infectious diseases
African Trypanosomiasis
Treatment of African Trypanosomiasis
Treatment of African trypanosomiasis is guided by species and stage of disease. Without CNS involvement,fexinidazoleor, alternatively,pentamidineforT. b. gambiense; suramin forT. b. rhodesiense With CNS involvement,fexinidazolefor nonsevereT. b. gambiense;eflornithine(if available) alone or in combination withnifurtimox, or melarsoprol (ifeflornithineis not available), for severeT. b. gambiense; melarsoprol forT. b. rhodesiense Fexinidazoleis the first-choice treatment for nonsevereT. b. gambiense, with or without CNS involvement. (See theWorld Health Organization.)Fexinidazoleis taken orally once a day for 10 days at the following doses: For patients ≥ 35 kg: 1800 mg/day in the loading phase (4 days), followed by 1200 mg/day in the maintenance phase (6 days) For patients 20 to 34 kg: 1200 mg/day in the loading phase (4 days), followed by 600 mg/day in the maintenance phase (6 days) Criteria for outpatient treatment withfexinidazoleinclude reliable adherence to dosing, absence of psychiatric disorders, and body weight ≥ 35 kg. Criteria for inpatient treatment includes any of the following characteristics: Body weight < 35 kg At risk for poor compliance History of psychiatric disorders (to monitor for neuropsychiatric reactions) Patients with signs and symptoms of severe disease should be evaluated by lumbar puncture and cerebrospinal fluid (CSF) examination. Patients with severe disease (white blood cell count ≥ 100 cells/microL in CSF), where lumbar puncture is not feasible, or who cannot be treated withfexinidazoleshould be treated as outlined below. Fexinidazoleis the first-choice treatment for nonsevereT. b. gambiensewithout CNS involvement. Pentamidineand suramin are effective against bloodstream stages of bothT. bruceisubspecies but do not cross the blood-brain barrier and are not useful for CNS infection. Pentamidineis used forT. b. gambiensein patients not treated withfexinidazole. Suraminis the only drug effective for the hemolymphatic stage ofT. b. rhodesiense.Suraminis not used to treatT. b. gambiense, because although potentially effective, it has been associated with adverse effects, including nausea, vomiting, photophobia, hyperesthesias, peripheral neuropathy, nephrotoxicity, urticaria, and pruritus. Also, serious hypersensitivity reactions can occur in patients co-infected withOnchocerca volvulus, which is endemic in many areas of West Africa whereT. b. gambienseoccurs. The dosage ofpentamidineis 4 mg/kg IM or IV once a day for 7 to 10 days. An initial test dose ofsuramin(available from the Centers for Disease Control and Prevention [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. Fexinidazoleis the first-choice treatment for nonsevere disease with CNS involvement due toT. b. gambiense. 5 mg/kg orally 3 times a day for 10 days ( Treatment reference ). Melarsoprol, an organic arsenical, is often used in African countries because of the limited availability ofeflornithine, even though adverse effects can be severe and life threatening. Melarsoprol dosage is as follows: ForT. b. gambiense: 2.2 mg/kg (maximum dose 180 mg) IV once a day for 10 days ForT. 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 In the US,eflornithine,nifurtimox, and melarsoprol can be obtained from the CDC. 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. There is no test of cure. After treatment, patients should be monitored for relapse for 24 months. Recurrence of symptoms necessitates re-examination of CSF for parasites. 1.World Health Organization: WHO publishes new guidelines for the treatment of sleeping sickness; August 2019. 