ArticlePLoS neglected tropical diseases2026
Winning the endgame against sleeping sickness: Efficacy profiling of acoziborole against African trypanosomes with the focus on Trypanosoma brucei rhodesiense.
Article in PLoS neglected tropical diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Human African trypanosomiasis (HAT) is caused by two subspecies of Trypanosoma brucei, T. b. gambiense and T. b. rhodesiense, with the former accounting for over 95% of all cases. HAT is an elusive disease, which is fatal unless treated, with a focal prevalence in the rural areas of tropical Africa where the tsetse fly vectors are endemic. At the same time, HAT is one of the very few infectious diseases where global elimination seems possible. The incidence is at a historic low, and new orally bioavailable drugs have been developed that will expand the coverage of treatment in endemic regions. In particular, acoziborole has passed the clinical development as a single-dose oral cure of T. b. gambiense infection. However, to win the endgame against HAT, acoziborole also needs to be extended to T. b. rhodesiense. In order to strengthen the preclinical dossier of acoziborole, we conducted an in-depth evaluation of acoziborole against the bloodstream forms of all three T. brucei subspecies with a focus on T. b. rhodesiense. Acoziborole had consistent and high activity against different T. b. rhodesiense strains, including a multidrug-resistant field isolate, with IC50 values around 600 nM. Acoziborole is faster acting than fexinidazole, and it exhibits irreversible cidality against T. b. rhodesiense at concentrations of ≥4.3 μM (1.6 μg/ml) after 15 h of incubation. At very short exposure times (≤8 h), T. b. gambiense appeared to be more sensitive than T. b. rhodesiense. However, given the extremely long elimination half-life of acoziborole in the human body, this difference will be irrelevant for its trypanocidal action in patients. We therefore conclude that acoziborole is expected to be as effective against r-HAT as against g-HAT in patient populations.
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