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Abstract
Treatment of second-stage gambiense human African trypanosomiasis relied on toxic arsenic-based derivatives for over 50 years. The availability and subsequent use of eflornithine, initially in monotherapy and more recently in combination with nifurtimox (NECT), has drastically improved the prognosis of treated patients. However, NECT logistic and nursing requirements remain obstacles to its deployment and use in peripheral health structures in rural sub-Saharan Africa. Two oral compounds, fexinidazole and SCYX-7158, are currently in clinical development. The main scope of this article is to discuss the potential impact of new oral therapies to improve diagnosis-treatment algorithms and patients’ access to treatment, and to contribute to reach the objectives of the recently launched gambiense human African trypanosomiasis elimination program.
Financial & competing interests disclosure
C Mowbray and O Valverde are employees of DNDi, a not-for-profit research and development organization involved in HAT drug development. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Writing assistance was provided by A Tarral (reviewing the manuscript) and C Power (editing the manuscript), both employees of DNDi.
Key issues
Human African trypanosomiasis (HAT) is a neglected tropical disease transmitted by tsetse flies in sub-Saharan Africa; over 95% of cases are caused by Trypanosoma brucei gambiense. Gambiense HAT evolves from first (hemolymphatic) to second (meningoencephalitic) stage and is generally lethal if left untreated.
Treatment of second-stage gambiense HAT relied on melarsoprol, an arsenic-based derivative, for over 50 years. Melarsoprol is associated with a wide range of adverse effects, the most feared being an encephalopathic syndrome that kills 3–6% of patients.
Eflornithine-based treatments, initially developed and used in monotherapy for 14 days and more recently for 7 days in combination with 10-day oral nifurtimox (NECT), are associated with improved safety and efficacy profiles; NECT has been adopted as first-line treatment for second-stage gambiense HAT in all endemic countries.
Access to newer anti-trypanosomal drugs, in particular eflornithine, has been a long battle; donation agreements between WHO and the producers, which included funding for preparation, storage and transport of kits, drastically improved patients’ access to treatment.
While NECT is safe and very effective, its use in remote endemic areas is impaired by the heavy nursing and logistic resources required for it to be properly administered.
The decreasing trend in reported cases triggered WHO to launch a gambiense HAT elimination program with various partners. The strategy includes partial reintegration of control activities within existing health structures, which usually have low human and logistic resources in rural sub-Saharan Africa.
Two oral drugs are being evaluated in clinical trials: fexinidazole, a 5-nitroimidazole, and SCYX-7158 (AN5568), a benzoxaborole. Provided that these oral drugs show good safety and efficacy profiles, they may lead to drastic simplification of diagnostic algorithms and better patient access to treatment in peripheral health structures.
The development of simplified diagnosis-treatment algorithms, incorporating the newly developed rapid diagnostic tests and oral therapies, will also facilitate passive case detection and disease surveillance, which are crucial requirements to reach sustained disease elimination.