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African trypanosomiasis
is infection with protozoa of the genus Trypanosoma transmitted by
the bite of a tsetse fly. Symptoms include characteristic skin lesions,
intermittent fever, headache, rigors, transient edema, generalized lymphadenopathy,
and often-fatal meningoencephalitis. Diagnosis is by identifying
the organism in blood, lymph node aspirate, or CSF, or sometimes
serologic tests. Treatment is with suramin, pentamidine,
melarsoprol, or eflornithine, depending on the subspecies and clinical stage.
Etiology
and Pathophysiology
African trypanosomiasis is caused by T. brucei gambiense in West and Central Africa and by T.
brucei rhodesiense in East Africa, which are transmitted by tsetse flies. Both species are endemic in Uganda. Metacyclic trypomastigotes inoculated by flies transform into bloodstream trypomastigotes that multiply by binary fission and spread through the lymphatics and bloodstream after inoculation. Bloodstream trypomastigotes multiply until specific antibodies produced by the host sharply reduce parasite levels. However, a subset of parasites escapes immune destruction by a change in their variant surface glycoprotein and starts a new multiplication cycle. The cycle of multiplication and lysis repeats. Late in the course of infection, trypanosomes appear in the interstitial fluid of many organs, including the myocardium and eventually the CNS. African trypanosomiasis can also be transmitted by blood transfusion.
Symptoms and Signs
A papule may develop at the site of the tsetse fly bite within a few days to 2 wk. It evolves into a dusky red, painful, indurated nodule (trypanosomal chancre). A chancre is seen in about half of Caucasians with T.b. rhodesiense but is seldom evident in Africans with T.b.
gambiense. Over several months in T.b. gambiense infection, but a period of weeks with T.b. rhodesiense, intermittent fever, headaches, rigors, and transient swellings occur. An evanescent, circinate erythematous rash may develop. It is most readily visible in light-skinned patients. Generalized lymphadenopathy often occurs. Winterbottom's sign (enlarged lymph nodes in the posterior cervical triangle) is characteristic with T.b. gambiense sleeping sickness.
In the Gambian form, CNS involvement occurs months to several years after onset of acute disease. In the Rhodesian form, disease is more fulminant, and CNS invasion occurs within a few weeks to several months. CNS involvement causes persistent headache, inability to concentrate, personality changes (eg, progressive lassitude and indifference), daytime somnolence, hyperphagia, tremor, ataxia, and terminal coma. If untreated, death usually occurs within months of disease onset with T.b. rhodesiense and during the 2nd or 3rd yr with T.b. gambiense. Untreated patients die in coma from malnutrition or secondary infections.
Diagnosis
Early in the disease, diagnosis is made by finding trypanosomes in wet mounts or in Giemsa-stained thin or thick smears of peripheral blood (more useful in the Rhodesian type) or in fluid aspirated from an enlarged lymph node (more useful in the Gambian type). Centrifugation of blood or fluid samples may be useful in concentrating trypanosomes. In advanced stages, trypanosomes may be found only in centrifuged CSF. Serologic tests (immunofluorescent assay, enzyme-linked immunosorbent assay, card agglutination) are useful for T.b. gambiense.
When the CNS is involved, CSF pressure is increased, and CSF levels of lymphocytes (≥ 5 cells/μL), total protein, and IgM are elevated. In addition to trypanosomes, characteristic Mott cells (morula-like plasma cells filled with immunoglobulin) may be present. Laboratory findings include anemia, monocytosis, and markedly elevated serum levels of polyclonal IgM.
Treatment
Suramin and pentamidine are each effective against bloodstream stages of both T. brucei subspecies but do not cure CNS infection. Pentamidine is preferred for T.b. gambiense, and suramin for T.b. rhodesiense. The dosage of pentamidine isethionate is 4 mg/kg IM once/day for 10 days. An initial test dose of suramin 100 mg IV (to exclude hypersensitivity) is followed by 20 mg/kg IV up to 1 g on days 1, 3, 7, 14, and 21 for adults. For children, 20 mg/kg IV is given after the 100-mg test on days 1, 3, 7, 14, and 21. Eflornithine (availability limited) is effective against both early and late stages of T.b. gambiense (not T.b. rhodesiense) trypanosomiasis. It is given 100 mg/kg IV qid for 14 days. It is the drug of choice for T.b. gambiense when available.
Melarsoprol is used in most African countries for CNS disease. It is usually given as 3-day courses of 2 to 3.6 mg/kg IV once/day. After 7 days, 3.6 mg/kg once/day is given for 3 days. Seven days later, the 3-day course of therapy is repeated. Alternative regimens have been proposed for debilitated patients with severe CNS involvement. Serious adverse effects include reactive encephalopathy and exfoliative dermatitis in addition to the usual toxicity of arsenicals on the GI and renal systems. Corticosteroids decrease the risk of reactive encephalopathy.
Prevention
Prevention includes avoiding endemic areas and protecting against tsetse flies. Visitors to game parks should wear substantial wrist- and ankle-length clothing (tsetse flies bite through thin clothes) and use insect repellents with DEET appropriately.
Pentamidine confers some protection against T.b. gambiense, but because pentamidine may cause renal failure and hypoglycemia and lead to diabetes, it is not warranted for prophylaxis.
Last full review/revision November 2005
Content last modified November 2005
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