Version August 2025
| Patient characteristics | Clinical evaluation and staging | CSF findings | Preferred therapy | Alternative therapy* | Rescue therapy¶ |
| <6 years old or <20 kg body weight | Perform lumbar puncture | First-stage disease: WBC ≤5 cells/microL and no trypanosomes | PentamidineΔ: 4 mg/kg/day IM or IV (infuse over 1 to 2 hours) once daily for 7 days | Nifurtimox-eflornithine combination therapy (NECT):
| NECT (dosing in column to left) |
| Second-stage disease: WBC >5 cells/microL, and/or trypanosomes (or unable to perform lumbar puncture) | NECT (dosing as above) | Eflornithine monotherapy: 100 mg/kg IV every 6 hours for (infuse over 2 hours) 14 days | NECT-long◊:
| ||
| ≥6 years old and ≥20 kg body weight | If no suspicion for severe disease§, lumbar puncture not needed | None | Fexinidazole¥ (taken with food) Body weight ≥35 kg:
Body weight 20 to <35 kg:
| Lumbar puncture needed‡ First-stage disease (WBC ≤5 cells/microL and no trypanosomes): Pentamidine (dosing as above) Second-stage disease (WBC >5 cells/microL, and/or trypanosomes): NECT (dosing as above) If NECT not available: treat with eflornithine monotherapy (dosing as above) | NECT or NECT-long (dosing as above) |
| If suspicion for severe disease§, perform lumbar puncture | Nonsevere second-stage disease: WBC <100 cells/microL | Fexinidazole¥ (dosing as above) | First-stage disease (WBC ≤5 cells/microL and no trypanosomes): Pentamidine (dosing as above) Second-stage disease (WBC >5 cells/microL, and/or trypanosomes): NECT (dosing as above) If NECT not available: treat with eflornithine monotherapy (dosing as above) | NECT (dosing as above) | |
| Severe second-stage disease: WBC ≥100 cells/microL or unable to perform lumbar puncture | NECT (dosing as above) | Fexinidazole (dosing as above) | NECT-long◊ (dosing as above) |
CSF: cerebrospinal fluid; IM: intramuscular; IV: intravenous; NECT: nifurtimox-eflornithine combination therapy; WBC: white blood cell count.
* Alternative treatment should be given in cases where the preferred treatment is not available or not appropriate for a particular patient. It is not the same as rescue treatment which is when a patient fails first-line therapy.
¶ Rescue treatment is given in cases of treatment failure with a preferred or alternative agent.
Δ Pentamidine is usually given as an IM injection because IV administration is frequently associated with severe hypotension and can cause extravasation injury. Patients should lie down for at least 1 hour after injection (IM or IV) to prevent hypotension and should eat or drink sugar to prevent hypoglycemia. Monitor vital signs before and 1 hour after administration (and continue if hemodynamic instability). Electrocardiogram and serum glucose monitoring should be considered when feasible.
◊ If NECT-long is not an option, melarsoprol may be used as an agent of last resort for patients with recurrent relapse of second-stage gambiense HAT following first-line and rescue treatments (including NECT, NECT-long, fexinidazole, or eflornithine monotherapy). Dosing for melarsoprol is 2.2 mg/kg/day IV once daily for 10 days (maximum dose: 180 mg). Melarsoprol is associated with high frequency of severe, life-threatening adverse effects and should be coadministered with prednisolone 1 mg/kg per day orally once daily (maximum dose: 50 mg) for 9 days, followed by a 3-day taper (day 10: 0.75 mg/kg; day 11: 0.5 mg/kg; day 12: 0.25 mg/kg). Melarsoprol should not come into contact with water due to risk of precipitation. Care must be taken if using plastic syringes; after drawing up the liquid, it must be administered immediately but slowly. Refer to UpToDate text for further discussion.
§ Refer to separate UpToDate table in topic text summarizing neuropsychological symptoms and signs that raise suspicion for severe second stage disease.
¥ Fexinidazole should be administered only if there is high confidence that the patient will have appropriate follow up to detect relapse early. Concomitant solid food intake (minimum 250 mL) is required for adequate absorption; avoid liquid food as it inhibits absorption. It should be administered under directly observed treatment. Outpatient treatment is possible under certain conditions; refer to UpToDate text for further discussion.
‡ If fexinidazole cannot be given, lumbar puncture is required to determine therapy.