Trypanosomiasis, African

The diagnosis rests upon demonstrating trypanosomes by microscopic examination of chancre fluid, lymph node aspirates, blood, bone marrow, or, in the late stages of infection, cerebrospinal fluid. A wet preparation should be examined for the motile trypanosomes, and in addition a smear should be fixed, stained with Giemsa (or Field), and examined. Concentration techniques can be used prior to microscopic examination. For blood samples, these include centrifugation followed by examination of the buffy coat; mini anion-exchange/centrifugation; and the Quantitative Buffy Coat (QBC) technique. For other samples such as spinal fluid, concentration techniques include centrifugation followed by examination of the sediment. Isolation of the parasite by inoculation of rats or mice is a sensitive method, but its use is limited to T. b. rhodesiense. Antibody detection has sensitivity and specificity that are too variable for clinical decisions. In addition, in infections with T. b. rhodesiense, seroconversion occurs after the onset of clinical symptoms and thus is of limited use.

The CDC currently does not offer any serologic or molecular tests for African trypanosomiasis.

Treatment

Antitrypanosomal treatment is indicated for all persons diagnosed with African trypanosomiasis. Choice of therapy depends on the infecting subspecies of the parasite and on the disease stage. The first line drugs for both first and second stage disease are highly effective. Pentamidine, given by intravenous infusion over 2 hours or by intramuscular injection, is used to treat first stage T. b. gambiense infection. It is generally well tolerated, but adverse reactions of hypoglycemia, injection site pain, diarrhea, nausea and vomiting occur. Suramin is used to treat first stage T. b. rhodesiense. Suramin is also effective against T. b. gambiense, but it is not often used because severe reactions occur in persons who are co-infected with Onchocerca volvulus. Adverse reactions to suramin are frequent, but usually mild and reversible. These include drug rash, nephrotoxicity, and peripheral neuropathy. In rare instances, suramin administration results in a hypersensitivity reaction, and, for this reason, a small test dose is usually given prior to the full first dose.

Second stage T. b. gambiense is treated with eflornithine, which is given in 4 intravenous infusions daily for 14 days. Adverse effects of eflornithine include bone marrow suppression, gastrointestinal symptoms, and seizures. Eflornithine is highly effective, but the difficulty in administering 4 infusions daily in rural African facilities has led to the use of eflornithine (dosed less frequently) in combination with nifurtimox. The efficacy of the combination regimen appears to be at least as high as eflornithine monotherapy. Eflornithine is not effective against T. b. rhodesiense and it is not recommended for treating the East African form of the disease. Melarsoprol, an organoarsenic compound, is the only drug available for treating second stage T. b. rhodesiense. Adverse reactions to melarsoprol can be severe and life-threatening. An encephalopathic reaction occurs in 5-10% of patients with a case-fatality rate of approximately 50% when it occurs. Prednisolone is often given to patients who are being treated with melarsoprol to reduce the risk of encephalopathy. Other adverse reactions observed with melarsoprol include skin reactions, gastrointestinal upset, and peripheral neuropathy. Intravenous injections of melarsoprol are painful and can cause phlebitis. The drug is administered by use of lengthy and complicated dosing schedules, however, an abbreviated 10-day regimen appears promising.

Species	Drug of choice	Adult Dosage	Pediatric Dosage
T. b. rhodesiense, hemolymphatic stage	Suramin1	1 gm IV on days 1,3,5,14, and 212	20 mg/kg IV on days 1, 3, 5, 14, and 213
T. b. rhodesiense, CNS involvement	Melarsoprol4	2-3.6 mg/kg/day IV x 3 days.5 After 7 days, 3.6 mg/kg/day x 3 days. Give a 3rd series of 3.6 mg/kg/d after 7 days.	2-3.6 mg/kg/day IV x 3 days.5 After 7 days, 3.6 mg/kg/day x 3 days. Give a 3rd series of 3.6 mg/kg/d after 7 days.
T. b. gambiense, Hemolymphatic stage	Pentamidine6	4 mg/kg/day IM or IV x 7-10 days	4 mg/kg/day IM or IV x 7-10 days
T. b. gambiense, CNS involvement	Eflornithine7	400 mg/kg/day in 4 doses x 14 days	400 mg/kg/day in 4 doses x 14 days

There is no test of cure for African trypanosomiasis. Patients should be followed with a lumbar puncture every 6 months (or sooner, if symptoms return) for 2 years after treatment to detect a relapse should it occur.

For treatment advice and to obtain suramin, melarsoprol, or eflornithine, physicians should contact the Division of Parasitic Diseases and Malaria (telephone, 404-718-4745; email, parasites@cdc.gov).

More on:  Human African trypanosomiasis, WHO

1. Pentamidine is also effective against T. b. rhodesiense in the hemolymphatic stage, but suramin may have somewhat higher efficacy.
2. A test dose of 100 mg should be given prior to the first dose and the patient should be monitored for hemodynamic stability.
3. A test dose of 2 mg/kg should be given prior to the first dose and the patient should be monitored for hemodynamic stability.
4. Corticosteroids have been used to prevent melarsoprol encephalopathy.
5. The dose of melarsoprol is progressively increased during the first series.
6. Suramin is also effective against T. b. gambiense in the hemolymphatic stage.
7. Eflornithine (400 mg/kg/d IV in 2 doses x 7 days) given in combination with oral nifurtimox (15 mg/kg/d x 10 days) is also highly effective against T. b. gambiense with CNS involvement (Priotto G et al. Lancet 2009:374; 56-64). Nifurtimox is not FDA-approved for this indication.