African trypanosomiasis is infection with protozoa of the species Trypanosoma brucei, 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 cerebrospinal fluid 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. Trypanosoma brucei gambiense accounts for 98% of all cases of African trypanosomiasis, and T. brucei rhodesiense accounts for 2%. African trypanosomiasis has been targeted for eradication by the World Health Organization and as a result of control efforts, there has been a dramatic decrease (>95%) in the number of reported cases worldwide over the past 20 years, which fell below 1000 in 2018. On average, 1 case is diagnosed in the US each year, always in travelers returning to the US from endemic regions.
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.
Another trypanosomal species, Trypanosoma cruzi, is endemic in South and Central America and causes Chagas disease (American trypanosomiasis).
Pathophysiology of African Trypanosomiasis
Metacyclic trypomastigotes inoculated by tsetse 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 African trypanosomiasis, trypanosomes appear in the interstitial fluid of many organs, including the myocardium and eventually the central nervous system. 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 of African Trypanosomiasis
African trypanosomiasis has 3 stages:
- Central nervous system
A papule may develop at the site of the tsetse fly bite within a few days to 2 weeks. It evolves into a dusky red, painful, indurated nodule that may ulcerate (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.
Central nervous system (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 can result in 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 year with T. b. gambiense. Untreated patients die in coma of undernutrition or secondary infections.
Diagnosis of African Trypanosomiasis
- Light microscopy of blood (thin or thick smears) or other fluid sample
Diagnosis of African trypanosomiasis is made by identifying trypanosomes in fluid from a chancre, lymph node aspirate, blood, bone marrow aspirate, or, during the late stage of infection, cerebrospinal fluid (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. The concentration of trypanosomes in blood is often low, and concentration techniques (eg, centrifugation, miniature anion-exchange centrifugation, quantitative buffy coat technique) 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.
A lumbar puncture should be done in all patients with African trypanosomiasis. When CSF is involved, opening pressure may be increased, and CSF has elevated levels of lymphocytes (≥ 6 cells/mcL), total protein, and nonspecific 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 of African Trypanosomiasis
Treatment of African trypanosomiasis varies by species and stage of disease.
- Without CNS involvement, pentamidine 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
Pentamidine and suramin 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 used for T. b. gambiense, and suramin is the only drug effective for the hemolymphatic stage of T. b. rhodesiense. The dosage of pentamidine is 4 mg/kg IM or IV once a day for 7 to 10 days. An initial test dose of suramin (available from the CDC) 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. Suramin is not used to treat T. b. gambiense. It is potentially effective, but it has been associated with side effects including nausea, vomiting, photophobia, hyperesthesias, peripheral neuropathy, nephrotoxicity, urticaria, and pruritus. Also, serious hypersensitivity reactions can occur in patients co-infected with Onchocerca volvulus, which is endemic in many areas of West Africa where T. b. gambiense occurs.
Flexinidazole, which is in the World Health Organization's interim guidelines for the treatment of T. b. gambiense infection in endemic regions, is used in people with hemolymphatic and non-severe CNS involvement. It is not available or recommended for use in the US.
With CNS involvement
When available, eflornithine 100 mg/kg IV 4 times a day for 14 days is used for CNS disease due to T. b. gambiense (eflornithine is ineffective for T. b. rhodesiense). The WHO recommends eflornithine in combination with nifurtimox 5 mg/kg 3 times a day for 10 days (1). Adverse effects of eflornithine include gastrointestinal symptoms, bone marrow suppression, and seizures. Common side effects of nifurtimox are anorexia, nausea, vomiting, weight loss, polyneuropathy, headache, dizziness, and vertigo.
In the US, eflornithine, nifurtimox, and melarsoprol can be obtained from the Centers for Disease Control and Prevention (CDC).
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. Melarsoprol dosage is as follows:
- For T. b. gambiense: 2.2 mg/kg IV once a day for 10 days
- For T. b. rhodesiense: 2 to 3.6 mg/kg IV once a day for 3 days; after 7 days, 3.6 mg/kg once a day 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 cerebrospinal fluid analysis, are recommended every 6 months (sooner if symptoms return) for 2 years.
Serious adverse effects of melarsoprol include encephalopathic reactions, exfoliative dermatitis, cardiovascular toxicity (hypertension, arrhythmia, heart failure), and the gastrointestinal and renal toxicity of arsenicals.
Corticosteroids have been used to decrease the risk of encephalopathic reactions.
- 1. Büscher P, Cecchi G, Jamonneau V, et al: Human African trypanosomiasis. Lancet, 390(10110):2397-2409m 2017. doi: 10.1016/S0140-6736(17)31510-6
Prevention of African Trypanosomiasis
Prevention of African trypanosomiasis 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 beta cells, resulting in insulin release and hypoglycemia followed later by diabetes; thus, it is no longer used for prophylaxis.
- 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 of African trypanosomiasis varies by species and stage of disease.
- Without CNS involvement, use pentamidine for T. b. gambiense and suramin for T. b. rhodesiense.
- With CNS involvement, use eflornithine (if available) alone or in combination with nifurtimox, or melarsoprol (if eflornithine is not available) for T. b. gambiense; use melarsoprol for T. b. rhodesiense.
- CDC: Resources for health professionals: African trypanosomiasis
Drugs Mentioned In This Article
|Drug Name||Select Trade|
|suramin||No US brand name|