00Worms & H.D. - Prelims.

20/11/01 1:41 PM Page i

Worms and Human Disease

2nd Edition
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Dedicated to the memory of Annie

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Worms and Human Disease

2nd Edition

Ralph Muller, DSc, PhD, FIBiol

Department of Infectious and Tropical Diseases

London School of Hygiene and Tropical Medicine
University of London, UK

and

Former Director
International Institute of Parasitology
St Albans, Hertfordshire, UK

With contributions and the chapter on Immunology of Helminths from

Derek Wakelin, DSc, PhD, FRCPath

School of Life and Environmental Sciences

University of Nottingham, UK

CABI Publishing
00Worms & H.D. - Prelims. 14/11/01 4:24 PM Page iv

CABI Publishing is a division of CAB International

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A catalogue record for this book is available from the British

Library, London, UK.

Library of Congress Cataloging-in-Publication Data

Muller, Ralph, 1933-
Worms and human disease / Ralph Muller ; with contributions and the chapter on
immunology from Derek Wakelin.- - 2nd ed.
p. ; cm.
Rev. ed. of: Worms and disease / Ralph Muller. c1975.
Includes bibliographical references and index.
ISBN 0-85199-516-0 (pbk.)
1. Medical helminthology. 2. Helminthiasis. I. Wakelin, Derek. II. Muller, Ralph,
1933- Worms and disease. III. Title.
[DNLM: 1. Helminths- -pathogenicity. 2. Helminthiasis. QX 200 M958w 2001]
RC119.7 .M84 2001
2001025591

ISBN 0 85199 516 0

Typeset in Melior by Columns Design Ltd, Reading.

Printed and bound in the UK by Biddles Ltd, Guildford and King’s Lynn.
00Worms & H.D. - Prelims. 14/11/01 4:24 PM Page v

Contents

Acknowledgements ix

Introduction 1

1. The Trematodes 3
Morphology 5
Life Cycle Stages 6
Classification 6
Family Schistosomatidae 9
Schistosomes 9
Family Paragonimidae 32
Paragonimus westermani 32
Family Achillurbainiidae 37
Family Opisthorchidae 38
Clonorchis sinensis 38
Opisthorchis viverrini 43
Opisthorchis felineus 44
Family Dicrocoeliidae 45
Dicrocoelium dendriticum 45
Family Fasciolidae 46
Fasciola hepatica 46
Fasciolopsis buski 49
Family Heterophyidae 51
Heterophyes heterophyes 51
Metagonimus yokogawai 53
Family Paramphistomidae 55
Gastrodiscoides hominis 55
Family Echinostomidae 56
Echinostoma ilocanum 56
Other Echinostomids 56
Other Occasional and Rare Human-parasitic Trematodes 58
Family Diplostomidae 58
Family Lecithodendriidae 58
Family Plagiorchiidae 58
Family Troglotrematidae 58
Other families 59

v
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vi Contents

2. The Cestodes 63
Classification 64
Order Pseudophyllidea 65
Diphyllobothrium latum 65
Sparganosis 70
Order Cyclophyllidea 71
Family Taeniidae 71
Taenia saginata 71
Taenia solium 76
Cysticercosis 80
Taenia multiceps 83
Echinococcus granulosus 85
Echinococcus multilocularis 94
Echinococcus oligarthrus 97
Echinococcus vogeli 97
Family Hymenolepididae 98
Hymenolepis nana 98
Hymenolepis diminuta 101
Family Dipylididae 102
Dipylidium caninum 102
Very occasional human tapeworms 102

3. The Acanthocephala 106

Moniliformis moniliformis 106
Macranthorhynchus hirudinaceus 107

4. The Nematomorpha 108

5. The Nematodes 109

Classification 109
A Key to Nematodes Parasitic in Humans 113
Intestinal Nematodes 115
Geohelminths 115
Order Rhabditida 115
Family Strongyloididae 115
Strongyloides stercoralis 115
Order Strongylida 126
Family Ancylostomatidae 126
Necator americanus 126
Ancylostoma duodenale 134
Other Strongyles 137
Family Trichostrongylidae 138
Trichostrongylus spp. 138
Family Chabertiidae 139
Ternidens deminutus 139
Oesophagostomum bifurcum 140
Family Syngamidae 142
Mammomonogamus laryngeus 142
Family Angiostrongylidae 143
Parastrongylus cantonensis 143
Parastrongylus costaricensis 145
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Contents vii

Order Ascaridida 147

Family Ascarididae 147
Ascaris lumbricoides 147
Lagochilascaris minor 153
Baylisascaris procyonis 153
Family Anisakidae 154
Anisakis and other anisakids 154
Larva Migrans 156
Visceral larva migrans 156
Toxocara and Toxascaris 156
Cutaneous marva migrans or ‘creeping eruption’ 159
Order Oxyurida 160
Family Oxyuridae 160
Enterobius vermicularis 160
Order Enoplida 164
Family Trichuridae 164
Trichuris trichiura 164
Tissue Nematodes 173
Order Enoplida 173
Family Trichuridae 173
Aonchotheca philippinensis 173
Calodium hepaticum 175
Eucoleus aerophilus 175
Family Trichinellidae 176
Trichinella spiralis 176
Family Dioctophymidae 184
Dioctophyma renale 184
Superfamily Mermithoidea 184
Order Spirurida 184
Superfamily Gnathostomoidea 184
Gnathostoma spinigerum 184
Other Spirurids 187
Superfamily Filarioidea: the Filariae 188
Wuchereria bancrofti 190
Brugia malayi 202
Loa loa 206
Onchocerca volvulus 211
Mansonella perstans 221
Mansonella streptocerca 223
Mansonella ozzardi 225
Accidental filarial infections 226
Superfamily Dracunculoidea 228
Dracunculus medinensis 228

6. Other (Non-helminth) Groups 240

Pentastomes 240
Armillifer (= Porocephalus) armillata 240
Linguatula serrata 240
Leeches 241
Myiasis 241
00Worms & H.D. - Prelims. 14/11/01 4:24 PM Page viii

viii Contents

7. Immunology of Helminths 243

8. Epidemiological Aspects of Helminth Infections 252

9. Helminthological Techniques 255

Appendix 1 Summary of Some Landmarks in Medical Helminthology 271

Appendix 2 Glossary of Helminthological Terms 273
Appendix 3 Location of Helminths in the Human Body 279

General References and Further Reading 282

Index 287
00Worms & H.D. - Prelims. 14/11/01 4:24 PM Page ix

Acknowledgements

It is a pleasure to thank SmithKline McLaren (Figs 5 and 80), Prof. C.

Beecham (now GlaxoSmithKline) for a Macpherson (Plate 10), Prof. Y. Matsukado
grant that has made possible the plates of (Fig. 20), Prof. M. Murray (Plate 7), Dr
colour pictures, which have greatly Nagano (Plate 21), Prof. G.S. Nelson (Fig.
increased the usefulness of the whole book, 44), Dr M.J. Taylor (Fig. 95), Dr A.C.
and Dr John Horton of SmithKline Templeton (Fig. 40), Dr S. Townson (Plate
Beecham for his advice and also for the 31), Dr S. Vajrasthira (Fig. 18), Dr E. Watty
provision of colour photographs (Plates 24 (Plate 17), Prof. G. Webbe (Plate 3) and the
and 25). Thanks also to Dr R. Neafie for WHO (Plates 26 and 32). Thanks to Edward
providing photographs from the Armed Arnold and Professor D. Crompton for per-
Forces Institute of Pathology collection mission to reproduce Fig. 65, to CAB
(Figs 54, 62, 66, 67, 68, 75, 77 and 96 and International, and Dr P. Jordan and Dr
Plate 18), to Dr L. Savioli for photographs R. Sturrock for permission to reproduce
and a booklet from the World Health Fig. 17 and to Dr J. Baker and Harcourt for
Organization (WHO) and to Professor T. permission to publish Fig. 132.
Polderman for a photograph of My daughter Harriet kindly helped with
Oesophagostum (Plate 17). Other pho- maps and drawings and I would also like
tographs were kindly provided by Dr J. to acknowledge the help and information
Anderson (Fig. 100 and Plates 29 and 30), provided by many colleagues.
Dr Kemal Arab (Plate 23), Dr N. Ashton Professor Derek Wakelin has, in addi-
(Fig. 72), Prof. E.A. Bianco (Plate 27), Dr A. tion to writing the sections on immunology
Bryceson (Fig. 46), Dr P. Choyce (Fig. 107), for various groups of parasites as well as
Dr D. Denham (Plate 21), Prof. D. Dennis the general chapter on the subject, provided
(Plate 28), Dr F. Etges (Fig. 14), Dr R. useful criticism and advice on statements
Feachem (Plate 5), Dr D. Flavell (Plate 6), on immunology and immunodiagnosis
Dr H. Fuglsang (Fig. 106), Dr L.M. Gibbons included in the treatments of many of the
(Figs 34, 57, 61 and 85), Prof. D.B. individual parasites (possible errors in
Holliman (Figs 64 and 71 and Plates 11, 12, these parts are, of course, not his responsi-
13, and 16), Prof. S. Lucas (Plate 19), Dr D. bility).

ix
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01Worms Intro. & Chap 01 14/11/01 4:24 PM Page 1

Introduction

While this book is the second edition of concerned with tropical and exotic dis-
Worms and Disease: a Manual of Medical eases and for students taking postgraduate
Helminthology (1975), because of the long degrees and diplomas in aspects of tropical
time that has elapsed since the publication and infectious diseases. It should also
of the earlier book, it has been so exten- prove useful as an accessory text and refer-
sively revised and brought up to date that ence source for undergraduate medical,
virtually every chapter has had to be zoological and tropical health engineering
almost completely rewritten. In the inter- students, and for medical technologists,
vening years the importance to humans of microbiologists and physicians in temper-
some new helminths has emerged, such as ate climates. With increase in air travel,
Oesophagostomum bifurcum and Para- most hospitals and medical practitioners in
strongylus costaricensis, but principally developed countries are meeting cases of
the changes have been necessitated by the parasitic infections that may have been
great strides that have been made in knowl- very rare occurrences in the past, and it is
edge of the diagnosis, treatment, immunol- becoming increasingly necessary to ask of
ogy and molecular biology of parasites. The almost all patients ‘Unde venis?’. Also, if
chapter on the immunology of helminths global warming increases, it is likely that
(now written by Derek Wakelin) has been the endemicity of some helminth infec-
greatly amplified, with the addition of tions will extend to higher latitudes.
more detailed paragraphs in the appropri- The format of this book is fairly conven-
ate sections, together with the latest infor- tional, with parasites considered in order
mation on the prospects for specific of their zoological relationships rather than
vaccines. There has also been exciting their location in the body. The latter
progress in the field of global control of approach may be useful for diagnosis but is
various helminths, such as the schisto- not practical for other aspects of the sub-
somes, soil-transmitted nematodes, filariae ject, as some parasites can occupy a wide
(both those causing lymphatic filariasis and range of sites in the body, so that there
those causing onchocerciasis) and the would be a great deal of repetition, and
guinea worm. Most of these campaigns also because the relationships between
have been possible because of recent many similar parasites that occupy differ-
advances in chemotherapy and, in some ent organs would be obscured. However,
cases, of diagnosis; many have been linked the various possible locations in the body
with efforts to improve sanitation and of all the important helminths are shown
general health. in Fig. 132 and alternative diagnoses are
The book is intended principally as a discussed in the appropriate individual
practical guide in human helminthology sections. An attempt has also been made to
for physicians and medical technologists have the best of both worlds, e.g. all the

1
01Worms Intro. & Chap 01 14/11/01 4:24 PM Page 2

2 Introduction

intestinal nematodes are considered in the reported, however occasionally (a total of

same section so that the new global mea- 267 species), and includes a brief consider-
sures being advocated for all the geo- ation of other metazoan parasites some-
helminths can be considered together, even times found in humans, such as the
though they are not all closely related. pentastomids, dipteran fly larvae and
Most of the figures for infection rates leeches, which may be confused with the
have been obtained from the CD-ROM true helminths.
PARASITE database produced by CAB While the title is Worms and Human
International or from MEDLINE. Maps Disease, it must not be assumed that
have concentrated principally on helminth helminth infection invariably results in
infections that have a focal distribution. disease; most of the helminths that are pre-
The term helminth (Greek µ) means dominantly human parasites are patho-
worm, although it is usually restricted to genic only when worm burdens are high
the parasitic worms. The term does not and, as there is no multiplication within
refer to any one zoological taxon but those the body, light infections become clinically
members parasitic in humans belong important only following reinfection. The
almost entirely to two main groups; the majority of helminth infections are light
phylum Platyhelminthes, which includes and cause little morbidity (although in
the trematodes (flukes) and the cestodes some cases more than was previously
(tapeworms), and the phylum Nematoda, thought), but many are so widespread that
comprising the nematodes (roundworms). the low percentage of patients who suffer
This book provides a comprehensive severe clinical disease represents a prob-
account of all important helminths found lem of great medical and economic
in humans, with a mention of all others importance.
 1
The Trematodes

Adult trematodes, or flukes, may be found means synonymous with the presence of
in the intestinal tract, bile-ducts, lungs or disease. In contrast to viruses, bacteria or
blood of humans. Some details concerning protozoans, trematodes do not multiply
the medically most important species are within the human body and the few organ-
shown in Table 1. All the trematodes men- isms present in the great majority of
tioned in the table are normal human para- infected persons are tolerated with the
sites, except some species of Paragonimus minimum of inconvenience and are often
and Fasciola and some heterophyids and not diagnosed. It is the small percentage of
echinostomes, which are accidental para- patients with large worm burdens (so-
sites with humans not being involved in called ‘wormy people’) or in whom the par-
their transmission cycles. However, almost asites or their eggs are in ectopic sites in
all trematodes are very catholic in their the body who give cause for alarm.
choice of definitive hosts (a notable excep- The digenetic trematodes are members
tion is Schistosoma haematobium) and of the phylum Platyhelminthes, which also
have a wide range of animal reservoirs; 144 includes the cestodes (tapeworms), mono-
species that have been found in humans geneans (ectoparasites of fishes and
are mentioned in the text, most of which amphibians) and free-living turbellarians
are natural animal parasites. Not shown in (planarians, etc.). Platyhelminthes, or flat-
the table are various aberrant forms, such worms, are acoelomate bilateria (bilaterally
as the cercarial larvae of animal and bird symmetrical and lacking a coelom). The
schistosomes, which can penetrate the skin excretory system is based on the flame cell,
of humans but are not able to mature. or protonephridium, and often the pattern
Pre-eminent in medical and economic of flame cells can be of importance in clas-
importance are the schistosomes, or blood sification. Trematodes are characteristically
flukes, which are the cause of one of the flat and leaflike, or occasionally globular,
major human diseases, schistosomiasis. hermaphroditic organisms (except for the
This is a source of suffering in many warm schistosomes, which have a male folded
countries and is a major cause of morbid- about its long axis and a cylindrical female
ity. No other trematode is the cause of such (Figs 3 and 4)). All have complicated life
widespread morbidity, but liver flukes cycles with alternating sexual and asexual
(Clonorchis and the closely related development in different hosts. Asexual
Opisthorchis) and lung flukes (Paragonimus) multiplication takes place in a snail, and
are important parasites in areas of Asia and for parasites of medical importance this is
their presence may result in severe disease always a gastropod snail. It is believed that
and possibly death. the trematodes were originally parasites of
It needs to be stressed that the presence molluscs and they are still always very
of trematode parasites in the body is by no specific in their choice of snail host;

3
 4
Table 1. Trematodes of medical importance.

Chapter 1
Situation of Eggs recovered Snail intermediate Other intermediate Geographical
Habitat Species adult from host or transport hosts distribution
Blood Schistosoma Mesenteric veins Faeces Biomphalaria spp. None (active penetration Africa, South America
mansoni by cercariae)
S. japonicum Mesenteric veins Faeces Oncomelania spp. None (active penetration China, South-East Asia
by cercariae)
S. mekongi Mesenteric veins Faeces Neotricula None (active penetration Cambodia, Laos
by cercariae)
S. intercalatum Mesenteric veins Faeces Bulinus spp. None (active penetration Central Africa
by cercariae)
S. haematobium Vesicular veins Urine Bulinus spp. None (active penetration Africa, Middle East
by cercariae)
Lungs Paragonimus Cysts in lungs Sputum and faeces Semisulcospirura Edible crustaceans South-East Asia,
westermani Thiara containing China, Japan
Oncomelania metacercariae
Paragonimus spp. Cysts in lungs Sputum and faeces Various Edible crustaceans South-East Asia,
containing West Africa, South and
metacercariae Central America
Liver Clonorchis sinensis Bile and pancreatic Faeces Bulimus Freshwater food fish South-East Asia
ducts Parafossarulus containing metacercariae
Opisthorchis felineus Bile and pancreatic Faeces Bithynia Freshwater food fish Siberia, East Europe
ducts containing metacercariae
O. viverrini Bile and pancreatic Faeces Bithynia Freshwater food fish Thailand, Laos
ducts containing metacercariae
Fasciola hepatica Bile ducts Faeces Lymnaea Metacercariae encysted Cosmopolitan (mainly
on plants temperate areas)
Intestine Fasciolopsis buski Small intestine Faeces Segmentina Metacercariae on South-East Asia, India
water plants
Heterophyes Small intestine Faeces Pirenella Freshwater food fish South-East Asia,
heterophyes Cerithidea containing metacercariae Middle East, Egypt,
southern Europe
Metagonimus Small intestine Faeces Semisulcospira Freshwater food fish South-East Asia, Russia
yokogawai containing metacercariae (Siberia), southern Europe
Other heterophyids Small intestine Faeces Various Freshwater food fish Worldwide in warm
containing metacercariae countries
Echinostomes Small intestine Faeces Various Freshwater fish or snails Mostly South-East
containing metacercariae Asia, India
Gastrodiscoides Caecum and colon Faeces Helicorbis Metacercariae on South-East Asia
hominis water plants
 The Trematodes 5

identification and study of the biology of Morphology

the particular snails involved in transmis-
sion form an important aspect of the epi- The outer surface or tegument is a non-
demiology of trematode diseases, known as cellular syncytial extension of the
medical malacology. sunken tegumental cells, and may have
Detailed consideration of snail inter- spines embedded in it. During the last
mediate hosts is outside the scope of this few years a great deal of interest has
book. For the practical field worker it is nec- been shown in the physiology and fine
essary to consult a specialized monograph structure of the tegument of both trema-
(e.g. Malek, 1963; Brown, 1980) or send todes and cestodes, because of its impor-
specimens to an expert, as in most habitats tance in nutrition and in antigenic
there are species of snails present which do stimulation (it is considered in more
not transmit human helminth infections but detail on p. 63 in the section on
closely resemble those that do. Some of the cestodes).
important snail intermediate hosts involved Two suckers are present in all trema-
in the dissemination of trematodes of med- todes found in humans, an anterior oral
ical importance are shown in Fig. 1. sucker into which the alimentary canal

Fig. 1. Snails that act as first intermediate hosts of the trematodes of medical importance.
(a) Biomphalaria glabrata from Brazil, host of Schistosoma mansoni. (b) Bulinus (Physopsis) globosus
from Nigeria and (c) Bulinus (Bulinus) truncatus from Iran, hosts of S. haematobium. (d) Oncomelania
hupensis nosophora from Japan, host of S. japonicum. (e) Thiara granifera from China and
(f) Semisulcospira libertina from China, hosts of Paragonimus westermani and Metagonimus yokogawai.
(g) Polypylis hemisphaerula from China, host of Fasciolopsis buski. (h) Parafossarulus manchouricus
from China, host of Clonorchis sinensis. (i) Codiella (= Bithynia) leachi from Germany, host of
Opisthorchis felineus. (j) Pirenella conica (from Egypt) host of Heterophyes heterophyes. (k) Lymnaea
trunculatula from England, host of Fasciola hepatica.
6 Chapter 1

opens and a more posterior ventral Life Cycle Stages

sucker, or acetabulum, by which the
worm attaches itself to its host. In Adults are hermaphrodite, except for the
Heterophyes there is also an accessory schistosomes, which have separate sexes –
genital sucker. the egg reaches water (in the schistosomes,
The features of importance in the opisthorchiids and heterophyids the egg
recognition and classification of a trema- contains a larva, termed a miracidium,
tode are shown in Fig. 2 and the morphol- when passed out; in other trematodes the
ogy of the flukes of medical importance larva develops inside the egg over a few
in Fig. 3. weeks) – the ciliated miracidium larva
hatches from the egg and penetrates a spe-
cific freshwater snail (except in
opisthorchiids, where the egg containing a
larva is ingested by the snail) – inside the
snail the miracidium develops into an
irregular sac-like sporocyst – germ cells
inside this primary sporocyst form the next
larval stage (these are termed rediae in
most trematodes, where they have a rudi-
mentary gut, but secondary sporocysts in
schistosomes, where they are similar to the
primary sporocysts), which burst out and
invade new tissues of the snail (principally
the digestive gland) – germ cells inside
these in turn develop into the next larval
stages, the tailed cercariae, which escape
from the snail into the water (in some
forms there are two redial generations).
Thus one miracidium can give rise to many
thousands of cercariae, the process taking
several weeks or even months. The cer-
cariae actively penetrate through the skin,
as in the schistosomes, or form cysts
(metacercariae) in a second intermediate
host or on vegetation and are passively
ingested in all other trematodes.

Classification

The classification given below is based prin-

cipally on that of La Rue (1957), in which
the life history and the larval stages are con-
sidered as well as the morphology of the
adult; more conservative classifications were
based entirely on the adult. The divisions at
the family level are generally accepted by
most authorities, but those taxa above this
level are still controversial (Gibson and Bray,
Fig. 2. Diagram of Clonorchis sinensis to show 1994). Recent studies utilizing computer-
the features of taxonomic importance in the based cladistic analysis and molecular biol-
digenetic trematodes. ogy might alter the familiar groupings in the
 The Trematodes 7

future (Brooks et al., 1985; Rohde et al., The modes of infection of trematodes
1993), but changes are not generally of medical importance shown in Table 2
accepted. Only a very few of the numerous reflect quite well the taxonomic divisions
families comprising the subclass Digenea are (the odd one out being Echinostoma, in
included (Yamaguti, 1971) – those which which it might be expected that the
have members of medical importance. cercariae would encyst on vegetation).

Fig. 3. Diagrams of the shape and principal organ systems of the hermaphrodite trematodes of medical
importance (schistosomes are shown in Fig. 4). Comparative sizes shown in silhouette.
8 Chapter 1

Table 2. Mode of infection of trematodes of medical importance.

Cercaria liberated from snail

Active penetration Encystment to give

of skin of definitive host metacercaria, which is
ingested by definitive host

Schistosoma

Encystment on vegetation 2nd intermediate host required

ˇ

Fasciolopsis
Fasciola
Gastrodiscoides?

Fish Crustacean Snail Insect

Clonorchis Paragonimus Echinostoma Dicrocoelium

Opisthorchis Plagiorchis
Heterophyes
Metagonimus

KEY: Members of the group occur in Dioecious

M = mammals, B = birds, R = reptiles, Schistosoma
A = amphibians, F = fish.
SUPERFAMILY DIPLOSTOMOIDEA
Family Diplostomidae (MB)
PHYLUM PLATYHELMINTHES
Body usually divided into two regions.
CLASS TREMATODA Metacercariae in fishes or amphibians.
Alaria, Neodiplostomum
SUBCLASS DIGENEA
Endoparasites with an indirect life cycle SUPERFAMILY GYMNOPHALLIOIDEA

utilizing a snail as an intermediate host. Family Gymnophallidae (MB)

Uterus has numerous coils containing Large oral sucker, small ventral sucker.
many eggs. Single excretory pore at post- Tegument with spines.
erior end of the body. Gymnophalloides

SUPERORDER ANEPITHELOICYSTIDA Order Echinostomomida

The cercaria has a thin-walled, non-epithelial Eggs operculate. Cercariae encyst on
bladder. herbage or in other molluscs.
SUPERFAMILY ECHINOSTOMATOIDEA
Order Strigeida
Cercaria fork-tailed. Testes in tandem behind ovary.
Family Echinostomatidae (MBRF)
SUPERFAMILY SCHISTOSOMATOIDEA Head collar with row of spines.
Family Schistosomatidae (MB) Echinostoma
 The Trematodes 9

Family Fasciolidae (M) Family Paragonimidae (MB)

Suckers close to each other. Large, spiny, Many are parasites of the lungs. Vitellaria
lanceolate flukes, usually found in herbivores. compact and dense. Cuticle spinous. Testes
Fasciolopsis, Fasciola adjacent behind ovary. Cercariae encyst in
crustaceans.
SUPERFAMILY PARAMPHISTOMATOIDEA (MB)
Paragonimus
Sucker at anterior and posterior extremities
of body but no oral sucker.
Family Paramphistomatidae (or Zygo- Family Plagiorchiidae (MBRAF)
cotylidae) Cuticle spinous. Suckers well apart. Testes
Body thick and fleshy. Testes in tandem in in tandem behind ovary. Metacercariae in
front of ovary. Metacercariae on vegetation insects.
or on snail. Plagiorchis
Gastrodiscoides, Watsonius
Family Troglotrematidae (M)
SUPERORDER EPITHELIOCYSTIDA Cercariae encyst in fish or crustaceans.
Cercaria has an additional thick-walled
Genital pore posterior to ventral sucker.
epithelial bladder.
Spinous body.
Order Plagiorchiida Nanophyetus
Eggs operculate.

SUPERFAMILY DICROCOELIOIDEA
Cercariae encyst in arthropods and have an
oral stylet. Family Schistosomatidae
Family Dicrocoeliidae (MBRA)
Found in intestine, liver, gall-bladder and Schistosomes
pancreas. The oral sucker is subterminal.
Testes adjacent or in tandem, anterior to At least seven species are parasites of
ovary. Vitellaria posterior to ventral humans: Schistosoma haematobium
sucker. (Bilharz, 1852); Weinland, 1858; S. mansoni
Dicrocoelium Sambon, 1907; S. japonicum Katsurada,
1904; S. intercalatum Fischer, 1934; S.
SUPERFAMILY OPISTHORCHIOIDEA (MBR) malayensis Greer, Ow-Yang and Yong,
Cercariae encyst in or on fish. 1988; S. mekongi Voge, Bruckner and
Family Opisthorchiidae (MB) Bruce, 1978; S. sinensium Pao, 1959.
Suckers weak. Semi-transparent flukes
found in bile-ducts and gall-bladder. Testes
in tandem behind ovary.
SYNONYMS (for S. haematobium)
Clonorchis, Opisthorchis, Metorchis
Distoma haematobia Bilharz, 1852;
Family Heterophyidae (MB) Bilharzia haematobium Diesing, 1859.
This is a large family. All members are
potential parasites of humans. They are
minute flukes with a spinose tegument. LOCAL NAMES
Testes adjacent behind ovary. Au chung (Chinese), Tsagiya (Hausa, S.
Heterophyes, Metagonimus haematobium), Katayamabayo, Suisho-
SUPERFAMILY PLAGIORCHIOIDEA choman or Harapari (Japanese), Laremo
Family Lecinthodendriidae (MBRA) (Luo, S. haematobium haematuria), Kadi
Small spiny flukes with gonads in fore- dhig (Somali, S. haematobium haema-
body. Oral sucker large, ventral sucker turia), Kichocho (Swahili), Pa-yard bai-
small. Metacercariae in aquatic insects. mai lohit (Thai), Atosi eleje (Yoruba, S.
Phaneropsolus, Prosthodendrium haematobium).
10 Chapter 1

DISEASE AND POPULAR NAMES S. japonicum. China, Indonesia,

Schistosomiasis or schistosomosis*, uri- Philippines, Thailand (an S. japonicum-
nary schistosomiasis (S. haematobium), like parasite which is probably distinct).
intestinal schistosomiasis (S. mansoni, S.
japonicum, S. intercalatum and S. S. malayensis. Malaysia.
mekongi), schistosomiasis haematobium,
intercalatum, japonicum, mansoni or S. mekongi. Cambodia, Laos.
mekongi; Katayama disease (early phase of
S. japonicum); bilharziasis; bilharzia. S. sinensium. China, Thailand.
GEOGRAPHICAL DISTRIBUTION
MORPHOLOGY
It has been estimated that about 220
Unlike all the other trematodes of medical
million people are infected in the world
importance, the sexes are separate (dioe-
in 74 countries, with 600 million at risk;
of those infected 20 million have severe cious). In all species the male worm is
disease, 120 million have mild symptoms characteristically boat-shaped, with a cen-
and 80 million are symptomless (WHO, tral canal (gynaecophoric canal) in which
1993). the female lives. The cuticle of the male is
smooth in S. japonicum (the adults of S.
S. haematobium. Africa: most of the coun- malayensis and S. mekongi are identical)
tries of North Africa; widespread in Central but has tuberculations in the other three
and West Africa; in eastern Africa present important species. There are two small
from Somalia to the Cape and on the suckers and a varying number of testes in
islands offshore, including Madagascar and the different species. The female is longer
Mauritius. Middle East: present in most than the male but much thinner and circu-
countries. There might also be small foci in lar in cross-section. The two suckers of the
India around Bombay and in Madras State. female are very small and weak. The char-
A total of about 90 million people are acteristics of the various species are given
infected worldwide. in Table 3 and Fig. 4.

S. mansoni. Africa: North Africa (Morocco, S. haematobium. The male measures

Tunisia, Egypt, southern Sudan); East 10–20 mm
0.9 mm and the cuticle has
Africa (from Ethiopia down to South Africa fine tuberculations. There are 4–5 testes.
and Madagascar); most countries of Central The female has a long uterus, with the
and West Africa; Middle East (Lebanon, ovary in the posterior third of the body.
Oman, Saudi Arabia, Somalia, Yemen); There are 10–100 eggs in the uterus at one
Americas: in South America and some of time.
the Caribbean islands.
S. mansoni (Fig. 5). The adults are smaller
S. intercalatum. There are limited foci in than those of the other species. The male
Central Africa including Cameroon, Congo, measures 6–13 mm
0.75–1.0 mm and the
Congo Democratic Republic (Zaire), cuticle has coarse tuberculations. There are
Equatorial Guinea, Gabon, São Tomé and 4–13 (usually 6–9) testes. The ovary of the
Principe, and possibly in Central African female is situated anteriorly. There is usu-
Republic, Chad, Mali and Nigeria. ally only 1 egg in the uterus at one time.

*This is the standardized nomenclature for parasitic diseases advocated by the World Association for
the Advancement of Veterinary Parasitology (WAAVP) (Kassai et al., 1988. Veterinary Parasitology 29,
299–326) and the World Federation of Parasitologists (WFP), but has not been widely adopted in
medical helminthology, particularly by the World Health Organization (WHO). For instance, of the titles
of references in this book, 112 have -iasis endings and 16 -osis, most of which are mentioning
cysticercosis or echinococcosis – used in both systems.
 The Trematodes 11

Map 1. Distribution of Schistosoma haematobium, S. japonicum and S. mekongi.

S. japonicum (S. malayensis and S. ium. Eggs of each species can be recognized
mekongi). The male measures 12–20 mm
by differences in size and morphology
0.5–0.55 mm and has no cuticular tubercu- (Table 3 and Fig. 6). On immersion in fresh
lations. There are 6–7 testes. The female water, particularly under conditions of
has the ovary at about the middle of the warmth and light, they hatch almost imme-
body. There are 5–200 eggs in the uterus at diately. The miracidium larvae (Fig. 7)
one time. swim actively by means of the cilia with
which they are covered and attempt to pen-
S. intercalatum. The male measures etrate any freshwater snail they come into
11–14 mm
0.3–0.4 mm. There are 2–7 contact with. The miracidia die in 16–32 h
testes. The female has 5–60 eggs in the if they do not succeed in reaching a suitable
uterus at one time. snail intermediate host. Like all trematodes
Of the complete 270 Mb genome of they are extremely host-specific in regard to
Schistosoma, 18–24% has so far been the snails in which they will develop, often
deposited in a database (Williams and far more so than in the definitive host. The
Johnston, 1999). species of snail parasitized depends on the
geographical region, but S. haematobium
LIFE CYCLE and S. intercalatum develop in snails of the
The eggs are passed in urine in S. haemato- genus Bulinus, S. mansoni in Biomphalaria
bium and in the faeces in all the other and S. japonicum in Oncomelania.
species and contain a fully formed miracid- Oncomelania differs from the other two
12 Chapter 1

Map 2. Distribution of Schistosoma mansoni and S. intercalatum.

genera of snails in that it is amphibious, weeks and those of S. japonicum after 7

rather than aquatic, and dioecious (with weeks. The principal stimulus for emer-
separate sexes) and has an operculum on gence is light and different species emerge
the bottom surface of the foot (to prevent at various times in the day. The cercariae
drying up). Once in a susceptible snail, the measure 300–400 µm
50–70 µm and
miracidium loses its outer ciliated epider- have forked tails (furcocercus type) (Fig. 8).
mal layer and develops into a mother They swim around in the water, usually tail
sporocyst. This becomes filled with germ first, and often hang from the surface film.
balls, which burst out after about 8 days, They are infective for only a day or so in
and most of these migrate to the digestive water. Not all the cercariae mature at the
gland, where each develops into a thin- same time and usually a proportion
walled daughter sporocyst. A further continue to emerge throughout the life of
process of asexual multiplication takes the snail, which may be many months.
place and each daughter sporocyst becomes When humans enter the water the cercariae
filled with the final larval stages, the penetrate the skin, often between the hair
cercariae. Thus one miracidium can give follicles, by means of the anterior spines
rise to thousands of cercariae, all of the and the cytolytic secretions of the cephalic
same sex. At about 26°C, the cercariae of S. glands. The tail is shed in the penetration
intercalatum begin to emerge 3 weeks after process, which takes 3–5 min, and the
infection, those of S. mansoni after 4–5 immature schistosomes (known as schisto-
weeks, those of S. haematobium after 5–6 somula) enter peripheral lymphatics or
Table 3. Differential features of schistosomes of humans.
Schistosoma Schistosoma Schistosoma Schistosoma Schistosoma
japonicum mansoni haematobium intercalatum mekongi

Situation in human Mesenteric veins Mesenteric veins Vesical veins Mesenteric veins Mesenteric veins
Male
Length (mm) 10–20 6–12 10–14 11–14 15
Width (mm) 0.5 1.1 0.9 0.3–0.4 0.4
No. of testes 6–7 4–13 (usually 6–9) 4–5 2–7 (usually 4–5) 6–9
Tuberculations None Coarse Fine Fine None
Caecal junction Posterior third of body Anterior third of body Middle Middle Posterior third of body
Female
Length (mm) 20–30 10–20 16–20 10–14 12
Width (mm) 0.3 0.16 0.25 0.15–0.18 0.23
Uterus Anterior half of body Anterior half of body Anterior two-thirds of body Anterior two-thirds of body Anterior half of body
Number of eggs in
uterus 50–200 1–2 10–50 5–60 10+
Position of ovary Middle Anterior third of body Posterior third of body Posterior half of body Posterior half of body
Mature egg shape Round with small knob Lateral spined Terminal spined Terminal spined Round, small knob
and mean size 85 µm
60 µm 140 µm
61 µm 150 µm
62 µm 176 µm
61 µm 57 µm
66 µm
Mode of voiding eggs Faeces Faeces Urine Faeces Faeces
Egg production per 3500 100–300 20–300 150–400 ?
female per day (in
experimental animals)
Reaction of egg to Positive Positive Negative Positive Positive?
Ziehl–Neelsen stain
Intermediate Oncomelania Biomphalaria Bulinus Bulinus Tricula
host snail






























The Trematodes
Distribution overlap None Over most of Africa Throughout range None

13
14 Chapter 1

Fig. 4. Diagram of the structures of the three major schistosome species. Only the male of
S. mansoni is shown. The males of the other species differ principally in the number of testes, while
that of S. japonicum has a smooth tegument.

Fig. 5. Integument and double outer membrane of S. mansoni. Electron micrograph. Original
magnification
83,500.

venous vessels and are carried to the lungs pairs. The schistosomula are usually
4–7 days after penetration (Figs 9 and 10). assumed to travel to the liver via the blood
The schistosomula move from the lungs to system (against the blood flow) but, at least
the portal vessels and there grow into adult for those of S. japonicum, some penetrate
schistosomes, which mate and remain in directly through the diaphragm. The adult
Fig. 6. Eggs of (a) S. haematobium, (b) S. mansoni and (c) S. japonicum. Actual size of (a) is 125 µm.

The Trematodes
15
16 Chapter 1

Fig. 7. Ciliated miracidium of S. mansoni. Note anterior penetration glands. Dark field. Actual size 80 m.

worm pairs migrate to the mesenteric veins

(S. intercalatum, S. japonicum, S. mansoni
and S. mekongi) or the veins of the vesical
plexus surrounding the bladder, migrating
through the anastomoses between the
portal and systemic veins in the pelvis (S.
haematobium).
Eggs of S. japonicum and S. mansoni first
appear in the stools 25–28 days after cercar-
ial penetration, those of S. intercalatum
after 50–60 days and those of S. haemato-
bium in the urine after 54–84 days. Adult
worms of each species can live for as long as
25 years in people who have moved from a
non-endemic area, but it is probable that
longevity is usually considerably less in
endemic areas (3–10 years) and in children
is about 2–5 years. Large numbers of worms
may be present, up to 400 having been
found at autopsy, but in most cases there are
fewer than ten worm pairs present. Each
female of S. japonicum produces about 3500
eggs per 24 h, of S. mansoni 100–300, of S.
haematobium 20–30 and of S. intercalatum
150–400. The number of eggs produced by
S. haematobium decreases with age (Agnew
et al., 1996).
It has been reported that S. japonicum
can undergo vertical transmission (cf.
Alaria; p. 59), but this appears to be coin-
Fig. 8. Diagram of the cercaria of S. japonicum. cidental (Shoop, 1994).
 The Trematodes 17

HUMAN
ADULTS mature
in 6–12 weeks.
In veins of bowel:
S.m., S.j., S.i.
In veins of bladder:
S.h.

liver
Some EGGS retained
lungs in tissues
lymph and veins
to heart

SCHISTOSOMULA
in skin
EGGS
Male and female In urine: S. haematobium
CERCARIAE In faeces: all others
penetrate skin

MIRACIDIA (0.1 mm)

hatch immediately
in water and can
live for 24 h.
CERCARIAE (0.4 mm) Penetrate suitable
infective for 8 snail
hours in water.
Penetrate skin

SNAIL S.m.
CERCARIAE emerge
Asexual Biomphalaria spp. .
reproductive S .j
SECONDARY
SPOROCYSTS stages in
i.
S.

in digestive snail 4–7

d

gland weeks
an
h.
S.

PRIMARY Oncomelania spp.

SPOROCYSTS

MIRACIDIA
penetrate snail

Bulinus spp.

Fig. 9. The life cycle of schistosomes. Figure from Book of the Dead papyrus. S.m., S. mansoni; S.j.,
S. japonicum; S.h., S. haematobium; S.i., S. intercalatum.

CLINICAL MANIFESTATIONS AND PATHOGENESIS bladder, while with S. japonicum, S. man-

The clinical manifestations and pathogene- soni, S. mekongi and, to a lesser extent, S.
sis of S. haematobium infection differ from intercalatum, the granulomas surrounding
those caused by the other species and will the eggs cause colitis, and eggs reaching
therefore be considered separately. Briefly, the liver cause presinusoidal block to the
this is because with S. haematobium the hepatic portal flow, leading to portal hyper-
eggs accumulate progressively in the blad- tension. However, with all species, the
der and ureters and the reaction to them pathology depends on the target organs,
leads to cystitis, hydronephrosis, ureteric intensity and duration of infection, host
obstruction and occasionally cancer of the human leucocyte antigen (HLA) type and
18 Chapter 1

Fig. 10. Diagram of a 12-day-old schistosomulum

of S. mansoni recovered from the lungs.

race, host immunological responses and

concomitant infections such as hepatitis.

S. haematobium

Invasive stage. A cercarial dermatitis

(‘swimmer’s itch’) may appear 24 h after
first infection but seldom lasts more than Fig. 11. Inner surface of the bladder showing
nests of calcified ova (‘sandy patches’) (arrowed)
48 h. It is rarely met with in people
of S. haematobium.
indigenous to an endemic region and is
more common after penetration by cer-
cariae of non-human species of schisto- micturition are typical clinical signs and
somes. may persist intermittently for years. Cystitis
is caused by hyperplasia of the epithelium
Acute phase. There are usually no symp- (which occasionally becomes 2–3 cm thick),
toms until 5–10 weeks after infection, sometimes with papilloma formation, and a
when there may be mild allergic manifesta- markedly reduced bladder capacity often
tions in visitors but these are rare in results. This, together with the ureteritis,
indigenous populations. can lead to hydroureter, hydronephrosis
(Fig. 12) and uraemia. Hydronephrosis is
Chronic phase. Maximum egg production not necessarily only a late sequel of infec-
begins 10–12 weeks after infection. In tion, as it has been observed in over 8% of
schistosomiasis it is the egg that is the preadolescent children in both East and
important pathogenic agent. The majority West Africa. It may be reversible after anti-
of eggs pass through the bladder but an schistosomal treatment (Subramanian et al.,
unknown proportion are trapped in the 1999) and is probably caused by oedema,
bladder wall and ureters and eventually congestion, inflammation and possibly pro-
die and calcify. The earliest bladder lesion liferative lesions (although granulomas of
is the pseudotubercle, but in long-standing the kidneys are very rare).
infections nests of calcified ova (‘sandy Fibrosis of the ureteral wall usually leads
patches’) (Fig. 11) are surrounded by to dilatation, while strictures occur in less
fibrous tissue in the submucosa and make than 1% of patients. Cancer of the bladder is
the bladder wall visible on X-ray or by particularly common in Egypt and
ultrasonography (Hatz, 2000). Mozambique and is clearly predisposed to
Haematuria (found in about 50% of by urinary schistosomiasis (IARC Working
cases), dysuria and increased frequency of Group, 1994) but some other precipitating
 The Trematodes 19

Fig. 12. Intravenous pyelogram of a woman infected with S. haematobium showing bilateral hydronephrosis
with deformity of both ureters.

factors, such as the presence of nitrosamines parts of the genital tract, including the
in the urine, are probably involved (Mostafa cervix, vagina and vulva, and about 6–27%
et al., 1995). Squamous carcinoma is more of such cases result in sterility.
common than transitional carcinoma (Fig.
13). It has been estimated that schistosomia-
S. japonicum, S. mekongi, S. mansoni
sis is responsible for about 16% of cases of
and S. intercalatum
bladder cancer in Egypt. In the Nile Delta
region, men do most of the agricultural
work and thus become infected, resulting in Invasive phase. As for S. haematobium.
a 12:1 male-to-female bladder cancer ratio.
Pulmonary arteritis progressing to irrevers- Acute phase. Allergic manifestations, such
ible and lethal cor pulmonale because of as pyrexia, headache, oedema, cough,
capillary damage by eggs sometimes occurs dysenteric symptoms, pruritus and
when eggs are swept back into the lungs. urticaria, occur 3–8 weeks after infection
The presence of adult worms in the lungs with S. japonicum. This is known as the
following drug treatment is also a possible Katayama syndrome and may be accompa-
cause of pulmonary damage. In women, nied by tenderness in the liver region, mild
eggs may cause lesions in the ovaries, abdominal pain, lymphadenopathy and
Fallopian tubes and uterus or in the lower splenomegaly, with an accompanying
20 Chapter 1

Fig. 13. Section of bladder. Eggs of S. haematobium (many are calcified or ‘black’ eggs) can be seen
with epithelial squamous cell metaplasia (arrowed).

eosinophilia. This is possibly caused by a associated with chronic lesions of S. japon-

form of ‘serum sickness’ (acute immune icum in a small proportion of cases (IARC
complex disease) resulting from an excess Working Group, 1994). The increasing fibro-
of antigen when eggs are first produced. sis of the colon wall means that eggs are
The acute phase of S. mansoni and S. inter- repeatedly carried to the liver in the portal
calatum infection is rarely recognized in veins and become lodged in the portal
an indigenous population. tracts or, less frequently, in the lobules or
sinusoids. The eggs become the centre of a
Chronic phase. In the majority of individu- pseudotubercle, in which they are engulfed
als, infection is light and symptoms are by multinucleate giant cells and sur-
entirely absent, but in heavy infections rounded by inflammatory cells (eosinophils,
about 50% of the eggs are trapped in the macrophages and polymorphonuclear
mucosa and submucosa of the colon, result- leucocytes). In the early stages there is a
ing in the formation of pseudotubercles, microabscess surrounding each egg, resem-
which coalesce and form larger granuloma- bling miliary tuberculosis (Fig. 14).
tous reactions and pseudopapillomas. Eggs However, the cell types differ from a typical
of S. japonicum, in particular, are inclined tubercle. As the lesion heals, some degree
to die and eventually to calcify in the colon of fibrosis is usually left. Finally the
and many thousands of calcified eggs may miracidium in the egg dies and the
be found in the thickened mucosa (Plate 1). mononuclear cells form Langhans-type giant
Intestinal damage, however, is usually cells. Experiments in mice have demon-
accompanied by few symptoms except a strated that CD4+ T lymphocytes are neces-
vague feeling of ill health, with perhaps sary for the formation of granulomas. While
headache, abdominal pain and diarrhoea. the formation of granulomas is usually
Papillomas and inflammatory polyps often taken to be a host response to sequester the
develop, and in severe cases, can lead to eggs, it is possible that mobile granulomas
obstruction of the lumen of the colon. The can aid in ‘transporting’ the eggs across tis-
ulceration of the colon caused by the eggs sues to reach the faeces or urine (Doenhoff
of S. mansoni can result in a blood loss of et al., 1986; Damian, 1987). Pigment, chemi-
up to 12.5 ml day1 by patients in Egypt, cally but not structurally indistinguishable
where papillomas are particularly common. from malarial pigment, becomes deposited
Carcinomas of the large intestine are also in the Kupffer cells, portal tracts and
 The Trematodes 21

Fig. 14. Egg granuloma of S. mansoni in liver with surrounding epitheloid cells and some leucocytic
infiltration (see Plate 1 for more advanced stage).

Fig. 15. Two boys with advanced schistosomiasis mansoni. Note collateral venous circulation in nearest
patient.

lobules. Liver enlargement is common and Sahara and signs of portal hypertension are
splenomegaly often follows the portal hyper- always present in such cases. Anaemia may
tension (Fig. 15). Hepatosplenic schisto- be found when there is splenomegaly and is
somiasis mansoni is more common in more severe after repeated haematemesis.
Brazil and Egypt than in Africa south of the The reaction to the eggs in the liver may
22 Chapter 1

Fig. 16. ‘Symmer’s clay pipestem’ fibrosis caused by eggs of S. japonicum surrounding portal veins in liver.

eventually cause the periportal fibrotic distributed throughout the body, and the
reaction termed ‘Symmer’s clay pipestem’ greater longevity of the adult worms.
fibrosis (Fig. 16). Liver function tests, how- Brain involvement is most common in S.
ever, are not altered in schistosome fibrosis, japonicum infections and two types of brain
as they are in true cirrhosis, and, although lesions have been reported. In the first type
there may be severe pathological lesions, there is diffuse involvement with scattered
there is no liver failure. Severe disease, lesions, probably caused by eggs being car-
with hepatosplenomegaly, occurs in about ried to the brain in the bloodstream, and
10% of cases of schistosomiasis mansoni, this type usually results in no symptoms. In
but takes 5–15 years to develop, and in the second type a localized granulomatous
children infection can have effects on nutri- mass is present, containing large numbers of
tion (Stephenson, 1993). eggs deposited by ectopic adult worms in
As the portal pressure increases, a the blood-vessels of the brain. These granu-
collateral venous circulation becomes lomas can cause a wide range of symptoms,
established and severe or even fatal depending on the anatomical location of the
episodes of bleeding can result from the lesion in the brain.
oesophageal varices. The portal systemic A transverse myelitis can result from the
shunt results in the eggs bypassing the presence of eggs in the spinal cord and is
liver and being deposited in the lungs. An most commonly found in infections with S.
obstructive and destructive arteritis may mansoni and S. haematobium.
follow, which can lead to systematic arter- In order for the eggs to make their way
ial hypertension and eventually to hyper- through the tissues into the gut, the
trophy of the right ventricle. miracidia release proteolytic enzymes and
The adult worms in the blood-vessels do other material, which diffuses through
little damage when living but their death pores in the eggshell. This material (solu-
can lead to focal necrosis of the liver cells ble egg antigen (SEA)) is highly immuno-
and to granulomas. The more severe genic, and the immune response made
pathology thought to be produced by infec- against it leads to the formation of the large
tion with S. japonicum is usually granulomas that are responsible for most of
explained by the greater egg production, the pathology in this phase. Evidence for
the spherical shape of the egg lacking a this and analysis of the mechanisms involved
large spine resulting in more eggs being have come largely from experiments in
 The Trematodes 23

mice. Granulomas can be induced in the occur against these species (Wilkins et al.,
lungs of mice by intravenous injection of 1984, 1987; Butterworth, 1998; Kabatereine
eggs, and this process is prevented by et al., 1999), and studies in Brazil link resis-
immunosuppressive treatments that inter- tance to particular genetic characteristics
fere with cellular responses. The degree of (Abel and Dessein, 1997). Infections with S.
response to eggs and the pathology that japonicum do not show this picture,
results, following infection in mice, are although there appears to be an age-related
strongly influenced by genetic factors, and reduction in pathology (Ross et al., 2000).
this also reflects different degrees of The slow acquisition of immunity against S.
immune responsiveness. It has recently haematobium and S. mansoni correlates
been shown in humans that at least some with a change in the balance between
of the variation in pathology seen in antiparasite immunoglobulin E (IgE) and
infected populations is due to the activity IgG4, the former promoting protective
of particular major genes, which are associ- responses against incoming larvae, perhaps
ated with T-cell function (e.g. a codomi- by antibody-dependent cellular cytotoxic
nant major gene, SM1, on chromosome 5). (ADCC) mechanisms directed against anti-
The immunology of granuloma formation gens expressed on the surface tegument. As
is complex and involves the activity of shown by work carried out in the 1960s,
both major subsets of CD4+ T-helper (Th) adult schistosomes are largely unaffected by
cells. SEA is a powerful inducer of Th2 immunity and continue to survive in hosts
responses, but Th1 cells also play a role. immune to larval stages (concomitant immu-
The cellular response is initiated and con- nity). One way in which this is achieved is
trolled by the cytokines released and in by the adult schistosomes masking the for-
mice the phenomenon of immunomodula- eign nature of their surface antigens by
tion occurs – i.e. early granulomas tend to incorporating host-derived molecules into
be much larger than those formed later in the tegument and by rapid replacement of
infection. the tegument (antigenic disguise).
Antigen–antibody complexes have been Schistosomes, like many other helminths,
shown by fluorescent antibody studies to exert profound effects on the host’s immune
be the cause of the Splendore–Hoeppli response. Not only do these parasites tend to
phenomenon that occurs in sensitized polarize the T-cell response selectively
hosts. Glomerulonephritis has been towards Th2 activity, but they may also
reported as an immune-complex disease in modulate other components in ways that
schistosomiasis mansoni. result in a more general suppression of
immune and inflammatory responses.
IMMUNOLOGY OF SCHISTOSOMES Immunomodulation can influence the
Although it has been established for many ability of the host to respond successfully
years that laboratory animals, including pri- to other infections, and there is recent evi-
mates, develop immunologically mediated dence that schistosomes and soil-transmit-
resistance to experimental infections, defi- ted nematodes may increase susceptibility
nite proof that acquired immunity to schisto- to both AIDS and tuberculosis (Bundy et
some infections occurs in humans has been al., 2000).
very difficult to demonstrate. It is clear that
intensity of infection and prevalence with S.
DIAGNOSIS
haematobium and S. mansoni is greatest in
10–14-year-olds and declines in older age- Parasitological. The presence of eggs in the
groups, but this could be explained by a faeces or urine is still the most widely used
decrease in water contact. However, longitu- method of diagnosis. This usually poses no
dinal studies and detailed monitoring of problems in heavy infections but diagnosis
reinfection after elimination of an existing may not be so easy in light infections, as
infection by chemotherapy have demon- occur in the majority of cases, particularly
strated that age-dependent resistance does in tourists, who have probably been infected
24 Chapter 1

only once. In general, it is only the presence each species more accurate estimates are
of eggs containing live miracidia that possible (Guyatt et al., 1999).
indicates an active infection requiring treat- Portable ultrasound can be used for
ment. diagnosis of the degree of pathology, partic-
The eggs of S. haematobium, which occur ularly in the liver or bladder, and can
in the urine, can be detected by sedimenta- screen populations at the community level;
tion of a 10 ml sample (best collected around it can also be used for determining the
midday) in a urinalysis flask, the deposit effect of chemotherapy (Hatz, 2000).
being examined under the microscope for
eggs. Alternatively, a 10 ml sample can be Immunological. There are numerous
passed through a polycarbonate or poly- immunological tests for diagnosis but those
amide membrane, washed, removed and involving various ELISA and immunoblot-
stained in 1% trypan blue (or 2.5% ninhy- ting techniques are the most convenient. A
drin, 5% iodine, eosin or methylene blue) dipstick ELISA for urine samples, using an
for a few minutes. After washing again (and SEA can effectively diagnose schistosomia-
drying at 37°C if wished), the filter is exam- sis and correlates well with quantitative
ined in a few drops of saline on a micro- egg counts. Circulating cathodic antigen
scopic slide. It is probably not wise to reuse (CCA) is the dominant antigen in the urine
filters. In about 5% of patients, eggs may also of S. mansoni patients and can be detected
be found in the faeces. by a monoclonal antibody (mAb) of 41/42
Cytoscopy may be performed as a final kDa. There are also circulating soluble
diagnostic measure when no eggs can be adult-derived antigens (Sm31/32 and
found in the urine, but the danger of Sj31/32) in serum, which can be detected
secondary infection makes this a possibly by dot ELISA, and an IgG ELISA can be
hazardous procedure. used to detect antibodies against them.
The eggs of the other species occur in
the faeces and concentration techniques, TREATMENT
such as the formol–ether or Kato–Katz Chemotherapy. Praziquantel (usually in a
thick-smear methods (p. 258), are necessary. single oral dose of 40 mg kg1) is the drug of
A modification of the thick-smear method choice for all species of schistosome and has
can be used for quantitative determinations virtually superseded almost all the agents
and, in some studies, has given a good previously used. It has few side-effects
indication of the number of adult worms, (except sometimes in patients with very
as can filtration staining techniques. In the heavy worm loads), although it is probably
latter, eggs from faeces are stained with better not to give it during early pregnancy.
ninhydrin on filter-paper and counted. Praziquantel is a heterocyclic pyrazine-
Rectal biopsy is often effective (even in isoquinoline unrelated to other
about 50% of cases of S. haematobium), an anthelminthics – chemical formula 2-(cyclo-
unstained squash being examined under hexylcarbonyl)-1,2,3,6,7,11-b-hexahydro-4H-
the microscope. pyrazino[2,1a]isoquinolin-4-one. It is quickly
metabolized, crosses the blood– brain barrier
Clinical. In the field, haematuria can provide and appears to act by causing spastic paraly-
a quick and inexpensive indicator of urinary sis and vacuolization of the tegument of the
schistosomiasis; microhaematuria (measured worm, possibly from interference with inor-
by means of a reagent strip) or proteinuria ganic ion transport and an increase in mem-
correlates well with the intensity of infec- brane permeability; it may also destroy
tion. Even self-reporting by children can lysosomes. Two target antigens are also
provide a useful epidemiological record of affected (a surface tubercle glycoprotein of
community prevalence, although this is 200 kDa and an esterase of 27 kDa) and
likely to give an overestimate, depending on maybe epitopes become exposed so that the
the species of worm and level of infection drug evokes an effective immune response
(Ansell and Guyatt, 1999); using models for (Brindley, 1994; Dupre et al., 1999).
 The Trematodes 25

Metrifonate is cheap and safe to use recently (Chitsulo et al., 2000).

against S. haematobium infection. Its main
disadvantage is that repeated treatment is S. japonicum. China 1.06 (0.09% of total
necessary (usually 7.5–10 mg kg1 given population), Philippines 0.43 (0.6%),
orally in each of three doses at fortnightly Indonesia (Sulawesi) 0.0002 (0.0001%),
intervals). As an organophosphate com- Thailand very rare (‘S. japonicum-like’).
pound, it inactivates the enzyme, destroy-
ing acetylcholinesterase, but its mode of S. mansoni. Antigua fewer than 0.0001*,
action against the worms is obscure. Brazil 7.01 (4%), with a mortality rate of
Atropine sulphate can be used if symptoms 0.44 per 100,000, Burundi 0.84 (13%),
of cholinergic activity occur. Dominican Republic 0.23 (3%), Eritrea 0.26
Oxamniquine is a tetrahydroquinoline (7%), Guadeloupe 0.033 (8%)*, Martinique
derivative that has activity only against S. 0.005 (1.3%)*, Puerto Rico 0.015 (0.4%)*,
mansoni (given at a single oral dose of 15 St Lucia 0.0019 (1.2%)*, Rwanda 0.38
mg kg1 ) and can be used for advanced (6%), Surinam 0.0037 (0.9%) and rising in
cases of the disease. It should be avoided children, Venezuela 0.0338 (0.2%).
in early pregnancy and in cases of epilepsy,
and can cause drowsiness. Resistance to S. haematobium. Algeria 2.1 (7.5%), India
the drug has also been reported, and it is in (Bombay area) very rare, Iran 0.042
limited supply. The mode of action is (0.07%), Iraq 0.042 (0.2%), Jordan 0.0001
unknown. (0.002%), Lebanon very rare*, Libya 0.27
The antimalarial compound artemether (5%), Mauritius 0.016 (1.5%)*, Syria 0.003
or artesunate (oil and water soluble forms (0.02%)*, Turkey 0.0006 (0.001%)*.
of an artemisinin derivative) is being tested
as a prophylactic against S. japonicum in S. mansoni and S. haematobium. Angola 4.8
China and in one trial was shown to reduce (44%), Benin 1.95 (35%), Botswana 0.15
egg production of S. mansoni and S. (10%), Burkina Faso 6.24 (60%), Cameroon
haematobium by 15% after 12 weeks when 3.02 (23%), Central African Republic 0.33
given in the usual dose for malaria. It also (10%), Chad 2.78 (43%), Congo 0.89 (34%),
acts principally against developing worms, Congo Republic (Zaire) 13.84 (28%), Côte
unlike the two compounds at present in d’Ivoire 5.6 (40%), Egypt 10.06 (17%),
use; cyclosporin has similar modes of Equatorial Guinea 0.008 (2%), Ethiopia 4.0
action but would be too expensive for gen- (7%), Gabon 0.5 (45%), Gambia 0.33 (30%),
eral use. Caution needs to be exercised in Ghana 12.4 (73%), Guinea 1.7 (26%),
relation to malaria resistance. Guinea Bissau 0.33 (30%), Kenya 6.14
(23%), Liberia 0.648 (24%), Madagascar
Surgery. In advanced cases with liver fibro- 7.54 (55%), Malawi 4.2 (43%), Mali 5.88
sis, portocaval shunt and occasionally (60%), Mauritania 0.63 (27%), Mozambique
splenectomy have been used to relieve the 11.3 (70%), Namibia 0.009 (0.6%), Niger
portal hypertension, but the results have 2.4 (27%), Nigeria 25.83 (23%), Senegal 1.3
been disappointing. (15%), Sierra Leone 2.5 (60%), South Africa
4.5 (11%), Swaziland 0.23 (26%), Togo 1.03
EPIDEMIOLOGY (25%), Uganda 6.14 (32%), Tanzania 15.24
Schistosomiasis, particularly when due to (51%), Yemen 2.23, Zambia 2.39 (27%),
S. haematobium, is very much a focal dis- Zimbabwe 4.4 (40%).
ease and many prevalence figures are based
on limited surveys, which are not always S. intercalatum. Cameroon locally in forest
typical of the country as a whole. However, areas, Congo (16% in children in one area),
estimates in millions of overall prevalence Congo Republic (Zaire) sporadic,
in each endemic country have been made Equatorial Guinea (13% in Bata city),

*It is probable that in these countries transmission has now ceased and these are residual cases.
26 Chapter 1

Gabon (29% in one area), São Tomé and munity that has levels of egg output likely
Principe 0.005 (4%). Confirmation needed to cause morbidity (Jordan et al., 1993).
for presence in Central African Republic, This demonstrates the importance of quan-
Chad, Mali and Nigeria. titative determinations of egg output in
schistosomiasis (p. 260). The ecological fac-
S. mekongi. Cambodia 0.07 (0.7%), Laos tors associated with the transmission of
0.12 (2%) and recent cases in refugee schistosomiasis vary markedly with the
camps in Thailand. species of schistosome, owing to the differ-
ing habitats of the snails involved. The
S. malayensis. Malaysia very rare (Shekar, amphibious snail hosts of S. japonicum live
1991). mainly in rice paddies and muddy habitats
beside rivers; the aquatic snail hosts of S.
In most areas endemic for S. haematobium mansoni live principally in gently flowing
there is a very high prevalence rate, with running water (less than 0.3 m s1 ) such as
almost everyone in the community lightly irrigation channels, streams, lakes and
infected before the age of 10 years. Studies ponds (Plate 2); those transmitting S.
in Brazil, St Lucia, Tanzania and Uganda haematobium live almost entirely in still
demonstrated a relationship between egg water, such as ponds, pools, lakes and
output and prevalence of S. mansoni in marshy areas. Snail populations usually
children (Fig. 17). Above 50–60% preva- show marked seasonal fluctuations, the
lence, a small extra rise is accompanied by most important factors influencing numbers
a considerable increase in egg output and being rainfall and temperature. The effect
thus in the severity of disease. Post-mortem of rainfall varies, depending on the yearly
studies and blood-filtration studies after rainfall figures. In drier regions of Africa
chemotherapy for counting adults have rainfall stimulates the production of young
shown a good relationship between the last bulinid and planorbid snails, while in
two parameters so that intensity of infec- equatorial regions with a higher rainfall,
tion can be expressed in terms of eggs per snails are washed away during the rainy
gram of faeces or per 10 ml of urine. To season and breeding takes place principally
determine the intensity of infection of dif- in the months following. Temperature is
ferent age-groups, the frequency of occur- another factor limiting population densi-
rence of the different levels of egg output ties, the temperature range for optimal
can be conveniently plotted and provides a expansion of snail numbers being
good indicator of the proportion of the com- 20–28°C.

100 x ZAIRE

x KENYA
Prevalence (%)

75 x EGYPT
x BRAZIL
x ST LUCIA x ZAMBIA

50 x KENYA
x ETHIOPIA
x BURUNDI
x BURUNDI

25
x ETHIOPIA

200 400 600 800

Geometric mean of egg output (e.p.g. faeces)

Fig. 17. Relationship between overall prevalence and intensity of S. mansoni infection as determined by
egg output (measured by Kato–Katz technique) in various endemic areas. Each determination is based
on studies by different workers. e.p.g., eggs per gram. (From Jordan et al., 1993.)
 The Trematodes 27

Seasonal variations in the cercarial trans- hemisphere B. glabrata is the most impor-
mission rates in snails are most marked with tant snail host, with seven other species
the bulinid hosts of S. haematobium living locally involved.
in temporary bodies of water. In hyper-
endemic habitats, such as canals, there may S. haematobium. Bulinus is a turreted pul-
be large numbers of snails producing cer- monate snail with a left-handed opening
cariae of S. mansoni throughout the year. when looked at with the spire upwards
Diurnal fluctuations in the production (Fig. 1). The height varies from 4 to 23 mm.
of cercariae occur; cercariae of S. japon- The subgenus B. (Physopsis) is differenti-
icum (which is adapted for transmission ated from B. (Bulinus) by having a truncate
among the nocturnal animal reservoir columella and a pointed end to the foot in
hosts) are mostly produced in the evening, living specimens. Two main groups of
while those of S. mansoni and S. haemato- bulinid snails are important as hosts: (i) the
bium are produced in the middle of the africanus group (ten species) of the sub-
day. This factor is not usually of practical genus Physopsis is the more important
importance except where S. mansoni trans- group in eastern and southern Africa and
mission occurs in running water, in which in most parts south of the Sahara; and (ii)
case washing and bathing are likely to be the truncatus, forskali and reticulatus
much safer in the morning and evening, groups (27 species) of the Bulinus sub-
when cercariae are less abundant. genus of snails act as hosts in the Near East
(Iran, Egypt and Sudan), in Madagascar
SNAIL HOSTS OF SCHISTOSOMES and in parts of both East and West Africa.
S. japonicum. Oncomelania is a conical,
amphibious, prosobranch snail measuring S. intercalatum. B. (Physopsis) africanus acts
3–10 mm and having 4–8 whorls, a dextral as snail intermediate host in Congo Republic
opening and an operculum covering the foot. and B. (Bulinus) camerunensis in Cameroon.
Species involved are O. hupensis from main- It must be borne in mind when attempting
land China, O. nosophora from south-west to identify a snail that there are usually
China (and Japan), O. formosana from many other types of snail present in the
Taiwan, O. quadrasi from the Philippines same body of water as the ones transmit-
and O. lindoensis from Sulawesi. ting schistosomiasis, and they may be
difficult to differentiate. Specialized mono-
S. mekongi. Neotricula aperta is an aquatic graphs need to be consulted (Brown, 1980)
snail found in the Mekong River and it or expert advice sought. It is also important
probably also transmits S. sinensium. to distinguish clearly the cercarial species
Robertsiella spp. are found in Malaysia and emerging, because of the large number of
transmit S. malayensis. animal and bird schistosomes that use the
same snail hosts and produce cercariae
S. mansoni. Biomphalaria is a flattened pul- similar to the human schistosomes. In
monate, planorbid snail with 3.5–7 whorls, detailed epidemiological studies, it may be
measuring 7–22 mm. Four main groups are necessary to expose laboratory animals to
found in Africa: (i) the pfeifferi group (four the cercariae and to identifiy any adult
species), which include the most important schistosomes that develop.
hosts in Africa and the Middle East; (ii) the
sudanica group (three species), which occur
in both East and West Africa; (iii) the PREVENTION AND CONTROL
choanomphala group (three species), which Personal prevention is by avoidance of
live in the great lakes and act as hosts in water sources containing cercariae, impos-
Lake Victoria; and (iv) the alexandria group sible for fishermen to carry out and
(two species), which occur sporadically in extremely difficult for children to be con-
North, East and South Africa. In the western vinced of the necessity thereof. The most
28 Chapter 1

common source of infection in tourists to the intensity of transmission is also impor-

Africa appears to be swimming in Lake tant. Campaigns have been carried out in
Malawi. Thorough and speedy towelling many countries, often with great success,
after swimming or wading in marshes may and at the outset are vertical, involving spe-
prevent cercariae from penetrating. cialized control units that have identified
Before attempting any control measure, and mapped transmission sites, assessed the
it is essential to define its objectives – i.e. level of morbidity and educated health
whether it is intended to prevent apread of workers and the community about the con-
the disease, to reduce morbidity or trans- trol programme (WHO, 1993; Savioli et al.,
mission or to permanently interrupt trans- 1997). Later, community-based control pro-
mission (elimination in an area or grammes can be instigated, utilizing trained
eradication in a country or worldwide). community health workers. If transmission
Until the aims of a project have been is intense (over 50% in children), then the
clearly defined, it is difficult to work out whole population can be treated; otherwise,
techniques and costings, or even to evalu- 7- to 14-year-old schoolchildren can be
ate its eventual success. While eradication targeted, since they can be easily tested,
must be the ultimate objective, it is not yet treated and followed up and are likely to be
a feasible proposition in many areas. the most heavily infected section of the pop-
There are five principal methods of con- ulation. A small number of heavily infected
trol: mass chemotherapy, destruction of
individuals produce a large percentage of
snails, environmental sanitation, preven-
the eggs reaching the environment (in one
tion of water contact and the possible use
classic study with S. mansoni, 51% of
of mass vaccination. Which method or
patients had fewer than ten worm pairs
methods are to be employed will depend
while only 7% had more than 80 – although
very much on the conditions where they
one girl who died had 1600 worm pairs). In
are to be applied but it is usually essential
all campaigns periodic re-treatment is
to provide alternatives or to use two or
essential in order to have a lasting effect.
more methods simultaneously (e.g.
chemotherapy, snail control and health After campaigns with praziquantel in China,
education). It is also important to deter- Indonesia and the Philippines, reduction in
mine at the beginning how the success of the size of the liver and spleen was reported
the campaign is to be measured, and vari- (WHO, 1993), while in patients with schisto-
ous indices can be used. The most common somiasis mansoni, hepatomegaly and peri-
assessment is that of prevalence, but inci- portal fibrosis have regressed after treatment
dence (measurement of the rate at which as measured by ultrasound (Boisier et al.,
people become infected) is more sensitive 1998; Frenzel et al., 1999).
and is particularly useful in mass
chemotherapy campaigns. Other measures CONTROL OF SNAILS
of assessment that can be used are the
effect on egg output (i.e. on intensity of Chemical control. The relationship between
infection) or on severity of clinical disease the population dynamics of snail interme-
(morbidity), immunological methods and diate hosts and disease transmission to
various indirect biological methods. The humans is poorly understood and complete
most common biological method of assess- eradication of snails from large areas is not
ing the success of measures against the feasible. Mollusciciding is likely to be most
intermediate host is a periodic snail count effective in targeted focal sites, say where
but determinations of the infection rates in children habitually bathe. Infection van-
snails have been used. ished from Tunisia in 1983 after treatment
of oases.
Mass (universal) chemotherapy. The primary Niclosamide (Bayluscide) can be used at
objective should be the reduction and pre- a concentration of 8 p.p.m. hours (e.g. 0.33
vention of morbidity, although a decrease in p.p.m. for 24 h) for aquatic snails (Plate 3)
 The Trematodes 29

or 0.2 g m2 on moist soil for amphibious avoiding contaminated water needs to be
hosts of S. japonicum. effectively communicated, particularly to
children and adolescents. While it is prob-
Biological control. Carnivorous snails, such ably impossible in Africa to prevent chil-
as Marisa cornuarietis, or competitors, dren swimming in the water, they could be
such as Melanoides tuberculata and taught to urinate (and perhaps defecate)
Tarebia granifera, have been added to habi- before entry.
tats in Guadeloupe, Martinique, Puerto
Rico and St Lucia, with the result that Present position and future outlook for con-
Biomphalaria has vanished from all or trol. Present control methods are capable of
almost all areas (Giboda et al., 1997; substantially reducing transmission and
Pointier and Jourdane, 2000). particularly morbidity in most areas pro-
vided that they are properly designed and
Ecological methods of control. Habitats can carried out and if adequate funds are avail-
be made unsuitable for snails by alternate able. However, new irrigation and hydro-
flooding and drying of water channels or electric schemes in many endemic
covering and lining of canal systems, as in countries have increased the number of
Egypt and Sudan, and filling in of marshy snail habitats. New human-made lakes
areas. In many areas such measures are have followed the building of dams in
likely to be permanently successful, but many countries: Côte d’Ivoire (Lakes
they require close cooperation between Kossou and Taasbo), Egypt and Sudan
irrigation engineers and public health (Lake Nasser); Ghana (Volta Lake); Nigeria
workers. In rice-growing areas of mainland (Kainji Lake); Zambia and Zimbabwe (Lake
China and in Leyte Island (Philippines) Kariba); Senegal (Lake Guiers below the
widespread cleaning of irrigation ditches Diama dam and Manantali dam in Mali).
and filling in of ponds have resulted in a The incidence of schistosomiasis in the
great reduction in schistosomiasis japon- populations bordering these lakes or the
icum infection in recent years. irrigation channels coming from them (as
in Egypt and the Gezira scheme in Sudan)
Prevention of water contact. The provision almost always rises. In Côte d’Ivoire
of piped water supplies and alternative around Lake Kossou there used to be an
bathing and clothes-washing places can be infection rate of 14% with S. haemato-
effective in preventing human contact with bium, which has now risen to 53%, and
infested water and, while expensive, does around Lake Taabo the rate has risen from
have wide-ranging health benefits. 0% to 73% (although the 2% infection rate
For visitors and tourists, prevention can with S. mansoni has not changed so far);
be achieved by avoidance of contact with around Lake Kainji the infection rate with
water in ponds, canals, slow-flowing S. haematobium is now 14% in children
streams and the shallow edge of lakes in (from nothing); around Lake Kariba there is
endemic areas (although in Lake Victoria in now a 70% infection rate in children with
East Africa the snail Biomphalaria S. haematobium; infection has spread
choanomphala transmits S. mansoni in greatly in the Senegal River basin since the
water 2 m deep). For tourists, swimming in building of the dams and there is now a
Lake Malawi or Lake Kariba is often fol- prevalence of 91% with S. mansoni (from
lowed by infection. Dibutyl phthalate or 1%) and of 28% with S. haematobium
hexachlorophene spread over the skin will (Southgate, 1997). One trend in Africa
protect for about 4 h. caused by changes in ecology following the
building of dams in Africa (e.g. in delta
Health education. Knowledge of the role of areas of Cameroon, Ghana and Egypt) is the
indiscriminate defecation and urination in replacement of S. haematobium by S. man-
spreading the disease to members of a com- soni. The new opportunities for agriculture
munity and the personal importance of are also attracting possibly infected
30 Chapter 1

migrants and this is particularly apparent Progress to date indicates that a vaccine is
in the Gezira and in Ethiopia (although the feasible, since protection against sheep
building of the Koka dam initially reduced schistosomiasis (a problem in Sudan) using
transmission). irradiated cercariae has been successfully
Infection has been eliminated from achieved. However, any human vaccine
Japan, Tunisia and Montserrat recently and will have to consist of defined components,
campaigns against S. haematobium are as cercariae might introduce viruses.
being mounted in Mauritius (1.3% in adults Various types of vaccine are being inves-
only), Morocco (2.3% overall) and Tanzania tigated (Capron, 1998). These include the
(45% in Zanzibar), against S. mansoni in following.
Brazil, Burundi, St Lucia and Venezuela
1. Peptide components of protective anti-
(risen from 0.1% to 0.9% in under-10-year-
gens. These can be used to generate
olds in the last few years) and against both
differential responses, e.g. one elicits
species in Egypt, Ghana, Madagascar,
eosinophil-dependent ADCC, another stim-
Malawi, Mali, Nigeria, Saudi Arabia, Sudan
ulates delayed-type hypersensitivity (DTH)
and Zimbabwe; against S. japonicum in
reactions with macrophage activation.
China, Indonesia (1% overall infection rate)
and the Philippines (3.6%); and against S. Recently a multiple antigen peptide (MAP)
mekongi in Laos (72%) (WHO, 1993). vaccine has shown very promising results,
China has had control campaigns involv- inducing both T-cell and B-cell responses
ing mass treatment of people and cattle with in mice and in monkeys, reducing parasite
anthelminthics (nowadays praziquantel), fecundity and egg viability and decreasing
snail control and environmental engineering liver pathology by over 70%.
for the last 50 years but there were still esti- 2. Excretory/secretory (ES) antigens. ES
mated to be 1.06 million cases in humans material obtained from postcercarial schisto-
and 0.25 million cases in cattle in 1997. somula kept in vitro is effective in immu-
However, S. japonicum has been eliminated nizing rats to subsequent infection. The
from 150 of the formerly 378 endemic coun- secretions contained proteins in the range
ties in 12 provinces south of the Yangtze 22–26 kDa (amplified by PCR) and induce
River (Ross et al., 1997), while in 1955 there an IgE-dependent ADCC.
were estimated to be over 11 million cases. 3. Membrane antigens. Molecules with a
Unfortunately, recent flooding has increased molecular weight of 23 kDa (e.g. Sm23 and
the extent of snail habitats. The Three Sj23) occur in the tegument of all stages of
Gorges dam under construction on the the parasite but are often species-specific.
Yangtze River will, within the next 10 years, 4. Paramyosin. This 97 kDa internal anti-
create the largest lake in the world in a gen (e.g. Sm97), obtained from schisto-
highly populous region where schistosomia- somula or adults, induces responses that
sis japonicum already occurs and where affect the muscles and tegument of adults
there will have to be about 2 million extra (Gobert, 1998).
migrants from highly endemic areas, which 5. DNA vaccines. Direct injection of the
will be flooded. The building of the dam coding sequence for known antigens is
should reduce the overall density of snails being investigated. Such a vaccine can be
along the river banks but will provide many used alone or combined with chemother-
more suitable, contaminated, marshland apy, e.g. immunization with DNA for Sm28
habitats and an increased contact with water. glutathione-S-transferase (GST) together with
praziquantel prevented the formation of
Towards a vaccine. The need for a vaccine pathological lesions in mice (Dupre et al.,
against schistosomiasis is underscored by 1999).
the fact that, although chemotherapy with 6. Irradiated live cercarial vaccines.
praziquantel is very effective, in the Although these are not directly suitable for
absence of an effective immune response human use, they might provide useful
reinfection tends to occur quite quickly. pointers to promising leads (Coulson, 1997).
 The Trematodes 31

The most promising six antigens were on the island of Leyte in the Philippines,
recently selected by the World Health although many other species of animals are
Organization (WHO) for testing as vaccines infected, as they are on Sulawesi (Indonesia)
but at best gave only a maximum of 60% and used to be in Japan. Molecular studies
protection (Katz, 1999). indicate that S. japonicum is a species com-
A general problem facing the develop- plex of many sibling species, and in Taiwan
ment of vaccines against any infectious dis- the local form of S. japonicum occurs only
ease is the generation of an appropriate in animals and is not infective to humans.
T-cell response (e.g. CD4+ or CD8) and, if The dog appears to be the only reservoir host
CD4+, then the appropriate Th subset, Th1 of S. mekongi in Laos. S. sinensium is a little
or Th2. In addition, where the disease asso- known species with a laterally spined egg
ciated with infection is immune-mediated, found a few times in humans and rodents in
as in schistosomiasis, vaccination must not China and Thailand (Greer et al., 1989),
induce pathological responses. There is while the ‘Tonle Sap schistosome’ has been
controversy about whether Th1 or Th2 newly discovered in humans living around
responses are most important and appro- Lake Tonle Sap in Cambodia (Pecoulas et al.,
priate for vaccine-induced resistance to 1995).
schistosome infection, but it is probable S. mansoni has been reported frequently
that a balanced response would be best from animals (of 38 species) but in many
(Wynn and Hoffmann, 2000). cases they do not appear to have any epi-
The route of administration of any vac- demiological significance. However, baboons
cine is also very important, as is the choice and green monkeys are apparently main-
of a suitable adjuvant. Presentation of anti- taining infections among themselves in
gens via an engineered vector organism can areas of East Africa and rodents may act as
overcome both problems. For example, reservoir hosts in East Africa, Senegal and
Bacillus Calmette–Guérin (BCG) has been Guadeloupe and particularly in Brazil,
engineered to produce an intracellular where up to 15 species appear to be of
schistosome GST and this has induced a increasing importance in maintaining
strong and long-lasting response in mice infection in urban and periurban areas of
when given by the intranasal route (a the north-east (Mott et al., 1995).
mixed response of GST-specific immuno- Animals appear to be of little or no
globulin – IgG2a, IgG2b and IgA in serum importance in the transmission of S.
and IgA in bronchial lavage fluids). A vac- haematobium, although various primates
cine against schistosomiasis haematobium have been found infected, nor are they for
(Sh28GST – Bilhvax) together with prazi- S. intercalatum.
quantel treatment is undergoing field trials The schistosomes found in humans and
in Senegal. animals in Africa can be divided into two
groups of sibling species. Hybridization
ZOONOTIC ASPECTS can occur experimentally within members
Animal hosts are extremely important in the of each group but is not common in nature.
transmission of S. japonicum and S. In the S. haematobium/S. intercalatum
mekongi and in some countries can maintain group, S. mattheei Veglia and Le Roux,
the parasite in the absence of humans. In 1929, is a parasite of sheep, cattle, wild
mainland China infection occurs in 40 animals and occasionally humans in south-
species of domestic and wild animals ern Africa. The eggs in the faeces or urine
(Jordan et al., 1993) and is important as a have a terminal spine and measure
serious cause of morbidity and mortality in 120–180 µm in length (Fig. 124). Curiously,
cattle and goats. In the Dongting Lake area of in all human cases, the eggs have occurred
Hunan, 60% of cattle and buffaloes, 24% of together with those of S. haematobium or
pigs, 9% of dogs and 7% of people were S. mansoni; the females of S. mattheei are
found to be infected. Dogs and pigs play an known to be capable of producing eggs
important part in maintaining transmission parthenogenetically and are perhaps carried
32 Chapter 1

by excess males of the other species. S. Family Paragonimidae

bovis (Sonsino, 1876) Blanchard, 1895, is
similar to S. haematobium and is found in Paragonimus westermani
cattle in southern Europe, in Iraq and over (Kerbert, 1878) Braun, 1899
much of Africa, but there have been very
few genuine infections in humans SYNONYMS
(Mouchet et al., 1988). S. margrebowiei Le Distoma westermani (D. westermanii)
Roux, 1933, is a common parasite of Kerbert, 1878; D. ringeri Cobbold, 1880.
antelopes in Africa but the few human
cases reported might be spurious. S. rod- DISEASE AND COMMON NAMES
haini Brumpt, 1931, is closely related to S. Paragonimiasis or paragonimosis; pul-
mansoni and is found in rodents and carni- monary distomiasis, Oriental lung fluke
vores in Central Africa; it has been infection.
reported once from a human. S. curassoni,
Brumpt 1931, is a parasite of domestic LOCAL NAMES
ruminants in West Africa and has been Pa-yard bai-mai nai pod (Thai).
doubtfully reported from humans.
The cercariae of various mammal and GEOGRAPHICAL DISTRIBUTION
bird schistosomes penetrate the skin of Paragonimus westermani is widely distrib-
humans in many areas of the world but do uted in the Chekiang Province of China,
not develop further. In a sensitized host Korea, Laos, the Philippines, Taiwan and
they cause dermatitis at the site of entry, Thailand and also occurs in smaller areas of
with irritation, pruritus, macules and India, Indonesia, Japan, Malaysia and
papules (‘swimmers’ itch’ or ‘schistosome Vietnam, with one or two cases in Russia
dermatitis’). Examples are the cercariae of and Poland. Although there are at least 14
the bird parasites Austrobilharzia terri- other species that have been reported from
galensis (Australia), Bilharziella polonica humans, most of the estimated 21 million
(Europe), Gigantobilharzia sturniae (Japan), cases in 39 countries worldwide are due to P.
G. huttoni (Florida, USA), Microbilharzia westermani, with 195 million people at risk.
variglandis (Delaware, USA), Tricho-
bilharzia brevis (Japan), T. maegraithi LOCATION IN HOST
(Thailand), T. ocellata (worldwide) and T.
The adults are typically found in pul-
stagnicolae (USA) and cercariae of mam-
monary cysts, usually in pairs.
malian species of schistosomes, such as
Heterobilharzia americana (Louisiana,
MORPHOLOGY
USA), Orientobilharzia turkestanica (China
A living Paragonimus is a thick fleshy fluke
and Iran), Ornithobilharzia turkestanicum
measuring 8–16
4–8 mm and is reddish-
(Iran), Schistosoma bovis (Africa), S. spin-
dale (Asia) and Schistosomatium douthitti brown in colour, with a tegument covered in
(North America). simple or toothed spines. The ventral sucker
Schistosome dermatitis is more of a nui- lies just anterior to the middle of the body
sance than a serious medical problem and is about the same size as the oral sucker.
when it occurs in bathers or water-sports The testes are almost side by side in the pos-
enthusiasts using lakes frequented by terior part of the body. The large excretory
waterfowl, but is of real economic impor- bladder is usually apparent in sections of
tance among rice planters in China, the worm (Fig. 18 and Plate 4). The yellow-
Malaysia and Vietnam. ish-brown egg is ovoid and thick-shelled. It
measures 80–110 µm
50–60 µm, with a
rather flattened operculum, which gives the
impression of being too small, and is unem-
bryonated when laid (Fig. 123).
 The Trematodes
Map 3. Distribution of Paragonimus spp. and Opisthorchis felineus.

33
34 Chapter 1

LIFE CYCLE the water, where they can survive for only
The eggs are usually swallowed and pass 24–48 h.
out in the faeces but may also escape in If cercariae find freshwater crabs, princi-
sputum. For further development they pally Eriocheir, the mitten crab in Asia and
have to reach water. The miracidia hatch also Potamon (Fig. 19) and Sesarma, or
after 3 weeks in water (at an optimum tem- freshwater crayfish (Astacus), they penetrate
perature of 27°C) and penetrate freshwater and encyst in the gills or muscles as meta-
snails. These are operculate genera, of cercariae (measuring 250–500 µm).
which the most important is Semisulcospira Freshwater crustaceans can probably also
(S. libertina is an intermediate host species become infected by ingesting unencysted
in China, Japan, Taiwan and Korea). Other cercariae in the water or even inside an
important snails are S. amurensis, Thiara infected snail.
granifera and Oncomelania nosophora (see The crustacean intermediate hosts are
Fig. 1). eaten by humans as food. If they are eaten
In the snail the miracidia develop into raw, the metacercariae hatch in the duode-
sporocysts followed by two generations of num and young worms penetrate through
rediae, and finally, in about 3 months, give the intestinal wall and pass across to the
rise to very short-tailed cercariae. The cer- abdominal wall in about 6 h. The immature
cariae emerge from the snail and swim in flukes burrow through the diaphragm to the

Fig. 18. Cut portion of lung (of a tiger) with cysts containing pairs of adult Paragonimus. Note large
excretory bladder in each fluke.

Fig. 19. Potamon, a crab second intermediate host of Paragonimus in Asia.

 The Trematodes 35

pleural cavity in 6–10 days and enter the become surrounded by a cyst, possibly
lung capsule in 15–20 days. The first eggs caused by softening followed by fibrosis
are passed 60–70 days after infection. (Plate 4). However, as the cyst wall is usu-
Although Paragonimus is hermaphrodite, ally lined with columnar epithelium, it is
two worms are necessary for fertilization to probable that, in most cases, it represents
take place (Fig. 19 and Plate 4). This is true the expanded wall of a bronchus. The cap-
for the usual diploid form of P. westermani, sule is collagenous and oedematous, with
but there is also a triploid form, in which plasma cells, eosinophils, neutrophils,
parthenogenesis can occur; the adults of the macrophages and fibroblasts. The cyst mea-
latter are larger and more pathogenic and sures about 1 cm in diameter after 90 days
the eggs differ in size and shape (see Blair and is filled with a thick brownish fluid
et al., 1999). The adult worms can live for containing eggs. Bronchopneumonia may
20 years but usually die after about 6 years. result when a cyst bursts or retains an
opening into a bronchus. Eggs are often
CLINICAL MANIFESTATIONS present in the lung tissues and cause
There are no recognizable symptoms pseudotubercles similar to those caused by
accompanying the migratory phases. schistosome eggs, with infiltration by
The first signs are usually fever with a eosinophils and lymphocytes, followed by
dry cough, sometimes accompanied by giant cells and fibroblasts.
bloodstained sputum containing eggs after
rupture of the cysts. Chest pain can be Extrapulmonary. Adults are sometimes
severe and, if the infection is heavy, there found in many parts of the body, particu-
is sometimes increasing dyspnoea and larly in the organs of the abdominal cavity
bronchitis. Many patients with haemo- or subcutaneous tissues. In these sites the
ptysis are diagnosed as suffering from worms are rarely fertilized and presumably
pulmonary tuberculosis. have developed from larvae that lost their
Cerebral paragonimiasis may result in way. This occurs more frequently with
epileptic seizures, as well as headaches, species of Paragonimus which are less
visual disturbances and symptoms of adapted to humans than P. westermani.
meningitis. Most serious complications follow the
presence of flukes in the brain (Fig. 20).
PATHOGENESIS
This may be common in areas of high
Pulmonary. As flukes grow in the lungs endemicity (e.g. over 5000 cases per
they cause an inflammatory reaction and annum in South Korea). Adults found in

Fig. 20. Radiograph of head of a girl with soap-bubble type of calcification surrounding cysts containing
adult Paragonimus in occipital lobes.
36 Chapter 1

the brain usually have eggs, unlike those Immunological. The intradermal (ID) test has
recovered from other extrapulmonary been widely used for many years and is use-
sites; it is believed that they migrate from ful in differentiating paragonimiasis from
ruptured lung cysts along the soft tissues tuberculosis, but it is very non-specific and
surrounding the veins into the cranium. the test lasts for many years after cure or the
The flukes cause necrosis of the surround- death of parasites. There have been numer-
ing brain substance and are eventually ous trials of ELISA tests in the last 20 years,
encapsulated, with granulomas surround- some using crude antigens, but recently
ing released eggs lying along the fibrous more specific ES antigens (probably cysteine
wall of the cyst. When a fluke dies, the proteases) and tests for parasite antigen
cavity of the lesion becomes filled with using mAbs have increased sensitivity and
purulent material. Lesions may occur in specificity (Ikeda, 1998; Blair et al., 1999).
the cerebral cortex, cerebellum, basal gan- Dot ELISAs using dried antigens dotted on
glia and medulla oblongata. Cerebral nitrocellulose plates are also being used.
paragonimiasis can easily be confused Immunological techniques can differentiate
with brain disease caused by other between species of Paragonimus, particu-
helminths, such as Schistosoma japon- larly between P. heterotremus and P. wester-
icum, Gnathostoma spinigerum and mani (Dekumyoy et al., 1998).
Parastrongylus cantonensis or larvae of
Echinococcus granulosus and Taenia TREATMENT
solium, as well as with viral or bacterial The drug praziquantel has revolutionized
infections and with brain tumours. treatment in the last few years when given
Levels of non-specific IgE are elevated at 25 mg kg1, three times a day after meals
in infection and IgG4 levels are also very for 3 days. Side-effects are usually minor
high, possibly to obstruct IgE-mediated and short-lived. Triclabendazole at 5 mg
immunopathogenicity. Immune evasion kg1 daily for 3 days has also proved to be
mechanisms are probably employed by the effective in cases in Africa and South
parasites, with periodic sloughing of the America, one of which was resistant to
outer calyx layer on the tegument. praziquantel.
Surgery, which used to be necessary for
cerebral cases, is now rarely used since the
DIAGNOSIS
advent of effective drug therapy, except for
Clinical. A cough with brown sputum but some cases of cutaneous infection where
otherwise good health is often indicative of flukes can be easily removed.
a light infection in a patient from an
EPIDEMIOLOGY
endemic area. Characteristic nodular or ring
Paragonimiasis can be contracted from
shadows apparent on X-ray or computer-
both raw and pickled crabs and crayfish. In
assisted tomography (CT) scan can be recog-
the Philippines a dish called kinagang is
nized by an expert, but the disease is often
made from crab juice and in the Chekiang
mistaken for tuberculosis.
province of China ‘drunken crabs’
(Potamon sp.) are eaten alive after steeping
Parasitological. A certain method of diagno- in rice wine. In Japan crabs (usually
sis is to find the characteristic eggs in spu- Eriocheir sp.) are usually eaten well-
tum or faeces, which need to be cooked but the metacercariae contaminate
differentiated from those of Achillurbainia knives, hands and chopping-boards during
(see below). Various concentration tech- preparation in the kitchen and are then
niques may be necessary for detection of accidentally transferred to salad vegetables.
eggs in faeces (see p. 258) as, in chronic Crushed crayfish juice is used as a treat-
infections, very few eggs may be passed; ment of measles in Korea and in this way
centrifugation with 2% NaOH is a method young children become infected. In Japan,
that can be used. wild boar, hens and ducks appear to act as
 The Trematodes 37

paratenic hosts. Paratenic hosts (including eastern Nigeria and occasionally also in 12
rodents) are likely to be important in trans- other countries of West and Central Africa
mission to large carnivores. (WHO, 1995).
Metacercarial cysts accumulate during
the life of the crab and in large specimens Americas. P. caliensis Little, 1968, is a nat-
there may be as many as 1000 cysts g1 of ural parasite of opossums in Central and
tissue. South America. P. kellicotti Ward, 1908, is
found in many carnivores, pigs and opos-
PREVENTION AND CONTROL sums in North America, with a few cases in
Metacercarial cysts in the crustaceans are humans in Canada and two in the USA. P.
killed by heating in water at 55°C for 5 min mexicanus Miyazaki and Ishii, 1968, is
and even light cooking renders them safe. found in many carnivores and opossums and
However, cysts can live for up to 48 h occasionally humans in North, Central and
when frozen at 20°C, although they die in South America; most cases are in Ecuador
minutes when dried. and cerebral infections are not infrequent.
Where zoonotic infections are rare, sani-
tary improvements to prevent eggs reaching Asia. P. bangkokensis Miyazaki and
snail habitats in water can be used. In Vajrasthira, 1967, is found in cats and other
Korea there has been a reduction in preva- carnivores in China, Russia and Thailand.
lence caused by increasing industrialization P. heterotremus Chen and Hsia, 1964, is
and pollution of habitats. found in carnivores and rodents in China,
National campaigns need to involve Laos, Thailand and Vietnam. P. miyazaki
public awareness and community participa- Kamo et al., 1961, is a parasite of carni-
tion, food control, sanitary waste disposal vores in Japan, and adults do not mature in
and adequate monitoring and surveillance humans. P. ohirai Miyazaki, 1939, is a para-
(WHO, 1995). site of rats and mice in Japan. P. philip-
pinensis Ito et al., 1978, is primarily a
ZOONOTIC ASPECTS parasite of dogs in the Philippines. P. pul-
Paragonimus westermani is a natural parasite monalis (Baelz, 1883) Miyazaki, 1978, is
of carnivores; in fact, the specific name hon- found in cats and dogs in Japan, Korea and
ours a director of Amsterdam zoo, where the Taiwan. P. sadoensis Miyazaki et al., 1968,
first specimens were found in the lungs of a has been found only in humans in Japan. P.
tiger. It is found especially in the members of (= Pagumogonimus) skrjabini Chen, 1960
the cat family, such as the tiger, leopard and (= P. hueitungensis Chung et al., 1975) is a
domestic cat, in most parts of its range but has parasite of cats, dogs and palm civets in
also been reported from dogs, pigs and mon- China: in human infections worms do not
keys. In China, Japan and Korea, animal hosts mature and the young migratory worms are
are probably not of importance in transmis- often subcutaneous or cerebral.
sion to humans, while in Indonesia, Malaysia
and Sri Lanka infection is confined entirely to
animals and human cases do not occur. Family Achillurbainiidae
Over 30 probably valid species of
Paragonimus have been described (Blair et Achillurbainia nouveli Dolfuss, 1939, was
al., 1999) differing (often slightly) in mor- first found in a palpebro-orbital abscess from
phology and life cycle. Many cause zoonotic a Malayan leopard in a zoo in France. An
infections in humans in various parts of the adult was subsequently found in a 10-year-
world (WHO, 1995), as outlined below. old Chinese girl. The adults are common in
the lungs of rats (Rattus muelleri) in West
Africa. P. africanus Voelker and Vogel, Malaysia and freshwater crabs probably act
1965, and P. uterobilateralis Voelker and as second intermediate hosts. A. recondita
Vogel, 1965, are parasites of the mongoose, Travassos, 1942, developmental stages have
civet cat and humans in Cameroon and been found in humans in Brazil, Honduras
38 Chapter 1

and Louisiana, USA; adults are usually in MORPHOLOGY

opossums. Adult flukes measure 11–20 mm
3–4.5
Poikilorchis (or probably Achillurbainia) mm and are elongated and extremely flat,
congolensis Fain and Vandepitte, 1957, is a tapering anteriorly and rounded post-
similar parasite and was first found in a eriorly; when living they are almost trans-
retroauricular cyst in Congo Republic. parent. There can be a wide variation in the
Similar eggs have been found in cysts in size of adults, depending upon the intensity
two boys in Sarawak and in Cameroon and of infection and on the diameter of the bile-
Nigeria. The eggs are similar to those of ducts in which they are living. The tegu-
Paragonimus but are smaller (63 µm
40 ment has no spines. The ventral sucker is
µm). smaller than the oral and is situated about a
quarter of the length from the anterior end.
The two deeply lobed testes lie one behind
Family Opisthorchidae the other at the posterior end. They provide
an important identification feature, particu-
Clonorchis sinensis larly in stained specimens (Fig. 2).
(Cobbold, 1875) Looss, 1907

SYNONYMS LIFE CYCLE (Fig. 21)

Distoma sinense Cobbold, 1875; In most infections there are usually only
Opisthorchis sinensis Blanchard, 1895. a few adults present but there can be up
Clonorchis was erected as a genus on to 6000 and a daily egg production of
the basis of the shape of the testes, but it is 1000 eggs ml1 bile or 600 g1 faeces may
doubtful that this is sufficient to warrant be recorded.
separation from the very closely related The small yellowish-brown eggs (Fig.
genus Opisthorchis. However, it still per- 123) measure 23–35 µm
10–20 µm and
sists in the literature and, unless there is a have an operculum at one end and a small
formal decision by the International knob at the other. The eggs contain a fully
Commisssion on Zoological Nomenclature, formed miracidium when laid and pass from
it is reluctantly retained here. the bile-ducts into the intestine and out with
the faeces. They have to reach water, where
DISEASE AND POPULAR NAMES
they do not hatch but are ingested by various
Clonorchiasis or clonorchiosis, opisthor- species of snails (Alocinma longicornis in
chiasis sinense; Chinese liver fluke disease. southern China, Bulimus fuchsiana in north-
ern China and Parafossarulus manchouricus
LOCAL NAMES
in most endemic areas are commonly
Oogyubyo, Hareyamai or Suishobyo
infected species). The miracidia hatch in the
(Japanese).
rectum of the snail and develop into sporo-
GEOGRAPHICAL DISTRIBUTION cysts in the hepatopancreas, where they give
About 7 million cases in nine countries in rise to numerous rediae.
the world (with 290 million people at risk); Cercariae are produced 21–30 days after
in China (4.7 million cases), Hong Kong infection. These have an unforked keeled
(0.3 million), India (rare in Assam), North tail, and emerge into water, where they live
Korea (0.95 million), Russia (Siberia), for only 1–2 days, unless they can pene-
Taiwan and Vietnam (1 million). trate beneath the scales of freshwater fish
and form a metacercarial cyst in the sub-
LOCATION IN HOST cutaneous connective tissues, usually those
Adults inhabit the bile-ducts just under the near the caudal fin.
liver capsule, but in massive infections Over 100 species of fish have been
may be found in the gall-bladder, pancre- implicated as secondary intermediate
atic ducts and all bile-ducts as well. hosts of C. sinensis and up to 3000 cysts
 The Trematodes 39

Map 4. Distribution of Clonorchis sinensis and Opisthorchis viverrini.

have been found in a single fish. CLINICAL MANIFESTATIONS

Metacercarial cysts measure 140 µm
The majority of infections (about 70%) are
120 µm and are infective in about 23 days. symptomless and the presence of worms is
When fish are eaten raw or undercooked, only diagnosed at autopsy, when up to 100
the metacercarial cysts hatch out in the flukes may be found in the bile-ducts.
human duodenum and the young flukes Moderate infections, due to the presence of
migrate up the bile-ducts, maturing in 3–4 100–1000 flukes, result in diarrhoea, abdomi-
weeks. The adult flukes can live for up to nal discomfort and some splenomegaly. When
26 years but on average survive for 10 a heavy infection, which may consist of many
years (Chen et al., 1994). thousands of worms (the maximum recorded
being 21,000), is contracted at one time, there
40 Chapter 1

oral sucker ADULTS live in bile ducts,

mature in 3–4 weeks
uterus

10 mm
fish Embryonated EGG
raw (30m
16m) in
n
nu d i faeces reaches water
but does not hatch.
uode te

EG
m
testis
st in d inges

GS Can survive for over

METACERCARIA in 3 months in water
Found in subcutaneous fae
IAE

tissues and muscles of fish, ce operculum

particularly near caudal fin. s
CAR
CER
Excy

Cats and dogs

META
0.1 mm

act as
reservoir hosts ed
excretory bladder st
ge
in
S il
G a
rectum EG sn
by
gland
CE ave snail digestive gland
a n RCARIAE le
d p enetrate fresh water
fish gills

0.01 mm
snail
stages in MIRACIDIUM
hatches in gut of
REDIA in LATE snail (unlike most
digestive gland SPOROCYST trematodes where
CERCARIA by 17th day miracidium hatches
hangs in water then pharynx in water and actively
developing penetrates snail)
attaches and penetrates developing redia
into any fish it comes cercaria
into contact with.
0.05 mm

Can live 1–2 days EARLY SPOROCYST

in water in gut or rectum
of snail
0.1 mm
0.3 mm

0.1 mm

excretory eye spot

bladder penetration
glands

Fig. 21. Life cycle of Clonorchis sinensis. Figure of courtesan and cat by Kaigetsudo.

are additional symptoms, such as a sudden onset of symptoms is more insidious.

onset of fever, acute pain in the upper right Portal hypertension may occur with
quadrant, liver enlargement and tenderness, splenomegaly (this is found in 20–40% of
oedema, an increased erythrocyte sedimenta- autopsies) and ascites is almost always pre-
tion rate and up to 40% eosinophilia; symp- sent in fatal cases, although not usually
toms of cholecystitis and hepatitis follow a diagnosed during life.
few weeks later, and there may also be bouts Prognosis depends largely on the number
of recurrent gall-bladder colic. There is usu- of parasites present and, as the great majority
ally loss of weight, with slight jaundice, and of cases have only light infections, no ill
later there may be tachycardia, with palpita- health ensues. However, the prevalence can be
tions and vertigo. However, in an endemic so high in endemic regions that even the low
area, parasites are often acquired progressively proportion of heavily infected individuals can
over a period of months or years, and the provide an important source of morbidity.
 The Trematodes 41

Death is only likely to occur where there found in about 10% of autopsies, but there
is an intercurrent bacterial infection (apart is no evidence that it is directly related to
from the possibility of cholangiocarcinoma); the presence of the parasite and it may be
salmonellae in particular flourish in bile- coincidental or accentuated by an accom-
ducts attacked by Clonorchis. A similar rela- panying bacterial infection. Clonorchis
tionship has been reported with urinary often enters the pancreatic ducts and
schistosomiasis, where it has been shown causes pancreatitis, with adenomatous
that Salmonella typhi may live on the inside hyperplasia; occasionally there may be
and outside of the body of the schistosomes. acute inflammation.
Carcinoma of the bile-ducts is found in
PATHOGENESIS association with clonorchiasis in Canton
At operation the presence of severe infec- and Hong Kong and is far more common
tion is obvious from gross examination of than in non-endemic regions (IARC
the liver because the thickened bile-ducts Working Group, 1994); it has also been
appear as pale patches on the surface. If the reported from experimental infections in
liver is cut, the slimy, brownish flukes dogs and cats.
often emerge from the ducts.
The adult worms presumably feed mainly IMMUNOLOGY OF LIVER FLUKES
on the biliary epithelium but, unlike Immunological aspects of infection with
Fasciola hepatica, have no spines on the Fasciola hepatica (see p. 46) have been
tegument to cause mechanical damage. In extensively studied in domestic ruminants
the early stages there is an inflammatory and in laboratory rodents. Infections are
reaction in the biliary epithelium and in associated with blood eosinophilia, strong
heavy infections there is cellular infiltration, antibody responses and immune-mediated
consisting mainly of lymphocytes and leuco- inflammation in the liver and bile-ducts.
cytes, particularly in the outer part of the Evidence sluggests that infection elicits
fibrous wall. This is followed by hyperplasia strongly polarized Th2 responses but also
and metaplasia of the epithelium, with that flukes are capable of down-regulating
much mucus, and there may be the forma- host immunity in various ways. Infections
tion of new biliary ductules (Fig. 22). with Clonorchis sinensis similarly induce
Because immature Clonorchis migrate up the eosinophils and profound inflammatory
bile-ducts, there is not the pathology associ- responses in the liver (in some cases result-
ated with early Fasciola infections, which ing in cholangiocarcinoma) as well as para-
burrow through the liver parenchyma (see p. site-specific IgA, IgE and IgG; it can be
47). In the chronic stage there is an encapsu- assumed therefore that a similar polariza-
lating fibrosis of the ducts and destruction of tion of the immune response occurs.
the adjacent liver parenchyma. A fibrotic Evidence for immunity to reinfection in
reaction surrounds eggs that reach the liver humans is not strong, there being no decline
parenchyma, but there is not the granuloma in prevalence or intensity of infection
formation around intact eggs which occurs in chronically exposed populations.
in schistosomiasis (Fig. 14). Experimental studies using Opisthorchis
Stones are common in the bile-ducts viverrini in hamsters have clarified some
and gall-bladder in cases of C. sinensis aspects of the immune response and sug-
infection and were found in 70% of autop- gested the operation of a degree of immune
sies in a study in Hong Kong. The remains protection. This has also been proposed in
of adult worms are sometimes found inside human infections with this species. In an
the stones. Recurrent pyogenic cholangitis endemic area individuals who were egg-
is one of the most important complications negative had higher levels of IgA, IgG and
of clonorchiasis, as well as of ascariasis (p. IgM than those who were egg-positive and
151). The cholangitis often follows a long they showed recognition of specific anti-
relapsing course, eventually leading to bodies not detected by antigens of infected
widespread fibrosis. Cirrhosis of the liver is individuals. Studies in hamsters have also
42 Chapter 1

Fig. 22. Section of liver with two adult Clonorchis in bile-duct. There is marked epithelial proliferation,
oedema of the mucosa and some fibrosis (see also Plate 6). The ventral sucker, uterus filled with many
eggs and testes (in fluke on left) are apparent.

shown that parasite antigen accumulates in TREATMENT

the tissues around the worms and is associ- Praziquantel at three times 25 mg kg1
atated with marked inflammatory responses. daily for 1–3 days or at a single dose of 40
mg kg1 (given in Korea to reduce side-
DIAGNOSIS effects) is stated to be effective for adults
or children over the age of 4. However,
Parasitological. The most important method Clonorchis is not nearly as sensitive to the
of diagnosis is examination of the faeces paralytic action of the drug as are the
for eggs (p. 254). When eggs are scanty, schistosomes.
concentration methods (Kato–Katz or sedi-
EPIDEMIOLOGY
mentation techniques) can be used or a
duodenal aspirate taken. In symptomless Infection is widespread in some endemic
infections large numbers of eggs are usu- areas: 40% in adults in the Red River
delta region of North Korea, 24% in some
ally produced. Any eggs found need to be
villages of the Amur River area of Siberia,
distinguished from those of Heterophyes,
23% in Hong Kong, 15% in Guangdong
Metagonimus, Metorchis or rarely
(China).
Dicrocoelium, which are similar.
Infection is usually contracted from eat-
ing raw or undercooked fish and fish dishes
Immunodiagnosis. Intradermal and comple- (usually cyprinids, such as Carassius caras-
ment fixation tests have been in use for sius, Cyprio carpus and Pseudorasbora
many years but remain positive for many parva, but about 110 species have been
years after cure and they also cross-react incriminated (see WHO, 1995)). However,
with Paragonimus and Schistosoma. the metacercarial cysts are very sticky and
An ELISA using a purified recombinant can stick to the hands and to knives and
antigen of adult worms (mol. weight 28 boards, which are subsequently used for
kDa) looks promising (Yong et al., 1998), as chopping salad vegetables, so that the para-
does application of a dot-immunogold– site can sometimes be transmitted even
silver stain (Liu et al., 1995). when fishes are cooked before eating.
 The Trematodes 43

In South Fukien province in China, fish about 30% of dogs are infected and these
is not commonly eaten raw, but decoctions are almost entirely responsible for perpetu-
of raw crushed fish are used as a cure for ating infection.
asthma and freshwater shrimps (which can
act as a secondary intermediate host in this
area) are eaten as a cure for nosebleeds.
Opisthorchis viverrini
Human cases in this province are mostly in
(Poirer, 1886) Stiles and Hassall, 1896
children; the parasite being maintained in
dogs. In South Korea, infection formerly
occurred in men, who traditionally eat raw
SYNONYM
fish to increase their thirst at rice wine
Distoma viverrini Poirer, 1886. The name
drinking parties.
should more correctly have been O.
In rural areas of China, human faeces
viverrinae.
(‘night-soil’) was commonly used to enrich
ponds containing food fish and, as these
DISEASE AND LOCAL NAME
ponds also often contain suitable snails,
Opisthorchiasis or opisthorchiosis viverrini;
maximum opportunities for continuation
Pa-yard bai-mai nai tub (Thai).
of the life cycle were provided (Plate 5).
Nowadays, however, untreated faeces are
GEOGRAPHICAL DISTRIBUTION
not commonly used in mainland China.
Thailand, Cambodia and Laos, with about
There is a recent tendency in many peo-
9 million cases (and 50 million at risk), of
ple in Europe and North America to eat
which 7.3 million are in Thailand (see Map
more raw and lightly cooked fish and there
4, p. 39).
is a danger of cases of food-borne
helminths increasing in tourists and from
LOCATION IN HOST
imported foodstuffs.
Adults inhabit the bile-ducts.
CONTROL AND PREVENTION
The most obvious method of prevention is MORPHOLOGY
thorough cooking of fish, but this is not The adults are very similar to those of C.
always feasible as raw fish is a traditional sinensis but the testes are lobed rather than
item of diet in endemic regions. Deep- dendritic, and there are differences in the
freezing of fish at 30°C for 32 h is recom- flame-cell pattern.
mended for killing cysts.
Control is possible by sanitary disposal LIFE CYCLE
of faeces to prevent eggs reaching ponds or Very similar to that of C. sinensis. Snails
slow-flowing streams and canals. Even involved in Thailand are subspecies of
storage of faeces for a few days or addition Bithynia siamensis, with 15 species of fish
of ammonium salts as fertilizer before belonging to seven genera acting as second
adding to ponds is an effective measure. intermediate hosts (WHO, 1995), such as
The use of molluscicides is difficult Puntius orphoides (‘pla pok’ in Thai) and
because of toxicity to fish. Hampala dispar (‘pla suud’), which are
National campaigns should follow the eaten either raw (‘koi pla’) or semi-
same guidelines as for Paragonimus and other fermented (‘pla ra’).
food-borne trematodes (see WHO, 1995).
CLINICAL MANIFESTATIONS AND PATHOGENESIS
ZOONOTIC ASPECTS The majority of infected individuals (about
Dogs are the most important reservoir hosts 80%) show no symptoms or signs attribut-
but infections occur in most fish-eating able to the parasite apart from eosinophilia
carnivores. Pigs and rats can also be and there are likely to be less than 1000 eggs
naturally infected. g1 faeces. Although there may be local
In the South Fukien province of China, damage to the bile-duct epithelium, there is
44 Chapter 1

no noticeable damage to liver function. With ponds dry in March. Infection is very uncom-
heavier infections (10,000–30,000 eggs g1 mon in children under the age of 5.
faeces), diarrhoea, epigastric and upper The metacercarial cysts are slightly less
right-quadrant pain, anorexia, lassitude, resistant to pickling than those of C. sinen-
jaundice and mild fever may slowly sis, but thorough cooking or deep-freezing
develop. In long-standing infections there of fish is the only sure method of personal
may be oedema of the legs, accompanied by prevention.
ascites, mild periportal fibrosis, hepato-
megaly, inflammation and biliary epithe- ZOONOTIC ASPECTS
lium hyperplasia. O. viverrini is a natural parasite of the civet
In heavy infections the gall-bladder cat but is common in domestic cats and
becomes enlarged and non-functional, with dogs, which play a role in maintaining
cholecystitis, cholangitis, liver abscess and transmission, although human-to-human
gallstones. Cholangiocarcinoma is strongly transmission is common.
correlated with O. viverrini infection (Plate
6) and few patients live longer than 6
months after diagnosis (Elkins et al., 1990; Opisthorchis felineus
IARC Working Group, 1994). (Rivolta, 1884) Blanchard, 1895
The immunology of liver-fluke infec-
tions is discussed on p. 41.
SYNONYMS
DIAGNOSIS AND TREATMENT Distoma felineum Rivolta, 1884; D. sibir-
Diagnosis is by finding eggs in the faeces. icum Winogradoff, 1892 (first report from
They are similar to those of C. sinensis but humans).
are slightly narrower (30 µm
12 µm) and
more regularly ovoid, without such a clear DISEASE AND POPULAR NAME
shoulder at the operculum (Fig. 123). The Opisthorchiasis or opisthorchiosis felineus;
eggs of an intestinal fluke, Phaneropsolus cat liver-fluke disease.
bonnei (see p. 59), which has been reported
from humans in north-east Thailand, are GEOGRAPHICAL DISTRIBUTION
similar in size but are smoothly ovoid and About 1.5 million cases (with 14 million at
contain an undifferentiated ovum when risk): Russia (Siberia with 1.2 million
passed in the faeces. cases), Belarus, Kazakhstan, Ukraine (0.3
Immunodiagnosis is not widely used million) (see Map 3, p. 33).
but a mAb ELISA using mAbs that can
detect an 89 kDa metabolic antigen from O. LOCATION IN HOST
viverrini in faeces is stated to be both sensi- Adults are found in the distal bile-ducts
tive and specific (Sirisinha et al., 1995). and sometimes proximal ducts also.
Praziquantel can be given as for
Clonorchis and is equally effective. MORPHOLOGY
Adults are identical to those of O. viverrini.
EPIDEMIOLOGY Differentiation is based on differences in
There are prevalence rates of over 70% in the flame-cell patterns of the cercariae and
ethnically similar rural communities of in the life cycle.
north-eastern Thailand (35% overall) and
Laos, and it has been estimated that infection LIFE CYCLE
costs $120 million annually in lost wages Very similar to the previous two species.
and medical care. Infection in humans occurs The snail intermediate hosts are species of
principally at the end of the rainy season and Codiella (= Bithynia), particularly C.
the beginning of the dry season (September leachi. Twenty-two species of fish belong-
to February), as fish contain more metacer- ing to 17 genera transmit infection (see
cariae and are more easily caught before WHO, 1995).
 The Trematodes 45

CLINICAL MANIFESTATIONS latter species was responsible for infection

Similar to the other two species, except in 19 people in Canada who ate sashimi in
that symptoms are more likely to occur in a restaurant. They suffered from upper
the acute phase (2–4 weeks after infection), abdominal pain, low-grade fever and
such as high fever, abdominal pain and eosinophilia, lasting for up to 4 weeks;
hepatitis-like symptoms, accompanied by praziquantel was very effective in treat-
eosinophilia (possibly because more infec- ment (MacLean et al., 1996).
tions are in adult immigrants).
Pseudamphistomum truncatum (Rudolphi,
The connection with cholangiocarcinoma
1819), Luhe, 1909 is a liver parasite of wild
is not as clear as with O. viverrini or C.
carnivores, cats and dogs and has occasion-
sinensis (IARC Working Group, 1994),
ally been found in humans in Russia
although the ratio of hepatic cell carcinoma
(Siberia) from eating raw fish. P. aethiopicum
to bile-duct carcinoma in uninfected indi-
Pierantoni, 1942, was reported once from a
viduals from an endemic area of Siberia was
human in Ethiopia.
found to be 8:1, while in infected people the
ratio was reversed. In a fatal case in Russia, a
total of 7400 worms were recovered.
Family Dicrocoeliidae
DIAGNOSIS AND TREATMENT
Eggs, which are identical to those of O. Dicrocoelium dendriticum
viverrini, can be recognized in the faeces. (Rudolphi, 1818) Looss, 1899
They are likely to be scanty in clinically
important infections and concentration SYNONYMS
techniques may be necessary. Immuno- Fasciola lanceolata, F. dendritica, D. lance-
diagnostic tests are being investigated. olatum.
Treatment as for C. sinensis.
DISEASE AND POPULAR NAME
EPIDEMIOLOGY Dicrocoeliasis or dicrocoeliosis; lancet-
In the central area of western Siberia there fluke infection.
are prevalence rates of 40–95% and the
highest infection rates in Russia in general GEOGRAPHICAL DISTRIBUTION
are found in river basin areas. In endemic Dicrocoelium is a cosmopolitan parasite of
areas of Ukraine rates vary from 5% to the bile-ducts of sheep and other herbi-
40%. There may be very heavy infections vores. True human infections are rare, but
of metacercariae in food fish. spurious infections from ingestion of eggs
A popular raw fish dish, ‘stroganina’, is in liver are not uncommon. Real or spuri-
responsible for many infections. ous infection was found in 0.2% of about
27,000 patients in a hospital in Riyadh,
ZOONOTIC ASPECTS Saudi Arabia, and in 0.2% of a rural popu-
Cats provide an important reservoir host lation in Turkey, and occasional human
and may have high infection rates. Infection cases are reported worldwide.
in a range of animals, such as foxes, dogs,
cats and pigs, is found over a wide area of LOCATION IN HOST
eastern Europe. O. guayaquilensis is a para- Adults live in the bile-ducts.
site of cats and dogs with a human focus in
an area of Ecuador and O. noverca is a com- MORPHOLOGY
mon parasite of pigs and dogs with two Adult worms are flat and lancet-shaped,
human cases in India. measuring 5–15 mm
1.5–2.5 mm. The
Metorchis albidus (Braun, 1893) Looss, testes are in tandem just behind the ventral
1899, and M. conjunctus (Cobbold, 1864) sucker. The vitellaria are restricted and the
Looss, 1899, are two liver flukes found in uterus takes up most of the posterior part
North American fish-eating carnivores. The of the body.
46 Chapter 1

LIFE CYCLE DISEASE AND POPULAR NAMES

This is of great interest zoologically, as Fascioliasis or fasciolosis, distomiasis;
Dicrocoelium is one of the few trematodes liver-fluke infection, liver-rot (in sheep).
that utilize terrestrial snails as intermediate
hosts (Zebrina or Helicella in Germany). GEOGRAPHICAL DISTRIBUTION
The snail ingests the eggs containing About 2.4 million human cases in 61 coun-
miracidia and eventually the cercariae tries worldwide (with 180 million at risk).
leave the snail in slime balls, each contain- Fasciola is primarily an animal parasite of
ing 200–400 cercariae. These are then great veterinary importance and is found in
ingested by ants, and the ants infected with sheep and cattle kept on damp and muddy
metacercariae are eaten by sheep (or rarely pastures in all the sheep- and cattle-raising
humans) on vegetation. Dicrocoelium was areas of the world. Human infections have
present in the livers of 37 autopsy cases in been reported most frequently from
Uzbekistan and infected ants were found on Bolivia, Cuba, Ecuador, Egypt, France, Iran,
local mulberry trees (Azizova et al., 1988). Peru, Portugal and North Africa and are
much more common than previously
CLINICAL MANIFESTATIONS AND PATHOGENESIS thought.
In the few proven cases detected in life,
symptoms have been of mild hepatitis. LOCATION IN HOST
Pathology in animals is similar to that of Adult worms inhabit the bile-ducts.
Fasciola but less severe.
MORPHOLOGY
DIAGNOSIS AND TREATMENT The hermaphroditic adult flukes measure
Characteristic eggs, measuring 38–45 µm
20–30 mm
13 mm wide (specimens are
22–30 µm, may be found in the faeces (Fig. usually smaller in heavy infections) and
124). It is essential that patients are kept on are flat and leaflike, with a spiny tegument
a liver-free diet for a few days in order to (Plate 7).
rule out spurious infections. Treatment of The oral sucker measures 1.0 mm in
one case with triclabendazole was not diameter and the ventral sucker, which lies
successful. close behind it, about 1.6 mm. The male
and female reproductive systems are both
Dicrocoelium hospes Looss, 1907, is found very dendritic, as in Fasciolopsis buski, but
in domesticated and wild herbivores in in Fasciola the two gut caeca are also
Africa and human cases have been highly branched.
reported from Ethiopia, Ghana, Kenya, The dendritic testes lie one behind the
Mali and Sierra Leone. other in the middle portion of the body.
Eurytrema pancreaticum (Janson, 1889) The small, highly branched, ovary is in
Looss, 1907, is a parasite of the pancreatic front of the anterior testis. The dendritic
ducts of domestic herbivores in Asia and vitellaria lie in the lateral fields and have
South America. Grasshoppers act as second vitelline ducts leading to the ootype. The
intermediate hosts. Three cases have been uterus, filled with eggs, is confined to the
reported from humans (Ishii et al., 1983), anterior third of the body.
with worms in the dilated pancreatic ducts.
LIFE CYCLE
In sheep the eggs are laid in the biliary
tracts, reach the intestine and are passed out
Family Fasciolidae in the faeces. The undifferentiated ovum
develops into a miracidium under moist
Fasciola hepatica Linnaeus, 1758 conditions in 9–15 days at 22–25°C. The
miracidium that hatches out of the egg lives
SYNONYM for only about 8 h and can move in a film of
Distomum hepaticum L., 1758. moisture on damp pastures. For further
 The Trematodes 47

development the free-living miracidium in the wall of the peritoneal cavity, and
must penetrate an amphibious snail, usually cause granulomas.
a species of Lymnaea (mainly L. truncatula The parasite is responsible for few
in Europe, L. tomentosa in north-west deaths but in one case 40 flukes were found
Africa and L. viatrix in South America). to be blocking the bile-ducts at autopsy.
Once inside the snail, there is a sporo-
cyst, followed by two redia stages; the cer- PATHOGENESIS
cariae, which emerge 30–40 days after Most of the knowledge on pathology is
penetration at 24°C, encyst as metacercariae based on studies in animals. In sheep, the
on vegetation (Fig. 23). This is usually wet tracts of the migrating flukes show a coagu-
grass, but watercress, water mint (in Iran) or lation necrosis of the liver cords, with
other salad vegetables are of most impor- numerous neutrophils, lymphocytes and
tance in human infections (or perhaps erythrocytes. The traumatic damage caused
sometimes in drinking water). When cysts is roughly proportional to the number of
are ingested, the larvae excyst in the duode- parasites present and, in sheep, death is
num, migrate through the intestinal wall usually caused by the presence of over 600
and reach the bile-ducts by eating their way worms. The mature flukes in the bile-ducts
through the hepatic parenchyma from the cause a secondary adenomatous hyper-
surface of the liver. The adult worms mature plasia and desquamation of the lining
in 3–4 months and live for 5–12 years. epithelium of the bile-ducts (which
becomes over 2.0 mm thick) with exagger-
CLINICAL MANIFESTATIONS ated Aschoff–Rokitansky crypts. The
There is an acute phase corresponding to plasma cells, lymphocytes and eosinophils
the period when the young flukes are in the periductal tissues are replaced by a
migrating through the liver tissues (4–8 fibrotic reaction leading to great thickening
weeks). Symptoms of dyspepsia, nausea of the walls and a much reduced lumen
and vomiting, abdominal pain localized to (Plate 7). Bile-duct hyperplasia and fibrosis
the right hypochondrium or epigastrium of portal tracts has been seen in biopsy
and high fever (up to 40°C) ensue, often specimens in human infections.
with sudden onset. Allergic symptoms, The immunology of liver-fluke infec-
such as pruritus and urticaria, can also tions in general is discussed on p. 41.
occur. Anaemia is found in a proportion of
cases and the erythrocyte sedimentation
rate is often raised. There is a leucocytosis
in 50–100% of cases, with high
eosinophilia (up to 60%).
The chronic phase ensues when the
flukes reach the bile-ducts. There is often
painful liver enlargement and occasionally
an obstructive jaundice develops later;
there may also be pains in the lower chest,
with loss of weight. Symptoms are due to
inflammation of the epithelial lining of the
duct or to obstruction of its lumen and they
closely resemble those of biliary disease,
with obstructive jaundice and centrilobular
cholestasis. Cholelithiasis can also occur as
a complication. Many chronic cases are
probably asymptomatic and undiagnosed,
so the proportion of such cases is
unknown. Sometimes parasites in humans Fig. 23. Metacercariae of Fasciola hepatica on
develop in ectopic sites in other organs or blades of grass (actual size 0.3 mm).
48 Chapter 1

DIAGNOSIS this for a child) and this is still used.

Recently triclabendazole at 10 mg kg1 for
Clinical. Clinical signs are often variable but 1 or 2 days has given cure rates of 80–90%
a triad of fever, liver enlargement and high and is now the drug of choice.
eosinophilia is very suggestive, particularly
if combined with a history of having eaten EPIDEMIOLOGY AND ZOONOTIC ASPECTS
home-grown watercress a few weeks There are occasional human cases reported
before. from many countries (61 in total) following
CT and ultrasound can be of use in visu- ingestion of infected watercress or lettuce
alizing worms in the bile-ducts. and epidemics may occur locally in partic-
ularly wet years (e.g. in France a total of
Parasitological. Eggs in the faeces are often 10,000 cases were recorded between 1956
scanty and duodenal or bile-duct aspirates and 1982, principally in two wet and warm
can be used. Eggs are large, measuring periods). Infection is spreading in many
130–150 µm
60–85 µm, and ovoid, with parts of the world and it is clear that there
an inconspicuous operculum (Fig. 123). are some human endemic regions where
Faeces concentration techniques can be
human-to-human transmission takes place
employed, but in about 30% of human
(Mas Coma et al., 1999). In the Andean alti-
cases no eggs can be found in faeces or
plano areas of Bolivia there are prevalences
bile. Spurious infections from ingestion of
of 15–100% and in children in central Peru
infected liver can be ruled out by keeping
of 10–34% and probably many cases also
the patient on a liver-free diet for a week.
at high altitudes in Ecuador. There are also
much higher infection rates in the Nile
Immunological. An intradermal test has
delta, in the Tadzhik Republic (Samarkand)
been used for many years but is not very
and in the Caspian region of Iran than pre-
specific and only becomes positive after a
viously thought. In these areas of high
few weeks. Passive haemagglutination is
another test that is well established. In the intensity, infections are more common in
last few years there have been many stud- children (Dalton, 1998).
ies utilizing ELISAs. For instance an IgG4 Infection occurs in up to 50% of sheep
ELISA, using either recombinant or native and 70% of cattle in many parts of the
protein (cathepsin L1 cysteine proteinase) world and is a major veterinary problem in
as antigen, gives very sensitive results with many countries, but flukes may also be
finger-prick blood (O’Neill et al., 1999). An found in goats, donkeys, pigs, camels,
antigen-detection test using sandwich horses, rabbits and deer.
ELISA detected infection by 1 week, with The eggs of Fasciola do not usually
an optimum at 3 weeks. Western develop below 10°C (or over 30°C) and in
immunoblots are useful for confirmation of many temperate countries they rest over
infection. Tests for detection of Fasciola the winter on pastures, the miracidia
coproantigens also show great promise. hatching out in the spring. However, eggs
These recent immunological tests can be can develop at lower temperatures in the
used for detecting early infections and also high Andes foci. Studies of the tempera-
for assessing the success of a cure. ture, of developmental factors in the inter-
mediate and definitive hosts and of rainfall
TREATMENT have enabled accurate forecasts of the
Praziquantel, which has been so effective likely build-up of infection in domestic
against almost all other trematode infec- stock in countries in Europe (Fig. 24).
tions, has little effect in fascioliasis. The
standard treatment for many years was PREVENTION AND CONTROL
with bithionol (30–50 mg kg1 given orally In commercial watercress beds there must
on alternate days for 10–15 days or as a be precautions to prevent pollution by
single dose of 45 g for an adult and half faeces of domestic stock.
 The Trematodes 49

A vaccine for infections in cattle and Lymnaea truncatula acts as first intermedi-
sheep is being investigated (Dalton, 1998). ate host for all three species.
Fasciola gigantica Cobbold, 1856, is a
common parasite of cattle, camels and
Fasciolopsis buski
other herbivores in Africa, in Asia and on
(Lankester, 1857) Odhner, 1902
some Pacific islands. The eggs are larger
than those of F. hepatica (160–190 µm

SYNONYMS
70–90 µm) and the adults are longer
Distoma buski Lankester, 1857, Distoma
(25–75 mm
12 mm), with more anterior
crassum Busk, 1859.
testes, a larger ventral sucker and not so
pronounced ‘shoulders’. Sporadic cases
DISEASE, POPULAR AND LOCAL NAMES
have been reported from humans in tropi-
Fasciolopsiasis or fasciolopsiosis; Busk’s
cal Africa, China, Egypt, Hawaii, Iran,
fluke infection; Pa-yard bai-mai nai lumsi
Thailand, Turkey and Uzbekistan. The life
(Thai).
cycle and clinical effects are similar to
those of F. hepatica except that the snail
GEOGRAPHICAL DISTRIBUTION
hosts, such as Lymnaea natalensis in
The largest endemic foci of infection are in
Africa, are often aquatic, not amphibious.
the Yangtze basin provinces of China but
Immunodiagnostic tests, such as SDS-
infection also occurs in Bangladesh,
PAGE using an ES antigen of 27 kDa or a
Cambodia, India (particularly Assam, but
somatic antigen of 38 kDa, or IgM or IgG
also in Bihar, Madras and Orissa), Indonesia,
ELISA, appear to be as effective as for F.
Laos, Taiwan and central Thailand.
hepatica and do not cross-react with schisto-
somiasis.
LOCATION IN HOST
Fasciola indica Varma, 1953, is found in Adult flukes are found in the small intes-
buffaloes and other herbivorous mammals tine, attached by the ventral sucker. In
in Asia, with a very few human cases heavy infections they may also be present
reported from India and Korea. In Russia in the stomach and colon.

Fig. 24. Effect of weather on the life cycle of F. hepatica in western Europe.
50 Chapter 1

MORPHOLOGY When ingested on edible plants, the

Fasciolopsis is the largest human trema- metacercariae excyst in the duodenum and
tode, measuring on average 30 (20–70) mm the young flukes take 3–4 months to

12 (8–20) mm (Fig. 3). It is a thick, mature in the ileum. The adult worms can
ovoid worm without a cephalic cone and, produce up to 28,000 eggs 24 h1 but live
when living, is pinkish in colour. The for only about 6–12 months in humans.
tegument is covered with transverse rows
of small spines, which are most numerous CLINICAL MANIFESTATIONS
around the ventral sucker. The ventral In the majority of cases infection is light
sucker is a short distance behind the oral (fewer than 20 worms or 5000 eggs g1
sucker and is about four times as large. faeces) and there are no symptoms. With a
The testes are highly branched and lie one heavy worm burden there is nausea and
behind the other in the posterior part of diarrhoea, accompanied by intense griping
the body. The organs of the female repro- pains in the morning which are relieved by
ductive system are also branched, as is food. Oedema, including a characteristic
typical of members of the family facial swelling more prominent in the peri-
Fasciolidae but, unlike the liver fluke orbital region, is often found. In children
Fasciola, the two gut caeca are with more than 100 worms the abdomen is
unbranched. The egg is large, 130–140 µm usually distended and there may be stunt-

80–85 µm (Fig. 123); the yellowish- ing of growth. The presence of more than
brown shell is clear and thick and has a 400 worms usually proves fatal to young
small operculum. The egg is unembry- children.
onated when laid and is almost identical In about 40% of cases there is an
to that of Fasciola hepatica; they can eosinophilia of up to 30%.
sometimes be differentiated with difficulty
when living by the distribution of the lipid PATHOGENESIS
granules in the yolk cells, which are uni- The adult worms cause traumatic inflam-
formly arranged in Fasciolopsis and con- matory damage to the mucosa at the site of
centrated around the nucleus in Fasciola, attachment, often leading to ulceration and
by differences in the number of yolk cells haemorrhage, and make the mucosa hyper-
and by the size of the germinal area. Daily aemic. They also provoke an excessive
egg production is about 25,000 per fluke. secretion of mucus. Toxic by-products pro-
duced by the adults are said to cause the
LIFE CYCLE facial oedema that is sometimes found and
Eggs passed in the faeces need to reach can result in a toxic diarrhoea, but this may
water for further development and they be due to a protein-losing enteropathy.
take 3–7 weeks at 27–32°C to embryonate When many worms are present, there is
fully (they can survive for 3–4 months at also the possibility of obstruction of the
4°C but do not develop). The miracidium bowel, with resultant stasis.
that hatches out enters a freshwater plan-
orbid snail, such as Gyraulis chinensis, DIAGNOSIS
Hippeutis cantori or Polypylis (= Recovery of eggs in faeces is the only
Segmentina) hemisphaerula, in which a method used in practice and various con-
sporocyst and two redial stages are found. centration methods can be employed if nec-
The xiphidocercous cercariae, which essary. The eggs can be easily differentiated
emerge from the second-generation rediae, from those of Gastrodiscoides and are larger
leave the snail and swim in the water. They than those of echinostomes but cannot usu-
encyst on the roots or fruits of various ally be distinguished from those of Fasciola.
freshwater plants, such as the water caltrop
(Trapa bicornis and T. natans) or water TREATMENT
chestnut (Eliocharis tuberosa), to give an Praziquantel (15–60 mg kg1) and albend-
encysted metacercarial stage. azole have both been used successfully,
 The Trematodes 51

although the latter had some failures with Night-soil, as once commonly used in
children. China, should be stored before being added
as fertilizer to submerged fields. Sanitary
EPIDEMIOLOGY disposal of faeces would probably be effec-
There are often high prevalence rates in tive, although there is still the possibility
endemic areas: 39% in Dacca, Bangladesh, of zoonotic infections. Molluscicides could
70% in Jiangxi, China, 70% in Maharashtra possibly be used for snail control but their
and 29% in Bombay, India, 27% in South efficacy has not been tested.
Kalimantan, Indonesia (57% in children),
3.8% in Vientiane, Laos, and 17% in ZOONOTIC ASPECTS
Supanburi, Thailand (Yu and Mott, 1994). Pigs act as important reservoir hosts. The
The seed pods of water caltrop (also endemic region in central Thailand is a
known as water ling) are probably the most perennial flood basin where rice is grown
important source of human infection, and houses are built on stilts. Pigs are also
because this plant is grown in ponds fertil- kept in pens on stilts and fed on water
ized with night-soil, while the other plants plants; the faeces of the pigs passes into the
involved are usually grown in running water below, in which snails live and food
streams. Before the nuts of the water cal- plants are grown.
trop or the bulbs of water chestnut are There are high prevalence rates in pigs
eaten, the outer covering is removed with in areas of Bangladesh, Burma (Myanmar),
the teeth and this provides the principal Cambodia and India but few human infec-
mode of infection. This habit is particu- tions, as the appropriate plants are not
larly common in children, who are usually eaten raw.
more heavily infected than adults. In
markets caltrop nuts are kept fresh by
sprinkling with water and thus the cysts Family Heterophyidae
are prevented from drying.
In Vietnam the roots of the water bam-
Heterophyes heterophyes
boo (Zizania aquatica, Salvinia natans and
(von Siebold, 1852) Stiles and Hassall, 1900
Lemna polyrhiza) and water hyacinth
(Eichornia crassipes) are also eaten, and in
Thailand lotus (Nymphoea lotus), a water-
SYNONYMS
cress (Neptunia cleracea) and water morn-
Distoma heterophyes von Siebold, 1852;
ing glory (Ipomea aquatica).
Heterophyes aegyptiaca Cobbold, 1866;
In Taiwan and Thailand water plants are
Heterophyes nocens Onji and Nishio, 1915.
collected and fed to pigs, which helps to
maintain a reservoir of infection. In
Thailand infection is confined to regions DISEASE AND POPULAR NAMES
growing water caltrops although the nuts Heterophyiasis, heterophyosis; von Siebold’s
are grown in many other non-endemic fluke infection, dwarf-fluke infection.
areas also; this is probably because cysts
dry up during transport or because the nuts GEOGRAPHICAL DISTRIBUTION
are only eaten cooked in these other Asia (southern China, Japan, Indonesia,
regions. Korea, the Philippines, Taiwan), North
Africa and Middle East (Egypt, Iran, Sudan,
PREVENTION AND CONTROL Tunisia, Turkey) and southern Europe
Water vegetables need to be carefully (Greece and Romania).
peeled and washed. Boiling for 1–2 min is
sufficient to kill the metacercarial cysts. In LOCATION IN HOST
some areas free metacercarial cysts have Adults are attached to the wall of the
been found floating on the water surface jejunum and upper ileum, often in the
and may be ingested in drinking water. crypts of Lieberkühn (Fig. 25).
52 Chapter 1

0.05 mm

Fig. 25. Section of the intestinal mucosa (of cat) with adult Heterophyes attached by the oral sucker. The
ventral sucker and uterus filled with eggs can also be seen.

MORPHOLOGY about 14 large follicles in a limited post-

Heterophyes is a small hermaphroditic erior area of the body.
fluke, measuring 1.0–1.7 mm
0.3–0.7 mm
(Fig. 3). It has an elongate ovoid shape and LIFE CYCLE
is greyish when living. The tegument is The brown eggs are about the same size as
covered by fine scale-like spines, most those of Clonorchis (30 µm
15 µm) and
numerous at the anterior end. The oral have a very slight shoulder to take the
sucker is much smaller (90 µm) than the operculum (Fig. 123) and there may be a
ventral (230 µm), which lies in the middle small knob at the opposite end. The egg
third of the body. A genital sucker (150 µm contains a fully developed miracidium
in diameter), capable of protrusion but not when discharged in the faeces, which
adherence, lies near the left posterior mar- hatches out only when the egg is ingested
gin of the ventral sucker; it bears a number by a suitable water snail (these are of the
of radiating rows of small spines and is operculate type, with a cap on the base of
interrupted at the end part nearest the ven- the foot to close the shell). Important
tral sucker. The alimentary tract consists of species are Pirenella conica in the Nile
a narrow prepharynx, a small bulbous Delta (Fig. 1) and Cerithidea cingulata
pharynx, a narrow oesophagus and two gut microptera in China and Japan.
caeca, which arise towards the middle of Asexual multiplication in the snail con-
the body and extend to the posterior end of sists of a sporocyst and one or two redial
the fluke. The tubular excretory bladder generations before the cercarial stage is
lies in the posterior fifth of the body. reached. The lophocercous cercariae
The two ovoid testes lie side by side, emerge 3–4 weeks after ingestion of the egg
near the posterior end of the body. The and encyst in a folded position under the
male duct has a large seminal vesicle, scales, on the fins, tail and gills and in the
which opens into the genital atrium in the superficial muscles of various freshwater
genital sucker by a muscular ejaculatory fishes. The metacercariae measure about
duct. The rounded ovary is situated in the 160 µm and are infective in 15–21 days.
midline about one-third of the way from Species of fish involved include Mugil
the posterior end of the body and there is a cephalus (brackish water mullet), Aphasia
seminal receptacle and Laurer’s canal. The fasciatus and Tilapia nilotica in Egypt and
closely coiled uterus opens into the genital Greece and Mugil spp. and Acanthogobius
sucker. The vitelline glands consist of spp. in Japan. When the fish is eaten
 The Trematodes 53

uncooked the metacercariae escape and knob. The contained miracidium also has
develop in the small intestine. The flukes bilaterally symmetrical penetration glands
mature in 15–20 days and the adults live (Fig. 123).
for about 2 months.
TREATMENT
CLINICAL MANIFESTATIONS Niclosamide (2 g day1 for 2 days for an
In light infections there are usually no adult) has been used for many years but
symptoms. In heavy infections, nausea and more recently praziquantel (a single dose
intermittent chronic diarrhoea, sometimes of 20 mg kg1) has become the drug of
with the passage of blood and abdominal choice.
discomfort with colicky pains and tender-
ness, have been reported beginning 9 days EPIDEMIOLOGY
after ingestion of cysts. Symptoms resem- Transmission is by eating fresh or salted
ble those of amoebiasis or heartburn and uncooked fish. There may be heavy infec-
there may be vomiting, simulating a peptic tions in both rural and urban communities
ulcer. Slight eosinophilia is sometimes in the Nile Delta region of Egypt, who tra-
found. ditionally eat pickled mullet (‘fessik’) at
the feast of Sham-el Nessim. An infection
PATHOGENESIS rate of 10% has been reported from school-
A mild inflammation of the mucosa at the children in the area. However, most infec-
site of attachment and sometimes a superfi- tions are in 20–40-year-olds, who eat
cial necrosis occur if there are thousands of freshly salted mullet; metacercariae can
worms present; up to 4000 have been live for up to 7 days in these.
reported.
Eggs of many species of heterophyids PREVENTION AND CONTROL
have been found at necropsy from various Personal prevention is by thorough cooking
sites in the body, either because the eggs of fish. Partial cooking (mostly of Tilapia
themselves have succeeded in filtering nilotica) carried out around Lakes Manzala,
through the intestinal wall to the mesen- Borollos and Edco in the Nile Delta
teric lymphatics or venules or because the destroys only about 70% of cysts.
adults have penetrated the gut wall and Preventing pollution of the water with
laid eggs in the peritoneal cavity. This faeces, which in Egypt is mainly by fisher-
phenomenon appears to be a reaction to men, is a possible long-term objective.
humans as abnormal hosts, and emboliza-
tion of the eggs may occur. Cardiac lesions ZOONOTIC ASPECTS
caused by Heterophyes or other members Dogs, cats, foxes and other fish-eating
of the same family include fibrosis sur- mammals act as reservoir hosts and can
rounding eggs in the mitral valve and maintain the infection in the absence of
myocardium, with consequent heart fail- humans.
ure. Eggs have been found in the brain on a
few occasions, as have encapsulated
adults.
Metagonimus yokogawai
DIAGNOSIS Katsurada, 1912
This is by recovery of eggs following sug-
gestive clinical findings, either by direct SYNONYM
faecal smears or by concentration methods. Heterophyes yokogawai Katsurada, 1912.
The eggs can be differentiated from those
of opisthorchids by the less well-developed DISEASE AND POPULAR NAME
shoulders at the operculum giving a more Metagonimiasis or metagonimosis;
oval outline and by the smaller posterior Yokogawa’s fluke infection.
54 Chapter 1

GEOGRAPHICAL DISTRIBUTION Pathological changes are characterized

This is probably the most common human by villous atrophy and hyperplasia of the
intestinal fluke in the Far East and is crypts, with inflammatory cell infiltration.
endemic in China, Indonesia, southern Eggs may be carried by intestinal capillar-
Japan, Korea, Manchuria, Taiwan and ies and lymphatics to the myocardium,
Siberia. It has also been reported from brain, spinal cord and other tissues, where
Israel, Serbia and Spain. granulomatous changes or embolisms can
be provoked by their presence.
LOCATION IN HOST
Adults are found in the upper and middle DIAGNOSIS AND TREATMENT
parts of the jejunum, rarely in the duode- As for Heterophyes. The eggs can, with dif-
num, ileum and caecum. The flukes are ficulty, be differentiated from those of
embedded in the crypts of Lieberkühn in Heterophyes, as the latter have a thinner
the early stages or in the mucus found on shell and are light brown in colour.
the surface.
EPIDEMIOLOGY
MORPHOLOGY Since the eggs of this species are so similar
This genus is closely related to to those of many other parasites in this fam-
Heterophyes, the adults being similar in ily that can infect humans, it is difficult to
size and structure. The principal differ- know the true prevalence. In ethnic minori-
ences are that in Metagonimus the ventral ties in Khabarovsk Territory of Siberia,
sucker is situated to the right of the midline there are high rates of 20–70% and, in
and there is no accessory sucker (Fig. 3). endemic areas of coastal Korea, there
appear to be 10–20% of villagers infected.
LIFE CYCLE
In Japan the cercariae do not emerge
The eggs measure 27 µm
16 µm and are from the snail intermediate hosts below
very similar to those of Heterophyes (Fig. 18–20°C and infection does not occur in
123). The life cycle is also similar. In areas where summer temperatures are
China, Japan and Korea the snail species below this figure.
involved is Semisulcospira libertina. The
ZOONOTIC ASPECTS
second intermediate fish hosts are
Plecoglossus altivelis (a trout, the ‘ayu’ or Dogs, cats, rats and pigs (and perhaps peli-
sweetfish), Leuciscus hakuensis, Mugil cans and other fish-eating birds) act as
cephalus, Odontobutis obscurus and Salmo reservoir hosts and infection in animals is
perryi in Japan and Siberia and also common worldwide. Potentially all species
Pseudorasbora parva and Carrasius carra- of the family Heterophyidae could become
sius (silver carp) in Korea. Each adult fluke human intestinal parasites where raw fish
produces about 1500 eggs 24 h1. is eaten and it is likely that many others
will be recorded as occasional human para-
CLINICAL MANIFESTATIONS AND PATHOGENESIS sites (particularly in the Far East) when
Similar to Heterophyes, with abdominal expelled adult worms are examined. The
pain, diarrhoea and lethargy. A heavy following species have been recorded from
infection in Japan caused intractable diar- humans and, in some, eggs or occasionally
rhoea and weight loss and from the faecal adults have been found in the heart, brain
egg count it was estimated that or spinal cord: Apophallus donicus (east-
50,000–70,000 adult worms were present ern Europe, Canada and USA),
(63,587 have been recovered from one Centrocestus armatus (Korea), C. caninus
patient who had only slight symptoms (Taiwan), C. cuspidatus (Egypt and
(Chai and Lee, 1990)). Headache, abdomi- Taiwan), C. formosanus (China and Japan),
nal and muscular pains, fever and urticaria C. kurokawai (Japan), C. longus (Taiwan),
have also been reported. Cryptocotyle lingua (Greenland),
 The Trematodes 55

Diorchitrema amplicaecale (Taiwan), D. MORPHOLOGY

formosanum (Taiwan), D. pseudocirratum Gastrodiscoides is the only human-para-
(Hawaii and Philippines), Haplorchis sitic member of the paramphistomes,
microrchis (Japan), H. pleurolophocerca which are important parasites of domestic
(Egypt), H. pumilio (Egypt, Iran and Far herbivores. It is a dorsally convex fluke
East), H. taichui (Bangladesh, Egypt, Iran measuring 5–8 mm
3–5 mm and, when
and Far East), H. vanissimus (Philippines) living, is reddish in colour. The body is
and H. yokogawai (Far East and Egypt), disc-shaped with an anterior conical pro-
Heterophyes dispar (Korea and Thailand), jection bearing the oral sucker (Fig. 3). Like
H. equalis (Egypt), H. heterophyes nocens all other members of the family, the ventral
(Korea and Japan), H. katsuradai (Japan), sucker is close to the posterior end. The
Heterophyopsis continua (Far East), tegument is smooth. The alimentary tract
Metagonimus minutis (China and Taiwan), consists of a pair of lateral pouches arising
M. takahashi (Japan and Korea), Phagicola from the oral sucker and a slightly tortuous
longa (Brazil and Mexico), P. ornamenta, P. pharyngeal tube, which bifurcates into two
ornata and Pharyngostomum flapi (Egypt), gut caeca that extend only to the middle of
Procerovum calderoni (China, Philippines the discoid region. The large excretory
and Egypt), P. varium (Japan), Pygidiopsis bladder is in the midline behind the ven-
summa (Japan and Korea), Stellantchasmus tral sucker. The two lobate testes lie in tan-
amplicaecalis (Egypt), S. falcatus (Korea, dem just behind the bifurcation of the
Laos, Thailand and Hawaii), Stictodora fus- caeca. The common genital opening is on a
cata and S. manilensis (Korea). See Coombs cone just anterior to the bifurcation. The
and Crompton (1991), Yu and Mott (1994), ovoid ovary lies just posterior to the testes
WHO (1995), Ashford and Crewe (1998) near the midline. The vitelline glands are
and Muller (2001), and for details of inter- scattered and surround the caeca behind
mediate hosts, rarity and original refer- the testes. The loosely coiled uterus opens
ences. on the genital cone.

LIFE CYCLE
Family Paramphistomidae The eggs measure 146 (127–160) µm
66
(62–75) µm. They are rhomboidal in shape,
Gastrodiscoides hominis have a small well-fitting operculum and are
(Lewis and McConnell, 1876) Leiper, 1913. transparently greenish in colour (Fig. 123).
They contain about 24 vitelline cells and a
central unembryonated ovum. After the
SYNONYMS AND DISEASE eggs are expelled in the faeces and reach
Gastrodiscoidiasis or gastrodiscoidosis; water, a miracidium develops in 9–14 days
Amphistomum hominis Lewis and at 24°C. The miracidium that emerges from
McConnell, 1876, Gastrodiscus hominis the egg can develop experimentally in the
Fischoeder, 1902. snail Helicorbis coenosus found in Uttar
Pradesh and cercariae emerge 28–152 days
GEOGRAPHICAL DISTRIBUTION after infection. The cercariae form meta-
Infection is most common in India, particu- cercarial cysts on water plants; probably
larly Assam, Bihar and Orissa, but also the water caltrop is involved in human
occurs in Burma (Myanmar), China, infection but the life cycle has not been
Kazakhstan, the Philippines, Thailand and elucidated in nature.
Vietnam.
ZOONOTIC ASPECTS
LOCATION IN HOST Pigs, monkeys (rhesus), apes (orang-utan),
Adults attach to the wall of the caecum and field rats and the Napu mouse deer are
ascending colon by their suckers. natural hosts, but it is not known what the
56 Chapter 1

relationship is between human and animal occasional cases have been reported since
hosts. from China (Yunnan), Indonesia, the
Philippines (11–44% in northern Luzon),
Watsonius watsoni (Conyngham, 1904)
Thailand (8.2% in one area) and recently
Stiles and Goldberg, 1910 (synonym
India (Grover et al., 1998).
Amphistomum watsoni, Conyngham,
1904), has been reported once from north-
LOCATION IN HOST
ern Nigeria in a patient who died of severe
Adults live in the jejunum; they attach by
diarrhoea. Many worms were seen in the
insertion of the oral end into the mucosa.
stools and after autopsy many more were
found attached to the wall of the duode-
LIFE CYCLE
num and jejunum and a few in the colon.
This is a natural parasite of dogs and cats,
Presumably infection was contracted from
and eggs (measuring 100 µm
65–70 µm)
ingestion of metacercarial cysts on vegeta-
in the faeces are undifferentiated. If they
tion. Watsonius is a natural parasite of
reach water, the contained miracidia
monkeys in West Africa and Singapore.
develop in about 8–14 days at 26°C. They
Fischoederius elongatus (Poirer, 1883) emerge and penetrate into suitable fresh-
Stiles and Goldberger, 1910, is a parasite of water snails (particularly Hippeutis) and
ruminants in Asia, contracted from ingest- multiply asexually. Cercariae that emerge
ing cysts on vegetation. Human infection then enter a wide range of other snails
has been reported from China. (such as Pila) and encyst as metacercariae.
When these snails are eaten raw by dogs,
cats or humans, they excyst and develop
into adult worms. Other echinostomes
utilize fish and amphibians (usually frogs)
Family Echinostomidae
as second intermediate hosts, which are
also eaten raw. It appears that cercariae can
Most of the members of this large and
also be swallowed while swimming and
rather heterogeneous group are parasites of
cause infection.
the gut of birds and lower vertebrates, but a
few are found in mammals and at least 24
species are occasional parasites of humans.
Typically, members have a collar of spines Other Echinostomids
behind the oral sucker.
E. echinatum (= lindoense) (Zeder, 1803)
formerly had a high infection rate
Echinostoma ilocanum (24–96%) around Lake Lindu in central
(Garrison, 1908) Odhner, 1911 Sulawesi but has been very uncommon
since the 1970s because of changes in eat-
SYNONYMS ing habits consequent on the introduction
Fascioletta ilocanum Garrison, 1908; of tilapia into the lake. The first intermedi-
Euparyphium ilocanum Tubangui and ate host is a planorbid snail or a type of
mussel (Corbicula) and the metacercariae
Pasco, 1933.
encyst in edible pulmonate and bivalve
snails, which used to be eaten raw and are
DISEASE AND POPULAR NAME
now rare (partly because they are eaten by
Echinostomiasis or echinostomosis;
the fish).
Garrison’s fluke infection.
E. hortense Asada, 1926, has an infection
GEOGRAPHICAL DISTRIBUTION rate of up to 22.4% in southern Korea and
Five human cases were found by Garrison is not uncommon in north-eastern China,
in prisoners in Manila jail in 1907 and where loach (the usual second intermediate
 The Trematodes 57

host) are eaten raw as a cure for jaundice; it Taiwan), Echinostoma melis (= Euparyph-
has also been reported from Japan. The nat- ium jassyense) (China, Romania and
ural definitive hosts are rats and dogs. Taiwan), Episthmium caninum (Thailand)
and Himasthala muehlensi (one case in
E. malayanum Leiper, 1911, has been
Colombia or USA).
recovered from humans in India, Indonesia
(Irian Jaya and Sumatra), the Philippines
MORPHOLOGY
(20% in areas of Luzon) and north-east
These species of echinostomes are mostly
Thailand (3–8%). It is probably a natural
small flukes measuring 2.5–8.0 mm and all
parasite of dogs or rats and human infec-
have a collar of spines behind the oral
tion is through ingestion of edible molluscs
(particularly Pila and Vivipara), which act sucker (Fig. 3).
as second intermediate hosts.
CLINICAL MANIFESTATIONS

E. revolutum (Froelich, 1802) Looss, 1899, In most infections there are no signs apart
is a common parasite of the caeca of duck, from the presence of eggs in the faeces. In
goose and muskrat, and most human cases heavy infections (e.g. 14,000 worms were
come from Taiwan (2.8–6.5% infection) recovered from one child at autopsy),
and north-east Thailand, with reports from symptoms are similar to those of
China and Indonesia. Edible molluscs, Fasciolopsis buski, with vague abdominal
such as Corbicula, act as second intermedi- manifestations, such as flatulence, intesti-
ate hosts. nal colic and diarrhoea (Graczyk and Fried,
1998). Vomiting, diarrhoea, abdominal
Hypoderaeum conoideum (Bloch, 1872) pain and swelling of the feet were reported
Dietz, 1909, is a parasite of birds, but there in one case in a child (Grover et al., 1998)
can be up to 55% infection rates in nort- and there may be anaemia and oedema.
east Thailand. Snails, such as Planorbis There have been fatalities in children from
and Lymnaea spp., act as both first and dehydration. The adult worms attach to the
second intermediate hosts. mucosa of the small intestine and may pro-
duce inflammatory lesions and necrosis at
There are many species of echinostomes
the site of attachment, with increased cel-
that can act as occasional or rare parasites
of humans, the numbers increasing as the lular infiltration in the intestinal mucosa.
use of praziquantel allows voided adult There may also be a generalized toxic
worms to be examined (for further informa- process. In an experimental infection with
tion, see Haseeb and Eveland, 2000): 113 metacercariae of Echinochasmus
Artyfechinostomum malayanum (Thailand), japonicus, abdominal pain, diarrhoea and
A. mehrai (India), A. oraoni (India), A. (= intestinal gurgling developed about 10
Paryphostomum) sufrartyfex (four cases in days after infection (Lin et al., 1985).
India), Echinochasmus fujianensis (up to
7.8% in southern Fujian, China), E. japoni- DIAGNOSIS
cus (China, Japan, Korea and Taiwan), E. Eggs found in the faeces are similar to
jiufoensis (one fatal case in Canton, China), those of Fasciolopsis or Fasciola, although
E. liliputanus (up to 23% in areas of Anhui somewhat smaller (most are about 100 µm
province, China), E. perfoliatus (Japan,
70 µm); specific identification is almost
Taiwan and Europe), Echinoparyphium impossible without recovery of adults after
paraulum (Russia), E. recurvatum (Egypt, treatment.
Indonesia and Taiwan), Echinostoma (=
Echinochasmus) angustitestis (two cases in TREATMENT
China), E. cinetorchis (Japan, Korea and Cure is simple with a single oral dose of
Taiwan), E. japonicum (Japan and Korea), 10–20 mg kg1 of praziquantel (or 5 mg
E. macrorchis (Indonesia, Japan, Korea and kg1 for Echinochasmus fujianensis).
58 Chapter 1

Other Occasional and Rare Human- site of birds, with metacercariae in the eyes
parasitic Trematodes of fish, and there have been a few cases of
swimmer’s itch in the former Czecho-
Family Diplostomidae slovakia, but more importantly cercariae
have entered the eye and caused cataracts
Alaria americana Hall and Wigdor, 1918, in the lens.
and A. marcianae (La Rue, 1917) Walton,
1950, are very similar parasites of wild
carnivores and dogs and cats in North Family Lecithodendriidae
America, in which the anterior portion of
the body is spoon-shaped, with an organ Phaneropsolus bonnei Lie Kian Joe, 1951,
that secretes proteolytic enzymes. They and Prosthodendrium molenkampi Lie Kian
have an unusual life cycle. When eggs from Joe, 1951, were both discovered in Indonesia
faeces reach water, the miracidia hatch out at autopsy and are also present in rural pop-
and penetrate and multiply in suitable ulations of north-east Thailand and Laos.
species of snails (including Heliosoma Eggs of both species are similar to those
spp.). The emerging cercariae develop in of Opisthorchis and heterophyids, and
amphibian tadpoles into a larval stage insects act as second intermediate hosts.
known as a mesocercaria (midway between Phaneropsolus spinicirrus, Paralecithoden-
a cercaria and a metacercaria). Frogs and drium obtusum and P. glandulosum are
snakes ingest tadpoles and act as paratenic three other poorly characterized species
hosts. When these are eaten by young commonly found in Thais (Yu and Mott,
carnivores, metacercariae develop in the 1994).
lungs, are coughed up and become adults
in the small intestine in about 20 days.
However, in pregnant animals the mesocer- Family Plagiorchiidae
cariae migrate to the mammary glands and
infect the suckling young through the milk, Plagiorchis harinasutai Radomyos, Bunnag
and adults develop in these (known as and Harinasuta, 1989, P. javensis
‘amphiparatenesis’). They can also infect Sandground, 1940, P. muris Tanabe, 1922,
subsequent litters (Shoop, 1994). A fatal and P. philippinensis Sandground, 1940,
case in Canada occurred in a man who have insects as second intermediate hosts
ingested frogs’ legs while hiking. He was and have been found in humans in
thought to be suffering from gastric flu but Thailand, Indonesia, Japan and the
died 9 days later from extensive pulmonary Philippines, respectively.
haemorrhage and at autopsy was found to
have thousands of mesocercariae in many
tissues. In other cases mesocercariae have Family Troglotrematidae
been found in the eye (Smyth, 1995).
Another species in carnivores, A. alata Nanophyetus salmincola Chapin, 1927, is
(Goeze, 1782), has occasionally infected an intestinal parasite of wild carnivores,
humans with mesocercariae in the Middle birds and domestic dogs in the Pacific
East. Neodiplostomum (= Fibricola) north of the USA and in Siberia.
seoulensis (Seo, Rim and Lee, 1964) Hong Metacercariae encyst in salmonid fishes
and Shoop, 1994, a parasite of rats, has and in the USA, in dogs that eat the fish.
developed to adulthood in the human Adults cause a haemorrhagic enteritis, with
small intestine in a few cases in South high fever, anorexia, vomiting and lymph-
Korea and is contracted from eating raw adenopathy (‘salmon poisoning’), with a
amphibians or snakes (paratenic hosts). high mortality 10–14 days after infection,
Diplostomum spathaceum (Rudolphi, caused by a rickettsia (Neorickettsia
1819) Olsson, 1876, is a cosmopolitan para- helminthoeca), which is transmitted by the
 The Trematodes 59

trematode. Following ingestion of raw fish, Other families

some patients in both areas suffered from
diarrhoea, weight loss, nausea, vomiting, Species of trematodes belonging to various
fatigue, anorexia and a high eosinophilia of other families that have occasionally been
up to 43%; in one case there was also a found in humans include: Carneophallus
high fever but the possible role of the rick- (= Spelotrema) brevicaeca (from shrimps
ettsia was not investigated (Eastburn et al., and has caused fatalities in the
1987). Symptoms usually resolved after a Philippines), Cathaemasia cabreri
few months. The parasites have been sepa- (Philippines), Clinostomum complanatum
rated into two subspecies: N. s. salmincola (from fish in Japan and Middle East),
in the USA and N. s. schikhobalowi in Cotylurus japonicus (China), Gymnoph-
Siberia. Diagnosis is by finding eggs in fae- alloides seoi (from oysters in a village in
ces (measuring about 80 µm
45 µm) and Korea), Isoparorchis hypselobagri (China,
treatment is with praziquantel. Prevention India), Microphallus minus (Japan),
is by not eating raw or smoked salmon in Paryphostomum bangkokensis (Thailand),
endemic areas, although there has been one P. sufrartyfex (India), Philophthalmus
case of infection through handling fish. lacrymosus (in the eye in Serbia),
There is a 4.2% infection rate in a focus on Philophthalmus sp. (eye in Sri Lanka),
the lower Amur River in Siberia (and up to Prohemistomum vivax (from fish in Egypt)
60% in local ethnic minorities), and the and Psilorchis hominis (Japan). See Yu and
ranges of both subspecies appear to be Mott (1994), WHO (1995), Ashford and
spreading. Crewe (1998) and Muller (2000) for further
details of intermediate and definitive hosts.

References

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Vennerwald, B.J., Ouma, J.H., Butterworth, A.E. and Deelder, A.M. (1996) Age dependent reduc-
tion of schistosome fecundity in S. haematobium but not S. mansoni infections in humans.
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Further Reading

Bergquist, N.R. (1992) Immunodiagnostic Approaches in Schistosomiasis. John Wiley & Sons,
Chichester, UK.
Jordan, P., Webbe, G. and Sturrock, R. (eds) (1993) Human Schistosomiasis. CAB International,
Wallingford, UK.
Rollinson, D. and Simpson, A.J.G. (eds) (1986) The Biology of Schistosomes: from Genes to Latrines.
Academic Press, London, UK.
Wellcome Trust (1998) Schistosomiasis. Topics in International Health CD-ROM, CAB International,
Wallingford, UK.
 2
The Cestodes

All adult cestodes (or tapeworms) inhabit proglottid just anterior to the vagina. The
the intestinal tract or associated tracts of female organs lie ventrally in the proglot-
vertebrates. tid. The ovary is usually bilobed and lies
They are flat, ribbon-shaped worms con- posteriorly. The ova pass into the oviduct,
sisting of a chain of a few or many separate which joins the spermatic duct from the
proglottides, the whole chain being known terminal part of the vagina or seminal
as a strobila. At the anterior end is the receptacle. The ova then pass into the
scolex or holdfast organ, which usually oötype, where fertilization occurs. The
attaches to the intestinal mucosa by means vitelline ducts from the vitellaria also open
of suckers or sucking grooves and often has into the oötype and provide shell material
hooks. Posterior to the scolex is the narrow and yolk cells. The uterus extends anteri-
undifferentiated neck region, from which orly from the oötype and ends blindly. The
growth takes place to give rise to the devel- uterus fills with eggs and, when gravid, has
oping proglottides. a shape characteristic of its family (e.g.
In the order Cyclophyllidea, to which with lateral branches in taeniids and a
most of the adult tapeworms of humans lobate transverse sac in hymenolepids).
belong, the proglottides become succes- Members of the order Pseudophyllidea
sively mature and then gravid, when they show structural and life-history differences
are filled with eggs. At the gravid stage from the Cyclophyllidea, which are
they become detached and pass out with mentioned in the section dealing with the
the faeces. All tapeworms of humans are only member that is an important parasite
hermaphroditic, the male organs develop- of humans, the broad fish tapeworm,
ing first. Thus male organs alone are found Diphyllobothrium.
in the mature proglottides nearer to the As cestodes have no gut, all nutritive
scolex; further back the organs of both and waste material must pass through the
sexes are present but the female organs outer covering or tegument; this functions
only are functional. With large tapeworms almost as an inside-out gut wall and con-
there is often a single specimen present tains specific systems of molecular and ion
and cross-fertilization occurs between transport, e.g. of amino acids, hexose sug-
proglottides. The genital organs are well ars, nucleotides, lipids, vitamins, purines
developed in each proglottid. The male and pyrimidines. The tegument consists of
system consists of the testes (three in num- a syncytial distal cytoplasm with a superfi-
ber in Hymenolepis to over 500 in Taenia), cial anucleate zone and an inner nucleated
the vasa efferentia, which unite to form a cytosomal zone. The external surface is
vas deferens, and a protrusible, muscular covered with a row of michrotriches,
cirrus or penis. The cirrus opens into a similar to intestinal microvilli, which
common genital pore on the margin of the increases the surface area in a similar way

63
64 Chapter 2

(increasing the functional area by 1.7–11.8 operculate. Life cycle includes procercoid
in some cestodes investigated, compared and plerocercoid larvae.
with a 26 times increase for mouse Diphyllobothrium, Spirometra
microvilli). On the tip of each microtriche
Order Cyclophyllidea (MBRA)
there is a glycocalyx, composed of
Length variable, from 3 mm to 10 m.
mucopolysaccharide and glycoprotein
Holdfast typically with 4 large suckers.
acidic groups, which absorbs and incorpo-
Apical end often with row of hooks.
rates hexose sugars and amino acids, con-
Proglottides usually wider than long.
centrates inorganic and organic ions, binds
Genital apertures marginal. Vitellaria sin-
host amylase and carries out ‘contact diges-
gle, compact, postovarian. Gravid uterus
tion’ (Smyth and McManus, 1989).
without aperture and sometimes broken
In the great majority of infections the
into capsules. Eggs non-operculate. Larva
adult tapeworms that normally occur in
commonly a cysticercus (bladder-worm) in
humans do not cause any serious pathol-
a vertebrate, or a cysticercoid in an arthro-
ogy, although their presence can be
pod.
extremely unpleasant. Accidental adult
tapeworms contracted zoonotically are Family Taeniidae (MB)
encountered rarely, principally in children, Rostellum of scolex non-retractable and usu-
and are usually short-lived. However, ally with 2 circles of hammer-shaped hooks.
infection with larval tapeworms is poten- Testes numerous. Gravid proglottides longer
tially very serious and in some countries than broad. Gravid uterus has median stem
cysticercosis (caused by the metacestodes and lateral branches. Larva a cysticercus,
of Taenia solium) and echinococcosis are coenurus or hydatid in a vertebrate.
important public health problems (56 Taenia, Echinococcus
species of adult and larval cestodes are
Family Hymenolepididae (MB)
included as having occurred in humans).
Rostellum retractable, hooks thornlike.
Testes rarely more than 4. Gravid uterus a
transverse tube. Larva a cysticercoid in
Classification
insects (except H. nana).
Hymenolepis
KEY: Members are parasites of M = mammals,
B = birds, R = reptiles, A = amphibians, F = Family Dipylididae (M)
fish. Rostellum retractable, hooks typically
thorn-shaped. Genitalia single or double.
PHYLUM PLATYHELMINTHES
Testes usually numerous. Mature proglot-
CLASS CESTODA tides longer than wide. Gravid uterus a
No digestive system. Presence of calcare- transverse lobed sac or replaced by egg
ous corpuscles. Usually hermaphrodite. sacs. Larval stage a cysticercoid in insects.
Dipylidium
SUBCLASS EUCESTODA
Body typically divided into short proglot- Family Anoplocephalidae (MBR)
tides with anterior holdfast organ, often No rostellum. Testes numerous. Gravid
with suckers and hooks. Egg with 6 hooks. proglottides much wider than long. Gravid
There are many orders of no medical uterus often replaced by paruterine organs.
importance, which are not included (see Eggs often with characteristic membrane
Khalil et al., 1994). drawn out into a pair of cross-tapered
processes (pyriform apparatus). Larva a
Order Pseudophyllidea (MBRAF)
cysticercoid in oribatid mites.
Length very variable but may be up to
Bertiella, Inermicapsifer
30 m. Holdfast typically with dorsal and
ventral sucking grooves. Genital apertures Family Davaineidae (MB)
usually on ventral surface. Testes and vitel- Rostellum retractable, hooks T-shaped.
laria scattered and follicular. Eggs usually Suckers often spinose. Gravid uterus
 The Cestodes 65

replaced by egg pouches. Larva a cysticer- Volga Rivers), Poland and Ukraine, with
coid in insects. sporadic cases in Italy/Switzerland (Lake
Raillietina Maggiore) and Slovakia (Danube basin); in
Asia, in Japan, north-eastern Russia (Amur
Family Mesocestoididae (MB)
River basin) and with a few cases in China,
No rostellum. Mature proglottides wider
India (one case) and Korea; in the
than long, genital apertures median.
Americas, in the Great Lakes regions of
Posterior paruterine organ. First larval
Canada and the USA, Argentina and Chile
stage probably in oribatid mites, second
(Valdiva River basin).
tetrathyridium in vertebrates.
Mesocestoides
LOCATION IN HOST
The adult worm or worms inhabit the
Order Pseudophyllidea lumen of the small intestine with the
scolex embedded in the mucosa.
Diphyllobothrium latum
(Linnaeus, 1758) Lühe, 1910 MORPHOLOGY
Diphyllobothrium is the longest tapeworm
SYNONYMS infecting humans. It measures 3–10 m in
Taenia lata Linnaeus, 1758; Dibothrio- length and may have 4000 proglottides.
cephalus latus Lühe, 1899; Bothrio- Each proglottid measures 2–7 mm

cephalus latus Bremser, 1918. 10–12 mm, and contains both male and
female reproductive organs (Fig. 26).
DISEASE, POPULAR AND LOCAL NAMES Diphyllobothrium differs from all other
Diphyllobothriasis or diphyllobothriosis; human tapeworms in having a uterine pore
broad fish tapeworm infection; Lapamato through which eggs are discharged (this is
(Finnish), Breda binnikemaskens (Swedish). typical of the order Pseudophyllidea and
similar to the situation in trematodes). This
GEOGRAPHICAL DISTRIBUTION pore and the cirrus and vagina open on the
It is estimated that there are about 20 mil- ventral surface, not at the lateral margin as
lion cases worldwide. In Europe it is found in the Cyclophyllidea. The scolex measures
principally in countries with many lakes, 1–2 mm and has no suckers but attaches to
such as Finland, Estonia, Russia (Don and the mucosa by two sucking grooves (Fig. 27).

cirrus
testes genital pore
uterus vagina
vas deferens

vitellaria
1 mm
ovary vitelline duct
ootype

Fig. 26. Mature proglottid of Diphyllobothrium latum. The vitellaria are shown principally on the right-
hand side, the testes on the left. Note genital uterine pore, through which eggs emerge.
66 Chapter 2

to many weeks, depending on the tempera-

ture, into a ciliated larva (termed a coracid-
ium) measuring 40–50 µm and with six
small hooks (Fig. 29a). The coracidium
larva escapes into the water through the
opened operculum and swims around in
Fig. 27. Scolex with two sucking grooves. an apparently aimless manner. The
coracidium can survive for 1–2 days but for
further development must be ingested by a
LIFE CYCLE (Fig. 28) suitable planktonic copepod belonging to
Up to 1 million eggs can be produced daily the genus Diaptomus or, more rarely in
and these pass out in the faeces. The ovoid Europe, Cyclops, living in large bodies of
eggs measure 55–80 µm
40–60 µm and water (about 40 species including D. vul-
are similar in structure to those of trema- garis, D. gracilis, C. vicinus and C.
todes (Fig. 123). They are yellowish-brown, strenuus). Inside the stomach of the crus-
operculate and with a small knob at the tacean, the outer epithelium is lost and the
end opposite to the operculum. The ovum enclosed larva penetrates the gut wall with
is unsegmented when laid and is sur- the aid of the hooks. In the body cavity a
rounded by yolk cells. If the egg reaches procercoid larva, measuring 0.5 mm in
fresh water, the ovum develops in 12 days length, develops in 14–21 days (Fig. 29b).

ADULTS in
small intestine
mature in 3–5
weeks

Unsegmented
EGGS (55–80m
x 40–60m)
in faeces

Fish ingested
by human

EGGS develop
in 2 to many
weeks in water

CORACIDIUM
larva lives for
Copepod ingested by 1–2 days
fish: PLEROCERCOID
in muscles infective
in 4 weeks Ingested by copepod:
PLEROCERCOID
develops in 2–3 weeks

Fig. 28. Cartoon illustrating the life cycle of Diphyllobothrium latum (after Tiedoksianto Information,
1971, 12, 3–9).
 The Cestodes 67

Fig. 29. Larval stages of D. latum. (a) Free-living coracidium. (b) Procercoid from copepod.
(c) Plerocercoid from fish.

If the copepod is ingested by a plankton- life of the fish. The small copepods (about
eating freshwater fish, the procercoid larva 1 mm long) are often ingested by small fish
penetrates the intestinal wall in about 4 h and, when these are eaten by a larger fish,
and develops into a plerocercoid larva in such as pike, perch, burbot or salmon, the
the connective tissues and muscles. The released plerocercoids can penetrate the
plerocercoid is an elongate wormlike larva intestinal wall and remain viable. In this
with an inverted scolex and takes about 4 way the larval parasites become concen-
weeks to become infective (Fig. 29c). The trated in the larger carnivorous food fishes,
larvae eventually become encysted but which act as paratenic hosts (e.g. the pike).
usually remain infective throughout the Human infection occurs when fish are eaten
68 Chapter 2

raw or semi-cooked. The released larva up the gut, in the jejunum and nearer to the
attaches to the intestinal wall by the everted stomach; (ii) because of a reduction in
scolex and develops proglottides. Diphyllo- intrinsic factor resulting from damage to
bothrium reaches maturity in 3–5 weeks and the gastric mucosa; (iii) principally because
can live for up to 25 years in humans. of a low dietary intake of B12 (supported by
Usually only a single worm is present. After the finding that pernicious anaemia has
voiding eggs, a chain of the oldest proglot- decreased greatly since the diet has
tides breaks off and is often passed out in the improved); (iv) because of human genetic
faeces (pseudoapolysis). A small form of D. factors. There can be up to 25%
latum, measuring about 60 cm
2.3 mm, eosinophilia in early infections.
has been reported from Japan. Occasional cases of multiple infection
have been known to cause obstruction of
CLINICAL MANIFESTATIONS AND PATHOGENESIS the small intestine.
Often none. In a proportion of cases there
is abdominal pain, loss of weight, anorexia DIAGNOSIS
and vomiting. Sometimes the worm This is by discovery of the characteristic
becomes lodged in the jejunum, where it eggs in the faeces but they need to be dif-
causes acute pain and vomiting of seg- ferentiated from similar trematode eggs,
ments. such as those of Paragonimus (Fig. 123).
The most important pathological effect Sometimes a chain of proglottides is
of diphyllobothriasis is anaemia, which passed in the faeces at intervals and these
occurs only in Finland and is of the perni- can be recognized by the characteristic
cious megablastic (macrocytic) type. It shape of the uterus (Fig. 30), but there is no
used to occur in about 20% of cases but is regular expulsion of gravid proglottides, as
not so common since diet has improved. with taeniid tapeworms.
The cause appears to be a competitive
uptake of vitamin B12 by the worm, rather TREATMENT
than any substance released by it interfer- Praziquantel is the drug of choice at a sin-
ing with Castle’s intrinsic factor (von gle oral dose of 15–30 mg kg1, but it is
Bonsdorff, 1977). Diphyllobothrium has a important to make sure that the scolex has
vitamin B12 content 50 times that of Taenia been expelled .
saginata and absorbs 80–100% of radio- Niclosamide (2,2-dichloro-5,4-nitro-
active B12 added to the diet of symptomless salicylanilide) at 1 g first thing in the morn-
carriers. The North American strain of ing and then 1 g 1 h later (scolex is
Diphyllobothrium takes up only 6–7%, destroyed) and bithionol (50–60 mg kg1,
however, and anaemia is very rare. repeated a day or so later if no scolex is
Anaemia in Finland possibly occurs: (i) recovered) have been used for many
because the strain of worm is found higher years.

uterus
0.5 mm

Fig. 30. Chain of proglottides as sometimes passed in the faeces. The characteristic branched uterus
can be recognized by the tanned eggs.
 The Cestodes 69

EPIDEMIOLOGY Rausch, 1969, a natural parasite of monk

Raw or smoked freshwater fish is an impor- seal, in Japan; D. cordatum Cobbold, 1879,
tant item of diet in many countries. In found naturally in seals and walrus, in
reservoirs in the Krasnoyarsk region of Alaska; D. dalliae Rausch, 1956, and D.
Siberia the tipping of untreated sewage has dendriticum (Nitzsch, 1824), parasites of
caused 100% infection in pike living in gulls and freshwater fish, in Alaska; D. ele-
lakes and 5% in rivers, with 35,000 cases gans (Krabbe, 1865), naturally in seals and
reported annually in Russia overall. sea lion, in Japan; D. giljacicum (= D. luxi)
‘Caviar’ made from the roe of pike is a pop- Rutkevich, 1937, in freshwater fish and
ular dish in that area and is the cause of a adults only known from humans in Siberia;
seasonal rise in the infection rate in the D. hians (Diesing, 1850), naturally in seals,
spring when the fish have roe. In the in Japan and Siberia; D. klebanovskii (= D.
Archangel region (as in Finland) infection luxi) Muratov and Posokhov, 1988, natu-
has been much reduced by improved treat- rally in brown bears and salmon, in
ment of sewage. Belarus and Siberia; D. lanceolatum
Around the Baltic Sea, slices of raw fish (Krabbe, 1865), naturally in seals, in
known as ‘strogonina’ are a popular item of Alaska; D. minus Cholodkovsky, 1916, nat-
diet and are important in transmission, as urally in seagulls, in Russia; D. nenzi
is ‘sashimi’ in Japan. Petrov, 1938, in Russia; D. nihonkaiense (=
D. luxi) Yamane et al., 1986, is apparently a
PREVENTION AND CONTROL human parasite in Japan and Siberia con-
The plerocercoid larvae in fish are killed tracted from salmon; D. orcini Hatsushika
by freezing at 10°C for 15 min. They are and Shirouzu,1990, naturally in killer
also killed by complete drying or by thor- whale, in Japan; D. scoticum (Rennie and
ough pickling. Reid, 1912), naturally in seals and sea lion,
Proper disposal and treatment of faeces in Japan; D. skrjabini Plotnikov, 1932, in
are also of great importance in reducing dogs and freshwater fish, in Russia; D. tan-
incidence. gussicum Podjapolskaia and Gnedina,
1932, is apparently a human parasite in
ZOONOTIC ASPECTS Russia; D. ursi Rausch, 1954, naturally in
Infection with D. latum has been recorded bears, in Canada and Alaska; D. yona-
from many mammals, including dogs, cats goense Yamane et al., 1981, natural cycle
and bears. However, with the exception of unknown, in Japan and Korea.
dogs, animals are probably not of impor- Diplogonoporus grandis (= D. balan-
tance in transmission; tapeworms in cats opterae) (Blanchard, 1894) Lühe, 1899, is a
last only for a matter of weeks. parasite of whales and has been reported
Numerous other species of Diphyllo- over 50 times from humans in Japan (caus-
bothrium and related genera are occasion- ing abdominal discomfort) and Korea, with
ally found in humans, mostly contracted a single case in Spain. Each proglottid has
from marine fish (Ruttenber et al., 1984). a double set of reproductive organs and the
However, the taxonomic status of species eggs measure 63–68 µm
50 µm. Other
within this genus is rather confused and it species are D. brauni Leon, 1907, in
is often very difficult to differentiate them Romania and D. fukuokaensis Kamo and
on adult characters alone, although the Miyazaki, 1970, in Japan. Ligula intesti-
structure and size of eggs can be useful. nalis Linnaeus (1758) Bloch, 1782, a com-
Diphyllobothrium pacificum (Nybelin, mon and widespread parasite of fish-eating
1931) Margolis, 1956, is a natural parasite birds, has been found in humans in Poland
of fur seals and sea lions with plero- and Romania; Schistocephalus solidus
cercoids in marine fish (e.g. mackerel) and (Mueller, 1776) Creplin, 1829, another
has been found in humans in Chile, common bird parasite, has been recorded
Ecuador and Japan. Other species with a from humans in Alaska; Pyramicocephalus
few cases in humans include: D. cameroni anthocephalus (Fabricius, 1780) Monticelli,
70 Chapter 2

1890, is a pseudophyllid tapeworm of transmitting Gnathostoma and Dracunculus)

seals, which has been recorded from (Fig. 31); also the plerocercoids do not
humans in Alaska and Greenland. develop in fish but, in most parts of the
world, in amphibians, reptiles and small
mammals and, in East Africa, in large game
Sparganosis animals. A wide range of vertebrates,
including humans, in which adult tape-
Sparganosis is the term used to describe worms will not develop, can also act as
infection with the plerocercoid larvae (= paratenic hosts. Human infection may
spargana) of diphyllobothriid tapeworms of occur in one of three ways:
the genus Spirometra (in some textbooks
they are included in the genus 1. By ingestion of cyclops containing pro-
Diphyllobothrium, but it is clearly a valid cercoid larvae in drinking water from
genus, although more correctly it should be ponds or open wells; this is the most likely
Luheella). mode of infection in many parts of the
The adult tapeworms are parasites of world.
carnivores in tropical and subtropical 2. By application of the flesh of an infected
regions of Africa, the Americas, Australia, frog to ulcers, sores and infected eyes; the
Europe and Asia. The mature proglottides procercoid is activated by warmth and
can be easily differentiated from those of enters the flesh. This form of traditional
Diphyllobothrium by the structure of the poultice is used only in areas of South-East
uterine coils, which form compact loops in Asia, particularly Thailand and Vietnam,
the midline rather than a rosette shape and spargana in the eye can result in severe
(Fig. 30). The eggs can also be differenti- oedema and eventually nodule formation,
ated. usually of the upper eyelid; when removed
The life cycle resembles that of the contained larva has often degenerated
Diphyllobothrium except that the procer- into a caseous mass.
coids develop in cyclopoid species that 3. By ingestion of raw or undercooked meat
inhabit small ponds rather than lakes of infected frogs, snakes, mammals or birds;
(Eucyclops serrulatus and Mesocyclops the contained plerocercoids burrowing
leuckarti and probably the other species through the wall of the intestine (Plate 8).

Fig. 31. Cyclops with procercoids of Spirometra sp. in the haemocoel. Calcareous bodies can be seen
in the bodies of the parasites.
 The Cestodes 71

Spargana wander in the deep tissues of adult or larval worms which works
and usually migrate to the subcutaneous well.
tissues, where they eventually encyst, ‘Sparganum proliferum’ is a rare form,
resulting in a fibrous nodule about 2 cm in of unknown relationship, in which the
diameter. Surgical excision of the nodule is plerocercoids become disorganized and
usually possible, and the enclosed larva, proliferate in the tissues by lateral budding
which has a scolex similar to that of (DNA analysis shows that they are of the
Diphyllobothrium but with a tail many cen- genus Spirometra but of unknown species).
timetres in length, is sometimes mistaken In human cases found at autopsy many
for a guinea worm in Africa. The most seri- thousands of larvae have been present in
ous effects are caused by larvae in the the viscera as well as in the subcutaneous
brain, which can cause repeated seizures tissues. It is possible that virus infection of
(in 84% of patients), hemiparesis (59%) a normal sparganum may be responsible.
and headache (56%) with convulsions, and Three fairly recent similar cases, probably
can be diagnosed by computer-assisted of proliferating spargana, have been
tomography (CT) or magnetic resonance described, one in an abdominal mass from
imaging (MRI) scans (Chang et al., 1992). an Amerindian in Paraguay (Beaver and
The lesions need to be removed surgically; Rolon, 1981) and two others from the lungs
high dosages of praziquantel have not of a man and the spinal cord of a woman in
always been successful. Very rarely, larvae Taiwan (Lo et al., 1987).
may enter the eye and cause endoph-
thalmitis, leading to blindness (Sen et al.,
1989) and larvae may also enter various
visceral organs. Sparganosis can be diag- Order Cyclophyllidea
nosed by a chemiluminescence ELISA.
Many species of Spirometra have been The majority of tapeworms of medical and
described from various areas of the world, veterinary importance belong to this order.
but most are morphologically variable and
the species position is very confused.
Parasites from Asia or Europe are usually Family Taeniidae
termed S. mansoni (Cobbold, 1882), S.
houghtoni (Kellogg, 1927) or S. erinacei (= This group of taeniid tapeworms includes
S. erinaceieuropei) (Rudolphi, 1819), with the most important cestode parasites of
plerocercoids in frogs and snakes and humans. The adults of two species, Taenia
adults occurring naturally in carnivores, saginata and T. solium, are only found in
including cats and dogs (16% in Thailand), humans but are usually of minor medical
those from Africa S. theileri (Baer, 1925), importance. The larval stages are always in
with plerocercoids in wild herbivores and mammals and consist of a fluid-filled cyst,
adults in large carnivores, and worms from which may contain a single or many proto-
the Americas S. mansonoides (Mueller, scolices, each of which is capable of devel-
1935), with plerocercoids in frogs and oping into an adult tapeworm in a
snakes and adults in wild carnivores and definitive host (Fig. 32). Human infection
cats and dogs (the adults of this species can with larval cestodes can be a very serious
be differentiated morphologically from all medical problem indeed.
the others and produce a growth hormone-
like cysteine proteinase that causes weight
Taenia saginata
gain in experimentally infected mice).
Goeze, 1782
The presence of spargana is becoming
more commonly identified with an increas- SYNONYMS
ing concern about strange growths, and Taeniarhynchus saginatus Weinland, 1848;
there is an ELISA using crude antigens Taenia africana Linstow, 1900; T. confusa
72 Chapter 2

Fig. 32. The various types of taeniid larvae. They contain one or many protoscolices.

Ward, 1896; T. hominis Linstow, 1902. In MORPHOLOGY

the literature from eastern Europe this tape- The scolex is pear-shaped, 1–2 mm in
worm is commonly called Taeniarhynchus diameter, but with no rostellum or hooks.
saginatus, because some authorities believe The adult worm is very long, sometimes
that the lack of rostellum and hooks is suffi- exceeding 20 m. Usually, however, it is
cient to warrant a genus separate from about 5 m long with 1000–2000 proglot-
Taenia (Bessenov et al., 1994). However, tides. Each mature proglottid measures
there is evidence that there are rudimentary about 12 mm wide and 10 mm long and
hooks in the cysticerci and it is likely that each gravid proglottid contains about 0.8–1
these have been secondarily lost.
105 eggs.

DISEASE AND POPULAR NAME Female organs. The ovary is in the post-
Taeniasis or taeniosis saginata; beef tape- erior part of the proglottid and has two
worm infection. large lobes. The follicular vitellaria (which
produce the eggshell and nutrient yolk
LOCAL NAMES cells) lie in a band behind the ovaries. The
Dooda shareatia or dedan (Arabic), Than uterus extends forwards as a tube, slightly
kaung (Burmese), San-chik (Cantonese), dilated anteriorly. In contrast to the uterus
Sanadu mushi (Japanese), Miliny (Luo), of Diphyllobothrium, it has no opening to
Tegu (Swahili), Nada puchi (Tamil), Pa- the exterior. Gravid proglottides contain a
yard tua tued (Thai), Sonsono (Twi), Arán characteristic taeniid type of uterus filled
inú (Yoruba). with eggs (Figs 33 and 34).

GEOGRAPHICAL DISTRIBUTION Male organs. The numerous follicular testes

Infection is cosmopolitan and occurs in are scattered throughout the anterodorsal
almost all countries where beef is eaten raw part of the proglottid. The vas deferens
or undercooked. In most countries it is more opens through the muscular cirrus at the
common than the pork tapeworm (T. common genital pore, which is situated
solium), with about 60 million cases in the irregularly on alternate lateral margins.
world.
LIFE CYCLE
LOCATION IN HOST The eggs measure 43 µm
31 µm and are
The scolex of the adult tapeworm is identical to those of T. solium and many
embedded in the mucosa of the wall of the other taeniids. They are deposited in human
ileum, with the rest of the tape extending faeces (about 0.7–1
106 24 h1), often
throughout the lumen. inside the gravid proglottid, or the latter
 The Cestodes 73

0.5 mm

1 2 7

T. solium
T. saginata

uterus

testes
1 mm

genital
opening ovary
cirrus vagina

vas
deferens
Mehlis’ gland
excretory
duct
vitellarium
nerve

Either species
4
5

gravid
uterus

T. solium T. saginata

Fig. 33. Comparative morphological features of Taenia solium and Taenia saginata.
1 and 2. Scolices (6 and 7 are the scolices of Hymenolepis nana and H. diminuta at the same scale).
3. Mature proglottid of either species. 4 and 5. Gravid proglottides showing the typical numbers of
branches of the uterus in each species.
74 Chapter 2

Fig. 34. Section of proglottides of T. saginata in the appendix. The uterus contains eggs.

may pass out through the anus and for fur- umbilical pain, nausea, weakness, loss of
ther development need to be ingested by weight, alteration of appetite, and head-
cattle, when the contained oncosphere larva ache. These symptoms and signs are possi-
hatches in the duodenum. The oncospheres bly caused by toxic products produced by
penetrate through the intestinal wall with the worms or are allergic reactions, and are
the aid of the six hooklets and enter the characteristically alleviated by taking
venous capillaries (or the mesenteric lym- food.
phatics) in about 30 min. The embryos are Occasionally, generalized allergic mani-
carried by the circulation until they reach festations, such as urticaria with pruritus
the voluntary muscles, where they lose the ani or widespread pruritus, result. The
hooks and develop into an infective cys- presence of a lump in the throat is a not
ticercus larva in 10–12 weeks, or sometimes uncommon symptom, reported particularly
longer. The fully formed cysticercus is by middle-aged women in Poland. Perhaps
ovoid and white in colour and measures unsurprisingly, symptoms often increase in
about 8 mm
5 mm (it is known to veteri- frequency and severity once patients are
narians as a ‘cysticercus bovis’). The invagi- aware they have a tapeworm. Occasionally
nated protoscolex has four suckers but no a worm causes obstruction due to bolus
hooks. The outer wall of the fluid-filled impaction in the intestine and it has been
bladder has microvilli, possibly serving a known for proglottides to be vomited and
trophoblastic function. then aspirated.
Humans become infected from eating A moderate eosinophilia occurs in
raw or undercooked beef. The protoscolex 5–45% of patients.
of the cysticercus evaginates in the duode-
num, attaches to the wall of the ileum and PATHOGENESIS
begins to form proglottides. Little pathology can be directly attributed
to the physical action of the scolex on the
CLINICAL MANIFESTATIONS mucosa, although inflammation of the
Often the first and only sign of infection is mucosa of the ileum sometimes occurs.
the presence of active proglottides in the Over 100 cases of intestinal obstruction,
faeces, perhaps preceded by the feeling of perforation or appendicitis have been
them ‘crawling’ out through the anus. reported. In a recent case in Reunion
As the tapeworm matures, 6–8 weeks island, intestinal perforation led to death
after infection, there may be epigastric or from septic shock.
 The Cestodes 75

DIAGNOSIS Albendazole at a single oral dose of 800 mg

has about 80% effectiveness. Niclosamide
Parasitological. The presence of gravid (2 g for an adult given in a divided dose
proglottides with the characteristic taeniid over 2 days) has been in use for many years
branched uterus in the faeces provides the but has (usually mild) side-effects and is
usual method of diagnosis. These are not always effective. With newer com-
passed out in short chains of 5–8 proglot- pounds the scolex is destroyed and so fol-
tides, are very active and sometimes can be low-up is necessary to determine that the
felt migrating out of the anus. When complete worm has been expelled (if the
pressed between glass slides, the number of scolex should remain embedded, a new
lateral branches of the uterus can be worm can develop within weeks).
counted in order to differentiate T. saginata
(15–32, usually 20–23, main branches) from EPIDEMIOLOGY
T. solium (7–13, usually 9, main branches). The prevalence of T. saginata infection has
However, in South Africa at least some remained high in areas of Europe; various
degree of overlap was reported, but it is not recent regional estimates are 0.4–9.5% in
clear how much. The two species can be Belgium, 1.3–1.7% in northern Italy, 4.0%
clearly differentiated if the scolex is passed in northern Germany, 20,000 cases annually
in the faeces after chemotherapy, because of in Russia, 0.9% in Slovakia and 2.5% in
the lack of rostellum and hooks in that of T. Turkey. It is rare in the UK (627 cases in
saginata. There are also small differences in England and Wales between 1990 and
the mature proglottides: those of T. saginata 1998). In other parts of the world estimates
have a vaginal sphincter muscle and testes are 1.3% in Afghanistan, 0.5% in Brazil,
confluent posteriorly to the vitellarium, 0.4–1.0% in Egypt, 1.0% in Ethiopia, 0.3%
while those of T. solium have a third lobe to in Honduras, 7.7% in Iran and 2.3% in east-
the ovary. Unfortunately, special prepara- ern and 11.5% in northern Nigeria.
tion is often necessary in order to see these Estimates of cysts in cattle are 1.9% in
features. Brazil, 8.3–28.8% in Botswana, 0.1% in
Free eggs may be found in the faeces if Chile, 1.3% in Bulgaria, 0.72% overall in
the gravid proglottides have been auto- Egypt, 3.5–6.0% in northern Germany,
lysed, particularly using concentration 0.43–15.9% in Kenya, 3.2% in Poland,
techniques, and may also be found by tak- 1.7% in Sudan, 29% in Swaziland, 4.5% in
ing possibly repeated anal swabs with Switzerland, 0.6–16% in Tanzania,
sticky tape (p. 163) or a sticky glass spat- 6.8–59% in Togo, 0.5–88% in Texas, USA,
ula, as used in Russia, and examining 1.6% in Vietnam and 3.2% in Zimbabwe.
under the microscope, although species of Raw minced beef or very rare steaks are
taeniids cannot be differentiated. popular items of diet in many countries.
The eggs can survive on pastures for
Serological. The detection of coproantigens in 60–180 days, in sewage for 16 days at
faeces by capture ELISA techniques has 18°C. and in river water for many weeks
proved sensitive and also specific and they can survive for up to 1 h at 50°C.
(Machnicka et al., 1996). There are various (Muller, 1983). In Russia eggs withstand
techniques for diagnosis of cysticerci in the winter better than summer (at the opti-
cattle. The best probably recognize circulat- mal temperature of 4°C, they survive for
ing excretory/secretory (ES) antigens of 62–64 days). Moisture is a very important
cysticerci by monoclonal antibody-based dot factor governing their survival and they die
ELISA, SDS-PAGE or immunoblotting (which rapidly when desiccated (Muller, 1983).
recognizes antigens of 65, 87 and 100 kDa). Infection of cattle occurs mainly when
they are young calves, sometimes from the
TREATMENT hands of stockmen, but more usually from
Praziquantel at a single oral dose of 5–10 faecal matter spread on pastures.
mg kg1 is usually completely effective. Proglottides can also migrate out through the
76 Chapter 2

anus and may contaminate pastures when an inspection is the most important public-
infected person walks over them. In devel- health measure possible. The most heavily
oped countries transmission is primarily due infected muscles for inspection may vary
to inadequate treatment of sewage. Eggs are from region to region but usually include
very resistant and can survive the activated the heart, masseters, shoulder muscle and
sludge process; thorough drying or sand fil- tongue, and also the liver of cattle or pigs
tration is necessary to remove them. In some in Asia. The cysts can be easily recognized
parts of the world improperly treated efflu- in ‘measly beef’ (or pork) about 6 weeks
ent finds its way back to the fields. after infection.
The role of birds, particularly seagulls, in Infection rates have been reduced some-
the dissemination of T. saginata eggs from what in recent years in eastern Europe and
sewage beds to fields has not been clearly East Africa by sanitation measures, and
established but they have been implicated mass diagnosis and treatment campaigns
in Denmark and England. Flies have also have been tried in Russia.
been implicated in Russia and in one survey
4.8% of all flies, particularly sarcophagid ZOONOTIC ASPECTS
flies, were found to be infected. In the strict sense this is an obligatory
Cysts in calves survive for longer (for up cyclo-zoonotic infection, the life cycle nec-
to 2 years) than those in mature cattle essarily involving both cattle (or pig) and
(maybe as little as 3 weeks). Cysticerci in humans (sometimes termed a euzoonosis
cattle are economically very important and or an anthropozoonosis). However, there is
are estimated to cost $1000 million annu- no animal reservoir host of the adult tape-
ally in Africa. In addition to cattle, cys- worms, which occur only in humans.
ticerci occur in buffalo and have been
reported from reindeer in Siberia, from
Taenia solium
wild game animals in Africa and from pigs
Linnaeus, 1758
in Asia and Africa (but see below).
Taenia saginata asiatica Fan, Lin, Chen SYNONYM
and Chung, 1995, is a recently named sub- Taenia cucurbitina Pallas, 1766.
species, in which cysticerci are found in the
liver and mesenteries of pigs and wild boars, DISEASE AND POPULAR NAME
as well as in cattle (and goats and monkeys), Taeniasis or taeniosis solium; pork tape-
in Burma (Myanmar), China, Indonesia worm infection.
(western islands), Korea (Cheju Island) and
Taiwan (Ito, 1992); a similar form has been LOCAL NAMES
reported from areas of Africa. The cysticer- As for T. saginata.
cus has a sunken rostellum with two rows of
rudimentary hooks and there are many GEOGRAPHICAL DISTRIBUTION
branches to the uterus in gravid proglottides Taenia solium infection has a cosmopolitan
(Fan et al., 1995). It has been estimated to distribution in countries where pork is eaten
cause an annual economic loss of $34 mil- raw or undercooked. It is most common in
lion in Indonesia, Korea and Taiwan (Fan, Africa, Central and South America (particu-
1997). Cysticercosis can also occur in larly Mexico and Chile) and China.
humans, as with T. solium. In Taiwan, cysts Prevalences fell greatly in eastern European
of T. s. saginata, as well as T. s. asiatica, can countries but with less efficient control are
develop in pigs as well as in cattle. beginning to rise again.

PREVENTION AND CONTROL LOCATION IN HOST

Personal protection is by thorough cooking The scolex is embedded in the mucosa of
of all beef and pork (above 56°C.) or by the jejunum, with the rest of the tape
freezing at 10°C. for 10 days. Meat extending through the ileum.
 The Cestodes
Map 5. Distribution of Taenia solium (and cysticercosis) on a country basis.

77
78 Chapter 2

nata (which have 15–32 main branches).

There are usually one to three tapeworms
present but there may be as many as 25.

LIFE CYCLE
The eggs are roughly spherical and measure
47–77 µm in diameter (Fig. 123). They have
an outer vitelline layer, which is often lost,
and then a thick brown embryophore made
up of keratin blocks, giving it a striated
appearance (the true outer eggshell is lost).
Inside there is an embryo, termed an oncos-
phere or hexacanth, which has six hooklets.
The eggs are morphologically identical to
those of T. saginata.
Eggs may burst free from the proglottid,
whether in the gut or on the ground, and
can survive on soil for weeks. Often, how-
ever, the pig, which acts as the intermediate
host, ingests the gravid proglottid in human
faeces. The cement substance between the
embryophore blocks is dissolved by the gas-
Fig. 35. Stereoscan photograph of the scolex of tric secretions and the oncosphere hatches
T. solium. in the duodenum. It penetrates through the
intestinal wall with the aid of the hooklets
and enters the venous capillaries (or the
MORPHOLOGY
mesenteric lymph vessels) in about 30 min.
Taenia solium is a long tapeworm, 2–3 m
The embryos are carried by the circulation
in length and having up to 4000 proglot-
until they reach the voluntary muscles,
tides (usually around 1000). The scolex
where they lose the embryonic hooks and
measures 1 mm in diameter with four large
develop into cysticerci (known to veterinar-
suckers and a conspicuous rostellum with
ians as ‘cysticerci cellulosae’) or bladder-
two rows of alternating large and small worms in 60–75 days. Cysts in pigs are
hooks. There are 25–30 of these hooks, the commonly found in the heart muscle (in
large hooks measuring about 170 µm in 80% of infected animals), masseters (50%),
length and the short ones about 130 µm diaphragm (50%) and tongue (40%).
(Fig. 35). The shape of the hooks is charac- Cysticerci may also be found in the liver,
teristic of the family Taeniidae. The neck kidneys, brain and eyes. The fully formed
region is thin and measures 5–10 mm. cysticerci are ovoid and white in colour
The mature proglottides are roughly and measure about 8 mm
5 mm. They are
square (12 mm
10 mm) (Fig. 33) and are thus easily visible to the naked eye as white
superficially identical to those of T. sagi- dots and give rise to the condition known
nata. The gravid proglottides are about as ‘measly’ pork. Each cyst consists of a
12 mm long by 6 mm wide. Eight to ten are fluid-filled bladder with a minute proto-
usually passed in the faeces each day, often scolex invaginated into the lumen; the
in a short chain. The uterus ends blindly, protoscolex has four suckers and two rows
as in all cyclophyllidean tapeworms, and of hooks (Fig. 36a,b).
when it becomes filled with eggs (up to Humans can become infected with cys-
90,000) it has branched lateral extensions. ticerci from ingestion of eggs (or possibly
There are 7–13 main branches and this is occasionally by retroinfection of gravid
the feature used to differentiate the gravid proglottides), similarly to pigs; this is dis-
proglottides in faeces from those of T. sagi- cussed on p. 81.
 The Cestodes 79

Fig. 36. The invaginated protoscolex of a cysticercus of T. solium. That of T. saginata is identical apart
from the absence of hooks. (a) In section. (b) In solid view, arrow indicates beginning of evagination. (c)
Whole cysticercus after invagination in stomach of new host.

Human infection with the adult tape- perforate the wall of the intestine, very
worms occurs through eating raw or inade- rarely causing death.
quately cooked pork. The protoscolex There is often an eosinophilia of
invaginates in the duodenum (Fig. 36b, c), 10–13%.
and attaches to the mucosa of the small intes- Far more serious than the presence of an
tine, and the worm matures in 5–12 weeks. adult tapeworm of T. solium is human
infection with cysticerci.
CLINICAL MANIFESTATIONS AND PATHOGENESIS
Usually the presence of an adult tapeworm DIAGNOSIS
causes no distinct clinical symptoms or As for T. saginata. An immunoblot assay
signs. Sometimes vague abdominal pain, utilizing ES antigens is specific to adult T.
with diarrhoea or constipation, is found. solium infections (Williams et al., 1999),
Excessive appetite is also occasionally not reacting to T. saginata or to cases of
reported, with loss of weight and weak- cysticercosis. There are also specific anti-
ness. Symptoms may be psychological in body-based dot ELISAs for diagnosis of
origin or perhaps due to toxic waste prod- cysticercus antigens.
ucts produced by the worm.
There is usually slight traumatic damage TREATMENT
to the mucosa at the site of attachment of The theoretical risk with T. solium infec-
the scolex, although it has been known to tion that regurgitation of proglottides
80 Chapter 2

caused by chemotherapy will lead to Jaya) 3–42.7%, (Sumatra) 9.5%, Mexico

hatching of the eggs and subsequent cys- 1.5%, Nigeria (plateau) 3.8%, (eastern) 8.6%,
ticercosis does not appear to be important (northern) 11.5%, Peru 3.0% (8.6% in
in practice. None the less, it may be advis- chicharroneros or pork sellers), Reunion
able to give an antiemetic and follow treat- 1.4% and Zimbabwe 12%. Cysticerci rates in
ment with a saline purge. pigs are: Cameroon 24.6%, Colombia 26%,
Praziquantel at 5–10 mg kg1 in a single Egypt 0.1%, Honduras 4.0%–27%, India
oral dose is usually completely effective (Andhra Pradesh) 4.5–8.0%, (Karnataka)
against adult worms. 7.0%, (Uttar Pradesh) 9.3–15.5%, (Assam)
Niclosamide at an oral dose of 2 g for an 27.5%, Indonesia (Bali) 13%, Mexico
adult given in a divided dose over 2 days is 4–33%, Nigeria (northern) 3.3%, (eastern)
effective and causes only minor side- 20%, Tanzania 13.3% and Togo 17%.
effects, although syncope has been
reported. It appears to disturb mitochon- PREVENTION AND CONTROL
drial phosphorylation. Thorough cooking of pork and pork prod-
ucts is essential. Cysticerci are killed by a
EPIDEMIOLOGY temperature of 45–50°C, but may survive in
Infection with T. solium is nowhere near as large pieces of meat if the centre does not
common as with T. saginata, presumably reach that temperature. Deep-freezing at
because pork is not so often eaten under- 10°C for 4 days kills all cysts, but they
cooked as beef. In Bali, however, ‘lawal’, a can survive for 70 days at 0°C. Pickling and
dish of often uncooked spiced pork is popu- salting is not usually effective. At 18–20°C,
lar and taeniasis is common (although this cysts can survive the death of the host for
is probably due to T. saginata asiatica). In up to 4 weeks.
many areas the recorded infection rate in Inspection of meat at the abattoir is
pigs (and sometimes also the cysticerci rate important; the underside of the tongue can
in humans) is very much higher than the be examined in life and the intercostal and
recorded infection rate of adult tapeworms cervical muscles after slaughter.
in humans would indicate and it is likely
that gravid proglottides are sometimes mis- ZOONOTIC ASPECTS
taken for those of T. saginata. Humans are the only definitive hosts for
Unhygienic disposal of human faeces is the adult tapeworms. Both humans and
the primary means of dissemination; the pigs are necessary for the complete life
eggs surviving on pastures for many weeks. cycle. Cysticerci can develop in wild boars
In a rural area of Mexico many households and have been found in the lar gibbon
(38%) have pigs and all eat pork (often (Hylobates lar), in which adult tapeworms
measly or ‘granos’ pork). There are poor will also develop experimentally. Cysts
personal and household standards of have also been reported from sheep, dogs
hygiene and pigs routinely eat human fae- and cats but these may not be those of T.
ces (Sarti et al., 1992, 1994). solium.
It is not known how long cysticerci can
survive in the pig, but, since degenerated Cysticercosis
cysts are rare, it is probable that they
remain viable throughout the lifetime of In addition to infection with adult Taenia
the animal. solium, human infection with the cysticer-
Estimated human infection rates in areas cus stage normally found in pigs can also
of various countries are: Brazil 13%, Bulgaria occur and is the cause of an important and
1.4% (0.7% in 1989), Cambodia 2.2%, Chile serious disease.
0.1% (0.7% in 1977), China (Shandung
Province) 0.3%, Guatemala 3.5%, Honduras SYNONYM
0.3 (large-scale survey)–17%, India (Uttar Taenia solium cysticercosis, cysticercus
Pradesh) 2.0%, Indonesia (Bali) 7.1%, (Irian cellulosae (in pigs).
 The Cestodes 81

DISEASE AND LOCAL NAME CLINICAL MANIFESTATIONS

Cysticercosis; bladder-worm infection. Clinical disease is usually caused by the
presence of cysts in the brain (Plate 9). The
GEOGRAPHICAL DISTRIBUTION incubation period from ingestion of eggs to
All areas where adult T. solium infection the development of symptoms of cerebral
occurs. Estimated cysticercosis infection cysticercosis is normally 5–15 years,
rates in some endemic areas are: Benin although it can be much less.
4.0%, Brazil (São Paulo) 0.27%, (Minas Characteristic nervous manifestations
Gerais) 18.3%, China (Shandung Province) are epilepsiform attacks of the Jacksonian
0.7%, Ecuador 14.4%, Guatemala 3.5%, type, but minor symptoms are also very fre-
Indonesia (Irian Jaya) 17–43%, Madagascar quent. Cysticerci scattered throughout the
(large-scale survey) 18%, Peru 6–10% in brain may produce a variety of symptoms,
endemic areas, Reunion 8.2%, South motor, sensory or mental, with the result-
Africa (Transkei) 5.5–13.5% and Togo ing classical features of any focal lesion,
(north) 2.4%. Other endemic areas are and various focal symptoms and signs
Colombia, India, Korea, Mexico, New may occur in the same patient. The most
Guinea, West Africa and Zimbabwe. frequent of these are transient monoplegic
paraesthesia, localized anaesthesia, visual
MORPHOLOGY and aural symptoms, aphasia and amnesia.
The fully developed cysticercus measures Convulsions and seizures are common
10 mm
5 mm with an opaque invagi- (1.5% of cysticercosis patients in Benin,
nated scolex (protoscolex) with four suck- 9.5–14.2% in Brazil, 14.4% in Ecuador),
ers and hooks and a fluid-filled bladder; it but there may be unconsciousness without
is identical to the cyst normally found in convulsions, and headaches can be severe.
pigs. Development to the infective stage There is some evidence that in Latin
usually takes 9–10 weeks. A characteristic America cases of neurocysticercosis have
feature, apparent in sections of most ces- fewer subcutaneous cysts than similar
tode tissues, is the presence of numerous cases in other parts of the world.
calcareous corpuscles.
PATHOGENESIS
TRANSMISSION This depends very much on the localiza-
This is by the accidental ingestion of eggs tion of the cysts in the body. They are nor-
of T. solium which have been passed in mally spread throughout the body roughly
human faeces, presumably on vegetables or in proportion to the weight of each organ,
in water. In Indonesia, very young children the most important serious effects being
may have cysts, apparently from ingesting caused by cysts in the central nervous sys-
eggs on sweet potatoes, but rarely have tem.
adult tapeworms below the age of 5 years
DIAGNOSIS
(Simanjuntak et al., 1997). About 25% of
patients with cysticercosis also harbour an Clinical and parasitological. Palpable subcu-
adult tapeworm and this led to the belief taneous nodules can sometimes be felt and
that autoinfection may follow the regurgita- diagnosis confirmed by biopsy (Fig. 37),
tion of proglottides into the stomach, although the hooks are not always seen in
caused by antiperistalsis; however, there is tissue sections.
no proof of this. It has been shown experi-
mentally that oncosphere (hexacanth) lar- Radiological. X-rays will only detect old
vae in eggs must pass through the stomach cysts that have calcified (Fig. 38). CT and
before they can excyst and the usual course MRI scans are helpful, particularly for neu-
of self-infection is likely to be from anus to rological cases, and portable ultrasound
fingers to mouth or from eggs on vegetables has been useful in the field (Macpherson,
or perhaps in water. 1992).
82 Chapter 2

Fig. 37. Section of cysticercus in human muscle. Arrow points to the hooks.

sensitive and specific (Hubert et al., 1999).

A Western blot technique, using commer-
cially available affinity purified glyco-
protein antigen strips, is even more
sensitive.

TREATMENT
Treatment with praziquantel at 50 mg kg1
daily for 10–15 days has some effect while
the cysts are still alive (treatment at double
this dose for 21 days has been used in non-
responding cases). Albendazole at 15 mg
kg1 daily for 30 days and flubendazole at
40 mg kg1 daily for 10 days have also been
used, with variable results..
Neurocysticercosis may need to be
treated with anti-inflammatory agents and
anticonvulsants.

EPIDEMIOLOGY
It has been estimated that in Latin America,
where about 75 million people live in
endemic areas there are 0.4 million sympto-
Fig. 38. Radiograph of the thigh region of a young
matic cases, with 24,000–39,000 cases in
adult with numerous calcified cysticerci (these can
be visualized while still living by CT or ultrasono- Peru in highland and high jungle areas
graphy (US) scans). (Bern et al., 1999); in a survey of soldiers in
Mexico City, 14.7% were infected (they
often ate pork from street vendors).
Serological. There have been numerous
recent studies and an ELISA using Taenia crassiceps (Zeder, 1800) Rudolphi,
recombinant antigens was found to be both 1810, is a tapeworm of dogs and wild car-
 The Cestodes 83

nivores with cysticerci in various rodents, lymph) and normally develops only in the
and human cases have been reported from brain or spinal cord. Once lodged, the
Canada and the USA. The cysticercus (‘cys- embryo grows into a bladder-worm stage,
ticercus longicollis’) in the intermediate known as a coenurus. This differs from a
host is unusual, as it multiplies by a cysticercus in measuring about 3 mm in cir-
process of asexual budding and produces cumference and in having as many as 100
many hundreds of new cysticerci. In a protoscolices invaginated from the wall into
recent patient who also had AIDS, there the central cavity. Each protoscolex mea-
was a painful spreading tumour in the sub- sures 3 mm in length and has 26–36 hook-
cutaneous tissues containing a tapioca-like lets in two rows.
material with numerous cysticercus-like The normal intermediate hosts are
small vesicles and with a marked granulo- sheep and goats, in which the coenurus in
matous reaction (Francois et al., 1998). the brain is known as a ‘gid worm’, produc-
Small tapeworm cysts (up to 1 mm) were ing the ‘staggers’, but development may
recovered post-mortem from all the deep also occur in cattle, horses and other rumi-
organs of a man in the USA who died with nants, as well as humans.
Hodgkin’s lymphoma (Connor et al., 1976).
These might be multipying metacestodes of CLINICAL MANIFESTATIONS AND PATHOGENESIS
an animal taeniid, such as T. crassiceps, or In the majority of human cases from tem-
aberrant cysticercoids of Hymenolepis perate countries, including Australia,
nana, which behave similarly in immuno- France, Great Britain, Russia, South Africa
suppressed mice (Lucas et al., 1979). and the USA (six cases), the coenurus has
been in the brain. However, in many cases
from tropical Africa; in Ghana, Nigeria,
Taenia multiceps
Senegal and Uganda, a cyst often presents
Leske, 1780
as a subcutaneous or intramuscular nodule,
SYNONYMS diagnosed as a lipoma, ganglion or neurofi-
Multiceps multiceps (Leske, 1789) Hall, broma (Fig. 39). A papillary oedema with
1910; Coenurus cerebralis (Batsch, 1780) punctiform haemorrhages occurs about a
Rudolphi, 1808 (larvae); Multiceps gaigeri month before the onset of clinical signs.
Hall, 1916 (larvae in goats). Symptoms include headache and vomiting.
In many human cases (over 50%) cysts are
DISEASE sterile, without the presence of protoscol-
Coenurus infection; cerebral coenuriasis or ices, which makes diagnosis difficult.
coenuriosis; multicepsosis (adults in carni- There is no clinical way of differentiating
vores). infection with this parasite from cases of
cysticercosis or echinococcosis (apart from
MORPHOLOGY AND LIFE CYCLE imaging techniques).
The adult taeniid tapeworm is a natural par- A fatal cerebral case in a Nigerian
asite of dogs and wild Canidae. The strobila resulted in intermittent seizures, dizziness,
measures 40–60 cm and the scolex has a ros- headaches and blindness. At autopsy
tellum with two rows of hooks (large hooks numerous cysts measuring 0.5–2.0 cm were
measuring 150–170 µm, small ones 90–130 found in both cerebral hemispheres
µm) of typical taeniid shape. The gravid (Malomo et al., 1990).
proglottid has 18–26 small branches to the Treatment has been with praziquantel
uterus and is passed in the dog’s faeces. The but concern has been expressed that it
eggs are identical to those of Echinococcus might cause inflammation.
in dogs or human Taenia and measure 31–36 In Uganda, cases in the eye may be due
µm in diameter; when ingested by a suitable to Taenia brauni (Setti, 1897), with dogs
intermediate host, the oncosphere is liber- and wild carnivores as normal definitive
ated and bores through the wall of the intes- hosts and rodents as intermediate hosts
tine. It is then carried by the blood (or (Fig. 40).
84 Chapter 2

sucker
0.5 mm

hooks

Fig. 39. Section of a portion of a coenurus cyst removed from the neck of a child.

Fig. 40. Sagittal section through an eye with a coenurus in the vitreous chamber from Uganda (possibly
of Taenia brauni).

Taenia serialis (Gervais, 1847) is a tape- from the USA, usually in nervous tissue
worm of the dog and other carnivores with and sometimes with extensive involvement
coenuri in herbivorous mammals (rabbits (Ing et al., 1998). One case was treated with
and hares) and primates in Africa (Senegal, praziquantel but this caused marked
South Africa and Uganda), the Americas inflammation. Intramuscular cysts in a man
(Brazil and the USA) and Europe (France in Nigeria were ascribed to Taenia glomer-
and the UK). Six cases have been reported atus Railliet and Henry, 1915.
 The Cestodes 85

Adults of Taenia longihamatus immature, the penultimate sexually

Morishita and Sawada, 1966, have been mature, with both male and female organs,
recovered from the intestine of humans in and the last gravid, with a uterus filled
Japan and Okinawa, probably from ingest- with eggs. The gravid proglottid measures
ing cysts in rabbits. 2.0 mm
0.5–1.0 mm, more than half the
length of the whole tapeworm, and con-
tains about 5000 eggs. In the mature
Echinococcus granulosus
proglottid there are usually 45–60 follicu-
(Batsch, 1786) Rudolphi, 1805
lar testes scattered throughout. The cirrus
SYNONYMS sac is well developed and the common
Taenia echinococcus Von Siebold, 1853 genital pore opens, irregularly alternating,
and many others. on the lateral margin. The principal mor-
phological features are shown in Fig. 41
DISEASE, POPULAR AND LOCAL NAME and the differences between the species
Cystic echinococcosis (CE); hydatid dis- that occur in humans in Table 5.
ease. Espespes (Turkana). The egg measures 30–37 µm in diameter
and is indistinguishable from that of
GEOGRAPHICAL DISTRIBUTION Taenia species found in the dog. It can sur-
Echinococcus granulosus is found in most vive for 6–12 months on soil and is the
sheep- and cattle-raising areas of the world infective stage for humans.
(Table 4) and there are also wild carni-
vore/wild herbivore cycles. Most human LIFE CYCLE
cases occur in the countries bordering the The gravid proglottides disintegrate in the
Mediterranean (European, Asian and North intestine and the eggs are passed out in the
African), sub-Saharan Africa (East Africa, faeces of the dog. Eggs can live for 200 days
Nigeria and South Africa), South America in the environment at 7°C, 50 days at 21°C
(Argentina, Bolivia, Brazil, Chile, Peru and but only a few hours at 40°C. They are
Uruguay), eastern Europe and Eurasia ingested on pasture by the intermediate
(Bulgaria, Central Asian Republics, Poland, host, which is usually sheep in the strain
Romania and Russia) and in Asia transmissible to humans, but may be other
(Bangladesh, north-western and central herbivores coming into contact with dogs
China, northern India and Nepal). It was such as cattle, buffalo, goat, pig or camel.
introduced into the western USA (Arizona, Ingested eggs hatch in the duodenum, the
California, New Mexico and Utah) about 60 embryophore being digested by the action
years ago and is important in Australia. of pancreatin and trypsin, and the con-
tained oncosphere probably being activated
LOCATION IN HOST by the action of bile salts. The released
The larval cysts (hydatid cysts) are found oncosphere uses the hooklets to penetrate
in various sites in humans, principally the the mucosa and reach a blood-vessel. It is
liver and lungs. carried by the bloodstream to all parts of
the body but settles most frequently in the
MORPHOLOGY liver (in up to 76% of cases), due to capil-
The adult tapeworm becomes attached to the lary filtering. Arrived at its final destina-
small intestine of dogs and other carnivores tion, the hooklets disappear and a small
and comprises a scolex, neck and 3–5 cyst forms. The cyst (metacestode stage)
proglottides. It is always less than 1 cm in measures about 1 mm in diameter after 1
length, usually 3–8.5 mm. The spherical month and 10–55 mm after 5 months, by
scolex has a rostellum with 28–40 hooks in which time brood capsules and protoscole-
two rows (with large hooks measuring 30–40 ces are forming. The cyst wall consists of an
µm in length and small hooks 22–34 µm) and external, anucleate, laminated cuticular
four suckers. membrane (composed of a chitin-like sub-
The first one or two proglottides are stance), about 1 mm thick, and an inner
86 Chapter 2

Table 4. Estimates of percentage prevalence of hydatid cysts in humans and domestic animals and of
adult Echinococcus granulosus in dogs in various countries.
Hydatid cysts (%)
Country Humans Sheep and cattle Adults in dogs

Argentina
La Pampa 0.03
Chaco 0.019 2.3
Australia 170 cases in 10.2
3 years 48–93 (wild)
Azerbaijan 0.0014 20 15
Bulgaria 0.003–0.006 32 7
Chile 0.009 5–22 8
China
Xinjiang 0.044 10–89 10–40
6.8–18.2 locally
Gansu 12 locally 2 (4 in yaks) 7–27
Ningxa 56
Quinghai 7.6 locally 22–80 11–47
Germany
Bavaria 0.0011
India 60
Iraq 10 20–56
Iran 3 2–7 3–63
Israel 0.01 8
Italy
North 0.002
Sardinia 0.017 50
Jordan 0.0029 9.4
Kazakhstan 0.0044
0.015 locally
Kenya 10–16 5–30 10–72
Kuwait 0.0036
Libya 0.0017–2 16 (48 in camels) 30
Morocco 5–45 33
Nepal
Kathmandu 1.8–5.7
Peru 0.009 8–46
Southern Sudan 0.5–3.5
Switzerland 0.0004
Tanzania
Maasailand 0.011 30
Tunisia 0.057–3.5
Turkey 3 (Izmir) 50 8–29
Uruguay
USA
Florida 0.0056 60 13.2
Mid-Wales 0.0023 13 9.2

germinal layer, 10–25 µm thick, with many develop into invaginated protoscolices with
nuclei (Fig. 42). The germinal layer forms four suckers and a double row of hooks.
small masses, which give rise to the brood Many small brood capsules and freed proto-
capsules. These enlarge and 5–20 small scolices are released into the fluid of the
buds, about 0.1 mm in diameter, appear on original cyst and, together with calcareous
the inner surface of their walls. They bodies, form the ‘hydatid sand’ (Fig. 43). In
 The Cestodes 87

(b)

(a)

0.5 mm

testes

Mature
proglottid ovary

vitellaria

Gravid
proglottid

eggs in
uterus

genital
pore

Fig. 41. Diagrams of adult (a) E. multilocularis and (b) E. granulosus.

addition to the sand grain-like proto- The cysts are ingested in offal by dogs and
scolices, there may be many large, thin- the adult worms become mature in the intes-
walled, daughter cysts inside the outer tine of the carnivore in 6–7 weeks. There
hydatid cyst. The host tissues, especially in may be many thousands of worms in wild
the liver, form an adventitious fibrous wall carnivores in tropical Africa and Australia
around the cyst. Fertile cysts may vary in but usually only a few hundred in domestic
size from 10 to 300 mm. The cyst cavity is dogs (Macpherson and Craig, 2000).
filled with a bacteriologically sterile fluid,
which is clear or slightly yellowish, with a CLINICAL MANIFESTATIONS
specific gravity less than 1.012. The fluid These depend very much on how many
contains salts (with a higher concentration hydatid cysts are present and where they
of sulphur than in other parasitic cysts) and are found. Cysts are usually single and in
enzymes, plus a little protein and toxic sub- about 50% of infected adults are in the
stances. right lobe of the liver towards its lower
88 Chapter 2

Table 5. Differences between Echinococcus species.

E. granulosus E. multilocularis E. oligarthrus
Length of adult 3.0–6.0 mm 1.2–3.7 mm 2.2–2.9 (2.5) mm
Size of gravid More than half Less than half More than half
segment body length body length body length
Position of genital pore Behind midline On or anterior Anterior to
in gravid segment to midline midline
Average number of testes 56 (45–65) 22 (16–26) 29 (14–46)
Number of testes anterior 15.8 (9–23) 2.3 (0–5) 8.9 (3–14)
to genital pore
Shape of ovary Bilobed or Two lobes Two lobes
kidney-shaped united by a fine tube united by a fine tube
Shape of uterus Branching of central No side-branching No side-branching
column (12–15 of central column of central column
lateral branches)
Number of rostellar hooks 32 (28–40) 28 (20–36) 35 (26–40) (larger
hooks than the others)
Number of segments 3–4 3–5 3
Position in intestine Middle and lower Upper and middle Upper and middle
third ileum jejunum jejunum
Usual definitive Dog, coyote, dingo, Red fox, Arctic fox, Puma, bobcat,
hosts wolf, hyena, jackal cat (dog) jaguarundi
Usual intermediate Ruminants Microtine rodents Agouti
hosts and insectivores
Time for development 48–61 days 30–35 days ?
to maturity in final host
(i.e. eggs in faeces)
Structure of cyst Usually a thick- Thin-walled multilocular, Polycystic
walled hydatid cyst with many small hydatid
interconnected cysts
Rate of development Slow. Adapted Rapidly developing. Probably
to long-lived Adapted to short-lived rapidly
intermediate hosts. intermediate hosts. developing
Protoscolices Infective protoscolices
after 1–2 years after 2–3 months

brood capsule

protoscolices

germinal
layer
laminated
cuticular layer
outer fibrous
layer

Fig. 42. Section of a portion of an early hydatid cyst of E. granulosus (the outer fibrous layer
consists of host tissues).
 The Cestodes 89

hooks

sucker

calcareous
bodies

(a)

50 m (b)

Fig. 43. Protoscolex of E. granulosus free inside a cyst (‘hydatid sand’). (a) Invaginated as in cyst.
(b) Evaginated in gut of a new definitive host (dog).

surface, while the lungs are involved in up and sometimes not for 20 years after expo-
to 40% of cases. In children cysts are some- sure (Fig. 44). In a proportion of cases (pos-
times diagnosed more often in the lungs sibly up to 60%; Eckert et al., 2000) the
than in the liver. presence of the hydatid never becomes
Symptoms and signs are those of slowly apparent during life and the cysts eventually
increasing pressure in the area of the cyst, calcify and are only diagnosed at autopsy.
resembling a slowly growing tumour. The If a cyst ruptures, allergic reactions,
incubation period is usually at least 5 years such as pruritus and an urticarial rash,
and, except for cysts in the brain or orbit, occur. If the patient has been previously
symptoms rarely appear before adolescence sensitized by slow leakage of antigenic

Fig. 44. Group of Turkana people waiting for an operation to remove hydatid cysts.
90 Chapter 2

material from the cyst, there may be acute

anaphylactic shock, with gastrointestinal
disturbances, dyspnoea and cyanosis.
Death may result from pulmonary oedema
caused by the shock of a cyst rupturing in
the lung, the severity of the effect possibly
being potentiated by anaesthesia. In a few
cases the anaphylactic shock reaction pro-
vides the first intimation of disease.
Eosinophilia is present in less than a
quarter of cases of hydatid.

PATHOGENESIS
The pathology caused by the presence of a
single unilocular cyst depends very much
on its site in the body.
In over 90% of liver cysts, the onco-
sphere is trapped in the central veins of the
hepatic lobules; only occasionally does it
lodge in the portal vein. The resultant cyst
may be deep or superficial and it causes
compression of the liver cells, which can
lead to biliary stasis and cholangitis. The Fig. 45. Bronchogram showing blockage of
cholangitis arises because of secondary bronchus caused by a cyst of E. granulosus.
infection, sometimes following the rupture
of a cyst into the biliary tract. Because of
compression, the cyst may take many
result, many small cysts form, which
shapes and often gives the mistaken
destroy the cancellous bone, long bones
impression of being multivesicular with
sometimes collapsing without warning.
many finger-like processes.
Renal cysts sometimes occur and, if they
Lung cysts are more spherical than
burst into the kidney pelvis, may become
those in the liver because of the spongy
secondarily infected, but these and pancre-
nature of the pulmonary tissues (Fig. 45).
atic cysts are usually silent. Splenic cysts
The cysts are always intracapsular and
are often palpable and cause pain and dis-
their rupture may result in protoscolices
comfort in the left upper quadrant.
being coughed up in the sputum.
Sometimes only hooks can be seen, which
DIAGNOSIS
can be recognized microscopically. The
presence of bile in the sputum is suggestive Clinical and parasitological. Symptoms of a
of a hepatic cyst that has ruptured through slow-growing tumour if accompanied by
the diaphragm. Haemoptysis (blood in the eosinophilia in a patient from an endemic
sputum) can result from rupture of the pul- area are suggestive of a hydatid.
monary capillaries. Occasionally, the hydatid ‘thrill’ can be
About 3% of hydatid cysts occur in the elicited by tapping an abdominal cyst.
brain or spinal cord. The cysts are usually Protoscolices or hooks may be found in the
small and cause symptoms earlier than in sputum following rupture of a pulmonary
other sites. Most brain cysts are in the cyst. Needle aspiration is not to be advo-
white matter and are surrounded by a thin cated because of the danger of producing
adventitious layer. secondary infection or anaphylactic shock,
Osseous cysts, which form 1–2% of the but sometimes protoscolices are found
total, grow very slowly and have no wall as unexpectedly on a subsequent stained
they do not elicit any host reaction. As a smear.
 The Cestodes 91

Radiological. The cavity of a cyst usually ELISA kit is available (LMD Laboratories,
shows up as a characteristic shadow on X- Carlsbad, California). Immunoglobulin G4
ray, although cysts in the lungs cannot (IgG4) subclass antibodies appear to be most
always be differentiated from tumours important in serodiagnosis. E. granulosus
unless they become detached and float free. can be differentiated from E. multilocularis
The water-lily sign (sign of Camelotte) is infections by Western blotting using specific
caused by air filling the space between ecto- antigens and the test does not cross-react
cyst and pericyst, and the characteristically with any other parasitic infection or other
shaped air cyst containing debris shows up condition (Ito et al., 1999).
on X-ray. In the last few years many new and
more accurate non-invasive techniques have TREATMENT
been used. CT is widely used (Fig. 46) and
both CT and MRI can be used for diagnosing Surgery. This is still the most common
deep-seated cysts and also for estimating the form of treatment, particularly when the
size of cysts (this can be useful for evaluating cysts are large and in a site such as the
chemotherapy). Thin, ring-shaped or cres- brain or heart. Great care must be taken
centic calcifications surround the cysts in that the cyst wall does not burst, as
5–10-year-old infections. Completely calci- released living protoscolices can be carried
fied cysts are not likely to be pathogenic if to new sites by the bloodstream and form
causing no symptoms. Ultrasonography (US) new cysts (Plate 10). The cyst cavity can be
is another cheaper technique that can be sterilized with an injection of 0.5% silver
very helpful for diagnosis of liver cysts and a nitrate or 2% formalin. For further safety
portable apparatus can be employed in the an exposed portion of the cyst can be deep-
field, making it particularly useful for epi- frozen before removing the sterilized con-
demiological surveys in remote areas. tents. The laminated membrane of the
parasite usually separates readily from the
Immunodiagnosis. The indirect haemaggluti- fibrous host tissue reaction. No attempt
nation (HA) test with cyst fluid as antigen should be made to remove the adventitious
has been used for the last 25 years and gives fibrous layer in the liver, because of the
a sensitivity of about 80%. More recently, serious danger of bleeding. If the cyst is too
ELISA and dot ELISA techniques, using large for closure of the cavity to be possi-
hydatid cyst fluid (fraction B, containing an ble, marsupialization may be necessary.
antigen of 8 kDa) as antigen, give over 90% Pulmonary cysts are preferably removed
specificity and sensitivity and a commercial by enucleation of the intact cyst by making

Fig. 46. A computer-assisted tomography (CT) scan of the liver visualizing a large cyst of E. granulosus.
92 Chapter 2

an incision through the adventitia, aided Four species of Echinococcus are gen-
by increasing the intrapulmonary pressure erally recognized (E. granulosus, E. multi-
with an inflated cuff tube in the trachea. locularis, E. oligarthrus and E. vogeli) but
Cysts in the long bones are very difficult to the characteristics of E. granulosus differ
deal with and may call for amputation. greatly in various parts of the world and in
Removal of a cyst is followed by a recur- different intermediate hosts (Thompson
rence in up to 25% of cases, possibly and Lymberry, 1995; Thompson et al., 1995;
caused by release of protoscolices during Eckert and Thompson, 1996; Lymberry and
operation, but more probably by increase Thompson, 1996). These are usually desig-
in size of another small silent cyst when nated as strains, but with sequence data
the first is removed. Mortality is about 2% from mitochondrial and nuclear genes the
in primary operations but is much higher if molecular distances between some strains
another operation is required. can be greater than between the recognized
Percutaneous aspiration under US guid- species (Bowles et al., 1995).
ance, followed by irrigation with hyper- The principal strains are given below,
tonic (20%) saline, has been used for liver with suggested specific names in square
cysts causing obstructive jaundice and brackets (Rausch, 1995; Thompson et al.,
endoscopy for evacuating biliary cysts and 1995):
for irrigating the main liver cyst. Similar
guided percutaneous aspiration of liver 1. Dog/sheep (also goat and other herbi-
cysts in general, followed by injection of vores) strain, which is cosmopolitan and
95% sterile ethanol, puncture, aspiration, uniform (European biotype) [E. granulosus].
injection and reaspiration (PAIR) and then 2. Wolf/wild cervids (moose and reindeer)
a course of chemotherapy is proving to be strain in northern Alaska, Canada, Eurasia
an alternative to surgery. and Scandinavia (northern sylvatic bio-
type) [E. granulosus].
Chemotherapy. This is with albendazole or 3. Dog/cattle or buffalo strain is found in
mebendazole at high dosages over a long Asia, Europe and South Africa and is
period; the former is slightly more effective genetically very distinct from the others
as it is absorbed better. Albendazole is given [E. ortleppi].
at 10 mg kg1 daily and mebendazole at 50 4. Dog/horse strain is widely distributed
mg kg1 daily, both for at least 3 months. but does not appear to be infective to
Prognosis is uncertain but about one-third humans [E. equinus].
of patients appear to be cured and about 5. Dog/pig (and camel?) strain in North
two-thirds improved. Side-effects are com-
and East Africa and the Middle East, east-
mon while the drugs are in use, including
ern Europe, Russia and Mexico is also
possible liver toxicity. The drugs will prob-
probably not infective to humans [E. suis?].
ably be of use before and after surgery (to
6. Dingo/marsupial strain in Australia and
prevent the growth of new cysts).
wild carnivore/wild suid strain in Africa
Praziquantel is also being evaluated but its
are probably the same as dog/sheep strain
effectiveness has not been proved (Craig,
[E. granulosus].
1994); however, there is evidence that it has
a synergistic effect when used at 25 mg kg1
week1 for 7–14 days and then 40–50 mg PREVENTION AND CONTROL
kg1 once a week for 8 weeks together with Personal prevention is by taking hygienic
albendazole. measures to avoid eggs voided from dogs
being ingested, particularly by children.
EPIDEMIOLOGY Control measures should include the sani-
Although echinococcosis is not a common tary disposal of offal following slaughter of
disease in most endemic areas, its serious sheep, goats and cattle, both in small abat-
nature and the difficulty of cure make it an toirs and at home (often for religous festi-
important public health problem in many vals), and campaigns to treat dogs (Meslin
countries. et al., 2000). Dogs can be successfully
 The Cestodes 93

treated with praziquantel (at 5 mg kg1) or cestodes. There have been many experi-
the older arecoline hydrobromide, mental studies on taeniid metacestodes in
although reinfection is common. Infections domestic animals, such as sheep, as well as
in dogs can be specifically diagnosed using in rodents, and detailed studies have been
an ELISA for detection of coproantigens made of hydatid disease and cysticercosis
(Craig et al., 1996). In sheep-rearing areas, in humans. Humans infected with these
the treatment of farm dogs is particularly parasites make strong antibody responses
important. In North African countries, and these can be used in diagnosis. The
there are often high infection rates in feral antigens of hydatid cysts and the cysticerci
dogs which feed on discarded offal, and of T. solium have been analysed in detail;
these might have to be killed. two (antigen 5 and antigen B) can be used
The disease has been eliminated from as diagnostic antigens for both conditions.
Iceland in the last 100 years by a combina- The immunological relationships between
tion of treatment of dogs and public health hydatid cysts and the host are complex.
measures, particularly by preventing offal There is evidence for antiparasite
from reaching dogs. There used to be very responses, and for specific and non-specific
high infection rates and pamphlets pointing immune suppression. Established cysts can
out the importance of control, first distrib- survive in hosts that are resistant to incom-
uted in 1863, provided welcome reading ing larvae (concomitant immunity) and evi-
matter in the long winter nights. Changes in dence from animal studies suggests that
animal husbandry, involving slaughtering of resistance operates against larvae at an
lambs rather than older sheep, so that cysts early stage, particularly invading oncos-
have no time to develop, also aided eradica- pheres and developing cystic stages. Fully
tion (the last case was diagnosed in 1960). developed cysts are surrounded by thick
The disease was eradicated in New Zealand protective layers and possess a variety of
50 years ago by similar measures, including defensive mechanisms that reduce the
compulsory dosing strips, followed by effectiveness of host responses (e.g. inacti-
infection checks for dogs, and a successful vation of complement).
campaign was carried out in Tasmania. Recombinant vaccines have been devel-
Infection has returned (or was not com- oped that provide protection against the
pletely eliminated) in Cyprus, which is now cysts of Taenia ovis in sheep, T. solium in
in the consolidation phase, and there are pigs and E. granulosus in sheep. The anti-
control campaigns under way in regions of gen Eg95, a specific protein on the onco-
Argentina and Chile, the Falkland Islands, sphere coat of E. granulosus has been
northern Kenya, Extramadura (Spain) and expressed as a fusion protein with soluble
western Australia. However, prevalences are glutathione-S-transferase (GST) from a
rising in most countries of eastern Europe, schistosome. Purified and injected into
as controls have been relaxed. sheep, this fusion protein gave 98% protec-
tion against subsequent egg infection for at
IMMUNOLOGY OF TAPEWORM INFECTIONS AND least 12 months in field trials in Argentina
POSSIBILITIES FOR VACCINES and Australia. The vaccine, which is stable
There is little or or no evidence for immu- for over 1 year, protects against the estab-
nity in humans against adult tapeworms lishment of cysts in sheeps; human trials are
and reinfection occurs readily. Infected also envisaged. A similar vaccine against
humans do make immune responses, how- the larvae of T. ovis, which is of veterinary
ever, and antibodies can be demonstrated importance with a cycle involving dogs and
in serum. Immunity can be demonstrated sheep, is already commercially available,
against intestinal tapeworms in rodents, with 98% protection against natural infec-
but the underlying mechanisms are still tions in pastures, and is also likely to have
not clear. Much more is known about future relevance for human tapeworm infec-
immunity and immune responses to larval tions (Lightowers et al., 2000).
94 Chapter 2

Echinococcus multilocularis (Vulpes vulpes) fox, and occasionally the

(Leuckart, 1863) Vogel, 1955 dog and cat, while the usual intermediate
hosts are the field mouse in Europe and the
SYNONYMS field or red-backed vole and lemming in
Echinococcus alveolaris Klemm, 1883; E. Alaska and Siberia (and possibly 27 other
sibiricensis Rausch and Schiller, 1954; species of rodent). On Rebun Island, Japan,
Alveococcus multilocularis Abuladse, 1959. the cat and red fox act as hosts for E. multi-
locularis but cannot be infected with E.
DISEASE granulosus.
Alveolar echinococcosis (AE). When natural hosts, such as the vole
(Microtus) ingest eggs on vegetation passed
GEOGRAPHICAL DISTRIBUTION out by the definitive host, growth of the cyst
Infection in animals is principally holarctic in the liver is rapid, with extensions from the
and occasional human cases occur in germinal membrane invading the adventitia
Austria (Tyrol), central Europe, southern and forming numerous, minute, intercon-
Germany, Switzerland, Belarus, Russia nected, secondary vesicles in about 9 days.
(northern tundra areas, Caucasus and By 150 days the alveolar vesicles are almost
Siberia), Ukraine, Central Asiatic filled with protoscolices and the weight of
Republics, China, Alaska (and nine other the liver may exceed that of the rest of the
states in the USA), Canada, Bering Sea body (Fig. 47). This rapid growth is an essen-
islands, Japan (Hokkaido and Rebun) and tial adaptation to a short-lived intermediate
north-western Pacific. host. In the winter, when the hosts are hiber-
nating, the cysts stop developing. It is proba-
MORPHOLOGY ble that when they continue growing in the
The adult tapeworms are one-third to one- spring they impair the vitality of the animal,
half the size of E. granulosus; other differ- so that it is more easily caught by a carnivore.
ences are shown in Fig. 41 and listed in Infected rodents rarely live for more than 5–6
Table 5. months. Ingested protoscolices take 26–28
days to develop into mature adults in the
LIFE CYCLE intestine of the carnivores.
This is similar to that of E. granulosus
except that adult tapeworms are found in CLINICAL MANIFESTATIONS
about seven species of wild carnivore, prin- Cysts resemble a slowly growing malignant
cipally the Arctic (Alopex lagopus) and red growth in the liver, making this the most

Fig. 47. Section of alveolar cyst of E. multilocularis from a liver of vole. The wall is thin and protoscolices
are embedded in a semi-solid matrix (cysts in humans are almost always sterile without protoscolices).
 The Cestodes
Map 6. Distribution of Echinococcus multilocularis.

95
96 Chapter 2

dangerous helminth infection of humans. cysts may be present in the lymph glands,
There are no symptoms due to pressure lungs and brain – almost always fatal.
effects, because of the absence of a thick- In patients susceptible to disease, there
walled hydatid cyst surrounded by a is a specific lymphoproliferative host
fibrous host reaction, although there is an response to cyst antigens containing pre-
outer laminated cyst layer, which appears dominantly CD8+ cells and a T-helper
to protect the parasite from host immune (Th2) cell response develops slowly, with a
responses. still unknown functional potential of inter-
The parasite destroys the liver paren- leukin 5 (IL-5). In a proportion of cases the
chyma, bile-ducts and blood-vessels, result- symptomless cysts become calcified and
ing in symptoms of biliary obstruction and contain no living cells and there is a
portal hypertension; necrosis of the cyst, marked host response containing primarily
with abscess formation may also occur. CD4+ T cells in the periparasitic granuloma
Hepatomegaly is often the first sign of infec- (Gottstein and Felleisen, 1995).
tion. There may be wasting in the later stages
and the condition is often mistaken for a car- DIAGNOSIS
cinoma. The cysts often metastase via the As for E. granulosus. US can be helpful.
bloodstream to form new cysts, particularly Serological tests using antigen obtained
in the lungs and brain. Clinical symptoms from protoscolices (Em2 or Em18) are
may not appear for 10–15 years after infec- extremely specific. Early diagnosis is very
tion but in untreated cases there is 94% important in determining the success of
fatality within 10 years. There is an surgery.
eosinophilia of over 5% in 15–20% of
patients. TREATMENT
Surgical resection of the liver is very difficult
PATHOGENESIS and prognosis is rather poor; however, about
In humans the multilocular or alveolar cysts 90% of non-resectable patients die within 10
form pseudo-malignant growths with a years. Liver transplantation has been
spongy mass of proliferating vesicles attempted in patients with advanced infec-
embedded in a dense fibrous stroma, almost tions (mortality rate of 30%).
always in the liver. They differ from the Very long-term chemotherapy with
hydatid cyst by the thinness of the outer albendazole (10–15 mg kg1 day1) or
layer, by exogenous budding and usually by mebendazole (50 mg kg1 day1) inhibits
the absence of protoscolices. The germina- the growth of cysts and prevents the occur-
tive membranes are hyperplastic and folded rence of metastases. Patients have a better
on themselves and the vacuole is filled with quality of life and greater longevity,
a gelatinous matrix rather than with fluid. although disease may recur, as both these
The germinal layer is often absent in human drugs appear to be parasitostatic, not para-
infections, so that there are no protoscolices sitocidal. Albendazole is better absorbed
present in 85% of cases, and many cysts but can occasionally be hepatotoxic, while
atrophy and disappear. Calcified cysts may there should be breaks – say, every 28 days
be found in Inuit at autopsy, undiagnosed – with both drugs to prevent leucopenia
during life. The relatively slow growth and (Tornieporth and Disko, 1994).
few germinal cells indicate that humans are
not very suitable hosts. EPIDEMIOLOGY
In humans cysts cause necrosis of the Prevalence rates in various countries (per
surrounding liver tissue with an oblitera- 100,000 population) are: Alaska 7–98,
tive endarteritis. The outer zone consists of China (Gansu) 2200, Central Europe
an inflammatory response, with the pres- 0.02–1.4, Germany (Bavaria) 0.6, northern
ence of giant cells and jaundice, and ascites Siberia 170, northern Russia in general 10,
might result from portal hypertension. Switzerland 0.18. There can be high infec-
Cysts sometimes metastase and secondary tion rates with adult tapeworms in the red
 The Cestodes 97

fox: Austria 3.6%, Czech Republic 10.6%, India, Panama, Surinam and Venezuela;
Germany 18.4%, Japan (Hokkaido) characteristic cysts have also been reported
52–67%, Poland 2.6%, Slovakia 10.7% from Argentina, Chile, Costa Rica, Mexico,
and Switzerland 35%. Nicaragua and Uruguay (these might have
The life cycle of E. multilocularis, been due to E. vogeli but are outside the
involving wild carnivores and rodents, usu- host range of the bush dog, its natural
ally involves ecosystems separate from definitive host).
humans so that human infection is much Cysts in humans are usually in the liver
less likely than with E. granulosus. (80% of cases), with most of the remainder
However, the distribution appears to be in the lungs, although there have been two
spreading in Europe, Japan and North orbital infections. Clinically, cysts in the
America (Eckert et al., 2000). In Arctic liver have caused abdominal pain,
regions 50% of tundra voles (Microtus hepatosplenomegaly, marked weight loss
oeconomus) may be infected at some time and fever, with the presence of hard, round,
of the year and 100% of Arctic foxes may masses. Ascites and obstructive jaundice
have up to 200,000 adult tapeworms. Many can also occur. Portal hypertension is found
human infections are reported from fur in about 25% of cases and often results in
trappers, who ingest eggs when skinning death following biliary drainage or partial
wild canids. Eggs may also be ingested on hepatectomy. The cysts are of the hydatid
salad vegetables during Arctic summer, as type but form polylobed masses (polycystic
they can withstand very low temperatures echinococcosis (PE) spilling into the peri-
(240 days at 18°C: a temperature as low as toneal cavity (Plate 11); the rostellar hooks
70°C is necessary to be sure they are are larger than those of other species.
killed). In Alaska and areas of Russia over Treatment is with albendazole at 10 mg
50% of dogs are infected. kg1 daily for 2–8 months and has given
In woodland and agricultural areas of encouraging results in most cases. Side-
central Europe, human infection is thought effects stop when treatment is finished.
to be primarily from eating fruits, berries
and vegetables (wild strawberries, cran-
berries, fallen apples and lettuce) picked Echinococcus vogeli
off the ground and contaminated with Rausch and Bernstein, 1972
faeces from foxes or dogs. Adults of this species are found in the bush
dog (Spetheos venaticus), with cysts in the
PREVENTION AND CONTROL paca (Cuniculus paca), in South and
Thorough washing of fruit and vegetables Central America. Human cases have been
likely to become contaminated. Chemo- reported from Argentina, Brazil (Amazon),
therapy of dogs is possible, as for E. granu- Ecuador and Surinam. Infection is very
losus. rare in humans, partly because the bush
dog avoids human habitations, and may
Echinococcus oligarthrus result from dogs that have been fed on the
(Diesing, 1863) Lühe, 1910 viscera of pacas. The polycystic hydatid
cysts (causing PE) are similar to those of E.
This species is in many features intermedi- oligarthrus but the outer membrane is
ate between the other two (see Table 5). thicker and the rostellar hooks on the
Adults occur in the jaguarundi (Felis protoscolices are smaller and morphologi-
yagouaroundi) in Panama, the puma (Puma cally distinct. Clinical effects are similar
concolor) in Panama and Brazil and the also, with both exogenous budding of cysts
bobcat (Lynx rufus) in Mexico. The inter- into the peritoneal cavity which grow in
mediate hosts are agoutis (Dasyprocta other organs and also endogenous budding
aguti). It is an infection of tropical sylvatic with daughter cysts inside the main cyst.
areas and identified human cases have Treatment with albendazole at 10 mg kg1
been reported from Brazil (Minais Gerais), daily for up to 10 months has some effect.
98 Chapter 2

Family Hymenolepididae Taenia solium) and has a short retractile

rostellum with a single row of 20–30 small
Hymenolepis nana hooks and four round suckers or acetabula.
(Von Siebold, 1852) Blanchard, 1891 The hooks are spanner-shaped, which is
typical of the family Hymenolepidiidae.
SYNONYMS
The neck region is long and slender (Fig.
Taenia nana Von Siebold, 1852;
48). Mature proglottides are broader than
Hymenolepis fraterna Stiles, 1906;
long (0.22 mm
0.85 mm), with a single
Vampirolepis nana.
common genital pore on one side of the
strobila or chain.
DISEASE AND POPULAR NAME
There are three round testes, which lie
Hymenolepiasis or hymenolepiosis nana;
dwarf tapeworm infection. in the posterior part of each proglottid. The
bilobed, coarsely granular, ovary lies post-
GEOGRAPHICAL DISTRIBUTION
eriorly between the testes with the compact
Cosmopolitan, particularly in children. vitelline gland behind it (Fig. 49). The
gravid uterus forms a sac filled with
LOCATION IN HOST 80–200 eggs.
The adults inhabit the lumen of the upper
three-quarters of the ileum, with the scolex LIFE CYCLE
embedded in the mucosa. There may be This is the only known human tapeworm
many thousands of tapeworms present in a that does not require an intermediate host.
heavy infection. The gravid proglottides are usually bro-
ken up in the colon so that free eggs are
MORPHOLOGY found in the faeces. The eggs measure
Hymenolepis nana is a very short tape- 30–47 µm (Fig. 123). They are spherical or
worm, measuring 15–40 mm
ovoid and are enclosed in two transparent
0.5–1.0 mm, and has approximately 200 membranes, the inner of which, the
proglottides. embryophore, is lemon-shaped and has
The scolex is spherical, about 0.3 in polar thickenings, from which arise 4–8
diameter (one-third the size of that of slender filaments (these are not always evi-

0.1 mm

H. nana H. diminuta
Fig. 48. Diagrams of the scolices of Hymenolepis nana and H. diminuta (see also Fig. 33).
 The Cestodes 99

vitellaria
ovary
cirrus

testis

0.1 mm
0.3 mm
0.25 mm

1 mm

Fig. 49. Mature proglottides of H. nana (left) and H. diminuta (right). Note the different scales – the
proglottides of H. diminuta are comparatively much larger than shown.

dent when the eggs are preserved). The with abdominal pain, diarrhoea, irritabil-
enclosed oncosphere measures about 18 ity, loss of appetite, vomiting and dizzi-
µm in diameter and has the usual six hook- ness, presumably due to systemic toxaemia
lets. The egg is immediately infective. caused by the waste products or to allergic
When ingested by another person, the responses. Epileptoid fits have been
oncosphere is liberated in the small intes- reported from children. Necrosis of the
tine and penetrates a villus by means of the mucosa has been found in rats but has not
hooklets. It then loses the larval hooklets been demonstrated to occur in humans.
and becomes a tailless cysticercoid (some- An eosinophilia of up to 15% occurs in
times known as a cercocystis) in about 90 about 7% of infected individuals.
h. This stage re-enters the intestinal lumen
after 4 days and develops into a tapeworm DIAGNOSIS
with mature proglottides in 10–12 days This is by the identification of eggs in the
(Fig. 50). Eggs are passed in the faeces faeces (p. 254 and Fig. 123).
about 30 days after infection.
Autoinfection is possible, eggs and freed TREATMENT
oncospheres having been obtained by Praziquantel at a single dose of 15 mg kg1
intestinal aspiration from an infected child. has about 80% effectiveness; the presence
This accounts for reports of infections last- of cysticercoids in the tissues may necessi-
ing many years although, in children tate re-treatment.
removed from an endemic area, the adult Niclosamide can be given at 60–80 mg
tapeworms live for only a few months. kg1 for 5 days and perhaps repeated 10
days later.
CLINICAL MANIFESTATIONS AND PATHOGENESIS
In most cases no symptoms can be attrib- EPIDEMIOLOGY
uted to a light infection but the presence of H. nana is more common in children than in
more than 2000 worms results in enteritis, adults, particularly children from institutions
100 Chapter 2

0.3 mm

Fig. 50. Diagrammatic section of adult and cysticercoid of H. nana in a villus of the ileum. In heavy
iinfections the mucosal lining may become abraded.

in tropical countries. Estimates in children 11 days. Infection is often from hand to

in regions of various countries are: mouth, although it may also be by food or
Argentina 10–15%; Bahrain 3%; Brazil water.
(Amazon) 11%, (Minais Gerais) 7%, (Rio)
1.4%, (Sao Paulo) 9–15%; Chile 0.4–4%; PREVENTION AND CONTROL
Côte d’Ivoire 1–7%; Egypt 6–20%; Ethiopia Hygienic measures are not always immedi-
0.6–1%; Honduras 8%; India 1–12%; Japan ately effective and eradication has been
2.3%; Mexico 3–5%; Nepal 7%; Pakistan very difficult in the past. As the eggs have
7–18%; Peru 23%; Romania 5%; Sudan so little resistance to desiccation, measures
7–10%; Tunisia 2%; Turkey 6–14%; can be directed against direct hand-to-
Uganda 0.5%; Venezuela 6–12%; mouth transmission and to cleaning of
Zimbabwe 21%. Large-scale estimates in clothes and bed-linen. The much improved
the general population are: Albania 1.5%; chemotherapy available in the last few
Australia (aboriginals) 55%; Bolivia 9%; years makes control considerably easier.
Cuba (overall) 0.008%; Dominican
Republic 2%; Ecuador 3–4%; Egypt (Cairo) ZOONOTIC ASPECTS
0.2%; Iraq 7%; Kenya 5%; Korea The role of animals in the spread of human
0.03–0.4%; Madagascar 9%; Mexico 5%; infection is not clear. A morphologically
Namibia 1%; Nigeria (Plateau) 0.3–3%; identical parasite, H. nana var. fraterna, is
Russia (Siberia) 0.1%; Saudi Arabia common in rats and mice and often has as
0.4–3%; Senegal 1.5%; Turkey 0.6–2%; intermediate hosts either fleas (Xenopsylla
Venezuela 2%. cheopis, Ctenocephalides canis) or beetles
The eggs are not resistant to heat or des- (Tenebrio molitor, Tribolium confusatum).
iccation and are viable for a maximum of However, the rodent variety differs physio-
 The Cestodes 101

logically and does not usually cause infec- (Fig. 49). The reproductive organs are simi-
tion in humans. The situation is further lar in structure to those of H. nana,
complicated because the human tapeworm although the three testes are more widely
can also develop in insects and these are separated.
subsequently infective when ingested, and The egg is slightly ovoid and has a thick
possibly rodents sometimes act as reservoir yellow outer shell and a thin colourless
hosts of the human strain without the pres- inner membrane (embryophore), with a
ence of an intermediate host. granular intermediate layer. There are no
polar filaments. The egg measures 60–80
µm in maximum diameter (Fig. 123).
Hymenolepis diminuta
(Rudolphi, 1819) Blanchard, 1891
LIFE CYCLE
For further development, the eggs passed
SYNONYMS in the faeces need to be ingested by an
Taenia diminuta Rudolphi, 1819; Taenia insect intermediate host. They can survive
flavopunctata Weinland, 1858; Taenia min- in the environment for about 1 week.
ima Grassi, 1886. The most important intermediate hosts
are flour beetles (Tribolium confusatum
DISEASE AND POPULAR NAME and Tenebrio molitor) and rat fleas
Hymenolepiasis or hymenolepiosis dimin- (Xenopsylla cheopis and Nosophyllus fas-
uta; the rat tapeworm. ciatus). When ingested, often on contami-
nated grain, the oncosphere larva inside
GEOGRAPHICAL DISTRIBUTION the egg develops into a tailed, solid, cysti-
This is a common and cosmopolitan para- cercoid larva in the body cavity of the
site of rats, mice and wild rodents in many insect. If the infected insect is ingested by a
parts of the world. It is an occasional para- rat (or a child), the liberated cysticercoids
site of humans, most cases being reported attach to the intestinal mucosa and the
from children. In a few countries infection worm matures in 18–20 days. There is not
in children is not uncommon (1.9% in the the invasive tissue phase characteristic of
New Guinea highlands; 1.3% in India H. nana.
(Uttar Pradesh); 0.4% in Morocco (Agadir); Infection in children appears to cause
0.05–0.1% in Turkey). no clinical symptoms apart from diarrhoea.
Some cases have been referred for neuro-
LOCATION IN HOST psychiatric problems but these may be
Adults are found in the upper three-quar- coincidental. Diagnosis is by finding the
ters of the ileum, with the scolex usually characteristic eggs in the faeces, and treat-
embedded in the mucosa. However, in rats ment is as for H. nana; repeated doses have
it has been shown that the tapeworm proved necessary in some cases. A single
moves backwards and forwards in the dose of 500 mg of niclosamide is an older
intestine and this may be generally true of treatment.
this and other tapeworms in humans. Although H. diminuta has little direct
medical importance, it is of great scientific
MORPHOLOGY interest as a laboratory model, and is being
In spite of its name this species is consider- used in many research studies on the phys-
ably larger than H. nana. The entire tape- iology, biochemistry and immunology of
worm measures 300–600 mm
4 mm and cestodes and for chemotherapeutic screen-
has 800–1000 proglottides. The scolex ing tests.
(0.2–0.4 mm in diameter) is spherical and Drepanidotaenia lanceolata (Bloch,
has four small suckers and a retractable 1782) Railliet, 1892, is a hymenolepid par-
rostellum; but no hooks (Fig. 48). asite of water-birds with cysticercoids in
The mature proglottides are broader copepods and with a single case in a boy in
than long and measure 0.75 mm
0.25 mm Germany.
102 Chapter 2

Family Dipylididae Human infection is presumably from

ingestion of fleas and is almost always in
Dipylidium caninum children. There is no definite pathogenesis
(Linnaeus, 1758) Railliet, 1892 associated with this species and treatment
is with praziquantel (25 mg kg1 in a single
SYNONYMS, DISEASE AND POPULAR NAME oral dose). Diagnosis is by finding the
Taenia canina L., 1758 and many others; mobile, gravid, barrel-shaped, proglottides
dipylidiasis or dipylidiosis; double-pored (with remains of double organs or pores) or
dog tapeworm. egg capsules in the faeces (Fig. 124).

GEOGRAPHICAL DISTRIBUTION
This is a very common and cosmopolitan
parasite of dogs and cats and is found Very occasional human tapeworms
sporadically in humans; a few hundred
cases having been reported, almost all in Bertiella studeri (Blanchard, 1891) Stiles
children. Recent reported cases in children and Hassall 1902 and B. mucronata
and infants have been from Austria, (Meyner, 1895) Stiles and Hassall, 1902
Bulgaria, Chile, China, India, Italy, Japan, (family Anoplocephalidae)
Russia, Sri Lanka and the USA. These are parasites of monkeys with cysti-
cercoids in oribatid mites. About 60 cases
MORPHOLOGY
of B. studeri in humans, mostly in children,
Dipylidium caninum is a short tapeworm
have been reported from Equatorial Guinea,
measuring 200–400 mm
2.5–3 mm and
India, Indonesia, Japan, Kenya, Malaysia,
has 60–175 proglottides. The scolex mea-
sures about 0.37 mm, has four prominent Mauritius, Nigeria, Philippines, Sri Lanka,
suckers, a retractable rostellum and 30–150 Thailand and Yemen and of B. mucronata
thorn-shaped hooks in 3–4 rows. Mature in Argentina, Brazil, Cuba and Paraguay
proglottides are longer than broad. The (Denegri and Perez-Serrano, 1997). A chain
genital organs are in two sets, one set each of thick, very broad proglottides passed in
side of the midline. The two common geni- the faeces usually provides the first evi-
tal pores open at the centre of both lateral dence of infection. A woman in Equatorial
margins. Guinea had suffered abdominal discomfort
The gravid proglottides are filled with for 6 years before proglottides were passed
eggs in egg capsules (Fig. 124), each con- and she was cured by 40 mg kg1 of prazi-
taining up to 20 eggs, proglottides are quantel (Galan-Puchades et al., 1997).
passed in the faeces. In shape, the proglot-
tides are an elongate oval, measuring
12 mm
2.7 mm, and are very active when Inermicapsifer madagascariensis
passed; frequently they are mistaken for (Davaine, 1870) Baer, 1956 (syn. I. cubensis)
trematodes when seen in the faeces of dogs (family Anoplocephalidae)
or children.
This is a small tapeworm (5 cm) of rodents
LIFE CYCLE and hyraxes with cysticercoids presumably
The egg capsules are liberated on the in mites. Human cases have occurred in
ground or stick to the anal hairs of dogs. Cuba, Comoros Islands, Congo, Kenya,
They cannot survive drying for more than Madagascar, South Africa, Venezuela,
1–2 days and live only 1–2 minutes in Zambia and Zimbabwe. It is not uncom-
water. The eggs are ingested by the larval mon in children around Havana, Cuba, and
stages of ectoparasitic insects, such as is probably more common in East Africa
Ctenocephalides canis or C. felis (the dog than reported.
and cat fleas) and develop in the body Mathevotaenia symmetrica (Baylis,
cavity into tailed cysticercoids in about 18 1927) Akhumian, 1946, is widely distrib-
days. uted in rodents in Thailand, with cysticer-
 The Cestodes 103

coids in flour beetles and moths (and one Raillietina spp.

case in a human). (family Davaineidae)
Species found in humans include R. asiat-
Mesocestoides lineatus (Goeze, 1782) ica (Von Linstow, 1901) Stiles and Hassall
Railliet, 1893 and M. variabilis Mueller, 1927 (a single case in Russia, a doubtful case in
(family Mesocestoididae) Iran); R. celebensis (Janicki, 1902)
M. lineatus is a parasite of carnivores prob- Fuhrmann, 1924, a parasite of rats and
ably with an arthropod as the first interme- mice with cysticercoids in ants (a few cases
diate host and amphibians, reptiles, small in children from Australia, China, Japan,
mammals and birds as second (with a mod- Moorea, Philippines, Tahiti and Taiwan);
ified cysticercoid known as a tetrathyrid- R. garrisoni Tubangui, 1931 (one case in a
ium, of the plerocercoid type). Human child in the Philippines); R. madagas-
cases have been reported from China (two cariensis (Davaine, 1869) Joyeux and Baer,
cases), Japan (12), Korea (one) and Sri 1919, a common parasite of rats in Asia
Lanka (one). The man infected in Korea ate with cysticercoids probably in cockroaches
raw chicken viscera and passed 32 worms (human cases from Comoros, Indonesia,
after treatment with niclosamide. M. vari- Mauritius, Philippines and Thailand); R.
abilis has a similar life cycle and human siviraji Chandler and Pradatsundarasar,
cases have been reported from Greenland 1957, a common parasite of rats in
and the USA (6 cases). Thailand (and with a few cases in chil-
dren). Buginetta (= R.) alouattae Spaskii,
1994 is found in South American monkeys
and occasionally humans.

References

Beaver, P.C. and Rolon, F.A. (1981) Proliferating larval cestode in a man in Paraguay: a case report
and review. American Journal of Tropical Medicine and Hygiene 30, 625–637.
Bern, C., Garcia, H.H., Evans, C., Gonzalez, A.E., Verastegul, M., Tsang, V.C.M. and Gilman, R.H.
(1999) Magnitude of the disease burden from neurocysticercosis in a developing country.
Clinical Infectious Diseases 29, 1203–1209.
Bessenov, A.S., Movsession, S.O. and Abuladze, K.I. (1994) On the classification and validity of
superspecies taxons of the cestodes of the suborder Taeniata Skrjabin et Schulz, 1937.
Helminthologia 31, 67–71.
Bowles, J., Blair, D. and McManus, D.P. (1995) A molecular phylogeny of the genus Echinococcus.
Parasitology 110, 317–328.
Chang, K.H., Chi, J.G., Cho, S.Y., Han, M.H., Han, D.H. and Han, M.C. (1992) Cerebral sparganosis:
analysis of 34 cases with emphasis on CT features. Neuroradiology 34, 1–8.
Connor, D.H., Sparks, A.K., Strano, A.J., Neafie, R.C. and Juvelier, B. (1976) Disseminated parasitosis
in an immunosuppressed patient – possibly a mutated sparganum. Archives of Pathological
Laboratory Medicine 100, 65–68.
Craig, P.S. (1994) Current research in echinococcosis. Parasitology Today 10, 209–211.
Craig, P.S., Rogan, M.T. and Allan, J.C. (1996) Detection, screening and community epidemiology of
taeniid cestode zoonoses: cystic echinococcosis, alveolar echinococcosis and neurocysti-
cercosis. Advances in Parasitology 38, 170–250.
Denegri, G.M. and Perez-Serrano, J. (1997) Bertiellosis in man: a review of cases. Revista do Instituto
de Medecina Tropical de Sao Paulo 39, 123–127.
Eckert, J. and Thompson, R.C.A. (1996) Intraspecific variation of Echinococcus granulosus and
related species with emphasis on their infectivity to humans. Acta Tropica 64, 19–34.
Eckert, J., Conraths, F.J. and Taekmann, K. (2000) Echinococcosis: an emerging or re-emerging zoo-
nosis? International Journal for Parasitology 30, 1283–1294.
Fan, P.C. (1997) Annual economic loss caused by Taenia saginata asiatica taeniasis in East Asia.
Parasitology Today 13, 194–196.
104 Chapter 2

Fan, P.C., Lin, C.Y., Chen, C.C. and Chung, W.C. (1995) Morphological description of Taenia saginata
asiatica (Cyclophyllidea: Taeniidae) from man in Asia. Journal of Helminthology 69, 299–303.
Francois, A., Favennec, L., Cambon-Michot, C., Gueit, I., Biga, N., Tron, F., Brasseur, P. and Hemet, J.
(1998) Taenia crassiceps invasive cysticercosis: a new human pathogen in acquired immuno-
deficiency syndrome? American Journal of Surgical Pathology 22, 488–492.
Galan-Puchades, M.T., Frentes, M.V., Simarro, P.P. and Mas Coma, S. (1997) Human Bertiella studeri
in Equatorial Guinea. Transactions of the Royal Society of Tropical Medicine and Hygiene 91,
680.
Gottstein, B. and Felleisen, R. (1995) Protective immune mechanisms against the metacestode of
Echinococcus multilocularis. Parasitology Today 11, 320–326.
Hubert, K., Andriantsimahavandy, A., Michault, A., Frosch, M. and Muhlschlegel, F.A. (1999)
Serological diagnosis of human cysticercosis by use of recombinant antigens from Taenia
solium cysticerci. Clinical and Diagnostic Laboratory Immunology 6, 479–482.
Ing, M.B., Schantz, P.M. and Turner, J.A. (1998) Human coenurosis in North America: case reports
and review. Clinical and Infectious Diseases 27, 519–523.
Ito, A. (1992) Cysticercosis in Asian-Pacific regions. Parasitology Today 8, 182–183.
Ito, A., Ma-LiAng, Schantz, P.M., Gottstein, B., Liu-Yuetlan, Chai JunJie, Abdel-Hafez, S.K., Altintas,
N., Joshi, D.D., Lightowers, M.W., Pawlowski, Z.S., Ma-La, Liu, Y.H. and Chi, J.J. (1999)
Differential serodiagnosis for cystic and alveolar echinococcosis using fractions of Echinococcus
granulosus cyst fluid (antigen B) and Echinococcus multilocularis protoscolex (Em18).
American Journal of Hygiene and Tropical Medicine 60, 188–192.
Khalil, L.F., Jones, A. and Bray, R.A. (1994) Keys to the Cestode Parasites of Vertebrates. 768 pp. CAB
International, Wallingford, UK.
Lightowers, M.W., Flisser, A., Gauci, C.G., Heath, D.D., Jensen, O. and Rolfe, R. (2000) Vaccination
against cysticercosis and hydatid disease. Parasitology Today 16, 191–196.
Lo, Y.-K., Chao, D. and Yan, S.-H. (1987) Spinal cord proliferative sparganosis in Taiwan: a case
report. Neurosurgery 21, 235–238.
Lucas, S.B., Hassounah, O.A., Doenhoff, M. and Muller, R. (1979) Aberrant form of Hymenolepis
nana; possible opportunistic infections in immunosuppressed patients. Lancet 22 Dec. (ii),
1372–1373.
Lymberry, A.J. and Thompson, R.C.A. (1996) Species of Echinococcus: pattern and process.
Parasitology Today 12, 486–491.
Machnicka, B., Dziemian, E. and Zwierz, C. (1996) Detection of Taenia saginata antigens in faeces by
ELISA. Applied Parasitology 37, 99–105 and 106–110.
Macpherson, C.N.L. (1992) Ultrasound in the diagnosis of parasitic disease. Tropical Doctor 22,
14–20.
Macpherson, C.N.L. and Craig, P.S. (2000) Dogs and cestode zoonoses. In: Macpherson, C.N.L.,
Meslin, F.X. and Wandeler, A.I. (eds) Dogs, Zoonoses and Public Health. CAB International,
Wallingford, UK, pp. 177–212.
Malomo, A., Ogunniyi, J., Ogunniyi, A., Akang, A., Akang, E.E.U. and Shokunbi, M.J. (1990)
Coenurosis of the central nervous system in a Nigerian. Tropical and Geographical Medicine 42,
280–282.
Meslin, F.X., Miles, M.A., Vexenat, J.A. and Gemmell, M.A. (2000) Zoonoses control in dogs. In:
Macpherson, C.N.L., Meslin, F.X. and Wandeler, A.I. (eds) Dogs, Zoonoses and Public Health.
CAB International, Wallingford, UK, pp. 333–372.
Muller, R. (1983) Taenia, taeniasis and cysticercosis. In: Feachem, R.G., Bradley, D.J., Garelick, H.
and Marr, D.D. (eds) Sanitation and Disease: Health Aspects of Excreta and Wastewater
Management. John Wiley & Sons, Chichester, UK, pp. 463–472.
Rausch, R.L. (1995) Life cycle patterns and geographic distribution of Echinococcus species. In:
Thompson, R.C.A. and Lymberry, A.J. (eds) Echinococcus and Hydatid Disease. CAB
International, Wallingford, UK, pp. 89–119.
Ruttenber, D.J., Weniger, F., Sorvillo, R., Murray, R.A. and Ford, S.L. (1984) Diphyllobothriasis asso-
ciated with salmon consumption in Pacific coast states. American Journal of Tropical Medicine
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Sarti, E., Schantz, P.M., Plancarte, A., Wilson M., Gutierrez O., I., Lopez, A., Roberts, J. and Flisser, A.
(1992) Prevalence and risk factors for Taenia solium taeniasis and cysticercosis in a village in
Morelos, Mexico. American Journal of Tropical Medicine and Hygiene 46, 677–685.
 The Cestodes 105

Sarti, E., Schantz, P.M., Plancarte, A., Wilson, M., Gutierrez, O., I., Aguilera, J., Roberts, J. and Flisser,
A. (1994) Epidemiological investigation of Taenia solium taeniasis and cysticercosis in a rural
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Sen, D.K., Muller, R., Gupta, V.P. and Chilana, J.S. (1989) Cestode larva (sparganum) in the anterior
chamber of the eye. Tropical and Geographical Medicine 41, 270–273.
Simanjuntak, G.M., Margono, S.S., Okamoto, M. and Ito, A. (1997) Taeniasis/cysticercosis in
Indonesia as an emerging disease. Parasitology Today 13, 321–322.
Smyth, J.D. and McManus, D.P. (1989) The Physiology and Biochemistry of Cestodes. Cambridge
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Thompson, R.C.A. and Lymberry, A.J. (eds) (1995) Echinococcus and Hydatid Disease. CAB
International, Wallingford, UK.
Thompson, R.C.A., Lymberry, A.J. and Constantine, C.C. (1995) Variation in Echinococcus: towards a
taxonomic revision of the genus. Advances in Parasitology 35, 145–176.
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03Worms & H.D. - Chap 03 14/11/01 4:26 PM Page 106

3
The Acanthocephala

Members of the phylum Acanthocephala Italy, Japan, Madagascar, Papua New

are all parasitic and show similarities in Guinea, Russia, the USA and Zimbabwe.
structure to both the nematodes and the Infection is common and cosmopolitan in
platyhelminthes (Crompton and Nickol, rodents and also occurs in dogs and cats.
1985). Most species are under 1 cm in
length but some may be up to 70 cm. The LOCATION IN THE HOST
principal diagnostic character is the pres- Adults inhabit the small intestine, the pro-
ence of an eversible proboscis armed with boscis being deeply embedded in the
rows of hooks (thorny-headed worms). mucosa.
Acanthocephalans are pseudocoelomate
animals (that is, they have a body cavity MORPHOLOGY
but it is not homologous to a true coelom) The adult worms appear to be made up of a
with separate sexes and, like cestodes, series of bead-like annulations, but these
have no digestive tract. The life cycle usu- are only superficial. The anterior proboscis
ally involves an insect or crustacean as is cylindrical and has 12–15 rows of
intermediate host. Many acanthocephalans curved hooks, with 7–8 hooks per row.
have a low specificity for the definitive Females measure 10–25 cm in length,
host but are not found in humans because males 4–14 cm.
the intermediate hosts are not likely to be
ingested (e.g. cockroaches). LIFE CYCLE
Two genera, both belonging to the class The ovoid eggs measure 70–120 µm 
Archiacanthocephala, are occasional para- 30–60 µm and are passed in the faeces. The
sites of humans (Taraschewski, 2000). egg has three envelopes characteristic of
members of the phylum and contains a
spiny acanthor larva when passed. The
Moniliformis moniliformis larva inside can survive for months in soil
(Bremser, 1811), Travassos, 1915 but develops further if the egg is ingested
by various beetles or cockroaches. The lar-
vae require several weeks before they reach
SYNONYMS the infective stage. The encysted juvenile
Echinorhynchus moniliformis Bremser, stages (cystacanths) are ingested by a
1811; Moniliformis dubius Meyer, 1932. mammalian host (usually the rat) and
develop into adults in 5–6 weeks.
DISTRIBUTION Human infection is probably usually
Moniliformis is a very occasional human from grain beetles and it is of interest that
parasite. Cases have been reported from 15% of coprolites from grain-eating prehis-
Australia, Bangladesh, Belize, Iran, Israel, toric humans in a cave in Utah (USA)

106
03Worms & H.D. - Chap 03 14/11/01 4:26 PM Page 107

The Acanthocephala 107

contained acanthocephalan eggs, which MORPHOLOGY AND LIFE CYCLE

were probably of Moniliformis. These are large parasites, the female mea-
suring 20–65 cm  4–10 cm and the male
CLINICAL MANIFESTATIONS AND PATHOGENESIS 5–10 cm  3.5 cm. The most important
The clinical manifestations have been intermediate hosts are soil-inhabiting bee-
known since Calandruccio in 1888 infected tle larvae belonging to the family
himself experimentally. Nineteen days Scarabeidae. Development is similar to that
after ingesting cystacanth larvae, he had of Moniliformis. Recent cases in China
gastrointestinal disturbances with diar- have had acute abdominal colic with mul-
rhoea, exhaustion and a ringing in the ears. tiple perforations in the jejunum (Leng et
Eggs appeared in his faeces about 2 weeks al., 1983).
later. In a recent case in Florida, USA, an
infant had repeated episodes of diarrhoea, Macranthorhynchus ingens, normally
accompanied by coughing and fever; after found in the raccoon, has been reported
each episode an adult worm was passed in from a child in Texas, USA (Dingley and
the faeces (Counselman et al., 1989). Beaver, 1985).
Other genera (belonging to the class
TREATMENT
Mebendazole and pyrantel pamoate have Palaeacanthocephala) found once or twice
been used in recent cases with variable in humans are: Acanthocephalus rauschi
results. Golvan, 1969 from an Inuit in Alaska, with
a fish probably acting as a paratenic host;
Pseudoacanthocephalus bufonis (Shipley,
Macranthorhynchus hirudinaceus 1903) Southwell and Macfie, 1925, a toad
(Pallas, 1781) Travassos, 1917 parasite, with one case reported from
Indonesia; Corynosoma strumosum
SYNONYMS AND POPULAR NAME (Rudolphi, 1802) Luhe, 1904, one human
Taenia hirudinaceus Pallas, 1781; case being reported from Alaska (adults are
Gigantorhynchus gigas (Pallas, 1781); the normally found in seals with fish acting as
giant thorny-headed worm. paratenic hosts).

DISTRIBUTION Bolbosoma sp., a parasite of cetaceans, has

Occasional human cases have been been recorded once from the jejunum of a
reported from Australia, Brazil, China, Japanese, probably contracted from eating
Czech Republic, Iraq, Russia and Thailand. raw marine fish.

References

Counselman, K., Fied, C., Lea, G., Nickol, B. and Neafie, R. (1989) Moniliformis moniliformis from a
child in Florida. American Journal of Tropical Medicine and Hygiene 41, 88–90.
Crompton, D.W.T. and Nickol, B.B. (eds) (1985) Biology of the Acanthocephala. Cambridge
University Press, Cambridge, UK.
Dingley, D. and Beaver, P.C. (1985) Macranthorhynchus ingens from a child in Texas. American
Journal of Tropical Medicine and Hygiene 34, 918–920.
Leng, Y.J., Huang, W.D. and Liang, P.N. (1983) Human infection with Macranthorhynchus hirudi-
naceus Travassos, 1916 [sic], in Guangdong Province with notes on its prevalence in China.
Annals of Tropical Medicine and Parasitology 77, 107–109.
Taraschewski, H. (2000) Host parasite interactions in Acanthocephala – a morphological approach.
Advances in Parasitology 42, 1–180.
04Worms & H.D. - Chap 04 14/11/01 4:26 PM Page 108

4
The Nematomorpha

This phylum includes the gordiids or Numerous species have been implicated:
hair-worms, in which the adults are free- Gordius aquaticus, G. chilensis, G. ges-
living in water and the larvae are para- neri, G. inesae, G. ogatai, G. perronciti,
sitic in insects. Often adults have been G. reddyi (a case in India with worms in
found in water in a toilet bowl from an the orbit), G. robustus (abscess in orbit),
insect that fell into the water and were G. setiger, G. skorikowi, Chordodes
thought to have been passed in the faeces capensis, Neochordades columbianus
or urine. However, in isolated cases from (from the ear in Colombia),
many parts of the world, worms do seem Parachordodes alpestris, P. pustulosus, P.
to have been passed in the faeces or per raphaelis, P. tolusanus, P. violaceus, P.
urethra or have been vomited out wolterstoffi, Paragordius cinctus, P. esa-
(Uchikawa et al., 1987) or removed from vianus (in urethra), P. tanganyikae, P. tri-
the eye or ear; in some cases, infection cuspidatus and P. varius (see Coombs
was probably acquired while swimming. and Crompton, 1991).

References

Coombs, I. and Crompton, D.W.T. (1991) A Guide to Human Helminths. Taylor and Francis, London,
UK. pp. 177–190.
Uchikawa, R., Akune, K., Tinone, I., Akune, K., Inove, J., Kagei, N. and Sato, A. (1987) A human case
of hair worm (Gordius sp.) infection in Kagoshima, Japan. Japanese Journal of Parasitology 36,
358–360.

108
 5
The Nematodes

The nematodes are unsegmented pseudo- of nematodes of most medical importance

coelomate worms, usually cylindrical but are summarized in Tables 6 and 7.
tapering at the anterior and posterior ends. All nematodes are dioecious and the
As a group they are remarkably uniform in features typical of the male and female
structure, although differing in size and phasmid nematode are shown in diagrams
habitat. Their uniformity is partly imposed of the pinworm, Enterobius (Fig. 51).
by high internal hydrostatic pressure and
has resulted in fewer external protruber-
ances than are found in most invertebrates. Classification
They are probably one of the most abun- (mainly based on Anderson et al.,
dant and widespread of all animal groups, 1974–1983)
occurring in the sea, fresh water and soil
and as parasites of vertebrates, inverte- KEY: M = mammal, B = bird, R = reptile,
brates and plants. A = amphibian, F = fish.
Species parasitic in humans (63 species PHYLUM NEMATODA
in total here) vary in size from threadlike Elongate, bilaterally symmetrical, cylindri-
objects just visible to the naked eye cal parasites. Unsegmented, with a gut and
(Strongyloides, Trichinella), to elongate anus. Pseudocoelomate. Sexes separate.
stringlike worms attaining a length of With four larval stages.
50 cm (Dracunculus).
The outer layer of the body forms a CLASS SECERNENTEA (‘Phasmidia’)
multilayered proteinaceous cuticle. It con- These have the presence of small sensory
tains collagen fibres arranged in a trellis-like structures on the tail end (phasmids) and a
pattern, thus allowing some contraction and characteristic excretory system. With
extension of the body. The surface of the liv- numerous caudal papillae.
ing worm is biologically inert (in contrast to
Order Rhabditida (MBRA)
that of trematodes and cestodes) and the
Family Strongyloididae
main antigenic stimulus to the host occurs
Free-living and parasitic generations can
at various orifices with the production of
alternate. The parasitic females are
excretory and secretory (ES) antigens.
parthenogenetic. Small buccal capsule
During the life history the cuticle is shed
without teeth. Oesophagus of free-living
periodically, the process being termed a
adults and of first-stage larva with posterior
moult or ecdysis. There are four moults
bulb (rhabditoid).
during development from ovum to adult,
Strongyloides
and in the majority of phasmidian species
the third-stage larva is responsible for infec- Order Strongylida (MBRA, occasionally F)
tion of a new host. The geographical distri- Male with cuticular copulatory bursa sup-
bution, location in the body and life cycles ported by rays and with two similar

109
110 Chapter 5

Table 6. Outline of nematode life cycles.

1. Direct cycle: no intermediate host required

Vertebrate host

Egg contains Unembryonated egg Embryonated egg Rhabditiform larva

rhabiditiform larva in faeces in faeces in faeces
on perianal skin

Larva develops in Egg hatches on Free-living

egg but does not ground generation with
hatch (L1 in Trichuris rhabditiform
L2 in Ascaris) larvae in soil

Egg hatches in intestine when swallowed by humans Rhabditiform Larva develops to

larvae develops to L3 in soil
L3 with sheath in soil

Larva (L1) develops Larva reaches L3 ingested L3 penetrates L3 penetrates

directly to adult in intestine after skin skin
intestine entering blood
and via lungs

Enterobius Trichuris Ascaris Necator Strongyloides

Ancylostoma
Ancylostoma
Mammomonogamus*
Oesophagostomum
Ternidens
Trichostrongylus

2. Indirect cycle: intermediate host required

Vertebrate host

Rhabditiform L1 L1 larva in water Microfilaria L1 larva encysted

larva in faeces (pre L1) larva in in muscles
blood or lymph

To L3 in land To L3 in To L2 in To L3 in biting
snail or slug cyclopoid cyclopoid insect

L3 ingested L3 L2 ingested L3 enters skin L1 ingested

ingested and to L3 in and to L3 in
fish, frog or snake intestine

L3 ingested

Parastrongylus* Gnathostoma* Trichinella*

Dracunculus Brugia
Loa
Mansonella
Onchocerca
Wuchereria

*Humans are accidental or aberrant hosts.

 The Nematodes 111

Table 7. Nematodes of medical importance.

Mode of
infection and Geographical
Species infective Stage Site of adult distribution
Directly Enterobius Mouth (L1 in Large intestine Cosmopolitan
contaminative vermicularis eggs)
Sometimes Skin (L3) Small intestine Africa, Asia,
Strongyloides America, Pacific
stercoralis
Soil-transmitted Strongyloides Skin (L3) Small intestine Africa, Asia,
(geohelminths) stercoralis America, Pacific
Necator Skin (L3) Small intestine Africa, Asia,
americanus America, Pacific
Ancylostoma Mouth or skin Small intestine Asia, Africa,
duodenale (L3) Middle East, Pacific
Trichostrongylus Mouth (L3) Small intestine Asia, Middle East,
spp. Africa
Ascaris Mouth (L2 in egg) Stomach and Cosmopolitan
lumbricoides small intestine
Trichuris trichiura Mouth (L1 in egg) Caecum Cosmopolitan
Aberrant Ancylostoma spp. Skin (L3) Larvae in skin Africa, America,
infections (dermal larva Asia, Pacific
migrans)
Toxocara, etc. Mouth (L2 in egg) Larvae in liver, Cosmopolitan
(visceral larva eye, brain
migrans)
Insect-transmitted Onchocerca Simulium skin Subcutaneous Africa, Yemen, Central
volvulus (L3) and South America
Wuchereria Culex, Anopheles Lymphatics Asia, Africa, South
bancrofti and Aedes skin (L3) America, Pacific
Brugia malayi Mansonia skin (L3) Lymphatics South-East Asia
Loa loa Chrysops skin (L3) Subcutaneous Africa (rain forest)
Mansonella Culicoides skin (L3) Peritoneal cavity Africa, South America
perstans
Mansonella Culicoides skin (L3) Peritoneal cavity Africa (rain forest)
streptocerca
Mansonella Culicoides, Peritoneal cavity South America,
ozzardi Simulium skin (L3) West Indies
Crustacean- Dracunculus Cyclopoids mouth Subcutaneous Africa, Middle East,
transmitted medinensis (L3) [India, Pakistan]
Aberrant Gnathostoma Cyclopoids mouth Subcutaneous South-East Asia
infection spinigerum (L2)
Snail-transmitted
Aberrant Parastrongylus Misc. snails and
infection cantonensis crustaceans mouth Larvae in Pacific
(L3) meninges
Parastrongylus Misc. snails and Larvae in Americas, Japan,
costaricensis crustaceans mouth mesenteric Africa (?)
(L3) arteries
Meat-transmitted
Accidental Trichinella Mouth (L1) Small intestine Cosmopolitan
infection spiralis
Fish-transmitted
Aberrant Anisakis Mouth (L3) Intestine Europe, Japan
infection
Accidental Aonchotheca Mouth (L1) Small intestine Philippines, Thailand
infection philippinensis
112 Chapter 5

Fig. 51. Diagram of (a) a female (8–13 mm long) and (b) male (2.5 mm long) Enterobius vermicularis to
illustrate typical nematode features (oesophagus = pharynx).

spicules. Oesophagus club-shaped posteri- Order Ascaridida (MBRAF)

orly, but without definite bulb (rhabditoid Large stout intestinal worms. Mouth usually
in first-stage larva). Mouth without lips. with three lips. Oesophagus without valvu-
Direct life cycle usually includes two free- lar apparatus and not divided into two por-
living and feeding larval stages (except in tions. Male and female similar in size. Male
superfamily Metastrongyloidea). with equal spicules. Life cycle either direct
or indirect with intermediate host.
SUPERFAMILY ANCYLOSTOMATOIDEA (M)
Family Ancylostomatidae SUPERFAMILY ASCARIDOIDEA

Buccal capsule well developed, usually Family Ascarididae

with ventral teeth or cutting plates. Caudal Direct life cycle.
bursa of male usually supported by rays. Ascaris, Toxocara, Toxascaris
Ancylostoma, Necator Family Anisakidae
SUPERFAMILY STRONGYLOIDEA
Indirect life cycle.
Buccal capsule globular, strongly devel- Anisakis, Pseudoterranova
oped and cuticularized. Order Oxyurida (MBRAF)
Family Chabertiidae (M) Small stout nematodes. Oesophagus with
posterior bulb with valvular apparatus.
Mouth surrounded by leaf crown.
Female with long pointed tail. Direct life
Oesophagostomum, Ternidens
cycle, with two moults in egg. Female with
Family Syngamidae (MB) large embryonated eggs, often flattened on
Leaf crown rudimentary. Male and female one side. Parasites of colon or rectum.
attached. SUPERFAMILY OXYUROIDEA
Mammomonogamus Family Oxyuridae
SUPERFAMILY TRICHOSTRONGYLOIDEA (MBRA) Enterobius
Family Trichostrongylidae (MB) Order Spirurida (MBRAF)
Filiform worms with the buccal capsule Oesophagus in two parts, anterior muscular
absent or feebly developed. Caudal bursa and posterior longer part glandular. Indirect
with reduced or absent dorsal lobe. life cycle with larvae in arthropods.
Trichostrongylus
SUPERFAMILIES GNATHOSTOMATOIDEA, GONGYLO-
SUPERFAMILY METASTRONGYLOIDEA (M) NEMATOIDEA, THELAZOIDEA, HABRONEMATOIDEA,
Family Angiostrongylidae (M) PHYSALOPTEROIDEA (‘Spirurids’)
Filiform with reduced buccal capsule. Filiform. Mouth usually has two lips.
Caudal bursa of male usually asymmetrical Female longer than male, with vulva in the
and may be reduced. Parasites of repiratory anterior region. Spicules of male very
or circulatory system. Require an inter- unequal. Mainly non-intestinal.
mediate host. Gnathostoma, Gongylonema, Thelazia,
Parastrongylus Habronema, Physaloptera
 The Nematodes 113

SUPERFAMILY FILARIOIDEA (MBRA) (‘Filariae’) Many members are parasites of plants and
Family Onchocercidae insects.
Filiform. Mouth usually without lips.
Female longer than male with vulva in Order Enoplida (MBRAF)
anterior region and double uterus. Spicules SUPERFAMILY TRICHINELLOIDEA
very unequal in male. Non-intestinal para- Family Trichuridae
sites. Usually ovoviviparous, with larvae in Sexes separate. Anterior region of body
bloodsucking insects (or arachnids). much thinner than posterior. Vulva near end
Wuchereria, Brugia, Loa, Onchocerca, of oesophagus. Male with single spicule.
Mansonella, Dirofilaria Trichuris, Aonchotheca, Calodium, Eucoleus
SUPERFAMILY DRACUNCULOIDEA (MBRF) Family Trichinellidae
Family Dracunculidae
Sexes separate. Anterior region of body
Similar in structure to filariae but females
slightly thinner than posterior. Male with
very much longer than males, with vulva
single or no spicule. Female with one
and anus atrophied in gravid female and
single uterus. Ovoviviparous with larvae in ovary and uterus, vulva near middle of
copepods. oesophagus. Ovoviviparous.
Dracunculus Trichinella

CLASS ADENOPHOREA (‘Aphasmidia’) SUPERFAMILY DIOCTOPHYMATOIDEA

Phasmids absent. Caudal papillae absent Family Dioctophymidae

or few in male. Oesophagus usually form- Male tail modified to form ventral sucker.
ing a stichosome. First-stage larvae, often Well-developed oesophagus.
with stylet and infective to final host. Dioctophyma, Eustrongylides

A Key to Nematodes Parasitic in Humans

1. Heterogenic. Parasitic form parthenogenetic with direct life cycle.

Small buccal capsule without teeth RHABDITIDA
Strongyloides
Not heterogenic. Parasitic forms sexually differentiated 2
2. Pharynx consisting of a narrow tube running through the
centre of a single row of cells ENOPLIDA
(TRICHUROIDEA)
Aonchotheca
Calodium
Eucoleus
Trichuris
Trichinella
Pharynx muscular and not consisting of intracellular tube 3
3. Males with copulatory bursa 4
Males without copulatory bursa 5
4. Copulatory bursa muscular and without rays ENOPLIDA
(DIOCTOPHYMATOIDEA)
Dioctophyma
Eustrongylides
Copulatory bursa cuticular and supported by rays STRONGYLIDA
see subkey below
5. Pharynx dilated posteriorly into a bulb, usually
containing a valvular apparatus and often separated
from rest of pharynx by constriction. Usually small
forms OXYURIDA
Enterobius
Pharynx not dilated posteriorly into a bulb 6
114 Chapter 5

6. Relatively stout worms. Head with 3 large lips ASCARIDIDA

Ascaris
Toxocara
Relatively slender filiform worms. Head with 2
lateral lips or 4 or 6 small lips or absent.
Arthropod intermediate hosts 7
7. Usually 2 lateral lips. Chitinous buccal capsule.
Vulva in middle of body or posterior. Parasites of
alimentary canal, respiratory system or orbital, nasal or
oral canal SPIRURIDA
(except FILARIOIDEA
and DRACUNCULOIDEA)
Gnathostoma
Habronema
Physaloptera
Thelazia
Usually without lips. Buccal capsule absent. Vulva in
pharyngeal region. Parasites of circulatory or lymphatic
system, serous cavities, muscles or connective tissues 8
8. Females not more than three times longer than males.
Vulva not atrophied SPIRURIDA
(FILARIOIDEA)
Filariae
Females enormously longer than males. Vulva atrophied
in gravid female SPIRURIDA
(DRACUNCULOIDEA)
Dracunculus

Subkey to the order Strongylida

(a) Parasites of alimentary canal or rarely in renal tissue (b)

Parasites of respiratory system (d)
(b) Buccal capsule feebly developed or absent.
Threadlike worms TRICHOSTRONGYLOIDEA
Trichostrongylus
Buccal capsule well developed (c)
(c) Buccal capsule with ventral teeth or cutting plates ANCYLOSTOMATOIDEA
Ancylostoma
Necator
Buccal capsule without teeth, etc. but mouth typically
with a leaf crown STRONGYLOIDEA
(Family Chabertiidae)
Oesophagostomum
Ternidens
(d) Well-developed chitinous buccal capsule. Male often
attached to female STRONGYLOIDEA
(Family Syngamidae)
Syngamus
Rudimentary buccal capsule or absent. Filiform METASTRONGYLOIDEA
Parastrongylus
 The Nematodes 115

The section on the nematodes has been worms but the prevalence is usually much
split into two parts, those that are intesti- lower – an estimated 100 million cases
nal and others that are tissue parasites. worldwide (Grove, 1996).
This has allowed the control of the com-
mon intestinal nematodes to be considered LOCATION IN HOST
together. However, it has resulted in treat- Parthenogenetic females live embedded in
ment of one of the main zoologically the mucosa of the small intestine – the
related group of nematodes being divided duodenum and the first part of the jejunum
by the other as below: in light infections, back to the terminal
Intestinal nematodes | Tissue nematodes
ileum in heavy infections.
Class Secernentea | Class Adenophorea |
MORPHOLOGY
Class Secernentea
Parasitic females are small, transparent, fili-
form nematodes, measuring 2.0–2.7 mm in
Intestinal Nematodes length by 0.03–0.075 mm in width. The cuti-
cle is finely striated and the tail pointed. The
Geohelminths oesophagus occupies the anterior third of the
body and joins the midgut, which opens at
This is a group of intestinal nematodes the ventral anus a short distance from the
which, while not closely related zoologi- posterior end. The vulva opens ventrally at
cally, are all soil-transmitted and have the junction of the middle and posterior
great similarities in epidemiology and in thirds of the worm. The uteri, oviducts and
methods of control: it includes ovarian tubules are paired, one branch
Strongyloides, the hookworms (Necator extending forwards from the vulva and the
and Ancylostoma), Ascaris and Trichuris. other backwards. About 10–20 eggs are pre-
sent in the two uteri at one time. The eggs are
Order Rhabditida thin-shelled, transparent and ovoid; they
Family Strongyloididae measure 50–60 µm
30–35 µm when laid.
The eggs are partially embryonated and usu-
Strongyloides stercoralis ally hatch in the tissues of the mucosa, so
(Bavay, 1876) Stiles and Hassall, 1902 that larvae rather than eggs are passed out in
the faeces (Figs 123 and 125).
SYNONYMS The females produce eggs partheno-
Anguillula stercoralis, Bavay, 1876 (larvae genetically and, although parasitic males
from faeces); A. intestinalis, Bavay, 1877 similar to free-living ones described below
(parasitic females from intestine); were recorded twice, they have never been
Pseudorhabditis stercoralis Perroncito, 1881 seen since.
(free-living adults). Strongyloides is also capable of undergo-
ing a complete life cycle in the soil, living
DISEASE AND POPULAR NAME as a free-living nematode with a distinct
Strongyloidiasis or strongyloidosis, anguil- morphology. The free-living female is
losis; Cochin-China diarrhoea. Included as shorter and stouter than the parasitic form
one of the geohelminths. (1.0 mm
0.06 mm) and has a short rhab-
ditiform oesophagus (muscular and with an
GEOGRAPHICAL DISTRIBUTION enlarged posterior bulb, similar to that of
Strongyloides infection is widely distrib- the saprophytic soil nematode Rhabditis).
uted in tropical regions of Africa, Asia and The free-living male measures about
Central and South America (particularly 0.7 mm
0.04 mm and has a pointed tail,
Brazil, Colombia and Guyana); it also curving ventrally, with two spicules and a
occurs in eastern Europe and sporadically gubernaculum (this is a chitinous sheath in
in the USA and southern Europe. which the spicules can slide up and down;
Distribution is similar to that of hook- it is presumed to aid in the transference of
 116
Chapter 5
Map 7. Distribution of Strongyloides stercoralis (and S. fuellebornius in New Guinea).
 The Nematodes 117

sperm during copulation and is often of sure 250 µm
20 µm and can be differenti-
taxonomic importance). The oesophagus is ated from those of hookworms by the
rhabditiform. smaller buccal capsule (Fig. 53). The larvae
feed on bacteria in the soil and moult twice
LIFE CYCLE (Fig. 52) to give the infective filariform stage, mea-
Parasitic (= direct) life cycle. Eggs are laid in suring 550 µm
20 µm, in the surface lay-
the mucosa and submucosa of the small ers of the soil. The infective larvae differ
intestine. There they hatch as rhabditiform from those of hookworms by the lack of a
first-stage larvae, which escape into the sheath, by the triradiate tip to the tail and
intestinal lumen and pass out in the faeces, in the greater length of the pharynx. They
where they are very active. The larvae mea- ascend soil particles and damp vegetation

Autoinfection can occur

when larvae develop on
perianal skin or rarely
in intestinal tract

3RD-STAGE
Parthenogenic ADULT LARVA
FEMALE in small intestine (2.0 mm) 1ST-STAGE
matures in 17 days LARVA
in faeces and
Penetrates skin and reaches soil
reaches gut via blood,
lungs, trachea, 1ST-STAGE
oesophagus RHABDITIFORM
LARVA (0.25 mm)
Ei
Direct th
er
Moults twice
t
direc
Or in

3RD-STAGE FILARIFORM
LARVA (0.55 mm)
lives about 12 days vulva
in soil
FREE-LIVING
FEMALE (1.0 mm)

ovary

1ST-STAGE RHABDITIFORM testis

LARVA (0.25 mm) spicules

FREE-LIVING MALE
(0.8 mm)

Fig. 52. The possible life cycles of Strongyloides stercoralis. (Portrait of Dionysus from a Greek cylix.)
118 Chapter 5

Fig. 53. The anterior ends of the first-stage larva (L1) of Strongyloides (left) and hookworm (right) in soil.
The former has a shorter buccal capsule.

in the surface film, often standing on their for only a few months. In severely ill
tails in tufts or aggregates. Under optimum patients or in chronic carriers, rhabditiform
conditions the larvae live in the soil for larvae passing down the gut may develop
about 2 weeks but, when they come into into filariform larvae without reaching the
contact with the skin, usually of the feet (or exterior at all, and these then penetrate the
more rarely the buccal mucosa), they pene- intestinal mucosa. Exceptionally, when the
trate and reach the small cutaneous blood- patient’s resistance is low, all larval stages
vessels and then the lungs. After may be found in many of the visceral organs
penetration of the alveoli, the larvae moult and rhabditiform and filariform larvae may
twice and the young adults pass up the even appear in the sputum.
bronchi and trachea and then down the
oesophagus to reach the small intestine Free-living (= indirect or heterogonic) life
(although it has recently been suggested cycle. A free-living cycle often occurs in
that they may use other routes). Once there, warm climates, provided that there is plenty
the female burrows into the mucosal tis- of moisture and nutrients in the soil. The
sues, becomes mature and lays its partheno- rhabditiform larvae passed out in faeces
genetically produced eggs in the mucosa feed and undergo four moults in the soil to
and crypts about 17 days after penetration. become free-living adult males and females
Very unusually among human helminths in 24–30 h. The eggs, which develop in the
is the possibility of replication within the uterus of the free-living female after mating,
human host. Autoinfection is usually occupy a large portion of the body and are
brought about because the rhabditiform lar- laid in a partly embryonated state. They
vae in faecal matter are deposited on the hatch in a few hours after completing devel-
perianal skin and develop into filariform lar- opment and rhabditiform first-stage larvae
vae, which penetrate through the skin. This emerge. These first-stage larvae moult twice
accounts for the persistence of strongyloidia- and develop into non-feeding, filariform,
sis in patients up to 65 years after they have third-stage larvae in a few days. The infec-
left an endemic region (most notably in for- tive larvae survive on soil and vegetation in
mer Second World War prisoners in the Far warm moist conditions and penetrate the
East, who are still suffering from recurrent skin when they come in contact. There is no
larva currens), although the adult worms live second free-living cycle.
 The Nematodes 119

The factors determining whether direct or with malignant lymphoma or acute

indirect development occurs is not well leukaemia, on immunosuppressive drugs,
understood but it is believed that the after renal transplantation, or suffering from
higher the immune status of the host the malnutrition. It does not seem to be strongly
more likely that larvae passed in the faeces associated with cases of AIDS, although
will undergo an indirect cycle. In other there is a correlation with HTLV-1 infection
species at least there are genetically deter- and it is possible that Strongyloides leads to
mined strain differences and environmen- immunoglobulin E (IgE) deficiency (Phelps
tal factors also help to determine whether and Neva, 1993). Hyperinfection may also
males and females or infective larvae be potentiated by a decrease in mobility of
develop in soil. the intestine, which allows first-stage larvae
to mature into infective forms before being
CLINICAL MANIFESTATIONS passed out in the faeces. This postulate is
There may be pruritic eruption at the site supported by the fact that, in cases of hyper-
of entry of the larvae (‘ground itch’) in infection, ulcerations caused by infective
heavy infections, followed by a cough after larvae are always present in the colon as
a few days. well as the ileum. It has been postulated
The majority of cases are of chronic, that hyperinfection is not an immune phe-
uncomplicated, strongyloidiasis and are nomenon but is caused by corticosteroid
symptomless, with just a few worms present therapy stimulating the production of
and no alteration to the mucosa. There may, ecdysteroids (moulting hormones) (Genta,
however, be abdominal discomfort, with 1992). However, hyperinfection occurs in
intermittent gastric pains, accompanied by many patients who have not received corti-
nausea, diarrhoea, weight loss and a gener- costeroids.
alized urticaria. Recurrent, linear, rapidly There is evidence that the immunomod-
progressive, urticarial weals (‘larva currens’) ulatory effect of many helminths may
can occur on the buttocks, groins or trunk. increase susceptibility to tuberculosis (TB)
Lesions in the gluteal region indicate that and AIDS (Borkow and Bentwich, 2000;
autoinfection is occurring and are likely to Bundy et al., 2000).
be present in all clinically important cases.
In a proportion of heavily infected PATHOGENESIS
cases, more serious clinical disease ensues, This can be divided into three stages.
characterized by enteritis with malabsorp- 1. The penetration of the skin by filariform
tion syndrome and electrolyte imbalance larvae usually causes no symptoms in non-
(Plate 12). Such infections in children may sensitized patients, provided infection is
have serious consequences, precipitating light. Larvae secrete a metalloprotease of
kwashiorkor and emaciation. molecular mass 40 kDa, which is immuno-
Disseminated (complicated, hyperinfec- genic; in heavier infections a rash often
tive or overwhelming) strongyloidiasis is appears at the site of entry (‘ground itch’)
always serious and often fatal and can have and there may be severe pruritus. Where
a variety of manifestations, depending on autoinfection is occurring there may also
the intensity of infection and the organs be perianal and perineal ulceration.
involved. Complications affect particularly 2. The larvae that reach the lungs and pass
the bowel, lungs and central nervous system into the alveoli can cause a pneumonitis
(CNS) and are often accompanied by sec- similar to Loeffler’s syndrome in ascariasis
ondary bacterial infection. Parasitic ileus (p. 150).
(pseudo-obstruction), pneumonitis with 3. The adult females live in the depths of
pulmonary infiltrates, meningitis, brain the crypts of the ileum and lay their eggs
abscess and septicaemia are all possible. there. Larvae hatching from deposited eggs
Disseminated strongyloidiasis occurs burrow through the lumen and cause
when the body’s cell-mediated immune superficial catarrhal damage to the mucosa,
responses are deficient, often in patients often with excessive production of mucus.
120 Chapter 5

In severe cases of autoinfection, parasites IMMUNOLOGICAL ASPECTS OF INTESTINAL

are present in the submucosa, which NEMATODES
becomes oedematous. The mucosa becomes Infections with intestinal nematodes generate
flattened and atrophic (Fig. 54), the patho- characteristic patterns of immune responses
logical picture resembling that of tropical in their hosts. Typically, infected individuals
sprue or of infection with Aonchotheca have elevated levels of IgE, high peripheral
philippinensis (p. 173). There may be severe eosinophilia and a variety of allergic symp-
ulceration with a non-reversible fibrosis and toms, some of which are generalized, others
often a pronounced inflammatory response being localized to the tissues invaded. For
to secondary bacterial invasion. Larvae in example, where infection occurs through the
the lymphatics cause a granulomatous lym- skin (e.g. hookworms, Strongyloides) there
phangitis; this, coupled with the inflamma- may be dermatitis and pruritus, where para-
tion, atrophic mucosa and fibrosis, causes a site development involves the lungs (e.g.
marked congestion and loss in elasticity of Ascaris, hookworms) there may be bronchitis
the gut. Paralytic ileus can result and there or pneumonitis, while invasion of muscles
can also be a severe haemorrhagic, ulcera- (Trichinella) causes myositis. Collectively
tive enterocolitis, with massive invasion of these symptoms imply that intestinal nema-
the whole bowel wall by larvae. In cases of todes generate responses dominated by the T-
complicated disease, larvae can be found in helper 2 (Th2) subset, and this is in agreement
almost any organ, particularly the intestinal with experimental studies in laboratory
lymph nodes, lungs, liver, heart, urinary rodents. Many species cause forms of intes-
tract and nervous system. tinal pathology that again can be related to
immunological causes, e.g. the protein-losing
enteropathy seen in patients infected with
Strongyloides spp. or Aonchotheca philip-
pinensis, and the dysentery syndrome seen in
children heavily infected with Trichuris
trichiura, although the extent to which these
are Th2-related is debatable. A major differ-
ence between experimental studies and obser-
vations on human infections is that, whereas
laboratory rodents mount strong protective
responses against the majority of species used
(e.g. Nippostrongylus brasiliensis, Strongy-
loides ratti and S. venezuelensis, Trichinella
spiralis, Trichuris muris), evidence for protec-
tive responses in humans is very limited. The
rapid reacquisition of infection with the com-
mon geohelminths after chemotherapy sug-
gests little immunity to reinfection, but,
against this, in some species, is evidence of an
age-related decline in infection intensity, if
not in prevalence (Crompton, 1998; Fig. 55).
Experimental studies suggest that Th2
cells mediate immunity against intestinal
nematodes through changes in mucosal
structure and function, resulting in an
Fig. 54. Section of colon of patient with
altered parasite environment (Wakelin,
hyperinfective strongyloidiasis. The section is at 1996). Changes in mucosal architecture
the edge of an ulcer and shows inflammation. (through villous atrophy) and epithelial
Adults of S. stercoralis are in the crypts and function, development of mucosal masto-
rhabditiform larvae in the lumen. cytosis, increased secretion of mucus from
 The Nematodes 121

(d) 20

16 Ascaris lumbricoides

Mean worm burden

(a) 100 12

80
Prevalence (%)

8
60

40 4
Ascaris lumbricoides
20
0
0 10 20 40 60
0 20 40 Age (years)
Age (years)
(e) 3
(b) 100
e.p.g. (
10–3)
Prevalence (%)

60
2
80
Trichuris trichiura
40 Trichuris trichiura 1
20
0 0
0 10 20 30 40 0 10 20 30 40 50
Age (years) Age (years)
(c) 100 (f) 3
Prevalence (%)

e.p.g. (
10–3)

80
2 Hookworm
60
Hookworm
40
20 1
0
0 1 2 3 4 5 6 7 8 9 10 11 0
Age (years) 0 1 2 3 4 5 6 7 8 9 10 11
Age (years)
Fig. 55. Left: Graphs showing the relationship between prevalence and age for (a) Ascaris, (b) Trichuris,
(c) hookworms. Each graph is based on a different research study. Right: Graphs showing the
relationships between intensity of infection and age for (d) Ascaris, (e) Trichuris, (f) hookworms. Curve
(d) is based on recovery of worms after chemotherapy and (e) and (f) on egg counts. e.p.g., eggs per
gram. Each graph is based on a different research study (all graphs from Crompton, 1998).

goblet cells and altered muscular activity between levels of IgA and level of infection
have all been implicated. Although infec- with Trichuris and between the levels of
tion does elicit Th2-dependent antibodies IgE and development of Necator.
(e.g. in mice IgA, IgE and IgG1), these are The reasons for the apparent lack of pro-
not thought to play a major role. Little or tective immunity against intestinal worms
nothing is known of comparable mucosal are not fully understood, although many
changes in infected humans and, although suggestions have been made. In countries
antibody responses are made, these are where these infections are common, nutri-
often positively correlated with the dura- tional levels are often low and immunity
tion and intensity of infection, suggesting impaired as a consequence. The pathologi-
no role in protection. Arguments have been cal consequences of the worm infection may
made, however, for inverse correlations exacerbate nutritional problems, leading to
122 Chapter 5

a vicious circle. Infections are sometimes

associated with reduced immune respon-
siveness, and it is clear that worms them-
selves can interfere with the protective
responses of the host in a variety of ways
(Prichard, 1993). It is also possible that
genetic factors influence the ability to con-
trol infections, as has been amply demon-
strated in experimental systems (Wakelin,
1994). It is characteristic of infections with
intestinal nematodes in populations that
their distributions are highly aggregated, i.e.
most individuals have low infections while
a few are heavily infected (Crompton, 1998).
There has been much debate about the
cause of such aggregation, with polarized
views that it is due primarily to environ-
mental exposure or that it is a consequence
of variation in immune responsiveness. It
would be unlikely that genetic factors did
not influence the ability to respond protec-
tively to intestinal worms, and indeed there Fig. 56. Radiograph of lungs in a patient with
have been claims that possession of particu- disseminated strongyloidiasis, showing diffuse
infiltrations.
lar major histocompatibility complex
(MHC)-linked genes does correlate with an
individual’s likely level of infection.
layered gauze pad on a coarse sieve with a
wooden applicator and placed in a sedimen-
DIAGNOSIS
tation flask that has been filled 25 mm
Clinical. There is no well-defined clinical pic- below the rim with 0.9–1.2% saline or water
ture, although watery diarrhoea with mucus, at 37°C. Alternatively, a funnel can be used
perhaps interrupted by constipation, abdomi- with a length of plastic tubing clamped at
nal pain and with a high eosinophilia, may the bottom. If the faeces is watery, it can be
suggest strongyloidiasis. The lesions in the spread on filter-paper, which is then placed
gluteal region and larva currens are almost face down on the gauze. After 2 h, 5 ml of
pathognomic if present. Imaging techniques the bottom sediment can be removed with a
can show infiltration in the lungs (Fig. 56). Pasteur pipette and transferred to a 5 cm
Petri dish. This is examined under a dissect-
Parasitological. The presence of rhabditi- ing microscope for first-stage larvae. If no
form first-stage larvae in a fresh faecal sam- larvae are found, the flask can be left
ple provides a positive diagnosis (Figs 123 overnight at room temperature and re-
and 125). In an old sample mixed with soil, examined; then a drop of iodine can be
hookworm larvae could have hatched from added and the larvae examined on a micro-
eggs and must be differentiated (when liv- scope slide for generic identification.
ing, Strongyloides larvae lash like a whip, There are various culture methods that
while hookworm larvae move sinuously like can be used if no larvae can be found but
a snake). Also in old faeces (30 h) free-living disease is clinically indicated.
adults of Strongyloides might be found.
To concentrate the larvae, Baermann fil- 1. The Harada–Mori, filter-paper, test-tube
tration or formol–ether concentration (p. 263) culture and formol–ether concentration
can be used. In the Baermann technique methods, which can also be used for hook-
10 g (or more) of faeces is spread on a six- worms, are given on p. 263.
 The Nematodes 123

2. In the agar plate method, 2 g of faeces is infections. A skin test using extracts of
placed in the centre of an agar medium in a filariform larvae has been in use for 70
9 cm plastic Petri dish, covered and sealed years. It measures IgE and is about 80%
round the edge with adhesive tape, and reliable, although, like other tests, it cross-
incubated at room temperature (about reacts with filarial infection.
28°C) for 48 h. For greater safety, a double- The ELISA is fast and efficient, using
walled Petri dish (or a smaller dish inside stored antigen, and is in routine use in
the larger) can be used, the outer area con- some laboratories (Mangali et al., 1991).
taining 25% glycerine to prevent infective The test gives sensitivity and specificity of
larvae from reaching the edge of the lid. about 95% when measuring IgG. Specificity
The tracks of larvae can be seen with the of the indirect test can be improved by
naked eye but the dish should also be prior absorption with filarial and hook-
examined under a compound microscope worm antigens (Conway et al., 1993).
with a green filter at
40 magnification. The indirect fluorescent antibody (IFA)
For generic identification, a hole can be test has been used with living larvae as anti-
made in the agar with hot forceps, 10% for- gen, preabsorbed against other nematodes,
malin added, liquid removed from the bot- and recently a simple gelatine agglutination
tom with a Pasteur pipette, sedimented and test has been proposed (Sato et al., 1991).
the sediment examined on a microscope There is as yet no method for measuring
slide at high power. This is probably the circulating antigens.
most sensitive method.
3. In the watch-glass culture method sev- TREATMENT
eral grams of faeces are spread out on a Chemotherapy is principally by benzimida-
watch-glass, moistened with water, placed zoles, which appear to act by binding to
in a Petri dish containing a 2–3 mm layer tubulin and disrupting the assembly of
of water, covered and re-moistened as microtubules and by altering transmembrane
required. Free-living adults may be seen on proton discharge (Grove, 1996).
the watch-glass after several days or infec-
tive larvae after 3 days. Thiabendazole. Given orally twice a day for
4. A charcoal culture method is also some- 3–7 days, 25 mg kg1 body weight has a
times employed. Five to 10 g of faeces is cure rate of about 80%. This is still the
mixed with activated charcoal in a 10 cm drug of choice – unfortunately, since side-
diameter Petri dish, well dampened with effects (nausea, dizziness and anorexia) are
distilled water and left covered for 4 days common – chemical formula: (2-(4-thia-
in an incubator at 26–28°C. The infective zolyl)-1-H-benzimidazole-2-yl)-carbamate.
larvae can be recovered with a soft paint-
brush from the condensation drops on the Mebendazole. If given at 100–200 mg twice
lid. For large quantities of faeces, a sealed daily for 3 days, it is probably effective
jam jar can be used, 5 cm full, and large against adult worms but not against migrat-
numbers of larvae will be found in the ing larvae. Treatment for several weeks is
meniscus around the edge of the mixture more effective, probably because it kills
when left as before. autoinfecting larvae when they develop
5. The entero-test involves swallowing a into adults. Higher dosages may be more
brushed-nylon thread inside a gelatin cap- effective for cases of disseminated strongy-
sule and then withdrawing it together with loidiasis – chemical formula: methyl(5-
entrapped larvae, fixing in 10% formalin (benzyl)-1-H-benzimidazole-2-yl)-carbamate.
and examining under the microscope. In
cases of hyperinfection, larvae may be Albendazole. When given at 400 mg twice
found in sputum or even urine. daily for 3 days, it has given variable
results in trials, with 50–85% cure rates.
Immunological. These tests cannot usually Long-term treatment will probably prove to
differentiate between current and past be as effective as mebendazole, perhaps with
124 Chapter 5

fewer side-effects and greater action against below 8°C or above 40°C for more than a few
larvae – chemical formula: methyl-(5- days. They have little resistance to drying,
propylthio-1-H-benzimidazol-2-yl)-carbamate. excessive moisture or marked changes in
temperature. Infective larvae live for about
Ivermectin. In clinical trials of uncompli- 14 days in soil.
cated cases, this macrocyclic lactone was Where Strongyloides occurs together
fairly effective (over 80% cure rate) against with hookworms, the former is almost
adults and larvae at a single dose of 0.2 mg always found to be rarer. This is rather sur-
kg1 body weight (Marti et al., 1996). Long- prising when it is considered that the para-
term treatment (0.2 mg kg1 once a week for sitic females are more prolific than female
4 weeks) with ivermectin may prove to be hookworms and the presence of free-living
the best option for complete cure in patients generations should increase the numbers of
who fail to respond to initial treatment. For larvae in the soil. There are three possible
disseminated strongyloidiasis, treatment explanations: the first is that the first-stage
over 3–4 weeks is necessary (Grove, 1996). larvae in the faeces are not as resistant as
It is very difficult to treat cases of dissemi- hookworm eggs; the second that the filari-
nated strongyloidiasis with intestinal form larvae have shorter longevity; and the
obstruction, where patients usually need third that reported prevalence rates are
suction and drainage, intravenous fluids and much too low because of the difficulties of
thiabendazole given daily for a week, per- diagnosis.
haps rectally, since there is no intravenous Infection rates reported recently from
formulation. Since patients often die, par- surveys in various countries are:
enteral ivermectin or use of cyclosporin (3 Aborigines in Queensland, Australia (large-
mg kg1 daily) could be tried as a last resort. scale survey) 2%; north-eastern Brazil
5.3% and 9.6%, São Paulo (infants) 2%;
EPIDEMIOLOGY Dagestan (large-scale) 1–1.4%; Bihar, India
In many areas strongyloidiasis is coextensive 10%; Jamaica 1%; Laos 19% (10% in
with hookworm infection since the environ- under-10s); Bauchi in Nigeria 0.4%;
mental conditions favouring the free-living Okinawa (Ryuku Islands) 4–22%; USA
stages and the mode of infection are similar, (large-scale) 0.2%, Kentucky 0.9%,
but this is not always true. Like hookworm, Tennessee 3%.
it is primarily a disease of poverty and
insanitary conditions, particularly where PREVENTION AND CONTROL
there are poor conditions for disposal of Personal prevention is aided by the wear-
human waste and inadequate water sup- ing of shoes. Control is principally by the
plies. In a study in Bangladesh, occupants of provision of adequate sanitation facilities
an urban slum community were more likely consequent on a rise in living standards; it
to be infected if they used communal is sobering to realize that 2400 million
latrines rather than individual latrines, if people (45% of the population of the
they had an earth floor rather than a concrete world) still do not have sanitation. In some
floor and if they were aged between 7 and 10 areas water is recycled from sewage sys-
(Hall et al., 1994). Both are primarily rural tems and larvae can still survive on the soil
infections, particularly common in coffee, or grass, and water thus needs further treat-
cocoa and banana plantations. Infection is ment or storage. Targeted chemotherapy of
also common in closed communities, such those groups most at risk may prove to be
as mental institutions. Infection appears to of use (Conway et al., 1995), but occasional
be acquired progressively between the ages mass chemotherapy is unlikely to be effec-
of about 6 and 20 and then prevalence tive. However, the repeated mass chemo-
remains constant for the whole of adult life. therapy campaigns against all geohelminths
The larvae of both parasitic and free-living in general being carried out in many coun-
forms are unable to survive temperatures tries may have some effect (see p. 134).
 The Nematodes 125

ZOONOTIC ASPECTS counts but no clinical disease. Clinical dis-

Transmission is almost entirely between ease might be potentiated by prenatal
humans, although chimpanzees and dogs infection from symptomless mothers, fol-
have been found naturally infected. lowed by a very high exposure to faecal
contamination in bags used to carry babies.
Another species, S. fuelleborni Linstow, Treatment with thiabendazole was very
1905, is a common parasite of monkeys in effective. The parasite has been designated
Africa and Asia and occurs in humans in S. fuelleborni kellyi Viney, Ashford and
the forest areas of Central Africa Barnish, 1991, because of small differences
(Cameroon, Central African Republic, from the African parasite.
Congo, Congo Republic, Ethiopia, Malawi, There are many species of Strongyloides
Ruanda, Togo and Zimbabwe). In these from a wide range of mammals in which
countries it appears to be a natural parasite the infective, third-stage, larvae can pene-
of humans and in some areas is the pre- trate into the skin of humans but develop
dominant species of Strongyloides, with an no further. They include: S. canis Brumpt,
infection rate of 25%. 1922 in dogs, S. cebus Darling, 1911 in
S. fuelleborni can be differentiated from monkeys (human case in Panama), S. felis
S. stercoralis as eggs, not larvae, are found (Chandler, 1925) in cats (Australia), S.
in the faeces; these measure on average myopotami Artigas and Pacheco, 1933 in
53 µm
35 µm (range 48–61 µm
30–40 rodents and carnivores (Brazil), S. papillo-
µm) (Fig. 124). The eggs are smaller than sus (Wedl, 1956) Ransom, 1911 in sheep, S.
hookworm eggs and in a later stage of planiceps Rogers 1943, in dogs, cats and
cleavage. The eggs hatch quickly in faecal foxes (Japan), S. procyonis Little, 1965 in
samples and in cases of doubt a specific carnivores (USA, experimental), S. ransomi
diagnosis can be made by culturing to the Schwarth and Alicata, 1930 in pig and rab-
free-living adult stage, since these differ bit, S. simiae in primates (Guinea-Bissau,
from those of S. stercoralis (Grove, 1996). experimental), S. westeri Ihle, 1917 in
Free-living generations of S. fuelleborni horse and pig. The free-living males of var-
tend to develop under semi-aerobic condi- ious species can be differentiated by the
tions. structure of the spicules (Grove, 1996).
An experimental infection resulted in Halicephalus (= Micronema) deletrix
an intense itching at the site of entry, fol- (Anderson and Bemrick, 1965) is a rhabditi-
lowed by fever, lymphangitis, lymphadeni- form saprophyte living in soil (family
tis and cough, with an eosinophilia of 48% Cephalobidae) but on three occasions it has
in the early stages. Abdominal pain invaded the brain, liver and heart of
occurred after 20 days and eggs appeared humans in the USA through deep lacera-
in the faeces after 28 days. tions and caused death through meningo-
What appeared to be a morphologically encephalitis (Gardiner et al., 1981). It has
identical parasite has been reported in the been found more often in horses (female
last few years from Papua New Guinea worms only) in North America and Europe;
(PNG) and Western New Guinea (Irian albendazole with diethylcarbamazine was
Jaya), although there are no non-human effective in one cutaneous equine case.
primates on this island. In some areas of Rhabditids (family Rhabditidae) are
PNG an almost invariably fatal disease small, free-living, saprophytic nematodes
(‘swollen belly syndrome’) was found in that are commonly found in soil and there
babies 1–6 months old, with swollen have been many sporadic reports of infec-
abdomen, respiratory distress, enteric pro- tions in humans; adults are usually recov-
tein loss and peripheral oedema. There was ered from faeces and some infections may
no fever but over 100,000 eggs g1 faeces, be spurious. Species reported are:
the eggs often being passed in strings Cheilobus quadrilabiatus Cobb, 1924, in
(Ashford et al., 1992). faeces of children in Slovakia, Diploscapter
In other areas there are equally high egg coronata Cobb, 1913, in the stomach of
126 Chapter 5

patients with low gastric acidity in Texas, LOCAL NAMES

Pelodera strongyloides Schneider, 1866, Chek kaung (Burmese), Au chung
found under the skin of an infant in (Cantonese), Nsunsuma (Fanti), Aonobyo,
Alabama, USA, and of a child in Poland Junishichochu, Kochu, Koekabure,
(this is a widespread species often found in Koemake, Sakanoshita or Tsuchikabure
the lachrymal fluid of voles), P. teres (Japanese), Njowni (Luo), Kokki pulu or
Schneider, 1866, found in faeces, Rhabditis Koku panuwa (Singalese), Gooryan
axei (Cobbold, 1884) in urine samples in (Somali), Njuka safura (Swahili), Puchi
China and Zimbabwe, R. elongata (Tamil), Pa-yard pak khow (Thai), Sondono
Schneider, 1866, found twice in girls in (Twi), Aran inu (Yoruba).
South Korea, R. inermis (Schneider, 1860)
Dougherty, 1955, in faeces of 17 school- GEOGRAPHICAL DISTRIBUTION
children in Japan, R. niellyi Blanchard, Necator was at one time confined almost
1855, in skin of a patient in France, R. pel- entirely to the tropics and subtropics but
lio (Schneider, 1866) Bütschli, 1873 in the has spread widely and is now the domi-
vagina of a girl in Mexico, R. taurica nant hookworm in Portugal, northern
Mireckij and Skrajabin, 1965, in the faeces Turkey, the Caspian Sea area of Iran and
of a child in Russia, R. terricola Dujardin, areas of Japan. It is widespread in Africa
1845, in the faeces of children in Slovakia south of the Sahara, the Americas (Brazil,
and Rhabditis sp. in faeces of five children Colombia, Venezuela, West Indies, south-
in South Korea. ern USA), where it was probably intro-
duced with the slave trade (although
Ancylostoma has been reported from pre-
Order Strongylida Columbian mummies), the Far East (south-
ern and eastern India, Sri Lanka, Malaysia,
The human hookworms comprise two par- China, Indochina, Japan, Indonesia, north-
asites, Necator americanus and ern Queensland) and the South Pacific. It is
Ancylostoma duodenale. They both cause absent from most arid zones and temperate
similar disease, including anaemia, have climates.
similar life histories and require the same
control measures. Perhaps because of the LOCATION IN HOST
movement of peoples, they also have Adult worms are present in the second and
widely overlapping distributions. In addi- third portions of the jejunum and rarely in
tion, there are animal hookworms that are the duodenum with the buccal capsule
occasionally found in humans, and related attached to the mucosa. In heavy infections
nematodes, which in some cases are locally they may be found as far back as the cae-
important, adults being found in the intes- cum.
tine or, in the metastrongyles including
Parastrongylus, the respiratory passages.
MORPHOLOGY
The adults are cylindrical, greyish-yellow,
nematodes tapering anteriorly and slightly
Family Ancylostomatidae curved, with the head bent back dorsally
(forming a ‘hook’).
Necator americanus The cuticle is smooth with fine trans-
(Stiles, 1902) Stiles, 1906 verse striations and has lateral cervical
SYNONYMS papillae just behind the nerve ring, at
Uncinaria americana Stiles, 1902. about the level of the middle of the oeso-
phagus. The large buccal capsule opens
DISEASE AND POPULAR NAME slightly dorsally and has a pair of short tri-
Ancylostomiasis or ancylostomosis (neca- angular lancets at the bottom of the cavity
torosis), uncinariasis; New World hook- (Figs 57 and 58). These aid in attachment
worm infection. of the worm to the mucosa and also in cut-
 The Nematodes 127

Fig. 57. Stereoscan of the anterior end of the

hookworm N. americanus.

ting off portions for food. A pair of anti-

coagulant-secreting glands open into the
buccal capsule, producing a histolytic pro-
tease with a molecular mass of 37 kDa.
The muscular oesophagus is cylindrical
with a slight expansion posteriorly and is Fig. 58. Anterior end and caudal bursa of male of
about one-sixth of the total length of the N. americanus (left) and A. duodenale (right).
worm. The intestine is straight and opens
at the posterior end.
The male measures 7–9 mm
0.3 mm. orly to open into the oviducts, followed by
A single testis lies along the intestine and long, slender, coiled ovaries.
leads through the seminal vesicle and ejac-
ulatory duct into the cloaca. Immediately LIFE CYCLE (Fig. 59)
noticeable is the broad, membranous, sym- The transparent egg is thin-shelled and
metrical, caudal bursa, reinforced by rib- ovoid, with blunt, rounded ends; it mea-
like rays. Within the bursa there are two sures 60 (64–76) µm
40 (36–42) µm. The
bristle-like spicules about 2 mm long, ovum is unsegmented when discharged by
which are fused at their distal ends to form the worm but continues to develop and is
a barb. The cloaca opens into the bursa. usually at the 4- or 8-celled stage when
The shape of the bursa differs in Necator passed in the faeces. It develops quickly
and Ancylostoma and the two species can and may already be at the morula stage in
also be differentiated by the dorsal ray, old faecal samples. On reaching soil the
which in the former is split to its base (Fig. embryo develops into a first-stage larva,
58). The female measures 9–11 mm
which hatches out in 24–48 h. The condi-
0.4 mm. The vulva usually opens just ante- tions for maximum rate of development are
rior to the middle of the body and from it warmth (+25°C), shade, moisture and a
paired vaginae lead anteriorly and posteri- light sandy loam. These larvae are termed
128 Chapter 5

ADULTS
in ileum
Via skin, venules,
heart, lungs (alveoli,
bronchi, trachea),
oesophagus, ileum

HUMAN

Penetrate skin (or

may be ingested with Segmenting
Ancylostoma) EGGS (60 m
40 m)
3RD-STAGE FILARIFORM in faeces. Hatch
LARVAE do not in soil in
feed and live in 24–48 h
soil for about
5 weeks SOIL

1ST-STAGE RHABDITIFORM
LARVAE. Feed on
bacteria

Moult twice
3 and 5 days

Fig. 59. Life cycle of human hookworms.

rhabditiform because the structure of the Hookworm larvae may also need to be dif-
oesophagus (with an anterior portion con- ferentiated from other nematode larvae in
nected by a thin region to a posterior bulb) soil or cultured from faeces (Table 9).
resembles that of the free-living nematode The filariform larvae are most numerous
Rhabditis. They measure 280–300 µm
17 in the upper 2 cm of soil, or they may be
µm and resemble closely the first-stage lar- supported singly or in tufts in the surface
vae of Strongyloides, except that hook- film of water on blades of grass. They wave
worm larvae are slightly longer, less their anterior ends in the air in a questing
pointed posteriorly and have a longer buc- (nictating) manner. They thrive best in
cal cavity (Fig. 53). The larvae feed on bac- shady, moist open soils covered with vege-
teria and organic debris in the soil and tation; drying, flooding or direct sunlight
moult twice; once on the 3rd day when 400 are rapidly fatal (Plate 2). Their average life
µm long and again on the 5th day when in the tropics is about 2–6 weeks but some
500–700 µm long. The third-stage or filari- larvae may survive under favourable condi-
form larvae do not feed and retain the shed tions for up to 15 weeks. The optimal tem-
cuticle for a time. The mouth becomes perature range is 28–35°C. They are
closed with a plug and the oesophagus capable of ascending 60–90 cm of sandy
occupies one-third of the length of the loam but lateral movement is probably lim-
body. The larvae are now infective; those of ited to about 30 cm (Udonsi and Atata,
Necator and Ancylostoma can be differen- 1987).
tiated by the apparent space between the On coming into contact with human
oesophagus and intestine in Necator and skin, the larvae become active and pene-
by differences in the structure of the trate, usually between the toes or fingers.
oesophageal spears (Fig. 60 and Table 8). The penetrating larvae respond to essential
 The Nematodes 129

fatty acids; they release proteolytic venules and are carried by the venous cir-
enzymes and secrete eicosanoids, which culation to the heart and then to the lungs.
are immunomodulative. They enter The larvae grow in the lungs, penetrate
through into the alveoli and ascend the
bronchi and trachea. They are then swal-
lowed and reach the small intestine within
about 7 days after infection, where they
undergo a third moult; this is followed
about the 13th day by a fourth moult, by
which time they are sexually differenti-
ated. Fertilized females begin egg-laying
4–7 weeks after infection and each pro-
duces 2000–11,000 (usually 3000–6000)
eggs per 24 h. Each female contains only
about 200 eggs at one time, so that the pro-
tein turnover involved in egg production is
enormous.
The adults can live for 1–14 years but
usually for about 4. However, in endemic
areas, continuous reinfection and loss
occur. This is demonstrated by the fact that
in many areas infection rates are much
higher after the rainy season (e.g. in west-
ern Tanzania there is a variation from 15 to
85%).

CLINICAL MANIFESTATIONS
There is an intense itching and burning at
the site of entry. Pruritis may be followed
by secondary infection, leading to the con-
dition known as ‘ground itch’, with
papulovesicular dermatitis, subsiding in
about a fortnight (Fig. 61).
The larval migration through the lungs
can cause a cough due to bronchitis or
pneumonitis and patients may pass blood-
stained sputum containing eosinophils, but
pulmonary manifestations are less marked
than with Ascaris larvae and these early
signs are not usually reported among
indigenous populations.
Enteritis, with Charcot–Leyden crystals
in the faeces (resulting from breakdown of
eosinophils) and a high eosinophilia char-
acterize the early stages of intestinal infec-
tion but there is not usually any
eosinophilia in the chronic phase.
A variety of gastrointestinal symptoms,
Fig. 60. The third-stage infective larvae (L3s) of such as abdominal pain, diarrhoea, nausea
Necator (left) and Ancylostoma (right). (a) and (b) and loss of appetite, have sometimes been
Anterior ends; (c) and (d) junction of oesophagus attributed to hookworm infection, but the
and intestine; (e) and (f) tail ends. most serious possible effect of an established
130 Chapter 5

Table 8. Differential features of Necator and Ancylostoma.

Necator Ancylostoma

Adults
Size
5–9 mm
0.3 mm
8–11 mm
0.45 mm
 9–11 mm
0.35 mm  10–13 mm
0.6 mm
Shape Head small, bent acutely in Bow-shaped curve; head
opposite direction to general curve in same line as body

Buccal capsule Almost spherical Elongated, pear-shaped

Mouth Guarded by 2 semilunar Guarded by two pairs of curved
cuticular cutting plates teeth
Female
Tail No spine Sharp spine (often lost)
Vulva anterior to middle posterior to middle
Male
Bursa Narrow, longer than wide Outspread, wider than long
Dorsal ray Deeply cleft. Tip of each cleft Shallow cleft. Tip of each cleft
divided into two divided into three
Spicules Tips usually united and recurved Tips not united
Eggs Indistinguishable
First- and second-
stage larvae Indistinguishable
Third-stage
infective larvae
Size Body length 590 µm Body length 550 µm
Overall length 660 µm Overall length 720 µm
Tail Short and pointed (63 µm) Long and blunt (85 µm)
Sheath Marked striations, especially at Faint cuticular striations
posterior end
Head Pointed Blunt
Intestine Apparent gap between intestine and No apparent gap between
oesophagus intestine and oesophagus
Oesophageal spears Prominent. Anterior and shaped like Not so prominent. Tips
thistle funnel do not diverge

infection is the development of a PATHOGENESIS

hypochromic microcytic anaemia, present In light and moderate infections anaemia is
in about 36 million individuals worldwide. due primarily to insufficient iron intake
Hookworms are blood feeders and there is exacerbated by the presence of the worms
a daily loss of about 5 ml of blood in light but in heavy infections it occurs even
infections to 100 ml in heavy infections when the dietary intake is adequate
(very roughly equivalent to 2 ml day1 for (Pawlowski et al., 1991). This applies to
every 1000 eggs g1 faeces). There may be areas such as western Nigeria, where hook-
many symptoms accompanying anaemia, worm anaemia only occurs when many
including lassitude, mental apathy, skin worms are present (i.e. where there are
pallor, syncope and angina pectoris. In 1000 worms with over 20,000 eggs g1
children, stunting of growth is characteris- faeces day1). On the other hand, in
tic of severe chronic infections (Fig. 65) Mauritius, where the average iron intake is
and there is evidence that infection also only about 5–10 mg day1, severe anaemia
lowers cognitive ability (Sakti et al., can result from the presence of 100 worms.
1999). The time factor must also be considered, as
 The Nematodes 131

Table 9. The differentiation of infective filariform larvae found in cultures from human faecal specimens.
Strongyloides Trichostrongylus Ancylostoma Nectator Ternidens Oesophagostomum

Length (m) 500 750 660 590 680 (630–730) 720–950

Sheath Absent Present Sheath 720 m, Sheath 660 Present Present and
striations not m, striated
clear striations
clear at tail
end

Length of
 





oesophagus
as proportion
of total body
length

Intestine Straight Intestinal lumen Anterior end Anterior end Following Large triangular
zigzagged narrower in as wide as the oesophagus cells and lumen
diameter than oesophagus is a pair of zigzagged
oesophageal bulb. Gap sphincter cells.
bulb. No gap between the Intestinal
between the oesophagus lumen
oesophagus and the somewhat
and the intestine intestine zigzagged

Tail Divided End of tail Blunt Sharply pointed Pointed Sharply pointed
into three knoblike
at the tip

Head Blunt Rounded Rounded

Mouth Mouth spears Mouth spears Buccal capsule +
not very clear clear and oesophagus make
and parallel divergent inverted Y shape

Fig. 61. ‘Ground itch’ at site of entry of larvae of Necator in a sensitized individual. With some non-
human species of hookworms, the larvae continue to wander in the skin, causing creeping eruption (also
see p. 160).

anaemia will not become apparent until This is usually because of an adequate diet,
the iron reserves have been completely as in Costa Rica or the southern USA but it
depleted. may also be because other resistance fac-
In many areas there is widespread infec- tors limit the numbers of hookworms pre-
tion but hookworm anaemia is uncommon. sent, as in India.
132 Chapter 5

Anaemia occurs because the adult nutrition, malaria, amoebiasis and other
worms pass a steady stream of blood helminthiases.
through their intestines in order to obtain
oxygen for respiration as well as food, with Parasitological. Recovery and recognition of
a consequent loss of erythrocytes and pro- eggs in faecal samples (Fig. 123) are the
tein-containing fluid. The amount of blood standard method of diagnosis. The eggs are
passed by an adult Necator (0.03–0.05 ml identical to those of Ancylostoma and very
per worm day1) is less than in an equiva- similar to those of Ternidens and
lent Ancylostoma infection (0.14–0.25 ml Oesophagostomum. Ova must be cultured
per worm day1) because of its smaller to the infective larva stage if it is required
size. Reabsorption of haemoglobin from the to differentiate between the two hookworm
intestine occurs, but the amount (about species (Table 8 and Fig. 59). The Harada–
11%) is less than often assumed in the Mori culture method is given on p. 262).
past; in many areas an adequate diet
accompanied by intravenous iron would be Serological. Not often employed.
more effective in suppressing the clinical Complement fixation and indirect haemag-
signs than anthelminthic treatment. glutination tests work well with antigen
There is no proof that hookworms obtained from adult worms. ELISA and
depress haemopoiesis but they do appear radioimmunological assay (RIA, measuring
to decrease erythrocyte life. In addition to IgE) both have good specificity when ES
anaemia, a characteristic hookworm antigens are used.
oedema occurs in heavy infections, resem- Recently a gene for Ancylostoma
bling the nephrotic syndrome. This is secreted polypeptide (ASP), a protein pro-
caused by low plasma protein (particularly duced by infective larvae of A. caninum,
albumin) but usually only becomes appar- has been cloned and the amino acid
ent when there is a low iron intake. sequence determined. This is very similar
However, a heavy worm load of about 2000 to an insect venom that elicits a strong
adults can cause a loss of 4 g of albumin immune response and is being researched
even with an adequate dietary supply of as a possible vaccine (Hotez and Prichard,
iron. 1995).
The extensive damage to the mucosa,
including necrosis and haemorrhage, some- TREATMENT
times recorded in cases of hookworm infec- A single course of chemotherapeutic treat-
tion is probably due to secondary causes, ment aimed at permanent cure in outpa-
as is vitamin B12 and folic acid deficiency. tients living in an endemic area is unlikely
Similarly, there does not appear to be a to be successful, but it is nevertheless
direct relationship between hookworm important to reduce the number of worms
infection and malabsorption (contrast present below the level causing clinical
Strongyloides (p. 119)). symptoms. This level will vary in different
As with the other geohelminths parts of the world, depending mainly on
(Haswell-Elkins et al., 1987a) and the iron intake and nutritional status. Any
schistosomes, a small minority of infected drug given should also be supplemented by
individuals have high worm burdens with oral (or intravenous where supervision is
serious disease and are responsible for not possible) iron therapy. In light infec-
most of the eggs reaching the environment tions a single annual treatment is suffi-
(Anderson and Schad, 1985). cient, but in heavy infections 6- monthly
treatment is necessary. The properties of
DIAGNOSIS the various drugs are given in Albonico et
al. (1998).
Clinical. Chronic anaemia and debility in
patients living in an endemic area are sug- Albendazole. A single dose of 400 mg for all
gestive, but may also be caused by mal- ages above 2 (60–90% effective) is also
 The Nematodes 133

active against most other intestinal nema- ern Nigeria, 68% in Bobei County in China,
tode and cestode infections. 2.5% in Burma (Myanmar), 69% in
Indonesia and 54% in Surinam.
Mebendazole. A single dose of 500 mg for Soil type is of great importance to the
all ages above 2 or 100 mg twice daily for 3 larvae, which migrate up against the water
days (20–90% effective) is also effective flow and down again when the top layer of
against other intestinal nematodes. soil is drying. Clay soils are less well aer-
ated and, where there is heavy rainfall, the
Levamisole. A single dose of 3 mg kg1 larvae are not able to survive so well as in
body weight is more effective against sandy soils. This is in contrast to the situa-
Ancylostoma than against Necator tion with Ascaris and Trichuris eggs, which
(20–60%). survive better on clay soils, as they dry out
less in drought and have better adhesive
Pyrantel pamoate. A daily dose of 10 mg properties. Larvae are also better able to
kg1 body weight (max. 1 g) for 3 days. migrate in well-filled soil that has a crumb
More effective against Ancylostoma than structure than in highly compacted soil.
against Necator (20–90%) – chemical for-
mula: (E)-1,4,5,6-tetrahydro-1-methyl-2-(2- PREVENTION AND CONTROL
(2-thienyl)vinyl]-pyrimidine. Personal prevention is provided by the
wearing of shoes.
Bitoscanate, bephenium and tetrachlor- The control of hookworms has a long
ethylene can no longer be recommended, history, beginning with the campaign of the
while ivermectin is not effective. Rockefeller Sanitary Commission to elimi-
In a study of 3000 young children in nate the infection from the southern USA
Zanzibar, it was estimated that 1260 cases in 1909, followed by the international
of moderate and 276 cases of severe efforts of the Rockefeller Foundation in
anaemia were prevented by treatment with 1913. The strategies used then of mass
mebendazole, with improved motor devel- chemotherapy and improvements in sanita-
opment. In children in East Africa learning tion are still appropriate today. Such mea-
potential improves for months after treat- sures were also very effective in Japan in
ment, with much higher school attendance the 1950s–1980s (from 4.5% with hook-
(about 100 million children worldwide do worms and 60% with Ascaris in 1950 to 0
not attend school because of soil-transmit- and 0.01% in 1987).
ted nematode infections). The newer single-dose, broad-spectrum,
anthelminthics are a great advance for
EPIDEMIOLOGY mass campaigns against morbidity caused
It has been estimated that there are from by all the geohelminths, which are under
1050 to 1277 million cases worldwide way in many countries, funded by many
(about two-thirds due to Necator) with international and national agencies and by
90–130 million suffering morbidity and non-governmental organizations (NGOs).
65,000 deaths annually, principally from For instance, a campaign for annual treat-
the anaemia. Hookworm infection is essen- ment of all schoolchildren (6–14 years old)
tially a rural disease of poverty and is par- in Ghana with albendazole has begun, pri-
ticularly common in cocoa, coffee and marily to reduce disease rather than inter-
banana plantations, owing to the dense rupt transmission, which is not feasible at
shade and high rainfall (Plate 13). Heavy present. The World Health Organization
infections are not found in areas with (WHO) target is that by 2010 regular
much less than 100 cm of rain per year and chemotherapy will be provided for at least
are rare in arid regions. 75% of schoolchildren in endemic coun-
Recent estimates of infection rates in tries at risk of morbidity (a global school
various regions are: 46% in Cameroon, 6% health initiative against both geohelminths
in peninsular Malaysia, 14–50% in south- and schistosomes is being supported by
134 Chapter 5

many international agencies). However, the infection, although the fecundity of the
possibility of resistance to drugs needs to parasites is suppressed.
be carefully monitored, particularly
because of the sale of substandard products
Ancylostoma duodenale
in some countries (Crompton, 2000).
(Dubini, 1843) Creplin, 1845
There are three possible strategies for
chemotherapy campaigns against all the
SYNONYMS
geohelminths.
Agchylostoma duodenale Dubini, 1843;
1. Universal (= mass) campaigns, in which Ankylostomum duodenale; Uncinaria duo-
communities are treated irrespective of denalis.
infection status, age, sex or social charac-
teristics. DISEASE AND POPULAR NAMES
2. Targeted campaigns with group-level Ancylostomiasis or ancylostomosis, unci-
application, irrespective of infection status. nariasis; Old World hookworm infection.
3. Selective campaigns with individual
application, based on diagnosis of current LOCAL NAMES
infection or on level of infection. As for Necator.
The first is feasible if there are sufficient
GEOGRAPHICAL DISTRIBUTION
funds; otherwise, the second is most cost-
Ancylostoma extends into more temperate
effective, with treatment aimed at high-risk
regions than Necator. It is present in the
groups, such as school and preschool chil-
North African and European
dren and women of childbearing age, while
Mediterranean littoral; Asia (northern
the third is expensive, difficult to imple-
India, Myanmar, Cambodia, Laos, Vietnam,
ment and likely to be unacceptable to the
Malaysia, Indonesia, China, Taiwan,
majority of infected individuals.
Japan); the South Pacific; and the Americas
Wider utilization of cheap and effective
(particularly Chile, Mexico, Venezuela).
sanitation technologies, such as the venti-
lated improved pit (VIP) latrine, first intro-
LOCATION IN HOST
duced in Zimbabwe, or the pour-flush
As for Necator.
toilet, which provides a water seal and
does not require piped water, needs to be
MORPHOLOGY
encouraged in addition to chemotherapy.
Ancylostoma is a larger and more robust
Health education and the provision of
worm than Necator. The head is curved
latrines are also needed to prevent indis-
dorsally in a smooth curve so that speci-
criminate defecation in the fields.
mens do not have the hook-like appearance
Integrated campaigns, together with
characteristic of Necator. The large buccal
immunization or general school health
capsule has bilaterally symmetrical curved
efforts, can often make the most effective
cutting processes, consisting of two fused
use of primary health-care workers.
There are large-scale control campaigns teeth, and there is a pair of internal teeth at
under way in Mexico, Seychelles, South the bottom of the capsule, with histolytic
Africa (Natal), Sri Lanka and Zanzibar glands at the base. These aid the attach-
(Albonico et al., 1998). ment of the worm to the mucosa and also
assist in cutting off portions for food (Figs.
ZOONOTIC ASPECTS 62 and 63). The features differentiating
Virtually none, although Necator is found Ancylostoma from Necator are shown in
occasionally in chimpanzees and pigs. Table 8.
Young hamsters can be successfully The male measures 8–11 mm

infected in the laboratory, which is stimu- 0.4–0.5 mm; the shape and structure of the
lating research into the physiology, pathol- caudal bursa differs from that of Necator
ogy and particularly the immunology of (Fig. 58).
 The Nematodes 135

Fig. 62. Stereoscan of anterior end of A. duodenale showing two pairs of cutting teeth in mouth capsule.

LIFE CYCLE
The larger females of Ancylostoma lay
about twice as many eggs (20,000–30,000
per female per 24 h) than those of Necator.
The eggs of the two genera in faeces are
identical and develop in a similar manner
in the soil.
In contrast to Necator, oral infection
with infective third-stage, filariform, lar-
vae, presumably principally on salad veg-
etables, is thought to be more important
than skin penetration. Following oral infec-
tion, the larvae travel directly to the intes-
tine without visiting the lungs. They enter
the mucosa of the duodenum for 2–3 days
before emerging and undergoing the third
moult. Adults mature in 4–7 weeks and
usually live for about 1 year.

CLINICAL MANIFESTATIONS
If infection is by skin penetration, there
Fig. 63. Section of jejunum with anterior portion of
can be an itching and burning at the site of
Ancylostoma biting off a piece of mucosa.
entry, followed by a pruritic response.
Pulmonary reactions are more pronounced
than with Necator. In Japan, ‘Wakana dis-
ease’, caused by the migrating larvae, was
The female differs principally in having characterized by dyspnoea, cough, nausea,
the vulval opening posterior to the middle vomiting and high sputum and blood
of the body (Fig. 64). eosinophilia (up to 90%).
136 Chapter 5

testis
spicule
seminal vesicle
intestine
ejaculatory duct

cement gland
ovary gubernaculum
uterus
dorsal ray

Fig. 64. Vulval region of female of A. duodenale and caudal bursa of male showing process of fertilization.

Weakness, anorexia and pica (dirt-eat- China (Fujien Province) 50%, (Sichuan
ing) are sometimes found in heavy chronic Province equally with both species) 74%,
infections. Egypt 6–8%, Ethiopia 67%, Kenya
(preschool children in Kilifi) 29%, south-
PATHOGENESIS ern Nepal 11–79%, Paraguay (school chil-
This is similar to infection with Necator dren) 59% with both species.
but, because an adult Ancylostoma is The ova can develop at a lower tempera-
larger, the anaemia caused by an equivalent ture (a minimum of 14°C) than those of
number of worms is more severe. Necator, so that infection is more common
in subtropical and temperate climates. The
DIAGNOSIS AND TREATMENT optimum temperature for hatching of eggs
As for Necator. is 20–27°C and they fail to develop above
40°C. Infection was formerly common in
EPIDEMIOLOGY tin miners in England and in workers
As for Necator. In many areas both types of building the St Gotthard tunnel between
hookworm are present, possibly in the Switzerland and Italy.
same patient.
Infection rates recorded recently for var- PREVENTION AND CONTROL
ious areas where specific identification has As for Necator except that the thorough
been made are: north-eastern Australia in washing of salad vegetables is more impor-
Aboriginals 31–77%, Benin 25–35%, tant than the wearing of adequate footwear.
 The Nematodes 137

1996). In this area this is the leading cause

of eosinophilic enteritis and patients may
have aphthous ulcers of the terminal
ileum, caecum and colon. In 15 cases,
adults were seen in situ and in nine the
typical buccal capsule with three teeth
could be recognized in biopsy tissue sec-
tions. The adults produced no eggs but
were diagnosed by biopsy or by an IgG
ELISA. Recently, a Western blot using ES
antigens from adult worms to identify IgG4
antibodies to a protein of 68 kDa (Ac68)
was found to be more specific and sensi-
tive than the ELISA. However, human
species are likely to cross-react and the
specific IgE ELISA for Necator may be nec-
essary in order to differentiate.
All patients had dogs and walked
around the garden in bare feet and it is
assumed that infection was contracted
from front lawns, which were watered with
sprinklers and thus washed dog faeces into
the lawn. There were fewer cases in the
winter months. The patients were in an
Fig. 65. Severe stunting of growth in children with affluent area with good hospital facilities
very heavy hookworm infections. The eldest child for the difficult diagnosis and it is likely
is aged 15 with a haemoglobin level of 1.8 g dl1 . that infection with this species also occurs
Height of windowsill equals 85 cm. in other parts of the world. One case has
been reported from New Orleans, USA, in
ZOONOTIC ASPECTS an 11-year-old girl who had chronic
None. abdominal pain, vomiting, anorexia and
weight loss, which resolved after two doses
Ancylostoma ceylanicum Looss, 1911, is a of mebendazole.
parasite of dogs in Asia and South America Various hookworms of animals very
but also occurs as a human parasite in occasionally parasitize humans: A. japon-
India and the Philippines. Infection is by ica Fukuda and Katsurada 1925, possibly
the oral route, with a prepatent period of in Japan; A. malayanum (Allesandrini,
about 25 days. Infections are light and 1905), a natural parasite of bears;
blood loss does not appear to have any Cyclodontostomum purvisi Adams, 1933,
clinical significance; the larvae do not in Thailand and naturally in the rat;
cause creeping eruption. Diagnosis is by Necator argentinus Parodi, 1920 (doubtful);
culturing the larvae to the third stage. N. suillus Ackert and Payne, 1922, once or
Chemotherapy is effective. twice in humans and widespread in pigs.
Recently, 200 cases of infection with Species causing cutaneous larva migrans
the dog hookworm, Ancylostoma (creeping eruption) are considered on
caninum, have been diagnosed in p. 160.
Queensland, Australia, with another 200
probable cases. All were Caucasians and
presented with severe abdominal pain, Other Strongyles
sometimes also with diarrhoea and weight
loss, followed by blood eosinophilia As well as the hookworms, there are vari-
(Croese et al., 1994; Prociv and Croese, ous other bursate intestinal nematodes that
138 Chapter 5

can sometimes be recovered from humans. pointed ends, and they usually contain a
Almost all are principally zoonotic infec- segmented ovum at the morula stage when
tions, but a few, such as Trichostrongylus, passed in the faeces.
Ternidens and Oesophagostomum, do have
human-to-human transmission in some LIFE CYCLE
areas. Eggs passed in the faeces at the morula
stage hatch in the soil in about 24 h. The
larvae reach the infective third stage in
Family Trichostrongylidae about 3 days. These occasionally penetrate
the skin, but in human infections they are
almost always ingested. When this hap-
Trichostrongylus spp.
pens, the larvae develop into adults in 25
Looss, 1905
days; in contrast to hookworms, they never
undergo a lung migration.
POPULAR NAME
Wireworms (when in domestic stock). CLINICAL MANIFESTATIONS AND PATHOGENESIS
Infection is usually light and causes no
DISTRIBUTION clinical symptoms. In heavier infections (a
Species of Trichostrongylus occur locally few hundred worms) there may be abdomi-
in humans in Iran (67% in Isfahan), Iraq nal pain, diarrhoea and a slight anaemia,
(up to 10%), Israel, Egypt (11–60%), accompanied by a mild eosinophilia
Ethiopia (23%), Armenia, Japan, Korea (under 10%).
(80% in one area), Indonesia and the Cape The head of the adult worm produces
Verde Islands. Sporadic cases may occur in traumatic damage to the mucosa, with
many areas where people and cattle are in inflammation at the site of attachment. The
close proximity (e.g. Africa, Australia, worms may also suck blood but the amount
India and South America). is not sufficient to cause anaemia.

LOCATION IN HOST DIAGNOSIS

The adults attach to the wall of the duode- This is by recognition of eggs in the faeces
num and jejunum by the anterior end. (Fig. 124), which gives identification to the
generic level.
MORPHOLOGY The larvae can also be cultured, using
These are small thin strongyle worms the techniques for hookworms (p. 262).
(family Trichostrongylidae) measuring The infective third-stage larvae must be
5–10 mm in length; most species are nor- differentiated from those of hookworms
mally parasitic in ruminants. They have no and Strongyloides (Table 9). The species of
buccal capsule and live with the head trichostrongyle involved can only be deter-
embedded in the mucosa of the small intes- mined if adults are obtained after
tine. The males have a well-developed cop- chemotherapy, and veterinary textbooks
ulatory bursa, and the structure of the should be consulted.
spicules provides the most useful feature
used to differentiate the 11 species (T. affi- TREATMENT
nis, axei, brevis, calcaratus, capricola, col- All the drugs used for hookworms work
ubriformis, lerouxi, orientalis, probolurus, well against trichostrongyles, which are
skrjabini and vitrinus) recovered from usually easier to eliminate. Mebendazole
humans; in all they are short, equal, stout has been used successfully at 100 mg twice
and spoon-shaped but have small specific daily for 3 days for adults.
differences.
Eggs found in the faeces are similar to EPIDEMIOLOGY, PREVENTION AND CONTROL
those of hookworms but are longer and nar- Larvae are usually ingested on contami-
rower (75–100 µm
30–50 µm) with more nated vegetables and these should be
 The Nematodes 139

thoroughly washed or cooked. The eggs LOCATION IN HOST

and infective larvae are both very resistant Adults occur in the colon and occasionally
to desiccation, which makes control diffi- the ileum, with the anterior end attached.
cult. In areas of Iran and Iraq cattle are kept
in the backyards of houses (Plate 14) and a MORPHOLOGY
particularly heavy build-up of larvae The adults superficially resemble hook-
occurs after the rainy season. worms but are rather larger. The subglo-
It was reported in 1953 that there were bose buccal capsule of Ternidens is
48 million human cases worldwide; it is directed anteriorly and has forked teeth in
not known if prevalence is now much its depths. The mouth is surrounded by a
lower. double ‘leaf crown’ or corona radiata of
cuticular bristles.
ZOONOTIC ASPECTS Females measure 12–16 mm
0.65–
In many areas infection is contracted from 0.75 mm. The vulva opens just in front of
livestock, although with T. orientalis from the anus. Males measure 9.5 mm

sheep and camels, which is the most com- 0.55 mm and have a caudal bursa with the
mon species in humans in China, Japan, rays arranged in a characteristic pattern.
Iran, Iraq, Korea and Taiwan, there is prob- The spicules are long and equal, measuring
ably a human cycle involved. about 0.9 mm in length.
Other trichostrongylids that are com-
mon parasites of domestic stock in many LIFE CYCLE
areas of the world, such as Haemonchus Eggs measure 81 (70–94) µm
52 (47–55)
contortus, Marshallagia marshalli, µm. They pass out in the faeces, usually in
Mecistocirrus digitatus, Nematodirus the 8-celled stage, and develop into rhab-
abnormalis, Ostertagia circumcincta and ditiform larvae in about 30 h. The larvae
O. ostertagi, may occasionally occur in feed on bacteria and moult twice (once on
humans, particularly in Iran and the 6th day and again in 8–10 days at
Azerbaidjan. For further details of these 29°C). The third-stage larva retains the cast
cuticle as a sheath, but it is not known how
parasites, textbooks of veterinary medicine
transmission to humans occurs. All
should be consulted (see General
attempted experimental infections either
References, p. 282).
by mouth or by skin penetration have
failed. It is possible that an invertebrate
intermediate host, such as the termite, is
Family Chabertiidae required (Goldsmid, 1991).

Ternidens deminutus CLINICAL MANIFESTATIONS

Railliet and Henry, 1909 The great majority of cases have a light
worm load and appear to be symptomless,
although little is known of the effects of the
SYNONYMS
parasites and they could be involved in the
Triodontophorus deminutus Railliet and formation of intestinal nodules.
Henry, 1905.
PATHOGENESIS
DISEASE AND POPULAR NAME The parasites feed on blood and probably
Ternidens infection (ternidensiasis or cause ulceration of the mucosa. While the
ternidensosis), false hookworm infection. loss of blood from the large bowel could be
more serious than that caused by hook-
GEOGRAPHICAL DISTRIBUTION worms in the jejunum, as no reabsorption
Comoros Islands, Congo Republic, occurs, anaemia has not been reported.
Mauritius, southern Tanzania and This might be because usually only a few
Zimbabwe (up to 87% in one area). worms are present.
140 Chapter 5

In experimental studies in rhesus mon- found in ruminants and pigs. O. aculeatum

keys, adults eventually become encapsu- (Linstow, 1879) has been reported once
lated in nodules, but it is not known if a each from a human in Brunei and
similar effect occurs in humans. Indonesia (Ross et al., 1989), Oesopha-
gostomum sp. from the peritoneal cavity of
DIAGNOSIS AND TREATMENT a patient in Malaysia and O. stephanosto-
Diagnosis is by recognition of the eggs in mum Railliet and Henry, 1909, very rarely
faeces (Fig. 124); concentration methods from Côte d’Ivoire, with a case from Brazil
can be used if necessary. The eggs must be and probably another from Surinam.
differentiated from those of hookworms,
which can be done with difficulty by the LOCATION IN HOST
larger size and particularly by the larger Adults in nodules in the wall of the colon
volume occupied by the dividing ovum. and caecum.
For more positive identification the larvae
can be cultivated to the infective third MORPHOLOGY
stage (p. 262 and Table 9). These have char- Species of Oesophagostomum resemble
acteristic paired sphincter cells at the junc- hookworms in shape and size but have a
tion of the oesophagus and intestine. buccal capsule that opens forwards, with a
Ternidens is still frequently misdiagnosed cuticular ‘leaf crown’ surrounding the
as hookworm. mouth opening, and a cylindrical rather
Chemotherapy is the same as for hook- than globose buccal capsule. The caudal
worm; albendazole at 400 mg was success- bursa of the male is symmetrical and the
ful in a trial in children (Bradley, 1990). long spicules are equal. Each female has
been estimated to produce about 5000 eggs
EPIDEMIOLOGY AND ZOONOTIC ASPECTS 24 h1.
Ternidens is a very common parasite of
monkeys in tropical areas of Africa and LIFE CYCLE
Asia (China, Indonesia, Malaysia, southern The eggs closely resemble those of hook-
India and Vietnam) and these probably act worms, measuring 58–69 µm
39–47 µm.
as reservoir hosts. It is not known why Larvae hatch in 2 days at 30°C and develop
human infection is restricted to areas of in the soil into third-stage infective larvae
Africa, where it may be very common, but in 5–7 days. These are ingested, invade the
this is presumably related to its (unknown) wall of the colon and caecum and become
mode of transmission. One case has been encapsulated. A nodule forms, measuring
diagnosed from Surinam. about 1.5 cm in diameter, with a fibrous tis-
sue wall and having a living worm in the
centre of an unruptured abscess (Fig. 66).
Oesophagostomum bifurcum
When the worms mature, they break out of
(Creplin, 1849)
the nodule in about 6–7 days and some-
times become attached to the caecal wall.
DISEASE AND POPULAR NAME Shrunken third-stage larvae inside the
Oesophagostomiasis or oesophagostomosis; sheath can survive for a considerable
nodular worm (for species in veterinary period in the environment under desic-
practice). cated conditions.

GEOGRAPHICAL DISTRIBUTION CLINICAL MANIFESTATIONS AND PATHOGENESIS

Oesophagostomum bifurcum is a Some worms apparently mate in the lumen
strongylid nematode (family Chabertiidae) of the colon and cause no symptoms.
and has been reported many times from However, others may stay in small nodules
humans in West Africa and also from East in the intestinal wall or penetrate through
Africa and Asia. It is a common parasite of into the abdominal cavity, where they can
monkeys, while some other species may be cause significant pathology. There can be
 The Nematodes 141

Fig. 66. Nodular lesion caused by O. bifurcum presenting as a para-umbilical mass in an 8-year-old girl
in Nigeria. At laparotomy the mass was found adhering to muscles and fascia of the anterior abdominal
wall of the ascending colon (magnification
11). Sections of the nematodes can be seen.

dozens of nodules, each 2–3 cm in diame- (Polderman et al., 1991, 1999; Polderman
ter. The wall of the colon becomes grossly and Blotkamp, 1995). Nodules sometimes
thickened, although the mucosa and serosa calcify and then show up on X-ray. In a
remain intact. There is no definite cyst wall case of infection in Brunei, probably
but there is a layer of macrophages, epithe- caused by O. aculeatum, a single worm
lial cells and fibroblasts, and often many was removed from a painless lump on the
plasma cells and eosinophils. Nodules con- back measuring 3 cm and containing thick
tain thick pus or caseous material. In the brown pus. Infection may have been con-
majority of cases the infection is self- tracted by direct penetration (Ross et al.,
limiting and eventually resolves without 1989).
treatment.
In northern Ghana and Togo and proba- DIAGNOSIS
bly southern Burkina Faso, infected indi- Clinical diagnosis is often difficult and
viduals often have an epigastric or oesophagostomiasis has often been mis-
periumbilical swelling recognized by local taken for other conditions, such as carci-
people and known as a ‘tumeur de noma, appendicitis or amoebiasis;
Dapaong’ (Plate 15). These may be accom- laparotomy will provide a positive diagno-
panied by considerable pain, and abdomi- sis and ultrasound can be useful.
nal occlusion or the presence of the In order to differentiate the eggs in fae-
abscesses may require surgical interven- ces from those of hookworms, the larvae
tion. Many cases are in children, most have to be cultivated to the third stage
about 10 years old. The wall of the colon is (Table 9). An activated charcoal/faeces
often oedematous and the whole of the filter-paper technique for 5–7 days works
bowel loop becomes hardened and sur- well (p. 123). The larvae measure 720–950
rounded by adhesions. There may also be µm and have a cuticle with prominent stri-
involvement of the liver, and worms in the ations, 28–32 (or sometimes 20) large, char-
abdominal cavity can cause peritonitis acteristic triangular-shaped intestinal cells
142 Chapter 5

and a buccal capsule that differs from that name Syngamus is now used only for the
of hookworm larvae (Blotkamp et al., 1993; species in birds, such as S. trachea causing
Pit et al., 1999). ‘gapeworm’ in poultry, although S. laryn-
An ELISA based on detection of specific geus may still be found in some textbooks.
IgG4 in sera had a specificity of over 95%
in one study and may prove useful in DISEASE NAME
differentiating Oesophagostomum from Mammomonogamiasis or mammomonog-
hookworm in epidemiological studies amosis.
(Polderman et al., 1993).
GEOGRAPHICAL DISTRIBUTION
TREATMENT There have been over 90 reported cases
Surgery to resect the infected portion of the from humans, the majority in South
colon is sometimes necessary. America (25 from Brazil), with a few cases
Albendazole (400 mg or better 10 mg in North America, the West Indies and
kg1 body weight daily for 5 days) and China and single cases from Australia,
pyrantel pamoate (two doses of 10 mg Korea, the Philippines and Malaysia (or
kg1) are both effective but thiabendazole possibly Thailand).
and levamisole are not.
LOCATION OF ADULTS
EPIDEMIOLOGY AND CONTROL Adults inhabit the air passages of the upper
It is likely that infection with O. bifurcum respiratory tract, particularly the larynx or
in northern Ghana and Togo and maybe pharynx.
Uganda now involves human-to-human
transmission and monkey reservoirs are no
MORPHOLOGY AND LIFE CYCLE
longer necessary. In the focus identified in
West Africa it is estimated that there are The male worm (4 mm
0.35 mm) is
about a quarter of a million cases and in much smaller than the female (20 mm

some villages in rural areas there are infec- 0.5 mm) and the two are joined in perma-
tion rates of 30–60%, although infections nent copulation, giving a characteristic Y
are rarely found in young children shape (family Syngamidae). The buccal
(Polderman et al., 1991, 1999; Polderman capsule of both sexes is well developed
and Blotkamp, 1995). Transmission is lim- and globular. It is used to attach the worms
ited to the rainy season, but it is not clear to the air passages, where they suck blood.
exactly how humans become infected. The copulatory bursa and supporting rays
Another species, O. apiostomum (Willach, of the male have characteristic structures
1891) Railliet and Henry, 1905, a parasite that are of specific importance.
of monkeys in West Africa, has been The eggs measure 85–90 µm
50 µm
reported from the colon of a patient in and have a sculptured appearance.
Togo, but specific identification of human Infective third-stage larvae develop from
cases is difficult unless adults are expelled. eggs in 9–15 days at 26–30°C and are prob-
Infections are easier to treat than hook- ably ingested on salad vegetables. Larvae
worm infections and should be much are believed to reach the trachea via the
reduced by any hookworm control campaign. bloodstream and lungs.

CLINICAL MANIFESTATIONS AND PATHOGENESIS

Family Syngamidae
There is an incubation period of 25–40
days. Worms are found in the trachea, lar-
Mammomonogamus laryngeus
ynx and sometimes the smaller bronchi
(Railliet, 1899) Ryzhikov, 1948
and produce headache, nausea, irritation
SYNONYMS and a severe dry cough. There may also be
Syngamus laryngeus Railliet, 1899. blood in the sputum (haemoptysis). An
Syngamus kingi Leiper, 1913. The genus eosinophilia of 23% has been reported.
 The Nematodes 143

DIAGNOSIS AND TREATMENT MORPHOLOGY

Adults can usually be seen in the larynx The third-stage larva measures
and pharynx and eggs may be found in the 0.46–0.5 mm
26 µm when ingested. It
sputum. Adults are sometimes expelled has small lateral alae and characteristic
after coughing and a recent Thai patient chitinous rods in the buccal cavity.
who had worked in Malaysia coughed up The adult worms are normally found in
96 worms. the main branches of the pulmonary artery
Benzimidazoles, such as albendazole or of rats, but not in humans. They are
mebendazole would probably be effective. slender strongyloid nematodes (superfam-
Treatment with thiabendazole was effective ily Metastrongyloidea; many species in
in one case. livestock are known as lungworms), with a
small buccal capsule containing two lateral
ZOONOTIC ASPECTS triangular teeth. Females measure
This is entirely a zoonotic infection. 22–34 mm
0.34–0.56 mm. The vulva
Natural hosts are cattle, water-buffaloes, opens near the anus and the red, blood-
goats and, in Thailand, wild felids. A sin- filled gut and white uterus give a character-
gle human case of infection with M. nasi- istic ‘barber’s pole’ effect. The male
cola (Buckley, 1934), a similar species measures 20–25 mm
0.32–0.42 mm and
found in a wide range of herbivores, has has a well-developed caudal bursa, with
been reported. subequal spicules (1.02–1.25 mm long).

LIFE CYCLE
Family Angiostrongylidae In rats, the eggs hatch in the lungs and first-
stage larvae are passed out in the faeces;
they can survive up to 2 weeks in water. For
Parastrongylus cantonensis
further development the larvae need to be
(Chen, 1935) Chabaud, 1972
ingested by or to penetrate into snails or
SYNONYMS slugs. They moult twice in the muscles and
Pulmonema cantonensis Chen, 1935; Angio- the infective larvae remain coiled up in the
strongylus cantonensis Dougherty, 1946. mantle. They are infective in 2–3 weeks at
26°C. When an infected mollusc is eaten by
DISEASE another rat, the larvae penetrate the intesti-
Parastrongyliasis or parastrongylosis, nal wall and are carried by the circulatory
angiostrongyliasis. A cause of eosinophilic system via liver, heart and lungs to the main
meningitis. arterial circulation. They then reach the
CNS and congregate in the spinal cord,
GEOGRAPHICAL DISTRIBUTION medulla, cerebellum and diencephalon.
This is entirely a zoonosis, occasional After moulting, the fourth-stage larvae
cases occurring in Indonesia, Laos, migrate into the subarachnoid space and
Malaysia, many Pacific islands, the 26–33 days after infection they reach the
Philippines, Taiwan, Thailand and pulmonary arteries. Here they become sexu-
Vietnam. In recent years it has also been ally mature in another 7 days.
reported from humans in Australia, China, In humans the third-stage larvae
Côte d’Ivoire, Cuba, Dominican Republic, ingested in snails or slugs can migrate via
India, Japan, Mauritius, Puerto Rico, the liver, heart and lungs to reach the CNS.
Reunion and the USA and the infection
appears to be spreading. CLINICAL MANIFESTATIONS
There is an incubation period of 12–36
LOCATION IN HOST days before symptoms of severe headache,
P. cantonensis does not usually develop to back and neck stiffness, extreme tiredness,
maturity in humans, the third-stage larvae photophobia, nausea, vomiting and vertigo
migrating to the brain, CNS or eyes. occur. There is a generalized hyperaesthesia
144 Chapter 5

of the skin, with signs of paralysis of one or granulomatous lesions with necrotic debris
more nerves and eye muscles and facial in the cerebellum, pons and medulla, death
paraesthesia (burning, tingling, etc.). The in these cases probably being due to impair-
symptoms usually last for about 2 weeks ment of the bulbar functions.
but may be prolonged. Eosinophilia is common in this infec-
Mortality due to the disease is generally tion and there is a raised cell count in the
low (although in Thailand a mortality rate cerebrospinal fluid (in one fatal case there
of 1.2% has been reported) and most cases were 880 cells mm3, of which 92% were
are self-limiting, with recovery occurring eosinophils). In experimental animals an
in about 4 weeks. inflammatory reaction develops after a few
weeks, with leucocytic infiltration and a
PATHOGENESIS preponderance of eosinophils in the
There are two distinct forms of the disease; meninges and the parenchyma of the CNS.
more typical is the cerebral form, with a The severity of the disease is related to the
meningitic syndrome, but there is also a number of third-stage larvae that reach the
much rarer ocular form, with acute inflam- CNS, most of the pathology being caused
mation of the eye but no signs of meningi- by the dead worms.
tis (Wariyapola et al., 1998).
Most of the knowledge of the pathology of DIAGNOSIS
the disease has been obtained from experi- Clinical diagnosis is usually possible, par-
mental infections in animals. However, in ticularly if there is evidence of raw snails
autopsy cases, worms have been found in having been eaten. Particularly important
the brain, with inflammation spreading is the eosinophilic pleocytosis of the cere-
along the perivascular spaces into the brain brospinal fluid (at least 25% eosinophils)
substance. The inflammatory reaction in the with Charcot–Leyden crystals; foreign-
brain and meninges is localized, particularly body giant cells and sometimes larval
in the vicinity of the parasites under the worms can also be seen in a lumbar punc-
arachnoid (Fig. 67). Eosinophils, Charcot– ture (about 10% of patients).
Leyden crystals and giant cells are apparent The meningitis must be differentiated
histologically. Dead larvae are found inside from that caused by a cerebral tumour or

Fig. 67. Larvae of P. cantonensis migrating through the meninges of the central nervous system, exciting
meningeal infiltration, eosinophilic pleocytosis in the cerebrospinal fluid and sometimes subarachnoidal
haemorrhage (magnification
50).
 The Nematodes 145

haemorrhage or from the presence of other The natural hosts are many species of
helminths, such as T. solium cysticerci and rodents, for human infections principally
Gnathostoma, or possibly Paragonimus, Rattus norvegicus and R. rattus (now com-
Schistosoma eggs, Echinococcus, Trichinella monly infected in ports such as
and Toxocara. Isolated instances of Alexandria, New Orleans and Port
eosinophilic meningitis have been reported Harcourt, Nigeria, although human infec-
from parts of the world where P. cantonen- tion has not yet been proved). The bandi-
sis is not known to occur and may be due to coot rat is another natural host.
other helminths, although this is clearly a
Parastrongylus mackerrasae possibly
helminth that is being carried to new parts
causes eosinophilic meningitis in Australia
of the world inside the rat hosts (Cross,
and P. malaysiensis in South-East Asia
1987; Kliks and Palumbo, 1992).
(Prociv et al., 2000). Another species, P.
Recently there has been a good deal of
vasorum, which occurs in dogs and foxes
work on serodiagnostic tests. Two mono-
in Europe and South America, does not
clonal antibodies (AcJ1 and AcJ20) are able
have a neurotropic cycle.
to recognize the epitope on an antigen with
a molecular mass of 204 kDa. A double-
antibody sandwich ELISA showed good Parastrongylus costaricensis
specificity with sera, but not with CNS (Morera and Céspedes, 1971) Ubelaker,
fluid (Chye et al., 1997), and an 1986
immunoblot technique is promising.
Larvae have been recovered from the SYNONYM AND DISEASE
eye on three occasions (a recent case in Sri Angiostrongylus costaricensis Morera and
Lanka may have been of a new species). Céspedes, 1971; Morerastrongylus costa-
ricensis Chabaud, 1972. Abdominal para-
TREATMENT strongyliasis or parastrongylosis (or
It is not certain that chemotherapy is advis- abdominal angiostrongyliasis).
able, as live worms cause far less tissue
reaction than dead ones and the infection GEOGRAPHICAL DISTRIBUTION
is usually self-limiting. This parasite was discovered by Morera
and Céspedes in the mesenteric arteries of
EPIDEMIOLOGY patients in Costa Rica in 1971. In the fol-
Human infection usually occurs from eating lowing 30 years it has been found in
the giant African land snail (Achatina humans in Argentina, Brazil, Colombia,
fulica), which is popular among people of Costa Rica, Dominican Republic, Ecuador,
Chinese descent and has been introduced by El Salvador, Guadeloupe, Guatemala,
them to Hawaii and other Pacific islands. Honduras, Japan, Martinique, Nicaragua,
Another snail, Pila, is similarly eaten in Panama, Peru, the USA and Venezuela,
Thailand, as are freshwater prawns in with a possible case in Congo Republic
Tahiti. In addition, small slugs (e.g. (Zaire).
Veronicella), snails and planarians may be
ingested inadvertently in salads. It is poss- LOCATION IN HOST
ible that larvae escape from the invertebrates Adult worms that lay eggs but do not pro-
in faeces or slime and are ingested on veg- duce larvae are found in the ileocaecal
etables or fruit. At least six species of terres- branches of the anterior mesenteric artery
trial snails, nine species of aquatic snails or occasionally in the liver or testicles. Full
and five species of slugs, freshwater prawns, development occurs in the natural host, the
frogs and toads have been found naturally cotton rat, Sigmodon hispidus.
infected, and many other invertebrates and
probably fish can serve as paratenic hosts. MORPHOLOGY
In some Asian countries some of these hosts Adult males measure 17.4–22.2 mm

are ingested for medicinal purposes. 0.28–0.31 mm. The caudal bursa is well
146 Chapter 5

developed and symmetrical with six papil- usually some degree of leucocytosis, with
lae and equal spicules. Females measure 20–50% eosinophilia. In children, symptoms
28.2–42.0 mm
0.32–0.35 mm, with the may mimic appendicitis, Crohn’s disease or
vulval opening about 0.26 mm from the tip Meckel’s diverticulum. Some cases have
of the tail. Both sexes lack a buccal cap- bright red blood in the faeces.
sule. The adult worms and eggs in the arteries
provoke damage to the endothelium, caus-
LIFE CYCLE ing thrombosis and necrosis of tissues, and
Twelve species of rodents can act as final the eggs cause inflammatory reactions in the
hosts, as well as marmosets, dogs and the small vessels. The whole wall of the intes-
coatimundi. First-stage larvae (L1s) in the tine can become thickened and hardened,
faeces of these hosts enter slugs as interme- with yellowish granulatomous areas of
diate hosts, where they develop into the inflammation (Fig. 68). In lighter infections
infective third stage (L3) and are often only the appendix is damaged but in heavy
excreted into the mucus left on vegetation. infections the terminal ileum, caecum and
In Central America the veronicellid slug, ascending colon may have to be excised.
Vaginulus plebeius, which is common up to If the liver is infected, there is likely to be
an altitude of 2000 m, is commonly pain in the upper right quadrant, with some
infected (50% overall in Costa Rica) some- degree of hepatomegaly. Palpation is painful
times with large numbers of larvae (Morera, and there are enzyme abnormalities and a
1994). When these slugs are ingested by high eosinophilia; the syndrome resembles
cotton rats or other natural hosts, the L3s visceral larva migrans (p. 157). The presence
penetrate the intestinal wall within 4 h and of adult worms in the spermatic cords of
migrate to the lymphatics of the intestinal males can result in acute pain from obstruc-
wall and mesentery. Following a further tion by adult worms, leading to haemor-
two moults, the young adults (females mea- rhagic necrosis of the testicular parenchyma.
suring 28–44 mm and males 20 mm in Even without treatment, recovery usually
length) migrate to the mesenteric arteries takes place in a few weeks to many months.
after 10 days. They mature and release eggs
by 18 days. The eggs are deposited in the DIAGNOSIS
intestinal wall, where they hatch, and the Symptoms in children of an appendicitis-
L1s are excreted in the faeces by 24 days like illness with a high eosinophilia are
postinfection. Humans become infected by suggestive. Clinical diagnosis can be greatly
ingesting infected slugs, either intention- aided by X-ray. Contrast medium shows fill-
ally, in the case of young children, or acci- ing defects in the terminal ileum, caecum
dentally, on salad vegetables. The L1s in and ascending colon, with irritability and
mucus can also be ingested from food or thickening of the wall. There is also a sud-
from the hands of children after playing den contraction of the caecum observed by
with slugs. fluoroscopy after a barium enema, typical of
chronic granulomatous inflammatory reac-
CLINICAL MANIFESTATIONS AND PATHOGENESIS tions and found also in tuberculosis and
Infection is found predominantly in children, amoebic abscesses. Newer imaging tech-
but all ages can be susceptible. If worms are niques would probably be even more use-
present in the tissues of the caecal region, ful. Parasitological diagnosis is only
there is usually pain in the right flank and possible following biopsy or resective surgery
iliac fossa. There may be fever, often accom- since L1s are not produced in the faeces.
panied by anorexia and vomiting and consti- Serological diagnosis is thus very
pation or diarrhoea in children. In many important. There is a latex agglutination
patients a tumour-like mass can be palpated test and an ELISA, both of which are sensi-
in the lower right quadrant (although this tive and specific, and immunoelectrophore-
procedure may be painful), and this may be sis or Ouchterlony immunodiffusion can
mistaken for a malignant tumour. There is also be employed.
 The Nematodes 147

Fig. 68. Cross-sections of five adult P. costaricensis in a mesenteric vessel. The inflammatory exudate
and eosinophils surrounding them are undergoing necrosis (perhaps following the death of the
worms), suggesting both immediate and delayed hypersensitivity responses.

TREATMENT Metastrongylus elongatus Railliet and

Surgery is the most common form of treat- Henry, 1911 (Family Metastrongylidae), a
ment, but with more experience many parasite of pigs with earthworms as inter-
cases have been found to resolve in time mediate hosts, has been recovered once
without it, and conservative palliative from the human respiratory tract.
treatment can be employed unless there is
an acute flare-up.
Chemotherapy with thiabendazole, alben-
Order Ascaridida
dazole and diethylcarbamazine has been
tried and may have some effect but there is
Family Ascarididae
evidence from experimental infections in
rats that it causes the parasites to wander
Ascaris lumbricoides
erratically and cause further lesions.
Linnaeus, 1758
EPIDEMIOLOGY
DISEASE AND POPULAR NAMES
This infection is widespread in rodents in
Ascariasis or ascariosis; roundworm infec-
the Americas and the numbers of human
tion. One of the geohelminth infections.
cases is rising in many countries, probably
because it is being increasingly recognized
as a public health problem rather than a LOCAL NAMES
rare and curious infection. Most cases have Dedan (Arabic), Cacing (Bahasa Malay),
been reported from Costa Rica, more than Than kaung (Burmese), San’chik (Canton-
650 in 1993 in a population of 3 million ese), Nsunsuma (Fanti), Agan afo (Ibo),
(Morera, 1994). Almost all of these are in Kaichu (Japanese), Njowni (Luo), Wata
children, and boys are twice as likely to be panuwa (Singalese), Gooryan (Somali),
infected as girls; both are more likely to be Lumbris (Spanish), Safura njoka (Swahili),
infected in the wet season. In Costa Rica, Nakupoochi (Tamil), Pa-yard sai-doen
43% of cotton rats were found to be infected. (Thai), Aràn inú (Yoruba).
148 Chapter 5

GEOGRAPHICAL DISTRIBUTION by a small vulva on the ventral surface

Cosmopolitan. Ascaris infection is com- about a third of the body length from the
mon in both temperate and tropical coun- anterior end. The average daily output of
tries where there are both adequate eggs is about 200,000 per female and each
moisture and low standards of hygiene and may lay a total of 25 million during her
sanitation. It is one of the most common lifetime. The posterior end of the male is
human helminths with an estimated 1400 curved ventrally and there are two almost
million infected persons in the world (23% equal copulatory spicules (measuring
of the world population), with about 2.0–3.5 mm) and numerous preanal and
60,000–100,000 deaths annually. postanal papillae. There is no gubernacu-
lum.
LOCATION IN HOST The eggs are broadly ovoid and measure
Adults are normally found in the lumen of 45–70 µm
35–50 µm. The shell is thick
the small intestine but do not attach to the and transparent and usually has a coarsely
mucosa. mammilated outer albuminous coat,
stained light brown with bile pigments
MORPHOLOGY (Fig. 69). The ova are unsegmented when
These are large, stout nematodes, tapering passed in the faeces. Occasionally eggs are
at both ends. The females (200–400 mm
passed without the outer coat and a pro-
3–6 mm) are slightly larger than the males portion of eggs (about 15%) are infertile;
(150–300 mm
2–4 mm) but may show these are longer and narrower (90 µm
40
great variation in size, depending on age µm), with a thin shell, more irregular outer
and worm load. The mouth opens termi- covering and disorganized contents (Fig.
nally and has three lips, each of which has 69). They occur either because the rapid
a pair of sensory papillae on its lateral mar- production of eggs allows some to pass
gin, and rows of small denticles or teeth. through unfertilized or because only
The principal structural protein of the cuti- female worms are present.
cle is collagen, stabilized by disulphide
bonds. LIFE CYCLE (Fig. 70)
In the female the paired, tortuous, tubu- The unsegmented, fertilized, ova, passed in
lar ovaries, oviducts, seminal receptacles the faeces, take 10–15 days to develop to
and uteri lead into a vagina, which opens the infective stage at 20–30°C in moist soil

Fig. 69. Egg of Ascaris. Left: Fertile unembryonated egg as seen in faeces. Centre: Infertile egg from
faeces. Right: Second-stage infective larva in egg after at least 10–15 days’ development in soil (original
magnification
350).
 The Nematodes 149

ADULTS
in ileum
Duodenum, blood or
lymphatics, lungs
(bronchi, trachea),
oesophagus, ileum

HUMAN
swallowed and hatch

Unsegmented EGGS
2ND-STAGE LARVA (60m
40m) in
in egg. Can survive faeces reach soil
in soil for up to 7 years

SOIL

1ST STAGE LARVA

develops in egg
10
–1
ne 5d
O

ays
mo
ult
in e
gg

Fig. 70. Life cycle of Ascaris lumbricoides.

or water. The first-stage larva inside the egg oesophagus to reach the ileum. They
moults after about a week and it is the egg develop into adult males and females in
containing the second-stage larva that is about 65 days and live for 1–2 years.
infective (Fig. 69). In moist loose soil with
moderate shade, infective eggs may survive CLINICAL MANIFESTATIONS
for up to 7 years (Plate 2). Although the majority of infections are
When the infective eggs are ingested, apparently symptomless (about 85%), the
the larvae hatch in the duodenum. The presence of even a few worms can be
eggshell is dissolved when there is a tem- potentially dangerous and there are still
perature of 37°C, high CO2 concentration, over 200 million cases showing morbidity.
low oxidation-reduction potential and a pH The first clinical signs and symptoms are
of around 7.0. The second-stage larvae a pneumonitis with cough, dyspnoea, sub-
measure 0.2–0.3 mm
0.014 mm and have sternal pain, fever and sometimes a blood-
a rhabditiform oesophagus extending back stained sputum (which may contain larvae).
about a quarter of the length of the body. These symptoms begin 5 to 6 days after infec-
They penetrate the mucosa and are carried tion and usually last 10–12 days. This is
in the lymphatics or veins through the liver known as Loeffler’s syndrome and the X-ray
and heart to reach the lungs in 3 days. findings often show dense pulmonary infil-
With A. suum in pigs, at least, the larvae trations, resembling acute tuberculosis. There
penetrate the colon and caecum, not the is moderate eosinophilia (which increases to
ileum, and reach the liver in 6 h causing a maximum of 40% 3 weeks after infection).
lesions (Murrell et al., 1997). The larvae The severity of symptoms depends both
moult twice in the lungs (at 5–6 days and on the number of eggs ingested and on the
10 days) and then penetrate the alveolae, previous infection history; hypersensitive
ascend the trachea and pass down the individuals may have severe symptoms,
150 Chapter 5

with perhaps urticaria and asthma from the Adult worms causing obstruction can often
presence of only a few larvae. The relation- be seen outlined as a shadow on X-rays
ship between pneumonitis and ascariasis after a barium meal. In many areas this is
was well shown by a study in Saudi the commonest cause of intestinal obstruc-
Arabia, where there is a short transmission tion in children. Occasionally worms may
season in spring when infection can occur. cause peritonitis or may wander in the
In young adults (and probably children) appendix and possibly give rise to appen-
Loeffler’s syndrome occurs at this time of dicitis (but see p. 163).
year, with eggs appearing in the faeces 2–3 Adult Ascaris appear to be particularly
months later. However, in Colombia, where prone to a ‘wanderlust’, perhaps an attempt
there is constant transmission, this syn- to repeat the migrations of their youth
drome does not occur. when the larvae were only 0.3 mm long
The second phase of clinical disease is (Plate 17). They may migrate up the bile-
due to the presence of the adult worms in duct or even up the pancreatic ducts. In
the intestinal lumen (Fig. 71). The usual children this causes severe colicky pain in
symptoms of heavy infections are digestive almost all patients, with nausea and vomit-
disorders, nausea, vomiting and colic and, ing. After a few days fever develops,
in children, restless sleep and tooth grind- accompanied by a slight jaundice.
ing. Complications include ascending cholangi-
Intestinal obstruction is a serious com- tis (in about 15% of cases), obstructive
plication of Ascaris infection, which usu- jaundice (1%), acute pancreatitis (4%), and
ally occurs in children, often as young as 2 occasionally multiple liver abscesses. Such
(Plate 16). Mortality in such cases admitted worms can be removed endoscopically. In
to hospital is about 9%. Because of the China ascariasis has been estimated to
danger of causing obstruction, it is advis- account for about 13% of all cases of bil-
able in an endemic area to examine the iary obstruction (Zhou Xianmin et al.,
faeces, followed by appropriate treatment if 1999).
necessary, before carrying out an intestinal Sometimes adults may develop in
operation or before giving chemotherapy ectopic sites such as the abdominal cavity
for other parasites, which may irritate and infrequently worms pass out through
Ascaris. The symptoms of intestinal various orifices – mouth, nose, lachrymal
obstruction are recurrent abdominal pain, duct, urethra, vagina – much to the con-
loss of appetite, nausea and vomiting. sternation of the infected person.

Fig. 71. Portion of ileum removed at autopsy containing many adult Ascaris.
 The Nematodes 151

Surgical complications are more com- DIAGNOSIS

mon in areas where patients have greater
Clinical. The pneumonitis caused by the
worm loads, which in turn are found
migrating larvae is often not diagnosed, but
where the intensity of transmission and
the accompanying high eosinophilia is sug-
prevalence are high.
gestive. The adult worms can sometimes be
The amount of host food material
seen as clear spaces on X-rays after a bar-
removed by Ascaris is not negligible and
ium meal (the gut of the worms may show
this, together with concomitant anorexia
as a thin central line of contrast medium)
and malabsorption, probably potentiates
or on a computer-assisted tomography (CT)
kwashiorkor in areas where protein intake
scan. Ultrasound is particularly useful for
is only just adequate. Parasitism is often so
worms in the biliary or pancreatic ducts,
widespread in many developing countries showing up as long, narrow, moving
that the effect on the nutrition of already images maybe with two inner parallel
malnourished children should not be lines. Endoscopy is also useful.
underestimated. It has been estimated that
a child who has 26 worms may lose one- Parasitological. Eggs are usually plentiful in
tenth of its total daily intake of protein. the faeces, although infertile eggs may not
There is also some evidence that ascariasis be recognized. Direct faecal smears, using
in children can contribute to vitamin A about 2 mg of faeces, are usually adequate,
and C deficiency. The most important while the Kato–Katz thick-smear technique
effect of disease in children aged 2–10 is its (p. 257) works well. Concentration meth-
effect on height and weight, development ods using sedimentation or brine flotation
and probably cognitive ability (Crompton may be used but are not really necessary.
et al., 1989; Thien Hlang, 1993; Crompton, Unlike most other nematodes, the number
2000). of eggs in the faeces often gives a good
indication of the number of adults present
PATHOGENESIS (although a few parasites produce propor-
The larvae cause lesions in the liver, spleen tionally more eggs and very many parasites
and lymph nodes. Sometimes necrotic foci too few). However, since there are marked
are also found, encapsulated larvae causing variations in fecundity in different coun-
a granulomatous reaction. In the lungs they tries, the WHO threshold of 50,000 eggs g1
cause petechiae and in severe reactions faeces indicating a heavy infection needing
there is also ulceration of the bronchial regular re-treatment may not be universally
mucosa and abundant mucus. Charcot– applicable (Hall and Holland, 2000).
Leyden crystals may be present from the
breakdown of eosinophils. Immunodiagnosis. All immunodiagnostic
High IgE production may function to tests are very non-specific and none are
protect both the host and the parasite. used in practice. A 25 kDa antigen from the
Ascaris induces a Th2 cell-mediated body fluids of larvae and adults of A. lum-
response, producing interleukin 4 (IL-4) bricoides and the pig ascarid A. suum
and resulting in production of IgE. It is (ABA-1) is highly allergenic against mast
possible that the parasite also produces an cells in vitro and could possibly provide the
IL-4-type molecule that stimulates the host basis for a test, at least at the community
to produce non-specific superfluous IgE, level – preferably if it could utilize saliva. It
thus swamping the immune response is possible to identify Ascaris metabolites in
(Prichard, 1993). Attempts to demonstrate urine but this is not so far a practical test.
that immune responses can explain the
TREATMENT
clear predisposition to infection have not
been successful (see Crompton, 2000). The Clinical. Intestinal obstruction in children
immunology of intestinal nematodes is dis- can usually be treated conservatively with
cussed on p. 120. intravenous fluids, but acute infections
152 Chapter 5

may require surgical removal. Biliary faeces up to 7 days after the adults have
obstruction, which is more common in been expelled. Males are expelled first, so
adults than in children, can sometimes be that in long-established infections without
treated by using retrograde endoscopy. reinfection there is a preponderance of
females.
Chemotherapy The use of human faeces as a fertilizer
(‘night-soil’) is common in some parts of
● Albendazole
the world and can result in eggs getting on
This is 100% effective at a single oral
to salad vegetables. In China and other
standard dosage of 400 mg for all indi-
areas raw faeces is now being stored. Over
viduals except pregnant women and the
90% of ova are killed by storage for 15 days
under-5s and will have action against all
at 29°C or 6 days at 33°C; but for complete
the geohelminths.
destruction 40 days at 30°C is required
● Mebendazole (Muller, 1983).
This can similarly be used at a standard Untreated sewage is sometimes dis-
single oral dose of 400 mg for all geo- charged into rivers and lakes, which repre-
helminths although best against Ascaris sents a clear health hazard. Even more
(100%). common is discharge into the sea and eggs
are able to continue development in sea
● Pyrantel pamoate (= embonate)
water, as is said to occur in coastal villages
This is given as a single oral dose at
of Samoa.
5–10 mg kg1 body weight. It is not
Properly designed modern sewage treat-
effective against Strongyloides and
ment plants will remove or destroy all
Trichuris (0–20% cure rate) and only
Ascaris eggs, the bacterial bed treatment
partially against hookworms (20–90%);
not being so effective as the activated
possibly it may also encourage obstruc-
sludge process or sand filtration. However,
tion by paralysed worms.
eggs need to be retained for 10–12 months
● Levamisole in septic tanks and cesspits before they are
When given at 150–250 mg (2.5–5 mg all destroyed. Eggs will not embryonate
kg1) it is completely effective (para- below 18°C but can survive for many
lysing Ascaris) but less so against other weeks at much lower temperatures and
intestinal nematodes. continue development when the tempera-
ture is raised. In experiments in Russia
EPIDEMIOLOGY eggs have survived in soil for 7 years, but
Ascariasis is prevalent in most tropical in most natural habitats they will be
countries, with estimated infections of: destroyed by sunlight, fungi or acarines in
China 523–539 million, Côte d’Ivoire 17% 2–6 months and in temperate climates they
and Kenya 38%. Infection rates are often survive for shorter periods in summer.
high in urban (particularly slum) areas: The soil type is important in transmis-
25% in Brazil (Rio de Janeiro), 47% in sion; clay soils favour survival of eggs,
Egypt (Alexandria), 35% in India since they retain water better. Complete
(Hyderabad), 64% in Malaysia (Kuala lack of aeration is not lethal, ova remaining
Lumpur), 55% in Mexico (Coatzacoalcos), viable for months without oxygen,
68% in Nigeria (Lagos), 80% in the although their development is interrupted
Philippines (Manila) and 43% in Sierra (Mizgajska, 1993).
Leone (Freetown).
The adults are not usually very long- PREVENTION AND CONTROL
lived and there is often an annual cycle of Where there is a marked rise in standards
infection. Evidence from people who move of sanitation over a large area, Ascaris
to a non-endemic area shows that eggs infection falls quickly, usually within a
cease to be passed in under 18 months. year. At the personal level, thorough wash-
Eggs may continue to be passed in the ing and preferably cooking of vegetables
 The Nematodes 153

and supervision of children’s play areas are abscesses, so that repeated life cycles occur
important. However, it is difficult to pre- (de Aguilar Nasumento et al., 1993). In the
vent infection and reinfection in young mastoid region, temporal bone can be
children, particularly where pica (geopha- invaded, with numerous mastoid sinuses
gia) is common (Geissler et al., 1998). Mass and perhaps involvement of the CNS. In
chemotherapy campaigns for all geo- one woman worms emerged into the mouth
helminths are discussed on p. 133. and in a young girl a worm was recovered
from a tooth abscess. The zone of indura-
ZOONOTIC ASPECTS tion grows deeper and sinus tracts develop,
The relationship of human A. lumbricoides the openings oozing pus. Eventually a
to the very common parasite of the pig still chronic granulomatous inflammation
remains unresolved. Slight morphological ensues, which can last for months. Some
differences have been described, such as cases are fatal, including one with worms
the labial denticles being concave in the in the lungs.
former and straight-sided in the latter, but The natural definitive hosts are
these have been challenged by other workers unknown but are probably carnivores or
(Gibson, 1983). Cross-infection can opossums. Cats have been found naturally
undoubtedly occur but in Guatemala, for infected in Argentina and Brazil and, in
instance, there appears to be little gene cats experimentally infected with cysts
flow between infections of humans and of from mice containing third-stage infective
pigs, which is encouraging for control cam- larvae, the larvae excysted in the stomach
paigns. In North America, however, a non- and penetrated the oesophagus, trachea,
endemic region, molecular evidence pharynx and cervical lymph nodes, devel-
indicates that most human cases are of pig oping to adults in 9–20 days postinfection.
origin (Anderson and Jaenike, 1997). There However, the worms did not produce eggs,
also appear to be genetic differences although they did in animals fed infected
between the two forms (Xingquan et al., mice. In mice infected orally with ova from
1999) and pig parasites are usually humans, the first-stage larvae hatched in
regarded as a separate species, A. suum the gut, penetrated the wall and migrated
Goeze, 1782. It is probable that human to the liver, lungs, skeletal muscles and
infections originally came when pigs were subcutaneous tissues, where they encysted
first domesticated in neolithic times, possi- as third-stage larvae. How humans become
bly in China (Peng Weidong et al., 1998; infected is not known, although presum-
Crompton, 2000); infections of A. lumbri- ably it is either from ingestion of wild ani-
coides in other primates appear to have mals containing cysts or from ingestion of
been contracted from humans (cases of eggs in the environment.
‘nosozootic’ infections). Long-term treatment with levamisole
and thiabendazole has not been effective,
but albendazole (200–400 mg each day for
Lagochilascaris minor
5 days) and perhaps mebendazole (200 mg
Leiper, 1909
each day) have some (although perhaps a
There have been occasional human cases temporary) effect. Ivermectin (300 µg kg1
recorded from Bolivia, Brazil, Costa Rica, daily for 4 weeks) has resulted in long-term
Ecuador, Mexico, Surinam, Trinidad and cure in single cases in Ecuador and Brazil.
Venezuela.
In humans the first sign of infection is a
Baylisascaris procyonis
pustule, usually on the neck, which grows
(Stefanski and Zarnowski, 1951)
in size to give a large swelling. After the
skin breaks, living adults, larvae and eggs This is a common parasite of racoons in the
are expelled at intervals in the pus. Eggs USA. In humans and small rodents, such
are continually developing into larvae and as squirrels, or porcupines, rabbits, birds
then adults in the tissues at the base of and dogs, it causes a form of visceral,
154 Chapter 5

neural or ocular larva migrans. There are tion of eggs in the environment. A biologi-
about a dozen species of Baylisascaris from cal quirk, shared with A. suum, is that
carnivores and the full life cycle is known nuclear DNA is greatly reduced in all
only for a species in badgers, which somatic cells but not in germ cells.
requires an intermediate host. It is likely
that racoons ingest small mammals and
birds with granulomas containing larvae in Family Anisakidae
the somatic and particularly CNS tissues
(although eggs can also be infective); the Anisakis and other anisakids
worms then develop into adults in the
intestinal lumen and eggs are evacuated in DISEASE AND POPULAR NAMES
the faeces, with second-stage larvae devel- Anisakiasis or anisakidosis; herring-worm
oping inside them in soil. They are then disease, cod-worm disease (from
infective to the mammalian and bird inter- Pseudoterranova).
mediate hosts, where development to the
third stage takes about 2 weeks. GEOGRAPHICAL DISTRIBUTION
In a fatal case in a 10-year-old boy, the Anisakis simplex (Rudolphi, 1809), syn-
larvae evoked a sessile polyploid mass in onym A. marina, is a natural parasite of
the left ventricular myocardium, protrud- marine fish-eating mammals. Human cases
ing into the ventricular lumen (Boschetti occur where fish are eaten raw and was
and Kasznica, 1995). In other cases, with first recognized in The Netherlands in
larvae in the brain, a sometimes fatal 1960. Cases (almost 34,000 in total) have
eosinophilic meningoencephalitis ensues been reported from Japan (over 16,000),
(Plate 18). In an infant who recovered after Korea (196 up to 1992), Canada, France,
treatment with a single dose of ivermectin Germany, Italy, The Netherlands, Russia,
and multiple doses of thiabendazole and Spain, the UK and the USA.
prednisolone, there was permanent neuro-
logical damage (Cunningham et al., 1994). LOCATION IN HOST
Other cases in adults have resulted in lar- Larvae are found in abscesses in the wall of
vae in one eye causing a diffuse neuro- the intestinal tract, usually the stomach in
retinitis. In most cases diagnosis is based Japan but also the small intestine and
solely on ELISA or immunoblot techniques colon.
although L3 larvae have been found in usu-
ally granulomatous biopsy specimens. MORPHOLOGY AND LIFE CYCLE
Larvae measure 930–1300 µm
50–65 µm L3s in humans measure about 29 mm

and have well-developed lateral alae. 0.45 mm, with the typical ascarid three lips
Neurological cases present with extreme and a dorsal boring tooth at the anterior
lethargy, with 30–40% eosinophilia end. The tail is short and rounded, with a
(Kazacos, 1983). small projection at the end. Occasionally
The adult worms resemble those of larvae in humans develop to the fourth
Ascaris in size but have cervical alae and an stage but never to adults.
area rugosa, while the eggs are pitted. The Thin-shelled eggs (50 µm
40 µm) are
larvae inside eggs can survive for long peri- discharged in the faeces by the adults,
ods in soil, and infection is widespread in which inhabit the stomach of marine mam-
racoons throughout North America; similar mals. Larvae develop inside the egg and
species parasitize skunks, martens and bears. moult once to give the L2. The sheathed
larvae hatch and can live in sea water for
Parascaris equorum (Goeze, 1782) Yorke many weeks. If ingested by planktonic
and Maplestone, 1926, is a widespread par- euphausid crustaceans (krill), the larvae
asite of horses and other equines that has penetrate the gut wall and develop to the
caused occasional cases of human visceral L3 stage. When krill is ingested by many
larva migrans and pneumonitis from inges- (164) species of fish, such as herring, mack-
 The Nematodes 155

erel, cod and salmon, or by squid, the lar- may be severe erosive gastritis, hyperaemia
vae encyst in the muscles or viscera. These and bleeding. There are usually only one to
act as paratenic hosts, since the larvae do nine worms, but in one patient 56 worms
not develop further, but if they are eaten by were removed (Kagei and Isogaki, 1992).
any of many species of marine mammals Contrast X-rays can reveal filling defects
(26 cetacean and 12 species of pinniped) and oedematous, obstructed, areas in the
the contained larvae develop into adults in stomach wall (Ishikura et al., 1992).
the stomach.
Immunodiagnosis. Various monoclonal anti-
CLINICAL MANIFESTATIONS AND PATHOGENESIS bodies have been discovered that recognize
If the parasite is in the stomach, the most specific epitopes from A. simplex larvae.
common symptoms are nausea, vomiting One (An2) recognizes epitopes from intesti-
and epigastric pain, simulating a peptic nal cells and ES products and has been
ulcer or a tumour, beginning 1–12 h after used in a micro-ELISA. Another IgG1κ
ingestion of infected fish (Plate 19). antibody (UA3) of 139 kDa is more specific,
Sometimes there may be symptoms of but both only detect the presence of the
acute chest pain. The parasites can elicit worms about 4 weeks after infection. An
severe IgE-mediated hypersensitivity, immunoblot technique with larval whole-
which might require emergency treatment. body antigen to detect IgE is positive after a
There is sometimes urticaria, angioedema few days (Garcia et al., 1997). An antigenic
and even anaphylaxis. If abscesses are pre- -galactosidase helminth-derived recombi-
sent in the intestine or colon, there is likely nant fusion protein (FP) obtained by
to be lower abdominal pain, but sometimes recombinant DNA techniques and used in
it can resemble acute appendicitis (Plate an ELISA is stated to be completely spe-
20). This develops after about 2 days and cific, in contrast to soluble antigens
lasts for a further few days before ileus or (Sugane et al., 1992).
perhaps ascites results. Gastric cancer is The most effective method of treatment
much more common in Japan than in any for gastric worms is by endoscopy and
other country and the presence of Anisakis removal of the larval worms using biopsy
larvae has been suggested as a cofactor forceps; symptoms clear up within hours of
(Petithory et al., 1990). Occasionally removal.
worms may penetrate through to the
abdominal cavity and in one patient a larva EPIDEMIOLOGY AND PREVENTION
was discovered in the liver. With the ability to easily remove larval
In the early stages there is an abscess worms, it is becoming increasingly evident
infiltrated by neutrophils and later an that other anisakids may be involved, as
eosinophilic granulomatous reaction. The well as Anisakis simplex. There is A. phy-
affected portion of the intestinal tract setis Baylis, 1923 (previously known as
becomes oedematous (up to 1.5 cm thick), Anisakis type II larvae), Pseudoterranova
with ulcerations and petechial haemor- decipiens (Krabbe, 1878) in Japan and
rhages in the mucosa, each containing a North America, Contracaecum osculatum
larval worm. Dead worms become sur- (Rudolphi, 1802) and Hysterothylacium
rounded by foreign-body giant cells. (syn. C.) aduncum (Rudolphi, 1802). Larvae
Submucosal lesions of the ileum or colon of all are found in marine fish; C. oscula-
also have larvae in them, surrounded by an tum caused an infection in Spain from eat-
area of necrosis. ing sardines and H. aduncum, with adults
in piscivorous fish, not mammals, was
reported from Chile. All cause similar
DIAGNOSIS AND TREATMENT
lesions in the gastric and possibly the
Clinical and parasitological. Endoscopy can intestinal wall. A fourth-stage larva of P.
be very useful for viewing the stomach decipiens that had been removed measured
abscess, which is oedematous, and there 29.7 mm
0.94 mm (Sohn and Seol, 1994)
156 Chapter 5

and an adult worm (reported once only) Infection can be divided into two cate-
33 mm
1.0 mm. This is a natural parasite gories:
of seals and requires two crustacean inter-
1. Visceral larval migrans results when
mediate hosts (a copepod and an amphipod).
ingestion of eggs or larvae leads to the pres-
The various larvae can be distinguished.
ence of wandering larvae in the deep
Those of Anisakis have no lateral alae and
organs. Potentially, this group constitutes
in section have characteristic Y-shaped lat- the most serious danger to humans.
eral cords. A. simplex larvae measure on Species that may be involved include the
average 28.4 mm
0.45 mm and have a larvae of Toxocara canis, T. cati,
short tail with a terminal spine, while Lagochilascaris major, Parascaris equorum,
those of A. physetis measure 27.8 mm
Gnathostoma spinigerum and other
0.61 mm and have a long tail without a ter- spirurids, Parastrongylus cantonensis, P.
minal spine. Larvae of Pseudoterranova costaricensis, Anatrichosoma cutaneum,
decipiens measure 32.6 mm
0.8 mm and Alaria spp. and Spirometra spp. This defi-
have a short tail with a spine and the nition does not strictly include Ascaris
proventricular–caecal junction is not suum and Calodium hepaticum, which
straight but diagonal. reach maturity in the human body,
A high proportion of food fish may be Baylisascaris procyonis, which develops in
infected with anisakid larvae, up to 90% in humans as in its usual intermediate hosts,
herring and cod. Fish should be gutted as or Anisakis simplex, which develops nor-
soon as caught, since larvae are thought to mally in humans until it dies in the tissues,
move into the tissues after death, and deep- although these species are often included.
freezing (20°C) will kill the larvae. Raw 2. Cutaneous larva migrans is caused by
(green) herrings are popular in The skin-penetrating larvae that continue to
Netherlands but infection appears to have wander in the superficial layers of the body.
vanished, since all fish sold must now be Larvae that may be responsible include
deep frozen first. Thorough cooking will hookworms, Strongyloides, Gnathostoma
also kill the larvae, but raw fish are eaten hispidum, fly larvae and spargana of
in some countries, particularly Japan, Spirometra spp. Some animal schistosomes,
where ‘sashimi’ is popular. Also, it has including zoophilic strains of Schistosoma
been reported recently that cases of severe japonicum, Heterobilharzia and
allergic symptoms, such as urticaria, dysp- Orientobilharzia and bird parasites, such as
noea and even anaphylaxis, have occurred Australobilharzia, Bilharziella, Gigantobil-
in patients after eating thoroughly cooked harzia, Microbilharzia, Schistosomatium
fish and it is probable that the individuals and Trichobilharzia, cause ‘swimmers’ itch’
had become sensitized by previous infec- at the site of penetration but without wan-
tion with live larvae. dering in the superficial layers.

Larva Migrans Visceral larva migrans

This is a term used to describe human Only the dog and cat ascarids will be con-
infection with helminth larvae that do not sidered in this section, the other possible
grow to maturity but wander in the body, causative agents being considered in their
sometimes with serious results. The condi- appropriate sections.
tion is caused by natural parasites of ani-
mals, with humans acting as abnormal Toxocara and Toxascaris
paratenic hosts, in which the parasites do
not develop but are not destroyed, and may DISEASE AND POPULAR NAME
also result from invasion by larvae belong- Toxocariasis or toxocarosis; ‘arrowhead
ing to zoophilic strains of species normally worms’. Most important cause of visceral
found in humans. larva migrans (VLM).
 The Nematodes 157

Toxocara canis (Werner, 1782) Johnston, when a ‘tracheal’ type of migration similar
1916, is a very common ascarid nematode to that of Ascaris results. Adult females in
of dogs in many parts of the world. T. cati the ileum produce eggs in the faeces after
(synonym T. mystax) (Schrank, 1788) 4–5 weeks.
Brumpt, 1927, is found in cats and foxes Eggs hatch as second-stage larvae in
and Toxascaris leonina (von Linstow, mice (or in the case of Toxocara cati or
1902) Leiper, 1907, in dogs, cats and many Toxascaris leonina in invertebrates such as
wild carnivores. Each of these parasites is cockroaches and earthworms also) and
more common in young animals during the these act as paratenic hosts, the larvae
first few months of life. invading many tissues and becoming
encapsulated after 12 days. Further devel-
MORPHOLOGY opment occurs if these are eaten by the
The adults are smaller than those of definitive hosts.
Ascaris and have characteristic cervical In humans the eggs are ingested and the
alae or wings (Table 10). second-stage larvae hatch out in the intes-
tine and undergo a similar ‘somatic’ migra-
LIFE CYCLE tion but do not develop further. They
The egg is unsegmented when passed, but measure 350–530 µm and are considerably
in soil the ovum inside embryonates to thinner than the larvae of Ascaris and this
give the infective second-stage larva in 9 may explain why they are not filtered out
days at 26–30°C and 11–18 days at 20°C in the liver and lungs.
with a relative humidity above 85%.
The natural hosts are usually infected CLINICAL MANIFESTATIONS AND PATHOGENESIS
before birth by the mother ingesting eggs Disease occurs mainly in young children
containing second-stage larvae. The (typically 1–4 years old) who have had
hatched larvae penetrate the gut wall and close contact with infected household pets
then undergo a ‘somatic’ migration, reach- or have been exposed to eggs in the envi-
ing the lungs, liver and kidneys and, in ronment and is due mainly to T. canis. In
pregnant females, penetrating through the over 80% of cases there is a marked
placenta to infect the fetus. Young puppies eosinophilia (over 50% with 20,000
or kittens may also be infected with larvae eosinophils mm3) and hepatomegaly. In
through the milk or by ingesting eggs, over 50% of cases, pulmonary symptoms,

Table 10. Differentiation of the dog and cat ascarids.

Toxocara canis Toxocara cati Toxascaris leonina

Length: Length: Length:

Females 6–18 cm Females 4–12 cm Females 4–10 cm
Males 4–10 cm Males 3–6 cm Males 3–7 cm
Head bent ventrally Head bent ventrally Head straight
Cervical alae elliptical Cervical alae broad and end Cervical alae elliptical
abruptly posteriorly
Oesophagus with a Oesophagus with a posterior Oesophagus with no
posterior muscular bulb muscular bulb posterior bulb
Tail of male with digitiform Tail of male with digitiform Tail of male conical with no
appendage and caudal alae appendage and caudal alae caudal alae
Eggshell pitted Eggshell pitted Eggshell smooth
(75–85 µm) (65–70 µm) (75–85 µm)
Specific to dog Specific to cat Found in dog or cat
158 Chapter 5

such as coughing and wheezing with dysp- Another form of the disease, which usu-
noea and fever (Loeffler’s syndrome), last- ally occurs in older children or adults
ing up to 3 weeks, are found and there may when larvae invade the eye but do not
be acute bronchitis with pneumonia. Chest cause the typical visceral symptoms, can
X-rays often show bilateral infiltrates. be termed ocular larva migrans (OLM). The
These are followed by gastrointestinal dis- larvae cause unilateral chronic granuloma-
turbances, with larvae present in the liver tous endophthalmitis (in 60% of cases) or
and maybe the brain as well as the lungs, peripheral retinitis (in 10% of cases).
causing eosinophilic granulomas. These granulomata cause distortion or even
Hepatomegaly and eosinophilia can last for detachment of the retina, and blindness is
many months. Larvae in the brain can common (Gillespie, 1993; Gillespie et al.,
cause convulsions or hemiplegia (Plate 21). 1993). There can also be papillitis, leading
There is the possibility that Toxocara lar- to glaucoma. One danger is that the lesion
vae are responsible for carrying viral will be mistaken for a retinoblastoma and
(including poliomyelitis and Japanese B the eye hurriedly removed. However, the
encephalitis), bacterial and protozoal eye lesions in toxocariasis are raised and
pathogens into the brain and other organs. always unilateral (Fig. 72).
Very rarely there can be myelitis. A few human infections with adult T.

Fig. 72. Top: Ophthalmoscope view of the retina with raised area near the optic disc (haemorrhage on
left). Bottom: Section of granulomatous lesion of retina, with a larva in the centre of fibrinoid necrosis.
 The Nematodes 159

canis and T. cati have been recorded, possi- nized by infected sera show a very high
bly from ingestion of larvae in an inverte- specificity in an SDS-PAGE or enzyme
brate intermediate host. immunotransfer blot assay.

Histopathology. In experimental animals, TREATMENT

petechial haemorrhages occur in the liver Albendazole (400 mg or 10–15 mg kg1
when the larvae leave the sinusoids and day1 for 10–21 days) or mebendazole (100
burrow through the tissues, leaving mg daily for 10–21 days) have been suc-
necrotic trails behind. These are inflamma- cessfully used in recent trials. Diethyl-
tory at first but then become granuloma- carbamazine can no longer be
tous, containing eosinophils, lymphocytes, recommended, although thiabendazole is
fibroblasts, epitheloid cells and giant cells. still used. The majority of cases resolve in
The live larvae become encapsulated and a few months even without treatment,
can sometimes live for months or even although corticosteroids (e.g. 30 mg of
years but usually soon die. Similar lesions prednisone day1 for 21 days) can be given
occur in the lung and there can also be to reduce inflammation and relieve symp-
myocardial or CNS involvement. In experi- toms in severe cases.
mentally infected mice, larvae of T. canis
entered the brain in all cases and the eye in EPIDEMIOLOGY, PREVENTION AND CONTROL
5%, while those of T. cati migrated to the Infection is very common in dogs and cats
brain in 8% of cases but never to the eye. in most parts of the world, e.g. Chile (19%
The migrating larvae evoke both T. canis, 65% T. cati), Slovakia (70% T.
delayed-type and immediate-type hyper- cati). Many children also react positively
sensitivity reactions. The levels of both IgG in serological tests, e.g. 33% in Corunna,
and IgM are raised greatly but much is non- Spain, 35% in Malaysia. It is clear that the
specific. There is a carbohydrate (trisaccha- great majority of children exposed do not
ride) cuticular-associated epitope that is suffer clinical disease (Gillespie, 1988).
immunogenic (Kayes, 1997). Puppies and kittens should always be
dewormed as a routine. There are often
DIAGNOSIS many infective eggs around houses from
the faeces of household pets and measures
Clinical. Hepatomegaly with eosinophilia is should be taken to prevent indiscriminate
suggestive, as is elevated gammaglobulin defecation and also to prevent young chil-
and isohaemoagglutinin titres. Ultra- dren from playing in and ingesting contam-
sonography and magnetic resonance imag- inated soil (pica). In many developed
ing (MRI) show hepatic granulomas as countries children’s play sandpits are now
characteristic multiple hypoechoic nodular protected with a fence.
lesions. Toxocara pteropodis Baylis, 1926, is a par-
asite of fruit bats on the Pacific islands
Parasitological. Liver biopsies may show comprising Vanuatu. It has been suggested
granulomatous lesions but it is rare to find as the cause of a disease outbreak known as
a portion of a larva in tissue sections. The Palm Island mystery disease with hepatitis-
second-stage larva measures 350–450 µm
like symptoms, but this may have been due
18–21 µm and, if one is seen, can be differ- to poisoning (Prociv, 1989).
entiated from an Ascaris larva in sections
by its smaller diameter.

Immunodiagnosis. ELISA, using antigens Cutaneous larva migrans or ‘creeping

from second-stage larvae or their ES prod- eruption’
ucts, has about 90% specificity and 80%
sensitivity. Low-molecular mass (26.9 to Of the various possible causes of this con-
38.9 kDa) polypeptides from L2s recog- dition, Spirometra is considered on page
160 Chapter 5

70, Strongyloides on page 115, Gnatho- and fox in Europe and North America and
stoma on page 184 and fly larvae on page Bunostomum phlebotomum (Railliet,
241, and only the animal hookworms are 1900) is a widely distributed parasite of
considered here. cattle.

Ancylostoma braziliense Gomez de Faira,

1910, is a hookworm of dogs and cats in Order Oxyurida
many tropical regions of the Americas. The
buccal capsule has a smaller aperture than Family Oxyuridae
that of A. duodenale and has a small inner
tooth and a large outer one. When the Enterobius vermicularis
infective filariform larvae penetrate the (Linnaeus, 1758) Leach, 1853
skin of humans, they follow a tortuous
SYNONYMS
path under the skin, progressing at 2–5 cm
day1. An erythematous inflammatory Ascaris vermicularis L., 1758; Oxyuris ver-
reaction follows the tunnel made by the micularis Lamark, 1816.
larvae between the germinal layer of the
DISEASE AND POPULAR NAMES
epidermis and the dermis. The tunnel fills
with serum and the surrounding oedema- Enterobiasis or enterobiosis, oxyuriasis;
tous tissues contain many polymorphs and pinworm, seatworm or threadworm infec-
eosinophils. The larval movement results tion.
in intense itching and pruritus, and often
secondary bacterial infection is caused by Local names
scratching; the larvae die after a few weeks,
even without treatment, and the symptoms Deedan dabousia (Arabic), Cacing kerawit
subside (Jelinek et al., 1994). Other species (Bahasa Malay), Toke kaung (Burmese),
of animal hookworms, such as A. caninum, Kira panuwa (Singalese), Njoka safura
A. tubaeforme, Bunostomum phlebotomum (Swahili), Keeri pulu (Tamil), Pa-yard sen-
or Uncinaria stenocephala may also be deri or Kem-mood (Thai), Nnoko-boa (Twi).
responsible. The condition is similar to the
‘ground itch’ that sometimes follows pene- GEOGRAPHICAL DISTRIBUTION
tration by the larvae of human species of Taking into account the difficulty of diag-
hookworms and by Strongyloides sterco- nosis, enterobiasis is undoubtedly one of
ralis, but lasts longer. Local treatment with the most common human helminth infec-
an ethyl chloride spray or topical applica- tions worldwide, certainly in temperate cli-
tion of thiabendazole is effective. mates, with an estimate of 1000 million
cases worldwide (Cook, 1994). In general,
A. caninum (Ercolani, 1859) is a common infection is less common in tropical and
and important parasite of dogs and cats in less developed countries, presumably
most tropical and semi-tropical parts of the because of the fewer clothes worn.
world and the larvae can be a cause of folli-
culitis; development to adults in humans is LOCATION IN HOST
discussed on p. 138, together with A. cey- The adults are located in the lumen of the
lanicum, which is morphologically very caecum and appendix, sometimes with the
similar to A. braziliense and is found in anterior end attached to the mucosa. In
dogs in Asia and South America, but does heavy infections they may also be present
not appear to cause creeping eruption. in the ascending colon and ileum.

A. tubaeforme (Zeder, 1800) is a cos- MORPHOLOGY

mopolitan parasite of the cat, Uncinaria Pinworms are small cylindrical nematodes,
stenocephala (Railliet, 1884), a similar pointed at either end. They have three lips
parasite to Necator, is found in the dog, cat around the mouth but no buccal capsule.
 The Nematodes 161

The oesophagus is muscular and has a pos- LIFE CYCLE

terior bulb characteristic of the order The gravid female migrates out of the anus
Oxyurida. The cuticle has cervical alae in the evening or at night and lays numer-
continued as lateral projections, which ous sticky eggs on the perianal and per-
enable Enterobius to be easily recognized ineal skin. The female normally dies after
in sections of appendix, etc. (Figs 51 and oviposition. Often she bursts, releasing all
73). The female measures 8–13 mm
the eggs, which number about 11,000
0.3–0.5 mm and has a long pointed tail (4000–17,000).
(about one-third of the total length). The The eggs measure 50–60 (average 54) µm
vulva opens midventrally almost a third of
20–30 µm and have a thin semi-transpar-
the way down the body. The paired uteri ent shell composed of an outer albuminous
are usually filled with thousands of eggs layer, two chitinous layers and an inner
and the whole body becomes distended. lipoidal membrane. They are ovoid and flat-
The male is much smaller, measuring 2–5 tened on one side (Fig. 123). Eggs are usually
mm
0.2 mm. The posterior end is curved laid partially embryonated and contain
ventrally and has a single copulatory infective rhabditiform larvae in 4–7 h at
spicule 100–140 µm long. There is no 35°C (they require oxygen for complete
gubernaculum. The bursa is reduced and development and do not develop below
there are various caudal papillae. The about 22°C). However, if the female has
males die after copulation and often appear burst, eggs may be only at the four-celled
in the faeces. stage and then require about 48 h at 25°C to
Another species, E. gregorii Hugot, become infective. The outer albuminous
1983, is usually present together with E. layer of the egg is very sticky and in sensi-
vermicularis and has been described from tized individuals can cause an intense itch-
France, England, Japan, New Guinea and ing, as does the adult female. This often
South Korea (Hugot and Tourte-Schaefer, leads to scratching and eggs then lodge
1985; Chittenden and Ashford, 1987). under the fingernails. They are also carried
Males of this species differ by having a in dust and, when ingested, the larvae (mea-
shorter, simple, spicule (60–80 µm long suring 145 µm
10 µm) hatch in the duode-
rather than 100–140 µm) and other slight num. From comparison with other members
morphological differences. The eggs and of the order, they are presumably at the third
females cannot be differentiated. stage. The larvae lodge in the crypts of the

Fig. 73. Section of appendix with adult female Enterobius vermicularis in lumen.
162 Chapter 5

ileum and moult twice. The young adults apart from a mild inflammation. Ulcerative
move down to the colon, attach to the and haemorrhagic lesions of the small and
mucosa and become mature in 15–43 days. large intestine have been reported but may
Retroinfection can occur if the larvae be coincidental.
hatch on the perianal skin and migrate The relationship of pinworm infection
back up the anus. The adult females live to acute appendicitis has not been clearly
for 5–13 weeks and males for 7 weeks, but demonstrated, although Enterobius has
infection in humans is usually maintained been found in many patients with symp-
for very much longer by repeated reinfec- toms of appendicitis and where no other
tion. Retroinfection is more common in cause has been found. Sometimes
adults than in children and results in eosinophilic granulomas are found (Al
recurrent infections with a few worms Rabia et al., 1996), but recent large-scale
every 40–50 days. examinations have not supported an asso-
Biologically, this group of nematodes is ciation between Enterobius, or any other
interesting since it appears to be the only helminth, and appendicitis. In one study in
endoparasitic haplodiploid taxon, i.e. Venezuela, 3500 removed appendices were
females are diploid while males are hap- examined and Enterobius found in 11%,
loid and derived from unfertilized eggs Trichuris in 33% and Ascaris in 25%, but
(Adamson, 1989). there were just as many in normal organs
as in diseased ones (Dorfman et al., 1995).
CLINICAL MANIFESTATIONS Indeed, in another study in Denmark, look-
The majority of cases are symptomless, ing at 2267 appendices, 4.1% had E. ver-
although children often suffer from loss of micularis but in 72% they were in normal
appetite and irritability; it is usually organs and only 7.4% were in inflamed
regarded as primarily an infection of chil- organs. Possibly E. vermicularis is the
dren. cause of appendicitis-like symptoms
The most common symptoms are due to (pseudo-appendicitis) or, on the other
the pruritus ani, which can be very severe hand, worms may leave an appendix that is
and lead to disturbed sleep. In females the inflamed (Addiss and Juranek, 1991). A
vulva can also be involved from vaginal few cases of perianal mass have been
migration of adult worms and in girls is the reported with recurrent cellulitis.
commonest cause of pruritus vulvae; there Occasionally worms lodge in ectopic sites,
may also be acute urinary tract infection. such as the Fallopian tubes or the ovary
Scratching may lead to secondary infection and in peritoneal granulomatous nodules.
of the anal region. In about 20% of infected young girls gravid
Mild catarrhal inflammation, with nausea female worms migrate into the vagina and
and diarrhoea, sometimes occurs and symp- uterus, occasionally evoking an endometri-
toms of appendicitis have been reported. tis (Sun et al., 1991). Eggs are sometimes
Low eosinophilia of 4–12% may be found, found in cervical Papanicolaou smears.
but eosinophilia is not so pronounced as in
many other intestinal nematodes, perhaps DIAGNOSIS
because there is no tissue phase. Adult worms are often observed on the sur-
If female worms reach the peritoneal face of stools. Sometimes they can also be
cavity from intestinal perforations or fol- seen around the anus or in the vulva in the
lowing migration into the female reproduc- evening.
tive tract, worms can die and become Ova are rarely found in the faeces and
surrounded by granulomas (Gilman et al., are better looked for in the perianal and
1991). perineal regions, using a swab technique.
The National Institutes of Health cello-
PATHOGENESIS phane swab has been in use since 1937, but
Little internal pathology can be directly nowadays cellophane is replaced by adhe-
attributed to the presence of Enterobius, sive tape (Sellotape or Scotch tape). The
 The Nematodes 163

tape is usually stuck by one end to a micro- µg kg1, has given about 85% activity in
scope slide and turned back over a tongue clinical trials.
depressor or finger to make a swab
Levamisole (2.5 mg kg1 body weight in a
(Graham swab). The sticky tape is rubbed
single dose) and piperazine adipate (9 mg
over the anal region and stuck to the slide.
kg1 daily for 7 days) have been used for
A very convenient single-use flexible plas-
many years and can still be employed.
tic slide is manufactured in Japan. In
Russia an adhesive-covered glass ocular
EPIDEMIOLOGY
spatula is stated to be more sensitive and
Enterobiasis is particularly a group infec-
cheaper. Ideally the swab should be taken
tion, being most common in large families
first thing in the morning and repeated for
and in institutions, such as boarding-
7 days before a negative diagnosis can be
schools, hospitals, mental homes and
made (and even then only at about the 90%
orphanages. Transmission may be termed
level). If it is necessary to confirm whether
contaminative, as the eggs are immediately
the eggs are viable, the slide can be gently infective, and normally takes place
heated, when the enclosed larvae should indoors; this is in contrast to the soil-
become active. Where there is a lot of transmitted geohelminths, in which the
extraneous material, a drop of toluene may eggs or larvae continue development in the
be placed on the slide first to increase soil. Eggs may be found in large numbers
transparency. inside houses, particularly in soiled bed-
clothes, in night clothes and in dust in bed-
TREATMENT rooms and lavatories (up to 50,000 m2).
Enterobius is one of the easiest of helminth Once embryonated (at above 22°C), the
infections to treat and a wide range of eggs can survive for 6–8 weeks under cool,
anthelminthics are effective. The benzimi- moist, conditions but are killed in a few
dazole compounds inhibit microtubule days by a dry atmosphere. Direct contami-
function and glycogen depletion and are nation from anus to fingers to mouth is also
the most effective. However, whichever a common mode of infection.
drug is used, it is advisable to treat the Recent estimates of infection rates in
entire family or group on several occasions; various countries using sticky tape are:
otherwise reinfection is almost inevitable. preschool institutes in Azerbaijan 36%;
Where the cost is important, treatment is Brisbane, Australia 43% (adults 23%);
probably not worthwhile for symptomless mental patients in Tasmania, Australia
cases unless used primarily for other 19%; Bulgaria 6.5%; Chile 16–22%; chil-
helminths. dren’s homes in Santiago in Chile 87%;
Denmark 12.5%; the Dominican Republic
Albendazole. The standard treatment of a 12.5%; Shoubra, Egypt 45%; children in
single dose of 400 mg, or a divided dose of hospital in England 55%; Germany 34%;
200 mg twice a day, usually gives 100% Greece 22%; adults in Bengal, India 12%;
cure rates in children over 2 and adults Tamil Nadu, India 14%; Basrah, Iraq 18%;
(but should not be given to pregnant women). children in Lithuania 21%; Macao 23%;
Penang, Malaysia 58%; Quetta, Pakistan
Mebendazole. At a single dose of 100 mg 4%; children in Peru 43%; Poland 30%;
with the same proviso, this is equally effec- South Korea 2077%; orphanages in South
tive. Korea 74–84%; Slovenia 40%; children in
Moscow, Russia 30%; Tainen City, Taiwan
Pyrantel pamoate. Given in a single dose of 38%; Turkey 40–97%; primary schools in
10 mg kg1 body weight or with a repeat California, USA 12–22%; Venezuela
dose 1 week later, this is also effective. 12.5%. Numerous other studies have been
carried out using faecal examination only
Ivermectin. At a single dosage of 50–200 µg and these have given much lower infection
kg1 body weight or two doses of 100–200 rates.
164 Chapter 5

As with other intestinal nematode infec- The generic name Trichocephalus is

tions, there appears to be a predisposition probably more correct as the original
to infection, with a small percentage of description by Roederer and Wagler in
patients having very heavy infections and 1761 naming the organism Trichuris did
being responsible for most of the eggs not obey the rules of binary nomenclature
reaching the environment (Haswell-Elkins and probably represented the species
et al., 1987a, b). name. The fact that the name Trichuris
Enterobius eggs have also been found in (‘hair tail’) is not so apt as the later correc-
10,000-year-old coprolites from caves in tion Trichocephalus (‘hair head’) is irrele-
Tennessee and Utah, USA, and Chile, so it vant to the argument, however. The name
is a well-established human parasite. Trichuris is preferred in this edition partly
because it was chosen by the Committee on
PREVENTION AND CONTROL Nomenclature of the American Society of
Hygienic measures are of primary impor- Parasitologists in 1941 (although there has
tance and include frequent washing of been no ruling from the International
hands and changing and washing of sheets Commission on Zoological Nomenclature)
and night garments every morning during but mainly because it is becoming more
an outbreak. The area around the anus firmly established each year, except per-
should be washed every morning. Dust haps in eastern Europe.
should not be allowed to collect and there
should be good ventilation. The eggs are DISEASE AND POPULAR NAME
very light and easily become airborne. Trichuriasis or trichuriosis, trichocephalia-
sis; whipworm infection. One of the geo-
ZOONOTIC ASPECTS helminths.
None. Almost exclusively a parasite of
humans, although monkeys (chimpanzee, LOCAL NAMES
baboon, gibbon and marmoset) have been Cacing kerawit (Bahasy Malay), Njowni
found infected in zoos. Other species are (Luo), Keeri pulu (Tamil), Wakanabbyo
found in apes and monkeys and related (Japanese).
genera occur in rabbits, rats, mice and
horses. GEOGRAPHICAL DISTRIBUTION
Syphacia obvelata (Rudolphi, 1802) Cosmopolitan but more common in warm
Seurat, 1916, is a common and cosmopoli- humid countries. There are about 800 mil-
tan parasite of rats and mice, both in the lion (Bundy and Cooper, 1989) to 1300
wild and in the laboratory. Three cases million (Chan et al., 1994) cases in the
have been reported from children in the world, with one individual in about 500
Philippines. showing evidence of morbidity and 10,000
deaths annually (8–13%; Bundy, 1994).

Order Enoplida LOCATION IN HOST

The adults usually occur in the caecum but
Family Trichuridae may also be present in the appendix, rec-
tum and upper colon with the thin anterior
Trichuris trichiura end embedded in the mucosa (Figs 74–76).
(Linnaeus, 1771) Stiles, 1901
MORPHOLOGY
SYNONYMS The male measures 30–45 mm, with a
Trichocephalos trichiura (Goeze, 1782) tightly coiled posterior end and a single
Trichocephalus trichiurus (Shrank, 1788); spicule. The female is slightly longer
T. dispar (Rudolphi, 1802); T. hominis (30–50 mm) and both sexes have a narrow
(Shrank, 1788); T. intestinalis; (Hooper, anterior portion and a much wider poste-
1799) Ascaris trichiura (Linnaeus, 1771). rior end (hence the popular name of whip-
 The Nematodes 165

two-thirds from the anterior end. (The

whole row is called a stichosome and each
cell is known as a stichocyte.) The oesoph-
agus opens into the midgut at the end of
the anterior thin part of the worm. The
anus is terminal. These features are typical
of the class Adenophorea, which have no
phasmids.
In the female the vulva opens at the
junction of the oesophagus and intestine,
the reproductive organs being confined to
the wider posterior portion. The uterus
contains about 60,000 eggs at one time.

LIFE CYCLE
The female lays about 2000–20,000 eggs
24 h1. The characteristically shaped egg is
barrel-shaped with transparent terminal
polar prominences with a high chitin con-
tent, and measures 57–58 µm
26–28 µm,
with an outer, brown bile-stained, shell
and two inner shells (Fig. 123). The very
resistant egg contains an unsegmented
ovum when laid, which takes from 2 weeks
to many months to develop in moist soil,
depending on the ambient temperature
(4–6 months at 15°C, 3–4 weeks at 26°C, 17
days at 30°C, 11 days at 35°C).
Embryonated eggs are usually ingested on
contaminated food, such as salad vegeta-
bles, or ingested in soil by infants. The
contained second-stage larvae, measuring
260 µm
15 µm, hatch in the distal por-
tion of the small intestine or colon. They
penetrate the crypts of Lieberkühn of the
colon or caecum, where they live coiled up
and after about a week move under the
Fig. 74. Adult male of Trichuris trichiura. Insert epithelium to the tip of the villus. The thin
shows two females and a male (with coiled tail) anterior end of each worm remains buried
attached to the mucosa of the colon by their in a tunnel in the mucosa, while the rest
anterior ends. emerges and hangs freely in the lumen.
After the usual four moults, the females
worm, as they resemble the coaching whip mature and lay eggs about 60–90 days after
once used in Europe or a stock-whip (Fig. ingestion of the eggs.
74). The mouth is simple, without lips, but The adult worms normally live for about
with a stylet for penetration of the mucosa. 1–2 years where there is repeated reinfec-
In the living worm the stylet is constantly tion, but can survive for much longer in
probing and slashing, like a fencer wield- some circumstances.
ing a rapier. The mouth is followed by a
simple non-muscular oesophagus, sur- CLINICAL MANIFESTATIONS
rounded by a single row of cells with an In the great majority of infected individuals,
intracellular lumen and extending about only a few eggs can be found in a faecal
166 Chapter 5

Fig. 75. Adults of T. trichiura in colon showing the slender anterior ends ‘threaded’ beneath the
epithelium.

Fig. 76. Section of colon with adult T. trichiura. Note thinner anterior end embedded in mucosa.

sample and no overt symptoms can be Cooper et al., 1995; Ramdath et al., 1995;
attributed to the presence of the worms, Gardner et al., 1996).
except perhaps for diarrhoea; there is also
usually an eosinophilia of up to 25% in PATHOGENESIS
the early stages. In heavy infections, The anterior portions of the worms embed-
Trichuris causes dysentery with blood in ded in the mucosa cause petechial haemor-
the stools, abdominal or epigastric pain, rhages and there is evidence that the
headache, anorexia and weight loss, with presence of T. trichiura predisposes to
prolapse of the rectum in children (in amoebic dysentery, presumably because
about 30% of cases) (Plate 22). Iron- the ulcers provide a suitable site for tissue
deficiency anaemia, pallor, malnutrition, invasion by Entamoeba histolytica, and it
stunting of growth, clubbing of fingers and may also be involved in the spread of viral
poor school performance are associated and bacterial pathogens (particularly
with heavy chronic infections in children Shigella). Cases have been reported in
(Forrester et al., 1990; Simeon et al., 1994; which the lumen of the appendix was
 The Nematodes 167

filled with worms and consequent irrita- In heavy infections sigmoidoscopy may
tion and inflammation has led to appen- show the white bodies of adult worms
dicitis (but see p. 163) or granulomas. The hanging from the inflamed mucosa – the
mucosa of the large intestine becomes so-called coconut-cake rectum.
chronically inflamed, the extent depending
on the number of worms present. In heavy TREATMENT
infections there may be at least 1000 adult This is entirely by chemotherapy and,
worms present (with about 30,000 eggs g1 because of the sites of the adults, complete
faeces), which can cause an insidious elimination used to be difficult. Recently,
chronic colitis, similar to Crohn’s disease, the newer benzimidazoles are proving to be
with inflammation extending to the rec- very effective.
tum. A flexible fibre-optic colonoscope Albendazole is given at a single oral
shows that the wall of the caecum and dose of 200 mg but for symptomatic cases
ascending colon is also hyperaemic and should be given each day for 3 days. It is
oedematous, with ulceration and bleeding. not recommended for pregnant women or
The bleeding might be partly due to blood infants under 1 year old (Savioli, 1999).
ingestion by the parasites but is mainly Combined treatment with albendazole and
caused by enterorrhagia. Blood loss has ivermectin, as recommended for filariasis
been estimated at about 0.005 ml per worm (p. 199), appears to have a synergistic effect
day1. The rectal prolapse results from also in trichuriasis.
straining (tenesmus) consequent on irrita- Mebendazole at a single oral dose of
tion and oedema of the lower colon simu- 400–500 mg is similarly effective.
lating a full bowel (Plate 22). Oxantel pamoate with pyrantel (for
Immune responses in humans have only other intestinal nematodes), at 10–15 mg
recently been demonstrated; ES antigens of kg1 body weight, has the advantage that it
16–17 kDa appear to be immunogenic in does not cause ectopic migration of
children (Needham and Lillywhite, 1994). Ascaris, but it does require weight mea-
Previously all knowledge on immunology surements – chemical formula: (E)-3-(2-
of infection was based on T. muris in the (1,4,5,6-tetrahydro-1-methyl-2-pyrimidinyl)-
mouse. In this host, parasites are rapidly ethenyl)-phenol.
expelled, with subsequent immunity to Thiabendazole is unpleasant to take and
challenge infection, unlike the situation in not very effective and is no longer recom-
human infection. However, predisposition mended.
to infection has been demonstrated for all
the geohelminths, some individuals not EPIDEMIOLOGY
becoming infected in spite of being exposed Trichuris infection is very common in
as much as those who do (Crompton, many countries where there is heavy rain-
1998). The immunology of all the intestinal fall, dense shade and a constant tempera-
nematodes is discussed on p. 122. ture between 22 and 28°C.
Recent estimates of infection rates are:
DIAGNOSIS 25% in South and Central America, 31% in
This is by finding the characteristic eggs in Africa (with 76% in Nigeria and 70% in
the faeces. In very light infections concen- Cameroon), 12% in the Middle East, 12%
tration techniques can be used. More than in southern India, 36% in Bangladesh,
1000 eggs in a 50 mg Kato–Katz faecal 58% in South-East Asia except China and
smear (20,000 eggs g1 faeces) (p. 257) rep- 0.01% in Japan.
resents a heavy infection with overt symp- Fertile eggs are ingested with soil or on
toms. It has been estimated that 2000 eggs salad vegetables. This is similar to the mode
g1 faeces indicates the presence of 5–15 of infection in Ascaris and the two worms are
adult worms but the relationship is not commonly present together. They are both
reliable. Each female worm produces about particularly common where human faeces is
200–370 eggs g1 stool 24 h1. used as a fertilizer (‘night-soil’). The larvae
168 Chapter 5

inside the eggs develop only under moist are taking place against all the soil-
conditions and are killed by direct sunlight or transmitted nematodes (see p. 135).
a low relative humidity. Under conditions of Sanitation measures are likely to be very
poor sanitation both infections are peri- slow to act. For instance, a campaign in
domestic and the areas around houses may be northern Italy in the 1950–1960s took 25
heavily contaminated with eggs (Plate 2) up years to reduce prevalence from 25 to 5% in
to a depth of 20 cm; the habit of eating earth is schoolchildren. The basic reproductive rate
an important reason why infants are often of Trichuris is much higher than that of
infected by the age of 1. In the past, infection hookworms or Ascaris, which makes it more
was also common in temperate countries, resistant to control. Children acquire approx-
even though the eggs took a long time to imately 90 new parasites per year and, in the
become infective in the soil. Infection is absence of constraints, each female worm
overdispersed with a small proportion of the would produce four to six new egg-laying
infected population having a high worm females (Bundy and Cooper, 1989).
burden and producing most of the eggs reach-
ing the environment (Bundy and Medley, ZOONOTIC ASPECTS
1992). The same species occurs in monkeys and
Eggs of Trichuris were found in the rec- primates, such as lemurs, catarrhine mon-
tum of the Alpine ‘ice man’, who lived about keys and the orang-utan, but they are of no
5300 years ago. He also had a bag containing importance as reservoir hosts. The pig par-
a fungal purgative and anthelminthic asite, T. suis Schrank, 1788, is almost iden-
(Capasso, 1998). tical to the human parasite, although the
eggs are stated to be slightly larger (64 µm
PREVENTION AND CONTROL
30 µm). Experimental infections in
Personal protection is by the thorough humans are possible and it is likely that
washing of salad vegetables. natural infections also occur where there is
Until recently, control was almost intensive pig farming. A few cases of
entirely by sanitary disposal of faeces, but human infection with the dog and fox
mass chemotherapy has recently become whipworm, T. vulpis (Froelich, 1789), have
much more practical, with the develop- been reported. Other species occur in
ment of broad-action agents that can be sheep and cattle (T. ovis) and mice (T.
used in a standard single oral dose against muris) and over 70 species have been
many intestinal helminths, and campaigns reported altogether; all from mammals.

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Further Reading

Bundy, D.A.P., Chan, M.S., Medley, C.F., Jamison, D. and Savioli, L. (2001) Intestinal nematode infec-
tions. In: Murray, C.J.L. and Lopez, A.D. (eds) The Global Epidemiology of Infectious Diseases.
Harvard University Press, Cambridge, Massachusetts, USA (in press).
Farthing, M.J.G., Keusch, G.T. and Wakelin, D. (eds) (1995) Enteric Infections 2: Intestinal Helminths.
Chapman and Hall, London, UK.
Gilles, H.M. and Ball, P.A. (eds) (1991) Hookworm Infections. Human Parasitic Diseases, Vol. 4.
Elsevier, Amsterdam, The Netherlands.
Grove, D.I. (ed.) (1989) Strongyloidiasis: a Major Roundworm of Man. Taylor and Francis, London, UK.
Holland, C. (1987) Neglected infections – trichuriasis and strongyloidiasis. In: Stephenson, L.S. (ed.)
Impact of Helminth Infections on Human Nutrition. Taylor and Francis, London, UK, pp.
161–201.
Miller, T.A. (1979) Hookworm infection in man. Advances in Parasitology 17, 315–384.
Sakanari, J.A. and McKerrow, J.H. (1989) Anisakiasis. Clinical Microbiology Reviews 2, 278–284.
Schad, G.A. and Warren, K.S. (eds) (1990) Hookworm Disease: Current Status and New Directions.
Taylor and Francis, London, UK.
 The Nematodes 173

Tissue Nematodes males 1.3–3.9 mm. In the female, the vulval

opening is just behind the oesophagus and
All the nematodes considered in this sec- the male has a single very long spicule in a
tion invade the tissues of the host, includ- sheath. Both sexes have a small spear at the
ing those of the intestine, and have a life anterior end.
cycle involving an intermediate host.
Members of the first group, including LIFE CYCLE
Trichinella, are only distantly related to all The life cycle has been determined experi-
the rest and have vertebrate intermediate mentally in monkeys and Mongolian jirds.
hosts, in contrast to the others where these Freshwater fishes indigenous to the
are always arthropods and all of which Philippines were fed eggs from patients
belong to the order Spirurida. embryonated for 5–10 days in water.
Larvae hatched in the intestines of the fish
and reached the infective stage in about 3
weeks but could live for months; larvae
Order Enoplida
developed into adults in 12–14 days when
fed to monkeys or jirds.
Family Trichuridae
Following copulation and fertilization,
the females produce larvae. The first-
Aonchotheca philippinensis
generation larvae are retained and develop
(Chitwood, Velasquez and Salazar, 1968)
into second-generation males and females
Moravec, 1982
in another 2 weeks. The second-generation
SYNONYM females produce eggs passed out in the fae-
Capillaria philippinensis Chitwood, ces about 26 days after fertilization.
Velasquez and Salazar 1968. Autoinfection occurs in jirds and almost
certainly in humans, as all stages of devel-
DISEASE AND COMMON NAME opment, including viviparous and
Intestinal capillariasis or capillariosis; a larviparous females, have been found at
cause of non-vibrio cholera. autopsy. In one experiment, two larvae
from fish produced 5353 worms in a jird.
GEOGRAPHICAL DISTRIBUTION Several species of freshwater and brack-
This parasite was first described 30 years ish-water fish have been experimentally
ago from villages bordering the China Sea infected; Hypeleotris bipartita, Ambassis
on the west coast of the island of Luzon in miops and Eleotris melanosoma are often
the Philippines. It has been reported since eaten raw in the Philippines and Cyprinus
from the islands of Bohol, Mindanao and carpio in Thailand.
Leyte. Numerous cases have also been The natural definitive hosts are probably
found in Thailand and others from Egypt, fish-eating birds, which can be infected
India, Indonesia, Iran, Japan and South experimentally and one bittern has been
Korea. found naturally infected.

LOCATION IN HOST CLINICAL MANIFESTATIONS

The adults become embedded in the In the initial epidemic in 1967, when over
mucosa of the small intestine, especially 100 people died, all patients with eggs in
the jejunum. the faeces had intermittent diarrhoea, with
borborygmi and diffuse recurrent abdomi-
MORPHOLOGY nal pain. The syndrome resembled tropical
Aonchotheca is related to Trichinella and sprue, with five to ten voluminous stools
Trichuris and there are many species of cap- per day. Weight loss, anorexia and vomit-
illarids that are parasites of a wide range of ing were common. Patients who recovered
vertebrates. The adult worms are very small, from the initial attack usually suffered sev-
females measuring 2.5–5.3 mm in length and eral relapses and, in a study conducted 3
174 Chapter 5

years after the initial epidemic, patients

who were still symptomatic were found to
have depression of the D-xylose test and
impairment of fat and protein digestion
and absorption. A mortality rate of 35% in
untreated males and 19% in untreated
females was reported from one village in
the initial epidemic.
Nowadays, only the early symptoms of
borborygmi, diarrhoea and abdominal pain
are present before treatment is sought.

PATHOGENESIS
The stools contain large amounts of fat,
protein and minerals, particularly potas-
sium, which results in a marked protein-
losing enteropathy. Malabsorption also
occurs. Muscle wasting, emaciation, weak-
ness and cardiopathy were reported from
73% of early patients. Without treatment,
death often ensues 2 weeks to 2 months
after the onset of symptoms, due to cardiac
Fig. 77. Section of ileum with female
failure or to intercurrent infection.
Aonchotheca (cut tangentially) invading the villi
Necropsy studies on ten Philippinos and containing many unembryonated thick-shelled
showed the presence of adults and larvae eggs in the vagina. A section of the same worm
embedded in the mucosa of the jejunum, above shows a portion of the stichosome and
together with numerous eggs (Fig. 77). oesophagus.

DIAGNOSIS

Clinical. The early symptoms are typical

and easily recognized.
be affected and there is multiplication
Parasitological. Eggs, larvae and adults may within the host.
be found in the faeces. Eggs measure 36–45 Albendazole: In the few patients treated
µm and have a flattened bipolar plug at this drug appears to affect larvae as well as
each end (Fig. 124). They could be mis- adults at a dose of 200 mg twice daily for
taken for the eggs of Trichuris but differ in 14–21 days and may be more effective.
having a pitted shell, a more ovoid shape, a Thiabendazole can be given at 25 mg
slightly smaller size and no protuberance kg1 body weight day1 for at least a
of the plugs. Some eggs may contain larvae. month, but relapses are common.
The eggs of both parasites may be found
EPIDEMIOLOGY
together in the faeces.
Raw fish are a popular item of diet in the
Serological. ELISA, double diffusion and Philippines and Thailand and were impli-
indirect haemagglutination assay (IHA) cated in the cases in Japan and Iran.
have been tried but are not satisfactory. Presumably infection could be pre-
vented by thorough cooking of fish or even
TREATMENT by removing the intestines.
Mebendazole at 400 mg day1 in divided Capillarid eggs passed over a period by
doses for 20–30 days is the current drug of a patient in Irian Jaya differed in size from
choice. If treatment is curtailed there is those of all the species considered here
likely to be a relapse, since larvae may not (Bangs et al., 1994).
 The Nematodes 175

Calodium hepaticum eggs in the faeces is evidence of a spurious

(Bancroft, 1893) Moravec, 1982 infection from eating an infected animal
liver. A recent case was treated success-
SYNONYMS fully with albendazole at 10–20 mg kg1
Trichocephalus hepaticus Bancroft, 1893; body weight day1 for 20 days and then
Hepaticola hepatica (Bancroft, 1893) Hall, thiabendazole at 25 mg kg1 day1 for 27
1916; Capillaria hepatica (Bancroft, 1893) days, although hepatomegaly was still pre-
Travassos, 1915. sent 2 years later (Choe et al., 1993). Most
infections have been in children and a
DISEASE AND POPULAR NAMES recent case in a 14-month-old girl was
Hepatic capillariasis or capillariosis; the treated. Eggs are presumably ingested in
capillary liver worm. vegetables or on soil after passing through
the gut of a predator.
GEOGRAPHICAL DISTRIBUTION
About 25 human cases have been reported
Eucoleus aerophilus
from many countries, including Brazil,
(Creplin, 1839) Dujardin, 1845
England, Germany, India, Italy, South
Korea, Mexico, Nigeria, Slovakia, South
SYNONYM AND DISEASE
Africa, Turkey, continental USA and
Capillaria aerophila Creplin, 1839.
Hawaii. C. hepaticum is a natural parasite
Pulmonary capillariasis or capillariosis.
of the liver tissues of rats, mice, prairie
dogs, muskrats, beavers, hares and mon-
CLINICAL MANIFESTATIONS AND PATHOGENESIS
keys.
This is a worldwide parasite of wild carni-
vores and 11 human cases have been
CLINICAL MANIFESTATIONS AND PATHOGENESIS
reported from France, Iran, Morocco and
Female worms measure about 70 mm long
Russia. Adults live buried under the
by 0.12 mm wide, males 22 mm by
mucosa of the respiratory tract, the female
0.05 mm. The anterior portion of the worm
measuring 20 mm
0.1 mm and the male
contains the stichosome, oesophagus and
18 mm
0.07 mm. Eggs reach the intestine
bacillary bands, the posteror part the intes-
from the lungs and are passed out in the
tine and reproductive organs. Eggs measure
faeces. Infection is common in dogs in the
48–66 µm
28–38 µm (larger than those
USA but this might be a separate species
of Trichuris) and are thick-shelled, with
(E. boehmi).
surface pits and bipolar caps that do not
Clinical symptoms include a painful dry
protrude. The adults live in the liver
cough, fever, dyspnoea and acute tracheo-
parenchyma. The females lay eggs in the
bronchitis. There is some eosinophilia. In
tissues and these accumulate and form
one biopsy there were numerous small
large whitish spots under the liver surface.
granulomatous lesions in the wall of a
The eggs do not pass out in the faeces but
small bronchus. Ivermectin at 200 µg kg1
reach the soil after the death of the host or
has had encouraging results and repeated
after the host is eaten by another and the
doses of thiabendazole have been tried.
eggs are passed in the faeces.
Clinical symptoms resemble those of Three cases of Anatrichosoma cutaneum
visceral larva migrans, with an initial (Swift, Boots and Miles, 1922) Chitwood
hepatitis. The liver is tender and enlarged, and Smith, 1956, a parasite of the rhesus
with persistent fever, anorexia, weight loss monkey, have been reported from humans
and a very high (over 90%) eosinophilia. in Japan, Malaysia (Marwi et al., 1990) and
There is focal destruction of parenchyma Vietnam. Adults and eggs are found in
and fibrosis in chronic infections. lesions in the skin. Eggs removed from the
Diagnosis is by needle liver biopsy or facial skin were similar to those of
usually at post-mortem. The presence of Trichuris but larger (59 µm
28 µm).
176 Chapter 5

Family Trichinellidae

Trichinella spiralis
(Owen, 1835) Railliet, 1895

SYNONYM
Trichina spiralis Owen, 1835.

DISEASE AND POPULAR NAME

Trichiniasis or trichinellosis, trichinosis;
trichina worm infection.

GEOGRAPHICAL DISTRIBUTION
Infection with Trichinella species is world-
wide in carnivorous or scavenging animals
but is particularly important in humans in
Alaska and Canada in Inuit, Chile, eastern
Europe, Kenya and Russia. Other endemic
areas include Central and South America
(including the Caribbean), central and
western Europe, China, Indonesia, Japan,
New Zealand, the Pacific area (particularly
Hawaii) and the Aleutians.

LOCATION IN HOST
The short-lived adults are partially embed-
ded in the mucosa of the ileum. The larvae
are present in cysts in all the striated mus-
cles.

MORPHOLOGY
The adults are minute, threadlike worms,
the females measuring 2.8 (2.4–3.4) mm

0.06 mm and the males 1.5 (1.3–1.6) mm

0.03 mm. Both sexes are wider posteriorly Fig. 78. Adult female and male of Trichinella
than anteriorly. The oesophagus differs spiralis.
from that of all other animal-parasitic
nematodes (apart from Trichuris and capil-
larids), as its posterior part is non- LIFE CYCLE
muscular but is surrounded by a column of The muscle cysts containing larvae are
cuboidal cells, known as a stichosome or ingested in raw or semi-cooked meat. The
cell body (Zellenkörper), with an intracel- cyst wall is digested out in the stomach
lular canal. The oesophagus connects with and the larvae emerge in the duodenum.
a thin-walled intestine, which ends in a The released first-stage larvae invade the
terminal anus. The male has two copula- mucosa of the duodenum and jejunum and
tory appendages at the posterior end but no undergo four moults. The immature worms
spicules. The reproductive system of the emerge into the lumen of the intestine
female consists of a single ovary, oviduct, 22–24 h after ingestion of cysts and, in
seminal receptacle, uterus, vagina and mice, fertilized females have been observed
vulva. Trichinella is ovoviviparous, so that at 30 h. In most experimental hosts,
in the mature female the uterus is filled approximately twice as many females as
with larvae (Figs 78–80). males are present and both sexes re-enter
 The Nematodes 177

by the lymphatics and blood-vessels. After

reaching the muscles and penetrating the
sarcolemma with the help of a stylet, the
larvae grow, measuring about 1 mm in
length 17–20 days after infection. The
sexes can be differentiated at this time. The
larvae coil and by 17–21 days after infec-
tion are capable of transmission to a new
host, as they can resist the action of diges-
tive juices. The normal lifespan of the
female worms in the intestine of humans is
not known but from autopsy studies
appears to be less than 2 months.
From the point of view of the parasite,
humans are dead-end hosts. Transmission
normally takes place from one flesh-eating
animal (including carrion eaters) to
another, often of the same species, as with
rats and mice.

CLINICAL MANIFESTATIONS
Fig. 79. Portion of the stichosome of T. spiralis. The first signs and symptoms can be
caused by the development of the adults
and production of larvae in the intestine;
the mucosa. The female begins to produce in heavy infections they can be protean
first-stage larvae (measuring 80–129 µm
and infection is often misdiagnosed. With
5–6 µm) approximately 5 days after inges- about 1000 larvae g1 muscle tissue, there
tion of cysts. Each female produces may be a sudden onset of illness, with nau-
200–2000 larvae during its lifetime. The sea, vomiting, epigastric pain and severe
larvae are deposited in the mucosa and watery diarrhoea, followed by pyrexia
reach the active skeletal muscles, travelling (38–40°C), myalgias, facial or generalized

Fig. 80. An electron micrograph of the cuticle and epicuticle of T. spiralis (original magnification
82,000).
178 Chapter 5

oedema (Plate 23) and urticarial manifesta- phobia and blurred vision. Scleral or reti-
tions. There are also likely to be cardiovas- nal haemorrhages with pain on pressure or
cular, renal and central nervous system movement of the eyes and diplopia may
symptoms. Eosinophilia is often the first also occur.
clinical sign and becomes apparent about Flame-shaped splinter haemorrhages
10 days after infection, reaching a maxi- under the fingernails are sometimes seen
mum (usually 25–50%, but may be as high and are almost diagnostic.
as 90% with 4000 eosinophils mm3) dur- About 90% of infections are light, with
ing the 3rd or 4th week, and slowly dimin- fewer than ten larvae g1 of muscle. One of
ishing over a period of months. There is the heaviest infections known was a fatal
also some degree of leucocytosis. When one in a young boy in East Africa, who had
only a few cysts are ingested, these may be over 5000 cysts g1 of tongue muscle and
the only signs and symptoms, and the 6530 cysts g1 in another boy (see T. nel-
majority of cases of trichiniasis are diag- soni below). With massive infections like
nosed only at routine autopsy. this, there is a greater volume of cyst sub-
Larvae in the muscles can cause many stance than of muscle fibre. However, death
effects (Fig. 81). Transient cardiac manifes- may result with as few as 100 cysts g1, the
tations (feeble pulse, cardiac dilatation and severity of the reaction probably being
apical systolic murmur and palpitations), more important than the number of larvae
various nervous system manifestations present. In very heavy infections, death is
(meningitis or meningoencephalitis, hemi- more likely between the 4th and 8th weeks,
plegia, coma and neuritis with muscular from exhaustion, pneumonia or cardiac
paralysis) and pulmonary manifestations failure.
(effort dyspnoea, cough, hoarseness, Some infections in Inuit in northern
bronchopneunomia, chest pain and pul- Canada and Alaska from eating raw walrus
monary oedema) are all possible (Capo and or seal show atypical symptoms of pro-
Despommier, 1996). Ocular signs and longed diarrhoea, with no fever or oedema,
symptoms occur in over one-third of clini- short myalgia, but a high eosinophilia (this
cal cases and characteristically include is caused by T. nativa – see below); this
orbital oedema and waxy yellow chemosis possibly occurs in patients who have been
of the bulbar conjunctiva, with photo- previously infected (infections are likely to

Fig. 81. Section of skeletal muscle with cysts of Trichinella and interstitial inflammatory cells between the
muscle cells. From a fatal case with severe myositis (original magnification
65).
 The Nematodes 179

be high since they are almost entirely meat necrosis around each parasite are found in
eaters). the subcortical white matter.
There is usually eventual complete
recovery in most patients, but muscular Lungs. There may be oedema, disseminated
pain (in 60% of sufferers), fatigue (in 52%) haemorrhages and eosinophilic abscesses
and cardiovascular pains may persist for surrounding larvae, indicative of an aller-
1–6 years. The presence of two cysts per gic response.
gram of muscle is likely to result in mild
In general many more migrating larvae are
clinical symptoms.
destroyed in humans than in experimental
A few cases are recorded where death
animals and this is accompanied by more
has occurred about 10 days after infection
pronounced inflammatory changes.
owing to the action of the stages in the
intestine.
Histopathology of muscle stages. Within 2
days of larval invasion, the muscle fibres
PATHOGENESIS
lose their cross-striations and become more
In the early stages the mucosa of the diges-
basophilic. The fibres are changed bio-
tive tract may be hyperaemic, with inflam-
chemically and become oedematous and
mation consisting of eosinophils,
swell. About 17 days postinfection, the
neutrophils and lymphocytes and petechial
remains of the muscle fibres become more
haemorrhages at the site of attachment.
dense and apparently help to form
Antigen–antibody complexes form in the
‘Nevinny’s basophilic halo’ surrounding
tissues and are probably involved in the
each larva. This halo area is actually fluid
occasional severe gut reactions found in
heavy infections (antibodies are produced and contains proliferating, enlarged and
particularly to the stichocyte contents). altered nuclei. The redifferentiation
Most of the important pathology is due changes in the muscle fibres near each
to the larval stages in the muscles. These larva, with an increase in nuclear numbers
cause myositis, which makes the muscle and in mitochondria and with enlargement
tougher than normal, and there may also be of the Golgi apparatus, are followed by an
contractures. The extraocular muscles, inflammatory response, with invasion by
masseter, muscles of the tongue and larynx, lymphocytes, polymorphs and histiocytes.
diaphragm, muscles of the neck, intercostal The larvae become progressively encapsu-
muscles, deltoid muscles and sites of lated and the oedema subsides by the 5th
attachment to tendons and joints are most week.
often involved. The outer homogeneous capsule that
Larvae that invade other organs may be surrounds each larva is derived from the
responsible for more specific pathology, as sarcolemma. It is usually translucent and is
shown below. probably composed of collagen. The size of
the cysts formed varies with the host and
Heart. Larvae often invade the myocardium with the muscle involved. In humans, the
but cardiac muscle cannot form nurse cells cysts measure on average 0.4 mm

and cysts are never found. At autopsy of 0.26 mm. There is usually only one larva
fatal cases, the myocardium is usually soft per cyst, but two may be present and infre-
and flabby and there may be fatty degenera- quently even more. The Trichinella larvae
tion. in the cyst may live for years but the cyst
walls usually calcify a few months or years
Nervous system. Migratory larvae are often after infection (Fig. 82).
present in the cerebrospinal fluid and The cysts in meat are very resistant and
meninges and the brain substance becomes the larvae can probably remain viable until
oedematous and hyperaemic. There may decomposition occurs (at least 10 days).
also be many punctate haemorrhages. They have large glycogen reserves and an
Microscopic nodules, with a clear area of anaerobic type of respiration.
180 Chapter 5

Fig. 82. Calcified cysts seen in the voluntary muscles of a silver fox.

Trichinella down-regulates the host tioning and staining of the other. The best
immune response by antigen-dependent time for obtaining a positive biopsy speci-
mechanisms (molecular mimicry, antigen men is after the 4th week – rather late for
shedding and renewal, anatomical seclu- chemotherapy aimed at killing the adult
sion of the larvae in the cysts and stage worms to be of much use. Digestion of
specificity) and by immunomodulation pooled muscle samples is of use in epi-
(Bruschi, 1999). demiological surveys of prevalence in ani-
mals or in autopsy material. It is carried
DIAGNOSIS out for 30 min in 1% pepsin in saline
containing 1% HCl at 37°C and the freed
Clinical. Blood eosinophilia is usually the larvae are examined under the lower power
earliest sign and almost invariably has of the microscope.
appeared by the 10th day of infection; the
level can be extremely high (90%). It usu- Immunological. Because of the difficulties of
ally continues to rise for 2–5 weeks, parasitological diagnosis, particularly in
remains stable for a further few weeks and the early stages, immunological methods
slowly falls by the 9th week. The combina- are more important for individual diag-
tion of eosinophilia, orbital oedema, mus- nosis than in most other helminth infec-
cle pain, fever and gastrointestinal tions.
disturbances following ingestion of pork is Antibodies can be detected by an ELISA
very suggestive. None the less, trichiniasis as early as 12 days after infection
is often misdiagnosed as typhoid fever or (Ljungstrom, 1983) and there is a commer-
influenza. cial kit available, or by Western blotting of
a characterized fraction of sonicated larvae
Parasitological. Occasionally adults and lar- in an immunoglobulin G (IgG) ELISA with
vae can be seen in the stools and larvae in a molecular mass of 109 kDa, reacted with
the blood during the 2nd to 4th weeks after specific antibodies (Chan and Ko, 1990).
infection. More certain is the recovery of Recently the use of recombinant antigens
larvae by muscle biopsy. A sample of 1 g of (with an excretory/secretory (ES) antigen of
biceps or gastrocnemius is sufficient for 53 kDa) and of DNA probes has given
compression of one half (Fig. 83) and sec- encouraging results in trials.
 The Nematodes 181

larva

0.1 mm

remnant of degenerated muscle fibre

Fig. 83. Cysts of Trichinella as seen in muscle squash.

TREATMENT 3.0% (locally by ELISA: this is a new

Albendazole (at 14 mg kg1 or 400–800 mg endemic area), Lithuania 0.02% and
daily for 3–8 days), albendazole sulphox- Poland 0.03%. Infection is spreading in
ide or mebendazole (200 mg daily for 5 Belarus, Bulgaria, China (Yunnan
days) are effective in removing adult Province), Lithuania, Romania, Russia,
worms from the small intestine but unfor- Ukraine (ten cases year1 between 1984
tunately diagnosis is not usually made and 1996), former Yugoslavian countries
before the majority of larvae have already (there was an outbreak in Bosnia in 1996)
been produced and moved to the muscles and northern Canada. There have been
(3–5 weeks after infection). Thiabendazole recent epidemics in France (there were 538
(at 25–45 mg kg1 for 5–6 days) is equally cases in 1993 from a horse imported from
effective but has more side-effects. Pyrantel Canada) and Italy from eating raw horse-
pamoate at 5 mg day1 for 5 days has also meat; the horses had probably been fed on
been used successfully. animal products. A recent outbreak in
Massive doses of corticosteroids (e.g. Lebanon was caused by eating ‘kubeniye’, a
40–60 mg daily of prednisolone, 200 units local uncooked pork dish, at New Year and
of adrenocorticotrophic hormone (ACTH) a source in China is from eating under-
or 25 mg of cortisone, four times daily for cooked pork dumplings. Infection is com-
4–5 weeks) have been given to relieve the mon in pigs in some countries: 11% in
effects of the allergic response to the Bolivia, up to 2% in Chile, up to 57% in
muscle phase but are most important for China, 4% in Costa Rica, up to 22% in
relieving neurological manifestations. Croatia, 4% in Egypt, up to 30% in Mexico,
Anthelminthics should always be given 7% in Nigeria and up to 4% in Poland
first, as corticosteroids could prolong the (Murrell and Bruschi, 1994).
presence of adult worms in the intestine. While various strains of Trichinella have
been recognized for many years based on
EPIDEMIOLOGY infectivity to domestic or wild animals
Some estimates of prevalences are: Belarus (Fig. 84), recent studies based on biologi-
0.06%, Chile 0.26% (1989–1995), Bolivia cal, biochemical and genetic data of 300
182 Chapter 5

geographical isolates indicate that there are PREVENTION AND CONTROL

five separate species (Pozio et al., 1992; Larvae in pork are killed by heating above
Kapel et al., 1998), although more conserv- 55°C or (for T. spiralis) by deep-freezing at
ative authorities (e.g. Bessonov, 1998) 15°C for 20 days. The number of cases in
believe that there are only the two gener- the USA has dropped recently (with only
ally agreed (T. spiralis and T. pseudo- 38 cases each year for 1991–1996, with
spiralis Garvaki, 1972), while the others are three deaths), chiefly because most pork is
subspecies of T. spiralis. deep-frozen and pig swill is sterilized.
Trichinella britovi has a sylvatic cycle in However, it is estimated that inspection
wild carnivores in Europe (Estonia, France, costs $1000 million annually in the USA
Italy, Netherlands, Poland and Spain), and $570 million in the European Union
often in national parks with no exposure to (Murrell and Pozio, 2000).
humans. This species (or subspecies) is Pork can be examined for infection by
similar to T. nativa but is less resistant to means of the trichinoscope at the abattoir;
freezing for 3 weeks, differs in distribution this is a projection microscope that projects
and genetic make-up and has less severe an image of cysts in compressed samples of
intestinal symptoms. muscle (best from the tongue). A pooled
T. nativa is found in holarctic sylvatic digestion technique with muscle samples
animals (polar bear, Arctic fox, mink, wolf, from groups of pigs has replaced the
seal and walrus), but not in mice, rats or trichinoscope in those countries which still
pigs. It has a high resistance to freezing. It undertake routine examinations, since it is
has still not been proved how marine mam- more suitable for low prevalences. An
mals become infected; seals may possibly eat ELISA test is good for diagnosing infection
infected amphipod crustaceans that ingest in live animals. It is not possible to recog-
larval cysts in fragments of meat when feed- nize infected pigs from clinical symptoms,
ing on dead walruses or polar bears. as there is often an absence of morbidity,
T. nelsoni is found only in Africa in even with large numbers of cysts.
wild suids and has no resistance to freez- Most developed countries now have
ing. It is also found in many large wild car- laws to prevent feeding pigs with
nivores in East Africa (hyena, jackal, uncooked swill (primarily to control vesic-
leopard and lion), while human infection ular erythema in pigs) and this has lowered
is from eating uncooked bushpig or warthog. the incidence of infection. Rats in piggeries
T. pseudospiralis is cosmopolitan in should be destroyed and meat from wild
wild birds and mammals and has no resis- carnivores should never be fed to pigs.
tance to freezing. This form differs from all All pork and pork products should be
others, as the larvae do not form cysts in thoroughly cooked, as should the meat
the muscles. It is not common in humans from wild suids or carnivores.
but can cause muscle pain and fatigue with
polymyositis and a raised creatine kinase ZOONOTIC ASPECTS
level (Andrews et al., 1994). This is an entirely zoonotic infection,
T. spiralis is cosmopolitan, mainly in except possibly among the Turkana of East
domestic pigs and sometimes rodents, and Africa, who put dead bodies out to be eaten
is responsible for the great majority of by wild carnivores.
human cases, the symptoms and pathogen- Rats and other rodents are frequently
esis of which are described above. infected with T. spiralis subspecies, but are
There have been recent outbreaks from not usually important in transmission;
eating wild boar in Croatia (5.7% boars dogs and cats may become infected from
infected), Ethiopia, France, Italy, Poland ingesting them but do not maintain trans-
(0.5%), Spain (0.2%), northern Canada and mission. However, wild carnivores are
the USA. In the USA, bear and cougar important in transmitting T. nativa and T.
‘jerky’ are another source of infection in nelsoni. T. murrelli has recently been
hunters. described from wildlife in the USA (Pozio
 The Nematodes 183

WILD BOAR

BEAR, FOX,
WILD CAT
T , HUMAN
MAR Y
YNX,

RAT
A
AT DOMESTIC
PIG

TEMPERATE

HYENA, JACKAL, BUSHPIG

HUMAN
LEOPARD, LION WARTHOG

AFRICA

HUMAN

POLAR BEAR R
,
ARCTIC FOX,
WOLF, MINK, DOG

WALRUS, SEAL

ARCTIC

Fig. 84. Life cycles of Trichinella species from various regions. Top: T. spiralis; centre: T. nelsoni; bottom:
T. nativa.

and La Rosa, 2000), although not so far Norway and T. spiralis and T. nativa in
from humans. Finland (Pozio, 1998).
In some areas, more than one species (or Experimentally a wide range of mam-
subspecies) is present: for instance in mals can be infected, but cysts do not form
Europe, T. spiralis and T. britovi occur in in Chinese hamsters.
France and Spain, T. britovi alone in Italy Another non-cyst-forming species, T.
and Switzerland, T. spiralis alone in papuae, has been recently described from
Belgium and Germany, T. spiralis, T. britovi pigs in Papua New Guinea, but not so far
and T. nativa in Sweden, T. nativa in from humans (Pozio et al., 1999).
184 Chapter 5

Family Dioctophymidae raw fish. In one patient in New Jersey, raw

minnows were eaten when being used as
Dioctophyma renale fish bait – 48% of the minnows in the area
(Goeze, 1782) Stiles, 1901 contained larvae (Eberhard et al., 1989).

SYNONYMS, DISEASE AND POPULAR NAME

Superfamily Mermithoidea
Dioctophyme renale; Eustrongylus gigas
(Rudolphi, 1802) Diesing, 1951. Dioc-
The mermithids are free-living, aphasmid
tophymosis. Giant kidney worm infection.
nematodes with larvae that are parasitic in
insects. There have been occasional reports
CLINICAL MANIFESTATIONS AND PATHOGENESIS
of recovery of larvae from humans
Dioctophyma is a natural parasite of the (Agamomermis hominis once in faeces, A.
pelvis of the kidney or the body cavity of restiformis once in the urethra, Mermis
carnivores, including the dog, fox, mink, nigrescens once in the mouth, Mermis sp.
ottter, racoon and rat. About 20 human once in urine), but these are probably spu-
cases have been reported from Europe, rious infections (Hasegawa et al., 1996),
North and South America, Iran, China and with one presumably genuine report of a
Thailand. male mermithid beneath the tunica in a
These are very large nematodes, reddish case of hydrocele of the scrotum in a
in colour when alive. The female measures Nigerian (Hunt et al., 1984); one can only
20–100 cm
5–12 mm and the male speculate how this occurred.
14–20 cm
4–6 mm. The male has a
single spicule set in the middle of a post-
erior bursal cup. The unembryonated eggs Order Spirurida
(measuring 64–68 µm
40–44 µm) have a
thick, deeply pitted shell (Fig. 124) and are Superfamily Gnathostomoidea
passed out in urine. Embryonated eggs
must reach water for further development, Gnathostoma spinigerum
where they are ingested by aquatic Owen, 1836
oligochaetes. These are then ingested by
final hosts; fish or amphibians may also act DISEASE AND POPULAR NAMES
as paratenic hosts and this is probably the Gnathostomiasis or gnathostomosis; a
source of human infections. cause of visceral larva migrans and of
Adult worms in the kidney cause renal creeping eruption (the latter usually due to
colic and later dysfunction, the worms eat- another species, G. hispidum).
ing the kidney tissue. Larvae have also
been found in subcutaneous nodules. GEOGRAPHICAL DISTRIBUTION
A related parasite, Eustrongylides ignotus Most common in Japan (Kyushu, Shikoku
(or E. tubifex), a parasite of fish-eating and south Honshu) and Thailand
birds and with larvae in oligochaetes and (Daengsvang, 1980); occasional cases occur
fish has been reported from humans a few in Bangladesh, Burma, China, Ecuador,
times along the Atlantic coast of the USA. India, Indonesia, Malaysia, Mexico, New
Symptoms of acute pain in the right lower Guinea and Vietnam.
quadrant with vomiting, diarrhoea and
fever indicating acute abdomen or appen- LOCATION IN HOST
dicitis, required surgery. Red-coloured Adults live in small nodules in the stom-
fourth-stage larvae measuring 4–6 cm have ach wall of carnivores but are rarely found
been removed from a perforated caecum in humans. Third-stage larvae in humans
and from the peritoneum. One patient in migrate through the tissues, usually subcu-
New York had eaten raw oysters and goose taneously, and may be present in any part
barnacles (Wittner et al., 1989) and others of the body.
 The Nematodes 185

MORPHOLOGY the one- or two-celled stage. They measure

Adults measure 1.1–3.3 cm and have a 69 (62–79) µm
39 (36–42) µm and have a
characteristic head bulb with eight rows of finely granulated surface and a characteris-
hooks (Fig. 85). The mouth has two large tic polar thickening (Fig. 124). The eggs
lips. The anterior part of the body is cov- develop in water and the first-stage larvae
ered with cuticular spines. Third-stage lar- hatch in 7 days at 27°C. The larvae are
vae migrating in humans measure about ingested by species of cyclopoid copepods
4 mm and also have a head bulb with fewer (e.g. Cyclops varicans, C. vicinus, C.
rows of hooks (Fig. 86). strenuus, Eucylops agilis, E. serrulatus,
Mesocyclops leuckarti, Thermocyclops sp.),
LIFE CYCLE which live in ponds, moult in the body cav-
The eggs in the faeces of carnivores are ity in 7–10 days (Plate 24), and develop fur-
yellowish-brown and contain an ovum in ther when the freshwater microcrustaceans

Fig. 85. Stereoscan of head bulb of adult Gnathostoma hispidum.

Fig. 86. Third-stage larva of G. spinigerum removed from human subcutaneous tissues.
186 Chapter 5

are ingested by a second intermediate host. Mature adult worms in intestinal nod-
These are usually freshwater fish, frogs ules have also been reported in a few cases.
(such as Rana limnocharis) or snakes. The
second-stage larvae pierce the gastric wall DIAGNOSIS
and moult in about 1 month, and the third-
stage larvae are eventually surrounded by a Clinical. A painless, migrating, intermittent,
cyst in the muscles, measuring around subcutaneous oedema is characteristic,
1 mm in diameter. The natural definitive particularly when there is an eosinophilia
hosts are the dog, cat and large carnivores, of over 50%.
such as the tiger and leopard, which are
infected by eating fish or by eating a Immunological. A purified antigen from
paratenic host (possibly a rodent) that has advanced third-stage larvae (L3s) of 24 kDa
eaten fish. Suitable paratenic hosts are can be used in an indirect ELISA, which is
other fish, amphibians, snakes, rats, mice or stated to be 100% sensitive and specific
chickens, new cysts being formed in these. (Nopparatana et al., 1991). A Western
Twenty-five species of animals from all immunoblot technique with an antigen of
vertebrate classes can act as paratenic hosts 16 kDa has also given good results.
and multiple transfers are also possible.
Prenatal transmission of larvae from TREATMENT
mother to offspring can occur in mice and Surgical excision of worms is often possi-
may account for human cases of gnatho- ble when they are in subcutaneous sites.
stomiasis reported from babies. Albendazole at 400 mg twice daily for
The adult worms take about 100 days to 10–21 days has been used successfully in a
become mature in the stomach of carnivores. few cases (Kraivichian et al., 1992) and is
stated to stimulate larvae to move to the
CLINICAL MANIFESTATIONS AND PATHOGENESIS surface so that they can be easily excised
Many patients suffer from epigastric pain, (Suntharasamai et al., 1992). Mebendazole
fever, nausea and diarrhoea 24–48 h after at 300 mg daily for 5 days was also effec-
ingestion of the larvae, presumably caused by tive in one case.
the larvae penetrating through the intestinal
wall. There is often a very high eosinophilia EPIDEMIOLOGY AND PREVENTION
of up to 90%, with leucocytosis. Infection in humans usually follows eating
Some of the pathology is apparently raw fish dishes, such as ‘sashimi’ in Japan,
caused by toxic substances secreted by ‘somfak’ in Thailand or ‘ceviche’ (if made
Gnathostoma larvae; these include a with freshwater fish) in Latin America.
haemolytic substance, acetylcholine, Important species of food fish in Japan are
hyaluronidase-like substances and a proteo- crucian carp, Ophiocephalus spp. or goby
lytic enzyme. (Acanthogobius hasta); chicken can also be
The larvae migrate through the liver and a source of infection to humans. The
cause disturbances of liver function. They encysted larvae in fish are killed by cook-
then usually reach the subcutis, moving at ing for 5 min in water at 70°C or by pick-
a rate of about 1 cm h1, where they cause ling in vinegar for 6 h. Skin penetration is
a painless, migrating oedema. The oedema possible experimentally in cats and might
is generally erythematous and remains for occur during preparation of fish dishes.
about 2 weeks in one place (Plate 25). A Prevention is by thorough cooking of
few cases of ocular and pulmonary fish and chicken.
gnathostomiasis have also been reported
and most importantly, an eosinophilic There are at least seven other species of
myelencephalitis, in which the cerebro- Gnathostoma that could infect humans. G.
spinal fluid is grossly bloody or xantho- doloresi Tubangui, 1925, and G. hispidum
chromic. Some fatal cases have presented Fedchenko, 1872, are parasites of pigs in
with paraplegia. Asia and there have been a few cases of
 The Nematodes 187

human infection in China and Japan fol- humans in Austria, Bulgaria, China,
lowing ingestion of raw freshwater fish or Hungary, Italy, Morocco, New Zealand,
snakes, usually causing creeping eruption, Russia, Serbia, Sri Lanka and the USA.
sometimes accompanied by stomach con- Adult females measure about 145 mm

vulsions (Akahane et al., 1998). In one case 0.5 mm, males 63 mm
0.3 mm and the
G. doloresi caused colonic ileus, due to anterior end of both sexes is covered with
eosinophilic nodular lesions. G. nippon- cuticular thickenings. The worms live in
icum Yamaguti, 1941, has been recently serpentiginous tunnels in the squamous
described from humans in Japan, where it epithelium of the oesophagus and oral cav-
has caused itching and creeping eruption ity, where they can cause painful abscesses
after eating freshwater fish. (Ando, 1989; of the buccal mucosa (Jelinek and Loscher,
Ando et al., 1991). There has been a ‘rash’ 1994), sometime accompanied by pharyn-
of cases of creeping eruption in Japan gitis, vomiting and irritability. Eggs pro-
recently after eating raw marine fish or duced in these tunnels reach the mouth
squid, with one patient having larvae in cavity and are passed out fully enbry-
the eye (‘type x’ spirurid larvae). onated in the faeces. The eggs from natural
Larvae of the different species can be hosts containing first-stage larvae are
differentiated, although this is likely to be ingested by dung-beetles or, experimentally
impossible in tissue sections (Ando et al., at least, cockroaches, which act as interme-
1991). diate hosts. Adults take about 80 days to
develop when third-stage larvae are
ingested inside these insects. Diagnosis is
by identifying the characteristic tunnels
Other Spirurids
and by extracting adult worms after giving
anti-inflammatory drugs (Jelinek and
Thelazia callipaeda Railliet and Henry,
Loscher, 1994): eggs have been seen in spu-
1910, is a parasite of the conjunctival sac
tum but not in faeces.
and lachrymal ducts of dogs in the Far
East. It has been recorded about 60 times Abbreviata (= Physaloptera) caucasica
from humans in China, Indonesia, Japan, (von Linstow, 1902), is a natural parasite of
Korea, Thailand and Russia (Siberia). The monkeys in the tropics. The adult females
adults of both sexes are filariform and have measure 20–100 mm
2.5 mm, males
a serrated cuticle. The female measures 14–34 mm
1.0 mm, and both live with
7–19 mm, the male 4–13 mm. The move- their heads embedded in the mucosa of the
ment of the adults under the eyelids in the stomach or intestinal wall. Cockroaches
conjunctival sac causes intense irritation and grasshoppers can act as experimental
and the scratching of the cornea can lead to intermediate hosts. It has been reported
scar formation and opacity. Worms can be from humans in Brazil, Colombia, Congo
removed after local anaesthesia. Republic (Zaire), India, Indonesia, Israel,
The intermediate hosts are dipteran Namibia, Panama, Zambia and Zimbabwe.
flies, including Musca domestica (Shi et In a recent case in an Indonesian woman,
al., 1988). adult worms were recovered from the bil-
iary duct, where they had caused biliary
Thelazia californiensis Price, 1930, an eye pain, jaundice and fever. Another species,
parasite of ruminants, particularly deer, Physaloptera transfuga Marits and
has been reported five times from humans Grinberg, 1970, a parasite of cats and dogs,
in the USA, causing keratoconjunctivitis, has been recovered once from the lip of a
and is also transmitted by flies. woman in Moldova.
Gongylonema pulchrum Molin, 1857 (the Cheilospirura sp. Diesing, 1861 (or
gullet worm), is a natural parasite of the Acuaria sp.), a parasite of the gizzard of
oesophagus of herbivores (sheep, cattle, birds with insect intermediate hosts, has
goats, camels, equines, pigs and deer). It been recovered once from a nodule on the
has been reported about 40 times from conjunctiva of a Philippine farmer.
188 Chapter 5

Spirocerca lupi (Rudolphi, 1809) is a com- most important helminth diseases of

mon parasite of dogs and other carnivores humans. Bancroftian filariasis (caused by
in warm countries, forming tumours in the infection with Wuchereria bancrofti) and
stomach wall, with dung-beetles as inter- onchocerciasis (due to Onchocerca volvu-
mediate hosts and birds or mammals as lus) in particular are the cause of much
paratenic hosts. It has been found once morbidity and the former shares with
embedded in the wall of the ileum of a schistosomiasis the dubious distinction
newborn baby in Italy; it is assumed that among helminth infections of increasing in
infection was prenatal. incidence each year. All human filariae are
Rictularia spp. Froelich, 1802, are parasites transmitted by the bite of a bloodsucking
of rodents or bats, and a gravid female worm insect (Fig. 87). The adults are ovovivi-
has been recovered once from a section of an parous and the early first-stage larvae,
appendix of a man in New York. known as microfilariae, are found in the
blood or skin. Microfilariae measure from
Superfamily Filarioidea: the Filariae 150 to 350 µm in length and some retain
the much expanded eggshell as a thin
Members of the superfamily Filarioidea of sheath; their specific identification can be
the order Spirurida are tissue-dwelling of great importance in diagnosis (Figs 88
nematodes, responsible for some of the and 89).

INSECT MAN

3rd-STAGE Injected on to skin

LARVAE next to bite
ADULTS
Develop in fat body: Lymphatics:
Loa Wuchereria
2nd-STAGE LARVAE Develop in thoracic Brugia
muscles: Subcutaneous
all others tissues:
MICROFILARIAE Loa
1st-STAGE Skin tissue fluids: Onchocerca
LARVAE Onchocerca Mansonella
M. streptocerca streptocerca
Blood: Peritoneal or
all others pleural cavity:
Mansonella ozzardi
M. perstans

Fig. 87. The life cycles of human filariae.

Fig. 88. A generalized microfilaria showing the features of use in identification (some features can be
seen only with special staining techniques and the stylet and sheath are not always present).
 1 2 3 4 5 6 7 8

10 m

The Nematodes
Fig. 89. The tails of human microfilariae in smears: 1. W. bancrofti; 2. B. malayi; 3. Loa loa (stained in haematoxylin); 4. L. loa (stained in Giemsa); 5. Mansonella
perstans; 6. M. ozzardi; 7. Onchocerca volvulus; 8. M. streptocerca.

189
190 Chapter 5

Wuchereria bancrofti (hence the name ‘filaria’ from Latin). The

(Cobbold, 1877) Seurat, 1921 head end is slightly swollen and has two
rows of ten sessile papillae. The cuticle is
SYNONYMS smooth, with very fine transverse striations,
Filaria sanguinis hominis; Filaria bancrofti and the posterior end of the female is finely
Cobbold, 1877; Wuchereria pacifica. tuberculated. The female measures
80–100 mm
0.25 mm, the male 40 mm

DISEASE 0.1 mm. The ovoviviparous female has two
Lymphatic filariasis or filariosis (LF); posterior ovaries; from these two oviducts
Bancroftian filariasis or filariosis; cause of lead into the paired uteri, which coil back
elephantiasis. and forth through the greater part of the body
before they fuse and open by a short vagina at
LOCAL NAMES the vulva, 0.8 mm from the anterior end. The
Jakute (Burmese), Etow = hydrocele and proximal portions of the uteri are filled with
Barawa gyeprim = elephantiasis (Fanti), eggs and embryos, while near the vulva the
Wagaga or Wagana (filarial fever) (Fijian), microfilariae are crowded and remain in the
Tundermi (Gwaina = hydrocele) (Hausa), sheath formed by the elongation of the egg
Kusafurui (filarial fever) or Kusa in Kyushu membrane. Cross-sections of females of all
and Ryuku Island (Henki, Senki or human filariae show this double-uterine
Oogintama = hydrocele) (Japanese), Apipa = structure. The male has the posterior end
elephantiasis (Luo), Mumu (filarial fever) curved ventrally and on the ventral surface of
(Samoan), Watharoga = hydrocele the tail are 12–15 pairs of sessile papillae.
(Singalese), Sheelo = hydrocele and Lugo There are two unequal spicules, measuring
marodi = elephantiasis (Somali), Matende 0.6 and 0.2 mm, and a gubernaculum (the
(Mshipa = hydrocele) (Swahili), Fee fee and number and arrangement of the papillae and
Mariri (Tahitian), Yanaikal (Tamil), Gypeym the structure and lengths of the spicules of
(Etwo = hydrocele) (Twi). the male worms are of great taxonomic
importance among the filariae).
GEOGRAPHICAL DISTRIBUTION The microfilariae are found in the
It has been estimated recently that 119 mil- bloodstream and can live for 3–6 months;
lion people are infected with LF, of whom they measure 210–320 µm by 7.5–10 µm
107 million are due to W. bancrofti. (the mean lengths of microfilariae from var-
Infection is present in most equatorial ious geographical regions vary from 250 to
countries of tropical Africa between 20°N 290 µm). The anterior end is rounded and
and 20°S and in Madagascar, Asia the posterior end pointed. Each micro-
(Bangladesh, China, India, Indonesia, filaria is surrounded by a long sheath,
Japan, Korea, Myanmar, Pakistan, which stains pale pink in Giemsa stain. In
Philippines, Sri Lanka, Thailand), the wet preparations the microfilaria moves
Pacific (New Guinea, Melanesia, Polynesia, vigorously in a serpentine manner; in
including Fiji, Samoa, Tahiti), the West stained preparations it often assumes
Indies and northern South America. graceful curves. The posterior end is free of
nuclei and thus differs from the microfilar-
LOCATION IN HOST ial larvae of Brugia malayi (Fig. 90) and
The adults live in the lymphatics, either of Loa loa.
the lower limbs and groin region or of the The microfilariae have various struc-
upper limbs, and breasts in women. tures (nerve ring, excretory pore and cell,
Sheathed microfilariae are found in the inner body or innenkörper, rectal cells and
bloodstream. anus) whose size and position can be of
help in recognition. However, it must be
MORPHOLOGY remembered that these features are only of
Like all filariae of humans the adults of use in well-fixed and stained preparations
Wuchereria are long, threadlike worms and some individual variation may occur.
 The Nematodes
Map 8. Distribution of Wuchereria bancrofti.

191
192 Chapter 5

Fig. 90. Microfilariae of (top) Wuchereria bancrofti and (bottom) Brugia malayi.

Microfilariae described from eastern small blood-vessels of the lungs principally

Madagascar (Malagasy Republic) had some because of the difference in oxygen tension
characters resembling W. bancrofti and oth- between the arterial and venous capillaries
ers resembling those of Brugia malayi and in the lungs. Perhaps the peripheral circula-
were designated as belonging to W. ban- tion represents an unfavourable environ-
crofti var. vauceli. ment and the microfilariae remain there for
the minimum time necessary to maintain
LIFE CYCLE transmission.
The sheathed microfilariae circulate in the When the microfilariae are ingested with
bloodstream and, in most parts of the world, a blood meal by a suitable species of mos-
show a marked periodicity; they are found quito, they lose their sheath within 15–30
in the peripheral circulation from 22.00 to min in the stomach of the insect. A propor-
02.00 h, while during the day they hide in tion manage to penetrate the stomach wall
the capillaries of the lungs. In areas of the before the formation of a peritrophic mem-
Pacific east of longitude 160°, such as Fiji, brane and migrate to the thoracic muscles
Samoa and Tahiti, where the vectors are day- in 1–24 h. Two days later they have meta-
biting mosquitoes, the periodicity is partially morphosed into sausage-shaped larvae,
reversed and the strain is said to be diur- measuring 150 µm
10 µm, and by the end
nally subperiodic. Investigations on the of a week (usually at 5 days) the larvae have
mechanism of microfilarial periodicity have moulted, the alimentary canal is developed
shown that during the day, in the periodic and the second-stage larvae then measure
form, the microfilariae are held up in the 250 µm
25 µm. During the 2nd week
 The Nematodes 193

(9–10 days) the larvae moult again, grow more and mature and the females produce
much longer (1.2–1.8 mm) and migrate to microfilariae within 1 year (206–285 days in
the head, where they enter the labium and experimental infections in leaf monkeys).
emerge through the tips of the labella while The adult female worms probably produce
the mosquito is feeding. The infective third- microfilariae for about 5 years (Vanamail et
stage larvae can be differentiated from other al., 1996), although greater longevity has
filarial larvae, if the mosquito is dissected been reported in the past (10–17 years).
in a drop of saline, by size and by the three
subterminal papillae (Fig. 91) (there may be CLINICAL MANIFESTATIONS
larvae of various animal filariae in mosqui- It has been estimated that currently about
toes, such as Dirofilaria and Setaria). The 44 million people suffer from overt mani-
parasite cannot be transmitted from one festations of lymphatic filariasis. The other
person to another until the larvae have 76 million cases appear to be symptomless,
undergone this essential development to a condition that may last for years, and the
the infective stage in the mosquito. only overt evidence of infection is the pres-
Optimal conditions for filarial develop- ence of microfilariae in the blood.
ment in mosquitoes are about 26°C (range However, recent studies using lym-
16.5–31°C) and 90% relative humidity. Many phoscintigraphy indicate that even these
mosquitoes are killed by heavy infections apparently symptomless cases are probably
and in others larvae often fail to mature, so suffering from subclinical lymphatic and
that the infection rate in mosquitoes is usu- renal damage (Freedman et al., 1994;
ally low (below 0.5%), though under some Noroes et al., 1996).
conditions it can be much higher.
Development in the mosquito takes 11 or Acute disease. From the 3rd month after
more days and the infective larvae escape entry of the larvae, there may be recurrent
through the labella when the insect bites a attacks of acute lymphangitis (inflamma-
new individual and enter the skin through tion of the lymph ducts), with inflamed,
the puncture wound (this is likely to be tender lymph nodes, headache, nausea and
more successful in areas of high humidity, sometimes urticaria (‘filarial fever’), each
where the skin will be moist, although the attack lasting from 3 to 15 days. At this
mosquito does deposit a drop of fluid on the time microfilariae vanish from the blood
skin while feeding). After entering the skin (amicrofilaraemia) and there may be many
of a human, the larvae migrate to the lymph attacks in a year. There is often
vessels and glands, where they moult twice eosinophilia accompanied by chyluria (the

10 m

Wuchereria bancrofti Brugia malayi

Fig. 91. Tails of third-stage larvae of W. bancrofti and B. malayi from mouth-parts of mosquito.
194 Chapter 5

presence of whitish lymph containing fatty nodes), lymphoedema, lymphoceles, lym-

acids from the intestinal lymph vessels in phuria, chyluria and, in males, genital
the urine). In many areas acute symptoms lesions, including hydrocele and lymph
start at the age of about 6, with a peak at scrotum, in which lymph drips from the
age 25. In many areas infection probably spermatic cord. In Ghana, hydrocele but
occurs in very young children. In a study not adenolymphangitis was associated
in Haiti, 6% of 2-year-olds and 30% of 4- with a high infection prevalence and inten-
year-olds had filarial antigens but only one sity (Gyapong, 1998).
child was microfilaraemic; some of these
children already had dilated lymphatics, Chronic disease. True elephantiasis, in
shown by ultrasound (Lammle et al., 1998). which the oedema is hard and non-pitting,
The most serious clinical manifestations takes about 10–15 years to develop.
are due to disturbances of the lymphatic Secondary bacterial and fungal infection
system (Fig 92), which may result in often follows, with the develop of verru-
lymphadenitis (inflammation of the lymph cous growths (Fig. 93).

Fig. 92. Radiograph showing blocked lymph ducts.

Fig. 93. Cases of elephantiasis in Guyana caused by W. bancrofti. It is not so evident in males because
of the trousers worn. In the man third from the right there are verrucous lesions of the foot (‘mossy foot’).
 The Nematodes 195

The changes in the lymphatics are often

stated to be due to blockage caused by the
dead worms but recent experimental stud-
ies indicate that it is caused mainly by an
allergic response to the still-living worms.
The nature of the lesions varies in dif-
ferent parts of the world, reflecting particu-
larly the different sites of obstruction. In
India, chyluria is rarely reported, but it was
common in Japan. In Africa, elephantiasis
is less common than in the Pacific and is
usually confined to the legs. Hydrocele
(Figs. 94 and 95), with probable reduction
in fertility, is particularly common in
males in East Africa (up to 50% of infected
individuals) and India (with about 27 mil-
lion cases) and has very serious social/sex-
ual implications (Dreyer et al., 1997). In
West Africa, there are often high micro-
filarial rates (40–50% of the population)
but few clinical manifestations. In those
Pacific islands where the subperiodic Fig. 94. A case of filarial hydrocele.
strain of the parasite occurs, slowly devel-
oping gross elephantiasis of the arms, legs,
breasts, scrotum or vulva was common presence of a lymphatic filarial infection
until transmission was reduced in the last and is sometimes known as occult filaria-
few years. sis. The symptoms include bouts of severe,
Tropical pulmonary eosinophilia is paroxysmal, dry, wheezy coughing, resem-
caused by an abnormal host reaction to the bling an asthma attack, with dyspnoea,

Fig. 95. Section of dilated lymphatic of the testis with adult female of W. bancrofti. The vessel wall is
thickened and there is a granulomatous reaction to the worm (magnification
55).
196 Chapter 5

chest pain and fever, resulting from dense lymphatics probably play an important
eosinophilic infiltrations in the lungs last- part in the development of lymphoedema
ing for weeks or months. It occurs particu- and elephantiasis (Dreyer et al., 2000). In
larly in India or Singapore (in persons of chronic infections, lymphoid aggregates
Indian extraction). Patients are amicrofila- and germinal centres develop and eventu-
raemic but have strong filarial serology, ally cause complete occlusion of the
with a high eosinophilia (about 35%). lumen, so that the lymph vessels are no
A similar reaction is known as longer functional. Worms die and become
Meyers–Kouwenaar’s syndrome, found in surrounded by fibrotic tissue, which even-
the Pacific and East Indies. There is a benign tually calcifies. It is not known what trig-
lymphadenitis with enlargement of the gers the initial inflammatory response.
lymph nodes, liver and spleen and with pul- Chyluria is caused by rupture of lymph
monary symptoms but no microfilaraemia. varices into any part of the urinary tract,
Histologically the lymph nodes are hyper- with fatty lymph appearing in the urine. In
plastic with dead microfilariae surrounded cases of renal chyluria there may be pas-
by eosinophils and then hyaline material to sage between the renal pelvis and a dilated
form nodular, granulomatous, abscesses lymphatic to the cisterna chyli. Such cases
(‘M–K bodies’). The condition can easily be show up on intravenous or retrograde pyel-
mistaken for Hodgkin’s disease and the ograms but are not serious and do not
symptoms of both filarial conditions are require surgery. The rupture of varicose
diagnostically rapidly alleviated by treat- lymph vessels near the skin of the scrotum
ment with diethylcarbamazine (DEC). results in lymph oozing on to the surface
(lymph scrotum).
PATHOGENESIS Adults of Wuchereria and Brugia con-
The first phase of clinical disease is charac- tain a bacterium, Wohlbachia, in the lateral
terized by dilatation of the afferent lym- cords and it has recently been postulated
phatic vessels reacting to the presence of that these bacteria are responsible for
masses of adult worms. Initially the inflammatory responses, inducing
sinuses of the smaller lymph vessels cytokines (Fig. 96). The chronic release of
increase in size (lymphangiectasia), but fol- Wohlbachia might lead to desensitization
lowing the repeated attacks of adenolym- of the innate immune response and the
phangitis the enlarged lymph nodes bacterial catalase may protect the filariae
become progressively firm and fibrotic. The from the action of hydrogen peroxide-
nodes become hyperplastic and micro- mediated damage (Taylor, 2000). The pres-
scopical sections show inflammation of the ence of the bacterium appears to be
endothelial lining, with many lympho- essential for the long-term survival of the
cytes, plasma cells and particularly filaria.
eosinophils, and there may be foci of
necrosis, with sections of adults in the Immune responses. Many of the symptoms
lumen. Lymphatics often become invaded associated with filarial infection (e.g.
by bacteria, but some clinical (Dissanayake eosinophilia, urticaria, lymphangitis and
et al., 1995) and experimental (Denham lymphoedema) are immunological in origin
and Fletcher, 1987; Lawrence, 1996) and confirm that infection induces strong
studies indicate that this is not the primary immune responses. Epidemiological stud-
cause of pathogenesis, which is caused by ies show that, in endemic areas, there are
an allergic reaction to the adult worms, individuals who appear to be parasitologi-
allied to cofactors such as a high worm cally negative, despite evidence of expo-
burden, lymphangiectasia, location of adult sure to infection (the so-called endemic
worm nests (e.g. in spermatic cord) and normals). A key question is whether
chronology of adult worm deaths. How- immune responses have the potential to be
ever, recurrent secondary bacterial infec- host-protective as well as pathogenic.
tions superimposed on the damage to the Analysis of immune responses has been
 The Nematodes 197

Fig. 96. Section of W. bancrofti with the bacterium Wohlbachia in the lateral cords (the numerous bodies
on right side of electron micrograph).

carried out in many infected populations tant in all of these phenomena and there
and there has been a large amount of labo- have been many attempts to explain each
ratory research with experimental models. in terms of differential T-helper 1 (Th1)
However, it has to be said that no clear pic- and Th2 responses. However, there is no
ture has emerged. straightforward relationship between sub-
Immunological relationships between set activity and host response. It is true
filarial nematodes and their hosts are com- that patients with high microfilarial loads
plex and the cause of much contention. tend to show reduced Th1 responses and
Particular difficulties are caused by the high Th2 (e.g. reflected in high IgG4 levels,
fact that in filarial-infected populations possibly acting as blocking antibody), but
some individuals apear to be immune, oth- not all type 2 cytokines are produced nor-
ers suffer immune-infected pathology, mally. T cells from microfilaraemic indi-
while yet others (microfilaraemic individ- viduals show much reduced proliferation
uals) show a depression of responses to to worm antigens, but can still release
filarial antigens that is reversed after interleukin 4 (IL-4), though IL-5 responses
chemotherapy. T cells appear to be impor- are reduced. The cytokine IL-10 may be
198 Chapter 5

involved in down-regulating proliferative DIAGNOSIS

responses, although antigen overload from
the large numbers of circulating micro- Parasitological. Routine diagnosis is by
filariae may also be involved. Filarial finding microfilariae, usually in stained
worms are also thought to release thick blood films (see p. 262 for various
immunomodulatory molecules that depress techniques). Blood should be taken from
specific T-cell functions, such as prolifera- the ear or finger at 22.00–02.00 h for the
tion, gamma interferon (IFN-) secretion nocturnally periodic forms and at
and, surprisingly, IL-5 production. 10.00–14.00 h for the subperiodic Pacific
Children born to mothers who are microfi- form. Microfilariae can sometimes be
laraemic may show a profound T-cell obtained during the day by taking blood
unresponsiveness, both Th1 and Th2 smears about 1 h after giving two tablets
responses being down-regulated, which (100 mg) of diethylcarbamazine (DEC)
presumably results from placental transfer (provocation test). Concentration tech-
of antigen or immunomodulatory factors. niques can be employed (counting chamber
Immune-mediated protection against or Nuclepore filter (p. 264)).
infection may act independently against
the three major life-cycle stages (infective Clinical. Lymphangitis, lymphadenitis or
L3s, adults and microfilariae). Individuals manifestations of lymph stasis in a patient
who remain uninfected in endemic areas in an endemic area, often with
tend to show Th1-biased responses, and eosinophilia, are very suggestive. Recent
mice lacking the capacity to make IL-4 (a studies, particularly in Brazil, using ultra-
major Th2 cytokine) retain the ability to sound have enabled direct visualization of
kill incoming infective larvae of B. malayi. adult worms in the lymphatics (Amaral et
However, neither Th1 nor Th2 responses al., 1994; Noroes et al., 1996). It has been
appear to eliminate adult B. malayi from found that the worms are in ceaseless
the body cavity. It is clear that the different movement, undergoing what has been
stages also induce quite different patterns termed a ‘filarial dance’.
of host responses. Thus, in mice, adult
worms and L3s elicit Th2 responses with Immunological. These tests are most suc-
high IL-4 and IgG4 production, as well as cessful in cases without microfilariae in the
IgG1 and IgE antibodies (although IgE blood. A new simple immunochromato-
responses are depressed), whereas expo- graphic test (ICT) card kit is commercially
sure to microfilariae alone can induce Th1 available, using 100 µm of whole-blood
responses, with high initial IFN- produc- finger-prick samples (or serum or plasma),
tion and IgG2 antibody. How worms are which can be taken at any time by
killed is still controversial, despite clear untrained staff and put on a nitrocellulose
evidence from in vitro studies that anti- layer on a sample pad (Weil et al., 1997).
body and antibody-dependent cellular The pink sample pad contains a dried
cytotoxic (ADCC) mechanisms can damage polyclonal antibody (AD12.1) specific to W.
or eliminate parasites. Eosinophils partici- bancrofti attached to colloidal gold and
pate in ADCC mechanisms against infec- migrates up the pad to reach a specific
tive L3s, and IgM and IgG2a antibody can monoclonal antibody immobilized in a line
clear microfilariae. It is likely that nitric on the pad; this traps free antibody–antigen
oxide mechanisms are important in attacks complexes to form an intense pink line,
against larvae (Maizels et al., in Nutman, which can be compared with a control line.
2000). People probably become resistant The test takes 5–15 min and detects early
following repeated reinfection and, as in infections in children, which is very
schistosomiasis, may develop a state of important for assessing the success of any
concomitant immunity, with existing adult control campaign, as well as for individual
worms remaining alive but invading larvae diagnosis, and is negative for all filarial
being destroyed. infection apart from Bancroftian filariasis
 The Nematodes 199

(this kit is commercially available from Long-term treatment with antibiotics,

www.amrad.com.au or amradict@amrad. such as rifampicin or oxytetracycline, is
com.au). A commercially available dot showing promise in research and clinical
ELISA with monoclonal antibodies (usu- trials (Townson et al., 2000).
ally Og4C3), using whole dried blood sam-
ples, can even give an indication of the Surgical. Traditionally hydrocele has been
number of parasites present but is not easy treated by adding sclerosing agents and
to use in the field (from JCU Tropical lymphoedema by bandaging and elevation
Biotechnology, Townsville, Queensland). of limbs. Radical surgery has also been used
Circulating parasite DNA detection by a to remove adventitious tissue in elephantia-
PCR is both sensitive and specific, particu- sis. Recently, regular washing and hygienic
larly when microfilariae are present, but is care of inflamed lymph vessels and hydro-
highly labour-intensive and expensive. celes has been shown to resolve manifesta-
tions and prevents further development.
TREATMENT Following 5 years of chemotherapy and
simple medical treatment in New Guinea,
Chemotherapy. Recent ultrasonic studies 87% of patients were cured of hydrocele
have enabled the action of chemotherapeu- and in 69% lymphoedema had resolved.
tic agents to be directly observed and worm
nests can be surgically removed and worms EPIDEMIOLOGY
examined to ascertain drug-induced Of the 107 million cases of Bancroftian
changes in somatic tissues or in the ability filariasis in the world, 49% are in South-
to produce new larvae (embryogenesis) East Asia (particularly India, with an esti-
(Dreyer et al., 1995). Previously the effects mated 48 million infections), 31.3.% in
on adult worms required studies over Africa, 16% in the western Pacific, 3.4% in
many years. the Americas and 0.3% (or now probably
DEC has been used for the last 50 years, nil) in the eastern Mediterranean; alto-
usually at an oral dose of 72 g over 3 weeks, gether it occurs in over 80 countries, where
and was thought to kill microfilariae but 750 million people are at risk. The geo-
not adults. Recent studies indicate that it graphical distribution of the disease is
does kill about 50% of adult worms as well. determined largely by climate, being found
Recently, much smaller doses (6 mg kg1) in areas with a hot, humid climate; the
have been found to be effective. However, it local distribution can be forecast by geo-
cannot be used in patients from Africa (see graphical information systems (GIS) imag-
p. 201). In vitro DEC has no effect on micro- ing (Brooker and Michael, 2000) and by the
filariae and its action may be mediated by distribution of the vectors, but other factors
platelets; excreted filarial antigens are also may be involved, such as local variations
necessary to trigger the reaction. in the density, susceptibility, longevity and
Ivermectin at an oral dose of 400 µg human-biting habits of the vector and in
kg1 every fortnight for 6 months (total the density, sleeping habits and natural
dose of 4.8 mg kg1) completely inhibits and acquired resistance of the human pop-
production of microfilariae but has no ulation.
effect on adults when examined by ultra- Many species of mosquitoes have been
sonography, even at the end of long-term shown to act as vectors in various parts of
treatment. For mass chemotherapy, 200 µg the world (WHO, 1992; Kettle, 1995;
kg1 once yearly has been advocated. It Service, 2001), including at least 31 species
probably acts by binding to glutamate- of Anopheles (An. aquasalis, bellator, dar-
gated chloride channels. lingi in the Americas; An. funestus, gam-
Albendazole in a single oral dose of 400 biae, arabiensis, bwambae, melas, merus,
mg can be given with DEC or ivermectin nili in Africa; An. aconitus, anthropopha-
and appears to have some action against gus, kewiyangensis, nigerrimus, sinensis
adults (possibly synergistic). complex, letifer, whartoni, flavirostrus,
200 Chapter 5

minimus, candidiensis, balabacensis, leu- tration of one larva inhibits the passage of
cosphyrus, maculatus, philippinensis, sub- others, so that only a few larvae are usually
pictus, tesselatus, vagus in Asia; An. found in each mosquito (it also has a pha-
bancrofti, farauti, koliensis, punctulatus, in ryngeal armature, which destroys many
Papua New Guinea), five species of Culex microfilariae). However, there may be many
(C. quinquefasciatus in the Americas, mosquitoes biting each night (over 100 per
Africa and Asia; C. pipiens molestus in the night is common) and in Calcutta it has
Middle East; C. bitaeniorhynchus, sitiens been estimated that one person may be bit-
complex, pipiens pallens in Asia; C. pipi- ten by 6000–7000 infected C. quinquefas-
ens pallens in the western Pacific; C. ciatus per year. This species is extending its
annulirostris, bitaeniorynchus in Papua) 15 range alarmingly in both Asia and Africa.
species of Aedes (Ae. scapularis in the On Polynesian islands (east of longitude
Americas; Ae. niveus group, harinasutai, 160°), such as Fiji, Samoa and Tahiti, a
togoi, poicilius in Asia; Ae. togoi in the diurnally periodic form of LF occurs and
western Pacific; Ae. fijiensis, oceanicus, the vectors are species of Aedes, which can
samoanus, vigilax, futunae, polynesiensis, breed in small bodies of water, such as
pseudoscutellaris, tabu, tongae, upolensis opened coconut shells, leaf bracts, crab
in the South Pacific) and two species of holes and manufactured containers, such
Mansonia (M. titillans in the Americas; M. as pots, tin cans and car tyres. In Thailand
uniformis in Asia and Papua). there is a nocturnally periodic form of LF
Vector Anopheles species breed in transmitted by Ae. niveus.
ponds, slow-flowing streams, rice paddies To determine transmission rates in mos-
and fresh- or salty-water swamps, and LF quitoes they can be dissected individually
transmitted by them is principally a rural (Davies, 1995) or, where rates are very low,
disease. Members of the An. gambiae a pool method using 1000–2000 (possibly
group (An. gambiae, arabiensis, melas, dried) mosquitoes can be employed and
merus) are very susceptible vectors and the presence of larvae shown by DNA
show facilitation, whereby the penetration determination after PCR amplification.
of one larva through the stomach wall facil-
itates the entry of others; this can result in PREVENTION AND CONTROL
high mortality of mosquitoes when microfi- Lymphatic filariasis was identified recently
larial rates are high (Dye, 1992). In rural as one of six potentially eradicable diseases
areas of East Africa, infection rates of by an International Task Force (1993), and
1–1.5% are found in An. gambiae, An. ara- the World Health Organization (WHO) is
biensis and An. funestus, but 0–0.3% in C. coordinating campaigns to eliminate it as a
quinquefasciatus (although this is the only public health problem in the next few
vector in urban areas). In West Africa, years (Ottesen et al., 1997; WHO, 1999; see
transmission is entirely due to Anopheles; also WHO web site: www.filariasis.org).
although C. quinquefasciatus is common in The reason for optimism is partly because
urban areas, it cannot be infected. of new regimes of chemotherapy and from
Culex quinquefasciatus is the most the success of campaigns already carried
important vector in urban areas of Asia and out in various countries. It is possible that
East Africa, as it can breed in very small there is a window of opportunity such as
bodies of water contaminated with organic in retrospect can be seen to have con-
matter (especially leaking septic tanks, pit tributed to the success of the smallpox
latrines and drains). The adult females campaign: just after its eradication mass
readily enter houses, tend to rest indoors vaccination would not have been possible
and are night biters; they can sometimes fly because of the spread of AIDS.
for up to 1 km. They are almost entirely Control is aimed at both alleviating the
anthropophilic and in Singapore infection suffering caused by the disease (morbidity
rates of 20% occur. Culex species show the control) and stopping the spread of infec-
phenomenon of limitation, whereby pene- tion (transmission control).
 The Nematodes 201

Morbidity control. Mass treatment cam- Campaigns using these schedules have
paigns with DEC have been tried with started in American Samoa and western
varying degrees of success over the last 40 Samoa and Niue (25 countries by August
years. China, where compliance is good, is 2001). It is intended that 50 million indi-
now in the final stages of a long-term cam- viduals will have been treated at least once
paign: in 1950 there were estimated to be by the end of 2001 and that the disease will
30 million cases, while there were only be eliminated as a problem in any country
about 1.65 million in 1995. In China and by 2020. There is a concerted campaign
other countries, such as Samoa, Solomon starting in all Pacific islands that hopes to
Islands and Tahiti and particularly in the eliminate infection there by 2010. This area
Ryuku Islands (Japan), South Korea and consists of 22 island states with a total
Taiwan, DEC has been added to cooking population of 7 million but extends over
salt (at a dose of about 3 mg kg1 ) and has one-third of the world’s surface. The manu-
greatly reduced disease. In the past it was facturers of both albendazole (GSK) and
thought that DEC only acted against micro- ivermectin (Merck) have donated enough
filariae (at a total dose of 72 g usually of these agents to carry out the programme.
given over 12 days), but recently studies It is very important in ivermectin treatment
have indicated that a single annual dose is that coverage and pattern of attendance at
effective and also has some action against mass clinics should be satisfactory (Plaisier
adults. If microfilarial rates fall below a et al., 2000).
critical breakpoint, then infection should To treat adenolymphangitis and hydro-
die out (this level probably differs in dif- cele, thorough and frequent washing and
ferent areas and with different popula- possibly antibiotic and antifungal treat-
tions). ment can help to prevent bacterial infec-
The real breakthrough in mass treatment tion and this appears to prevent
was the recent finding that combined treat- subsequent elephantiasis also.
ment schedules are much more effective
than the use of a single drug (Ottesen et al., Transmission control. There is no animal
1999; Plaisier et al., 2000). In the new reservoir host and so all efforts can be
WHO initiative two main regimes are rec- directed to breaking the human transmis-
sion cycle.
ommended:
1. Insecticide-impregnated (usually perm-
1. All areas except sub-Saharan Africa: ethrin) bed nets and curtains, as used for
(a) DEC (6 mg kg1 body weight) combined malaria control, which can be effective for
with albendazole (400 mg) once yearly for months even if the net has a few holes.
4–6 years is the preferred regime; Spraying walls is not as popular as it once
(b) or DEC (6 mg kg1) once a year for 4–6 was, as many mosquitoes, particularly
years alone (this has fewer side-effects than Culex species, are exophilic and do not rest
the traditional 12-day treatment; inside houses. Screening of doors and win-
(c) or DEC in salt (0.2–0.4% w/w) for 6–12 dows and provision of ceilings reduced the
months. biting rate from 200 to 5 per night in a trial
2. Sub-Saharan Africa: in Tanzania.
DEC cannot be given because there may 2. The use of long-lasting polystyrene
also be infections with loiasis or oncho- beads in enclosed breeding sites, such as
cerciasis and this drug can then be danger- latrines, cesspools and ponds to prevent
ous (see p. 210) or very unpleasant (see the air breathing of mosquito larvae and
p. 218). pupae. The ventilated improved pit (VIP)
(a) Single yearly dose of ivermectin (200 latrine with a screened air pipe, which
µm kg1) plus albendazole (400 mg) for traps emerging C. quinquefasciatus adults
4–6 years (optimal); as they move towards the light, can help
(b) or ivermectin alone at same dose. in controlling mosquito numbers. New
202 Chapter 5

biocides, such as Bacillus sphaericus, a Brazil differ in nuclear number and were
self-reproducing, toxin-producing bac- given the name W. lewisi Schacher, 1969,
terium specific against C. quinquefasciatus, but no differences have been found in
will also kill larvae. adults recovered from the same area.
3. Environmental engineering can be
designed to prevent open drains and
sewage systems and to remove unwanted Brugia malayi
water and solid waste safely to prevent (Brug, 1927) Buckley, 1960
mosquito breeding. Cesspools should also
be covered. Measures against Culex are
often welcomed by the local population as SYNONYM
it is an important nuisance biter (Plate 26). Wuchereria malayi Brug, 1927.
Where the same Anopheles vectors are
involved, malaria control measures can DISEASE
help to control LF also and, indeed, in the Lymphatic filariasis or filariosis (LF),
Solomon Islands the latter has almost van- Malayan filariasis or filariosis, cause of ele-
ished in this way, although malaria is still phantiasis.
common. The situation is similar in
Vanuatu, which at present has a prevalence LOCAL NAMES
of 2.8%. In Polynesia, clearing up small As for W. bancrofti. Baku (Japanese in
containers containing water or adding safe Hachijo Koshima Island).
organophosphorus insecticides to drinking-
water pots can help to control Aedes vec- GEOGRAPHICAL DISTRIBUTION
tors. Infection is confined to Asia and occurs in
The use of larvivorous fish has long Cambodia, southern China, southern India,
been advocated and might have a limited Indonesia, Korea, Laos, Malaysia,
effect against Anopheles vectors. Philippines (Palawan Islands), Vietnam
Integrated control measures are likely to and until recently in Japan.
be necessary for successful control
schemes, involving community participa- LOCATION IN HOST
tion and possibly primary health-care ini- The adults inhabit the lymphatic glands
tiatives. and lymph vessels, usually of the lower
4. Chemotherapy also plays a large part in limbs and groin. Sheathed microfilariae
reducing transmission and in New Guinea occur in the peripheral bloodstream.
the annual transmission potential (ATP) of
the vector Anopheles punctulatus was MORPHOLOGY
reduced enormously after the first year’s The adults are very similar to those of W.
treatment. bancrofti but there are small differences in
the papillae and spicules at the tail end of
ZOONOTIC ASPECTS the male worm.
None, although microfilariae of Wuchereria The sheathed microfilariae in the blood
type have been reported once from a potto can be clearly differentiated from those of
(Peridicticus potto). In experimental infec- W. bancrofti. They measure 170–260 µm

tions, complete development has been 5–6 µm and in stained smears appear stiff
obtained in leaf monkeys (Presbytis and kinky, unlike the smooth curves of W.
cristata) and macaques (Macaca cyclopis) bancrofti microfilariae (Fig. 90). The sheath
and slight development in male jirds. is much longer than the body and stains
Another species, W. kalimantani, is a nat- bright pink in Romanowsky stains, such as
ural parasite of the leaf monkey in Giemsa, at a pH of 6.8 (the sheaths of
Kalimantan (Borneo) and is used in drug microfilariae are sometimes lost in the
trials but has not been recorded from process of making a smear, so more than
humans. Microfilariae from humans in one should be examined). The round
 The Nematodes
Map 9. Distribution of Brugia malayi, B. timori, Loa loa and Mansonella ozzardi.

203
204 Chapter 5

anterior end is free of nuclei for 12–16 µm

and has a double stylet process. The tail is
pointed and has two distinctive nuclei at
the posterior extremity. Of the complete
100 Mb genome of B. malayi, 33% has now
been deposited in a database (Williams and
Johnston, 1999).

LIFE CYCLE
The microfilariae are usually nocturnally
periodic: a subperiodic form occurs in
peninsular Malaya, the Palawan Islands,
Sabah and Thailand.
On being ingested by a mosquito vector
from the blood capillaries of an infected
person, the microfilariae lose their sheaths
in the stomach and penetrate the wall of the
gut. The larvae develop similarly to those of
W. bancrofti and moult twice in the tho-
racic muscles before migrating to the
labium in 6–12 days. Infective third-stage
larvae, measuring 1.3–1.7 mm in length,
migrate out through the tips of the labella
when the mosquito bites another individual
and enter the skin through the puncture
wound (Figs 91 and 97). The larvae reach
the lymph glands, moult twice more and
reach maturity in about 3 months. Fig. 97. Infective larva of Brugia emerging from
labella palp of mosquito.
CLINICAL MANIFESTATIONS AND PATHOGENESIS
Brugia malayi causes similar disturbances
of the lymphatic system to those already not cross-react. Specific tests for B. malayi
described under W. bancrofti. Elephantiasis are also being investigated, one of which
is usually confined to the lower leg below uses recombinant ES antigens (Kumari et
the knee and is a common complication in al., 1994).
Malaysia (Plate 27), while hydrocele is In blood films microfilariae of the noc-
uncommon in males. There is also a higher turnally periodic form often lose their
proportion of apparently symptomless car- sheaths, which can be seen separately.
riers than with bancroftian filariasis (proba-
bly because of a lower intensity of TREATMENT
infection). As for bancroftian filariasis, except that
In animals experimentally infected with with DEC only one-third of the normal
Brugia species, developing worms can dose should be given on the first 2 days,
cause dilatation of the lymph vessels and due to likely febrile reactions. These are
enlargement of the nodes within weeks of probably more severe in malayan filariasis
infection (Denham and Fletcher, 1987); because the drug is more effective against
ultrasound studies could help to determine their microfilariae and the count is usually
whether this occurs in humans. higher.

DIAGNOSIS EPIDEMIOLOGY
As for W. bancrofti, although new commer- In all endemic areas of malayan filariasis
cial immunological tests for the former do except for Sulawesi (Borneo), bancroftian
 The Nematodes 205

filariasis also occurs. However, the infec- copra and, with the help of weed-killers
tion patterns of the two infections differ, as and insecticides against adults (used prin-
explained below. cipally for malaria control), infection has
The nocturnally periodic form of been virtually eliminated. Unfortunately,
malayan filariasis is transmitted by night- bancroftian filariasis is still spreading in
biting species of mosquito; by Mansonia Sri Lanka.
uniformis in most areas, by Anopheles bar- The worldwide measures being started
birostris and Anopheles campestris in against LF should be particularly effective
southern China, India and Japan, and by against the nocturnally periodic form of
Aedes togoi, which breeds in swampy malayan filariasis: a mass treatment cam-
areas, in Cheju Island (Korea) and coastal paign in north-west Malaysia reduced
areas of China. Species of Mansonia (M. microfilarial rates from 26% to below 1%.
anullifera, indiana, uniformis), which
transmit the nocturnally periodic form of ZOONOTIC ASPECTS
infection, lay their eggs in small batches on Subperiodic B. malayi is one of the most
the undersurface of the leaves of water- catholic of filarial worms and natural infec-
plants, such as the water hyacinth in tions have been reported from four species
Assam, mangrove in western Malaysia or of monkeys (particularly the leaf monkey,
water lettuce (Pistia stratiotes) in southern Presbytis obscurus), civet cats, domestic
India and Sri Lanka. The larvae and pupae cats and pangolins. Experimentally it will
attach to the underwater stems of these also develop to maturity in various
plants by the specially adapted respiratory rodents.
siphon through which they obtain air from
the plant. This form of B. malayi is also Brugia pahangi (Buckley and Edeson,
transmitted by species of Anopheles (An. 1956) is a natural parasite of cats and wild
aconitus, anthropophagus, barbirostris, carnivores in western Malaysia and has
campestris, donaldi, kewiyangensis, niger- developed to maturity in humans in exper-
rimus, letifer, sinensis complex, whartoni) imental infections. The different forms of
and by Aedes togoi. These species, unlike B. malayi may reflect the presence of a
the Culex vectors of W. bancrofti, cannot species complex with the sibling species B.
breed in small temporary bodies of water pahangi. The microfilariae of subperiodic
and so malayan filariasis is a more rural B. malayi occurring in wild animals can be
disease than bancroftian. The periodic differentiated from those of B. pahangi by
form is highly adapted to humans and the fact that only the former will develop
reservoir hosts are not important. in Mansonia bonneae.
The subperiodic form, with microfilar-
iae occurring in the peripheral circulation Brugia timori Partano, Purnomo, Dennis,
during the day, is transmitted by species of Atmosoedjono, Oemijati and Cross, 1977,
Mansonia (M. annulata, annulifera, bon- causes timoran filariasis or filariosis in
nae, dives, indiana, uniformis), which bite humans on the islands of Timor, Flores and
by day as well as by night and are predomi- Alor (see Map 9, p. 203). Microfilariae are
nantly zoophilic. This form is probably a nocturnally periodic and in blood smears
natural parasite of monkeys and civet cats can be differentiated from those of B.
and human infections occur when rice- malayi as the sheath does not stain in
fields adjoin areas of, often cleared, forest. Giemsa stain.
Clinical manifestations are similar to
PREVENTION AND CONTROL those of B. malayi but the presence of adult
Clearing of the water-weeds necessary for worms in the lymphatics often causes
the development of Mansonia larvae can be abscesses to develop in the groin region
difficult as they re-establish so quickly. (Plate 28). It is transmitted by mosquitoes
However, in Sri Lanka, they have been of the Anopheles barbirostris group (proba-
removed from the ponds used for treating bly An. campestris).
206 Chapter 5

Brugia beaveri Ash and Little, 1964, is a males 30–35 mm
0.3–0.4 mm. The head
natural parasite of wild carnivores (bobcat, is truncated and has a ring of six papillae
mink and racoon) in Louisiana, USA, and just behind the mouth. The cuticle has
an adult male worm has been recovered numerous, randomly arranged, smooth,
once from an enlarged human lymph node round bosses; they are absent from the
(Schlesinger et al., 1977). head end of the female and from both ends
of the male (these bosses must be differen-
Brugia guyanensis Orihel, 1964: adults tiated from the regular annulations found
have been reported once from a human cer- in Onchocerca (Fig. 98), as portions of
vical lymph node in Peru (Baird and either species could be found in biopsy
Neafie, 1988). It is a natural parasite of the material). The lateral cords are much more
coatimundi (Nasua nasua). conspicuous than in other human filariae.
In the female the vulva opens 2.5 mm
from the anterior end. The posterior end is
Loa loa rounded and has a pair of terminal papil-
(Cobbold, 1864) Castellani and Chalmers, lae. The females are ovoviviparous, the
1913 twin uteri containing all stages of develop-
ing eggs and larvae enclosed in egg mem-
SYNONYMS branes (the sheath). The male has a tail
Filaria oculi humani, Microfilaria diurna. curved ventrally, with two lateral, posteri-
orly placed, cuticular expansions and five
DISEASE AND POPULAR NAMES pairs of asymmetrically placed, peduncu-
Loiasis or loaosis; Loa filariasis or filariosis. lated papillae around the cloaca and three
Eye-worm infection. Cause of Calabar pairs of small, sessile papillae. There are
swellings. two unequal spicules, measuring 150 and
100 µm.
LOCAL NAMES The microfilariae are sheathed and mea-
Agan anya (Ibo), Aroro or Aján oju sure 250 (230–300) µm
6–8 µm. They
(Yoruba). have a kinked appearance in stained prepa-
rations (in contrast to the smooth curves of
GEOGRAPHICAL DISTRIBUTION W. bancrofti microfilariae). The tail is short
Confined to forest areas of West and and relatively thick, with large nuclei con-
Central Africa, particularly where equator- tinuing to the tip. The sheath does not
ial rain forest has been cleared and on the stain with Giemsa or Wright’s stain
fringes of guinea savannah. In northern (although it does with haematoxylin) so
Angola, southern Cameroon, Central that the microfilariae are sometimes mis-
African Republic, Congo, Democratic takenly identified as being unsheathed
Republic of Congo (Zaire), Gabon, Ghana, (Figs 99 and 109).
Guinea-Bissau, Ivory Coast, Nigeria (Niger
delta region), Sierra Leone, southern Sudan LIFE CYCLE
and western Uganda, with a few infections Microfilariae found in the peripheral blood
reported from Ethiopia (see Map 9, p. 204). show a diurnal periodicity, being most
plentiful from 08.00 to 17.00 h, when up to
LOCATION IN HOST 40 ml1 may be present.
Adults are found in the subcutaneous con- The vectors are large (7 mm long), day-
nective tissues and the sheathed microfilar- biting, tabanid flies, principally Chrysops
iae circulate in the peripheral blood during dimidiata and C. silacea ( also C. centurio-
the day. nis, distinctipennis, langi, longicornis,
zahrai and possibly streptobalius).
MORPHOLOGY Chrysops, known as the mango, mangrove
The adults are thin transparent worms, the or softly-softly fly, usually bites (painfully)
females measuring 70 mm
0.5 mm, the below the knee and is a pool feeder. The
 The Nematodes 207

Loa loa

0.1 mm

Onchocerca volvulus

Fig. 98. Portions of Loa and Onchocerca as may be recovered in tissue biopsies.

microfilariae are picked up in a blood which disappear in a few hours or days to

meal, lose their sheaths inside the stomach reappear elsewhere. These non-pitting
of the fly and penetrate the gut wall after oedematous swellings, which can be easily
about 6 h. They develop in the cells of the differentiated from onchocercal nodules by
fat body and moult twice. The third-stage their fugitive nature, appear 6–12 months
larvae, measuring 2 mm
25 µm, migrate after infection, most commonly in the hand
first to the thorax and then to the head and or ankle, and reappear at intervals for
are infective after 10–12 days. The larvae another year or so. The Calabar swellings
move down the labium when the fly bites a are sometimes accompanied by intense
new host and enter at the site of the itching, with arthralgia, pruritus and fever,
wound. Because the vector takes such a and, if near a joint, may cause difficulty in
large blood meal, up to 100 larvae can be flexion. In chronic infections the worms go
found in one fly. They migrate through the deeper and may migrate through all the
human subcutaneous connective tissues viscera of the body; they do not then cause
and muscle fasciae, moulting twice and swellings and microfilariae may no longer
developing into adults in 6–12 months. be found in the blood, but there have usu-
The adults live for 4–17 years. ally been often undiagnosed symptoms of
fatigue, recurrent fever and perhaps
CLINICAL MANIFESTATIONS arthritic pains for a long time. In general,
A weal appears at the site of the bite if the indigenous inhabitants have higher micro-
individual has been previously infected. filaraemias but fewer swellings and symp-
The adult worms migrate through the toms than visitors or expatriates. Adult
connective tissues in any part of the body, worms sometimes cross the conjunctiva at
the resulting hypersensitivity reaction some- a rate of about 1 cm min1 and can then be
times causing painless Calabar swellings, extracted (Fig. 100); they usually pass
208 Chapter 5

20 m

Fig. 99. Microfilaria of Loa loa (stained in haematoxylin – compare Fig. 109).

Fig. 100. Adult of Loa moving under the conjunctiva.

across the eye in minutes but can remain PATHOGENESIS

for days, causing considerable discomfort. Biopsy sections of swellings sometimes
In most cases loiasis is a relatively benign show adults in the centre of an oedematous
disease with a good prognosis. reaction. In chronic cases the skin may
A hypereosinophilia of 60–90% (20,000 become lichenified. Dying worms in the
–50,000 eosinophils mm3) is frequently subcutaneous tissues can cause a chronic
found and may contribute to the endocar- abscess, followed by a granulomatous reac-
dial fibrosis sometimes reported; pul- tion and fibrosis (Fig. 101); worms have
monary infiltrations have also been been excised from many parts of the body.
reported rarely. IgE levels are typically It is likely that in chronic sufferers who
raised, although it is not clear what role are amicrofilaraemic, microfilariae are being
this plays in the host response. destroyed by immune responses in these
 The Nematodes 209

Fig. 101. Section of subcutaneous tissues with dying male Loa causing a host reaction.

hypersensitized individuals, and the endo- DIAGNOSIS

myocardial fibrosis and nephrotic syndrome The most common method of diagnosis is
sometimes reported from such cases resem- by finding microfilariae in thick blood
ble the situation in the collagen diseases. smears taken during the day. In chronic
Various visceral lesions have been infections and those in visitors, microfilar-
attributed to loiasis, but the most serious iae may be very scanty and concentration
complication is meningoencephalitis, techniques can be used (see p. 263). The
which can be fatal and is not uncommon in microfilariae also live for many years and
areas of high endemicity. It may be accom- can continue to circulate even after adults
panied by retinal haemorrhages and is are dead.
associated with DEC in patients with very The presence of the fugitive (‘wasp
high microfilaraemia. Microfilariae may be sting’) swellings with high eosinophilia in
found in the cerebrospinal fluid of such a patient who lives in or who has visited
cases and encephalitis is presumably an endemic region is characteristic of an
caused by an allergic reaction to dead or early infection. Biopsy sections of
dying microfilariae obstructing the capillar- swellings sometimes show portions of
ies of the brain (Pinder, 1988). adults in the centre of an oedematous reac-
The relatively mild pathology usually tion. Adult worms seen moving across the
associated with this infection includes a conjunctiva can be removed and identified.
number of allergic manifestations. These Detection of antibodies is possible but is
may include pruritus, oedema and arthri- not very specific. Recently, methods for
tis, all indicative of immune-mediated detection of circulating antigens have been
reactions to the parasite. Studies in man- more successful. An ELISA using parasite-
drills have shown both Th1 and Th2 specific IgG4 can recognize specific Loa
responses during infection, although there antigens of low molecular mass (12–30
is some stage specificity (L3s preferentially kDa) and works in patients with or without
stimulated Th2, while microfilariae pro- microfilaraemia. The test can also differen-
voked both Th2 and Th1 cytokines). The tiate from other filarial infections, particu-
adverse reactions to DEC seen in loiasis larly Mansonella perstans (Akue et al.,
patients are, as in onchocerciasis patients, 1994). Antigen detection by coelectro-
associated with immunological hyper- syneresis (Co-ES) has also shown promise.
responsiveness to microfilarial antigens A PCR amplification method to detect Loa
(Wahl and Georges, 1995). DNA using a Southern blot technique is
210 Chapter 5

stated to be very sensitive and specific of infection are 30% in Calabar and 10% in
(Toure et al., 1997). Gongola State in Nigeria, 30% in
Cameroon, 19% in Bantu and 11% in pyg-
TREATMENT mies in Congo, 10–70% in the Republic of
Congo, 12% in Equatorial Guinea, 30% in
Chemotherapy. DEC kills both adults and Gabon; everywhere infection rates are
microfilariae when given at 2–6 mg kg1 higher in adults than in children.
(usually 300 mg for an adult) for 14–21 Chrysops breeds in densely shaded
days. However, side-reactions, such as streams covered with leaves, in which the
transient oedema, generalized eruptions, sandy bottom is overlaid with mud and
arthralgia, nausea, diarrhoea and fever, decaying vegetation, on which the slowly
often occur and, where there is a high developing larvae feed. In West Africa,
microfilaraemia (over 1000 mm3), more adult Chrysops are particularly common in
serious effects are possible, such as meningo- the rainy season (June–September). The
encephalitis, coma and renal damage. It is adult female flies live in the high canopy of
wise to commence treatment at a very low the forest and possibly feed on monkeys.
dosage in all patients with more than 20 They are attracted to movement below or to
microfilariae ml1, perhaps under corticos- wood smoke rising, and humans get bitten
teroid cover. most often in cleared areas, such as rubber,
Ivermectin (200 µg kg1 body weight cocoa, teak or oil-palm plantations on the
every 3 months for 2 years) decreased forest fringes, where the flies can see a
microfilarial levels by 90% and reduced break in the canopy. C. dimidiata and C.
prevalence from 30% to 10% in a trial in silacea are the principal vectors in West
Cameroon, but these slowly returned to Africa and C. distinctipennis in Central
previous levels after about 2 years. Side- Africa. Flies bite during the day and
effects of pruritus, headache, arthralgia and (except sometimes for C. silacea) do not
maybe fever are common (Chippaux et al., usually enter native houses as they are too
1992). Rare reports (1 per 10,000 persons dark inside. Chrysops ingests 10–20 µl of
treated in one trial) of encephalopathy, blood per meal; it probably feeds about
coma and renal damage have been noted. once a fortnight, since it requires one full
The use of a single dose of ivermectin (200 blood meal in each gestation period of
µg kg1 ) to reduce microfilaraemias before about 12 days.
DEC treatment has also been advocated.
Albendazole (200 mg twice daily for 21 PREVENTION AND CONTROL
days) causes microfilarial numbers to fall For individual protection, repellents and
slowly and may have an adulticidal protective clothing can be used. It has also
(macrofilaricidal) action, since immunolog- been reported that DEC kills infective larvae
ical tests become negative after a few and 5 mg kg1 daily for 3 days every month
months and eosinophilia falls. has been suggested as a prophylactic.
In the past dieldrin sucessfully con-
Surgery. When a worm is seen moving trolled larvae and pupae in forest streams
across the eye, a curved, bayonet-edge, in Cameroon, but treatment (nowadays
surgical needle can be passed under the probably with temephos) is not practical
worm and it can then be removed with a over large areas. A mass campaign with
mounted needle. The conjunctiva and DEC in Nigeria was not successful, but
worm are first anaesthetized with a few prevalence was reduced from 30% to 10%
drops of 10% novocaine. in an area of Cameroon after mass treat-
ment with ivermectin.
EPIDEMIOLOGY
The disease is restricted to equatorial forest ZOONOTIC ASPECTS
regions and prevalence is falling in some A sympatric but ecologically separate cycle
areas as forest is cleared. Recent estimates of Loa loa is also found in many species of
 The Nematodes 211

forest-dwelling primates, such as the drill Congo, Côte d’Ivoire, Equatorial Guinea,
(Papio = Mandrillus leucophaeus), the Ethiopia, Gabon, Ghana, Guinea, Liberia,
mona monkey (Cercopithecus mona) and Malawi, Mali, Nigeria, Republic of Congo,
the putty-nosed guenon (C. nictitans). Senegal, Sierra Leone, Sudan, Tanzania,
However, the microfilariae in these hosts Togo and Uganda, with limited foci in
are larger and show a nocturnal periodic- Burkina Faso, Guinea-Bissau, Niger and
ity, while the species of Chrysops acting as Yemen) and Central and South America
vectors (C. centurionis and C. langi) are (Brazil, Guatemala, southern Mexico,
also night biters. The parasite is sometimes Venezuela and possibly still Colombia and
given subspecific status as L. loa papionis, Ecuador). It is estimated that there are
with the human parasite called L. l. loa. about 17.5 million cases in Africa and
The monkey and human strains have been 140,000 in the Americas, of whom 0.8 mil-
hybridized experimentally, but it is lion have visual impairment and 0.27 mil-
unlikely that humans become infected with lion are blind.
the monkey strain, because the flies bite
almost entirely in the upper canopy; there LOCATION IN HOST
is also some evidence that humans cannot The adult worms live in the subcutaneous
be infected with the monkey strain (or sub- tissues and in long-standing infections they
species). It is possible, though, that mon- form tangled masses inside fibrous nodules
keys living near the ground sometimes (onchocercomas). Microfilarial larvae are
become infected with the human form and found in the skin (probably mostly in lym-
could then act as reservoir hosts. phatic channels in the dermis) but not usu-
ally in the blood.
A similar parasite, Loaina sp., of rabbits,
transmitted by mosquitoes, has been recov-
MORPHOLOGY
ered once from the anterior chamber of the
Both ends of the filiform adults are tapered
eye in a man in Colombia (Orihel and
but the tail terminates bluntly. The anterior
Eberhard, 1998).
end has two circles of four papillae and a
large lateral pair. The cuticle has conspicu-
ous annular thickenings (rugae), which are
Onchocerca volvulus important in identification as usually only
(Leuckart, 1893) Railliet and Henry, 1910 portions of worms can be obtained from
nodules (Fig. 98).
SYNONYMS The adult female measures 300–500 mm
Filaria volvulus Leuckart, 1893; Oncho-
0.25–0.4 mm and the male 20–40 mm

cerca caecutiens Brumpt, 1919. 0.15–0.20 mm. The vulva of the female
opens about 0.85 mm from the anterior end
DISEASE AND POPULAR NAMES and the uterus is bicornate. The male has a
Onchocerciasis or onchocercosis; river variable number of anal papillae and two
blindness, craw-craw (West Africa), blind- unequal spicules.
ing filaria. The microfilariae measure 280–330 µm

6–9 µm. They are unsheathed and have a
LOCAL NAMES tapered tail, and the head and tail are free
Amar eljur (N. Sudan), Aràn oju (Yoruba), of nuclei (Fig. 102). The head is character-
Firkaw and Ekraw (Twi), Kirci (Hausa), istically expanded and the cuticle is stri-
Sowda (Yemen), Ungoujwa ya usinyi ated. The microfilariae wander in the skin
(Sambaa). but are not usually found in the blood-
stream, except after DEC treatment; they
GEOGRAPHICAL DISTRIBUTION can survive for 6–24 months. Sometimes
Africa (including Angola, Benin, microfilariae are also present in the urine
Cameroon, Central African Republic, Chad, and sputum.
212 Chapter 5

Map 10. Distribution of Onchocerca volvulus.

20 m
Onchocerca
volvulus

Mansonella
streptocerca

Fig. 102. Microfilariae of Onchocerca volvulus and Mansonella streptocerca.

 The Nematodes 213

LIFE CYCLE in Simulium (including the cattle species

Microfilariae in the skin are ingested by bit- O. ochengi, which occurs in West Africa
ing flies of the genus Simulium (known as and has morphologically identical larvae);
black-flies or buffalo gnats. Figs 103 and they measure 560 (440–700) µm
19 µm
104). The microfilariae are probably and have a single small knob at the tail.
attracted to the site of the bite by saliva These larvae probably enter through the
injected into the puncture wound. The flies puncture wound when an infected fly bites
have a short scarifying proboscis and are another individual. They migrate to the
pool feeders on tissue fluids released by subcutaneous tissues, moult twice and
their bite. Some of the microfilariae reach sexual maturity in about 10–15
ingested by the fly leave the midgut before months. Microfilariae can first be found in
the formation of the peritrophic membrane the skin by 18 months after infection and
and penetrate the thoracic muscle cells, take 4–6 weeks to reach the skin after leav-
particularly the flight muscles; others are ing the vulva of the adult worm (about 1000
trapped in the midgut and die. After two actively leave the vulva of each female per
moults in the muscles of the fly, the first day). The adults live on average for 9–11
moult giving rise to a sausage stage, the few years and very rarely survive for more than
infective larvae move to the head and pro- 13 years, while microfilariae can live in the
boscis, complete development taking 6–12 skin for up to 2 years.
days, depending on the ambient tempera-
ture (no development occurs below 18°C). CLINICAL MANIFESTATIONS AND PATHOGENESIS
For studies of transmission rates, the infec- Most of the severe manifestations are due
tive third-stage larvae must be differenti- to the presence of the microfilariae; the
ated from other animal filarial larvae found adults are of secondary importance (contrast

Fig. 103. Diagram of head of Simulium feeding on human skin with infective larvae of O. volvulus
emerging from the labium (it is probable that they usually emerge from the posterior surface of the labium
or from the hypopharynx).
214 Chapter 5

pelvic region, knees and lateral chest and

spine, while in the Americas (except for
Venezuela) the nodules are more com-
monly seen in the upper part of the body,
including the head.
Death of adult worms deep in the tis-
sues can lead to the formation of an abscess
and nodules on the scalp may erode the
bone.
As in many helminth infections, there is
a blood eosinophilia, in this case of
10–75% (usually with 700–1500 eosino-
phils mm3 blood).
The majority of lightly infected indige-
nous individuals living in an endemic area
show few or no signs, although at some
time many will have pruritus, with skin
lesions leading to the characteristic presby-
dermia. In the early stages, or in lightly
infected persons, the presence of the adult
worms cannot be detected, but the micro-
Fig. 104. The black-fly Simulium damnosum s.l. filariae usually cause pruritus with a per-
feeding on human. sistent and intensely itchy rash of the skin
in their vicinity (filarial itch), often con-
infections with the lymphatic filariae). In fined to one anatomical quarter of the body.
long-standing infections the adults are The rash consists of many raised papules,
often found in characteristic non-tender 1–3 mm in diameter, and often becomes
nodules, known as onchocercomata, which secondarily infected following scratching
can be felt and often seen, especially over (‘craw-craw’ or ‘gale filarienne’). There is
bony prominences (Fig. 105). There may be usually lymphadenopathy in the groin or
a single nodule or many present. In Africa axilla of the affected side, sometimes
nodules are usually found around the accompanied by aches and pains. The

Fig. 105. Section of subcutaneous nodule with adult female and microfilariae (one arrowed) in the fibrous
connective tissues.
 The Nematodes 215

onchodermatitis can lead in months or shins, is common and can resemble leprosy
years to a secondary stage of thickening (Fig. 106). Skin changes often mimic those
due to intradermal oedema (often giving a seen in vitamin A deficiency. Progressive
‘peau d’orange’ effect) and to pachydermia skin lesions can be roughly divided into
(lichenification or crocodile skin). The loss stages: acute and then chronic papular
of elastic fibres in the skin can lead to onchodermatitis (Fig. 107); lichenified
‘hanging groin’, pendulous sacs containing onchodermatitis; atrophy and depigmenta-
inguinal or femoral glands (Fig. 106) or tion (Murdoch et al., 1993).
hernias, which are particularly found in In Central America, patients, particu-
males in East Africa, and probably to the larly children, may have reddish-mauve
leonine facies encountered in Guatemala. lesions on the face, known as erisipela de
Elephantiasis of the scrotum can also occur la costa. The condition of ‘sowda’ is found
in males but, in contrast to that caused by in Yemen and in East and West Africa, in
Bancroftian filariasis, there is not usually which there are very few microfilariae in
an associated hydrocele. the skin, but the skin of a localized area,
The last stage is characterized by atro- usually one or both legs, is itchy, papular
phy of the skin, with loss of elasticity, giv- and pustular, hyperpigmented and thick-
ing a striking prematurely aged appearance ened, with accompanying groin lymph-
and a paper-thin skin. Mottled depigmenta- adenopathy, distinguishable clinically from
tion (‘leopard skin’), particularly of the ‘hanging groin’. This hyperreactive oncho-
dermatitis, with frequent acute exacerba-
tions, is also encountered in visitors or
new residents to an endemic region.
The most important consequence of

Fig. 106. A case of ‘hanging groin’ with loss of

elasticity in the skin. There is also vitiligo of the Fig. 107. Section of skin with marked dyskeratitis
shins (‘leopard skin’). and presence of microfilariae of O. volvulus.
216 Chapter 5

infection is blindness, which has led to the phobia and watering, with chronic con-
popular name for the disease of river blind- junctivitis. This can be followed by a scle-
ness. Blindness occurs more commonly in rosing keratitis, usually starting in the
savannah areas of Africa and America than lower half of the cornea, with an ‘apron’
in forest zones, where it is seldom over 1%. coming in from the sides and below (Plate
In some savannah areas of Africa and 29). Microfilariae may also be seen in the
Guatemala, over 10% of the population may anterior chamber of the eye and their death
be completely blind and another 20% have may produce iridocyclitis and uveitis, with
impaired vision on account of onchocercia- loss of the pigment ruff and a distorted
sis. In endemic savannah areas the sight of a pupil. Secondary glaucoma and cataract
small boy leading a band of blind men to may follow.
their work in the fields is not uncommon. A 2. The aetiology of the posterior-segment
few years ago there were reckoned to be lesions is not so clear but they are associ-
about 70,000 adults with ‘economic blind- ated with heavy O. volvulus infection in
ness’ in the upper Volta basin. both savannah and forest areas. The
The eye lesions can be separated into ‘Ridley–Hissette’ fundus is a well-defined
two types. patch, usually bilateral, in which all retinal
elements have vanished except for the reti-
1. Anterior lesions are caused by micro- nal vessels and in which the choroidal ves-
filariae reaching the cornea from the skin of sels may show marked sclerosis (Plate 30).
the face through the conjunctiva. By the Optical atrophy is of the postneuritic type,
use of the slit lamp, live microfilariae may with dense sheathing of the retinal vessels.
sometimes be seen in the cornea, usually Active optic neuritis appears to be com-
just below Bowman’s membrane, without moner than once thought (WHO, 1995) and
causing any reaction. When microfilariae lasts for several weeks to over 1 year, with
die they first cause a punctate keratitis scarring and pigment disturbance at the
with numerous opacities, with a diameter disc margin. It has a reported prevalence of
less than 0.5 mm, around each dead micro- 1–4% in hyperendemic communities in
filaria (Fig. 108). The fluffy opacities are Cameroon and 6–9% in the guinea savan-
often symptomless, but there may be photo- nah of northern Nigeria. Complete blind-

Fig. 108. Snowflake opacities in onchocercal keratitis (slit-lamp view and section).
 The Nematodes 217

ness may result or tubular vision may mectin, carries the risk of adverse reac-
remain. Onchocerciasis can cause severe tions. In part, these follow increased pro-
reduction in peripheral visual fields, so duction of proinflammatory mediators,
that functional blindness might be much such as IL-6, tumour necrosis factor-α
higher than the standard ‘below 3/60 visual (TNF-α) and C-reactive protein, but there
acuity in the better eye’ definition shows. are also changes in T cells and eosinophils.
A new field test, the Wu–Jones computer- Major histocompatibility complex
ized visual function test, should make it (MHC)-linked influences on patterns of
easier to obtain accurate and reproducible infection and pathology have been estab-
measurements of paracentral visual fields, lished and the interesting idea proposed
as well as acuity. that possession of one human leucocyte
antigen (HLA) locus (DQB1*0501), associ-
IMMUNOLOGY OF ONCHOCERCIASIS ated with protection against severe malaria,
There are some overall similarities between may carry the cost of reduced resistance to
the immunobiology of onchocerciasis and onchocerciasis – an example of a trade-off
lymphatic filariasis, but some important between two endemic diseases in West
differences associated with the differences Africa (Meyer and Kremsner, 1996).
in parasite location.
As with lymphatic filariasis, infected DIAGNOSIS
individuals show a spectrum of pathologi-
cal responses and these may reflect genetic Clinical. The acute pruritic onchocercal
as well as environmental influences. rash has to be distinguished from those
Individuals with high microfilarial loads caused by scabies, insect bites, prickly
may show a degree of both specific and heat, contact dermatitis, hypersensitivity
non-specific immune unresponsiveness reactions, post-traumatic or inflammatory
and low-grade skin inflammatory changes. depigmentation, tuberculoid leprosy, dermato-
A small percentage of patients show hyper- mycoses, trepanonemoses and the similar
reactive responses, with severe localized parasite Mansonella streptocerca (see
skin changes typical of sowda. When tested p. 223). The presence of the typical nod-
against worm antigens, patients with ules measuring 0.5–10 cm in diameter,
hyperreactive onchocerciasis showed evi- from which portions of adult worms may
dence of a Th2 bias in their antibody be obtained on excision, allows a positive
responses – for example, making greater diagnosis to be made if no microfilariae can
IgE and IgG1 and lower IgG4 and IgM be found in skin snips. Ultrasound can also
responses than those with generalized be used to confirm whether a nodule is
onchocerciasis. These differences in onchocercal. The presence of nodules in
classes of antibody associated with differ- more than 20% of young males over the
ences in pathology may also be relevant to age of 20 in a savannah area is estimated to
protection – IgE and IgG1 participating in give a sensitivity of 94% and specificity of
ADCC-mediated killing, while IgG4 and 50% (Whitworth and Gemade, 1999) in
IgM antibodies may block effector activity. epidemiological surveys, while skin depig-
Th1-biased responses have been implicated mentation might give a better rapid, but
in the development of immunity, although rough, method in forest regions. In chronic
both infected patients and endemic nor- infections, skin and eye changes are usu-
mals appear to make mixed Th1/Th2 ally pathognomic.
responses. Production of both Th1 and Th2 The Mazzotti or DEC provocation test is
cytokines in putatively immune individu- still sometimes used, in which 50 mg of
als may allow the involvement of both DEC is given orally and, hopefully short-
macrophages and eosinophils in ADCC- lived, itching, rash and lymphadenitis
mediated killing of infective L3 stages. occur 1–24 h later. A much better recent
Chemotherapeutic treatment of oncho- modification uses a DEC-impregnated
cerciasis with drugs, such as DEC and iver- patch and results in a small localized rash.
218 Chapter 5

Parasitological. Microfilariae may some- for recognizing antigens in tears for ocular
times be seen in the cornea and anterior onchocerciasis, in dermal fluid for skin
chamber of the eye and, in heavy infec- microfilariae and in urine for microfilariae
tions, in urine and blood. (Ngu et al., 1998).
The most widely used diagnostic proce-
dure in onchocerciasis is the skin snip. TREATMENT
After cleaning with spirit, a needle is used
to raise a small cone of skin, which is then Surgery. Nodulectomy under local anaes-
cut off under the needle point with a sharp thetic (2% lignocaine) has been widely
razor-blade or fine pair of scissors (the used in Central America and has been
Walser or Holth corneosceral punch is used claimed to markedly reduce the number of
to give a standard-sized sample of skin and microfilariae in the skin and more impor-
enables quantitative microfilarial counts to tantly around the eyes (Plate 31). Results
be made). It is important to take the snip have not been so striking in Africa, where
from an area of maximum microfilarial nodules are often impalpable or the larger
density – from above the iliac crest in ones are merely fibrous reactions around
Africa, from the trapezius in Guatemala dead and dying worms.
and from the lower calf in Yemen. The
bloodless skin snip, measuring about 3 mm Chemotherapy. Ivermectin (Mectizan – a
in diameter and 0.1–1 mm deep (preferably macrocyclic lactone) is the only drug in
taken in the afternoon), is placed in a drop widespread use and has completely
of physiological saline or water and, after replaced DEC, which is no longer advo-
gentle teasing, is allowed to stand for 30 cated. It is given as a single oral dose of
min before being examined under the 150 µg kg1 of body weight once or twice a
microscope. Microfilariae show active year. It should not be given in cases of
thrashing movements and in West Africa severe illness. Side-effects are very rarely
must be separated from those of M. strepto- severe but can include itching and rashes,
cerca, also found in the skin. Microfilariae fever and glandular pain (severe allergic
of the latter have a shivering mode of activ- reactions used to be common after treat-
ity and in stained smears have a thinner ment with DEC, which kills microfilariae
shape, small caudal space and non-over- more rapidly). Ivermectin appears to have
lapping of the anterior nuclei (Fig. 102). little effect against adult female worms
Recently, skin scarification is being widely when given at the standard dose but does
used as an alternative to skin snips. prevent the release of microfilariae from
the uterus for over 6 months. Moxidectin, a
Immunological. Superficial skin scrapings, promising long-persisting relation of iver-
which can be dried on microscope slides, mectin, is now undergoing clinical trials,
can also be used in a PCR-based assay to as is long-term treatment with antibiotics,
show the presence of onchocercal DNA probably directed against Wohlbachia (see
(Toe et al., 1998), but is still expensive. p. 197. (Townson et al., 2000).
This test can also be used to specifically Intravenous suramin (Antrypol or Bayer
identify infections in black-flies and to dif- 205) is the only drug which has a clear
ferentiate between savannah and forest macrofilaricidal effect, but it is toxic and
strains of parasite (WHO, 1995). should only be given rarely and under
Most immunological tests are more use- close medical supervision in hospital
ful for epidemiological studies than for (WHO, 1995).
individual diagnosis. ELISAs using a cock-
tail of recombinant antigens (e.g. MBP/10, EPIDEMIOLOGY
11 and 29) have been tested in many areas Persons involved in agriculture and other
with different levels of endemicity (WHO, outdoor activities, such as fishing, are at
1995; Bradley and Unnasch, 1996; Bradley the highest risk, and in some parts of West
et al., 1998), and tests have been devised Africa in the past onchocerciasis has ren-
 The Nematodes 219

dered whole areas bordering rivers unin- in Africa and Central America are probably
habitable. caused by differences in the biting habits of
In Africa, the most important vectors are the species of black-flies.
black-flies belonging to the Simulium Although all species of Simulium are
damnosum complex, small (4 mm long) confined to running water for breeding,
nematocerous flies, which breed on vegeta- adult flies have been found many kilo-
tion and on rocks in a great variety of river metres from water and are probably carried
systems, including the largest rivers, such by winds. In savannah areas of West Africa,
as the Niger, Volta and Nile, as well as flies have a shorter flight range than those
small streams, provided that they are well in forest areas, so that infections tend to be
oxygenated. Members of the S. damnosum heavier but more localized.
subcomplex acting as vectors (S. damno- The epidemiology of onchocerciasis dif-
sum sensu stricto (s.s.), S. sirbanum, S. fers over its range because different disease
rasyani and possibly S. dieguerense) are patterns are associated with different
found in savannah areas, while those of the strains of parasite, with differences in the
S. sanctipauli (S. sanctipauli s.s., S. abundance, anthropophilic nature and vec-
soubrense, S. leonense and S. konkourense) tor capacity of vectors and with differences
and S. squamosum (S. squamosum s.s., S. in the responses of the human host to the
yahense, S. mengense and S. kilibanum) parasite. Because of strain differences
subcomplexes are mostly found in forest between parasites in Africa, microfilariae of
areas. Most of these sibling species are mor- savannah forms will not infect forest flies
phologically identical and can only be dif- and vice versa; also, anterior eye lesions are
ferentiated by the banding patterns of the more common in savannah than in forest
larval chromosomes; many other areas in infections of comparable severity.
cytospecies not known to act as vectors
have also been described. Members of the PREVENTION AND CONTROL
S. neavei complex (S. neavei s.s., S. woodi Control campaigns in the past have con-
and S. ethiopense) are local vectors in east- centrated on the vectors. The disease was
ern Congo Republic (Zaire), Tanzania and eradicated from Kenya and from large areas
Ethiopia; all members breed in small high- of Uganda in the 1950s by using the insec-
land streams and have an obligatory associ- ticide (dichlorodiphenyltrichloroethane:
ation with freshwater crabs or other DDT). In Kenya the Simulium species
crustaceans. S. albivirgulatum is a local responsible (S. neavei) has a short flight
vector in central Congo Republic. range and lived on land crabs which inhab-
In the Americas, members of the S. itated water-filled holes, and these were
ochraceum complex are high-biting flies easy to treat. In Uganda infection was con-
that are the principal and efficient vectors fined to the Nile, which could be treated.
in highland foci in Mexico and Guatemala. The largest control campaign is that of
They breed in small rivers, streams and the Onchocerciasis Control Programme
small trickles of water flowing through (OCP) (funded principally by the World
highly wooded volcanic slopes of coffee- Bank, Food and Agriculture Organization
growing areas between 1000 and 2000 m (FAO), United Nations Development
above sea level. S. callidum and S. metal- Programme (UNDP) and WHO), which
licum sensu lato (s.l.) are secondary vec- commenced in 1974, dedicated to control-
tors; the latter is low-biting and mainly ling the disease in savannah regions of
zoophilic and is also found in Venezuela. seven West African countries of the Volta
Various other species (S. exiguum s.l., S. River basin, comprising a land area of 0.7
guianense, S, incrustatum, S. oyapockense million km2 (Benin, Burkina Faso, Côte
s.l., S. quadrivittatum and probably S. lim- d’Ivoire, Ghana, Mali, Niger and Togo). In
batum) act as vectors in South America some infected villages in the control area,
(WHO, 1995). more than 10% of the infected population
Variations in the localization of nodules was blind and as many as 30% had
220 Chapter 5

irreversible eye lesions. At first, control 2. 125,000–200,000 adults prevented from

was entirely by the addition of the larvi- becoming infected, with 1.5 million hav-
cide temephos (Abate) to rivers and ing lost their infection.
streams, mostly from helicopters and fixed- 3. 25 million ha that can now be used for
wing aircraft (Plate 32). In 1980 insecticide agriculture – enough to support 17 million
resistance was encountered and the bacter- people.
ial agent Bacillus thuringiensis H14 4. Infection no longer being a problem in
replaced it for a while until black-fly popu- Burkina Faso, Niger, northern Benin, Côte
lations became susceptible again. By 1986 d’Ivoire, Ghana, Togo or south-eastern
vector control had interrupted transmis- Mali.
sion almost completely in 90% of the area, 5. An estimated 20% return on the invest-
with blindness reduced by 40%, while the ment in the programme.
incidence of infection in children was
In Central America insecticidal control
reduced by 99%. However, in the remain-
has not been successful because of the dif-
ing 10% western area, reinvasion by flies
ficulties in treating all the small mountain
borne on the monsoon winds occurred, so
streams in which Simulium larvae breed.
the control area was extended to a further
However, mass treatment campaigns with
four countries (Guinea, Guinea-Bissau,
Mectizan are proving very effective in both
Senegal and Sierra Leone). Since 1987 the
Central and South America.
microfilaricide ivermectin (Mectizan) has
been donated by the manufacturers and
ZOONOTIC ASPECTS
this has augmented the use of insecticides.
Probably none, although a natural infection
To date, over 20 million people have
has been found in a gorilla, and chim-
received at least one dose and some up to
panzees can be experimentally infected (an
nine doses. The drug is given at 150 µm
infection reported from a spider monkey
kg1 once or twice a year, as it does not kill
appears to have been mistaken). Other
adult worms. With the use of both regular
species of Onchocerca are found in a wide
Mectizan and larviciding, treatment needs
range of herbivores (O. gutturosa in the
to be continued for about 12 years to
nuchal cartilage, O. lienalis in the gastro-
reduce infection by 99% (this represents
splenic region and O. gibsoni in the sub-
the average lifespan of adult worms).
cutaneous tissues of cattle and O. cervicalis
The campaign currently costs about $27
and O. reticulata in the ligaments of horses
million per annum but is due to end in
occur in many parts of the world and O.
2002, when responsibility will be handed
armillata parasitizes the aorta of cattle in
over to the African Programme for
Africa and Asia). The horse species are
Onchocerciasis (APOC). The maintenance
transmitted by species of Culicoides, but
phase of control will be almost entirely by
the cattle species are transmitted by
repeated community-based administration
Simulium species and so could be con-
of Mectizan (Remme, 1995) and a commu-
fused with O. volvulus in the vector. This
nity-directed treatment programme is
is most important for a subcutaneous cattle
already under way in 19 African countries,
species in West Africa, O. ochengi, as the
which will become part of primary health
infective larvae are almost identical to
care. It has been realized recently that the
those of the human species and are found
severe skin lesions, which also occur in the
in the same species of black-fly (differentia-
forest zones, can be very debilitating and
tion requires DNA probes and can be
treatment will be much more widespread
carried out on large pooled samples of
than just the OCP area.
flies).
The benefits of the OCP to date can be
A few amicrofilaraemic infections, pre-
enumerated as below (Samba, 1994).
sumably zoonotic from cattle or horse
1. 10 million children prevented from species, have been reported from Canada,
becoming infected. Japan, Russia, Switzerland and the USA.
 The Nematodes 221

Mansonella perstans were all found to belong the same genus

(Manson, 1891) Orihel and Eberhard, 1982 (Muller, 1987). M. perstans and M. strepto-
cerca are included in the subgenus
Esslingeria while M. ozzardi is in the sub-
SYNONYMS
genus Mansonella, i.e. the full names are M.
Filaria sanguinis hominis minor, F. s. h.
(Esslingeria) perstans, M. (Esslingeria)
perstans and F. perstans Manson, 1891;
streptocerca and M. (Mansonella) ozzardi.
Acanthocheilonema perstans Railliet,
Henry and Langeron, 1912; Dipetalonema
perstans Yorke and Maplestone, 1926; DISEASE
Tetrapetalonema perstans Chabaud and Perstans filariasis or filariosis, mansonellia-
Bain, 1976. This species and M. strepto- sis or mansonellosis perstans.
cerca (below) have had many rather confus-
ing name changes. For many years they GEOGRAPHICAL DISTRIBUTION
were included in the very large and hetero- West and Central Africa, including Benin,
geneous genus Dipetalonema and were Cameroon, Congo, Republic of Congo,
split off as Tetrapetalonema just before Equatorial Guinea, Ethiopia, Gabon, Ghana,
adults of Mansonella ozzardi were recov- Guinea, Guinea-Bissau, Mali, Mozambique,
ered from experimental animals, when they Nigeria, Sierra Leone, Togo, western

Map 11. Distribution of Mansonella perstans.

222 Chapter 5

Uganda, Zimbabwe and limited areas of genus Culicoides, which are pool feeders.
South America (Colombia, Guyana and The larvae enter the thoracic muscles, moult
Venezuela). twice and reach the infective third stage by 9
days, when they migrate to the head. They
LOCATION IN HOST exit from the labium of the midge while it is
Adults inhabit the body cavities, mesen- feeding. The parasites take a few months to
teric, retroperitoneal and perirenal tisues; become mature, moulting twice more, in the
unsheathed microfilariae can be found in human body.
the peripheral bloodstream at any time.
CLINICAL MANIFESTATIONS AND PATHOGENESIS
MORPHOLOGY There are often none, but infection has
The adult females measure 70–80 mm
been associated with allergic symptoms,
0.12 mm, males 35–45 mm
0.06 mm; such as itching, pruritus, joint pains,
both sexes have a smooth cuticle and a enlarged lymph glands and vague abdomi-
ventrally curved tail, which has a trilobed nal symptoms, accompanied by high
appearance (Baird et al., 1987). The tail of eosinophilia.
the male has four pairs of preanal and one
pair of postanal papillae and there are two, DIAGNOSIS
very unequal, rodlike spicules. The micro- By identification of the microfilariae in
filariae in the blood are unsheathed and stained blood smears. More than ten micro-
measure 200 (190–240) µm
4.5 µm (they filariae per millilitre may be present, often
look appreciably smaller and thinner than together with those of L. loa and W. ban-
the sheathed microfilariae of Wuchereria, crofti. Differences in the morphology of
Brugia or Loa); they assume graceful curves microfilariae in various African countries
when fixed and stained. The tail ends have resulted in the name M. semiclarum
bluntly and contains nuclei to the tip (Figs being given to a longer microfilaria (198 µm
89 and 109).
5.2 µm in thick films, 221 µm
5.0 µm
in thin) found in the blood of a man in
LIFE CYCLE Congo Republic (Dujardin et al., 1982).
There is no marked periodicity but microfi-
lariae are slightly more numerous in the TREATMENT
peripheral circulation at night. The microfi- DEC has no effect. Albendazole and
lariae are ingested in a blood meal by small mebendazole given for 10 days have given
(2 mm) female ceratopogonid midges of the equivocal results. Ivermectin appears to

Fig. 109. Microfilariae of Loa loa and Mansonella perstans in same blood smear (stained in Giemsa so
that sheath of Loa has not stained).
 The Nematodes 223

reduce microfilaraemia for a period but Mansonella streptocerca

probably has no long-term effect. (Macfie and Corson, 1922) Orihel and
Eberhard, 1982
EPIDEMIOLOGY
Recent reports of infection rates are south- SYNONYMS
ern Cameroon 15–27%, southern Congo Agamofilaria streptocerca Macfie and
16% in Bantu and 81% in pygmies, Congo Corson, 1922; Acanthocheilonema
Republic (Zaire) 42%, Equatorial Guinea streptocerca Faust, 1949; Dipetalonema
52%, Gabon 25–80%, Abia and Imo States streptocerca Peel and Chardome, 1946;
29%, Bauchi State 1.4%, Gongola State Tetrapetalonema streptocerca Chabaud and
11%, Jos Plateau 13% (all in Nigeria). Bain, 1976.
In Africa the vector species are
Culicoides grahami and C. milnei. These DISEASE
have a short flight range of about 100 m. Streptocercal filariasis or filariosis; strepto-
Eggs are laid in mud or wet soil in batches cerciasis or streptocercosis.
or in water in banana stumps.
There is usually only one larva per GEOGRAPHICAL DISTRIBUTION
infected midge, but midges are numerous Confined to the rainforest areas of Benin,
and a high percentage may be infected. Cameroon, Central African Republic, Congo,
This results in a high infection rate in the Congo Republic, Côte d’Ivoire, Equatorial
human population, but almost all infec- Guinea, Gabon, Ghana, Nigeria, Togo and
tions are light. western Uganda.

ZOONOTIC ASPECTS
Possibly identical microfilariae are found
in chimpanzees and gorillas in Central
Africa and similar ones in New World
monkeys. Recently, new species have been
reported from African primates.
Meningonema peruzzii has been described
from the leptomeninges of Cercopithecus
spp. in Zimbabwe. The microfilariae are
almost identical to those of M. perstans but
have an indistinct sheath that does not
stain with Giemsa. Recently, a fourth-stage
female larva of Meningonema was recov-
ered from the cerebrospinal fluid of a
patient in Cameroon (Boussinesq et al.,
1995). It is possible that the nervous mani-
festations reported from humans in
Rhodesia (now Zimbabwe), with the pres-
ence of microfilariae in the spinal fluid,
which led Patrick Manson to postulate that
M. perstans was the cause of sleeping sick-
ness, was due to this species.
Microfilariae found in the blood of a
patient in Thailand may be of Mansonella
digitatum (Sucharit, 1988). Map 12. Distribution of Mansonella streptocerca.
224 Chapter 5

LOCATION IN HOST CLINICAL MANIFESTATIONS AND PATHOGENESIS

The adults are tightly coiled in the subcu- Used to be regarded as non-pathogenic, but
taneous tissues of the dermis, microfilariae it is responsible for mild pruritus, with
occur in the skin (Fig. 110). unpigmented spots (in about 60% of cases),
papules and oedema, and thickening of the
MORPHOLOGY skin has been reported. Infection is often
Adult worms are very thin and females mistaken for onchocerciasis and sometimes
measure 27 mm
0.08 mm. Males have leprosy.
been recovered only once from patients in
the Congo Republic in the dermal collagen DIAGNOSIS
(Meyers et al., 1977) and measured 17 mm By finding the microfilariae in skin snips

0.05 mm. Microfilariae are unsheathed taken in the shoulder region. Living speci-
and measure 180–240 µm
3–4 µm. The mens in saline can be differentiated from
tail is tapered and curved to form a hook; it microfilariae of Onchocerca by their shiv-
ends bluntly and has a quadrate nucleus to ering mode of activity in contrast to the
within 1 µm of its bifid end. The cuticle is active twisting of the latter. In stained
striated. smears they are thinner with a hooked and
bluntly rounded tail, small caudal space
LIFE CYCLE and non-overlapping anterior nuclei (Figs.
Complete development has been observed 89 and 102).
experimentally in the midge Culicoides gra-
hami. Ingested microfilariae moved rapidly TREATMENT
to the thoracic muscles and moulted twice, DEC (2–6 mg kg1 body weight day1 for 21
and infective third-stage larvae, measuring days) kills microfilariae and probably
574 µm, were seen in the mouth-parts on the adults but can cause unpleasant itching.
8th day. Natural infection rates of up to 1% Ivermectin (150 µg kg1) effectively removes
have been found in these insects. microfilariae for long periods.

Fig. 110. Section of subcutaneous tissues with adult M. streptocerca above and microfilariae below
(compare with Figs 105 and 107 showing microfilariae of O. volvulus).
 The Nematodes 225

EPIDEMIOLOGY French Guiana, Guyana, Surinam and

Infection rates were 36% in children in Venezuela; Caribbean, including Desirade
western Uganda, 0.4% in Nigeria (Bauchi Island, Dominica, Guadeloupe, Haiti,
State). M. streptocerca is transmitted by Martinique, St Lucia, St Vincent and
Culicoides grahami and possibly by C. mil- Trinidad (see Map 9, p. 203).
nei, so the epidemiology is similar to that
of M. perstans. LOCATION IN HOST
Adults inhabit the abdominal mesenteries
ZOONOTIC ASPECTS and subperitoneal tissues, microfilariae cir-
Adults have been found in chimpanzees culate in the blood.
and gorillas in Congo Republic, but it is
unlikely that they act as reservoir hosts. MORPHOLOGY
Adult females from monkeys measure
Sheathless microfilariae of Mansonella rod-
49 mm
0.15 mm, with a smooth cuticle
haini, measuring 300 µm
2.2 µm, have
and two lappets at the caudal extemity,
been recovered from skin snips taken from
while males measure 26 mm
0.07 mm.
both sexes in Gabon. It was impossible to
The unsheathed microfilariae in the
determine pathogenicity since most also
blood are similar in size to those of M. per-
had M. streptocerca and M. perstans
stans, measuring 175–240 µm
4.5 µm.
(Richard-Lenoble et al., 1988). It is a natural
They differ in that the posterior end of the
parasite of chimpanzees in Congo Republic.
body is free of nuclei for 3–4 µm, giving
the appearance of a sharp tail (Fig. 111).
Mansonella ozzardi
(Manson, 1897) Faust, 1929 LIFE CYCLE
The microfilariae in the blood show no
SYNONYMS periodicity.
Filaria demarquayi Manson, 1897; F. The intermediate host in St Vincent is
ozzardi Manson, 1897; F. tucumana Biglieri the minute (1 mm) female midge Culicoides
and Araoz, 1917. furens, in Trinidad C. phlebotomus and
experimentally in Argentina C. paraensis.
DISEASE However, in Brazil the vector is a member
Mansonelliasis or mansonellosis ozzardi, of the black-fly Simulium amazonicum
Ozzard’s filariasis or filariosis. complex. In this area microfilariae are also
found in the skin as well as the blood.
GEOGRAPHICAL DISTRIBUTION The microfilariae penetrate the stomach
Central America, including Mexico wall of the insect and develop in the tho-
(Yucatán) and Panama; South America, racic muscles, moulting twice. Infective,
including northern Argentina, Bolivia, third-stage larvae migrate to the head and
Brazil, Colombia, Dominican Republic, proboscis by 8 days. Nothing is known of the

Fig. 111. Microfilaria of M. ozzardi.

226 Chapter 5

development in humans, but it has recently 1. Subgenus Dirofilaria: Dirofilaria (Diro-

been followed experimentally in patas mon- filaria) immitis, D. (D.) magalhaesi, D. (D.)
keys, in which patency took 163 days. louisianensis and D. (D.) spectans. These
parasites have been recovered from the
CLINICAL MANIFESTATIONS AND PATHOGENESIS lungs, heart and blood-vessels and are rela-
The majority of cases appear to be symp- tively thin (diameter 0.1 mm) and imma-
tomless, but allergic reactions have been ture with a smooth cuticle.
reported, particularly from Brazil. These 2. Subgenus Nochtiella: Dirofilaria (Noch-
include pruritus, joint pains, headache, tiella) repens, D. (N.) tenuis (D. (N.) con-
hypopigmented blotchy papules and junctivae is a synonym of either of these),
enlarged and painful inguinal lymph nodes, D. (N.) striata, D. (N.) ursi. Members of this
accompanied by a blood eosinophilia. group from humans have also been recov-
ered from the subcutaneous or conjunctival
DIAGNOSIS tissues. They are usually stouter (0.2–
By finding the characteristic microfilariae 0.5 mm in diameter) than those in the first
in stained blood smears. group and have longitudinal ridges in the
cuticle with transverse striations.
TREATMENT
DEC (2–6 mg kg1 body weight for 21 days) Dirofilaria immitis (Leidy, 1856). This is an
kills microfilariae for a period. Ivermectin important and common parasite of the right
reduces microfilarial numbers greatly, but ventricle and pulmonary artery of the dog in
most warm parts of the world and is trans-
they often return after a few years. Side-
mitted by both anopheline and culicine
effects are common but minor.
mosquitoes. Immature or unfertilized adult
worms have been found about 230 times in
EPIDEMIOLOGY AND ZOONOTIC ASPECTS
lung abscesses or in the pulmonary artery of
Infection is most common in Amerindians
humans, but microfilariae are not present in
living in rainforest areas. In Brazil it is
the peripheral blood. They usually cause a
found particularly in outdoor workers of
pulmonary infarct, which is seen on X-ray
both sexes but is rare in children under 8.
and often mistakenly removed as a neo-
Infection rates of over 50% in the
plasm. In sections the parasite can be recog-
Roraima area of Brazil, 81–94% over the
nized by the smooth laminated cuticle, long
border in Venezuela and 22% in Trinidad
muscle cells, broad lateral cords and, in
have recently been reported. Older figures
mature females, by the typical filarial twin
are 45% in Panama, 96% in Amerindians
uteri (Fig. 112). In the dog this is a larger
in forests of southern Colombia, 85% in
filaria than D. repens (250–300 mm
1 mm
Yucatán (Mexico) and 4–15% in Surinam.
as against 100–170 mm
0.4–0.7 mm), but
Little is known of the epidemiology of
specimens from humans are usually very
this parasite in the Amazon basin.
immature. One case of a gravid female of
Although no reservoir host is known, mon-
what was probably D. immitis was reported
keys can be experimentally infected.
from the lung of a man who had lymphoid
leukaemia (Beaver et al., 1990).
Accidental filarial infections
Dirofilaria repens Railliet and Henry, 1911.
DIROFILARIA This species is a natural parasite of the
Those members of the genus Dirofilaria subcutaneous tissues of dogs in Europe,
that have been found as parasites of Asia and possibly Africa and is transmitted
humans are all natural parasites of dogs or, by mosquitoes, particularly Aedes (proba-
more rarely, primates in tropical and sub- bly A. albopictus in Italy). It has been
tropical areas of the world. They can be reported about 400 times from 30 coun-
divided into two groups, depending on tries, most (168) from Italy (Muro et al.,
their structure and on their location in the 1999). There are also a few cases reported
body: each year from Spain, France and Russia
 The Nematodes 227

Fig. 112. Section of lung with immature Dirofilaria immitis in a branch of the pulmonary artery. A
pulmonary infarct may follow the death of the worm.

(Pampiglione et al., 1995). D. repens in Dirofilaria tenuis Chandler, 1942. About 40

humans produces a painful migratory sub- human cases have been reported from the
cutaneous nodule, which at biopsy shows a USA, mostly from women in Florida. The
threadlike parasite (0.3 mm in diameter) in natural host is the racoon and 14–45% were
the centre of an inflammatory reaction with found to be infected in Florida, with mos-
many tissue eosinophils (Fig. 113). Many quito intermediate hosts. It causes subcuta-
cases are under the conjunctiva or around neous lesions, often around or in the eye,
the eye, probably because these are most similar to those of D. repens (Beaver, 1987).
likely to be diagnosed. A technique using
PCR amplification of DNA can differentiate Dirofilaria striata (Molin, 1858). This
between D. immitis and D. repens infec- species is a natural parasite of various wild
tions (Faria et al., 1996). cats and has been found a few times in the

Fig. 113. Section of breast from a woman with adult of D. repens, which has evoked a granulomatous
reaction. Note ridges on the cuticle of the worm.
228 Chapter 5

subcutaneous tissues and eye of humans in south of the Sahara (Benin, Burkina Faso,
the USA. It is transmitted by mosquitoes. Central African Republic, C ôte d’Ivoire,
Ghana, Mali, Mauritania, Niger, Nigeria,
Dirofilaria ursi Yamaguti, 1941. This is a Sudan, Togo and Uganda). There are also
natural parasite of the bear and subcuta- very small foci in Cameroon and Ethiopia
neous lesions have been found very rarely and possibly still in Chad, Kenya and
in humans in Canada and the USA. It is Senegal. Infection has been officially elimi-
transmitted by the black-fly Simulium. nated from the formerly endemic areas in
India (1999) and Pakistan (1994) in the last
few years and the disease has probably
Superfamily Dracunculoidea now vanished from Saudi Arabia and
Yemen.
Dracunculus medinensis
(Linnaeus, 1758) Gallandant, 1773 LOCATION IN HOST
Adult females emerge from the subcuta-
SYNONYMS neous tissues, usually of the foot or lower
Gordius medinensis Linnaeus, 1758; limbs but sometimes from any part of the
Filaria medinensis L.; Fuellebornius medi- body.
nensis Leiper, 1926.
MORPHOLOGY
DISEASE AND COMMON NAMES The mature female measures 500–800 mm

Dracunculiasis or dracunculosis, dracontia- 1.0–2.0 mm. The mouth has a triangular oval
sis; guinea or medina worm, le dragonneu, opening surrounded by a quadrangular
filaire de Medine. cuticularized plate, with an internal circle of
four double papillae. The vulva opens
LOCAL NAMES halfway down the body but is non-func-
Farentit (Arabic), Mfa (Fanti and Twi), tional in the mature worm. The uterus has
Kurkunu (Hausa), Naru (Hindi), Reshteh or an anterior and a posterior branch and is
Piyook (Persian), Rishta (Uzbek), Orok al filled with 1–3 million embryos; it fills the
Mai (Yemen), Sobiya (Yoruba). entire body cavity (pseudocoel), the gut
being entirely flattened.
GEOGRAPHICAL DISTRIBUTION Males recovered from experimental
Dracunculus is now found only in the infections in animals measure 15–40 mm
countries of West and Central Africa just
0.4 mm (Fig. 114). The tail has 4 (3–6)

Fig. 114. Adult female and smaller male of D. medinensis.

 The Nematodes 229

pairs of preanal and 4–6 pairs of postanal aequatorialis and M. kieferi), Metacyclops
papillae; the subequal spicules are (M. margaretae) and Thermocyclops (T.
490–750 µm long, with a gubernaculum crassus, T. incisus, T. inopinus and T.
measuring about 117 µm. Males remain in oblongatus). The larvae penetrate the gut
the connective tissues surrounding deeper wall of cyclops (Fig. 116) and, after two
muscles, usually in the thoracic region, moults in the haemocoel, reach the infec-
and are either absorbed or eventually cal- tive third stage in 14 days at 24°C. The
cify; they have only doubtfully been recov- infective larva measures on average 450 µm
ered in human infections.
14 µm and has a short bilobed tail. When
infected cyclops are ingested in drinking
LIFE CYCLE water, the released larvae burrow into the
The mature female worm moves to the sur- wall of the duodenum, migrate across the
face of the skin and forms a blister, which abdominal mesenteries and penetrate
bursts. The first-stage larvae are expelled through the abdomen and thorax in about
from the ruptured uterus when the affected 15 days. There is no increase in size during
part of the body (usually the foot or leg) this early migration but, after two moults,
comes into contact with water. The larvae the sexually mature worms meet and mate
on average measure 643 (490–737) µm
in the subcutaneous tissue, approximately
23 (18–24) µm and have a fully formed gut, 100 days after infection. After fertilization,
although they do not feed. The tail is long the males become encapsulated and even-
and pointed and the cuticle is striated. The tually die. They are usually absorbed,
larvae in water are very active, their thrash- although occasionally calcified specimens
ing movements resembling those of a free- have been seen on X-ray. The females move
living nematode (Fig. 115). They live for down the muscle planes, reaching the
4–7 days in pond water and for further extremities 8–10 months after infection; by
development have to be ingested by vari- 10 months the uterus contains fully formed
ous predatory species of small (1–2 mm) larvae. The mature females emerge from
microcrustacean cyclopoids. Intermediate the tissues about 1 year after ingestion of
hosts belong to the genera Mesocyclops (M. larvae.

Fig. 115. First-stage larvae of Dracunculus medinensis in water (phase contrast) after being expelled by
adult female (actual size 0.66 mm).
230 Chapter 5

(Fig. 117). In many patients (30–80%),

urticaria, sometimes accompanied by fever,
giddiness, gastrointestinal symptoms,
dyspnoea and infraorbital oedema, appears
the day before the blister forms but van-
ishes in a few hours. The blister is the first
sign in about 60% of cases. It is minute
when first noticed but may grow to a few
centimetres in diameter before it bursts,
usually in 1–3 days. The formation of the
blister is accompanied by local itching and
often an intense pain, which can be
relieved by immersion of the affected part
in cold water. A portion of the worm is
extruded through the ulcer formed by the
bursting of the blister, the edges of which
Fig. 116. Cyclops with larvae of Dracunculus in consist of pinkish granulation tissue. In
the haemocoel. simple cases the anterior end of the worm
is exposed by sloughing of the white cen-
tral eschar of the ulcer and more of the
CLINICAL MANIFESTATIONS worm protrudes, particularly after immer-
There are usually none while the female sion in water; after many thousands of lar-
worms are moving freely through the con- vae are expelled the portion of worm
nective tissues, but when about to emerge outside the body becomes flaccid.
to the surface a few larvae are released into Complete expulsion of the worm occurs,
the subdermis through a rupture at the on average, in 4 weeks and the lesion then
anterior end of the worm (the uterus is rapidly resolves.
non-functional). The host reaction results Secondary bacterial infection of the
in the formation of a burning, painful, blis- track of an emerging worm occurs in about
ter, which bursts in a few days to give a 50% of cases and patients then become
shallow ulcer, and there is then a marked seriously incapacitated (Fig. 118). In a
inflammatory response against the cuticle study in an area of Nigeria, 58% of cases,
of the entire worm, preventing its removal almost all of whom belonged to the 14–40-

Fig. 117. Section of subcutaneous tissues with portion of an adult female. Removed just after blister
formation so that there is a strong tissue reaction.
 The Nematodes 231

proportion of apparently uninfected per-

sons who live in an endemic area.
Occasionally an encysted worm may cause
more serious effects if in an unusual site;
these include constrictive pericarditis,
paraplegia, lymph node abscess and uro-
genital complications.

PATHOGENESIS
The blister fluid consists of a bacteriologi-
cally sterile fluid containing lymphocytes,
neutrophils, eosinophils and larvae.
In a proportion of cases the female
worm bursts in the tissues before emer-
gence, releasing many thousands of larvae.
This results in an intense tissue reaction,
with myositis and formation of an abscess
containing up to 0.5 l of pus, which can
lead to chronic ulcerations, bubo or epi-
didymo-orchitis in males. Adult females
sometimes enter joints and liberate larvae
into the synovial fluid, causing oedema,
congestion and plasma-cell infiltration of
the synovial membrane. This can lead to
arthritis or fibrous ankylosis of joints and
Fig. 118. Female of D. medinensis emerging from contractures of tendons, but in most cases
ankle of woman. There is secondary bacterial the condition resolves eventually.
infection up the track of the worm. Once larvae have been released from
the emerging female worm, there is a
strong adhesive reaction at the cuticle
year-old working population or were along the whole length of the worm. In the
schoolchildren, were disabled for an aver- early stages, the tissue reaction consists of
age of 12.7 weeks during the yam and rice inflammatory cells and is followed by a for-
harvest time and about 12,000 were perma- eign-body giant-cell reaction. This makes
nently incapacitated (Smith et al., 1989). extraction of the worm difficult and
Permanent physical impairment occurs in increases the chances of secondary bacter-
about 0.5% of infected individuals and in ial infection along the track of the worm,
one study in Ghana 28% of patients had with cellulitis.
continuing pain 12–18 months after infec- In many endemic areas, the track of a
tion (Hours and Cairncross, 1994), while in guinea worm on the foot provides an
another study in Benin there was 0.3% important mode of entry for tetanus spores.
mortality from tetanus and septicaemia
(Chippaux and Massougbodi, 1991). DIAGNOSIS
Infection is a major cause of school absen-
teeism and the parasite is unusual among Clinical and parasitological. Patients in an
parasitic helminths as it does not appear to endemic area usually have no doubt of the
confer any immune response, so that indi- diagnosis as soon as, or even before, the
viduals can be reinfected year after year. first signs appear. Local itching, urticaria
Sometimes female worms fail to reach and a burning pain at the site of a small
the surface, usually when unfertilized, and blister are usually the first signs of infec-
become encysted and calcify and are then tion, although sometimes a palpable and
only apparent on X-ray. This occurs in a sometimes moving worm may have been
232 Chapter 5

recognized earlier. The blister bursts in may act as anti-inflammatory agents.

about 4 days and active larvae, obtained by Ivermectin had no action in one field trial
placing cold water on the resulting small or against pre-emergent D. insignis in
ulcer, can be recognized under a low-pow- ferrets.
ered microscope.
EPIDEMIOLOGY
Immunological. Not useful in practice. Dracunculiasis is typically a disease of
ELISA, dot ELISA and SDS-PAGE/Western poor rural communities and is the only
blotting worked well for patent infections. infectious agent that is transmitted entirely
The most specific reaction appears to be for through drinking water. In all areas trans-
detection of IgG4 antibodies and might be mission is markedly seasonal and in most
able to detect infections up to 6 months parts of Africa (and formerly in India) the
before patency (Saroj-Bapna and maximum incidence coincides with the
Renapurkar, 1996; Bloch and Simonsen, planting season, resulting in great eco-
1998). The fluorescent antibody test using nomic hardship. In semi-desert (Sahel)
deep-frozen first-stage larvae was shown to areas of Africa (Burkina Faso, Chad, north-
demonstrate prepatent infections in mon- ern Cameroon, Mauritania, Niger, northern
keys 30 years ago. No evidence has been Nigeria, Senegal and Sudan), drinking
found for the presence of circulating anti- water is obtained from ponds during the
gens (Bloch et al., 1998). rainy season but from deep wells for the
rest of the year when the ponds are dry.
TREATMENT However, in the humid (guinea) savannah
regions of West Africa where rainfall
Surgery. Guinea worms have been wound exceeds 150 cm year1 (Benin, C ôte
out on sticks since antiquity (e.g. in the Rg d’Ivoire, Ghana, southern Nigeria and
Veda of about 1350 BC and possibly they Togo), there is no transmission during the
represent the fiery serpents afflicting the rainy season, when ponds turn into
Israelites in the wilderness, which Moses streams and cyclops densities are low
recommended should be set upon a pole). because of the large volume and turbidity
Provided that bacterial infection or other of the water. Similarly, infection was high-
complications have not occurred, regular est during the dry season in step wells in
winding out of the worm on a small stick, India.
combined with sterile dressing and acri- The life history of the parasite is well
flavine cream, usually results in complete adapted to provide the maximum chances
expulsion in 3–4 weeks with little pain. of transmission, as the female takes almost
This should be commenced as soon after exactly a year to mature and release its lar-
emergence as possible. vae at the optimum period each year.
Surgical removal of mature female
worms before emergence is sometimes pos- PREVENTION AND CONTROL
sible using a small incision. At this stage The United Nations World Health
there is no host reaction to the cuticle of Assembly in 1991 endorsed a campaign to
the worm, as occurs once emergence com- eradicate dracunculiasis from the world
mences, but care must be taken that the and originally set a date of the end of 1995.
worm is not wound around a ligament. Although this date has had to be postponed
by another 10 years, the prevalence and dis-
Chemotherapy. There is no evidence that tribution of the infection have diminished
any chemotherapeutic agent has a direct markedly in the last few years and it has
action against guinea worms. However, already been eliminated from Asia. The sit-
many compounds, including thiabend- uation in most African countries is not so
azole, niridazole, metronidazole, mebend- far advanced, but active campaigns are
azole and albendazole have been reported being carried out in all endemic countries
as hastening the expulsion of worms and and some are free of the disease, while most
 The Nematodes 233

are at the stage of case containment, p.p.m. kills cyclops for 5–6 weeks but, in
whereby all infected individuals can be areas with a long transmission season, has
quickly identified and stopped from enter- to be added a few times a year. The amount
ing ponds. of temephos estimated to be needed for
There are various possible interventions total eradication in Africa has been
once active surveillance measures have donated by the manufacturer.
been initiated, based on knowledge of the
life cycle of the parasite. It has been esti- Health education interventions by local
mated that passive surveillance identifies health workers are a very important com-
about 2% of cases. ponent of any control or eradication cam-
The provision of safe drinking water, paign, and village development committees
principally from tube-wells, is a priority in are able to assist in other primary health
rural areas of Africa and Asia, and assis- problems.
tance is being provided by many aid agen- Guinea worm was eliminated from the
cies in order to prevent other water-borne Bokhara area of Uzbekistan in the early
diseases, such as typhoid, infantile diar- 1930s and from the south of Iran, where
rhoea, etc., as well as guinea worm. It has infection was confined to large covered cis-
recently been estimated that 1100 million terns (known as ‘birkehs’), in the 1970s. It
people (about 21% of the world’s popula- is interesting to note that infection has not
tion) do not have access to clean water. returned to Bokhara in spite of the fact that
There are various interventions possible still only 33% of the population has piped
but the use of chemotherapy has no part in water (Cairncross et al., 2002). It was elimi-
control, except sometimes in aiding patient nated from Pakistan in 1994, India in 1997,
compliance. Interventions which are being Kenya and Senegal in 1996 and Cameroon,
made include the following. Chad and Yemen by 1999. There are also
very few cases left in Benin, Burkina Faso,
1. Filtering or boiling all drinking-water. Central African Republic, Côte d’Ivoire,
Boiling water is not usually feasible, Ethiopia, Mali, Mauritania, Niger, Togo and
because wood fuel is a scarce commodity, Uganda. However, there are three countries
but filters are playing an important role in which still have appreciable numbers of
all countries now mounting campaigns. cases. These are Nigeria, which had 11,617
The manufacturer of a monofilament nylon cases in 1999 (but 650,000 cases in 1988),
material has provided enough to provide Ghana, with 5524 cases in 1999 (but
filter nets for all endemic villagers. These 180,000 cases in 1989), and Sudan, with
nets are long-lasting, have a regular pore 56,226 cases reported in 1999. The appar-
size, are easily washed and dry quickly and ent number of cases went up substantially
are being widely used. in 2000 in Ghana, which demonstrates the
2. Persuading or preventing infected per- difficulties in identifying the many hun-
sons with an emerging worm from entering dreds of small isolated endemic villages.
ponds used for drinking water. The identi- However, there are now intensive cam-
fication and bandaging of very early lesions paigns in both Ghana and Nigeria and it is
can also help to prevent subsequent likely that elimination will follow in the
immersion. The cooperation of local teams next few years. The future for elimination
and of schoolchildren can be useful in con- in Sudan is more uncertain. Because of
vincing infected persons of the need for a political problems it has been difficult to
change in behaviour. actively survey, let alone treat, many
3. Treating water sources. The chemical infected villages and there is also the prob-
treatment of ponds can prove a useful adju- lem of migrants from Sudan reintroducing
vant to other measures, particularly when infection into neighbouring countries.
there is only a low level of transmission Thirty-seven other countries where the dis-
remaining. The insecticide temephos has ease used to be present in historical times
low toxicity to mammals and fish and at 1 have been certified as free by the WHO.
234 Chapter 5

ZOONOTIC ASPECTS In most highly endemic areas occasional

Female worms of the genus Dracunculus infections, principally in dogs and occa-
have been reported as emerging from a sionally other mammals, have been
wide range of mammals and reptiles from reported, but there is no evidence that they
many parts of the world, both endemic and have any part in maintaining transmission.
non-endemic for the human disease What is presumably the human parasite
(Muller, 1971). Those found in reptiles can still be found in dogs in the formerly
clearly belong to other species but the situ- endemic areas of Tamil Nadu in India and
ation in regard to those in mammals is not Uzbekistan, but no new human cases have
clear. For instance guinea worm is common been reported. Infection has also been
in wild carnivores in North America and found in dogs and cats in previously non-
was named D. insignis by Leidy in 1858 endemic Central Asian Republics;
but there is very little morphological evi- Azerbaijan, Kazakhstan and possibly
dence for separating this from the human Turkmenia (Cairncross et al., 2002). There
species. has also been a recent report of D. medi-
There have been three documented cases nensis from a cat in China (Fu et al., 1999)
of human zoonotic infections, from Japan in and it is very likely that in many parts of
1986 (Kobayashi et al., 1986) and from the world there are widespread but under-
Korea and Indonesia in 1926. In both cases reported animal cycles completely inde-
the patients had eaten raw freshwater fish pendent of human infection. However, it is
which have been proved experimentally to unlikely that zoonotic infections have any
be capable of acting as paratenic hosts. importance in human transmission.

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Further Reading

Cairncross, S. (1992) Guinea Worm Eradication: a Selected Bibliography. Bureau of Hygiene and
Tropical Diseases, London, UK.
Chippaux, J.-P. (1994) Le Ver de Guinée en Afrique: Méthodes de Lutte pour l’Èradication. ORSTOM,
Paris, France.
Cross, J.H. (1995) Capillaria philippinensis and Trichostrongylus orientalis. In: Farthing, M.J.G.,
Keusch, G.T. and Wakelin, D. (eds) Enteric Infection 2: Intestinal Helminths. Chapman and Hall,
London, UK, pp. 151–163.
Daengsvang, S. (1980) A Monograph on the Genus Gnathostoma and Gnathostomiasis in Thailand.
Seamic, Tokyo, Japan.
Dissanaike, A.S. (1986) A review of Brugia sp. with special reference to Brugia malayi and to
zoonotic infections. Tropical Biomedicine 3, 67–72.
Goddard, J. (1996) Physicians’ Guide to Arthropods of Medical Importance, 2nd edn. CRC Press,
Boca Raton, Florida, USA.
Grenfell, B.T. and Michael, E. (1992) Infection and disease in lymphatic filariasis: an epidemiological
approach. Parasitology 104 (suppl.), S81-S90.
Hinz, E. (1996) Helminthiasen des Menschen in Thailand. Peter Lang, Frankfurt am Main, Germany,
pp. 137–141.
Hopkins, D.R. and Ruiz-Tiben, E. (1991) Strategies for dracunculiasis eradication. Bulletin of the
World Health Organization 69, 533–540.
Muller, R. (1979) Guinea worm disease; epidemiology, control and treatment. Bulletin of the World
Health Organization 57, 683–689.
 The Nematodes 239

Peters, W. (1992) Colour Atlas of Arthropods in Clinical Medicine. Wolfe, London, UK.
RSTM&H (2000) Elimination of lymphatic filariasis as a public health problem. Transactions of the
Royal Society of Tropical Medicine and Hygiene 94, 589–602.
Sasa, M. (1976) Human Filariasis. University Park Press, Tokyo, Japan.
06Worms & H.D. - Chap 06 14/11/01 4:29 PM Page 240

6
Other (Non-helminth) Groups

Included in this section are a hetero- reasons when calcified, or probably are
geneous collection of endoparasites that absorbed and never diagnosed. Severe
are not strictly helminths, but which may pathology is rare and is associated with
be confused with them, particularly in migration of the primary larvae before they
biopsy tissue sections. become encysted, or in a few cases consid-
erable tissue damage has been caused by
the third-stage larvae leaving the fibrous
capsule and undergoing another migration;
Pentastomes
in both cases a form of visceral larva
migrans results.
The members of this small group of para-
Human infection is common in some
sites form a separate phylum
areas of the world, such as Malaysia and
(Pentastomida), usually placed somewhere
West Africa (Benin, Cameroon, Congo,
between the annelids and the arthropods.
Gabon, Nigeria and Senegal).
Larvae of seven species have been reported
On X-ray Armillifer may be mistaken for
from humans but only two are of any
guinea worm and in tissue sections they
importance.
are superficially similar to spargana,
gnathostomes, fly larvae or the chigoe flea
Armillifer (= Porocephalus) armillata (Tunga penetrans). In tissue sections penta-
stomes may be differentiated by the pres-
This is a parasite of the respiratory tract of ence of a body cavity and intestine (as have
snakes in Africa and Asia, while the larvae all the others except spargana), chitinous
are found encysted in the tissues of rodents tracheae (as have fly larvae and Tunga),
and other mammals. Human infection is striated muscle fibres and the presence of
presumed to be by ingestion of eggs on veg- reproductive organs.
etation or in water. The egg contains an Armillifer agkistrodontis, a parasite of the
embryo (0.2 mm in length), which bores viper, has been recovered once in China
through the intestinal wall and encysts in after treatment with mebendazole at 400
the mesenteries of the peritoneal cavity mg three times daily for 3 days in a patient
(particularly the liver). The coiled larva with abdominal pain who had drunk snake
moults twice and grows until it measures bile and blood (Zhang et al., 1997).
20–25 mm in length. These third-stage lar-
vae have characteristic annulations, giving
a beaded appearance (Fig. 119). Larvae may Linguatula serrata
produce a considerable inflammatory
response but usually cause no symptoms Known as the ‘tongue worm’ this is a nat-
and are only seen on X-rays taken for other ural parasite of the nasal passages of dogs

240
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Other (Non-helminth) Groups 241

genus is Limnatis, reported from humans

in southern Europe, North Africa, North
America and Asia. Limnatis nilotica is a
parasite of cattle and lives in water-holes
and springs. Adults may measure 15 cm in
length but are capable of great contraction
and extension. The body is greenish-black
in colour with thin orange stripes, and
there are two suckers, one around the
mouth, the other at the posterior end.
When a very young worm is ingested in
drinking water, it attaches to the mucous
Fig. 119. Early encysted larva of Armillifer
membranes of the mouth, pharynx, vocal
armillata on intestinal wall ( 6).
cords or trachea, where it may remain
attached for days or weeks. The leech feeds
and other carnivores, with the larval stages on blood and secretes an anticoagulant,
occurring in herbivores. In Lebanon a type which can cause excessive bleeding and
of pharyngitis known as ‘halzoun’ occurs even death. Usually, however, clinical
in humans from ingestion of insufficiently symptoms result from the mechanical
cooked liver of sheep and goats containing action of worms, which cause an oedema-
larvae; in Sudan the similar ‘Marrara syn- tous reaction with paroxysmal coughing
drome’ is found, with an allergic and dyspnoea. Various species of leeches
nasopharyngitis accompanied by itching in have attached to the conjunctiva (in Turkey
the throat, deafness, tinnitus and facial and the USA), causing periorbital
palsy (Yagi et al., 1996). Larvae can migrate haematomas, and invaded the nose (India),
from the stomach to the tonsils and symp- vaginal wall (India) and urethra (Malaysia).
toms often include sneezing and coughing Engorged leeches can be removed with
also. The condition usually recovers spon- forceps; otherwise an anaesthetic (0.5%
taneously in about a week when the para- tetracaine) or irritant substance may be
sites become dislodged. Ocular cases have necessary to induce them to detach.
been reported from Ecuador, Israel and the
USA (five cases), with conjunctivitis and a
larval worm in the anterior chamber. A Myiasis
larva has been found in the pericardial sac
of a woman in Georgia, USA, two cases Accidental myiasis may be caused by lar-
with larvae causing tortuous tunnels and vae of flies belonging to various families,
lymphatic nodules in the abdomen in such as the blowflies, flesh-flies and house-
Costa Rica and larvae in the bile-duct, flies. The larvae or eggs are usually
causing jaundice and gallstones, in a ingested with contaminated food or water
patient in Turkey. and the larvae are found in the intestinal
tract or passed out in the faeces.
The larvae of some flies are obligate par-
Leeches asites in the tissues of various vertebrates,
the adults being known as warble flies or
Leeches belong to the phylum Annelida bot-flies. The larvae can be mistaken for
and many species are adapted to sucking helminths when causing larva migrans,
the blood of vertebrates. Most are external although they can be recognized easily
blood feeders and, although they may be a when removed. In tissue sections fly larvae
major nuisance in areas of Asia, are not can be differentiated by the chitinous
likely to be mistaken for parasitic tracheae, lack of reproductive organs and
helminths. There are a few forms causing non-striated muscles.
internal infection, of which the best known Dermatobia hominis (the tropical warble
06Worms & H.D. - Chap 06 14/11/01 4:29 PM Page 242

242 Chapter 6

fly of South America) is the only genus that fortunately was eradicated before it spread
can complete its entire larval development to the rest of Africa (Hall and Wall, 1995).
in humans. The larvae are found in a wide Chrysomya bezziana (the Old World screw-
range of mammalian hosts and in humans worm) is a similar fly in Asia and Africa.
occur in unprotected parts of the body. The Gasterophilus sp. (the horse bot-fly)
eggs are laid by the female fly on mosqui- first-stage larvae occasionally wander
toes, other flies or ticks, which transport under the skin of humans (particularly in
them to humans. The eggs hatch when the Russia, with a recent case in an infant in
mosquito feeds and the larvae penetrate the the USA). The dark transverse bands of the
skin, with a channel remaining to the sur- larvae can sometimes be seen under the
face. The posterior ends of the larvae poke skin (particularly if mineral oil is rubbed
out from an ulcer on the skin at intervals into the skin to make it transparent) inside
before they drop out in 6–12 weeks after a serpiginous tunnel. The larvae may move
infection and pupate in the soil. Larvae several millimetres a day, producing a pru-
produce a severe pruritus, and a suppurat- ritus similar to creeping eruption.
ing wound may result from scratching. Hypoderma bovis (the cattle bot-fly) lar-
Cochliomyia hominovorax (the New vae may bore down deeply into the tissues,
World screw-worm) is widely distributed in while those of Oestrus ovis (the sheep bot-
cattle in the Americas. Eggs are deposited fly) are usually found in humans in the
on the skin next to a wound or on mucous external membranes of the eye, and those
membranes of the nose, mouth or vagina. of Rhinoestrus purpureus (the Russian gad-
The hatched maggots (up to 400) tunnel fly) in the nose.
deeply to produce a communal boil-like Cordylobia anthropophaga (the African
lesion, oozing pus, which often becomes tumbu fly) belongs to a different group
secondarily infected and leads to death in from the previous forms and has larvae that
about 8% of untreated cases. After 1 week of produce a boil-like swelling at the site of
feeding the mature maggots exit and drop to penetration in many animals. The eggs
the ground to pupate. One case was success- hatch in moist soil and penetration is usu-
fully treated with topical application of 1% ally through the feet. The larvae leave the
ivermectin, which killed all larvae by 24 h body in 8–9 days. A recent case in the
(Victoria et al., 1999). This fly was acci- breast of a Nigerian woman appeared to be
dently introduced into Libya in 1988, but a tumour on a mammogram.

References

Hall, M. and Wall, R. (1995) Myiasis of humans and domestic animals. Advances in Parasitology 35,
257–334.
Victoria, J., Trujillo, R. and Barreto, M. (1999) Myiasis: a successful treatment with topical iver-
mectin. International Journal of Dermatology 38, 142–144.
Yagi, H., El Bahari, S., Mohamed, H.A., Ahmed, E.R.S., Mustafa, M., Saad, M.B.A., Sulaiman, S.M.
and El Hassan, A.M. (1996) The Marrara syndrome: a hypersensitivity reaction of the upper respi-
ratory tract and buccopharyngeal mucosa to nymphs of Linguatula serrata. Acta Tropica 62,
127–134.
Zhang, Q.Y., Wang, B.F., Huang, M. and Cheng, T.F. (1997) Viper’s blood and bile. Lancet British edi-
tion 349, 250.

Further Reading

Hall, M. and Wall, R. (1995) Myiasis of humans and domestic animals. Advances in Parasitology 35,
257–334.
07Worms & H.D. - Chap 07 14/11/01 4:34 PM Page 243

7
Immunology of Helminths

Introduction The Immune Response

Parasites, like all pathogens, elicit a wide Immune responses to infection can be
range of immune responses in their hosts. divided into two categories, innate and
The nature of these responses is deter- adaptive. In general terms, the first covers
mined both by the host and by the parasite. responses that are expressed immediately
Even within a single host species there is on exposure to infection, show little mem-
variation in the capacity to express ory or enhancement on re-exposure, have
immune responses, which reflects genetic broad molecular specificity (termed pattern
differences as well as differences in such recognition) and are associated with the
variables as age, sex, nutrition, physiologi- activities of non-lymphoid cells. In con-
cal status and the presence of concurrent trast, adaptive responses depend upon the
infections. Parasite-determined variation in activity of lymphocytes, are induced in an
response arises from differences in the antigen-specific manner, show memory and
level and frequency of infection, as well as consequently are enhanced when the host
from the genetic variation that exists is re-exposed to the same infection. The
within widely distributed species. Much of focus here will be on adaptive responses,
our current knowledge of antiparasite but it should be emphasized that the dis-
responses has come from experimental tinction between the two categories is often
studies in laboratory rodents, and the blurred, that innate responses may be
extent to which this can be extended to essential for the correct induction of adap-
humans is sometimes controversial. tive responses, and that both can con-
However, there is no doubt that the essen- tribute to the overall response be it
tial principles of immune responsiveness protective or pathological.
to parasites apply to all mammalian hosts.
An important principle, which has particu-
lar relevance to helminths, is that very few Adaptive Responses
of the responses elicited by infection are
likely to be functionally protective. Many Adaptive immunity is dependent upon the
are irrelevant to protection and some, as recognition of and the response to specific
seen very clearly in schistosomiasis, may sequences (antigenic determinants or epi-
have severe pathological consequences. topes) associated with molecules that are
One of the important goals for immuno- foreign to the body (i.e. are ‘non-self’).
parasitologists is to identify those Recognition is absolutely dependent upon
responses that are beneficial and devise lymphocytes, a unique population of cells,
ways of promoting these while reducing characterized by possession of epitope-
immunopathological responses. specific receptors on their cell membranes.

243
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244 Chapter 7

Lymphocytes are divided into two major respond directly to certain types of antigen
populations – T (thymus-dependent) cells, (particularly polysaccharides), in almost all
which carry T-cell receptors (TCR) and B cases involving parasites B cells require T-
(bursa- or bone-marrow-derived) cells, in cell help, the T cells helping to determine
which the B-cell receptor is immunoglobu- the class of antibody by the pattern of
lin (Ig). As far as parasitic infections are cytokines they produce. The specificity of
concerned most adaptive immune the antibodies produced is the same as that
responses are initiated when T cells recog- of the surface receptor carried by the B
nize epitopes, and this requires the suc- cells involved initially, but plasma cells
cessful completion of two distinct release large amounts of the molecule in a
processes. The first is presentation of epi- soluble form and modify the molecules to
topes to T cells by non-lymphoid antigen- perform a variety of biological functions.
presenting cells, such as macrophages, Ig molecules are formed from paired
dendritic cells and B cells, and the second heavy and light glycoprotein chains and
is recognition of those epitopes by TCR. can be divided into two functional regions,
Recognition is a complex process that the Fab region, which determines epitope
involves multiple receptor–ligand inter- recognition, and the Fc region, which
actions between antigen-presenting cells determines other biological functions (Fig.
and the T cell concerned, as well as 121). Differences in the Fc regions define
epitope–receptor binding. These inter- the five major classes of antibodies (IgM,
actions involve a variety of molecules car- IgD, IgG, IgA, IgE). Binding of antibody to a
ried on each cell surface, as well as binding target epitope may itself have protective
of receptors on the T-cell surface to soluble value, e.g. if the target is carried by a cru-
signalling molecules (cytokines). Once acti- cial enzyme or sensory cell; more fre-
vated, T cells themselves release cytokines quently, antibody binding serves to
and interact directly and indirectly with identify the target immunologically and
other cells. thus act as a focus for other effector mecha-
T cells can be categorized into a number nisms. An important mechanism involves
of subsets by the surface molecules they the activation of complement, a complex
carry (e.g. CD4+ helper cells or CD8+ cyto- series of plasma proteins capable of trigger-
toxic cells) and by the cytokines they ing non-lymphoid effector cells, of increas-
release (e.g. helper cells can be divided ing phagocytic activity and of damaging
into at least three subsets on this basis). cell membranes to bring about cell lysis.
Different T-cell subsets regulate different Bound antibody also acts to increase inter-
components of the immune system’s effec- actions between the target and non-lym-
tor and memory responses. Key effector phoid cells that carry the appropriate Fc
mechanisms are mediated via antibody receptor. Antibody binding and comple-
production, cytotoxicity and inflammation; ment activation can therefore both be
all three involve the coordinated activity of involved in what is collectively termed
lymphocytes and non-lymphoid cells. antibody-dependent cellular cytotoxicity
The interactions of these components in (ADCC), a mechanism thought to be
the initiation of the immune response are involved in immune protection against a
shown in Fig. 120. number of helminths (Fig. 122).

Antibody Production Cytotoxicity

Antibodies (circulating Ig) are produced by In addition to ADCC, cytotoxicity can be

B cells that have been appropriately stimu- brought about directly by T cells, particu-
lated and have gone through a sequence of larly CD8+ cells and specialized natural
developmental steps to produce plasma killer (NK) cells These bind to targets
cells. Although it is possible for B cells to through the TCR or other receptors and
07Worms & H.D. - Chap 07 14/11/01 4:34 PM Page 245

Immunology of Helminths 245

ANTIGEN-
PRESENTING T CELL
CELL Costimulatory
ES molecules
antigen

Processing Cytokine
and binding Activation release
to MHC II and clonal
expansion
WORM Somatic CD4
antigen

Effector function

MACROPHAGE
ACTIVATIO
A
ATIO N Type 1
T
ANTIBODY EFFECTOR CELLS
Cytokine
release
MEMORY CELLS
ANTIBODY Type 2
T
INFLAMMATIO
A
ATIO N

Fig. 120. Initiation of the immune response to a parasitic worm. Worms release antigens in their
excretions/secretions (ES antigens), from their cuticle, and from their bodies (somatic antigens) when the
worm is killed. Antigen is taken up by antigen-presenting cells and presented by major histocompatibility
complex (MHC) molecules to T cells. Recognition of antigen by the T-cell receptor and ligation of
accessory and costimulatory molecules activate the T cell. The activated cells release cytokines and
undergo clonal expansion to produce clones of cells with identical T-cell receptors. These cells, acting
through cytokines, become effector cells or memory cells. Effector cells, through release of type 1 or type
2 cytokines, coordinate a variety of effector activities against the parasite. Key to symbols: MHC
molecule;  Antigen; T-cell receptor.

release a number of potent molecules that damage tissues, but it is probable that
damage cell membranes or cause intra- immune-mediated inflammation plays a
cellular damage. T-cell cytotoxicity is well major role in a majority of infections
established as a protective mechanism in involving helminths. This form of inflam-
infections involving intracellular proto- mation can be mediated by antibodies, par-
zoans, but there is little evidence for its ticularly when complement is involved,
importance in helminths. and by T cells. Antibody of the IgE class is
particularly important in this respect, as it
binds to cells that have the potential to
Inflammation release powerful biological mediators (e.g.
amines) when the bound antibody becomes
Parasites bring about inflammatory changes complexed with its specific antigen. T-cell-
in a variety of ways. Their invasion and mediated inflammation is the result of
activities in tissues cause mechanical and cytokine release and the increased produc-
chemical damage, and their interactions tion, or increased activity, of a wide variety
with non-lymphoid cells cause the release of non-lymphoid cells. Again it is the
of potent mediators, which themselves can release of potent mediators that initiates
07Worms & H.D. - Chap 07 14/11/01 4:34 PM Page 246

246 Chapter 7

Hinge region

VL CL

Light chain
X CH2 CH3
Heavy chain

VH CH1

Antigen-binding X
site

Fab Fc

Variable region

Constant region

Disulphide bond

X Carbohydrate group

Fig. 121. Diagrammatic representation of an immunoglobulin molecule (based on IgG). The molecule is
made up of two light (L) chains and two heavy (H) chains, held by disulphide bonds. The bond between
the paired chains can be split by enzymes to break up the molecule into the Fab and Fc fragments. Each
chain forms a number of regions (domains): the variable (V) regions form the antigen-binding site of the
Fab fragments; the constant (C) regions of the Fc fragment confer the biological properties of the
molecule, e.g. binding to receptors and activation of complement.

the inflammatory damage. Some of the cells, the macrophage–monocyte line and
mediators released during inflammation, the granulocyte line. Monocytes circulate
however caused, can damage parasites in the blood and mature as macrophages in
directly; in other cases the tissue changes the tissues. Three groups of granulocytes
associated with inflammation may affect (neutrophils, eosinophils and basophils)
the parasite indirectly, essentially by bring- mature in the bone marrow and move into
ing about dramatic changes in its environ- tissues from the blood, while the fourth
ment. (mast cells) matures in tissues. All non-
lymphoid cells can participate in innate
and adaptive responses through their
Non-lymphoid Cells phagocytic activities and through their
ability to release powerful mediators.
Lymphocytes and non-lymphoid cells both Macrophages, neutrophils and eosinophils
arise from precursors in the bone marrow, often infiltrate tissues around worms and
but then follow divergent pathways of may form granulomas when parasite stages
development – the lymphoid and the become trapped in tissues. Basophils and
myeloid. The latter pathway gives rise to mast cells – the amine-containing cells –
the two major categories of non-lymphoid are involved primarily through the capac-
07Worms & H.D. - Chap 07 14/11/01 4:34 PM Page 247

Immunology of Helminths 247

EOSINOPHILS, MACROPHAGES, NEUTROPHILS

(NK cells and Mast cells)

FcR- and/or C3R-

mediated
adhesion
C3R Fc FcR C3R STEP 2

Complement activated IgG, IgA, IgE Complement activated

by alternative pathway bound to antigen by classical pathway STEP 1

OOOOOOO XXXXXXX XXXXOOO

WORM

XXXXXXX OOOOOOO OO
X X
XXX

Adhesion not
involving
FcR or C3R
Immune complexes bound Strong adherence Weak adherence
to cell through FcR; by activated (e.g. sugar–lectin)
MACROPHAGES by
EOSINOPHILS, MACROPHAGES
MACROPHAGES

Fig. 122. Mechanisms by which cells mediate cytotoxic activity against parasitic worms. Adhesion
between cells and parasites can involve cellular receptors for the Fc portion of immunoglobulin
molecules (FcR), or receptors for components of complement such as C3(C3R), when these molecules
are bound to the parasite’s surface. Adhesion can also occur through mechanisms not involving direct
binding of immunoglobulin or complement to the parasite (e.g. via immune complexes, lectin–sugar
binding and intermolecular forces).

ity to release a variety of mediators. parasite-derived foreign molecules, which

Whereas phagocytosis is an effective can be recognized by the immune system.
defence mechanism against protozoans, These are commonly proteins, glycopro-
worms, even larvae, are too large to be teins or carbohydrates, but molecules such
taken in by single cells. A more character- as glycolipids can also be antigenic. In the
istic response is for cells to bind closely to case of helminths, antigens may be present
the parasite surface, through antibody- or on the parasite surface, released from the
complement-mediated mechanisms, and worm as it develops, reproduces and
then to release mediators directly on to the metabolizes (collectively referred to as
worm surface. In that way the outer surface excretory/secretory (ES) antigens) or
is damaged, often irreversibly, and the released when the worm dies and is
worm killed. destroyed. Antigens of intracellular proto-
zoans may be expressed on the surface of
the host cell, and this also occurs in the
Parasites and their Antigens nematode Trichinella spiralis during its
intramuscular phase.
Parasites, and helminths in particular, are The antigens presented by helminths
complex organisms, often with complex frequently change as the parasite goes
life cycles. The presence of an infection through its life cycle, i.e. there is stage
therefore exposes the host to a battery of specificity in antigen expression. This can
07Worms & H.D. - Chap 07 14/11/01 4:34 PM Page 248

248 Chapter 7

result in the responses raised against one thus decrease protective immunity (‘block-
life-cycle stage being ineffective against a ing antibodies’).
later stage. Equally life-cycle stages may
differ in their immunogenicity (their ability
to generate immune responses), although Expression of Immune Responses
this is also influenced by their location.
Metabolically active stages that migrate The detailed understanding of the immune
through tissues, or remain there for long system that we now have enables us to
periods, are often potently immunogenic, interpret in mechanistic terms many of the
Ascaris larvae and schistosome eggs being characteristics of the immune responses
excellent examples. Resting larval stages, that parasitic infections generate. It seems a
particularly those that become encysted or general rule that, whereas many protozoa,
enter immunologically privileged sites, particularly the intracellular species, elicit
such as the central nervous system (CNS), lymphocyte responses dominated by the T-
may generate much less response – tape- helper 1 (Th1) subset, helminth infections
worm larvae are good examples. Some elicit Th2-dominated responses. Th1
parasites living in the intestine (e.g. hook- responses are associated with cellular
worms) can stimulate strong immune immunity (e.g. activation of macrophages)
responses, their antigens being taken up and production of specific classes of IgG
across the mucosa, but others, notably the antibodies. In contrast, Th2 cells coordinate
tapeworms, appear much less immuno- a pattern of antibody responses, which
genic. Many nematodes and larval trema- includes IgE, and regulate the production
todes release antigens that act as allergens and activity of inflammatory cells, particu-
– i.e. stimulate the formation of IgE – and larly eosinophils and mast cells. The reason
thus the host develops hypersensitivity to for this Th subset bias is not fully under-
the parasite, allergic symptoms being com- stood, but it reflects the nature of particular
mon in many helminth infections. antigens, the ways in which these are pre-
Not all molecules released by helminths sented to T cells and the cytokine environ-
act as immunogens, in the sense of stimu- ment in which T-cell responses take place.
lating positive immune responses. Many Thus T-cell responses occurring in the pres-
worms are now known to release ence of the cytokine interleukin 12 (IL-12)
immunomodulatory molecules, which (derived from previously activated NK
suppress, divert or inactivate components cells) become polarized to the Th1 subset,
of the immune response. Good examples while those occurring in the presence of IL-
have been described in infections with 4 (derived from cells such as mast cells)
filarial worms and with hookworms, but become polarized to the Th2 subset.
immunomodulation is probably a wide- The nature and degree of the immune
spread phenomenon. Helminths also response elicited by infection are not only
express, or acquire, molecules that act as dependent on the level and frequency of
immunological disguises (glycolipids in infection and the characteristics of the para-
adult schistosomes, albumin in micro- site concerned, they are also influenced by
filaria larvae, host proteins in cestode lar- the location of the parasite. Helminths
vae), which enable them to reduce the occupy a very wide variety of habitats in
degree of ‘foreignness’ they present to the the host’s body, and the capacity of these to
host’s immune system, effectively being respond to infection and the nature of the
seen as self rather than non-self. Some response expressed can differ quite
molecules, although immunogenic, have markedly. A useful distinction in immuno-
been shown to elicit antibody responses logical terms is seen in the responses to
(e.g. IgM antibodies to carbohydrate anti- parasites living within the intestine and
gens of S. mansoni) that block the protec- those elsewhere in the body, i.e. between
tive action of other antibody classes and parasites living in mucosal and systemic
07Worms & H.D. - Chap 07 14/11/01 4:34 PM Page 249

Immunology of Helminths 249

locations. Although the mucosal and sys- responses in parasitized humans can be
temic immune systems are clearly intercon- measured in a variety of ways. These
nected, the populations of lymphocytes in include tests that demonstrate the presence
each and their patterns of migration are dis- of specific antiparasite antibody, lympho-
tinct. The responses occurring within the cyte responses and cytokine production,
intestinal wall itself are similar in many skin sensitivity to antigen, increased pro-
respects to those elsewhere in the body, but duction of ‘non-specific’ IgM and increased
a major difference is seen in the predomi- numbers of eosinophils, as well as
nant class of Ig produced there and secreted histopathological demonstration of the
into the gut lumen (IgA), whereas the sys- presence of immune cells in infected tis-
temic immune system is dominated by IgG sues. In addition, the capacity of antibodies
and IgM antibodies. The mucosal tissues and cells taken from infected individuals to
are readily infiltrated by inflammatory cells, kill parasites or parasite-infected cells can
characteristically including a discrete pop- be tested in vitro. Demonstrable protection
ulation of mast cells. Interactions between against reinfection, in individuals or in
these cells and IgE can trigger hypersensi- populations (e.g. Leishmania major), is
tivity reactions, which lead to major clear evidence of immunity, but is rela-
changes in intestinal structure and func- tively rare in helminth infections. Evidence
tion. The mucosal immune system operates of age-related declines in infection rates in
not only in the intestine, but also in the endemic areas (e.g. in malaria and in
lungs and urogenital tissues. Systemic helminth infections) suggests the operation
immunity has different characteristics in of host-protective immunity, as does protec-
different locations, and these influence the tion against the pathological effects of
antiparasite responses generated by infec- infection (e.g. malaria), but neither is neces-
tion. Important differences are seen, for sarily conclusive. ‘Experiments of nature’ –
example, between responses in the CNS, i.e. study of infections in individuals with
usually regarded as an immunologically compromised immune systems – can indi-
privileged site (i.e. with reduced respon- cate the importance of immune competence
siveness), and those in the skin, where a in preventing the consequences of infection
separate population of antigen-presenting (e.g. giardiasis, cryptosporidiosis or
cells (Langerhans cells) operates and where strongyloidiasis). However, these lines of
cellular inflammatory responses are readily evidence can often only be deduced from
generated. In contrast to protozoans, rela- detailed and extensive population studies
tively few helminths live for any length of and sophisticated statistical analysis. More
time in the blood, adult schistosomes and direct evidence that host-protective immu-
microfilaria larvae being exceptions. nity can operate effectively against para-
Despite being bathed in antibodies and sites can be gained from studies in
complement and potentially exposed to a experimental models, although it is often
variety of non-lymphoid cells, both survive not possible to use in such models (particu-
for prolonged periods, because they possess larly rodents) the species of parasite that
effective evasion mechanisms which pre- are of interest in humans.
vent them from being recognized. There are experimental models for most
of the major human helminth infections, the
majority of these being in rodent hosts.
Protective Immune Responses in Under controlled conditions, it is possible
Infected Hosts to show that, in many cases, infections elicit
strong immune responses and that these
Although it is easy to demonstrate that may confer substantial protection on the
parasitic infections elicit immune host. Protection developing during an initial
responses in their human hosts, it is more infection can be quantified by determining
difficult to demonstrate the relation of these the numbers of worms recovered at intervals
responses to protective immunity. Immune after infection or by the levels and duration
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250 Chapter 7

of larval and egg output. In other cases pro- Demonstration of protective immunity
tection is not seen, and worms persist for in human populations that are naturally
long periods in the presence of specific exposed to helminth infections is much
immune responses. Good examples from more difficult than it is in the laboratory,
work with mouse models include the long- because of the number of confounding fac-
term survival of schistosomes, larval ces- tors that have to be taken into account.
todes, liver flukes, microfilariae and certain Unlike experimental animals, individual
intestinal nematodes. Immunity to reinfec- humans are exposed to varying intensities
tion can be seen in models where there is no and frequencies of infection and differ from
resistance to the primary infection, but the one another in factors that are known to
nature of this reinfection immunity needs to influence immunity (e.g. age, sex, infection,
be examined carefully. For example, the nutritional and physiological status and
resistance of mice to reinfection with genetics), as well as access to anthelminthic
Schistosoma mansoni reflects the pathologi- treatment. What was a general view that
cal changes that the primary infection has there is little immunologically mediated
brought about in the liver, rather than spe- resistance to helminths, despite abundant
cific immune destruction of the incoming evidence of immune responses as such, has
worms. Resistance to reinfection with been considerably modified as a result of
Taenia taeniaeformis in mice carrying immunoepidemiological and in vitro stud-
mature cysticerci reflects the operation of ies. For example, it now seems quite clear,
immune responses against the penetrating from detailed treatment/reinfection studies,
oncospheres and early cysticerci before that humans do develop protective immu-
these have developed resistance to comple- nity to infection with S. mansoni and S.
ment-mediated damage. Resistance of mice haematobium. Correlative studies have
to reinfection with Heligmosomoides poly- linked resistance to levels of parasite-spe-
gyrus (an intestinal nematode widely used cific IgE and to eosinophil activity, data that
as a model of chronic infection) is expressed are supported by in vitro work. Although
only if the previous adult infection and its the picture is much less clear with the
associated immunosuppressive effects have major gastrointestinal nematodes, there are
been removed by anthelminthic treatment. data suggesting that a level of protective
Once the existence of host-protective immu- immunity is acquired, at least in hookworm
nity has been established, potential mecha- and Trichuris infections. Knowledge of the
nisms of immune-mediated resistance and cellular and molecular mechanisms under-
the response components involved can be lying immune responses has increased the
studied using in vitro approaches. Good predictive value of studies that attempt to
examples include analysis of ADCC mecha- correlate infection status with particular
nisms against schistosomula and microfilar- immune components. This is best seen with
iae. However, the demonstration of effective the many studies that now use T-cell and
immune killing under in vitro conditions cytokine data as analytical tools. The vari-
does not necessarily correlate with in vivo ous clinical categories found in populations
patterns of response. The capacity of hosts exposed to lymphatic filariasis (from the
to become immune can also be studied in putatively immune, parasite-negative
experimental models by using attenuated endemic normals to infected individuals
parasites or isolated parasite molecules as with obstructive disease) have been corre-
vaccine antigens. For example, mice can be lated with particular patterns of Th-cell
effectively vaccinated against S. mansoni response and cytokine production,
using irradiated cercariae, rats against the although the relationship is clearly com-
same species with defined recombinant plex. Epidemiological and genetic studies
antigens (e.g. glutathione-S-transferase) and on populations exposed to S. mansoni have
mice against intestinal nematodes with pinpointed a major gene that controls the
defined antigens or synthetic peptides from expression of protective immunity, and
these antigens. have revealed positive correlations between
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Immunology of Helminths 251

resistance and the genetic control of Th2- iting factor in all diagnostic tests is the
related cytokines. For many helminth infec- availability of purified antigens to give
tions, however, evidence for protective high levels of both sensitivity and speci-
immunity is slight, and there is little infor- ficity. The use of recombinant and syn-
mation about the underlying basis of the thetic techniques for antigen production is
immune responses that infection elicits. overcoming this limitation.
A number of older diagnostic tests used
cellular responses to injected antigen as an
Exploitation of Immune Responses indicator of infection. These have largely
been phased out, largely because of low
Diagnosis specificity and the danger of adverse reac-
tions.
Whether or not immune responses confer The immunology of trematodes is dis-
any protection against helminths their cussed on p. 23 and p. 41, of cestodes on
presence can be used as a means of diag- p. 93, of intestinal nematodes on p. 121 and
nosing infection. A majority of diagnostic of filarial nematodes on pp. 196 and 217.
tests make use of antibody responses, and
these can be measured by many tech-
niques. Perhaps the most widespread at Vaccination
present is the ELISA, which can be used
with very small quantities of serum, can be As with all infectious diseases, vaccination
automated for large-scale surveys and is against helminths is seen as one of the most
read using colorimetric assays. One draw- effective ways in which infections could be
back of antibody-based tests is that the controlled. Until quite recently, success in
presence of antiparasite antibody does not this field has been negligible compared
necessarily imply the presence of a current with the progress made with viral and bac-
infection, although measurement of partic- terial vaccines. Although many of the latter
ular classes of antibody (e.g. IgG4) is a good were initially developed quite empirically,
indicator. The ELISA can be adapted to test this approach has not been successful with
for antigen rather than antibody, and of helminths, where the problems of eliciting
course this is a positive indicator of para- the required protective responses are much
sites in the body. Antigen detection has greater. Experimental vaccines using atten-
been widely used in schistosome and filar- uated larval stages have proved effective in
ial infections. An exciting new develop- rodents against parasites such as schisto-
ment is the development of non-invasive somes, hookworms and some filarial nema-
detection of ES antigens by an antigen-cap- todes. Attenuated larvae have also been
ture ELISA in faeces (coproantigens), urine used to reduce disease in schistosome-
and perhaps saliva (e.g. see p. 24 for schis- exposed cattle, but the ethical problems
tosomiasis in urine and p. 77 for cestodes involved with the use of live vaccines in
in faeces). humans have prevented further develop-
Conventionally, ELISA tests have used ment. Most progress has been achieved
multiwell plates to provide the solid-phase with the development of recombinant vac-
substrate on which antigen or antibody can cines, which were first used successfully
be bound, and they require spectrophoto- against larval cestodes in sheep, show
metric readouts. Recent development of the promise against gastrointestinal nematodes
dipstick technique, where reagents are in sheep and are being tested in trials for
bound to a nitrocellulose strip and coupled use against S. mansoni in humans. The lat-
with built-in controls, allows immediate ter vaccine is based on the use of recombi-
identification of a positive or negative nant glutathione-S-transferase, a molecule
response and can be used in the absence of that also has protective value against other
sophisticated laboratory equipment. A lim- schistosome species.
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8
Epidemiological Aspects of
Helminth Infections

Epidemiology may be defined as the study provides the most convenient basic unit of
of the factors influencing the occurrence study, and measurements of worm burden
and distribution of infection. In general, it (e.g. directly by counting worms in faeces
is concerned with populations rather than after chemotherapy, or indirectly, by egg
with individual cases. counts or recently by immunological esti-
Epidemiological studies serve two main mates of circulating worm antigens) can be
functions: first, they provide the necessary very important.
data for determining the medical, eco- Epidemiological studies can be divided
nomic and social importance of an infec- into two main categories. Descriptive stud-
tion, in order to evaluate and plan the ies can be used in order to determine the
effort and funds that should be devoted to frequency and intensity of infections,
it; secondly, they can help to discover the where and when they occur and what kind
relevant factors whose manipulation could of people become infected; repeated stud-
lead to prevention or control of disease. ies over a period of time (longitudinal
There have been many recent studies that cross-sectional studies) are often more use-
have provided important findings on the ful than studies at one period in time (hori-
relative importance of helminth infections zontal cross-sectional studies) and are
as causes of the morbidity discussed in the essential for determining the rate of acquir-
various sections and these are helping in ing infection (incidence).
the evaluation of the benefits (including In general, epidemiology is a quantita-
economic) of control campaigns. tive science and properly designed and
Unlike microorganisms, such as viruses, statistically valid techniques are of critical
bacteria and protozoa, in which a few importance and there should be standard-
organisms can multiply quickly and cause ization of the methods employed. Changes
serious disease, helminths are large para- in technique can often make it difficult to
sites which, in most cases, do not multiply compare older with more recent figures.
directly within the body of their hosts. For For instance, newer serological techniques
this reason the number of parasites present are often considerably more sensitive than
at any one time can be of great importance older parasitological methods (e.g. micro-
in determining the likelihood of morbidity, filarial counts compared with the
and thus helminth infections tend to be immunochromatographic (ITC) test in lym-
chronic and insidious, with increase in the phatic filariasis).
intensity of infection possible through Attempts to control or eradicate human
repeated reinfection. For microorganisms helminth infections are usually aimed at
the infected host provides the most conve- breaking the life cycle by manipulating one
nient unit of study in epidemiological sur- or more of the various transmission factors.
veys, while the individual helminth However, with a well-established endemic

252
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Epidemiological Aspects of Helminth Infections 253

parasite, this might be very difficult to 1998), although R0 will vary within the
accomplish. Helminths are almost invari- host population from one geographical
ably overdispersed or aggregated (a nega- locality to another.
tive binomial distribution) within their The search for a more quantitative
hosts, so that many hosts harbour just a expression of the factors involved in the
few parasites while a small proportion transmission of parasitic diseases has con-
(about 15% in the case of ascariasis) have tinued since Ronald Ross applied a system
heavy infections. Thus large sample sizes of differential equations (known as a math-
are necessary in order to obtain accurate ematical model) to the description of
figures of intensity of infection. malaria transmission. A model can be con-
The regulation of the abundance and structed based on the life cycle of the para-
prevalence of helminth infections is mostly site and, provided that the parasite
by density-dependent (or negative-feed- population is at equilibrium, the net repro-
back) factors in the host population or indi- ductive rate should equal unity. For
vidual host, so that herd immunity, degree instance, with the schistosomes, this rate
of input of susceptibles and fluctuations in can be expressed as the product of various
transmission rates do not tend to regulate factors:
the number of parasites present and infec-
net reproductive = (net reproductive rate
tions can be long-lived and stable. While
rate of parasite of parasite in snail
the likelihood of heavy infections is obvi-
population) 
ously affected by differences in host behav-
(probability of infecting a
iour, there is also clear evidence, at least
definitive host)  (net
for the schistosomes, that it is genetically
reproductive rate of
determined. The age of the host is often an
parasite in definitive
important factor in the occurrence and
host)  (probability of
severity of infection and age prevalence
infecting a snail)
and age intensity curves can be calculated
(see Fig. 55). Provided that figures are available in order
The basic reproductive rate or, more to calculate these various components, it
accurately, number (R0) determines the should be possible to predict the effect of
ability of the parasite to perpetuate itself. It variations in each on the overall transmis-
can be defined as the average number of sion picture. Preferably any model should
offspring (or of female offspring in the the include all the factors that have a signifi-
case of dioecious parasites) produced cant influence on transmission, even if this
throughout the lifetime of a female para- complicates the analysis.
site, which themselves achieve maturity in The transmission threshold is the level
the absence of density-dependent con- of parasite transmission, reproduction and
straints. R0 must be > 1 for the parasite to mortality rates that maintain infection and
maintain itself, while, if there were no con- below which the parasite will die out (R0 <
straints, the numbers of parasites would 1) and, by manipulation of various parame-
increase exponentially (provided R0 was > ters in the model, the effect of each on the
1). In practice, helminth populations tend likely ease of elimination of the parasite
to remain stable over time (Anderson, can be forecast.

References and Further Reading

Anderson, R.M. (1998) Epidemiology of parasitic infections. In: Cox, F.E.G., Kreier, J.P. and Wakelin,
D. (eds) Topley and Wilson’s Microbiology and Microbial Infections, 9th edn, Vol. 5. Arnold,
London, UK, pp. 39–55.
Anderson, R.M. and May, R.M. (1985) Helminth infections of humans: mathematical models, popula-
tion dynamics, and control. Advances in Parasitology 24, 1–101.
08Worms & H.D. - Chap 08 14/11/01 4:30 PM Page 254

254 Chapter 8

Bundy, D.A.P. and Medley, G.F. (1992a) Epidemiology and population dynamics of helminth infec-
tion. In: Moqbel, R. (ed.) Allergy and Immunity to Helminths: Common Mechanisms or Divergent
Pathways. Taylor and Francis, London, UK, pp. 17–37.
Bundy, D.A.P. and Medley, G.F. (1992b) Immuno-epidemiology of human geohelminthiasis: ecologi-
cal and immunological determinants of worm burden. Parasitology 104 (suppl.), S105-S110.
Giesecke, J. (1994) Modern Infectious Disease Epidemiology. Arnold, London, UK.
Woolhouse, M.E.J. (1992) On the application of mathematical models of schistosome transmission
dynamics. II. Control. Acta Tropica 50, 189–204.
09Worms & H.D. - Chap 09 14/11/01 4:30 PM Page 255

9
Helminthological Techniques

The most important laboratory techniques which are passed after eating infected liver,
in medical helminthology are those con- those of free-living or plant-parasitic nema-
cerned with the diagnosis of infection. todes, such as Heterodera, which are
Routine diagnostic techniques include the ingested in or on vegetables, and mite eggs.
recovery of eggs or larvae in faeces or, for The inexperienced operator needs to
the filarial worms, identification of micro- exercise caution in identifying helminth
filariae in blood or skin snips. eggs. Provided eggs are present and are
Immunodiagnostic methods are advanc- seen, it is usually a comparatively simple
ing at a rapid rate and are now the methods matter to recognize them for what they are.
of choice for the diagnosis of fascioliasis, However, when eggs are absent, all too fre-
cysticercosis, echinococcosis, aberrant tis- quently other objects serve as acceptable
sue helminths and lymphatic filariasis, substitutes. Particularly popular are mite
although not, as yet, for the diagnosis of eggs, starch grains, pollen grains and plant
intestinal helminths. Immunodiagnostic cells; but sometimes even air bubbles are
tests are discussed on page 250 and in the mistaken for eggs. Starch grains and plant
diagnosis sections of various helminths cells can be differentiated from eggs by
and details of relevant texts (such as Walls their lack of internal structures and by
and Schantz, 1986; Garcia and Bruckner, their irregular outlines and great size range.
1997; Garcia, 1999) are given in the general Pollen grains are more difficult to distin-
references. guish, as they appear to have an opercu-
While not strictly a helminthological lum, but they are kidney-shaped and much
technique, it is often useful to stain denser than the Clonorchis type of egg,
eosinophils and mast cells in tissues and with which they are usually confused. An
the methods of Ball and Hay or expert system has been devised for identifi-
Kermanizadeh and colleagues (see Cassella cation of helminth eggs (Esterre et al.,
and Hay, 1995) can be used. 1987).
In order to minimize mistakes, the size
of objects seen under the microscope
Faecal Examination should always be considered. As a rough
guide, an egg measures about 1/15
The eggs of helminths commonly encoun- (Clonorchis) to 1/3 (Fasciolopsis) of the
tered in the faeces of humans are shown in diameter of the microscope field at a mag-
Fig. 123 and those of rarer or spurious par- nification of 400 (40 objective and 10
asites in Fig. 124. The eggs most commonly objective).
found in spurious infections (i.e. when no Any larvae found in fresh faeces will be
adults are present) are those of the sheep those of Strongyloides (Fig. 125), but it is
liver flukes, Dicrocoelium and Fasciola, possible for larvae of hookworms to be

255
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256 Chapter 9

Fig. 123. Helminth eggs and larva commonly found in human faeces. T1. Schistosoma haematobium (in
urine); T2. S. mansoni; T3. S. japonicum; T4. Paragonimus westermani; T5. Fasciolopsis buski (egg of
Fasciola hepatica is identical); T6. Gastrodiscoides hominis; T7. Clonorchis sinensis; T8. Opisthorchis
felineus (egg of O. viverrini is identical); T9. Metagonimus yokogawai; T10. Heterophyes heterophyes;
C1. Diphyllobothrium latum; C2. Taenia saginata or T. solium ; C3. Hymenolepis nana; N1. Ascaris
lumbricoides; N2. A. lumbricoides (infertile); N3. Enterobius vermicularis; N4. Trichuris trichiura; N5.
Hookworms (eggs of Necator and Ancylostoma are identical); N6. Larva of Strongyloides stercoralis.
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Helminthological Techniques 257

Fig. 124. Rarer eggs found in human faeces. T11. Schistosoma intercalatum; T12. S. mattheei; T13.
Dicrocoelium dendriticum (often spurious from eating infected liver); C4. Dipylidium caninum egg mass;
C5. Hymenolepis diminuta; N7. Strongyloides fuelleborni; N8. Ternidens deminuta (egg of
Oesophagostomum bifurcum is similar); N9. Trichostrongylus spp.; N10. Physaloptera sp.; N11.
Aonchotheca philippinensis; N12. Gnathostoma spinigerum (rarely reaches adult stage in humans); N13.
Toxocara canis (not found in human faeces, although the similar egg of T. cati has been found a few
times); N14. Dioctophyma renale; N15. Ascaris lumbricoides (decorticated); N16. Hookworms
(embryonated as sometimes found in very old faeces); N17. Meloidogyne sp. (root-knot nematodes,
spurious infection from eating root vegetables).
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258 Chapter 9

Fig. 125. First-stage larva of Strongyloides stercoralis as found in human faeces (actual size 250 m).

present in old faeces or even adults of Sodium acetate/acetic acid/formalin

coprophilic nematodes in old stools col- (SAF) fixative can also be used for preserv-
lected from the ground. ing eggs and protozoa in faeces (sodium
Freshly passed stool specimens should acetate 1.5 g, glacial acetic acid 2.0 ml,
be collected in waxed paper or plastic stool 40% solution of formaldehyde 4.0 ml and
containers (although the latter are often distilled water 92.0 ml).
found very useful for other purposes and
not returned), using a wooden applicator,
and can be stored for a few days in the Kato–Katz cellophane thick-smear
refrigerator or preserved in 10% formalin. technique
Alternatively large numbers of samples can
be collected in sealed polyethylene tubing In this method, a faecal sample on scrap
(12.5 cm  7.6 cm  0.1 mm thickness) and paper is pressed through a small screen and,
preserved in merthiolate/iodine/formalin with a spatula, a roughly 50 mg sample of
(MIF) stain and preservative (200 ml of sieved faeces is placed on a microscope
1: 1000 merthiolate, 25 ml of 40% formalde- slide (Fig. 126a, b, c and d). For a quantita-
hyde solution, 5 ml of glycerol and 250 ml tive measurement, the faeces sample is
of distilled water; 0.15 ml of 5% Lugol’s placed on a template with a central hole
iodine can be added just before use for the over the slide, excess faeces removed with
detection of protozoal cysts (great care the spatula and the template carefully
should be taken with formaldehyde as it is removed, leaving a cylinder of faeces (Fig.
an irritant and can be carcinogenic). The 126e). The template should be 1 mm thick,
simplest method for the detection of eggs is with a hole of 9 mm, which will deliver 50
direct microscopical examination of a smear mg of faeces, and it can be made of metal,
of about 5 mg of faeces, diluted with freshly plastic or cardboard; many should be made.
filtered tap water or saline, on a slide cov- A cellophane square (obtainable from ciga-
ered with a coverslip. rette packets, etc.) measuring 25 mm  30
The use of small disposable polyethylene or 35 mm which has been soaked in a mix-
envelopes 7 cm  4 cm  0.03 mm thick and ture of 100 ml glycerine, 100 ml of distilled
a single microscope slide has been advocated water and 1 ml of 3% aqueous malachite
for mass surveys to save expense of slides green or 3% methylene blue is placed over
and coverslips. With this method a larger it as a coverslip (Fig. 126f and g). The micro-
100 mg sample can be smeared. However, scope slide can be turned over and pressed
these direct methods are not very sensitive. against a hard surface until newsprint can
09Worms & H.D. - Chap 09 14/11/01 4:30 PM Page 259

Helminthological Techniques 259

Fig. 126. Illustrations of Kato–Katz technique: (a) Equipment, (b) Strips of hydrophilic cellophane and a
jar with lid, (c, d, e, f, g. and h). Pressing faeces through sieve so that an amount above sieve can be put
into template, covered with cellophane and compressed so that a newspaper can be read through it.

be read through the faecal sample (Fig. ful for measuring the intensity of an infec-
126h); alternatively, a rubber bung can be tion because so many eggs may be present
used. Carefully remove the slide by gently in a sample that they cannot be easily
sliding it sideways and leaving it for 20–30 counted.
min at 37°C or 1 h at room temperature for
the faeces to clear progressively. Hookworm
Formol–ether technique
eggs clear first and will not be visible by 2 h,
while Ascaris, Trichuris and schistosome The advantage of this method is that it is
eggs will still be visible weeks or even quick and can be used to search for proto-
months later. The slide can be turned over zoal cysts and Strongyloides larvae, as well
on to filter-paper to prevent drying tem- as helminth eggs. Using an applicator stick,
porarily. In a modification to allow almost 1 or 2 g of faeces is emulsified in a cen-
immediate observation and long storage, a trifuge tube with 10 ml of 10% formalin.
mixture of 100 ml polyethylene glycol, The suspension is then passed through a
100 ml formalin and 200 ml saturated saline metal or plastic sieve (400 µm mesh) or
(plus 2 ml colour, as above, if desired) can two layers of gauze (for single use) into a
be substituted. beaker, evaporating dish or another cen-
The smear should be examined in a sys- trifuge tube. Replace into another cen-
tematic manner and the number of eggs of trifuge tube (if necessary). Add more 10%
each species recorded. Multiply by 20 to formalin to bring up to 10 ml again, and
give eggs per gram. (A hole of 6.5 mm in a 3 ml of ether or ethyl acetate (or even
0.5 mm thick template will give a sample petroleum, if the others are unavailable).
size of 20 mg, which should be multiplied Ether is very volatile and can explode in
by 50. This has the advantage that clearing the refrigerator so great care is needed. The
time is reduced to 15 min.) Naturally, if tube is then stoppered and shaken vigor-
quantitative measurements are not ously for at least 30 s. It is then centrifuged
required, the template is unnecessary. at 300–500 r.p.m. for 1–3 min until there
are four layers: a top layer of ether or ethyl
acetate, a second layer consisting of a fatty
Concentration methods deposit, a third layer of formalin and a
small deposit containing the eggs at the
Concentration methods are useful for bottom. The fatty deposit at the interface of
prevalence surveys, but are not always use- the liquids is loosened with a glass rod and
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260 Chapter 9

the centrifuge tube quickly inverted at an its volume of tap water, using a pestle and
angle of 45° to the ground so that the liq- mortar.
uids run out (Fig. 127). Drops of water from 2. About 10 ml is strained through a gauze
a tap can be run down the glass tube while or sieve (350 µm pore size) into a round-
the debris is being cleaned off from the bottomed centrifuge tube.
tube with the rod (the liquid from many 3. After centrifugation for 1 min the super-
samples can be poured into a small beaker, natant is discarded and 2–3 ml of water
centrifuged and the ether recovered and added. After breaking up the deposit by
used again if in short supply). Some water tapping the bottom of the tube, more water
will run up the rod by capillary action and is added to fill the tube.
the deposit at the bottom of the tube is 4. The previous step is repeated until the
shaken and an aliquot removed with a supernatant is clear.
Pasteur pipette when the tube is upright 5. The last supernatant is poured off and
and placed on a microscope slide, covered 2–3 ml of 33% zinc sulphate (or saturated
with a large coverslip and examined using salt solution) added. The sediment is broken
a 10 objective. If there is no tap handy, up by tapping the tube and then this is filled
the debris at the interface can be loosened with more of the zinc sulphate solution.
with an applicator stick and the contents of 6. The tube is centrifuged rapidly for 1
the tube carefully poured away, allowing min and brought to a stop.
one or two drops to return to the bottom. 7. A loopful of the material floating on the
For protozoal cysts, a drop of 1% Lugol’s surface is taken up and placed on a slide
iodine, or Sergeaunt’s stain for amoebae, for examination. The loop should be about
can be added and the sample examined 6 mm in diameter and of wire that is stiff
under a higher power. enough not to bend in routine handling.
The loop is bent at right angles to the wire
and must not be dipped below the surface
Zinc sulphate centrifugal flotation method
of the liquid.
This method is not suitable for trematode
or Diphyllobothrium eggs, as they become
very distorted. Quantitative techniques in faecal
examinations
1. A faecal suspension is made by emulsi-
fying 5–10 g of faeces with about ten times
For the schistosomes and most of the
intestinal nematodes, figures have been
given of the average egg production per
female per 24 h. Thus, in theory at least, by
estimating the number of eggs in the faeces,
a measure of the number of adults present
can be obtained. An estimate of the number
of worms present can be of importance in
determining the success of chemotherapy
and in epidemiological studies. The most
commonly used quantitative egg-counting
techniques are given below.

Kato–Katz and formol–ether techniques

Kato–Katz can detect as few as 100 eggs g1
of faeces and is now regarded as the stan-
Fig. 127. Running supernatant off down a glass dard. As is true for all such methods, it
rod, leaving sediment behind at bottom of centri- assumes that eggs are randomly dispersed
fuge tube (a conical tube is often used). in the faeces, which appears to be true in
09Worms & H.D. - Chap 09 14/11/01 4:30 PM Page 261

Helminthological Techniques 261

most cases; allowance could be made for However, it is not suitable for less than
the state of the faeces, as shown below for about 200 eggs g1 of faeces.
the Stoll method, but this is not usually
done. The formol–ether method can be 1. Add 0.1 N sodium hydroxide solution
used as a semi-quantitative estimate and up to the 56 ml mark in a Stoll diluting
has the advantage that it is quick, many flask. The diluting flask is made from a
samples being treated simultaneously, and Ehrlenmeyer flask with a neck of 20 mm
that it also picks up protozoal cysts. The diameter glass tube fused on the top and
faecal sample size should be 0.2 g and all graduated at 56 and 60 ml (Fig. 129). They
the deposit counted (or a specified number are closed with a rubber stopper.
of drops of the total in the pipette). Fig. 128 2. Faeces is carefully added with an appli-
shows good correlation between the two cator stick until the meniscus has been dis-
techniques. placed to the 60 ml mark. For greater
accuracy 4 g of faeces can be weighed out.
3. A few glass beads are added, a rubber
The Stoll dilution egg-counting technique
stopper inserted and the flask well shaken.
The method was originally devised in 1926 It is set aside for several hours preferably
for the study of hookworm infection and is overnight, and then shaken again to thor-
still one of the best available today. oughly comminute the specimen.

is
ris ur
sc
a ich
4 A Tr
Log no. of eggs g–1 (Kato)

tor
ca
Ne
3

1
Occ. Light Mod. Heavy V. heavy
0 1 2 3 4 5
Estimate (formol/ether)

Fig. 128. Comparison of eggs per gram (e.p.g.) of faeces as determined by Kato–Katz technique and
estimate by formol–ether method on the same 40 faecal samples (occasional = 1–500 e.p.g.; light =
501–2500; moderate = 2501–10,000; heavy = 10,001–20,000; very heavy = 20,000 +). The good
correlation shows that a quick approximate procedure is likely to be satisfactory in many surveys.
09Worms & H.D. - Chap 09 14/11/01 4:30 PM Page 262

262 Chapter 9

4. The flask is shaken well to resuspend is therefore 0.15 cm3. It is used principally
the specimen and 0.075 ml removed with a in veterinary studies and is not suitable for
wide-bore Pasteur pipette graduated at this heavy eggs such as those of Fasciola.
level. This must be done with one squeeze
1. 2 g of the well-mixed faecal sample is
of the bulb to prevent loss of eggs.
weighed out and placed in a glass jar con-
5. The drop is expelled on to a microscope
taining a few glass beads. Alternatively, a
slide and covered with a 22 mm  40 mm
pestle and mortar can be used to mix the
coverslip. All the eggs in the preparation are
faeces.
counted, using a low-powered objective. It
2. 58 ml of a saturated salt solution (or a
is desirable to count several drops to obtain
40% sugar solution or a 33% salt solution)
an average count from each specimen.
is added and the faeces mixed to form a
6. The stool samples can be classified as
smooth emulsion.
formed (F), soft formed (SF), mushy (M) or
3. The suspension is passed through a
diarrhoeic (D) and the egg counts multi-
400 µm metal or plastic sieve or gauze and
plied by the following factors – SF  1,
a sample removed with a wide-bore
M  2 and D  3 – to compensate for the
Pasteur pipette.
amount of fluid in these types of specimen.
4. The suspension is run into the counting
The results are multiplied by 200 for
chamber, which is then set aside for 1–2
expression as eggs per gram. Also 24 h fae-
min to allow the eggs to float to the surface.
cal samples can be weighed and the total
5. The eggs come to rest against the under-
output per 24 h obtained.
surface of the top slide and are in the same
focal plane as the two ruled areas. They are
McMaster counting chamber counted using a low-power objective.
The chamber is commercially available and
consists of two glass slides kept 1.5 mm
Macdonald pipette
apart by glass bridges at the ends and in
the centre. A 1 cm2 square is ruled on the This is an extremely rapid and simple field
underside of the top slide of the two cham- procedure provided there is a glass-blower
bers. The volume beneath each ruled area who can make lots of the special pipettes
(Fig. 130).
Five grams of faeces are weighed out and
45 ml of tap water measured out. The faeces
is mixed with some of the water in a pestle
and mortar, transferred to a closable jar and
washed out with more water. The total vol-
ume is made up to 45 ml, the jar closed and
shaken vigorously and 0.1 ml samples are
withdrawn using a Macdonald pipette and
examined on a microscope slide under low
power. The mean figure is multiplied by
100 to give eggs per gram. With freshly
passed faeces the pestle and mortar can be
replaced by shaking with 45 ml of water
and some glass beads.

Diagnosis of Larvae in Human Faeces

by Culturing to the Infective Stage

It is necessary to culture larvae to the infec-

Fig. 129. Stoll flask. tive third stage before a differential diagno-
09Worms & H.D. - Chap 09 14/11/01 4:30 PM Page 263

Helminthological Techniques 263

6. The tube can be placed in water at 50°C

for about 15 min in order to kill the larvae
without distorting them.
7. When cool, the tubes are shaken and the
contents transferred to a centrifuge tube,
which is spun gently for 2 min.
8. The supernatant is pipetted off and the
sediment examined on a microscope slide,
using a coverslip.
Alternative methods for Strongyloides lar-
vae are given on p. 121 and the differential
features used in identification are shown in
Table 9 (p. 131).

Methods in Filariasis

Staining of microfilariae

Wet preparations made from a drop of

blood under a coverslip can first be exam-
ined for the presence of microfilariae under
the microscope and are easily seen moving
Fig. 130. Macdonald pipette. under the low power (100 magnification).
This method avoids the lengthy process of
staining negative material, but many light
sis of hookworm species (and possibly infections will be missed.
Oesophagostomum, Ternidens and
Trichostrongylus in some areas) can be
Method A: Giemsa
made. A simple method of accomplishing
this is the Harada–Mori test-tube filter- There are various Romanowsky stains that
paper method. may be used for staining blood parasites
(Wright, Leishman and May-Grunwald), but
1. Test tubes are filled with 7 ml of dis-
Giemsa is one of the best for microfilariae.
tilled water and placed in a rack.
The sheaths of Loa loa microfilariae
2. About 0.5 g of the fresh faecal sample is
never stain by this method. The sheaths of
smeared along the length of a strip of filter-
Wuchereria stain faintly, while those of
paper (15 cm  1.5 cm) creased longitudi-
Brugia malayi stain an intense pink
nally, leaving 5 cm clear at one end. The
colour.
strip is placed in the test-tube with the
unsmeared portion reaching to the bottom 1. A large drop of blood (20 mm3 ) from a
of the tube. Sahli-type pipette is spread out to form a
3. The top of each is covered with a cello- thick smear (25 mm  7 mm) on a grease-
phane strip, held in place by a rubber band free microscope slide by means of a needle.
and the rack of tubes incubated at 28°C for 2. The smear is dried overnight (be careful
10 days. of cockroaches and ants in the tropics),
4. The top and filter-paper are removed with dehaemoglobinized in distilled water for
forceps and both destroyed (use caution in about 2 min and, when completely colour-
handling as the larvae are now infective). less, left to dry.
5. The larvae will be in the water at the 3. The smear is preserved with absolute or
bottom of the tube and can be seen with methyl alcohol by flushing for 30 s and
the aid of a magnifying glass. allowed to dry.
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264 Chapter 9

4. Ten drops of concentrated Giemsa stain Microfilarial counting techniques

are added to 10 ml of distilled water (pH
7.2) and placed into a staining dish. The 1. For quantitative studies, 20 mm3 of blood
blood film is left in the stain for 30 min. can be taken in a haemoglobin pipette to
5. The slide is removed from the stain, make a thick film, stained as above and the
flushed briefly and very gently under run- result expressed in microfilariae per millil-
ning water and left to dry. itre of blood. However, this is time-consum-
6. When completely dry, the film can be ing and a proportion of microfilariae are lost
mounted in a neutral mounting medium during the staining procedure.
(DPX or euparol) with a cover glass. 2. One of the simplest and most sensitive
methods of detecting microfilariae (down
to one microfilaria 100 mm3) is to mix a
Method B: haematoxylin measured quantity of blood with about ten
times its volume of distilled water in a sim-
1. A thick drop made from peripheral
ple slide counting chamber and then to
blood is spread over an area of about 2 cm2
examine immediately. The chamber can be
on a microscope slide and allowed to dry in
made by sticking thin strips of a glass slide
air, preferably overnight. (For special pur-
with an adhesive to form a rectangle on
poses or if it is necessary to measure micro-
another slide at about 30 magnification. It
filariae, a sequestrinated blood film can be is difficult to identify microfilariae by this
left in a humid chamber overnight at 10°C method and, if necessary, stained prepara-
and then left to dry. Alternatively, a thin tions may need to be made as well.
smear can be fixed while wet in three parts 3. If very few microfilariae are expected, as
of methyl alcohol to one part of glacial in cases of amicrofilaraemic filariasis,
acetic acid.) It is important when reporting 1–10 ml of blood can be filtered through a
measurements of microfilariae to state the Nuclepore or Millipore membrane filter
method of preparation and fixation. (pore size 5 µm) fitted to a hypodermic
2. The smear is dehaemoglobinized in tap syringe by a Swinney adaptor and the mem-
water and again dried. It is then fixed for a brane examined either fresh or stained as
few minutes in methanol or absolute alco- above. Using the Nuclepore membrane
hol (fixed smears can be stored for (General Electric Company, Pleasanton,
months). California), sequestrinated or citrated blood
3. When dry, the slide is stained with hot is passed through the filter on a syringe, fol-
haematoxylin (Mayer, Delafield, Ehrlich or lowed by 0.85% saline solution. Finally, air
Harris). The staining time is variable, is passed through to partially dry the mem-
depending on the batch of stain and on the brane, which can be examined directly
age of the film, but 10–15 min is usually under a coverslip using 50–70 magnifica-
sufficient. tion, or fixed in methanol, stained in hot
4. The slide is rinsed in tap water and haematoxylin, blued, dried and a drop of
examined under the low power of a micro- chloroform added in order to make the
scope. If understained, more hot haema- membrane transparent before viewing. This
toxylin can be applied and, if overstained, method can detect microfilariae in a con-
the slide can be differentiated in acid alco- centration 1/50 that of a thick film.
hol (1% hydrochloric acid in 70% alcohol). 4. Knott’s concentration technique has
It is better to slightly overstain and then been widely used for the last 60 years but is
differentiate as this removes the blue back- not as sensitive as the previous techniques.
ground from the film. In a quick modification, 1 ml of blood is
5. The slide is blued in tap water (add lysed with 10 ml of 1% formalin in a cen-
drop of ammonia if not alkaline) for 15 min trifuge tube, centrifuged at 500 g for 1 min
and allowed to dry. and the supernatant poured off. The sedi-
6. The slide can be mounted in a neutral ment is then spread out on microscope
resin mountant. slides and dried and stained as above.
09Worms & H.D. - Chap 09 14/11/01 4:30 PM Page 265

Helminthological Techniques 265

5. Another modification of the Knott tech- 3. About 1 ml is run into a Syracuse

nique involves spinning in QBC® tubes watch-glass (these can be made by a glass-
and examining the buffy layer under fluo- blower by pressing in the end of a heated
rescent light (Bawden et al., 1994). test tube and cutting the end off) and
examined for larvae under a stereoscopic
microscope.
Staining of filarial larvae in insects before 4. Most of the saline is removed with a
dissection Pasteur pipette under the microscope and
replaced by fixative. TAF (7 ml of 10% for-
1. Insects are killed and identified and malin, 2 ml of triethanomaine and 2 ml of
placed in 80% alcohol, where they can be distilled water) is excellent but 70% alco-
kept indefinitely. hol containing 10% glycerol can be used.
2. They are taken through descending Fixation is for 5 min.
dilutions of alcohol to distilled water and 5. Fixative is removed with a fine pipette
are then stained for 3 days at room temper- and replaced by 96% alcohol containing
ature in Mayer’s acid haemalum stain. 5% glycerol and the watch-glass is left in
3. Insects are removed and differentiated an incubator for 30 min at 37°C (or
in distilled water for 3 days. They are then overnight at room temperature) until only
stored in glycerol until required for dissec- pure glycerol is left. Larvae can be stained
tion; 100–200 mosquitoes can be stored in with new fast blue R or examined when
a McCartney bottle. mounted under phase contrast.
4. Insects are dissected under the stereo- 6. Larvae are transferred with a mounted
scopic microscope (35 magnification) by cat’s whisker to a small drop of anhydrous
reflected light, using fine needles. All glycerol on a clean 22 mm square cover-
stages of developing larvae are stained and slip. Excess glycerol is removed with a
can be easily detected. very fine pipette, leaving only a smear.
5. Larvae should be mounted in glycerol 7. The coverslip is turned over on to a cav-
for detailed morphological study. ity slide and sealed around and under the
edge with mounting medium. For cheap-
Technique for mass dissection of filarial ness, three short pieces of glass wool can
vectors and mounting of filarial larvae be used instead of using a cavity slide or a
obtained small chamber can be made.
Caution needs to be exercised when this
1. Insects are immobilized by cold or by a technique is used for Onchocerca volvulus
pyrethrum spray and then sorted into sepa- in Simulium as larvae may be of the morpho-
rate species. All females of one species are logically indistinguishable O. ochengi.
crushed by gently rolling with a test-tube
on a glass or Perspex plate in physiological
saline. This is repeated for each species Preservation and Examination of
separately. Adult Helminths
2. Insects are transferred to sieves (bolting
silk with a pore size of 50 µm is suitable), Before fixing, specimens should preferably
glued across the bottom of the top half of a be washed in 0.85% saline.
cut plastic cup and suspended in a
clamped glass funnel containing physiolog-
ical saline. Care must be taken that there Trematodes and cestodes
are no air bubbles below the sieve. Each
sieve is left for 3 h at room temperature For examining the various organ systems in
(the procedure can also be used for obtain- whole mounts of these organisms, some
ing larvae for infection experiments, when degree of flattening is usually necessary
a tissue culture medium should be used, but, as this causes distortion, material
with incubation at 37°C). should also be fixed unflattened for
09Worms & H.D. - Chap 09 14/11/01 4:30 PM Page 266

266 Chapter 9

subsequent sectioning. Extension of trema- Carmine 17 g

todes can be obtained by constant shaking Distilled water 200 g
and of cestodes by suspension or by wind-
These should be gently heated in a large
ing around a test-tube, while fixing in hot
flask, as the mixture is liable to froth when
5–10% formalin.
boiling. The mixture is boiled until the
colour changes from the bright red of the
Staining trematodes or tapeworm segments carmine to a deep red colour. When cool,
20 ml of glacial acid is added. For use the
METHOD
stain is diluted to a rose-pink colour (1 in 5
1. The trematode or proglottides should be
to 1 in 10).
flattened between glass microscope slides
held at the ends with rubber bands or, for
smaller specimens, with a dab of petro- Nematodes
leum jelly at each end of the slide. They
are fixed in 80% alcohol or 10% formol If possible, nematodes should be looked at
saline (a few drops of acetic acid added to alive and measurements made; small speci-
either of these fixatives improves the stain- mens can often be immobilized by adding a
ing) or Carnoy’s fixative. drop of propylene phenoxetol or tetramisole.
2. The flattened specimen is taken from
between the slides when fixed and
Fixation
immersed in the diluted aceto alum carmine
stain in a small glass dish. The staining time 1. Hot 70% alcohol with constant shaking.
depends in each case on the size of the spec- Simple and usually satisfactory.
imen – from 20–30 min for a small trema- 2. Hot formol–acetic 4:1 (formalin 40% 10
tode to several hours for larger specimens. ml; glacial acetic acid 1 ml; distilled water
3. Specimens are washed in 50% alcohol up to 100 ml) over a boiling water-bath.
to remove excess stain and examined 3. TAF (formalin 40% 7 ml; triethanolamine
under the microscope. 2 ml; distilled water to 100 ml). Hygroscopic
4. If understained the specimen can be so prevents drying of specimens.
returned to the stain, and if overstained it
can be differentiated in acid alcohol (100 ml Storage
70% alcohol and 2 ml hydrochloric acid).
5. When stained, the specimen is washed Storing in 70% alcohol with 10% glycerol
well in water to remove acid, dehydrated in or pure glycerol will prevent drying up;
several changes of alcohol, cleared in beech- 10% formalin is not as satisfactory, as
wood creosote and mounted in Canada bal- specimens go mushy after a time.
sam or another mounting medium.
Mounting
RESULT
The internal structures of the specimens 1. Temporary (these mounts are probably
are stained in precise shades of red against the most satisfactory).
a clear to pink background of the connec- (a) Glycerine. Worms are left overnight in
tive tissues. a partly opened Petri dish or solid watch
glass in 70% alcohol plus 10% glycerol in
The above technique may be carried out an oven at about 40°C, mounted in pure
using alum haematoxylin instead of the glycerol and returned to the bottle after
carmine. Ehrlich’s haematoxylin diluted examination. Specimens can be turned
with an equal volume of water has proved over for examination of all sides and exam-
satisfactory for this method. ined under phase contrast.
(b) Lactophenol. Some lactophenol is added
ACETO ALUM CARMINE STAIN
to the specimen in 70% alcohol and slowly
Boil together: replaced with pure lactophenol over a few
Potassium aluminium sulphate 27 g hours until specimen clears (hot lactophenol
09Worms & H.D. - Chap 09 14/11/01 4:30 PM Page 267

Helminthological Techniques 267

at 65°C may be used for rapid clearing). 2) should be consulted in order to under-
Worms are replaced in 70% alcohol after stand which organs will be present in
examination. cross-sections cut at different levels (there
2. Permanent. is some variation in different species, par-
(a) Mounts are made in Canada balsam or ticularly in the relative positions of the
DPX after dehydration slowly through alco- ovaries and testes).
hols and xylene. Specimens can be stained If the organism in the tissues is dead
with haematoxylin if desired; however, the and surrounded by a host reaction, then
results often leave much to be desired identification is more difficult. However, a
because of distortion. parasite can usually be identified as a
(b) Specimens are transferred to polyvinyl platyhelminth or nematode even if no
lactophenol from lactophenol. However, organs are recognizable.
specimens go on clearing until completely
transparent. Cotton blue can be dissolved
in the polyvinyl lactophenol for staining. Cestodes
(c) Glycerine. A tiny drop of glycerol on a
coverslip with a cavity slide is used for lar- Larval cestodes in humans may be found in
vae, and ringed slides for adults. Results any tissue. The most important larvae
are good but the preparations are rather encountered in sections are the hollow
fragile. cysts of taeniid tapeworms, which include
(d) Glycerine jelly. A tiny warmed drop on the cysticercus of Taenia solium, the coenu-
a coverslip is used for en face mounts of rus of Multiceps spp. and the hydatid of
the anterior end on a cavity slide Echinococcus spp. In sections the proto-
(Aquamount needs no heat). scolex (or protoscolices) will usually show
clearly demarcated suckers and possibly
hooks (the latter are birefringent and show
Recognition of Helminths in Sections up well under a polarizing microscope).
The characteristic structure of each type of
Before a tentative diagnosis is made of pos- cyst can be seen from Fig. 32. Two solid lar-
sible helminth material seen in a section, it vae may also be found in tissues (ignoring
is important that the size of the specimen the cysticercoid of Hymenolepis nana,
is considered. It is useful first to look at the which occurs only in the villi of the ileum):
slide against the light before placing it on the tetrathyridium of Meocestoides and the
the microscope stage; the cysticercus larva sparganum (plerocercoid) of Spirometra.
of Taenia, for instance, can often be recog- These may show few diagnostic features,
nized in this way. but the former have many large calcareous
The descriptions given below are based corpuscles and perhaps suckers and the lat-
on sections stained in haematoxylin and ter the circular muscles which separate the
eosin. parenchyma into inner and outer zones,
typical also of adult tapeworms.

Trematodes
Nematodes
In sections of living trematodes an outer
tegument, often with spines, is always pre- Adults encountered in sections can usually
sent. Depending on the region of the worm be easily recognized as belonging to the
cut through, one or more of the following phylum. In cross-section they are seen to
organs should also be seen embedded in a have an outer acellular cuticle, enclosing a
loose ground tissue (parenchyma): vitel- thin hypodermis layer, which often con-
laria; gut caeca (usually double); ovaries; sists of longitudinal cords that separate the
testes; suckers; uterus, probably filled with somatic muscles into longitudinal fields
eggs. The diagram of a complete fluke (Fig. and contain the excretory canals (when
09Worms & H.D. - Chap 09 14/11/01 4:30 PM Page 268

268 Chapter 9

present). The number and form of the mus- the tissues are filariae; females of non-
cle cells are an important feature in deter- human species are usually not fertilized but
mining to which order a specimen belongs. have the double uterus typical of the group.
The gut is separated from the outer layers A key for differentiating the larvae of
by a body cavity (pseudocoel). Ascaris, Toxocara, Necator, Ancylostoma
The characteristic structures seen in and Strongyloides in tissue sections can be
cross-sections of the various groups of made based on their relative diameters, the
nematodes are shown in Fig. 131. The most structure of the excretory cells and the pres-
common adult nematodes recovered from ence or absence of lateral alae.

Fig. 131. Cross-sections of females belonging to the various groups of nematodes. The dorsal and
ventral cords are not shown (Trichocephalus = Trichuris).
09Worms & H.D. - Chap 09 14/11/01 4:30 PM Page 269

Helminthological Techniques 269

Identification Key for Sections of 4. A. Lateral alae present. Vagina long and
Nematodes muscular. Oesophagus has posterior
bulb. Many eggs in uterus. Excretory
1. A. Hypodermal cords few to many gland cells absent. Enterobius
arranged asymmetrically. Lateral excre-
tory canals absent. In the ovaries and B. Lateral alae absent. Vagina very short.
testes the germinal region extends the Ova large. Ovoviviparous, with eggs
entire length of the gonad and gametes developing into larvae. Excretory cells
at various stages of development can be single or paired. Very small and often lar-
found at any level. Oesophagus non- vae (or eggs) in tissues. Strongyloides
muscular. TRICHURIDS
5. A. Somatic musculature divided by
(Aonchotheca, Calodium, Eucoleus,
large lateral cords (often very wide and
Trichinella, Trichuris)
flattened) into two crescent-shaped
B. Hypodermal cords 2–4 arranged sym- fields. 6
metrically. Excretory canals in lateral
cords except at extremities. In the B. Somatic musculature divided into
ovaries and testes the germinal region four fields. 7
confined to proximal extremity of gonad
and gametes at uniform stage of develop- 6. A. Females have double uterus often
ment at any one level. 2 containing microfilariae. Diameter less
than 0.5 mm. FILARIIDS
2. A. Intestine composed of a few large (Brugia, Dirofilaria, Loa, Mansonella,
multinucleate cells rarely with more Wuchereria)
than two cells in a cross-section.
Anterior paired excretory gland cells B. Females with single uterus contain-
present. STRONGYLIDS ing larvae with long pointed tails.
(hookworms, trichostrongyles, Diameter more than 1 mm. Dracunculus
Oesophagostomum, Ternidens)
7. A. Lateral cords very large, stalked and
B. Intestine composed of few to many project into body cavity; frequently
small uninucleate cells. Excretory unequal in size. SPIRURUDS
glands single, paired or absent. 3 (Gnathostoma, Thelazia)
3. A. Somatic muscle cells few, large and
B. Lateral cords large and project into
flat. Lateral alae present or absent. 4
body cavity but not stalked; usually
B. Somatic muscle cells many, U- unequal in size . ASCARIDS
shaped in cross-section. Lateral alae (Anisakis, Ascaris, Toxascaris,
usually absent. 5 Toxocara)

References and Further Reading

Ash, L.R. and Orihel, T.C. (1991) Parasites: a Guide to Laboratory Procedures and Identification.
ASCP Press, Chicago, USA.
Bawden, M., Slaten, D. and Malone, J. (1994) QBC®: rapid filaria diagnoses from blood. Mansonella
ozzardi and Wuchereria bancrofti. Transactions of the Royal Society of Tropical Medicine and
Hygiene 88, 66.
Cassella, J.P. and Hay, J. (1995) Tissue eosinophil and mast cell staining in helminth infections.
Parasitology Today 11, 464–465.
Chitwood, M.B. and Lichtenfels, J.R. (1972) Identification of parasitic metazoa in tissue sections.
Journal of Parasitology 32, 407–519.
Esterre, P., Vignes, R. and Lebbe, J. (1987) Identification assistée par ordinateur de principaux oeufs
d’helminthes en coprologie humaine. Bulletin de la Société Française de Parasitologie 5, 241–244.
09Worms & H.D. - Chap 09 14/11/01 4:30 PM Page 270

270 Chapter 9

Gillespie, S.H. and Hawkey, P.M. (eds) (1995) Medical Parasitology: a Practical Approach. IRL Press,
Oxford, UK.
Petithory, J.C. and Ardoin-Guidon, F. (1995) Parasitologie: vrais et faux parasites en coprologie
microscopique. Cahier de Formation – Biologie Médicale no. 3. Bioforma, Paris, France.
Price, D.L. (1993) Procedure Manual for the Diagnosis of Intestinal Parasites. CRC Press, Boca Raton,
USA.
WHO (1991) Basic Laboratory Methods in Medical Parasitology. World Health Organization, Geneva,
Switzerland.
10W. & H.D. - Appendix 1 14/11/01 4:30 PM Page 271

Appendix 1
Summary of Some Landmarks in
Medical Helminthology

1500 BC Ebers papyrus possibly described various helminth diseases.

400 BC–AD 1200 Taenia, Ascaris, Enterobius and Dracunculus described in Greek,
Roman, Arabic and Chinese writings.
AD 1379 Jehan de Brie illustrated Fasciola hepatica from sheep.
1674 Textbook by Velschius on Dracunculus.
1684 Redi described many new helminths from domestic and wild animals.
1700 Textbook by Andry on human helminths.
1835 Paget discovered larval Trichinella spiralis in a man, which was described
by Owen.
1845 Dujardin elucidated the relationship between adult and cycticercus of
Taenia saginata.
1851 Küchenmeister, Van Beneden, etc. described the life cycle of Taenia solium.
1851 Adult Schistosoma haematobium were found in the vesical veins by
Bilharz in Cairo.
1852 Life cycle of Echinococcus granulosus determined by Von Siebold.
1857–1898 Textbooks by Küchenmeister (1857), Davaine (1860), Cobbold (1864),
Leuckart (1867) and Manson (1898).
1865 The life cycle of Enterobius was worked out by Leuckart.
1870 Fedchenko observed larval development of Dracunculus in Cyclops.
1876 Adult Wuchereria bancrofti found in lymph glands by Bancroft; surpris-
ingly in Australia.
1878 Life cycle of Wuchereria bancrofti shown to involve mosquito by Manson.
1882–1883 Leuckart and Thomas showed that the life cycle of Fasciola hepatica
involves a snail.
1887 Hymenolepis nana shown not to need an intermediate host by Grassi
and Rovelli.
1896 Looss demonstrated the active penetration of hookworm larvae through
the skin (by accidentally infecting himself).
1897 Eosinophilia first associated with Trichinella spiralis infection by Brown.
1900 W. bancrofti infective larvae shown to enter through the puncture
wound of mosquito by Low.
1901–1913 Weinland’s studies on Ascaris biochemistry and physiology.
1904 Adult Schistosoma japonicum found by Katsurada.
1907 Schistosoma mansoni differentiated from S. haematobium by Sambon.
1909 Rockefeller Sanitary Commision established to combat hookworm disease.
1911 An intradermal test for the diagnosis of hydatid disease described by
Casoni.

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272 Appendix 1

1912 Complement fixation test used for diagnosis of Trichinella.

1911–1919 Role of snail and fish in the transmission of Clonorchis and of snail and
crab in that of Paragonimus determined in Japan.
1913 Life cycle of S. japonicum involving snail discovered by Miyagawa.
1914–1921 Life cycle of Loa loa involving Chrysops shown by Leiper, Kleine and Connal.
1915 Leiper elucidated the life cycle of S. haematobium.
1918 Connection between blindness and onchocerciasis recognized by
Pacheco-Luna and Robles in Guatemala.
Antimony tartrate advocated for treatment of schistosomiasis by
Cristopherson.
1918 Life cycle of Diphyllobothrium latum determined by Rosen and Janicki.
1920 Chandler suggested copper sulphate for the control of snail intermediate
hosts of trematodes.
1921 Migration of Ascaris larvae through body discovered by Koino and Koino.
Life cycle of Fasciolopsis buski worked out by Nagagawa.
1926 The vector of Onchocerca volvulus shown to be Simulium by Blacklock.
1927 Brug found microfilariae of Brugia malayi in blood.
1928 Stoll described ‘self-cure’ phenomenon in gastrointestinal nematodes of
domestic stock.
1929 Faust’s Human Helminthology published.
1930s–1950s Work of Culbertson, Taliaferro, Vogel and Minning on mechanisms of
immunity to helminth infections.
1932 Löffler described pulmonary lesions and eosinophilia due to larval
migration of Ascaris.
1934 Development of Mansonella in Culicoides shown by Buckley.
1947 Diethylcarbamazine (DEC) first used in treatment of filariasis.
1951 Piperazine used for treatment of Ascaris and Enterobius.
Role of Angiostrongylus cantonensis in causation of eosinophilic menin-
gitis elucidated by Alicata and by Rosen and coworkers.
1952 Importance of Toxocara larvae in visceral larva migrans shown by Beaver.
1954 Onchocerciasis eradicated from Kenya by McMahon.
Increasing use of new synthetic insecticides (chlorinated hydrocarbons
and organophosphates) in control of filariasis.
Discovery of new synthetic molluscicides for the control of schistosomiasis.
1956 Work by Buckley and Edeson on tropical pulmonary eosinophilia and
zoonotic aspects of Brugia infection (genus Brugia erected by Buckley in
1959).
1964 Discovery of intestinal capillariasis in the Philippines.
1971 Discovery of abdominal capillariasis in Costa Rica.
For a much fuller account the book by Grove (1990) (see p. 284) should be consulted.
It is not always easy to assess the importance of recent work but some of the most
notable advances in medical helminthology have been in the fields of immunity, immuno-
diagnosis and immunopathology, the search for human vaccines, the action of broad-
action anthelminthics, such as praziquantel, the benzimidazoles and ivermectin, the
importance of strain differences in many human helminths, such as Echinococcus,
Trichinella and Onchocerca, the epidemiology and medical importance of soil-transmit-
ted nematodes, molecular biology, including the sequencing of the complete genome of
the free-living nematode Caenorhabditis elegans, and the global control campaigns,
whether under way or envisaged, for onchocerciasis, dracunculiasis, lymphatic filariasis,
schistosomiasis and geohelminths.
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Appendix 2
Glossary of Helminthological Terms

These terms should be regarded as explanations rather than as strict definitions and do
not necessarily apply to all other helminths not found in humans.

aberrant parasite A parasite that is never (e.g. Strongyloides, Aonchotheca and

transmitted between humans and which Hymenolepis nana).
develops abnormally in humans (e.g. carrier A host that harbours a particular
Echinococcus multilocularis, Parastrongylus, pathogen without manifestations of disease.
Toxocara). caudal bursa (= bursa copulatrix)
accidental parasite One that is not usually Umbrella-like expansion of the caudal end
transmitted between humans but which of the male in strongylid nematodes, used
develops in a similar manner to that in its to clasp the female when mating.
normal host (e.g. Fasciola, Dipylidium, cercaria The free-living larva, usually pos-
Taenia solium cysticerci, Trichinella). sessing a tail, which escapes from a sporocyst
aggregation See overdispersal. or redia generation of a trematode within the
alae (‘wings’) Extensions of the cuticle of snail host, and constitutes the transfer stage
nematodes (e.g. in Enterobius); sometimes to the next (usually definitive) host.
present only at the head (cervical alae, e.g. cirrus Retractile muscular organ at the ter-
Toxocara) or tail end (caudal alae, e.g. male minal end of the male reproductive system
Dirofilaria). of Platyhelminthes, which serves as a penis
amphid One of a pair of receptors situated during fertilization.
at the anterior end of nematodes. coenurus Larval cystic stage of the tape-
anthelminthic Any chemotherapeutic sub- worm Multiceps, containing an inner ger-
stance directed against a helminthic minal layer producing multiple scolices
infection. within a single fluid-filled cavity (see
antibody An immunoglobulin molecule cysticercus and hydatid cyst).
that recognizes a specific antigen. commensal A symbiotic relationship in
antigen A molecule that is foreign to the which one individual gains without having
body and is recognized. Because of the beneficial or detrimental effects on its partner.
large size of helminths in relation to invad- concomitant immunity A state of immu-
ing microorganisms, most functional anti- nity that prevents establishment of a new
gens of helminths are excretory or infection but is ineffective against any
secretory. The tegument of Platyhelminthes existing parasites that may be present (e.g.
is also a site for attack by host defences, as in schistosomiasis).
but the tough cuticle of nematodes is control Attack on an infection so that it
largely resistant. will no longer be clinically or economi-
autoinfection Reinfection without expo- cally important (e.g. projected global cam-
sure from the environment; self-infection paigns against lymphatic filariasis or

273
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274 Appendix 2

schistosomiasis plus intestinal helminths. endoparasite Living within another organ-

See elimination or eradication). ism, including the digestive and respira-
cuticle The outer chitinous body layer of tory tract of the latter.
nematodes (see tegument). eradication Complete elimination of a
cysticercoid The solid second larval stage helminth infection throughout the world
of tapeworms containing an invaginated (e.g. hopefully Dracunculus soon. (See con-
scolex. Usually tailed and found in inverte- trol and elimination.)
brates (e.g. Dipylidium and Hymenolepis). evasion of the immune response
cysticercus (= bladderworm) The hollow Mechanisms by which helminths avoid the
fluid-filled second larval stage of Taenia, immune response of the host either by
containing a single invaginated scolex (see occupying a privileged site or by covering
coenurus, hydatid cyst and metacestode). themselves with host or host-like antigens
digenetic Three or more generations (liter- (e.g. schistosomes).
ally two) required for completion of one feral cycle (= sylvatic cycle) Life cycle of a
life cycle, as in digenetic trematodes. zoonotic parasite involving wild animals
dioecious Having female and male and having a low risk of infecting humans
reproductive organs in different (except hunters) (e.g. Echinococcus multi-
individuals (e.g. schistosomes and locularis) (see domestic cycle).
nematodes). filariform larva A non-feeding nematode
domestic cycle (= pastoral or synanthropic larva characterized by its delicate elongate
cycle) Life cycle of a zoonotic parasite structure and by its slim, capillary oeso-
involving domestic stock or pets, with a phagus without a posterior bulb (e.g. in
high risk of infecting humans (e.g. usually hookworms, Strongyloides and filariae).
in Echinococcus granulosus and Trichinella flame cell See solenocyte.
spiralis). furcocercous cercaria Fork-tailed, as in
ectoparasite Living upon or in the superfi- the cercaria of schistosomes.
cial tissues of a host. genital atrium In Platyhelminthes, the
ectopic site Outside the normal location, chamber collecting the terminal ends of the
as in the position of a parasite that lodges genital tubules and opening to the exterior
in an atypical part of the body. by the genital pore.
egg count A quantitative measure of the geohelminth A term applied to any nema-
number of eggs present in the faeces, usu- tode that is transmitted to humans after
ally expressed as eggs per gram, in order to development in the soil (e.g. Strongyloides,
estimate the number of adults present. hookworms, Ascaris and Trichuris).
ejaculatory duct The muscular terminus of gonotyl Genital sucker, retractile and asso-
the male genitalia of nematodes, opening ciated with or incorporated into the ventral
into the cloaca. sucker, in some genera of trematodes (e.g.
elimination Campaign resulting in the Heterophyes).
complete absence of an infection in a coun- gravid Filled with eggs, as in the terminal
try or region (e.g. Dracunculus in Asia). Can proglottides of a cyclophyllidean tape-
also refer to absence of disease rather than worm or Enterobius.
of the causative parasite (e.g. intention of gubernaculum A small, sclerotinized,
global elimination of lymphatic filariasis accessory structure in male nematodes,
campaign). (See control and eradication.) which serves to guide the spicules out of
embryo The stage in development follow- the cloaca.
ing cleavage of the zygote up to, but not gymnocephalous cercaria Literally naked-
including, the first larval stage. headed; refers to cercariae without orna-
embryophore In tapeworms, the envelope mentation of body or tail, as in that of
immediately around the oncosphere and Fasciola hepatica.
derived from it. In taeniids it forms a thick gynaecophoric canal In male schisto-
protective layer composed of a keratin type somes, the ventral incurved fold of the
of protein. body extending from the ventral sucker to
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Glossary of Helminthological Terms 275

the caudal extremity, for carrying the hyperendemic High prevalence of infec-
female. tion in a human community.
hermaphroditic Containing both male and hypodermis In helminths, the layer of tis-
female organs in the same individual; sue immediately below the tegument
monoecious (e.g. cestodes and trematodes (trematodes and cestodes) or cuticle
except schistosomes). (nematodes).
heterogonic Development in which both immunomodulation An alteration, either
males and females are present in a colony negative or positive, of the immune
(see hologonic). response (see immunosuppresion).
hexacanth embryo ‘Six-hooked’ embryo, immunopathology Damage to tissues
the mature embryo containing six hooklets caused directly or indirectly by immune
within the egg of many tapeworms, includ- mechanisms (the importance of this in
ing all species that parasitize humans. helminth infections is being increasingly
hologonic Development in which only one recognized).
sex (usually the female) is present in a immunosuppression A down-regulation of
colony, as in parasitic Strongyloides. the immune response.
host An organism that harbours and nour- incidence of infection The number of new
ishes a parasite. cases of an infection reported in an area in
definitive host One that harbours the a unit of time (taken to be a year if not
sexually mature stage of the parasite (e.g. given) (see prevalence of infection).
humans are the only definitive hosts for infestation Existence of parasitic organ-
Taenia saginata). isms on the outside of the body of a host or
intermediate host An obligate host that in the superficial tissues; ectoparasitism
alternates with the definitive host and (e.g. lice and fleas).
harbours the larval stage of the parasite intensity of infection Number of parasites
(e.g. snails are intermediate hosts for all harboured by a host. The mean intensity is
human trematodes). calculated for the whole host population
paratenic host A carrier or transport (including those uninfected).
host. One in which the parasite remains larva The postembryonic stage of a
viable but does not develop. helminth, in which internal organs are
reservoir host An animal host in which developing or are developed and are at
infection usually resides; also one which least partially functional.
harbours the infection when humans are Laurer’s canal In trematodes, a tubule
not infected (e.g. ruminants are reservoir leading from the dorsal surface to the
hosts for many Trichostrongylus species). region of the ootype and seminal recepta-
hydatid cyst Larval cystic stage of the cle; it may be patent, vestigial or lacking. It
tapeworm Echinococcus granulosus, con- probably functions as a copulatory canal.
taining an inner germinal layer producing LD50 (= lethal dose 50) and LC50 (= lethal
many protoscolices, which when set free concentration 50). The dose or concentra-
into the cystic cavity, develop into daugh- tion of a chemotherapeutic, insecticidal or
ter cysts and usually have a thick lami- molluscicidal agent estimated statistically
nated wall surrounded by an outer fibrous to kill 50% of the helminths, insects or
capsule of host origin (see coenurus and snails being treated (also LD90 and LC90).
cysticercus). Mehlis’ glands In Platyhelminthes, the
hydatid cyst, alveolar (= multilocular) glands surrounding the ootype. They pro-
Larval cystic stage of the tapeworm duce mucus to lubricate the uterus and
Echinococcus multilocularis (AE), similar probably participate in eggshell formation.
to the hydatid cyst (above) but in which metacercaria The stage of trematodes fol-
budding is external (exogenous) as well as lowing the cercaria, with loss of tail, which
internal (endogenous), so that many small becomes encysted and awaits passive trans-
cysts are formed. There is no thick outer fer to the definitive host (present in all
capsule. trematodes of humans except schistosomes).
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276 Appendix 2

metacestode A collective term for any of obligate One that necessarily lives a par-
the various larval stages of cestodes which asitic existence, e.g. all the other human
are found in the intermediate host (e.g. helminths.
oncosphere, procercoid, plerocercoid, parasitocoenosis (= parasite mix) The
tetrathyridium, cysticercus, cysticercoid, assemblage of parasites associated with a
coenurus, hydatid). host population.
microcercous cercaria Cercaria with a parenchyma In Platyhelminthes, the
short, stumpy tail (e.g. cercaria of loose, usually undifferentiated tissue that
Paragonimus westermani). forms a matrix in which the viscera are
microfilaria The first prelarval stage of a embedded.
filaria, which either escapes from the parthenogenesis Production of progeny
eggshell (i.e. is unsheathed) or stretches the from the ovum without fertilization (e.g.
shell into an elongated sac (i.e. is sheathed) parasitic female of Strongyloides).
and is found in the blood or skin. pastoral cycle See domestic cycle.
miracidium The ciliated free-living first-stage patent infection Open or apparent, as indi-
larva hatched from the eggs of trematodes. cated by unmistakable signs, like eggs in
nosogeography Knowledge concerning the the faeces or microfilariae in circulating
geographical distribution of diseases. blood (see prepatent period).
oncosphere The stage that hatches from pathogen A parasite causing injury to a
the eggshell and later escapes from the host (see commensal and parasite).
embryophore of tapeworms; in human phasmid One of a pair of caudal organelles
tapeworm infections it is six-hooked (i.e. a (sensory receptors?) found in most para-
hexacanth embryo). sitic nematodes (i.e. the Phasmidia),
ootype The chamber in the reproductive including all those in humans except
system of Platyhelminthes where the sev- Aonchotheca, Dioctophyma, Trichinella
eral components of the eggs are assembled. and Trichuris.
ovejector A muscular organ in some pipestem fibrosis (Symmer’s) A fibrotic
female nematodes that forces eggs from the reaction formed around a vein in schistoso-
uterus into the vagina. miasis, so called because of its resemblance
overdispersal Situation where most hosts in section to the stem of an old-fashioned
harbour a few parasites while a few hosts clay pipe.
harbour many parasites. Gives a negative plerocercoid larva A second larval stage
binomial distribution. of pseudophyllid tapeworms in which the
oviparous Producing and laying eggs (see scolex is embedded in a greatly enlarged
ovoviviparous). tail (e.g. larva of Dyphyllobothrium latum)
ovoviviparous Discharging living young (see sparganum and procercoid larva).
rather than eggs (e.g. Dracunculus, filariae, prepatent period The period that a para-
Strongyloides and Trichinella) (see site is present in the body before it gives
oviparous). rise to parasitological evidence of its pres-
papillae Small sensory knobs, either at the ence (e.g. eggs in the faeces or microfilariae
anterior end (dierids) or at the posterior in the blood).
end in the male, where their number and prevalence of infection The number of cases
position may be of taxonomic importance. of an infection present in an area (actually
parasite An organism that lives at the per unit of population) at a fixed point in
expense of another larger organism, its time. Prevalence = incidence  average
host; which is physiologically dependent duration (see incidence of infection).
on its host, has a higher reproductive proboscis In acanthocephalans and in the
capacity than it and may kill the host in dog tapeworm Dipylidium caninum an
heavy infections. anterior protrusible organ, typically stud-
facultative One that may employ either ded with hooklets.
a free-living or a parasitic mode of life. procercoid larva The first larval stage
e.g. Strongyloides. of pseudophyllidean tapeworms, which
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Glossary of Helminthological Terms 277

develops from the oncosphere; it consists of solenocyte Literally canal cell. In

a body proper and a caudal vestige of the Platyhelminthes, the cell with a tuft of cilia
oncosphere containing the hooklets called a at the head of each capillary in the excre-
cercomer (see plerocercoid larva). tory system; commonly called a flame cell.
proglottid One complete unit of a tape- sparganum The second plerocercoid larval
worm, commonly called a segment. In stage of the pseudophyllidean tapeworm
cyclophyllideans the most anterior are Spirometra, which occurs in mammals
immature; further back they are mature, (particularly when in humans), character-
containing the male and female sex organs; ized by its elongated shape and lack of a
and the posterior proglottides are gravid, cystic cavity.
being filled with eggs. specificity (of an immunodiagnostic test)
pseudocoel Body cavity of nematodes, not The probability that a real negative host is
lined completely with mesothelium and recognized by the test to be negative (i.e.
not equivalent to a coelomic cavity. number of real negatives divided by num-
pseudotubercle A foreign-body reaction ber of real negatives plus number of false
resembling a tubercle but not provoked by positives).
tubercle bacilli (e.g. by schistosome eggs). spicules (copulatory) Two (or sometimes,
refractory host One that is not readily in aphasmids, one) bristle-like, lanceolate
infectible by a particular parasite (see sus- sclerotinized structures in the outer genital
ceptible host). chamber of male nematodes, introduced
retrofection A variety of autoinfection in into the vulva or vagina of the female dur-
which larvae hatch from eggs in the anal ing copulation to guide the sperm.
region, migrate up the large bowel and strobilization The production of proglot-
develop into adults (e.g. Enterobius). tides from the neck region of tapeworms.
rhabditiform larva A feeding first-stage superinfection New infection superimposed
nematode larva (of strongylids and on an existing one of the same species.
Strongyloides) in which the oesophagus is susceptible host A host that is readily
functional, is usually muscular and has an infected by a particular parasite (see refrac-
enlarged posterior bulb. tory host).
rostellum The somewhat protuberant api- sylvatic cycle See feral cycle.
cal portion of the scolex of certain tape- symbiosis State of two organisms living
worms, frequently bearing a circle of together for mutual advantage, the relation-
hooklets, as in Taenia solium. ships being so intimate that the participat-
schistosomulum Immature stage of schis- ing species rely on one another for their
tosomes, from the time of entry into the existence. Mutualism is similar but the two
definitive host until the worm reaches sex- organisms can live apart.
ual maturity. symptom Any subjective evidence of dis-
scolex Attachment end of a tapeworm, ease in a patient (see sign).
commonly referred to as the anterior end or tegument The outer layer of the body wall
holdfast, which often bears suckers and of helminths.
hooks. tetrathyridium In the tapeworm genus
seminal receptacle (= Receptaculum sem- Mesocestoides, the second larval stage, in
inis) The storage reservoir for spermatozoa which the scolex with its four suckers is
in the female. invaginated into the anterior end of a plero-
seminal vesicle (= Vesicula seminalis) The cercoid type of body.
storage reservoir for spermatozoa in the uterus The tubule in helminths containing
male. the fully formed eggs before they are
sensitivity (of diagnostic procedure) The voided.
probability that the procedure will diag- vagina An outer chamber of the female
nose a real positive reaction. genitalia in nematodes; also the tubule
sign Objective evidence of disease (see leading from the genital atrium to the
symptom). ootype in cestodes (see vulva).
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278 Appendix 2

vas deferens The common male duct aris- the action of piperazine against Ascaris
ing from one or more vasa efferentia and and Enterobius).
leading into the seminal vesicle. vitellaria (= vitelline glands) The glands
vas efferens The male duct conveying sper- in Platyhelminthes which produce yolk
matozoa from the testis to the vas deferens. material and the shell of the egg.
vector An intermediate host that carries vulva The outermost, unpaired chamber of
the parasite to the definitive host. the female genitalia in nematodes.
biological vector A host essential to the worm burden The number of worms pre-
development and transmission of a para- sent in the host (this is often estimated
site, in which the parasite undergoes from the egg count).
development (e.g. insects and filariae). xiphidiocercaria Cercaria with a stylet,
mechanical vector A non-essential dis- median dorsal in position in the oral
seminator of parasites, in which the par- sucker; having associated penetration
asite does not develop (e.g. flies glands with duct openings on either side of
sometimes carrying the eggs of Taenia or the stylet (as in Paragonimus).
Ascaris). zoonosis Infection or disease naturally
vermicide Therapeutic agent producing the transmitted between humans and other
death of a helminth (see anthelminthic). vertebrates.
vermifuge Therapeutic agent producing zooprophylaxis The prevention or amelio-
evacuation of a helminth from the intestine ration of disease in humans by prior expo-
without necessarily causing its death (e.g. sure to a heterologous infection of animals.
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Appendix 3
Location of Helminths in the Human Body

(a)

TRACHEA
Mammomonogamus* → irritation & cough

STOMACH
Gnathostoma* (larva) → abscess
Anisakis* (larva) → abscess

SMALL INTESTINE
Fasciolopsis → enteritis
Heterophyes → enteritis
Metagonimus → enteritis
Diphyllobothrium → anaemia*
Taenia spp. → nausea
Hymenolepsis spp. → diarrhoea
Hookworm → anaemia
Trichostrongylus → diarrhoea
Strongyloides → dysentery (malabsorption)
Ascaris → obstruction
Trichinella → dysentery
Capillaria philippinensis* → dysentery (malabsorption)
Pseudoterranova* (larva) → abscess

COLON AND CAECUM

Schistosoma spp. (eggs) → dysentery
Gastrodiscoides* → diarrhoea
Enterobius → anal pruritus
Trichuris → dysentery
Ternidens → diarrhoea?
Angiostrongylus → necrosis &
costaricensis* granulomas
(adults + eggs)

URINOGENITAL SYSTEM
S. haematobium (eggs) → bladder fibrosis

Wuchereria funiculitis & hydrocele

Brugia → in males, chyluria

*RARE
Fig. 132. Location in the human body of helminths and other metazoa with the possible pathology that
may result. Organs through which a parasite passes without causing any pathology are ignored. Not
included: Oesophagostomum bifurcum in the colon and caecum causing nodules. (Name changes:
Angiostrongylus = Parastrongylus; Capillaria philippinensis = Aonchotheca philippinensis; Capillaria
hepatica = Calodium hepaticum.) (After Muller and Baker, 1990.)

279
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280 Appendix 3

(b)
EYES
Taenia solium (larva) → blurring of vision*
T. multiceps (larva) → space-filling lesion

Loa → conjunctivitis
Onchocerca volvulus (mf) → keratitis & retinopathy
& nerve atrophy
Toxocara canis (larva) → granuloma*
Dirofilaria* (larva) → conjunctivitis
Oestrus (larva) → inflammation

LYMPHATICS
lymphangitis
Wuchereria
→ lymphoedema
Brugia
ephantiasis

BLOOD
Schistosoma spp. → fever?
Microfilariae of:
Wuchereria
Brugia → fever?
Loa
Mansonella

BONE MARROW
Echinococcus granulosus → space-occupying lesion*
(larva)

MUSCLES
Taenia solium (larva) → oedema
Trichinella (larva) → oedema

SUBCUTANEOUS TISSUES
Spirometra* (larva) → oedema
T. solium (larva) → nodules
Wucheraria → elephantiasis
Brugia → elephantiasis
Loa → fugitive (Calabar) swelling
Onchocerca → nodules
Dirofilaria* (larva) → nodule
Dracunculus → cellulitis
Gnathostoma* (larva) → oedema
Dermatobia (larva) → abscess
Cochliomyia (larva) → abscess

SKIN
Bird schistosome (larva) → creeping eruption
Onchocerca (mf) → thickening then atrophy

Dracunculus → ulceration
Mansonella streptocerca (mf) → oedema & papules
Hookworm (larva) → ground itch
Animal hookworm (larva) → creeping eruption
Strongyloides (larva) → larva currens
Sarcoptes → scabies
Tunga (larva) → boil
Demodex → dermatitis*

*RARE

Fig. 132. Continued.

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Location of Helminths in the Human Body 281

(c)
BRAIN + CNS
Paragonimus (+eggs) → abscess
Schistosoma spp. (+eggs) (& granulomas)
E. granulosus (larva) space-
T. solium (larva) → occupying
T. multiceps (larva) lesions
Gnathostoma* (larva) → myelencephalitis
Trichinella (larva) → encephalitis*
Angiostrongylus → meningitis
cantonensis* (larva)
Loa (mf) → encephalitis*
Toxocara canis (larva) → granuloma*

LUNGS
Paragonimus → pneumonia
E. granulosus (larva) → space-occupying
lesion
Larvae of:
Ascaris, hookworm
Strongyloides, Toxocara,
→ diffuse pneumonitis
Trichinella, Schistosoma
spp., Paragonimus
Wuchereria (mf) → tropical pulmonary
Brugia (mf) eosinophilia
Dirofilaria immitis* (larva) → coin lesion

HEART
Larvae of:
T. solium
Trichinella → cardiomyopathy
Dirofilaria immitis*
Loa (mf) → endomyocardial fibrosis*

LIVER
Clonorchis
→ biliary pathology
Opisthorchis
Fasciola
Ascaris → cholangitis
Schistosoma spp. (eggs) → portal hypertension

Larvae of:
Fasciola Toxocara → necrosis
Capillaria hepatica*
Ascaris
E. granulosus (larva) → space-occupying
lesion
E. multilocularis* (larva) → pseudomalignant
growths
Armillifer (larva) → inflammation*

KIDNEYS
S. haematobium (eggs) → hydronephrosis
E. granulosus (larva) → space-occupying lesion*
Dioctophyma* → renal colic

SPLEEN
E. granulosus (larva) → space-occupying lesion*

PANCREAS
Clonorchis → pancreatitis
Opisthorchis → pancreatitis
Ascaris → pancreatitis
*RARE

Fig. 132. Continued.

13W. & H.D. - Further Reading 14/11/01 4:31 PM Page 282

General References and Further Reading

Abdi, Y.A. (1994) Handbook of Drugs for Tropical Parasitic Diseases, 2nd edn. Taylor and Francis,
London, UK.
Ash, L.R. and Orihel, T.C. (1990) Atlas of Human Parasitology. American Society of Clinical
Pathologists, Chicago, USA.
Ashford, R.W. and Crewe, W. (1998) The Parasites of Homo sapiens. Liverpool School of Tropical
Medicine, Liverpool, UK.
Barnard, C.J. and Behnke, J.M. (eds) (1990) Parasitism and Host Behaviour. Taylor and Francis,
London, UK.
Bennet, E.-M., Behm, C. and Bryant, C. (eds) (1989) Comparative Biochemistry of Parasitic
Helminths. Chapman and Hall, London, UK.
Bogitsch, B.J. and Cheng, T.C. (1998) Human Parasitology, 2nd edn. Academic Press, San Diego, USA.
Boothroyd, J.C. and Komuniecki, R. (1995) Molecular Approaches to Parasitology. Willey-Liss, New
York, USA.
Brooker, S. and Michael, E. (2000) The potential of geographical information systems (GIS) and
remote sensing in the epidemiology and control of human helminth infections. Advances in
Parasitology 47, 246–288.
Bryant, C. and Behm, C. (1989) Biochemical Adaptation in Parasites. Chapman and Hall, London, UK.
Campbell, W.C. and Rew, R.S. (1986) Chemotherapy of Parasitic Diseases. Plenum, New York, USA.
Chowdhury, N. and Tada, I. (eds) (1994) Helminthology. Springer-Verlag, Berlin, Germany.
Combes, C. (1995) Interactions durables: Écologie et évolution du parasitisme. Masson, Paris, France.
Cook, G.C. (1990) Parasitic Disease in Clinical Practice. Springer-Verlag, Berlin, Germany.
Cook, G.C. (ed.) (1996) Manson’s Tropical Diseases. Saunders, London, UK.
Coombs, I. and Crompton, D.W.T. (1991) A Guide to Human Helminths. Taylor and Francis, London, UK.
Cox, F.E.G., Kreier, J.P. and Wakelin, D. (eds) (1998) Topley and Wilson’s Microbiology and Microbial
Infections. Vol. 5 Parasitology, 9th edn. Arnold, London, UK.
Dailey, M.D. (1996) Meyer, Olsen and Schmidt’s Essentials of Parasitology, 6th edn. Brown,
Dubuque, Iowa, USA.
Despommier, D.D., Gwadz, R.W. and Hotez, P.J. (1994) Parasitic Diseases, 3rd edn. Springer-Verlag,
New York, USA.
Esch, G.W. and Fernández, J.C. (1993) A Functional Biology of Parasitism: Ecological and
Evolutionary Implications. Chapman and Hall, London, UK.
Euzeby, J. (1981) Diagnostic expérimental des helminthoses animales (animaux domestiques – ani-
maux de laboratoire – primates), 2 vols. Ministère de l’Agriculture, Paris, France.
Farthing, M.J.G. and Keusch, G.T. (eds) (1995) Enteric Infections 2: Intestinal Helminths. Chapman
and Hall, London, UK.
Freedman, D.O. (1997) Immunopathogenic Aspects of Disease Induced by Helminth Parasites.
Chemical Immunology, Vol. 66, S. Karger, Basle, 236 pp.
Garcia, L.S. (1999) Practical Guide to Diagnostic Parasitology. American Society for Microbiology,
Washington, USA.

282
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Garcia, L.S. and Bruckner, D.A. (1997) Diagnostic Medical Parasitology. American Society for
Microbiology, Washington, USA.
Gentilini, M. (1993) Médecine Tropicale. Flammarion, Paris, France.
Gillespie, S.H. and Hawkey, R.M. (1995) Medical Parasitology: a Practical Approach. Oxford
University Press, New York, USA.
Goldsmith, R. and Heyeman, D. (1989) Tropical Medicine and Parasitology. Appleton and Lange,
Hemel Hempstead, UK.
Gutterierrez, Y. (2000) Diagnostic Pathology of Parasitic Infections with Clinical Correlations, 2nd
edn. Oxford University Press, New York, USA.
Hall, A. (1982) Intestinal helminths of man: the interpretation of egg counts. Parasitology 85,
605–613.
Halton, D.W., Behnke, J.M. and Marshall, I. (eds) (2001) Practical Exercises in Parasitology.
Cambridge University Press, Cambridge, UK.
Hugh-Jones, M.E., Hubbert, W.T. and Hagstad, H.V. (1995) Zoonoses: Recognition, Control and
Prevention. Iowa State University Press, Ames, USA.
Hyde, J.E. (1990) Molecular Parasitology. Open University, Buckingham, UK.
Hyde, J.E. (1993) Protocols in Molecular Parasitology. Humana Press, Totowa, New Jersey, USA.
James, D.M. and Gilles, H.M. (1985) Human Antiparasitic Drugs: Pharmacology and Usage. John
Wiley & Sons, Chichester, UK.
Kassai, T., Cordero del Campo, M., Euzeby, J., Gaafar, S., Hiepe, Th. and Himonas, C.A. (1988)
Standardized nomenclature of animal parasitic diseases (SNOAPAD). Veterinary Parasitology 29,
299–326.
Leventhal, R. and Cheadle, R. (1996) Medical Parasitology: a Self-instructional Text. Davis,
Philadelphia, USA.
Littlewood, T. and Bray, R. (eds) (2001) Interrelationships of the Platyhelminthes. Taylor and Francis,
London, UK.
Macpherson, C.N.L. and Craig, P.S. (eds) (1991) Parasitic Helminths and Zoonoses in Africa. Unwin
Hyman, London, UK.
Maizels, R.M., Blaxter, M.L., Robertson, B.D. and Selkirk, M.E. (1991) Parasite Antigens, Parasite Genes.
A Laboratory Manual for Molecular Parasitology. Cambridge University Press, Cambridge, UK.
Markell, E.K., John, D.T. and Krotoski, W.A. (1999) Markell and Voge’s Medical Parasitology, 8th edn.
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Marquardt, W.C., Demaree, R.S. and Grieve, R.B. (2000) Parasitology and Vector Biology. 2nd edn.
Academic Press, Orlando, Florida, USA.
Marr, J.J. and Muller, M. (1995) Biochemistry and Molecular Biology of Parasites. Academic Press,
London, UK.
Meyers, W. (2000) Pathology of Infectious Diseases. Vol. 1. Helminthiases. Armed Forces Institute of
Pathology, Washington, USA.
Miyazaki, T. (1991) An Illustrated Book of Helminthic Zoonoses. International Medical Foundation
of Japan, Tokyo, Japan.
Muller, R. (1997) Parasitology. In: Wyatt, H.V. (ed.) Information Sources in the Life Sciences, 4th edn.
Bowker-Sauer, East Grinstead, UK, pp. 195–202.
Muller, R. and Baker, J.R. (1990) Medical Parasitology. Lippincott, Philadelphia, USA.
Neva, F.A. and Brown, H.W. (1994) Basic Clinical Parasitology, 6th edn. Appleton and Lange,
Norwalk, Connecticut, USA.
Nokes, C. and Bundy, D.A.P. (1994) Does helminth infection affect mental processing and educa-
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Orihel, T.C. and Ash, L.R. (1995) Parasites in Human Tissues. American Society of Clinical
Pathologists, Chicago, USA.
Palmer, P.E.S. and Reeder, M.M. (2000) The Imaging of Tropical Diseases, 2 vols. Springer,
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Palmer, S.R., Lord Soulsby and Simpson, D.I.H. (eds) (2000) Zoonoses. Oxford University Press, New
York, USA.
Peters, W. and Gilles, H.M. (1999) A Colour Atlas of Tropical Medicine and Parasitology, 5th edn.
Mosby, London, UK.
Price, D.L. (1993) Procedure Manual of the Diagnosis of Intestinal Parasites. CRC Press, Boca Raton, USA.
Rogan, M.T. (ed.) (1997) Analytical Parasitology. Springer-Verlag, Berlin, Germany.
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Salfelder, K., Liscans, T.R. and de Sauerleig, E. (1992) Atlas of Parasitic Pathology. Kluwer,
Dordrecht, The Netherlands.
Schmidt, G.D. and Roberts, L.S. (1989) Foundations of Parasitology. Mosby, Missouri, USA.
Scott, M.E. and Smith, G. (eds) (1994) Parasitic and Infectious Diseases: Epidemiology and Ecology.
Academic Press, New York, USA.
Smyth, J.D. (ed.) (1990) In vitro Cultivation of Parasitic Helminths. CRC Press, Boca Raton, Florida, USA.
Smyth, J.D. (ed.) (1994) Introduction to Animal Parasitology. Cambridge University Press, Cambridge, UK.
Soulsby, E.J.L. (ed.) (1987) Immune Responses in Parasitic Infections. CRC Press, Boca Raton, USA.
Spicer, W.J. (2000) Clinical Bacteriology, Mycology and Parasitology. Harcourt, London, UK.
Stephenson, L.S. (1987) The Impact of Helminth Infections on Human Nutrition: Schistosomes and
Soil-transmitted Helminths. Taylor and Francis, London, UK.
Strickland, T. (ed.) (2000) Hunter’s Tropical Medicine and Emerging Infectious Diseases, 8th edn.
Saunders, Philadelphia, USA.
Sun, T. (1993) Progress in Clinical Parasitology, Vol. 3. Field and Wood, New York, USA.
Taylor, A.E.R. and Baker, J.R. (eds) (1987) In vitro Methods for Parasite Cultivation. Academic Press,
London, UK.
Thienpont, D., Rochette, F. and Vanparijs, O.F.G. (1979) Diagnosing Helminthiasis through
Coprological Examination. Janssen Research Foundation, Beerse, Belgium.
Ubelaker, J.E. (1993) Stedman’s ASP Parasite Names. Williams and Wilkins, Baltimore, USA.
Urquhart, G.M., Armour, J., Duncan, J.L., Dunn, A.M. and Jennings, F.W. (1987) Veterinary
Parasitology. Churchill Livingstone, New York, USA.
Van den Bossche, H. (1995) Principles of anthelmintic chemotherapy. In: Farthing, M.J.G., Keusch,
G.T. and Wakelin, D. (eds) Enteric Infections 2: Intestinal Helminths. Chapman and Hall, London,
UK, pp. 267–286.
van Lichtenberg, F. (1991) Pathology of Infectious Diseases. Raven Press, New York, USA.
Wakelin, D.M. (1988) Helminth infections. In: Wakelin, D.M. and Blackwell, J.M. (eds) Genetics of
Resistance to Bacterial and Parasitic Infection. Taylor and Francis, London, UK, pp. 83–100.
Walls, K. and Schantz, P. (eds) (1986) Immunodiagnosis of Parasitic Diseases. I. Helminthic Diseases.
Academic Press, Orlando, USA.
Whitfield, P.J., Molyneux, D.H., Anderson, R.M., Bryant, C., Hart, D.T., Chappell, L.H., Gutteridge,
W.E. and Cox, F.E.G. (1993) Modern Parasitology: a Textbook of Parasitology, 2nd edn. Blackwell
Scientific Publications, Oxford, UK.
WHO (1987) Prevention and Control of Intestinal Parasitic Diseases. World Health Organization,
Geneva, Switzerland.
WHO (1990) WHO Model Prescribing Information: Drugs Used in Parasitic Diseases. World Health
Organization, Geneva, Switzerland.
Working Group on Parasite Control – The Hashimoto Intitiative (1998) The Global Parasite Control
for the 21st Century. Government of Japan, Kobe, Japan.
Wyler, D.J. (1990) Modern Parasite Biology: Cellular, Immunological and Molecular Aspects. W.H.
Freeman, New York, USA.

Trematodes

Kumar, V. (1999) Trematode Infections and Diseases of Man and Animals. Kluwer, Dordrecht, The
Netherlands.
Smyth, J.D. and Halton, D.W. (1983) The Physiology of Trematodes, 2nd edn. Cambridge University
Press, Cambridge, UK.

Cestodes

Adams, A.M. and Rausch, R.L. (1999) Diphyllobothriasis. In: Connor, D.H., Chandler, F.W., Schwartz,
D.A., Manz, H.J. and Lack, E.E. (eds) Pathology of Infectious Diseases. Vol. 2. Appleton and
Lange, Norwalk, Connecticut, USA, pp. 1377–1390.
Arai, H.P. (ed.) (1980) Biology of the Tapeworm Hymenolepis diminuta. Academic Press, New York, USA.
13W. & H.D. - Further Reading 14/11/01 4:31 PM Page 285

Further Reading 285

Smyth, J.D. and McManus, D.P. (1989) The Physiology and Biochemistry of Cestodes. Cambridge
University Press, Cambridge, UK.
Wardle, R.A., McLeod, J.A. and Radinovsky, S. (1974) Advances in the Zoology of Tapeworms,
1950–1970. University of Minnesota Press, Minneapolis, USA.

Nematodes

Anderson, R.C. (2000) Nematode Parasites of Vertebrates – their Development and Transmission, 2nd
edn. CAB International, Wallingford, UK.
Bird, A.F. and Bird, J. (1991) The Structure of Nematodes. Academic Press, New York, USA.

Immunology

Allen, J.E. and Maizels, R.M. (1997) Th1–Th2 paradigm: reliable paradigm or dangerous dogma?
Immunology Today 18, 387–392.
Bancroft, A.J., Grencis, R.K. and MacDonald, T.T. (1998) Th1 and Th2 cells and immunity to intesti-
nal helminths. Chemical Immunology 71, 198–208.
Capron, A. (1998) Schistosomiasis: forty years’ war on the worm. Parasitology Today 14, 379–384.
Finkelman, F.D., Shea-Donahue, T., Goldhill, J., Sullivan, C.A., Morris, S.C., Madden, K.B., Gause,
W.C. and Urban, J.F., Jr (1997) Cytokine regulation of host defense against parasitic gastrointestinal
nematodes: lessons from studies with rodent models. Annual Review of Immunology 15, 505–533.
Janeway, C. and Travers, P. ( 1999) Immunobiology, 4th edn. Churchill-Livingstone, London.
Kennedy, M.W. and Harnett, W. (eds) (2001) Parasitic Nematodes – Molecular Biology, Biochemistry
and Immunology, CAB International, Wallingford, UK.
Kierszenbaum, F. (ed.) (1994) Parasitic Infections and the Immune System. Academic Press, San
Diego, USA.
Liew, F.Y. and Vickerman, K. (eds) (1997) Immune effector mechanisms in parasitic infections.
Philosophical Transactions of the Royal Society B 352, 1293–1394.
Moqbel, R. (ed.) (1992) Allergy and Immunity to Helminths: Common Mechanisms or Divergent
Pathways. Taylor and Francis, London, UK.
Parham, P. (2000) The Immune System. Elsevier Science, London, UK.
Prichard, D.I. (1995) The survival strategies of hookworms. Parasitology Today 11, 255–259.
Roitt, I., Brostoff, J. and Male, D. (1998) Immunology, 5th edn. Mosby, London, UK.
Röllinghof, M. and Rommel, M. (1994) Immunologische und molekulare Parasitologie. Gustav
Fischer, Berlin, Germany.
Wakelin, D. (1994) Host populations: genetics and immunity. In: Scott, M.E. and Smith, G. (eds)
Parasitic and Infectious Diseases. Academic Press, London, UK, pp. 83–100.
Wakelin, D. (1996) Immunity to Parasites: How Parasitic Infections are Controlled. Cambridge
University Press, Cambridge, UK.
Wakelin, D. (1997) Parasites and the immune system: conflict or compromise? Bioscience 47, 32–40.
Wang, C.C. (ed.) (1991) Molecular and Immunological Aspects of Parasitism. American Association
for the Advancement of Science, Washington, USA.
Warren, K.S. (ed.) (1993) Immunology and Molecular Biology of Parasitic Infections, 3rd edn.
Blackwell Scientific Publications, Boston, USA.

History

Cox, F.E.G. (ed.) (1996) The Wellcome Trust Illustrated History of Tropical Diseases. Wellcome Trust,
London, UK.
Dunlop, R.H. and Williams, D.I. (1996) Veterinary Medicine: an Illustrated History. Mosby Year Book,
St Louis, USA.
Farley, J. (1991) Bilharzia. A History of Imperial Tropical Medicine. Cambridge University Press,
Cambridge, UK.
13W. & H.D. - Further Reading 14/11/01 4:31 PM Page 286

286 Further Reading

Foster, W.D. (1965) A History of Parasitology. Livingstone, Edinburgh, UK.

Garnham, P.C.C. (1971) Progress in Parasitology. Athlone Press, London, UK.
Grove, D.I. (1990) A History of Human Helminthology. CAB International, Wallingford, UK (available
on-line at www.red-e2.com).
Hoeppli, R. (1959) Parasites and Parasitic Infections in Early Medicine and Science. University of
Malaya Press, Singapore.
Kean, B.H., Mott, K.E. and Russell, A.J. (eds) (1978) Tropical Medicine and Parasitology: Classic
Investigations, Vols 1 and 2. Cornell University Press, Ithaca, USA.
14Worms & H.D. - Index 20/11/01 1:46 PM Page 287

Index

Abbreviata (= Physaloptera) caucasia 187 intestinal nematodes 120, 156

Acanthocephalans 106–107 tissue nematodes 179, 181, 196, 209,
Acanthocephalus rauschi 107 218, 222, 226, 230
Accidental filarial infections 226–228 Amoebiasis 53, 141, 146, 166
Achillurbainia Amphibians as hosts 56, 58, 70, 71, 107, 145,
nouveli 37–38 184, 186
recondita 37–38 Anaemia and helminths 21, 47, 57, 68,
Acuaria sp. 187 130–132, 138, 166
Adhesive (= Scotch/Sellotape) tape technique Anatrichosoma cutaneum 156, 175
75, 162–163 Ancylostoma
ADCC (antibody dependent cell–mediated braziliense 160
cytotoxicity) 23, 30, 198, 217, 244, caninum 137, 160
250 ceylanicum 137
Aedes differential features from Necator 130
as vectors of bancroftian filariasis 200 duodenale 134–137
as vectors of dirofilariasis 226 clinical manifestations 135
as vectors of malayan filariasis 205 epidemiology 136
African Programme for Onchocerciasis geographical distribution 134
(APOC) 220 immunology 120–122
Agamomermis life cycle 135
hominis 184 morphology 134
restiformis 184 pathogenesis 136
Agar plate culture method for larvae 123–125 prevention and control 136
Aggregation of helminth infections 122, 132, japonica 137
168 malayanum 137
AIDS 23, 83, 119, 200 secreted polypeptide (ASP) 132
Alaria tubaeforme 160
alata 58 Angiostrongylus see Parastrongylus
americana 58, 156 Anisakis simplex 154–156
marcianae 58, 156 clinical manifestations 155
Albendazole diagnosis 155
cestodes 82, 92, 96, 97 epidemiology 155–156
intestinal nematodes 123–124, 125, geographical distribution 154
132–133, 140, 142, 147, 152, 153, 159, life cycle 154
167 location in host 154
tissue nematodes 174, 175, 181, 186, morphology 154
199, 201, 210, 222, 232 pathogenesis 155
trematodes 51–52 prevention 156
Allergic responses to 241, 248 treatment 155
cestodes 94 Annelids as hosts 157, 147, 184

287
14Worms & H.D. - Index 20/11/01 1:46 PM Page 288

288 Index

Anopheles B cells 30, 244

as vectors of bancroftian filariasis Bacteria 3, 41, 119, 158, 160, 166, 196, 202, 230
199–200 Baermann technique 122
as vectors of malayan filariasis 205 Bancroftian filariasis see Wuchereria bancrofti
as vectors of timoran filariasis 205 Bats as hosts 159, 188
Anorexia 58, 68, 129, 137, 150, 166, 173, Baylisascaris procyonis 153–154, 156
175 Bears as hosts 71, 137, 154, 182–183, 228
Antibiotics and lymphatic filariasis 199 Beetles as hosts 103, 106, 107, 188
Antibodies, monoclonal 24, 36, 44, 75, 145, Bertiella
155, 198–199 mucronata 103
Antigenic disguise 23 studeri 102
Antigens Bile ducts and helminths 41, 44, 45, 47, 150,
coproantigens 48, 75, 93 187
excretory/secretory (ES) 30, 75,109, 132, Bilharziella polonica 32
155, 159, 180, 204, 251 Biomphalaria
Ants as hosts 46, 103, 139 alexandria group 27, 29
Aonchotheca (= Capillaria) philippinensis choamphala group 27, 29
173–174 glabrata 27, 29
clinical manifestations 173–174 pfeifferi group 27, 29
diagnosis 174 spp. 5, 27
epidemiology 174 sudanica group 27, 29
geographical distribution 174 Biopsy 24, 47, 81, 137, 146, 155, 175, 180, 209,
life cycle 173 227
location in host 173 Birds
morphology 173 as hosts of
pathogenesis 174 cestodes 69, 70, 71, 103
treatment 174 nematodes 153, 173, 182, 186, 188
Apophallus donicus 54 trematodes 31, 47, 54, 58
Appendicitis and helminths 74, 141, 150, 155, in transmission of Taenia 76
162, 167, 184 Bithionol 48
Armillifer Blindness see Eye lesions
agkistrodontus 240 Bolbosoma sp. 107
armillatus 240 Brain involvement 22, 35–36, 53, 71, 81, 85, 86,
Artemisins (Artemether and Artesunate) in 90, 96, 144, 154, 158, 159
schistosomiasis 25 Brugia
Artyfechinostomum beaveri 206
araoni 57 guyanensis 206
malayanum 57 malayi 202–206
mehrai 57 clinical manifestations 204
sufratyfex 57 diagnosis 204
Ascaris epidemiology 204–205
lumbricoides 147–153 geographical distribution 202
clinical manifestations 141–150 life cycle 204
diagnosis 151 location in host 202
epidemiology morphology 202
geographical distribution 148 pathogenesis 204
life cycle 148 prevention and control 205
location in host 148 treatment 204
morphology 148 zoonotic aspects 205
pathogenesis 151 pahangi 205
prevention and control 152–153 timori 205
treatment 151–152 Buffaloes as hosts 49, 92
zoonotic aspects 153 Buginetta alouattae 103
suum 153 Bulimus fuchsianus 38
Aspiration of cysts of Echinococcus 92 Bulinus
Australobilharzia terrigalensis 32, 156 africanus group 27
Autoinfection 120, 153, 162, 173 camerunensis 27
14Worms & H.D. - Index 20/11/01 1:46 PM Page 289

Index 289

forskali group 27 Cirrhosis 22, 41

reticulatus group 27 Classification of
spp. 5, 11, 27 cestodes 64–65
truncatus group 27 nematodes 109–113
Bunostomum phlebotomum 160 trematodes 6–9
Clinostomum complanatum 59
Clonorchis sinensis 38–43
Calabar swellings 207 clinical manifestations 39
Calodium (= Capillaria) hepaticum 156, 175 control and prevention 42
Camels as hosts 49, 140 diagnosis 42
Cancer and helminths 18–19, 41, 44, 45, 83, epidemiology 42–43
155, 226 geographical distribution 38
Capillaria immunology 41–42
aerophila see Eucoleus aerophilus life cycle 38
hepatica see Calodium hepaticum location in host 38
philippinensis see Aonchotheca morphology 38
philippinensis pathogenesis 41
Cardiac damage 22, 53, 84, 97, 120, 143, 147, treatment 42
179, 226, 241 Coatimundi as host 146, 206
Carneophallus brevicaeca 59 Cochliomyia hominovorax 242
Carnivores (wild) as hosts 37, 45, 59, 71, 84, 85, Codiella leachi 5, 44
92, 98, 99, 108, 154 Coenurus larva 83
Cathaemasia cabreri 59 Cognitive ability and nematodes 130, 151, 166
Cats as hosts of Computerized axial tomography (CT) 36, 48, 81, 91
cestodes 69, 71, 94 Concentration methods for faeces examination
intestinal nematodes 153, 157, 160 260–262
tissue nematodes 187, 205, 234 Concomitant immunity 23, 198
trematodes 45, 54, 56 Contracaecum osculatum 155
Cattle as hosts 31, 46, 49, 56, 75–76, 86, 92, 139, Copepods as intermediate hosts of
187 cestodes 66–67, 70, 101
Central nervous system (CNS) involvement 22, nematodes 185, 229
83, 84, 90, 120, 125, 159,179, 186, 209 Corbicula sp. 57
Centrocistus Cordylobia anthropophaga 242
armatus 54 Corticosteroids 119, 159, 181, 210
caninus 54 Corynosoma strumosum 107
cuspidatus 54 Cotylurus japonicus 59
formosanus 54 Counting techniques for microfilariae 264–265
kurokawai 54 Creeping eruption see Cutaneous larva migrans
longus 54 Crustaceans as hosts 145, 154, 156, 184
Cerithidea cingulata 52 crabs and crayfish 34, 36, 37, 219
Cervical smear 162 see also Copepods
Cestodes 63–105 Cryptocotyle lingua 54
classification 64–66 Culex as vectors of bancroftian filariasis
recognition in sections 267 annulirostris 200
Ceviche 186 bitaeniorhynchus 200
Cheilobus quadrilabiatus 125 pipiens molestus 200
Cheilospirura 187 pipiens pallens 200
Chemotherapy, mass or universal 28, 133–134, quinquefasciatus 200
201, 220 Culicoides
Chordodes capensis 108 as vectors of Mansonella ozzardi
Chrysomyia bezziana 242 furens 225
Chrysops spp. as intermediate hosts of loiasis paraensis 225
centurioni 206, 210 phlebotomus 225
dimidiatus 206, 210 as vectors of Mansonella perstans and M.
distinctipennis 206, 210 streptocerca
langi 206, 210 grahami 223, 225
silicea 206, 210 milnei 223, 225
14Worms & H.D. - Index 20/11/01 1:46 PM Page 290

290 Index

Cultivation of first-stage nematode larvae nihonkaiense 69

122–123, 262–263 orcini 69
Cutaneous larva migrans 159–160, 187 pacificum 69
Cyclops see Copepods scoticum 69
Cyclodontostomum purvisi 137 skjrabini 69
Cyclophyllidea 64, 71–103 tangussicum 69
Cyclosporin 25, 124 ursi 69
Cysticercosis 80–83 yonagoense 69
Cysticercus Diplogonoporus
bovis 74 brauni 69
cellulosae 78, 80–83 fukuokaensis 69
longicollis 83 grandis 69
Cystitis 18 Diploscapter coronata 125
Cytokines 23, 197, 209, 217, 244, 245, 249 Diplostomum spathaceum 58
Dipylidium caninum 102
Dirofilaria
Dams and schistosomiasis 29 immitis 226
Dermatitis 32, 156, 160, 214–215 louisianensis 226
Dermatobia hominis 241–242 magalhaesi 226
Diagnostic techniques for repens 226–227
eggs in faeces 258–260 spectans 226
microfilariae in blood 263–264 striata 227–228
Diaptomus see Copepods tenuis 227–228
Dicrocoelium ursi 227–228
dendriticum 45–46 Dogs as hosts of
hospes 46 cestodes 69, 71, 83, 84, 85, 94, 97,
Diethylcarbamazine 147, 159, 199, 201, 210, 102
218, 222, 224, 226 intestinal nematodes 137, 145, 153, 157,
Dioctophyma renale 184 160
Diorchitrema tissue nematodes 175, 183, 184, 187, 188,
amplicaecale 55 234
formosanum 55 trematodes 31, 43, 45, 54, 57, 58
pseudocirratum 55 Dracunculus
Diphyllobothrium insignis 234
cameroni 69 medinensis 228–234
cordatum 69 clinical manifestations 230–231
dalliae 69 diagnosis 231–232
dendriticum 69 epidemiology 232
elegans 69 geographical distribution 228
giljacicum 69 life cycle 229
hians 69 location in host 228
klebanovskii 69 morphology 228–229
lanceolatum 69 pathogenesis 231
latum 65–68 prevention and control 232–233
clinical manifestations 68 treatment 232
diagnosis 68 zoonotic aspects 234
epidemiology 69 Drepanidotaenia lanceolata 101
epidemiology 69
geographical distribution 65
life cycle 66 Ecdysteroids 119
location in host 65 Echinochasmus
morphology 65 fujianensis 57
pathogenesis 68 japonicus 57
prevention and control 68 jiufoensis 57
treatment 68 liliputanus 57
zoonotic aspects 69 perfoliatus 57
minus 69 Echinococcosis 85–87
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Echinococcus epidemiology 163–164

equinus 92 geographical distribution 160
granulosus 85–93 life cycle 161–162
clinical manifestations 87–90 location in host 160
diagnosis 90–91 morphology 160–161
epidemiology 87, 93–94 pathogenesis 162
geographical distribution 85 prevention and control 164
immunology 93 treatment 163
life cycle 85–87 zoonotic aspects 164
location in host 85 Entero-test 123
morphology 85 Eosinophilia and
pathogenesis 90 cestodes 74
prevention and control 92–93 intestinal nematodes 144, 146, 149, 158,
treatment 91 166
vaccines 93 tissue nematodes 175, 178, 186, 193, 195,
multilocularis 94–97 214, 226
clinical manifestations 94–96 trematodes 19, 40, 47, 53, 59
diagnosis 96 Eosinophils, staining for 255
epidemiology 96–97 Epidemiology of helminths 252–254
geographical distribution 94 Episthmium caninum 57
life cycle 94 Eucoleus (= Capillaria)
morphology 94 aerophilus 175
pathogenesis 96 boehmi 175
prevention and control 97 Eurytrema pancreaticum 46
treatment 96 Eustrongylides
oligarthrus 97 ignotus 184
ortleppi 92 tubifex 184
spp. differentiation 88 Eye lesions and
vogeli 97 acanthocephalans 241
Echinoparyphium cestodes 71
paraulum 57 intestinal nematodes 144, 154, 158
recurvatum 57 leeches 242
Echinostoma tissue nematodes 178, 208, 211, 216–217,
angustitestis 57 226
cinetorchis 57
echinatum (= lindoense) 57
hortense 57 Facilitation in mosquitos 200
ilocanum 56 Faecal examination
japonicum 57 for diagnosis of larvae 261–263
macrorchis 57 for eggs 255–262
malayanum 57 quantitative techniques 260–262
melis 57 Fasciola
revolutum 57 gigantica 49
Egg hepatica 46–49
counting techniques 260–262 clinical manifestations 47
identification 256–257 diagnosis 48
production epidemiology 48
cestodes 66 geographical distribution 46
intestinal nematodes 129, 135, 148, 161, 165 immunology 41–42
trematodes 13, 16, 38, 50 life cycle 46–47
Elephantiasis 194–195, 204 location in host 46
Endoscopy for anisakids 155 morphology 46
Enterobius pathogenesis 47
gregorii 161 prevention and control 45
vermicularis 160–164 treatment 48
clinical manifestations 162 zoonotic aspects 48
diagnosis 162–163 indica 49
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292 Index

Fasciolopsis buski 49–51 geographical distribution 185

clinical manifestations 50 life cycle 185–186
diagnosis 50 location in host 184
epidemiology 51 pathology 187
geographical distribution 49 Goats as hosts 31, 76, 92
life cycle 50 Gongylonema pulchrum 187
location in host 49 Gordius
morphology 50 aquaticus 108
pathogenesis 50 chilensis 108
prevention and control 51 gesneri 108
treatment 50–51 inesae 108
zoonotic aspects 51 ogatae 108
Fibrosis 18, 21–22, 41, 48, 120. 141, 178, 196, perronciti 108
208 reddyi 108
Filarial robustus 108
infections, accidental 226–228 setiger 108
infective larvae skorikowi 108
mounting 265 Granulomas 20, 22–23, 36, 48, 153, 155, 159,
staining before dissection 265 227
vectors, dissection of 265 ‘Ground itch’ see Cutaneous larva migrans
Fish Gymnophalloides seoi 59
freshwater as intermediate hosts 42–43, 53, Gyraulis chinensis 50
54, 56, 58–59, 69, 174, 185, 186, 187
marine as final hosts 155
marine as intermediate hosts 71, 154–155, Haematuria in schistosomiasis 18
156, 187 Haemonchus contortus 139
Fish dishes, in transmission 45, 89, 156, 186, Hairworms see Nematomorpha
187 Halicephalus (= Micronema) deletrix 125
Fischoederius elongatus 56 Halzoun 241
Fleas as hosts 102 ‘Hanging groin’ in onchocerciasis 215
Flies as hosts 187 Haplorchis
Flubendazole 82 microchis 55
Formol–ether egg concentration method pleurolophocerca 55
259–260 pumilio 55
Foxes as hosts 94, 97, 145, 182 tachui 55
vanissimus 55
yokogawai 55
Gasterophilus sp. 242 Harada–Mori larval cultivation technique
Gastrodiscoides hominis 55–56 262–263
geographical distribution 55 Heart involvement 22, 53, 54, 125, 179, 226
life cycle 55 Helminths
location in host 55 preservation 205–207
morphology 55 recognition in sections 267–269
zoonotic aspects 55–56 Heliosoma sp. 58
Geohelminths 115–168 Hepatitis 18, 40, 45, 46, 159, 175
Geophagia 153, 168 Hepatomegaly 22, 44, 96, 146, 158, 159, 175
Gigantobilharzia Herbivores in general as hosts 46, 49, 56, 70, 76,
huttoni 32 86, 92, 139, 140, 187
sturniae 32 Heterobilharzia americana 32
Gnathostoma Heterophyes
doloresi 186 dispar 55
hispidum 156, 186 equalis 55
nipponicum 187 heterophyes 51–53
spinigerum 184–186 clinical manifestations 53
clinical manifestations 186 diagnosis 54
diagnosis 186 epidemiology 54
epidemiology 86 geographical distribution 51
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life cycle 52 immunodiffusion 146, 174

location in host 51 immunoelectrophoresis 146
morphology 52 indirect fluorescent antibody (IFA) test 232
pathogenesis 53 indirect haemagglutination (IHA) 93, 132,
prevention and control 53 174
treatment 53 intradermal (ID) test 36, 42, 48
zoonotic aspects 53 latex agglutination 146
heterophyes nocens 55 radioimmunoassay (RIA) 132
katsuradai 55 sodium dodecyl sulphate – polyacrylamide
Heterophyopsis continua 57 gel electrophoresis (SDS–PAGE) 49, 75,
Himasthla muehlensi 57 159, 232
Hookworms 126–127, 160 Immunoglobulins 244
Horses as hosts 92, 125, 154 IgA 31, 41, 121, 149, 244
HTLV-1 and Strongyloides 119 IgD 243
Human leucocyte antigen (HLA) 17, 217 IgE 23, 41, 121, 123, 198, 217, 244, 249
Hydatid 64, 85, 86, 87, 89, 90, 91, 97 IgG 24, 41, 123, 159, 180, 244, 248
Hydrocele 194, 195, 199, 201 IgG1 121, 155, 198, 209, 217
Hydronephrosis 18 IgG2 31, 198
Hymenolepis IgG4 23, 142, 198, 209, 217, 232, 251
diminuta 101 IgM 42, 59, 198, 217, 244, 248
geographical distribution 101 Immunology of
life cycle 101 cestodes 93
location in host 101 helminths 243–251
morphology 101 intestinal nematodes 120–122
nana 98–101 liver flukes 41–42
clinical manifestations 99 lymphatic filariae 196–198
diagnosis 99 Onchocerca 217
epidemiology 99–100 schistosomes 23
geographical distribution 98 Immunomodulation 23, 119, 180, 198
life cycle 98 Inermicapsifer madagascariensis 102–103
location in host 98 Inflammation due to
morphology 98 cestodes 74, 84
pathogenesis 99 intestinal nematodes 120, 144, 146, 147,
prevention and control 100 153, 160, 162, 167
treatment 100 tissue nematodes 179, 193, 244
zoonotic aspects 100–101 trematodes 18, 41, 47, 53
Hyperinfection 119, 124 Insects, in general, as hosts 46, 58, 102, 103,
Hypodereum conoideum 57 157, 188
Hypoderma bovis 242 Interleukins 96, 197, 214, 248
Hysterothylacium aduncum 155 Intestinal obstruction and
cestodes 68, 74
intestinal nematodes 119, 150
Immunodiagnostic techniques trematodes 20, 50
complement fixation (CF) 42, 132 Isoparorchis hypselobagri 59
coelectrosyneresis (Co–ES) 209 Ivermectin 124, 153, 154, 163, 167, 175, 199,
DNA probes 218, 227 201, 210, 218, 222, 224, 232
enzyme linked immunosorbent assay
(ELISA) and
cestodes 71, 75, 79, 93 Katayama syndrome 19–20
intestinal nematodes 123, 132, 145, 146, Kato–Katz faecal technique 258–259
154, 155, 159 Key to nematodes in sections 269
tissue nematodes 174, 180, 186, 199, 209, Kidney worm see Dioctophyma
218, 232 Kidneys and
trematodes 24, 36, 42, 44, 48 cestodes 78, 90
immunoblotting techniques 24, 48, 75, 93, intestinal nematodes 119, 157
145, 155, 159, 180, 186, 209 tissue nematodes 184, 178, 193, 210, 222
immunochromatographic test (ICT) 198 trematodes 20, 50
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294 Index

Lagochilascaris minor 153, 156 Mammomonogamus

Larva currens 119, 122 laryngeus 142–143
Larva migrans 156–160 clinical manifestations 142
cutaneous 159–160 diagnosis 143
ocular 158 geographical distribution 142
visceral (VLM) 159 life cycle 142
Larvae morphology 142
cultivation of 122–124, 261–263 pathogenesis 142
filarial, in insects, staining and mounting treatment 143
265 zoonotic aspects 143
Leeches 241 nasicola 143
Levamisole 133, 152, 153, 163 Mansonella
Ligula intestinalis 69 digitatum 223
Limitation in mosquito infections 200 perstans 221–223
Limnatis nilotica 241 ozzardi 225–226
Linguatula serrata 240–241 rodhaini 225
Liver flukes, immunology of 41–42 semiclarum 222
Liver involvement and streptocerca 223–225
cestodes 87, 91, 96, 97 Mansonia
intestinal nematodes 150, 155, 157 as vectors of bancroftian filariasis
tissue nematodes 175, 186 200
trematodes 21–22, 40–41, 43–44, 45, 46, 47 as vectors of malayan filariasis 205
Loa loa 206–211 as vectors of subperiodic malayan filariasis
clinical manifestations 207–208 205
diagnosis 209 Marisa cornuarietus in schistosomiasis control
epidemiology 210 29
geographical distribution 206 Marrara syndrome 241
life cycle 206–207 Marshallagia marshalli 139
location in host 206 Marsupials as hosts 38, 92, 153
morphology 206 Mathematical models 253
pathogenesis 208–209 Mathevotaenia symmetrica 102–103
prevention and control 210 Mazzotti (provocation) test 217
treatment 210 McMaster egg counting chamber 262
zoonotic aspects 210–211 Mebendazole 92, 123, 133, 138, 153, 163, 174,
Loaina sp. 211 181, 186, 232
Loeffler’s syndrome 149–150, 158 Mecistocirrus digitatus 139
Lung involvement and Melanoides tuberculata in schistosomiasis
cestodes 71, 90, 97 control 29
intestinal nematodes 119–120, 129, 149, Meningitis 35, 119, 144, 145, 178
153, 157–158, 179 Meningonema peruzii 223
tissue nematodes 186, 195–196, 208 Mermis nigrescens, M. sp. 184
trematodes 19, 35, 37, 58 Mesocestoides
Lymphatic filariasis 190–206 lineatus 103
Lymphoscintigraphy 193 variabilis 103
Lymphatic involvement 43, 193–196, 198, 204, Metagonimus
206, 214, 222, 226 minutis 55
takahashi 55
yokogawai 53–55
Macdonald pipette for egg counts 262 clinical manifestations 54
Macranthorhynchus diagnosis 54
hirudinaceus 107 epidemiology 54
ingens 107 geographical distribution 54
Magnetic Resonance Imaging (MRI) 81, 91 life cycle 54
Malabsorption syndrome 120, 151, 174 location in host 54
Malnutrition 119, 132, 161, 166 morphology 54
Mammals, marine, as hosts 69–70, 107, pathogenesis 54
155–156, 182 Metastrongylus elongatus 147
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Metorchis argentinus 137

albidus 45 suillus 137
conjunctus 45 Necrosis due to
Metrifonate 25 cestodes 96, 99
Metronidazole 232 intestinal nematodes 132, 144, 155
Meyers–Kouwenaar’s syndrome 196 tissue nematodes 179, 196
Mice as hosts trematodes 22, 36, 47, 53, 57
experimental 23, 71, 83, 120, 159, 250 Nematodes 109–239
natural 37, 100, 153, 157, 164, 175 classification of 109–115
Microbilharzia variglandis 32 identification key for sections of 269
Microfilariae key to those parasitic in humans
counting techniques 164–165 113–114
differentiation 189 life cycles 110
staining 263–264 mode of transmission 113
Microphallus minus 59 recognition in sections 267–269
Microtriches 63–64 Nematodirus abnormalis 139
Millipore membrane filter 264 Nematomorpha 108
Mites Neochordades columbianus 108
as hosts 64, 65, 102 Neodiplostomum seoulensis 58
Molluscicides 28 Neorickettsia helminthoeca 58
Molluscs, bivalves, as intermediate hosts 56, 57, Neotricula aperta 27
59, 158, 184 ‘Nevinny’s basophilic halo’ 179
Moniliformis moniliformis 106–107 Niclosamide 28, 53, 69, 75, 80, 99
clinical manifestations 107 Nippostrongylus brasiliensis 120
life cycle 106 Nodulectomy 218
location in host 106 Nodules 184, 186, 214, 218, 226
morphology 106 Nuclear DNA reduction 154
pathology 107
treatment 107
Monkeys as hosts 31, 56, 55, 103, 125, 140, 146, Oedema due to
164, 168, 175, 187, 203, 211, 223 cestodes 90
Mortality rate 24, 92, 96, 144, 150, 174, 231 intestinal nematodes 120, 132, 141, 167
Mosquitoes tissue nematodes 178, 179, 186, 194, 209,
control 201–202, 205 215, 224, 230
as intermediate hosts 199, 200, 205, trematodes 50, 57
226 Oesophagostomum
Myiasis 241–242 aculeatum 140, 141
apiostomum 142
bifurcum 140–142
Nanophyetus salmincola, N. s. schikhobalowi clinical manifestations 140–141
58–59 diagnosis 141
Natural killer (NK) cells 244 epidemiology and control 142
Necator geographical distribution 140
americanus 126–134 life cycle 140
clinical manifestations 129–130 morphology 140
diagnosis 132 pathogenesis 140–141
differentiation from Ancylostoma 130 treatment 142
epidemiology 133 stephanostomum 140
geographical distribution 126 Oestrus ovis 242
immunology 120–122 Oligochaetes see Annelids
life cycle 127–128 Onchocerca
location in host 126 armillatus 220
morphology 126–127 cervicalis 220
pathogenesis 130–132 gibsoni 220
prevention and control 133–134 gutturosa 220
treatment 132–133 ochengi 220
zoonotic aspects 134 reticulata 220
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296 Index

Onchocerca continued Palm Island mystery disease 159

volvulus 211–220 Pancreatitis 41, 150
clinical manifestations 213–217 Pangolins as hosts 205
diagnosis 217–219 Parachordodes
epidemiology 218–219 alpestris 108
immunology 217 pustulosus 108
geographical distribution 211 raphaelis 108
life cycle 213 tolusanus 108
location in host 211 violaceus 108
morphology 211 wolterstoffi 108
pathogenesis 213–217 Parafossarulus manchouricus 5, 38
prevention and control 219–220 Paragonimus
treatment 218 africanus 37
zoonotic aspects 220 bangkokensis 37
Onchocerciasis Control Programme (OCP) caliensis 37
219–220 heterotremus 36, 37
Oncomelania kellicotti 37
mexicanus 37
formosana 34
miyazaki 37
hupensis 27
ohirai 37
lindoensis 27
philippinensis 37
nosophora 34
pulmonalis 37
quadrasi 27
sadoensis 37
spp. 5, 11–12, 27
skrjabini 37
Opisthorchis
uterobilateralis 37
felineus 44–45
westermani 32–37
clinical manifestations 45
clinical manifestations 35
diagnosis and treatment 45 diagnosis 36
epidemiology 45 epidemiology 36–37
geographical distribution 44 geographical distribution 32, 33
immunology 41–42 life cycle 34–35
life cycle 44 location in host 32
location in host 44 morphology 32
morphology 44 pathogenesis 35
zoonotic aspects 45 prevention and control 37
guayaquitensis 45 treatment 36
noverca 45 zoonotic aspects 37
sinensis see Clonorchis sinensis Paragordius
viverrini 43–44 cinctus 108
clinical manifestations and pathogenesis esavianus 108
43 tanganyikae 108
diagnosis 44 tricuspidatus 108
epidemiology 44 varius 108
geographical distribution 39, 43 Paralecithodendrium
immunology 41–42 glandulosum 58
life cycle 43 obtusum 58
location in host 43 Parascaris equorum 154, 156
morphology 43 Parastrongylus (= Angiostrongylus)
treatment 44 cantonensis 143–145, 156
zoonotic aspects 44 clinical manifestations 143–144
Orientobilharzia turkestanica 32 diagnosis 144–145
Ornithobilharzia turkestanicum 32 epidemiology 145
Ostertagia geographical distribution 143
cicumcincta 139 life cycle 143
ostertagi 139 location in host 143
Oxamniquine in schistosomiasis 25 mophology 143
Oxantel pamoate in trichuriasis 167 treatment 145
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costaricensis 145–147, 156 Portal hypertension 21–22, 40, 41

clinical manifestations 146 Praziquantel
diagnosis 146 cestode infections 68, 75, 80, 82, 84, 92, 99,
geographical distribution 143 101, 102
life cycle 146 trematode infections 24, 36, 42, 44, 50, 53,
location in host 145 57, 59
morphology 145–146 Prehistoric helminth infections 106, 164, 168
treatment 147 Preservation of helminths 165–167
mackerrasae 145 Primates (non human) as hosts 23, 84, 125, 153,
malaysiensis 145 168, 209, 211, 226
vasorum 145 Procerovum
Paratenic hosts calderoni 55
acanthocephalans 107 varium 55
cestodes 67, 70 Prohemistomum vivax 59
intestinal nematodes 145, 155 Prosthodendrium molenkampi 58
tissue nematodes 184, 186, 188, 234 Proteases 26, 119, 127
trematodes 37, 58 Protozoans (except amoebiasis) 132, 249
Paryphostomum Pruritis 74, 119, 120, 129, 135, 209, 214, 222,
bangkokensis 59 224, 230
sufrartyfex 59 pruritis ani and pruritis vulvae 162
PCR (polymerase chain reaction) amplification Pseudamphistomum
30, 199, 200, 209, 218, 227 aethiopicum 45
Pelodera truncatum 45
strongyloides 126 Pseudoacanthocephalus bufonis 107
teres 126 Pseudoapolysis 68
Peritonitis 141, 150 Pseudophyllidea 64, 65–71
Phagicola Pseudoterranova decipiens 155
longa 55 Pseudotubercle 20, 35
ornamenta 55 Psilorchis hominis 59
ornata 55 Pygidiopsis summa 55
Phaneropsolus Pyramicocephalus anthocephalus 69–70
bonnei 58 Pyrantel pamoate 133, 152, 163, 181
spinicirrus 58
Pharyngostomum flapi 55
Philophthalmus lacrymosus, P. sp. 59 Rabbits and hares as hosts 85, 175, 211
Physaloptera transfuga 187 Radiography 18, 36, 81, 91, 146, 149, 151, 155,
Pica see Geophagia 158, 229
Pigs as hosts Raillietina
domestic of asiatica 103
cestodes 78, 80, 92 celebensis 103
intestinal nematodes 137, 140, 149, garrisoni 103
153 madagascariensis 103
tissue nematodes 182, 183, 187 siviraji 103
trematodes 31, 43, 45, 54, 55 Rats as hosts 37, 43, 54, 57
wild 80, 182, 183 Recognition of helminths in sections 267–269
Pila sp. 56, 57 Rectal prolapse 166
Pirenella conica 5, 52 Reptiles as hosts 70, 71
Plagiorchis snakes 187, 240
harinasutai 58 Rhabditis
javensis 58 axei 126
muris 58 elongata 126
philippinensis 58 inermis 126
Planarians as hosts 145 niellyi 126
Planorbis sp. 57 pellio 126
Platyhelminthes 3 sp. 126
Poikilorchis congolensis 38 taurica 126
Polypylis (= Segmentina) hemisphaerula 50 terricola 126
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298 Index

Rhinoestrus purpureus 242 Americas 219

Rictularia spp. 188 as vector of Mansonella ozzardi 225
‘Ridley–Hissette’ fundus 216 as vector of Dirofilaria ursi 228
Rodents (apart from mice and rats) as hosts 31, Skin snip 218, 224
41, 55, 94, 97, 100, 101, 120, 146, 153, Slugs as hosts 143, 146
164, 188 Snails
Robertsiella sp. 27 control of 28–29
Ruminants see Herbivores hosts of intestinal trematodes 5, 50, 52, 54,
55, 56, 57, 58
hosts of liver flukes 38, 43, 44, 46, 47, 49,
Sanitation and 50
geohelminths 133–134 hosts of lung flukes 34
lymphatic filariasis 201–202 hosts of nematodes 145
schistosomiasis 29 hosts of schistosomes 27
‘Sashimi’ in transmission 45, 69, 156, 186 infected with larval trematodes
Schistocephalus solidus 69 Snakes see Reptiles
Schistosoma Soluble egg antigen (SEA) 22, 24
bovis 32 Sowda 215
curassoni 32 Sparganosis 70–71
haematobium 9–17 Sparganum proliferum 71
intercalatum 10, 11, 13, 16, 17 Spirocerca lupi 188
japonicum 10–17, 156 Spirometra
malayensis 10, 11 erinacei 71
mansoni 10, 12–13, 15–17 houghtoni 71
margrebowiei 32 mansoni 71
mattheei 31 mansonoides 71
mekongi 10, 16, 31 spp. 70–71, 156
rodhaini 32 theileri 71
sinensium 10, 31 ‘Splendore–Hoeppli’ phenomenon 23
spindale 32 Splenomegaly 19, 21, 40, 97
Schistosomatium douthitti 32, 156 Sputum 35, 36, 90, 129, 138, 142, 149, 187, 211
Schistosomes 9–32 Staining of
clinical manifestations 17–23 filarial larvae in insects 265
differential features 10–11, 13 microfilariae 263–264
diagnosis 23–4 trematodes and cestodes 265
epidemiology 25–27 Stellantchasmus
geographical distribution 10 amplicaecalis 55
immunology 23 falcatus 55
life cycles 11–17 Stichosome 165, 177
morphology 10–11 Stictodora
pathogenesis 17–23 fuscata 55
prevention and control 27–31 manilensis 55
snail hosts 27 Stoll egg counting technique 161–162
treatment 24–25 ‘Strogonina’ in transmission 71
zoonotic aspects 31–32 Strongyloides
Schistosomula 12–14 canis 125
Semisulcospira cebus 125
amurensis 5, 34, 54 felis 125
libertina 5, 34, 54 fuelleborni 125
Sections, recognition of helminths in 267–269 fuelleborni kellyi 125
Sheep as hosts myopotami 125
acanthocephalans 241 papillosus 125
cestodes 85, 93 planiceps 125
nematodes 125, 139, 187 procyonis 125
trematodes 30, 31, 46, 47, 48, 49 ransomi 125
Simulium spp. ratti 120
as vectors of onchocerciasis in Africa 219 simiae 125
as vectors of onchocerciasis in the stercoralis 115–126
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clinical manifestations 119 immunology 93

diagnosis 122–123 life cycle 78–79
epidemiology 124 location in host 76
geographical distribution 115 morphology 78
immunology 120–122 pathogenesis 79
life cycle 117–119 prevention and control 80
location in host 115 treatment 79–80
morphology 115–117 zoonotic aspects 80
pathogenesis 119–120 taeniaeformis 250
prevention and control 124 Tarebria granifera 29
treatment 124–125 T cells 20, 23, 30, 31, 96, 120, 198, 209, 217,
zoonotic aspects 125–126 244–245
westeri 125 Temephos 220, 233
venezuelensis 120 Ternidens deminutus 139–140
Stunting of growth 130, 137 clinical manifestations 139
Suramin 218 diagnosis 140
‘Swimmer’s itch’ 18, 32, 156 epidemiology 140
Swine see Pigs geographical distribution 139
Swollen belly syndrome 125 life cycle 139
Symmer’s pipestem fibrosis see Fibrosis location in host 139
Syphacia obvelata 164 treatment 140
zoonotic aspects 140
Test tube culture of larvae (Harada–Mori)
T cells 20, 23, 30, 31, 96, 120, 198, 209, 217, 262–263
244–245 Tetrathyridium larva 103
Taenia Thelazia
brauni 83 californiensis 187
crassiceps 83 callipaeda 187
glomeratus 84 Thiabendazole 123, 147, 153, 154, 159, 167,
longihamatus 85 175, 181, 232
multiceps 83 Thiara granifera 5, 34
clinical manifestations 83 ‘Tonle sap’ schistosome 31
life cycle 83 Toxascaris leonina 157
morphology 83 Toxocara
pathogenesis 83 canis 157
ovis 93 cati 157
saginata 71–76 pteropodis 159
clinical manifestations 74 Trematodes 3–62
diagnosis 75 classification 6–9
epidemiology 75–76 life cycle stages 6
geographical distribution 72 medically important species 4
immunology 93 mode of infection 8
life cycle 72–74 morphology 5, 7
location in host 72 preservation of 265–266
morphology 72 recognition in sections 267
pathogenesis 74 snail hosts of 5
prevention and control 76 staining for 266
treatment 75 Trichinella
zoonotic aspects 76 britovi 182–183
saginata asiatica 76 murrelli 182
serialis 84 nativa 182–183
solium 76–82 nelsoni 182–183
cysticercosis 80–82 papuae 183
clinical manifestations 79 pseudospiralis 182–183
diagnosis 79 spiralis 120, 176–183
epidemiology 80 clinical manifestations 177–179
geographical distribution 76–77 diagnosis 180
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300 Index

Trichinella continued Tunga penetrans 240

spiralis continued
epidemiology 182–184
geographical distribution 176 Ulceration 20, 50, 53, 70, 119, 120, 137, 139,
life cycle 176–177 151, 155, 162, 230
location in host 176 Ultrasound (US) 18, 49, 81, 92, 96, 143, 151,
morphology 176 194, 198, 199, 217
pathogenesis 179–180 Uncinaria stenocephala 160
prevention and control 182 Urine 16, 18, 24, 29, 31, 110, 123
treatment 181
zoonotic aspects 182–183
Trichobilharzia Vaccines 30–31, 48, 96, 251
brevis 32, 156 Ventilated improved pit (VIP) latrine 134
maegraithi 32, 156 Viruses 3, 30, 71, 158, 166
ocellata 32, 156 Visceral larva migrans 156–159
stagnicolae 32, 156 Vitamins
Trichocephalus see Trichuris A 215
Trichostrongylus B12 68, 132
affinis 139 C 151
axei 139 Vivipara sp. 57
brevis 139
calcaratus 139
capricola 139 ‘Wakana disease’ 135
colubriformis 139 Watch glass culture method for larvae 123
lerouxi 139 Water plants and
orientalis 139 fascioliasis 48
probolurus 139 fasciolopsiasis 51
skjrabini 139
malayan filariasis 205
vitrinus 139
Watsonius watsoni 56
Trichuris
Whipworms see Trichuris
muris 120, 168
WHO (World Health Organization) initiatives 1,
ovis 168
200, 219, 233
suis 168
Wohlbachia in filariae 196–197, 218
trichiura 164–168
Wuchereria
clinical manifestations 165–166
bancrofti 190–202
diagnosis 167
clinical manifestations 193–196
epidemiology 167–168
diagnosis 198–199
geographical distribution 164
life cycle 165 epidemiology 199–200
location in host 164 geographical distribution 190
morphology 164–165 immunology 196–198
pathogenesis 166–167 life cycle 192–193
prevention and control 168 location in host 190
treatment 167 morphology 190–191
zoonotic aspects 168 pathogenesis 196
vulpis 168 prevention and control 200–202
Triclabendazole 48 treatment 199
Tropical pulmonary eosinophilia 195–196 zoonotic aspects 202
Tuberculosis 20, 36, 119 bancrofti var. vauceli 192
‘Tumeur de Dapaong’ 141 kalimantani 202
Tumours in lewisi 202
cestodes 83, 89, 90–91
intestinal nematodes 96, 99
myiasis 242 X-rays see Radiography
tissue nematodes 132, 144, 155
trematodes 36
Tumour necrosis factor (TNF) 217 Zinc sulphate flotation for eggs 260