This happens when human ac- microgamete (from microgamont) and macrogamont.
cidentally ingests an oocyst and a sarcocyst develops j-k: Two types of OOCYST then formed.
within his muscle (Fig. 4.18). • Thick-walled oocysts are excreted from the host
into the environment
Treatment • Thin-walled oocysts remain in the intestine and
Since infection is mostly asymptomatic, treatment cause autoinfection.
may not be necessary. However, the following are Infective stage: Sporulated thick-walled oocyst
used to address muscular problems (myositis): alben- Diagnostic stage: Sporulated thick-walled oocyst
dazole, metronidazole, and cotrimoxazole for myosi- Mode of transmission: ingestion of contaminated
tis. Use of corticosteroids may also be considered. food and water

Cryptosporidium parvum
• Cryptosporidiosis is both human transmitted and a
Cryptosporidium is a minute coccidian parasite with
zoonosis.
worldwide distribution. The species of Cryptospo-
• Infections may be symptomatic in immunocompe-
ridium that infects humans and most mammals is
tent individuals.
C. parvum.
• Self-limited diarrhea that usually lasts about
2 weeks and, less commonly, is accompanied by
abdominal discomfort, anorexia, fever, nausea, and
weight loss.
• Symptomatic infections in immunodeficient indi-
viduals are characterized by severe diarrhea accom-
panied by the symptoms enumerated above.
• Life-threatening disease in patients with AIDS
(found in sputum, in lung biopsy material, and
in the biliary tract and is associated with malab-
sorption)
• A case of cryptosporidiosis caused by C. baileyi,
a species of avian hosts, has been reported in a
patient with AIDS.
• Diagnosis is through:
• Identifying organisms in intestinal biopsy mate-
FIG. 4.18 Sarcocysts of Sarcocystis in muscle tissue rial (meronts containing merozoites and gam-
(H&E). (https://www.cdc.gov/dpdx/sarcocystosis/index.html.) onts containing micro- and macrogametes).
FIG. 4.19 Life cycle of Cryptosporidium parvum. (https://www.cdc.gov/dpdx/cryptosporidiosis/index.

html.)
• Identifying oocysts in stool specimens. • Serology for fecal specimens for the detection of oo-
• Enterotest (duodenal string test) is also used to re- cysts (indirect immunofluorescence, direct immu-
cover oocysts. nofluorescence, ELISA).
• Biopsy.
• H&E-stained material will show lightly staining Epidemiology
organisms appearing as small (2–4 µm) round • Cryptosporidiosis is now recognized as a significant
bodies on the mucosal surface cause of diarrhea in humans.
• With Masson’s stain, a small red nucleus and • Infection is more common in children than in
blue cytoplasm can be distinguished in many of adults and non-breast-fed infants have more crypto-
the organisms. sporidiosis than breast-fed infants.
• In duodenal biopsy specimens, gamonts or • Infection clinically resembles giardiasis.
meronts, either immature or mature, containing • The organism is highly resistant to the chemi-
four or eight merozoites averaging 2 to 4 µm are cals used to treat drinking water, and its removal
seen. by filtration is important in the water treatment
• Concentration methods. process.
• Modified zinc sulfate flotation technique. • Waterborne outbreaks of cryptosporidiosis are
• Sheather’s sugar flotation. common, as no current water treatment process
• Formalin-ethyl acetate sedimentation followed can guarantee complete removal of oocysts.
by layering and flotation over hypertonic sodium • Infections may also be acquired by swimming
chloride solution to separate oocysts from stool in pools, drinking apple cider, and drinking un-
debris. chlorinated deep well water.
• Microscopic morphology. • Specific measures to help reduce the risk of wa-
• Smears are best examined using phase-contrast terborne cryptosporidiosis:
microscopy • Boil drinking water for 1 minute (most cer-
• Oocysts appear as highly refractile spherical tain method).
bodies (4–6 µm), each containing four sporo- • Filter drinking water with devices that remove
zoites (without sporocyst) and one to six dark particles 1 µm and larger.
granules. • Use bottled drinking water.
• In the modified acid-fast method, oocysts • High-temperature short-time pasteurization
stain red, whereas fecal yeasts stain green or (71.7°C for 15 seconds) is sufficient to destroy
blue if methylene blue is used as counterstain the infectivity of C. parvum oocysts in water or
(Fig. 4.20). milk.
• With an iodine preparation, oocysts are colorless
and yeasts are brown. Treatment
• Giemsa staining may also be employed on air- • Nitazoxanide effectively treats cryptosporidiosis,
dried, methanol-fixed fecal smears. but the infection is usually self-limited in immuno-
competent patients.
• In AIDS patients, there is no effective treatment for
cryptosporidiosis.
Cyclospora cayetanensis
An organism encountered in cases of prolonged wa-
tery diarrhea and associated with spherical bodies 8 to
10 µm in diameter, once called large Cryptosporidium,
coccidian-like body, cyanobacterium-like body, blue-
green alga, is now named Cyclospora cayetanensis, with
the spherical bodies called oocysts.

1-3. Unsporulated noninfective oocysts are passed in
stool of an infected host. Sporulation occurs 1-2
FIG. 4.20 Cryptosporidium oocysts in feces (modified
acid-fast stain). weeks in a conducive environment resulting into a
FIG. 4.21 Life cycle of Cyclospora cayetanensis. (https://www.cdc.gov/dpdx/cyclosporiasis/index.html.)
mature oocyst with 2 sporocysts each having 2 elon- • Schizogony cycle begins producing Type I
gated sporozoites. MERONTS which may remain in asexual phase
4-5. Infection starts when one ingests food or water or transform into Type II MERONTS.
containing sporulated oocyst. • Sporogony cycle begins when Type II MERONTS
6. In the gastrointestinal tract, EXCYSTATION happens release merozoites and undergo sexual develop-
releasing the sporozoites which eventually invade ment to become macrogametocytes and micro-
epithelial cells of the small intestine. gametocytes.
• Fertilization happens to form a zygote which de-

velop into an oocyst. This is released in the stool
unsporulated.
Infective stage: Mature (sporulated) oocyst.
Diagnostic stage: Unsporulated oocyst.
Mode of transmission: ingestion of contaminated
food and water.

• Cyclosporiasis is clinically indistinguishable from
cryptosporidiosis and isosporiasis. FIG. 4.22 Cyclospora cayetanensis unsporulated oocysts in
• Illness is characterized by watery diarrhea that tends feces (phase-contrast). (Courtesy of Dr. Ynes R. Ortega and
to occur in a relapsing or cyclical pattern. Dr. Charles R. Sterling, University of Arizona, Tucson, AZ.)
• Incubation period: 2 to 11 days.
• Average length of time of illness is more than Epidemiology
3 weeks. • The first cases were reported from Papua New
• Abdominal cramping, nausea, vomiting, de- Guinea in 1979.
creased appetite, weight loss, low-grade fever, • Epidemiologic evidence indicates that Cyclospora in-
and fatigue. fection is acquired by drinking contaminated water.
• The illness is self-limited, but may last for weeks • Outbreak was traced from contaminated water stor-
with profound fatigue, anorexia, and weight loss age tank.
overshadowing the persisting diarrheal symptoms. • In Nepal, outbreaks of cyclosporiasis have coincided
• Prolonged, severe illness with a high rate of recur- with the rainy season.
rence in AIDS patients. • Sources of infection include contaminated water
• Biliary disease has also been described in AIDS and contaminated fruits (Guatemelan raspberries,
patients. lettuce, basil).
• The parasite infects the upper small bowel.
• Inflammatory changes, villous atrophy, and crypt Treatment
hyperplasia of jejunal tissue. • Trimethoprim-sulfamethoxazole is the effective
treatment for cyclosporiasis (Hoge et al., 1995).
Laboratory diagnosis • Higher doses and long-term maintenance in
• Diagnosis is by microscopic identification of oocysts AIDS patients (Pape et al., 1994).
in fecal specimens.
• Oocysts are spherical, 8 to 10 µm in diameter, The Apicomplexa (sporozoa) – Tissue
and, when first passed, unsporulated, with a Coccidians
greenish central morula (mulberrylike mass) con- Toxoplasma gondii
taining 6 to 9 refractile globules. Toxoplasma is a parasite of cosmopolitan distribution,
• Specimen may be concentrated using the forma- able to develop in a wide variety of vertebrate hosts, but
lin-ethyl acetate procedure; however, some reports its definitive host is the house cat and certain other Fe-
claim that concentrated specimens have fewer oo- lidae. It was originally described in a North African ro-
cysts than unconcentrated specimens. dent called the gundi, from which it derives its specific
• Acid-fast staining. name. Serologic evidence indicates that human infec-
• Iodine solutions will stain the internal globules tions are common in many parts of the world, but most
brown. are of a benign nature or are completely asymptomatic.
• Autofluorescence is an important criterion for identify-
ing C. cayetanensis oocysts. Life cycle (Fig. 4.23)
• Under UV light, oocysts will appear as bluish- This coccidian parasite requires animals belonging to
green circles. the family Felidae (cats and their relatives) which act at
• Asexual stages of Cyclospora have also been detected its exclusive definitive host.
in jejunal biopsy specimens examined by light and Stages happening in CATS:
electron microscopy. 1. Cats become infected in 3 ways:
• Phase contrast microscopy of fecal sample to dem- • Ingestion of infected meat that contains tissue
onstrate oocyst stage (Fig. 4.22). cyst (bradyzoites).
FIG. 4.23 Life cycle of Toxoplasma gondii. (https://www.cdc.gov/parasites/toxoplasmosis/biology.html.)
• Ingestion of infective oocycst. 3. In humans, infection starts via the following routes:
• Transplacental transmission from a pregnant cat • Ingestion of undercooked meat of animals
to its kittens. (sheep, pig, rabbit) that harbor the tissue cyst
2. In the intestinal tract, schizogony (to produce schiz- • Ingestion of infective oocyst from excreta of cats
ont), gametogony (to produce gametocytes) and spo- and which may contaminate food and water. Oo-
rogony (to produce oocyst) happens. Since asexual cyst may also be recovered from cat’s fur.
cycle happens inside the cat, cats may also be regard- • Blood transfusion or organ transplantation.
ed as an intermediate host. • Transplacental from mother to fetus.
3. Unsporulated oocysts, 9 to 11 µm in width by 11 to • Drinking unpasteurized goat’s milk that contains
14 µm in length, are shed in the stool and become tachyzoites (Mc Pherson and Pincus, 201l, Leven-
infective in 1-5 days in the environment. This now thal and Cheadle, 2012).
has 2 sporocysts inside each having 4 sporozoites. 4. Crescent-like tachyzoites invade any nucleated cell
Stages happening in non-feline vertebrate host acting during acute infection resulting to cell death and injury
as intermediate host: to the host. Once immunity develops, tissue pseudo-
1. Mature oocyst (sporulated) once ingested from con- cysts develop within which bradyzoites multiple. This
taminated food or water, transform into fast dividing now characterizes chronic infection. Most commonly
rapidly growing intracellular forms called tachyzoites. in skeletal muscle, myocardium, brain, and eyes, these
2. Tachyzoites may localize in neural and muscle tissue cysts may remain throughout the life of the host.
and develop into slow multiplicative forms called Note: All stages of the life cycle occur in felines, but
bradyzoites that are enclosed in a pseudocyst. only trophozoite (tachyzoites and bradyzoites) and
cyst stages occur in humans and other intermediate • Intrauterine infections.

hosts (Mc Pherson and Pincus, 201l). • Most infections are quite severe.
• Multiplication of the parasites within an infected • Retinochoroiditis, encephalomyelitis, and hydro-
cell usually leads to death and rupture of the cell, cephalus or microcephaly are common sequelae
freeing the parasites to spread the infection to new • Encephalomyelitis may result in cerebral calcifi-
cells, or it may lead to formation of a cyst. cations demonstrable in radiographs.
• Tachyzoites – quickly multiplying forms respon- • Newborn infections.
sible for initial spread of infection and tissue de- • Fever, pneumonitis, hepatosplenomegaly.
struction. • Convulsions are common.
• Bradyzoites – slower-developing forms that form • Most infections result in blindness or severe visu-
cysts more characteristic of older infections (may al impairment and mental retardation and there
form as a consequence of increased host immu- is seldom complete recovery.
nity). • There may be a causal relationship between poly-
• In trophozoites stained by any routine method, myositis and toxoplasmosis.
a spherical nucleus is seen, situated closer to the • AIDS patients.
rounded than to the pointed end. • Reactivation of cerebral toxoplasmosis results in
• A smaller, dark-staining mass called the conoid encephalitis.
may be visible at the end opposite the nucleus in • Toxoplasmic encephalitis occurs in 10% to 50%
organisms stained with certain silver stains, giv- of AIDS patients who are seropositive for Toxo-
ing a resemblance to the amastigotes of hemofla- plasma and have CD4+ T lymphocyte counts of
gellates. less than 100/µL.
• The conoid is part of the apical complex. • Headache, confusion, ataxia, hemiparesis,
Infective stage to the intermediate host: Mature (sporu- and retinochoroiditis
lated) oocyst or bradyzoite in infected meat. • Spinal fluid lymphocytic pleocytosis, de-
Diagnostic stage: tachyzoites in blood or body fluids/ tectable Toxoplasma-specific IgG antibod-
bradyzoites in tissue (strongly Periodic Acid Schiff ies in serum, lesions on the brain (CT) are
positive). suggestive.
Mode of transmission: ingestion of undercooked • Necrotic foci, with Toxoplasma organisms in
meat/ingestion of oocyst/transplacental/organ brain biopsy, or organisms demonstrable in
transplantation/blood transfusion. spinal fluid are diagnostic, as may be a rise of
spinal fluid IgG antibodies in the absence of a
Symptoms and pathogenesis similar response in serum IgG.
• Majority of infections are benign. • Tachyzoites are more commonly seen than
• Usually asymptomatic in adults and in children bradyzoites.
past the neonatal period. • Lack of IgM antibody or a change in IgG antibody
• The disease picture may simulate infectious mononu- titers suggest reactivation of a chronic latent infec-
cleosis (chills, fever, headache, myalgia, lymphadeni- tion rather than an acquired primary infection.
tis, and extreme fatigue). • Toxoplasma orchitis – nontender testicular mass
• Severe infections may be accompanied by a • Pulmonary toxoplasmosis.
maculopapular rash, with evidence of hepatitis, • Toxoplasma myocarditis and myositis of colonic
encephalomyelitis, or myocarditis. In a very few muscularis propria.
cases retinochoroiditis occurs, which may prog- • Primary infections are promoted by immunosup-
ress to produce blindness pression (transplant patients).
• Retinochoroiditis may be either a hypersensitiv- • Reactivation of toxoplasmosis is also seen in medi-
ity response to cyst rupture (the more evanescent cally immunosuppressed hosts, such as those with
and sporadic attacks) or a chronic progressive Hodgkin disease, non-Hodgkin lymphoma, leuke-
effect of the proliferation of tachyzoites in the mia and other malignancies, collagen-vascular dis-
retina, an immunologically deficient tissue. eases, organ transplantation.
• Focal areas of necrosis, surrounded by lymphocytes, • Reactivation usually results in neurologic symp-
monocytes, and plasma cells, result from death of toms (diffuse encephalopathy, meningoencepha-
the infected cells. litis, or cerebral mass lesions).
• Cysts form in many organs but particularly in the • Endogenous interferon gamma appears to be an im-
muscles and brain. portant mediator of host resistance to Toxoplasma.
• Diagnosis is seldom made by recovery of the organ-
isms.
• Cell cultures such as Vero or MRC5 fibroblasts may
be used to isolate and cultivate Toxoplasma, but it is
not commonly performed.
• The only useful laboratory tests are the serologic
procedures employed for diagnostic purposes.
• Sabin-Feldman dye test – Toxoplasma organisms be-
come resistant to staining with methylene blue if
the patient’s serum contains Toxoplasma-specific
antibodies, which indicates that the patient may
have or has had toxoplasmosis. FIG. 4.25 Trophozoites of Toxoplasma gondii in brain
• Toxoplasmin skin test impression film (Giemsa stain).
• EIA and IFA tests
• Toxo IgG and IgM Epidemiology
• Indirect fluorescent and dye test antibodies are • Infection from ingestion of undercooked meat, pre-
demonstrable within the first 2 weeks after infec- sumably beef, has been documented.
tion and may rise to levels of 1:4096 or greater • Experimental studies have shown that infected ani-
early in infection, falling slightly thereafter but mals are able to transmit tachyzoites to their suck-
persisting at an elevated level for many months ling young by way of milk.
before declining to low levels after many years. • Humans can also be infected by drinking raw
• IFA and hemagglutination antibodies appear milk from infected goats.
slightly later than the dye test. • Oocysts shed in the feces are resistant to acids, al-
• Congenital toxoplasmosis. kalis, and common laboratory detergents but are
• Detection of Toxoplasma IgM antibodies in fetal killed by drying or by exposure to temperatures of
blood 55°C for 30 minutes.
• Isolating organisms in mice or cell culture from • Sporulated oocysts will survive a temperature of
fetal blood or amniotic fluid –21°C for 28 days, though the muscle cysts are
• Ultrasound examination of the fetus to detect en- killed by freezing at –6°C for 1 day or immedi-
largement of cerebral ventricles. ately at –21°C.
• Body fluid examination and brain impression • Toxoplasma encephalitis is an important cause of sea
(Figs. 4.24 and 4.25). otter mortality along the California coast (Miller
et al., 2002).
• Source of infection may be filter-feeding benthic
invertebrates (clams and mussels).
• Oysters may also serve as reservoirs of infection
• Transplacental transmission takes place in the
course of an acute but inapparent or undiagnosed
maternal infection.
• May lead to abortion in some domestic animals.
• Blood transfusion is a means by which tachyzoites
in blood may be transmitted to another person.
Treatment
• The only accepted treatment for toxoplasmosis is a
combination of pyrimethamine with trisulfapyrimi-
dines for 1 month.
• Inhibits the production of dihydrofolate reduc-
tase by the parasite and the synthesis of DNA,
FIG. 4.24 Toxoplasma gondii tachyzoites from peritoneal RNA, and protein.
exudate of mouse. (Photomicrograph courtesy of Dr. Leon • Folinic acid may be administered to counteract
Jacobs, National Institutes of Health.) bone marrow depression.
• Corticosteroids may be administered for their anti- several merozoites which are usually arranged in
inflammatory action. tetrads: “Maltese Cross formation”.
• For AIDS patients with encephalitis, intravenous • In human, merozoites from infected red cells
clindamycin has been used for treatment. may infect another red cells.
• Clindamycin targets plastids (nonphotosynthetic • In mouse, merozoites from infected red cells may
chloroplast-like organelles that occur in apicom- infect another red cells or transform to become
plexan parasites). gametes.
• Spiramycin has been used in France to prevent in 3. Once gametes are ingested by another tick, they
utero infection in pregnant women. travel in the gut for fertilization to happen forming
a zygote which transforms to an ookinite that enters
Prevention the salivary gland.
• Meat should be heated throughout to 150°F (66°C) 4. Sporogony happens resulting to numerous sporozo-
before consumption, and hands should be washed ites ready to be transmitted in a new intermediate
with soap and water after handling uncooked meat. host through another blood meal.
• Indoor cats are less likely to get infected if fed on • Multiplication of the blood stage parasites is re-
dry, canned, or boiled food. sponsible for the clinical manifestations of the
• Cat litter pans should be cleaned daily and disin- disease.
fected with boiling water. • Humans are dead-end hosts and there is probably
• Disposable gloves should be worn to clean litter little, if any, subsequent transmission that occurs
boxes or work in soil that may have been con- from ticks feeding on infected persons. However,
taminated with cat feces. human to human transmission is well recognized
• Pregnant women should avoid contact with cats to occur through blood transfusions.
whose source of food is not controlled and should • Infective stage to the intermediate host: sporozoite.
not empty litter pans. • Diagnostic stage: trophozoite and merozoites ar-
ranged in Maltese cross appearance.
• Mode of transmission: through a bite of an infected
Other Apicomplexa (sporozoa) Ixodes tick.
Babesia spp.
Apicomplexan parasites belonging to the genus Babesia Symptoms and pathogenesis
have long been known as parasites of domestic and wild • Infection is usually self-limited and characterized
animals, causing at times inapparent infections but also by gradual onset of malaise followed by fever, head-
causing such economically important disease as Texas ache, chills, sweating, arthralgias, myalgias, fatigue,
cattle fever and malignant jaundice in dogs. Human and weakness.
infections have been reported from North America, Eu- • Fever does not show periodicity.
rope, Taiwan, and Japan. The organisms infect the red • Mild hepatosplenomegaly, mild to moderately
blood cells, in which they appear as somewhat pleo- severe hemolytic anemia.
morphic ring-like structures. Most resemble ring stages • Serum bilirubin and transaminase levels are
of plasmodia. Infection is transmitted by various species slightly elevated.
of ixodid ticks, in which a sexual multiplicative cycle oc- • Splenectomy places a person at risk of getting
curs. infected.
• Transfusion-induced babesiosis from an asymptom-
Life cycle (Fig. 4.26) atic donor.
The B. microti life cycle involves two hosts:
a. Rodent – white-footed mouse (Peromyscus leuco- Laboratory diagnosis (Fig. 4.27)
pus) – the intermediate hosts • Diagnosis is through the identification of intraeryth-
b. Ticks – Ixodes; the definitive hosts rocytic parasites in Giemsa-stained blood films.
1. Babesia–infected tick bites a susceptible host (mouse • The parasites can be differentiated from malarial
or human) releasing the infective sporozoites. Tick parasites by the absence of pigment (hemozoin)
has to be in contact for 12 hours for effective trans- in the infected erythrocytes.
mission. (Zeibig, 2013) • The organisms frequently occur in pairs, or as tet-
2. Schizogony cycle (asexual reproduction by bud- rads (known as “Maltese cross” forms).
ding) starts inside the red blood cells producing • Confused with Plasmodium falciparum.
FIG. 4.26 Life cycle of Babesia microti. (https://www.cdc.gov/dpdx/babesiosis/index.html.)
• Parasitemia can be detected within 2 to 4 weeks after • Ixodes dammini is considered to be the tick vector of
inoculation (Hamster intraperitoneal inoculation human babesiosis on Nantucket Island.
test). • This is also the vector for Lyme disease; simulta-
• IFA. neous human infections of babesiosis and Lyme
• Immunoblotting. disease have been reported.
• PCR. • White-footed mice (Peromyscus leucopus) have been
identified as the principal reservoir host of B. microti
Epidemiology on Nantucket island.
• European cases of human babesiosis have been • Patients with co-infections of babesiosis, Lyme
caused by Babesia divergens, a parasite of cattle. disease, and human granulocytic ehrlichiosis have
• Human babesiosis in North America usually is not been reported.
fatal and is caused by Babesia microti, a parasite of • In the Philippines, Babesia bigemina and Babesia bo-
rodents. vis infections have been noted in blood samples of
• Historically, Babesia is related to cases of Texas cat- cattle and water buffaloes in the province of Nueva
tle fever or red water fever. (Beaver, 1984; Zeibig, Ecija using nested-PCR technology. Prevalence rang-
2013). es from 10.81–11.49%. (Herrera, 2017).
• Malarial complications may include cerebral malaria,

anemia, renal disease, blackwater fever, dysenteric
malaria, algid malaria, pulmonary edema, tropical
splenomegaly syndrome, hyperparasitemia, and
hypoglycemia.
• Malarial parasites are obligate intracellular parasites
infecting primarily liver parenchymal cells and
erythrocytes.
• The infective stage of the Plasmodium spp. to
the intermediate host (Human) is the sporozoite
stage. However, mosquitoes, the parasites’
definitive hosts, acquire infection by sucking human
blood with gametocytes (microgametocytes and
macrogametocytes). Therefore, gametocytes act as
the parasite’s infective stage to the definitive host.
• Mode of infection of the parasite includes: bite of an
infected anopheline vector, blood transfusion, and
congenital transmission.
FIG. 4.27 Babesia in red blood cells. (Photomicrograph • Definitive hosts are the female anopheline mosquitoes.
by Zane Price.) • Intermediate hosts are humans and monkeys.
Treatment • In the intermediate host, two stages of parasitic
development are exo-erythrocytic and erythrocytic
• Combination therapy using clindamycin and oral
stages. Schizogony (asexual reproduction) also
quinine.
happens in the intermediate hosts.
• Combination therapy using atovaquone and
• In the definitive host, the process of sporogony
azithromycin has also been used.
(sexual reproduction) happens.
• Chloroquine provides symptomatic relief but has no
• Quinine and its related alkaloids are the
effect on the degree of parasitemia or its duration.
most popular antimalarial drugs available as
• The aromatic diamidines pentamidine and dim- chemoprophylaxis and cure treatment.
inazene (Berenil) have been found to suppress the
• Preventive measures include breaking the human-
parasitemia but not to eliminate infection. mosquito cycle, mosquito repellants, mosquito and
• Pyrimethamine and quinine, either alone or in com- larval traps, and vaccine development.
bination, failed to eliminate experimental B. microti • Coccidians are parasites characterized by having
infections in hamsters. alternating sexual and asexual life cycles.
• Distribution of permethrin-treated cotton in wood- • Important species implicated in human infections
ed areas, which the rodents use as nesting material, include Cryptosporidium parvum, Cyclospora
reduces tick infestation in white-footed mice. cayetanensis, Toxoplasma gondii, Isospora belli
(Cystoisospora belli), Sarcocystis, and Babesia.
SUMMARY • Infections caused by coccidians are usually
asymptomatic, but are severe in immunosuppressed
• The clinical disease of the Plasmodium spp. is individuals, such as those infected with HIV.
called Malaria. • The infective stage for humans for the intestinal
• There are 5 known malarial parasites infecting coccidians (C. parvum, I. belli (C. belli), C.
humans namely: P. falciparum, P. vivax, P. ovale, cayetanensis, Sarcocystis) is the acid-fast oocyst.
P. malariae, P. knowlesi. • T. gondii causes a tissue infection that is usually
• P. vivax and P. ovale are known to cause RELAPSE asymptomatic in immunocompetent hosts. In
due to activation of hypnozoites. patients with AIDS, a latent infection can reactivate
• P. vivax is the most prevalent species worldwide. and cause encephalitis. Congenital transmission
can result in serious complications.
• P. vivax and P. falciparum account for the majority of
malarial infections (~95%). • Babesia microti, an intraerythrocytic parasite, infects
humans through the bite of a tick from the genus
• Malarial paroxysm is a distinct feature of the disease
Ixodes. The parasite morphologically resembles
process including a chill, hot, and sweating stage.
P. falciparum on blood smears, but clinically, no
• The paroxysm may be tertian, sub-tertian, quartan, periodicity in the fever is observed.
and quotidian in nature depending on the cycling time.
REVIEW QUESTIONS c. Alter DNA properties disabling parasitic

1. What is the range for the typical Plasmodium vivax functions
and Plasmodium ovale incubation period? d. None of the above
a. 10–17 days
b. 10–12 days 11. Autofluorescence is an important diagnostic tool
c. 18–40 days for the identification of which of the following
d. 8–11 days organisms?
a. Cyclospora cayetanensis
2. What is the periodicity of the Plasmodium falciparum b. Cryptosporidium parvum
paroxysm? c. Cystoisospora belli
a. 44–48 hours d. Toxoplasma gondii
b. 48–50 hours
c. 72 hours 12. What constitutes a positive result in the Sabin-Feld-
d. 36–48 hours man dye test?
a. Agglutination
3. What Plasmodium species demonstrate distinct ame- b. Toxoplasma oocysts stained blue after immersion
boid characteristic? in methylene blue solution
a. P. vivax c. Refractoriness of the oocyst wall to methylene
b. P. ovale blue staining
c. P. falciparum d. Loss of color
d. P. malariae
13. Which of the following coccidians is associated
4. What Plasmodium species demonstrate increase in with congenital infections?
erythrocytic size upon invasion? a. C. parvum
a. P. malariae b. C. belli
b. P. ovale c. T. gondii
c. P. falciparum d. S. hominis
d. P. vivax
14. Intraerythrocytic Maltese cross forms are seen in
Match the stippling with the characteristic malarial species which parasite?
a. Maurer’s cleft a. P. falciparum
b. Schüffner’s dots b. B. microti
c. Ziemann’s stipplings c. C. belli
d. T. gondii
5. P. ovale
15. Most sensitive and accurate method for the detec-
6. P. vivax tion of C. belli oocysts from fecal specimens.
a. Zinc-sulfate flotation technique
7. P. falciparum b. Auramine-rhodamine staining
c. Direct microscopic examination
8. P. malariae
d. Sheather’s sugar flotation technique
9. What malarial parasite is responsible for most of the
16. This coccidian is associated with free sporocysts
cases of known nephrotic syndrome?
found in feces due to fragile oocyst walls.
a. P. malariae
a. C. belli
b. P. knowlesi
b. Sarcocystis
c. P. falciparum
c. T. gondii
d. P. vivax
d. C. cayetanensis
10. What is the mechanism of action of the drug Chlo-
17. This organism is characterized as having oocysts
roquine on the malarial parasite?
ranging from 4 to 6 µm in diameter.
a. Inhibit ribosomal protein synthesis
a. C. parvum
b. Inhibit mitochondrial respiratory processes
b. C. cayetanensis
c. C. belli Haditsch M. Quality and reliability of current malaria

d. Sarcocystis diagnostic methods. Travel Med Infect Dis. 2004; 2:149–
160.
18. This was formerly known as cyanobacterium-like Herrera PCT, Viloria VV, Balbin MM, Mingala CN. Prevalence
body of babesiosis (Babesia bovis and Babesia bigemina) in
a. C. parvum cattle and water buffalo in Nueva Ecija, Philippines
using Nested Polymerase Chain Reaction. Ann Parasitol.
b. C. cayetanensis
2017;63(4):309–316. doi: 10.17420/ap6304.117.
c. C. belli
Hoge CW, et al. Placebo-controlled trial of co-trimoxazole
d. Sarcocystis for Cyclospora infections among travellers and foreign
residents in Nepal. Lancet. 1995;345:691–693.
19. Which is considered the definitive host for Babesia Leventhal R and Cheadle RF. Medical parasitology: A self-
microti instructional text. 6th ed. Philadelphia: F.A. Davis
a. Humans Company; 2012.
b. Ixodes tick Lobel HO. Discussion, in “Update and roundtable on malaria
c. White-footed mice prophylaxis.” Am Comm Clin Trop Med Trav Health,
d. Cattle 45th Annual Meeting American Society of Tropical
Medicine and Hygiene, Baltimore, MD, December 4,
20. The primary means for diagnosing toxoplasmosis 1996.
a. Microscopic identification of organisms McPherson RA, Pincus MR. Henry’s clinical diagnosis and
b. Cell culture management by laboratory methods. 22nd ed. Singapore:
c. Serology Elsevier; 2011.
Miller MA, et al. Coastal freshwater runoff is a risk factor
d. PCR
for Toxoplasma gondii infection of southern sea otters
Answers to review questions are available at the end of this (Enhydra lutris neresis). Int J Parasitol. 2002;32:
997–1006.
book.
Pape JW, et al. Cyclospora infection in adults infected with
HIV–Clinical manifestations, treatment, and prophylaxis.
Ann Intern Med. 1994;121:654–657.
REFERENCES
Whiteside ME, et al. Enteric coccidiosis among patients with
Ansell J, et al. Short-range attractiveness of pregnant women to
the acquired immunodeficiency syndrome. Am J Trop
Anopheles gambiae mosquitoes. Trans R Soc Trop Med Hyg.
Med Hyg. 1984;33:1065–1072.
2002;96:113–116.
WHO. Global report on malarial cases, World Malaria Report
Beaver PC, Jung RC and Cupp EW. Clinical parasitology. 9th
of the World Health Organization, 2018.
ed. Philadelphia: Lea & Febiger; 1984.
Zeibig, E.A. Clinical parasitology, 2nd ed. Elsiever Saunder;
Centers for Disease Control and Prevention DPDx- Laboratory
2013.
Identification of Parasites of Public Health Concern.
Website: https://www.cdc.gov/dpdx/index.html.
CHAPTER 5
Phylum Nemathelminthes:
Roundworms
KYLE PATRICK R. MAGISTRADO
INTRODUCTION • Female nematodes have two cylindrical ovaries,

There are an estimated 500,000 species of nematodes. uteri, a vulva, and vagina. Meanwhile, males may ei-
They are considered as parasites and disease-causing to ther possess: (a) a pair of copulatory spicules, or (b)
animals, plants, and humans. thin-walled copulatory bursa supported by thick-
ened rays.
General Morphology
• Nonsegmented Life Cycle
• Generally cylindrical • Egg → Larva → Adult
• Bilaterally symmetrical • Eggs vary in size and shape.
• Tapered at both ends • Larva
• Covered by cuticle (a tough protective covering • Rhabditiform larva is the stage that hatches from
made up of chitin) the egg.
• Complete digestive tract (with oral and anal open- • Larva undergo several molts until it reaches the
ings) third stage larva which is the filariform.
• No circulatory system • Filariform larvae generally characterizes the infec-
• Sexes are separate (generally males are such smaller tive forms of the parasite.
than female worms) • Adult worms have separate sexes. They are also
• Majority are free-living. equipped with a digestive and reproductive
• The nematodes can also be divided into two classes system.
based on the presence of chemoreceptors:
• Class Phasmidia – possesses caudal chemorecep- Modes of Transmission
tors called phasmids The parasitic nematodes can be transmitted to humans
• Class Aphasmidia – lacks caudal chemorecep- and animals in a variety of ways.
tors
• Examples include: Trichinella, Trichuris and Ingestion
Capillaria Embryonated egg/ova (may be acquired from contaminated
• Some nematodes also possess anterior or cephalic food, drinks, or unwashed hands).
sensory organs called amphids. • Ascaris lumbricoides
• The appearance of the esophagus also confers • Trichuris trichiura
terms for the nematodes. If the esophagus is uni- • Enterobius vermicularis
form throughout, the type is called filariform. If the
esophagus expands posteriorly into a bulb with a Larva
valve mechanism, it is referred to as rhabditiform. • Capillaria philippinensis
• Nematodes have longitudinally oriented muscles • Angiostrongylus cantonensis
important for locomotion. There are three types of • Trichinella spiralis
musculature of nematodes: (a) polymyarian (more
than five rows of cells), (b) meromyarian (between Skin penetration
two to five rows), and (c) holomyarian (less than • Strongyloides stercoralis
two rows) (Garcia, 2016). • Hookworms
135
Inhalation • Fertilized
• E. vermicularis • Round or oval.
• With albuminoid coat (stained golden brown by
Transmammary bile).
• S. stercoralis • Unfertilized
• Ancylostoma duodenale • Longer and narrower.
• Both the inner shell and outer albuminoid coat
Vectors may be thin.
• Filarial worms • If solely found in stool, this suggests infection by
only female Ascaris.
• Layers
INTESTINAL NEMATODES • Outer: mammillated, albuminous layer (coarse).
Ascaris lumbricoides • If present: corticated
• Common name: Giant intestinal roundworm. • If absent: decorticated (resembles hookworm
• Most common intestinal nematode. eggs).
• Largest intestinal roundworm. • Middle: glycogen layer
• The requirement for high temperature and high • Present in both fertilized and unfertilized
humidity confines distribution of Ascaris to tropical eggs.
and subtropical regions only. • Inner: lipoidal, vitelline layer
• Life span: Ascaris adult is not a long-lived worm and • Absent in unfertilized eggs.
usually dies in about a year. • Egg resemblance:
• Soil-transmitted helminthes. • Fertilized decorticated egg: Hookworm egg
• Final host: man. • Unfertilized decorticated: Trichostrongylus spp.
• Habitat: small intestine.
General morphology • Infective stage: embryonated egg
Adults Embryonation takes about 2-3 weeks in favorable
• Creamy-white to pink in color. conditions.
• Polymyarian muscle arrangement. • Diagnostic stages: ova (fertilized or unfertilized) in
• Mouth: trilobate lips. stool, adult worm.
• Cuticle: with fine circular striations. • Mode of transmission: ingestion of embryonated
• Females: egg. 2-3 months after ingestion of eggs, the mature
• 20 to 35 cm in length. worms start laying eggs in the intestinal tract.
• Two sets of reproductive organs.
• Pointed or straight tail. Diagnostic tests
• Oviparous: Mature female worms have been es- • Direct fecal smear (DFS).
timated to produce an average of 200,000 eggs/ • Kato–Katz stool examination.
day. • Concentration techniques (Formalin Ether/Ethyl
• Males: Acetate Concentration Technique, Merthiolate Io-
• Seldom longer than 30 cm long. dine Formaldehyde Concentration Technique, Brine
• Slenderer flotation, Zinc sulfate flotation).
• Incurved tail with two spicules. • Radiography (as worm-shaped radiolucent areas in
barium-filled intestine).
Eggs • Cholangiograms.
• Unsegmented when passed.
• After embryonation occurs in the soil, the embryo- Pathogenesis
nated egg act as the infective stage. • Bowel obstruction with fever and malaise.
• Two to three weeks outside the host to develop to • Vomiting
the infective stage. • Pneumonitis during larval migration to the lungs
• Killed by excessive heat and dryness. (Loeffler syndrome). Asthma which developed
• Remain viable in moist soil. among nonasthmatics who travelled in an area with
• Hatch in the duodenum. poor sanitation may be associated with Ascariasis.
CHAPTER 5 Phylum Nemathelminthes: Roundworms 137
FIG. 5.1 Life cycle of Ascaris lumbricoides.
• Intestine perforation. Infection with intestinal helminthes has been found

• Occlusion of the appendix. to protect against severe inflammatory diarrhea.
• Lactose maldigestion or intolerance (moderate Asca- • The possible protective mechanism may be the pro-
ris infection). duction of antimicrobial substances by the worms
• Eosinophilia during period of tissue migration or the increase in mucosal resistance through mod-
(present: Charcot-Leyden crystals). ulation of the mucosal immune response.
• Increased IgG and IgE. • Infection with intestinal helminthes has also been
• Ectopic migration to extraintestinal sites: pancreas, used as an experimental remedy for inflammatory
bile ducts, gall bladder, liver, esophagus, lungs. bowel disease (Wickelgren, 2004).
Treatment Eggs
• Drug of choice: Albendazole. • 50 to 60 µm in length, 20 to 32 µm in width.
• Mebendazole, Thiabendazole, Pyrantel pamoate. • Plano-convex, lopsided, D-shaped (asymmetrical).
• Mass treatment with ivermectin was an effective means • Thick, translucent shell.
of reducing the prevalence of intestinal helminthic dis- • The flattened appearance, reduced size, and the
eases in a poor community in northeast Brazil. thick shell distinguish the egg from a hookworm.
• Eggs may be found in the stools (in 5% of the cases),
Epidemiology but this is exceptional, as the females ordinarily do
• Ascariasis affects more of the world’s popula- not oviposit until they leave the intestinal tract.
tion than any other parasitic disease—perhaps as • Fully embryonated and infective within a few hours
many as 1.3 billion persons. While cosmopolitan after deposited (4-6 hours).
in distribution, it is more prevalent in areas of • Live longest under conditions of high humidity and
poor sanitation and where human feces are used moderate temperature.
for fertilizer. Ascaris eggs are able to survive for • Reinfection of patient by contamination of the hands.
some months in fecal matter, sewage, or even in • Development into adult worms requires about
the 10% formalin solution used for stool preser- 6 weeks.
vation! • Eggs may survive for some days in dry dust and air-
• The swine ascarid, Ascaris suum, is distinct from A. borne eggs may infect a person.
lumbricoides but can infect humans and even cause • Retroinfection – a type of autoinfection involving mi-
intestinal obstruction. gration of hatched embryonated eggs in the perianal
area back into the rectum and large intestine.
Enterobius vermicularis • 2 layers
• Common names: Pin worm, Society worm, Seat • Outer: albuminous covering (for mechanical
worm. protection).
• Other name: Oxyuris vermicularis. • Inner: lipoidal membrane (for chemical protec-
• Most common helminth parasite of temperate regions tion).
and crowded indoor living. • Obtained through perianal swab.
• Life span: one to two months. • Causes pruritus ani (perianal itching).
• Only one host: man.
• Habitat: large intestine (cecum). Life cycle (Fig. 5.2)
• Infective stage: embryonated egg.
General morphology • Diagnostic stages: ova (perianal swab), adult worm.
Adults • Mode of transmission: ingestion of embryonated egg,
• Light yellowish white. retroinfection (autoinfection), inhalation.
• Meromyarian muscle arrangement. • Eggs have been associated with the existence of Di-
• Distinct cephalic alae (lateral cuticular expansions entamoeba fragilis, a flagellate.
or lateral wings).
• Possesses an esophageal bulb (flask-shaped). Diagnostic tests
• Inhabit the cecum and adjacent portions or large • Direct fecal smear (low survival in stool).
and small intestines. In 6 weeks time, adult will de- • Cellulose tape swab (perianal swab).
velop. • Best time for collection: early in the morning be-
• Females: fore defecation, taking a bath, and urination (for
• 8 to 13 mm in length. females).
• Long, thin, sharply pointed tail. • A drop of TOLUENE may be added on the slide
• Migrate down to the anus at night and deposit prior to placing the scotch tape after swabbing. It
their eggs. allows greater visibility of the egg by displacing
• Die after oviposition. air bubbles, clearing epithelial cells, and dissolv-
• Lays approximately 15,000 eggs. ing adhesive materials.
• Males: • Swellengrebel (use of pestle).
• Inconspicuous in terms of size. • At least 5-7 consecutive swabs before one declares a
• 2 to 5 mm in length. negative diagnosis.
• Curved tail with a single spicule. • Nail clippings alternatively maybe examined for di-
• Die after copulation. agnosis.
FIG. 5.2 Life cycle of Enterobius vermicularis.
• Recovered adult worms maybe placed in alcohol for • Ectopic deposition of eggs in the liver and lung
further examination. have also been reported. Appendicitis and salpin-
gitis (inflammation of uterine tubes) have been re-
Pathogenesis ported.
• Nocturnal pruritus ani.
• Local irritation of the vagina (migration from the anus).
Treatment
• Inflammation of the intestinal wall.
• Drug of choice: Albendazole.
• Formation of granulomas around eggs or worms (in
• Mebendazole, Pyrantel pamoate.
the peritoneal cavity) which may cause chronic pel-
• Warm tap water enemas.
vic peritonitis.
Epidemiology • Transparent, protuberant bipolar mucus plugs (re-

• Spread of pinworm infection is no doubt facilitated fractile or intralaminar prominences).
by crowded indoor living in temperate climates, but • Nonstriated border.
it is also common in the tropics. Less attention is • Football-, barrel-, lemon-, Japanese lantern-shaped.
paid to pinworm in tropical areas, probably because • Prone to desiccation.
of the relative prevalence of more important para- • Resembles Capillaria philippinensis ova.
sites. • 3000 to 7000 eggs are produced daily.
Trichuris trichiura Life cycle (Fig. 5.3)

• Common name: Human Whip worm. • Infective stage: embryonated egg.
• Other name: Trichocephalus trichiura. • Diagnostic stage: ova.
• Life span: 4 to 8 years. • Mode of transmission: ingestion of embryonated egg.
• Only one host: man.
• Habitat: large intestine. Diagnostic tests
• Generic name: Trichuris ~ hair tail. • Direct fecal smear.
• Kato–Katz stool examination.
General morphology • Zinc flotation method: extremely efficient in dem-
Adults onstration of eggs.
• 3 to 5 cm long.
• Holomyarian muscle arrangement. Pathogenesis
• Anterior: • Larvae lodge temporarily in the small intestine. Af-
• 3/5 of the body. ter a period of growth, larvae pass to the cecal area,
• Thin, slender, attenuated (appears the “lash” of a where they attach themselves permanently with their
whip). attenuated anterior ends embedded in the mucosa.
• Almost colorless. • Ault attaches and buries its anterior end in the intes-
• With narrow, reduced esophagus resembling tinal mucosa in a pin-fashion manner.
string of beads. • In heavy infections, worms may be found as far
• Posterior: down as the rectum.
• 2/5 of the body. • Abdominal pain and distention (heavy infection).
• Thick, robust. • Asymptomatic (light infection).
• Resembling handle of a whip (appears the • Rectal prolapse.
“stock” or handle of a whip). • Anemia and moderate eosinophilia (heavy infection).
• Pinkish gray. • Nutritional deficiency.
• Contains intestines and single set of reproductive • Bacterial infection.
organs. • Appendicitis
• Females: • Blood loss: 0.005 ml per worm per day.
• Larger than males. • Infection of 200 worms or more may cause chronic
• Whip-like appearance. dysentery, profound anemia, and growth retardation.
• Bluntly rounded at the posterior end.
• Single uterus and single ovary. Treatment
• Vulva open at the anterior end. • Drug of choice: Albendazole.
• Males: • Mebendazole
• Coiled caudal extremity (of about 360 degrees or • Loperamide HCl (Imodium) increases contact time
more). between drug and parasites in diarrheic patients.
• Single lanceolate spicule with a spiny retractile
penile sheath. Epidemiology
Prevalence and intensity of whipworm infection vary
Eggs greatly with the level of sanitation and scarcity of water
• Passed unsegmented. supply. Where defecation onto the soil takes place or
• Require a period of 10 days or more outside the where human feces are used for fertilizer, prevalence
body to become infective. rates are high—as high as 50% to 80% in some parts
• Shell is digested in the small intestine. of Asia. In North America, whipworm infection is seen
FIG. 5.3 Life cycle of Trichuris trichiura.
primarily in rural areas of the southeastern states and in - 1963 - Bacarra, Ilocos Norte, Philippines
immigrants from tropical areas. - Male Patient from Philippine General Hospital
died 3 days after admission due to malabsorp-
Capillaria philippinensis tion syndrome (3 weeks of intractable diarrhea)
• Common name: Pudoc worm. - First recovered by Nelia G. Salazar and this find-
• Historical Note (Chitwood, Velasquez and Salazar, ing became the first proven case of human intes-
1968) tinal capillariasis.
- 1967 - Tagudin, Ilocos Sur, Philippines • Peanut- or guitar-shaped.

- Full medical attention was given due an epidemic. • Ingested by freshwater and brackish-water fish
• Belong to the superfamily Trichinelloidea (with (where larvae develop).
Trichuris and Trichinella).
• Characterized by a thin, filamentous anterior end Life cycle (Fig. 5.4)
• Final/incidental host: man. • Larvae retained in the gut lumen and which develop
• Natural host: Migratory birds (fish-eating). into adults cause hyperinfection and autoinfection.
• Intermediate host: Brackish and freshwater fish • Fish-eating birds are the natural hosts of C. philip-
(guppy, common names of local freshwater fish: pinensis.
Bagsang, Birot, Bactu, Ipon, Bagsit). • Humans are considered incidental hosts.
• Habitat: small intestine. Infective stage: larval stage in the infected fish.
• Zoonotic disease (animal-transmitted). Diagnostic stage: ova.
Mode of transmission: ingestion of raw or under-
General morphology cooked fish containing the larva.
Adults
• 4 to 5 mm long. Diagnostic tests
• live primarily in the jejunum. • Direct fecal smear.
• Females: • Concentration techniques.
• Measure 2.3 to 5.3 mm in length.
• Contains eggs in its body (gravid). Pathogenesis
• Body is divided into two equal parts. • Mystery disease or Pudoc disease: intestinal capilla-
• Anterior: esophagus, esophageal glands. riasis.
• Posterior: intestine, reproductive organs with • Villi are flattened or completely obliterated.
slightly prominent vulva. • Abdominal pain.
• 2 types: • Borborygmi: gurgling sound of the stomach.
• Typical female • Severe diarrhea.
• oviparous: lays unembryonated egg (8- • Electrolyte imbalance.
10) which appears peanut or guitar shape • Hypoproteinemia.
which lines up in a single row. • Intestinal malabsorption.
• Atypical female: (responsible for cases of au- • Autoinfection can occur.
toinfection) • Ovoviviparous females may produce embryo-
• ovoviviparous (oviviparous) nated eggs which hatch larvae and reinvade
- lays embryonated or multisegmented eggs intestinal mucosa leading to internal autoin-
(40-45) observed in multiple rows (2-3) fection.
and usually hatches within the human host
• larviparous Treatment
- this type is common among the first genera- • Drug of choice: Mebendazole.
tion female which lays first a larva. How- • Albendazole.
ever, eventually, it produces a typical egg. • High protein diet and electrolyte replacement.
• Males:
• Measure 1.5 to 3.9 mm in length. Epidemiology
• Caudal alae. • It reached epidemic proportions (1400 cases and 95
• Single spicule with unspined sheath. deaths) from 1967 to 1970.
• Slender than female. • Since 1973, there has been a considerable decline in
• Stichosome: esophageal structure with rows of se- incidence of the infection, perhaps because of suc-
cretory cells called stichocytes. cessful treatment and, with fewer eggs contaminat-
ing the surrounding waters, a decrease in the num-
Eggs ber of infected fish.
• 45 by 21 µm. • It also occurs elsewhere in the Philippines and
• Develop outside the host. in Thailand, and there have been scattered re-
• Thick and pitted shell. ports from Taiwan, Japan, Korea, Egypt, Iran, and
• Flat, bipolar mucus plugs. Colombia.
FIG. 5.4 Life cycle of Capillaria philippinensis.
• Two other capillarias cause rare human infections: Ancylostoma duodenale

C. hepatica, causing hepatic capillariasis, and C. • Only hookworm of Europe and the areas border-
aerophila, causing pulmonary capillariasis. ing the Mediterranean, of the west coast of South
America, and of parts of India and China.
HOOKWORMS • Grayish white or pinkish.
• Blood-sucking nematodes causing anemia. • Head has a slight bend in relation to the rest of the
• Attach to intestinal mucosa. body.
• Soil-transmitted helminthes. • Females:
• Capable of heart-lung migration. • Longer and stouter.
• Meromyarian muscle arrangement. • Egg output/day: 25,000–30,000 (Beaver, et al,
• Only one host: man. 1984) 10,000–30,000 (Hotez and Pritchard,
• Habitat: small intestine. 1995).
• Males: Larval stages

• Measure 1.0 cm by 0.5 mm. • L1: Rhabditiform (feeding stage).
• Prominent copulatory bursa. • Mouth: open.
• Life span: 1 to 5 years. • L3: Filariform (infective stage)
• Mouth: closed.
Necator americanus • Live in the upper layers of the soil.
• Important agent of “laziness” among poor Ameri- • When the soil is cool and moist, they climb to
cans and “tropical anemia” among Puerto Ricans the highest point covered by a film of moisture.
(Beaver, 1984). • They extend their bodies into the air until driven
• Prevalent over large portions of the Western Hemi- down by drying or heat, or until they come in
sphere. contact with the skin of a host.
• Introduced from Africa with the slave trade.
• Only hookworm found in North America and large Eggs
areas of South America. • 56 to 60 µm long by 36 to 40 µm wide.
• Native hookworm of Africa south of the Sahara. • Unsegmented when passed.
• Resemble but are slightly smaller than Ancylostoma. • Shell is thin and colorless.
• Head is sharply bent in relation to the rest of the • Bluntly round edges.
body, forming a definite hook shape at the anterior • Presence of developing blastomeres.
end. • Indicates 2 to 8 cell stages
• Females: • A. duodenale and N. americanus eggs are identical.
• 1 cm long.
• Egg output/day: 5,000–10,000 (Hotez and Life cycle (Fig. 5.5)
Pritchard, 1995). • In penetrating the skin, the larvae may cause an
• Males: allergic reaction known as ground itch. This is less
• 5 to 9 mm in length. common with Ancylostoma than with the New World
• Prominent copulatory bursa. hookworm, N. americanus.
• Life span: 3-5 years (Hotez and Pritchard, 1995). Infective stage: L3 – Filariform larva.
• Transport host: Pigs (Steenhard, et al., 2000). Diagnostic stage: ova.
Point of Ancylostoma Necator Diagnostic tests

Differences duodenale americanus • Direct fecal smear.
• Concentration techniques.
Common Old world hookworm New world
name hookworm /
• Kato–Katz.
American • Harada–Mori.
hookworm / • Recovery of larval stage.
American murderer • Requires filter paper to which fecal material is
or killer added and then inserted into a tube.
Mode of Skin penetration, Skin penetration • Moisture needs to be maintained by adding
transmission oral, transmammary, boiled or distilled water.
transplacental • Incubation period: 10 days.
Curvature C-shaped: Head is S-shaped: Head is • Suitable incubation conditions will favor hatch-
continuous as the curved opposite to ing of ova.
curvature of body the curvature of the • Once the larva is cultured up to the filariform
body stage, the movement of the larva inside the tube
Dental Two pairs of teeth Semilunar cutting can determine whether it is a hookworm larva or
pattern plates a Strongyloides larva.
• Hookworm filariform larva will generally
Spicule Plain and bristle-like Fused and barbed
move downwards against the upward capil-
Male bursa Bell-shaped Fan-like lary movement of the water and can be recov-
Dorsal rays Tripartite / Tridigitate Bipartite / Bidigitate ered from the water at the bottom of the tube.
Others A. duodenale is slightly larger than • Strongyloides larva may instead move upwards
N. americanus and more likely to bring about and accumulate at the upper end of the filter
iron deficiency anemia. paper strip (Belizario and De Leon, 2015).
FIG. 5.5 Life cycle of hookworms.

Pathogenesis • Cutaneous larva migrans or creeping eruption.

• 3 phases: cutaneous, pulmonary and intestinal. • Intense pruritus.
• Attach by means of their stout mouth to the intesti- • Secondary bacterial infection due to scratching.
nal mucosa. • Treatment
• Suck blood and tissue juices out of the host. • Drug of choice: Albendazole.
• Anemia (microcytic, hypochromic). • Ivermectin, thiabendazole (for lesions).
• Blood loss (Roberts and Janovy, 2013) N. ameri-
canus (0.03 ml/day) A. duodenale (0.26 ml/day). Ancylostoma braziliense
• Eosinophilia • Cat hookworm.
• Hypoproteinemia • Infects both cats and dogs.
• Ground/dew/Coolie itch (dermatitis or urticarial re- • One or two pairs of ventral teeth.
action at the site of larval penetration). • Trapped larvae of A. braziliense may survive for some
• Pneumonitis (Wakana disease, pulmonary phase). weeks or even months, migrating through the sub-
• Gastrointestinal discomfort/pain and diarrhea (in- cutaneous tissues.
testinal phase). • Most common cause of CLM in southeastern United
• Increased flatulence. States and New World Tropics (Hotez and Pritchard,
• Nausea, vomiting. 1995).
Treatment Ancylostoma caninum

• Drug of choice: Albendazole. • Dog hookworm.
• Mebendazole, Pyrantel pamoate. • Three pairs of ventral teeth.
• Ferrous sulfate (200 mg) three times daily for severe • Trapped larvae of A. caninum encyst and remain
infections until about 3 months after the hemoglo- dormant in skeletal muscle after a shorter cutaneous
bin value returns to normal. migratory period.
• Produces an abortive infection in humans, in which
Epidemiology the larvae, unable to complete their life cycle, mi-
• Because initial infection occurs through the skin, grate through the subcutaneous tissues.
prerequisite to widespread hookworm infection • Rarely, it can complete its cycle and establish an in-
is a population whose significant parts of which testinal infection.
defecate directly onto the soil and do not customar- • Most common hookworm of domestic dogs (Hotez
ily wear shoes, at least during part of the year. and Pritchard, 1995).
• Additional factors include appropriate ambient
temperature, sufficient rainfall, and a loose sandy Ancylostoma ceylanicum (Beaver et al., 1984)
loam soil. • Observed from the intestine of a civet cat from Cey-
• These conditions limit areas of endemicity primarily lon, (Sri Lanka) and in other carnivores.
to the tropics and subtropics, although they extend • Mistaken as A. braziliense.
into some more temperate zones. • Presence of 2 pairs of ventral teeth: larger outer pair
• Paratenic host: rabbits, lambs, calves, pigs. and smaller inner pair whose tip can be seen pro-
truding out from the middle buccal cavity.
Cutaneous larva migrans • Human case reported in the Philippines (Velasquez
• Caused by animal hookworms Ancylostoma brazil- and Cabrera, 1968).
iense and Ancylostoma caninum
• If humans come in contact with infective larvae of Strongyloides stercoralis
the dog or cat hookworms A. braziliense or A. cani- • Common name: Thread worm.
num, penetration of the skin may take place, but the • Smallest nematode of man.
larvae are then usually unable to complete their mi- • Capable of heart-lung migration.
gratory cycle. • Only one host: man.
• Common in the same tropical and subtropical re- • Habitat: small intestine.
gions where human hookworms complete their life • Mode of living: facultative (free-living or parasitic).
cycle • Soil-transmitted helminth.
• Common in sandy beaches or children’s sandboxes • When environmental conditions are optimal, S. ster-
• Pathogenesis: coralis exist for some time as free-living nematode.
General morphology • Aside from invading the intestinal mucosa, the

Adults larva can reinfect the host by being passed out
• 1 mm long. in the feces and penetrating the host on reaching
• Females: the perianal or perineal skin.
• Slightly over 2 mm. • Rhabditiform larvae that pass out of the host in the
• Lay eggs in the mucosa of the intestinal tract. stools may also transform into filariform larvae di-
• Parthenogenetic: can self-fertilize without male. rectly, without developing into free-living adults.
• Most commonly found in the jejunum. Infective stage: L3 – Filariform larva.
• Males: Diagnostic stage: L1 – Rhabditiform larva.
• If indeed they exist, they are eliminated from the Mode of transmission: skin penetration, autoinfection.
body early in the infection.
• Have 2 spicules and no caudal alae. Diagnostic tests
• They have not been reliably identified, only para- • Direct fecal smear
sitic females that are able to reproduce through • With severe diarrhea, embryonated eggs may be
parthenogenesis are said to exist. present in stool and can be differentiated from
hookworm eggs by the fact that they always con-
Larval stages
tain well-developed larvae.
• L1: Rhabditiform (feeding stage).
• Concentration techniques for larva (zinc sulfate)
• L3: Filariform (infective stage).
• Baermann technique
The larval stages of hookworms and S. stercoralis can
• Beale’s string test
be differentiated by various characteristics.
• Entero test
L1 Hookworm Strongyloides • Harada–Mori culture
Buccal capsule Long Short • ELISA
Genital primordium Small Prominent
L3 Hookworm Strongyloides
Pathogenesis
• Capable of autoinfection.
Esophagus Short Long
• Vietnam/Cochin China diarrhea.
Tail Pointed Notched/forked • Honeycomb appearance of intestinal mucosa.
Sheath Sheathed Unsheathed • Intestinal ulcerations caused by embedded eggs.
• Villi atrophy
Eggs • Lesions resembling ground itch.
• Similar in appearance to those of hookworms. • Pneumonitis (larva may be found in sputum).
Life cycle (Fig. 5.6) • Malabsorption with steatorrhea.
• The eggs, similar in appearance to those of hook- • Duodenal ulcer/ulcerative colitis.
worms, hatch in the mucosa and liberate rhabditi- • S. stercoralis is an opportunistic parasite.
form larvae, which make their way to the lumen of • Debilitated or immunocompromised patients
the intestine. should always be suspected of having strongyloi-
• The larvae may feed and molt once before being diasis, particularly if they experience unexplained
passed in the feces. bouts of diarrhea and abdominal pain, repeated
• When they molt within the intestinal tract, they usu- episodes of sepsis or meningitis with intestinal
ally retain their rhabditiform characteristics but may bacteria, or unexplained eosinophilia.
transform into infective filariform larvae. • The mortality rate in immunocompromised pa-
• If filariform larvae are formed, they may penetrate tients is over 80%.
immediately into the wall of the gut and enter the • Patients with a drug-induced immunocompro-
bloodstream, where they begin the same types of mised state (corticosteroids), lymphoma, malig-
migratory cycles as the larvae that penetrate the skin nancy, or other condition that causes T-cell deple-
from the soil. tion can develop severe infections, referred to as
• Autoinfection, which involves development of disseminated strongyloidiasis or hyperinfection.
filariform larvae in or on the body may account • Hyperinfection syndrome
for continued infection 30 to 40 years after the • Gastrointestinal tract and lungs are in-
host has left the original area where the infection volved.
is endemic. • May cause severe debilitation or death.
FIG. 5.6 Life cycle of Strongyloides stercoralis.
• Disseminated strongyloidiasis. Treatment

• Involves other organs such as the liver, • Albendazole and Ivermectin
heart, adrenals, pancreas, kidneys, or CNS.
• Seen in immunocompromised patients Epidemiology
(with HTLV-I or AIDS). • Strongyloidiasis occurs in much the same tropical
• Larva currens: strongyloid track that advances much and subtropical areas of relatively heavy rainfall as
faster (5–10 cm/hour) than that of the dog hook- does hookworm infection, though prevalence rates
worm. seem generally lower.
• It differs importantly from hookworm infection in • Raccoons (Procyon lotor) and nutria (Myocastor coy-
that, while the infection dies out over a period of pu) are common in these swamps; each is infected
some years in persons with hookworm infection with its own species of Strongyloides.
who have moved from an endemic area, strongy- • S. myopotami of nutria and S. procyonis of rac-
loidiasis may persist by virtue of autoinfection, and coons, and larvae of both, are abundant in swamp
prolonged absence from an endemic area is no guar- waters.
antee of freedom from infection. • Application of larvae of either species to the skin of
a human volunteer produces creeping eruptions es-
Strongyloides fuelleborni sentially identical to those accompanying S. stercora-
• A parasite of monkeys which also infects humans. lis infection.
• Common in infants under 6 months of age.
• Found in Central Africa and Papua New Guinea. Trichostrongylus spp.
• Zoonotic • This genus contains a number of species that are
primarily parasites of herbivores and are found
General morphology
throughout the world.
• S. fuelleborni differs morphologically from S. sterco-
• Human infections have been reported on occasion
ralis in some minor respects.
from many regions and are accidental.
Larva
• Larvae have been found in the milk of nursing General morphology
mothers. Adults
Eggs • Related to the hookworms, and the adults are rather
• Its eggs (and not larvae) are found in the feces. similar in appearance.
• The various species reported from humans are
Pathogenesis smaller than the hookworms.
• Swollen belly sickness Eggs
• Abnormal distention, respiratory distress, gener- • Identification of the various species of Trichostrongylus
alized edema, and hypoproteinemia. from the eggs is difficult, but differentiation of the eggs
• Swamp itch from those of hookworm can be readily accomplished.
• Symmetrical and thin shelled.
Epidemiology • Larger than hookworms (73–95 µm by 40–50 µm).
• In Papua New Guinea and at least one area of Irian • Have more pointed ends.
Jaya, a subspecies, S. fuelleborni kellyi, not only dif- Infective stage: L3 – filariform larva.
fers from the African worm in minor details of mor- Diagnostic stage: ova.
phology, but produces in some infants a syndrome Mode of transmission: ingestion of larva from con-
not known in other types of strongyloidiasis. taminated vegetation (Beaver et al., 1984).
• While S. fuelleborni in Africa has a primate reservoir,
there are no nonhuman primates in Papua New Pathogenesis
Guinea, and no areas of S. fuelleborni infection be- • Trichostrongylus spp. ingest blood.
tween the two localities. • Larvae do not undergo pulmonary migration but,
• While larvae of S. fuelleborni are found in the when swallowed, attach themselves to the intestinal
milk of at least some African mothers with this mucosa.
infection, extensive efforts have failed to reveal • Principally zoonotic but human to human infection
evidence of transmammary transmission in Papua may happen due to the use of human excreta as fer-
New Guinea. tilizers.
Zoonotic strongyloidiasis/creeping eruption Treatment
• Bearing an interesting relationship to “swimmer’s • Drug of choice: Mebendazole.
itch” caused by penetration of the skin by avian
schistosome cercariae, the “swamp itch” seen in Epidemiology
hunters, trappers, and oil workers exposed to the • Trichostrongylus orientalis is fairly common in Japan,
swampy waters of the Mississippi River delta in Korea, China including Taiwan, and Armenia.
southern Louisiana is considered to be a zoonotic • A number of other species infecting humans have
infection. also been reported from the former Soviet Union.
FIG. 5.7 Life cycle of Anisakis.
Anisakis spp. cal importance are parasites of marine mammals

• Common name: Cod worm, Herring worm. (seals, sea lions, whales, and dolphins).
• Final host: marine mammals. • Eggs, passed in the feces of the mammalian host,
• Paratenic host: fish and squids. hatch to liberate larvae, which may then be ingested
• Accidental host: humans. by marine crustaceans.
• Intermediate host: microcrustaceans. • In these crustaceans the larvae grow and molt, and
• Types of anisakid larvae: Anisakis, Pseudoterranova, if the crustacean is then eaten by fish or squid, the
Contracaecum. contained third-stage larvae are liberated to pen-
etrate into the body cavity or muscles of that host.
Life cycle (Fig. 5.7) • The fish or squid acts as a transport, or paratenic, host, in
• Adult anisakids are parasites of the gastrointestinal which the larvae may grow but do not molt to become
tract of a wide variety of animals, but those of medi- adults. If, as is often the case, the first transport host is in
turn ingested by a larger fish or squid, the larva contin- • In fish frequently consumed raw on the Pacific
ues to infect the new host. In this manner, fish at the top coast, the prevalence of anisakid worms may be
of the food chain may become very heavily infected. higher than 80%.
• When these fish are eaten by marine mammals, the
larvae develop into adult worms. UNCOMMON INTESTINAL NEMATODES
• If infected fish are consumed, either raw or improp- Eustrongylides spp. (Wittner et al., 1989)
erly prepared, by humans, the larvae are unable to • Parasitic as an adult in various wading birds,
complete their development and attempt once again • The larvae of various species of Eustrongylides are
to adapt to a paratenic host. found in fish.
Infective stage: L3 Larvae. • Four instances of human infection have involved
Diagnostic stage: demonstration of larva. fishermen who consumed live bait minnows,
Mode of transmission: ingestion of raw or under- • Eustrongylides is closely related to Dioctophyma renale,
cooked seafood containing the larva. the giant kidney worm of carnivores and mustelids.
Diagnostic tests Gongylonema spp. (Eberhand and Busillo, 1999)

• Demonstration of worms by gastroscopy, surgery, or • Cosmopolitan parasites of ruminants.
vomiting. • Threadlike nematodes found in swine, bears, hedge-
• If vomited larvae are well preserved, they may be hogs, monkeys, and occasionally humans. The adult
cleared in glycerin and identified by the structure of worm migrates within the wall of the duodenum,
the digestive tract, which differs in the three types of stomach, esophagus, and (in humans) the buccal
anisakid larvae. cavity.
• Intermediate hosts are cockroaches and other in-
Pathogenesis sects, and human infection must be the result of
• Abdominal pain ingestion of these insects or of water containing the
• Tingling throat syndrome larval stages derived from disintegrating insects.
• Nausea
• Vomiting Oesophagostomum spp. (Storey et al., 2000;
• Diarrhea de Gruijter et al., 2004)
• Peritoneal irritation • These worms are parasitic in ruminants, pigs, and
• Eosinophilic granulomatous reaction monkeys in China, the Philippines, Indonesia, and
• Thickening of the intestinal wall Africa.
• The worms resemble hookworms; their eggs are in-
Treatment/Prevention distinguishable.
• Gastroscopic removal of the worm • Larvae develop in the soil, and when ingested, by
• Albendazole both their human and animal hosts, penetrate the
• Fish kept frozen at –20˚C for at least 5 days are intestinal wall, where some develop rapidly into
considered safe for consumption in dishes such as adults and reenter the intestine.
sashimi, sushi, ceviche, and poisson cru. • Other remain in an immature state for long periods,
• When fish are iced (but not frozen) for transpor- forming nodules in the intestinal wall, the omen-
tation to harbor processing plants, larvae tend to tum, or even the abdominal wall.
migrate from the gut into the muscles. • The unilocular disease, referred to as “Dapaong tu-
• Smoking fish kills the parasites only if the tempera- mor” or as “turtle in the belly” by indigenous heal-
ture of the flesh reaches 65˚C during the process (a ers, is a painful abdominal mass that frequently
temperature not achieved by all types of smoking). adheres to the abdominal wall.
• In some species, such as herring, if the fish are • The multilocular disease involves hundreds of pea-
cleaned promptly, the flesh will be free of larvae. sized nodules in the submucosa and subserosa of
the large intestine.
Epidemiology Acanthocephala
• The prevalence of larval anisakids in fish depends in • The Acanthocephala, or thorny-headed worms, while
turn on the prevalence of marine mammals, which superficially resembling nematodes, belong to their
is high in the North Sea, in Japanese and Alaskan own phylum.
coastal waters, and is increasing along the Pacific • Acanthocephalans are cylindrical worms with a
coast of North America. spiny proboscis.
• The adult worms possess no digestive tract, and all veloping further until ingested by their intermediate
are parasitic in the intestinal tract of vertebrates. host, an insect vector.
• Larvae require an arthropod as intermediate host, • In the insect, the microfilariae molt and grow, trans-
and some go through a juvenile stage in a second forming into infective larvae (L3), which are depos-
intermediate host ited on the skin when the insect next takes blood
• The vertebrate becomes infected by ingesting the from a suitable host.
first or second intermediate host.
• Moniliformis moniliformis is a rodent parasite of cos- Wuchereria bancrofti
mopolitan distribution. • Common name: Bancroft’s filarial worm.
• Male worms are 4 to 5 cm long, and females 10 • Widely distributed throughout the tropics and sub-
to 27 cm. tropics.
• Beetles and cockroaches are intermediate hosts. • Originated in Southeast Asia.
• Macracanthorhynchus hirudinaceus is a parasite of • Final host: man.
pigs, both domestic and wild. • Intermediate host: mosquitoes (Anopheles, Aedes,
• Adult worms are about twice the size of Moniliformis. Culex).
• Beetles serve as intermediate hosts of this parasite.
• Macracanthorhynchus ingens, a common intestinal General morphology
parasite of raccoons, has been reported from an in- Microfilariae
fant who presumably acquired it by ingesting an in- • Nucleus: regularly spaced.
fected beetle. • Sheath: sheathed (low affinity to Giemsa stain).
• Acanthocephalans, in addition to anisakid and eu- • The sheath is actually the egg shell.
strongylid nematodes, may be acquired by eating • Terminal nuclei: none.
sashimi. • Cephalic space length-width ratio: 1:1.
• Bulbosoma has a life cycle involving crustaceans as • General appearance: graceful.
first intermediate hosts, fish as a second intermedi- • No alimentary canal.
ate host; the adult worms are found in sea mammals • Bluntly rounded anteriorly.
such as whales. • Tapered posteriorly.
Adults
VECTOR-BORNE NEMATODES • Threadlike white worms.
Filariae • Males:
Generalities • 2.5 to 4 cm
• Long, threadlike nematodes. • Females:
• Inhabit portions of the human lymphatic system, • 5 to 10 cm.
subcutaneous, and deep connective tissues. • Habitat: lower lymphatic system.
• The adults of all species of filariae are parasites of
vertebrate hosts. Life cycle (Fig. 5.8)
• The adult female worms produce eggs within the • The mosquito is more than a simple agent of trans-
uterus that eventually hatch into microfilariae (high- mission of the parasite; an essential developmental
ly modified egg whose membrane may or may not cycle takes place within the body of the insect.
rupture). Egg membrane is differentiated to become • Upon taking blood from an infected person, the
the sheath and if it ruptures, it will make the micro- mosquito may ingest microfilariae. The microfi-
filaria naked or unsheathed (Beaver et al., 1984). lariae bore through the stomach wall to enter the
• Thus, females are considered ovoviviparous, pro- body cavity of the insect, where they migrate to the
ducing thousands of juveniles called microfilaria thoracic musculature for a period of growth. The
(Roberts and Janovy, 2013). larvae grow and molt to become infective-stage
• Presence or absence of a sheath the microfilarial larvae.
stage is a basis of differentiation. • The infective larvae enter the proboscis of the mos-
• Microfilariae, during their development, become quito and, when the next blood meal is taken, escape
elongate and wormlike in appearance. from the proboscis onto the skin. They enter through
• Microfilariae are generally capable of living for a the puncture hole left by the mosquito to infect their
long period within the vertebrate host but not of de- new host.
FIG. 5.8 Life cycle of Wuchereria and Brugia.
• Infective larvae gain access to the peripheral lym- Intermediate host/vector:

phatics and then to the regional lymph nodes and • Culex
larger lymph vessels, where they mature. If male and • Aedes
female worms are present in the same area, they • Anopheles
mate and microfilariae are produced. Infective stage to man: L3 – Filariform larva.
• The time necessary for the worms to grow to sexual Infective stage to vector: Microfilaria.
maturity is probably several months; adult worms Diagnostic stages: microfilaria in blood.
are known to live for some years. Mode of transmission: skin penetration through mos-
Periodicity: quito vectors.
• Nocturnal (10 pm to 2 or 4 am).
• Subperiodic (12 nn to 8 pm) throughout the Pa- Diagnostic tests
cific islands and Vietnam. • Demonstration of microfilaria in blood.
• When absent from peripheral circulation, the mi- • Examination of fresh blood film.
crofilariae are found primarily in the capillaries • Thick smear (20–60 µl of blood) if present in
and small vessels of the LUNGS. small numbers (Giemsa-stained).
• Reversal in patient’s sleeping pattern causes rever- • Diethylcarbamazine “provocative” test: stimulates
sal of periodicity so that microfilaremia becomes microfilaria to come out to the peripheral blood.
DIURNAL. This adaptive value of periodicity is • Concentration techniques
difficult to explain (Robert’s and Janovy, 2013). • Knott’s concentration technique.
• 1 mL of blood + 10 mL of 2% formalin. • An effective microfilaricidal drug, but it elimi-

• Centrifuge and then examine the sediment nates the adult worms more slowly.
(Giemsa-stained). • DEC + Ivermectin
• 2 drops of HCl may be used to hasten lysis. • Better long-term suppression of microfilaremia.
• Nucleopore filtration
• Use of filter paper. Epidemiology
• Residue: microfilariae remaining in the filter. • Night-biting Anopheles and Culex mosquitoes are
• Serology vectors of the nocturnally periodic W. bancrofti,
• Detection of circulating filarial antigens. whereas the subperiodic Pacific strain is carried by
• Skin test using an extract of Dirofilaria immitis. the daytime-biting Aedes polynesiensis.
• Radiography • As there are no reservoir hosts for this species, ende-
• Ultrasonography micity of the infection demands both an adequate
human reservoir and sufficient numbers of circulat-
Pathogenesis ing microfilariae in the blood of those infected.
• Lymphangitis and lymphadenitis. • In many areas, clinical infection appears to be more
• Funiculitis, epididymitis, orchitis (scrotal lymphat- common in males than in females.
ics). • Transmission is restricted to the more humid areas,
• Lymphedema and it is thought that this restriction may be a result
• Elephantiasis: disfiguring and disabling condition of the way in which invasion of the definitive host
marked by woody induration of tissues with thick- takes place. When infective larvae escape onto the
ening and verrucous changes of the skin. skin from the proboscis sheath of the biting mos-
• Hydrocele quito, they carry with them minute drops of mos-
• Chyluria (passage of lymph fluid in the urine) quito hemolymph, which protects the larvae from
• Scrotal lymphatics: preferential site for localization desiccation while they are finding and penetrating
of adult worms. the puncture wound left by the mosquito bite. In
• Amicrofilaremic states. less humid areas, this protection would be quickly
• Tropical pulmonary eosinophilia. lost.
• A syndrome characterized by persistent hype-
reosinophilia (greater than 3000 eosinophils Brugia malayi
per ul of blood), cough and wheezing with • Common name: Malayan’s filarial worm.
scanty production of sputum, and a variable • Primarily seen in southeast Asia.
x-ray appearance. • Final host: man.
• Microfilariae are not found in the peripheral • Intermediate host: mosquitoes.
blood, even by membrane filtration tech-
niques, but they may be found in biopsy spec- General morphology
imens from the lung and elsewhere. Microfilariae
• Meyers and Kouwenaar syndrome • 200 to 275 µm in length.
• Occult filariasis • Nucleus: irregularly spaced (overlapping).
• It is a hypersensitivity reaction to microfilarial • Sheath: sheathed (stained pink with Giemsa).
antigens. • Terminal nuclei: two.
• Characterized by: • Cephalic space length-width ratio: 2:1.
• Lymphadenopathy with splenomegaly. • General appearance: kinky.
• Pulmonary infiltrates. Adults
• Hypereosinophilia. • Smaller than W. bancrofti.
• Sowda: pruritic papular eruption where the skin • Habitat: upper lymphatic system.
is swollen and dark.
• Intraocular filariasis is an extremely rare condi- Life cycle
tion. Since eye has no lymphatics, entry to the • The life cycle of B. malayi is similar to that of W. ban-
eye is via hematogenous route. crofti.
Periodicity:
Treatment • Nocturnal (10 pm to 2 or 4 am).
• Diethylcarbamazine (DEC) • Subperiodic (12 nn to 8 pm).
Intermediate host/vector: General morphology

• Mansonia Microfilariae
• Anopheles • 310 µm in length.
Reservoir host: • Sheath: sheathed (does not stain deeply with
• Macaques (Macaca spp.) Giemsa).
• Leaf monkeys (Pesbytis spp.) • Body nuclei extend to the tip of the tail.
Infective stage to man: L3 – Filariform larva. • Cephalic space length-width ratio: 3:1.
Infective stage to vector: microfilaria.
Diagnostic stages: microfilaria in blood. Life cycle
Mode of transmission: skin penetration through Periodicity:
mosquito vectors. • Nocturnal (10 pm to 2 or 4 am).
Intermediate host/vector:
Diagnostic tests • Anopheles barbirostris
• Demonstration of microfilaria in blood. Infective stage to man: L3 – Filariform larva.
• Examination of fresh blood film Infective stage to vector: microfilaria.
• Thick smear Diagnostic stages: microfilaria in blood.
• Diethylcarbamazine “provocative” test Mode of transmission: skin penetration through mos-
• Concentration techniques quito vectors.
• Knott’s concentration technique
• Nucleopore filtration Treatment
• Serology • Diethylcarbamazine (DEC)
• Detection of circulating filarial antigens.
• Radiography Loa loa
• Ultrasonography • Common name: African eye worm.
• found throughout Sudan, Congo, and West Africa.
Pathogenesis • Final host: man.
• Lymphadenitis and lymphangitis • Intermediate host: Chrysops (Mango fly).
• Lymphedema • Habitat: subcutaneous tissue.
• Elephantiasis
General morphology
• Tropical pulmonary eosinophilia
Microfilariae
• 250 to 300 µm in length.
Treatment
• Body nuclei are continuous to the tip of the tail.
• Diethylcarbamazine (DEC)
• Present in the bloodstream.
• Ivermectin
• Albendazole Adults
• Present in subcutaneous and deeper connective
Epidemiology tissues.
• Some 30% of cases of the Malayan form of lym- • Males:
phatic filariasis occur in South China and 20% oc- • 2 to 3.5 cm long.
cur in India, while the rest are found in Indonesia, • Females:
Thailand, Vietnam, Malaysia, the Philippines, and • 5 to 7 cm long.
South Korea.
• The distribution of this species obviously overlaps Life cycle (Fig. 5.9)
that of W. bancrofti. Periodicity:
• Diurnal
Brugia timori Intermediate host/vector:
• First reported from the island of Timor in 1964. • Chrysops (Tabanid fly, deerfly, horsefly, mango
• Resembles bancroftian filariasis in its clinical expres- fly, mangrove fly)
sion, though the rate of abscess formation seems Infective stage to man: L3 – Filariform larva
higher. Infective stage to vector: microfilaria
• Final host: man. Mode of transmission: skin penetration through the Man-
• Intermediate host: mosquitoes. go fly.
FIG. 5.9 Life cycle of Loa loa.
Diagnosis • Urticaria
• History of Calabar swellings. • Lymphadenitis
• Appearance of worm in the conjunctivae (microfi-
lariae do not appear in the blood until years after Treatment
the worms become apparent). • Surgical removal of migrating adult worms
• Circulating microfilariae early in the disease. • Diethylcarbamazine (DEC)
• Ivermectin
Pathogenesis
• Migration of the adult worms through the tissues is Epidemiology
not painful and seldom is noticed unless they hap- • In hyperendemic areas, estimates of infection rates
pen to pass over the bridge of the nose or through in adults range from 9% to 70% of the population.
the conjunctival tissue across the eyeball. • Several species of African monkeys harbor a Loa that
• They can often be immobilized with a few drops of is morphologically indistinguishable from the L. loa
10% cocaine instilled into the eye and excised while of humans; the monkey strain exhibits nocturnal
passing through the conjunctiva. periodicity and is carried by a species of Chrysops
• Edema of conjunctiva and lids. that is arboreal and bites at night.
• Calabar swellings or fugitive swellings
• Patches of localized subcutaneous edema. Mansonella ozzardi
• May be several inches in diameter and are often • Only filaria parasitizing humans that is confined to
preceded by localized pain and pruritus. the New World.
• Hydrocele and orchitis • Final host: man.
• Intermediate host: Culicoides gnats (Biting • Body nuclei extend to the tip of the tail.
midges). • Tail is characteristically bent in the form of a shep-
• Habitat: mesenteries and visceral fat. herd’s crook.
General morphology Life cycle

Microfilariae Periodicity:
• Unsheathed • Nonperiodic
• Nonperiodic Intermediate host/vector:
• Found in the blood • Culicoides gnats (Biting midges)
• May be obtained by skin biopsy (confined to the Infective stage to man: L3 – Filariform larva.
capillaries). Infective stage to vector: microfilaria.
• Body nuclei do not extend to the tip of the tail. Mode of transmission: skin penetration through the Cu-
• Tail is shorter and less tapered than Onchocerca vol- licoides gnats.
vulus.
Adults
Diagnosis
• Skin biopsy
• Inhabit the mesenteries and visceral fat.
Life cycle Pathogenesis

Periodicity: • Pruritic dermatitis with hypopigmented macules.
• Nonperiodic • Inguinal adenopathy.
• Culicoides gnats (Biting midges). Treatment
• Others: Simulium blackfly (in the Amazon basin). • DEC
Infective stage to man: L3 – Filariform larva. • Ivermectin
Infective stage to vector: microfilaria.
Mode of transmission: skin penetration through the Cu- Mansonella perstans
licoides gnats. • Formerly known as Dipetalonema perstans.
• a common parasite of humans and apes.
Diagnosis • Intermediate host: Culicoides gnats (Biting
• Microfilariae in the blood midges).
• Skin biopsy
General morphology
Pathogenesis Microfilariae
• Generally an asymptomatic infection. • Unsheathed
• Inguinal adenopathy. • Found in the blood and in the skin.
• Pruritic and maculopapular skin lesions. • Body nuclei extend to the tip of the tail.
• Arthritis • Terminal nucleus or pair of nuclei is separated
• Marked eosinophilia. slightly from the other caudal nuclei.
• Tail is characteristically bent in the form of a shep-
Treatment herd’s crook.
• Asymptomatic cases do not require treatment.
• DEC apparently has no effect. Adults
• Ivermectin may be used in a single oral dose. • Habitat: deep connective tissues.
Mansonella streptocerca Life cycle

• Formerly known as Dipetalonema streptocerca. Periodicity:
• Found in both moneys and humans. • Nonperiodic
• Intermediate host: Culicoides gnats (Biting midges). Intermediate host/vector:
• Culicoides gnats (Biting midges).
General morphology Infective stage to man: L3 – Filariform larva.
Microfilariae Infective stage to vector: microfilaria.
• Unsheathed Mode of transmission: skin penetration through the
• Found primarily in the skin but also in the blood. Culicoides gnats.
Diagnosis Periodicity:
• Circulating microfilaria in the blood. • Nonperiodic
Pathogenesis • Simulium (black fly)
• Kampala or Ugandan eye worm. Infective stage to man: L3 – Filariform larva.
• The result of invasion of the conjunctiva or peri- Infective stage to vector: microfilaria.
orbital connective tissues by adult M. perstans. Mode of transmission: skin penetration through the black
• Calabar-like swellings, pruritus, hives, fever and fly.
headache.
• Bone and joint pains.
Diagnosis
• Lymphadenitis
• Skin snips
• Hydrocele
• Fold of skin may be squeezed between the thumb
Treatment and forefinger of one hand while a thin slice of
• Albendazole for 10 days is recommended skin is removed with a razor blade held in the
• DEC and Ivermectin seem ineffective other, or
• A needle may be used to catch and raise a small
Onchocerca volvulus cone of skin, which is then removed with scissors
• Common name: Blinding worm, Craw craw. or a razor blade.
• Widely distributed throughout Central Africa. • The tissue is then placed in saline and may be
• Final host: man. teased to facilitate liberation of the microfilariae,
• Intermediate host: Simulium (Black fly or buffalo gnat). or incubated for 4 hours in a culture medium such
• Habitat: subcutaneous tissue. as NCTC 135 in Hanks’ balanced salt solution.
• Mazzoti test
General morphology
Microfilariae Pathogenesis
• Unsheathed • Acute inflammatory reaction involving usually the
• 150 to 350 µm in length. face, eyes, ears, neck, or shoulders
• Migrate actively through the dermis and connective • Onchodermatitis.
tissues. • Mal morado or erisipela de la costa: patchy purplish or
• May be found in urine, blood, or sputum. reddish eruption.
• “Leopard skin” appearance in African patients (atro-
Adults
phy of the skin and lymphedema).
• Wire-like, whitish
• Sowda
• Coiled within fibrous tissue capsules.
• Hanging groin
• Males:
• Blindness
• Not more than 5 cm
• Wolbachia bacteria have been known to be endo-
• Females:
symbionts of filarial parasites. Soluble extracts of O.
• As long as 50 cm.
Volvulus were injected into the corneal stroma and
• Less than 0.5 mm in diameter.
it was observed that the predominant inflammatory
Life cycle (Fig. 5.10) response in the cornea was due to the endosymbi-
• Upon biting an infected person, the simuliid ingests otic Wolbachia.
microfilariae, which have a developmental cycle in the • Microfilaria maybe found in urine (microfilauria),
insect, transforming into infective forms that may enter blood (microfilaremia) and sputum samples after
a new host when the simuliid again takes a blood meal. DEC treatment.
• After introduction into the new host, the develop- • Craw-craw: localized lesions
ing worms wander through the subcutaneous tissues
but settle down, usually in groups of two or more Treatment
• Most worms finally become encapsulated. • Diethylcarbamazine (DEC)
• Nodules, produced by encapsulation of the adult • Ivermectin
worms in a fibrous tissue tumor-like mass, usually • Suramin
form within a year after infection. • Nodulectomy
FIG. 5.10 Life cycle of Onchocerca volvulus.
Epidemiology TISSUE-DWELLING NEMATODES

• Widely distributed throughout Central Africa. Dracunculus medinensis
• It is also present in Saudi Arabia, Yemen, and in the • Common names: Guinea worm, Fiery serpent of the
Western Hemisphere in limited areas in Mexico, Israelites, Medina worm, Dragon worm.
Guatemala, Venezuela, Colombia, Ecuador, and • Named by Galen.
Brazil. • a parasite of dogs and other carnivores in North
• It is generally considered to have been introduced America.
into the Americas by the slave trade. • Not a true filaria.
• In all of these areas, its distribution is restricted by
the breeding habits of its vector, larvae and pupae of General morphology
which develop in rivers or streams. Adults
• Females:
Other Filarial Infections in Humans • Measure up to a meter or slightly more, with a
• Dirofilaria tenuis: commonly found in the subcuta- diameter of less than 2 mm.
neous tissues of raccoons. • Dracunculus medinensis is an ovoviviparous para-
• Dirofilaria ursi: found in bears and transmitted by site. When female is gravid, the thousands of
blackflies. embryos in the uteri cause high internal pressure
• Dirofilaria repens: a parasite of dogs and cats, also and migrate to the skin of the infected host. Al-
transmitted by mosquitoes. lergic reactions cause BLISTER to form (Roberts
• Dirofilaria immitis: the heartworm of dogs. and Janovy, 2013).
FIG. 5.11 Life cycle of Dracunculus medinensis.
• Males: • Females migrate to the subcutaneous tissues when

• Inconspicuous and 2 cm in length. they become gravid.
• A papule is produced in the skin where the head
Larva of the female lies just under the dermis, and this
• Have a well-developed digestive tract. becomes vesicular and finally ulcerates, exposing
• Never found in the blood or tissues of the host. the worm. A loop of uterus prolapses through
• Discharged directly into water. the body wall of the worm, to lie in the ulcer
• Mature in copepods into infective forms in 2 weeks. opening.
• When the ulcer is immersed in water, larvae are dis-
Life cycle (Fig. 5.11) charged in large numbers.
• Whenever the ulcer of an infected person is im- Infective stage: larval stage in the infected copepod.
mersed in water, larvae are liberated, and copepods Diagnostic stage: larva obtained from ulcer.
may be infected. Mode of transmission: ingestion of infected copepods.
• If such copepods are swallowed, the contained lar-
vae are liberated to penetrate through the digestive Diagnosis
tract, entering the deep connective tissues where • Diagnosis usually presents no problems in endemic
they mature. areas, as the development of the local lesion is quite
• Maturation apparently takes about 1 year. characteristic.
• Once the ulcer is formed, larvae may be obtained for • Single testis.
diagnostic purposes by flooding the area with water. • Cloacae is found at the caudal end.
• Absent spicule.
Pathogenesis
• Urticaria Larva
• Localized erythema and tenderness. • 80 to 120 µm long.
• Nausea, vomiting, diarrhea. • Fully developed: 1 mm long.
• Painful reaction around the site of the ulcer. • Anterior: spear-like burrowing tip.
• Secondary bacterial infection. • Enter the lymphatic vessels.
• Leave the capillaries in striated muscles.
Treatment • Coiled in a spiral and gradually become surrounded
• Surgical removal of the worms by methods as primi- by a sheath derived from muscle fiber.
tive as twisting them around a stick has been prac- • Encysted larva: diagnostic and infective stage.
ticed for centuries and may be quite successful if the • Encysted larva remains viable for years even after the
worm is removed whole. capsule has calcified.
• Drug of choice: Metronidazole.
• Thiabendazole and Metronidazole only facilitate re-
moval of the worm.
• Infection is initiated by the consumption of raw
• Mebendazole kills the worms.
or undercooked pork or other meat containing the
encysted larvae.
Epidemiology
• The larvae excyst after the cysts are digested and pen-
• In 1986 there were an estimated 3,600,000 cases
etrate into the intestinal mucosa, developing to adult
worldwide, and by the end of 1996 that figure had
worms within the short space of 30 to 40 hours. Mating
dropped to approximately 100,000.
may take place as soon as the worms are mature, and lar-
• The disease has been almost completely wiped out
vae may be produced within 3 days after fertilization.
in Asia, and great progress made in Africa.
• The larvae enter lymphatic vessels and from them
Trichinella spiralis gain access to the general circulation.
• Common names: Muscle worm, Trichina worm. • They leave the capillaries in striated muscle to pen-
• A parasite of carnivorous mammals. etrate through the sheaths of the muscle fibers. De-
• Common in rats and in swine fed uncooked garbage. generative and inflammatory changes are seen in
• It may occur in humans who consume uncooked infected fibers, and within about a month the larvae
pork. have reached their full size.
• Final host: swine. Infective stage: Encysted larva found in final host.
• Dead-end host: man. Diagnostic stage: Encysted larva in striated muscle tissue.
• Habitat: small intestines (adult forms), striated Mode of transmission: ingestion of raw or uncooked
muscles (larvae). pork.
General morphology Diagnostic tests

Adults • Adults and larva may be found in stool during the
• Live and develop in the intestinal mucosa. diarrheal stage.
• Females: • Muscle biopsy (usually of gastrocnemius).
• Almost 5 mm in length • Definitive diagnostic test
• Pinkish in color • Demonstration of encysted larva
• Larger, straight, pointed tail. • Ultrasound/videographic procedures.
• Viviparous/larviparous. • Bachman intradermal test
• Single club-shaped uterus containing larva. • Beck’s xenodiagnoses
• Single ovary. • In vivo test
• Males: • Use of animal inoculation (rats allowed to feed
• Less than 2 mm in length. on infected tissue).
• Yellowish in color. • Bentonite flocculation test
• Curved posteriorly. • Serologic test
• Possess two pairs of conical papillae. • Specimen: serum
FIG. 5.12 Life cycle of Trichinella spiralis.
• Antibody-detecting test Epidemiology

• Knott or membrane filtration concentration (during • Trichinella is cosmopolitan in its distribution but oc-
larval migration). curs much more frequently in areas where raw gar-
bage containing pork scraps is fed to hogs.
Pathogenesis • It was once prevalent in many European countries,
• Intestinal symptoms but enlightened sanitation practices have markedly
• Minor and usually go unnoticed. lowered the rate in many areas.
• Nonspecific gastroenteritis. • The highest incidence of trichinellosis is now report-
• Muscle invasion. ed from China (10,000 cases annually).
• Muscle pain, myocarditis. • It is also still common in Spain, France, Italy, and
• Vasculitis Yugoslavia.
• Fever and eosinophilia. • Six European outbreaks have been traced to infected
• High IgE levels. horsemeat, and infected cattle are reported from
• Circumorbital edema. China.
• Photophobia
• Diplopia
• CNS involvement.
Visceral Larva Migrans
Treatment Larvae of nonhuman ascarids such as Toxocara canis or
• Corticosteroids (Prednisone) Toxocara cati are capable of limited development in hu-
• Drug of choice (Trichinellosis): Mebendazole. man hosts.
FIG. 5.13 Life cycle of Toxocara.
General morphology • In puppies younger than 5 weeks, the larvae com-

Adults plete a migratory and developmental cycle similar
• Similar to Ascaris lumbricoides in appearance but to that of A. lumbricoides in man and become mature
only a quarter to half its size. Toxocara in the intestinal tract.
• Live in the small intestine of dogs and cats. • In older puppies or adult dogs, or in humans, the
larvae are unable to complete their development.
Eggs • They may wander for some time in the tissues, fi-
• Require a period of maturation outside the host. nally encysting as second-stage larvae.
• Infective for dogs, cats, and humans. • These larvae may excyst in a pregnant bitch and
• Resemble those of Ascaris, but are larger, less elon- cross the placenta, to grow to adult worms in the
gate, and have a thinner shell and albuminoid outer pups.
covering. • Eggs of T. cati, ingested by cats, apparently complete
• T. canis eggs: measure about 85 by 75 µm their developmental cycle and become adult worms
• T. cati eggs: measure 65 to 70 µm in the intestine.
• Fertile Ascaris eggs: measure 75 by 50 µm • If humans or any of a variety of other animals ingest
infective eggs of T. canis or T. cati, development pro-
ceeds only as far as second-stage larvae, which after
• Infective eggs hatch in the intestine and liberate lar-
a period of migration encyst in the tissues.
vae that burrow into the wall of the intestine.
• When infected rats or mice are eaten by dogs or cats, • Other name: Parastrongylus cantonensis.
the larvae complete their development in the new • Final/definitive host: rats: Rattus norvegicus and Rat-
host, becoming adult worms in the intestine. tus rattus (Beaver et.al., 1984).
Infective stages: ova. • Accidental host: humans.
Mode of transmission: ingestion of the infective egg is • Intermediate host: mollusk/snail: Achatina fulica or
the primary mode of transmission. the giant African land snail (Beaver, et al., 1984).
• Paratenic host: prawn, crab, vegetation.
Diagnostic test • Habitat: lungs of definitive host.
• Diagnosis of visceral larva migrans in humans is
generally made on clinical grounds. General morphology
• Serologic tests using cultured second-stage Toxocara Adults (Roberts and Janovy, 2013; Beaver, et al., 1984)
larvae antigen. • Female:
• Laparoscopy and biopsy of suspicious-looking liver • 21 to 25 mm.
nodules. • Uterine tubules wrapped spirally around the in-
testine (Barber’s pole appearance).
Pathogenesis • 15,000 eggs per day.
• Hypereosinophilia • Male:
• Hepatomegaly • 16 to 19 mm.
• Chronic pulmonary inflammation with cough and • Kidney-shaped, single-lobed caudal bursa.
fever.
• Visual difficulties
• Larval stages develop in slugs and land snails.
• Epilepsy
• When eaten by rats, the larvae migrate to the menin-
• Myocarditis
ges and develop in the brain for about a month.
• Ocular larva migrans
• Young adults then migrate to the pulmonary artery,
Treatment where they attain maturity.
• Disease is self-limited. • In human hosts, Angiostrongylus does not complete
• Corticosteroids (for patients who are severely symp- its developmental cycle.
tomatic except in the ocular form). • When third-stage larvae are ingested, they pen-
• Drugs of choice: Albendazole and Mebendazole. etrate into blood vessels in the intestinal tract
and are carried to the meninges but are unable to
Epidemiology migrate to the lungs, as they do in rats.
• Seroprevalence rates in children are in the range of • Worms develop to the young adult stage in the
5% in the United States. meninges, but they soon die, and it is the death
of the larvae and the inflammatory reaction pro-
Angiostrongylus cantonensis voked by it that cause the characteristic signs and
• Common name: Rat Lungworm. symptoms of human infection.
FIG. 5.14 Life cycle of Angiostrongylus cantonensis (Parastrongylus cantonensis).

Infective stages • In humans, the larvae penetrate the wall of the in-
• Infective stage to rats: L3 Larva. testine and first enter lymphatic vessels, migrating
• Infective stage to slugs and land snails: L1 Larva. usually to the ileocecocolic branches of the anterior
Mode of transmission: ingestion of raw or undercooked in- mesenteric artery.
fected snails; ingestion of raw leafy vegetables contaminat- Mode of transmission: ingestion of larva in infected
ed with slimy secretions of snails; drinking contaminated slugs or contaminated salad vegetables.
water; ingestion of paratenic host (prawns and crabs).
Diagnosis
Diagnosis • Skin test and precipitin test
• A presumptive diagnosis on the basis of meningitis • Surgery
with blood and spinal fluid eosinophilia. Pathogenesis
• Computed tomography (CT). • Localized thrombosis and necrosis of tissues.
• ELISA • Granuloma formation.
• Pain in the right flank and iliac fossa.
Pathogenesis • Thickening of intestinal wall.
• EME: Eosinophilic Meningoencephalitis. • Leukocytosis
• Radiculomyeloencephalitis • Eosinophilia (20-50%)
• CSF pleocytosis (marked increase in eosinophil • Appendicitis-like symptoms
count).
• Nausea and vomiting. Treatment
• Visual impairment. • Surgery
• Marked tissue necrosis. • Thiabendazole and Mebendazole.
• Immature worms have been found in spinal fluid
Epidemiology
obtained by lumbar puncture.
• It has been encountered as a human parasite prin-
• Adult worms have been found in the eye and the
cipally in Costa Rica, though additional cases have
pulmonary artery.
been reported from most other parts of Central
America, from Mexico, and from Brazil.
Treatment
• Most infections have been found in children.
• Thiabendazole and mebendazole.
Epidemiology Gnathostoma spinigerum

• The infection seems to be increasing in rats and • Common name: stomach worm
bandicoots in the tropics and subtropics. • Habitat: stomach wall of cats and dogs
• First reported in the United States in 1987, A. canto- • Natural host: tiger
nensis is now endemic in Louisiana wildlife. • Accidental host: man
• Two other species are possible agents of human eo-
sinophilic meningitis. General morphology: (Beaver, et.al., 1984)
• A. mackerrasse in Australia. Adults
• A. malaysiensis in Malaysia, Thailand, and Indonesia. • Stout, reddish worms with subglobose cephalic
swelling separated by a cervical constriction.
Angiostrongylus costaricensis • Curved ventrad at both ends.
• Ordinarily inhabits the mesenteric arteries of the • 50% of the body with leaf-like spines.
cotton rat (Sigmodon hispidus). • Mouth with fleshy lips.
• Intermediate host: Physid snails
Male
Life cycle • Pseudo bursa with 4 pairs of perianal nipple-shaped
• Egg-laying takes place in arterioles of the intestinal papillae.
wall of the rodent host. • Copulatory spicules (chitinoid rods).
• Eggs hatch to produce larvae, which migrate through
the intestinal wall to appear in the feces. Female
• First stage larvae, ingested by the slug Vaginulus ple- • Vulva: post equatorial.
beius, grow and undergo two molts, after which they • Vagina: long and anteriorly located.
are infectious to rats or humans. • Oviparous.
Eggs Malaysia, Indonesia, the Philippines, Israel, Tanza-

• Ovoidal, transparent, superficially pitted, have mu- nia, and other areas where raw or pickled fish are
coid plug at one end (monopolar), unembryonated part of the diet.
when laid
Uncommon Tissue Nematodes
Life cycle Baylisascaris procyonis
• Involves 2 intermediate hosts. • An ascarid found in raccoons.
• First: a copepod. • Produces a visceral larva migrans syndrome in
• Second: fresh-water food fish, frogs, snakes, or humans.
birds. • Apparent predilection for the central nervous
• The larval worms, about 4 mm long with numerous system.
spines on the head and body, encyst in the second
intermediate host. Dioctophyma renale
• Adult worms are normally found in dogs and cats, • Found in the kidneys of dogs, mink, and other fish-
where they live coiled in the wall of the alimentary eating mammals.
tract. • They may invade and destroy the kidney and are
• When ingested by humans, the larvae do not mature also found in the abdominal cavity.
but migrate throughout the body. • Eggs are passed in the urine and then ingested by
Mode of transmission: ingestion of raw, undercooked, annelids.
or fermented fresh-water fish, amphibians, or • Diagnosis is made by finding the barrel-shaped eggs
paratenic hosts such as birds and snakes. with thick pitted brownish shells in the urine.
• Mode of transmission: Eating raw fish with infective
Diagnosis
larva.
• Clinical symptoms and the patient’s history in rela-
tion to food habits and residence.
Lagochilascaris minor
• Definitive diagnosis rests on the recovery and iden-
• Parasite of the cloudy leopard, Felis nebulosi.
tification of the worm.
• Occurs in such aberrant loci as the tissues of the
• Intradermal test.
neck, mastoid, eye, and lungs in humans.
Pathogenesis • Eggs resemble those of Toxocara cati.
• Epigastric pain
• Anorexia Micronema deletrix
• Edema • Ordinarily not parasitic.
• Lesions similar to those of cutaneous larva migrans. • Known to cause nasal, maxillary, and renal granulo-
• Eosinophilic myeloencephalitis. mas and meningoencephalitis in horses.
• Subarachnoid hemorrhage. • Human meningoencephalitis have been reported.
• Ocular involvement (blindness, exophthalmos, or • Mode of transmission not fully established.
subconjunctival hemorrhage).
• Gnathostomiasis externa: development of abscess Syngamus laryngeus
pockets or indurated nodules and formation of tun- • Parasite of the upper respiratory tract of ruminants.
nels where worms migrate (creeping eruptions). • Causes respiratory distress and coughing, and at
• Gnathostomiasis interna: development coiled times a transient pulmonary infiltrate.
adult worms inside tumors of the digestive tract. • Eggs, occasionally found in the feces, have a shell
Treatment resembling that of Capillaria but without polar
• Surgery plugs.
• Albendazole • Life cycle and mode of transmission are unknown.
• Ivermectin
Thelazia californiensis
Epidemiology • Commonly known as the eyeworm of deer, jack rab-
• Gnathostomiasis was first reported in Mexico in bits, and coyotes.
1970. • Occasionally found in the conjunctival sac of hu-
• Human infections are fairly common in Japan and mans (and of dogs and cats).
have also been reported from China, Thailand, • Transmitted by a fly of the genus Fannia.
• An eyeworm of dogs, T. calipaeda, is reported to in-

fect humans in China, Korea, Japan, Thailand, and • Angiostrongylus cantonensis
the former Soviet Union. • Angiostrongylus costaricensis
• Transmitted by the housefly, Musca domestica • Gnathostoma spinigerum
(China).
SUMMARY REVIEW QUESTIONS

1. An Ascaris egg that lacks the mamillated, albumin-
Nematodes or roundworms are considered parasites ous layer can be termed as
and disease-causing to animals, plants, and humans. a. Fertilized
General morphology b. Unfertilized
• Nonsegmented c. Corticated
• Cylindrical d. Decorticated
• Bilaterally symmetrical
2. Enterobius vermicularis infection is usually diagnosed
• Sexes are separate by finding.
• No circulatory system a. Eggs in the feces
• Complete digestive tract b. Eggs in perianal specimens
Life cycle c. Larvae in feces.
• Egg → Larva → Adult d. Larvae in perianal specimens
• Eggs vary in size and shape.
The nematodes can be subdivided into 3 major 3. What is the infective stage of Trichuris trichiura in hu-
classifications: mans?
Intestinal nematodes: a. Embryonated egg
• Ascaris lumbricoides b. Rhabditiform larva
• Enterobius vermicularis c. Filariform larva
• Trichuris trichiura d. Adult worm
• Capillaria philippinensis
• Ancylostoma duodenale 4. Rectal prolapse can be seen in infections with which
• Necator americanus
parasite?
a. Hookworm
• Strongyloides stercoralis
b. Threadworm
• Strongyloides fuelleborni
c. Pinworm
• Trichostrongylus spp. d. Whipworm
• Anisakis spp.
Vector-borne nematodes: 5. All of the following are characteristics of the L3 lar-
• Wuchereria bancrofti va, except:
• Brugia malayi a. It is the infective stage of Ancylostoma duodenale.
• Brugia timori b. It has a closed mouth.
• Loa loa c. It is the feeding stage of the larva.
• Mansonella ozzardi d. It is also known as the filariform larva.
• Mansonella streptocerca
• Mansonella perstans 6. Which intestinal nematode is larviparous?
• Onchocerca volvulus
a. Necator americanus
b. Enterobius vermicularis
• Dirofilaria spp.
Tissue-dwelling nematodes:
c. Capillaria philipinensis
d. Ascaris lumbricoides
• Dracunculus medinensis
• Trichinella spiralis
7. Semilunar cutting plates are the dental pattern of
• Toxocara canis which nematode?
• Toxocara cati a. Ancylostoma duodenale
b. Necator americanus
c. Ancylostoma ceylanicum c. 10 mL of blood + 2 mL of 2% formalin

d. Ancylostoma braziliense d. 2 mL of blood + 10 mL of 10% formalin
8. Which is true for Strongyloides stercoralis? 16. This disease refers to a disfiguring and disabling
a. Male S. stercoralis is parthenogenetic condition characterized by woody induration of
b. Tail of the filariform larva is notched/forked tissues with thickening and verrucous changes of
c. Rhabditiform larva has a small genital primor- the skin.
dium a. Calabar swelling
d. All of the above b. Onchodermatitis
c. Funiculitis
9. What is the causative agent of swollen belly syn- d. Elephantiasis
drome/sickness?
a. Strongyloides fuelleborni 17. It is commonly known as the heartworm of
b. Ancylostoma ceylanicum dogs.
c. Ascaris suum a. Dirofilaria tenuis
d. Capillaria aerophila b. Dirofilaria ursi
c. Dirofilaria immitis
10. The intermediate hosts of Anisakis are: d. Dirofilaria repens
a. Aquatic plants
b. Microcrustaceans 18. Which of the following is incorrectly matched?
c. Snails a. Subperiodic: Mansonella ozzardi
d. Humans b. Nonperiodic: Onchocerca volvulus
c. Nocturnal: Wuchereria bancrofti
11. Which of the following best describes W. d. Diurnal: Loa loa
bancrofti?
a. Irregularly spaced nucleus 19. Which female adult worm possesses a uterus with a
b. Unsheathed characteristic barber’s pole appearance?
c. No terminal nuclei a. T. spiralis
d. Kinky appearance b. A. cantonensis
c. A. costaricensis
12. What is the vector of Loa loa? d. T. trichiura
a. Aedes mosquito
b. Mansonia mosquito 20. Which among the following does NOT characterize
c. Mango fly the microfilaria of Brugia malayi?
d. Black fly a. Sheathed
b. Cephalic space ratio: 2:1
13. Which of the following nematodes is commonly c. Graceful appearance/movement
called the blinding worm? d. Two terminal nuclei
a. W. bancrofti
b. M. streptocerca Answers to review questions are available at the end of this
c. Loa loa book.
d. O. volvulus
REFERENCE
14. What is the habitat of adult T. spiralis worms? Beaver P.C., Jung R.C. Cupp E.W. Clinical Parasitology. 9th ed.
a. Nonstriated muscles Philadelphia: Lea and Febiger, 1984.
b. Striated muscles Chitwood M.P., Velasquez C., Salazar N.G. Capillaria
c. Lymphatic vessels philippinensis sp. n. (Nematoda: Trichinellida), from
d. Small intestine the intestine of man in the Philippines. Journal of
Parasitology, 1968, 54:368-371.
15. What is the reagent for Knott’s concentration tech- De Gruijter JM et al: Genetic substructuring within
Oesophagostomum bifurcum (nematode) from human and
nique?
non-human primates from Ghana based on random
a. 1 mL of blood + 2 mL of 2% formalin amplified polymorphic DNA analysis, Am J Trop Med Hyg
b. 1 mL of blood + 10 mL of 2% formalin 2004; 71:227–233.
De Leon WU, Belizario VY. Philippine Textbook of Medical Steenhard N.R., P.A. Storey., L. Yelifary, D.S. S. Pit, P. Nansen
Parasitology. Manila, Philippines: University of the A.M. Polderman. The role of pigs as transport host of
Philippines Manila. 2015:42–45, 325, 395–397. humans helminths Oesophagostomum bifurcum and Necator
Eberhard ML, Busillo C. Human Gongylonema infection in a americanus. Acta Trop. 2000. 76: 125-130.
resident of New York City. Am J Trop Med Hyg 1999;61: Storey PA et al. Clinical epidemiology and classification of
51–52. human oesophagostomiasis. Trans R Soc Trop Med Hyg
Garcia LS: Diagnostic Medical Parasitology, 6th ed., ASM Press, 2000;94:177–182.
2016, 323-324, 332, 1031. Velasquez CC, Cabrera BC. Ancylostoma ceylanicum (Looss, 1911)
Hotez P.J., D.I. Pritchard. Hookworm infection. Sci. Am. 1995. in a Filipino woman. J Parasitol. 1968 Jun;54(3):430-1.
272:68-74. Wittner M et al. Eustrongyliasis—a parasitic infection acquired
Roberts L.S. J. Janovy. Foundations of Parasitology. by eating sushi. N Engl J Med 1989; 320:1124–1126.
Mc. Graw-Hill, NY. 2013.
CHAPTER 6
Phylum Platyhelminthes: Class Trematoda

JEREMIE FAYE B. UMALI, RMT
INTRODUCTION form two intestinal ceca, which run parallel to each

The trematodes, also known as flukes, constitute one other, ending blindly near the posterior end of the
of the phylum Platyhelminthes. Adult trematodes are worm.
parasites of vertebrates. These parasites can cause hu- • There is also a nervous system present.
man infections by mechanical obstruction or by local • Trematodes have no special respiratory system yet if
inflammatory processes damaging the affected organ oxygen is needed, it must be taken up through the
(Pottinger and Jong, 2017). Life cycle and structural tegument. Most trematodes are able to live under
arrangement differ depending on the type of parasitic aerobic conditions while some live anaerobically.
existence, ranging from ectoparasitism on aquatic hosts For example, Schistosomes live within the blood-
to extreme endoparasitism in the vascular system of stream and are capable of metabolizing oxygen but
vertebrates (Neva and Brown, 1994). if interrupted, they can respond to an anaerobic
mechanism (Beaver et al., 1984).
General Morphology • Most of the rest of the body is taken up with repro-
Adult trematodes ductive organs and associated structures. There are
• Most are hermaphroditic or monoecious, and many usually two testes leading to the genital pore, which
are capable of self-fertilization, with the exception usually lies in the region of the ventral sucker. There
of blood flukes that are said to be dioecious requir- is a single ovary. A series of glandular structures
ing one female and one male adult to reproduce. called vitellaria, usually in two masses lying lateral
• Most trematodes are described as leaf-shaped and to the intestinal ceca, produce the shell material. Vi-
bilaterally symmetrical, but they vary considerably telline ducts lead inward to the region of the ovary
in form. where the shell is formed over the ovum. The uterus
• Largest human parasite belonging to this group: winds forward to the genital pore. In most trema-
Fasciolopsis buski (may attain a length of 75 mm todes, it is the largest organ in the body, filled with
and a breadth of 20 mm but is not over 3 mm thousands of eggs.
thick).
• Smallest human parasite belonging to this group: Trematode eggs
Heterophyes heterophyes (under 2 mm in length The following are the characteristics of trematode eggs
and 0.5 mm in breadth). (shown in Fig. 6.1):
• The body of a trematode is covered with a resistant • Trematode eggs have smooth, hard shell that is
cuticle, which may be smooth or spiny. transparent.
• Adult trematodes posses two suckers or attachment • Generally yellow-brown or brown, ranging in length
organs: from under 30 µm to as much as 175 µm, depend-
1. Oral sucker is the anterior portion surrounding ing on the species.
the mouth; mainly for nutrition. • The majority have close to what would be consid-
2. Ventral sucker or acetabulum is a more posterior ered a conventional egg shape.
one on the ventral surface used for attachment. • Most have an operculum or lid at one end, an
3. Third sucker, also known as genital sucker or “escape hatch” through which the miracidium
gonotyl, is only present in Heterophyes for copu- emerges.
lation. • This operculum may be difficult to detect, but it
• They have the oral cavity that leads to a muscular can usually be seen by careful focusing with re-
esophagus, from which the intestine branches to duced illumination. The miracidium is covered
171
FIG. 6.1 Some trematode eggs; A, Fasciolopsis buski. B, Schistosoma mansoni. C, Schistosoma
haematobium. D, Paragonimus westermani. E, Schistosoma japonicum. F, G, Clonorchis sinensis. All eggs
photographed at same magnification; scale equals 50 µm.
with cilia, and in some species, it is fully devel- a. very small and inconspicuous as in Clonorchis or
oped when the eggs are passed in the feces. Opisthorchis, or
• The shell may be smoothly continuous in outline, b. large and striking as in certain species of Schisto-
or there may be a slight flare, marking the line soma.
of cleavage between shell and operculum, known • On the other hand, eggs of the schistosomes are
as the opercular shoulders. Possession of these nonoperculate, and the egg is irregularly ruptured in
shoulders is characteristic of the eggs of certain hatching.
species. • Trematode eggs cannot successfully be concentrated
• Spines may be present, either: by the zinc-sulfate technique, as both the operculate
CHAPTER 6 Phylum Platyhelminthes: Class Trematoda 173
and the nonoperculate forms rupture and fail to narrow-bodied worms that tend to localize in the
float. smaller, more distal parts of the biliary tree. Only in
• Formalin-ether concentrates are quite satisfactory, heavy infections are these worms found in the com-
or the sediment of the zinc-sulfate concentrate may mon bile duct or gallbladder.
be examined for the eggs, which are still recogniz- • Adult worms may also be found in the bile ducts
able even when ruptured. of dogs, cats, pigs, and six other species acting as
reservoir hosts.
Life Cycle • C. sinensis and Opistorchis spp. are similar in the
All have complex life cycles, requiring one or more in- location of their vitellaria positioned in the mid-
termediate hosts. Life cycles of trematodes are complex dle third of the body, same level with its uterus.
and varied; they illustrate an extraordinary range of • Only difference between C. sinensis and Opistor-
evolutionary adaptations. A “typical” life cycle is shown chis spp. is the morphology and arrangement of
in Fig. 6.2. their testes.
1. Formation of miracidium: Eggs laid by the adult a. C. sinensis adults have two large testes that are
within the vertebrate host pass outside, and a larva highly branched, arranged in tandem posi-
develops within them. This larva, called a miracidi- tioned in the posterior half of its body, where-
um, may hatch and swim away, or in some species, as Opistorchis spp. adults have lobate testes ar-
emergence may have to wait upon ingestion of the ranged obliquely.
egg by the next host. In either case, development b. O. viverrini adults can be differentiated from
cannot proceed unless the proper first intermedi- O. felineus due to its testes morphology as the
ate host—a mollusk (snail or clam)—is available. former have more deeply lobulated testes po-
Following the entry of miracidium, the following sitioned close to each other compared to the
intramolluscan stages are observed: sporocyst, redia latter.
and cercaria. • Fasciola, a much larger worm, is confined by its size
2. Formation of cercariae: Each species of trematode to the larger passages. These worms all produce
requires certain species of molluscan intermedi- hyperplastic changes in the epithelium of the bile
ate hosts for development, lacking which it dies. ducts and fibrosis around them. Massive infection
A complex series of generations follows within the by any of them may lead to portal cirrhosis, with all
mollusk, resulting finally in the liberation of large its associated manifestations.
numbers of larvae known as cercariae.
a. In some species, the cercaria must penetrate di- Trematode eggs
rectly through the skin of the vertebrate host; • The eggs of the opisthorchid flukes are similar in ap-
b. In others it enters an insect, fish, or other second pearance to those of the heterophyids.
intermediate host; • Eggs of Fasciola closely resemble both Fasciolopsis
c. In still others it must attach to vegetation and se- and the echinostomes.
crete a resistant cyst wall, waiting to be eaten by • If eggs of one of these forms are found in the stool,
the final host. and the diagnosis of hepatic or intestinal infection
3. Formation of metacercariae: The forms found in a sec- cannot be made on clinical grounds, examination of
ond intermediate host or encysted on vegetation are bile obtained by duodenal drainage will provide the
known as metacercariae, considered as the infective correct answer. If uncontaminated bile is obtained
stage to the definitive host. Ingestion of metacercar- and eggs are found in this material, they must have
iae is the mode of transmission of most trematode been produced by worms in the liver or gallbladder.
infections with the only exception in Schistosomes
wherein mode of transmission is skin penetration of Clonorchis sinensis
cercaria. Also known as the “Chinese or Oriental liver fluke”
(Figs. 6.3 and 6.4), occurs in large areas of China (in-
cluding Taiwan), Japan, Korea, and Vietnam.
LIVER FLUKES
General Morphology General morphology
Adult trematodes Adults
• Several trematodes are parasites of the biliary pas- • It is of moderate size, from 1 to 2.5 cm by 0.3 to
sages of humans. Three of them, Clonorchis, Opis- 0.5 cm. It is broadest in the midportion of the body,
thorchis, and Dicrocoelium, are relatively elongate and tapering toward both ends.
FIG. 6.2 Paragonimus, an example of a trematode life cycle: (eb) excretory bladder; (in) intestine; (o)
ovary; (os) oral sucker; (t) testis; (ut) uterus; (ve) vas efferens; (vi) vitellaria; (vs) ventral sucker. (Adapted from
Porter in Burrows, Textbook of Microbiology.)
• “Spatula-like” appearance. its end, (3) testes are described as dendritic, (4) anterior
• Its body is composed of the following: to the testes is a small slightly lobate ovary positioned
(1) ventral sucker, smaller than the oral sucker, lying in the midline, (5) a loosely coiled uterus ending in the
about one-fourth of the body length from its anterior common genital pore, and (6) in the lateral midpor-
end, (2) a long intestinal ceca extending posteriorly to tion of its body is a minute follicular vitellaria.
leave the first intermediate host to encyst in the skin

or flesh of the fresh-water fish losing its tail chang-
ing into an ovoid metacercaria.
4. Once the human host or any definitive host ingested
the raw or uncooked fresh-water fish encysted with
FIG. 6.3 Clonorchis sinensis. (Photomicrograph by Zane metacercaria, enzyme degradation in the duodenum
Price).
will liberate the metacercaria allowing it to migrate to
the ampulla of Vater to the common bile duct, and
Eggs then to the distal biliary capillaries where it matures
• The light yellowish-brown ovoid eggs have a distinct into an adult worm. Attachment of the adult fluke to
convex operculum and at the thicker posterior end is the mucosa of the bile duct does not cause permanent
a small median protuberance. It has been described ulceration of the epithelial lining. Said flukes may also
as “old-fashioned light bulb”. be found in the gallbladder and pancreatic duct and
• These eggs that are passed in feces are mature and may feed on tissue fluids, mucus and red blood cells.
embryonated containing a fully developed miracidia 5. When the embryonated eggs are passed again in the
that do not hatch upon contact to water. Eggs of C. feces, the cycle repeats itself.
sinensis (see also Fig. 6.1F, G) resemble very closely Adult worms live in the bile ducts and apparently
those of Heterophyes and Metagonimus but may have localize first in the more distal portions, just under the
a small comma-shaped process at the abopercular capsule of the liver. In more massive infections, they
end. The average length is 29 µm, and breadth is occupy most of the bile passages and may even be
16 µm, which falls within the Heterophyes-Metagon- found in the gallbladder and pancreatic duct. Worms
imus range. The extreme measurements are signifi- are known to live as long as 30 years. Human infection
cantly larger than those of the heterophyid worms, results from the consumption of fresh-water fish con-
about 35 µm in length and 19.5 µm in breadth for taining the encysted metacercariae.
eggs of C. sinensis. • Fish may be eaten raw, pickled, smoked, or dried.
The disease has been reported in native Hawaiians
Life cycle as a result of the consumption of infected fish im-
1. When deposited by the adult worms, the embryo- ported from the Orient.
nated eggs are directly or indirectly passed in feces • Dogs and cats are the most important reservoir
(Fig. 6.5). The miracidium contained in the egg will hosts; their wholesale slaughter in the People’s
only be released upon ingestion by the first inter- Republic of China has probably reduced transmis-
mediate hosts, which are mollusks or snails from sion of the disease in that area.
different genera, especially of Parafossarulus, Bulinus,
Semisulcospira, Alocinma, Thiara, and Melanoides. Diagnostic tests
2. Once ingested, the miracidium will undergo chang- • Diagnosis is by recovery of the eggs from the feces
es into a sporocyst, rediae then into a cercariae. or from duodenal aspirates, or the enteric capsule or
3. The cercariae will serve as the infective stage to the EnteroTest. Complement fixation and intradermal
secondary intermediate host which is usually a tests have been described but are not generally avail-
fresh-water fish. The free-swimming cercariae will able.
FIG. 6.4 Clonorchis sinensis; (eb) excretory bladder; (in) intestine; (l) Laurers’ canal; (o) ovary; (os) oral
sucker; (sr) seminal receptacle; (t) testis; (ut) uterus; (va) vas deferens; (vd) vitelline duct; (ve) vas efferens;
(vi) vitellaria; (vs) ventral sucker. Drawing made with the aid of a camera lucida.
FIG. 6.5 Life cycle of Clonorchis sinensis.
Symptoms have any recognizable symptoms from a chronic

Light infections, which are the rule, are generally as- low-grade infection.
ymptomatic. Heavier infections, if acquired over an ex- • An epidemic of early-onset symptomatic clonor-
tended period, seldom cause early symptoms. chiasis occurred among Jewish refugees, unaware
• The ingestion of large numbers of metacercariae of the dangers of eating uncooked fish, living in
over a short period of time may produce symptom- Shanghai at the end of World War II. Treatment
atic early infections. at that time was not very effective, and many of
• Acute phase lasts less than a month and may be those persons still harbored an asymptomatic in-
characterized by fever, diarrhea, epigastric pain, fection 20 years later.
anorexia, enlargement and tenderness of the liv- • Heavy worm burdens—the result of repeated infec-
er, and sometimes jaundice. tion over a period of years—may result in a degree
• There may be leukocytosis, and eosinophilia is of functional impairment of the liver;
generally present. • This impairment is secondary to localized biliary
• Eggs appear in the feces about a month after obstruction (Fig. 6.6) and is at times aggravated
infection takes place, and the acute symptoms by intrahepatic stone formation, cholangitis, and
subside. Once this has happened, persons not the formation of multiple liver abscesses.
subject to repeated reinfection generally do not
• Heavy chronic infections are strongly associated

with cholangiocarcinoma, a severe and fatal form of
bile duct cancer.
Treatment
• Drug of choice: Praziquantel, with cure rates in
the neighborhood of 100% when administered at
25 mg/kg three times daily for 1 day.
• Albendazole,* a member of the benzimidazole group
of drugs that includes thiabendazole and mebenda-
zole, seems equally effective (Liu et al., 1991) when
given at 10 mg/kg daily for 7 days.
• Both drugs have minimal toxicity.
Opisthorchis felineus
• As the name suggests, O. felineus, also known as “cat
liver fluke”, parasitizes cats.
• In central and eastern Europe and in Siberia, it is
prevalent in both cats and dogs; in various sectors
where the human population eats raw or pickled fish,
humans are also infected. It is particularly prevalent
as a human parasite in East Prussia, Poland, and parts
of Siberia. Human infections have also been reported
from the Philippines, Korea, Japan, North Vietnam,
and India, although there is a question whether or
FIG. 6.6 Clonorchiasis. T-tube cholangiogram not the parasite is indigenous to all of these areas.
demonstrates dilated bile ducts filled with flukes. (Courtesy • Like C. sinensis, O. felineus inhabits the bile ducts,
of the Armed Forces Institute of Pathology. #69–5522–3.) and much the same disease picture is produced by
both parasites. The life cycle of the two parasites is
• Cholecystitis and cholelithiasis may be the result likewise similar.
of invasion of the gallbladder by these worms,
General morphology
which have also been considered to cause acute
The adult O. felineus differs from C. sinensis only in
pancreatitis. Such symptoms may come on after
some relatively minor details of structure. Eggs of O.
years of asymptomatic infection.
felineus are narrower than those of C. sinensis, averaging
• Cirrhosis is probably a rare complication, related
30 µm by only 11 to 12 µm. They are otherwise indis-
more to chronic malnourishment than to the
tinguishable.
parasitic infection.
Treatment
Pathogenesis Praziquantel is effective if administered at the rate of
• Thickening and localized dilatation of the bile ducts 25 mg/kg three times daily for 1 or 2 days.
are seen in heavy infections, accompanied by mod-
erate to marked hyperplasia of the small mucinous Opisthorchis viverrini
glands of the duct mucosa. The degree to which both A third species of liver fluke also known as “Southeast
of these changes may take place bears a direct rela- Asian liver fluke”, O. viverrini, is a major health problem
tionship to the intensity of infection. However, these in northern Thailand, Cambodia and Laos. The overall
adenomatous changes may persist for many years in prevalence is reported to be from 80% to 90% in rural
patients whose infections have become very light. people, and 55% in urban dwellers, increasing with age
• Adenocarcinomas arising from the hyperplastic bile up to 10 years, after which it remains fairly constant.
duct mucosa in persons chronically infected with
C. sinensis have long been considered to be related Pathogenesis
to that infection, although dietary and other factors The infection is acquired by the consumption of un-
may also play a role. cooked fresh-water fish.
• Mild to moderate infections seem to produce few • Many apparent human infections with this parasite
symptoms, but heavier ones are associated with ab- have in fact been spurious, the result of the con-
dominal distress, epigastric pain, and generalized sumption of infected liver with subsequent appear-
malaise. ances of the ingested eggs in the feces. Other report-
• As in clonorchiasis, there seems to be a strong reed cases, from many parts of the world, have been
lationship between long-standing heavy infections true Dicrocoelium infections.
and the development of cholangiocarcinoma (Chiu
et al., 1996). Life cycle
• As a consideration of the life cycle will show, such
General morphology human infections must be uncommon. Dicrocoelium
The adult O. viverrini differs only slightly in structure spp. is similar to Clonorchis spp. as regards both lo-
from the other two opisthorchids. The eggs are relative- calization and the pathologic lesions it produces.
ly short and broad, with an average length of 26.7 µm After ingestion, the metacercariae excyst in the duo-
and breadth of 15 µm. denum and pass through the common bile duct to
invade the biliary system.
Epidemiology • The life cycle of this parasite is most unusual.
O. viverrini mainly occurs in Northeast Thailand 1. Eggs, fully embryonated when passed in the fe-
(where almost 1/4 of population is infected), Cambo- ces, are ingested by land snails, in which they un-
dia, Malaysia, Laos, central and southern Vietnam. It dergo a developmental cycle.
is quite possible that opisthorchid infections, reported 2. Cercariae are liberated from the snails during
from neighboring areas such as North Vietnam, and rainy periods and become massed in “slime
attributed to O. felineus, may in reality be caused by balls” shed on vegetation as the snail crawls.
O. viverrini. 3. These slime balls, each of which contains a
large number of cercariae, are eaten by ants. In
Treatment this host, the cercariae become encysted to form
Praziquantel is reported to have had an almost 100% ef- metacercariae.
ficacy when given as a single dose of 40 mg/kg to a large 4. For humans to acquire this disease, they must in-
group of mildly to moderately infected Thais studied gest an infected ant. Drabick et al. (1988) report
over a 2-year period (Pungpak et al., 1994). Alterna- a case, considered by them not to be a spurious
tively, praziquantel may be administered at 75 mg/kg infection, acquired through ingestion of bottled
in 3 doses for 1 day. However, because of the efficacy of water contaminated by ants.
this therapy, many Thais continue the consumption of
raw fish, interspersed with periodic praziquantel treat- General morphology
ments. Adults. The adult worm is easily distinguishable
from Clonorchis in that its testes are slightly lobed and
Dicrocoelium dendriticum situated in the anterior third of the body, while in Clo-
• A common parasite of the biliary tree of herbi- norchis they are highly branched and in the posterior
vores in many parts of the world is D. dendriticum third.
(Fig. 6.7), a fluke of about the same size and shape
as Clonorchis. Eggs. The eggs, passed in the feces, are dark brown in
• It is also known as Fasciola dendriticum, Fasciola lan- color, are thick shelled, and have a large operculum.
ceolata, Lanceolate fluke or Lancet fluke. They measure 38 to 45 µm in length by 22 to 30 µm
in breadth.

Human infections are almost invariably light and of-
ten asymptomatic. Biliary colic and digestive distur-
bances have been described. With the heavy infections
sometimes seen in animals, enlargement of the bile
ducts and hyperplasia of biliary epithelium may oc-
FIG. 6.7 Dicrocoelium dendriticum. (Photomicrograph by cur, with periductal fibrosis and eventual portal cir-
Zane Price.) rhosis.
Treatment prevalent in cattle in Uruguay, Argentina, and Chile

The patient previously referred to (Drabick et al., 1988) (Hillyer and Apt, 1997). In Cuba, southern France, and
was treated with praziquantel, 20 mg/kg body weight Algeria, human infections are not uncommon. Inter-
three times in 1 day, with apparent success. mediate forms have also been reported from Asia.
Fasciola hepatica
General morphology
Also known as “sheep liver fluke” (Figs. 6.8 and 6.9), Adults. Fasciola is a large fluke, measuring as much as
it is a common parasite of herbivores and one that is 3 cm long and nearly 1.5 cm in width. It has a charac-
cosmopolitan in its distribution. teristic “cephalic cone” at the anterior end. The adult
Human infections have been reported from many worms reside in the larger biliary passages and the gall-
areas of the world and are of considerable importance bladder.
in parts of South America. A minimum of 350,000 hu-
man infections is estimated for the highlands of Boliv-
Eggs. Eggs of Fasciola are found in the feces but can-
ia, with similarly high rates of infection in correspond-
not readily be differentiated from those of Fasciolopsis
ing areas of Peru; in other South American countries
(see Fig. 6.1) and the echinostomes. They are opercu-
human infections are sporadic, though the disease is
lated and measure 130 to 150 µm in length and 63 to
90 µm in breadth. Use of the enteric capsule (Entero-
Test) may be helpful in recovering eggs and making a
differential diagnosis.
Life cycle
• Infection follows consumption of aquatic vegetation
upon which metacercariae of Fasciola have encysted
(Fig. 6.10), which presupposes exposure of such
vegetation to the feces of infected animals. Human
FIG. 6.8 Fasciola hepatica. (Photomicrograph by Zane cases can usually be traced to watercress or similar
Price.) plants, taken from water to which herbivores have
access. Moreover, cercariae may encyst even in the
absence of aquatic vegetation and may just encyst
directly into the water.
• Usually, maturation of metacercaria into adult
flukes may take 3 to 4 months in humans.
• Spurious infections, in which eggs ingested during the
consumption of infected liver appear in the stools,
may be detected by reexamination of the stools at a
time when such food has not been ingested. Most hu-
man infections reported from this country are seen in
immigrants or travelers (Price et al., 1993).
• Unlike the opisthorchids, which enter the biliary
tree by passing through the ampulla of Vater and
ascending the common bile duct, Fasciola metacer-
cariae burrow into and through the duodenal wall,
migrate actively across the peritoneal cavity, and en-
ter the bile ducts by way of Glisson’s capsule and the
liver parenchyma. It is not surprising that some are
lost on the way and occasionally may develop in the
peritoneal cavity or other ectopic foci.
FIG. 6.9 Fasciola hepatica, anterior end of worm: (gp)
genital pore; (in) intestine; (o) ovary; (os) oral sucker; (sr)
seminal receptacle; (sv) seminal vesicle; (t) testis; (ut) Symptoms
uterus; (vd) vitelline duct; (ve) vas efferens; (vi) vitellaria; Because of the size of these worms, even light infections
(vs) ventral sucker. Drawing made with the aid of a camera (though often asymptomatic) may produce signs and
lucida but somewhat diagrammatic. symptoms of biliary obstruction and cholangitis.
FIG. 6.10 Life cycle of Fasciola hepatica.
• Fever, chills, right-upper-quadrant pain with radia- al mucosa, causing pain, bleeding, and edema that
tion to the scapula, jaundice, an enlarged tender liv- sometimes interfere with respiration.
er, and eosinophilia may appear and prove puzzling
unless eggs are found in the stool or biliary aspirate. Pathogenesis
• The adult worms may be visualized in the liver by In human infections, symptoms are occasionally seen
means of ultrasonography. that suggest that there may be considerable local irrita-
• Computed tomography with enhancement may tion during the migration of the young worms to the
demonstrate the burrow tracts made by worms mi- liver. In sheep, migration through the liver parenchyma
grating in the liver parenchyma, and dilatation of gives rise to such massive tissue destruction that the dis-
the bile ducts; endoscopic retrograde cholangiopan- ease at this stage is known as liver rot. Once established
creatography may show the worms in the pancreatic in the bile ducts, the worms may produce both mechan-
duct (Han et al., 1993). ical and toxic effects, which differ from those seen with
• A pharyngeal form of the disease, known as Hal- infection by the opisthorchids or Dicrocoelium only in
zoun, has been described in the Middle East and as much as Fasciola is a larger and more powerful worm.
results from eating raw animal liver infected with Mechanical irritation, the effects of toxic metabolites of
Fasciola. Young adult worms attach to the pharynge- the worms on host tissue, and mechanical obstruction
may bring about hyperplasia of the biliary epithelium, Africa, Hawaii and Iran. Intermediate forms have
proliferation of connective tissue around the ducts, and also been reported from Asia.
partial or total biliary obstruction. The adult worms
may erode through the walls of the bile ducts to invade Life cycle
once again the liver parenchyma. Secondary bacterial • The life cycle of the parasite is very similar to that
infection may occur; portal cirrhosis is usually the final of F. hepatica, and the clinical picture in the two
outcome in severe infections. infections is also much alike. The eggs of F. gigan-
tica are large, measuring 150 to 190 µm by 70 to
Treatment 90 µm.
• Bithionol,* administered orally at the rate of 30 to • Development of F. gigantica from metacercaria into
50 mg/kg every other day for 10 to 15 doses, is rec- adult flukes may take longer than F. hepatica.
ommended for treatment of fascioliasis.
• Its use is associated with frequent photosensitiv-
ity skin reactions, urticaria, vomiting, diarrhea, INTESTINAL FLUKES
and abdominal pains (see further discussion un- Fasciolopsis buski
der treatment of Paragonimus). • Also known as the “giant intestinal fluke”, F. buski
• Praziquantel, even when given at the rate of 25 mg/ (Fig. 6.11) is found in China (including Taiwan),
kg three times daily for 5 to 7 days, seems only to Vietnam, and Thailand, and in parts of Indonesia,
lessen the severity of infection. Malaysia, and the Indian subcontinent.
• Dehydroemetine and albendazole have likewise
been found to give unsatisfactory results. Life cycle
• A more promising drug is triclabendazole, unfor- 1. Snails, such as Segmentina spp. and Hippeutis spp.,
tunately approved only for veterinary use in the are said to be the first intermediate hosts that are
United States. The drug is well tolerated, and doses infected by the miracidium once eggs are passed in
of 10 mg/kg body weight twice in 1 day produce the feces by an infected definitive host. (Fig. 6.12)
cure rates approaching 100% (Apt et al., 1995; 2. Miracidium undergoes development to sporo-
Richter et al., 2002) Triclabendazole (Egaten; cyst, redia, and then to a cercaria which leaves the
Novartis) is available from Victoria Pharmacy, snail.
Zurich, Switzerland. 3. The cercaria will find its second intermediate host
to transform into a metacercaria. Infection is ac-
Control quired by ingestion of the metacercariae, encysted
• Infection follows consumption of aquatic vegetation on its second intermediate host, the fresh-water
upon which metacercariae of Fasciola have become vegetation, such as bamboo shoots, water chestnuts
encysted (see Fig. 6.10). Human cases can usually be (Eliocharis tuberosa), water caltrop (Trapa bicornis),
traced to infected watercress, which should never be kangkong (Ipomea obscura) or lotus (Nymphaea lotus),
grown for human use in water to which herbivores which may be consumed raw or peeled with the
have access. teeth. Reservoir hosts include pigs, dogs, and rab-
• Spurious infections, in which eggs ingested by the bits.
consumption of infected liver appear in the stool,
may be detected by reexamining the patient’s stools
at a time when he or she has not consumed such
food.
Fasciola gigantica
• Also known as the “giant liver fluke”; may attain
a length of 7.4 cm. It has a more attenuated shape
than has F. hepatica, from which it also differs in
some details of structure. F. gigantica is a parasite
of herbivores, particularly camels, cattle, and water
buffalo in Africa and the Orient. It is mainly found
in tropical and subtropical regions as human cases
FIG. 6.11 Fasciolopsis buski. (Photomicrograph by Zane
have been reported from several regions of Asia, Price.)
FIG. 6.12 Life cycle of Fasciolopsis buski.
• Adult worms live attached to the bowel wall, primar- Eggs. The ellipsoid eggs are yellow-brown in color
ily in the duodenum and jejunum; in heavy infec- (130 to 140 µm by 80 to 85 µm). It is may also be de-
tions they may be found throughout the intestinal scribed as “Hen’s egg appearance” and may be hard to
tract. Their life span seldom exceeds 6 months. An differentiate with Fasciola eggs. The shell is transparent,
estimated 10 million infections occur annually. with a small operculum at the more pointed end. Eggs
are unembryonated when first passed, containing early
General morphology cleavage stages (Fig. 6.1A).
Adults. Adult worms are seen only following purga-
tion after specific anthelminthic treatment. They are Symptoms and pathogenesis
fleshy worms (2 to 7.5 cm long by 0.8 to 2 cm wide). • Attachment of these large worms to the mucosa of
This adult worm has no cephalic cone, no well-devel- the bowel causes local inflammation and ulceration,
oped shoulders, with branched ovary, and a pair of sometimes accompanied by hemorrhage. A few
dendritic testes arranged in tandem. To differentiate worms do not give rise to any recognizable symp-
Fasciolopsis from Fasciola, the intestinal ceca of Fasciolop- toms, but with heavier infections there may be ab-
sis buski is unbranched or lacks its side branches and its dominal pain, at times suggestive of duodenal ulcer
ventral sucker is much larger than its oral sucker. disease, and diarrhea.
• In heavy infections (with hundreds or perhaps thou- evidence that echinostomes may also occur in East
sands of worms in the bowel), the stools are profuse, Africa.
light yellow in color, and contain much undigested
food; Life cycle
• They are suggestive of a malabsorptive process The life cycle (Fig. 6.13) involves not one but two snail
such as is seen in giardiasis. intermediate hosts; metacercariae encyst in the second.
• Vitamin B12 absorption has been found to be im- These flukes live attached to the wall of the small intes-
paired in some infected persons. tine, where they may produce an inflammatory reac-
• Intestinal obstruction may occur. tion and ulceration, leading to diarrhea.
• Edema and ascites, which may develop in severe
infections, have traditionally been considered to Echinostoma ilocanum
be secondary to the absorption of worm toxins,
The most important species is Echinostoma ilocanum,
but these symptoms can perhaps more rational-
which occurs in the Philippines. Human infections
ly be ascribed to a hypoalbuminemia resulting
are generally inadvertent, except in the Philippines,
from long-continued malabsorption or from a
where the second snail host is customarily eaten
protein-wasting enteropathy.
raw; the worms are found in a variety of mammals
• Marked eosinophilia is usually seen.
whose food habits promote infection. When the de-
finitive host defecates and passes the immature eggs
Treatment
to feces, the eggs will mature upon contact in water
• Drug of choice: Praziquantel (Biltricide)
and hatches from the egg to infect the first snail in-
• an isoquino-linepyrazine derivative, which seems
termediate host (Gyraulus convexiusculus and Hippeutis
an almost idea platyhelminthicide.
umbilicalis). Inside the snail, E. ilocanum miracidium
• It is administered orally, 25 mg/kg body weight
develops into a mother redia then into daughter redia
three times in 1 day.
to become a cercaria. Once, liberated from the first
• The mode of action of praziquantel is uncer-
snail, the cercaria may now infect the second snail in-
tain, but it seems to work by altering the per-
termediate host (Pila luzonica and Vivipara angularis)
meability of cell membranes to mono- and
and develops into a metacercaria, thus, the infective
divalent cations, especially calcium. Causing a
stage to the definitive host.
massive influx of calcium, it initiates a tetanic
contractile process on the part of the worm.
It also leads to disruption and vacuolization Artyfechinostomum malayanum
of the tegument (covering) of the worm, with The life cycle for this parasite is similar to E. ilocanum
subsequent eosinophil attachment. The mam- but only differ in that of which the A. malayanum mi-
malian host metabolizes the drug rapidly and racidium in the first snail intermediate host will first
tolerates it well. be a sporocyst then become a mother redia, daughter
• Side effects, including epigastric pain, dizziness, redia and lastly, a cercaria. The first snail intermediate
and drowsiness, are minimal and disappear with- host for this parasite has not been identified yet but
in 48 hours. may be suspected to be the same with E. ilocanum. As
• Experimental testing has failed to reveal evidence for the second snail intermediate hosts, they may either
of teratogenicity, mutagenicity, or other adverse be Lymnaea cumingiana or Ampullaris canaliculatus. The
effects. same cycle happens.
• At the time of this writing, praziquantel is ap-
proved by the United States Food and Drug Ad- General morphology
ministration (FDA) only for the treatment of clo- Adults. They average under 1 cm in length and 0.2 cm
norchiasis, opisthorchiasis, and schistosomiasis. in width and are distinguished by a collarette of spines
on a disk surrounding the oral sucker (Fig. 6.14). The
Echinostomes adult worms are seen only after treatment but can be
• A number of medium-sized intestinal flukes belong- recognized by the circumoral spines.
ing to the genus Echinostoma and to several related • Echinostoma ilocanum
genera have been reported from Japan, the Philip- The adult worm of this parasite is a (1) reddish-gray
pines, Malaysia, Sumatra, Java, Sulawesi, India, and worm tapered posteriorly; (2) has 49 to 51 collarette of
a few other localities in Asia. There is suggestive spines; (3) its oral sucker can be seen in the center of its
FIG. 6.13 Life cycle of Echinostoma.
circumoral disk while its ventral sucker is positioned an-

terior fifth of its body; (4) it has two deeply lobed tes-
tes that are arranged in tandem in the third quarter of it
body; (5) its ovary is situated in front of the anterior tests;
(6) Intestinal ceca is simple; (7) its follicular vitellaria can
be found at the posterior half of the body; and (8) uterine
coils are in between the ovary and ventral sucker.
• Artyfechinostomum malayanum
The adult worm of A. malayanum is (1) slightly larg-
er than that of E. ilocanum and has a rounded posterior
end; (2) it has 43 to 45 collarette of spines; (3) it has
FIG. 6.14 A, Echinostoma sp. B, anterior end two large testes, each of it has six to nine lobes and
of Echinostoma, showing circumoral spines. are arranged in tandem; (4) and its ovary is small and
(Photomicrographs by Zane Price.) rounded positioned anteriorly in the testes.
Eggs. E. Ilocanum eggs are straw-colored, operculat-

ed and ovoid and are smaller than that of A. malaya-
num. A. malayanum has golden-brown operculated
eggs larger than E. ilocanum. The unembryonated eggs
are similar in shape to those of Fasciolopsis and vary
in size in the different species. Some species overlap
the size range of Fasciolopsis, and therefore an exact
identification cannot be made from examination of
the eggs. Frequently a diagnosis can be established
on the basis of the patient’s history or the clinical
findings.

Little damage is caused to the intestinal mucosa by at-
tachment of these flukes. Heavy infections may pro-
duce inflammation and mild ulceration, with diarrhea
and abdominal pain, while light ones are probably as-
ymptomatic.
FIG. 6.15 Heterophyes heterophyes and Metagonimus
Treatment yokogawai: (gs) genital sucker; (o) ovary; (os) oral sucker;
• Drug of choice: Praziquantel, 25 mg/kg body weight (sr) seminal receptacle; (sv) seminal vesicle; (t) testis; (ut)
three times in a single day. uterus; (vi) vitellaria; (vs) ventral sucker. Drawings made
• Tetrachloroethylene is also known to be effective. with the aid of a camera lucida (approximately ×40).
The dose is 0.1 ml/kg, taken on an empty stomach
after a light meal the preceding night. The maxi- Life cycle
mum adult dose is 5 ml. Heterophyids are acquired by ingesting raw or pickled
• Alcohol and fats should be avoided for 24 hours fresh-water fish of many kinds. The life cycle is similar
before and after treatment, and nothing other than to that of the opisthorchids (see Fig. 6.5), except that
water should be taken for 3 hours after ingestion of heterophyids parasitize the small intestine.
the medication. Metacercariae of the heterophyid flukes encyst un-
der the scales or in the flesh of fish. They are not killed
Heterophyids by the various pickling processes to which fish is some-
Two-minute flukes, Heterophyes heterophyes (“Von- times subjected. Thorough cooking will, of course, kill
Siebold’s fluke) and Metagonimus yokogawai (Fig. 6.15), them.
occur in Japan, Korea, China (including Taiwan), the A variety of fish-eating mammals serve as reservoir
Philippines, and western India. Heterophyes has also hosts for both of the heterophyids that infect humans.
been reported from Egypt and Israel, and Metagonimus Human infections outside the endemic area may result
from the Balkans, Spain, Israel, the former USSR, and from the consumption of pickled fish or of sushi made
Indonesia. from fish imported from the endemic areas. Such infec-
• The parasites live attached to the wall of the small tions are known to have occurred in the United States.
intestine. Metagonimus is somewhat larger than Het-
erophyes but does not exceed 2.5 mm in length by General morphology
0.75 mm in width. Adults. Only following anthelminthic treatment are
• Heterophyes has a third sucker, surrounding the geni- the adult worms seen in the feces. In Heterophyes het-
tal pore; this structure is not present in Metagonimus. erophyes, the adult worm is said to be (1) avocado- or
• Many other species of heterophyids have been pear-shaped with three suckers, (2) it has two ovoid tes-
found as occasional human parasites; it has been tes, (3) the ovary is lobed and (4) it is very small, thus,
stated that all heterophyids have this potential. called the smallest fluke of man.
In one area of Laos, serologic techniques indicat-
ed the probable presence of heterophyids (Hap- Eggs. The eggs, which contain fully developed mira-
lorchis spp.) in 75% of persons tested (Giboda cidia and possess prominent opercular shoulders, are
et al., 1991). brownish yellow. Those of Heterophyes are, on average,
slightly larger than those of Metagonimus, but differ- Life cycle

ences are too slight to be of value. The size range for The life cycle is not known, but by analogy with related
the two species is 26.5 to 30 µm by 15 to 17 µm. The worms, infection of the mammalian host is probably
eggs closely resemble in size and shape those of worms contracted by ingesting metacercariae encysted on veg-
belonging to the genera Clonorchis* and Opisthorchis, etation.
Heterophyid eggs do not have the abopercular protru-
berance that is present in the latter. Some morphologic Symptoms and pathogenesis
differences have been described, but these are slight The worms live attached to the mucosa of the cecum
and not constant. and ascending colon, where they produce local inflam-
mation and mucous diarrhea.
Attached to the intestinal wall, the adult worms pro- Treatment
duce no symptoms unless present in large numbers. • Tetrachloroethylene, administered as outlined for
Chronic intermittent diarrhea, nausea, and vague ab- echinostomiasis, is said to be effective.
dominal complaints have been reported. Occasionally • It is probable that praziquantel, given in the usual
the worms invade the mucosa, and their eggs depos- dose of 25 mg/kg three times in 1 day, would be
ited in the tissues may gain access to the circulation preferable, as it is less toxic.
leading to formation of brain or spinal cord embo-
lisms. Seizures, neurologic deficits, and cardiac insuf-
ficiency have been ascribed to granulomas that form LUNG FLUKE
around these eggs. Eggs of this parasite may be en- At least eight different species of lung flukes, all belong-
capsulated in the cardiac muscle may lead to hetero- ing to the genus Paragonimus, are known to infect hu-
phyid myocarditis and may lead to death of the host mans. It is probable that others may do so from time
due to cardiac arrest. There were cases in Hawaii that to time. Worldwide, at least 28 species of Paragonimus
refer to heterophyid myocarditis as “mystery death” have been identified. These are primarily parasites of
among Filipino descent due to aberrant heterophyid wild felines such as tigers, lions, leopards, and civet
eggs. Moreover, around 14% of cardiac failures in the cats; of canines such as dogs, foxes, and wolves; and
Philippines have been associated with heterophyid of a variety of other mammals, including wild pigs,
myocarditis. badgers, mongooses, opossums, raccoons, minks, and
others that eat fresh-water crabs and crayfish. Humans,
Treatment then, are accidental hosts of these parasites, to some of
• Drug of choice: Praziquantel, administered as indi- which they seem better adapted than others.
cated for treatment of fasciolopsiasis (again unap-
proved for this indication by the FDA). Paragonimus spp.
• An alternative drug is tetrachloroethylene, as used in • Paragonimus westermani (Fig. 6.16) is the best known
treatment of the echinostomes. of the lung flukes affecting humans, and the one
Gastrodiscoides hominis
Gastrodisciasis is commonly seen in Assam and other
parts of India, where it also occurs in pigs. It has also
been reported from Southeast Asia and Malaysia; in the
latter area the reservoir host is the mouse deer Tragulus
napu.
General morphology
Adults. The worm is pear shaped, the flattened ventral
surface of the enlarged posterior end being composed
of a much enlarged ventral sucker, or acetabulum.
Worms range in size from 5 to 14 mm by 4 to 6 mm.
Eggs. The ovoid, greenish brown eggs measure about FIG. 6.16 Paragonimus westermani. (Photomicrograph by
150 µm by 60 to 72 µm. Zane Price.)
with the widest geographical range. It also behaves prominent operculum. Opposite its operculum is a
in humans much as in its feline and other wild thickened abopercular protruberance.
hosts, and we can assume that the host-parasite rela-
tionship is good. Life cycle
• P. westermani is a common human parasite in the 1. Infection results from the ingestion of raw or insuf-
Far East, including Japan, Korea, Manchuria, the ficiently cooked crayfish or fresh-water crabs (Sun-
People’s Republic of China (including Taiwan), dathelphusa philippina, formerly known as Parathel-
Southeast Asia (including Philippines), and phusa grapsoides) (Fig. 6.17), in which the encysted
Papua New Guinea. In the Pacific area it is found metacercarial stage occurs.
in the Solomons and Samoa. In the Indian sub- • Humans acquire paragonimiasis in a variety of
continent it occurs in Bengal, Madras, Mani- ways. Some eat infected crabs or crayfish un-
pur, Assam, the area around Bombay, and in Sri cooked or pickled, either as food or as folk rem-
Lanka. In Africa it has been reported from the edies. In much of the Orient, live crabs are im-
Congo, Nigeria, and the Cameroon. Two other mersed in wine and the “drunken crab” is eaten
species are reported as human parasites in Africa, as a delicacy. Crab soup is boiled and safe for the
and two have been reported in Japan (one of consumer, but in its preparation live crabs are
which occurs also in Korea and Taiwan). At least crushed, and living metacercariae may contami-
two other species infect humans in China and nate the fingers and utensils of the person pre-
Southeast Asia. The identity of the species infect- paring the meal.
ing humans in the Philippines is in question, but 2. Metacercariae excyst in the small intestine, pen-
at any rate it is closely related to P. westermani. etrate through its wall into the peritoneal cavity,
• Paragonimus kellicotti is enzootic throughout the and normally make their way to the diaphragm,
eastern and midwestern United States, affecting a through the esophageal hiatus, and pleura into the
wide variety of animals that from time to time eat lungs. A cystlike capsule surrounds the developing
crayfish. There have been only two reported human parasite, which grows to maturity in a period of
cases of presumed P. kellicotti infection—one in 6 weeks.
1934 and the other in 1984 (Pachucki et al., 1984). 3. Rupture of the cyst capsule into a bronchiole leads
The latter case involved a young man who ate raw to a discharge of eggs but not of the parasite, which
river crayfish in Missouri, developed pulmonary in- continues to produce eggs for a long time. Chronic
filtrates and eosinophilia, and had eggs in his spu- infections may persist for many years after the pa-
tum. He was successfully treated with praziquantel. tient leaves an endemic area.
Refugees from Southeast Asia may be infected with 4. The immature eggs passed in feces embryonates
P. westermani (Yee et al., 1992) and possibly other in the water, moist soil or leached feces, and mi-
species. P. mexicanus occurs from Mexico down racidium develops with 2 to 7 weeks. In addition,
through most of South America; human infections immature eggs may also be passed out through the
with this parasite are sporadic in most areas. In sputum.
Ecuador human paragonimiasis is endemic; in Peru 5. The miracium swims freely in search for its first
it is focally important, and at least two different (as intermediate host, a snail. In the Philippines, Ante-
yet unidentified) species infect humans (Hillyer and melania asperata and Antemelania dactylus, formerly
Apt, 1997). known as Brotia asperata serve as the first intermedi-
ate hosts and once the miracidium is eaten by the
General morphology snail, it passes through one sporocyst and two redial
Adults. Adult worms are reddish brown and thick stages to finally mature into a cercaria.
bodied resembling a coffee bean. They measure 0.8 to 6. The cercaria emerges from the snail to find the
1.6 cm in length, 0.4 to 0.8 cm in width, and 0.3 to second intermediate host, the mountain crabs, or
0.5 cm in thickness. Typically, they are encapsulated in snails with cercaria may be ingested by the crabs
cystic structures adjacent to the bronchi. The eggs are wherein the cercaria penetrates the soft parts of the
discharged into the bronchi or bronchioles; they may said crustacean and encysts as a metacercaria in the
be expectorated or, if swallowed, appear in the feces. body muscles, legs, gills or viscera.
7. The definitive host will become infected again upon
Eggs. Paragonimus eggs are oval, yellowish-brown, ingestion of raw or uncooked crabs harboring meta-
thick-shaped unembryonated eggs with flattened but cercaria and the cycle continues.
FIG. 6.17 Life cycle of Paragonimus westermani.
Diagnostic tests Symptoms

• Diagnosis depends on identification of the charac- • No recognizable symptoms attend the migration of
teristic dark golden-brown eggs (see Fig. 6.1D) in the parasites.
sputum or feces, although the clinical picture may • As they grow in the lungs there is an inflammatory
be suggestive. The ovoid eggs have a flattened oper- reaction, which may be sufficient to produce fever.
culum, distinctly set off from the rest of the shell When the cysts rupture, a cough develops, and there
by raised opercular shoulders. They measure 80 to may be increased production of sputum.
120 µm by 48 to 60 µm and are immature when • The sputum is frequently blood tinged and may
found in the sputum or feces. Various serologic tests contain numerous dark brown eggs and Charcot-
have been developed (see Chapter 16). Leyden crystals.
• The chest film (Fig. 6.18) may show a patchy in- • The appearance of the eggs in sputum has sug-
filtrate with nodular cystic shadows or calcifica- gested iron filings to some observers. Hemopty-
tion; pleural effusion may be seen. Cerebral calci- sis may occur after paroxysms of coughing.
fications may also occur. Eosinophilia is generally • There may be severe chest pain. The severity and
present. progression of symptoms depend on the number
visual disturbances, and motor weakness

culminating in convulsive seizures, especial-
ly focal (Jacksonian) ones, and often with
meningeal signs as well as motor and sen-
sory disturbances. Cutaneous paragonimiasis
seems characteristic of certain species such as
Paragonimus skrjabini (also known as Paragoni-
mus szechuanensis) in China, which may also
invade and severely damage the liver. These
abnormal wanderings may be characteristic
of the behavior of a parasite in an unfamiliar
host.
Pathogenesis
• Migration of larval Paragonimus though the intes-
tinal wall and into the pleural cavity is generally
accomplished in experimental animals within 5 to
10 days. Some young flukes wander about in the
peritoneal cavity for 20 days or more, growing con-
FIG. 6.18 Pulmonary paragonimiasis with ring
shadows (black arrows) and linear lucency (white arrows)
siderably in size and penetrating into various organs
representing burrow tract. (Courtesy of R. Suwanik, en route. Those reaching sexual maturity in ectopic
Dhonburi, Thailand.) sites apparently remain there. Worms that reach the
brain do so by way of the soft tissues of the neck and
the cranial foramina. Passage of worms through the
of parasites present and on whether or not the tissues produces local hemorrhage and leukocytic
infection is treated successfully, but as time goes infiltration of a transitory nature and without clini-
on there is increasing dyspnea, and chronic bron- cal significance except for rare cases in which they
chitis develops. wander subcutaneously.
• Bronchiectasis may result, and pleural effusion is • When the worms settle down, either in the lungs
sometimes seen. Increasing fibrosis of the lungs or in ectopic foci, more pronounced tissue reac-
occurs with longstanding infection. The clinical tions occur. In the lungs a leukocytic infiltrate forms
picture may closely resemble that of pulmonary around the parasite, and fibrous tissue surrounds
tuberculosis. the infiltrate to form a cyst wall. Communication
• Symptoms of Paragonimiasis resemble those of the cyst with the respiratory tree may result from
of pulmonary tuberculosis. In the developing inclusion of a bronchiolar branch within the cyst or
country like the Philippines, where both para- from erosion of the cyst into adjacent bronchioles.
gonimiasis and pulmonary tuberculosis are en- Eggs may infiltrate the surrounding pulmonary tis-
demic, there should be care in making a correct sues (Fig. 6.19) or may be carried by the circulation
diagnosis so as to avoid wastage of resources. to other parts of the body, in which they evoke a
• Humans may not be as suitable a host as the normal granulomatous reaction similar to that surround-
one for many of these parasites, and as is often the ing schistosome eggs in tissues. Such lesions have
case under such circumstances, the worm may behave been observed in many organs and tissues, includ-
in an abnormal manner. Instead of taking its usual ing both pericardium and myocardium, but they are
migratory path to the lungs, it may enter other parts apparently rare in the central nervous system.
of the body such as brain, spinal cord, or abdominal • Worm cysts in the peritoneal cavity or other sites
cavity, or wander through the subcutaneous tissues. outside the lungs are similar to pulmonic cysts. Peri-
• The most serious consequence of such migration tonitis and abdominal adhesions resulting from in-
is cerebral paragonimiasis, in which the fluke en- fection have been reported, although there is usually
ters the cranial cavity through the jugular fora- little or no inflammatory reaction, and suppurative
men and invades the brain tissue. and ulcerative lesions are uncommon.
• The onset of symptoms is usually insidious, • In the brain (Fig. 6.20) lesions may occur in both
with fever and headache, nausea, vomiting, gray and white matter, and sometimes they are
the worms die or escape, the cysts gradually shrink

as their contents are absorbed, eventually leaving a
nodule of fibrous tissue and eggs, which may partly
calcify.
Epidemiology
• In some areas human paragonimiasis may be com-
mon enough that human-to-human transmission
(via the appropriate snail and crab intermediate
hosts) occurs. In most areas the disease is princi-
pally one of the local crab-eating mammals, and
humans enter into the life cycle accidentally. Many
different species of crabs and crayfish may be infect-
ed in various parts of the world, and only seldom
are these part of the human diet. Thus, endemicity
of the disease rests on dietary habits, methods of
FIG. 6.19 Paragonimus westermani eggs in section of food preparation, and the presence of appropriate
lung tissue; note operculum (hematoxylin and eosin stain). snail hosts, fresh-water crustaceans, and the reser-
voir host.
• Paratenic (transfer) hosts may play an important
role in the life cycle of Paragonimus in the wild and
may also contribute to human disease. In southern
Kyushu, Japan, hunters customarily eat thinly sliced
raw wild boar meat, which may contain migrating
larvae of Paragonimus. These larvae can pass through
the intestinal wall of their new host and continue
their development in humans. Tigers in Sumatra are
heavily infected, and this infection is believed to re-
sult from infected paratenic hosts such as wild boar,
wild pigs, monkeys, and other small mammals.
Treatment
• Praziquantel, 25 mg/kg three times daily for 2 days,
is the drug of choice for treatment of pulmonary
paragonimiasis and presumably for cutaneous
forms of the disease. Smaller daily doses, even when
administered over a longer period to achieve the
FIG. 6.20 Eggs of Paragonimus westermani in human
same cumulative dose, have been found ineffec-
brain; note extensive collagen scar beneath the eggs.
tive. We have seen no reference to its use in cerebral
(Courtesy of Dr. W. Jann Brown, University of California Los
Angeles School of Medicine.) paragonimiasis but suspect that (as in cerebral cys-
ticercosis) it might have to be administered over an
extended period.
connected by passageways. Lesions in the gray mat- • An alternative drug for the treatment of pulmonary
ter may cause a thickening of the pia and adhesive paragonimiasis is bithionol,* administered orally at
arachnoiditis. In older lesions a more or less defini- the rate of 15 to 25 mg/kg body weight twice daily
tive cyst wall develops. on alternate days for a total of 10 to 15 days.
• Since the majority of worms migrate to the lungs, • Bithionol was formerly used in the formulation
and since most infections are light, extrapulmo- of medicated soaps but is no longer used for this
nary paragonimiasis is rarely seen in humans. Cysts, purpose because of its association with contact
in whatever location, may contain living or dead dermatitis. Skin rashes and urticaria are not in-
worms; a yellow to brownish, thick fluid, sometimes frequently seen in the course of bithionol treat-
hemorrhagic; eggs; and Charcot-Leyden crystals. If ment.
• Abdominal cramps, nausea and vomiting, and upon reaching the pancreatic duct and will imply
diarrhea are rather frequent side effects, as are damage.
dizziness and headache. Hepatic and renal in-
volvement, hypertension, extrasystoles, and General morphology
first-degree heart block have all been reported to Adults. The adult worm is a reddish-brown, leaf-
occur during the course of treatment but are ap- shaped parasite (Taylor et al., 2016) with ruffled bor-
parently transient. ders, oral sucker is larger than the ventral sucker, two
• Bithionol is contraindicated in patients with a notched testes, and one notched ovary.
clear history of sensitization to preparations con-
taining this drug. A list of such preparations is Eggs. The eggs are similar to the eggs of the lan-
given in the informational leaflet supplied by the cet fluke, Dicrocoelium dendriticum, and may be seen
CDC Drug Service. through direct examination of feces.
• Reports indicate that triclabendazole (approved
by the FDA only for veterinary use) in one or two Treatment
oral doses of 10 mg/kg body weight is effective in Praziquantel may be used for treatment.
treatment of pulmonary paragonimiasis (Calvopiña
et al., 2003; Ripert et al., 1992), as in human fascio-
liasis. BLOOD FLUKES
Blood flukes are the most important flukes. Schistoso-
miasis is a neglected tropical disease so with the food-
PANCREATIC FLUKE borne trematodiases caused by Paragonimus, Fasciola,
Eurytrema pancreaticum Heterophyids, Clonorchis, Opistorchis and Echinostoma
A common parasite of the domestic animals and her- species.
bivores such as hogs, sheep, goat and cattles in Japan, Three species of schistosomes that parasitize hu-
E. pancreaticum, has also affected cosmopolitan popu- mans are of major importance: Schistosoma mansoni, S.
lation in Korea, India, China, Malaysia, Madagascar, japonicum, and S. haematobium. Less common are Schis-
Mauritius, and former USSR. Human infections are tosoma intercalatum in Africa and Schistosoma mekongi in
seen in China and Japan. It is a parasite infecting the the Mekong Basin. Although the adult worms live in
pancreas resulting to chronic inflammation of the pan- the blood vascular system, the eggs of S. mansoni, S.
creatic duct that may lead to Chronic Granulomatous japonicum, S. intercalatum, and S. mekongi are generally
Pancreatitis, enlargement of the pancreas, and may also found in the feces. Eggs of S. haematobium are occasion-
lead to diabetes. ally seen in the stool but usually occur in the urine.
Life cycle General morphology

1. When the infected definitive host defecates feces The schistosomes differ in a number of ways from other
containing the embryonated eggs, eggs are now ex- trematodes.
posed to the environment and are available to be • They are dioecious (i.e., the sexes are separate), and
eaten by the first intermediate host, the snail Macro- the two sexes are dissimilar in appearance.
chlamys indica. Upon ingestion, the eggs hatch and • Female worms are long (1.2 to 2.6 cm) and slen-
release the miracidium. der, with a body almost circular in cross section
2. The miracidium will now undergo development to and 0.3 mm or less in diameter.
sporocyst, redia and eventually into a cercaria. The • Male worms (Fig. 6.21) are 0.6 to 2.2 cm long,
cercaria may now be shed and adhere to grass where and Although the body is flattened behind the
the second intermediate host, the grasshopper or ventral sucker, it looks cylindrical, as it is char-
ant (Technomyrmex deterquens), may come in contact acteristically incurved ventrally to form a gy-
with. necophoral canal in which the female reposes
3. Cercaria will invade the said host and will encyst (Figs. 6.22 and 6.23).
into metacercaria. Infection may now be acquired • The body structure of the schistosomes, and partic-
through ingestion of raw grasshoppers or ants by the ularly that of the long, thin females, seems clearly
definitive hosts. Infection in human is only possible an adaptation to an intravascular existence. The fe-
upon accidental ingestion of the secondary interme- males leave the male worms to deposit their eggs
diate hosts of this parasite. Metacercaria will excyst in small venules close to the lumen of the intestine
FIG. 6.21 Schistosoma mansoni, male: (gy) gynecophoral

canal; (in) intestine; (os) oral sucker; (t) testes; (vs) ventral
sucker. FIGURE 6.23 Scanning electron micrograph of male and
female Schistosoma mansoni. (Courtesy of Dr. Ming-Ming
Wong.)
egg shell and helps to digest the overlying tissue.

The action of this enzyme, together with necrosis
of the tissue caused by pressure and the effect of
the spine, works to liberate the egg from the tissues
into the lumen of the intestine or bladder.
• Schistosome eggs are not operculated, and they
hatch by rupture if liberated into fresh water. The
miracidium that escapes swims in search of an ap-
propriate snail host. If successful, it penetrates the
snail, where it undergoes a cycle of development,
giving rise to a large number of cercariae (infective
stage) that affects for humans.
• Redia and metacercaria are not included in its life
cycle. Only one (1) host is involved. Eggs are the
cause of its pathology and not its adult worms.
Life Cycle
All other trematode parasites of humans are acquired
through ingestion of metacercariae, but infection with
schistosomes follows exposure to water in which in-
FIGURE 6.22 Schistosoma mansoni, male and female in fected snails have liberated their cercariae.
copula. (Photomicrograph by Zane Price.)
Human infection takes place by direct penetration
of the cercariae through the skin to invade the circula-
or bladder. The worms dilate the vessels when they
tory system.
penetrate into them for oviposition and withdraw
• Cercariae of the schistosome parasites (Fig. 6.24),
as the eggs are laid, so that the eggs are wedged firm-
both of humans and of other animals, have a forked
ly into the small vessels. Sharp spines on the eggs
tail and glands at the anterior end that assist pene-
of S. mansoni and S. haematobium probably assist
tration through the skin. During this process, the tail
in their retention in the blood vessels. An enzyme
is lost, and profound metabolic changes take place
elaborated by the miracidium diffuses through the
they have been found on rare occasions infecting both

African and West Indian monkeys and rodents in Africa
and South America, it is not thought that any of these
animals is of importance as a reservoir host.
• Diagnosis during the acute period of the disease is
based on the recovery of the characteristic eggs in
the stool.
• The light yellowish-brown eggs (see Fig. 6.1B)
FIGURE 6.24 Cercaria of Schistosoma mansoni showing measure 114 to 118 µm by 45 to 73 µm. They
penetration glands. (Courtesy of Dr. David Bruckner, are elongate, regularly ovoid, and possess a
University of California Los Angeles School of Medicine.) large lateral spine, shaped rather like a rose
thorn, which projects from the side of the egg
(e.g., an almost instantaneous change from aerobic near one pole.
to anaerobic respiration). • In the chronic stage of the disease, eggs may not be
• The immature fluke, referred to as a schistosomu- found in the stools. Rectal biopsy may be of value in
lum, remains in the subcutaneous tissues for about such cases, as eggs can be demonstrated in the tis-
2 days. After invasion of a blood vessel, the young sue (Fig. 6.26) by flattening between two glass slides
flukes are carried to the lungs and thence to the liver and examination under the microscope. Adequate
sinusoids, where they begin their growth. Two weeks sampling involves taking four snips, on the anterior,
or longer after infection, the maturing worms com- posterior, and both lateral walls. Various specialized
mence a migration against the flow of the blood in techniques employed in the laboratory diagnosis of
the portal system to their final location in mesenter- schistosomiasis are described in Chapter 14. Sero-
ic or vesicular veins. Their final locations in the host logic tests are discussed in Chapter 16.
differ in the different species and will be discussed
separately for each. Schistosoma japonicum
The Oriental blood fluke S. japonicum (Figs. 6.27
Schistosoma mansoni and 6.28) is confined to the Far East, where it occurs
A consequence of the African slave trade was the es- in parts of China (including Taiwan), Japan, the Philip-
tablishment of S. mansoni (Fig. 6.25) in the Western pines, and Indonesia (Sulawesi).
Hemisphere. This fluke, which occurs over extensive
areas of Africa and in the Arabian Peninsula and Mala- General morphology and diagnosis
gasy, has also become well established in Brazil, Suri- • Among the other pathogenic schistosomes, S. japon-
nam, and Venezuela, as well as in parts of the Carib- icum is the most virulent as it lays the most number
bean. Of special interest is infection in Puerto Rico. of eggs and is highly zoonotic.
The influx of people from this island into New York • Unlike S. mansoni, which rarely infects other ani-
and other larger cities has resulted in a more frequent mals, S. japonicum is found in virtually all mammals
diagnosis of schistomiasis caused by S. mansoni in this exposed to infected water. During World War II,
country. It does not seem to present a public health larger numbers of American and Australian troops
problem, however, and there is little reason to expect serving on the island of Leyte in the Philippines
that the infection could become successfully estab- acquired the infection. Vigorous control measures,
lished in North American snail hosts. involving both patient treatment and snail eradica-
tion, have resulted in marked reduction in preva-
General morphology and diagnosis lence of this infection in recent years.
Adults of S. mansoni usually live in the smaller branches • S. japonicum adults inhabit the branches of the supe-
of the inferior mesenteric vein in the region of the low- rior mesenteric vein adjacent to the small intestine;
er colon. They may be found elsewhere in the portal the inferior mesenteries and caval system may also
system, in the vesical venous plexus, or in other ectopic be invaded, as the worms tend in time to migrate
foci on occasion. They subsist on ingested blood. farther and farther from the liver. The males may
S. mansoni is the smallest of the schistosomes that reach a length of 2.2 cm and the females 2.6 cm.
infect humans: males attain a length of only 1 cm This species produces more eggs than the other two
and females an extreme length of 1.6 cm. Although schistosomes, and the eggs are smaller and more
nearly spherical. For a combination of these reasons,
FIG. 6.25 Life cycle of Schistosoma mansoni.
more eggs become free in the general circulation, to opsy is sometimes helpful in making the diag-
be filtered out in the liver, lungs, or other organs. nosis in chronic cases, as are serologic tests (see
• Infection with even a few worms of this species may Chapter 16).
be very serious. Hepatic and pulmonary cirrhosis are
commonly seen in the chronic stage of this infec- Schistosoma haematobium
tion, and CNS symptoms may occur following lodg- Urinary schistosomiasis is generally caused by S. hae-
ment of eggs in or near nerve tissue. matobium (Fig. 6.29) although, as has been mentioned,
• Diagnosis may be made by identification of the eggs the other two species may sometimes inhabit the vesi-
in the stool. cal plexus. The original focus of this disease was appar-
• The eggs are spherical to oval in shape (see ently the Nile Valley, where it is highly endemic. From
Fig. 6.1E). They may have a minute lateral spine there it has spread widely throughout Africa and now
(Fig. 6.28), but this structure may be absent in occurs also in the islands off the east coast of that con-
some strains. The size range is from 55 to 85 µm tinent, in Asia Minor, on the island of Cyprus, and in
by 40 to 60 µm. Examination for eggs should be southern Portugal. There is an isolated focus in India,
carried out as indicated for S. mansoni. Rectal bi- and it has recently been introduced into Jordan.
FIG. 6.28 Egg of Schistosoma japonicum. Material

for this figure courtesy of the Shanghai Institute for
Parisitic Diseases, the People’s Republic of China.
FIG. 6.26 Schistosoma mansoni eggs, as seen in rectal

biopsy. (Courtesy of Dr. W. Jann Brown, University of
California Los Angeles School of Medicine.)
FIG. 6.27 Life cycle of Schistosoma japonicum.

FIG. 6.29 Life cycle of Schistosoma haematobium.
General morphology and diagnosis tion or sedimentation of the urine. Containers

After the worms mature in the sinusoids of the liver, used for collection of urine specimens must not
they migrate from that organ, and in the case of S. contain preservatives if the hatching test is to be
haematobium the majority of them reach the vesical, done.
prostatic, and uterine plexuses by way of the hemor- • The eggs contain a fully developed miracidium
rhoidal veins. Adult male worms may reach a length when deposited and are from 112 to 170 µm in
of 1.5 cm, and the females 2 cm. The eggs are depos- length and 40 to 70 µm in breadth. They have a con-
ited in the walls of the bladder or to a lesser extent spicuous terminal spine and are a light yellowish-
in the uterus, vaginal wall, prostate, or other organs. brown color. Terminal hematuria in a patient from
Those deposited in the wall of the bladder may break the endemic areas should make one highly suspi-
through into the lumen and escape with the urine. cious of this infection. It may be possible to find the
• Diagnosis is most readily made by recovery of the eggs in biopsy material from the bladder wall, the
characteristic eggs (see Fig. 6.1C) by centrifuga- uterine cervix, or the vagina.
Schistosoma mekongi • A cross-sectional survey of more than 1200 persons

A schistosome from the Mekong River basin in in the city of Bata, Equatorial Guinea, revealed an
southern Laos and Cambodia resembles S. japonicum overall prevalence of 21% S. intercalatum infection.
in adult structure and in its ability to infect vertebrate This was the only schistosome found in stools or
hosts other than humans, but it has a different snail urine in this area. Peak prevalence and highest para-
intermediate host, the freshwater snail Neotricula ap- site load were in 5- to 14-year-old children.
erta, and seems to produce a milder disease in humans. • The disease produced by this infection is relatively
Domestic pigs have been shown to be reservoir hosts benign, and hepatomegaly is usually not marked.
for S. mekongi in Laos (Strandgaard et al., 2001). There may be severe digestive disturbances accom-
panied by pain and bloody stools.
General morphology
• The eggs of S. mekongi are consistently smaller than Symptoms
those of S. japonicum, having a size range of 30 to • Before we discuss symptoms in detail, it must be
55 µm by 50 to 65 µm. Those of S. japonicum show emphasized that many patients with brief exposure
regional size differences, but the overall size range is to schistosomiasis (i.e., travelers) may have either
40 to 60 µm by 55 to 85 µm. no symptoms or symptoms that do not differ ma-
• Human infections with a schistosome having eggs of terially from those of noninfected control travelers.
a similar size have also been reported from Malay- This seems to be more true of those infected with S.
sia. The identity of this latter schistosome remains mansoni than of those who acquire S. haematobium,
to be determined. although acute symptoms, occurring in a small per-
centage of patients, are more likely to been seen in
Schistosoma intercalatum S. mansoni infections. As even a mild infection may
• This species occurs in humans in Western and lead to serious complications, it is good to perform
Central Africa. serologic tests on all travelers who give a history of
• Adult worms are found in the mesenteric vessels, possible exposure to infection and to treat all those
and eggs are voided in the feces. who prove to be infected.
• The eggs of S. intercalatum closely resemble those of • Following penetration of the skin by cercariae of a
S. haematobium but can be differentiated by a slight schistosome that infects humans, a transient reac-
bend in the terminal spine (Fig. 6.30); the egg shell tion may be seen. Petechial hemorrhages occur at
is Ziehl-Neelsen positive, whereas those of the other the site of penetration, with some localized edema
schistosomes are not. and pruritus, which reach a maximum in 24 to
36 hours and disappear in 4 days or less. During the
succeeding 3 weeks there may be transient toxic and
allergic manifestations. These may be mild and may
pass unnoticed, or there may be generalized malaise,
fever, giant urticaria, vague intestinal complaints,
and so forth, partly depending on the intensity of
infection. Migration of the worms throughout the
lungs may cause cough or hemoptysis. Soon after
the developing schistosomes reach the liver, acute
hepatitis may develop.
• When the flukes reach the mesenteric or vesical ve-
nules and egg laying commences, the acute stage of
the disease is seen. The onset of this stage may oc-
cur 1 to 3 months after infection. Symptoms of the
acute stage may range from mild to severe, and the
degree of reaction is not necessarily proportional to
the number of parasites involved. Clinical disease at
this stage is usually seen only in relatively heavy in-
FIG. 6.30 Egg of Schistosoma intercalatum. Note fection or in persons recently arrived in an endemic
curvature of terminal spine. (From Odongo-Aginya et al. Am area. With the extrusion of eggs through the wall
J Trop Med Hyg 1994; 55:724. Courtesy of the authors.) of the intestine or bladder, there may once again
be generalized malaise, fever, urticaria, abdominal

pain, and liver tenderness. In S. mansoni or S. japoni-
cum infections there may be diarrhea or dysentery at
this stage, while in S. haematobium infections there
is often hematuria at the end of micturition, and
sometimes dysuria.
• Schistosomiasis japonicum
• The early symptoms tend to be quite severe in
heavily infected persons, with abrupt onset of
fever, chills, and the other signs and symptoms
mentioned previously coming from 4 to 6 weeks
after infection. There is often a significant mor-
tality rate at this stage of the disease, which is
called Katayama fever for the locality in Japan
from which it was first described. A Katayama-
like syndrome may be seen with the other types
of schistosomiasis, but is not as common.
• The chronic stage of the disease comes on gradu- FIG. 6.31 Schistosomiasis mansoni. Note development
ally. Egg deposition takes place in the smaller of collateral circulation secondary to severe hepatic
vessels, close to the lumen of the intestine or involvement. (Photograph by F. Etges. From Zaiman H [ed.].
bladder. Many eggs remain where deposited; A pictorial presentation of parasites.)
secretions of the contained miracidia evoke the
formation of minute abscesses around them, • The disease may involve the entire intestinal tract
and they are liberated into the lumen of the af- but is more likely to be confined to the large
fected organ. Other eggs are dislodged and swept bowel. It may present a picture suggestive of
into the circulation; it is these embolic eggs that granulomatous colitis, with abdominal cramps
produce most of the pathologic changes seen in and tenderness and intermittent bloody mucoid
chronic schistosomiasis. stools.
• Hepatosplenic schistosomiasis • Intestinal polyposis is not uncommon in schisto-
• the most common form of chronic infection in somiasis mansoni, and in such patients the diar-
patients with S. mansoni or S. japonicum, also oc- rhea is more pronounced, and the protein-losing
curs regularly in S. haematobium infections, but enteropathy results in marked weight loss and
tends to be subclinical or mild in schistosomiasis anemia. Colonoscopy is often the most success-
japonicum. ful means of diagnosing this condition. Hepato-
• Hepatic parenchymal damage, unresolved after splenic and intestinal involvement are present in
successful treatment with praziquantel, may be every case of S. mansoni or S. japonicum infection,
found in approximately 50% of patients with S. ja- but clinically one or the other almost always pre-
ponicum infections (Watt et al., 1991). Eggs, carried dominates. In their more advanced forms, they
back through the mesenteric vessels, lodge in the are usually readily diagnosed, although the hep-
liver, where granulomas form around them. Over atosplenic form of the disease can be confused
a period of time, which may range from as little with other conditions such as chronic viral hepa-
as 18 months in heavy infections to many years titis and protein malnutrition, and the intestinal
in lighter ones, the liver becomes grossly enlarged form with granulomatous colitis.
and the left lobe disproportionately so. The chron- • Urinary schistosomiasis is seen with S. haematobium in-
ically enlarged liver is not tender. The spleen may fections, and as with the other two types of disease,
be barely palpable or massively enlarged. Portal light infections are usually asymptomatic Dysuria,
hypertension, resulting from the obstructive liver urinary frequency, and hematuria are early symp-
disease, leads to esophageal varices, which may toms and signs, but in endemic areas they are so fre-
bleed, and finally to massive ascites (see Fig. 6.31). quent as to be in large measure disregarded—in fact,
• Intestinal schistosomiasis is also more common in S. hematuria is so common among adolescent boys in
mansoni and S. japonicum infections, although not the Nile River valley as to have been widely consid-
unknown in schistosomiasis haematobium. ered a phenomenon analogous to the menarche in
girls. Terminal hematuria is usually the first sign of lower limbs, and another 12 had fever, diarrhea, mal-
infection. aise, and weight loss. These 14 and 1 asymptomatic
• Eosinophiluria is a constant finding in urinary students were found to have S. mansoni infections.
schistosomiasis.
• Chronic bacteriuria is common. Immunology and pathogenesis
• Obstructive uropathy occurs primarily in persons Immunologic processes have been more exhaustively
with high total egg burdens. studied in schistosomiasis than in any other worm
• Bladder cancer, usually a squamous cell carci- disease. They are complex and not fully understood,
noma, is seen much more frequently in patients and they will be discussed in brief outline. In part, the
with heavy S. haematobium infections than in the complexity results from profound antigenic differences
general population, and occurs primarily in areas among the various stages of the life cycle within the hu-
of the bladder where there has been heavy egg man host: cercaria, schistosomulum, adult worm, and
deposition. It is thought that these heavy egg con- egg.
centrations promote urothelial carcinogenesis. • A mild localized reaction, perhaps mediated by cer-
• A nephrotic syndrome is occasionally seen in caria-provoked histamine release by mast cells, may
both S. mansoni and S. haematobium infections; be seen on initial infection though a marked dermal
immune complex nephropathy has occasionally reaction is unusual in persons who had no previous
been demonstrated. exposure. When such a local reaction occurs, it sub-
• Pulmonary involvement may be seen in all forms of sides within about a week.
schistosomiasis but is more common with S. haema- • In previously infected, immunocompetent hosts,
tobium infections. schistosomula are subject to two kinds of antibody-
• Egg deposition in the lungs leads to fibrosis of dependent cell-mediated cytotoxic assault.
the pulmonary bed and resultant cor pulmonale, (1) Antischistosomular antibodies cover the para-
characterized by exertional dyspnea, cough, and sites, and the Fc portions of the IgG antibodies
occasional hemoptysis. Dilatation of the pulmo- attach to the Fc receptors of eosinophils, which
nary arteries and right ventricular enlargement degranulate with the release of eosinophilic ma-
may be evident on x-ray examination, and there jor basic protein, with consequent damage to the
may be electrocardiographic evidence of right schistosomular membrane and possible death of
ventricular hypertrophy and strain. the parasite.
• Cerebral manifestations of schistosomiasis are most (2) Macrophages may also contribute to elimina-
commonly seen in S. japonicum infections but may tion of the parasites at this stage, through the ac-
also be caused by S. haematobium and S. mansoni, tion of specific IgE, effecting the release of lyso-
which more frequently affect the spinal cord. somal enzymes from these cells.
• Early in the course of the disease, more general- After a few days within the host, the schistosomules
ized neurologic symptoms, such as lethargy and either become covered with host antigens or produce
confusion, may occur and have been thought to antigens that so resemble those of the host that the
have a toxic cause. antibody-related responses mentioned above no longer
• Later, focal neurologic symptoms are probably are effective. The maturing schistosomule and the adult
due to egg deposition in the cerebral or spinal worm do not evoke a measurable protective response
cord vasculature and subsequent inflammatory on the part of the host, although it is possible to detect
reaction around them. Focal and generalized sei- in vitro antibodies produced against the adult worms.
zures, speech difficulties, and optical field defects This may be something of a trade-off; although the host
characterize the cerebral infection. is not well protected against the adult worms, these
• Transverse myelitis, usually in the lumbar area, is worms do not cause any apparent damage to the host;
seen in spinal cord involvement. That such involve- however, the “immunologic camouflage” that protects
ment may come on very early is seen in a report the adult worm does not extend to its eggs.
concerning 18 American students participating in • Early in S. mansoni infections, local damage caused
a travel-study program in Kenya. The students were by egg deposition and abscess formation may give
exposed to schistosomiasis by bathing in a small rise to schistosomal dysentery, accompanied by
stream, which they dammed for that purpose. Within abdominal pain, cramping, and frequent bloody
21/2 to 3 months, 2 of the students developed rap- or blood-flecked stools. There may be consider-
idly progressive weakness and flaccid paralysis of the able hypertrophy of the affected sections of bowel
FIG. 6.33 Schistosoma mansoni. Human liver showing

“pipestem” fibrosis. (Photograph by L. Millman. From
Zaiman H [ed.]. A pictorial presentation of parasites.)
Around them granulomas develop. Granuloma forma-

tion is responsible for much of the pathology associ-
ated with schistosomiasis, which would be worse were
it not for the fascinating though incompletely under-
stood process of immunologic modulation, which re-
sults (in the S. mansoni-infected mouse model and pre-
sumably in humans) in a reduction, after some weeks,
FIG. 6.32 Schistosomiasis mansoni from the Nile delta. in the granulomatous reaction around the eggs. Modu-
Multiple strictures (large arrow) in ascending colon and lating mechanisms have been shown to include both
rectum, with multiple polyps (small arrow) and much altered cellular and humoral elements and to be T-cell depen-
mucosal pattern. (Courtesy of Dr. N. Avad El-Nasry, U.S. dent. They are not exhibited by athymic (Nu/Nu) mice.
Naval Medical Research Unit 3, Cairo, Egypt.) If the infection is heavy enough, periportal fibrosis may
develop as well. This fibrous tissue may finally come
(Fig. 6.32) with polyp formation. Fibrosis of the to surround the branches of the portal vein in a thick
submucosa in areas of egg deposition has long been white layer, visible grossly as the “clay pipestem” fibro-
advanced to explain the decrease in egg passage that sis of Symmers (Fig. 6.33). Ultrasonograms of the liver
is noted as the infection progresses. (Fig. 6.34) clearly and characteristically demonstrate
Eggs swept back to the liver with the portal blood periportal fibrosis, the severity of which can be graded
flow lodge in the finer branches of the portal system. and which (at least in the Sudan) may occur in children
FIG. 6.34 Sonogram of liver shows schistosomal periportal fibrosis. A, Liver. B, Liver above normal
kidney. Both show dense echogenic bands (arrows) surrounding intrahepatic portal radicles. (Courtesy of
Dr. Lester Hollander, Kaiser Foundation Hospital, Oakland, CA.)
younger than 8 years. Such periportal fibrosis has been ies to the superior mesenteric vein and those of S.
reported in about 20% of patients who die of schisto- mansoni in the corresponding venules leading to the
somiasis or its complications. The majority of patients inferior mesenteric vein. The eggs that escape into
exhibit granuloma formation around eggs in the liver the lumen of the intestine cause permanent damage,
and fibrosis of small portal tracts but no generalized but those that are unable to escape provoke the for-
liver involvement. Cirrhosis is no more common than mation of granulomas and an intense inflammatory
in uninfected controls. On the other hand, cirrhosis is reaction, with fibrosis and patchy ulceration. Adhe-
very commonly seen in Egyptian patients with this dis- sions to other loops of bowel and to mesentery and
ease, possibly because of nutritional factors. Even if cir- constrictions secondary to the fibrosis compound
rhosis does not develop, evidence of marked portal hy- the functional problems. Polyps may form from
pertension (splenomegaly, esophageal varices) is seen masses of eggs deposited in the submucosa, with
in nearly all patients with Symmers’ fibrosis. their surrounding granulomas, and if in the rectum
Cor pulmonale (Fig. 6.35) has been reported in may prolapse through the anal sphincter.
over 15% of patients with periportal fibrosis. The col- • Urinary symptoms usually are not seen for 3 to
lateral circulation that develops in severe hepatosplenic 6 months after infection with S. haematobium and
schistosomiasis mansoni and japonicum carries eggs may not develop for a year or more. As the bladder
past the hepatic bed and into the pulmonary capillar- wall becomes increasingly infiltrated with eggs that
ies, where they lodge and granuloma formation takes have become entrapped, and around which granulo-
place. mas form, papillomas appear, and there may be areas
• Eggs of S. haematobium may bypass the liver en- of ulceration. Ultrasonography detects bladder wall
tirely. Venous blood from the vesical, prostatic, and irregularities and polyps (but not calcification) and
uterine plexuses enters the hypogastric vein, from congestive changes in the kidneys. Obstruction of the
whence it goes by way of the common iliac vein to ureteral openings or of the neck of the bladder may
the vena cava, the right heart, and the lungs. lead to back pressure and a predisposition to ascend-
• Eggs of S. japonicum may be deposited at any point ing bacterial infection. The subsequent involvement
along the distribution of the microvascular tributar- of ureters and kidneys is similar to that seen in urinary
FIG. 6.35 Pulmonary schistosomiasis: Progressive pulmonary hypertension and cor pulmonale. A, There
are numerous linear and nodular densities in the pulmonary parenchyma (short broad arrows). The heart
is enlarged, and the right pulmonary arteries are greatly enlarged (slender arrows). The main pulmonary
artery (large broad arrows) is almost aneurysmal. B, Three years later, the main pulmonary artery (short
broad arrows) has increased further in size; the heart and right pulmonary artery (slender arrows) are
also much larger. The pulmonary markings are considerably decreased, owing to obliteration of the
peripheral pulmonary vasculature. The extreme dilatation of the pulmonary artery caused by pulmonary
schistosomiasis is unequaled by almost any other disease. (Courtesy of Z. Farid, Cairo, Egypt.)
• An association between chronic salmonellosis and

schistosomiasis has been reported from many areas,
involving all three of the major species of human
schistosomes. There is usually a long history of a
mild febrile illness, with frequent isolation of one
or another species of Salmonella from the blood.
Salmonella has on occasion been cultured from the
treatment of adult schistosomes removed surgically
from patients with chronic salmonellosis.
Epidemiology
• Even though S. mansoni is widely distributed through-
out the world, humans are apparently the only impor-
tant host in most areas of high endemicity. In Africa,
nonhuman primates, insectivores, and wild rodents
are found to harbor the schistosomes, whereas in
Brazil several species of marsupials and rodents carry
the infection. The importance of these reservoir hosts
in maintaining and spreading the disease to humans
probably varies from one area to the next.
• Extension of the disease into new areas still occurs
with the migration of infection people and the agri-
cultural development of virgin land where the snail
FIG. 6.36 Hydronephrosis and hydroureter in patient with vector is present. Irrigation and the establishment
schistosomiasis haematobium. of artificial bodies of water, combined with unsani-
tary practices, may quickly result in new foci of high
tract obstruction from any source (Fig. 6.36). The endemicity. Since the snail intermediate host is en-
uterine cervix is the most common site of S. haema- tirely aquatic, the aqueous environment (water flow,
tobium infection in women, and granulomatous in- vegetation, water temperature, and pH) determines
flammation of the cervix is a common manifestation snail density and distribution.
(Poggensee et al., 2001). In males, heavy infections • As far as is known, humans are the only important
may involve the urethra, prostate, seminal vesicles, host for S. haematobium. The snail intermediate
and even the spermatic cord and penis. Elephantiasis host apparently has less stringent requirements for
of the penis may follow blockage of scrotal lymphat- water temperature than the snail host of S. mansoni.
ics by egg deposition and subsequent granuloma for- This may partly explain the relatively wide distribu-
mation. Both S. haematobium and S. mansoni may tion of S. haematobium on the African continent.
invade the placenta to give rise to a granulomatous In some areas of high endemicity in East Africa, the
placentitis, with adults and eggs of S. mansoni in the snail lives in relatively small bodies of water that
intervillous spaces and decidual vessels. may dry up during part of the year. The snails then
• Neurologic involvement is facilitated by anasto- estivate while buried in the mud but retain the in-
moses among mesenteric, pelvic, and spinal veins, fection and resume shedding of cercariae when the
the means by which both the worms and their eggs rainy season begins. Thus, special adaptations of the
can reach the central nervous system. Inflammatory snail host may be of prime importance in maintain-
reactions around them may produce focal lesions. ing and perpetuating the disease in foci where water
Symptoms of spinal cord schistosomiasis may oc- is not at all times plentiful.
cur early in the course of the infection, particularly • The complexity of the epidemiologic problems of
in immunologically naive persons, and the rapidly schistosomiasis is further enhanced in S. japoni-
progressive myelopathies are believed to represent cum because so many domestic animals are effi-
hypersensitivity reactions to the deposited eggs. cient reservoirs of the infection. Cats, dogs, cattle,
Transverse myelitis is generally rare, and eggs have horses, and pigs, as well as some wild mammals,
been found on autopsy in the spinal cord of persons are susceptible and may show a high infection rate
who had no symptoms of spinal cord involvement. in certain areas. Prevention of the disease is further
complicated by the semiaquatic habits of the snail dose depends on the origin of the infection. A
intermediate hosts, which visit water only for the single dose of 15 mg/kg body weight is suggested
purpose of egg laying, so that molluscicides applied for adults who acquire their infection in South
to the water are virtually useless. Rice, the staple America, the Caribbean islands, and West Africa;
crop in almost all areas where S. japonicum is en- for children from these areas, two doses of 10 mg/
demic, grows in water, so infection of the agricul- kg, at an interval of 3 to 8 hours, is suggested. In
tural population is a constant occupational hazard. East and Central Africa and the Arabian Penin-
It is estimated that about 80 million people are in- sula, 15 mg/kg twice in 1 day is required. This
fected with S. japonicum. must be increased to 20 mg/kg twice in 1 day in
Ethiopia, Zaire, and the West Nile. Elsewhere in
Treatment Egypt and in the Sudan and South Africa, 20 mg/
• Praziquantel is the drug of choice for treatment of kg daily for 3 days is recommended.
all schistosome infections. • Generalized seizures have been reported after the
• For infection with S. mansoni, S. haematobium, use of this drug but seem to be rare.
and S. intercalatum, a single dose of 40 mg/kg • Metrifonate* (Bilarcil), an organophosphorus com-
body weight produces cure rates of 63% to 90%, pound, is an alternative to praziquantel for treat-
while three doses of 20 mg/kg body weight in a ment of S. haematobium infections. It seems equal-
single day give rates that approach 100% in schis- ly effective against any S. mansoni that are located in
tosomiasis mansoni and haematobium. This the perivesical plexus but not those in the mesenter-
higher dose is required for successful treatment ic venules. The drug is administered orally, 10 mg/
of S. japonicum or S. mekongi. kg body weight, once every other week for a total of
• Administration of the drug while the worms are three doses. Side effects are transient and mild and
in the schistosomula or immature stages seems include abdominal pain, diarrhea, vomiting, weak-
to have little effect and may actually worsen ness, headache, and dizziness. A cure rate of about
acute-stage symptoms. 90% is achieved 5 to 6 months after treatment.
• In severe Katayama fever, steroids may be re-
quired initially, with definitive treatment post- Control
poned until the acute symptoms subside. Education is the prerequisite for all control measures,
• Both periportal fibrosis and bladder wall thick- since without an understanding of the life cycle of the
ening and polyps respond to praziquantel ther- parasite, attempts at its eradication are doomed to
apy as evaluated by ultrasonography. Yearly re- failure.
treatment may be necessary in advanced cases. • With education programs brought to the people, it
Praziquantel has been used in mass distribution has been demonstrated in areas such as China that
programs and is shown to be safe to use during progress can be made. Differences in the snail hosts
pregnancy (Adam et al., 2004). of the various schistosome species in some cases dic-
• Praziquantel in standard doses seems effec- tate different control measures, which may involve
tive in cerebral schistosomiasis japonicum, mollusciciding, biologic control by means of snail-
and has proved so in the less common cerebral eating fish or birds (or even competing species of
form of schistosomiasis haematobium (Pollner snails, as has been done with some success in Puerto
et al., 1994). Schistosomal transverse myelitis, Rico and Brazil [Giboda et al. 1997]), environmen-
seen most commonly in infections with S. man- tal modification, or various combinations of these
soni and S. haematobium, does not respond well measures. Proper disposal of urine and feces keeps
to praziquantel therapy alone; large doses of ste- eggs from hatching to initiate the cycle, but such
roids may be needed, and laminectomy may be measures are difficult to enforce if foreign to the
necessary for decompression. cultural (and at times the religious) practices of the
• Oxamniquine (Vasnil), 6-hydroxymethyl-2-isopro- people and in places where human excrement is of
pylamino-methyl-7-nitro-1,2,3,4-tetrahydroquino- great economic importance as fertilizer.
line, is effective for treatment of S. mansoni infec- Teaching people to avoid snail-infested waters is im-
tions. practical in areas where their economic livelihood de-
• Considerably less expensive than praziquantel, pends on planting crops such as rice in these waters and
it may be preferred for mass treatment programs where potentially snail-infested water is the only kind
when dual infections do not exist. The effective available for bathing, washing clothes, and so forth.
• Niclosamide, a chloronitrosalicylanilide, applied as which are present in the endemic areas of human schis-
a 1% lotion to the skin before contact with snail-in- tosomiasis, may increase humans’ resistance to infec-
fested waters, seems to have some value in preventing tion with the human species.
penetration of cercariae (Abu-Elyazeed et al., 1993).
This agent was first developed as a molluscicide, and
only later was found to have antiparasitic activity. UNCOMMON TREMATODE PARASITES OF
Topical N,N-diethyl-m-toluamide (DEET), when ap- HUMANS
plied as a 50% solution to the skin, has been shown Humans are incidental hosts to a variety of flukes,
to provide protection against cercarial penetration usually acquired by eating uncooked or undercooked
(Jackson et al., 2003). Mass treatment programs of meats. A few examples follow.
infected humans are costly, both in terms of drugs
and the personnel necessary to carry them out. Ef- Acanthoparyphium
forts to control S. japonicum by treatment are further Originally described as an echinostomatid intestinal
complicated by its many reservoir hosts. Cobalt-irra- parasite of ducks in Korea, Acanthoparyphium tyose-
diated cercariae of Schistosoma bovis have been used nense has also been reported as an intestinal parasite
with promising results to protect cattle from this par- of humans in the Republic of Korea (Chai et al., 2001).
asite. Several schistosome proteins have good poten- The patients were nine adults, ages 35 to 66, and one
tial for vaccines, and one of these has been cloned 7-year-old child, all of whom resided in two coastal vil-
and found to be immunogenic in humans and to lages. Patients were treated with 10 mg/kg praziquantel
have some protective power in baboons. in a single dose, and worms were recovered following
purgation with magnesium salts. An epidemiological
Schistosomal dermatitis investigation of intermediate hosts determined that
Many schistosome cercariae that ordinarily infect birds brackish water mollusks were the source of human
and semiaquatic mammals are capable of penetration infection.
into human skin but not of producing a permanent infec-
tion. A dermatitis may be produced from penetration by Alaria
the cercariae of the human species of schistosomes; der- Mammalian hosts of adult Alaria in the United States
matitis caused by species that are not ordinarily human and Canada are foxes and other canids, which become
parasites is frequently more severe. Fresh-water lakes as infected by eating frogs and other small game contain-
well as some marine beaches are plagued by the presence ing the metacercariae of this parasite. Human infec-
of cercariae of the blood flukes of aquatic birds, which tions, including at least one fatality, are reported fol-
cause a dermatitis known as swimmer’s itch (Fig. 6.37). lowing ingestion of such undercooked meats (Kramer
There is suggestive evidence that exposure to the et al., 1996).
schistosome cercariae of nonhuman species, many of
Gymnophalloides
The minute trematode Gymnophalloides seoi, belonging
to a family of worms ordinarily infecting shore birds,
was first discovered in the stools of a patient complain-
ing of epigastric pain and diarrhea, from a small island
village off the southwest coat of Korea. Subsequent
investigation revealed eggs of this parasite in 49 of 98
inhabitants of the village, and worm burdens averaging
more than 3000 worms per individual. The life cycle
is unknown, but other gymnophallids infect marine
bivalves, and raw oysters are a common food in this
village. Worms are broadly flattened, less than 0.5 mm
in length; operculate eggs measure 20 to 23 µm by 13
to 15 µm (Lee et al., 1994).
FIG. 6.37 Swimmer’s itch. Papular eruption caused by

Haplorchis taichui
penetration of skin by cercariae of various schistosome A focus of human infection by the heterophyid trema-
parasites of lower animals. tode Haplorchis taichui has been reported in Mindanao
Island, southern Philippines (Belizario et al., 2004).

Previously, occasional cases had been reported from
Thailand and the Philippines. In the present study, the
prevalence of infection was 36%. An intestinal fluke,
H. taichui, lives attached to the wall of the small bow-
el, producing symptoms of abdominal discomfort or
pain, nausea, diarrhea, and borborygmi. Praziquantel,
75 mg/kg divided in three doses in 1 day, was an effec-
tive treatment. The source of infection likely was fresh-
water fish, which serve as second intermediate hosts
harboring metacercariae. Dogs, cats, and swine have
been reported as definitive hosts for H. taichui in the
Philippines.
Metorchis conjunctus FIG. 6.38 Eggs of Nanophyetus salmincola. The egg on

An important cause of death in sled dogs, this opis- the left shows the operculum; that on right show the blunt
thorchid fluke infects a wide range of carnivores in the abopercular projection. Scale, 50 µm. (Eggs courtesy of Dr.
United States and Canada. Metacercariae are found Thomas R. Fritsche, University of Washington, Seattle, WA.)
in various fresh-water fish, notably the white sucker,
Cataostomus commersoni. Seventeen of 20 persons con-
suming sashimi prepared from these fish, caught in a • Praziquantel, 20 mg/kg body weight, three times in
river north of Montreal, developed an acute febrile ill- 1 day, has been found effective in treatment.
ness with epigastric pain and eosinophilia. Eggs similar • Eggs of N. salmincola are light brown, ovoid, and
to those of Opisthorchis were found in the feces. Iden- operculate at one end, with a small blunt projection
tification of the parasite was accomplished by feeding at the aboperculate end. They mesure 64 to 97 µm
metacercariae from the fish to hamsters. Symptoms by 34 to 55 µm (Fig. 6.38).
responded promptly to treatment with praziquantel
(MacLean et al., 1996). Phaneropsolus
Members of the genus Phaneropsolus are intestinal para-
Nanophyetus (Troglotrema) salmincola sites of reptiles, birds, and mammals. P. bonnei has been
• A minute intestinal fluke less than 1 mm long, N. reported as a human parasite in Indonesia and Thai-
salmincola has long been associated in the Pacific land and P. spinicirrus similarly from Thailand. A single
northwest coast of North America and in Siberia dose of praziquantel was used to treat the 44-year-old
with a disease of dogs, wolves, and foxes that, if female patient with P. spinicirrus (Kaewkes et al., 1991)
untreated, is frequently fatal. The disease, “salmon and presumably is an effective form of treatment for
poisoning,” is caused not by the parasite itself but other species of Phaneropsolus as well.
by rickettsiae of which it is the vector. Cercariae of
Nanophyetus liberated from their snail hosts encyst Philophthalmus
in the tissues of salmonid fish. Numerous fish-eat- • Species of Philophthalmus, referred to as eyeflukes,
ing mammals, including humans and some fish-eat- infect the eyes of wild and domestic birds. A total of
ing birds, become infected upon ingesting the meta- 24 human cases have been reported worldwide from
cercariae, but apparently only canids (dogs, wolves, Europe, Asia, Israel, Mexico, and the United States.
foxes) are affected by the rickettsia, Neorickettsia hel- The patient from Mexico (Lamothe-Argumedo et al.,
minthoeca, that it carries, and can develop severe or 2003), a healthy 31-year-old male, experienced a
fatal enteritis from this infection. Until recently, it foreign-body sensation in his left eye lasting for
was thought that human infection with Nanophyetus 2 months. Examination revealed a small, approxi-
was asymptomatic, and it seems that this is usually mately 6 mm, elongated worm in the conjunctiva.
so; however, some patients present with gastroin- The patient’s symptoms ceased shortly after surgi-
testinal complaints, otherwise unexplained eosin- cal removal of the worm, which was identified as
ophilia, weight loss, or fatigue. Fish handlers may Philophthalmus lacrimosus.
become infected by hand-to-mouth transmission of Table 6.1 summarizes some important features of
the metacercariae. the more common trematode infections of humans
206
Markell & Voge’s Medical Parasitology
TABLE 6.1
Review of trematode infections in human.
Means of human Location of larvae Location of adults
Disease Parasite infection in humans in human Clinical features Laboratory diagnosis
LIVER FLUKES
Clonorchiasis Clonorchis sinensis Ingestion of larvae Duodenum, bile Bile ducts, Hepatomegaly, Embryonated opercu-
(Chinese liver fluke) encysted in fresh- ducts gallbladder diarrhea, jaundice, lated eggs in feces or
water fish eosinophilia (carcinoma duodenal aspirate
of biliary tract - Cholan-
giocarcinoma)
Opistorchiasis Opistorchis felineus Ingestion of larvae Bile ducts Bile ducts Abdominal distress, Embryonated opercu-
(Cat liver fluke) encysted in fresh- epigastric pain, and lated eggs in feces
Opistorchis viverrini water fish generalized malaise
(Southeast Asian
liver fluke)
Dicrocoeliasis Dicrocoelium den- Ingestion of larvae Duodenum Bile ducts Enlargement of the Embryonated opercu-
driticum encysted in ants bile ducts, hyperplasia lated eggs in feces
(lancet fluke) of biliary epithelium,
periductal fibrosis and
eventual portal cir-
rhosis
Fascioliasis Fasciola hepatica Ingestion of larvae Intestinal wall, Bile ducts, Hepatomegaly, eosino- Undeveloped opercu-
(Sheep liver fluke) encysted on aquatic peritoneal cavity gallbladder philia, jaundice, portal lated eggs in stools,
vegetation (biliary tree) cirrhosis serologic tests
INTESTINAL FLUKES
Fasiolopsiasis Fasicolopsis buski Ingestion of larvae Small Intestine Small Intestine Abdominal pain, diar- Undeveloped opercu-
(Intestinal fluke) encysted on aquatic (attached) rhea, edema, ascites, lated eggs in stool
plants eosinophilia
Echinostomiasis Echinostoma Ingestion of larvae Small Intestine Small Intestine Inflammation, mild Undeveloped oper-
ilocanum, encysted in fresh- (attached) ulceration, diarrhea and culated eggs in stool;
Artyfechinostomum water snails abdominal pain Patient’s history, clini-
malayanum cal findings
Heterophyidiasis Heterophyes hetero- Ingestion of larvae Small Intestine Small Intestine Chronic intermittent di- Embryonated opercu-
phyes (VonSiebold’s encysted in fresh- (attached) arrhea, nausea, vague lated eggs in feces
fluke) water fish abdominal complaints;
Metagonimus brain or spinal cord
yokogawai embolisms; Hetero-
phyid myocarditis
Gastrodisciasis Gastrodiscoides Ingestion of larvae Small intestine Attached to the Local inflammation and Embryonated opercu-
hominis encysted on veg- mucosa of the ce- mucous diarrhea lated eggs in feces
etation cum and ascend-
ing colon
LUNG FLUKE
Paragonimiasis Paragonium wes- Ingestion of larvae Intestinal wall, Lungs (in fibrous Hemoptysis, cough, Undeveloped opercu-
termani encysted in fresh- peritoneal cavity, capsule) fever, eosinophilia (ce- lated eggs in sputum
(lung fluke) water crabs of lung tissue rebral paragonimiasis) or feces, serologic
crayfish tests
PANCREATIC FLUKE
CHAPTER 6
Eurytremiasis Eurytrema pancre- Ingestion of larvae Pancreas Pancreatic duct Chronic inflammation of Embryonated opercu-
aticum encysted in ants the pancreatic duct that lated eggs in feces
and grasshopper lead to Chronic Granu-
lomatous Pancreatitis,
enlargement of the
pancreas, diabetes
Phylum Platyhelminthes: Class Trematoda

BLOOD FLUKES
Schistosomiasis Schistosoma man- Skin penetration by Subcutane- Mesenteric veins Hepatosplenomegaly, Embryonated un-
soni, Schistosoma larvae in water ous tissue, liver (vesical, prostatic diarrhea, portal fibrosis, operculated eggs in
japonicum, (sinusoids) or uterine veins: hypertension (Hematu- stool (urine or feces
Schistosoma S. haematobium) ria bladder cancer with for S. haematobium),
haematobium, S. haematobium) serologic tests
Schistosoma
mekongi,
Schistosoma
intercalatum
207
c. Clonorchis sinensis
SUMMARY
d. Paragonimus westermani
• Trematodes, also known as flukes, are part of the
phylum Platyhelminthes that can contribute infection 3. Human Clonorchiasis is possible through ingestion
to humans either by mechanical obstruction or local of:
inflammatory mechanisms. a. Miracidium
• Adult trematodes and eggs differ in general b. Cercaria
morphology and some differ in its life cycle and c. Metacercaria
development. Generally, the following 5 larval d. Redia
stages develop: miracidium, sporocyst, redia,
cercaria and metacercaria. Miracidium is the 4. These members of platyhelminthes (flatworms)
infective stage to the 1st intermediate host (snails) penetrate snails and multiply in sporocysts to in-
and metacercaria found in the 2nd intermediate crease their numbers.
host is the infective stage to the definitive host and
a. Schistosomes
is aquired by ingestion. However, for Schistosomal
flukes, it is the cercaria that acts as infective stage
b. Echinostomids
that is transmitted by skin penetration. c. Heterophyids
• All trematodes require two intermediate hosts to
d. None of the above
complete its life cycle, except Schistosomes.
5. True/False: The greatest pathology produced by
• All trematode eggs are operculated, except
Schistosoma mansoni is caused by adults consuming
Schistosomes.
the blood of the host.
• All trematodes are hermaphrodite, except
Schistosomes that are dioecious.
6. True/False: Trematodes (flukes) are exclusively par-
• Trematodes that lay immature eggs that develops in
asites of internal organs.
aquatic environment: Paragonimus, Echinostoma,
Fasciola, Fasciolopsis (Belizario and De Leon,
7. Also known as Chinese Liver Fluke
2015).
a. Opistorchis felineus
• Trematodes that lay mature eggs when passed in
b. Clonorchis sinesis
feces: Schistosoma, Heterophyids, Opistorchis,
Clonorchis (Belizario and De Leon, 2015). c. Paragonimus westermanii
d. Opistorchis viverrini
• Trematodes can be differentiated according to its
habitat or location:
For numbers 8 to 11:
Mesenteric veins: Blood flukes
a. S. mansoni
Lung parenchyma: Paragonimus
b. S. japonicum
Liver: Fasciola
c. S. haematobium
Bile duct: Clonorchis, Opistorchis d. S. mekongi
Small Intestine: Fasciolopsis, Echinostoma, e. S. intercalatum
Heterophyids
8. Which among the Schistosoma spp. lays the smallest
egg?
REVIEW QUESTIONS
9. In its adult stage, which among the following spe-
1. In mode of transmission for Schistosoma mansoni,
cies of Schistosoma is considered the smallest?
penetration is in
a. Skin 10. Which is acid-fast positive, resembles S. haemato-
b. Intestine bium, and has a diamond body?
c. Blood
d. Mucous 11. Resembles S. japonicum but smaller and was seen
from a river
2. Sundathelphusa spp. is the second intermediate host
for the 12. Considered as the largest trematode with no ce-
a. Schistosoma mansoni phalic cone, no shoulders, elongated, and its intes-
b. Schistosoma japonicum tinal ceca are unbranched.
a. Fasciola hepatica REFERENCES

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d. Ascaris lumbricoides J Trop Med Hyg. 1993;49:403–409.
Adam I, et al. Is praziquantel therapy safe during pregnancy?
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help in immune modulation and migration of Apt W, et al. Treatment of human chronic fascioliasis with
worms. triclabendazole; Drug efficacy and serologic response. Am
a. Cercaria J Trop Med Hyg. 1995;52:532–535.
b. Schistosomule Beaver P, et al. Clinical parasitology. Philadelphia, USA: Lea &
Febiger; 1984. 26: 406-487.
c. Metacercaria
Belizario V, De Leon W. Medical parasitology in the Philippines.
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14. Harbors the rickettsia Neorickettsia heminthoeca
Belizario VY, et al. A focus of human infection by Haplorchis
a. Philophthalmus taichui (Trematoda: Heterophydiae) in the southern
b. Acanthoparyphium Philippines. J Parasitol. 2004;90:1165–1169.
c. Nanophyetus salmincola Calvopiña M, et al. Comparison of two single-day regimens of
d. Metorchis conjunctus triclabendazole for the treatment of human pulmonary
paragonimiasis. Trans R Soc Trop Med Hyg. 2003;97:451–454.
15. Technomyrmex spp. is an intermediate host for Chai JY, et al. Acanthoparyphium tyosenense: the discovery
which parasite? of human infection and identification of its source. J
a. Dicrocoelium dendriticum Parasitol. 2001;87:794–800.
b. Paragonimus westermanii Chiu A, et al. Late complications of infection with Opisthorchis
c. Eurytrema pancreaticum viverrini. West J Med. 1996;164:174–176.
d. Haplorchis taichui Drabick JJ, et al. Dicrocoeliasis (lancet fluke disease) in an
HIV-seropositive man. JAMA. 1988;259:567–568.
16. In copula behavior best describes which parasite? Giboda M, et al. Human Opisthorchis and Haplorchis infections
in Laos. Trans R Soc Trop Med Hyg. 1991;85:538–540.
a. Echinostomids
Giboda M, et al. Human schistosomiasis in Puerto Rico:
b. Heterophyids
Reduced prevalence rate and absence of Biomphalaria
c. Schistosomes glabrata. Am J Trop Med Hyg. 1997;57:564–568.
d. All of the above Han JK, et al. Radiologic findings in human fascioliasis.
Abdom Imaging. 1993;18:261–264.
17. True/False: Gonotyl is only present in Heterophy- Hillyer GV, Apt W. Food-borne trematode infections in the
ids including Metagonimus spp and Heterophyes spp. Americas. Parasitol Today. 1997;13:87–88.
Jackson F, et al. Schistosomiasis prophylaxis in vivo using N,
18. Which parasites have immature eggs when passed N-diethyl-m-toluamide (DEET). Trans R Soc Trop Med
in stool? Hyg. 2003;97:449–450.
a. Paragonimus, Echinostoma, Fasciola, Fasciolopsis Kaewkes S, et al. Phaneropsolus spinicirrus N. sp. (Digenea:
b. Schistosoma, Fasciola, Paragonimus Lecithodendriidae), a human parasite in Thailand. J
c. Schistosoma, Heterophyids, Clonorchis, Paragonimus Parasitol. 1991;77:514–516.
d. Paragonimus only Kramer MH, et al. Respiratory symptoms and subcutaneous
granuloma caused by mesocercariae. A case report. Am J
19. Which parasites have mature eggs when passed in Trop Med Hyg. 1996;55:447–484.
stool? Lamothe-Argumedo R, et al. The first human case in Mexico of
a. Paragonimus, Echinostoma, Fasciola, Fasciolopsis conjunctivitis caused by the avian parasite, Philophthalmus
lacrimosus. J Parasitol. 2003;89:183–185.
b. Schistosoma, Fasciola, Paragonimus Clonorchis
Lee S-H, et al. High prevalence of Gymnophalloides seoi
c. Schistosoma, Fasciola, Opistorchis, Clonorchis infection in a village on a southwestern island of the
d. Schistosoma, Heterophyids, Opistorchis, Clonorchis Republic of Korea. Am J Trop Med Hyg. 1994;51:281–285.
Liu Y-H, et al. Experimental and clinical trial of albendazole
20. True/False: Mode of transmission for all trema- in the treatment of Clonorchiasis sinensis. Chin Med J.
todes is ingestion of metacercaria 1991;104:27–31.
MacLean JD, et al. Common-source outbreak of acute
Answers to review questions are available at the end of this infection due to the North American liver fluke Metorchis
book. conjunctus. Lancet. 1996;347:154–158.
Neva F, Brown H. Basic clinial parasitology. Appleton & Lange: based study. Trans R Soc Trop Med Hyg. 1994;88:
Norwalk, Conneticut; 1994. 11:217-262. 561–564.
Pachucki CT, et al. American paragonimiasis treated with Richter J, et al. Fascioliasis. Curr Treat Opt Infect Dis.
praziquantel. N Engl J Med. 1984;311:582–583. 2002;4:313–317.
Poggensee G, et al. Diagnosis of genital cervical schistosomiasis: Ripert C, et al. Therapeutic effect of triclabendazole in patients
comparison of cytological, histopathological and with paragonimiasis in Cameroon: a pilot study. Trans R
parasitological examination. Am J Trop Med Hyg. Soc Trop Med Hyg. 1992;86:417.
2001;65:233–236. Strandgaard H, et al. The pig as a host for Schistosoma mekongi
Pollner JH, et al. Cerebral schistosomiasis caused by Schistosoma in Laos. J Parasitol. 2001;87:708–709.
haematobium: case report. Clin Infect Dis. 1994;18: Taylor M, et al. Veterinary Parasitology. Wiley-Blackwell:
354–357. Hoboken, NJ; 2016. 869.
Pottinger P, Jong E. Travel and tropical medicine manual. Watt G, et al. Hepatic parenchymal dysfunction in
Elsevier Inc.; 2017. 48: 588-597. Schistosoma japonicum infections. J Infect Dis. 1991;164:
Price TA, et al. Fascioliasis: case reports and review. Clin Infect 1186–1192.
Dis. 1993;17:426–430. Yee B, et al. Pulmonary paragonimiasis in Southeast Asians
Pungpak S, et al. Opisthorchis viverrini infection in Thailand: living in the Central San Joaquin valley. West J Med.
symptoms and signs of infection—a population- 1992;156:423–425.
CHAPTER 7
Phylum Platyhelminthes: Class

Cestoda
PATRICIA ALYANNA MARIE P. MADRIGAL
The cestodes, or tapeworms, constitute the class Cestoda structure, the rostellum, situated in the center of the
of the phylum Platyhelminthes. The adult tapeworms scolex. In some species the rostellum bears hooks and
found in both humans and animals all have a flat and is referred to as armed. While precise identification of
ribbonlike body and are white or yellowish. The cestode the tapeworms of humans is usually made on the basis
body consists of an anterior attachment organ, or sco- of eggs or proglottids, the scolex of each species is quite
lex, followed by a short neck, then a chain of segments characteristic and is sufficient for specific diagnosis.
or proglottids (Fig. 7.1) also known as a strobila. The Cestodes that parasitize humans have complex life
strobila grows throughout the life of the tapeworm by cycles that generally involve both a definitive and an
continuous proliferation of new segments or proglottids intermediate host. Some species utilize humans only as
in the neck, which is the region immediately posterior the definitive hosts, growing to adulthood in the intes-
to the scolex. The new segments are referred to as im- tine after ingestion of the infective larvae (e.g., Diboth-
mature because they do not yet contain fully developed riocephalus latus, Taenia saginata, Hymenolepis diminuta).
internal structures. The mature segments are larger and For some species, humans may serve as both definitive
are found near the middle of the chain, and each may or intermediate hosts (e.g., Taenia solium, Hymenolepis
contain either one or two sets of both male and female nana). Still others, such as Echinococcus, utilize humans
reproductive organs. The terminal portion of the stro- as one of their possible intermediate hosts but never as
bila contains the ripe or gravid segments, usually filled the definitive host. In general, extraintestinal infection
with eggs. The eggs are enclosed in the uterus, a structure with the larval forms is a much more serious matter
that varies in shape and size in different cestode species. than infection with the adult worm.
The form of the uterus is quite characteristic and serves
as an important diagnostic feature. Terminal proglottids
of some species may become detached in the intestine
and pass out with the stool in a process called apolysis.
However, some types may be too small to be seen in
gross examination.
Adult tapeworms inhabit the small intestine, where
they live attached to the mucosa. Tapeworms do not
have a digestive system. Instead, their food is absorbed
from the host’s intestine through the tegument of the
cestode. Attachment is accomplished by means of the
scolex, an organ that varies in morphology from spe-
cies to species. The tapeworms are classified into two
orders, order Pseudophyllidea and order Cyclophyl-
lidea. All cestodes of humans, except those that belong
to the order Pseudophyllidea, have four muscular, cup-
shaped suckers on the scolex. Cestodes under the or-
der Pseudophyllidea possess a scolex bearing grooves
called bothria instead of suckers. In addition to suck- FIG. 7.1 Entire tapeworm—Hymenolepis diminuta.
ers, the scolex may have an elongate and protrusible (Photograph by Zane Price.)
211
Unlike the trematodes whose eggs are usually oper-

culate, human tapeworms do not have operculate eggs
(with few exceptions). Cestode eggs vary considerably
in the appearance of the external shell as well as in the
number and thickness of the embryonic membranes.
These membranes serve as protective coverings of the
embryo, which is called an oncosphere and bears six
elongate hooks (see Fig. 7.10).
FIG. 7.3 Gravid proglottids of Dibothriocephalus latus.
(Photomicrograph by Zane Price, from material furnished
ORDER PSEUDOPHYLLIDEA by Dr. Justus F. Mueller.)
Dibothriocephalus latus
D. latus (formerly Diphyllobothrium latum), the “broad Life cycles (Fig. 7.4)
fish tapeworm,” is the most common agent of human • The life cycle of D. latus requires two intermediate
dibothriocephaliasis. It is almost worldwide in distri- hosts, freshwater crustaceans known as copepods
bution, occurring in northern temperate areas of the (1st IH) and freshwater fish (2nd IH).
world where pickled or insufficiently cooked fresh-wa- • Various species of freshwater fish and ones that live in
ter fish are prominent in the diet. Although infection brackish waters may be infected with the plerocercoid
with D. latus is, in many instances, relatively harmless, larvae, as may salmonids that spawn in fresh water.
it may produce in some persons a condition closely re- • Eggs passed in the feces hatch into small ciliated cor-
sembling pernicious anemia due to the selective absorp- acidium embryos, which swim about until ingested
tion of vitamin B12 from the host’s intestinal tract by by copepods.
D. latus. • The growth and development of the first larval stage,
the procercoid, is completed in the first intermedi-
General morphology ate host, the copepods.
• Eggs of D. latus (see also Fig. 7.10E) are ovoid, about • When copepods are ingested by the second intermedi-
70 mm long and 50 mm wide, and, unlike other ces- ate host, usually small fish, the larvae continue devel-
todes, possess an operculum for the escape of the oping to a second larval stage called the plerocercoid.
embryo. • Larger predator fish may be infected by the parasite
• The shell is smooth, of moderate thickness, and yel- when they consume the second intermediate host,
lowish brown. becoming transport or paratenic hosts in which the
• The adult worm may be several meters in length. plerocercoid larva will not continue to grow in.
• The scolex of D. latus (Fig. 7.2) is elongate, spoon • If the infected fish is then eaten by a human or other
shaped/almond shaped/spatulate and characterized fish-eating mammalian host, the plerocercoid larva
by two longitudinal grooves called bothria. is not digested but remains in the small intestine
• Mature and gravid segments (Fig. 7.3) are wider and grows to adulthood.
than they are long. • Both humans and a variety of fish-eating mammals,
• Gravid proglottids of D. latus contain a rosette- such as wild and domestic members of the dog and
shaped uterus confined to a relatively small area in cat families, bears, minks, pigs, walruses, and seals,
the center of the segment. may serve as definitive hosts for the parasite.
• D. latus possesses a uterine pore through which its Infective stages
eggs are released. PLEROCERCOID
• Once ingested along with the infected fish, adult
worm develops in the intestinal tract which causes
megaloblastic anemia
Diagnostic stages
• Both eggs and proglottids may be found in the stool.
• Ripe eggs escape through a uterine pore and are dis-
charged into the intestine.
FIG. 7.2 Dibothriocephalus latus, scolex. • In freshly passed or formalin-preserved segments, a
(Photomicrograph by Zane Price.) pronounced central elevation marks the site of the
CHAPTER 7 Phylum Platyhelminthes: Class Cestoda 213
FIG. 7.4 Life cycle of Dibothriocephalus latus.
egg-filled uterus, a coiled tube arranged similar to a • Species level identification requires molecular anal-
rosette, which is a characteristic feature of the parasite. ysis through PCR on DNA extracted from eggs or
proglottids.
• Transmission of the parasite occurs through inges- Pathogenesis
tion of uncooked fish. • The presence of adult worms in the intestinal tract
• Most human infections occur via consumption of causes no symptoms in most infected persons.
undercooked paratenic host fish because humans • If localization of the D. latus occurs in the proximal
do not generally eat the small second intermediate portion of the jejunum, vitamin B12 deficiency may
host fish raw. develop due to absorption of dietary vitamin B12 by
the parasite.
Laboratory diagnosis • Such tapeworm anemia, indistinguishable from
• Microscopic identification of eggs may be used for genuine pernicious anemia, is seen most frequent-
family level diagnosis; species identification is diffi- ly in areas such as Finland, where many persons
cult through microscopic observation due to similar have a genetic predisposition to pernicious anemia,
morphological characteristics to eggs of other species. suggesting that B12 deprivation through D. latus
infection is seldom sufficient to produce clinical Spirometra spp.

symptoms in an otherwise normal patient. Infection of humans by plerocercoid larvae of various
diphyllobothroid tapeworms belonging to the genus
Epidemiology Spirometra is known as sparganosis. The larvae are of-
• A high prevalence of D. latus in humans is seen in ten referred to by the generic name sparganum, a relic
Scandinavia and Finland as well as in Alaska and of the days in which this stage was thought to represent
Canada. a separate genus.
• In the United States, D. latus once occurred in the
lake region of Minnesota and Michigan but it is ap- General morphology
parently no longer endemic there. • The sparganum is a wrinkled, whitish, ribbon-shaped
• People whose dietary customs include eating raw organism, a few millimeters wide and up to several
or insufficiently cooked fish, such as Jews, Russians, centimeters long.
Finns, Scandinavians, and Japanese, are more vul- • The anterior end is capable of invagination and
nerable to infection. bears suggestions of the sucking grooves of the ma-
• In the coastal areas of Peru and other Latin American ture scolex.
countries, another species called Diphyllobothrium paci-
ficum, a natural parasite of seals, is the most common Life cycles
tapeworm infecting humans who acquire the infec- • Eggs shed in the feces of dogs and cats infected with
tion from eating ceviche, a local delicacy that consists the genus Spirometra embryonate in the environment.
of fish marinated in lime juice but not cooked. • The eggs hatch in the water and release coracidia,
• Diphyllobothrium nihonkaiense is the common tapeworm which are ingested by the copepod intermediate
acquired by the consumption of raw fish in Japan. host where they develop into procercoid larvae.
• Diplogonoporus, a related genus characterized by two • When the second intermediate hosts (i.e. fish, rep-
sets of reproductive organs in each proglottid, is re- tiles, and amphibians) ingest infected copepods,
ported from humans in Japan and Korea, probably they acquire the procercoid larvae which develop
acquired through consumption of raw anchovies. into plerocercoid larvae.
• Dogs and cats serve as the definitive host of the ge-
Treatment nus Spirometra.
• Praziquantel is the drug of choice for treatment, • Man cannot serve as definitive hosts; they are trans-
with a cure rate of over 95%, taken in a single oral port or paratenic hosts (Fig. 7.4).
dose of 5 to 10 mg/kg body weight.
• Niclosamide (Niclocide) is an effective and well-toler- Infective stages
ated alternative for persons unable to take praziquan- • PROCERCOID (once ingested accidentally by humans
tel, but may cause abdominal cramps, diarrhea, nau- through contaminated water containing infected cope-
sea, and vomiting in a small percentage of patients. pods, larval infection called sparganosis happens.
• Niclosamide is given in a single 2 g dose for adults, • PLEROCERCOID found in tissues of cold-blooded
1.5 g for children weighing over 34 kg, and 1 g for vertebrates
those weighing between 11 and 34 kg.
• As the worms are seldom passed spontaneously af- Laboratory diagnosis
ter administration of either drug, a saline purge may • Diagnosis is made following surgical removal of
be given 1 to 2 hours later to expel them in a more sparganum, which on section are seen to possess a
or less intact condition. rather homogeneous parenchyma in which are scat-
• Intraduodenal gastrografin has also been reported tered the laminated, intensely basophilic calcareous
to be an effective alternative therapy for diphyllo- corpuscles characteristic of cestode tissue (Fig. 7.5).
bothriasis (An et al., 2017).
Prevention • The infection may be acquired by drinking water
• In most areas, humans are the primary hosts of D. containing copepods infected with the procercoid
latum and proper disposal of human feces will help larval stage of the parasite.
break the infection chain. • In various areas, snakes or tadpoles are consumed
• Fish must be thoroughly cooked at a temperature raw for medicinal reasons; if they happen to be in-
of at least 55°C for 5 minutes, brine treated (12% fected with plerocercoids, these parasites may be
NaCl), or frozen at −10°C for 24 to 48 hours to kill capable of penetrating the intestinal wall to infect
plerocercoid larvae. humans, causing sparganosis.
• Ocular sparganosis produces an especially intense

reaction, with periorbital edema.
• If the larvae are retrobulbar in position, the orbit
may be forced out so that the lids do not close, and
corneal ulcers develop.
• Cerebral sparganosis is characterized by seizures, par-
esthesias, hemiparesis, and similar CNS symptoms.
• Under such circumstances humans serve as a trans-
port or paratenic host, in all ways analogous to the
fish that ingests the minnow originally infected with
D. latus, except that the full life cycle is unlikely to be
completed.
Epidemiology
• The genus Spirometra is found worldwide, although
most cases of human sparganosis have been report-
FIG. 7.5 Cross section of sparganum removed at surgery.
ed from southeast Asian countries.
• Another manner in which human infections have Treatment

been known to take place is through the practice • Surgical removal of one or a few sparganum larvae is
of placing poultices of frog or snake flesh on open usually possible.
wounds or other lesions, especially of the eyes. • Most reported cases of cerebral have been cured
by surgical resection after localization (though not
Laboratory diagnosis identification) of the lesion by computed tomog-
• Diagnosis is usually made through surgical removal raphy (CT) or magnetic resonance imaging (MRI)
of the worms from infected tissue. (Holodniy et al., 1991).
• A presumptive preoperative diagnosis might be • Praziquantel is apparently effective when admin-
made on demonstration of a painful migratory sub- istered at a total dose of 120 to 150 mg/kg body
cutaneous nodule. weight, over a 2-day period.
• Accurate species identification requires infecting an
appropriate definitive host with sparganum, allow- Prevention
ing it to mature within the host, then recovering the • In areas of endemic infection, people should be ad-
adult parasite for further study. vised of the dangers of drinking water from ponds
and ditches, which may contain infected copepods.
Pathogenesis • The use of potentially infected animals for medici-
• When humans are infected with the procercoid, the nal purposes, such as in the use of poultice to treat
larva penetrates the gut wall and works its way into open wounds, must be discouraged.
the muscles or subcutaneous tissues, where it grows
into the Sparganum larva which may migrate active-
ly in the subcutaneous tissues. ORDER CYCLOPHYLLIDEA
• In a few instances in Japan and in single case reports Taenia solium
from Florida, Taiwan, Paraguay, and Venezuela, hu- The pork tapeworm occurs wherever people eat cured
man infections with a peculiar budding type of larva or undercooked pork. Infection with T. solium is rarely
known as Sparganum proliferum have been reported. encountered in the United States except in immigrants
• Sparganum proliferum may occur almost anywhere in from areas where it is prevalent such as Mexico, Latin
the body, and the branched proliferating larvae may America, the Iberian Peninsula, the Slavic countries, Af-
break up into segments capable of further indepen- rica, India, Southeast Asia, and China.
dent development causing serious infection.
• The early migratory stages in the development of General morphology
the sparganum are asymptomatic, but when it has • Adult T. solium worms may attain a length of 2 to
reached its final site and begins to grow, its presence 7 m.
elicits a painful inflammatory reaction in the sur- • The armed scolex (Fig. 7.6) is muscular and bears
rounding tissues. in addition to the four suckers a double crown of
FIG. 7.8 Taenia solium, gravid proglottid.

Life cycles
• The life cycle of T. solium (Fig. 7.9) requires one in-
FIG. 7.6 Taenia solium, scolex. (Photomicrograph by Zane termediate host, the pig.
Price.) • Eggs may remain viable for many weeks in the soil
after they are passed in the feces
• Embryonated eggs ingested by a pig hatch into on-
cosphere larva and develop into the infective larval
stages or cysticerci in the muscles, which may then
infect humans who eat undercooked pork.
• Although the adult tapeworm develops in humans
after the ingestion of infected meat, infection with
the larval stage or cysticercus occurs after the inges-
tion of eggs, either from exogenous sources or from
their own stools.
• Ingested proglottids can rupture and release eggs
which hatch into oncosphere larva and then devel-
FIG. 7.7 Mature proglottid of Taenia: (ex) excretory canal; op into cysticerci.
(o) ovary; (t) testis; (ut) uterus; (va) vas deferens; (vg) vagina;
• The cysticercus larva completes development in
(vig) vitelline gland.
about 2 months.
• The cysticercus larva is semitransparent, opalescent
prominent hooks, which function in attachment to white, and elongate oval in shape and may reach a
the intestinal mucosa. length of 0.6 to 1.8 cm (Fig. 7.11).
• Mature segments (Fig. 7.7) are wider than they are • The bladder is fluid filled, and on one side is a dens-
long and contain one set of male and female repro- er area containing the scolex.
ductive organs.
• Gravid segments (Fig. 7.8) are usually longer than Infective stages
they are wide and contain a branched uterus filled • Cycticercus cellulosae (once ingested from an in-
with eggs. fected meat of pigs, intestinal infection of the adult
• A central uterine stem extends through the length worm happens)
of the gravid segment and from this stem arise side • Eggs (once ingested, larvae are released and invasion
branches, which project laterally and may have a of different organs happens). This type of infection
variable number of smaller secondary branches. is called cysticercosis. It is called neurocysticercosis
• In T. solium, the number of main branches on one if the brain is involved. Eggs are also responsible for
side of the central stem varies from 7 to 13. autoinfection.
• The oncosphere is enclosed in a thick, radially striat-
ed coat called the embryophore, usually dark brown Diagnostic stages
in color. • Taeniasis is diagnosed by microscopic identification
• The six-hooked embryo can be easily seen in living of eggs and proglottids.
eggs but frequently become shriveled and opaque in • The radially striated coat of Taenia eggs is sufficient-
preserved material. ly characteristic.
FIG. 7.9 Life cycle of Taenia solium.
• Eggs and mature proglottids of T. solium and of • Cysticercosis is only acquired from the fecal-oral
T. saginata are very much alike and do not provide a route of transmission, which involves the ingestion
means of specific differentiation. of infectious eggs.
• While gravid segments and eggs may be found in
stool specimens, specific identification cannot be Laboratory diagnosis
made on the basis of eggs alone but only on ex- • Taenia eggs (Fig. 7.10C, D) may be found free in the
amination of gravid proglottids wherein the uterine feces or recovered by means of a cellophane tape
branches are counted. swab (refer to Enterobius).
• T. solium typically has 7 to 13 primary uterine • Specific diagnosis of T. solium is made by counting
branches (described as fingerlike or dendritic) while the number of uterine side branches, which may be
T. saginata has 15 to 20 primary uterine branches done in living or in stained preparations.
(described as tree-like or dichotomous). • Surgical removal of subcutaneous or intracranial
cysts, with demonstration of the organism, radio-
Mode of transmission graphic demonstration of calcified cysts in the
• Infection with the pork tapeworm occurs wherever muscle, or visualization of the cysticercus within the
people eat cured or undercooked pork, causing in- orbit, is diagnostic.
testinal taeniasis.
FIG. 7.10 Cestode eggs. A, Hymenolepis nana. B, Hymenolepis diminuta. C, D, Taenia sp. E,
Dibothriocephalus latus. All eggs photographed at same magnification; scale equals 50 µm.
FIG. 7.11 A, Cysticercus larvae of Taenia solium. B, Scanning electron micrograph of scolex from
cysticercus, showing hooklets. (Courtesy of the U.S. Department of Agriculture.)
• Signs and symptoms of a space-occupying lesion of ticerci elsewhere in the body or of a positive sero-
the central nervous system may be highly suggestive logic test for cysticercosis.
of cysticercosis in the presence of demonstrable cys- • However, serologic test results are often negative in
cysticercosis of the central nervous system.
• Plain skull films may reveal calcified cysts within the

brain, but computed tomography (CT) shows both
calcified and uncalcified cysts, and with the use of con-
trast medium may show enhancement indicative of in-
flammatory changes, which may be used to distinguish
active cysts from inactive ones but is not useful for the
demonstration of intraventricular cysts (See Fig. 7.12
A–C, for comparison between CT and magnetic reso-
nance imaging (MRI) in visualization of cysts).
• Racemose cysts (Fig. 7.15) are aberrant cysticerci,
which at times are found developing in the ven-
tricles or subarachnoid space, and may resemble
Sparganum proliferum larvae but in section can be
distinguished by the presence of a cavity within the
parenchyma as well as by the demonstration of spe-
cific immune complexes.
• Racemose larvae form no scolex, and the cyst wall
grows in an irregular branching and budding fashion
to a diameter of several centimeters (Fig. 7.12D, E,
is an MR image of such a cyst, which is noted to
have the same density as the spinal fluid but is seen
to produce unphysiologic enlargements within the
ventricular system).
Pathogenesis
Intestinal taeniasis
• When humans eat insufficiently cooked cysticercus-
infected meat, all but the scolex portion is digested,
and the scolex attaches to the intestinal wall to be-
gin growing a chain of proglottids.
• Although proven, it is thought that reverse peristalsis
may carry intestinal contents with eggs to the upper
portions of the duodenum, where after hatching the
oncospheres penetrate directly into the intestinal wall.
• For these reasons, infection with adults of T. solium
is dangerous both to the patients and to those with
whom they come in contact.
• The adult worms probably cause no symptoms in
the majority of patients.
• Vague abdominal discomfort, hunger pangs, and
chronic indigestion have been reported but are un-
FIG. 7.12 Neurocysticercosis as seen by computed doubtedly seen more often in patients who are aware
tomography (CT) and magnetic resonance imaging (MRI). of their parasitic infection than in those who are not.
A, B, The same parenchymal cyst (A, CT with contrast; B, • Moderate eosinophilia frequently occurs.
proton density-weighted MRI). C, Proton density-weighted
MRI of intraventricular cyst. D, E, The same racemose Cysticercosis
intraventricular cyst (D, T1-weighted MRI; E, T2-weighted • Upon ingestion by hogs or by humans, the outer
MRI; curved arrows, cysts; straight arrows, lateral shell of the Taenia egg disintegrates in the small in-
ventricles). (Courtesy of Prof. T. Hans Newton, University of testine, and the contained embryo or oncosphere is
California San Francisco, CA.) able to invade the intestinal wall and enter a blood
vessel by means of the six hooklets that it bears.
• It may be carried in the bloodstream to any part of
the body and may lodge in any tissue, but it most
frequently develops in voluntary muscle.
• Though the majority of such infections are asymp- • Subcutaneous cysts are easily palpated and may re-
tomatic, invasion of muscle by the larvae may give semble small lipomas
rise to myositis, with accompanying fever and eosin- • In humans, cysticerci most commonly come to
ophilia, and in rare cases to a condition known as our attention when they occur in the central ner-
muscular pseudohypertrophy, with the initial mus- vous system; in swine they are usually found in the
cle swelling then leading to atrophy and fibrosis. muscles.
FIG. 7.13 Cerebral cysticercosis. (Courtesy of Prof. C. FIG. 7.15 Section of racemose cysticercus removed from
H. Hu.) ventricle of human brain. Note scalloped surface of bladder
wall. (Photomicrograph by Zane Price.)
FIG. 7.14 Extensive calcified cysticercosis of muscle. Numerous elliptical calcifications having variable
sizes are aligned along the long axis parallel to the muscle planes of the pelvis and lower extremities (large
arrows). Nearly all the calcifications have a small lucent center and resemble a ring calcification when
viewed from the side (small arrows). (From Keats T. Missouri Med 1961; 58:457.)
• While light infections with the bladder worm are of- no symptoms while alive, but an intense inflamma-
ten asymptomatic, in heavier infections, the chance tory reaction may develop around the dead or dying
of cysts lodging in the eye or brain (Fig. 7.13) where parasites, with an exacerbation of symptoms.
they are most likely to cause symptoms, is increased. • It has been suggested that this may be secondary not
• Frequently the cysticerci die and become calcified only to the release of antigenic substances by the dead
without giving rise to any symptoms (Fig. 7.14). or dying worms but also to cessation of their active
• Depending on their location, cysticerci may give rise immunosuppression, considered to deplete comple-
to visual difficulties that fluctuate with eye position, ment, suppress lymphocyte activity, reduce eosino-
or to a generalized decrease in visual acuity, retinal phil activity, and have an active cytotoxic effect.
edema, hemorrhage or vasculitis, or detachment • Meningeal cysts cause intense arachnoiditis, which
while cysts developing along the optic tracts may may lead to obstructive hydrocephalus, cranial
give rise to visual field defects. nerve involvement, intracranial hypertension, arte-
• Worldwide, neurocysticercosis (NCC) is the most rial thrombosis, and stroke.
common parasitic disease of the CNS. • Intraventricular cysts may be asymptomatic, or if
• NCC may present itself in many forms, depending they block the flow of CSF may cause intermittent
on localization of the cysts and disease activity and or continuously increased intracranial pressure, re-
as infection may take place over a period of many sulting in severe persistent headache, papilledema,
years, it is possible for one host to exhibit multiple progressive loss of vision, nausea, and vomiting.
forms of the disease.
Epidemiology
• The most common form of active NCC, character-
• Cysticercosis is seen principally in areas where pork is
ized by the presence of living cysts, is arachnoiditis
consumed raw or undercooked, and where poor hy-
with spinal fluid pleocytosis, increased cerebrospi-
giene allows contamination of foodstuffs by human
nal fluid protein, and a positive CSF serologic test
feces.
for cysticercosis (Sotelo et al., 1985).
• Immigrants from Mexico, Central and South America,
• The intense inflammatory reaction provoked by
and Southeast Asia account for most cases in the
meningeal localization may result in obstructive
United States.
hydrocephalus; other sequelae may be cranial nerve
involvement, intracranial hypertension, arterial Treatment
thrombosis, and stroke. • For intestinal taeniasis, Praziquantel, administered
• Parenchymally located active (noncalcified) cysts in a single dose of 5 to 10 mg/kg body weight, is the
may cause no symptoms while alive and often do drug of choice, with cure rates approximating 100%.
not result in CSF changes, but they may also give rise • Niclosamide, given as for diphyllobothriasis, is also ef-
to cerebral edema, epileptic seizures, focal deficits, fective for intestinal taeniasis; however, care must be
and intracranial hypertension. taken in administering this drug to patients with taeni-
• Other forms of active NCC include vasculitis with asis solium as it may cause rupture of the proglottids.
resultant brain infarction, mass effect produced by • Many cases of NCC are asymptomatic and require
large cysts or clumps of cysts, intraventricular cysts, no treatment.
and spinal cysts. • Until recent years, all that could be offered symp-
• Intraventricular cysts may be asymptomatic, or if tomatic NCC patients was anticonvulsants to re-
they block the flow of CSF they may cause intermit- lieve seizures, corticosteroids if necessary to control
tent or continuously increased intracranial pressure. symptoms secondary to meningitis or cerebral ede-
• Cysts developing within the spinal cord may pro- ma, and surgery in selected cases.
duce an arachnoiditis, or symptoms similar to those • Surgical treatment includes direct excision of ven-
resulting from any mass lesion. tricular cysts, shunting procedures to relieve hy-
• Classified as inactive NCC are calcified parenchymal drocephalus, and removal of cysts by means of
cysts, seen in about 60% of cases, and hydrocephalus stereotaxic endoscopy.
secondary to meningeal fibrosis, found in about 4%. • Spontaneous disappearance of parenchymal cysticerci
• Calcified parenchymal cysts may give rise to cerebral is well documented, especially in children, suggesting
edema, epileptic seizures of various types, focal defi- to some the advisability of symptomatic treatment in
cits, and intracranial hypertension. those for whom it is effective and following the evolu-
• Parenchymal cysticerci that do not come in contact tion of the lesions with CT or MRI (Gogia et al., 2003).
with the subarachnoid space and cysticerci in the ven- • In patients with untreated hydrocephalus or diffuse
tricles that do not obstruct the flow of CSF may cause cerebral edema, White et al. (2018) recommend
management of elevated intracranial pressure alone General morphology

and not antiparasitic treatment. • Adults of T. saginata exceptionally attain a length of
• Symptomatic treatment, including the administra- 25 m, but they are usually less than half this size.
tion of dexamethasone (24 to 32 mg/day during • The unarmed scolex (Fig. 7.17) bears four muscular
the acute stage), is advised by various authorities for suckers and a small rostellum without hooks (Pres-
those few patients who develop an acute cysticercot- ence or absence of hooks may thus serve to differen-
ic encephalitis, whose condition would probably be tiate T. saginata and T. solium).
exacerbated by anticysticercal treatment. • Mature proglottids are either wider than long or
• Albendazole, a member of the benzimidazole group nearly square, whereas gravid proglottids, which are
of drugs that includes thiabendazole and mebenda- eventually passed in the stool, are considerably lon-
zole, is generally well tolerated (but should not be ger than they are wide.
taken during pregnancy); side effects include dizzi- • Usually the gravid proglottids of T. saginata
ness or headache, abdominal pain, diarrhea, nausea, (Fig. 7.18) are longer than those of T. solium.
and vomiting. • The structure of the uterus is very much like that of
• For active parenchymal brain cysts and subarach- T. solium, but the number of main side branches on
noid (racemose) cysts, Del Brutto et al. (1992, each side of the central stem is 15 to 20 (Table 7.1).
1993) recommend albendazole, 15 mg/kg body • Eggs are similar to those of T. solium.
weight daily (maximum 800 mg per day) for 8 days
while others suggest treating for as long as 30 days. Life cycles
• Garcia et al. (2004) conclude from a study carried out • The life cycle is somewhat similar to that of T. so-
in Lima, Peru, that treatment of adult patients having lium, but cattle are the intermediate host, while hu-
neurocysticercosis with 800 mg of albendazole per mans are hosts only to the adult worms (Fig. 7.16).
day and 6 mg of dexamethasone per day for 10 days • Embryonated eggs are passed with the feces and
was safe and effective in decreasing the parasite bur- must be ingested by cattle.
den and in reducing the number of seizures. • The larva grows in the flesh of cattle and eventually
• Albendazole (15 mg/kg/day) combined with pra- develops into an infective cysticercus.
ziquantel (50 mg/kg/day) for 10 to 14 days is rec-
ommended for patients with more than two viable Infective stages
parenchymal cysticerci rather than albendazole • Cysticercus bovis (once ingested from an infected
monotherapy (White et al., 2018) cattle meat, intestinal infection of adult happens)
• Chemotherapy should not be used for intraocular
cysticercosis; surgical removal is often possible. Diagnostic stages
• Results of treatment may be monitored by contrast- • Eggs of different Taenia species have a similar ap-
enhanced CT, generally done after an interval of pearance thus species identification is not possible
3 months. Remission or marked improvement in through examination of eggs.
seizure activity is usually seen after therapy (Vasquez • T. saginata may be differentiated from T. solium by
and Sotelo, 1992). counting the number of primary uterine branches
on gravid proglottids.
Prevention
• Proper disposal of feces, to avoid contamination of Mode of transmission
food, soil, and water, is essential. • T. saginata is acquired by humans through the inges-
• Thorough cooking of pork or freezing to –5°C for tion of raw or insufficiently cooked beef.
4 days, –15°C for 3 days, or –24°C for 1 day kills the
larvae and if universally practiced would eliminate Laboratory diagnosis
the infection from both humans and pigs. • Diagnosis of T. saginata is made through microscop-
ic examination of eggs and/or proglottids found in a
Taenia saginata stool sample.
The beef tapeworm, T. saginata, has worldwide distri-
bution. Unlike T. solium, infection with T. saginata is Pathogenesis
frequently encountered in the United States. It has a • An important difference between T. solium and
similar life cycle to that of T. solium with cattle as the T. saginata is that cysticercosis of humans due to
intermediate hosts instead of pigs. T. saginata apparently does not occur.
FIG. 7.16 Life cycle of Taenia saginata.
FIG. 7.17 Taenia saginata, scolex. (Photomicrograph by FIG. 7.18 Taenia saginata, gravid proglottid.
Zane Price.) (Photomicrograph by Zane Price.)
would consider it a separate species, T. asiatica (Eom

TABLE 7.1
et al., 2002). It infects a range of intermediate hosts (cat-
Key to the gravid proglottids of the major human
tle, goats, monkeys, and wild boar) in addition to swine,
tapeworms.
with cysticerci being found primarily in the liver.
a. Uterus forms rosette in center D. latus
of proglottid Multiceps multiceps (coenurus disease)
Uterus otherwise disposed b The adult of M. multiceps, or the “gid worm”, is found in
b. Uterus with central stem c dogs and other Canidae. The larval stage, known as a coe-
running length of proglottid nurus, occurs in a variety of herbivorous mammals and
Uterus without central stem d has been reported occasionally from humans in various
c. Central stem with 7 to 13 main T. solium parts of the world, including the United States. It is pos-
lateral branches sible that more than one species of Multiceps can pro-
Central stem with 15 to 20 T. saginata duce human disease, but it is very difficult to distinguish
main lateral branches species in this genus.
d. Proglottid wider than long Hymenolepis spp.
Proglottid longer than wide Dipylidium caninum General morphology
• The coenurus larva is larger than a cysticercus (up
to 2 cm diameter); it is semitransparent, glistening
• Appendicitis and duodenitis white, and filled with fluid.
• Intestinal obstruction • Adult measures 40-60 cm in length with armed piri-
• Weight loss due to unusual appetite (tapeworm form scolex that has 4 strong suckers and a double
appetite) circle of 22-rostellar hooks. (Beaver, et al., 1984).
• Gravid uterus: 18-26 lateral branches.
Epidemiology
• Eggs: 31 - 36 um.
• The beef tapeworm, T. saginata, has worldwide dis-
tribution. Life cycles
• Unlike T. solium, infection with T. saginata is fre- • Eggs and gravid proglottids are released into the en-
quently encountered in the United States. vironment in the feces of infected dogs.
• The prevalent liking for rare steak is one means of • Following ingestion of the egg of Multiceps, the on-
successful survival of this species in the United States. cosphere hatches in the small intestine and makes
its way into a blood vessel in the intestinal wall in
Treatment the same manner as larvae of Taenia.
• The treatment is as outlined for Taeniasis solium. • The embryo is carried in the bloodstream to various
parts of the body but most frequently develops in
Prevention the central nervous system.
• Beef must be thoroughly cooked at an internal tem- • Multiple scolices bud from the inner surface of the
perature of 56°C (131°F) or freezing at –10°C for cyst wall, instead of the single one that characterizes
5 days (Lesh and Brady, 2019). the bladder worm.
• Numerous denser white spots on the wall indicate
Taenia saginata asiatica (Asian Taenia) the position of the attached scolices.
First reported from Taiwan, this Taenia species has now • The coenurus may form a single vesicle, or it may be
been found also in Korea, China, the Philippines, Thai- branched to a greater or lesser degree.
land, Malaysia, and Indonesia. In the latter country, par-
ticularly in North Sumatra and Bali, raw or rare roasted Infective stages
pork is consumed, and the adult worms found in hu- • Embryonated eggs and/or gravid proglottids
mans are the Asian Taenia. In Irian Jaya neurocysticercosis
Diagnostic stages
is pandemic, but there the adult worm is T. solium. Appar-
• Diagnosis is made through observation of coenurus
ently, the Asian taeniid does not produce cysticercosis in
larvae in a specimen.
humans (Flisser et al., 2004). DNA testing suggests that
this worm, morphologically similar to T. saginata but Mode of transmission
with a scolex suggestive of T. solium, is genetically dis- • The definitive hosts (members of the Canidae family)
tinct and should be considered a subspecies of T. saginata become infected through ingestion of tissue from an
(Fan et al., 1995; González et al., 2004) though some intermediate host containing a coenurus larva.
• Humans are accidental hosts; they become infected as nine “strains” of E. granulosus, on the basis of differ-
after ingestion of eggs in contaminated food and ing intermediate hosts (and definitive hosts—there is a
water or on fomites. strain in Africa in which the adult worm is found only
in lions), DNA sequencing, geographic location, and so
forth. Four of these “strains” are considered to be suf-
• Finding coenuri in biopsy or autopsy specimens is
ficiently different as to warrant being called separate
the basis for diagnosis of coenurus disease.
species (Lymbery and Thompson, 1996). Similarly, four
• A preoperative diagnosis of coenurus infection is
strains of E. multilocularis are recognized. The diagnostic
unlikely, as there are no specific serologic tests for it.
and therapeutic significance of these findings, if they are
• It may be impossible to distinguish a sterile coenu-
confirmed, remains to be determined.
rus from a racemose cysticercus.
Pathogenesis General morphology
• In sheep, the most common intermediate host, the par- • The adult worm (Fig. 7.20) is 0.6 cm or less in length
asite produces a disease known as gid, from the unsta- and possesses a scolex, neck, and usually three pro-
ble gait, or giddiness, that marks the infected animals. glottids.
• In humans, most reported patients have had coenuri • One proglottid is immature, one is mature, and one
in the brain or spinal cord and symptoms suggestive of is gravid.
space-occupying lesions of the central nervous system. • The eggs cannot be distinguished from those of
• Cerebral and ocular coenurosis Taenia.
• In tropical Africa, coenurus larvae, which may be • Eggs of Echinococcus contain an embryo, called an
those of a species other than M. multiceps, have been onchosphere or hexacanth because of the six hook-
found in the muscles or subcutaneous tissues. lets it bears.
Epidemiology Life cycles

• M. multiceps may be found worldwide although • The minute tapeworm E. granulosus lives as an adult
most human cases have been reported in Africa. in the intestines of dogs and other Canidae.
• Two different cycles—pastoral and sylvatic—and a
Treatment number of different strains have been recognized.
• Treatment is surgical. • Intermediate hosts: sheep (pastoral cycle) and
• There are no reports of the use of praziquantel or wolves (sylvatic cycle).
albendazole, but mebendazole has been found not • Eggs are passed in the feces of dogs and are immedi-
to be effective. ately infectious.
• Upon ingestion by the intermediate host, the em-
Prevention bryos, released from their surrounding membranes
• The spread of coenurosis in dogs may be controlled by action of the digestive juices, bore actively into
by regular anti-helminthic treatment at regular 6 to the intestinal wall and enter a blood vessel.
8 week intervals and proper disposal of sheep or • They may lodge in any organ or tissue but most
goat brain after slaughtering of animals to prevent frequently are found in the liver and lungs (In hu-
scavenging by dogs (Abera et al., 2016). mans, 80% to 95% of hydatids develop in these two
• Proper handling of food is advised to avoid acciden- organs, the majority in the liver).
tal ingestion of eggs in contaminated food by hu- • The embryo develops slowly into the hydatid cyst,
mans (Fig. 7.19). reaching a diameter of 1 cm in 5 months or so and
Echinococcus granulosus, E. multilocularis, thereafter enlarging steadily so that at the end of 10
and E. vogeli (hydatid disease) or more years’ growth it may contain some liters of
The genus Echinococcus contains three species for which fluid.
humans are host to the larval stage, or hydatid. These • Ultimate growth of the cyst depends on location; in
three species are all found as adult worms in Canidae. A some areas of the body they are unable to expand
fourth, E. oligarthrus, whose status as a human parasite is freely, whereas in others modest growth results in
disputed, occurs as an adult in felids. The life cycle of all serious impairment to the function of vital struc-
these worms is similar to that of E. granulosus (Fig. 7.21). tures or even in deathh.
There is no unanimity as regards classification of the ge- • By the time the cyst of E. granulosus has reached the
nus Echinococcus. Some authorities recognize as many diameter of 1 cm, its wall is differentiated into a thick
FIG. 7.19 Life cycle of Multiceps multiceps. (Photo from https://www.cdc.gov/dpdx/coenurosis/index.html)
outer laminated, noncellular layer, or limiting mem-

brane, which covers the thin germinal epithelium.
• From the germinal epithelium, masses of cells grow
into the cavity of the cyst; they become vacuolated
and are known as the brood capsules.
• Protoscolices bud from the inner wall of the brood
capsule.
• Occasionally, daughter cysts appear within the hy-
datid (Fig. 7.22); these in turn produce brood cap-
sules, which may contain protoscolices.
• The daughter cysts are replicas in miniature of the
FIG. 7.20 Echinococcus granulosus, adult worm.
complete hydatid, possessing even the laminated
outer layer; their mode of development is obscure.
FIG. 7.21 Life cycle of Echinococcus granulosus. (Photo from https://www.cdc.gov/parasites/echinococcosis/biology.html)
• Gradually, the brood capsules and daughter cysts

break down, liberating the developed scolices.
• “Hydatid sand,” a granular material, consisting of
free protoscolices, daughter cysts, and amorphous
material, is found in older cysts (Fig. 7.23).
Infective stages
• Embryonated egg
Diagnostic stages
• Echinococcosis may be diagnosed through finding
hydatid cysts with imaging techniques such as CT
scans.
FIG. 7.22 Numerous small and medium-sized daughter • Minor morphologic differences are seen between
cysts, recovered from a single hydatid cyst of the liver.
adults of E. granulosus and E. multilocularis, and the
(From Saidi F. Surgery of hydatid disease, Philadelphia,
hydatid cysts of the two species are quite distinct.
1976, WB Saunders.) (Saidi, 1976)
• The limiting membrane is thin in E. multilocularis,
and the germinal epithelium may bud externally, to
FIG. 7.25 Section through cyst of Echinococcus

multilocularis in liver. (Photomicrograph by Zane Price.)
FIG. 7.23 Echinococcus granulosus, hydatid sand.
FIG. 7.26 Echinococcus vogeli: Polycystic hydatid cyst,

human pericardium. (From D’Alessandro A et al. Am J Trop
FIG. 7.24 Hydatid cyst involving the upper humerus Med Hyg 1979; 28:303.)
of child. (From Saidi F. Surgery of hydatid disease,
Philadelphia, 1976, WB Saunders.) (Saidi, 1976)
inward, in the original cyst, forming septa that di-
proliferate in any direction or even to metastasize vide it into many sections (Fig. 7.26), and outward,
(It is because of their appearance that they are called to form new cysts. The vesicles forming a polycystic
alveolar or multilocular cysts). hydatid are relatively large and fluid filled.
• Unlike the unilocular hydatid cysts of E. granulo- • In humans, hydatids of E. vogeli are found in the
sus, there is little fluid in alveolar hydatids of E. liver, but also the lungs, pleura, pericardium, and
multilocularis which consist of many small vesicles heart; the intercostal muscles and diaphragm; and
embedded in a dense connective tissue stroma in the stomach, omentum, and mesenteries.
(Fig. 7.25). • Having its adult stage in wild felids, E. oligarthus is
• In E. vogeli infection (parasite of bush dog), the ger- likewise characterized by the formation of polycystic
minal membrane of the hydatid proliferates both hydatid cysts in its rodent intermediate hosts.
• The adult worms are acquired by sheep dogs or stray
dogs feeding on infected entrails that lie about abat-
toirs or that are discarded after slaughtering animals
at home.
• Feral dogs and other canidas acquire the infection by
scavenging or by preying on sheep or wild herbivores.
• Transmission to humans can occur by means of the
accidental ingestion of eggs passed by dogs or cats.
• In addition, hunters and trappers could be infected
while handling foxes or wolves.
• Radiographic examination (Fig. 7.27) may be used
to detect a hydatid cyst which shows a sharp outline;
fluid levels can sometimes be detected within it.
• Photoscans may indicate the presence of space-oc-
cupying lesions of the liver or spleen.
• Ultrasound and CT are also of value in the diagnosis
of hydatid disease (Fig. 7.28).
• If the cyst is abdominal and large, a characteristic FIG. 7.27 Echinococcus granulosus cyst of liver. There is
thrill can sometimes be elicited. a single, round, partially calcified hydatid cyst in the inferior
portion of the right lobe (white arrows). (From Teplick JG
• After surgical exposure of a presumed hydatid cyst,
et al. Roentgenologic diagnosis, vol. 1, ed 3, Philadelphia,
aspiration of a portion of its contents can be per-
1976, WB Saunders.)
formed, and examination of fluid removed in this
manner may reveal hydatid sand (It should be re-
membered that some hydatid cysts are sterile and
contain no sand).
• Serologic tests are also available for diagnosis of hy-
datid disease.
• The indirect hemagglutination test (IHA) and en-
zyme-linked immunosorbent assay (ELISA) are
most satisfactory for diagnosis.
• Serologic cross reactions have been noted between
cysticercosis and hydatid disease as well as between
cysticercosis and sparganosis.
Pathogenesis
• Symptoms of hydatid disease vary according to the
location of the cyst.
• The expanding hydatid cyst causes pressure necrosis
of surrounding tissues, although as growth is slow a FIG. 7.28 CT shows hydatid cyst of spleen. (Courtesy of
Dr. J. F. Catchpool, Sausalito, CA.)
good deal of accommodation may take place before
any vital structures are compromised.
• If, as is most commonly the case, the cyst is in the • Cysts in the lungs ordinarily are asymptomatic un-
liver, it may cause no symptoms and will be noted til they become large enough to give rise to cough,
only when its increasing size calls attention to its shotness of breath, or pain in the chest.
presence. • Rupture of a pulmonary cyst into a bronchus may be
• Hepatic cysts may cause early symptoms if the lo- marked by severe allergic symptoms and coughing
cation in the liver is such that their expansion pro- with the production of blood-flecked fluid, which
duces pressure on a major bile duct or blood vessel may contain recognizable hydatid tissue.
or if intrabiliary rupture occurs. • Secondary infection may lead to chronic lung abscess.
• Cysts in the central nervous system produce serious former Soviet republics including Siberia, northern
damage, symptoms very similar to those seen in oc- China, and the northern islands of Japan—as well as
ular sparganosis. Central Europe into Germany and in India.
• Slow leakage of hydatid fluid from the cyst sensitizes • There is growing concern in Europe about alveolar
the patient and elicits eosinophilia. hydatid disease as the number of foxes increases in
• Rupture of an abdominal hydatid cyst, either both rural and urban setting.
through trauma or in the course of surgery, carries • A study in southwestern Germany reported that
with it both the grave risk of anaphylactic shock and 75% of the foxes were infected with E. multilocularis
the possibility of spread of the infection through (Romig et al., 1999).
seeding the peritoneal cavity with hydatid sand or • E. vogeli occurs in Central and South America as a
bits of germinal epithelium, which are capable of parasite of the bush dog, with its polycystic larval
producing new cysts. stage in rodents (pacas and spiny rats).
• Circulating immune complexes have been detected • Human cases of E. vogeli have been reported from
and membranous nephropathy demonstrated in pa- Panama, Colombia, Brazil, Peru, and Ecuador.
tients with hydatid disease. • The fourth species, E. oligarthrus, is found in Central
• When the hydatid cyst is formed in bone (Fig. 7.24), and South America (Basset et al., 1998).
development is markedly abnormal, and the limit- • E. oligarthus been reported on rare occasions to cause
ing membrane is not formed. The hydatid develops hydatid disease in humans, but some believe that
first in the marrow cavity, from which it expands and these human cases were in fact misidentified E. vogeli.
frequently erodes large areas of bone (Saidi, 1976).
• Alveolar cysts usually occur in the liver in humans Treatment
and grow very slowly, so that they may be present for • The first drug found to have any effect against the
many years before causing symptoms, which are gen- hydatid stage of Echinococcus was mebendazole.
erally related to pressure from the expanding tissue. • Albendazole is better absorbed and penetrates
• Growth into the vena cava or portal vein may lead to well into hydatid cysts, and therefore is now gen-
metastases, usually to the lungs or brain. erally preferred over mebendazole (Gil-Grande
et al., 1993), although neither drug gives impressive
Epidemiology cure rates in most studies (Todorov et al., 1992).
• Although hydatid disease caused by E. granulosus is • Albendazole is generally administered at the rate
most prevalent in sheep-raising areas such as Australia of 10 mg/kg body weight, or 400 mg twice daily for
and New Zealand, other domestic and wild animals 4 weeks, repeated as necessary for up to 12 cycles each
serve as intermediate hosts of the parasite elsewhere. separated by an intrval of 2 weeks (Cook, 1990).
• Animal reservoirs are dogs, coyotes, and wolves; the • The results of therapy are best judged by ultrasonog-
hydatid cysts occur in sheep, pigs, deer, and other raphy or MRI, repeated at intervals of approximately
wild herbivores. 3 months.
• Hydatid disease is widely distributed throughout • It is generally agreed that chemotherapy should be
the South American continent. instituted a day or so before surgery or aspiration,
• Human infection is seen principally in the sheep- and continued for a month after such procedures.
raising areas of the world, including southern Brazil, • Yasawi et al. (1993) report excellent results when pra-
Argentina, Uruguay, Chile, and Peru; in Yugoslavia, ziquantel is given in conjunction with albendazole.
Bulgaria, Sardinia, Cyprus, Turkey, and Lebanon; in • Ivermectin injected directly into cysts has been
scattered parts of Africa; in central Asia and northern found to kill all protoscolices in experimental ani-
China; and in New Zealand and southern Australia. mals (Ochieng-Mitula and Burt, 1996).
• In North America, E. granulosus occurs in Alaska, • Until recently the surgical removal of hydatid cysts,
Canada, and the contiguous United States. was the only form of therapy possible; however,
• The sylvatic cycle occurs in wolves, the hydatids de- many reports now favor the use of percutaneous
veloping in wild ungulates (moose and reindeer) in aspiration for pulmonary, hepatic, and other cysts
Alaska, Canada, Scandinavia, and northern Eurasia. accessible to this type of procedure.
• E. multilocularis is somewhat more restricted in dis- • The most commonly used form of therapy is de-
tribution than is E. granulosus (see Figs. 1.7 and 1.8). scribed by the acronym PAIR (Percutaneous As-
• E. multilocularis is enzootic throughout much of the piration, Injection—of hypertonic saline or other
subarctic area of the world—in Alaska, Canada and scolicidal fluid—and Reaspiration), as detailed
the North Central states bordering on Canada, the by Akhan et al. (1994, 1996), Bastid et al. (1994),
Salama et al. (1995), Khuroo et al. (1997), and area for some time; it is probable that these contrac-
Smego et al. (2003) all of whom find it a safe and tions function in the release of the eggs, which are
effective form of therapy in selected cases. then ingested by the flea larvae.
• E. multilocularis is said to respond to albendazole, • Infection takes place through the accidental ingestion
given in the same dosage as recommended for of fleas containing cysticercoid larvae (Fig. 7.29).
E. granulosus, in a similar fashion (Liu et al., 1993) • The cysticercoids grow into adult worms in the
• A single report (Meneghelli et al., 1986) suggests small intestine.
that the same is true of E. vogeli.
Infective stages
Prevention • Cysticercoid larvae in fleas
• Where sheep-and-dog strains are chiefly responsible
for continuation of the cycle, the most successful Diagnostic stages
control programs to date have consisted of routine • Gravid proglottids (described as melon or pumpkin
6-weekly deworming of the dogs with praziquantel. seed shape) and egg packets found in stool are diag-
nostic of infection with D. caninum.
Dipylidium caninum
D. caninum, double-pored dog tapeworm, is common Mode of transmission
in cats and dogs all over the world. Occasionally it is • Humans acquire infection by ingestion of the inter-
found in humans, particularly small children. mediate host flea (Ctenocephalides spp.).
General morphology
• Adults of D. caninum are relatively small, averaging
• Diagnosis of this species is made on finding in the
about 15 cm in length.
stool the characteristic proglottids or, more rarely,
• They may reach a length of 80 cm.
egg packets.
• Many specimens may be present in one individual
host.
Pathogenesis
• The armed scolex bears four suckers and a coni-
• Light infections are often asymptomatic, but ab-
cal, retractile rostellum with several circles of small
dominal pain, diarrhea, and anal pruritus may occur
hooks (1-7 rows of rosethorn hooklets).
in some individuals.
• Mature proglottids (Fig. 7.30 A) are longer than they
are wide and contain two sets each of male and fe-
Epidemiology
male reproductive organs. Presence of a genital pore
• Human infection requires ingestion of infected dog
on each lateral side supports its common name.
or cat fleas and is thus most likely to occur in small
• The developing uterus appears in the form of a
children who kiss or are licked by their infected pets.
network, which, as the segment becomes gravid
(Fig. 7.30B), eventually breaks up into discrete units Treatment
called egg packets (Fig. 7.31) that may contain 5 • Praziquantel is very effective, given in a single oral
to 30 eggs or 8-15 eggs enclosed in an embryonic dose of 5 to 10 mg/kg body weight.
sheath or egg capsule (Beaver, et. al., 1984) • Niclosamide, administered as outlined for D. latus
• Gravid segments are considerably longer than they infections, is an alternative.
are wide and are barrel-like in outline as they appear
in the stool or perianal area (Table 7.1). These seg- Prevention
ments are also described as melon-seed, pumpkin • Periodic deworming of infected dogs and cats and
seed, or rice granule shape. control of fleas so that the animals do not become
reinfected are essential.
Life cycles • Niclosamide is now available in injectable form for
• The egg is infective to cat (Ctenocephalides felis) or veterinary use.
dog (Ctenocephalides canis) flea or human flea (Pulex
irritans) larva where it develops into a cysticercoid Hymenolepis nana
and is retained within the adult flea. • H. nana, the dwarf tapeworm of humans, is a com-
• The gravid proglottids contract and expand vigor- mon parasite of the house mouse and is found all
ously upon reaching the exterior of the host and over the world. Infection with H. nana is seen most
may remain attached to the fur surrounding the anal frequently in children but occurs in adults as well.
FIG. 7.29 Life cycle of Dipylidium caninum. (Photo from https://www.cdc.gov/parasites/dipylidium/biology.html)
FIG. 7.30 Dipylidium caninum. A, Mature proglottid. B,

Gravid proglottid. (Photomicrographs by Zane Price.)
FIG. 7.31 Egg packets of Dipylidium caninum.
(Photograph by H. J. Griffiths. From Zaiman H [ed.]. A
• Smallest tapeworm (25-40 mm) that parasitizes hu- pictorial presentation of parasites.)
man intestine
• Tapeworm that may or may not require an interme- General morphology
diate host to complete its natural cycle. • Adults of H. nana are relatively small worms, only a
• 2 cycles observed: direct cycle (embryonated egg is few centimeters long.
the infective stage) and indirect cycle (cysticercoid • The armed scolex has four suckers and a rostellum
larva is the infective stage) with one circle of hooks.
• All segments are wider than they are long (Table 7.1). the relative tissue immunity conferred by harboring
• Mature proglottids contain one set of male and one cysticercoids.
set of female reproductive organs. • Eggs produced by these worms, hatching in the in-
• The ovary is flanked by two testes on one side and testine, encounter less tissue immunity and may
one testis on the other side. give rise to the syndrome of hyperinfection.
• Gravid segments contain a saclike uterus filled with
eggs. Laboratory diagnosis
• Eggs are usually liberated from the gravid segments • Diagnosis is made through microscopic identifica-
before they become detached. tion of eggs in stool.
• The eggs of H. nana (see Fig. 7.10A) are broadly
ovoid, have a thin and smooth outer shell, and mea- Pathogenesis
sure 30 to 47 µm. • Light infections are asymptomatic.
• Eggs contain the six-hooked (hexacanth) onco- • When large numbers of worms are present, they
sphere within a rigid membrane which has two po- may give rise to abdominal pain, diarrhea, head-
lar thickenings or knobs from which project four to ache, dizziness, anorexia, and various nonspecific
eight long, thin filaments called polar filaments. symptoms.
Life cycles Epidemiology

• H. nana is unique in that the adult worm develops • A relatively high prevalence of this tapeworm has
following ingestion of the egg by humans. been reported in surveys conducted in central Eu-
• Swallowed eggs hatch in the small intestine and the rope and in Latin America.
six-hooked oncosphere burrows into a villus of the • Most infected persons are small children, and as
intestinal mucosa, where, within a few days, it devel- these infections are usually transmitted through the
ops into a cysticercoid larva. ingestion of eggs, nursery schools are an important
• The cysticercoid is a small larva (see Fig. 7.30), con- source of infection.
taining a single scolex but without the bladder char-
acteristic of a cysticercus. Treatment
• When fully grown, the larva breaks out of the villus • Praziquantel, given in a single oral dose of 25 mg/kg
into the lumen of the small intestine, where it grows body weight, is the drug of choice.
into an adult worm. • Niclosamide (see treatment of D. latus) must be giv-
• Experimental evidence obtained from studies on en daily for 5 days because of the tissue phase of the
mice suggests that in these animals a certain degree infection, with a daily dose of 2 g for adults, 1.5 g for
of immunity to reinfection results from the occur- children weighing over 34 kg, and 1 g for children
rence in them of the tissue phase. weighing between 11 and 34 kg.
• Eggs of H. nana may also develop into infective cys- • Nitazoxanide (Alinia), FDA-approved for Cryptospo-
ticercoids in various intermediate hosts, particularly ridium and Giardia, but considered investigational
grain beetles and when ingested accidentally with for H. nana, may be used as an alternative treatment
contaminated grain products, the larvae grow into (Ortiz et al., 2002). Administered orally, the adult
adult worms in mice, and probably in humans also dosage is 500 mg a day for 3 days and the pediatric
(Figs. 7.32 and 7.33). dosage is 100 mg twice a day for 3 days for children
1 to 3 years of age and 200 mg twice daily for 3 days
Infective stages for children 4 to 11 years old.
• Cysticercoid larvae in grain beetle
• Embryonated egg Prevention
• Proper handwashing as well as washing of fruits and
Diagnostic stages vegetables before consumption helps avoid acciden-
• The presence of polar filaments is diagnostic and tal ingestion of eggs.
serves to differentiate the eggs of H. nana from those • Proper sanitation must be practiced because infec-
of Hymenolepis diminuta described subsequently. tive eggs can be released through feces.
Mode of transmission Hymenolepis diminuta

• Humans infected through ingestion of grain prod- H. diminuta (rat tapeworm), despite its specific name,
ucts contaminated by infected insects do not possess is much larger than H. nana. While less frequent than
FIG. 7.32 Life cycle of Hymenolepis nana. (Photo from https://www.cdc.gov/dpdx/hymenolepiasis/index.html)
H. nana infections, infections with H. diminuta have Life cycles

been reported from various parts of the world. • Completion of the life cycle requires an arthropod
intermediate host.
General morphology • More than 20 different species of insects have been
• The size of adult worms varies considerably and, as shown to serve as suitable hosts for the develop-
in other tapeworm species, depends in part on the ment of the cysticercoid larvae.
number of worms in the intestine. • The most important are flour moths and flour beetles.
• Usually, adults are 20 to 50 cm long and as much as • Upon ingestion of infected insects from flour contam-
4 mm wide (see Fig. 7.1). inated by the droppings of infected rats, larvae grow
• The greatest length reported for an adult specimen into adults in the small intestine of humans or rats.
of H. diminuta from a person is 1 m.
• The unarmed scolex bears four suckers and a small Infective stages
rostellum without hooks. • Cysticercoid larvae in flour beetle
FIG. 7.33 Life cycle of Hymenolepis diminuta. (Photo from https://www.cdc.gov/dpdx/hymenolepiasis/index.html)
Diagnostic stages Laboratory diagnosis

• Eggs are slightly ovoid and brown; the shell is rela- • Diagnosis of this species is made on finding the
tively thick and possesses a striated coat. characteristic eggs (Fig. 7.10B) in the stool.
• In some specimens, fine concentric striations may
be observed in the outer shell. Pathogenesis
• The oncosphere is enclosed in a membrane that has • Most infections are asymptomatic, but patients
two polar thickenings but no polar filaments, which may present with mild gastrointestinal complaints
readily differentiates this species from H. nana. such as nausea, anorexia, abdominal pains, and di-
arrhea.
• Infection of humans occurs through accidental in- Epidemiology
gestion of the intermediate host containing the cys- • While H. diminuta commonly parasitizes rats, it may
ticercoid larva. occasionally be encountered in human beings, cases
• The arthropod intermediate hosts may be found in having been reported from many parts of the world,
precooked cereals or other food items or in the envi- including several areas of the United States.
ronment.
Treatment ing cysticercoid larvae. Molecular probes were used to

• Praziquantel is very effective, given in a single oral identify the worms in human mixed infections with
dose of 25 mg/kg body weight. H. nana.
• Niclosamide, administered as outlined for D. latus
infections, is an alternative. Mathevotaenia
• Presumably, nitazoxanide, as outlined for H. nana, This intestinal tapeworm was described from a patient
would be an effective alternative treatment. living in Bangkok, Thailand, following treatment with
niclosamide (Lamon and Greer, 1986). The worms
Prevention closely resembled Mathevotaenia symmetrica, a cosmo-
• Primarily a zoonosis, hymenolepiasis diminuta may politan intestinal tapeworm of rodents for which vari-
be prevented in humans by rodent control measures ous insects serve as intermediate hosts. The diarrhea as-
and by protection from rodents and their droppings sociated with the infection resolved after anthelminthic
and from insects of cereals, grains, and other food- treatment.
stuffs that may be consumed without cooking.
Mesocestoides
Uncommon cestode parasites of humans Twenty-seven cases of human Mesocestoides infection
As is the case with the trematodes, humans are inci- have been reported from Africa, Asia, and the United
dental hosts to various tapeworms. Here are a few ex- States. The cases in the United States were in California,
amples; many more exist. Louisiana, Mississipi, Missouri, New Jersey, Ohio, and
Texas (Fuentes et al., 2003). Adult worms are intestinal
Bertiella parasites of various primates, carnivores, and birds of
Bertiella studeri in Africa, India, Southeast Asia, and the prey. The infective metacestode stage (tetrathyridium)
Philippines and B. mucronata from South America are is found in the body cavity and tissues of reptiles, birds,
adult parasites of monkeys, with a cysticercoid stage in and small mammals. Human infection is acquired from
mites. Human infections involve ingestion of infected eating insufficiently cooked meat of some animal that
mites. serves as an intermediate host for the larval metaces-
tode stage. The species of Mesocestoides identified with
Diplogonoporus grandis human infection are M. variabilis and M. lineatus. Pra-
This tapeworm, related to Diphyllobothrium, is a parasite ziquantel, a single oral dose of 10 mg/kg body weight,
of whales, and has been reported a number of times is effective in treatment.
from Japanese patients, who probably acquired the in-
fection through the consumption of raw anchovies or Raillietina celebensis
sardines containing the plerocercoid larva. A parasite of rats, this tapeworm has been reported
in humans from Japan, Taiwan, the Philippines,
Hymenolepis microstoma Australia, and French Polynesia. As the entire life
The rodent tapeworm, H. microstoma, has been reported cycle of this parasite is not known, the method by
as an intestinal parasite of humans in Western Australia which humans become infected is still a matter of
(Macnish et al., 2003). Various insects serve as inter- speculation.
mediate hosts for the tapeworm, and rodent and hu- Table 7.2 summarizes some important features of
man infections follow the ingestion of insects contain- the more common cestode infections of humans.
TABLE 7.2
Review of cestode infections of humans.
Means of Location of Location of
human larvae adults Laboratory
Disease Parasite infection in humans in humans Clinical features diagnosis
Diphyllo- (Dibothrioceph- Ingestion of (Present as Small intestine Majority asymp- Undeveloped
bothriasis alus latus) (fish larvae in fish sparganosis) (attached) tomatic; can cause operculate
tapeworm) vitamin B12 defi- eggs or
ciency, anemia proglottids in
stool
Taeniasis Taenia saginata Ingestion Not present Small intestine Vague digestive Embryo-
(beef tapeworm) of larvae in (for T. solium (attached) disturbances, nated eggs or
T. solium (pork beef or pork see cysticerco- anorexia; majority proglottids in
tapeworm) sis below) asymptomatic stool
Cysticercosis Cysticercus cel- Ingestion of Subcutane- As for T. Asymptomatic to X-ray, CT, MRI,
lulosae (larva of eggs ous tissues, solium Jacksonian sei- serologic tests
T. solium) muscle, eye, zures, hydrocepha-
brain lus, visual problems
Echinococ- Echinococcus Ingestion of Liver, lungs, Not present Chronic space- X-ray,
cosis (hyda- granulosus eggs other organs (in canines) occupying lesions ultrasound,
tid disease) E. multilocularis of involved organs CT, aspirate
E. vogeli of “hydatid
sand,” sero-
logic tests
Hymenolepi- Hymenolepis Ingestion Villi of small Small intestine Enteritis, diarrhea, Embryonated
asis nana (dwarf of eggs (of intestine (not (attached) abdominal pain, eggs in stool
tapeworm) H. larvae in present in anorexia; majority
diminuta (rat insects for H. diminuta) asymptomatic
tapeworm H. diminuta)
SUMMARY while members of the order Pseudophyllidea have a

scolex with grooves instead of suckers.
• The cestodes, or tapeworms, all have a flat,
• Cestodes generally do not have operculate eggs
ribbonlike body consisting of an attachment organ,
except those belonging to order Pseudophyllidea.
the scolex, followed by a chain of proglottids or
segments. • Dibothriocephalus latus, the “broad fish tapeworm,”
is the causative agent of human diphyllobothriasis
• The chain of segments, known as strobila (strobilus,
and in some cases, may produce a deficiency in
singular), grows from the neck of the parasite.
vitamin B12 due to the absorption of the vitamin from
• Immature segments are located closest to the neck the host’s intestinal tract by D. latus.
and do not contain fully developed structures.
• A characteristic feature of D. latus is its rosette-
• Mature segments are found in the middle of the shaped uterus.
strobila and contain the reproductive organs.
• Spirometra species are responsible for sparganosis
• Gravid proglottids are found at the terminal end of wherein the larva migrate throughout the host’s
the strobila and are usually filled with eggs. subcutaneous tissues and may, in some cases,
• Tapeworms have no digestive system; they absorb affect the eyes or brain.
nutrients from the host’s intestinal tract. • Taenia solium and T. saginata are known as the pork
• The cestodes are classified into order tapeworm and beef tapeworm, respectively.
Pseudophyllidea and order Cyclophyllidea. • The two Taenia species may be differentiated by
• Members of the order Cyclophyllidea possess have counting the number of uterine branches they
four cup-shaped suckers attached to the scolex possess.
Match the following diseases with the parasites that

• Only T. solium is capable of causing cysticercosis, cause them.
a serious tissue infection caused by the cysticercus 5. Sparganosis a. T. solium
larvae. 6. Coenurus disease b. T. saginata
• Multiceps multiceps causes coenurosis disease 7. Cysticercosis c. Echinococcus
wherein the parasite is carried through the 8. Hydatid disease d. Spirometra
bloodstream and develops in various parts of the
e. Multiceps multiceps
body, frequently in the central nervous system.
• Echinococcus granulosus, E. multilocularis, and E. 9. Which Taenia species is capable of causing cysticer-
vogeli found in dogs and E. oligarthrus found in cats cosis?
are capable of causing hydatid disease when eggs a. T. solium
are accidentally ingested by humans.
b. T. saginata
• Dipylidium caninum is a common tapeworm of c. Both A & B
cats and dogs but may infect humans, especially
d. All Taenia species may cause cysticercosis.
children who frequently play with pets.
• Hymenolepis nana, the “dwarf tapeworm,” and H.
diminuta, the “rat tapeworm,” are parasites from
10. Which Taenia species does NOT have hooks on its
rodents that may also cause human infection. rostellum?
• The presence of polar filaments on the oncosphere
a. T. solium
differentiates H. nana from H. diminuta (H. diminuta b. T. saginata
has polar thickenings but no polar filaments). c. Both A & B
d. All Taenia species lack hooks on their rostellum.
11. T. saginata usually has how many primary uterine

REVIEW QUESTIONS branches?
1. Which of the following statements is true? a. 15 to 20
a. Cestodes possess an attachment organ known as b. 35 to 45
the strobila. c. 7 to 13
b. Immature segments do not have fully developed d. 20 to 25
organs and are found near the middle of the
chain. 12. What species of Echinococcus is/are capable of caus-
c. The gravid proglottids are located in the terminal ing hydatid disease in humans?
end of the chain and are usually filled with eggs. a. E. granulosus
d. Cestodes are also known as flatworms. b. E. multilocularis
c. E. vogeli
2. Members of order Pseudophyllidea differ from d. All of the above
those belonging to order Cyclophyllidea in that:
13. Eggs of E. granulosus are similar to the eggs of what
a. They possess a digestive system.
other species of tapeworms?
b. They have four cup-shaped suckers on the scolex.
a. Taenia
c. They have different numbers of segments.
b. Hymenolepis
d. Their eggs are operculated.
c. Diphyllobothrium
d. None of the above
3. D. latus may cause anemia in the host from a defi-
ciency in _______. 14. The commonly used therapy for treatment of hyda-
a. Iron tid cysts is known as:
b. Vitamin B12 a. RACE
c. Niacin b. PASS
d. Vitamin B6 c. PAIR
d. TORCH
4. One distinguishing feature of D. latus is:
a. An armed rostellum 15. Which tapeworm possesses a scolex with a retractile
b. Polar filaments on the oncosphere rostellum and circles of hooks?
c. Rosette-shaped uterus a. D. caninum
d. Radially striated shell b. H. nana
c. M. multiceps Eom KS, et al. Identification of Taenia asiatica in China:

d. D. latus molecular, morphological, and epidemiological analysis
of a Luzhai isolate. J Parasitol. 2002;88:758–764.
16. Which cestode is capable of causing a syndrome of Fan PC, et al. Morphological description of Taenia saginata
hyperinfection? asiatica Taeniidae from man in Asia. J Helminthol.
a. D. latus 1995;69:299–303.
b. T. solium Flisser A, et al. Portrait of human tapeworms. J Parasitol.
c. H. nana 2004;90:914–916.
Fuentes MV, et al. A new case report of human Mesocestoides
d. E. granulosus
infection in the United States. Am J Trop Med Hyg.
17. Eggs H. nana and H. diminuta may be differentiated 2003;68:566–567.
through the presence or absence of: Garcia HH, et al. A trial of antiparasitic treatment to reduce the
rate of seizures due to cerebral cysticercosis. N Engl J Med.
a. Radial striations
2004;350:249–258.
b. Polar filaments
Gil-Grande LA, et al. Randomized controlled trial of efficacy of
c. Operculum albendazole in intra-abdominal hydatid disease. Lancet.
d. Vitelline layer 1993;342:1269–1272.
Gogia S, et al. Neurocysticercosis in children: clinical findings
Match the following parasites and their common and response to albendazole therapy in a randomized
names. double-blind, placebo-controlled trial in newly diagnosed
18. Rat tapeworm a. D. latus cases. Trans R Soc Trop Med Hyg. 2003;97:416–421.
19. Broad fish tapeworm b. T. solium González LM, et al. Differential diagnosis of Taenia saginata
20. Pork tapeworm c. T. saginata and Taenia saginata asiatica taeniasis through PCR. Diag
Microbiol Infect Dis. 2004;49:183–188.
21. Dwarf tapeworm d. H. nana
Holodniy M, et al. Cerebral sparganosis: case report and
22. Beef tapeworm e. H. diminuta
review. Rev Infect Dis. 1991;13:155–159.
Khuroo MS, et al. Percutaneous drainage compared
Answers to review questions are available at the end of this with surgery for hepatic hydatid cysts. N Engl J Med.
book. 1997;337:681–687.
Lamon C, Greer GJ. Human infection with an anoplocephalid
tapeworm of the genus Mathevotaenia. Am J Trop Med
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An YC, et al. Molecular identification of Diphyllobothrium and process. Parasitol Today. 1996;12:486–491.
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subarachnoid cysticerci. Arch Neurol. 1992;49:335–338. Hyg. 1999;61:566–573.
Del Brutto OH, et al. Therapy for neurocysticercosis: a Saidi F. Surgery of hydatid disease. Philadelphia: WB Saunders;
reappraisal. Clin Infect Dis. 1993;17:730–735. 1976.
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Todorov T, et al. Chemotherapy of human cystic echinococcosis: 1993;44:192–194.
Comparative efficacy of mebendazole and albendazole.
Ann Trop Med Parasitol. 1992;86:59–66.
CHAPTER 8
Introduction to Medical Entomology

SHEILA GRACE ALARILLA-MARTIN
Medical Entomology is the scientific study of arthropods • Most important group of arthropods involved
which are involved in disease transmission. These ar- in disease transmission.
thropods represent a wide variety of insects acting both • Parasitic infections: malaria and filariasis.
as a mechanical or biological vector. They may serve as • Genera.
agents of transmission as they carry infective stages of • Anopheles: Plasmodium sp.; Wucheria
the parasites or act as an important intermediate host bancrofti; Brugia malayi
that participate crucially in the life cycle of the parasite. • Aedes: Wucheria bancrofti
This chapter provides an overview of the morphology • Culex: Wucheria bancrofti
of the arthropod and its significant role in the study of • Mansonia: Wucheria bancrofti; Brugia
parasites (Fig. 8.1 and Table 8.1). malayi
ARTHROPODA (Ross, 1982; Garcia, 1988;

Trigo, 2016)
• Largest phylum representing 80% of animal life.
• Consists of segmented invertebrates provided with
chitinous protective covering called exoskeleton and
bilaterally jointed appendages.
• Body divided into head, thorax, and abdomen.
• Medically important arthropods: Class Insecta,
Arachnida, Crustacea.
• Life cycle: Metamorphosis
• AMETABOLOUS: No change during its develop-
mental stages
• Examples: Silverfish, springtails, firebrats
• HEMIMETABOLOUS: Incomplete metamorphosis
• Egg – Nymph – Imago (sexually mature adult)
• Examples: Lice, true bugs (Hemiptera), arach-
nids, cockcroaches
• HOLOMETABOLOUS: Complete metamorphosis
• Egg – Larva – Pupa – Imago
• Examples: Mosquito, fly, beetle, fly, butterfly,
ants
A. Arthropods as biological vectors of parasitic infection FIG. 8.1 Representative examples of Important vectors of
• Mosquito Parasitic infections. A. Rhodnius prolixus, a vector of Chagas’
disease.; B. Glossina morsitans, a vector of African sleeping
• Order Diptera.
sickness.; C. Anopheles quadrimaculatus, female, a vector
• Family Culicidae. of malaria; D. Phlebotomus, a vector of leishmaniasis. (All
• Worldwide distribution with more than 3000 images photograph by Zane Price from material furnished
thousand species reported. by Dr. Ralph A. Barr.)
241
TABLE 8.1
Some important parasitic diseases transmitted by arthropods.
Non-Human
Arthropod Vector or vertebrate
group Disease intermediate host reservoir host Disease distribution
A. Crustacea
Copepods Diphyllobothriasis Cyclops spp. Dog, bear Scandinavia, Canada, Northern
United States, Finland, Russia
Dracunculiasis Cyclops spp. Carnivores Africa, India, Middle East
(dracontiasis) probably
Crabs/ Paragonimiasis Fresh-water crabs, Carnivores Asia, Africa, Philippines, Pacific Islands,
Crayfish crayfish South America
B. Arachnida
Ticks Babesiosis Ixodes spp. Rodents, cattle United States, Mexico, Europe
C. Insecta
Fleas Dipylidiasis Cat and dog fleas Cats, dogs Worldwide
Bugs Chagas’ disease Triatoma, Carnivores, South America, Central America,
(American Panstrongylus rodents, North America
trypanosomiasis) armadillos
Beetles Hymenolepiasis Flour beetle Mice, rats Worldwide
Flies African sleeping Glossina spp. Herbivores Africa
sickness (tse-tse fly)
Leishmaniasis Phlebotomus spp. Dogs and cats in Asia, Mediterranean, East Africa,
Lutzomyia spp. various areas southern Mexico, Central and
(sandfly) South America
Loiasis Chrysops spp. Monkeys Tropical Africa
(Tabanid fly/ deer fly)
Onchocerciasis Simulium spp. None Africa, Mexica, Central and South
(Black fly) America
Gnat Mansonelliasis Culicoides spp. Monkeys Africa, Central and South America,
(biting midges) West Indies
Mosquitoes Malaria Anopheles spp. None Worldwide
Bancroftian Anopheles, Aedes, None Worldwide, tropics and subtropics
Filariasis Culex
Malayan Filariasis Anopheles, Monkeys, Cats India, Malaysia, Philippines, Indonesia
Mansonia (Cat-Mosquito-
Human cycle)
Timoran Filariasis Anopheles None Indonesia
barbirostris
CHAPTER 8 Introduction to Medical Entomology 243
Anopheles Aedes Culex Mansonia
Description: Description: Description: Description:

• Slender bodies with 3 • <10 mm in length with • Common house • Medium-sized mosquito
divisions: head, thorax and distinct white and black mosquito with mottled brownish
abdomen pattern (Asian tiger mosquito) • Main vector of the appearance
• Head: segmented antennae, • Short flight range (less than disease Japanese • Nocturnal biters but may
forward projecting proboscis 200 m) encephalitis but may bite during shady days
two maxillary palps • Single silvery-white line of transmit also filarial • Breeds in bodies of water
• Thorax is specialized for tight scales worm with aquatic vegetation
locomotion • Strongly anthrophilic
• Abdomen is specialized for food • Biphasic biting profile
digestion and egg development
• Fly
Tse-tse fly • Strong, honey brown flies measuring <15 mm in length.
• Voracious blood feeders of the African region.
• Cleaver-shaped wings known as the “hatchet” cell.
• Long life expectancy and fly long distances.
• Genus: Glossina sp.
• Parasitic infections:
• African trypanosomiasis.
• Sleeping sickness.
• Biological Vector of the following hemoflagellates:
• Trypanosoma rhodesiense and Trypanosoma gambiense.
• Carries the infective metacyclic trypomastigote stage and is
transmitted through a bite.
Sand fly • 3× smaller than a tse-tse fly: ∼5 mm in length.
• Nocturnal blood feeders.
• Fly short distances.
• Genus: Phlebotomus and Lutzomyia.
• Parasitic infections: Leishmaniasis:
Leishmania tropica – P. papatasi/P. sergenti
Leishmania braziliensis – Lutzomyia/Psychodopygus
Leishmania donovani – Phlebotomus sp.
• Biological Vector of the following hemoflagellates:
• Leishmania.
• Carries the infective promastigote stage and is transmitted
through a bite.
Deer fly • Medium sized to large dull colored body.
• Enlarged eyes.
• Female is known to be a blood feeder.
• Genus: Chrysops.
• Parasitic infections: Loaiasis (“Calabar or Fugitive”
Swelling).
• Carries the infective L3 larvae and is transmitted through a
bite.
• Vector of Loa loa
Black fly • Small sized (<5 mm).

• Stout body and humped back.
• Female is known to be a blood feeder during daytime.
• Exophagic and fly long distances.
• Genus: Simulium.
• Parasitic infections: Onchocercoma/“Mal Morado”
(onchodermatitis)/“Leopard skin” (spotty depigmentation)/
Sowda (skin blackening)/River Blindness (ocular lesions).
• Carries the infective L3 larvae and is transmitted through a
bite.
• Vector of Onchocerca volvolus which is also transmitted by a
buffalo gnat.
• Bug: Reduviid bug/Cone-nosed bugs/Triatomid/Kissing bugs

Reduviid bug • Order Hemiptera (true bug).
• Also called assassin or kissing bug.
• Mostly are terrestrial.
• Blood sucking ectoparasites.
• Extended head with a unique tapering ‘neck’, long legs,
and prominent, segmented, tubular mouthparts called
proboscisor rostrum.
• Most species are appear brownish reddish or at times black.
• Known biological vector of Trypanosoma cruzi, causative
agent of Chagas’ disease or American trypanosomiasis.
• Bug carries the infective metacyclic trypomastigote from
its excreta and is transmitted through an open skin pore
produced after scratching the site of the bite.
• Tick: Ixodes sp.

Ixodes tick • Responsible for transmission of bacterium Borrelia
burgdorferi.
• Biological vector of Babesia microti, an apicomplexan that
resembles Plasmodium falciparum, and cause Nuntucket
fever.
• Medium in length (3 to 4 mm).
• Striated integument.
• Absence of eyes.
• A scutum is found in female only and a conscutum in the
male.
• Engorged: bulging appearance of the tick after blood meal.
B. Arthropods as mechanical vectors of parasitic infection (Mafham, 2005; Service, 2012)

• Cockcroach
• Order Blattodea.
• Estimated 5000 known species with about 30 nuisance thriving in human habitats.
• Well developed compound eyes.
• Multisegmented long and thin antennae.
• 1 pair of cerci on the terminal end of the abdomen.
CHAPTER 8 Introduction to Medical Entomology 245
• Fly
SUMMARY
• Order Diptera.
• Pair of functional wings (flight purposes). • Medical Entomology is the scientific study
• Pair of specialized hindwings called halteres of arthropods which are involved in disease
(insect balance). transmission.
• Complete metamorphosis. • Insects may participate in the life cycle of parasites.
• Mechanical vectors of Ascaris lumbricoides and • Mosquitoes, flies, and bugs are examples of
protozoans. biological vectors.
• Common house fly: Musca domestica. • However, flies and cockcroaches may act as
mechanical vectors carrying infective stages of the
parasites in their external coverings.
• Parasite control therefore may require integrated
approach including vector control. Breeding habitats
of the vectors may be addressed accordingly to
control their population.
REVIEW QUESTIONS
Multiple choice: choose the best answer.
1. All of the following are vector-transmitted parasitic
infection, except:
a. Filariasis
b. Malaria
c. Babesiosis
d. Toxoplasmosis
2. Which among the following acts as a mechanical 9. Phlebotomus is an example of _____:

vector? a. Deerfly
a. Cockcroach b. Sandfly
b. Tick c. Reduviid bug
c. Mosquito d. Tse-tse fly
d. Bug
10. What stage of Leishmania is carried by a sandfly?
3. Reduviid bug belongs to the order _____: a. Amastigote
a. Diptera b. Promastigote
b. Hemiptera c. Epimastigote
c. Coleoptera d. Trypomastigote
d. Lepidoptera
Matching type:
4. This is an example of a hemoflagellate. A. Vectors of medical importance
a. Ascaris lumbricoides 1. Glossina a. Bug
b. Plasmodium falciparum 2. Lutzomyia b. Deerfly
c. Babesia microti 3. Triatoma c. Tse-tse fly
d. Tryapanosma cruzi 4. Simulium d. Sand fly
5. Chrysops e. Black fly
5. Asian Tiger mosquito is associated with _____:
a. Anopheles B. Vector required for transmission
b. Aedes 1. Chagas’ disease a. Tick
c. Culex 2. Malaria b. Mosquito
d. Mansonia 3. Nuntucket fever c. Fly
4. River blindness d. Cockcroach
6. Which part of a fly is important in balance? 5. Sleeping sickness e. Bug
a. Antennae
b. Halteres Answers to review questions are available at the end of this
c. Tarsus book.
d. Squama
7. Which among the following is important in the REFERENCES

transmission of both Borrelia burgdorferri and Babesia Garcia LS, Bruckner D. Diagnostic medical parasitology.
microti? New York: Elsiever Science Publishing; 1988.
a. Triatoma Mafham KP. Encyclopedia of insects and spiders. An essential
guide to insects and spiders of North America and the
b. Musca domestica
world. Singapore: Thunder Bay Press; 2005.
c. Anopheles minimus flavirostris
Ross H. A textbook of entomology. New York: John Wiley;
d. Ixodes scapularis 1982.
Service MW. Medical Entomology for students. Cambridge:
8. To what parasite is Babesia microti confused to? New York: Cambridge University Press; 2012.
a. Trypanosoma cruzi Trigo V, Centeno N. Entomology and parasitology. New York:
b. Leishmania donovani Intelliz Press; 2016.
c. Plasmodium falciparum
d. Onchocerca volvulus
CHAPTER 9
Pseudoparasites: A Parasite Look Alike

SHEILA GRACE ALARILLA-MARTIN, RMT, MSc
Pseudoparasites are structures that are confused like • Presence of too much muscle fibers in stool is called
parasites. They are otherwise known as artifacts, con- creatorrhea.
taminants or simply confusers. Recognizing them in fe- • Suggestive of maldigestion.
cal samples and other specimens are equally relevant • Maybe confused with tapeworm proglottid.
because they might result in incorrect diagnosis. They
should be clearly distinguished to real parasites through
careful examination of their differences. However, this YEAST CELLS
requires certain diagnostic skills that can be developed • Normally present in the stool.
through several microscopic examinations and practices. • May be confused with cysts of some of the intestinal
(Centers for Disease Control and Prevention., 1997; protozoa.
Richards et al., 1983) • Variable in size and shape, although the majority are
ovoid.
• Budding forms usually aid in diagnostic identification.
OIL DROPLETS • Nuclei of yeast cells are solid, without obvious in-
• May be small and surprisingly uniform in size. ternal structure, and stain blue-black or black with
• Appears round with no internal structures. hematoxylin stains and dark red with trichrome.
• May represent remnants of oil used in oil immer- • It is generally assumed that intestinal yeasts are
sion objectives. harmless, but it must be remembered that Candida
• May suggest amoebic cysts. and, rarely, Blastomyces may occur in the feces.
FAT GLOBULES Blastocystis hominis (FIG. 9.1)

• Appears round with thin circular lining. • Has a spherical form resembling amoebic cysts in
• Absence of internal structures. both size and shape, with internal structure.
• May suggest amoebic cysts. • Stained specimens have a large, central fluid-filled
• Presence of too much fats in stool is termed: steat- vacuole surrounded by a layer of cytoplasm contain-
orrhea. ing the nuclei.
• Common finding in cases of Giardiasis (Giardia duo- • In iodine preparations, the central area does not
denalis (formerly Giardia lamblia)) and other malab- stain but the peripheral layer is light yellowish, and
sorption syndromes: sprue, Crohn’s disease, Cystic the peripheral position of the one or more nuclei is
fibrosis, Whipple’s disease. clearly indicated.
• 4 morphological forms: vacuolated (most common),
AIR BUBBLES amoeboid, granular, multiple fission. (Belizario, 2015)
• Appears round with thickened circular lining. • With permanent stains, the central material may
• Results from improper placement of coverslip. take an intense stain, stain lightly, or not stain at all;
• Represents trapped air in fecal smear. the nuclei stain darkly and may be seen embedded
• Confused with protozoan cyst and a Taenia egg. in the peripheral layer of cytoplasm.
• May exist in irregular forms. • Generally considered a nonpathogenic yeast in the
past, some maintain that this organism has proto-
zoan affinities, although on the basis of rRNA se-
MUSCLE FIBERS quencing (Johnson et al., 1989) its phylogenetic af-
• Appears rectangular in shape with or without stria- finities are less clear.
tions.
247
FIG. 9.1 Various structures that may be seen in stool preparations: 1–4, Blastocystis hominis; 5–8, various
yeasts; 9, 11, squamous cells from rectal mucosa; 10, deteriorated macrophage without nucleus; 12, 13,
polymorphonuclear leukocytes; 14, 15, “pollen grains.”
• It is frequently found in patients with gastrointesti- • Until there is more convincing evidence of pathoge-
nal disorders, but as stool examinations are seldom nicity, we do not consider its presence in the stool
done on asymptomatic patients, any such associa- to be any more significant than that of Iodamoeba or
tion must be regarded with caution. Endolimax.
• Studies by Udkow and Markell (1993) show, in a
blinded examination of the stools of approximately PLANT MATERIALS
180 asymptomatic persons and a similar number of • Pollen grains (Fig. 9.1).
symptomatic patients, essentially the same preva- • May mimic helminth eggs (Taenia sp.).
lence of Blastocystis in both groups. • Pseudo-outbreak of cyclosporiasis was attributed
• Much of the controversy may exist because this is a to pollen grain.
genetically diverse group of organisms, only some of • “Australian bee pollen” as a dietary supplement
which might cause illness (Clark 1997). (Fig. 9.2).
CHAPTER 9 Pseudoparasites: A Parasite Look Alike 249
FIG. 9.2 A, Trichuris egg. B–D, Egg-like objects from stools of persons taking “Australian bee pollen”
dietary supplement.
FIG. 9.3 Plant structures seen in the stool: 1, 2, aggregates of starch granules; 3, plant hair; 4, 6,
amorphous vegetable materials, superficially resembling ova or protozoan cysts; 5, vegetable spiral.
• Vegetable hairs may be confused with larval stage

• Plant or Vegetable cells, hairs, and fibers (Fig. 9.3). of nematodes but will be seen to have a homoge-
• Vegetable remnants may appear as a twisted neous, thick, refractile wall and a minute central
spring-like bodies (vegetable spiral) or assume canal extending the whole length of the structure.
a regularly sculpted surface (vegetable fiber). • Starch granules (Fig. 9.3).
• Plant cells may be recognized by their thick and • May be spherical and, if undigested, can be seen
frequently smooth walls. Some are about the to be composed of concentric layers of white, ho-
same size and shape as certain helminth eggs, mogeneous material.
but they seldom possess the regular shape that • Potato starch frequently occurs in irregular
characterizes the eggs. saclike aggregates of granules.
• Undigested starch stains blue-black when iodine POLYMORPHONUCLEAR LEUKOCYTES

is added to the fecal suspension; partially digest- (FIG. 9.1)
ed starch stains red. • May be mistaken for intestinal amoebae.
• A frequent source of confusion is the presence • When stained, may show a nucleus divided into
in the feces of undigested citrus fruit vesicles, four apparently separate spheres, each with periph-
the small spindle-shaped individual compo- eral chromatin and an apparent karyosome.
nents of sections of oranges or grapefruit. These • Nuclear material is larger in proportion to the
resemble in size and general outline the gravid amount of cytoplasm than in amoebic cysts of com-
female pinworm. Close observation shows that parable size, and the shapes of the nuclei are usually
they do not possess any obvious internal struc- more variable.
ture. • Macrophages may be differentiated from the intesti-
nal amoebae by their possession of numerous inclu-
sions within the dark-staining cytoplasm.
BEAVER BODIES (FIG. 9.4)
• The nucleus does not appear to have a karyosome
• In areas where fresh-water crayfish (crawfish) are
but instead has a fine network of chromatin as well
consumed in quantity (e.g., southern Louisiana;
as larger particles scattered throughout. Degenerate
northern and central Europe, western Russia), a pro-
macrophages that have lost their nuclei may also
tistan parasite of these tasty creatures, Psorospermium
be seen, still containing bits of ingested material.
haeckelii, (Fig. 9.4) may be simultaneously ingested
then passed in the stool.
• Also known as “beaver bodies” or corpora parasitica, MALARIAL PARASITE LOOK-A-ALIKE
they are of a size similar to schistosome ova but have
• Platelets on red blood cells (Fig. 9.5).
no clinical significance other than of recent diet.
• Resemblance to young trophozoites of Plasmodi-
um, but if the slide is correctly stained, their color
EARTHWORM will be altogether different.
• An annelid, with a well-developed circulatory sys- • While a malaria parasite has blue cytoplasm
tem, and the blood vessels. and red chromatin, the platelet stains in varying
• Superficial resemblance to ascarid nematodes but shades of purple. So, think “red and blue” when
are generally reddish brown, whereas ascarids are searching for malaria parasites.
white or pinkish white. • Platelets are rather fuzzy in outline whereas the
• The reproductive openings of the earthworm are malaria parasite will usually be quite sharp.
marked by an annular enlargement of the body, ex- • Howell-Jolly bodies or Cabot’s rings.
tending for several segments, which is not seen in • Do not stain in the same manner as the malaria
nematodes. parasites.
FIG. 9.4 Psorospermium haeckelii, or “beaver body,” a FIG. 9.5 Platelet, sometimes misidentified as a malaria
protistan parasite of crayfish that may be found in human parasite, overlying a red blood cell (arrow) in a Giemsa-
stools following the consumption of this delicacy. It is of no stained thin smear. Note true P. falciparum ring, to the right
clinical significance. and below the platelet-covered red blood cell.
CHAPTER 9 Pseudoparasites: A Parasite Look Alike 251
FIG. 9.6 A. Trophozoite of Entamoeba histolytica stained with Iron hematoxylin. Note Charcot-Leyden
crystals and clumped of red blood cells. (From Hunter GW et.al., Tropical Medicine, ed. 5, Philadelphia, 1976,
WB Saunders); B. Image of Charcot-Leyden crystal with quadrinucleated cyst of Entamoeba hartmanni.
CHARCOT-LEYDEN CRYSTAL (FIG. 9.6)

• Represents disintegrated products of eosinophil. • Platelets and stain debris might be confused with
malarial parasites and therefore requires careful
• Maybe recovered in stool or sputum specimen.
examination.
• Manner of reporting: Presence or Absence.
• Described as diamond-shaped crystal, its presence
may indicate hypersensitivity or allergic reactions
and parasitic infections. REVIEW QUESTIONS
• Differentiating stool marker between bacillary dys- 1. Plant hair seen in stool maybe mistaken as a/an
entery (bacterial) and amoebic dysentery (Entamoe- _____ of a helminth.
ba histolytica). a. Egg
• Observed in the following parasitic infections: b. Cyst
amoebiasis (Entamoeba histolytica), cystoisosporiasis c. Larva
(Cystoisospora belli), parastrongyliasis (Parastrongylus d. Adult
cantonensis), paragonimiasis (Paragonimus westermani).
2. Most clinically significant of all the artifacts
a. Fused platelets
b. Epithelial cells
SUMMARY c. Pollen grains
d. Charcot-Leyden
• Recognition of pseudoparasites is challenging in
clinical laboratory practice but must be addressed
3. Pollen grains maybe confused with _____:
accordingly.
a. Taenia spp. egg
• Charcot-Leyden crystals which represents
b. Ascaris decorticated egg
breakdown products of eosinophil degradation are
significant findings in certain parasitic infections c. Paragonimus operculated egg
such as amoebiasis and paragonimiasis. d. Entamoeba histolytica cyst
• Fecal structures from remnants of vegetables and
ingested proteins are confusers to certain stages of 4. Macrophage: E. histolytica :: ______ : Cryptosporidium
parasites. parvum
• Steatorrhea refers to presence of too much fats a. Plant hair
(> 6 grams/ 24 hours) in stools while creatorrhea b. Yeast
means presence of too much muscle fibers. c. Vegetable spiral
d. Cabot rings
5. Operculated eggs and Charcot-Leyden crystals were c. 1 only

observed in a sputum sample. Which among the d. 2 and 3 only
following is being considered?
a. Cystoisosporiasis 8. All of the following must be recognized carefully
b. Paragonimiasis to prevent misidentification as a malarial parasite,
c. Amoebiasis except:
d. Strongyloidiasis a. Howell-Jolly bodies
b. Clumped platelets
c. Cluster of crystal
6. Charcot-Leyden crystals represent breakdown prod- d. Precipitated Giemsa-stain
ucts of _____:
a. Platelets 9. Which among the following is the most commonly
b. Monocyte encountered form of Blastocystis hominis?
c. Eosinophil a. Multiple fission
d. Lymphocytes b. Granular
c. Amoeboid
d. Vacuolated
7. The following appears like a helminthic larva:
1. Charcot-Leyden crystal 10. Characteristic color reaction of starch granules
2. Vegetable fiber when stained with iodine
3. Plant hair a. Blue-black
4. Fungal element b. Blue-green
a. 3 only c. Blue-violet
b. All except 4 d. Light blue
Items 11-20: Identify (2 points each). Refer to the pointed structure.
Answers to review questions are available at the end of this book.
REFERENCES Johnson AM, et al. Blastocystis hominis: phylogenetic affinities

Belizario Jr, Vicente Y, de Leon WU. Medical parasitology in determined by rRNA sequence comparison. Exp Parasitol.
the Philippines. Diliman, Quezon City: UP Press; 2015. 1989;68:283–288.
Centers for Disease Control and Prevention. Outbreaks of Richards FO, et al. The question of a helminthic cause of
pseudo infection with Cyclospora and Cryptosporidium. Florida preeclampsia. JAMA. 1983;250:2970–2972.
and New York City, 1995. MMWR 1997; 46:354-358. Udkow MP, Markell EK. Blastocystis hominis: prevalence in
Clark CG. Extensive genetic diversity in Blastocystis hominis. symptomatic versus asymptomatic hosts. J Infect Dis.
Molec Bioch Parasitol. 1997;87:79–83. 1993;168:242–244.
CHAPTER 10
Diagnostic Parasitology
NOE RAPHAEL D. TARROSA, RMT
EXAMINATION OF STOOL SPECIMENS Macroscopic examination

Advantages of Physical Examination If the unpreserved specimen is available, its surface
• Allows the identification of any parasites present. should be examined for pinworms and tapeworm pro-
• Readily available in most laboratories. glottids, although both are rarely found in stool and are
• Should precede or accompany serologic examination more likely to be observed from cellulose tape swabs.
(if indicated). The stool should be broken up with applicator sticks to
further check for parasites.
Physical Characteristics of the Specimen
Age
Freshly passed specimens are essential for the detection of tro- Microscopic findings Possible etiology
phic amoebae or flagellates. Examination of a freshly passed Macroscopic parasites Pinworms, tapeworm
stool specimen is impractical or impossible in many in- proglottids, helminths
stances. For this reason, as well as for the convenience of Blood-tinged mucus Trophic amoebae
both the patient and laboratory personnel, most labora- (formed specimens)
tories now rely almost entirely on specimens preserved Bloody mucus (loose/ Amoebic ulcerations in the
immediately after passage in various fixative solutions. liquid specimens) large intestine
The specimens may then be submitted to the laboratory
Bright red blood Bleeding hemorrhoids
for examination at a convenient time. Kits containing
(formed specimens)
these solutions are commercially available or may be pre-
pared by the laboratory for distribution to patients. *Occult blood Other gastrointestinal disorders
The recommended time of examination of a stool (more likely)
Intestinal bleeding due to some
sample after its passage is determined by its consisten-
parasitic organisms
cy. If examination within the time period is impossible,
part of the specimen should be preserved.
• All liquid or soft stools are best examined within a
half hour of the time of passage. Techniques of Stool Examination
• Examination of fully formed stools may be done No single technique of stool examination yields entire-
within 3 or 4 hours after passage. ly satisfactory results, as none of the methods is equally
applicable to the detection of trophic protozoa, cysts,
Consistency and helminth eggs. For this reason, a combination of
• Protozoan trophozoites are usually found in liquid or two or more techniques of examination is desirable.
soft stools. Direct wet film
• Protozoan cysts are usually found in fully formed Utility
specimens. • Detection of trophic forms of amoebae and flagel-
• Helminth eggs may be found in either liquid or lates (with characteristic motility).
formed stools. • Immediate examination of bloody mucus and other
Protozoan cysts are rarely found in liquid stools un- samples recovered during endoscopic examination
less because of administration of a cathartic, in which of the lower intestinal tract.
case both trophic and cystic forms may be present. • Examination of other fresh specimens in which pro-
Helminth eggs are also difficult to detect in liquid tozoal disease is suspected.
stools, which are usually very dilute.
253
Preparation • Trophozoites will not be recognizable after the con-

A. Unstained saline mount. centration procedure.
1. A small portion of feces is mixed with a drop of nor- • Addition of an iodine stain may be helpful after the
mal saline on a clean slide. initial examination.
2. A coverslip is placed on the preparation and is first
examined unstained. Permanent stained slides
3. The preparation is checked thoroughly for trophic Utility
amoebae and flagellates. • Reveals cytologic details essential for accurate iden-
B. Iodine-stained preparation. The stain should not be tification of certain protozoa.
applied until after the specimen has been thoroughly • When used alone, it reveals a significantly higher
examined in the unstained condition. Trophozoites are percentage of E. histolytica and other protozoan para-
rapidly killed and are sometimes unidentifiable after sites than is detected when only direct examination
iodine staining. A modified D’Antoni’s iodine solution is and concentration methods are used.
preferable, but Gram’s iodine or Lugol’s solution gives
satisfactory results. Iodine staining may be done using Preparation (Fig. 10.1)
one of the following methods: 1. A small quantity of feces is transferred to a clean
1. Add a small drop of the reagent to a wet film of fecal slide with an applicator stick.
material before it is covered. 2. The material is streaked out in a thin, uniform
2. Add iodine to the edge of the coverslip so that it film.
gradually diffuses into the saline mount.
• Does not require a separate preparation.
• Stains the fecal material gradually (one may
find areas in which the intensity of stain is
optimal).
3. Stain with iodine a concentrate of stool specimen.
• Reveals any organisms that may be seen with di-
rect examination in larger numbers.
Considerations
• Take small amounts of material from several parts of
the stool specimen.
• The film preparation should not be too thick (i.e.,
just thin enough so that an ordinary newsprint can
easily be read through it).
• Examine the unstained preparation under low pow-
er of the microscope and using a low intensity of
illumination.
Concentration techniques
Utility
• Separation of protozoan cysts and helminth eggs
from the bulk of fecal matter through differences in
specific gravity
Preparation. In sedimentation methods, eggs and cysts

in suspending liquid become concentrated in the bot-
tom of a tube. In flotation techniques, a heavy liquid is
used to the surface of which lighter parasites rise.
Considerations
• The concentrated specimen may be examined di-
rectly for protozoan cysts and helminth eggs. FIG. 10.1 Preparation of fecal film from fresh specimen.
CHAPTER 10 Diagnostic Parasitology 255
use of purged specimens increases the chances of find-

ing parasites and the percentage of positive results
when they are examined immediately after passage.
• A saline purge of Epsom salts or Fleet Phospho-Soda is
recommended.
• Avoid castor and mineral oil, which makes examina-
tion of the specimen almost impossible.
• Parasites in the first bowel movement will probably
be distorted (subsequent movements will be most
likely to contain recognizable parasites).
Substances that Interfere With Stool

Examinations
Urine contamination
Urine contamination may destroy motile parasites and
trophozoites. It may also contain elements (e.g., hyphal
forms in the urine of females) that can be mistaken for
fecal parasites.
Administration of castor oil or mineral oil

Administration of castor oil or mineral oil prior to
specimen collection makes microscopic stool examina-
tion unfeasible. Oil globules interfere with microscopic
examination and identification of parasites.
Intake or administration of other compounds

Administration of barium or intake of bismuth, kaolin,
FIG. 10.2 Preparation of fecal film from polyvinyl alcohol
milk of magnesia, or antacids may interfere with stool
(PVA) - preserved specimen.
examination as these compounds produce crystalline
debris and other artifacts that may conceal parasites or
Considerations alter the appearance of parasitic forms (e.g., trophozo-
• With fresh stool specimens, the film must be placed in ites). Barium must not be administered within a week
fixative immediately to prevent drying. before stool collection.
• With fixed or preserved specimens, permanent slides
may be made after days or even weeks. (Fig. 10.2) Antibiotics and antimalarials
• With hard stools, add a small amount of saline to a Antibiotics that affect the intestinal flora, administered
portion of the stool. within the preceding month, and antimalarials (e.g.,
• With liquid stools, a thin layer of serum or of egg al- chloroquine) decrease the chances of finding protozoa.
bumin may increase adherence to the slide. In addition, antibiotics with side effects of mild diar-
rhea or loose stools may alter the natural consistency of
Number of Specimens to be Examined the specimen and may affect the appearance of charac-
Normally passed stools teristic parasite forms.
• For determining the presence or absence of hel-
minth parasites, one or two examinations may be Enemas
sufficient if concentration methods are used. Introduction of fluid into the lower intestines via the
• For determining the presence of E. histolytica, at least rectum cleanses the lower intestines of stool and may
six examinations are necessary if better than 90% ac- sufficiently lower the parasite burden, decreasing the
curacy is to be obtained (Sawitz and Faust, 1942). likelihood of recovery and identification of parasites.
Enemas may also alter the natural consistency and oth-
Purged specimens er physical characteristics of the stool specimen, as well
Many authorities recommend the routine use of purged as destroy or distort parasitic forms. These may unnec-
stools if one is searching for E. histolytica. The proper essarily complicate stool examination procedures.
Manner of Reporting of Stool Examination Mixed immunofluorescence (MIF) stain

(Cheesbrough, 1987). Preparation of stock solution
1. Report the appearance of the specimen • Combine in a small test tube to make sufficient
• Color: brown, yellowish, black, clay-colored, etc. quantity for 25 to 30 preparations.
• Consistency: formed, semi-formed, liquid, mucoid. Lugol’s solution 0.10 mL
• Report the presence of blood, mucus, pus, mac- Formaldehyde solution 0.125 mL
roscopic parasite forms. Tincture of merthiolate 0.775 mL
2. Saline and iodine mount preparation
• Count the number of each type of parasite seen
in the entire preparation. Considerations. The stock solution should be made
fresh daily, and Lugol’s solution should not be over
Reported Grade Microscopic Count 1 week old. To use the stain, add a small quantity of
Scanty 1–3 per preparation feces to 1 drop of MIF solution and 1 drop of distilled
water, mix thoroughly, and cover with a cover glass.
Few 4–10 per preparation
Moderate 11–20 per preparation
Preservative Solutions
Many 21–40 per preparation MIF stain-preservative solution
Very many >40 per preparation Preparation of stock solution
Distilled water 250 mL
• Report pus cells, red cells, fat globules, and Char-
Tincture of Merthiolate 200 mL
cot-Leyden crystals as many, moderate, or few per Formaldehyde 25 mL
high power field (40× objective). Glycerin 5 mL
Stains for Direct Smears • Store the solution in brown glass bottles.
Modified D’Antoni’s iodine • For use, combine with fresh Lugol’s solution (must
Preparation of stock solution. Store in brown, glass- not be over 1 week old):
stoppered bottles in the dark. The stock solution is 1. Measure 2.35 mL stock MIF solution into a small
ready for use after 4 days and remains good as long as test tube. Stopper with a cork.
an excess of iodine remains in the bottle. 2. Measure 0.15 mL Lugol’s solution into a second
tube. Close with a rubber stopper.
Distilled water 100 mL 3. The two solutions are combined immediately be-
Potassium iodide (KI) 1.0 g fore adding the fecal specimen.
Powdered iodine crystals 1.5 g
Considerations. The amount of fecal material to be

Considerations added to this volume of preservative should be about
• Potassium iodide solution should be saturated 0.25 g. The specimen is broken up in the MIF solution
with iodine, with some excess remaining in the and mixed thoroughly. The preparation may be exam-
bottle. ined immediately or stored in a well-stoppered tube for
• Sufficient quantity for daily use is decanted into a few months.
a brown glass dropping bottle and discarded after After storage, most protozoa and helminth eggs will
1 day. be found in the upper layers of sedimented feces. A
drop of mixed supernatant fluid and feces is withdrawn,
Lugol’s solution
placed on a slide, and covered with a coverslip.
Preparation of stock solution
Distilled water 100 mL PVA fixative solutions
Potassium iodide (KI) 10 g
Utility
Iodine crystals 5g
• For the preservation of material, which can then be
concentrated by the formol–ethyl acetate technique
Gram’s iodine
or made into permanent stained smears.
Preparation of stock solution
• Preserves both trophozoites and cysts of protozoa for at
Lugol’s solution 1 part least a month.
Distilled water 14 parts • Most eggs are recognizable after PVA preservation.
Preparation of stock solution 2. The sediment is used to prepare smears.

A. Original PVA fixative solution 3. Improve adherence to the slide by coating with
• A mixture of polyvinyl alcohol, glycerin, glacial albumin.
acetic acid, and Schaudinn’s solution. 4. After drying, slides may be placed in 70% alcohol.
• Mercuric chloride content poses disposal prob-
lems. Schaudinn’s solution
B. Modified PVA fixative solutions Utility
• Copper or zinc is substituted for the mercury. • A constituent of the original PVA solution (with
• Give less precise preservation of intestinal proto- the same disposal problems) that is also used as a
zoan morphology. fixative and preservative for fresh stool specimens or
1. If PVA solutions are obtained in bulk, dispense in scrapings from the intestinal mucosa.
screw-capped vials in 5-mL quantities. • When used on strictly fresh specimens, it provides
2. To this volume of fixative, about 1 g of formed feces the optimal fixation and preservation of structural
(somewhat more if liquid) may be added. detail.
3. Formed feces must be broken up and mixed thor-
oughly with the preservative solution. Preparation of stock solution. The stock solution
may be kept indefinitely. Immediately before use, 5 mL
Considerations. It is often advisable to include a sec- of glacial acetic acid is added to 100 mL of the stock
ond vial containing 10% formalin to allow for concen- solution.
tration of eggs from another aliquot of feces. If a series
of stool specimens is desired, the patients may preserve
HgCl2, saturated aqueous solution 2 parts
them immediately after passage and bring them all in
95% ethyl alcohol 1 part
at one time for processing.
Considerations
Preparation of slides for staining • Liquid or mucoid stool do not adhere well to
1. Shake the preserved specimen well or mix using ap- the slide without the application of Meyer’s albumin.
plicator sticks. • Specimens preserved in Schaudinn’s solution are not suit-
2. Pour some of the PVA mixture onto blotting paper able for concentration.
and allow excess PVA to be absorbed.
3. Apply the preserved stool to the slide and dry for Meyer’s egg albumin. Meyer’s egg albumin is an ad-
2 hours at 37oC, or overnight at room temperature. hesive prepared from equal parts of fresh egg white and
4. Stain the slides with trichrome. Dry slides may be glycerin, mixed thoroughly.
kept unstained for long periods of time. With Schaudinn-fixed specimens, a thin layer of
albumin is spread on the slide and allowed to dry be-
SAF fixative solution (Yang and Scholten, 1977) fore application of the specimen. With SAF-preserved
Utility. The SAF fixative solution is more fluid than specimens, drop-sized quantities of albumin and of the
PVA. It may be used for the preservation of material, concentrated SAF-preserved specimen may be mixed
which can then be concentrated by the formol–ethyl and spread out on the slide. It is unnecessary to use
acetate technique or made into permanent stained albumin with PVA-preserved specimens.
smears.
Concentration Methods
Preparation of Stock Solution Ritchie concentration method (Fig. 10.3)
Utility. The Ritchie sedimentation method is effective
Sodium acetate 1.5 g
for the recovery of most kinds of protozoan cysts and of
Acetic acid, glacial 2.0 mL
helminth eggs. While this type of concentrate originally
Formaldehyde, 40% 4.0 mL
Distilled water 92.5 mL employed ether, ethyl acetate is now more commonly
substituted. Both works equally well.
Preparation of slides for staining Preparation for examination

1. Strain the preserved specimen through gauze and 1. Emulsify approximately 1 mL of feces in 10 to 12 mL
centrifuge. of normal saline.
Preparation for examination

1. Place 1 to 2 mL of the fecal suspension in a 12-mL
conical centrifuge tube.
2. Add Sheather’s sugar flotation solution until the
tube is three-quarters full.
3. Stir vigorously with an applicator stick.
4. Fill the tube with sugar solution to 1 or 2 cm from
the top.
5. Centrifuge at 500 × g for 10 minutes.
6. Transfer surface material to a microscope slide by
means of a wire loop.
7. Cover with a coverslip and observe with phase-con-
trast microscopy.
Modified Ritchie’s concentration method

Utility. This modification is said to be capable of de-
tecting oocysts of Cryptosporidium at much lower concen-
trations than the original Ritchie procedure or modi-
fied Sheather’s sugar flotation (Weber et al., 1992).
Preparation for examination

1. The sediment produced by the standard Ritchie
concentration method, but centrifuged at 500 × g
for 5 minutes, is resuspended in 5 mL of deionized
FIG. 10.3 Preparation of formol-ether or ethyl acetate
concentrate.
water and layered over 5 mL of saturated NaCl using
a disposable plastic bulb pipette.
2. The mixture is centrifuged at 500 × g for 10 min-
2. Filter through two layers of moist gauze into a cen-
utes, at which point the oocysts are concentrated in
trifuge tube.
a layer just above the NaCl while most fecal debris is
3. Centrifuge at 900 × g for 1 minute; pour off the
at the bottom of the tube.
supernatant and resuspend in fresh saline.
3. The uppermost 3.5 or 4 mL of the top layer is re-
4. Centrifuge again at 900 × g for 1 minute; if the
moved by pipette.
supernatant is still cloudy, repeat.
4. The remainder of that layer plus approximately
5. Add 10 mL of 10% formalin to the sediment; allow
0.5 mL of the underlying saline layer is removed us-
to stand for 5 minutes.
ing the same pipette and resuspended in 13 mL of
6. Add 3 mL of ethyl acetate or ether; shake vigorously
deionized water.
and centrifuge for 1.5 minutes at 900 × g.
5. Centrifugation at 500 × g for 10 minutes yields a
7. Loosen the “plug” between formalin and ethyl ac-
sediment in which the oocysts are concentrated.
etate or ether, decant the supernatant, and examine
6. Slides are stained with Merifluor Cryptosporidium
the sediment.
(Meridian Diagnostics, Cincinnati, Ohio) and
Modified Sheather’s sugar flotation scanned using fluorescence microscopy at 400×
Utility. The sporozoites contained within the rounded oo- magnification.
cysts of Cryptosporidium (4–6 µm in diameter) are well
visualized by this method. Potassium hydroxide (KOH) concentration
method (for Cyclospora) (Berlin et al., 1994)
Preparation of sugar solution 1. Take aliquots from several areas of the specimen.
2. Place 2 mL of specimen in a 15-mL centrifuge tube.
Sucrose 500 g 3. Add 2 mL of 10% KOH; vortex well.
Tap water 320 mL
4. Allow to stand for 5 minutes at room temperature.
Phenol 6.5 g
5. Add 8-10 mL of saline and mix.
1. Boil the sugar solution until clear. 6. Filter through four layers of gauze into a clean cen-
2. Carefully add phenol and stir, using a fume hood. trifuge tube.
3. Cool the solution to room temperature. 7. Centrifuge at 2,000 rpm for 2 minutes.
8. Decant and discard the supernatant. 8. Repeat wash step 7. The supernatant should be
9. Resuspend the sediment in approximately 10 mL of fairly clear, or a third wash may be repeated.
saline. 9. Decant the supernatant and drain tube well onto a pa-
10. Centrifuge at 2,000 rpm for 2 minutes. per towel. Final sediment should be ∼0.5 to 1.0 mL.
11. Decant and discard the supernatant; examine the 10. Make slides for permanent stain smears before pro-
sediment. ceeding.
11. Add 8 mL of 10% neutral buffered formalin to the
Formalin-ether concentration method (FECT) sediment. Mix well with an applicator stick and al-
Utility. Formalin-ether concentration technique is a low the specimen to stand for at least 10 minutes.
widely used sedimentation technique used for the en- 12. Add 3 mL of diethyl ether, stopper well, and shake
hanced recovery of protozoa, helminth larvae, and ova vigorously for 1 minute. Do not vortex.
from various specimens. (Garcia and Bruckner, 1997). 13. After 15 to 30 seconds, carefully open the stopper
with the tube pointing away from the face to avoid
Specimen samples aerosols. Let off pressure and then re-cap the tube.
• Stool preserved in SAF (sodium acetate formalin). 14. Centrifuge at 2,000 rpm for 10 minutes. Four layers
• Preserved duodenal aspirates. should become visible.
• Aspirates from abscesses. • Top layer: ether
• A plug of fecal debris
Reagents • A layer of formalin
• Normal saline (0.85%). • Bottom layer: small amount of sediment
• 10% neutral buffered formalin (pH 7.0). 15. Carefully open the stopper away from the face. Free
• Diethyl ether. the plug of debris by “ringing” the plug with an ap-
Preparation of 10% neutral buffered formalin plicator stick.
16. Decant the supernatant fluid and fecal debris into a
Formaldehyde 1,200 mL discard container.
Na2HPO4 10.7 g 17. Mix the remaining fluid on the side of the tube
NaH2PO4 0.23 g
with the sediment. The final sediment volume
Distilled water 10.8 L
Triton X-100 12 mL should be ∼0.25 to 0.5 mL.
18. Leave the tubes open in the fume hood for 1 hour
1. Titrate pH to 7.0 using concentrated HCl or NaOH. to let residual ether evaporate. Re-cap the tubes un-
2. Mix thoroughly before dispensing. til ready to examine.
Preparation for examination (SAF-fixed samples) Stained Smears

1. Invert the preserved specimen several times to en- Iron hematoxylin (“Short Method” of the
sure uniform resuspension. United States Naval Medical School)
2. Examine the specimen macroscopically for worms, Preparation of stock solution. Exposure to sunlight
tapeworm segments, and any unusual features. and daily shaking hastens the ripening process. When
3. Strain approximately 3 to 4 mL of SAF-fixed stool fully ripened, a drop added to 100 mL of tap water pro-
through a commercial funnel filter into a 15-mL duces a delicate violet color. When unripe, a drop add-
disposable plastic centrifuge tube. It may be neces- ed to tap water produces a reddish or red-purple color.
sary to use more than 3 to 4 mL of diarrheic stool.
4. Wash as much of the specimen as possible through Hematoxylin crystals, certified 10 g
the filter device using normal saline from a wash bot- Ethyl alcohol, 85% 100 mL
tle until the volume in the centrifuge tube is 15 mL.
5. Centrifuge at 2,000 rpm (500 × g) for 10 minutes. 1. Dissolve hematoxylin crystals in the alcohol with
Check the amount of sediment (∼1.0 mL). gentle heating.
• If the sediment is >1.0 mL, remove the excess. 2. Ripen the stock solution for 6 to 8 weeks in a stop-
• If the sediment is <1.0 mL, add more strained pered bottle no more than two-thirds filled.
specimen.
6. Decant the supernatant then add 10 mL of normal
saline. Preparation of working solution
7. Mix the sediment well with an applicator stick and Hematoxylin stock solution 1 part
centrifuge at 2,000 rpm for 10 minutes. Distilled water 19 parts
Staining procedure 5. Stain in Gomori’s trichrome for 8 to 15 minutes.

• With unpreserved stool specimens, fix with freshly 6. Rinse in 90% alcohol with 1% acetic acid for
prepared Schaudinn’s fluid. 1-2 seconds.
• With PVA-fixed specimens, start with step 2. 7. Dip twice in 100% alcohol.
• With SAF-fixed specimens, start with step 4. 8. Dehydrate in second change of 100% alcohol
1. Fix in Schaudinn’s solution with acetic acid for for 30 seconds.
30 minutes. 9. Place in xylol for 1 minute.
2. Dehydrate in 70% alcohol for 15 minutes. 10. Cover with coverslip, using Permount or anoth-
3. Wash in 70% alcohol with iodine added, er mounting medium.
sufficient to give a port wine color, for 3 min-
utes. Modified acid-fast stain (Garcia et al., 1983)
4. Wash in 70% alcohol for 3 minutes. Utility
5. Rinse in tap water. • For staining of Cryptosporidium, Cyclospora, and
6. Mordant in 4% ferric ammonium sulfate for Cystoisospora (coccidia do not stain well with iron
15 minutes. hematoxylin or trichrome).
7. Rinse in tap water. • With a modified Kinyoun’s acid-fast stain, coccidia
8. Stain in hematoxylin working solution for appears pink to red. Yeasts and most other material
10 minutes. stains blue.
9. Rinse in tap water.
10. Decolorize in 0.25% ferric ammonium sulfate Preparation of Kinyoun’s carbolfuchsin
for 12 minutes.
Basic fuchsin 4g
11. Wash in running water for at least 5 minutes.
Phenol, liquefied 8g
12. Dehydrate in 70%, 95%, and two changes of Ethyl alcohol, 95% 20 mL
100% alcohol, each for 5 minutes. Distilled water 100 mL
13. Place in xylol, two changes each for 5 minutes.
14. Mount in Permount, or other mounting medi- 1. Dissolve the basic fuchsin in alcohol.
um, for examination. 2. Add the liquefied phenol, mix well.
3. Add distilled water.
Gomori’s trichrome stain
Preparation of working solution. Allow the mixture Preparation of Loffler’s alkaline methylene blue
to stand for 30 to 60 minutes, then add 100 mL of dis- Methylene blue (90% dye content) 0.3 g
tilled water. Ethyl alcohol, 95% 30 mL
Chromotrope 2R* 0.6 g KOH solution, 0.01% by weight 100 mL
Light green SF* 0.3 g 1. Dissolve the methylene blue in alcohol.
Phosphotungstic acid 0.7 g
2. Add KOH solution.
Acetic acid, glacial 1.0 mL
*Manufactured by National Aniline Division, Allied Chemical and
Dye Corp., New York, NY. Staining procedure
1. Make fecal smears either from the sediment of a cen-
trifuged formalinized specimen or from the unpre-
Staining procedure served stool and allow to air-dry.
• With mercury-containing PVA-fixed specimens, start 2. Place the slide on a staining rack and flood with car-
with step 3 of the procedure. bolfuchsin.
• With non-mercury-containing PVA-fixed or SAF- 3. Gently heat slide to steaming with Bunsen burner.
fixed specimens, start with step 4 of the procedure. Do not boil.
1. Fix in Schaudinn’s solution with acetic acid add- 4. Stain for 5 minutes, adding more carbolfuchsin if
ed for 30 minutes. necessary, without additional heating.
2. Wash in 70% alcohol for 15 minutes. 5. Rinse the slide with tap water.
3. Wash in 70% alcohol, to which sufficient iodine 6. Decolorize with 1% sulfuric acid for about 2 min-
has been added to produce a port wine color, for utes. Do not overdecolorize.
3 minutes. 7. Rinse with tap water. Allow to drain.
4. Wash in 70% alcohol, two changes, each for 8. Flood slide with methylene blue and stain for 1 minute.
1.5 minutes. 9. Rinse with tap water, drain, and air-dry.
Ryan’s trichrome blue stain • Some spores will have a diagonal or horizontal line
(Ryan et al., 1993) across them (polar tube).
Utility • The background appears blue, although bacteria,
• For staining of Microsporidia (microsporidial spores some yeasts, and various sorts of debris may also
are difficult to identify because of their small size). stain red.
• Microsporidial spores are stained pinkish red.
• Examples include Enterocytozoon bieneusi (1µm x Special Procedures for Recovery of
1.8 µm) and Enterocytozoon intestinalis (1.5 µm x 2.5 µm). Helminth Larvae and Eggs
Baermann apparatus
Preparation of trichrome blue stain Utility. Strongyloides larvae do not always concentrate
• Shelf life of the solution is at least 2 years. well with either of the concentration techniques. The
Chromotrope 2R 6.0 g Baermann technique (Fig. 10.4) yields a good concen-
Aniline blue 0.5 g tration of the living larvae of S. stercoralis. The tech-
Phosphotungstic acid 0.25 g nique is used when there is a high index of suspicion
Acetic acid, glacial 3.0 mL and routine stool examinations are negative and for
following the results of therapy.
1. Mix the ingredients above and allow to stand for
30 minutes at room temperature.
Procedure
2. Add 100 mL of distilled water.
1. A glass funnel with a diameter of at least 10 cm is set
3. Adjust pH to 2.5 with 1.0 M HCl.
up in a ring stand, with a short piece of rubber tub-
4. Store in a glass or plastic bottle at room tempera-
ing attached to its stem and a pinchcock closing the
ture, protected from light.
tubing.
2. A wire circle or sieve, of slightly smaller diameter
Preparation of acid-alcohol
than the top of the funnel, is covered with two lay-
Ethyl alcohol 995.5 mL ers of gauze.
Acetic acid, glacial 4.5 mL 3. The funnel is filled with lukewarm water to a level
just covering the gauze, and a specimen of stool is
Specimen preparation. Specimens preserved in forma-
lin or SAF must be concentrated at 500 × g for 10 minutes.
In cases of suspected disseminated Encephalitozoon
infection, Weber et al. (1997) suggest examination of
urine sediment obtained by centrifugation at 1,500 × g.
A 10-µL aliquot of the sediment is spread out over an
area 45 × 25 mm on a glass slide and allowed to air-dry.
Staining procedure
1. Immerse in absolute methyl alcohol for 5 to 10 min-
utes; allow again to air-dry.
2. Stain with trichrome blue for 90 minutes.
3. Rinse in acid-alcohol, not over 10 seconds.
4. Rinse in 95% alcohol by dipping several times (not
more than 10 seconds in total).
5. Place in two changes of 95% alcohol, 5 minutes in
each, then in 100% alcohol for 10 minutes.
6. Place in xylol for 10 minutes, add coverslip, and
mount with Permount or other mounting medium.
7. Examine under oil immersion (1000× magnifica-
tion).
Considerations
• Control positive slides for comparison are an absolute FIG. 10.4 Concentration of Strongyloides larvae by
necessity. Baermann technique.
placed on the gauze, partially in contact with the Considerations

water. • Rhabditiform larvae of Strongyloides exhibit whiplike
4. The apparatus is left to stand at room tempera- movements.
ture for 8 to 12 hours, then a few drops of fluid • Hookworm larvae exhibit snakelike gliding move-
are drawn off through the tubing into a small glass ments.
dish. • Microscopic examination may be necessary for final
5. Examine for larvae under low power of the micro- identification.
scope.
Cellulose tape swab
Filter paper strip procedure Utility
Utility. The Harada-Mori technique (Harada and Mori, • For recovery of Enterobius and Taenia eggs.
1955) requires minimal equipment and is used for the
recovery of Strongyloides and Trichostrongylus larvae. This Procedure
method takes too long to be clinically useful but is well- 1. Fold together sticky surfaces of a piece of cellulose
adapted for field or survey. tape, 1 × 8 cm, for about 1 cm at each end.
2. Stretch the tape, sticky side out, over the butt end of
Procedure a test tube or a wooden tongue blade, holding the
1. Place 0.5 to 1.0 g of feces at the center of a 20- × 13- nonsticky ends firmly with the thumb and forefinger.
mm filter paper strip. 3. Apply the tape to the anal area, rocking back and
2. Insert the filter paper strip into a 15-mL centrifuge forth to cover as much of the mucosa and mucocu-
tube containing 3 to 4 mL of distilled water. taneous area as possible.
3. Place the tube upright or in a slightly slanted posi- 4. Remove the tape and apply to a microscope slide,
tion so as to keep the filter paper moist by capillary sticky side down. Press firmly into position.
flow. Water may be added to maintain the original 5. Examine for eggs under low power magnification.
fluid level. Considerations
4. After 10 days, withdraw a small amount of fluid Pinworm eggs are generally deposited at night, scattered
from the bottom of the tube and examine for larvae. around the perianal region. The tape should be used in the
morning, before the patient washes or defecates.
Agar plate method Clear cellulose tapes must be used. Those with a
Utility. Described by Koga et al. (1991), it is more sen- frosted appearance obscures the eggs. If a frosted tape is
sitive for the recovery of Strongyloides larvae than either used, a few drops of xylene or toluene must be intro-
the Baermann or filter paper strip methods. duced under the edge to clear the tape.
Procedure Schistosomal hatching test

1. Agar medium (1.5% agar, 0.5% meat extract, 1.0% Procedure
peptone, and 0.5% NaCl) is autoclaved and dis- 1. A stool specimen is homogenized by shaking in nor-
pensed in sterilized dishes. The authors use 8.5– mal saline and is then strained through two layers of
9.0 mL of agar in a 9 × 2.5-cm plastic dish. gauze.
2. Plates are dried at room temperature for 4 to 5 days 2. The material is allowed to sediment, the supernatant
to eliminate excess moisture and then stored in is decanted, and the sediment is resuspended in sa-
sealed plastic bags. line. Repeat the process at least twice.
3. Approximately 2 g of fresh or refrigerated stool spec- 3. The saline is decanted and replaced with distilled
imen is placed in the center of the plate. water, and the suspension is placed in a side-arm
4. The plate is sealed with adhesive tape to prevent es- (Fig. 10.5) or Erlenmeyer flask. The side-arm flask is
cape of the infectious larvae and incubated at room covered with black paper, aluminum foil, or black
temperature (26°C–33°C) for 48 hours. paint, except for the side arm. If an Erlenmeyer flask
5. Plates are examined macroscopically for the pres- is used, it is covered to 1 cm below the level of fluid
ence of larval tracks or larvae. in the neck of the flask. Additional water is added if
6. If negative, they are reexamined under the micro- necessary.
scope at low magnification using a green filter. 4. The flask is allowed to stand at room temperature
7. If still negative, plates are washed with 10% forma- for several hours in subdued light.
lin, which is collected, and its sediment is examined 5. The side arm, or water in the neck of the flask, is
under high dry magnification. then illuminated strongly from the side.
FIG. 10.5 Side-arm flask used in hatching of miracidia.
6. The illuminated area is examined with a magnifying

glass to detect the presence of free-swimming mira-
cidia.
FIG. 10.6 Enteric capsule used for sampling duodenal
Considerations. Eggs hatch within a few hours, re- parasites.
leasing miracidia, if feces containing viable schisto-
some eggs are diluted with approximately 10 volumes 2. The free end of the line is taped to the patient’s neck
of water. Eggs of Schistosoma haematobium in the urine or cheek, and after 4 hours may be pulled up (the
may also be hatched with this technique, although they weight becomes disengaged in the intestine at the
are more easily concentrated by centrifugation or mem- time the thread is withdrawn).
brane filtration. The miracidia are positively photo- 3. The bile-stained mucus adhering to its distal end is
trophic. examined under the microscope.
Duodenal sampling and biopsy Culture Methods for Stool
Utility Limitations
• For the recovery of Strongyloides larvae, the eggs of Culture methods should never be used as a substitute
Clonorchis, Opisthorchis, and Fasciola, and other para- for routine and thorough microscopic examination.
sites of the small intestine (e.g., Giardia, Cystoisos- They must only be performed in laboratories where the
pora, and Cryptosporidium). number of specimens examined is sufficiently large to
• Biopsy of the small intestinal mucosa may reveal justify a considerable portion of time being spent on
Giardia, Cryptosporidium, Cystoisospora, and micro- their maintenance and examination.
sporidia, as well as Strongyloides larvae. • None of the culture media can be used to differenti-
• Specimens may be obtained by intubation or by use ate between the pathogenic E. histolytica and harm-
of the enteric capsule or string test (Enterotest). less E. dispar.
• The success with which E. histolytica is cultivated
Procedure (Enterotest)
depends largely on familiarity with the techniques
1. A number 00 gelatin capsule (Fig. 10.6) containing a
involved (i.e., sporadic use of culture techniques is
90-cm line (for children) or a 140-cm line (for adults)
not recommended).
composed of a 20-cm silicon rubber-covered thread
and a 70-cm or 120-cm soft nylon yarn is swallowed Diamond’s medium
by the patient while the thread, which protrudes from Diamond’s medium may be obtained as TYI-S-33 medi-
a hole in the capsule, is held firmly. To the end of the um, freeze-dried for reconstitution, from the American
nylon yarn is attached a 1-g weight, which eventually Type Culture Collection (ATCC). It is an axenic medium
helps carry the string into the duodenum. since antibiotics are added.
Utility Preparation of locke-egg-serum (LES) medium

• For axenic culture of Entamoeba and Trichomonas. 1. Wash four eggs, brush with alcohol to sterilize, and
break into a sterile flask containing glass beads.
Preparation of culture medium 2. Add 50 mL of Locke’s solution; shake until homoge-
TYI-S-33 broth base w/ 10% bovine serum 1 bottle
neous.
Distilled water 55 mL 3. Dispense in test tubes with sufficient quantity to pro-
duce a 2.5- to 3.5-cm slant in the bottom of the tube.
1. Dispense 13 mL of the medium per tube into
4. Slant plugged tubes and place in inspissator at 70°C
16 × 125-mm screw-capped culture tubes.
until slants are solidified. If an inspissator is not
2. Stored at ambient temperature (∼25oC) for up to
available, a substitute may be devised by leaving the
90 days. Recommended storage temperature is at
door of the autoclave partly open.
2oC to 8oC for longest shelf life.
5. When slants have solidified, autoclave at 15 pounds
• Some strains of E. hisolytica require 15% bovine
pressure for 20 minutes. Discard any badly broken
serum, necessitating addition of an extra 5% by
slants.
volume of bovine calf serum (inactivated at 56oC
6. Cover slants to a depth of about 1 cm with mixture
for 30 minutes prior to use).
of 8-parts sterile Locke’s solution to 1-part sterile
inactivated human blood serum. Sterility or mix-
Inoculation procedure
ture of Locke’s solution and serum should be en-
1. Add 100 units of penicillin and 100 µg of streptomycin
sured by filtration sterilization followed by incuba-
per mL of medium before inoculation. Gentamicin,
tion at 37°C for 24 hours or longer before use.
50 µg/mL, may substitute for penicillin and strep-
tomycin.
Inoculation procedure
2. Inoculate with vaginal or prostatic exudate, or a por-
1. Add a loopful of sterile rice starch or powder to each
tion of stool the size of a small pea.
tube prior to inoculation.
3. Incubate at 37oC and examine after 2, 3, or 4 days’
2. Inoculate with a portion of stool the size of a small
incubation by removing a small amount of sedi-
pea; break up well in the medium.
ment with a pipette.
3. Incubate at 37oC and examine as noted for Dia-
4. Transfer the sediment to a slide, cover, and examine
mond’s medium.
under lower power of microscope.
Modified thioglycolate medium
Considerations. Primary isolation may yield a few
Utility. This modification of the fluid thioglycolate me-
organisms, but subsequent transfers show a consid-
dium produced by Difco Laboratories (Detroit, Michi-
erable increase in numbers. Use of antibiotics for
gan) can be produced at a lower cost (Poch et al., 1996)
successive transfers is unnecessary after primary iso-
and is equally effective as Diamond’s medium for the
lation.
cultivation of Trichomonas vaginalis.
Boeck and Drbohlav’s locke-egg-serum (LES)
medium Preparation of modified thioglycolate medium
The LES is a solid medium with a liquid overlay that 1. Add 7.0 g of yeast extract to approximately 1 liter of
can be prepared in the laboratory. It is not an axenic me- Difco thioglycolate medium.
dium since antibiotics are not added. 2. Autoclave the solution and add the following ingre-
dients antiseptically:
Utility
• For recovery of amoebae. Horse serum 120 mL
Amphotericin B 2 mg
Preparation of Boeck and Drbohlav’s solution Penicillin G 1,000,000 U
Gentamicin 80 mg
NaCl 9.0 g
CaCl2 0.2 g
KCl 0.4 g 3. Dispense the fluid medium in 10-mL quantities in
NaHCO3 0.2 g screw-capped tubes stored at 4oC.
Glucose 2.5 g
Distilled water 1.0 L Inoculation procedure
• The solution must be autoclaved before storage. 1. Inoculate the tubes with vaginal or prostatic exudate.
2. Incubate at 35oC and examine 10 µL aliquots from of 100 mL pure glycerin, 100 mL water and, option-
the bottom of the tube daily for up to 7 days. ally, 1 mL of 3% malachite green.
2. Transfer feces to a clean slide and cover with a pre-
Methods for Estimation of Worm Burden soaked cellophane coverslip.
Utility 3. Invert the slide and press against an absorbent sur-
• Estimation of the total number of eggs in a 24-hour face until the fecal mass covers an area 20 to 25 mm.
stool specimen makes it possible to calculate the ap- in diameter.
proximate number of adult worms present. 4. Leave the preparation for 1 hour at room tempera-
• The results of therapy may be followed in a some- ture to allow clearing of the fecal material (but not
what quantitative manner by making periodic egg of the eggs.). Examine promptly afterwards.
counts as a basis for comparison of the efficacy of
Considerations
various medications.
• Samples taken from various portions of the speci-
men do not differ greatly in egg content.
Chinese liver fluke (female) ∼2,400 eggs/24 hours • To obtain 10-, 20-, or 50-mg samples, metal tem-
Ascaris (female) ∼200,000 eggs/24 hours plates containing calibrated holes are used.
Ascaris (1 pair) 1,000-2,000 eggs/g of 24- • For eggs of Schistosoma mansoni, a longer period of
hour stool clearing (i.e., 24 hours) is needed.
Necator (female) 12–44 eggs/g of 24-hour stool • Kato-Katz technique is a quantitative technique
<2,100 eggs/g (subclinical
used to establish burden of infection by calculat-
infection)
ing eggs per gram stool (EPG). Screened amount of
Ancylostoma (female) 2× the egg-laying capacity of
Necator stool is placed in a standard template situated on
Trichuris (female) ∼14,000 eggs/24 hours top of a glass slide prior to the placement of a green
Egg-laying capacity varies cellophane pre-soaked in 50% glycerol. Clearing is
inversely with the total necessary to heighten the appearance of the eggs.
number of worms present
Special Methods for Intestinal Helminths
Cestodes
Stoll’s egg-counting technique • Gravid proglottids of Dibothriocephalus latus (formerly
Procedure Diphyllobothrium latum) can usually be identified by
1. Save an entire 24-hour stool specimen and deter- the presence of a uterine rosette in the middle of each
mine its weight in grams. segment, which are absent in Taenia spp.
2. Weigh out accurately 4 g of feces. • To differentiate between the two species of Taenia:
3. Place the feces in a calibrated bottle or a large test 1. Rinse the proglottid segments in tap water.
tube. Add sufficient N/10 NaOH to bring the vol- 2. Place segments between two microscope slides
ume to 60 mL. that are separated at the edges by thin pieces of
4. Add a few glass beads and shake vigorously to make cardboard (preparation may be fastened by means
a uniform suspension. If the specimen is hard, the of rubber bands at each end of the slides so that
mixture may be placed in a refrigerator overnight be- the segments can become somewhat flattened).
fore shaking to aid in its comminution. 3. Visualize uterine branches clearly under low
5. With a pipette, remove immediately 0.15 mL of the power of a dissecting microscope.
suspension and drain onto a slide.
6. Do not use a coverslip; place the slide on the me- India Ink Preparation
chanical stage and count all the eggs on the slide. • Facilitates species identification on the basis of the
7. Multiply the egg count by 100 to obtain the num- uterine structure of gravid segments.
ber of eggs per gram of feces and by the weight of • Works best with fresh specimens but may also be
the specimen to get the total number of eggs per 24- successful with formalin-fixed segments if they are
hour specimen. first cleared by immersion in glycerin, after transfer
to 70% alcohol.
Kato’s thick-smear technique 1. A small amount of ink is drawn into a 1-mL tu-
Procedure berculin syringe.
1. Presoak wettable, medium-thickness cellophane 2. A No. 26 hypodermic needle is inserted into the
coverslips (22 × 30 mm) for 24 hours in a solution distal end of the proglottid or central uterine stem.
3. A small amount of ink is slowly injected. New diagnostic techniques

4. The branches of the uterus become black and can Serologic testing in conjunction with stool ex-
be easily counted. amination. Serologic tests were introduced to identify
many intestinal protozoa and helminths with increased
Small nematodes sensitivity but generally have the disadvantage of speci-
Clearing with glycerin ficity—that is, they indicate exposure to one particular
• Fix nematodes by immersing in 70% alcohol heated parasite but nothing about other organisms that may
to 75oC. be present or when the exposure occurred. There are
• If fixed in formalin, transfer to a mixture of equal specific situations in which serologic testing for intesti-
parts formalin and 70% alcohol, and after 3 hours nal parasites may be necessary on a regular basis.
to the first of two changes of 70% alcohol (each for • Precise diagnosis in the presence of organisms of
at least 3 hours). the E. histolytica/dispar complex (unless trophozoites
1. Transfer the specimens from 70% alcohol to a containing ingested red blood cells are found).
relatively large volume of 10% glycerin in 70% • In some areas where Giardia is the most common
alcohol, in a shallow dish. intestinal protozoan causing diarrheal disease
2. Leave uncovered in a dust-free location and allow • For initial testing, when Cryptosporidium is suspected
the alcohol to evaporate for several days. on epidemiologic grounds.
3. The specimens may be mounted on a slide in
glycerin and covered with a coverslip for exami- Stool antigen detection tests. Robust FDA-ap-
nation. proved stool antigen detection tests are available for
Cryptosporidium parvum, Giardia lamblia, and Entamoeba
Mounting in glycerin jelly histolytica. Where laboratory technology and finances
• For permanent preparations of glycerin-cleared permit, these tests should be used in place of stool mi-
small nematodes and helminth eggs. croscopy because of their superior performance (Chen
1. Transfer the specimen from glycerin onto a clean et al., 2002; Haque et al., 2003; Davis et al., 2001;
glass slide. Goodgame, 1996).
2. Cover the specimen with 2 to 3 drops of melted
glycerin jelly and then with a small round cover- DNA testing. Even greater sensitivity and specific-
slip. ity are achievable by real-time PCR amplification and
3. When the jelly has hardened, a few drops of Per- detection of parasite DNA in stool. As this technology
mount or similar mounting medium is placed on evolves and becomes less technically demanding and
top of the round coverslip, and a larger square cheaper, it will have a major if not dominant role in
coverslip is used to cover the entire preparation reference laboratories and eventually community labs
(sealed on all sides by glass or the mounting me- (Verweij et al., 2004; Ward et al., 2002).
dium).
EXAMINATION OF BLOOD AND
Preparation of glycerin jelly CEREBROSPINAL FLUID (CSF)
Gelatin, unflavored (Knox or other) 8g Fresh Blood
Distilled water 52 mL Utility
Glycerin 50 mL • For identification of trypanosomes and microfilari-
Egg albumin (fresh) 5 mL
ae via their characteristic motility.
Phenol crystals 0.1 g
• For specific identification of the organisms, a per-
1. Soak the gelatin in water for an hour. manent stain is essential.
2. Dissolve the gelatin with application of gentle
heat. Procedure
3. Add glycerin and egg white; stir until thoroughly 1. Place a small drop of blood on a slide and cover
mixed. with a cover glass to prevent clotting.
4. Heat to 75oC for 30 minutes. 2. A sufficiently thin preparation is required so that the
5. Filter through several layers of fine flannel, using a relatively small protozoan parasites are not masked
funnel with a hot water jacket if available. by several layers of red blood cells.
6. Add phenol crystals to the filtrate. 3. If the preparation is too thick, dilute with normal
7. Store in a tightly stoppered wide-mouthed bottle. saline.
Considerations
• For detection of trypanosomes, use high-dry objec-
tive with reduced illumination.
• For detection of microfilariae, use the lower power
of the microscope (LPO).
• Whiplike motions of microfilariae and rapid undu-
lating and twisting movements of trypanosomes are
usually seen before the precise shape of the organ-
ism is apparent.
Permanent Preparations
Considerations
Take the appropriate precautions to prevent infec-
tion. Cleanse the skin with alcohol before an incision
is made to remove all fatty substances. The incision
should be sufficiently deep so that blood flows freely.
It is preferable to use peripheral blood from the fin-
gertip or earlobe. With venous blood, a small amount
of heparin or other anticoagulant must be added (prep-
arations will usually show some distortion). Blood
“milked” from a finger is mixed with tissue fluids, dilut-
ing the parasites and making detection more difficult.
Prepare films as quickly as possible to prevent clotting.
All glassware must be free of dust and oil. New slides
should be used for the preparation of permanent
stains. Both slides and cover glasses must be washed
in alcohol and dried with a clean towel before a blood FIG. 10.7 Preparation of a thin blood film.
film is prepared.
Thin blood films blood touches the spreader and begins to run out
Utility toward the edges.
• The gold standard for detection of malarial infection. 6. Before the blood reaches the edge of the spreader,
• For the specific identification of malarial parasites, move the finger that supports it forward in an even,
trypanosomes, and microfilariae. quick motion, so that the drop is drawn out into a
• Preserves the structure of parasites with minimum thin film.
distortion. 7. Air-dry the film and stain.
Procedure (Fig. 10.7-A)

1. Place a small drop of blood near one end of a micro- Considerations. A thin film should consist of one
scope slide. layer of evenly distributed blood cells. Ideally, the
2. Raise the end of the slide farthest from the drop of film should not reach the edges of the slide, and it
blood by placing the end of the slide on your finger, should taper off into a “comet tail” toward the end of
as your hand rests on a table or other steady surface. the slide. Being intracellular parasites, piling up of red
3. With a second slide as a spreader, rest one end against blood cells makes specific identification of malarial
the first slide and one end on the middle finger of the parasites based on their morphologic characteristics
hand that is not supporting the first slide. more difficult.
4. Hold your hand so that the second slide makes an
angle of approximately 30o with the first. Do not Stains. Dry the slides in a vertical position after re-
grasp either slide but allow gravity to hold the two moval from either fixative or stain. After staining, the
in contact. films may be examined under oil immersion of the
5. Draw back the supporting finger to move the slide microscope. Immersion oil may be placed directly on
back toward the drop of blood until the drop of the uncovered blood film and, when no longer needed,
carefully removed with xylene and lens paper. With use portion is fixed for 1 minute in methyl alcohol and
of magnifications lower than oil immersion, a cover then dried before staining). When using Giemsa stain,
glass should be placed over the film. omit fixation in methyl alcohol.
Slides prepared for a permanent collection should Field’s stain is very rapid and gives satisfactory re-
always have the protection of a cover glass. A mounting sults. It has been used extensively for survey purposes
medium such as Permount should be used. To protect and when large numbers of slides must be prepared but
from fading, add an antioxidant such as butylated hy- it is not recommended for routine use.
droxytoluene (1% by volume).
A. Wright’s stain Microscopic examination for malaria parasites
• Incorporates methyl alcohol as its fixative in the Utility. Identification of species and stages of malarial
staining solution. parasites as well as the parasite load is invaluable in the
• Gives fair results and requires a short staining time clinical management of malaria patients. Accurate lab-
but is not recommended for parasitologic use. oratory data must also be obtained for epidemiological
B. Giemsa’s stain surveys, control programs, and drug efficacy trials.
• Does not contain a fixative, but gives more precise
detail. Malaria identification (WHO, 2016)
• Thin films must be fixed in absolute methyl alcohol A. Thick film examination
and air-dried prior to staining. 1. Place the Giemsa-stained blood film on the micro-
• Microfilariae stained with Giemsa will not show as scope stage under the 10× objective lens.
clear internal detail as those stained with hematoxy- 2. Adjust the light source optimally and adjust the fo-
lin, although it is usually sufficient for identifica- cus for optimal image clarity.
tion. 3. Select a well-stained portion of the blood film with
evenly distributed white blood cells.
Thick blood films (Fig. 10.7-B) 4. Place a small drop of immersion oil on the thick
Utility film and switch the 100× oil immersion objective
• For identification of malarial parasites, trypano- over the selected portion of the film.
somes, and microfilariae. 5. Use the fine focus adjustment for optimal image
• Increased quantity of parasites seen in each field due to a clarity.
thicker layer of blood. 6. Assess the blood film if it is acceptable for routine
examination
Procedure • Satisfactory film thickness: 15 to 20 white blood cells
1. Place three drops of blood, each about the size of per thick film field
that used in the thin film, close together near one • Films with less white blood cells per field will re-
end of the slide. quire more extensive examination.
2. With one corner of another absolutely clean slide, 7. Examine the slide for malarial parasites in a system-
stir the blood, mingling the three drops over an area atic manner.
2 cm. in diameter. • Begin at the top left of the film, at the periphery
3. Continue stirring for at least 30 seconds to prevent of the field.
formation of fibrin strands, which may obscure the • Move horizontally to the right, field by field,
parasites. while examining each field for malarial parasites.
4. Air-dry normally, or in very humid conditions, in • Upon reaching the other end of the film, move
a 37oC incubator. Do not heat as this will fix the the slide slightly downwards.
blood. • Move horizontally to the left, field by field, while
5. After the films are thoroughly dried, it must be laked examining each field for malarial parasites.
(to removed hemoglobin) by immersion in buffer 8. Continuously focus and refocus with the fine ad-
solution prior to staining, or in the Giemsa stain it- justment throughout the examination of each field.
self. Thick films that cannot be stained immediately 9. Read a minimum of 100 oil immersion fields before re-
should be laked in buffer solution before storage. porting that no malaria parasites were seen. If pos-
sible, the whole thick film should be examined.
Considerations. Increased distortion of parasites may 10. If parasites are found, an additional 100 fields must
be seen. Thick and thin films may be made on the same be examined before species identification to ensure
slide and stained simultaneously with Giemsa (the thin that a mixed infection is not overlooked.
B. Thin film examination • Record the actual number of parasites and white
1. Place a drop of oil on the feathery edge of the thin cells counted on a separate worksheet.
blood film. B. Thin film count
2. Move from the 10× objective lens to the 100× oil 1. Place the glass slide on the microscope, add a drop of
immersion lens. immersion oil, and focus with the 100× objective.
3. Examine the feathery end or edge of the thin film 2. Start the examination at the top section of the smear,
where red cells lay side by side with minimal overlap. on a typical field with about 250 red cells in total.
4. Examine the slide for malarial parasites in a system- 3. Begin counting the red cells and the number of para-
atic manner. sitized red cells.
• Move along the edge of the film. • Count all parasitized and other red cells in each
• Move the slide outwards by one field. field, even if the total count per field exceeds 250.
• Move the slide inwards by one field, returning in • Count parasitized and non-parasitized red cells
a lateral movement. separately.
• Repeat and continue examination until the pres- • In mixed infections all parasitized red cells are
ence and species of malaria parasites have been counted together.
confirmed. 4. After counting all the parasites and red blood cells
in one field, move to the next field following the
Malaria parasite counting (WHO, 2016). Parasite previous patterns of examination and continue
counts are performed for asexual stages of P. falciparum, counting. Be careful not to overlap fields.
P. vivax, P. malariae, and P. ovale. Gametocytes are not 5. Stop counting when ∼20 fields with ∼250 red cells
usually counted, unless indicated by individual proto- (∼5,000 red cells in total) have been counted.
cols, but their presence is always reported. All identi- • Record the actual numbers of parasitized and
fied parasite species should be reported, even if they are other red cells counted on a separate worksheet.
counted together.
Most parasite counts are performed on thick blood films in Recording and reporting of malaria microscopy
which malaria parasites are initially detected to be present. results (WHO, 2016)
If a thick film is not available or is damaged, a thin film • If no malarial parasites are seen, report as “No ma-
count may be performed. A thin film count may be per- laria parasites seen”, rather than “Negative”.
formed when a thick film is not available or damaged or • Report all malaria species and stages observed dur-
when there are >100 parasites in each oil immersion field ing microscopic examination of blood films.
of the thick film (corresponding to >80,000 parasites/µL). • Calculate the parasite density from the thick (or thin
A. Thick film count film), if performed.
1. Place the glass slide on the microscope, add a drop of • Report the presence of gametocytes and schizonts, if
immersion oil, and focus with the 100× objective. any.
2. Start the examination at the top left of the smear, on A. Thick film count
a field with a good number of white blood cells and • Use an estimated white cell count of 8,000/µL if the
parasites observed together. patient’s actual white cell count is unavailable. Oth-
3. Begin counting the parasites and white cells simulta- erwise, use the patient’s actual white cell count in
neously. computing for parasite density.
4. After counting all the parasites and white cells in
one field, move to the next field following the previ- Parasites/µL blood
ous patterns of examination and continue counting. Number of asexual parasites counted × 8,000 white cells/µL
=
Be careful not to overlap fields. Number of white cells counted
5. Stop counting when any of the following criteria are met:
• ≥100 parasites in 200 white blood cells have
been counted.
• ≤99 parasites in 500 white cells have been count-
ed.
6. Record the results and report as the number of para-
sites per 200 or 500 white cells, respectively.
• Count all parasites and white cells in the final
field, even if white cell count exceeds 200 or 500.
• Other filters of similar pore size are not as satisfac-

tory as the Nucleopore.
1. Blood is collected in tubes containing 3.8% sodi-
um citrate (20% by volume of blood specimen).
2. A Nucleopore filter of 5 µm pore size is placed
in a Swinney adapter; a 20- to 50-mL disposable
plastic syringe is attached to the adapter.
3. Several milliliters of normal saline are added to
the upright barrel.
• In mixed infections or infections by more than one 4. About 2 to 4 mL of the blood specimen is added
species, count all the species together (sexual and to the saline, and the mixture of blood and saline
asexual stages), and express the results as below. is forced through the filter.
5. Following several washes of small amounts of sa-
line or distilled water, the filter may be removed
from the adapter, placed on a microscope slide,
and examined for living microfilariae; it can also be
dried, fixed, and stained as for a thin blood film.
Gradient centrifugation technique

(Jones et al., 1975)
1. Thirty mL of 50% Hypaque is mixed with 14 mL of
distilled water; 1 part of this mixture is added to 2.4
B. Thin film count parts of 9% Ficoll.
• Use an estimated red cell count of 5,000,000/µL 2. Four mL of the Ficoll-Hypaque mixture is placed in
if the patient’s actual red cell count is unavailable. a 17- × 100-mm plastic centrifuge tube and overlaid
Otherwise, use the patient’s actual red cell count in with 4 mL of heparinized venous blood.
computing for parasite density. 3. The tube is centrifuged at 500 × g for 40 minutes.
4. Microfilariae will be found in the middle Ficoll-
Hypaque layer, which separates the overlying plas-
Parasites/µL blood
ma and white blood cell layers from the underlying
Number of parasitized red cells × 5,000,000 red cells/µL
= red blood cells.
20 fields × 250 red cells
Buffy coat films

Blood Concentration Procedures Utility
Modified Knott’s concentration • For detection of Leishmania donovani if present in the
• Hemolyzes the red blood cells and concentrates leu- circulation
kocytes and microfilariae. • Microfilariae and trypanosomes may be found in
1. Obtain 1 mL of blood by venipuncture and de- the buffy coat.
liver it directly into a centrifuge tube containing • Reveals Histoplasma capsulatum, a fungus, differenti-
10 mL of 2% formalin. Mix thoroughly. ated from L. donovani by details of internal structure
2. Centrifuge at 500 × g for 1 minute.
3. Decant the supernatant and spread the sediment Procedure
out to approximately the thickness of thick films 1. Obtain 5 mL of blood and deliver into a tube con-
on a slide or slides. Dry thoroughly. taining oxalate crystals (prepared as for the Win-
4. Stain with Giemsa’s stain. trobe hematocrit method).
2. Transfer blood with a capillary pipette into a Win-
Membrane filtration method (Dennis and trobe tube. Cap to prevent evaporation, and centri-
Kean, 1971) fuge for 30 minutes at 2000 × g.
• For detection of microfilariae present in blood in 3. With a fine capillary pipette, withdraw the layer of
small numbers cells of the buffy coat, situated between the packed
• Unsatisfactory for the isolation of Mansonella per- red blood cells and the overlying plasma.
stans microfilariae because of their small size 4. Spread out as thin film, dry, and stain with Giemsa’s
stain.
Acridine orange staining 5. Examine the sediment as a wet film or make a

Microhematocrit tubes were originally modified for thin film and stain with Giemsa’s stain.
quantitative buffy coat (QBC) analysis by the addi-
tion of plastic floats that, when inserted into the tubes, Examination of Cerebrospinal Fluid
leave a layer approximately 40 µm thick, in which the Utility
granulocyte, eosinophil, and lymphocyte layers may • For detection of trophozoites of Naegleria and try-
be distinguished after microhematocrit centrifugation. panosomes.
This detection is possible using fluorescence microscopy • For detection of Trichinella larvae in patients with
because the walls of the capillary tubes are precoated severe infections.
with acridine orange. • Eosinophilic pleocytosis may be caused by Angiostron-
gylus and Gnathostoma which are not found in blood,
Utility or transverse myelitis due to Schistosoma mansoni.
• Under UV light the dye does not stain erythro- • May reveal migrating larvae in severe infections
cytes. • Helminth eggs are very rarely seen in the CSF.
• Stains WBCs, platelets, plasmodia, trypanosomes,
and microfilariae.
Procedure
• Not recommended for laboratories doing small
1. Centrifuge the CSF at 7,000 × g for 10 minutes.
numbers of parasitologic examinations.
Remove the supernatant.
Levine et al. (1989) described the method in some
2. Examine the sediment under reduced illumination.
detail, and Wongsrichanalai et al. (1991) consider it
sensitive and specific for the detection of plasmodia
present in small numbers, some of which could not Considerations
be found on Giemsa-stained thick smears in their se- • Examine CSF promptly as trypanosomes survive for
ries. only about 20 minutes. Naegleria may also round up
and become nonmotile.
Equipment. The QBC tubes used for hematologic pur- • Motility of Naegleria may be enhanced by use of a
poses contain an agglutinating agent that does not al- warm stage.
low for the concentration of the less dense parasitized • Culture of CSF or its sediment may isolate Naegleria.
erythrocytes at the top of the erythrocyte column.
• Fluorescence microscope with a 50-power oil-im- CSF Concentration Procedures
mersion lens. Double-centrifugation technique for
• Microhematocrit centrifuge. trypanosomes in spinal fluid (World Health
• Modified QBC tubes and floats. Organization, 1986)
• Specially constructed lucite blocks to hold the QBC 1. Centrifuge CSF obtained by spinal puncture for
tubes for viewing under the microscope. 10 minutes at 900 × g. Decant the supernatant.
• QBC positive result for the presence of malarial 2. Resuspend the sediment in the small amount of
parasites reveals green and red fluorescence when fluid left in the bottom of the centrifuge tube.
excited by blue light at 460 nm wavelength. 3. Draw the suspension into a microhematocrit tube,
leaving 1 cm free of CSF.
Triple centrifugation method 4. Seal the free end of the hematocrit tube by inserting
• For detection of trypanosomes when they are too in the flame of the Bunsen burner.
few to be found even in thick blood film prepara- 5. Centrifuge the sealed tube in a microhematocrit
tions. centrifuge for 2 minutes.
1. Deliver 9 mL of blood obtained by venipuncture 6. Place the microhematocrit tube on a slide, with a
into a centrifuge tube containing 1 mL of 6% ci- coverslip over the sealed end and flood the space be-
trate solution. tween the microhematocrit tube and the slide (two
2. Centrifuge at 400 × g for 10 minutes. or more microhematocrit tubes may be needed to
3. Remove the supernatant fluid to another centri- stabilize coverslip) with water.
fuge tube; recentrifuge at 500 × g for 10 minutes. 7. Examine the sealed end of the microhematocrit tube
4. Remove the supernatant fluid once more to a under the microscope at 200× magnification for try-
clean centrifuge tube; centrifuge at 1,500 × g for panosomes, which will move away from sediment-
10 minutes. ed white blood cells.
EXAMINATION OF TISSUES AND OTHER Specimen considerations

BODY FLUIDS Sternal marrow aspiration is approximately as pro-
Tissue Impressions ductive as the more hazardous splenic or hepatic
Utility biopsy.
• For detection of intracellular parasites such as Leish- Leishmania tropica cannot be recovered from the
mania and Toxoplasma. surface of an oriental sore; if a hypodermic syringe is
• Samples may be fresh lymph nodes, liver biopsy ma- introduced through normal tissue at the side of the
terial, or bone marrow. ulcer to the area below the ulcer bed, intracellular
parasites may be demonstrated in the fluid that is
Procedure withdrawn after instillation of a few drops of normal
1. The sample is lightly impressed on a clean micro- saline.
scope slide. Aspiration of enlarged posterior cervical or other
2. The film is allowed to dry at room temperature and involved lymph nodes at times reveals trypanosomes
is stained with Giemsa’s or Wright’s stain in the when the blood is apparently free of them. The lymph
manner of a thin blood film. nodes are less often involved in Rhodesian sleep-
Considerations ing sickness than in the Gambian form or in Chagas’
• With lymph nodes or other solid tissue, prepare the disease. Biopsy of enlarged nodes from patients with
smear from a freshly cut surface. the latter disease may reveal intracellular (amastigote)
• Remaining tissue may be fixed for conventional his- forms of the parasite.
tologic procedures or may be cultured.
Examination of Sputum
Biopsy and Aspiration Utility
Utility • Indicated when pulmonary paragonimiasis is suspect-
• Spleen, liver, and bone marrow biopsies may be ed (swallowed eggs may be seen in feces).
used for diagnosis of visceral leishmaniasis. • Ruptured hydatid cysts may be recognized by the
• Biopsy material may also be used for culture or ani- presence of hooklets in the sputum.
mal inoculation. • Cryptosporidium may be found in both sputum and
lung biopsy material.
Tissue specimen Possible microscopic findings • E. histolytica may be detected in pulmonary ab-
Corneal scrapings Acanthamoeba trophozoites or cysts scesses.
or biopsy • Spores of microsporidia may appear in sputum.
Brain biopsy Toxoplasma, Naegleria, Acanthamoeba, • Migrating larvae of Ascaris, hookworm, and Strongy-
Balamuthia, Entamoeba
loides, as well as E. gingivalis and T. tenax (oral con-
Intestinal biopsy Cryptosporidium and other taminants), are rarely seen.
microsporidia
Biopsy of colonic E. histolytica (via PAS or
Procedure
ulcers immunoperoxidase stains)
• Examine by wet mount while fresh.
Biopsy of rectal mucosa Schistosoma mansoni eggs
• Preserve in PVA fixative for protozoa.
Biopsy of bladder Schistosoma haematobium eggs
• Preserve in formol-saline for other organisms or
mucosa
eggs.
Muscle biopsy Trichinella spiralis larvae (usually
gastrocnemius; larvae may be most
abundant in the diaphragm) Specimen considerations
Skin snips or Microfilariae of O. volvulus, • Sputum specimens should be induced, if pos-
scrapings M. ozzardi, and M. streptocerca sible.
Liver abscess aspirate Thick reddish-brown fluid, seldomly • Early morning specimens uncontaminated with sa-
containing amoebae liva are acceptable.
Amoebae are seen in the tissue • For very viscid specimens, dilute with an equal
surrounding the abscess cavity quantity of 3% NaOH, mix thoroughly, and centri-
Hydatid cyst fluid Hydatid sand, although certain fuge before examination or preservation. Note that
aspirate hydatid cysts may be sterile NaOH destroys any amoebae or flagellates that may
Absence of scolices or hooklets from be present.
the sediment is not evidence against
the parasitic nature of the cyst
Examination of Urine and Vaginal Secretions 4. Rinse as before for 2 to 3 seconds.

Utility 5. Place vertically against a rack to drain and dry.
Specimen Possible microscopic findings
Centrifuged or Schistosome ova, microfilariae, Giemsa’s Stain
membrane-filtered spores of microsporidia Staining procedure
urine • For thick films, omit steps 1 and 2.
Fresh or midday urine Schistosoma haematobium • If the slide has a thick film at one end and a thin
specimen film at the other, fix only the thin portion, then stain
Urine specimen with Microfilariae of Wuchereria and both parts of the film simultaneously. Dry with the
chyluria Brugia thick end down.
Urine specimen Microfilariae of Onchocerca 1. Fix thin blood films in absolute methyl alcohol
post-treatment with for 1 minute. Allow the slides to dry.
diethylcarbamazine 2. Immerse the slides in a solution of 1-part Giemsa
Fresh urine and Trichomonas vaginalis stock to 30- to 50-parts buffered water (pH 7.2)
vaginal or prostatic • Jerky motility for 30 minutes to 1 hour.
exudate • Flagella and undulating 3. Dip the slides briefly in buffered water; drain
membrane best seen via
quickly and thoroughly, and air-dry.
phase-contrast microscopy (or
Papanicolau smears)
Considerations
Giemsa’s stain is sold commercially as a concentrated
STAINING PROCEDURES FOR BLOOD stock solution. Each new lot should be thoroughly test-
FILMS AND TISSUE IMPRESSION SMEARS ed before it is put into use.
Fields’s Stain If the coloration of the red and white blood cells
Preparation seems satisfactory, it can be assumed that the stain will
1. Dissolve salts first, then add the stains, after grind- be adequate for the demonstration of malarial and
ing the azure I in a mortar. other parasites.
2. Let the solution stand for 24 hours, then filter. Re-
peat filtration if a scum forms or if dye precipitates. Hansel’s Stain
3. The solution may be used for many weeks, but Utility
the eosin should be renewed when it becomes • For demonstration of eosinophils in urine.
greenish. • Eosinophiluria appears to be a constant finding in uri-
nary schistosomiasis.
Solution A
Methylene blue 0.8 g Staining procedure
Azure I 0.5 g 1. Centrifuge approximately 10 mL of freshly voided
Na2HPO4, anhydrous 5.0 g urine at 1,000 × g for 5 minutes. Decant supernatant.
KH2PO4, anhydrous 6.25 g 2. Pipette the sediment onto 1 or more slides, spread out
Distilled water 500 mL thinly with an applicator stick, and allow to air-dry.
3. Cover the slide with Hansel’s stain and allow to
Solution B stand for 25 to 30 seconds.
4. Add distilled water and allow to stand for 30 sec-
Eosin 1.0 g onds. Pour off the stain, and rinse with distilled wa-
Na2HPO4, anhydrous 5.0 g ter to remove excess stain.
KH2PO4 6.25 g
5. Rinse with 95% methyl alcohol. Drain and allow
the slide to air-dry.
Staining procedure Considerations

1. Dip the slides in solution A for 1 second. Hansel’s stain stains the granules of eosinophils a very
2. Rinse by immersion in water, waving gently for a few bright red. Other cells will stain blue or pink, depend-
seconds until the stain ceases to flow from the film. ing on cell type and degree of destaining with methanol.
3. Dip the slides in solution B for 1 second. Hansel’s stain is not suitable for staining blood smears.
CULTURE METHODS FOR BLOOD, CSF, • 0.55% liver digest

TISSUES, AND OTHER BODY FLUIDS • 0.50% proteose peptone
Culbertson’s Medium for Acanthamoeba • 0.25% yeast extract
(Culbertson et al., 1965) • 0.30% glucose
Materials 2. Add 4% bovine calf serum to the above before use.
1. Prepare a neomycin sulfate solution, 0.56% in sterile 3. Add 1 µg hemin/mL to the above before use.
distilled water. Prepare a sterile nystatin suspension 4. If the material to be cultured is a clinical specimen
in distilled water to contain 1,500 units per milliliter. or an environmental sample, add 200 µg streptomy-
2. Prepare agar stock, 3 g of Bacto-Agar per 100 mL of cin/mL and 200 U penicillin/mL.
1.7% NaCl.
3. Prepare a suspension of Enterobacter aerogenes in Modified Nelson’s Culture Medium for
trypticase soy broth, giving 40% transmission on a Naegleria fowleri
Coleman Junior spectrophotometer against unin- Materials
oculated broth. Since both live and killed bacteria Page’s Amoeba Saline Solution (very dilute balanced
are to be used in medium preparation, place at least salt solution [2 mM])
5 mL of the suspension in a sealed ampule and im-
merse in a water bath at 65°C for 30 minutes to kill MgSO4 · 7H2O 0.4 mg
CaCl2 · 2H2O 0.4 mg
the organisms. Keep refrigerated until use.
Na2HPO4 14.2 mg
KH2PO4 13.6 mg
Procedure NaCl 12.0 mg
1. To a mixture consisting of 5 mL of each antibiotic Distilled water 100.0 mL
solution, 5 mL of killed bacterial suspension, and
85 mL of sterile distilled water, add 100 mL of melt- Nonnutrient Agar
ed and cooled 3% agar and combine all ingredients Page’s saline 100.0 mL
at 56°C in a water bath. Difco agar 1.5 g
2. Pour the mixture into Petri plates, 8 mL per plate;
allow excess moisture to evaporate by inverting the 1. Dissolve the agar in Page’s saline with gentle heat-
bottom plate and resting it at a slight angle. ing.
3. Place 0.05 mL of live Enterobacter suspension at the 2. Aliquot 20-mL quantities into 20- × 150-mm screw-
center of the plate and spread over an area 25 to capped tubes.
40 mm in diameter. Allow the surface to dry at room 3. Autoclave at 15 psi for 15 minutes. Store in the re-
temperature or at 4°C overnight. frigerator.
Inoculation Procedure
1. Place drops of fluid or small pieces of tissue speci- 1. Make up the following ingredients in Page’s amoeba
men near the center of the plate. saline then autoclave.
2. Check for the presence of amoebae at the edges of • 0.1% liver infusion (Oxoid, Wilson 1:20)
the inoculum during the following 4 to 5 days. • 0.1% glucose
2. Add 0.5 mL of inactivated calf serum to 9.5 mL of
Mix’s Amoeba Medium for Opportunistic above before use (5% serum). Inactivate the calf
Amoebae serum at 56°C for 30 minutes.
Utility 3. Prepare nonnutrient agar plates or store in refrigera-
• For cultivation of free-living amoebae (e.g., Acan- tor (up to 3 months). Warm to 37°C before use.
thamoeba, Hartmannella, and Naegleria). 4. Add 0.5 mL of suspension of Escherichia coli or En-
• Axenic culture via a medium consisting of an equal terobacter aerogenes in Page’s saline to the surface of
mixture of Balamuth’s medium and Nelson’s me- the plate and spread with a glass spreader; allow sa-
dium supplemented with 4% bovine calf serum and line to absorb into the agar.
1 µg hemin/mL (John, 1993).
Inoculation
Procedure 1. Inoculate a few drops of CSF sediment onto plate.
1. Mix the following ingredients in Page’s amoeba sa- 2. Incubate at 35°C to 37°C. Examine daily under low
line (see under Modified Nelson’s Culture Medium power.
for Naegleria fowleri) then autoclave.
3. Amoebae will grow on the moist agar surface and • Examine the cultures every day for a month before
produce plaques as they consume the bacteria. being discarded as negative.
4. Once good growth has been achieved on agar,
amoebae may be transferred to Nelson’s medium or Considerations
Mix’s amoeba medium, with streptomycin added at • If leishmanias are present, culture forms will usually
the rate of 100 µg/mL for axenic cultivation. be found within 2 to 10 days. Scarce numbers may
require much longer to be detected.
Considerations • Leishmanias will not grow in the presence of bacterial
• Cysts may appear within 4 to 5 days, and trophozo- contamination.
ites earlier.
• Acanthamoeba, from a suspected case of keratitis, Tissue Culture for Toxoplasma gondii (Shepp
may be isolated and cultivated in the same manner et al., 1985)
in Culbertson’s medium or Mix’s amoeba medium. • Applicable to blood, CSF, and placental tissues (and
possibly other tissues).
Novy-MacNeal-Nicolle (NNN) Medium for
Leishmania and Trypanosoma cruzi Inoculation (blood)
Materials 1. Collect 10 mL of blood in preservative-free heparin
Nonnutrient agar base tubes. Allow to sediment by gravity.
2. Remove the buffy coat with aseptic precautions and
Agar 14 g centrifuge at 800 × g for 10 minutes.
NaCl 6g
3. Wash buffy coat cells three times with Eagle’s mini-
mal essential medium.
1. Bring water to boiling point. Add and dissolve salt 4. Inoculate the washed buffy coat material onto com-
and agar. plete human foreskin (CF-3) fibroblast monolayers
2. Distribute in test tubes filled to about one-third capacity. and observe weekly for cytopathologic effects.
3. Plug the test tubes and autoclave for sterilization. • Other tissues may be inoculated directly onto the
• Tubes containing the agar base may be stored in tissue culture.
the refrigerator and used as needed. • If more than 1 mL CSF is available, it may be cen-
trifuged at 500 × g for 10 minutes. Use the sedi-
Defibrinated Rabbit’s blood ment for the inoculum.
• Obtained from the rabbit from the ear artery or via
cardiac puncture with sterile precautions.
• Place blood in a sterile flask containing glass beads. ANIMAL INOCULATION
Defibrinate by shaking. Parasite Laboratory animal host
Trypanosoma brucei Rats (low-grade parasitemia; survive
Procedure gambiense for several months)
1. Place the tubes in hot water to melt the agar. Cool to Trypanosoma brucei Rats (overwhelming parasitemia;
48°C to 50°C. rhodesiense shorter survival period)
2. Add one-third as much sterile defibrinated rabbit’s Trypanosoma cruzi White mouse (best for diagnostic
blood as the volume of agar to each tube. inoculation)
3. Mix the blood and agar thoroughly by rapid rota- Leishmania Hamsters
tion of the tube. Toxoplasma gondii White rats (chronic infection for
4. Place the tube in a slanting position on ice and cool. maintenance of the strain)
5. After cooling, place in an upright position and incu- Mice (survives only for a few days)
bate for 24 hours at 37oC to determine sterility. Opportunistic Weanling mice (test for pathogenicity)
amoebae
Inoculation
• Specimen may be peripheral blood or material ob- Trypanosomes
tained by biopsy, by marrow aspiration, or from cuta- Utility
neous ulcers by aspiration from below the ulcer bed. • Trypanosoma brucei gambiense and Trypanosoma brucei
• Incubate the tubes at room temperature (i.e., 22oC). rhodesiense (more virulent).
Organisms develop in the water of condensation • White rats, white mice, and guinea pigs are most
which collects at the bottom of the slanted agar. useful for diagnosis and the maintenance of
laboratory strains. Young animals are most readily Considerations

infected. • A highly virulent strain of amoeba will begin to pro-
duce deaths in 5 to 8 days.
Procedure • Amoebae may be cultivated from brain tissue in
1. Inoculate via intraperitoneal or subcutaneous route. Mix’s amoeba medium.
2. Amounts of blood up to 2 mL are injected, depend-
ing on the size of the animal used. Xenodiagnosis
• A special case of animal inoculation originally applied to
Considerations the diagnosis of Chagas’ disease.
• Check rats for the presence of their common para- • Uninfected animals are exposed to suspected tissue
site, T. lewisi, before inoculation. to allow them to contract the infection.
• When T. cruzi is first isolated, it is quite virulent. Re- Trypanosoma cruzi Reduviid bugs (blood)
peated animal passage diminishes its virulence and Trichinella spiralis Rats (muscle tissue)
may render it noninfective.
• T. rangeli multiplies in common laboratory animals
IMMUNODIAGNOSTIC AND MOLECULAR
but does not cause apparent disease.
TECHNIQUES
Leishmanias Variations in sensitivity, specificity, and reactivity
Procedure among laboratories must be considered in the determi-
1. Inoculate via intraperitoneal or intratesticular route. nation of the diagnostic potential of a specific test and
2. Hamsters will slowly develop a generalized infec- in the interpretation of test results.
tion with any form of Leishmania. Laboratory technique Clinical application
3. Organisms may be demonstrated in spleen impres- Bentonite flocculation Trichinosis
sion smears or in testicular aspirates. Latex agglutination Trichomoniasis
Indirect hemagglutination Amoebiasis
Considerations Chagas’ disease
• For isolation of leishmanias, the hamster is most satisfac- Toxoplasmosis
tory; other laboratory animals are infected only with Echinococcosis
difficulty Cysticercosis
• Culture methods are generally regarded as superior Filariasis
for diagnostic use. Immunoblot Echinococcosis
Schistosomiasis
Toxoplasma gondii Paragonimiasis
Utility Cysticercosis
Toxoplasma gondii shows little host specificity and will Western blot Echinococcosis
infect all common laboratory animals. White rats and Schistosomiasis
Cysticercosis
mice are generally used; rats develop a chronic infection.
Radioallergosorbent test Ascariasis
Considerations Anisakiasis
Rats develop a chronic infection (good for maintenance Direct immuno- Giardiasis
fluorescence (DFA) Trichominiasis
of the strain). Mice with intraperitoneal infection dem-
Cryptosporidiosis
onstrate tremendous proliferation of organisms in the
Indirect fluorescent Giardiasis
ascitic fluid and die within a few days. Mouse perito-
antibody (IFA) Cryptosporidiosis
neal fluid may be used as a source of Toxoplasma for the Malaria
dye test and other diagnostic procedures. Chagas’ disease
Leishmaniasis
Opportunistic Amoebae Toxoplasmosis
Procedure Babesiosis
1. Concentrate amoebae by centrifugation. Enzyme immunoassay Many parasitic diseases
2. Inoculate weanling mice by introducing a 10-µL ELISA Many parasitic diseases
drop containing the amoebae into a single naris of DNA probe Trichomoniasis
an anesthetized mouse using a micropipet (i.e., in- PCR Toxoplasmosis
tranasal route). Babesiosis
Immunodiagnostic Techniques slide is then washed to remove the serum, and the slide
Bentonite flocculation (BF) and latex is then covered with a solution containing a fluorescent
agglutination (LA) dye coupled with antihuman globulin. When this is in
These tests are of relatively low reactivity. They are per- turn washed, any fluorescent dye remaining indicates
formed by coating bentonite or latex particles with the the presence of the antibody in the serum specimen. By
test antigen and observing flocculation or agglutination use of the appropriate antihuman globulin, one may
on addition of the serum. Titration is achieved by serial test for IgG or IgM.
dilution of the serum.
Enzyme immunoassay (EIA) and ELISA
Indirect hemagglutination (IHA) Enzyme immunoassay is a general term for several dif-
One of the older test modalities, indirect hemaggluti- ferent procedures that determine the presence or ab-
nation depends on the agglutination of antigen-coated sence of a parasite by the reaction between the parasite
sheep erythrocytes by antibodies in the test serum. It antigen or antibodies, an enzyme-coupled correspond-
may be roughly quantitated by dilution of the test se- ing antibody or antigen, and the enzyme substrate,
rum. with production of a color that may be assayed either
qualitatively or quantitatively. Enzyme immunoassay is
Immunoblot (IB) and Western blot (WB) the most widely used of all the types of tests for detection of
Immunoblot is a more sensitive version of the IHA. parasitic infections.
Western blot is a type of immunoblot test used in diag- A specific variation of enzyme immunoassay, the
nosis of a variety of parasitic and viral infections. ELISA has become increasingly popular because of sen-
In both tests, a sample of protein-containing mate- sitivity and ease of interpretation. The appropriate anti-
rial from serum, cerebrospinal fluid, or other tissue or gen or antibody is bound to a solid support (microtiter
excreta is electrophoresed onto a polyacrylamide gel. The wells, beads, test tube walls). The specimen to be tested
electrophoretically separated proteins on the gel are (serum, cerebrospinal fluid, feces) is added and reacts
then transferred (by blotting) onto a sheet where they are with the already present antigen or antibody. Washing
recognized by radioactively labeled specific antibod- then removes unbound test material, after which en-
ies, whose presence can be assayed after the sheet is zyme-linked antibody or antigen is added, which reacts
washed. with the antigen or antibody of the test material. An
additional washing removes all unbound material, and
Radioallergosorbent test (RAST) finally a solution that reacts with the remaining en-
Developed as a test for antibodies to certain allergens, zyme to produce a color change is added. This change
RAST tests specifically for IgG and IgE. Known parasite may be measured either visually or colorimetrically.
antigen is bound to a complex carbohydrate matrix
known as a sorbent. Test serum is then added to the Molecular Techniques
sorbent, which is washed and then allowed to react DNA probe
with a radioactively labeled antibody to human IgG or Performance of this test involves transfer of DNA-
IgE. After removal of the excess labeled antibody, the containing material of any sort (insect salivary glands
presence and amount of radioactivity measure anti- or gut, human serum or feces, etc.) to a nitrocellulose
body present in the serum. membrane, where it is fixed. A DNA segment of known
sequence, characteristic of the parasite DNA (produced
Direct immunofluorescence (DFA) by a cloning technique by means of hybridomas and
Fluorescence of parasite antigen is induced by the in- then radioactively labeled), is hybridized to the DNA on
troduction of monoclonal antibodies (produced in vi- the membrane. Radioactivity remaining after the mem-
tro against the parasite in question and fluorescently brane is washed signals the presence of the parasite.
tagged) into a fluid or applied to a slide containing the
parasite. The organism fluoresces when viewed by fluo- Polymerase chain reaction (PCR)
rescence microscopy. Polymerase chain reaction is a complicated method
whereby low levels of specific DNA sequences may be
Indirect fluorescent antibody (IFA) amplified to reach the threshold of detection, through
A known parasite antigen is exposed to patient serum action of the enzyme DNA polymerase. In vitro am-
suspected of containing antibodies to that parasite. Anti- plification of target DNA fragments involve a cyclic
bodies in the serum bind to antigen of the parasites, the process of denaturation, hybridization of primers,
and DNA strand elongation occurring at different tem- field surveys, and surveillance of helminths. The use of
peratures. Amplicons may then be subjected to electro- LAMP assay for detection of Plasmodium species in RBC
phoresis and other techniques for identification and monolayers on COC plates was described in another
characterization. study by Hashimoto et al, 2018. Indeed, this novel
molecular amplification technique holds promise as
Kit Tests a more sensitive and specific diagnostic modality for
Kit tests for the diagnosis of a number of parasitic dis- parasitic diseases.
eases have come on the market within the past few
years. By far the largest number are for the serodiagnosis of Luminex technology
toxoplasmosis. Kits testing for both types of antibody by The Luminex xMAP® Technology is a multiplexed
EIA and by IFA are available. microsphere-based system that utilizes liquid suspensions
In general, antibody tests are performed on serum and containing different sets of microsphere beads that are
antigen tests on unpreserved fecal specimens. Specific in- uniquely dyed with fluorophores (Reslova et al., 2017).
structions for collection of specimens will accompany The surface of each microsphere set allows discrete bio-
each type of kit. assay formats to be performed simultaneously. Fluores-
cent signals are emitted by each individual bead when
Current Techniques in Parasite Diagnosis excited by lasers or LEDs. These are analyzed by high-
Entamoeba histolytica speed digital signal processors and allows for detection
A monoclonal EIA test for the rapid detection of the of different targets with a high throughput.
adhesin specific for Entamoeba histolytica in fecal speci- Luminex technology has been used as a multiplex
mens have been produced. This “E. histolytica test” assay for detection and differentiation of several dif-
(produced by TechLab), with its accompanying “Ent- ferent parasitic species. Parallel diagnosis of several dif-
amoeba test,” which recognizes the E. histolytica/dispar ferent parasites is important in areas where coinfections
complex, has the reliability of zymodeme analysis for are common. A study by Taniuchi et al. (2011) adapted
the differentiation of the pathogenic and nonpatho- multiplex qPCR assays to direct DNA hybridization for
genic species and is much more rapidly performed parallel diagnosis of seven intestinal parasites— 3-plex
(Haque et al., 1995). A second-generation test, “E. his- for protozoa and 4-plex for helminths. Another study
tolytica II test” (TechLab), has higher sensitivity (Haque by McNamara et al. (2006) utilized Luminex technol-
et al., 2000). ogy for simultaneous detection of infection by all four
human malaria species. The semi-quantitative assay
Malarial parasites had equal sensitivity and specificity with other PCR-
At least three malaria antigen detection systems based assays.
are available. ParaSight-F (Becton Dickinson) and The technology has also been used for differentiation of
ICT Malaria (Amrad ICT) detect histidine-rich pro- closely related parasite species. In a study by Bandyopad-
tein-2 (HRP-2), and OptiMAL (Flow, Inc.) detects hyay et al. (2007), Luminex technology was used in dif-
plasmodial lactate dehydrogenase (pLDH). The tests ferentiating C. hominis and C. parvum based on a single
based on the detection of HRP currently have the high- nucleotide difference in their microsatellite-2 region
est sensitivity and specificity (Grobusch et al., 2003; (ML-2). Using oligonucleotide probes specific for ML-2
Moody, 2002). regions of each species, the assay proved to be a sensi-
tive, more rapid, and less expensive alternative to DNA
Loop-mediated isothermal amplification sequencing analysis and DFA.
(LAMP)
Loop-mediated isothermal amplification is a DNA am-
plification technique wherein replication of DNA se- QUALITY ASSURANCE
quences is achieved at a constant temperature (isothermic). Quality assurance in any laboratory process must be en-
This is made possible through the use of a polymerase sured throughout the pre-analytic, analytic, and post-
with strand-displacement activity (i.e., Bst DNA poly- analytic phases. This involves the implementation of
merase) that allows binding of six different primers to administrative policies and protocols applicable to the
eight distinct regions on a target gene without the need entire laboratory, as well as some guidelines specific to
for denaturation at high temperatures. certain laboratory divisions. In addition, internal and ex-
A study by Deng et al. (2019) has demonstrated the ternal quality control must be observed regularly to moni-
potential applications of LAMP in clinical diagnosis, tor and verify the reliability of test results. This section
comprehensively discusses and emphasizes on parameters Post-analytic phase

particular to the parasitology section of a clinical labora- The post-analytic phase of laboratory testing includes
tory facility. initial assessment of test results, data transcription, and
transmission of provisional or final reports.
Pre-analytic phase • Results assessment: evaluation of results ensures ad-
The pre-analytic phase of laboratory testing includes herence to laboratory protocols regarding the man-
patient preparation as well as specimen collection, han- ner of reporting and serves as a final appraisal of the
dling, and identification. These processes may occur out- test process used.
side the laboratory and are, consequently, error-prone. • Laboratory information system (LIS): establishment of
• Patient preparation: note the ingestion of any sub- a LIS provides ease of access and uniformity in the
stance that may interfere with laboratory examina- transcription of results.
tions (e.g., bismuth, castor oil), as well as intake of • Transmission of reports: protocols for release of pa-
antimicrobial drugs. tient results must observe strict adherence to data
• Specimen identification: patient identification re- privacy regulations and other pertinent guide-
quirements may vary with each institution, al- lines.
though at least two identifiers (i.e., full name and
date of birth) are usually required.
• Specimen suitability: ensure that the submitted speci- SUMMARY
men is appropriate for the test procedures being re-
quested. EXAMINATION OF STOOL SPECIMENS
• Specimen quality: note the age of the specimen (i.e., • Macroscopic examination of stool specimens may
time of collection), transport and storage condi- suggest the presence of various parasites based on
tions, use of preservatives or anticoagulants, and specific characteristics.
other pertinent physical characteristics. • A direct wet film may be examined as a saline
• Assess specific parameters of specimen handling re- mount or as an iodine-stained preparation made
garding tissues and other body fluids – CSF, sputum, from fresh stool specimens.
genitourinary secretions, tissue scrapings and biopsies. • Concentration techniques separate parasite forms
from the bulk of fecal matter and may either be a
Analytic phase sedimentation method or a flotation technique.
The analytic phase consists of all laboratory processes • Permanent stained slides allow for accurate
involved in specimen testing. In a parasitology laborato- identification of certain protozoa in stool specimens,
especially E. histolytica.
ry, this includes a wide array of procedures such as speci-
men concentration, microscopic examination (includ- • The number of stool specimens to be examined
depends on the kind of parasite whose presence is
ing smear preparation and staining), culture methods,
to be detected.
serologic testing, and molecular diagnostics techniques.
• Substances that interfere with stool examinations
• Maintain strict adherence of laboratory personnel to
must be noted and relayed to patients for proper
testing protocols, especially complex and multistep specimen collection.
procedures such as those in serologic and molecular
• Stains for direct fecal smears include iodine
testing. solutions and the mixed immuno-fluorescence (MIF)
• Reference materials: this includes reference textbooks, stain.
images, and permanent slides available for continu- • Schaudinn’s solution provides optimal fixation and
ous education and training of personnel, as well as to preservation of structural detail when used strictly
limit interobserver variability when reading results of on fresh stool specimens.
microscopic examinations and other laboratory tests. • Ritchie’s concentration method is effective for
• Laboratory equipment: ensure proper maintenance recovery of most protozoan cysts and helminth
and calibration of centrifuges, laboratory refrigera- eggs from stool specimens.
tors and freezers, and other hardware. • Modified Sheather’s sugar flotation and modified
• Reagents and solutions: ensure appropriate labeling, Ritchie’s concentration method are used for
preparation, and storage conditions for stains, fixa- detection of Cryptosporidium oocysts.
tives, culture media, and other stock reagents. • Iron hematoxylin and Gomori’s trichrome stain may
• Observe appropriate use of positive and negative be used to stain stool specimens.
controls when indicated.
• Modified acid-fast stain is used for detection of blood smears.

Cryptosporidium, Cyclospora, and Cystoisospora in • Culture methods using blood, CSF, tissue
stool specimens. specimens, and other body fluids are available for
• Ryan’s trichrome blue stain is used for detection of cultivation of free-living amoebae, hemoflagellates,
Microsporidia in stool specimens. and Toxoplasma gondii.
• Strongyloides larvae may be recovered from stool • Animal inoculation is used for detection of
using the Baermann apparatus, Harada and Mori’s trypanosomes, leishmanias, Toxoplasma gondii, and
filter paper strip procedure, and the agar plate opportunistic amoebae.
method. • Xenodiagnosis is used for diagnosis of Chagas’
• Cellophane tape swab is used for detection of disease and trichinosis.
Enterobius and Taenia eggs.
IMMUNODIAGNOSTIC TECHNIQUES
• Duodenal sampling and biopsy (e.g., Enterotest) are
used for the recovery of larvae and ova of parasites • Various immunodiagnostic and molecular
in the small intestine. techniques are commercially available for detection
of parasite antigens and their corresponding
• Culture methods should never be used as a
antibodies, as well as specific DNA fragments.
substitute for routine and thorough microscopic
stool examination. • Kit tests for parasitic infections (e.g., toxoplasmosis
and malaria) allow for rapid screening of patients.
• Culture methods for specific parasites may be
classified as axenic if antibiotics are added. • Generally, antibody test kits are used on serum
specimens while antigen tests are performed on
• Estimation of worm burden may be utilized in
unpreserved fecal specimens.
quantitatively assessing the results of therapy.
EXAMINATION OF BLOOD AND CSF

• Fresh blood may be used for identification of REVIEW QUESTIONS
trypanosomes and microfilariae based on their
1. Which of the following will likely be found in fully
characteristic motilities.
formed stools specimens?
• Thin and thick blood films remain the gold standard
a. Protozoan trophozoites
for detection of malarial infection.
b. Protozoan trophozoites and helminth eggs
• Thick blood films yield increased quantity of
c. Protozoan cysts and helminth eggs
parasites seen due to a thicker layer of blood.
d. Microfilarial stages
• Various concentration techniques may be used
for enhanced detection of microfilariae and other
2. The preferred iodine solution for preparation of
parasites in blood.
iodine-stained films
• Cerebrospinal fluid may be examined for
a. Modified D’Antoni’s iodine
detection of amoebae, trypanosomes, and some
nematodes. b. Gram’s iodine
c. Lugol’s solution
EXAMINATION OF TISSUES AND OTHER BODY d. Tincture of iodine
FLUIDS
• Tissue impressions are used for detection of 3. Determining the presence of E. histolytica requires at
intracellular parasites, such as Leishmania and
least how many stool examinations?
Toxoplasma.
a. Three
• Biopsy and aspiration material may be used for
b. Four
diagnosis of visceral leishmaniasis and for culture or
c. Five
animal inoculation.
d. Six
• Sputum examination may be warranted when
pulmonary paragonimiasis is suspected. The
presence of other parasites in sputum may be noted. 4. In modified PVA fixative solutions, copper or zinc
• Examination of urine and vaginal secretions may replaces what component of the original PVA fixa-
be used for detection of Trichomonas vaginalis, tive solution
schistosomes, and various microfilariae. a. Sodium
• Hansel’s stain is used for demonstration of b. Lead
eosinophils in urine. It is not suitable for staining c. Mercury
d. Bismuth
5. The modified Sheather’s sugar flotation technique is c. Double centrifugation technique

used for concentration of stools when determining d. Triple centrifugation method
the presence of what parasite?
a. Cryptosporidium 12. For very viscid sputum specimens, an equal part of
b. Cyclospora this solution must be added
c. Cystoisospora a. 3% NaOH
d. Encephalitozoon b. 0.85% NaCl
c. Glacial acetic acid
6. The KOH concentration method is used for concen- d. None of the above
tration of stools when determining the presence of
what parasite? 13. Hansel’s stain is used for the demonstration of
a. Cryptosporidium what structure in urine?
b. Cyclospora a. Schistosoma haematobium ova
c. Cystoisospora b. Eosinophils
d. Encephalitozoon c. Red blood cells
d. Microfilaria
7. When fully ripened, a drop added of iron hematox-
ylin solution added to 100 mL tap water produces 14. Novy-MacNeal-Nicolle (NNN) medium is used for
what color? cultivation of what parasites?
a. Red a. Entamoeba histolytica
b. Green b. Leishmania
c. Violet c. Trypanosoma cruzi
d. Brown d. Both B and C
8. The Baermann apparatus is used primarily for the 15. A rat was injected with patient’s blood to test for
recovery of what parasite larvae? the presence of trypanosomes and survived for sev-
a. Capillaria philippinensis eral months. What trypanosome is presumed to be
b. Ancylostoma duodenale present?
c. Necator americanus a. Trypanosoma brucei gambiense
d. Strongyloides stercoralis b. Trypanosoma brucei rhodesiense
c. Both A and B
9. Axenic cultures achieve isolation and growth of only d. Equivocal
a single species of parasite due to what component
of the culture media? 16. Xenodiagnosis of Chagas’ disease involves the in-
a. Antibiotics oculation of what animal with patient specimens?
b. Agar a. Rat
c. Glucose b. Mouse
d. Distilled water c. Reduviid bug
d. Mosquito
10. Gravid proglottids of Diphyllobothrium can usually
be differentiated from those of Taenia spp. via the 17. For isolation of leishmanias, inoculation of what
presence of what structure? animal is most satisfactory?
a. Two genital pores a. Rat
b. Uterine rosette in the middle b. Mouse
c. Extensive uterine branching c. Hamster
d. Cannot be differentiated d. Guinea pig
11. The following are blood concentration procedures 18. Bentonite flocculation test is used in the diagnosis
except one of what parasitic infection?
a. Modified Knott’s technique a. Echinococcosis
b. Membrane filtration method b. Cryptosporidiosis
c. Trichinellosis Grobusch MP, et al. Comparison of three antigen detection

d. Ascariasis tests for diagnosis and follow-up of falciparum malaria
in travellers returning to Berlin, Germany. Parasitol Res.
19. The radioallergosorbent test (RAST) was developed 2003;89:354–357.
Haque R, et al. Current concepts: amoebiasis. N Engl J Med.
to test for what type of human antibodies to certain
2003;348:1565–1573.
parasites? Haque R, et al. Diagnosis of amoebic liver abscess and
a. IgG intestinal infection with the Techlab Entamoeba histolytica
b. IgE II antigen detection and antibody tests. J Clin Microbiol.
c. Both A and B 2000;38:3235–3239.
d. None of the above Haque R, et al. Rapid diagnosis of Entamoeba infection by
using Entamoeba and Entamoeba histolytica stool antigen
20. The malaria antigen detection test with the high- detection kits. J Clin Microbiol. 1995;33:2558–2561.
est sensitivity and specificity detects what parasite Harada Y, Mori O. A new method for culturing hookworm.
component? Yonago Acta Med. 1955;1:177–179.
Hashimoto M, Sakamoto H, Ido Y, et al. In situ loop-mediated
a. Plasmodium LDH (pLDH)
isothermal amplification (LAMP) for identification of
b. Hemozoin Plasmodium species in wide-range thin blood smears.
c. CD2 Malar J. 2018;17:235. doi: 10.1186/s12936-018-2381-7.
d. HRP-2 John DT. Opportunistically pathogenic free-living amoebae.
ed 2 In: Kreier JP, Baker JR, editors. Parasitic protozoa, vol
Answers to review questions are available at the end of this 3. San Diego, CA: Academic Press; 1993. p. 143–246.
book. Jones TC, et al. A technique for isolating and concentrating
microfilariae from peripheral blood by gradient
centrifugation. Trans R Soc Trop Med Hyg. 1975;69:
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CHAPTER 11
Therapy Against Parasitic Infections

NOE RAPHAEL D. TARROSA, RMT
LUMEN-DWELLING PROTOZOA Other treatment modalities. With the advent of met-

The Amoebae ronidazole therapy, aspiration of amoebic abscesses
Entamoeba histolytica is usually unnecessary. Introduction of percutaneous
Anti-amoebic drugs (amoebicides) catheter drainage under the guidance of CT or ultraso-
nography has greatly facilitated the drainage of amoe-
Drug Clinical indication bic abscesses that are resistant to conventional therapy
Metronidazole Mainstay for invasive disease (i.e., acute (Ken et al., 1989; Singh and Kashyap, 1989).
(Flagyl) amoebic colitis and hepatic abscess)
Approved for use during the last two Entamoeba polecki
trimesters of pregnancy All of the commonly employed antiamoebic drugs,
Tinidazole Mainstay for invasive disease with the exception of diloxanide furoate and metronidazole,
Requires a shorter treatment course and have been used without success.
better tolerated than metronidazole
Paromomycin Luminal amoebicide for intestinal Case report Dosage regimen
(luminal) infection Salaki et al. (1979) Metronidazole, 750 mg 3 times
daily × 10 days and then with
Diloxanide Luminal amoebicide for asymptomatic cyst
diloxanide furoate, 500 mg 3
furoate passers only
times daily × 10 days
(Furamide) Well-tolerated in children
Chacin-Bonilla (1980) Metronidazole, 750 mg 3 times
• Side effects of metronidazole include nausea, diar- and Gay et al. (1985) daily × 5, 7, or 10 days
rhea, metallic taste, and headache.
• Patients being treated with metronidazole should Other amoebae
be warned to abstain from alcohol. Generally, I. bütschlii and E. nana are nonpathogenic
and does not require treatment. Their presence in
Considerations. Treatment varies with the clinical
stools may indicate fecal contamination.
stage of the infection, although treatment for asymp-
tomatic cases and amoebic colitis are essentially iden- The Flagellates and Ciliates
tical. Treatment failure with metronidazole must be Giardia duodenalis (formerly Giardia lamblia)
followed with a luminal agent to eliminate intestinal Metronidazole and tinidazole are the first-line agents for
colonization and prevent relapse. treatment. Nitazoxanide has been used and is available
Clinical stage
in a liquid formulation for children (Bailey and Erra-
of infection Dosage regimen mouspe, 2004). Other effective drug therapies include
albendazole and mebendazole (Hall and Nahar, 1993;
Asymptomatic Paromomycin, 25 to 35 mg/kg/day in
intestinal 3 divided doses × 7 days
Al-Waili and Hasan, 1992).
amoebiasis Diloxanide furoate, 500 mg 3 times
daily × 10 days Trichomonads
Metronidazole, 750 mg 3 times Trichomonas species. Metronidazole is generally ef-
daily × 10 days fective in vaginal trichomoniasis and treatment of sexu-
Amoebic dysentery, Metronidazole, 750 mg 3 times al partners, and for nonspecific urethritis with demon-
liver abscess, and daily × 10 days (total dose not to stration of T. vaginalis (Lossick et al., 1986). It must not
amoeboma exceed 1.0 g) followed by a luminal be used in the first trimester of pregnancy and should
agent only be used during the second and third trimesters or
285
for nursing mothers when local palliative measures fail. nated Encephalitozoon cuniculi infection (De Groote
Infants beyond the fourth week of life with symptom- et al., 1995). The drug only reduces the number of
atic trichomoniasis can be treated with metronidazole bowel movements in intestinal disease caused by En-
10 to 30 mg/kg daily for 5 to 8 days. terocytozoon bieneusi, but does not clear the infection
Treatment for T. tenax infections is directed at the (Dieterich et al., 1994).
underlying conditions, if any. Topical fumagillin may be used for treatment
of ocular Encephalitozoon hellem infection (Diesenhouse
Dientamoeba fragilis. Iodoquinol is the first-line agent et al., 1993).
for treatment of infection. Tetracycline may be used as
an alternative first-line agent. Paromomycin (Humatin),
an aminoglycoside, is used for cases refractory to iodo- MALARIA
quinol and tetracycline (Yang and Scholten, 1977). Generalities
Gastrointestinal side effects of treatment are com- Types of therapy
mon. Eighth nerve and renal damage due to treatment Type of therapy Definition
are rare.
Suppressive Destroys parasites as they enter the
Balantidium coli therapy bloodstream
Treatment of balantidiasis with oxytetracycline (Terra- Clinical cure Eliminates large numbers of erythrocytic
mycin) or iodoquinol is usually effective. parasites in a clinical attack
Radical cure Eliminates the bloodstream infection
The Apicomplexa (Intestinal Sporozoa) and tissue stages in the liver
Cystoisospora (Isospora) belli
A trimethoprim-sulfamethoxazole (TMP/SMX) combination Suppressive therapy (chemoprophylaxis) utilizes
effectively eliminates chronic C. belli infection in immu- small doses of drugs effective against erythrocytic stages
nosuppressed persons, when given for 3 weeks (White- of malarial parasites. Drugs effective against the asexual
side et al., 1984). Combined pyrimethamine and sulfa- erythrocytic stages are not necessarily gametocyticidal
diazine has also been shown to be an effective treatment. or active against the pre-erythrocytic stages (including
A study involving 32 patients with chronic isospo- hypnozoites).
riasis and AIDS concluded that isosporiasis in patients Drugs used for clinical cure are administered in larger
with AIDS can be treated effectively with a 10-day doses and may be of the same type as those used in sup-
course of TMP/SMX and that subsequently recurrent pressive therapy or a different type when therapy has
disease can be prevented by ongoing prophylaxis with failed. A clinical cure may leave the patient infectious
either TMP/SMX or sulfadoxine-pyrimethamine (Pape because of gametocytes remaining in the circulating
et al., 1989). An alternative is pyrimethamine alone for blood or subject to relapse after reinvasion of the blood-
treatment and for prophylaxis (Weiss et al., 1988). stream by pre-erythrocytic forms that remain in the liver
or (in vivax and ovale malaria) by pre-erythrocytic schi-
Cryptosporidium parvum
zogony initiated by reactivated hypnozoites.
Cryptosporidiosis is treated effectively with nitazoxanide
but is usually self-limited in immunocompetent pa-
Drug classes and mechanisms of action
tients (Chen et al., 2002). There is no effective treat-
ment for AIDS patients, except treatment of the under- Commercially available drugs
lying HIV infection. Cinchona alkaloids Quinine, quinidine
4-aminoquinolines Choloroquine, amodiaquine
Cyclospora cayetanensis
8-aminoquinolines Primaquine, tafenoquine
Cyclosporiasis is treated effectively with trimethoprim-
Diaminopyrimidines Pyrimethamine
sulfamethoxazole (Hoge et al., 1995). HIV-infected
patients may require higher doses and long-term main- Sulfonamides and sulfones Sulfadoxine, dapsone
tenance (Pape et al., 1994). Quinoline methanols Mefloquine
Tetracyclines Tetracycline, doxycycline
Microsporidia Biguanides Proguanil
Oral albendazole may be used for treatment of intestinal
Phenanthrene methanols Halofantrine
and disseminated Encephalitozoon intestinalis infection
Hydroxynaphthoquinones Atovaquone
(Dore et al., 1995; Sobottka et al., 1995) and dissemi-
CHAPTER 11 Therapy Against Parasitic Infections 287
Drugs undergoing human testing or not available • Other blood schizonticides include pyrimethamine
for clinical use in the U.S. (Daraprim), mefloquine (Lariam), halofantrine, tet-
Sesquiterpene lactones Qinghaosu, artemisinin, racycline, doxycycline, proguanil (Paludrine), and
artemether, artesunate, artemisinin (qinghaosu).
artesunate suppositories
Others Pyronaridine, synthetic Tissue schizonticides. Tissue schizonticides act as
endoperoxides causal prophylactics that destroy the developmen-
(Fenozan B07), tal malarial stages in the liver. Primaquine is effective
substituted trioxanes, against tissue stages, including the hypnozoites of P.
trioxane dimers, nonane vivax and P. ovale. Tafenoquine has recently received reg-
endoperoxides, macrolides ulatory approval as chemoprophylaxis and as radical
(azithromycin), cure for P. vivax in patients greater than 16 years old.
8-aminoquinolines Several blood schizonticides (e.g. proguanil, pyrimeth-
(WR238605)
amine, the tetracyclines) also have mild tissue schizon-
Mechanisms of action ticidal activity.
Dihydrofolate reductase Proguanil, pyrimethamine
(DHFR) inhibition Gametocyticides. Chloroquine and amodiaquine
Folic acid (DHF) synthesis Dapsone, sulfadoxine are effective against the gametocytes of P. vivax, P.
inhibition ovale, and P. malariae and immature gametocytes of
(PABA competitor) P. falciparum. The drugs do not affect the mature P.
Unknown Artemisinin and related falciparum gametocytes. Primaquine is gametocyticidal
drugs: chloroquine, for all four species of human malaria parasites and thus
amodiaquine (binds acts to render the patient noninfectious to the mos-
to DNA, DNA-RNA quito.
polymerase? Alters pH of
parasitophagous vesicles?)
Primaquine (inhibits Chemoprophylaxis (suppressive therapy)
parasite mitochondrial The Centers for Disease Control and Prevention (CDC)
respiration?) recommends the following regimens for the preven-
Halofantrine, mefloquine, tion of malaria in travelers (recommended dosages are
quinine, quinidine, those given in the succeeding pages):
tetracyclines, pyronaridine,
endoperoxides, trioxanes, Clinical indication Recommended drug
macrolides Areas without reports of Chloroquine once weekly
chloroquine resistance
Drug therapy and life cycle stages All other malarious areas Mefloquine once weekly
Blood schizonticides
Blood schizonticides are used for suppression or treat-
When mefloquine is contraindicated, alternatives
ment of an acute attack of malaria. Most drugs have
are atovaquone-proguanil or doxycycline daily or chlo-
no effect on either the pre-(exo)erythrocytic stages or
roquine once weekly plus a treatment dose of Fansidar
gametocytes.
for use in case of fever, if professional medical care is
• Quinine and its isomer, quinidine, were the first
not available within 24 hours.
drugs employed to destroy asexual parasites in the
bloodstream. It is isolated from the bark of the Cin-
chona tree (“Jesuits’ bark”). Single Drug Therapy
• Chloroquine (Aralen, Nivaquine) is the mainstay of Quinine
blood schizonticidal therapy for all malarial species ex- Utility
cept for chloroquine-resistant Plasmodium falciparum • A drug of choice for treatment of resistant falciparum
(CRPF). malaria.
• Hydroxychloroquine (Plaquenil) and amodiaquine • Used for chemoprophylaxis in selected individuals.
(Camoquin) have virtually the same antimalarial Quinine is a potent blood schizonticide against all
activity as chloroquine and almost equally reduced four species of human malarial parasites. It is some-
usefulness due to increasing resistance. what slower acting than the 4-aminoquinolines.
Dosage and route of administration Quinine is often used to treat severe falciparum malaria
Age group Dosage regimen
during pregnancy. It may produce maternal and fetal hy-
perinsulinemia and hypoglycemia. The drug is also a
Adult suppressive 325 mg 2 times daily with meals,
possible abortifacient, but the risk to the fetus of severe
therapy continued for 4 weeks after leaving
the endemic area
maternal malaria greatly outweighs the possible risk of
quinine therapy.
Adult clinical cure 650 mg every 8 hours for 3 to 7 or
10 days
Shorter course (3–7 days) is given Drug resistance. Scattered resistance on the part of
when administered with another P. falciparum was described as early as 1908 in Brazil
drug or if the patient is known to and more recently in Vietnam, Thailand, Irian Jaya, and
have partial immunity to malaria West Africa.
Pediatric clinical 10 to 25 mg/kg every 8 hours for the
cure same interval Quinidine
Utility
In cases of quinine resistance, Looareesuwan et al. • A drug of choice for treatment of resistant falciparum
(1990) recommends an increase in the dose of paren- malaria.
teral quinine by 50% or a change to another rapidly Quinidine is a dextrorotatory stereoisomer of qui-
acting drug if parasitemia does not fall by 75% within nine with slightly superior antimalarial activity.
the first 48 hours of treatment. Another drug such as
doxycycline may also be routinely added. Dosage and route of administration. The great
advantage of quinidine is its ready accessibility when
Smaller daily doses may suppress symptoms with-
intravenous treatment is indicated. Quinidine gluco-
out completely eliminating the bloodstream infection,
nate or sulfate is administered intravenously while
causing a chronic, low-grade infection leading to black-
the patient is monitored electrocardiographically.
water fever. Quinine dihydrochloride has been used for
For this purpose, 0.8 g quinidine gluconate or 0.6 g
intravenous administration in patients who are unable
quinidine sulfate is diluted in 250 mL of 5% glucose
to take the oral drug, but it is now being supplanted
in water.
by intravenous quinidine, which is both more readily
available and somewhat more effective. Clinical indication Dosage regimen
Initial dose 24 mg/kg quinidine
Side effects and toxicity. Minor electrocardiographic (adults and children) gluconate or 18 mg/kg
changes (T-wave flattening with 10% lengthening of the quinidine sulfate, given
Q-T interval) may be anticipated with either oral or in- over a 2- to 4-hour period
travenous administration. Subsequent doses 12 mg/kg gluconate or 9 mg/
(if necessary) kg sulfate every 8 hours
Side effect classification Signs and symptoms
Minor side effects Tinnitus and headache • Higher dosages have been recommended to avoid
Effects of overdose Convulsions, hypotension, heart possible undertreatment (White, 1997).
block, ventricular fibrillation,
death Side effects and toxicity. The cardiotoxicity of quini-
Cinchonism (quinism) Nausea and vomiting, dine is somewhat more pronounced than that of qui-
abdominal pain, blurred nine. If the QRS interval increases more than 25% over
vision, transient loss of baseline, administration is discontinued until this in-
hearing, vertigo, and tremors terval becomes shorter. Quinine sulfate or a combina-
tion of drugs is given per os as soon as the patient’s
Cinchonism involves dose-related and reversible condition permits.
side effects of excessive ingestion of chinchona al-
kaloids that may be seen during the first 2 to 3 days Chloroquine (Aralen, Nivaquine)
of treatment with quinine. It may subside sponta- Utility
neously during therapy and always disappears after • Recommended for chemoprophylaxis and treatment of
drug withdrawal (seldom severe to warrant change in uncomplicated malaria in areas where resistance is not
therapy). known to occur
• May be used for suppressive therapy against all types chemotherapy and to be related to increased efflux of the
of malaria except CRPF and resistant strains of vivax drug from resistant forms of the parasite. Verapamil and
malaria (CRPV) other calcium channel blockers that reverse drug resis-
tance in cultured cancer cells have been shown to reverse
Dosage and route of administration
chloroquine resistance, presumably by inhibiting its ef-
Suppressive therapy (chemoprophylaxis) flux from the parasite food vacuole. Similar results have
Age group Dosage regimen been achieved using the tricyclic antidepressant drug de-
Adult 500 mg chloroquine phosphate (300 mg sipramine, which presumably works by the same mecha-
chloroquine base) once weekly starting 1 or 2 nisms. The therapeutic potential of such drug combina-
weeks before travel to the malarious area and tions is questionable because of the potential toxicity to
continuing 4 weeks after departure normal body cells of increased levels of chloroquine.
Pediatric Chloroquine or hydroxychloroquine 5 mg/kg
(base) once weekly Amodiaquine (Camoquin)
Clinical cure Utility
• Similar to chloroquine in efficacy and toxicity and
in development of resistance by P. falciparum.
Adult 1 g chloroquine phosphate (600 mg chloroquine
• May be effective against strains that are resistant to chlo-
base) initially, followed by 500 mg (300 mg
base) 6 hours later and a single dose of 500 mg roquine in some areas.
(300 mg base) on each of the two following • Not commercially available in the United States.
days (total dose = 1.5 g base)
Pediatric 10 mg/kg chloroquine or hydroxychloroquine
base initially, followed by 5 mg/kg in 6 hours Clinical cure
and on each of the two following days
For suppressive therapy, hydroxychloroquine sulfate Adult 1 g amodiaquine (600 mg amodiaquine
(Plaquenil), 400 mg weekly, is an alternative that some base) initially, followed by 500 mg (300 mg
patients may tolerate better. Hydroxychloroquine may base) 6 hours later and a single dose of
500 mg (300 mg base) on each of the two
also be preferred for pediatric suppressive doses as the
following days (total dose = 1.5 g base)
200-mg tablets (155 mg hydroxychloroquine base) are
Pediatric 10 mg/kg amodiaquine base initially,
more readily divided.
followed by 5 mg/kg in 6 hours and on
Side effects and toxicity. In the doses used for pro- each of the two following days
phylaxis or treatment, toxic effects of chloroquine are
generally mild, and toxicity is infrequent. There may be Side effects and toxicity. Some cases of severe neutro-
nausea and vomiting if the pills are taken without food. penia have been associated with its use for suppressive
Dizziness, headache, confusion, blurred vision, and fa- therapy, and the drug is not suitable for routine prophy-
tigue have also been reported. Chloroquine is not con- laxis. Amodiaquine may be given during pregnancy.
traindicated in pregnancy.
Pruritus, sometimes quite severe, occurs in a sub- Pyrimethamine (Daraprim)
stantial percentage of West African blacks after taking Pyrimethamine was historically used for chemoprophy-
chloroquine. It is less common but occurs in other eth- laxis extensively due to its long half-life and safety in preg-
nic groups, rarely after a single suppressive dose. nancy. Due to widespread resistance (P. falciparum and
P. vivax), its main use at present is in combination with
Drug resistance. Chloroquine-resistant P. falciparum sulfadoxine (Fansidar) and with dapsone (Maloprim).
(CRPF) may be seen in all areas except the Middle East,
Egypt, Central America west of the Panama Canal, Mex- Mefloquine (Lariam)
ico, and Hispaniola (Haiti and the Dominican Repub- Utility
lic). P. vivax from Papua New Guinea, Indonesia, Myan- • Effective against both chloroquine-sensitive and
mar (Burma), India, and the Solomon Islands may also –resistant strains of P. falciparum and P. vivax, and
exhibit chloroquine resistance. against P. malariae and P. ovale (with limited treat-
Resistance to chloroquine is often associated with ment experience).
resistance to other antimalarials; it is thought to mim- • Ineffective against the tissue stages and gametocytes
ic the multidrug resistance encountered in cancer of malaria.
Dosage and route of administration. Mefloquine to mefloquine in vitro and in vivo has been noted in
has an extremely long serum half-life of 13 to 24 days, strains of P. falciparum from areas in West Africa in
and in some studies even longer. Owing to its lengthy which the drug has never been used.
half-life and in case of therapeutic failure of meflo-
quine, consider that the substitution of quinine or Doxycycline
quinidine may expose the patient to increased risk of Utility
cardiac conduction problems or convulsions. • A blood schizonticide with some effect on the pre-
erythrocytic malarial stages.
Suppressive therapy (chemoprophylaxis)
• Less effective against P. vivax than against P. falci-
Age group Dosage regimen parum.
Adult 250 mg weekly starting a week before and The drug should not be not be used alone for pro-
continuing for 4 weeks after the potential phylaxis. Treatment must be followed by a 4- to 6-week
exposure course of chloroquine prophylaxis to prevent subse-
Pediatric Weekly dose: quent development of vivax malaria.
5 to 10 kg, one-eighth tablet
11 to 20 kg, a quarter tablet
Dosage and route of administration. Administra-
21 to 30 kg, a half tablet
tion should continue for 4 weeks after leaving the en-
31 to 45 kg, three-quarter tablet
>45 kg, one tablet (250 mg) demic area (as with other chemoprophylactic drugs).
Clinical cure Suppressive therapy (chemoprophylaxis)
Age group Dosage regimen Age group Dosage regimen
Adult 750 mg followed 12 hours later by 500 mg Adult 100 mg daily
Pediatric 15 mg/kg followed 12 hours later by 10 mg/kg Children >8 years old 2 mg/kg (maximum 100 mg)
daily
Side effects and toxicity. In prophylactic doses, me-
floquine usually gives rise to minor side effects similar
Proguanil (Paludrine)
to those seen with suppressive doses of chloroquine.
Utility
Neurologic changes have been reported following
• A blood schizonticide that was initially effective
treatment in adults given maximum treatment doses
against all four species of malaria.
(750 mg) and include convulsions, loss of conscious-
• Generally useful against P. falciparum in East Africa
ness, and acute psychoses. There is an increased risk
(less effective against P. vivax).
of convulsions when the drug is administered concur-
The drug is not available commercially in the
rently with chloroquine or quinine.
United States but may be obtained in Canada and
Mefloquine may also induce sinus bradycardia and
many European and African countries (used extensively
should not be given to patients with conduction defects
in East Africa).
or those taking beta blockers, calcium channel block-
ers, quinine, or quinidine. It should not be used during
Dosage and route of administration. Proguanil is
the first trimester of pregnancy.
well-tolerated in suppressive doses but should not be
Nevertheless, and despite considerable “bad press” in
used for treatment. Some authorities recommend add-
the popular travel literature, numerous case-control stud-
ing a weekly dose of chloroquine at the usual level.
ies have failed to show a causality of mefloquine to re-
ported side effects. Thus, on the basis of a review of more Suppressive therapy (chemoprophylaxis)
than 1 million European travelers and U.S. Peace Corps Age group Dosage regimen
volunteers, 90% of whom had used mefloquine continu-
Adult 200 mg daily, continued for 4 weeks after
ously for 2 to 3 years—plus an equivalent relative risk
leaving the malarious area
(1:13,300) for chloroquine prophylaxis—the U.S. Centers
Pediatric Less than 2 years, 50 mg daily
for Disease Control and Prevention (CDC) has concluded
2 to 6 years, 100 mg daily
that “mefloquine prophylaxis is safe, is well tolerated, and
7 to 10 years, 150 mg daily
has saved thousands of lives” (Lobel, 1996). After age 10 years, 200 mg daily
Drug resistance. Resistance has been noted in South-
east Asia (over 50% along the Thailand- Myanmar bor- Drug resistance. Proguanil is not effective against
der), Irian Jaya, the Philippines, and Africa. Resistance P. falciparum in West Africa, Thailand, or New Guinea
due to occurrence of significant resistance. Strains of P. tropical areas and may be avoided by the use of sunscreens
vivax and P. malariae that are resistant to this drug have with a sun protection rating (SPF) of 28 or greater.
also been found in scattered areas. Doxycycline should not be used during the latter
half of pregnancy or for children younger than 8 years
Halofantrine (Halfan) because it can discolor tooth enamel.
Utility. Halofantrine is a lipophilic phenanthrene-
methanol used for the treatment of multiple drug-resis- Pyrimethamine-sulfadoxine (Fansidar)
tant P. falciparum at doses similar to that of mefloquine. Utility
It is not used for suppressive therapy. • Limited indications for prophylactic use.
• May be used for presumptive treatment of malaria
Dosage and route of administration. Recommend- in situations when medical care is unavailable.
ed dosage is 8 mg/kg, repeated after 6 and 12 hours, Various combinations of pyrimethamine with sul-
and, in nonimmune patients, a further three daily fonamides or sulfones have proved to be effective an-
doses 1 week later (White, 1996). Halofantrine should timalarials. A combination of 25 mg pyrimethamine
not be given with fatty foods or with drugs known to with 500 mg sulfadoxine (Fansidar) is particularly ef-
prolong the Q-T interval. fective because of the long half-life of both components
and was widely used for prophylaxis of CRPF until its
Artemisinin (Qinghaosu) toxicity became appreciated.
Artemisinin (qinghaosu) is the active component of
Artemisia annua extracts. It is effective against both Dosage and route of administration
P. falciparum and P. vivax and acts more rapidly as a
blood schizonticide than either quinine or mefloquine, Clinical utility Dosage regimen
although with a high rate of recrudescences in treated Suppressive therapy One tablet weekly
patients. Several derivatives (e.g., artemether, arteether, Adult clinical cure Three tablets taken as a single
and sodium artesunate) seem to be even more active, dose (not usually associated
especially in patients with cerebral malaria. with any severe side effects in
Artemisinin may not be suitable for suppressive patients not allergic to either
therapy because of a short half-life. A potential for component)
neurotoxicity may become a significant concern in drug Pediatric clinical cure 5 to 10 kg, half tablet
use. Artemisinin and its derivatives are not available for 11 to 20 kg, one tablet
clinical use in the United States. 21 to 30 kg, one and one-half
tablets
31 to 45 kg, two tablets
Multiple Drug Prophylaxis and Treatment Over 45 kg, three tablets
of Resistant Falciparum Malaria
Quinine or mefloquine and doxycycline Side effects and toxicity. Cutaneous reactions and
Utility. Doxycycline may be administered for chemo- granulomatous hepatitis are complications of sulfon-
prophylaxis of malaria in multidrug-resistant areas amide therapy. Sulfonamide intolerance is an absolute con-
either alone, or in conjunction with mefloquine, qui- traindication to the use of Fansidar and treatment must be
nine, or other antimalarials. discontinued immediately.

Side effect classification Signs and symptoms
Clinical utility Dosage regimen Cutaneous reactions Stevens-Johnson syndrome,
Adult chemoprophylaxis 100 mg daily erythema multiforme, toxic
Adult clinical cure 100 mg twice daily over a epidermal necrolysis (severe
7-day period (with other reactions which have resulted in
antimalarials) fatalities)
Pediatric clinical cure 1.5 to 2 mg/kg twice daily Sulfonamide Itching, redness, rash, oral or
intolerance genital lesions, and sore throat
Side effects and toxicity. Side effects may include
allergic skin reactions, photosensitivity, and diarrhea. Drug resistance. Resistance to Fansidar has become a
Photosensitivity must be considered for persons going to major problem in Thailand and other Southeast Asian
countries, New Guinea, sub-Saharan Africa, and Brazil. Dosage and route of administration
Resistance also occurs in other parts of South America, Clinical cure
Indonesia, Kenya, and Ghana.
Drug Dosage regimen
Pyrimethamine-sulfadoxine-mefloquine Atovaquone 500 to 750 mg daily for 7 days
(Mepron)
(Fansimef)
Utility Atovaquone- 1,000 mg atovaquone with 400 mg proguanil
• Administration is intended to delay the development of proguanil (Malarone), once daily for 3 days
resistance to mefloquine. Suppressive therapy (Chemoprophylaxis)
Fansimef is composed of the same amounts of py- Clinical utility Dosage regimen
rimethamine and sulfadoxine found in Fansidar, with Suppressive 250 mg atovaquone/100 mg proguanil daily
the addition of mefloquine, 250 mg per tablet. In stud- therapy and continuing for 7 days after leaving the
ies in Thailand, the combination did not appear to risk area
be more effective than either mefloquine or Fansidar
alone. The drug is not available commercially in the The cure rates for atovaquone monotherapy and
United States or in Canada. atovaquone-proguanil in falciparum malaria cases are
67% to 76% and 99.5%, respectively (Looareesuwan
Dosage and route of administration et al., 1996).
Age group Dosage regimen Drug resistance. A significant drawback for long-
term use prospects was the observation that parasites
Adult clinical Areas without Fansidar resistance: two tablets
cure Areas with Fansidar resistance: three tablets remaining after currently infrequently unsuccessful
Malarone treatment are totally resistant to virtually
any dose of this agent. Also, apparent relapses have
Side effects and toxicity. Side effects are reported to occurred following treatment of P. vivax malaria.
be similar to those seen with mefloquine but with a
higher incidence of nausea and vomiting. Suppressive Treatment of Tissue Schizonts, Hypnozoites,
use of this combination cannot be recommended be- and Gametocytes
cause of the potential toxicity of sulfadoxine. Most of the blood schizonticides have little or no ef-
fect on other developmental stages in the life cycle of
Pyrimethamine-dapsone (Maloprim) the parasites. If these drugs are discontinued when a
Maloprim is a combination of pyrimethamine 12.5 mg traveler leaves the malarious area, tissue schizonts may
and dapsone 100 mg. It is not available in the United continue to develop and produce an attack of malaria a
States or in Canada. The standard adult dose is one tab- few days or weeks later.
let weekly. Twice weekly dosage is more effective but Continuing treatment for 4 weeks after the risk of
carries a risk of developing agranulocytosis. exposure is past should allow the tissue schizonts of
P. falciparum and P. malariae time to complete their de-
Atovaquone-proguanil (Malarone) velopment in the liver and enter the bloodstream to be
Utility destroyed. The hypnozoite stages of P. vivax and P. ovale
• Well tolerated and has been approved for use in may remain dormant in the tissues long after this pe-
drug-resistant falciparum malaria. riod, to produce attacks of malaria weeks, months, or
Atovaquone (Mepron) is a hydroxy-1,4-naphthoqui- even several years later.
none that has been used for the treatment of pneumo-
Primaquine
cystosis in patients intolerant to trimethoprim-sulfa-
Utility
methoxazole. It has significant antiplasmodial activity,
• Effective against hypnozoites of P. vivax and P. ovale.
apparently at the cytochrome bc1 complex. The drug
• Gametocyticidal for all four species of malaria.
combination should not be taken by pregnant women
Routine administration of primaquine after leaving
or children weighing less than 11 kg (25 pounds).
a malarious area safeguards against hypnozoite-induced
A report by Hartmeyer et al. (2019) indicated that
attacks of P. vivax infection and renders patients nonin-
treatment of a short-term traveler who contracted P.
fectious.
cynomolgi malaria during a trip to Southeast Asia with
atovaquone/proguanil (1,000/400 mg/day for 4 days), Dosage and route of administration. Treatment
followed by primaquine (26.4 mg/day for 14 days) re- doses should be given before completion of the sup-
solved symptoms within two days of treatment. pressive therapy.
Age group Dosage regimen However, because of the rapid course of the Rhodesian
type of infection, neurologic involvement may be ex-
Adult 30 mg primaquine base daily for 14 days
pected to occur very early, especially in non-Africans.
Pediatric 0.6 mg/kg primaquine base daily for 14 days
Side effects and toxicity. Primaquine should be given

Suramin
Utility
with caution in areas where glucose-6-phosphate dehydroge-
• Generally effective in the early stages of African sleep-
nase (G6PD) deficiency is common. Administration of the
ing sickness wherein there is no evidence of neuro-
drug is contraindicated in the presence of severe vari-
logic involvement.
ants of G6PD deficiency as it may precipitate a severe
Suramin is an enzyme inhibitor that seems to be
hemolytic episode.
taken up selectively by trypanosomes (and filariae) but
Tafenoquine (Arakoda; Krintafel) not by mammalian cells.
Utility
• Effective against hypnozoites of P. vivax (Kathrine Dosage and route of administration. A test dose of
et al., 2018). not more than 200 mg is administered intravenously. If
• Prophylaxis of malaria in adults. tolerated well, treatment doses may be administered.
Tafenoquine, an 8-aminoquinoline drug similar to
primaquine, has recently received regulatory approval by
the United States Food and Drug Administration (FDA).
Adult 1 g given on treatment days 1, 3, 7, 14, and 21
A long half-life of 2 weeks permits fewer doses, improving pa-
tient adherence to the dosage regimen (Tan and Hwang, Pediatric 20 mg/kg body weight on treatment days 1, 3,
2018). The drug has anti-hypnozoiticidal activity with 7, 14, and 21
similar prophylactic outcomes as that of mefloquine.
Suramin should not be given as a rapid bolus. If pro-
Dosage and route of administration. Tafenoquine teinuria appears in patients with preexisting renal dis-
should be administered with food. ease, the course of treatment should be discontinued.
Clinical utility Dosage regimen Side effects and toxicity. Suramin may be used dur-
Adult chemopro- 200-mg dose daily for 3 days prior to ing pregnancy. If an early response to treatment with
phylaxis travel, weekly during travel, and once suramin is not apparent, administration of pentami-
after returning
dine or melarsoprol should be considered.
Radical cure 300 mg, single dose
Side effect
Side effects and toxicity. Tafenoquine, as with pri-
classification Signs and symptoms
maquine, should be given with caution in areas where
Marked Nausea, vomiting, loss of consciousness,
glucose-6-phosphate dehydrogenase (G6PD) deficiency is
idiosyncrasy and seizures
common. It is contraindicated for patients with G6PD
deficiency and pregnant women (in which the fetus has Other side effects Fever, hepatitis, rash, pruritus, edema,
pains in the palms and soles of
an unknown G6PD status) as it may precipitate a severe
the feet, blepharitis, conjunctivitis,
hemolytic episode.
photophobia, and tearing
At prophylactic doses, tafenoquine is not recom-
mended in those with psychotic disorders. Common
Pentamidine (Lomidine)
adverse reactions with treatment are dizziness, head-
Utility
ache, nausea, and vomiting. Decreases in hemoglobin
• Effective in the hemolymphatic stages of African trypano-
have also been observed, but its clinical significance
somiasis.
has not been established.
• Ineffective during later stages of the disease as it
does not cross the blood-brain barrier.
OTHER BLOOD- AND TISSUE-DWELLING Pentamidine is a diamidine that apparently interacts
PROTOZOA selectively with kinetoplast DNA to kill trypanosomes.
African Trypanosomiasis (African Sleeping
Sickness) Dosage and route of administration. Pentamidine
The drugs used and the treatment schedules are the is given via intramuscular injection at a dose of 4 mg/kg
same for Gambian and Rhodesian sleeping sickness. body weight daily for 10 days.
Side effects and toxicity. Herxheimer reactions may Side effects and toxicity. Further neurologic compli-
be prevented or modified by pretreatment with corti- cations are seen in about one fifth of patients following
costeroids. With intravenous administration, marked melarsoprol therapy.
toxic reactions may occur. Mild and transient cardiovas- Reactive encephalopathy, a more common type of
cular (hypotension, tachycardia) and gastrointestinal complication, is a toxic disorder related to the interac-
(nausea, vomiting) symptoms may develop following tion of the drug, the diseased brain, and the infection.
intramuscular injection. It often clears with temporary cessation of therapy and
If pentamidine is given during pregnancy, it should sedation, allowing therapy to resume a few days after
not be administered prior to the fourth month and is the symptoms abate.
usually prescribed in reduced doses. A rare direct toxic effect of melarsoprol therapy is
hemorrhagic encephalopathy, which is usually fatal. Its
Arsenicals (Melarsoprol) onset is marked by sudden loss of consciousness and
Utility hyperpyrexia. BAL should be administered at the first
• Drug of choice for treating Gambian sleeping sickness sign of either reactive or hemorrhagic encephalopathy.
with neurologic involvement. Nausea and vomiting may be suppressed by pro-
The trivalent arsenical melarsoprol (Arsobal, mel B, chlorperazine or other antiemetic drugs. Herxheimer re-
or melarsen oxide complexed with dimercaprol [BAL]) actions may be prevented or modified by pretreatment
has the trypanocidal activity of melarsen oxide and also with corticosteroids. Oral prednisolone, 1 mg/kg to a
has that drug’s ability to penetrate the blood-brain bar- maximum of 40 mg in a single daily dose, given dur-
rier. Melarsoprol interferes with the enzyme systems of ing the melarsoprol treatment period has been shown
the trypanosome by inactivating its sulfhydryl groups. to reduce significantly the incidence of melarsoprol-in-
Because of its combination with BAL, it is considerably duced encephalopathy (Pepin et al., 1989). Arsenicals
less toxic. are contraindicated in pregnancy.
While some authorities recommend the use of
melarsoprol for treatment of all stages of Gambian Eflornithine (DFMO; Vaniqa)
sleeping sickness, less toxic drugs (e.g. suramin, pent- Utility
amidine) may be substituted in the early stages, during • A highly effective treatment for both early- and late-stage
which there is no evidence of neurologic involvement. Gambian sleeping sickness (even in many patients
with disease refractory to arsenical treatment)
Dosage and route of administration. Although me- • Trypanosomes are cleared from the blood in 1 to
larsoprol may be used alone in treatment of patients 4 days and from the CSF by the end of treatment.
with minimal CNS symptoms, a longer treatment • Not effective against Rhodesian sleeping sickness
course is employed in cases of moderately advanced to (considerable numbers of T. b. rhodesiense infec-
severe neurologic involvement wherein pretreatment tions have been found to be naturally resistant to
with suramin is recommended. Complete directions for eflornithine)
the administration of these drugs are furnished by the Eflornithine is an inhibitor of ornithine decarbox-
CDC Drug Service at the time the drugs are supplied. ylase.
Dosage and route of administration. Eflornithine is

Clinical stage of administered at a dose of 400 mg/kg per day in four
infection Dosage regimen doses for 14 days for treatment of Gambian trypano-
Mild neurologic 2.2 mg/kg body weight daily for somiasis.
involvement 10 days.
Side effects and toxicity. The most frequent side ef-
Moderately Pretreatment with suramin: 0.25 to
fects following therapy are diarrhea, abdominal pain,
advanced 0.5 g intravenously on alternate days
to severe for two to four doses followed by and anemia. All conditions are reversible and have not
neurologic melarsoprol required discontinuation of therapy.
involvement Melarsoprol dosage: successive daily or
alternate-day doses of 1.5, 2, and American Trypanosomiasis
2.2 mg/kg, followed after 1 week (Chagas’ Disease)
by 2.5, 3, and 3.6 mg/kg daily on Nifurtimox (Lampit; Bayer 2502)
successive days, and 1 to 3 weeks later Utility
by 3.6 mg/kg daily for 3 days • Drug of choice for treatment of Chagas’ disease.
Nifurtimox is a nitrofurfurylidine derivative that In a study involving 307 patients with Chagas’ dis-
inhibits intracellular development of T. cruzi in tissue ease in Cordoba, Argentina (Gallerano et al. 1990),
culture. It is better tolerated by younger patients but allopurinol was found to be as efficacious as either ni-
should not be used during pregnancy. furtimox or benznidazole in eliminating parasitemias
and in rendering patients seronegative.
Dosage and route of administration. Nifurtimox is
administered orally over an extended period. Dosage and route of administration. Allopurinol is
administered orally at a dose of 600 or 900 mg per day,
Age group Dosage regimen in 300-mg doses, for 60 days.
Adult 8 to 10 mg/kg per day orally in three to four
doses for 90 to 120 days Side effects and toxicity. Adverse reactions to the
Pediatric 1 to 10 years, 15 to 20 mg/kg orally per day in drug include generalized pruritic dermatitis, epigastric
four doses for 90 days pain, transient diarrhea, and transient polyneuritis.
11 to 16 years, 12.5 to 15 mg/kg orally per day
in four doses for 90 days Cutaneous Leishmaniasis
Sodium stibogluconate (Pentostam)
Benznidazole (Rochagan; Radanil) Utility
Utility. Benznidazole is an imidazole compound with • The most effective compound available for treatment of
consistent antiparasitic activity in clinical trials. The all cutaneous leishmaniasis except the Ethiopian form
drug inhibits nucleic acid synthesis, similar to metro- of diffuse cutaneous leishmaniasis (responds best to
nidazole on T. vaginalis. It is not available in the United pentamidine).
States. Sodium stibogluconate (antimony sodium gluco-
nate) is a less toxic pentavalent antimonial that inhib-
Dosage and route of administration. Benznidazole its glycolytic enzymes and fatty acid oxidation in leish-
treatment, 7.5 mg/kg orally per day for 60 days, of manial amastigotes.
early T. cruzi infection in 64 schoolchildren aged 7 to
12 years, in a rural area of Brazil with endemic Chagas’ Dosage and route of administration. Sodium sti-
disease, was found to be safe and 56% effective in pro- bogluconate may be administered intravenously or in-
ducing negative seroconversion of specific antibodies tramuscularly at a dose of 20 mg/kg body weight daily
(Andrade et al., 1996). for 20 days. Treatment course may be repeated at 10-day
intervals in resistant cases (maximum of three courses is
Age group Dosage regimen advised).
Adult 5 mg/kg orally per day in 2 doses for 60 days
Pediatric 10 mg/kg per day in two doses for children for Side effects and toxicity. The common side effects of
60 days treatment are coughing, headache, and vomiting.
Side effects and toxicity. The main side effects of Meglumine antimoniate (Glucantime)
benznidazole treatment include skin allergy and pe- Utility
ripheral neuropathy, which are both reversible. • Substitute for sodium stibogluconate in areas where it is
not available (e.g., Latin America).
Drug resistance. Strains of T. cruzi isolated from • Not available in the United States.
patients and from domestic and sylvatic reservoirs and
vectors have demonstrated resistance to both nifurti- Dosage and route of administration. Glucantime
mox and benznidazole. Verapamil was able to reverse may be administered intravenously or intramuscularly
the drug resistance of T. cruzi to nifurtimox in vitro. at a dose of 20 mg/kg body weight daily for 20 days.
Treatment course may be repeated or continued in pa-
Allopurinol tients that may need a longer duration of treatment.
Utility Some authorities have recommended continuous ad-
• An effective drug for treatment of T. cruzi infection ministration until healing is complete.
and leishmaniases.
• Enzyme systems of affected organisms transform al- Side effects and toxicity. EKG abnormalities due to
lopurinol into toxic adenine analogues. treatment, while rare, warrants cessation of therapy
until the EKG normalizes. A slightly reduced dose is ad- The vaccine’s efficacy in immunotherapy of
ministered thereafter. American cutaneous leishmaniasis was evaluated
in a clinical study involving 217 patients (Convit
Combination therapy with recombinant human et al., 1989). Clinical cure was observed in more than
IFN-γ. Antimony-resistant cutaneous leishmaniasis 90% of those who received the vaccine; the average
has been successfully treated with suboptimal doses of time for healing was 16 to 18 weeks and it was compa-
pentavalent antimonials (Glucantime, 10 mg/kg body rable to that for meglumine antimoniate (Glucantime).
weight daily for 30 days) and intramuscular recom- The effectiveness of the vaccine in prophylaxis has not
binant human interferon gamma, 100 µg/m2 of body yet been tested.
surface area daily for 30 days (Falcoff et al., 1994). In-
tradermal injections of interferon gamma around le- Mucocutaneous Leishmaniasis
sions caused by L. tropica and L. guyanensis reportedly Sodium stibogluconate
promote healing of ulcers (Harms et al., 1989). Appar- Sodium stibogluconate is effective for treatment of
ently, healing was accomplished by cell-mediated im- mucocutaneous leishmaniasis when administered at a
mune responses elicited by the interferon gamma. dose of 20 mg/kg body weight daily for 28 days. Side
effects may include coughing, headache, and vomiting.
Amphotericin B (Fungizone)
Amphotericin B has been used in patients with cuta- Cycloguanil pamoate (Camolar)
neous leishmaniasis that are unresponsive to pentava- Cycloguanil is a folic acid folic acid inhibitor adminis-
lent antimonials. The drug is administered as a slow tered intramuscularly as single dose. It is not available
intravenous infusion, gradually increasing the dose to in the United States.
1 mg/kg weight, at which level it should be contin-
ued on alternate days until a total of 2 to 3 g has been Age group Dosage regimen
given. Adult 300 mg
1-5 years old 20 mg
Miscellaneous treatment modalities Infants 140 mg
Azole antifungals. Oral ketoconazole, 400 mg daily
for 4 to 8 weeks, has been reported to be effective in Amphotericin B
treating longstanding cutaneous leishmaniasis (Vial- Amphotericin B (Fungizone) is reported to yield good
let et al., 1986). Itraconazole has been used in India to results when given intravenously at the rate of 0.5 to
treat cutaneous lesions. Clotrimazole (1%) cream was 1 mg/kg body weight, daily or every other day, for peri-
an effective topical treatment of cutaneous infection in ods up to 8 weeks. Side effects may include renal dam-
Saudi Arabia. age and bone marrow depression with extended peri-
ods of treatment.
Other drugs. Topical preparations containing chlor-
promazine (2%) or paromomycin (15%), used in clin- Visceral Leishmaniasis
ical studies in Israel, have demonstrated considerable
potential for the treatment of cutaneous leishmaniasis Treatment modalities
(El-On et al., 1988). Oral dapsone, 200 mg daily for Drug Dosage regimen
6 weeks, showed an 82% cure rate in a double-blind Sodium 20 mg/kg body weight daily for
trial in India (Dorga, 1991). stibogluconate 28 days
Meglumine 20 mg/kg body weight daily for
Heat treatment. Controlled, localized heat, three antimoniate 28 days
30-second treatments of 50°C at weekly intervals, Allopurinol 20 mg/kg body weight three times a day
has been used to treat cutaneous leishmaniasis in Miltefosine Orally, 2.5 mg/kg body weight daily in
Guatemala (Navin et al., 1990). The cure rate with heat (Impavido) two doses for 28 days
treatment was the same as with the pentavalent anti-
monial (73%). Antimonial drugs
• Sodium stibogluconate (Pentostam) is the drug of choice
Combined vaccine for initial therapy in all but Sudanese infections, which
• A combined vaccine of heat-killed L. amazonensis are resistant to antimonials (resistance has also been
plus viable bacille Calmette-Guérin (BCG). reported in Kenya).
• Treatment for Sudanese strains should be initiated apicomplexan parasites, including Plasmodium and
with pentamidine. Toxoplasma, have been the target of drugs such as
Animal experiments suggest that liposomal encap- clindamycin, used as salvage treatment for toxoplas-
sulation may be utilized to deliver antimonial drugs mosis in a sulfur-allergic patient.
to the reticuloendothelial system, allowing treatment In France, spiramycin has been used for many years
with much smaller doses than is now the case. Lipo- to treat toxoplasmosis during pregnancy, apparently
somal amphotericin B has been effective in treating preventing transmission in utero. However, spiramycin
antimony-resistant case of visceral leishmaniasis in the does not appear to be effective therapy for preventing
Mediterranean, France, India, and Brazil, as has am- relapse of neurotoxoplasmosis in immunosuppressed
photericin B. patients. Spiramycin is available in the United States on
Patients with visceral leishmaniasis have also been a case-by-case basis for toxoplasmosis.
treated with a combination of interferon gamma and
pentavalent antimony. Interferon gamma may enhance Babesiosis (Babesia spp.)
the intracellular killing of Leishmania amastigotes. Combination therapy
Treatment for babesiosis is a combination of clindamy-
Allopurinol cin and oral quinine. Combination therapy using ato-
• Used in the treatment of visceral leishmaniasis in vaquone and azithromycin has also been used.
patients with AIDS.
Drug Dosage regimen
Allopurinol plus sodium stibogluconate has been
found effective in treating antimony-resistant cases of Clindamycin- Clindamycin, 1.2 g intravenously twice a
quinine day or 600 mg orally three times daily
visceral leishmaniasis in Kenya.
for 7 to 10 days
Miltefosine Quinine, 650 mg orally three times daily
Miltefosine (Impavido), an alkylphosphocholine, has for 7 to 10 days
been used in India to treat visceral leishmaniasis (Sun- Atovaquone- Atovaquone, 750 mg twice daily for 7 to
dar et al., 2002). The drug appears to be an effective azithromycin 10 days
and safe oral treatment for visceral leishmaniasis. It is Azithromycin, 600 mg daily for 7 to
not available in the United States. 10 days
Toxoplasmosis (Toxoplasma gondii) Other treatment modalities

Pyrimethamine-based therapy Chloroquine, perhaps because of its antiinflammatory
Combination therapy with pyrimethamine and trisul- properties, affords symptomatic relief in most cases of
fapyrimidines has been found to be effective. The drugs babesiosis but seems to have no effect on the degree of
synergistically inhibit production of dihydrofolate reductase parasitemia or its duration.
(DHFR) by the parasite, inhibiting the synthesis of DNA, The aromatic diamidines pentamidine and diminaz-
RNA, and proteins. Folinic acid may be given to coun- ene (Berenil) have been found to suppress the parasit-
teract bone marrow depression due to pyrimethamine. emia but not to eliminate infection in experimental
animals. One patient who failed to respond symptom-
Drug Dosage regimen atically or parasitologically to chloroquine was treated
with diminazene; the parasitemia cleared completely,
Pyrimethamine 25 to 100 mg daily for 1 month (in
but the patient subsequently developed an acute Guil-
acute retinochoroiditis, a loading
dose of 75 mg daily may be used lain-Barré polyneuritis thought to be related to the use
for 3 to 5 days) of the drug.
Trisulfapyrimidines 2 to 6 g daily for 1 month
Pyrimethamine and quinine, either alone or in com-
bination, failed to eliminate experimental B. microti in-
fections in hamsters.
Other treatment modalities
Corticosteroids may have value for their anti-inflamma- Primary Amoebic Meningoencephalitis
tory action. Intravenous clindamycin has been used to (Naegleria fowleri)
treat Toxoplasma encephalitis in patients with AIDS, Amphotericin B-based therapy
with promising results. Plastids, nonphotosynthet- • Amphotericin B is the anti-Naegleria agent for which
ic chloroplast-like organelles that occur in several there is evidence of clinical effectiveness.
At present, there is no satisfactory treatment for Case report Treatment course

primary amoebic meningoencephalitis (PAM). The
Lalitha et al. 40-year-old man with Acanthamoeba
antibiotics used to treat bacterial meningitis are inef- (1985) meningitis who recovered following
fective, as are the antiamoebic drugs. Amphotericin B treatment with penicillin and
is a polyene compound that disrupts the selective per- chloramphenicol
meability of the plasma membrane, causing leakage (A. culbertsoni was repeatedly cultured
of the cellular components. All known survivors of PAM from CSF)
have been treated with amphotericin B given intravenously Cleland et al. 30-year-old man with chronic
and intrathecally. The typical dosage regimen is 1 to (1982) meningoencephalitis who was treated
1.5 mg/kg body weight administered intravenously or with sulfamethazine (A. rhysodes was
intrathecally daily for 3 days, followed by 1 mg/kg daily cultured from CSF)
for 6 days
Acanthamoeba keratitis
Sample regimen 1. Amphotericin B intravenously, • Propamidine remains the best documented treatment
(Seidel et al., 1982) 0.75 mg/kg twice daily × 3 days,
for Acanthamoeba keratitis.
then 1.0 mg/kg daily × 6 days
Most of the earlier cases of Acanthamoeba keratitis
2. Amphotericin B intravenously via
lumbar catheter, 1.5 mg daily × 2 required corneal transplants to manage the disease.
days, then 1.0 mg every other
Case report Treatment course
day × 8 days
3. Miconazole intravenously, 117 Wright et al. Combination of dibromopropamide ointment
mg/m2 body surface three times (1985) (Otamidyl), propamide isethionate drops
daily × 9 days (Brolene), and neomycin drops
4. Miconazole intrathecally via lumbar Ishibashi Oral itraconazole (Sporanox), in addition
catheter, 10 mg daily × 2 days, then et al. to topical miconazole and surgical
10 mg every other day × 8 days (1990) debridement of the lesions
5. Rifampin by mouth, 3.3 mg/kg D’Aversa et al. Propamidine isethionate, neomycin sulfate,
three times daily × 9 days (1995) and clotrimazole
Elder and 0.02% topical polyhexamethylene biguanide,
Other treatment modalities Dart (1995) a polymeric biguanide disinfectant
Goswick and Brenner (2003) have described the ef- Mathers et al. 0.02% chlorhexidine digluconate,
fective treatment of experimental PAM in mice with (1996) propamidine isethionate, and oral
azithromycin. Treatment was initiated 72 hours after itraconazole
infection and was continued for 5 days, with protec-
tion being 100% and greater than for the amphotericin Balamuthia spp. infections
B-treated mice. There are two reports describing the recovery of three
immunocompetent patients from Balamuthia infection.
Acanthamoeba spp. infections In the first (Deetz et al., 2003), two patients received
Granulomatous amoebic encephalitis. As with flucytosine, pentamidine, fluconazole, sulfadiazine,
Naegleria infection, there is no satisfactory treatment and azithromycin or clarithromycin. The third patient
for granulomatous amoebic encephalitis (GAE), received pentamidine, fluconazole, and clarithromycin
partly because most cases have been diagnosed after (Jung et al., 2004).
death and there has not been adequate opportunity to
evaluate therapeutic regimens. There are three reports
of persons having recovered from Acanthamoeba CNS TREMATODES
infections. Praziquantel (Biltricide)
Utility
• Drug of choice for treatment of intestinal flukes (i.e.,
Case report Treatment course
F. buski, G. hominis, echinostomes, and heterophy-
Ofori-Kwakye 7-year-old girl with a single Acanthamoeba- ids), clonorchiasis, opisthorchiasis, and all schisto-
et al. (1986) induced granulomatous brain tumor somal infections.
recovered following total excision of the
• Drug of choice for treatment of pulmonary paragon-
mass and treatment with ketoconazole
imiasis and presumably for cutaneous forms of the
(A. healyi was cultured from biopsy)
disease (Pachucki et al., 1984).
• Approved by the United States Food and Drug Ad- Praziquantel in standard doses seems effective in cere-
ministration (FDA) only for the treatment of clonor- bral schistosomiasis japonicum and has proved so in the
chiasis, opisthorchiasis, and schistosomiasis. less common cerebral form of schistosomiasis haemato-
Praziquantel is an isoquino-linepyrazine deriva- bium (Pollner et al., 1994). Schistosomal transverse my-
tive that alters the permeability of cell membranes to elitis, seen most commonly in infections with S. mansoni
mono- and divalent cations (i.e., calcium), initiating a and S. haematobium, does not respond well to praziquan-
tetanic contractile process. The drug also disrupts and tel therapy alone. Large doses of steroids may be needed,
vacuolizes the tegument of the worm, with subsequent and laminectomy may be necessary for decompression.
eosinophil attachment.
Praziquantel may be used for the treatment of D. Paragonimiasis
dendriticum A. tyosenense, H. taichui, N. salmincola, M. There is no reference to praziquantel use in cerebral
conjunctus, and Phaneropsolus infections. It may also be forms, but it may require an extended period of treat-
used to lessen the severity of fascioliasis infections. ment. Smaller daily doses, even when administered
over a longer period to achieve the same cumulative
Dosage and route of administration dose, have been found ineffective for treatment.
Praziquantel is administered orally.
Considerations
Clinical indication Dosage regimen Praziquantel is metabolized rapidly and well tolerated
Intestinal flukes 25 mg/kg body weight three by the mammalian host. It is less toxic than tetrachlo-
times in 1 day roethylene. Side effects may include epigastric pain,
O. viverrini infection Single dose of 40 mg/kg or dizziness, and drowsiness that usually disappear within
75 mg/kg in 3 doses for 1 day 48 hours. There is no evidence of teratogenicity, muta-
genicity, or other adverse effects. Praziquantel has been
D. dendriticum infection 20 mg/kg body weight three
times in 1 day used in mass distribution programs for schistosomal
disease and is shown to be safe for use during preg-
F. hepatica infection 25 mg/kg three times daily for
5 to 7 days
nancy (Adam et al., 2004).
S. mansoni, S. haematobium, Single dose of 40 mg/kg body Bithionol
S. intercalatum infections weight (63%–90% cure rate)
Three doses of 20 mg/kg body Utility
weight in one day (∼100% • Drug of choice for treatment of fascioliasis.
cure rate) • An alternative drug for the treatment of pulmonary
S. japonicum and S. mekongi Three doses of 20 mg/kg body paragonimiasis.
infections weight in one day
P. westermani (pulmonary, 25 mg/kg three times daily for
Bithionol is administered orally.
cutaneous paragonimiasis) 2 days
A. tyosenense infection 10 mg/kg in a single dose Clinical indication Dosage regimen
H. taichui infection 75 mg/kg divided in three Fascioliasis 30 to 50 mg/kg every other day for 10
doses in 1 day to 15 doses
N. salmincola infection 20 mg/kg body weight three Pulmonary 15 to 25 mg/kg body weight twice
times in 1 day paragonimiasis daily on alternate days for a total of
10 to 15 days
Schistosomal infections
Administration of praziquantel in the schistosomula or Considerations
immature stages have little effect and may actually wors- The drug was formerly used in the formulation of med-
en acute-stage symptoms of schistosomal infections. icated soaps and is associated with contact dermatitis. It is
In severe Katayama fever, steroids may be required contraindicated in patients with a clear history of sensi-
initially, with definitive treatment postponed until tization to preparations containing this drug. Frequent
the acute symptoms subside. Both periportal fibrosis side effects include photosensitivity skin reactions, skin
and bladder wall thickening and polyps respond to rashes, urticaria, nausea, vomiting, diarrhea, abdomi-
praziquantel therapy as evaluated by ultrasonogra- nal cramps, dizziness, and headaches. Transient side ef-
phy. Yearly retreatment may be necessary in advanced fects include hepatic and renal involvement, hyperten-
cases. sion, extrasystoles, and first-degree heart block.
Oxamniquine (Vasnil) Albendazole

Utility Albendazole is a member of the benzimidazole group
Oxamniquine is a less expensive but effective treatment of drugs that includes thiabendazole and mebenda-
for S. mansoni infections. The drug may be preferred for zole. It is administered at a dose of 10 mg/kg daily for
mass treatment programs when dual infections do not 7 days for treatment of clonorchiasis (Liu et al., 1991).
exist. The effective dose depends on the origin of the
infection. Side effects are rare and include generalized Metrifonate (Bilarcil)
seizures. Metrifonate is an organophosphorus compound used
as an alternative to praziquantel for treatment of S. hae-
Dosage and route of administration matobium infections at an oral dose of 10 mg/kg body
Oxamniquine is administered orally. weight, once every other week for a total of three doses
(90% cure rate after 5–6 months of treatment). It is ef-
Geographic area Dosage regimen
fective against S. mansoni located in the perivesical plex-
South America, the Caribbean Adult dose: single dose of us but not those in mesenteric venules. Side effects may
islands, and West Africa 15 mg/kg body weight
include abdominal pain, diarrhea, vomiting, weakness,
Pediatric dose: two doses
of 10 mg/kg, at an
headache, and dizziness.
interval of 3 to 8 hours
East and Central Africa, and 15 mg/kg twice in 1 day
the Arabian Peninsula
CESTODES
Praziquantel
Ethiopia, Zaire, and West Nile 20 mg/kg twice in 1 day
Utility
Egypt, Sudan, and South 20 mg/kg daily for 3 days
Praziquantel is the drug of choice for treatment of infec-
Africa
tions by Dibothriocephalus (Diphyllobothrium) spp., Taenia
spp., and H. nana. It is slightly less effective than alben-
Triclabendazole (Egaten; Novartis) dazole for treatment of cysticercosis. It is also effective
Utility for treating sparganosis, D. caninum, H. diminuta, and
• An alternative drug for treatment of fascioliasis (Apt Mesocestoides infections. Praziquantel may be given in
et al., 1995) and pulmonary paragonimiasis (Calvo- conjunction with albendazole for the treatment of hy-
piña et al., 2003; Ripert et al., 1992). datid disease (Yasawi et al., 1993).
Triclabendazole is available from Victoria Pharmacy,
Zurich, Switzerland, but is only approved for veterinary Dosage and route of administration
use in the U.S. Praziquantel is administered orally.
Dosage and route of administration Clinical indication Dosage regimen

Triclabendazole is administered orally. D. latum, Taenia spp., Single dose of 5 to 10 mg/kg
D. caninum, Mesocestoides body weight (10 mg/kg for
Clinical indication Dosage regimen infections Mesocestoides)
Fascioliasis 10 mg/kg body weight twice in 1 day Sparganosis Total dose of 120 to 150 mg/kg
Pulmonary One or two doses of 10 mg/kg body body weight, over a 2-day period
paragonimiasis weight Cysticercosis 50 mg/kg body weight in three
divided doses daily for 15 days
Other Drugs for Treatment of Trematode H. nana, H. diminuta Single dose of 25 mg/kg body
Infections infections weight
Tetrachloroethylene
Tetrachloroethylene is an alternative effective treatment Niclosamide (Niclocide)
for infection with echinostomes, heterophyids, and G. Utility
hominis at a dose of 0.1 mL/kg (maximum adult dose • An alternative drug for treatment of D. latum in pa-
of 5 mL). It must be taken on an empty stomach after a tients unable to take praziquantel.
light meal the preceding night. Patients must avoid al- Niclosamide inhibits oxidative phosphorylation in
cohol and fats for 24 hours before and after treatment. the mitochondria of the worm. The drug is well tol-
Nothing other than water should be taken for 3 hours erated and is also effective for treatment of taeniasis,
after ingestion. D. caninum, H. nana, and H. diminuta infections.
Dosage and route of administration Nitazoxanide (Alinia)

Niclosamide is administered orally. Utility
The use of nitazoxanide as an alternative treatment for
Clinical indication Dosage regimen
H. nana and H. diminuta infections is investigational
D. latum, Taenia spp., Adults, 2 g single dose (Ortiz et al., 2002). It is FDA-approved for treatment of
D. caninum, and H. Children weighing >34 kg, 1.5 g
infections by Cryptosporidium and Giardia.
diminuta infections single dose
Children weighing 11 to 34 kg,
1.0 g single dose Dosage and route of administration
Nitazoxanide is administered orally.
H. nana infection Same dosage as above but must be
given daily for 5 days because of
the tissue phase of the infection Age group Dosage regimen
Adult dose 500 mg a day for 3 days
Considerations Pediatric dose Children 1 to 3 years, 100 mg twice a
Niclosamide is administered after a light breakfast. Side day for 3 days
effects for a small percentage of patients may include Children 4 to 11 years, 200 mg twice
daily for 3 days
abdominal cramps, diarrhea, nausea, and vomiting.
Albendazole Other Treatment Modalities

Utility Pharmacotherapy for Neurocysticercosis (NCC)
Albendazole, a member of the benzimidazole group of Many cases of neurocysticercosis are asymptomatic and
drugs that includes thiabendazole and mebendazole, require no treatment. Until recent years, all that could
has been used for treatment of cysticercosis. It has been be offered to symptomatic patients were anticonvulsants
preferred over mebendazole for treatment of hydatid to relieve seizures, corticosteroids if necessary, to control
disease because it is better absorbed and penetrates well symptoms secondary to meningitis or cerebral edema, and
into hydatid cysts (Gil-Grande et al., 1993). However, surgery in selected cases.
neither drug gives impressive cure rates in most studies Spontaneous disappearance of parenchymal cysticer-
(Todorov et al., 1992). ci is well documented, especially in children, suggesting
to some the advisability of symptomatic treatment in
Dosage and route of administration those for whom it is effective and following the evo-
Clinical indication Dosage regimen lution of the lesions with CT or MRI. Such treatment,
including the administration of dexamethasone (24 to
Cysticercosis Del Brutto et al. (1992, 1993): 15 mg/kg
body weight daily (maximum 800 mg 32 mg/day during the acute stage), is advised by various
per day) for 8 days (or 30 days) for authorities for those few patients who develop an acute
treatment of active parenchymal brain cysticercotic encephalitis, whose condition would prob-
and subarachnoid (racemose) cysts ably be exacerbated by anticysticercal treatment.
Garcia et al. (2004): 800 mg The simultaneous administration of steroids (e.g., dexa-
albendazole and 6 mg dexamethasone methasone 24 to 32 mg/day) is considered essential in the
per day for 10 days (reduces parasite treatment of subarachnoid cysts, but not for parenchymal
burden and number of seizures)
cysts. Dexamethasone administration may result in de-
Hydatid disease Cook (1990): 10 mg/kg body weight creased plasma levels of praziquantel (for which some
or 400 mg twice daily for 4 weeks, upward adjustment of dosage may be indicated) but
repeated as necessary for up to 12
actually increases those of albendazole. For treatment
cycles each separated by an interval of
of other forms of NCC, Del Brutto’s papers and those
2 weeks
of Badres et al. (1992) should be consulted.
Considerations Surgical Interventions
The drug is generally well tolerated, although side ef- Surgical treatment of neurocysticercosis includes direct
fects may include dizziness or headache, abdominal excision of ventricular cysts, shunting procedures to
pain, diarrhea, nausea, and vomiting. Serum levels of relieve hydrocephalus, and removal of cysts by means
albendazole are increased if taken with a fatty meal. It of stereotaxic endoscopy. In addition, surgical removal
should not be taken during pregnancy. of intraocular cysts is often possible, as chemotherapy
should not be used in these cases.
Surgical removal of one or a few sparganum larvae nematodes; treatment should be repeated in 2 weeks to
for treatment of sparganosis is usually possible. It also kill any worms that might have hatched from eggs pres-
an option for treatment of M. multiceps infection (Coe- ent at the time of initial treatment.
nurus disease) as mebendazole was not found to be Albendazole may also be used for treatment of S.
effective and there are no reports of the use of praziqu- stercoralis infection, including associated conditions
antel or albendazole. such as hyperinfection syndrome and chronic strongy-
Until recently the surgical removal of hydatid cysts, loidiasis. In chronic strongyloidiasis, treatment resulted
discussed in detail by Saidi (1976), was the only form in a cure rate of 75%. Re-treatment of initial treatment
of therapy possible. Recently, many reports favor the use failures was successful in only about one third of cases.
of percutaneous aspiration for pulmonary, hepatic, and Albendazole may be used for treatment of infections
other cysts accessible to this type of procedure. The most by Trichostrongylus spp., although there are no published
commonly used form of therapy is described by the acro- reports on its use. It is also effective against anisakiasis
nym PAIR (Percutaneous Aspiration, Injection—of hypertonic (Moore et al., 2002) and intestinal worms of the Oesoph-
saline or other scolicidal fluid—and Reaspiration), as de- agostomum spp. (Krepel et al., 1993; Ziem et al., 2004).
tailed by Akhan et al. (1994, 1996), Bastid et al. (1994), It has been effective for C. philippinensis infections, al-
Salama et al. (1995), Khuroo et al. (1997), and Smego though there has been little experience with its use.
et al. (2003). All of whom find it a safe and effective form
of therapy in selected cases. Ivermectin injected directly Dosage and route of administration
into cysts has been found to kill all protoscolices in ex- Albendazole is administered orally.
perimental animals (Ochieng-Mitula and Burt, 1996).
Monitoring therapy A. lumbricoides, E. Adults, single dose of 400 mg
In D. latum infections, worms are seldom passed spon- vermicularis, hookworm, Children under 2 years of age,
Trichostrongylus spp., single dose of 200 mg
taneously after administration of either praziquantel or
and Oesophagostomum
niclosamide. A saline purge may be given 1 to 2 hours
spp. infections
later to expel them in a more or less intact condition.
Trichuriasis and Adults, 400 mg per day for 3 days
The results of treatment of neurocysticercosis (NCC)
cutaneous larva Children under 2 years of age,
may be monitored by contrast-enhanced CT, gener- 200 mg per day for 3 days
migrans
ally done after an interval of 3 months. Remission or
S. stercoralis infection 400 mg (for children under 2 years
marked improvement in seizure activity is usually seen
of age, 200 mg) twice daily
after therapy (Vasquez and Sotelo, 1992).
for 2 days; treatment may be
The results of hydatid disease treatment are best repeated if necessary in 3 weeks
judged by ultrasonography or MRI, repeated at inter- Hyperinfection syndrome:
vals of approximately 3 months. It is generally agreed 400 mg daily for 15 days
that chemotherapy should be instituted a day or so be- Chronic strongyloidiasis: 400 mg
fore surgery or aspiration, then continued for a month twice daily for 3 days
after such procedures. C. philippinensis infection 400 mg daily for 10 days
Anisakiasis 400 mg twice daily for 21 days
INTESTINAL NEMATODES Considerations

Albendazole (Albenza, Zentel) Stimulation of migratory activity by the worms (i.e., A.
Utility lumbricoides) may occur during treatment. Side effects
• Drug of choice in treatment of A. lumbricoides, E. ver- of treatment are minimal, consisting of diarrhea and
micularis, hookworm (A. duodenale and N. america- abdominal pain. Hypersensitivity to albendazole has
nus), and T. trichiura infections. been reported but is rare.
• Drug of choice for treatment of cutaneous larva mi-
grans (Albanese et al., 2001). Mebendazole (Vermox)
Albendazole is a nitroimidazole that binds irrevers- Utility
ibly to tubulin, blocking microtubule assembly and in- • Drug of choice for treatment of C. philippinensis and
hibiting glucose uptake by the worms. Trichostrongylus spp. infections.
The use of albendazole in E. vermicularis infections Mebendazole has the same side effects and much
is not as effective as it is in treatment of most intestinal the same spectrum of activity against intestinal
roundworms as does albendazole. It may also be used an effective treatment regimen. A patient with Strongy-
for treatment of A. lumbricoides, hookworm, and T. loides hyperinfection and paralytic ileus, who was un-
trichiura infections. able to tolerate oral therapy, was successfully treated
with ivermectin administered as a rectal enema (Tarr
et al., 2003).
Mebendazole is administered orally.
Clinical indication Dosage regimen Dosage and route of administration

A. lumbricoides, hookworm, Adults and children over Ivermectin is administered orally.
T. trichiura, Trichostrongylus 2 years, 100 mg twice daily
spp. infections for 3 days
T. trichiura: alternatively, a Cutaneous larva 200 mcg/kg body weight daily for
single dose of 500 mg migrans 1 to 2 days
C. philippinensis infection 200 mg twice daily for 20 days S. stercoralis infection 200 mcg/kg body weight daily for
Dosage may be repeated in 2 days (cure rate ∼100%)
some chronic cases
Other Treatment Modalities
Pyrantel Pamoate (Antiminth) Ascaris lumbricoides
Utility In mixed infections with Ascaris and other intestinal
• An alternative drug for treatment of A. lumbricoides, parasites, it is good practice to treat initially with a drug
E. vermicularis, and hookworm infections. effective against Ascaris to obviate the change of stimu-
• Ineffective in strongyloidiasis and trichuriasis. lating that worm to untoward activity.
Pyrantel pamoate is a pyrimidine drug that depolar- When Ascaris worms obstruct the sphincter of Oddi
izes the myoneural junction in the worms, paralyzing or migrate up the biliary tree, acute abdominal pain
them in a spastic condition. suggestive of the passage of a gallstone, pancreatitis
or cholangitis may result, and surgical or endoscopic
removal of the worm has often been necessary. Bili-
Pyrantel pamoate is administered orally.
ary ascariasis is a regularly encountered complica-
Clinical indication Dosage regimen tion in China, where traditional Chinese medicine,
A. lumbricoides, E. Single dose of 11 mg/kg body
using nonoperative procedures involving herbal pre-
vermicularis, and weight (maximum dose 1 g) scriptions, is used in treatment. Ninety-five percent
hookworm infection E. vermicularis: the dosage must be of 9,192 diagnosed cases of biliary ascariasis were
repeated in 2 weeks successfully treated by such noninvasive procedures
(Zhou et al., 1999).
Considerations Intestinal obstruction due to ascarids is treated by
Occasional side effects of headache, dizziness, fever, nasogastric suction until vomiting is controlled. One or
nausea, and vomiting occur; abdominal cramps and two hours after suction is discontinued, an anthelmin-
diarrhea may also be seen. tic may be administered through the nasogastric tube,
which is allowed to remain in place. Although albenda-
Ivermectin zole, also available as an oral suspension, would seem
Utility the logical choice for treatment of this complication, no
• Used effectively for the treatment of cutaneous larva reports of its use have been published, and its proclivity
migrans and S. stercoralis infections. to stimulate migratory activity on the part of the worms
Ivermectin is a macrocyclic lactone antibiotic be- might be a reason not to use it in a patient who is ob-
longing to the group of avermectins derived from structed. The present recommendation is to treat with
Streptomyces avermitilis. It was first used in veterinary an initial dose of piperazine, 150 mg/kg body weight
medicine for the treatment of various nematode and (maximum dose 3.5 g). If vomiting recurs and suction
cutaneous arthropod infections. The mechanism of must be resumed, additional doses may be given at the
action involves modification of the release of the neu- rate of 65 mg/kg (maximum 1 g) every 12 hours for six
rotransmitter gamma-aminobutyric acid (GABA), re- doses. If there is no vomiting, the second dose is given
sulting in paralysis of the worm. orally, 24 hours after the first, and is repeated at 12-
In a small number of AIDS patients, 200 mcg/kg hour intervals for a total of six doses. The amount given
body weight daily for 2 days, repeated in 2 weeks, was is again 65 mg/kg. If this treatment is not successful or
if the obstruction is complete, surgical intervention will BLOOD- AND TISSUE-DWELLING

probably be necessary. NEMATODES
Diethylcarbamazine (DEC) (Hetrazan, Notezine)
Enterobius vermicularis
Utility
The worms may be eliminated by a variety of drugs and
• A drug of choice for M. streptocerca infections (active
by means as simple as warm tap water enemas, yet their
against adult worms and microfilariae).
eggs are so resistant and widespread that their reintro-
• Response to DEC is the sine qua non in the diagnosis of
duction into a household containing small children is
tropical pulmonary eosinophilia.
generally only a matter of time. In a family situation in
• Ineffective in treating M. ozzardi and M. perstans in-
which reintroduction of the parasite seems probable,
fections.
one may treat only those persons who are symptomatic
Diethylcarbamazine (DEC) is an effective micro-
or empirically treat the entire family. Tap water enemas,
filaricidal drug that may be used for the treatment of
repeated as necessary, control symptoms.
lymphatic filariasis caused by W. bancrofti, B. malayi,
Hookworms and B. timori. It is an effective drug against loiasis and
Hookworm infections, if symptomatic, are so generally infections by O. volvulus.
because of the concomitant anemia, and unless this is In patients with loiasis, drug use is contraindicat-
corrected eradication of the worms will be of little ben- ed in persons with blood microfilaria counts of 500
efit. In severe infections, ferrous sulfate, 200 mg, should or more per 20 µL, as determined by samples taken
be administered three times daily, at the time anthel- on two or more occasions at the appropriate time of
mintic treatment is begun, and continued for about day.
3 months after the hemoglobin value returns to normal In vitro, DEC possesses no microfilaricidal activity;
in order to replenish depleted iron stores. in vivo, its effect is dependent on the integrity of the
cellular and humoral immune mechanisms of the host.
Cutaneous larva migrans Most of the microfilariae are destroyed by the reticulo-
Where lesions are few, thiabendazole ointment, applied endothelial cells of the liver. It eliminates both adult
several times daily for 10 days or longer, gives good re- worms and microfilariae, although microfilariae are
sults but is unavailable in the United States or Canada. destroyed more rapidly.
The oral suspension of this drug, applied to the area
surrounding the advancing end of the larval burrow,
may be used in its place. Dosage and route of administration
Diethylcarbamazine is administered orally.
Capillaria philippinensis
In management of the acute illness, fluid and electro-
lyte replacement and a high-protein diet are important.
W. bancrofti infection 6 mg/kg of body weight daily for
Trichuris trichiura 12 days or once a month for a year
In diarrheic patients, loperamide hydrochloride (Imodi- Mass treatment programs: single
um) may help by increasing contact time between drug annual dose
and parasites. B. malayi infection Malaysia: cumulative doses of
36 mg/kg body weight at the rate
Anisakiasis of 6 mg/kg weekly for 6 weeks or
Other than reassurance, no treatment is needed for tran- at a daily dose over a period of
sient anisakiasis. In the gastrointestinal form of infec- 9 days (with an interval of 3 days
tion, where worms are embedded in the stomach or between the first and subsequent
bowel wall, a diagnosis can be made only by gastros- doses)
copy or surgery, which should also be curative. A his- L. loa infection 2 mg/kg body weight, three times
tory of consuming raw fish shortly before the onset of daily for 21 days
symptoms should suggest the possibility of anisakiasis. Prophylaxis: 300 mg once a week
Depending on the symptoms, gastroscopy or surgery (adult dosage)
may be in order. M. streptocerca 6 mg/kg body weight per day orally
infection for 14 days
Oesophagostomum spp. Tropical pulmonary 2 mg/kg three times daily for 7
Surgery is the only treatment for worms in extraintesti- eosinophilia (TPE) to 10 days (repeated courses are
nal foci (Polderman and Blotkamp, 1995). occasionally necessary)
Side effects and adverse reactions 13%, and 2% of the pretreatment levels for the three
DEC treatment is effective in loiasis, but not without treatment strategies, 1, 2, and 3, respectively.
risk, as it readily penetrates the blood-brain barrier and
in heavily infected persons may cause a fatal encepha-
Timor filariasis. In one village on the island of
litis (Carme et al., 1991). Its administration has also
Flores, Southeast Indonesia, DEC was administered to
been associated with retinal hemorrhage and possibly
all the inhabitants at the rate of 5 mg/kg body weight
with exacerbation of renal lesions.
daily for 10 days. This was repeated for all the inhab-
Rapidity of onset of its action against microfilariae
itants 3 years later. Yearly, for the first 5 years of the
of Onchocerca (basis of the Mazzotti test) can lead to se-
program, all new residents, all of whom were initially
vere side effects. The sudden death of enormous num-
microfilaremic, and all of whom had an attack of ad-
bers of microfilariae in the skin may give rise to intense
enolymphangitis during the preceding year, received
pruritus and localized edema, while in the eye it may
the same course of treatment. Additionally, at the time
lead to chorioretinal damage and keratitis.
of an attack of adenolymphangitis, each adult received
During treatment of M. streptocerca infections, the
a course of DEC, 300 mg daily for 10 days (150 mg
appearance of cutaneous papules containing worms
daily for children under 10 years old). Eleven years
(dead when biopsies were taken toward the end of
after the program started, a complete clearance of mi-
treatment) has been described following therapy.
crofilaremia was noted, with resolution of elephan-
Other side effects of DEC therapy include mild to
tiasis in approximately three-quarters of those ini-
severe pruritus, myalgias and arthralgias, headache, diz-
tially infected, principally in those with less advanced
ziness, and rarely, hypotensive episodes.
disease. Filarial antigen levels dropped dramatically
(Partono et al., 1989).
Mass treatment programs Administration of DEC at low dosage over an ex-
The use of DEC in mass treatment programs against tended period has also been found effective. Weekly
lymphatic filariasis has been reported. A practical dosage of the drug for 18 months (25 mg to children
method of administration of DEC in mass treatment under 10 years of age, 50 mg to all others) resulted
programs is by addition to table salt. This has been in a drop in microfilarial levels to those detectable
utilized in several very successful Chinese programs only by membrane filtration at 1 year, a decline in
(Fan et al., 1995; Liu et al., 1992), and in Tanzania adenolymphangitis, and a slower but dramatic effect
(Meyrowitsch et al., 1996). Addition of 0.2 to 0.4% on elephantiasis. Side effects of this low-dosage treat-
by weight of DEC to either plain or iodized salt is ef- ment were mild and confined to the first few weeks
fective and safe, and this concentration, when used of therapy. A single oral dose of 6 mg/kg body weight
steadily for 6 months to a year, will virtually eradicate of DEC combined with 400 mg albendazole has
the infection. been shown to have a long-term suppressive effect
on B. timori microfilariae for at least 1 year (Fischer
Wuchereria filariasis. A single annual dose is more et al., 2003).
practical for mass treatment programs. With all such
treatment programs, microfilariae disappear from the
blood of most patients within 2 weeks, to reappear in Ivermectin (Mectizan)
smaller numbers within 3 to 6 months. Based on para- Utility
site antigen levels before and following treatment, it • A drug of choice for treatment of M. streptocerca in-
is suggested that DEC administered at 6 mg/kg body fections (active only against the microfilariae)
weight daily for 12 days has approximately a 50% mac- • Ineffective in treating M. perstans infections
rofilaricidal effect; the once-yearly administration has a Ivermectin is a macrocyclic lactone antibiotic be-
lesser impact on the adult worms. longing to the group of avermectins derived from
The long-term effect of three different treatment Streptomyces avermitilis. Its efficacy in the treatment of
strategies for mass DEC administration was assessed filarial infections in animals led to a trial of ivermec-
in Tanzania 10 years following treatment (Meyrowitsch tin in human onchocerciasis and other filarial diseas-
et al., 2004). The strategies included (1) the standard es. It has a slower onset of action then DEC.
12-day treatment, (2) a semiannual single-dose treat- The drug may be used for the treatment of lym-
ment, and (3) a monthly low-dose treatment. All treat- phatic filariasis (i.e., W. bancrofti, B. malayi, B. timori),
ments were for 1 year. Ten years after the treatment of loiasis, and infections by M. ozzardi, O. volvulus, and
infected individuals, microfilarial intensities were 11%, G. spinigerum.
Dosage and route of administration For mass treatment programs, it seems that such
Ivermectin is administered orally. yearly drug treatment should be continued for at least
4 years.
Onchocerciasis. It is prudent to check for the pres-
W. bancrofti infection A single dose of ivermectin of
ence of microfilariae in the anterior chamber or cornea
400 mcg/kg body weight
Repetition at 6-month intervals is and, if they are found, to pretreat with steroids (such as
even more effective than a 12-day prednisone 1 mg/kg body weight daily) for 2 to 3 days
course of DEC in suppressing before the administration of ivermectin.
microfilaremia (Nguyen Numbers of skin microfilariae drop sharply after a
et al., 1996), comparable to the single dose of ivermectin, but small numbers remain
results achieved with once-yearly after a year. Treatment is repeated every 6 to 12 months
administration of ivermectin, until microfilariae are eliminated.
400 mcg/kg plus DEC 6 mg/kg It has been found that the drug has little initial ef-
(Moulia-Pelat et al., 1996)
fect on the adult worms, and the sustained reduction
B. malayi infection Single dose of 20, 50, 100, or in microfilariae is due to interference with embryo-
20 mcg/kg repeated in 6 months genesis to the microfilaria stage. However, when iver-
L. loa infection Martin-Prevel et al., 1993: a mectin at a dosage of 150 mcg/kg was repeated every
single dose of 400 mcg/kg body 3 months, Duke et al. (1992) found progressive reduc-
weight tion in the numbers of microfilariae being produced
Ranque et al., 1996: 200 mcg/kg
(none after 24 months) and in percentages of live fe-
every 3 months for 2 years
male worms as compared with those in nodules from
M. ozzardi infection A single dose of 200 mcg/kg of
control subjects. In a very large study in Malawi, involv-
body weight
ing administration of 150 to 200 mcg/kg of ivermectin
M. streptocerca infection A single dose of 15 mcg/kg of body yearly for 3 years, no serious side effects were noted
weight
(Burnham, 1993).
O. volvulus infection A single dose of 150 mcg/kg Ivermectin has been distributed on an annual basis
body weight repeated every 6 to
to individuals at risk of exposure to infection. In areas
12 months until microfilariae are
of west and central Africa, where O. volvulus and L. loa
eliminated
coexist, encephalopathy may result from ivermectin
G. spinigerum infection 200 mcg/kg daily for 2 days
treatment of individuals with high Loa loa microfilare-
mias, further complicating mass distribution programs.
Side effects and adverse reactions Since 1988, Merck & Co., Inc., has donated ivermec-
Ivermectin exerts its microfilaricidal effect more slowly. tin for mass drug treatment programs in Yemen, sub-
All the side effects mentioned for DEC may occur with Saharan Africa, and the Americas, with the goal of elim-
the use of ivermectin, but are usually milder (Sheuoy inating onchocerciasis as a public health problem. Ten
et al., 1992). The most common is pruritus, and ocular countries in West Africa have subsequently eliminated
reactions are minimal with treatment of onchocerciasis. onchocerciasis as a disease of public health importance
Boussinesq et al. (1998) report several cases with (Molyneux et al., 2003).
severe neurologic complications, including coma, in
patients being treated for onchocerciasis who had con- Albendazole
comitant infections (50,000 or more microfilariae per • A drug of choice for visceral larva migrans.
mL of blood) with Loa loa. Albendazole may also be used for treatment of M.
perstans and G. spinigerum infections. Administration
Considerations of the drug for 2 weeks to treat trichinellosis seemed
Wuchereria Filariasis. Better long-term suppression effective (Jongwutiwes et al., 1998), as treatment with
of microfilaremia is obtained by the concurrent admin- thiabendazole and mebendazole was not curative.
istration of DEC plus ivermectin (Mectizan), on the Albendazole has also been used in combination
same, once-yearly dosage schedule. The combination with either DEC or ivermectin in areas where both in-
seems preferable because of the macrofilaricidal prop- testinal roundworms and filariasis is a problem. Annu-
erties of DEC. al administration suppresses microfilariae comparable
to that seen with DEC plus ivermectin, with the added Metronidazole
advantage of elimination of Ascaris. • Drug of choice for D. medinensis infections.
The usual dose for adults is 250 mg three times daily
Clinical indication Dosage regimen for 10 days, and for children 25 mg/kg body weight in
three divided doses, not to exceed the daily adult dose.
Visceral larva migrans 400 mg twice a day for 5 days
Drug treatment facilitates removal of the worm.
M. perstans infection 400 mg twice daily for 10 days
G. spinigerum infection 400 mg twice a day for 21 days Other Treatment Modalities
Trichinella spp. infection 400 mg twice a day for 8 to Surgical interventions
14 days Surgical removal of D. medinensis worms by methods as
W. bancrofti infection Adults: a single dose of 400 mg primitive as twisting them around a stick has been prac-
Children: a single 200-mg dose ticed for centuries and may be quite successful if the
worm is removed whole. If in the process of its removal
Mebendazole the worm is broken, secondary infection almost always
• The drug of choice for treatment of trichinosis and develops. Migrating adult L. loa worms may also be sur-
visceral larva migrans. gically removed when they are crossing the bridge of
Mebendazole has also been used for treatment of M. the nose or are in the conjunctiva.
perstans infections with a high cure rate. Administration Surgery is the only available form of treatment for
of mebendazole in patients infected with D. medinensis infections by A. costaricensis and D. renale. Moreover,
apparently kills the worms. diagnosis of A. costaricensis infections are usually made
Mebendazole is recommended as an investigational by surgery. Treatment of L. minor infections has also
drug for adults when specific antihelminthic treatment been primarily surgical. G. spinigerum may be surgically
seems necessary in A. cantonensis infections, although removed from subcutaneous and other accessible loci.
only symptomatic therapy is usually warranted. The
drug has also been recommended for treatment of A. Wuchereria bancrofti
costaricensis infections. Attacks of filarial lymphangitis often respond to the
administration of antihistamines and analgesics. In
more advanced cases in which secondary infection may
Clinical indication Dosage regimen be involved, antibiotic therapy is appropriate. In such
Trichinella spp. infection Adults and children over 2 years, cases, careful hygienic measures may help prevent re-
200 to 400 mg three times current infection and lymphangitis.
daily for 3 days Periodic checks of microfilarial load (either by mi-
Visceral larva migrans 100 to 200 mg twice a day for crofilaria counts on thick blood smear, by membrane
5 days filtration technique, or by one of the newer antigenic
M. perstans infection 100 mg twice daily for 30 days assays) may be used as a guide for re-treatment, both
D. medinensis infection 400 to 800 mg per day for 6 days of mass treatment programs and for the individual
patient.
A. cantonensis infection Adults, 100 mg twice daily for
5 days Allergic reactions to death of the microfilariae may
occur early in treatment and tend to be severe in fila-
riasis malayi; these reactions consist of fever, urticaria,
Thiabendazole and lymphangitis, and are usually well controlled with
• Recommended for A. costaricensis infections. antihistamines or smaller doses of DEC treatment. Later,
Thiabendazole has been used for treatment of D. bullous reactions may occur, requiring the use of corti-
medinensis, at a dose of 50 mg/kg daily for 2 days. How- costeroids. These uncommon reactions are also thought
ever, side effects are more common than with metroni- to be allergic in nature. Filarial abscesses, which may oc-
dazole. Both drugs facilitate removal, but neither kills cur at any point along a lymphatic chain, denote death
the worm. of the adult worm and a hypersensitivity reaction to its
A single report also suggests its efficacy in treating remains. Portions of the dead worm can at times be ob-
a S. laryngeus infection. Although thiabendazole treat- served when the abscess is drained. Generalized malaise,
ment has some effect in animal infections, it was found vertigo, headache, nausea, and vomiting are occasional
to be ineffective in reported human cases. side effects of administration of these drugs.
Surgical procedures for treatment of scrotal elephan- retina; there is no known effective systemic treatment.
tiasis are generally satisfactory; hydrocele may also be Treatment of L. minor infections has been primarily sur-
treated by the accepted surgical means. Newer surgical gical. Levamisole (approved in the United States and
techniques produce fair results in treatment of elephan- Canada only for treatment of colorectal carcinoma and
tiasis of the extremities. The use of elastic bandages or melanoma) is reported to have some value in treatment
Unna’s paste boots may gradually reduce the size of of this infection (De Aguilar-Nascimento et al., 1993).
affected limbs. Corticosteroids, administered with cau-
tious supervision and never in the presence of bacterial SUMMARY
or fungal infection, may be used for a short time in con-
junction with bandaging at the onset of treatment of el- LUMEN-DWELLING PROTOZOA
ephantoid extremities to soften the woody induration. • Metronidazole and tinidazole are the mainstay drugs
for treatment of invasive E. histolytica infections.
Onchocerca volvulus Diloxanide furoate is a luminal amoebicide indicated
Doxycycline treatment of individuals with 100 mg per for asymptomatic cyst passers.
day for 6 weeks, which acts against the Wolbachia endo- • Metronidazole and tinidazole are the first-line agents
symbionts, will produce permanent sterility in adult fe- for treatment of giardiasis.
male O. volvulus (Hoerauf et al., 2000). Elimination of • Metronidazole is effective for treatment of vaginal
the worm’s endosymbiotic bacteria by antibiotics may trichomoniasis and treatment of sexual partners.
become an adjunct to control in the overall manage- • Treatment of intestinal sporozoa involves TMP/SMX
ment of onchocerciasis. for C. belli and C. cayetanensis, and nitazoxanide
Suramin is a macrofilaricide when used for the treat- for cryptosporidiosis.
ment of onchocerciasis. It is quite toxic, and its use for
this purpose is now seldom warranted. MALARIA
Nodulectomy— the surgical removal of palpable • Suppressive therapy (chemoprophylaxis) destroys
nodules—has long been practiced in Mexico and Gua- parasites as they enter the bloodstream.
temala. It is credited with markedly decreasing the • Clinical cure (treatment dose) eliminates large
ocular complications of the disease. Special teams of numbers of erythrocytic parasites in a clinical attack.
paramedics make periodic visits to the remote coffee • Radical cure eliminates the bloodstream infection
plantations where the disease is most prevalent to per- and tissue stages in the liver.
form this procedure. • Blood schizonticides used for suppression of an
acute attack of malaria include quinine, quinine,
Trichinella spp. chloroquine, hydroxychloroquine, amodiaquine,
In severely symptomatic infections, corticosteroids are pyrimethamine, mefloquine, halofantrine,
beneficial and may at times be lifesaving. Recognition tetracycline, doxycycline, proguanil, and artemisinin.
that, as mentioned previously, the intestinal phase of • Tissue schizonticides used to destroy
the infection may be prolonged by their use suggests developmental malarial stages in the liver include
that they should be reserved for cases in which there primaquine and some blood schizonticides (e.g.,
is considerable toxicity. The initial dose may be 20 to proguanil, pyrimethamine, tetracyclines).
60 mg prednisone, or its equivalent, reduced after the • Gametocyticides include chloroquine and
first few days to the lowest dose that alleviates symp- amodiaquine for gametocytes of all malarial
toms and then gradually discontinued. parasites except mature P. falciparum gametocytes.
Primaquine is gametocyticidal for all four species of
Visceral larva migrans human malarial parasites.
The disease is self-limited, frequently first coming to • For chemoprophylaxis, the CDC recommends
the attention of the physician at a time when the symp- the use of chloroquine, or in areas with reported
toms are at their worst. Watchful waiting is advised, chloroquine resistance, mefloquine.
and corticosteroids (employed as in trichinellosis) are • Quinine and quinidine are the drugs of choice for
reserved for patients who are severely symptomatic ex- treatment of resistant falciparum malaria.
cept in the ocular form of infection, where their early • Chloroquine is the mainstay of blood schizonticidal
use may be of great benefit. therapy for all malarial species and is recommended
for chemoprophylaxis and treatment of
Uncommon tissue nematodes uncomplicated malaria in areas where resistance
In patients with B. procyonis infections, laser photoco- (i.e., CRPF) is not known to occur.
agulation has been employed to destroy larvae in the
• Hydroxychloroquine and amodiaquine is similar • Sodium stibogluconate is effective for treatment of

to chloroquine in terms of efficacy, toxicity, and mucocutaneous leishmaniasis. Other drugs used
development of resistance by P. falciparum. for treatment include cycloguanil pamoate and
• Proguanil is generally useful against P. falciparum in amphotericin B.
East Africa. It is less effective against P. vivax. • Sodium stibogluconate is the drug of choice for
• Doxycycline may be administered for initial therapy of all visceral leishmaniasis, except
chemoprophylaxis of malaria in multidrug- Sudanese infections which should be treated initially
resistant areas either alone, or in conjunction with with pentamidine. Other drugs used for treatment
mefloquine, quinine, or other antimalarials. include allopurinol and miltefosine.
• Pyrimethamine-based drugs include pyrimethamine- • Combination therapy with pyrimethamine and
sulfadoxine (Fansidar), pyrimethamine-sulfadoxine- trisulfapyrimidines has been effective for treatment
mefloquine (Fansimef), and pyrimethamine-dapsone of toxoplasmosis.
(Maloprim). • Combination therapy with clindamycin-quinine
• Primaquine is effective against hypnozoites of P. vivax or atovaquone-azithromycin has been used for
and P. ovale. It is also gametocyticidal for all four treatment of babesiosis.
species of human malarial parasites. Tafenoquine, • Treatment of primary amoebic meningoencephalitis
an 8-aminoquinoline drug similar to primaquine, has has mainly been through the use of amphotericin
recently been approved for chemoprophylaxis and is B-based regimens.
also effective against P. vivax hypnozoites. • Case reports for Acanthamoeba spp. infections,
including granulomatous amoebic encephalitis
OTHER BLOOD- AND TISSUE-DWELLING
and acanthamoeba keratitis, and Balamuthia spp.
PROTOZOA
infections provide various treatment protocols.
• Drugs and treatment schedules used for treatment
of Gambian and Rhodesian sleeping sickness are TREMATODES
the same. Neurologic involvement may occur earlier • Oral praziquantel is the drug of choice for treatment
in the Rhodesian type of infection. of intestinal flukes, clonorchiasis, opisthorchiasis, all
• Suramin is effective in early stages of African schistosomal infections, and both pulmonary and
sleeping sickness wherein there is no evidence of cutaneous forms of paragonimiasis.
neurological involvement. • Bithionol is the drug of choice for treatment
• Pentamidine is effective only in the hemolymphatic of fascioliasis. It is also an alternative drug for
stages of African sleeping sickness. treatment of pulmonary paragonimiasis.
• Melarsoprol is the drug of choice for treatment • Triclabendazole is an alternative drug for treatment
of Gambian sleeping sickness with neurologic of fascioliasis and pulmonary paragonimiasis.
involvement. • Oxamniquine may be used as a less expensive
• Eflornithine is highly effective for both early- and alternative drug for treatment of S. mansoni
late-stage Gambian sleeping sickness but is not infections. Metrifonate may be used as an
effective against the Rhodesian type of infection. alternative drug for treatment of S. haematobium
• Nifurtimox is the drug of choice for treatment of infections.
American trypanosomiasis (Chagas’ disease). • Tetrachloroethylene is an alternative drug for
• Other drugs used for treatment of Chagas’ disease treatment of infection with echinostomes,
include benznidazole and allopurinol. heterophyids, and G. hominis.
• Sodium stibogluconate is the most effective
CESTODES
compound available for treatment of all cutaneous
leishmaniasis, except the Ethiopian form of diffuse • Oral praziquantel is the drug of choice for treatment
cutaneous leishmaniasis which responds best to of infections by Dibothriocephalus (Diphyllobothrium)
pentamidine. spp. Taenia spp., and H. nana. It is also effective
against other tapeworm infections.
• Meglumine antimoniate is a substitute for sodium
stibogluconate for treatment of cutaneous • Niclosamide is an alternative drug for treatment of
leishmaniasis in areas where it is not readily available. D. latum in patients unable to take praziquantel.
• Other treatment modalities for cutaneous • Other drugs used in treatment of tapeworm
leishmaniasis include amphotericin B, azole infections include albendazole (for cysticercosis and
antifungals, topical medications, and heat hydatid disease) and nitazoxanide (for H. nana and
treatment. H. diminuta)
REVIEW QUESTIONS
• Symptomatic treatment of neurocysticercosis include 1. Mainstay drugs for treatment of invasive E. histolytica
corticosteroid therapy and surgical procedures.
disease include
• The most commonly used protocol for surgical a. Metronidazole
removal of hydatid cysts is described by the
b. Tinidazole
acronym PAIR (Percutaneous Aspiration, Injection,
c. Diloxanide furoate
and Reaspiration).
d. Both A and B
INTESTINAL NEMATODES
• Albendazole is the drug of choice for treatment 2. The type of antimalarial therapy that destroys ma-
of A. lumbricoides, E. vermicularis, hookworm (A.
larial parasites as they enter the bloodstream
duodenale and N. americanus), and T. trichiura
infections, and cutaneous larva migrans. It is also
a. Suppressive therapy
effective against other intestinal nematodes. b. Clinical cure
• Mebendazole is the drug of choice for treatment
c. Radical cure
of C. philippinensis and Trichostrongylus spp. d. None of the above
infections. It is also effective against other intestinal
nematodes. 3. The mainstay drug for blood schizonticidal therapy
• Pyrantel pamoate is an alternative drug for against all malarial species except for CRPF
treatment of A. lumbricoides, E. vermicularis, and a. Quinine
hookworm infections. Ivermectin has been used b. Quinidine
effectively for the treatment of cutaneous larva
c. Chloroquine
migrans and S. stercoralis infections.
d. Primaquine
BLOOD- AND TISSUE-DWELLING NEMATODES
• Diethylcarbamazine (DEC) is a drug of choice 4. A tissue schizonticide effective against tissue stages
for treatment of M. streptocerca infections. It is of malarial parasites (e.g., hypnozoites of P. vivax
active against both adult worms and microfilariae. and P. ovale)
Response to DEC has been used for diagnosis of a. Quinine
tropical pulmonary eosinophilia. It may also be used
b. Quinidine
for treatment of lymphatic filariasis and infections by
c. Chloroquine
other filarial worms.
d. Primaquine
• Ivermectin is a drug of choice for treatment of M.
streptocerca infections, although it is only active
against the microfilariae. It may also be used for 5. The CDC recommends this drug for chemoprophy-
treatment of lymphatic filariasis and infections by laxis in malarious areas with reported chloroquine
other filarial worms. resistance
• Albendazole is a drug of choice for treatment of a. Doxycycline
visceral larva migrans. It may also be used for b. Mefloquine
treatment of M. perstans, G. spinigerum, Trichinella c. Quinine
spp., and W. bancrofti infections. d. Quinidine
• Mebendazole is the drug of choice for treatment of
trichinosis. It is also a drug of choice for treatment 6. The drugs of choice for treatment of chloroquine-
of visceral larva migrans. The drug is effective
resistant falciparum malaria
against other filarial worms and nematodes.
a. Quinine and doxycycline
• Thiabendazole is recommended for treatment of A.
b. Quinine and quinidine
costaricensis infections. It has also been reported to
c. Fansidar and Fansimef
be effective against D. medinensis and S. laryngeus.
d. Maloprim and Malarone
• Metronidazole is the drug of choice for treatment
of D. medinensis infections. Treatment facilitates
removal of the worm. 7. A constellation of dose-related and reversible side
effects of quinine treatment
• Other treatment modalities for filarial and other
nematode infections include surgical interventions, a. Cardiotoxicity
symptomatic treatment of allergic reactions, and the b. Nephrotoxicity
use of other drugs. c. Cinchonism
d. Salicylism
8. The drug of choice for treatment of Gambian sleep- 15. An alternative drug for treatment of D. latum infec-
ing sickness with neurologic involvement tion in patients unable to take praziquantel
a. Suramin a. Niclosamide
b. Pentamidine b. Nitazoxanide
c. Melarsoprol c. Praziquantel
d. Eflornithine d. Albendazole
16. The most commonly used protocol for surgical re-

9. The drug of choice for treatment of American try-
moval of hydatid cysts is described by the acronym
panosomiasis (Chagas’ disease)
a. FAST
a. Nifurtimox
b. PASS
b. Benznidazole
c. PAIR
c. Allopurinol
d. PARE
d. Amphotericin B
17. The drug of choice for treatment of A. lumbricoides,
10. The most effective compound available for treat- E. vermicularis, hookworms, and T. trichiura
ment of all cutaneous leishmaniasis except the a. Albendazole
Ethiopian form of diffuse cutaneous leishmani- b. Mebendazole
asis c. Metronidazole
a. Sodium stibogluconate d. Pyrantel pamoate
b. Meglumine antimoniate
c. Allopurinol 18. Severe symptomatic hookworm infections may war-
d. Amphotericin B rant supplementation with this vitamin/mineral as
supportive therapy for the concomitant anemia
a. Zinc
11. All known survivors of primary amoebic menin- b. Ferrous sulfate
goencephalitis (PAM) have been treated with this c. Cobalamin
drug included in the treatment regimen d. Folate
a. Miconazole
b. Rifampin 19. The drugs of choice for treatment of M. streptocerca
c. Amphotericin B infections
d. Clotrimazole a. Diethylcarbamazine and albendazole
b. Ivermectin and albendazole
12. The drug of choice for treatment of clonorchiasis, c. Diethylcarbamazine and ivermectin
opisthorchiasis, and all schistosomal infections d. Mebendazole and albendazole
a. Praziquantel
20. The drug of choice for treatment of D. medinensis
b. Bithionol
infections
c. Oxamniquine
a. Diethylcarbamazine
d. Albendazole
b. Ivermectin
c. Albendazole
13. The drug of choice for treatment of fascioliasis d. Metronidazole
a. Praziquantel
b. Bithionol Answers to review questions are available at the end of this
c. Oxamniquine book.
d. Albendazole
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GLOSSARY
Signs and Symptoms of Parasitic

Disease
It must be emphasized that the following defined terms and may be referred to the tip of the right (less com-
are not intended as a complete differential diagnosis of monly the left) scapula (Martínez-Palomo, et al., 2017).
any of the symptoms discussed. Limitations of space do Amoebic Liver Abscess (ALA) is the most common
not permit even mention of the various nonparasitic manifestation of extraintestinal infection caused by
causes of many of these conditions. Entamoeba histolytica – an invasive form of amoebiasis.
ABDOMINAL PAIN ABSCESS, FILARIAL

Abdominal pain refers to increased spasmodic contrac- Abscesses may develop spontaneously or appear shortly
tion of abdominal muscle characterized by amoebic after antifilarial treatment is begun. They occur along
colitis, with tenesmus if ulcerations involve the rectal the course of lymphatics or at lymph nodes and may
area. It is observed in symptomatic infections that is be distinguished from pyogenic abscesses by the fact
usually associated with diarrhea accompanied by infre- that they are generally sterile when first opened and
quent, high-pitched bowel sounds. that fragments of the adult worms may be found in
In giardiasis, the pain is usually mild but may oc- the abscess drainage. Filarial abscesses are even more
casionally be severe; it is usually crampy and may be common in Brugia infections than in those caused by
accompanied by steatorrhea and a full-blown malab- Wuchereria.
sorption syndrome. On the other hand, pain is seldom
present in intestinal worm infections.
Intestinal or biliary obstruction (the former primarily ANEMIA
occurs in smaller children) can be the result of ascaria- Anemia is characterized by reduced red blood cell
sis, with signs and symptoms that mimic obstruction of counts, hemoglobin, and hematocrit. It is frequently
these passages from any other cause. Strongyloides sterco- associated with malaria, hookworm, and broad fish
ralis, invading the mucosal wall, may cause a severe duo- tapeworm infections, it may be observed in babesiosis,
denitis or jejunitis, with symptoms suggestive of duode- kala-azar, trypanosomiasis, schistosomiasis, fasciolop-
nal ulcer disease. Anisakid larvae, penetrating the wall of siasis, and trichuriasis.
the stomach or small bowel, may give rise to symptoms In P. falciparum malaria the red blood cell count may
suggestive of gastric or duodenal ulcer or appendicitis. fall to 2.5 to 4.0 million per mm3 in cases of average
Angiostrongylus costaricensis most frequently invades the severity, and fewer than 1.0 million per mm3 in severe
bowel wall in the region of the appendix, with pain in infections. Anemia is usually not severe in P. vivax ma-
the right iliac fossa. Moderate to heavy eosinophilia gen- laria and is still less pronounced in quartan infections.
erally accompanies these invasive worm infections. Iron deficiency anemia is the leading form of anemia
and is commonly associated with hookworm infec-
tions. The characteristic microcytic hypochromic anemia
ABSCESS, AMOEBIC of hookworm infection is the result of blood loss and is
Amoebic invasion of the liver is characterized by tender- thus proportional to the severity of infection, although
ness and enlargement of that organ, progressive mal- adequate dietary intake of iron may prevent its develop-
aise, an irregularly spiking fever with night sweats, leu- ment in light or moderate infections. The small amount
kocytosis, elevation and fixation of the right diaphragm of blood ingested per Trichuris worm makes anemia rare
(often seen on presenting chest radiograph), and some- except in massive infections. Persons heavily and chron-
times development of a right lower lobe pneumonitis. ically infected with Dibothriocephalus latus (formerly
With abscess formation, pain becomes more intense Diphyllobothrium latum) may develop megaloblastic
315
anemia (macrocytic hyperchromic anemia) on the basis CALABAR SWELLINGS (ALSO KNOWN AS
of vitamin B12 deprivation if the worm is attached to the FUGITIVE SWELLING)
jejunal wall. In kala-azar, and possibly also in Chagas’ Transient migratory angioedema or circumscribed
disease, anemia may be a consequence of proliferation subcutaneous swellings seen in Loa loa infections. The
of infected reticuloendothelial cells in the bone marrow. swellings are usually intensely pruritic and may be
In trypanosomiases, schistosomiasis, and certain intes- quite painful if they develop in areas where there is
tinal helminthic infections such as fasciolopsiasis, ane- little loose subcutaneous tissue, such as the elbows and
mia may result in part from nutritional causes. knees. They appear rapidly, developing within an hour
or so to a diameter of several centimeters, and persist
for several days; if in an area subject to repeated trauma
APPENDICITIS
they may last a week or longer.
Amoebic ulceration involving the cecal area or appendix
may simulate acute appendicitis; when there is extensive
cecal ulceration surgical intervention may be disastrous. CALCIFICATIONS, CEREBRAL
Ascaris may block the lumen of the appendix and give Calcification of areas of intracerebral infection in con-
rise to appendicitis; this is reported also for Trichuris. genital toxoplasmosis may be seen on radiographs,
Angiostrongylus costaricensis infection may also mimic and when intracerebral calcifications are found in a
appendicitis, as may the response to a black widow spi- patient who has retinochoroiditis, toxoplasmosis is
der bite. Appendicitis maybe reported in cases of amoe- highly probable. Calcified cysts of Taenia solium larvae
biasis, balantidiasis but in enterobiasis it is still unproven. within the brain may be distinguished by their size and
uniform rounded or oval shape, and subretinal lesions
may also be observed by funduscopy.
ASCITES
Ascites is the excessive accumulation of fluids in the
peritoneal cavity seen in schistosomiasis. CHAGOMA
Circumoval tissue proliferation leading to extensive The hard, reddened, raised primary lesion in Trypano-
fibrosis of the liver in Schistosoma mansoni and S. ja- soma cruzi infection (Chaga’s disease) usually develops
ponicum infections may lead eventually to a condition on the head or neck, and sometimes on the abdomen
clinically very similar to Laënnec’s cirrhosis, with por- or limbs, and may persist for 2 to 3 months.
tal hypertension, splenomegaly, and ascites. Although
hepatomegaly and splenomegaly occur early in kala-
azar, ascites is uncommon. It may occur in chronic cas- CHYLURIA
es, probably secondary to a nutritional cirrhosis (Ryan Chyluria refers to the urinary excretion of chyle, a lym-
and Tsochatzis, 2018). phatic fluid rich in chylomicrons.
The formation of lymphatic varices, consequent to
repeated attacks of filarial lymphangitis and obstruc-
ASTHMA, BRONCHIAL tion of lymphatic drainage, may lead to passage of lym-
Asthmatic attacks may occur in Ascaris infection dur- phatic fluid in the urine if varices rupture into any part
ing the stage of migration through the lungs, or later of the urinary tract. Chyluria usually occurs in attacks
in the course of the infection because of hypersensitiza- that last a few days; the urine may be milky white and
tion to the absorbed worm antigens. IgE sensitization to contain microfilariae.
A. lumbricoides is the most important risk factor for
asthma (Zakzuk et al., 2018). It is common in visceral
larva migrans infections, in which there is usually an COMA
accompanying hepatomegaly and marked eosinophil- Seen in cerebral malaria among patients with malarial
ia. House dust mites, belonging to the genus Derma- parasitemia. It is a sudden onset or unexplained coma
tophagoides, are important cause of nasal allergies and in a patient suffering from infection caused by P. fal-
asthma, especially in children. See also tropical eosino- ciparum, or in an apparently healthy person who is in
philia, under Eosinophilia. or has recently returned from a malarious area, should
always suggest cerebral malaria and requires emergency
treatment. Occurs less frequently in African trypanoso-
BLACKWATER FEVER miasis, but coma develops after a protracted period of
See Hemoglobinuria. increasingly severe complications meningoencephalitis.
GLOSSARY Signs and Symptoms of Parasitic Disease 317
It is also seen in primary amoebic meningoencephalitis, severe, often with the formation of papules or vesi-
in which a history of rapidly developing fever, menin- cles. It may last a couple of weeks or longer if there is
geal signs, confusion, loss of smell, and coma and of a secondary infection. The cutaneous larva migrans
recent swimming or diving in fresh water may often be (CLM) reaction caused by larvae of Ancylostoma bra-
elicited. ziliense or Ancylostoma caninum is characterized by a
Cerebral cysticercosis may be a diagnostic consider- reddened papule at the site of entry; the larva forms
ation in persons of Mexican or Latin American origin, a reddened serpiginous tunnel, at first covered with
who present with a variety of neurologic symptoms, vesicles, later dry and crusted, often with localized
including new onset seizures, headache, alteration of edema at the active end that advances at the rate of a
consciousness, coma, and internal hydrocephalus. Di- few millimeters to centimeters a day. The area itches
agnosis may be difficult, and eosinophilia (either pe- intensely; without treatment, infection may persist
ripheral or of the spinal fluid) is not always present. several weeks or months. Strongyloides larvae may pro-
duce similar cutaneous lesions, but because of their
more rapid subcutaneous movement, they are referred
CONJUNCTIVITIS to as larva currens.
Chronic conjunctivitis is seen in onchocerciasis or river Presence of adult Loa loa beneath skin may be indi-
blindness. Characterized with hyperpigmentation of cated by a thin, raised reddened line, a few centimeters
the conjunctiva, photophobia, and gradual develop- in length. The adult female Dracunculus also may be vis-
ment of corneal opacities; acute exacerbations of con- ible beneath the skin but usually produces no reaction
junctivitis and photophobia may be associated with until it is about to larviposit, when a vesicle forms over
attacks of onchocercal dermatitis. the point at which the worm will break through the
skin. In onchocerciasis, the presence of microfilariae
in the skin sometimes elicits an acute pruritic inflam-
CONVULSIONS matory reaction resembling erysipelas that is usually
Focal convulsive seizures seen in a number of para- confined to the face, neck, and ears. Repeated acute at-
sitic infections that involve the central nervous system. tacks may result in a chronic lichenification, with hy-
These are discussed under Neurologic Symptoms. Con- perpigmentation and fissuring. Itching may be intense
vulsions also may be seen in the malarial paroxysm, and scratching almost constant, with skin excoriations
in acute toxoplasmosis occurring in newborn children, present.
and in Ascaris infection in children. The migration of Sarcoptes scabiei through the skin
produces lesions resembling those of cutaneous larva
migrans but frequently seen in parts of the body that
DERMATITIS have no contact with soil. The mites invade the upper
Inflammation of the skin seen in leishmaniasis, schis- layers of the epidermis, in which they form sinuous
tosomiasis, filariasis, and larval strongyloidiasis and burrows. They seem to have a predilection for the in-
hookworm infections. terdigital, popliteal, and inframammary folds and the
Dermal leishmanoid is a secondary cutaneous mani- groin. Intense itching, with formation of small vesi-
festation of Leishmania donovani infection, occurring a cles and crusting of the chronic excoriated lesions, is
year or so after supposedly successful treatment of kala- typical.
azar. The lesions may be flattened or depressed depig- The larvae of the horse botfly, Gasterophilus, produce
mented macules, or erythematous nodules that, on the similar cutaneous lesions in man. Chiggers and other
face, often occur in a butterfly distribution reminiscent mites attack the skin, evoking a pruritic maculopapular
of lupus erythematosus or Hansen’s disease (leprosy). dermatitis. Pediculosis in hypersensitive persons, usu-
Leishmanial amastigotes are found in the lesions. ally as a result of repeated exposure, may give rise to a
Dermatitis occurs when schistosome cercariae pen- severe localized reaction, with reddish papules at the
etrate through the skin causing localized edema and feeding site, and surrounding vesiculation and a weep-
pruritus, mild in the case of the human schistosomes. ing dermatitis. Bronzing of the affected area may persist
Dermal irritation caused by bird schistosome cer- following healing.
cariae is also referred to as swimmer’s itch. A similar The chigoe flea, Tunga penetrans, produces local pru-
localized pruritic reaction occurs with penetration of ritus as it lies partly buried in the skin of the toes or
Strongyloides larvae through the skin; the reaction to elsewhere on the body; secondary infections by clos-
penetration of hookworm larvae is somewhat more tridia are not uncommon.
DIARRHEA diarrhea. Maturation of Trichinella within the wall of

Diarrhea in parasitic diseases may have diverse causes the duodenum and jejunum produces nausea, vom-
transmitted by the fecal-oral route through water, food iting, colicky abdominal pain, and diarrhea, starting
and to person-to-person transmission. Clinical patterns about 24 hours after infection and lasting up to 5 days.
of infectious diarrhea can be of: bloody diarrhea (dys- In Strongyloides infections there may be mild diarrhea
entery); acute watery diarrhea; and persistent diarrhea, alternating with periods of constipation, or the diar-
which may be accompanied by fecal fats (steatorrhea). rhea may be severe and prostrating. In heavy infections
In kala-azar, infiltration of the submucosa with ulceration and sloughing of the intestinal mucosa may
leishmania-containing macrophages may lead to mu- take place, with dysentery and often with secondary
cosal ulceration and diarrhea. Plugging of the mucosal bacterial infection and fever. Capillaria philippinensis in-
capillaries with parasitized red blood cells may lead, fections may result in profuse diarrhea, malabsorption,
in falciparum malaria, to a watery diarrhea so profuse and protein-wasting enteropathy.
as to suggest cholera. Blood containing parasitized red In Schistosomiasis mansoni and japonicum, there is di-
blood cells may be found in the stools. The diarrhea or arrhea, presumably of toxic origin, associated with nau-
dysentery is usually accompanied by nausea and vom- sea, vomiting, hepatic tenderness, fever, eosinophilia,
iting. Mucosal ulceration in amoebiasis or balantidia- and urticarial rash during the period when the worms
sis may produce diarrhea or, if the ulceration is more are maturing in the liver sinusoids. Somewhat later,
extensive, dysentery (q.v.). Cystoisospora belli (formerly with the beginning of egg deposition in the intestinal
Isospora belli) develops within the epithelial cells of the wall, there may be profuse diarrhea or dysentery.
lower ileum and cecum. Infection is self-limited, lasting In previously uninfected persons, the onset of a
usually a month or less. In some cases, there is mild heavy hookworm infection may be marked by nausea,
abdominal pain, nausea and vomiting, and diarrhea. vomiting, epigastric or midabdominal tenderness, and
Cryptosporidium invades the brush border of the epithe- diarrhea. The diarrhea is presumably caused by toxicity
lial cells of the intestine. In immunocompetent persons or hypersensitivity, although mechanical irritation may
it gives rise to a mild and self-limited diarrhea lasting play some part. The same may be said of the diarrhea
a week or so, whereas in immunodeficient persons, it in heavy whipworm infections, which may, in children,
produces a severe and prolonged infection like that be accompanied by rectal prolapse. In fasciolopsiasis,
seen in isosporiasis, often with malabsorption. diarrhea, which usually has its onset about a month
One of the most recently defined parasitic causes of after infection takes place, is characterized by the pas-
diarrheal disease is the coccidian Cyclospora cayetanen- sage of stools containing much undigested food; severe
sis, which produces a syndrome clinically indistinguish- infections are accompanied by symptoms of severe
able from those due to Cryptosporidium or Cystoisos- malnutrition: edema of the face, abdominal wall, and
pora belli. Uncreated cyclosporiasis encompasses the lower extremities; ascites; and prostration. The diarrhea
range of mild to moderate and self-limited (in immu- sometimes seen in Taenia and broad fish tapeworm in-
nocompetent persons) through profuse, watery diar- fections and in infections with the smaller intestinal
rhea, frequently prolonged for weeks to months (in flukes may be related to local irritation.
patients with AIDS), with an incubation period of 2 to Blastocystis hominis, a frequent, unicellular stool in-
11 days, and accompanied by a generalized enteropathy habitant of incompletely defined phylogenetic affinity,
manifested by nausea, vomiting, anorexia, abdominal is mentioned in the context of diarrheal disease for the
cramping, weight loss, and mild fever (Topazian and sake of both completeness and dismissal. Although
Bia, 1994; Wurtz, 1994). In addition, this coccidian has long the subject of controversy, recent studies have
recently demonstrated a significant common source again put to rest any serious consideration of this mi-
(water-borne) epidemic potential. croorganism as a pathogen (Markell, 1995; Zuckerman
The microsporidian Enterocytozoon bieneusi, which et al., 1994).
infects enterocytes, has been shown to cause a persis-
tent watery diarrhea in patients with acquired immu-
nodeficiency syndrome (AIDS). Giardia infections may DYSENTERY
be asymptomatic, accompanied by a mild mucoid diar- Acute amoebic dysentery is characterized by the passage of
rhea, or may give rise to a full-blown malabsorption six to eight, or sometimes a dozen or more, mucoid,
syndrome with steatorrhea. blood-flecked (or more overtly bloody) stools a day.
Development of the cysticercoids of Hymenolepis There may be generalized abdominal pain and ten-
nana within the intestinal villi may elicit a mucous derness if the entire colon is involved, tenderness over
McBurney’s point, nausea and vomiting with cecal in- and thickened, coarsened skin, often with verrucous
fection, or tenesmus, with relief of the accompanying changes.
pain after evacuation if the rectosigmoid is the main In Malayan and Timoran filariasis, elephantiasis is
diseased area. An untreated attack lasts a few days to less severe and generally is confined to the lower limbs
several weeks and usually subsides spontaneously to below the knees. Elephantiasis of the external genitalia
recur after an interval of some days of several years. Be- in both sexes, and hypertrophy of the femoral lymph
tween attacks the patient may be constipated. Balan- nodes, producing a peculiar condition known as hang-
tidial dysentery is similar to the amoebic type, and as ing groin, have been reported from some areas in Africa
in the latter disease, many infections are asymptomatic. where bancroftian filariasis is unknown and are as-
Dysentery accompanying kala-azar, falciparum malar- cribed to onchocercal infection, in which elephantiasis
ia infections, strongyloidiasis, and schistosomiasis is of the legs may also occur.
mentioned in the discussion of Diarrhea. In schistosomiasis haematobium, extensive egg depo-
sition may lead to fibrosis that blocks the lymphatic
drainage, and to subsequent elephantiasis of the penis.
EDEMA
Circumorbital edema, possibly resulting from vasculitis EOSINOPHILIA
provoked by the migrating larvae, is frequently seen in A retrospective study of 119 Caucasians returning
the early stages of trichinellosis; there also may be edema from the tropics with eosinophilia and referred to
of the hands. Unilateral circumorbital edema, with local the Hospital for Tropical Diseases in London (Harries
pruritus and sometimes intense pain, results from pas- et al., 1986) found that a parasite was the cause of the
sage of the adult Loa loa across the eyeball or lid. Passage eosinophilia in 46 patients (38.7%). Diagnoses and
of the worm across the eyeball can take less than half a mean eosinophil counts (per mm3) were as follows:
minute to as long as 10 minutes; the resulting inflam-
matory changes usually persist for several days. Calabar
Loa loa 6368/mm3
swellings (q.v.) are also seen in loiasis, whereas local- Schistosoma mansoni 3203/mm3
ized edema of the face, neck, ears, and other parts of the Mansonella (Dipetalonema) perstans 2884/mm3
body, accompanied by intense pruritus and erythema, Trichinella spiralis 2790/mm3
may be recurrent in onchocerciasis. Ocular sparganosis Hookworm 2330/mm3
is not uncommon in some areas where eye lesions are Schistosoma haematobium 2017/mm3
poulticed with split raw infected frogs. In the subcuta- Schistosoma intercalatum 1500/mm3
neous tissues around the eye, the sparganum produces Cutaneous larva migrans 1430/mm3
a violent tissue reaction with edema; retrobulbar devel- Trichuris trichiura 1408/mm3
Onchocerca volvulus 1353/mm3
opment of the sparganum may cause protrusion of the
Strongyloides stercoralis 978/mm3
eyeball and consequent corneal ulceration. Areas of lo- Ascaris lumbricoides 760/mm3
calized hard edema, of uncertain cause, are frequently
seen in Chagas’ disease, occurring after appearance of The proportionate numbers of eosinophils given
the chagoma (q.v.). The most common type is unilateral here may be misleading, as they reflect relatively small
edema of the eyelids (Romaña’s sign, q.v.). Edematous numbers of patients. Perhaps more important is the
patches may develop elsewhere on the body, especially fact that, even in a group of patients referred to a hospi-
involving the abdominal wall, pubic area, scrotum, and tal that specialized in tropical diseases, more than 60%
legs. Of equally obscure origin is the edema of the hips, were not found to have parasites. These authors sug-
legs, hands, and face that may accompany the acute gest that if eosinophilia persists undiagnosed for sev-
stage of African sleeping sickness. The edema of the face eral months, empirical therapy with a broad-spectrum
and legs, with a protuberant abdomen seen in severe anthelminthic (they suggest mebendazole or thiaben-
hookworm infections, fasciolopsiasis, and diphyllo- dazole, though recent experience might suggest alben-
bothriasis, may be related to malnutrition. dazole; depending on travel history, praziquantel or
ivermectin might be added).
Eosinophilia is a consistent finding in helminth infec-
ELEPHANTIASIS tions, though it may be quite variable in degree. In
Elephantiasis is a chronic enlargement of a limb, the general, tissue parasites provoke more pronounced eo-
scrotum, a breast, or the vulva, with hyperplasia of the sinophilia than those that live only in the lumen of the
connective tissue and skin, a woody nonpitting edema, bowel, nematodes more than cestodes.
India, Pakistan, Sri Lanka, China, Burma, Thailand, the

TABLE G.1
Philippines, Malaysia, Indonesia, tropical Africa, and the
Diseases with eosinophilia greater than 20%
West Indies. Filarial infection is considered to be a com-
(Mayo Clinic, 1944).
mon cause of this condition. Other agents may be the
Disease Eosinophils (%) pulmonary stages of Ascaris, Strongyloides, Toxocara, or
Atopic diseases (vasomotor rhinitis, 28 other helminths Treatment with conventional doses of
asthma, hay fever) diethylcarbamazine (DEC) is often effective; antimonial
Lymphoproliferative diseases 20 (stibophen) or arsenical (neoarsphenamine) drugs are
(lymphoma) sometimes effective when there is no response to DEC.
Dermatoses (pemphigus, dermatitis 10
herpetiformis)
EOSINOPHILIC CEREBROSPINAL FLUID
Nonparasitic infections (principally 11
streptococcal)
PLEOCYTOSIS
Cerebrospinal fluid eosinophilic pleocytosis is primarily as-
Periarteritis nodosa (with lung 10
sociated with parasitic infection, but a number of other
involvement)
disease entities may evoke this response. The agents
Parasitic infections 4 (modified from Asperilla, 1989 and Kuberski, 1979)
Nonlymphatic malignant tumors 4 that may result in eosinophils in the CSF are as follows:
and leukemia A. Parasitic infections
Miscellaneous 13 Angiostrongylus cantonensis
Ascaris lumbricoides
Data from Harris (1979). Baylisascaris procyonis
Coenurus
As many physicians equate eosinophilia with Cysticercus
parasitic disease, it may be well to report the result Dirofilaria immitis
of a Mayo Clinic study of 418 patients with an eosin- Echinococcus
ophilia of 20% or greater, as quoted by Harris (1979) Fasciola hepatica
(Table G.1), although these data represent a largely Gnathostoma spinigerum
U.S.-domiciled population. Hypoderma bovis
A marked eosinophilia (20% to 70% or more) is most Onchocerca volvulus
frequently seen with trichinosis, strongyloidiasis, hook- Paragonimus spp.
worm infection, visceral larva migrans, filariasis, schis- Schistosoma spp.
tosomiasis, and fasciolopsiasis, Moderate eosinophilia Toxocara spp.
(6% to 20%) often accompanies trichuriasis, ascariasis, Toxoplasma gondii
paragonimiasis, taeniasis, and eosinophilic meningitis. Trichinella spiralis
It must be realized that eosinophilia is an index of B. Fungal infections
host reaction to the parasite, so it varies considerably Coccidioides immitis
from one patient to another. Histoplasma capsulatum
Eosinophilia is not characteristic of any of protozoan C. Bacterial infections
infections with the exception of Cystoisospora belli (former- Treponema pallidum
ly Isospora belli) and perhaps Dientamoeba fragilis. Tropical Mycobacterium tuberculosis
eosinophilia or eosinophilic lung disease is characterized by D. Rickettsial infections
symptoms of chronic bronchitis or asthma, marked eo- E. Viral infections
sinophilia, accelerated erythrocyte sedimentation rate, Lymphocytic choriomeningitis
paroxysmal cough or wheezing, malaise, easy fatigabil- F. Miscellaneous
ity, anorexia, and weight loss. The chest film may show Malignancies (leukemia, lymphoma, meningeal
diffuse, patchy mottling and transverse branching stria- tumors)
tions, most prominent in the midlung and basal lung Allergies
fields, with enlargement of the hilar shadows. Occasion- Collagen vascular diseases
ally there may be unilateral densities in the upper lung Drug hypersensitivity
field that are suggestive of the picture seen in pulmonary Foreign material (dyes, contrast media, etc.) in the
tuberculosis. The disease is reported from such areas as central nervous system.
Hypereosinophilic syndrome gnathostomiasis, paragonimiasis, cysticercosis, and

Multiple sclerosis schistosomiasis. Table G.2 lists important features in
the diagnosis of the first four conditions.
EOSINOPHILIC MENINGITIS
(EM) while eosinophilic cerebrospinal fluid pleocytosis is EOSINOPHILURIA
seen in a number of parasitic and nonparasitic infec- Eosinophils in the urine are not regularly detected by
tions and in some noninfections conditions, when as- means of Wright’s stain, but Hansel’s stain seems to
sociated with meningitis it is typically associated with demonstrate them well. Eosinophiluria, a variable find-
certain helminthiases that affect the central nervous ing in diseases of the urinary tract, is frequently seen in
system. Important among these are angiostrongyliasis, drug-induced acute interstitial nephritis and is absent
TABLE G.2
Differential diagnosis of some CNS parasitic infections.
Condition Transmission Patient origin or travel history Comments
Angiostrongyliasis Contact with rat lung- South Pacific, Africa, Australia, Neutropenic
worm; consumption of Caribbean, Hawaii, US port Usually self-limited
snail, slug, crustacean, cities Symptoms: Headache; rarely sensory
mollusk, crab; frogs, impairment
fish, lizards; lettuce and Signs: Onset insidious or sudden, stiff
vegetables neck, cranial nerve impairment (optic,
facial, abducens)
Gnathostomiasis Contact with dog, cat; Southeast Asia, Japan, China, Peripheral eosinophila common
consumption of raw fish, Mexico, Central and South Symptoms: Migratory swellings,
poultry, crustaceans, America, Africa, and the Middle severe nerve foot pain
amphibians East Signs: Onset sudden: stiff neck,
paraplegia, impaired consciousness,
coma
Paragonimiasis Ingestion of raw fresh- Asia, Africa, South America Characterized with normal blood
water crabs, crayfish eosinophils
Symptoms: Cough and healthache
Signs: Onset insidious: convulsions,
hemiplegia, visual disturbances
Cysticercosis Food contamination Worldwide Neurocysticercosis is a rare cause of
with T. solium eggs EM
Symptoms: Headache, psychiatric
problems
Signs: Onset insidious: stiff neck,
convulsions, movement disorders,
cerebellar signs, hydrocephalus
Ascariasis Ingestion of embryo- Worldwide Rarely associated with EM
nated eggs from human
feces
Toxocariasis Exposure to eggs from Worldwide Rarely associated with EM
dogs and cats feces
Echinococcosis Exposure to eggs from Europe; North America and Rarely infects CNS and is associated
feces of sheep, wolves, Eurasia with EM
dogs, moose, reindeer
CNS, central nervous system; CSF, cerebrospinal fluid; EM, eosinophilic meningitis.
Adapted from: (1) Jaroonvesama (1988) and (2) Michaels and Posfay-Barbe (2018).
in acute tubular necrosis. In acute interstitial nephritis, fever curve in kala-azar. There is often no well-defined
eosinophilia is more often under 5%, but it may range sweating stage, though sweating may be continuous,
up to 50% of the white cells in the urine. A level of 1% periodic, or completely absent. Quartan fever is seen in
or greater is considered abnormal in these conditions. malaria caused by Plasmodium malariae. There is often
In urinary schistosomiasis, eosinophiluria is a constant a regular periodicity from the start; the paroxysms re-
finding; the percentage of eosinophils in the urinary cur at 72-hour intervals; while similar to those of vivax
sediment is always higher than that in the blood and malaria, they are generally more severe. The hot stage
can range from 15% to 95% (median of 73%). often lasts several hours and is frequently accompanied
by nausea and vomiting; the sweating stage may be
followed by prostration. Hyperpyrexia may develop as
EPIDIDYMITIS part of an attack of cerebral malaria or in the course of
Epididymitis is an early complication of bancroftian fila- an apparently uncomplicated attack of falciparum ma-
riasis, often associated with orchitis, and with or with- laria; as the result of injury to the heat-control center in
out accompanying lymphangitis and fever. the hypothalamus there is a rapid rise in temperature to
107°F or higher and death quickly ensues.
A doubly remittent or “dromedary” fever is fre-
FEVER quently found in kala-azar. Febrile attacks, which last
Patterns of fever may be characteristic in malaria and a few days to several weeks, are separated by afebrile
kala-azar, but it is a mistake to suppose that they must periods of equal irregularity. At some time during the
conform to the textbook pattern, although a “classical” course of a febrile attack there are usually one or more
pattern is more likely to be seen in cases of relapse or days during which a double or triple rise to a tempera-
even recrudescence. A quotidian fever (associated with ture of 103°F to 105°F can be demonstrated during a
Plasmodium knowlesi infection) is often seen in the 24-hour period.
initial attack of vivax malaria, two or more broods of An irregularly spiking fever with hepatic tender-
parasites completing their pre-erythrocytic phase at ness, suggestive of cholangitis, may be seen in amoebic
different times so that there may be a daily fever peak hepatitis, fascioliasis, and acute clonorchiasis and opis-
corresponding to rupture of the infected red cells and thorchiasis. The initial period of schistosome infec-
liberation of merozoites. Daily fever peaks usually are tion is likewise marked by irregular fever and hepatic
seen only for a few days; apparently within this time all tenderness, with nausea and vomiting, diarrhea, and,
broods of parasites become synchronized, and thereaf- often, giant hives. An irregular fever, usually with
ter the fever cycle exhibits tertian periodicity. Quartan evening peaks and night sweats, is an early finding in
and falciparum malaria may likewise exhibit quotidian or African trypanosomiasis, and a high remittent fever
irregular periodicity during the first few days of the primary lasting for several weeks occurs early in Chagas’ disease.
attack. Tertian fever is characteristic of vivax and ovale A remittent fever, with temperature to 104°F or 105°F,
malaria. The paroxysm has an abrupt onset, usually ini- frequently marks the stage of larval migration in trichi-
tiated with a chill, which varies from a moderate sensa- nosis. Filarial fever may occur very early in the course of
tion of cold to the intense, bed-shaking chill usually a filarial infection. There is usually a sudden onset, with
thought typical of malaria. The chill lasts up to an hour fever ranging in the neighborhood of 102°F to 104°F
and the fever (to 104°F or 105°F) for 2 hours or lon- and remaining elevated for several hours to a couple of
ger, followed by a profuse sweat, during the course of days, and gradually subsiding in the next several days.
which the temperature falls to normal over a period of Attacks of lymphangitis and lymphadenitis (q.v.) usu-
an hour or so. The sweating stage is usually followed by ally accompany the febrile episodes.
sleep, and when the patient awakens he or she gener-
ally feels well. The next paroxysm is initiated approxi-
mately 48 hours after the onset of the previous one. FUNICULITIS
Subtertian fever, seen in falciparum malaria, is so called Inflammation of the spermatic cord is frequently an
because the cycle may more nearly approach 36 than early sign of bancroftian filariasis.
48 hours. There is usually no frank chill, and the fe-
brile stage is prolonged, though the fever is not usually
as high as in vivax; it may not fall to normal even in HEMATURIA
the intervals between paroxysms. There may be double In Schistosoma haematobium (associated with bladder
peaks of fever in each 24-hour period, resembling the cancer) infections, beginning as early as 3 months after
infection or sometimes not until several years later, there hives often appear during the first few weeks of schisto-
may be intermittent hematuria. There is no dysuria, but some infections.
there may be some frequency and also bladder pain fol-
lowing urination. Hematuria is often referred to as ter-
minal hematuria limited to the last few drops of urine,
HYDATID THRILL
blood being forced out as the bladder wall contracts. In large unilocular echinococcal cysts of the abdominal
viscera that are situated close to the abdominal wall, a
characteristic thrill may be elicited by quick palpation
HEMOGLOBINURIA or percussion. This phenomenon may be simulated by
Blackwater fever usually is seen in conjunction with an percussion of a balloon filled with water.
attack of falciparum malaria, generally in patients who
have had previous attacks of malaria. The passage of
reddish or red-brown urine signals a bout of intravas- HYDROCELE
cular hemolysis, which may occur once or repeatedly Hydrocele is a common finding in areas where filariasis
and may lead to severe renal tubular damage and anuria. is endemic, developing as a sequela to repeated attacks
The cause of blackwater fever is unknown; hypotheses of orchitis. If lymphatic varices develop in the cord and
include quinine sensitivity, glucose-6-phosphate dehy- rupture into the scrotal sac, a condition known as lym-
drogenase deficiency in persons treated with primaquine phocele results.
and related drugs, and autohemolysis on the basis of an-
tibodies formed against altered infected red blood cells.
HYDROCEPHALUS
Although not as intimately associated with congeni-
HEPATITIS tal toxoplasmosis as are retinochoroiditis and cerebral
Amoebic hepatitis is described under the heading of calcifications, hydrocephalus or microcephaly is com-
Abscess, Amebic. monly seen in this condition. Cysticerci within the
ventricular system of the brain may lead to an internal
hydrocephalus.
HEPATOMEGALY
Any parasitic infection involving the liver may result
in enlargement of that organ. Thus, amoebic hepatitis
HYPERPIGMENTATION
or liver abscess, visceral larva migrans, liver fluke infec-
Kala-azar (Hindu for “black fever”) (visceral leishmani-
tions, and early schistosomiasis are all characterized by
asis) derives its name from intensification of the pig-
an enlarged and tender liver, which is also seen in some
mentation of the skin over the cheeks and temples and
cases of falciparum malaria and acute neonatal toxo-
around the mouth. It is most obvious in dark-skinned
plasmosis as well as in kala-azar and Chagas’ disease.
races. In onchocerciasis, repeated attacks of allergic der-
Hydatid infections of the liver and Schistosoma mansoni
matitis may result in hyperpigmentation of the area,
and S. japonicum infections may result in an enlarged
usually on the face, neck, or ears. Bronzing and indu-
but usually nontender liver. The hepatic fibrosis (“pipe-
ration of the affected skin areas may occur in chronic
stem fibrosis”) characteristic of chronic schistosome in-
pediculosis (vagabonds’ disease).
fections produces a clinical picture similar to that of
Laënnec’s cirrhosis, often with splenomegaly.
Helminth infections involving the liver are also
JAUNDICE
characterized by eosinophilia. In visceral larva migrans,
Obstructive jaundice may be seen in severe liver fluke in-
a leukocytosis of up to 80,000 per mm3 may be present,
fections but is not characteristic of light infections or
with a striking eosinophilia. In amoebic abscess of the
those of moderate intensity. The symptoms of the fal-
liver, on the other hand, though the white blood cell
ciparum malaria syndrome known as bilious remittent
count may be in the range of 25,000 per mm3, there is
fever include acute epigastric pain, nausea and vomit-
no eosinophilia.
ing, and marked enlargement and tenderness of the
liver, with jaundice appearing on about the second day.
HIVES Diarrhea, a high remittent fever, and oliguria are usu-
Giant hives and other allergic symptoms, such as bron- ally seen, and death may result from renal or hepatic
chial asthma, are commonly seen in ascariasis, and failure.
KERANDEL’S SIGN mononucleosis sometimes is seen in the acute stage

Noted in the stage of central nervous system involve- of toxoplasmosis, with fever, weakness, malaise, gen-
ment in African sleeping sickness, Kerandel’s sign may eralized adenopathy, and sometimes a rash. There may
be elicited by pressure on the palm of the hand or over be generalized lymphadenitis without fever or other
the ulnar nerve and consists of severe pain that occurs symptoms. In the early stages of African trypanosomia-
shortly after the pressure has been relieved. sis, there may be generalized adenopathy; the glands of
the posterior cervical triangle are most conspicuously
affected (Winterbottom’s sign). Generalized adenopathy
KERATITIS is seen in the acute stage of Chagas’ disease.
Ocular migration of the microfilariae of Onchocerca
volvulus frequently produces a characteristic keratitis,
or inflammation of the cornea. The keratitis (punctate LYMPHANGITIS
or sclerosing) may lead to blindness. Uveitis may also Acute lymphangitis is an early symptom of lymphatic
occur. Free-living amoebae of the genus Acanthamoeba filarial infection. It usually is accompanied by fever
are able to penetrate the cornea, which rapidly leads to and may affect the limbs, breast, or scrotum. When
visual deterioration and blindness. The amoebae also it occurs in a limb, it is usually centrifugal in devel-
cause conjunctivitis, iritis, and uveitis. opment, starting at a lymph node and progressing
distally. The course of the lymphatic is readily seen
because of local distension and erythema. Centrifu-
LEUKOCYTOSIS gal spread of the lymphangitis is the reverse of that
Leukocytosis seldom continues throughout the course of seen in bacterial lymphangitis (blood poisoning),
any of the parasitic infections. In amoebic hepatitis or in which the infection extends proximally from the
abscess there may be a white blood cell count of 25,000 point of origin.
to 30,000 per mm3 with 70% to 80% polymorphonu-
clear neutrophils. In visceral larva migrans a leukocy-
tosis of up to 80,000 per mm3 has been reported, with LYMPHOCYTOSIS
an eosinophilia of 20% to 80%. Trichinosis may be Relative or absolute lymphocytosis, unusual in parasitic
characterized by a white blood cell count of 30,000 per infections, is, however, generally seen in Chagas’ dis-
mm3 early in the infection, and strongyloidiasis by one ease. Initially there may be slight leukocytosis, usually
nearly as elevated; these usually decline and may be fol- followed by leukopenia. Increased numbers of lym-
lowed by leukopenia. Leukocytosis early in the course of phocytes are seen in the spinal fluid (though not the
infection, followed by leukopenia with a relative monocyto- blood) during central nervous system involvement in
sis, is common to many protozoan and helminth infections. African trypanosomiasis.
LEUKOPENIA LYMPH VARICES

A white blood cell count of 4000 per mm3 or less, with Dilatations of the lymphatic vessels may occur second-
a relative monocytosis, generally is seen throughout the arily to lymphatic blockage in filariasis. They are most
course of kala-azar, sometimes terminating in agranu- frequently seen in the inguinal and femoral areas, but
locytosis. other lymphatic tracts may be affected. The soft lobu-
In malaria, leukopenia of 3000 to 6000 white blood lated swellings may rupture and drain. When this oc-
cells per mm3 with a relative monocytosis may accom- curs on the scrotum, a chronic condition known as
pany the afebrile periods, only to be replaced by leuko- lymph scrotum may develop.
cytosis during the paroxysm.
MELENA
LYMPHADENITIS Upper gastrointestinal bleeding of a degree sufficient to
In filariasis, the femoral, inguinal, axillary, and epi- produce melena is rare in parasitic disease; it is men-
trochlear nodes are most commonly involved. The tioned here primarily with strongyloidiasis in mind.
nodes are enlarged, painful, and tender during an acute Infection with Strongyloides stercoralis may run the
attack of lymphangitis and tend to remain enlarged gamut from a complete absence of symptoms to those
between attacks. A condition resembling infectious infections of the duodenum and jejunum that are so
extensive as to produce ulceration of the mucosa, with it tends to occur in the early acute stage. There may be
blood loss to the point of clinical anemia, and with me- pericardial effusion. Congestive heart failure also has
lena. Especially in immunosuppressed patients, the co- been reported in African trypanosomiasis, probably in
incidental finding of anemia with melena and a signifi- the Rhodesian form of the disease, but the cause of the
cant eosinophilia should stimulate a thorough search heart failure is not as apparent. Myocarditis, occasion-
for this sometimes-elusive parasite. ally severe enough to cause death, has been reported
in trichinosis. It is the result of migration of the larvae
through the myocardium, in which they do not encyst.
MENINGOENCEPHALITIS Myocarditis also may be seen in acute toxoplasmosis
Invasion of the central nervous system by trypano- in both infants and adults, the result of invasion of the
somes is characterized in African sleeping sickness by myocardium.
increasing symptoms of meningoencephalitis. There may
be quite variable sensory and motor changes, person-
ality disorders, headache, confusions, drowsiness, and MYOSITIS
finally coma. Similar but milder symptoms are seen in Although myositis is a nonspecific symptom of many
Chagas’ disease. Minor neurologic symptoms are seen febrile illnesses, severe myositis is characteristic of the
during almost any attack of malaria (i.e., headache, stage of larval migration in trichinosis (Trichinella spira-
disorientation). Cerebral malaria is characteristic of lis infection). If accompanied by circumorbital edema,
falciparum infection and may develop slowly with in- eosinophilia, and a history of consumption of insuf-
creasing headache and drowsiness over several days or ficiently cooked pork, the diagnosis may be made with
present as a coma or mental disturbance of sudden on- some certainly. Myositis, usually involving a single
set. There may be signs of meningeal irritation; symp- muscle group, may also occur in Sarcocystis infection.
toms are quite varied, depending on the brain areas
affected. If the cord is affected, the symptoms may be
suggestive of multiple sclerosis. NEUROLOGIC SYMPTOMS
Primary amoebic meningoencephalitis (PAM), Neurologic symptoms in trypanosomiasis, malaria,
caused by invasion of the central nervous system by or- and amoebic and eosinophilic meningoencephalitis
dinarily free-living amoeboflagellates belonging to the are discussed under Meningoencephalitis. Variable
genus Naegleria, is an acute, rapidly progressive infection, neurologic symptoms may occur in schistosomiasis
acquired while swimming or diving in fresh water. It is when eggs carried by the bloodstream to the central
characterized by fever, headache, mental confusion, and nervous system lodge there and provoke a granuloma-
coma; death frequently occurs within a few days of on- tous reaction. Neurologic and other symptoms caused
set. Acanthamoeba and Balamuthia may produce a more by embolization of eggs are more common in Schis-
chronic granulomatous meningoencephalitis (GAM). tosoma japonicum infection than in the other two spe-
Eosinophilic meningoencephalitis (EME), seen cies, whereas in S. mansoni and S. haematobium, eggs
in various Pacific islands as well as Thailand, Taiwan, are found more frequently in the spinal cord than in
Central America, and Cuba in recent years, is believed, the brain, perhaps because of ectopic wanderings of
on strong epidemiologic grounds, to be symptomatic the adult worms. In S. japonicum infection, there may
of infection with Angiostrongylus cantonensis and thus a be severe neurologic symptoms, including coma and
form of larva migrans infection. It is characterized by paresis, during the incubation period or first few weeks
fever, headache, stiff neck, and increased cells (mainly after infection. Transitory neurologic symptoms of a
eosinophils) in the spinal fluid. It is generally a mild variable nature may be caused by the migration of as-
and self-limited infection. Micronema deletrix, ordinari- carid and trichina larvae in the central nervous system;
ly saprophytic, and Baylisascaris procyonis, usually found hemiplegia and focal epileptic attacks have been re-
parasitizing raccoons, are two other nematodes that ported in trichinosis. Hydatid, coenurus, and cysticercus
may produce meningoencephalitis in humans. cysts may develop within the central nervous system,
where they may produce symptoms related to a space-
occupying lesion or, if within the ventricular system,
MYOCARDITIS internal hydrocephalus. Cysticercus larvae may give
Myocardial infection is characteristic of Chagas’ dis- rise to epileptiform seizures, as may Sparganum pro-
ease and is seen in about 50% of chronic cases. Car- liferum and adults of Paragonimus westermani that have
diac failure may come on slowly, although in infants gone astray.
NODULES, SUBCUTANEOUS PAIN

Lipoma-like subcutaneous nodules include onchocerco- Abdominal pain, generally vague or ill defined, is said to
mas (q.v.) and cysticercus and coenurus larvae. The cys- accompany many of the intestinal parasitic infections.
ticercus larva of Taenia solium develops most frequently The presence or absence of such tenuous pains is of no
in the subcutaneous tissues, where it forms nodules 0.5 value from a diagnostic standpoint. Epigastric pain,
to 3.0 cm in diameter. In almost half the recorded hu- sometimes with nausea and vomiting, may be seen in
man cases of coenurus infection, the larvae have been giardiasis, cryptosporidiosis (especially in immunode-
found in the subcutaneous tissues; others have been pressed persons), trichinosis, and strongyloidiasis; it
recorded from the brain, spinal cord, and eye. Echinococ- is related to the duodenitis and jejunitis provoked by
cus cysts also may be found in the subcutaneous tissues. these infections. Moderate to severe abdominal pain
Spargana also form subcutaneous nodules, somewhat is seen in acute amoebic colitis; it may be confined to
elongate and several centimeters in length, which may the cecal area or may be generalized. Angiostrongylus cos-
resemble lipomas, but they may move through the sub- taricensis may give rise to similar symptoms, as may Eu-
cutaneous tissues at irregular intervals and often cause strongylides larvae. In ascariases, severe pain may signal
pain. Sparganum proliferum may develop as branched or intestinal obstruction (q.v.), perforation and peritonitis
multiple nodules and invade the viscera. (See also Ede- (q.v.), or bile duct blockage.
ma, for a discussion of ocular sparganosis.) Larvae of Muscle pain in trichinosis is discussed under Myo-
the botfly Hypoderma migrate through the subcutaneous sitis, and the delayed pain sensation seen in African
tissues, finally coming to rest beneath the skin, where trypanosomiasis under the heading of Kerandel’s Sign.
they produce elongate nodules several centimeters in
length. Considerable pain may accompany migration,
but the resting nodule is seldom painful or pruritic. The PERITONITIS
human botfly, Dermatobia hominis, burrows into the Penetration of Ascaris through the wall of the intes-
skin and subcutaneous tissues, producing an intensely tine usually leads to generalized peritonitis, with pain,
pruritic popular lesion, which has the appearance of a marked distension, generalized abdominal tenderness,
furuncle. There is a small central opening, from which and free air under the diaphragm, detectable by x-ray. In
comes a serous exudate and through which the poste- severe amoebic dysentery, ulcers may erode through the
rior end of the larva may protrude from time to time. wall of the intestine and cause peritonitis. Peritonitis may
Secondary infection is common. rarely result from perforation of the bowel wall by, or in
the course of infection with, a number of other parasites.
OBSTRUCTION, INTESTINAL
Ascaris, especially in children, may produce complete PICA
intestinal obstruction, with accompanying abdominal “A craving for unnatural foods … as seen in hysteria,
pain, vomiting, distention, and hyperperistalsis. Partial pregnancy, and in malnourished children”: this dic-
or complete intestinal obstruction may also character- tionary definition of pica must be broadened to include
ize infection by Angiostrongylus costaricensis. among its causes anemia, especially the anemia of
hookworm disease, and the realization that the con-
sumption of soil, a frequent form of pica, may increase
ONCHOCERCOMA exposure to such infections as hookworm, ascariasis,
Adult worms of Onchocerca volvulus lie in coiled masses toxocariasis, and toxoplasmosis.
beneath the skin, completely enclosed in a fibrous tis-
sue capsule. They are from a few millimeters to several
centimeters in diameter, generally freely movable, and PNEUMONITIS
resemble lipomas. In Mexico and Guatemala, they Pneumonitis is characteristic of severe Ascaris infection
frequently occur beneath the patient’s scalp; in Africa and is caused when the worm larvae break out of the
most occur on other parts of the patient’s body. capillaries into the alveoli, whence they are coughed
up to be swallowed, beginning the intestinal phase of
the disease. Symptoms and signs, first noted 1 to 5 days
ORCHITIS after the eggs are ingested, consist of cough, fever, re-
Filarial orchitis may occur early in the disease and at spiratory distress, and the physical and x-ray signs of
times in the absence of lymphangitis or fever; repeated a bronchopneumonia; in severe cases there may be
attacks lead to hydrocele. complete consolidation of one or more lobes. The
pneumonitis usually clears within a week or two; it PULMONARY SYMPTOMS, CHRONIC

may be accompanied by intense eosinophilia and an In all three types of schistosomiasis, but especially in
urticarial rash. Similar signs and symptoms may ac- Schistosoma haematobium infections, eggs may be car-
company the corresponding stage in Strongyloides infec- ried to the lungs, where pseudotubercle formation
tion, although the pneumonitis is generally not as se- around them may produce a radiologic picture sug-
vere. In hookworm infection there is seldom a clear-cut gestive of miliary tuberculosis, and increasing fibrosis
pneumonitis at this stage, but cough is frequently pres- may lead to cor pulmonale. Paragonimiasis is character-
ent. In schistosomiasis there may likewise be a transi- ized by chronic cough; the production of thick, blood-
tory cough, sometimes with hemoptysis and frequently specked sputum or sometimes frank hemoptysis; and
with dyspnea, during the stage of migration through increasing dyspnea. X-ray may show patchy infiltrates,
the lungs. rounded shadows suggestive of coin lesions, calcifica-
tions, and pleural thickening or effusion. In pulmo-
nary echinococcosis, cough is usually the first symp-
PROTEINURIA tom. There may be increasing dyspnea; with erosion
In falciparum malaria, proteinuria, with hyaline and of blood vessels there will be hemoptysis, and with
granular casts in the urine, is common. Rarely there may obstruction there results secondary bacterial infection
be oliguria or anuria, usually accompanying an attack of and fever. If the cyst ruptures into a bronchus, the con-
blackwater fever (q.v.). The nephrotic syndrome, with tents may be coughed up or the patient may become
proteinuria, is sometimes seen in quartan malaria. asphyxiated.
PRURITUS ANI RASH

The nocturnal pruritus that accompanies pinworm in- An allergic urticarial rash or hives (q.v.) is often seen in the
fection (Enterobius vermicularis) varies considerably in early stages of schistosome infection and in ascariasis. A
degree, probably depending upon hypersensitivity of macular or maculopapular eruption may occur early in
the host. In some persons there is no noticeable itch- the course of a trichina infection, and one of the variants
ing, whereas in others it may be sufficiently severe to of acute toxoplasmosis is a typhuslike fever, with a macu-
interfere with rest. Anal pruritus may be associated lar rash, prostration, and sometimes stupor and cardiac
with active migration of gravid proglottids of Taenia decompensation. During attacks of fever in the early
saginata out of the anus. Thus, perianal swab (scotch stages of African trypanosomiasis there may be an irregu-
tape swab) may be employed for collection these par- lar blotchy rash, often annular. The individual patches
asites. may be several inches across; they tend to fade in a few
hours and reappear at irregular intervals. A petechial rash
may occur with high parasitemias in any of the malarias,
PULMONARY INFILTRATES WITH but especially those due to P. falciparum or P. vivax.
EOSINOPHILIA (PIE)
A clinical classification of PIE modified from Pierce and
Crouch (1989) is as follows: RETINOCHOROIDITIS
A. Illnesses in which PIE is a major component: Infection of the retina and choroid by Toxoplasma or
Allergic bronchopulmonary aspergillosis. (rarely) Entamoeba histolytica may produce visual dis-
Chronic eosinophilic pneumonia. turbances, which can be profound if the macula is in-
Drug reactions (e.g., nitrofurantoin). volved. On ophthalmoscopic examination, a grayish
Hypereosinophilic syndrome. or yellow-white area surrounded by exudate is seen
Parasitic infections (e.g., tropical eosinophilia [q.v.]; early; with healing this leaves a white, atrophic patch
strongyloidiasis, ascariasis, and hookworm dis- bordered by pigment deposits. Invasion of the eye by
ease [during invasive stage]). microfilariae of Onchocerca volvulus or the larvae of Tox-
Polyarteritis nodosa. ocara or Angiostrongylus cantonensis may also produce a
B. Illnesses in which PIE occurs infrequently: retinochoroiditis.
Bacterial and fungal infections (e.g., tuberculosis,
brucellosis, histoplasmosis, coccidioidomycosis).
Neoplasms (e.g., Hodgkin’s disease). ROMAÑA’S SIGN
Immune disorders (e.g., rheumatoid lung disease, Unilateral palpebral edema, involving both upper
sarcoidosis). and lower eyelids, appears early in the course of an
infection with Trypanosoma cruzi. The edema is hard of those involved, and visceral leishmaniasis 5.3%.
and nonpitting; it may remain confined to the eyelids Other common diagnoses were portal hypertension of
or may spread to involve the cheek and neck. It may unknown cause (10.7%) and cirrhosis (6.9%).
subside promptly or persist for weeks or months.
SPLINTER HEMORRHAGES
SHOCK Sometimes occurring during the stage of active larval
When shock complicates falciparum malaria, the pa- migration in trichinosis, minute linear hemorrhages in
tient is pale, with a cold and clammy skin, thin fast the nail beds are a general sign of vascular injury.
pulse, and low blood pressure. There is often acute ab-
dominal pain, vomiting, and diarrhea. The cause may
be primary adrenal failure, through parasite-induced STEATORRHEA
ischemia or infarction, or it may be secondary to re- Malabsorption, characterized by the presence of fat in
duced blood volume and blood pressure caused by the stools, (> 6 grams/day) is seen in certain parasitic
widespread vascular injury. Rupture of an Echinococcus infections. The most common of these is giardiasis,
cyst may lead to anaphylactic shock. which may make its presence known by flatulence and
the production of foul-smelling, fatty stools. Unfortu-
nately, Giardia-induced malabsorption does not neces-
SPLENOMEGALY sarily disappear with eradication of the infection but
As part of generalized lymphoid hyperplasia in both may persist some time thereafter. Strongyloides infec-
African and American trypanosomiasis, splenomegaly tions may also cause steatorrhea, as may infection with
may be observed. In kala-azar the spleen is said to en- Capillaria philippinensis, and in immunosuppressed pa-
large downward about an inch per month, and it may tients, Cryptosporidium and Cystoisospora belli.
extend into the pelvis. It is not tender and reverts to
normal size after effective therapy. The spleen enlarges
during an acute attack of malaria and is usually palpa- TACHYCARDIA
ble within 2 weeks after onset, although in some non- A fast pulse is noted early in both African and American
immune individuals, palpable (acute) splenomegaly trypanosomiasis. In Chagas’ disease it persists into the
may appear within a day or two of initially detectable subacute and chronic stages, where it may be associated
parasitemia (approximately 50–100 parasities per µl of with heart block, Stokes-Adams syndrome, and fibril-
blood). Between attacks it may shrink, and in adults lation.
it may become fibrotic and smaller than normal. In
children, repeated attacks may lead to great enlarge-
ment of the organ, which may extend to the pelvis. ULCERS, CUTANEOUS
The “splenic index,” a guide to endemicity of malaria In leishmanial and trypanosomal diseases there is
obtained by examination of a population for evidence a primary multiplication at the site of infection. In
of enlarged spleens, obviously must be derived only Leishmania tropica–complex infections there is first a
through examination of children. The spleen is usually papule at the site of infection, which gradually trans-
tender during an acute attack of malaria, and tender- forms into a shallow ulcer with raised edges. The Chi-
ness may be apparent before the organ can be palpat- clero ulcer of Southern Mexico and Central America
ed. Splenic infarction or rupture is rare and tends not is similar to an oriental sore, except when it occurs
to produce catastrophic bleeding, but rather, an ooze. on the ear, where it may erode the pinna. L. brazil-
In Schistosoma mansoni and S. japonicum infections, iensis first produces cutaneous ulcerations, which may,
splenomegaly is secondary to hepatic fibrosis brought through extension or metastasis, come to involve the
about by egg deposition in the liver, and resulting por- nasal mucosa, the soft and the hard palate, the nasal
tal hypertension. septum, the pharynx, and the larynx, even after com-
In an area where malaria, schistosomiasis, and kala- plete healing of the initial cutaneous ulcer. In blacks,
azar all are common (Kenya), tropical splenomegaly granulomatous rather than ulcerative lesions are gen-
syndrome (hyperreactive malarial splenomegaly) ac- erally seen. In African sleeping sickness there may be
counted for 31% of cases of chronic splenomegaly. a firm, tender, raised lesion, up to 2 cm or more in
Hepatosplenic schistosomiasis was the cause in 17.6% diameter, at the site of infection. This “trypanosomal
chancre” is painful or pruritic, but like the chagoma WINTERBOTTOM’S SIGN

(q.v.) it apparently does not ulcerate unless second- Posterior cervical lymphadenitis is seen early in African
arily infected. Ulcerative cutaneous lesions are seen trypanosomiasis. Aspiration of the enlarged nodes may
rarely in amoebiasis, either in the perianal region or in reveal trypomastigotes at a time when none can be found
the skin surrounding fistulas or surgical drainage inci- in the peripheral blood.
sions from hepatic abscesses. A rounded ulcer, 2 mm
to several centimeters in diameter, marks the place at
which the guinea worm discharges its larvae. In the X-RAY EVIDENCE OF PARASITIC DISEASE
center of the ulcer, a portion of the worm may be vis- • Amoebiasis: Amoebic granulomas of the large bowel
ible. There is often secondary infection, and a painful simulate carcinoma in barium enema studies. Cecal
localized reaction may persist until discharge of the amoebiasis tends to produce a funnel-shaped defor-
larvae is complete. mity of that portion of the bowel as seen in barium
enema studies. In amoebic abscess of the liver there
may be elevation of the right diaphragm and some-
URETHRITIS times right lower lobe pneumonitis. CT, MRI, and
Trichomonas vaginalis has been found in up to a third of ultrasound are equally sensitive for the detection of
cases of “nonspecific” urethritis in men. liver abscess due to Entamoeba or Echinococcus.
• Giardiasis: Evidence of intestinal malabsorption.
• Toxoplasmosis: Intracerebral calcifications.
VAGINITIS • Dracunculiasis, filariasis, and loiasis: Calcified worms
A prolific, irritating, thin green or yellowish discharge may be seen in the tissues. Ascariasis: Pneumonitis.
may be seen in Trichomonas vaginalis infection; the va- Adult worms may be seen as cylindrical empty spac-
gina may be diffusely congested or covered by punctate es in the barium-filled bowel or common bile duct
hemorrhagic spots. The organisms may be present in in a small bowel series.
asymptomatic persons. Enterobius vermicularis may mi- • Strongyloidiasis and hookworm infection: Pneumoni-
grate from the anus and enter the vagina, where they tis. Loss of mucosal markings and a tubular defor-
produce a temporary, intense pruritus in some children. mity of the duodenum and jejunum may be seen in
small bowel studies on patients with strongyloidia-
sis.
VISUAL DIFFICULTIES • Cysticercosis: Calcified cysts in the subcutaneous tis-
Vision problems associated with parasitic disease in- sues, muscles, brain (MRI is more sensitive than CT
clude circumorbital edema (q.v.), conjunctivitis (q.v.), for visualizing CNS cysticercosis).
and retinochoroiditis (q.v.). Ascarid larvae (of Ascaris • Echinococcosis: Well-defined, rounded masses may
lumbricoides and Toxocara) may invade the eye, produc- be seen in the lung parenchyma; sometimes a fluid
ing iritis or other symptoms. Angiostrongylus cantonen- level is visible within them. Hepatic cysts are visible
sis also invades the eye, producing visual impairment, by CT, MRI, or ultrasound. Hydatid cysts of bone
iritis, retinal edema, and other signs and symptoms. produce extensive intramedullary erosion, demon-
Patients infected with Onchocerca actually may be strable by x-ray.
aware of the intraocular movement of the microfilar- • Paragonimiasis: Patchy infiltrates or rounded densi-
iae, and lesions of the anterior chamber, iris, ciliary ties in the lung parenchyma, pleural thickening, or
body, choroid, and retina developing in this condition fluid.
may lead to diminution of vision or total blindness. • Schistosomiasis: Pulmonary fibrosis, or a picture
Loa loa migration may produce ocular pain and con- suggestive of miliary tuberculosis. Cor pulmonale
junctivitis or frank subconjunctival hemorrhage, but with dilation of the pulmonary artery and its main
not visual difficulty. Cysticercus and coenurus larvae branches, right ventricular hypertrophy.
may develop within the eye. Pentastomids may invade • S. haematobium infections: Calcification in the wall
the anterior chamber. Ophthalmomyiasis, or invasion of the bladder; hydronephrosis, hydroureter.
of the orbit, is often caused by migratory larvae of • Pentastomiasis: C-shaped calcifications, less than
Hypoderma, the cattle grub. External ophthalmomyia- 1 cm in diameter, in the viscera or lungs.
sis is usually caused by larvae of Oestrus ovis, the sheep
botfly.
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Atlas of Medically Important Parasites
PLATE I 1, 2, Entamoeba histolytica trophozoites; 3, 4, E. histolytica cysts; 5, E. histolytica (5a without

arrow) and E. hartmanni (5b with arrow) cysts; 6, E. hartmanni trophozoite. (All color photographs are
enlarged to emphasize internal structures)
331
PLATE II 1, 2, Entamoeba coli trophozoite (unstained); 3a, E. coli cysts (iodine stained)), 3b, E. coli cyst
(unstained); 4, E. coli cyst; 5, Iodamoeba bütschlii trophozoite (a with arrow) and I. bütschlii cyst (b);
6, I. bütschlii cyst. (Part 3a and 3b: Courtesy Centers for Disease Control and Prevention (CDC).)
(All color photographs are enlarged to emphasize internal structures)
Atlas of Medically Important Parasites 333
PLATE III 1, Iodamoeba bütschlii trophozoite; 2, Endolimax nana trophozoite; 3, E. nana cysts; 4, 5,
Dientamoeba fragilis; 6, Giardia duodenalis trophozoite. (Part 1-3: Courtesy of CDC.)
PLATE IV 1, G. duodenalis cysts; 2, G. duodenalis cyst (a) and E. histolytica early cyst (b with arrow);
3, Trichomonas vaginalis trophozoites; 4, 5, Chilomastix mesnili trophozoites; 6, C. mesnili cysts.
(Part 3 and 6: Courtesy of CDC.) (All color photographs are enlarged to emphasize internal structures)
PLATE V 1, Blastocystis hominis cysts (1a trichrome stained, 1b iodine stained); 2, B. hominis cyst
(unstained); 3, Entamoeba gingivalis trophozoite; 4, Balantidium coli trophozoites; 5, B. coli cyst.
(Part 1-3: Courtesy of CDC.) (All color photographs are enlarged to emphasize internal structures)
PLATE VI Plasmodium vivax: 1, normal-sized red cell with marginal ring form trophozoite; 2, young signet
ring form trophozoite in a macrocyte; 3, slightly older ring form trophozoite in red cell showing basophilic
stippling; 4, polychromatophilic red cell containing young tertian parasite with pseudopodia; 5, ring form
trophozoite showing pigment in cytoplasm, in an enlarged cell containing Schüffner’s stippling (Schüffner’s
stippling does not appear in all cells containing the growing and older forms of P. vivax as would be indicated
by these pictures, but it can be found with any stage from the fairly young ring form onward); 6, 7, very
tenuous medium trophozoite forms; 8, three ameboid trophozoites with fused cytoplasm; 9–13, older
ameboid trophozoites in process of development; 10, two ameboid trophozoites in one cell; 14, mature
trophozoite; 15, mature trophozoite with chromatin apparently in process of division; 16, 17–19, schizonts
showing progressive steps in division (“pre-segmenting schizonts”); 20, mature schizont; 21, 22, developing
gametocytes; 23, mature microgametocyte; 24, mature macrogametocyte. (Courtesy of the National Institutes
of Health, USPHS.)
PLATE VII Plasmodium ovale. 1, young ring-shaped trophozoite; 2–4, older ring-shaped trophozoites; 5–7,
schizonts, progressive stages; 8, mature gametocyte. Free translation of legend accompanying original plate
in “Guide pratique d’examen microscopique du sang appliqué au diagnostic du paludisme” by Georges
Villain. (Reproduced with permission from “Biologie Medicale” supplement, 1935. Courtesy Aimee Wicox.
National Institutes of Health Bulletin no. 180.)
PLATE VIII The human plasmodia as seen in thick film. 1, Plasmodium vivax: young and older trophozoites
and schizont; 2, P. ovale: developing trophozoite and schizonts, one within a “ghost cell”; 3, P. malariae:
trophozoites and schizont; 4, P. falciparum: young trophozoites and gametocyte.
PLATE IX Plasmodium malariae. 1, young ring form trophozoite of quartan malaria; 2–4, young trophozoite
forms of the parasite showing gradual increase of chromatin and cytoplasm; 5, developing ring form
trophozoite showing pigment granule; 6, early band form trophozoite-elongated chromatin, some pigment
apparent; 7–12, some forms that the developing trophozoite of quartan may take; 13, 14, mature trophozoites-
one a band form; 15–19, phases in the development of the schizont (“pre-segmenting schizonts”); 20, mature
schizont; 21, immature microgametocyte; 22, immature macrogametocyte; 23, mature microgametocyte; 24,
mature macrogametocyte. (Courtesy National Institutes of Health, USPHS.)
PLATE X Plasmodium falciparum. 1, very young ring form trophozoite; 2, double infection of singled cell with
young trophozoites, one a “marginal form (a coliform),” the other “signet ring” form; 3, 4, young trophozoites
showing double chromatin dots; 5–7, developing trophozoite forms; 8, three medium trophozoites in one
cell; 9, trophozoite showing pigment, in a cell containing Maurer’s dots; 10, 11, two trophozoites in each
of two cells showing variation of forms that parasites may assume; 12, almost mature trophozoite showing
haze of pigment throughout cytoplasm; Maurer’s dots in the cell; 13, estivo-autumnal “slender forms”; 14,
mature trophozoite, showing clumped pigment; 15, parasite in the process of initial chromatin division;
16–19, various phases of the development of the schizont (“presegmenting schizonts”); 20, mature schizont;
21–24, successive forms in the development of the gametocyte-usually not found in the peripheral circulation;
25, immature macrogametocyte; 26, mature macrogametocyte; 27, immature microgametocyte; 28, mature
microgametocyte. (Courtesy National Institutes of Health, USPHS.)
PLATE XI Eggs of various helminthes. 1, Fasciolopsis buski; 2, Echinostoma sp.; 3, Gastrodiscus aegyptiacus
(similar to Gastrodiscoides); 4, Metagonimus yokogawai; 5, Fasciola gigantica; 6, Clonorchis sinensis;
7, C. sinensis; 8, Opisthorchis viverrini; 9, Schistosoma mansoni; 10, S. japonicum; 11, S. haematobium;
12, Paragonimus westermani; 13, Diphyllobothrium latum; 14, Taenia sp.; 15, Taenia sp. (unstained); 16,
Dipylidium caninum egg packet. (Gastrodiscus egg courtesy of Dr. Lawrence Ash; Part 7-8: Courtesy of CDC.)
PLATE XII Eggs and larvae of various helminthes. 1–2, Hymenolepsis nana; 3, Hymenolepis diminuta;
4, Strongyloides stercoralis larva (unstained); 5, S. stercoralis larva (trichrome stain); 6–7, hookworm;
8, Trichostrongylus orientalis; 9–13, Ascaris lumbricoides egg (9, unfertilized, corticated; 10, fertilized,
corticated; 11, fertilized, corticated; 12, hatched and unfertilized eggs; 13, unfertilized, corticated) 14, Trichuris
tirchiura unembryonated egg; 15, Capillaria philippinensis unembryonated egg; 16, Enterobius vermicularis
(unstained) (Part 1-3: Courtesy of CDC). (All color photographs are enlarged to emphasize internal structures)
PLATE XIII 1–4: Adult hookworm mouth structures. 1, Ancylostoma duodenale (2 pairs of prominent
ventral teeth); 2, Ancylostoma braziliense (1 pair prominent teeth and 1 pair less conspicuous teeth);
3, Ancylostoma caninum (3 pairs of prominent ventral teeth); 4, Necator americanus (semilunar cutting
plates); 5–6: Microfilaria: 5, Brugia malayi; 6, Wuchereria bancrofti; 7, Trichinella spiralis larva; 8–12: Blood
flukes life stages: 8, Schistosoma japonicum miracidium; 9, S. japonicum sporocyst; 10, S. japonicum
unstained cercaria (from research works of Dr. Gregorio L. Martin I); 11, S. japonicum male and female (with
arrow) in copula; 12, S. mansoni male and female (with arrow) in copula; 13–15: Blood flukes intermediate
hosts: 13, Biomphalaria sp.; 14, Bulinus sp.; 15, Oncomelania sp. (Part 1,4, 12–15: Courtesy of CDC) (All
color photographs are enlarged to emphasize internal structures)
Answers to Chapter Questions
Chapter Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 Q10 Q11 Q12 Q13 Q14 Q15 Q16 Q17 Q18 Q19 Q20
1 B D A C C D A B B A C A B A D C A B E D
Crossword Challenge: Learning basic concepts in Parasitology!
2 D D B C A C C B D B C A D A D C E C A B
343
Chapter Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 Q10
3 C C A B D A D C B C
True or False
Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 Q10
T F F T T T F T F F
4 A D A A B B A C A C A C C B D B A B B C
5 D B A D C C B B A B C C D D B D D A B C
6 A D C A F F B B A E D B C C C C F A D F
Chapter Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 Q10 Q11 Q12 Q13 Q14 Q15 Q16 Q17 Q18 Q19 Q20 Q21 Q22
7 C D B C D E A C A B A D A C A C B E A B D C
8 D A B D B B D C B B
Matching Type:
A. B.
Q1 Q2 Q3 Q4 Q5 Q1 Q2 Q3 Q4 Q5
C D A E B E B A C C
9 C D A B B C D C D A
Identification: 11-12: Muscle fiber

13-14: Vegetable fiber
15-16: Fat globule
17-18: Vegetable spiral
19-20: Air bubbles
Challenge image: Blastocystis hominis
10 C A D C A B C D A B C A B D A C C C C D
11 D A C D B B C C A A C A B C A C A B C D
Index
Note: Page numbers followed by “f” indicate figures, “t” indicate tables.
A Albendazole in Naegleria fowleri infections, 297,

Abdominal pain in Anisakis spp. infections, 151 298
in Artyfechinostomum malayanum in Ascaris infections, 303 Ancylostoma braziliense, 146
infection, 185 in Brugia malayi, 155 Ancylostoma caninum, 146
in cestode infections, 237t in Capillaria philippinensis, 142 Ancylostoma duodenale, 143
in dysenteric malaria, 114 in clonorchiasis, 300 effect on host, 4
in Entamoeba histolytica infection, 26 in Clonorchis sinensis, 177 Anemia in hookworm infections, 304
in Giardia lamblia (Giardia in cutaneous larva migrans, 146 Angiostrongylus cantonensis, 164, 165
duodenalis) infection, 54 in cysticercosis, 301 diagnosis of, 165
in cystisosporiasis, 118 in Echinococcus granulosus, 230 epidemiology of, 165
in microsporidia infection, 97 in Encephalitozoon intestinalis life cycle of, 164f
in whipworm infection, 142 infection, 286 morphology of, 164
Abscess in Enterobius vermicularis infections, pathogenesis of, 165
amoebic, of liver, 23, 32 139 treatment of, 165
Acanthamoeba. See also Acanthamoeba in G. spinigerum infections, 306 Angiostrongylus costaricensis, 165
keratitis in hookworm infections, 302 diagnosis of, 165
cyst of, 48 in hydatid disease, 301 epidemiology of, 165
eye infections from, 47 in Mansonella perstans, 158 life cycle of, 165
granulomatous amoebic in microsporidia, 286 pathogenesis of, 165
encephalitis from, 45 in microsporidia infection, 98 treatment of infection, 165
life cycle of, 44f, 47, 48 in M. perstans infections, 306 Animal inoculation, 264, 275
mode of transmission, 44 in Necator americanus, 146 Anisakiasis, 304
morphology of, 48 in neurocysticercosis, 301 Anisakis spp., 150, 151
Acanthamoeba keratitis, 49 in Strongyloides stercoralis, 148 diagnosis of, 151
Acanthamoeba spp., 73t in Taenia solium, 222 epidemiology of, 151
diagnosis of, 49 in Trichuris trichiura infection, 140 life cycle of, 150f, 151
epidemiology of, 49, 50 in visceral larva migrans, 306 pathogenesis of, 151
infection in, 49 Allergic reactions, 144 treatment of infection, 151
prevention of infection, 50 in Charcot-Leyden crystal infections, Anopheles mosquito
treatment of infection, 50 251 malaria from, 6
Acanthocephala, 151 in Echinococcus infections, 229 Anopheles mosquitoes, 243f
classification of, 9 in Schistosoma intercalatum Anoplura, 9
Acanthoparyphium, 204 infections, 197 Apicomplexa, 8, 126
Acanthoparyphium tyosenense, 204 Allopurinol Apicomplexa
Accolé form of Plasmodium, 106 in Chagas’ disease, 295 morphologic adaptations to
Acid-fast staining, 260 in visceral leishmaniasis, 297 parasitism, 3
for Cryptosporidium, 124f Amoebae Arachnida, 9
for Cyclospora, 124 comparison of, 85t Arsenicals in Gambian sleeping
for Cystoisospora belli, 120 Entamoeba, 23–39 sickness, 294
Acridine orange staining, 271 Amoebiasis Artemisinin in malaria, 291
Aedes mosquitoes, 243f asymptomatic intestinal, 34 Artesunate in malaria, 117
Aedes polynesiensis, 154 diagnosis of, 33 Arthemeter-Lumefantrine in malaria,
Aestivoautumnal malaria, 103t emetine, in treatment of, 34 117
African eye worm. See also Loa loa Entamoeba histolytica, 26, 32, 74t Arthropods, 241–245
African sleeping sickness, 242t extraintestinal, 32 classes of, 241, 243f, 244f
Glossina morsitans, 241f pleuro-pulmonary, 32 classification of, 9
African trypanosomiasis prevalence of, 11 diseases transmitted by, 242t
definitive host of, 2 Amoebic colitis, 26 as parasites, 241
epidemiology of, 11 American trypanosomiasis as vectors, 241f
pentamidine in, 293 epidemiology of, 11 Artyfechinostomum malayanum,
prevalence of, 11 Amodiaquine in malaria, 289 183–185
suramin in, 293 Amoeba, 23 egg of, 185
Agar plate method for recovery of Amphotericin B morphology of, 183, 184f
Strongyloides larvae, 262 in cutaneous leishmaniasis, 296 symptoms and pathogenesis of, 185
Alaria, 204 in mucocutaneous leishmaniasis, 296 treatment of infection, 185
345
346 INDEX
Ascariasis Biliary disorders in liver flukes epidemiology of, 142

epidemiology of, 11 infection, 173–181 life cycle of, 142, 143f
Ascaris lumbricoides, 114, 136 Biologic vector, definition of, 6 morphology of, 142
diagnosis of, 136 Bithionol pathogenesis of, 142
effect on host, 4 in Fasciola hepatica, 181 treatment of infection, 142
epidemiology of, 138 in fascioliasis, 299 Cataostomus commersoni, 205
life cycle of, 6, 136, 137f in Paragonimus spp., 190 Cat liver fluke, 177
morphology of, 136 Black fly, 244f Cats
pathogenesis of, 136, 137 Blackwater fever in malaria, 114 Clonorchis sinensis in, 175
treatment of, 138 Blastocystis hominis, 23, 247, 248 Opisthorchis felineus in, 177
Atovaquone in malaria, 292 gastrointestinal disorders Schistosoma intercalatum in, 202
Australian bee pollen in stool from, 248 Cellulose tape swab for Enterobius and
specimen, 248f, 249f morphological forms of, 247 Taenia eggs, 262
Azithromycin in Naegleria fowleri in stool specimen, 248f Centipedes, 9
infections, 298 Blood- and tissue-dwelling protozoa Cerebral cysticercosis, 220f
coccidians, 118 Cerebrospinal fluid examination, 271
B Cryptosporidium parvum, 122–124 in trypanosomes
Babesia divergens, 131 Cyclospora cayetanensis, 124–126 double-centrifugation technique
Babesia microti, 8, 131 Cystisospora, 118 for, 271
life cycle of, 131f Sarcocystis, 120–122 Cestodes, 211, 212
Babesia spp., 130–132 Blood films, 266–270 common infections of humans, 237t
diagnosis of, 130 buffy coat method for Leishmania, Dibothriocephalus latus, 212–214
epidemiology of, 131 270 Dipylidium caninum, 231
life cycle of, 130 concentration procedures for, 270, Echinococcus spp., 225–231
Maltese cross forms, 130 271 Hymenolepis diminuta, 233
in red blood cells, 132f in malaria Hymenolepis nana, 231–233
symptoms and pathogenesis, 130 thick films, 268, 269f identifying characteristics of, 211
treatment of infection, 132 thin films, 269, 270f Multiceps multiceps, 224, 225
Babesiosis, 242t staining of, 267 Spirometra spp., 214, 215
Atovaquone-azithromycin in, 297t Blood flukes, 191–204 Taenia saginata, 222–224
clindamycin-quinine in, 297t life cycle of, 192–193, 193f Taenia saginata asiatica, 224, 225
Bacille Calmette-Guérin morphology of, 191–192, 192f Taenia solium, 215–222
immunotherapy in Boeck and Drbohlav’s Locke-egg-serum uncommon infections in humans,
leishmaniasis, 296 culture medium for amoebae, 236
Baermann apparatus in stool 264 Cestodiases
examination, 261, 262 Brachiola vesicularum, 95 epidemiology of, 11
Balamuthia mandrillaris Brain Chagas’ disease, 242t
life cycle of, 44f, 47, 48 in cysticercosis, 220f, 219–221 Rhodnius prolixus, 241f
Balamuthia spp., 48 in Multiceps multiceps infection, 225 Charcot-Leyden crystal, 251f
cyst of, 48 Broad fish tapeworm. See Chemoprophylaxis in malaria therapy,
infections from, 298 Dibothriocephalus latus 287
morphology of, 48 Brugia malayi, 154, 155 Children
symptoms and pathogenesis, 48 diagnosis of, 155 amoebiasis in, 34
Balantidium coli epidemiology of, 155 Angiostrongylus costaricensis infections
cyst of, 93 life cycle of, 153f,154–155 in, 165
diagnostic test of infection, 94 morphology of, 154 celiac disease in, 54
epidemiology of, 95 pathogenesis of, 155 Cryptosporidium parvum infections
identifying characteristics of, 94 treatment of infection, 155 in, 124
infective stages of, 93 Brugia timori, 155 Dipylidium caninum infections in,
life cycle of, 93, 94f life cycle of, 155 231
mode of transmission morphology of, 155 Entamoeba moshkovskii infections
of infection, 94 treatment of infection, 155 in, 34
morphology of, 93 Buffalo skin in Entamoeba histolytica Giardia duodenalis infections in, 51,
pathogenesis of, 94, 95 infections, 32 54
prevention of infection, 95 Buffy coat method for Leishmania, 270 Hymenolepis nana infections in, 231
treatment of infection, 95 malaria in, 113
Bancroftian filariasis, 242t C hypoglycemia, 114
Baylisascaris procyonis, 166 Cachectin, 8 nephrotic syndrome, 113
Beaver bodies in stool specimen, 250f Calabar swellings in Loa loa infections, renal disease, 113
Benign tertian malaria, 103t 156 Schistosoma intercalatum infections
Bentonite flocculation test, 277 Capillaria philippinensis, 141, in, 197
Benznidazole in Chagas’ disease, 295 142, 304 schistosomiasis in, 201
Bertiella studeri, 236 diagnosis of, 142 Toxoplasma gondii infections
eggs of, 142 in, 128
INDEX 347
Chilomastix mesnili, 56 life cycle of, 122, 123f Dexamethasone in neurocysticercosis,

cysts of, 56 morphology, 124 301
identifying characteristics, 56t symptoms and pathogenesis, 122 Diamond’s culture medium, 263
morphology of, 56 Culbertson’s medium for for Entamoeba hisolytica, 263
Chloroquine Acanthamoeba, 274 for Trichomonas, 263
in Babesia spp. infection, 132 Culex mosquitoes, 243f for Trichomonas vaginalis, 59
in babesiosis, 297 Culture techniques, 274, 275 Diarrhea
in malaria, 117, 288 for Acanthamoeba, 274 in Cryptosporidium parvum infection,
dosage and route of for Amoebae, 274 124
administration, 289 for Leishmania, 275 in Entamoeba histolytica infections,
mechanisms of action, 287t for Naegleria fowleri, 274, 275 23, 26, 31
resistance to, 289 for Toxoplasma gondii, 275 in Entamoeba polecki infections, 38
Chromatoidal materials for Trypanosoma cruzi, 275 Dibothriocephalus latus, 212–214
of Entamoeba coli, 30f, 36 Cycloguanil pamoate in mucocutaneous diagnosis of, 212
of Entamoeba hartmanni, 35 leishmaniasis, 296 epidemiology of, 214
of Entamoeba histolytica, 25, 28f Cyclospora cayetanensis, 124–126 gravid proglottids of, 212f
of Entamoeba polecki, 31f, 38 diagnosis of, 126f human infections, 213
Ciliophora, 8, 93 epidemiology, 126 identifying characteristics
Cinchonism in quinine therapy, 288 life cycle, 124, 125f of, 213
Clam as intermediate host of symptoms and pathogenesis, 126 life cycles of, 212, 213f
trematodes, 173 treatment of infection, 126 morphology of, 212f
Clonorchiasis Cyclosporiasis pathogenesis of, 213
in Clonorchis sinensis, 206t trimethoprimsulfamethoxazole in, prevention of infection, 214
epidemiology of, 11 286 treatment of infection, 214
Clonorchis sinensis, 173–177 Cysticercoids Dicrocoeliasis
diagnosis of infection, 175 of Dipylidium caninum, 231 in Dicrocoelium dendriticum, 206t
eggs of, 172f, 175 of Hymenolepis nana, 233 Dicrocoelium dendriticum, 178f, 179
life cycle of, 175, 176f Cystitis in Trichomonas vaginalis eggs of, 178
morphology of, 173, 174 infection, 58 life cycle of, 178
pathogenesis of, 177 Cystoisospora belli, 118–120, 251 morphology of, 178
symptoms of infections, 177f, blood examination, 120 symptoms and pathogenesis of
175–189 diagnosis of, 118 infections, 178
treatment of infections, 177 life cycle of, 118, 119f treatment of infections, 179
Clotrimazole cream in cutaneous staining, 120 Dientamoeba fragilis, 60, 61
leishmaniasis, 296 symptoms and pathogenesis of cysts of, 60
Coenurus disease, 224, 225 infection, 118 diagnosis of infection, 61
Coleoptera, 10 treatment of, 120 epidemiology of, 61
Commensalism Cystoisosporiasis, 118 identifying characteristics
definition of, 2 malabsorption in, 118 of, 60t
Compromised host, 5 symptomatic, 118 morphology of, 60
Concentration techniques in stool Cysts prevalence of, 61
examination, 254 of Acanthamoeba spp., 48 symptoms of, 60, 61
Confusers, 247 of Balamuthia spp., 48 treatment of infection, 61
Congenital transmission of Balantidium coli, 93 Diethylcarbamazine
in malaria infection, 103, 116 of Chilomastix mesnili, 56 in Brugia malayi, 155
Contact transmitted infection of Dientamoeba fragilis, 60 in Brugia timori, 155
Enterobius vermicularis of Echinococcus granulosus, 225, in Brugia timori infections, 305
preventive measure, 7 227f in Loa loa, 156
Corpora parasitica in stool specimen, of Endolimax nana, 42, 43 in lymphatic filariasis, 304
250f, 250 of Entamoeba coli, 36 in Wuchereria bancrofti, 154
Corticosteroids therapy of Entamoeba hartmanni, 331f in Wuchereria infections, 305
in toxoplasmosis, 297 of Entamoeba histolytica, 331f Diloxanide furoate
Crayfish ingestion of Entamoeba polecki, 38 in Entamoeba histolytica infections, 34
Paragonimus infection from, 187, 188f of Enteromonas hominis, 61 in Entamoeba polecki, 285
Creatorrhea, 247 of Giardia duodenalis, 54 Dioctophyma renale, 166
Creeping eruption of Iodamoeba bütschlii, 42 Dipetalonema perstans, 157, 158.
in Strongyloides fuelleborni infection, of Naegleria fowleri, 45 See also Mansonella perstans
149 of Retortamonas intestinalis, 62 Dipetalonema streptocerca, 157. See also
Crustacea, 9 Mansonella streptocerca
Cryptosporidiosis D Diphyllobothriasis, 214, 242t
nitazoxanide in, 286 D’Antoni’s iodine staining, Diphyllobothrium latum
Cryptosporidium parvum, 122–124 256 (Dibothriocephalus latus), 9
diagnosis of, 122 Deer fly, 243f Diplogonoporus grandis, 236
epidemiology of, 124 Definitive host, definition of, 6 Diptera, 10
348 INDEX
Dipylidiasis, 242t in Echinostoma ilocanum, 206t Entamoeba dispar, 23

Dipylidium caninum, 231 Eflornithine in African focal intestinal lesions from, 35
diagnosis of, 231 trypanosomiasis, 294 identification of, 35
diagnostic test for, 231 Eggs morphology of, 35
egg packets of, 232f of Ascaris lumbricoides, 136, 341f prevalence of, 35
epidemiology of, 231 of Capillaria philippinensis, 142, 341f Entamoeba gingivalis, 23, 37
life cycles of, 231, 232f of Clonorchis sinensis, 172f, 175, 340f life cycles of, 6
mode of transmission of, 231 of Dibothriocephalus latus, 212 morphology of, 37
morphology of, 231, 232f of Dicrocoelium dendriticum, 178 pyorrhea alveolaris from, 37
pathogenesis, 231 of Diphyllobothrium latum Entamoeba hartmanni, 23, 35
prevention of infection, 231 (Dibothriocephalus latus), 340f identification of, 36t
treatment of infection, 231 of Dipylidium caninum, 340f morphology of, 35
Direct wet film technique in stool of Echinococcus granulosus, 225 Entamoeba histolytica, 23–35, 251, 331f
examination, 253, 254 of Echinostoma sp., 340f amoebic ulcer from, 31, 32
Dirofilaria immitis, 159 embryonated, definition of, 6 anti-amoebic drugs for infection,
Dirofilaria repens, 159 of Enterobius vermicularis, 138, 341f 285
Dirofilaria tenuis, 159 of Eurytrema pancreaticum, 191 asymptomatic infection, 29
Dirofilaria ursi, 159 of Fasciola gigantica, 340f clinical classification, 29
Disseminated strongyloidiasis of Fasciola hepatica, 179 cysts of, 25, 26, 28f, 31f
Strongyloides stercoralis, 148 of Fasciolopsis buski, 182, 340f diagnosis of infection, 33
DNA probe, 277 of Gastrodiscoides hominis, 186 diarrhea or dysentery from, 26
Dogs of Gastrodiscus aegyptiacus, 340f effect on host, 3, 4
Echinococcus granulosus in, 225 of Heterophyids, 185 EIA test for rapid detection of, 278
Multiceps multiceps in, 212, 225 of hookworm, 341f epidemiology of, 33, 34
Doxycycline of Hymenolepis diminuta, 341f hepatic infection from, 32
in malaria, 117 of Hymenolepis nana, 218f, 233, intestinal amoebiasis, 26
in Onchocerca volvulus, 308 341f intestinal infections from, 30, 31
Doxycycline in malaria, 290 of Metagonimus yokogawai, 340f life cycle of, 26, 27f
Dracunculiasis, 242t of Necator americanus, 144 metabolism in, 3
epidemiology of, 11 of Opisthorchis viverrini, 340f morphology of, 24, 25
Dracunculus medinensis, 159–161 of Paragonimus westermani, 340f mortality rate from, 26
diagnosis of, 160 schistosomal hatching test, 262, 263 nuclear structure of, 26–29
epidemiology of, 161 of Schistosoma mansoni, 340f prevention of infection, 34, 35
life cycle of, 159, 160f of Strongyloides stercoralis, 147, 341f serologic test, 33
morphology of, 159 of Taenia solium, 216, 217f sigmoidoscopic examination of, 32
pathogenesis of, 161 of Taenia sp, 340f small race of, 23
treatment of infections, 161 of Trematodes, 171, 172f in stool, 33–35
Dyak hair in Entamoeba histolytica of Trichostrongylus orientalis, 341f symptomatic infections, 29
infections, 32 of Trichostrongylus spp., 149 symptoms and pathogenesis in
of Trichuris trichiura, 140 infection, 26–33
E ELISA, 277 treatment of infection, 34
Earthworm in stool specimen, 250 Emetine, in treatement of trophozoite of, 24, 25
Echinococcus granulosus, 2, 225–231 amoebiasis, 34 with hyaline pseudopodium, 28f
diagnosis of, 227, 228f Encephalitis ingested bacteria and granular
diagnostic test, 228, 229f granulomatous amoebic, 45, 47, pseudopodium in, 30f
epidemiology of, 230 298 staining with iron hematoxylin,
geographical distribution Sappinia diploidea, 45 27f
of, 15f Encephalitozoon cuniculi, 95 trichrome staining, 27f
life cycle of, 6, 225, 227f, 228f Encephalitozoon hellem, 95 Entamoeba moshkovskii, 23, 35
morphology of, 225, 226f Encephalitozoon intestinalis, 95, 96f detection of infection, 35
pathogenesis of, 229 Endemic, definition of, 10t identification of, 34
prevention of infection, 231 Endolimax nana, 23, 42 prevalence of, 35
transmission, mode of, 229 cysts of, 42, 43 Entamoeba polecki, 23
treatment of infection, 230 identification characteristics of, 43t cysts of, 38
Echinococcus multilocularis, 228f morphology of, 42 diagnosis of, 39
geographical distribution of, 15f nuclear structure of, 42f, 43 identification characteristics
Echinococcus vogeli, 228f Endoparasite, 3 of, 38t
geographical distribution of, 15f Entamoeba chattoni, 23, 38 morphology of, 38
Echinostoma, 183 Entamoeba coli, 2, 23 treatment of infection, 39
life cycle, 183, 184f cysts of, 36 Enterobius vermicularis, 138
Echinostoma ilocanum, 183 identification of, 37 diagnosis of, 138
Echinostomiasis iodine staining of, 37 epidemiology of, 140
in Artyfechinostomum malayanum, 206t morphology of, 36 life cycle of, 6, 138, 139f
INDEX 349
morphology of, 138 Fasciolopsiasis in Fasciolopsis buski, Formalin-ether concentration

pathogenesis of, 139 206t technique, 259
treatment of, 139 Ferrous sulfate Free-living amoeba, 43–45
Enterocytozoon bieneusi, 95 in hookworm infections, 304 Fumagillin
electron micrograph of spore, 96f in Necator americanus, 146 in Encephalitozoon hellem infection,
Enteromonas hominis Fever 286
cysts of, 61 in Ascaris lumbricoides infections, 136 in microsporidia infection, 98
morphology of, 61 in malaria, 103, 105, 122, 128
Enterotest recovery of Cystisospora belli, in Mansonella perstans infections, G
120 158 Gametocytes
Enzyme immunoassay, 277 in Schistosomiasis japonicum of Plasmodium falciparum, 111, 112f
Epidemic, definition of, 10t infections, 198 of Plasmodium ovale, 108, 109f
Epidemiology of parasitic diseases, in sheep liver fluke infections, 180 of Plasmodium vivax, 106, 107f
10, 11 in taeniasis, 220 Gametocyticides in malaria therapy, 287
distribution of, 11–17 Fields’s stain, 273 Gastrodiscoides hominis, 186
prevalence, 10, 11 Filariae, 152–159 eggs of, 186
Epididymitis in Trichomonas vaginalis Brugia malayi, 154, 155 life cycle of, 186
infection, 59 Brugia timori, 155 morphology of, 186
Erythrocytic schizogony, 105 Loa loa, 155, 156 symptoms and pathogenesis of, 186
Estrogen in Trichomonas vaginalis Mansonella ozzardi, 156, 157 treatment of infection, 186
infection, 59 Mansonella perstans, 157, 158 Gastrointestinal disorders
Eurytrema pancreaticum, 191 Mansonella streptocerca, 157 in Balantidium coli infection, 93
eggs of, 191 Onchocerca volvulus, 158, 159 in Dientamoeba fragilis infection, 61
life cycle of, 191 Wuchereria bancrofti, 152–154 in microsporidiosis, 95, 98
morphology of, 191 Filariasis, 154 Giant intestinal fluke, 181–183
treatment of infection, 191 bancroftian, 155 Giant liver fluke, 181
Evolutionary adaptations to parasitism, effects of host, 5 Giardia duodenalis, 50–56
3, 4 risk factors for, 7 cyst of, 54
Exflagellation, 104 timoran, 242t diagnosis of, 55
Fish consumption epidemiology of, 55
F Clonorchis sinensis infections in, 175, giardiasis from, 50
Facultative parasite, 3 176f identifying characteristics of, 24t
Falciparum malaria, 103t Dibothriocephalus latus infections life cycle of, 51f, 51–53
Fasciola, 173 in, 213 morphology of, 53, 54
Fasciola dendriticum. See Dicrocoelium Heterophyids infections in, 185 prevention of infection, 56
dendriticum Metorchis conjunctus infections in, sucking disk and flagella of, 51f, 52
Fasciola gigantica, 181 205 symptoms and pathogenesis of,
life cycle of, 181 Nanophyetus salmincola infections 54, 55
Fasciola hepatica, 179f–181f in, 205 as traveller’s diarrhea, 54
control of infection, 181 Opisthorchis felineus infections in, treatment of infection, 55
eggs of, 179 177 Giardia lamblia (Giardia duodenalis), 247
life cycle of, 179, 180f Opisthorchis viverrini infections in, metabolism in, 3
life cycles of, 6 178 Giardiasis, 247
morphology of, 179 Flagellates, 50–62 Giardia duodenalis, 74t
pathogenesis of, 180 Chilomastix mesnili, 56 prevalence of, 11
symptoms of infection, 179, 180 Dientamoeba fragilis, 60, 61 Gid, 225
treatment of, 181 Enteromonas hominis, 61 Giemsa's stains, 268, 273
Fasciola lanceolata. See Dicrocoelium features of, 50 of Plasmodium, 106
dendriticum Giardia duodenalis, 50–56 Glycogen
Fascioliasis Retortamonas intestinalis, 62 in Entamoeba coli, 30f
epidemiology of, 11 Trichomonas hominis, 56, 57 in Entamoeba histolytica, 25, 28f
in Fasciola hepatica, 206t Trichomonas tenax, 60 in Entamoeba polecki, 38
Fasciolopsiasis Trichomonas vaginalis, 57–59 in Iodamoeba butschlii, 39, 41f
epidemiology of, 11 Flotation techniques in stool Gnathostoma spinigerum, 165
Fasciolopsis buski, 181f–183f examination, 254 diagnosis of, 166
effect on host, 4 Fluorescent antibody, indirect, 277 epidemiology of, 166
eggs of Food or Water-borne infection life cycle of, 166
Hen’s egg appearance, 182 Balantidium coli, 7 pathogenesis of, 166
life cycle of, 181, 182f Dibothriocephalus latus, 212–214 treatment of infection, 166
morphology of, 182 Giardia lamblia, 7 Gnathostomiasis in Gnathostoma
symptoms and pathogenesis of Paragonimus westermani, 7 spinigerum infections, 166
infection, 182, 183 Schistosoma spp., 7 Gomori’s trichrome stain, 260
treatment of infection, 183 Taenia solium, 215–222 Gongylonema spp., 151
350 INDEX
Gradient centrifugation technique for epidemiology of, 235 in cutaneous larva migrans, 146,
microfilariae, 270 life cycles of, 234 303
Granulomatous amoebic encephalitis morphology of, 234 in Loa loa, 156
(GAE), 49 pathogenesis of, 235 in Mansonella perstans, 158
course of infection, 49 transmission of, 235 in Streptomyces avermitilis infections,
diagnosis of, 49 treatment of infection, 236 305, 306
feature of, 49 Hymenolepis microstoma, 236 in Strongyloides stercoralis, 148
treatment of infection, 50 Hymenolepis nana, 9, 231–233 in Wuchereria infections, 306
Granulomatous amoebic diagnosis of, 233 Ixodes dammini, 131
meningoencephalitis (GAM) diagnostic test for, 233 Ixodes sp., 244f
Acanthamoeba spp., 73t eggs of, 218f, 233
Balamuthia mandrillaris, 73t epidemiology of, 233 K
Gymnophalloides seoi, 204 life cycles of, 233–235 Kampala or Ugandan eye worm in
mode of transmission of, 233 Mansonella perstans infection,
H morphology of, 218f, 232 158
Halofantrine in malaria, 291 pathogenesis of, 233 Katayama fever, 198
Hansel’s stain, 273 penetration of intestinal villus, 4 Kato’s thick-smear technique, 265
Haplorchis taichui, 204 prevention of infection, 233 Ketoconazole in cutaneous
Helminths treatment of infection, 233 leishmaniasis, 296
life cycles of, 5 Hymenoptera, 10 Kinyoun’s carbolfuchsin acid-fast stain,
metabolism in, 3 Hyperendemic, definition of, 10t 260
preventive measure, 7 Hyperinfection Kit tests, 278
Hemagglutination test, indirect, 277 Hymenolepis nana, 233
in Echinococcus granulosus, 229 Strongyloides stercoralis, 147 L
in Entamoeba histolytica infections, Hypnozoite of Plasmodium, 104f, 105f Laboratory animal inoculation, 275
33 latency period of, 105 Lagochilascaris minor, 166
Hematoxylin staining reactivation of, f0025, 105 Latex agglutination test, 277
of Chilomastix mesnili, 56 Leishmania
of Dientamoeba fragilis, 60 I immunity to reinfection, 5
of Entamoeba histolytica, 25, 27f, 33 Immunoblot test, 277 metabolism in, 3
of Entamoeba polecki, 38 Immunodiagnostic techniques, Leishmania donovani
Hemiptera, 10 276–278 buffy coat method for detection of,
Henneguya salminicola, 99 Immunofluorescence, direct, 277 270
Hepatosplenic schistosomiasis, 198 Insecta, classification of, 9, 10 Kala-azar from, 10
Heterophyes heterophyes, 185f Intermediate hosts, definition of, 6 Leishmaniasis, 242t
Heterophyidiasis in Heterophyes Intermittent parasite, 3 Buffy coat method in, 270
heterophyes infection, 206t Intestinal flukes, 181–186 epidemiology of
Heterophyids, 185f Intestinal polyposis in Schistosomiasis geographic distribution in, 12f–17f
eggs of, 185 japonicum infections, 198 prevalence of, 11
life cycle of, 185 Intestinal schistosomiasis, 198 Phlebotomus, 241f
morphology of, 185 Intestinal taeniasis, 219 prevalence of, 11
symptoms and pathogenesis, 186 Iodamoeba bütschlii, 23, 39–42 Leishmania tropica
treatment of, 186 cyst of, 42 tissues examination in, 274, 275
HIV-infection identification characteristics of, Liver flukes, 173–181
from Encephalitozoon hellem, 98 40t Loa loa, 155, 156
Hookworms, 143 morphological characteristics of, diagnosis of, 156
anemia from, 143 39, 41f epidemiology of, 156
in cats and dogs, 146 nuclear structure of, 39, 41f life cycle of, 155, 156f
cutaneous larva migrans from, 146 Iodine staining morphology, 155
epidemiology of, 11 of Endolimax nana, 43 pathogenesis of, 156
geographical distribution of of Entamoeba coli, 37 treatment of infection, 156
infection, 16f of Entamoeba histolytica, 25 Loeffler’s alkaline methylene blue
mouth structures of, 342f of Entamoeba polecki, 38 stain, 260
Host of Iodamoeba bütschlii, 39 Loiasis, 242t
definition, 2 Iodoquinol geographical distribution of, 17f
definitive or final, 2 in Balantidium coli, 286 Loop-mediated isothermal
intermediate, 2 in Dientamoeba fragilis, 286 amplification technique, 278
paratenic, 2 in treatment of Balantidium coli Loperamide hydrochloride in Trichuris
Hydatid disease, 230 infections, 95 trichiura infections, 304
Hydatid sand, 227, 228f, 229f Iron hematoxylin stain, 259 Lugol’s solution in stool examination,
Hydroxychloroquine in malaria, 289 Itraconazole in cutaneous 256
Hymenolepiasis, 242t leishmaniasis, 296 Luminex technology, 278
Hymenolepis diminuta, 233 Ivermectin Lung fluke, 186–191
diagnostic test for, 235 in Brugia malayi, 155 Lymphatic filarial diseases
INDEX 351
geographical distribution of, 17f commercially available drugs for, Mesocestoides, 236
Lymphatic filariasis 286 Metagonimus yokogawai, 185f
epidemiology of, 11 in life cycle stages of infection, Metorchis conjunctus, 205
287 Metrifonate
M mechanisms of action of drug, in Schistosoma haematobium
Macracanthorhynchus hirudinaceus, 152 287t infections, 300
Macracanthorhynchus ingens, 152 multiple drug in, 291–293 in Schistosoma intercalatum, 203
Macrophages in stool specimen, 250, single drugs in, 287–291 Metronidazole
251f suppressive therapy for, 286 in Dientamoeba fragilis infection, 61
Malaria, 103–132, 242t types of, 113t in Dracunculus medinensis infections,
aestivoautumnal, 103t vivax. See Plasmodium vivax 307
in AIDS patients, 128 Malarial malaria, 103t in Dracunculus medinensis, 161
algid, 114 Malayan filariasis, 242t in Entamoeba histolytica, 285
anemia in, 113 Malayan’s filarial worm, 154 in Entamoeba histolytica infection, 34
Anopheles quadrimaculatus, 241f Malignant tertian malaria, 103t in Entamoeba polecki, 285
antigen detection for, 278 Mansonella ozzardi, 156, 157 in Entamoeba polecki infection, 39
benign tertian, 103t diagnosis of, 157 in Giardia duodenalis infection, 55,
blackwater fever in, 114 life cycle of, 157 285
blood films in, 106, 111, 130 morphology of, 157 in protozoan infection, 7
thick films, 268, 269f pathogenesis of, 157 in Trichomonas, 285
thin films, 269, 270f treatment of infection, 157 in Trichomonas vaginalis infection, 59
cerebral, 113 Mansonella perstans, 157, 158 Meyers and Kouwenaar syndrome in
complications in, 114 diagnosis of, 158 Wuchereria bancrofti, 154
pathogenesis in, 114 life cycle of, 157 Meyer’s egg albumin preparation for
complications in, 113, 114 morphology of, 157 stool specimen, 257
development of vaccines, 117 pathogenesis of, 158 Microcytic hypochromic anemia, 4
diagnostic tests in, 111 treatment of infection, 158 Microfilariae
drug resistance Mansonella sp. of Brugia malayi, 154
to chloroquine, 117, 289 commensal filaria from, 10 of Brugia timori, 155
to mefloquine, 290 Mansonella streptocerca, 157 of Loa loa, 155
to quinine, 117, 288 diagnosis of, 157 of Mansonella ozzardi, 157
dysenteric, 114 life cycle of, 157 of Mansonella perstans, 157
epidemiology of, 116, 117 morphology of, 157 of Mansonella streptocerca, 157
epidemiology pathogenesis of, 157 of Onchocerca volvulus, 158
geographic distribution in, treatment of infection, 157 of Wuchereria bancrofti, 152
14f Mansonelliasis, 242t Micronema deletrix, 166
prevalence of, 11 Mansonia mosquitoes, 243f Microspora, 95
eradication programs, 116 Mastigophora, 8 diagnosis of infection, 96
global report on, 116f Mathevotaenia symmetrica, 236 diagnostic test of infection, 96, 97
hyperparasitemia in, 114 Maurer's dot in Plasmodium falciparum, electron micrograph of spore, 96f
hypnozoite theory, 106f 111 epidemiology of, 98
hypoglycemia in, 114 Mebendazole identifying characteristics of, 97
leukopenia, 116 in Angiostrongylus cantonensis, 165 infective form of, 96
malignant tertian, 103t in Capillaria philippinensis, 142 intestinal infection from, 97, 98
in newborn, 128 in Echinococcus granulosus, 230 life cycle of, 96, 97f
paroxysms, 106, 116 in Enterobius vermicularis infections, modes of transmission of infection,
pathogenesis of, 115f 139 96
from Plasmodium sp., 10 in hookworm infections, 302, 303 morphology of, 95
prevention of, 117 in Mansonella infections infections, pathogenesis of, 97
proteinuria, 113 307 treatment of infection, 98
proteinuria in, 113 in Necator americanus, 146 trichrome staining of, 97
pulmonary edema in, 114 in nematode infection, 7 Microsporidia, 10, 95
quartan, 103t in Trichostrongylus spp., 149 Microsporidia
recrudescence in, 105, 113t in Trichuris trichiura infection, 140 morphologic adaptations to
relapse in, 105, 106f, 113t Mechanical vector, 2 parasitism, 3
renal disease in infection, 113 Mechanical vector, definition of, 6 Microsporidial myositis, 98
rodent, 130 Medical Entomology, definition of, 241 MIF stain in stool examination
splenomegaly, 114f Medical Parasitology, definition of, 2 with preservative solutions, 256
symptoms of, 113 Mefloquine in malaria, 289, 290 Miltefosine in visceral leishmaniasis, 297
test for parasite counting in, 269 Meglumine antimoniate in cutaneous Mixed immunofluorescence (MIF)
treatment of, 117, 286–293 leishmaniasis, 295, 296 staining
antimalarial drugs, 117 Membrane filtration method for for direct smears, 256
combination therapy, 117 microfilariae, 270 Molecular techniques, 277, 278
352 INDEX
Mollusks as intermediate host of Strongyloides, 146–149 of Cystoisospora belli, 118, 120f

trematodes, 175 tissue-dwelling, 159–166 of Toxoplasma gondii., 129
Moniliformis moniliformis, 144 Trichostrongylus spp., 149 Operculum of trematodes, 172
Multiceps multiceps, 224, 225 Trichuris, 140 Opisthorchiasis
diagnosis of, 225 uncommon tissue, 166 epidemiology of, 11
epidemiology of, 225 vector-borne, 152–159 Opisthorchis felineus, 177
life cycles of, 224, 226f Nephrotic syndrome, 113 morphology of, 177
mode of transmission, 224 Neurocysticercosis treatment of, 177
morphology of, 224 treatment of, 301, 302 Opisthorchis viverrini, 177, 178
pathogenesis of, 225 Neurologic disorders epidemiology of, 178
prevention of infection, 225, 226f in Multiceps multiceps infection, 224 morphology of, 178
treatment of infection, 225 Niclosamide pathogenesis of, 177, 178
Musca domestica, 245f to control Schistosoma intercalatum treatment of, 178
Mutualism, definition of, 2 infection, 204 Opistorchiasis
Myocastor coypu, 149 in Dibothriocephalus latus infections, in Opistorchis felineus, 206t
Myxozoa, 98 300, 301 in Opistorchis viverrini, 206t
diagnostic test of infection, 98 in Dipylidium caninum, 231 Ovale tertian malaria, 103t
epidemiology of, 99 in Hymenolepis diminuta, 236 Oxamniquine
life cycle of, 98 in Hymenolepis nana, 233 in S. mansoni infections, 300
morphology of, 98 in Taenia solium, 221 Oxamniquine (Vasnil)
pathogenesis of, 99 Niclosamide (Niclocide) in in Schistosoma intercalatum, 203
Dibothriocephalus latus, 214 Oxytetracycline (Terramycin)
N Nifurtimox in Chagas’ disease, 294, 295 in treatment of Balantidium coli
Naegleria, 23 Nitazoxanide infections, 95
Naegleria fowleri, 45–47 in Cryptosporidium parvum, 286 Oxyuris vermicularis, 138
as brain-eating amoeba, 45 in Cryptosporidium parvum infection,
cyst of, 45 124 P
diagnosis of, 45–47 in H. diminuta infections, 301 Pancreatic fluke, 191
epidemiology of, 46 in H. nana infections, 301 Pandemics, definition of, 10t
life cycle of, 43f, 45 in Hymenolepis diminuta, 236 Papanicolaou smear in Dientamoeba
morphology of, 45 in Hymenolepis nana, 233 fragilis infection, 59
prevention of infection, 46 Nosema connori, 95 Paragonimiasis, 242t
symptoms and pathogenesis of, 45 Nosema corneum, 95 epidemiology of, 11
treatment of infection, 46, 47 Nosema ocularum, 95, 98 Paragonimus kellicotti, 187
Nanophyetus salmincola, 205f Novy-Macneal-Nicolle (NNN) medium Paragonimus spp., 186–191
Necator americanus, 144–146 for Leishmania, 275 diagnosis of, 188, 189f
diagnosis of, 144 Nuntucket fever, 244 eggs of, 187
effect on host, 4 Nutrition epidemiology of, 190
eggs of, 144 and pseudoparasites in stool life cycle, 187, 188f
epidemiology of, 146 specimen, 247–251 morphology of, 187
larval stages of, 144 pathogenesis of, 189, 190f
life cycle of, 144 O symptoms of, 188, 189
pathogenesis of, 146 Obligate parasite, 3 treatment of infection, 190, 191
treatment of infection, 146 Oesophagostomum spp., 151 Paragonimus westermani, 9, 186f, 187, 251
Nelson’s culture medium for Naegleria Onchocerca volvulus, 158, 159 in human brain, 190f
fowleri, 274, 275 diagnosis of, 158 in lung tissue, 190f
Nemathelminthes epidemiology of, 159 Parasitism, definition of, 2
classification of, 9 life cycle of, 158, 159f Parastrongylus cantonensis, 164, 165.
Nematodes morphology of, 158 See also Angiostrongylus
Ancylostoma, 143 pathogenesis of, 158 cantonensis
Anisakis spp., 150, 151 river blindness from, 10 Paromomycin in cutaneous
Ascaris, 114, 136 treatment of infection, 158 leishmaniasis, 296
Capillaria philippinensis, 141, 142 Onchocerciasis, 242t Pentamidine in African
Enterobius, 138 epidemiology of, 11 trypanosomiasis, 293
intestinal, 151, 152 geographical distribution of, 17f Pentastomida, 10
life cycle, 135 treatment of, 306 Pentatrichomonas hominis. See
modes of transmission, 135 Oncosphere Trichomonas hominis
ingestion, 135 of Echinococcus granulosus, 225, 227f Periplaneta americana, 244, 245f
inhalation, 136 of Hymenolepis diminuta, 235 Peromyscus leucopus, 131
larva, 135 of Hymenolepis nana, 233 Phaneropsolus, 205
skin penetration, 135 of Taenia solium, 216, 219 Philophthalmus, 205
transmammary, 136 Oocysts Philophthalmus lacrimosus, 205
morphology of, 135 of Cryptosporidium parvum, 122 Piperazine in Ascaris infections, 303
Necator, 144–146 of Cyclospora cayetanensis, 124 Pipestem fibrosis, 200f
INDEX 353
Plant structures in stool specimen, 249f Primaquine in malaria, 117, 292, 293 Respiratory disorders
Plasmodium falciparum, 103t, 111, 112f Primary amoebic meningoencephalitis in Trichomonas tenax infections, 60
in capillaries of brain, 115f (PAM) in Trichomonas vaginalis infections,
chloroquine-resistant, 289 Naegleria fowleri, 73t 59
effect on host, 4 Procyon lotor, 149 Retortamonas intestinalis, 62
host resistance, to Proglottids of cestodes, 211f cyst of, 62
in Sickle cell trait, 4 of Dibothriocephalus latus, 212f, 224t morphology of, 62
life history of, 104f of Dipylidium caninum, 231, 232f Retroinfection, 138
renal disease in infection, 113 of Echinococcus, 225 Ritchie sedimentation method, 257
Plasmodium knowlesi, 103f, 117 of Taenia saginata, 222, 224t modified for Cryptosporidium, 258
Plasmodium malariae, 103t, 108, 110f of Taenia saginata asiatica, 224 Ryan’s trichrome blue stain, 261
Plasmodium ovale, 103t, 108, 109f of Taenia solium, 216f, 219, 224t
Plasmodium vivax, 103t–108t Proguanil in malaria, 290 S
chloroquine-resistant, 289 Propamidine in Acanthamoeba keratitis SAF fixative solution for stool
effects of host, 4 infections, 298 examination, 257
Giemsa stain, 107f Prostate, Trichomonas vaginalis infection Sand fly, 243f
hypnozoite of, 105f of, 59, 74t Sarcocystis, 120–122
life cycle of, 106 Protozoa in bovine tissue, 121
pre-erythrocytic schizont in liver, 105f classification of, 8 diagnosis of, 121, 122
resting stage, 105 life cycles of, 5 hematoxylin-eosin staining, 122
signet ring appearance of, 108f Pseudoparasites, 247–251 life cycle of, 120, 121f
Platelets in malarial smear specimen, Pseudopodia, 23 in muscle tissue, 122f
250f of Dientamoeba fragilis, 60 symptoms and pathogenesis of, 120
Platyhelminthes of Endolimax nana, 42 treatment of infection, 122
classification of, 8, 9 of Entamoeba coli, 36 Sarcomastigophora, 8, 23
Plectroplites ambiguus, 99 of Entamoeba histolytica, 24 Scavengers, definition of, 1
Plerocercoid stage of Entamoeba polecki, 38 Schaudinn’s solution for stool
of Dibothriocephalus latus, 212, 213f of Iodamoeba bütschlii, 39 specimen, 257
Pollen grains in stool specimen, 248f, of Naegleria fowleri, 45 Schistosoma haematobium, 194–196
249f Psorospermium haeckelii, 250f eggs of, 196
Polymerase chain reaction techniques, Pulmonary eosinophilia in Wuchereria hydronephrosis and hydroureter
277 bancrofti, 154 from, 202f
Pork products Pulmonary paragonimiasis, 189f life cycle of, 196f
Taenia solium infections from, 215–222 Pulmonary schistosomiasis, 201f morphology and diagnosis of, 196
Potassium hydroxide stool PVA fixative solutions for stool in urine and vaginal secretions,
concentration method for examination, 256 273
Cyclospora, 258 Pyrantel pamoate Schistosoma intercalatum, 197–204
Praziquantel in Enterobius vermicularis infections, control measures for infection, 203,
in Clonorchis sinensis, 177 139 204
in Dibothriocephalus latus, 214 in hookworm infections, 303 egg of, 197f
in Dibothriocephalus latus infections, in Necator americanus, 146 epidemiology of, 202
300 Pyrimethamine immunology and pathogenesis of,
in Dicrocoelium dendriticum, 179 in malaria, 289 199–202
in Dipylidium caninum, 231 in multiple drug therapy, 291, 292 symptoms of infection, 197–199
in Fasciola hepatica, 181 in toxoplasmosis, 297 treatment of infection, 203
in Fasciolopsis buski infections, 298, 299 Schistosoma japonicum, 193–195
in Heterophyids, 186 Q eggs of, 194
in Hymenolepis diminuta, 236 Quality assurance in laboratory identification in stool, 194, 195f
in Hymenolepis nana, 233 process, 279 life cycle of, 195f
in Opisthorchis felineus, 177 Quinidine in malaria, 288 Schistosomal dermatitis, 204
in Opisthorchis viverrini, 178 Quinine Schistosomal hatching test, 262, 263
in paragonimiasis, 299 in malaria, 117, 287 Schistosomal periportal fibrosis
in Paragonimus spp., 190 dosage and route of in Schistosoma mansoni infection,
in Schistosoma intercalatum, 203 administration, 288 200f
in Schistosomal infections, 299 and hypoglycemia, 288 Schistosoma mansoni, 193, 200f
in Taenia solium, 221 mechanisms of action, 287t diagnosis of, 193
in trematodes and cestodes multiple drug therapy, 291 eggs of, 193
infection, 7 side effect, 288 in rectal biopsy, 195f
Preadaptation, definition of, 3 in stool, 193
Predation, 1 R life cycle of, 194f
Predator, definition of, 1 Radioallergosorbent test, 277 male and female in copula, 192f
Premunition, definition of, 5 Raillietina celebensis, 236 morphology of, 192f, 193
Prey, definition of, 1 Reduviid bug, 244f penetration glands of, 193f
354 INDEX
Schistosoma mekongi, 197 pathogenesis of, 215 Strongyloides stercoralis, 146–149

morphology of, 197 prevention of infection, 215 diagnostic tests of infevtion, 147
Schistosomiasis treatment of infection, 215 eggs of, 147
epidemiology of Sporadic, definition of, 10t epidemiology of, 148
geographic distribution in, 14f Sporogony, 8 larval stages of, 147
prevalence in, 11 Sporozoites life cycle of, 147, 148f
Schistosomiasis japonicum, 198 of Babesia spp., 130 morphology of, 147
Schistosomiasis mansoni, 198f of Cryptosporidium parvum, 122 pathogenesis of, 147, 148
Schistosomiasis mansoni, 200f of Cyclospora cayetanensis, 125 treatment of infection, 148
Schizogony, 8 of Cystoisospora belli, 118–120 Strongyloidiasis
Schizonticides in malaria of Plasmodium, 104f, 105 epidemiology of, 11
therapy, 287 of Sarcocystis, 120 Subtertian malaria, 103t
Schüffner’s dots, 106 Staining technique Suramin
Scolex of cestodes, 211 for direct smears, 256 in African trypanosomiasis, 293
of Dibothriocephalus latus, 212f for tissue impressions, 272 in onchocerciasis, 308
of Dipylidium caninum, 231, 232f Starch granules in stool specimen, Swamp itch
of Echinococcus, 225, 226f 249f, 250 in Strongyloides fuelleborni infection,
of Hymenolepis diminuta, 234 Steatorrhea, 247 149
of Hymenolepis nana, 232 Stoll’s egg-counting technique, 265 Swimmer’s itch, 204f
of Taenia saginata, 222, 223f Stool Swollen belly sickness
of Taenia solium, 216f, 218f, 219 antigen detection tests for, 266 in Strongyloides fuelleborni infection,
Second intermediate host, 2 Blastocystis hominis in, 248f 149
Sedimentation methods for stool DNA testing, 266 Syngamus laryngeus, 166
examination, 254 examination technique, 253–279 Systemic infections, 98
Serologic tests, 266 blood concentration procedures,
in Echinococcus granulosus, 229 270 T
Sexually transmitted infection concentration method, 253, 257 Taenia saginata, 222–224
Trichomonas vaginalis culture methods, 263, 264 epidemiology of, 224
preventive measure, 7 direct wet film, 253, 254 identifying characteristics of, 222
Sexually transmitted infections from egg-counting method, 265 life cycles of, 222, 223f
Trichomonas vaginalis, 58, 74t estimation of worm mode of transmission of, 222
Sheather’s sugar flotation procedure, burden, 265 morphology of, 222, 223f, 224t
258 Kato thick smear, 265 pathogenesis of, 222
in Cryptosporidium infections, 258 membrane filtration prevention of infection, 224
Sheep liver fluke, 179. See also Fasciola method, 270 treatment of infection, 224
hepatica modified Ritchie’s concentration Taenia saginata asiatica, 224
Sheep method, 258 Taenia solium, 215–222
Echinococcus granulosus in, 231 number of specimens, 255, 256 diagnosis of, 216, 217
Multiceps multiceps in, 212, 225 preservative solutions in, 256 diagnostic test of, 217–219
Siphonaptera, 10 slides preparation in, 257 eggs of, 216, 217f
Slide preparation stains in, 256, 259 epidemiology of, 221
preservative and fixative solutions stock solution in, 257 life cycles of, 216–218
in, 256 triple centrifugation mode of transmission of, 217
for stool examination, 254 method, 271 morphology of, 215, 216f
Sodium stibogluconate interfering substances with stool pathogenesis of, 219–221
in cutaneous leishmaniasis, 295 examinations, 255 prevention of infection, 222
in mucocutaneous leishmaniasis, antibiotics and antimalarials, 254 racemose cysts of, 219, 220f
296 barium, 255 treatment of infection, 221, 222
in visceral leishmaniasis, 296 castor oil or mineral oil, 255 Tafenoquine in malaria, 293
Soil-transmitted helminths (STH) enemas, 255 Tapeworms, 211–236
preventive measure, 7 urine contamination, 255 beef, 222–224. See also Taenia
Southeast Asian liver fluke, 177, 178 pollen grains in, 248f, 249f saginata
Sowda in Wuchereria bancrofti, 154 pseudoparasites in, 247–251 broad fish, 212–214. See also
Spiramycin in toxoplasmosis, 297 Strongyloides in Dibothriocephalus latus
Spirometra spp., 214, 215 filter paper strip procedure for dwarf, 231–233
cross section of, 215f larvae recovery, 262 fish, 212–214, 237t. See also
diagnosis of, 214 Trichostrongylus in Dibothriocephalus latus
epidemiology of, 215 filter paper strip procedure for intermediate host of, 211
identifying characteristics larvae recovery, 262 pork, 215–222. See also Taenia
of, 215 Strongyloides fuelleborni, 149 solium
life cycles of, 213f, 214 epidemiology of, 149 rat, 233. See also Hymenolepis
mode of transmission of, 214 morphology of, 149 diminuta
morphology of, 214 pathogenesis of, 149 vitamin B12 deficiency from, 213
INDEX 355
Temporary parasite, 3 pathogenesis of, 162 Trisulfapyrimidines in toxoplasmosis,

Terramycin treatment of infection, 162 297
in Balantidium coli, 286 Trichomonas hominis, 56, 57 Trophozoites
Tetrachloroethylene cysts of, 53f of Acanthamoeba spp., 48
in Echinostome infection, 300 identifying characteristics of Balantidium coli, 93f, 335f
in Gastrodiscoides hominis, 186 of, 57t of Chilomastix mesnili, 56, 334f
Tetracycline morphology of, 56, 57 definition of, 5
in malaria, 117 Trichomonas spp. of Dientamoeba fragilis, 60
Thelazia californiensis, 166 life cycles of, 6 of Endolimax nana, 42, 85t,
Thiabendazole Trichomonas tenax, 60 333f
in Angiostrongylus cantonensis, 165 morphology of, 60 of Entamoeba coli, 30f, 36,
in cutaneous larva migrans, 146, Trichomonas vaginalis, 57–59 85t, 332f
304 cell-detaching factor of, 59 of Entamoeba gingivalis, 37f,
in Dracunculus medinensis, infections culture of, 59 335f
infections, 307 diagnosis of, 59 of Entamoeba hartmanni, 35, 331f
in Dracunculus medinensis, 161 life cycle of, f0105, 57 of Entamoeba histolytica, 24–28,
Thioglycolate culture medium for morphology of, 57, 58 85t, 331f
Trichomonas vaginalis, 264 symptoms and pathogenesis of, of Entamoeba polecki, 38
Timoran filariasis, 242t 58, 59 of Enteromonas hominis, 61
Timor filariasis treatment of infection, 59 of Giardia duodenalis, 54, 55, 333f,
diethylcarbamazine trichomoniasis from, 58 334f
in, 305 urethritis from, 59 of Giardia lamblia, 52f
Tinidazole in urine and vaginal of Iodamoeba bütschlii, 39, 41f, 85t,
in Giardia lamblia, 285 secretions, 273 332f, 333f
Tissues examination, 272 vaginitis from, 59 of Naegleria fowleri, 45
culture methods in, 274, Trichomonas vaginalis of Plasmodium falciparum, 339f
275 metabolism in, 3 of Plasmodium malariae, 338f
staining in, 273 Trichomoniasis of Plasmodium ovale, 337f
Toxocara canis, 162–164 Trichomonas vaginalis, 74t of Plasmodium vivax, 336f
diagnosis of, 164 Trichostrongyliasis of Retortamonas intestinalis, 62
epidemiology of, 164 epidemiology of, 11 of Trichomonas hominis, 53f,
life cycle of, 163f, 164 Trichostrongylus spp., 149 56, 57
morphology of, 163 eggs of, 149 of Trichomonas tenax, 60
pathogenesis of, 164 epidemiology of, 149 of Trichomonas vaginalis, 57, 58f
treatment of infection, 164 morphology of, 149 Tropical splenomegaly
Toxoplasma gondii, 8, 126–130 pathogenesis of, 149 syndrome, 114f
diagnosis of, 129f treatment of infection, 149 Trypanosoma
epidemiology of, 129 Trichuriasis metabolism in, 3
life cycle of, 126, 127f epidemiology of, 11 Trypanosoma brucei gambiense
prevention of infection, 130 Trichuris egg, 249f sleeping sickness from, 10
symptoms and pathogenesis Trichuris trichiura, 140 Trypanosoma cruzi
of, 128 diagnosis of, 140 Novy-Macneal-Nicolle (NNN)
treatment of infection, 129 eggs of, 140 medium for, 275
Trachipleistophora hominis, 95 epidemiology of, 140 Trypanosoma lewisi
Transfusion-related infections life cycle of, 140, 141f infections in rats, 8
in malaria, 103 morphology of, 140 Trypanosomiasis
Transport or paratenic pathogenesis of, 140 distribution of, 13f
host, 2 treatment of, 140 Tse-tse fly, 243f
Trematodes, 171–208 Triclabendazole
blood flukes, 191–204 in Fasciola hepatica, 181 U
characteristics of eggs, 171–173 for treatment of fascioliasis, 300 Urinary schistosomiasis
intestinal flukes, 181–186 Trimethoprim-sulfamethoxazole in Schistosoma haematobium
life cycle of, 173, 174f in Cystoisospora belli infection, 120 infections, 198
liver flukes, 173–181 in treatment of cyclosporiasis, Urine examination, 255
lung fluke, 186–191 126
morphology of, 171 Trimethoprim-sulfamethoxazole V
pancreatic fluke, 191 in Cyclospora cayetanensis Vector-borne infection
uncommon, 204–206 infections, 286 Plasmodium sp.
Trichinella spiralis, 161, 162 Trimethoprim-sulfamethoxazole in preventive measure, 7
diagnosis of, 161 Cystoisospora belli infection, 286 Visceral larva migrans,
epidemiology of, 162 Triple centrifugation method 162–164
life cycle of, 161, 162f for detection of trypanosomes, Vittaforma corneae, 95, 98
morphology of, 161 271 Vivax malaria, 103t
356 INDEX
W Schistosoma japonicum, 193, 195f pathogenesis of, 154

Water-borne diseases Toxoplasma gondii, 126 treatment of infection, 154
Acanthamoeba keratitis, 49 Western blot test, 277
Balantidium coli, 94 Whipworm disease Y
Cyclospora cayetanensis, 124, 126 geographical distribution of, 16f Yeast in stool specimen, 247
Dicrocoelium dendriticum, 178 Whirling disease, 98
Echinostoma ilocanum, 183 Wright’s stain, 268 Z
Entamoeba histolytica, 34 Wuchereria bancrofti, 152–154 Zoonosis, 2
Fasciola hepatica, 179 diagnosis of, 153, 154 Zoonosis, definition of, 2
Giardia, 55 epidemiology of, 154 Zoonotic strongyloidiasis
Gongylonema spp., 151 life cycle of, 152, 153f in Strongyloides fuelleborni infection,
Naegleria fowleri, 46 lymphatic filariasis from, 10 149
Paragonimus spp., 187, 188f morphology of, 152

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10th South-East Asian edition

Markell and Voge’s

WILLIAM A. PETRI, JR., MD, PHD

Markell and Voge’s Medical Parasitology

Copyright © 2006, Elsevier Inc. All rights reserved.

Markell and Voge’s Medical Parasitology 10th South-East Asian edition

Copyright © 2020 Elsevier Singapore Pte. Ltd.

Senior Content Strategist: Chee Hooi Ping

Printed in the Philippines

Marietta Voge, 1918-1984

Rolter Lorenz M. Lee, RMT Haily Liduin Koyou, MLT, MSc

Noe Raphael D. Tarrosa, RMT

Jeremie Faye B. Umali, RMT

Patricia Alyanna Marie P. Madrigal

Kyle Patrick R. Magistrado

Preface iv 7 Phylum Platyhelminthes: Class

Introduction to Medical Parasitology

• Symbiosis (“living together”): This refers to associa- • Intermediate host

PATHOLOGY: SIGNS AND SYMPTOMS Effects of the Host on the Parasite

Examples: • In certain cases, like among the coccidians, a cer-

How to break the chain of Infection

Order Hemiptera • Derived from their body shape, which is elongate,

• Prevalence of parasitic infections • Heterophydiasis: 1.6% prevalence in 2004

FIG. 1.1 Distribution of cutaneous leishmaniasis.

FIG. 1.2 Distribution of mucocutaneous leishmaniasis.

FIG. 1.3 Distribution of visceral leishmaniasis.

FIG. 1.4 Distribution of trypanosomiasis.

FIG. 1.5 Distribution of malaria; distribution of chloroquine resistance (2004).

FIG. 1.6 Distribution of schistosomiasis.

FIG. 1.7 Distribution of Echinococcus granulosus.

FIG. 1.8 Distribution of Echinococcus multilocularis and Echinococcus vogeli.

FIG. 1.9 Distribution of hookworm infection.

FIG. 1.10 Distribution of clinically important whipworm disease.

FIG. 1.11 Distribution of lymphatic filarial diseases.

FIG. 1.12 Distribution of onchocerciasis and loiasis.

NEWS UPDATE ( Cont. ) Insights from the News Article:

3. Entamoeba coli is an example of _____: 10. Resistance to malarial infection caused by

Protozoa: Phylum Sarcomastigophora

INTRODUCTION • Entamoeba polecki, is a zoonotic protozoan of pigs

chromatin material of the nucleus, and • Encystation

FIG. 2.1 Life cycle of Entamoeba histolytica.

FIG. 2.2 Trophozotie of Entamoeba histolytica stained

• Although complement is amoebicidal, patho- • Asymptomatic infection

• Intestinal infections: • After attachment, the parasite kills the host

• If hepatic spread of the infection extends • A seroepidemiologic survey of antibody respons-

• The prevalence of amoebic infection, as of most en- Treatment

• With an iodine stain, glycogen may be seen in Entamoeba gingivalis

Entamoeba polecki • Sometimes larger granules are scattered among

Diagnosis basis for immediate identification of this genus in

Markell & Voge's Medical Parasitology

Entamoeba 10 to 35 Eight Glycogen 15 to 50 Sluggish Vacuolated; Large, eccentric

Endolimax 5 to 12 Four Glycogen vacu- 5 to 12 Sluggish Vacuolated; Large, irregularly

Iodamoeba 6 to 16 One With large 4 to 20 Sluggish Vacuolated; Large, eccentric

FIG. 2.12 Iodamoeba bütschlii. Variations in nuclear structure.

• The nuclear membrane is delicate, and if it

• Cyst Endolimax nana

I. Trophozoites, Not characteristic

FIG. 2.14 Life cycle of Naegleria fowleri.

FIG. 2.15 Life cycle of Acanthamoeba spp. and Balamuthia mandrillaris.