Flubendazole reduces emerging Dracunculus medinensis in dogs in Chad: Results from a two-year study.

Abstract

Since being targeted for eradication in the 1980s, global human cases of dracunculiasis (Guinea worm disease; GWD) have been reduced by over 99.9% through interventions aimed at interrupting the life cycle of the causative parasite, Dracunculus medinensis. However, the burden of GWD in dogs is higher than in humans and other monitored mammalian host species, threatening eradication of GWD. Expanding on a previous clinical trial of flubendazole (FLBZ) in dogs in Chad, we conducted a cluster-randomized controlled trial in which half of enrolled villages (N = 29) were assigned to receive FLBZ and the other half (N = 27) to receive no treatment. An annual difference-in-differences analysis revealed that treated villages had 59.3% fewer predicted emerging D. medinensis adult females (95% CI: 53.8% fewer to 69.2% fewer) per village per year during the second year of the study compared to control villages. Analyses examining effects of FLBZ monthly, at the individual dog level, and through histopathology of D. medinensis female reproductive morphology, all support the conclusion that FLBZ inhibits embryogenesis and larval development within the uterus of gravid female worms. Together these data are consistent with a hypothesis that although D. medinensis emerged from individually treated dogs, the L1s released from dogs treated with FLBZ exhibited reduced viability, thus reducing the risk of infection in the next mammalian host. This trial builds the body of knowledge about FLBZ's impacts on D. medinensis in the canine host and provides compelling evidence on the effectiveness of FLBZ in reducing the number of emerging D. medinensis in dogs, which can contribute to the eradication of this parasite. However, additional questions remain regarding the formulation, which need to be addressed in future studies before being deployed at scale.