Abstract
The twentieth century ended with human African trypanosomiasis (HAT) epidemics raging across many parts of Africa. Resistance to existing drugs was emerging, and many programs aiming to contain the disease had ground to a halt, given previous success against HAT and the competing priorities associated with other medical crises ravaging the continent. A series of dedicated interventions and the introduction of innovative routes to develop drugs, involving Product Development Partnerships, has led to a dramatic turnaround in the fight against HAT caused by Trypanosoma brucei gambiense. The World Health Organization have been able to optimize the use of existing tools to monitor and intervene in the disease. A promising new oral medication for stage 1 HAT, pafuramidine maleate, ultimately failed due to unforeseen toxicity issues. However, the clinical trials for this compound demonstrated the possibility of conducting such trials in the resource-poor settings of rural Africa. The Drugs for Neglected Disease initiative (DNDi), founded in 2003, has developed the first all oral therapy for both stage 1 and stage 2 HAT in fexinidazole. DNDi has also brought forward another oral therapy, acoziborole, potentially capable of curing both stage 1 and stage 2 disease in a single dosing. In this review article, we describe the remarkable successes in combating HAT through the twenty first century, bringing the prospect of the elimination of this disease into sight.
Highlights
The current drugs used for human African trypanosomiasis (HAT) (Figure 1) have served their purpose for many years
The one found in West and Central Africa is caused by Trypanosoma brucei gambiense, and the other, found in East and Southern Africa, is caused by Trypanosoma brucei rhodesiense
The twentieth century ended with human African trypanosomiasis epidemics raging across Africa
Summary
The current drugs used for human African trypanosomiasis (HAT) (Figure 1) have served their purpose for many years. For stage 2 disease, the highly toxic melarsoprol is still the treatment of choice for rhodesiense HAT. A number of pharmaceutical companies regained an interest in HAT, including GlaxoSmithKline (GSK) through their Tres Cantos Open Lab foundation [21] and the Novartis Institute for Tropical Diseases (NITD) [22]. Small companies too, such as Immtech Pharmaceuticals Inc., Scynexis and Anacor Pharmaceuticals Inc. in the USA, raised investment to develop new drugs against HAT. This article outlines the successes seen in the development of new drugs for HAT in the twenty first century
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