Clinical Care of Human African Trypanosomiasis

Key points

  • Treatment for human African trypanosomiasis (HAT) depends on the type and stage of infection.
  • The first line drugs for each stage of HAT are highly effective.
  • Consult with a subject matter expert to discuss treatment options for HAT.
  • Providers should monitor patients for relapse for 24 months after treatment.

Treatment options

Antitrypanosomal treatment is indicated for all persons diagnosed with HAT. 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.

Treatment during first stage of T. b. gambiense infection

Pentamidine is used to treat first stage T. b. gambiense infection in children < 6 years and < 20 kg without evidence of CNS disease. It is generally well-tolerated but may cause adverse reactions such as hypotension, hypoglycemia, injection site pain, diarrhea, nausea, and vomiting. Fexinidazole is now available for treatment of first stage T. b. gambiense infection as an oral alternative in patients > 6 years weighing > 20kg. Suramin is also effective in treating the first stages of both T. b. gambiense and T. b. rhodesiense but is recommended to be only used to treat the first stage of T. b. rhodesiense because of the risk of severe adverse reactions in patients co-infected with onchocerciasis, which can occur in T. b. gambiense-endemic areas. Adverse reactions to suramin treatment in patients with T. b. rhodesiense trypanosomiasis 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.

Treatment during second stage of T. b. gambiense infection

Second stage T. b. gambiense infection is treated with nifurtimox-eflornithine combination therapy (NECT) or fexinidazole (in patients > 6 years old weighing > 20 kg) depending on severity as measured by WBC in CSF and access to available regimens. There is limited data comparing fexinidazole to NECT but fexinidazole is preferred in low resource settings given the ease of administration as an oral drug. The NECT combination regimen appears to be more effective and less toxic than eflornithine monotherapy. Adverse events with eflornithine include fever, pruritus, hypertension, nausea, vomiting, diarrhea, abdominal pain, headaches, myelosuppression and more rarely, seizures. Eflornithine is not effective against T. b. rhodesiense and it is not recommended for treating rhodesiense HAT.

Treatment of T. b. rhodesiense infection

Currently, suramin is used to treat first stage T. b. rhodesiense infection. Melarsoprol, an organoarsenic compound, is used to treat 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. Prednisone or 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 gastrointestinal and skin reactions, pyrexia, and peripheral neuropathy. Intravenous injections of melarsoprol are painful and can cause phlebitis.

In December 2023, the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) adopted a positive scientific opinion of fexinidazole as treatment of first and second stage rhodesiense HAT in adults and children ≥6 years old and weighing ≥20 kg. Updated recommendations from the WHO are in progress.

The medications to treat T. b rhodesiense infection are not commercially available in the United States. Physicians can consult with CDC's parasitic diseases staff.

To consult with CDC's parasitic diseases staff or to obtain medications to treat these infections, please call 404-718-4745 or email parasites@cdc.gov. After hours or on weekends, call CDC's Emergency Operations Center at 770-488-7100.

Consult with an expert

Consultation with a subject matter expert at CDC is advised to discuss treatment options for patients with T. b. rhodesiense and T. b. gambiense infections. There is no test or cure for HAT. After treatment, patients should be closely followed for 24 months and monitored for relapse. Recurrence of symptoms will require examination of body fluids, including CSF, to detect the presence of trypanosomes.

Treatment recommendations

Current treatment recommendations of HAT by form and stage

Species Drug Age Group  CSF Findings Dosage and Duration Comments
T. brucei gambiense,
first stage
Pentamidine* < 6 years old or
weight < 20 kg
<5 WBC/uL, no trypanosomes 4 mg/kg/day, IM or IV, (diluted in saline in 2-hour infusions) for 7 days.
Fexinidazole♯ > 6 years old and weight > 20 kg Weight > 20 kg to < 35 kg:
Loading dose 1,200 mg on days 1-4
Maintenance dose 600 mg on days 5-10-Weight > 35 kg:
Loading dose 1,800 mg on days 1-4
Maintenance dose 1,200 mg on days 5-10
T. brucei gambiense, second stage Nifurtimox^ and Eflornithine† combination (NECT) < 6 years old or weight < 20 kg >5 WBC/uL, or trypanosomes Nifurtimox 15 mg/kg/day orally in three doses x 10 days and
Eflornithine 400 mg/kg/day, IV, in two 2-hour infusions (each dose diluted in 250mL of water for injection) x 7 days.
Eflornithine in children weighing <10 kg: dilute in 50 mL of water for injection. Children weighing 10–20 kg: dilute in 100 mL of water for injection. If water for injection is unavailable, eflornithine can be diluted in 5% dextrose or saline.
Eflornithine might not be effective in immunosuppressed patients because it is trypanostatic and not trypanocidal.
Fexinidazole♯ >6 years old and weight > 20 kg < 100 WBC/uL Weight > 20 kg < 35 kg:
Loading dose 1,200 mg on days 1-4
Maintenance dose 600 mg on days 5-10-Weight > 35 kg
Loading dose 1,800 mg on days 1-4
Maintenance dose 1,200 mg on days 5-10
Nifurtimox^ and Eflornithine† combination (NECT) >6 years old and weight > 20 kg > 100 WBC/uL Nifurtimox 15 mg/kg/day orally in three doses x 10 days and
Eflornithine 400 mg/kg/day, IV, in two 2-hour infusions (each dose diluted in 250mL of water for injection) x 7 days.
Eflornithine in children weighing 20–25 kg: dilute in 100 mL of water for injection. If water for injection is unavailable, eflornithine can be diluted in 5% dextrose or saline. Eflornithine might not be effective in immunosuppressed patients because it is trypanostatic and not trypanocidal.
Trypanosoma brucei rhodesiense, first stage Suramin Test dose of 4-5 mg/kg (day 0) slowly IV, then 20 mg/kg IV (max 1 g/injection) over several hours, on days 1, 3, 7, 14, and 21.
See comments for dosage in children
Suramin in children (test dose): 2 mg/kg; maximum, 100 mg. Suramin in children (treatment dose): 10–20 mg/kg, maximum 1 g. In case of renal toxicity, consider alternative treatment schedules adjusting the daily dose and the interval between doses.
T. brucei rhodesiense, CNS involvement Melarsoprol 2.2 mg/kg/day (max 180-200mg/day), IV x 10 days Corticosteroid pretreatment should be considered as it can reduce the risk of encephalopathic reaction to melarsoprol.