Genus: Trypanosoma

Hemoflagellates of the genus Trypanosoma occur in the blood of the mammals as mature elongated Trypomastigotes.

A multiplying epimastigote stage precedes the formation of infective trypomastigotes in the intermediate host (an insect vector) in all species if trypanosomes that infect humans.

Trypanosomiasis is expressed as African Sleeping sickness and Chaga’s disease of the Americas.

Trypanosoma brucei gambiense (West African or Gambian sleeping sickness) and

Trypanosoma brucei rhodesiense (East African or Rhodesian sleeping sickness).

African trypanosomiasis is a highly lethal meningoencephalitis transmitted to humans by the blood sucking flies of genus Glossina.

Trypanosoma cruzi causes Chaga’s disease.

T.b.g and T.b.r both undergo similar developmental changes in the course of passage between their insect and mammalian host.

Riverine tsetse flies Glossina palpalis found in the forest galleries that border the streams of West and Central Africa serve as the vectors of the Gambian disease.

Rhodesian sleeping sickness is transmitted by flies (Glossina morsitans,G.pallidipes, G.fuscipes) indigenous to the great Savannas of East Africa, that feed on the blood of the small antelopes living in the area,may serve as a reservoir.

The 3 week life cycle in the Tsetse fly begins with the ingestion of the trypomastigotes in a blood meal from the reservoir host.

After a period of multiplication in the midgut and the hindgut , they migrate to the salivary glands of the insect and assume the Epimastigote form.

They multiply further into metacyclic trypomastigotes , which are transmitted by the insect bite.

In the mammalian host, the parasites (every strain of T.b) acquire a highly variable surface glycoprotein that will keep on changing sequentially, periodically and predictably every 10 days. Helps evade immune response.

They multiply extracellularly and eventually invade the bloodstream, where they differentiate into blood-form trypomastigotes.

These do not have the Amastigote stage of multiplication through binary fission, in the tissues, unlike T.cruzi.

Pathogenesis and Clinical findings:

Infective trypanosomes of T.b.g and T.b.r multiply at the site of innoculation causing variable indurations and swelling (the primary lesion) which may progress to form a trypanosomal chancre.

The trypomastigotes spread to the lymph nodes , to the blood stream and in the terminal stages, the CNS where they produce the typical sleeping sickness syndrome: lassitude, inability to eat, tissue wasting, unconsciousness, coma and eventually death.

In the acute form, a cyclical fever pattern of every 2 weeks, is manifested which coincides with the antibody mediated agglutination and destruction of the trypomastigotes, and is related to the antigenic variation in the surface glycoprotein.

A few antigenic variants however do survive , multiply and cause a new fever spike.

During the course of the parasitemia, the trypanosomes localize in the small blood vessels of the heart and CNS.

The localization results in the endothelial proliferation and a perivascular infiltration of plasma cells and lymphocytes.

In the brain, hemorrhage and demyelinating panencephalitis may follow.

The circulating immune complexes are largely responsible for the anemia and vasculitis.

The CNS involvement is the most characteristic feature of African trypanosomiasis.

T.b.g will appear in the cerebrospinal fluid after several months.

Gambian sleeping sickness progresses slowly. Bouts of fever often persist for years before CNS manifestations gradually appear.

In the terminal stage, the patient develops a lethal infection or lapses into a final coma.

T.b.r appears in the CSF after about 1 month.

Myocarditis and CNS involvement begin within 3-6 weeks.

Heart failure, convulsions, coma and death follow in 6-9 months.

The general clinical findings include the initial lesion or trypanosomal chancre.

Intermittent weekly fever with lymphadenopathy follows once the trypomastigotes enter the bloodstream.

Enlargement of posterior cervical lymph nodes is a common finding.

The encephalitis stage is characterized by a headache, insomnia, mood changes, muscle tremors, slurred speech leading to coma and death usually due to a fatal bout of pneumonia.

Laboratory diagnosis:

Microscopic examination and the demonstration of trypomastigotes in the blood (wet, thick or thin smears), aspirate of the chancre or enlarged lymph node, for early stages.

Presence of Trypanosomes in CSF, and an increased levels of proteins and pleocytosis indicative of late, encephalitic stage.

ELISA for IgM antibody can be helpful.

Treatment:

Suramin for cure in early stages.Most effective. Suramin does not cross the blood-brain barrier a

nd hence cannot be used for treatment once the disease has developed into encephalitis. Pentamidine effective and alternative drug of choice.

Suramin followed by Melarsoprol for CNS symptoms.

Prevention:

Mets, protective clothing and protection against the fly bites.

Clearing forests around human habitation and insecticidal sprays may be helpful.

Trypanosoma cruzi

T.cruzi can be found in two forms as amastigotes and trypomastigotes.

The trypomastigote does not multiply extracellularly.

After circulating in the peripheral blood on innoculation, the circulating trypomastigotes must invade tissue cells of the reticuloendothelial system and skeletal and cardiac muscle cells, lose their flagella and assume the amastigote form before binary fission can occur.

Continued multiplication leads to distension and eventual rupture of the tissue cell.

The released parasites revert to trypomastigotes and regain the bloodstream.

These new generation can invade other cells and continue the mammalian cycle.

Small numbers however, do circulate in the blood and taken up by the feeding reduviid bug.

Once inside the bug, the trypomastigotes develop into epimastigotes and multiply within its hindgut and midgut.

They are transformed into the infectious metacyclic trypomastigotes and discharged through the feces at the site of feeding.

Transmission when the infected bug feces are rubbed or scratched into the conjunctiva, the bite site, break in the skin, or onto the mucous membranes of the eye, mouth or nose.

Once inside the host, the metacyclic forms invade a variety of cell types, including macrophages and muscle cells.

T.cruzi also may have different strains, each having its distinct geographic distribution, tissue preference and virulence.

Pathogenesis and clinical findings:

Multiplication at the site of bite stimulates the accumulation of neutrophils, lymphocytes and tissue fluid, resulting in the formation of a local chancre or Chagoma.

The subsequent dissemination of the organism with invasion of the tissue cells produce a febrile illness that may persist for 1-3 months and result in widespread organ damage.

Any nucleated host cell may be involved and following penetration the trypomastigote transforms into the amastigote form.

Amastigotes multiply freely producing a pseudocyst containing masses of transformed trypomastigotes.

With the rupture of the pseudocyst, many of the released trypomastigotes disintegrate, eliciting an intense inflammatory response, mainly of mononuclearcells.

The development of an antibody dependent cell-mediated response eventually leads to the destruction of the parasites and the termination of the acute stage of the illness.

Parasitic antigens released may bind to the surface of the tissue cells and elicit a hosts immune response leading to its destruction.

The organs most severely affected are the CNS and heart muscle.

Interstitial myocarditis is the most common complication of the Chaga’s disease.

Liver, spleen, and bone-marrow may be involved in chronic infection.

Toxic destruction of nerve plexus in the alimentary tract walls leads to megaesophagus and megacolon especially in the Brazilian Chaga’s disease, and

Cardiac muscle to cardiac arrythmias.

Acute stage manifestations include a rapidly developing disease.

Appearance of nodular, erythematous chagoma 1-3 weeks after the bite.

Unilateral swelling of the eyelids characteristic of the onset, especially in children.

If eye is the entry point, then patient will persist with Romana’s sign: reddened eye, swollen lid, enlarged preauricular lymph node.

Onset of parasitemia cinicides with the development of sustained fever, enlargement of liver, spleen and lymph nodes, signs of meningeal irritation, and appearance of transient skin rash or peripheral edema.

The acute stage resolves in about 2 months. Individuals with a chronic form may develop myo

carditis and megacolon.Megaesophagus leads to difficulty in swallowing and regurgitation, particularly in the night. Megacolon leads to constipation with irregular passage of voluminous stools.

Death in Chaga’s disease is mainly due to cardiac arrythmias or gongestive heart failure.

Laboratory diagnosis:

A stained microscopic examination of blood (wet, thick, thin smears) for trypomastigotes. Bone marrow aspirate or muscle biopsy specimen for amastigotes.

Xenodiagnosis: examination bug for parasites after allowing it to feed on the infectious patient.

Serological tests like Indirect fluorescent antibody test, Indirect hemagglutination and Complement fixation test are helpful.

Treatment involves:

Nifurtimox for the acute stage of the illness, to kill the trypomastigotes, but less effective against amastigotes.

Benznidazole is the alternative drug of choice.

No drug for chronic cases.

Prevention:

Protect against reduviid bites.Insecticidal sprays helpful.Blood for transfusion tested for T.cruzi anti

bodies and if present not used.