Nifurtimox plus Eflornithine for Late-Stage Sleeping Sickness in Uganda: A Case Series

Open Access
Publisher Website
Google Scholar
Abstract
We report efficacy and safety outcomes from a prospective case series of 31 late-stage T.b. gambiense sleeping sickness (Human African Trypanosomiasis, HAT) patients treated with a combination of nifurtimox and eflornithine (N+E) in Yumbe, northwest Uganda in 2002–2003, following on a previously reported terminated trial in nearby Omugo, in which 17 patients received the combination under the same conditions. Eligible sequential late-stage patients received 400 mg/Kg/day eflornithine (Ornidyl, Sanofi-Aventis) for seven days plus 15 mg/Kg/day (20 mg for children Trypanosoma brucei gambiense, threatens millions across remote and conflict-affected regions of sub-Saharan Africa, and causes about 15 000 reported cases every year. Untreated HAT progresses from stage 1 (infection of the blood and lymph) to stage 2 (invasion of the central nervous system), and ultimately death. Drugs for stage 2 are few. The historical mainstay, melarsoprol, is highly toxic and inefficacious in some areas due to parasite resistance. Eflornithine is the only viable alternative, already established as safe and efficacious, but difficult to administer and at risk of resistance if used in monotherapy. This paper reports on a series of 48 Ugandan patients treated with a novel combination of nifurtimox (a drug registered for Chagas disease) and eflornithine, 17 as part of a terminated trial, and 31 in a subsequent case series study. Despite the low sample size, findings are promising: no cases of treatment failure, no treatment terminations, and no HAT- or treatment-related deaths. Nifurtimox plus eflornithine may be the best treatment hope for stage 2 HAT patients in the next decade, while new drugs are developed. A larger, multi-centric trial of the combination is ongoing.