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

21 Apr 2022
Tom Pennance, M.I. Neves, Bonnie L. Webster, Charlotte M. Gower, Stefanie Knopp, Iddi Simba Khamis, Shaali M. Ame, Said M. Ali, Muriel Rabone, Aidan Emery, Fiona Allan, Mtumweni Ali Muhsin, Khamis Rashid Suleiman, Fatma Kabole, M. Walker, David Rollinson, Joanne P. Webster

The World Health Organization revised NTD Roadmap and its newly launched Guidelines target 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 interventions 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 population genetic composition of Schistosoma haematobium over space and time. Fifteen microsatellite loci were used to analyse individual miracidia collected from infected individuals across islands and intervention arms at the start (2012 baseline: 1,529 miracidia from 181 children; 303 from 43 adults; age-range 6-75, mean 12.7 years) and at year 5 (2016: 1,500 miracidia from 147 children; 214 from 25 adults; age-range 9-46, mean 12.4 years). Measures of genetic diversity included allelic richness (Ar), inbreeding coefficient (FST), parentage analysis, estimated worm burden, worm fecundity, and genetic sub-structuring. There was little evidence of differential selective pressures on population genetic diversity, outbreeding or estimated worm burdens by treatment arm, with only the MDA+snail control arm within Unguja showing a (non-significant) trend towards reduced diversity over time. The greatest differences overall, most notably in terms of parasite fecundity (mean number of eggs per adult female worm) 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 persistent infection hotspots (across three definitions). These findings highlight the important contribution of population genetic analyses to elucidate extensive genetic diversity and biological drivers, including potential gene-environmental factors, that may override short term selective pressures imposed by differential disease control strategies.