Human African Trypanosomes (HAT)

Biology, Classification and Structure� It involves two hosts: definitive mammalian hosts and

intermediate arthropod host� The HAT are T. brucei gambiense and T. brucei rhodesiense

(Salivarian species)� Epimastigote: Occurs in insect vector and is not infective for

human

� Trypomastigote: It is a long slender form found in mammalian blood

Epidemiology� In 1986, it was estimated that

approx. 70 million people lived in areas conducive to disease transmission

� HAT affects 36 countries in sub-Saharan Africa

� According to the World Health Organization, HAT causes ~40,000 deaths in Africa annually

Epidemiology Cont’d� The total amount of reported HAT cases has decreased

substantially over time.

� 1998: ~40,000 reported cases; >250,000 actual cases

� 2004: ~18,000 reported cases; between 50,000 and 70,000 actual cases

� 2010: ~7,000 reported cases; ~30,000 actual cases� Cases involving T.b. rhodesiense are much rarer than those involving

T.b. gambiense.

Geographical Distribution� T.b. gambiense is mostly found in western and central Africa.

� Over 95% of the cases of human infection found in the Democratic Republic of Congo, Angola, Sudan, Central African Republic, Chad, and northern Uganda.

� T.b. rhodesiense is found mostly in eastern and southernAfrica.� Over 95% of the cases of human infection occur in Tanzania,

Uganda, Malawi, and Zambia.

Causal Agents� Caused by the protozoan Trypanosoma

Brucei

� Has three subspecies:� Trypanosoma brucei gambiense

� Trypanosoma brucei rhodesiense

� Trypanosoma brucei brucei (animals only)• Trypanosoma brucei gambiense is usually

associated with the chronic form of the disease

• Trypanosoma brucei rhodesiense is usually associated with the acute form of the disease.

• T.b. rhodesiense is more virulent than T.b. gambiense and is less prone to cause large epidemics.

Life Cycle• T. brucei is transmitted by tsetse flies of the genus

Glossina• Parasites are ingested by the fly when it takes a blood

meal on an infected mammal.• The parasites multiply in the fly, going through several

developmental stages in the insect gut and salivary glands (trypanosomes, epimastigotes, trypanosomes).

• When the fly bites another mammal, trypanosomes are inoculated, and multiply in the host's blood and extracellular fluids such as spinal fluid.

• Humans are the main reservoir for T. b. gambiense, but this species can also be found in animals. Wild game animals are the main reservoir ofT. b. rhodesiense.

The Parasite� Polymorphic spindle-shaped

� Kinetoplast� Flagella & undulating membrane

� Trypomastigote� Epimastigote

Vector Biology � The vector for HAT is the tsetse

fly

� Biological Vector

� Inhabits rural areas

� Bites during daytime hours

� Both males and females are capable of carrying and transmitting the disease.

Vector Biology Cont’d� Tsetse flies belong to the genus

Glossina

� Glossina contains 3 subgroups� Glossina (includes G. morsitans

group) � Nemorhina (includes G. palpalis

group)

� Austenina (includes G. fusca group)

Vector Biology Cont’d� Vectors of T.b. gambiense�G. palpalis & G. tachinoides groups

� Vectors of T.b. rhodesiense�G. morsitans, G. swynnertoni, & G. pallidipes groups

ReservoirsT.b. gambiense T.b. rhodesiense

Clinical Manifestation� The symptoms of African trypansomiasis depend on host and the sub-species

of trypanosome. In T. gambiense infections (gives characteristic anaemia). Generalized pain, weakness, cramps and swelling of neck lymph nodes (Winterbottom sign).

� Parasites invade all organs of the body including heart and CNS. The latter leads to apathy, mental dullness, tremors, convulsions and sleepiness, coma.

� There is rapid weight loss and death a few months later from malnutrition, heart failure, pneumonia or a parasitic infection. In the case of T. brucei rhodesiense infections, there is no coma or nervous system symptoms as probably patient dies before these can develop.

Clinical Manifestation cont…� T.b. gambiense: characterised by long period of asymptomatic

infection, followed by early febrile stage when trypanosome are found in blood or lymph without CNS involvement

Early Stage illness: Symptoms similar to that of malaria fever� Most patients have lymphadenopathy and some have

splenomegaly and hepatomegaly.Late Stage illness: Progress to late stage CNS involvement� Weight loss, Constant headache, insomnia, become comatose if

untreated, onset of psychiatric disorders

Clinical Manifestation cont…� Deep hyperesthesia (Kerandel’s sign) may occur� Convulsion common in children� T.b. rhodesiense: this is acute infection, early and late stage with

CNS develop over a matter of weeks� An inoculation chancre 5 to 15 days after bite� Symptoms and signs of CNS involvement same as in T.b. gambiense

but progress more rapidly and may be fatal� Patients occasionally die of heart failure

Host Reactions to the Parasite

� The parasite is very antigenic which is one reason for the symptoms shown by the infected patient.

� But the number of parasites in the bloodstream does not go on increasing and increasing until the patient dies.

� The patient undergoes waves of fever and cycles in parasite infestation. The waves of parasitemia correlate with the fever observed.

Host Reactions to the Parasite cont…� It is found that all of the trypanosomes in that wave of organisms are

expressing the same single surface antigen whereas in other waves, all of the parasites are expressing a single but completely different antigen

� A different surface antigen gene is being expressed. The surface coast is therefore made of VARIABLE SURFACE ANTIGENS (VSA) or VARIABLE SURFACE GLYCOPROTEINS (VSGs).

� Thus escape from the immune response depends upon the ability to express a new VSG

Pathology� CNS involvement results in meningoencephalitis

� Oedema, haemorrhages and granulomatous present in brain

Diagnosis� Parasitological Diagnosis� The parasitologic assays are lymph node aspirate and wet and

thick smears blood.� (i) Lymph node aspirate� In the lymph node aspirate� Is especially useful for the diagnosis of Gambian Human

African Trypanosomiasis.� Lymph node fluid is aspirated from enlarged nodes with a

syringe and placed on a slide.

Diagnosis cont...� It is examined at high dry mag. (x 400)� The trypanosomes can found for short time at the edges of the

coverslipBlood Smear� Less frequently seen� Unstained blood smear between slide and coverslip� Thick smears are stained with Giemsa and view� Buffy coat technique (using acridine orange)

Diagnosis cont…Serology� This involved the use of card agglutination test for trypanosomes

(CATT)� This can be perform with less requirement of facility� It is highly sensitiveT b rhodesiense� Lymph node aspirate can be performed� Can be found in chancre on wet mount� Is acute and can be detected in CSF with time� Double centrifugation is the best for CSF examinationAnimal inoculation

Chemotherapy� Early stage - most recover

� Suramin� Melasporol� Pentamidine

� Late stage - upto 5% relapse� Only Melasporol

� Eflornithine is safe and effective 0% encephalitis - 5% fatal

Control• Destruction of animal reservoir

• Vector Control• Diagnosis & treatment

Differences between HATT.b. gambiense T.b. rhodesiense

Main vectors G. palpalis (riverine tsetse) G. morsitans (savanna tsetse)

Distribution West and Central Eastern and SouthernLocation Around water holes and rivers Savanna, cleared bushDisease Chronic, late CNS invasion Acute, early CNS

invasionDuration Months to Years Weeks to monthsDiagnosis Lymph node aspirate, CSF Peripheral blood exam,

CSF examTreatment Pentamidine (early stage) Suramin (early stage)

Melarsoprol or eflonirthine Melarsoprol(late stage) (late stage)