Detection of trypanosomes is a prerequisite for treatment of African trypanosomiasis because of the significant toxicity of most available therapies. Treatment recommendations depend on the type of trypanosomiasis (Table 35–1), which is determined by geography, and stage of disease, which requires examination of CSF. Eflornithine, nifurtimox, suramin, and melarsoprol are available in the United States from the CDC Drug Service (www.cdc.gov/laboratory/drugservice).
Table 35–1.Treatment of African trypanosomiasis.
A. West African Trypanosomiasis
Pentamidine (4 mg/kg intramuscularly or intravenously every day or every other day for 7 days) has been used to treat infection that does not involve the central nervous system (CNS). The side effects of pentamidine include immediate hypotension; tachycardia; gastrointestinal symptoms during administration; sterile abscesses; and pancreatic (hypoglycemia), liver, and kidney abnormalities. An alternate drug for early stage infection is eflornithine (100 mg/kg/day intravenously every 6 hours for 14 days).
The treatment of choice for CNS infection has been a combination of intravenous eflornithine (400 mg/kg/day in two doses for 7 days) and oral nifurtimox (15 mg/kg/day in three doses for 10 days), which has improved efficacy and less toxicity than older regimens. Eflornithine, though less toxic than older trypanocidal drugs, can cause gastrointestinal symptoms, bone marrow suppression, seizures, and alopecia. An alternative agent is melarsoprol. Fexinidazole is as effective and safe as eflornithine plus nifurtimox when administered orally over 10 days; this drug has been endorsed by the WHO for both early and CNS infection and will likely replace other therapies for all but advanced CNS disease. Fexinidazole is recommended for persons 6 years of age and older, with body weight at least 20 kg, and a CSF leukocyte count below 100/mcL (evaluation of CSF can be avoided if there is no suspicion of severe CNS disease). The drug has an acceptable safety profile, in particular compared to older therapies, but adverse events include headache, nausea, vomiting, insomnia, anxiety, weakness, tremor, and decreased appetite. For advanced CNS disease (CNS leukocytes more than 100/mcL), eflornithine plus nifurtimox is recommended.
B. East African Trypanosomiasis
Pentamidine and eflornithine are not reliably effective, and early disease is treated with suramin. The dosing regimens of suramin vary (eg, 100–200 mg test dose, then 20 mg/kg [maximum 1 g] intravenously on days 1, 3, 7, 14, and 21 or weekly for five doses). Suramin toxicities include vomiting and, rarely, seizures and shock during infusions as well as subsequent fever, rash, headache, neuropathy, and kidney and bone marrow dysfunction.
Suramin does not enter the CNS, so East African trypanosomiasis involving the CNS is treated with melarsoprol (three series of 3.6 mg/kg/day intravenously for 3 days, with 7-day breaks between the series or a 10-day intravenous course with 0.6 mg/kg on day 1, 1.2 mg/kg on day 2, and 1.8 mg/kg on days 3–10). Melarsoprol also acts against West African disease, but eflornithine plus nifurtimox is preferred due to its lower toxicity. Immediate side effects of melarsoprol include fever and gastrointestinal symptoms. The most important side effect is a reactive encephalopathy that can progress to seizures, coma, and death. To help avoid this side effect, corticosteroids are coadministered (dexamethasone 1 mg/kg/day intravenously for 2–3 days or oral prednisolone 1 mg/kg/day for 5 days, and then 0.5 mg/kg/day until treatment completion). In addition, increasing resistance to melarsoprol is a serious concern.