Background T.b. rhodesiense human African trypanosomiasis (r-HAT), the zoonotic, acute form of sleeping sickness in Eastern Africa, is lethal if untreated. Today only one arsenic-based, neurotoxic drug, melarsoprol, is available for intravenous treatment of advanced meningo-encephalitic disease, the most frequent presentation seen by health services. A new oral treatment would simplify HAT elimination as proposed by WHO. Fexinidazole was approved in 2018 as the first oral drug to treat T.b. gambiense HAT but was not yet evaluated for r-HAT.

Methods A single-arm clinical trial beginning October 2019 in the two main known foci in Malawi and Uganda tested fexinidazole for r-HAT as an alternative to existing treatment. Complementary actions included training of prescribers and laboratory technicians of peripheral health facilities to improve diagnostic capacity, and ethnographic research to understand health-seeking behaviours of populations at risk. These studies supported the creation of community awareness materials and activities.

Results The primary efficacy result of the clinical trial was achieved with no related deaths during hospitalisation: 0 (C.I.=0.0–8.43%), against a benchmark of 8.5% lethality attributable to melarsoprol. Training covered health staff from twelve provinces in Uganda and three in Malawi, beyond initial plans. Two ethnographic studies provided updated information about perceptions of communities at risk regarding r-HAT, leading to four articles. Posters and leaflets were developed and disseminated in health facilities and community gatherings.

Conclusion Fexinidazole has shown to be a good alternative to existing treatments for oral treatment of both stages of r-HAT. It will be submitted for EMA regulatory review in preparation for use in endemic countries. Disease awareness has increased among health staff and populations living in endemic areas of Uganda and Malawi. We expect fexinidazole to be deployed in 2024 as a new r-HAT therapeutic.

This project was funded by EDCTP and Fundação para a Ciência e a Tecnologia