Find information on medical topics, symptoms, drugs, procedures, news and more, written for the health care professional.

* This is the Professional Version. *

African Trypanosomiasis

(African Sleeping Sickness)

by Richard D. Pearson, MD

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 can be transmitted prenatally from mother to fetus. Rarely, the infection is transmitted through blood transfusions; theoretically, it could be transmitted through organ transplantation.


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 or animal. 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.

Symptoms and Signs

The disease has 3 stages:

  • Cutaneous

  • Hemolymphatic

  • CNS


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.


Over several months in T. b. gambiense infection but a period of weeks with T. b. rhodesiense, intermittent fever, headaches, rigors, muscle and joint pain, and transient facial swelling develop. An evanescent, circinate erythematous rash may develop. It is most readily visible in light-skinned patients. Generalized lymphadenopathy often occurs. Winterbottom 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 often occurs within a few weeks. CNS involvement causes persistent headache, inability to concentrate, personality changes (eg, progressive lassitude and indifference), daytime somnolence, 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.


  • 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) 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 see Lumbar puncture (spinal tap) 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.


  • Without CNS involvement, pentamidine or eflornithine for T. b. gambiense; suramin for T. b. rhodesiense

  • With CNS involvement, eflornithine or melarsoprol for T. b. gambiense; melarsoprol for T. b. rhodesiense

Without CNS involvement

Suramin and pentamidine 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. Pentamidine is preferred for T. b. gambiense, and suramin is preferred for the hemolymphatic stage of T. b. rhodesiense. The dosage of pentamidine is 4 mg/kg IM or IV once/day for 7 to 10 days. An initial test dose of suramin 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.

Eflornithine (from the WHO; 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

When available, eflornithine 100 mg/kg IV qid for 14 days should be used for CNS disease due to T. b. gambiense (eflornithine is ineffective for T. b. rhodesiense).

Melarsoprol, an organic arsenical, is often used in African countries because of the limited availability of eflornithine, even though adverse effects can be severe and life threatening. For T. b. gambiense, melarsoprol dosage is 2.2 mg/kg IV once/day for 10 days. 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. Serial follow-up examinations, including CSF analysis, are recommended for 2 yr.

Serious adverse effects of melarsoprol include encephalopathic reactions, exfoliative dermatitis, and the GI and renal toxicity of arsenicals.

Corticosteroids have been used to decrease the risk of encephalopathic reactions.


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) in neutral colors that blend with the background and should use insect repellents, although efficacy of repellents against tsetse flies may be limited.

Pentamidine 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.

Key Points

  • African trypanosomiasis is caused by Trypanosoma brucei gambiense in West and Central Africa and by T. b. rhodesiense in East Africa; tsetse flies are the main vector.

  • There are 3 stages of disease: cutaneous, hemolymphatic, and CNS (sleeping sickness).

  • Diagnose using light microscopy of blood (thin or thick smears) or another fluid sample.

  • Treatment varies by species and stage of disease.

  • Without CNS involvement, use pentamidine or eflornithine for T. b. gambiense and suramin for T. b. rhodesiense.

  • With CNS involvement, use eflornithine or melarsoprol for T. b. gambiense and melarsoprol for T. b. rhodesiense.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Brand Names
  • No US brand name

* This is a professional Version *