Treatment of Human African Trypanosomiasis (HAT)

Treatment of Human African Trypanosomiasis (HAT)
Patient Age and Body Weight	LP/CSF Examination and First-Line Medication*	Second-Line Medication*	Adverse Effects	Comments
Trypanosoma brucei gambiense HAT
< 6 years or < 20 kg	If WBC count ≤ 5 cells/mcL (≤ 0.005 × 10⁹/L) and no trypanosomes: Pentamidine/L) and no trypanosomes: Pentamidine	—	Pentamidine: Dizziness, nausea, vomiting, and pain at injection sitePentamidine: Dizziness, nausea, vomiting, and pain at injection site	Pentamidine can be given IM.Pentamidine can be given IM.
< 6 years or < 20 kg	If WBC count > 5 cells/mcL (> 0.005 × 10⁹/L), or trypanosomes: Oral nifurtimox/IV eflornithine combination therapy (NECT)/L), or trypanosomes: Oral nifurtimox/IV eflornithine combination therapy (NECT)	EflornithineEflornithine	Eflornithine: Fever, pruritus, hypertension, nausea, vomiting, diarrhea, abdominal pain, headaches, bone marrow suppression, and seizures Nifurtimox: Anorexia, nausea, vomiting, weight loss, polyneuropathy, headache, dizziness, and vertigo NECT: Abdominal pain, nausea, vomiting, and headache	Eflornithine is ineffective for T. b. rhodesiense HAT. Eflornithine monotherapy is given for CNS stage T. b. gambiense HAT when NECT is not feasible because nifurtimox is unavailable or contraindicated and when fexinidazole cannot be given.
≥ 6 years and ≥ 20 kg	Lumbar puncture not needed if no suspicion of severe HAT: FexinidazoleLumbar puncture not needed if no suspicion of severe HAT: Fexinidazole	LP needed: Pentamidine (hemolymphatic stage) or NECT (CNS stage)†LP needed: Pentamidine (hemolymphatic stage) or NECT (CNS stage)†	Fexinidazole: Vomiting, nausea, decreased appetite, headache, insomnia, QT interval prolongation, and neutropenia	Fexinidazole is given orally.Fexinidazole is given orally.
≥ 6 years and ≥ 20 kg	Lumbar puncture needed if suspicion of severe HAT: If WBC count < 100 cells/mcL (< 0.1 × 10⁹/L): Fexinidazole/L): Fexinidazole If WBC count ≥ 100 cells/mcL (≥ 0.1 × 10⁹/L) or failed LP: NECT	WBC count < 100 cells/mcL (< 0.1 × 10⁹/L): Pentamidine (hemolymphatic stage) or NECT (CNS stage)/L): Pentamidine (hemolymphatic stage) or NECT (CNS stage) WBC count ≥ 100 cells/mcL (≥ 0.1 × 10⁹/L): Fexinidazole/L): Fexinidazole	—	—
T. b. rhodesiense HAT
< 6 years or < 20 kg	≤ 5 WBC/mcL and no trypanosomes: Suramin	PentamidinePentamidine	Suramin: Nausea, vomiting, photophobia, hyperesthesias, peripheral neuropathy, nephrotoxicity, urticaria, and pruritus	Suramin is given IV. Suramin is the only drug effective for the hemolymphatic stage of T. b. rhodesiense. Suramin is not used to treat T. b. gambiense because although potentially effective, it has been associated with adverse effects. Caution must be exercised when administering suramin because 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.
< 6 years or < 20 kg	> 5 WBC/mcL, or trypanosomes: Melarsoprol	—	Melarsoprol: Encephalopathic reactions, exfoliative dermatitis, cardiovascular toxicity (hypertension, arrhythmia, heart failure), pruritus, and gastrointestinal and renal toxicity	IV 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.‡
≥ 6 years and ≥ 20 kg	LP not needed: FexinidazoleLP not needed: Fexinidazole	LP needed: Suramin or pentamidine (hemolymphatic stage) or melarsoprol (CNS stage)LP needed: Suramin or pentamidine (hemolymphatic stage) or melarsoprol (CNS stage)	—	—
* In the United States, pentamidine and nifurtimox are commercially available, fexinidazole is available from the manufacturer, and eflornithine, suramin, and melarsoprol can be obtained from the CDC.
† For T. b. gambiense HAT, patients with ≤ 5 WBC/mL (≤ 0.005 × 10⁹/L) and no trypomastigotes in CSF are in the hemolymphatic stage, whereas those with > 5 WBC/mL (> 0.005 × 10⁹/L) or trypomastigotes in CSF are in the CNS stage.
‡ Melarsoprol is only indicated for T. b. gambiense HAT for treatment of recurrent relapse after first-line and other treatment failure. Melarsoprol is only indicated for T. b. rhodesiense HAT for the following: Children < 6 years or < 20 kg who are in second-stage T. b. rhodesiense HAT. Other patients in second-stage HAT who cannot receive fexinidazole because of contraindications or inability to swallow.Other patients in second-stage HAT who cannot receive fexinidazole because of contraindications or inability to swallow.
CDC = Centers for Disease Control and Prevention; CNS = central nervous system; CSF = cerebrospinal fluid; LP = lumbar puncture; NECT = oral nifurtimox/IV eflornithine combination therapy; WBC = white blood cell.
Data fromWorld Health Organization: Guidelines for the treatment of human African trypanosomiasis. June 2024.

* In the United States, pentamidine and nifurtimox are commercially available, fexinidazole is available from the manufacturer, and eflornithine, suramin, and melarsoprol can be obtained from the CDC.

† For T. b. gambiense HAT, patients with ≤ 5 WBC/mL (≤ 0.005 × 10⁹/L) and no trypomastigotes in CSF are in the hemolymphatic stage, whereas those with > 5 WBC/mL (> 0.005 × 10⁹/L) or trypomastigotes in CSF are in the CNS stage.

‡ Melarsoprol is only indicated for T. b. gambiense HAT for treatment of recurrent relapse after first-line and other treatment failure.

Melarsoprol is only indicated for T. b. rhodesiense HAT for the following:

Children < 6 years or < 20 kg who are in second-stage T. b. rhodesiense HAT.
Other patients in second-stage HAT who cannot receive fexinidazole because of contraindications or inability to swallow.Other patients in second-stage HAT who cannot receive fexinidazole because of contraindications or inability to swallow.

CDC = Centers for Disease Control and Prevention; CNS = central nervous system; CSF = cerebrospinal fluid; LP = lumbar puncture; NECT = oral nifurtimox/IV eflornithine combination therapy; WBC = white blood cell.

Data fromWorld Health Organization: Guidelines for the treatment of human African trypanosomiasis. June 2024.

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African Trypanosomiasis