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 identification of the organism in blood, lymph node aspirate, or CSF or sometimes by serologic tests. Treatment is with suramin, pentamidine, melarsoprol, or eflornithine, depending on the infecting subspecies, clinical stage, and drug availability.

African trypanosomiasis is caused by Trypanosoma brucei gambiense in West and Central Africa and by T. brucei rhodesiense in East Africa; both species are endemic in Uganda. The organisms are transmitted by tsetse flies and occasionally by blood transfusion.

Pathophysiology

Metacyclic trypomastigotes inoculated by flies transform into bloodstream trypomastigotes, which 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 escape immune destruction by a change in their variant surface glycoprotein and start 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. The cycle is continued when a tsetse fly bites an infected human. Humans are the main reservoir of T. b. gambiense, but this species may also reside in animals. Wild game animals are the main reservoir of T. b. rhodesiense.

Trypanosoma brucei gambiense life cycle.

Symptoms and Signs

The disease has 3 stages:

• Cutaneous
• Hemolymphatic
• CNS

Cutaneous: 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 present in about half of Caucasians with T.b. rhodesiense but is less common in Africans with T. b. rhodesiense and seldom occurs with T.b. gambiense.

Hemolymphatic: Over several months in T. b. gambiense infection but a period of weeks with T. b. rhodesiense, intermittent fever, headaches, rigors, and transient swellings develop. 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.

CNS: 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 often occurs within a few weeks. CNS involvement causes persistent headache, inability to concentrate, personality changes (eg, progressive lassitude and indifference), daytime somnolence, hyperphagia, tremor, ataxia, and terminal coma. Without treatment, death 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 of undernutrition or secondary infections.

Diagnosis

• Light microscopy of blood (thin or thick smears) or other fluid sample

Diagnosis is made by identifying trypanosomes in fluid from a chancre, lymph node aspirate, blood, bone marrow aspirate, or, during the late stage of infection, CSF. Preferred sources are blood smears for T. b. rhodesiense and fluid aspirated from an enlarged lymph node for T. b. gambiense. Wet preparations should be examined for motile trypanosomes, and smears should be fixed, stained with Giemsa (or Field's) stain, and examined. Concentration techniques (eg, centrifugation of blood or CSF) enhance sensitivity.

Antibody detection assays are not very useful clinically because seroconversion occurs after the onset of symptoms. However, a card agglutination test for T. b. gambiense is useful in mass screening programs to identify candidates for microscopic examination.

When the CNS is involved, lumbar puncture is done. CSF pressure is increased, and CSF has elevated levels of lymphocytes (≥ 5 cells/μL), total protein, and IgM. In addition to trypanosomes, characteristic Mott cells (plasma cells with cytoplasmic vacuoles that contain immunoglobulin [Russell bodies]) may be present.

Other, nonspecific laboratory findings include anemia, monocytosis, and markedly elevated serum levels of polyclonal IgM.

Treatment

• Without CNS involvement, pentamidineSome Trade Names
  NEBUPENT
  PENTAM 300
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  or eflornithineSome Trade Names
  VANIQA
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  for T. b. gambiense; suraminSome Trade Names
  No US trade name
  Click for Drug Monograph
  for T. b. rhodesiense
• With CNS involvement, eflornithineSome Trade Names
  VANIQA
  Click for Drug Monograph
  or melarsoprol for T. b. gambiense; melarsoprol for T. b. rhodesiense

Without CNS involvement: SuraminSome Trade Names
No US trade name
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and pentamidineSome Trade Names
NEBUPENT
PENTAM 300
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are effective against bloodstream stages of both T. brucei subspecies but do not cross the blood-brain barrier and are not useful for CNS infection. PentamidineSome Trade Names
NEBUPENT
PENTAM 300
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is preferred for T. b. gambiense, and suraminSome Trade Names
No US trade name
Click for Drug Monograph
is preferred for the hemolymphatic stage of T. b. rhodesiense. The dosage of pentamidineSome Trade Names
NEBUPENT
PENTAM 300
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is 4 mg/kg IM or IV once/day for 7 days. An initial test dose of suraminSome Trade Names
No US trade name
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100 mg IV (to exclude hypersensitivity) is followed by 20 mg/kg (up to 1 g) IV on days 1, 3, 7, 14, and 21.

EflornithineSome Trade Names
VANIQA
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(availability limited) is effective against all stages of T. b. gambiense (but not T. b. rhodesiense) trypanosomiasis. Dosage is 100 mg/kg IV qid for 14 days. When available, it is the drug of choice for T. b. gambiense.

With CNS involvement: Melarsoprol, an organic arsenical, is used in most African countries for CNS disease. For T. b. gambiense, dosage is 2.2 mg/kg IV once/day for 10 days. Where available, eflornithineSome Trade Names
VANIQA
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can be used in the regimen above for T. b. gambiense CNS disease. For T. b. rhodesiense, dosage is 2 to 3.6 mg/kg IV once/day for 3 days; after 7 days, 3.6 mg/kg once/day is given for 3 days, followed 7 days later by another 3-day course at this dose. 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 GI and renal toxicity of arsenicals.

Corticosteroids have been used to 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 (diethyltoluamide) appropriately.

PentamidineSome Trade Names
NEBUPENT
PENTAM 300
Click for Drug Monograph
can help prevent T. b. gambiense infection, but it may damage pancreatic β-cells, resulting in insulin release and hypoglycemia followed later by diabetes; thus, it is seldom used for prophylaxis.

Last full review/revision December 2009 by Richard D. Pearson, MD

Content last modified February 2012