Blood & Tissue

Protozoa
By Moses Tamba
Momoh.
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 INTRODUCTION
• The medically important organisms in this category are:
• The sporozoans Plasmodium and Toxoplasma
• The flagellates Trypanosoma and Leishmania.

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 PLASMODIUM
• Malaria is caused primarily by four plasmodia:
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Plasmodium falciparum.
• A fifth species, Plasmodium knowlesi, is found in Southeast Asia.
• Plasmodium vivax and P. falciparum are more common causes of malaria than
are P. ovale and P. malariae.
• Plasmodium vivax is most widely distributed and P. falciparum causes the most
serious disease.
• Worldwide, malaria is one of the most common infectious diseases and one of
the leading causes of death. MOSEM
 Life cycle
• The vector and definitive host for plasmodia is the female Anopheles mosquito.
• Have two Phases of life cycles: Asexual (in man) and sexual (in mosquito).
• The sexual cycle is called sporogony because sporozoites are produced and the
asexual cycle is called schizogony because schizonts are made.
EXOERYTHROCYTIC PHASE
• The life cycle in humans begins with the introduction of sporozoites into the
blood from the saliva of the biting mosquito.
• The sporozoites are taken up by hepatocytes within 30 minutes and are then
converted into schizont following several cellular multiplication and
differentiation
• The mature schizonts repture to release the merozoites.
• Plasmodium vivax and P. ovale produce a latent form (hypnozoite) in the liver; this
form is the cause of relapses seen withMOSEM
vivax and ovale malaria.
 ERYTHROCYTIC PHASE
• Merozoites are released from the liver cells and infect red blood cells.
• During this phase the organism differentiates into a ring shaped
trophozoite
• The trophozoite grows into an ameboid form and then differentiate into a
schizont filled with merozoites.
• After release, the merozoites infect other erythrocytes.
• This cycle in the red blood cell repeats at regular intervals typical for each
species.
• The periodic release of merozoites causes the typical recurrent symptoms
of chills, fever, and sweats seen in malaria patients.
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 SEXUAL PHASE
• Begins in the human red blood cells when some of the merozoites(derived
from the erythrocytic trophozoites) develop into male and others into
female gametocytes.
• The gametocyte-containing red blood cells are ingested by the female
Anopheles mosquito
• Within the gut, it produces a female macrogamete and eight spermlike
male microgametes.
• After fertilization, the diploid zygote differentiates into a motile ookinete
that burrows into the gut wall, where it grows into an oocyst within which
many haploid sporozoites are produced.
• The sporozoites are released and migrate to the salivary glands, ready to
complete the cycle when the mosquito takes her next blood meal.
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 Pathogenesis
• Most of the pathologic findings of malaria result from the destruction
of red blood cells.
• Red cells are destroyed both by the release of the merozoites and by
the action of the spleen to first sequester the infected red cells and
then to lyse them.
• Splenomagely is due to congestion of sinusoids with erythrocytes,
coupled with hyperplasia of lymphocytes and macrophages.
• Malaria caused by P. falciparum is more severe than that caused by
other plasmodia.

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 Pathogenesis
It is characterized by:
Infection of far more red cells than the other malarial species
Occlusion of the capillaries with aggregates of parasitized red cells.
Causes a high level of parasitemia
It can infect red cells of all ages
• This leads to life-threatening hemorrhage and necrosis, particularly in the
brain (cerebral malaria).
• Furthermore, extensive hemolysis and kidney damage occur, with resulting
hemoglobinuria.
• The dark color of the patient’s urine has given rise to the term “blackwater
fever”.
• The hemoglobinuria can lead to acute renal failure.
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 Pathogenesis
• The timing of the fever cycle is 72 hours for P. malariae and 48 hours for the
other plasmodia.
• Disease caused by P. malariae is called quartan malaria because it recurs
every fourth day, whereas malaria caused by the other plasmodia is called
tertian malaria because it recurs every third day.
• Tertian malaria is subdivided into malignant malaria, caused by P.
falciparum, and benign malaria, caused by P. vivax and P. ovale.
• Plasmodium falciparum causes a high level of parasitemia because it can
infect red cells of all ages.
• In contrast, P. vivax infects only reticulocytes and P. malariae infects only
mature red cells; therefore, they produce much lower levels of parasites in
the blood.
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 Pathogenesis
• Individuals with sickle cell trait are protected against malaria because
their red cells have too little ATPase activity and cannot produce
sufficient energy to support the growth of the parasite.
• Sickle cell patients are also protected but rarely live long enough to
obtain much benefit.
• The receptor for P. vivax is the Duffy blood group antigen.
• People who are homozygous recessive for the genes that encode this
protein are resistant to infection by P. vivax.

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 Pathogenesis
• More than 90% of black West Africans and many of their American
descendants do not produce the Duffy antigen and are thereby
resistant to vivax malaria.
• People with G6PD deficiency are also protected against the severe
effects of falciparum malaria.
• Malaria is transmitted primarily by mosquito bites, but transmission
across the placenta, in blood transfusions, and by intravenous drug use
also occurs.

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 Pathogenesis

• Partial immunity(antibodies) against RBCs invading merozoites occurs

in infected individuals.
• A low level of parasitemia and low grade symptoms result; this
condition is known as premunition.
• In contrast, a non immune person, such as a first-time traveler to an
area where falciparum malaria is endemic, is at risk of severe, life-
threatening disease.

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 Epidemiology
• More than 200 million people worldwide have malaria, and more than
1 million die of it each year, making it the most common lethal
infectious disease.
• It occurs primarily in tropical and subtropical areas, especially in Asia,
Africa, and Central and South America.
• Malaria in the US is seen in Americans who travel to areas of endemic
infection without adequate chemoprophylaxis and in immigrants from
areas of endemic infection.
• Certain regions in Southeast Asia, South America, and east Africa are
particularly affected by chloroquine-resistant strains of P. falciparum
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 Clinical Findings
• Patients presents with fever and chills, accompanied by headache,
myalgias, and arthralgias, about two weeks after the mosquito bite.
• Fever may be continuous early in the disease.
• The typical periodic cycle does not develop for several days after
onset.
• The fever spike, which can reach 41°C, is frequently accompanied by
shaking chills, nausea, vomiting, and abdominal pain.
• The fever is followed by drenching sweats.
• Patients usually feel well between the febrile episodes.
• Splenomegaly is seen in most patients, and hepatomegaly occurs in
roughly one-third. MOSEM
 Clinical Findings
• Anemia is prominent.
• Untreated malaria caused by P. falciparum is potentially life-
threatening as a result of extensive brain (cerebral malaria) and kidney
(blackwater fever) damage.
• Malaria caused by the other three plasmodia is usually self-limited,
with a low mortality rate.
• However, relapses of P. vivax and P. ovale malaria can occur up to
several years after the initial illness as a result of hypnozoites latency in
the liver.

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 Laboratory Diagnosis

• Diagnosis rests on microscopic examination of blood using both thick

and thin Giemsa-stained smears.
• The thick smear is used to screen for the presence of organisms.
• The thin smear is used for species identification.
• Ring-shaped trophozoites can be seen within infected red blood cells.
• The gametocytes of P. falciparum are crescent-shaped whereas those
of the other plasmodia are spherical.
• If more than 5% of red blood cells are parasitized, the diagnosis is
usually P. falciparum malaria.

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 Laboratory Diagnosis

• Plasmodium species typically produce hemozoin pigment in infected red blood

cells whereas Babesia species do not.
• Plasmodia metabolize heme in the red cells to produce hemozoin.
• Also found within P. vivax and P. ovale-infected red cells are Schüffner’s dots.
• These are intracytoplasmic granules that stain red using the Romanovsky stain.
• NOTE: It is important to identify the species because the treatment of different
species can differ.
• If blood smears do not reveal the diagnosis, then a PCR-based test for
Plasmodium nucleic acids or an ELISA test for a protein specific for P. falciparum
can be useful.

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 Treatment
• The main criteria used for choosing specific drugs are the severity of
the disease and whether the organism is resistant to chloroquine.
• Chloroquine resistance is determined by the geographical location
where the infection was acquired rather than by laboratory testing.
• Chloroquine is the drug of choice for treatment of uncomplicated
malaria caused by non-falciparum species in areas without chloroquine
resistance.
• Chloroquine kills the merozoites, thereby reducing the parasitemia, but
does not affect the hypnozoites of P. vivax and P. ovale in the liver.
• These are killed by primaquine, which must be used to prevent
relapses.
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 Treatment
• Primaquine may induce severe hemolysis in those with G6PD
deficiency, so testing for this enzyme should be done before the drug is
given.
• If primaquine is not given, one approach is to wait to see whether
symptoms recur and then treat with chloroquine.
• Uncomplicated, chloroquine-resistant P. falciparum infection is treated
with either Coartem (artemether plus lumefantrine) or Malarone
(atovaquone and proguanil).
• In severe complicated cases of chloroquine-resistant falciparum
malaria, intravenous administration of either artesunate or quinidine is
used.
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 Treatment
• Outside the United States, the artemisinins, such as artesunate or
artemether, are widely used in combination with other antimalarial
drugs.
• The artemisinins are inexpensive and have few side effects.
• However, P. falciparum has developed resistance to artemisinins in
mainland Southeast Asia (e.g., Vietnam, Cambodia, Myanmar, and
Thailand).

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TREATMENT

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 Prevention
• Chemoprophylaxis of malaria for travelers to areas where chloroquine-
resistant P. falciparum is endemic consists of mefloquine or
doxycycline.
• A combination of atovaquone and proguanil (Malarone), in a fixed
dose, can also be used.
• Chloroquine should be used in areas where P. falciparum is sensitive to
that drug.
• Travelers to areas where the other three plasmodia are found should
take chloroquine starting two weeks before arrival in the endemic area
and continuing for 4 weeks after leaving the endemic area.
• This should be followed by a 2-week course of primaquine if exposure
was high. MOSEM
 Prevention

• Other preventive measures include the use of mosquito netting,

window screens, protective clothing, and insect repellents.
• Communal preventive measures are directed against reducing the
mosquito population.
• Many insecticide sprays, such as dichlorodiphenylchloroethane(DDT),
are no longer effective because the mosquitoes have developed
resistance.
• Drainage of stagnant water in swamps and ditches reduces the
breeding areas.

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 TOXOPLASMA GONDII
• Toxoplasma gondii causes toxoplasmosis, including congenital toxoplasma
LIFE CYCLE
• The definitive host is the domestic cat (in which both sexual and asexual cycles
take place) and other felines.
• Humans and other mammals are intermediate hosts(in which only the asexual
cycle takes place).

• T. gondii has two types of life cycles:

 Enteric cycle
 Exoenteric cycle.

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 Exoenteric Cycle (Human Cycle)
• Exoenteric cycle occurs in humans, mice, rats, sheep, cattle, pigs and
birds, which are the intermediate host
• Humans acquire infection after:
• Eating uncooked or undercooked infected meat, particularly lamb and
pork containing tissue cysts.
• Ingestion of mature oocysts through food, water, or fingers
contaminated with cat feces directly or indirectly.
• Intrauterine infection from mother to fetus (congenital toxoplasmosis).
• Blood transfusion or transplantation from infected donors.

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 Exoenteric Cycle (Human Cycle)
• Sporozoites from the oocysts and bradyzoites from the tissue cysts enter
into the intestinal mucosa and multiply asexually and tachyzoites are
formed (endodyogeny).
• Tachyzoites continue to multiply and spread locally by lymphatic system and
blood.
• Some tachyzoites also spread to distant extraintestinal organs like brain,
eye, liver, spleen, lung and skeletal muscles and form tissue cysts.
• The slowly multiplying forms inside the tissue cysts are known as
bradyzoites, which remain viable for years.
• The dormant bradyzoites inside the cyst may be reactivated in immune
suppression causing renewed infection in the host.
• Human infection is a dead end for the parasite.
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 Enteric Cycle (Feline Cycle)
• Other merozoites transform into male and female gametocytes and
sexual cycle (gametogony) begins, with the formation of microgamete
and macrogamete.
• A macrogamete is fertilized by motile microgamete resulting in the
formation of an oocyst, which passes through maturation stages
(sporulation) in the soil after being excreted from host through feces.
• A mature oocyst containing eight sporozoites is the infective form
which may be ingested by rats or other mammals to repeat the cycle.

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 Pathogenesis

• Toxoplasma gondii is usually acquired by ingestion of cysts in uncooked

meat or in food accidentally contaminated by cat feces.
• Transplacental transmission from an infected mother to the fetus
occurs also.
• Human-to-human transmission, does not occur, except transplacental
transmission.
• After infection of the intestinal epithelium, the organisms spread to
other organs, especially the brain, lungs, liver, and eyes. (BELL)
• Progression of the infection is usually limited by a competent immune
system. MOSEM
 Pathogenesis

• Cell-mediated immunity plays the major role, but circulating antibody

enhances killing of the organism.
• Most initial infections are asymptomatic.
• When contained, the organisms persist as cysts within tissues.
• There is no inflammation, and the individual remains well unless
immunosuppression allows activation of organisms in the cysts.
• Congenital infection of the fetus occurs only when the mother is
infected during pregnancy.

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 Pathogenesis
• If she is infected before the pregnancy, the organism will be in the cyst
form and there will be no trophozoites to pass through the placenta.
• The mother who is reinfected during pregnancy but who has immunity
from a previous infection will not transmit the organism to her child.
• Roughly one third of mothers infected during pregnancy give birth to
infected infants, but only 10% of these infants are symptomatic.

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 EPIDEMIOLOGY

• Infection by T. gondii occurs worldwide.

• Serologic surveys reveal that in the United States antibodies are
found in 5% to 50% of people in various regions.
• Infection is usually sporadic, but outbreaks associated with
ingestion of raw meat or contaminated water occur.
• Approximately 1% of domestic cats in the United States shed
Toxoplasma cysts

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 Clinical Findings
• Most primary infections in immunocompetent adults are asymptomatic, but
some resemble infectious mononucleosis, except that the heterophil antibody
test is negative.
• Congenital infection can result in abortion, stillbirth, or neonatal disease with
encephalitis, chorioretinitis, and hepato-splenomegaly.
• Fever, jaundice, and intracranial calcifications are also seen.
• Most infected newborns are asymptomatic, but chorioretinitis or mental
retardation will develop in some children months or years later.
• Congenital infection with Toxoplasma is one of the leading causes of blindness in
children.
• In patients with reduced cell-mediated immunity (e.g. AIDS), life-threatening
disseminated disease, primarily encephalitis,
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occurs.
 Laboratory Diagnosis
• For acute and congenital infections, an immunofluorescence assay for
IgM antibody is used.
• IgM is used to diagnose congenital infection, because IgG can be
maternal in origin. Tests for IgG antibody can be used to diagnose acute
infections if a significant rise in antibody titer in paired sera is observed.
• Microscopic examination of Giemsa-stained preparations shows
crescent-shaped trophozoites during acute infections.
• Cysts may be seen in the tissue.
• The organism can be grown in cell culture.
• Inoculation into mice can confirm the diagnosis.
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 Treatment & Prevention

• Congenital toxoplasmosis, whether symptomatic or asymptomatic,

should be treated with a combination of sulfadiazine and
pyrimethamine.
• These drugs also constitute the treatment of choice for disseminated
disease in immunocompromised patients.
• Acute toxoplasmosis in an immunocompetent individual is usually self-
limited, but any patient with chorioretinitis should be treated.

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 Treatment & Prevention

• Cook meat thoroughly to kill the cysts.

• Pregnant women should be especially careful to avoid undercooked
meat and contact with cat feces.
• Refrain from emptying cat litter boxes.
• Cats should not be fed with raw meat.
• Trimethoprim-sulfamethoxazole is used to prevent Toxoplasma
encephalitis in patients infected with HIV.

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 TRYPANOSOMA
• The genus Trypanosoma includes three major pathogens:
1. Trypanosoma cruzi
2. Trypanosoma gambiense
3. Trypanosoma rhodesiense.

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 Trypanosoma cruzi

The cause of Chagas’ disease (American trypanosomiasis).

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 LIFE CYCLE
• VECTOR: reduviid bug (Triatoma, cone-nose or kissing bug)
• RESERVOIR HOSTS: humans, cats and dogs and wild species such as the
armadillo, raccoon, and rat.
• The cycle in the reduviid bug begins with ingestion of trypomastigotes
in the blood of the reservoir host.
• In the insect gut, they multiply and differentiate first into epimastigotes
and then into trypomastigotes.

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 LIFE CYCLE
• When the bug bites again, the site is contaminated with feces
containing trypomastigotes, which enter the blood of the person and
form nonflagellated amastigotes within host cells.
• Many cells can be affected, but myocardial, glial, and
reticuloendothelial cells are the most frequent sites.
• To complete the cycle, amastigotes differentiate into trypomastigotes,
which enter the blood and are taken up by the reduviid bug.

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MOSEM
 EPIDIMIOLOGY
• Chagas’ disease occurs primarily in rural Central and South America.
• Acute Chagas’ disease occurs rarely in the United States, but the
chronic form causing myocarditis and congestive heart failure is seen
with increasing frequency in immigrants from Latin America.
• The disease is seen primarily in rural areas because the reduviid bug
lives in the walls of rural huts and feeds at night.
• It bites preferentially around the mouth or eyes, hence the name
“kissing bug”.

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 PATHOGENESIS
• The amastigotes can kill cells and cause inflammation, consisting
mainly of mononuclear cells.
• Cardiac muscle is the most frequently and severely affected tissue.
• In addition, neuronal damage leads to cardiac arrhythmias and loss of
tone in the colon (megacolon) and esophagus (megaesophagus).
• During the acute phase, there are both trypomastigotes in the blood
and amastigotes intracellularly in the tissues.
• In the chronic phase, the organism persists in the amastigote form.

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 Clinical Findings
• The acute phase of Chagas’ disease consists of facial edema and a
nodule (chagoma) near the bite, coupled with fever, lymphadenopathy,
and hepatosplenomegaly.
• A bite around the eye can result in unilateral palpebral swelling called
Romaña’s sign.
• The acute phase resolves in about 2 months.
• Most individuals then remain asymptomatic, but some progress to the
chronic form with myocarditis and megacolon.
• Death from chronic Chagas’ disease is usually due to cardiac
arrhythmias or congestive heart failure
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 Laboratory Diagnosis
• Acute disease is diagnosed by demonstrating the presence of trypomastigotes in
thick or thin films of the patient’s blood.
• Both stained and wet preparations should be examined, the latter for motile
organisms.
• Because the trypomastigotes are not numerous in the blood, other diagnostic
methods may be required, like:
• A stained preparation of a bone marrow aspirate or muscle biopsy specimen
which may reveal amastigotes
• Culture of the organism on special medium
• xenodiagnosis, which consists of allowing an uninfected, laboratory-raised
reduviid bug to feed on the patient and, after several weeks, examining the
intestinal contents of the bug for the organism.
• Serologic tests can be helpful also. MOSEM
 Treatment & Prevention
• The drug of choice for the acute phase is nifurtimox, which kills
trypomastigotes in the blood but is much less effective against
amastigotes in tissue.
• Benznidazole is an alternative drug.
• No effective drug against the chronic form.

• Prevention involves protection from the reduviid bite improved

housing, and insect control.
• No prophylactic drug or vaccine is available.
• Blood for transfusion is tested for the presence of antibodies to T. cruzi.
• Blood containing antibodies should not be used.
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 Trypanosoma gambiense & rhodesiense
• These organisms cause sleeping sickness (African trypanosomiasis).
• They are also known as Trypanosoma brucei gambiense and
Trypanosoma brucei rhodesiense.

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 Important Properties
• The morphology and life cycle of the two species are similar.
• The vector for both is the tsetse fly, Glossina, but different species of fly are
involved for each.
• Humans are the reservoir for T. gambiense, whereas T. rhodesiense has
reservoirs in both domestic animals (especially cattle) and wild animals
(e.g., antelopes).
• The 3-week life cycle in the tsetse fly begins with ingestion of
trypomastigotes in a blood meal from the reservoir host.
• These species are rarely found as amastigotes in tissue, in contrast to T.
cruzi and Leishmania species, in which amastigotes are commonly found.
• These trypanosomes exhibit remarkable antigenic variation of their surface
glycoproteins, with hundreds of antigenic types found.
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 Pathogenesis & Epidemiology
• The trypomastigotes spread from the skin through the blood to the
lymph nodes and the brain.
• The typical somnolence (sleeping sickness) progresses to coma as a
result of a demyelinating encephalitis.
• In the acute form, a cyclical fever spike (approximately every 2 weeks)
occurs that is related to antigenic variation.
• As antibody-mediated agglutination and lysis of the trypomastigotes
occur, the fever subsides.
• However, a few antigenic variants survive, multiply, and cause a new
fever spike. This cycle repeats itself over a long period.
• The lytic antibody is directed against the surface glycoprotein.
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 Pathogenesis & Epidemiology
• The disease is endemic in sub-Saharan Africa, the natural habitat of
the tsetse fly.
• Both sexes of fly take blood meals and can transmit the disease.
• The fly is infectious throughout its 2- to 3-month lifetime.
• Trypanosoma gambiense is the species that causes the disease along
water courses in west Africa,
• T. rhodesiense is found in the arid regions of east Africa.
• Both species are found in central Africa.

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 Clinical Findings
• Although both species cause sleeping sickness, the progress of the
disease differs.
• Trypanosoma gambiense–induced disease runs a low-grade chronic
course over a few years,
• T. rhodesiense causes a more acute, rapidly progressive disease that, if
untreated, is usually fatal within several months.
• The initial lesion is an indurated skin ulcer (“trypanosomal chancre”) at
the site of the fly bite.

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 Clinical Findings
• After the organisms enter the blood, intermittent weekly fever and
lymphadenopathy develop.
• Enlargement of the posterior cervical lymph nodes (Winterbottom’s
sign) is commonly seen.
• The encephalitis is characterized initially by headache, insomnia, and
mood changes, followed by muscle tremors, slurred speech, and
apathy that progress to somnolence and coma.
• Untreated disease is usually fatal as a result of pneumonia.

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 Laboratory Diagnosis
• During the early stages, microscopic examination of the blood
(either wet films or thick or thin smears) reveals trypomastigotes.
• An aspirate of the chancre or enlarged lymph node can also
demonstrate the parasites.
• The presence of trypanosomes in the spinal fluid, coupled with an
elevated protein level and pleocytosis, indicates that the patient
has entered the late, encephalitic stage.
• Serologic tests, especially the ELISA for IgM antibody, can be
helpful.

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 Treatment & Prevention
• Treatment must be initiated before the development of encephalitis, because
suramin, the most effective drug, does not pass the blood–brain barrier well.
Suramin will effect a cure if given early.
• Pentamidine is an alternative drug.
• If central nervous system symptoms are present, use suramin (to clear the
parasitemia) followed by melarsoprol.

• The most important preventive measure is protection against the fly bite, using
netting and protective clothing.
• Clearing the forest around villages and using insecticides are helpful measures.
• No vaccine is available.
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 LEISHMANIA

• The genus Leishmania includes four major

pathogens:
Leishmania donovani
Leishmania tropica
Leishmania mexicana
Leishmania braziliensis.

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 Leishmania donovani
• Causative agent of kala-azar (visceral leishmaniasis).

Important Properties
• The life cycle involves the sandfly as the vector and a variety of
mammals such as dogs, foxes, and rodents as reservoirs.
• Only female flies are vectors because only they take blood meals (a
requirement for egg maturation).
• When the sandfly sucks blood from an infected host,the cycle takes
approximately 10 days.

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MOSEM
LIFE CYCLE
 Pathogenesis
• In visceral leishmaniasis, the organs of the reticuloendothelial system
(liver, spleen, and bone marrow) are the most severely affected.
• Reduced bone marrow activity, coupled with cellular destruction in the
spleen, results in anemia, leukopenia, and thrombocytopenia.
• This leads to secondary infections and a tendency to bleed.
• The striking enlargement of the spleen is due to a combination of
proliferating macrophages and sequestered blood cells.
• The marked increase in IgG is neither specific nor protective.
• Kala-azar occurs in three distinct epidemiologic patterns.

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 Epidemiology
• In one area, which includes the Mediterranean basin, the Middle East,
southern Russia, and parts of China, the reservoir hosts are primarily
dogs and foxes.
• In sub-Saharan Africa, rats and small carnivores (e.g., civets) are the
main reservoirs.
• A third pattern is seen in India and neighboring countries (Kenya), in
which humans appear to be the only reservoir.

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 Clinical Findings
• Symptoms begin with intermittent fever, weakness, and weight loss.
• Massive enlargement of the spleen is characteristic.
• Hyperpigmentation of the skin is seen in light skinned patients (kala-
azar means black sickness).
• The course of the disease runs for months to years.
• Initially, patients feel reasonably well despite persistent fever.
• As anemia, leukopenia, and thrombocytopenia become more
profound, weakness, infection, and gastrointestinal bleeding occur.
• Untreated severe disease is nearly always fatal as a result of secondary
infection.
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 Laboratory Diagnosis
• Detection of amastigotes in a bone marrow, spleen
• Lymph node biopsy Culturing.
• Serologic (indirect immunofluorescence) tests are positive in most
patients.
• Although not diagnostic, a very high concentration of IgG is indicative
of infection.
• A skin test using a crude homogenate of promastigotes (leishmanin) as
the antigen is available.
• The skin test is negative during active disease but positive in patients
who have recovered. MOSEM
 Treatment & Prevention

• Drug of choice: either liposomal amphotericin B or sodium

stibogluconate. Recovery results in permanent immunity.

• Prevention sandfly bites by using bed net, protective clothing, and

insect repellents.
• Insecticide spraying.

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 Leishmania tropica, Leishmania
mexicana, & Leishmania braziliensis
• Leishmania tropica and L. mexicana both cause cutaneous
leishmaniasis
• The former organism is found in the Old World, whereas the latter is
found only in the Americas.
• Leishmania braziliensis causes mucocutaneous leishmaniasis, which
occurs only in Central and South America.

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 Pathogenesis & Epidemiology

• The lesions are confined to the skin in cutaneous leishmaniasis and to the
mucous membranes, cartilage, and skin in mucocutaneous leishmaniasis.
• A granulomatous response occurs, and a necrotic ulcer forms at the bite site.
• The lesions tend to become superinfected with bacteria.

• Old World cutaneous leishmaniasis (Oriental sore, Delhi boil), caused by L.

tropica, is endemic in the Middle East, Africa, and India.
• New World cutaneous leishmaniasis (chicle ulcer, bay sore), caused by L.
mexicana, is found in Central and South America.
• Mucocutaneous leishmaniasis (espundia), caused by L. braziliensis, occurs mostly
in Brazil and Central America, primarilyMOSEM
in forestry and construction workers.
 Clinical Findings
• The initial lesion of cutaneous leishmaniasis is a red papule at the bite
site, usually on an exposed extremity.
• This enlarges slowly to form multiple satellite nodules that coalesce
and ulcerate.
• There is usually a single lesion that heals spontaneously in patients
with a competent immune system.

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 Clinical Findings
• Individuals in which cell-mediated immunity does not develop, the
lesions can spread to involve large areas of skin and contain enormous
numbers of organisms.
• Mucocutaneous leishmaniasis begins with a papule at the bite site
• But then metastatic lesions form, usually at the mucocutaneous
junction of the nose and mouth.
• Disfiguring granulomatous, ulcerating lesions destroy nasal cartilage
but not adjacent bone.
• These lesions heal slowly, if at all.
• Death can occur from secondary infection.
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 Laboratory Diagnosis
• Microscopic observation of amastigotes in a smear taken from the skin
lesion.
• The leishmanin skin test becomes positive when the skin ulcer appears
and can be used to diagnose cases outside the area of endemic
infection.

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 Treatment & Prevention
• Drug of choice is sodium stibogluconate, but the results are
frequently unsatisfactory.

• Prevention involves protection from sandfly bites by using netting,

window screens, protective clothing, and insect repellents.

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Minor Protozoan Pathogens

Acanthamoeba
Naegleria
Babesia
Balantidium
Cyclospora
Isospora
Microsporidia
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 ACANTHAMOEBA & NAEGLERIA
• Acanthamoeba castellanii and Naegleria fowleri are freeliving amebas
that cause meningoencephalitis.
• The organisms are found in warm freshwater lakes and in soil.
• Their life cycle involves trophozoite and cyst stages.
• Cysts are quite resistant and are not killed by chlorination.
• Naegleria trophozoites usually enter the body through mucous
membranes while an individual is swimming.
• They can penetrate the nasal mucosa and cribriform plate to produce a
purulent meningitis and encephalitis that are usually rapidly fatal.
• Acanthamoeba is carried into the skin or eyes during trauma.
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 ACANTHAMOEBA & NAEGLERIA
• Acanthamoeba infections occur primarily in immunocompromised
individuals
• Naegleria infections occur in otherwise healthy persons, usually children.
• In the United States, these rare infections occur mainly in the southern
states and California.
• Diagnosis is made by finding amebas in the spinal fluid.
• The prognosis is poor even in treated cases.
• Amphotericin B may be effective in Naegleria infections.
• Pentamidine, ketoconazole, or flucytosine may be effective in
Acanthamoeba infections.
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 ACANTHAMOEBA & NAEGLERIA
• Acanthamoeba also causes keratitis—an inflammation of the cornea
that occurs primarily in those who wear contact lenses.
• With increasing use of contact lenses, keratitis has become the most
common disease associated with Acanthamoeba infection.
• The amebas have been recovered from contact lenses, lens cases, and
lens disinfectant solutions.
• Tap water contaminated with amebas is the source of infection for lens
users

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 BABESIA MICROTI
• Causes babesiosis
• A zoonotic infection acquired chiefly in the coastal areas and islands off
the northeastern coast of the United States (e.g., Nantucket Island).
• The sporozoan organism is endemic in rodents and is transmitted by the
bite of the tick Ixodes dammini (renamed I. scapularis), the same species
of tick that transmits Borrelia burgdorferi, the agent of Lyme disease.
• Babesia infects red blood cells, causing them to lyse, but unlike plasmodia,
it has no exoerythrocytic phase.
• Asplenic patients are affected more severely.
• The influenza like symptoms begin gradually and may last for several
weeks.
• Hepatosplenomegaly and anemia occur.
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 BABESIA MICROTI
• Giemsa-stained blood smears:
• Intraerythrocytic ring shaped parasites are seen.
• The intraerythrocytic ring-shaped trophozoites are often in tetrads in the form of
a maltese cross.
• Unlike the case with plasmodia, there is no pigment in the erythrocytes.
• The treatment of choice for mild to moderate disease is a combination of
atovaquone and azithromycin.
• Patients with severe disease should receive a combination of quinidine and
clindamycin.
• Exchange transfusion should also be considered in patients with severe disease.
• Prevention involves protection from tick bites and, if a person is bitten, prompt
removal of the tick.
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 BALANTIDIUM COLI
• The only ciliated protozoan that causes human disease (i.e., diarrhea).
• It is found worldwide but only infrequently in the United States.
• Domestic animals, especially pigs, are the main reservoir for the
organism, and humans are infected after ingesting the cysts in food or
water contaminated with animal or human feces.
• The trophozoites excyst in the small intestine, travel to the colon, and,
by burrowing into the wall, cause an ulcer similar to that of Entamoeba
histolytica.
• However, unlike the case with E. histolytica, extraintestinal lesions do
not occur.
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 BALANTIDIUM COLI
• Most infected individuals are asymptomatic; diarrhea rarely occurs.
• Diagnosis: large ciliated trophozoites or large cysts with a characteristic
V-shaped nucleus in the stool.
• No serologic tests.
• Treatment of choice is tetracycline.
• Prevention consists of avoiding contamination of food and water by
domestic animal feces.

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 CYCLOSPORA CAYETANENSIS
• An intestinal protozoan that causes watery diarrhea in both
immunocompetent and immunocompromised individuals.
• The diarrhea can be prolonged and relapsing, especially in
immunocompromised patients.
• It is classified as a member of the Coccidia.
• The organism is acquired by fecal–oral transmission (especially via
contaminated water supplies).

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 CYCLOSPORA CAYETANENSIS
• One outbreak in the United States was attributed to the ingestion of
contaminated raspberries.
• There is no evidence for an animal reservoir.
• Diagnosis: microscopic observation of the spherical oocysts in a
modified acid-fast stain of a stool sample.
• There are no serologic tests.
• The treatment of choice is trimethoprim-sulfamethoxazole.
• Infection occurs worldwide.

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 ISOSPORA BELLI
• An intestinal protozoan that causes diarrhea, especially in immunocompromised
patients (e.g.,AIDS).
• Life cycle parallels that of other members of the Coccidia.
• Acquired by fecal–oral transmission of oocysts from either human or animal
sources.
• The oocysts excyst in the upper small intestine and invade the mucosa, causing
destruction of the brush border.
• The disease in immunocompromised patients presents as a chronic, profuse,
watery diarrhea.
• Diagnosis is made by finding the typical oocysts in fecal specimens.
• Serologic tests are not available.
• The treatment of choice is trimethoprim-sulfamethoxazole.
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 MICROSPORIDIA
• A group of protozoa characterized by obligate intracellular replication and
spore formation.
• As the name implies, the spores are quite small, approximately 1 to 3 mm,
about the size of Escherichia coli.
• One unique feature of these spores is a “polar tube,” which is coiled within
the spore and extrudes to attach to the human cells upon infection.
• The protoplasm of the spore then enters the human cell via the polar tube.
• Enterocytozoon bieneusi and Encephalitozoon intestinalis are two important
microsporidial species that cause severe, persistent, watery diarrhea in AIDS
patients.

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 MICROSPORIDIA
• The organisms are transmitted from human to human by the fecal– oral
route.
• Microsporidia are also implicated in infections of the central nervous
system, the genitourinary tract, and the eye.
• It is uncertain whether an animal reservoir exists.
• Diagnosis is made by visualization of spores in stool samples or
intestinal biopsy samples.
• The treatment of choice is albendazole.

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