Repurposing Niclosamide Ethanolamine for Alveolar Echinococcosis Reveals a Disconnect Between In Vitro Efficacy and In Vivo Outcome

Abstract Background Echinococcosis is a zoonotic disease caused by cestodes of the genus Echinococcus . Alveolar echinococcosis (AE), caused by E. multilocularis , primarily affects the liver and shows infiltrative, tumor-like growth of the metacestode stage. If untreated, AE is lethal. AE remains a neglected disease with current treatments based on albendazole or mebendazole that are parasitostatic, and not curative, underscoring the need for more effective therapies. Niclosamide is a chlorinated salicylanilide derivative with proven activities against intestinal helminths but is inactive against tissue-dwelling helminths due to poor absorption and limited bioavailability. In this study, we repurposed niclosamide ethanolamine (NEN), a formulation with improved systemic exposure, for the treatment of E. multilocularis infection in vitro and in vivo . Methodology/Principal Findings We assessed the in vitro efficacy of niclosamide and NEN against E. multilocularis metacestode vesicles (IC 50