TRYPANOSOMIASIS
OLEH
DR. ATHARI FADHILA NAMANDA PUTRI
PEMBIMBING : DR. FADRIAN, SPPD-KPTI
PROGRAM PENDIDIKAN DOKTER SPESIALIS
ILMU PENYAKIT DALAM
RSUP DR. M. DJAMIL
2022
TRYPANOSOMIASIS
▰ Trypanosomes are hemoflagellates that reside in peripheral blood and
tissues of their host.
▰ Based on their geographical distribution, they can be classified into two
types:
▻ African trypanosomes : Trypanosoma Gambia, Trypanosoma Rhodesia
▻ American trypanosomes : Trypanosoma Cruzi
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TRYPANOSOMIASIS
African trypanosomes:
▰ Trypanosoma brucei complex.
▰ They are transmitted by the vector tsetse fly.
▰ Cause African sleeping sickness.
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TRYPANOSOMIASIS
American trypanosomes:
▰ Trypanosoma cruzi - causative agent of Chagas’ disease.
▰ Transmitted by insect vector reduviid bug (also called triatomine bug).
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LIFE CYCLE
CHAGAS’ DISEASE
(TRYPANOSOMA CRUZI)
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EPIDEMIOLOGY
▰ Chagas’ disease - mainly restricted to South and Central American
countries
▰ Currently, it is estimated that 16–18 million people are infected with T.
cruzi.
▰ Zoonotic disease - many animal reservoirs like dogs, and cats.
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LIFE CYCLE
▰ T. cruzi - transmitted to man by rubbing of its vector reduviid bug’s feces
on abraded skin.
▰ Human cycle: The trypomastigotes from the bite wound - carried to
various tissues - transform into amastigote forms.
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LIFE CYCLE
▰ Amastigotes multiply actively.
▰ They are the intracellular form found in tissues - reticuloendothelial cells
(spleen, liver, lymph node, bone marrow), muscles (cardiac, skeletal and
GIT) and nervous tissue
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LIFE CYCLE
▰ Trypomastigotes: Amastigotes transform back to trypomastigote forms,
which are motile C-shaped non-multiplying, extracellular forms found in
peripheral blood (as long slender or invasive forms and short stubby
forms).
▰ Invasive forms migrate to many organs.
▰ Short stubby forms - ingested by reduviid bugs during a blood meal.
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LIFE CYCLE
▰ Vector cycle: In the gut of reduviid bugs, the trypomastigotes transform
into epimastigotes -further develop into metacyclic trypomastigotes in the
hindgut - excreted in the bug’s feces.
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PATHOGENESIS AND CLINICAL
FEATURE
▰ Chagas’ disease occurs in four stages:
Early Stage Disease – Chagoma (an indurated inflammatory lesion
arising at the site of entry of the parasite (port d'entree). Romana’s sign
(classic sign in the acute stage of Chagas disease : malaise, fever,
anorexia, and edema of the face and lower extremities)
Acute Chagas’ disease : mild fever
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PATHOGENESIS AND CLINICAL
FEATURE
▰ Chagas’ disease occurs in four stages:
Indeterminate stage : presence of subpatent parasitemia, antibodies to
T. cruzi are easily detected, and there are no symptoms
Chronic Chagas’ disease : Cardiac disorders: ventricular wall thinning,
biventricular fusion, arrhythmias, congestive heart failure, tachycardia
and myocarditis
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LABORATORY DIAGNOSIS - PERIPHERAL BLOOD
MICROSCOPY
▰ In acute Chagas’ disease, the trypomastigotes are frequently found in
peripheral blood which can be detected by:
(1) wet mount preparation or
(2) thick and thin smear examination.
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LABORATORY DIAGNOSIS -
PERIPHERAL BLOOD MICROSCOPY
Trypanosoma cruzi:
A. Trypomastigote form (schematic);
B. Trypomastigote form (in thin blood
smear stained with Giemsa)
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LABORATORY DIAGNOSIS - OTHER
DIAGNOSTIC METHODS
▰ Culture - Epimastigotes
▰ Antibody and antigen detection
▰ Molecular methods
▰ Animal inoculation
▰ Xenodiagnosis Epimastigotes from NNN medium culture
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TREATMENT OF CHAGAS DISEASE
▰ Therapy for Chagas’ disease is still unsatisfactory.
▰ In acute disease:
Benznidazole - drug of choice in Latin America.
Nifurtimox or allopurinol - given alternatively.
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TREATMENT OF CHAGAS DISEASE
▰ In chronic disease:
These drugs lack efficacy and may cause many side effects.
Supportive treatment - pacemakers to manage arrhythmias and surgery
for correction of megaesophagus and megacolon may be useful.
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PROPHYLAXIS
▰ Prevention of the disease in endemic countries depends on control of
vector.
▰ Residual insecticides, health education, measures to reduce insect exposure
and housing improvement.
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AFRICAN SLEEPING
SICKNESS
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AFRICAN SLEEPING SICKNESS
▰ Trypanosoma brucei - named after Sir Bruce in 1909, proved that the
disease is transmitted by tsetse fly.
▰ T. brucei complex consists of three subspecies:
T. brucei gambiense
T. brucei rhodesiense
T. brucei brucei
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EPIDEMIOLOGY
▰ African trypanosomiasis is endemic in 36 countries of Africa with 60
million people at risk.
▰ Approximately 50,000 new cases occur annually.
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LIFE CYCLE
▰ T. brucei - transmitted to man by the bite of the vector tsetse fly (genus
Glossina), inoculating the infective form - metacyclic trypomastigote
forms into the skin.
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LIFE CYCLE
▰ Human cycle: At the site of inoculation, they transform into long slender
trypomastigote forms - multiply by binary fission. Subsequently they
transform into non-dividing short stumpy trypomastigote forms which
either:
▻ Invade the bloodstream and migrate to various organs or
▻ Ingested by the tsetse fly during a blood meal
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LIFE CYCLE
▰ Vector cycle: The short trypomastigote forms become long slender forms,
then to epimastigote forms and finally develop into metacyclic
trypomastigote forms which are the infective forms to man.
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PATHOGENESIS AND CLINICAL
FEATURE
▰ In general, T. brucei gambiense develops a chronic course with slow
progression.
▰ T. brucei rhodesiense runs an acute course with rapid progression and early
death.
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STAGE I DISEASE (HEMOLYMPHATIC
STAGE)
▰ Trypanosomal chancre - self-limited lesion that appear a week after the
bite of an infected tsetse fly.
▰ Asymptomatic period: Following this, the clinical course runs through an
asymptomatic phase - lasts for few months.
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STAGE I DISEASE (HEMOLYMPHATIC
STAGE)
▰ Systemic febrile illness: Months to years later, a systemic febrile illness
develops; due to dissemination of the parasite through the lymphatics and
bloodstream. It is characterized by:
Remittent irregular fever with night sweats
Lymphadenopathy: The posterior cervical nodes are commonly
involved, called as Winterbottom’s sign. 28
STAGE II DISEASE (CNS INVASION)
▰ It involves invasion of the CNS which leads to progressive chronic
meningoencephalitis.
▰ Patients develop characteristic daytime somnolence (hence called as
“sleeping sickness”), with restlessness and insomnia at night.
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COMPARISON BETWEEN TRYPANOSOMA
BRUCEI GAMBIENSE AND TRYPANOSOMA
BRUCEI RHODESIENSE
Trypanosoma brucei gambiense Trypanosoma brucei rhodesiense
Disease West African sleeping sickness East African sleeping sickness
Vectors Tsetse flies (Glossina palpalis group) Tsetse flies (Glossina morsitans
group)
Primary reservoir Humans Animals (Antelope and cattle)
Human illness Chronic central nervous system (CNS) disease Acute (early CNS disease)
Duration of illness Months to years <9 months
Lymphadenopathy Frequent, cervical lymphadenopathy (winter bottom Minimal (Axially and inguinal)
sign)
Virulence Less, as the parasitemia is low Less, as the parasitemia is high
Rodent inoculation Not useful Diagnostic
Drug of choice Stage I: Pentamidine, Stage II: Eflornithine Stage I: Suramin, Stage II:
Melarsoprol 30
LABORATORY DIAGNOSIS - DIRECT
MICROSCOPY
▰ Useful samples - multiple blood samples collected during the febrile
period, chancre fluid, CSF, lymph node and bone marrow aspirate.
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LABORATORY DIAGNOSIS -
DIRECT MICROSCOPY
Blood examination:
▰ Trypomastigote forms are seen by serial blood sample examination, which
is performed either by
(i) peripheral blood smear examination by thin and thick smear
(ii) concentration methods - microhematocrit centrifugation, if
parasitemia is low.
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LABORATORY DIAGNOSIS -
DIRECT MICROSCOPY
Trypomastigote form of T. brucei in peripheral blood smear examination (Giemsa
stain):
A. Thin smear; B. Thick smear 33
LABORATORY DIAGNOSIS -
DIRECT MICROSCOPY
▰ This is necessary to confirm the CNS invasion; either by -
(i) detection of trypomastigotes in CSF
(ii) WBC count of >20 cells/µL of CSF with parasite detected in blood
or lymph node aspirate
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LABORATORY DIAGNOSIS -
DIRECT MICROSCOPY
▰ Lymph node aspirate: useful for T. brucei gambiense and shows variable
sensitivity of 40–80%.
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LABORATORY DIAGNOSIS - ANTIGENS FROM
SERUM
AND CSF
▰ Antigen detection by ELISA in serum - useful for clinical staging of
disease to determine CNS infection and for monitoring the response to
treatment (antigens are rapidly cleared following improvement).
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LABORATORY DIAGNOSIS - ANTIBODIES
FROM SERUM AND CSF
▰ Card agglutination test for trypanosomes (CATT): detects antibodies to
VSG antigen.
▰ Semi-quantitative ELISA using VSG antigen of T. brucei gambiense is
available to detect various antibodies in serum and CSF.
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LABORATORY DIAGNOSIS -
CULTURE
▰ Samples can be inoculated into KIVI (kit for in vitro isolation) and
trypomastigotes are recovered in 7–10 days.
▰ However, culture is not routinely performed.
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TREATMENT OF AFRICAN
SLEEPING SICKNESS
▰ Drugs used for the treatment of African sleeping sickness - pentamidine
and suramin.
▰ Alternative drugs - eflornithine, and the organic arsenical melarsoprol.
▰ Treatment is based on type of disease (West or East African) and presence
or absence of CNS invasion.
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