Abstract
<jats:title>Abstract</jats:title> <jats:p> Large-scale treatment with praziquantel (PZQ) monotherapy is used to control schistosomiasis, leading to concerns about the emergence of PZQ-resistance. In Western Kenya, schistosome-infected patients frequently remain egg-positive following PZQ treatment, and several “hotspot” villages have been observed where transmission remains high, despite annual mass PZQ treatments. This project asks (i) whether PZQ-resistant parasites are found in Western Kenya and (ii) whether “hotspot” villages can be explained by a higher prevalence of PZQ-resistant parasites. We established a simple platform for directly assaying worm motility following <jats:italic>in vitro</jats:italic> PZQ-exposure in adult schistosomes isolated from a field setting. To do this, we established snail and hamster breeding colonies, and generated large populations of field-derived adult worms, by (i) harvesting <jats:italic>S. mansoni</jats:italic> eggs from multiple infected patients; (ii) infecting <jats:italic>Biomphalaria</jats:italic> spp snails with miracidia; (iii) infecting hamsters with released cercariae; (iv) perfusing adult worms from hamsters, and (iv) examining drug response following exposure to PZQ (1 µg/ml for 1 day) in individual <jats:italic>S. mansoni</jats:italic> worms using an automated movement assay. We measured PZQ-response in 1,800 adult male parasites, representing an estimated 185 parasite genotypes. We identified a single worm that remained motile after PZQ-exposure among the 185 parasite genotypes surveyed (frequency = 0.54%; 95% CI 0.01 - 2.97%, exact binomial) consistent with PZQ-resistant worms being extremely rare or absent. Our direct phenotypic screening results suggests that (i) PZQ-resistance is not currently an obstacle for <jats:italic>S. mansoni</jats:italic> control in Western Kenya, and (ii) that other factors explain the existence of persistent hotspots. </jats:p>