Potential drivers for schistosomiasis persistence: Population genetic analyses from a cluster-randomized urogenital schistosomiasis elimination trial across the Zanzibar islands

The World Health Organization’s revised NTD Roadmap and the newly launched Guidelines arget elimination of schistosomiasis as a public health problem in all endemic areas by 2030. Key to meeting this goal is elucidating how selective pressures imposed by interven-ions shape parasite populations. Our aim was to identify any differential impact of a unique cluster-randomized tri-armed elimination intervention (biannual mass drug administration (MDA) applied alone or in association with either mollusciciding (snail control) or behavioural change interventions) across two Zanzibarian islands (Pemba and Unguja) on the popula-ion genetic composition of Schistosoma haematobium over space and time. Fifteen micro-satellite loci were used to analyse individual miracidia collected from infected individuals across islands and intervention arms at the start (2012 baseline: 1,522 miracidia from 176 children; 303 from 43 adults; age-range 6–75, mean 12.7 years) and at year 5 (2016: 1,486 miracidia from 146 children; 214 from 25 adults; age-range 9–46, mean 12.4 years). Mea-sures of genetic diversity included allelic richness (Ar), Expected (He) and Observed hetero-zygosity (Ho), inbreeding coefficient (FST), parentage analysis, estimated worm burden, worm fecundity, and genetic sub-structuring. There was little evidence of differential selec-ive pressures on population genetic diversity, inbreeding or estimated worm burdens by reatment arm, with only the MDA+snail control arm within Unguja showing trends towards reduced diversity and altered inbreeding over time. The greatest differences overall, both in erms of parasite fecundity and genetic sub-structuring, were observed between the islands, consistent with Pemba’s persistently higher mean infection intensities compared to neighbouring Unguja, and within islands in terms of infection hotspots (across three defini-tions). These findings highlight the important contribution of population genetic analyses to elucidate extensive genetic diversity and biological drivers, including potential gene-environ-mental factors, that may override short term selective pressures imposed by differential disease control strategies.