by Watson JA, Strub-Wourgraft N, Tarral A, Ribeiro I, Tarning J, White NJ. Antimicrobial Agents and Chemotherapy 2019, doi: 10.1128/AAC.02515-18.
Summary: Fexinidazole, a novel oral treatment for Trypanosoma brucei gambiense, human African trypanosomiasis: g-HAT, also has activity against T. cruzi, the causative agent of Chagas disease. During a dose ranging assessment for Chagas disease, delayed neutropenia and significant increases in hepatic transaminases were observed, resulting in suspension of clinical investigations. The authors retrospectively analysed all available pharmacokinetic and pharmacodynamic data on fexinidazole in healthy volunteers and in patients with Chagas disease and g-HAT, to assess the determinants of toxicity. They conclude that fexinidazole treatment results in a dose-dependent liver toxicity and transient bone marrow suppression in Chagas disease, and that regimens of shorter duration should therefore be trialled for Chagas. However, the currently recommended regimen for sleeping sickness provides exposures within a satisfactory safety margin for bone marrow suppression and does not cause hepatotoxicity.