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 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: 1,522 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). Measures of genetic diversity included allelic richness (Ar), Expected (He) and Observed heterozygosity (Ho), 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, inbreeding or estimated worm burdens by treatment 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 terms 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 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. Trial Registration: ClinicalTrials.gov ISRCTN48837681.

A 5-Year intervention study on elimination of urogenital schistosomiasis in Zanzibar: Parasitological results of annual cross-sectional surveys.

BACKGROUND: The Zanzibar Elimination of Schistosomiasis Transmission (ZEST) project aimed to eliminate urogenital schistosomiasis as a public health problem from Pemba and to interrupt Schistosoma haematobium transmission from Unguja in 5 years. METHODOLOGY: A repeated cross-sectional cluster-randomized trial was implemented from 2011/12 till 2017. On each island, 45 shehias were randomly assigned to receive one of three interventions: biannual mass drug administration (MDA) with praziquantel alone, or in combination with snail control or behavior change measures. In cross-sectional surveys, a single urine sample was collected from ~9,000 students aged 9- to 12-years and from ~4,500 adults aged 20- to 55-years annually, and from ~9,000 1st year students at baseline and the final survey. Each sample was examined for S. haematobium eggs by a single urine filtration. Prevalence and infection intensity were determined. Odds of infection were compared between the intervention arms. PRINCIPAL FINDINGS: Prevalence was reduced from 6.1% (95% confidence interval (CI): 4.5%-7.6%) to 1.7% (95% CI: 1.2%-2.2%) in 9- to 12-year old students, from 3.9% (95% CI: 2.8%-5.0%) to 1.5% (95% CI: 1.0%-2.0%) in adults, and from 8.8% (95% CI: 6.5%-11.2%) to 2.6% (95% CI: 1.7%-3.5%) in 1st year students from 2011/12 to 2017. In 2017, heavy infection intensities occurred in 0.4% of 9- to 12-year old students, 0.1% of adults, and 0.8% of 1st year students. Considering 1st year students in 2017, 13/45 schools in Pemba and 4/45 schools in Unguja had heavy infection intensities >1%. There was no significant difference in prevalence between the intervention arms in any study group and year. CONCLUSIONS/SIGNIFICANCE: Urogenital schistosomiasis was eliminated as public health problem from most sites in Pemba and Unguja. Prevalence was significantly reduced, but transmission was not interrupted. Continued interventions that are adaptive and tailored to the micro-epidemiology of S. haematobium in Zanzibar are needed to sustain and advance the gains made by ZEST.

Urogenital schistosomiasis transmission on Unguja Island, Zanzibar: characterisation of persistent hot-spots.

BACKGROUND: Elimination of urogenital schistosomiasis transmission is a priority for the Zanzibar Ministry of Health. Preventative chemotherapy together with additional control interventions have successfully alleviated much of the disease burden. However, a persistently high Schistosoma haematobium prevalence is found in certain areas. Our aim was to characterise and evaluate these persistent "hot-spots" of transmission and reinfection in comparison with low-prevalence areas, to support the intervention planning for schistosomiasis elimination in Zanzibar. METHODS: Prevalences of S. haematobium were annually determined by a single urine filtration in schoolchildren from 45 administrative areas (shehias) in Unguja in 2012, 2013 and 2014. Coverage data for biannual treatment with praziquantel were available from ministerial databases and internal surveys. Among the 45 shehias, five hot-spot (≥ 15 % prevalence) and two low-prevalence (≤ 5 %) shehias were identified and surveyed in mid-2014. Human-water contact sites (HWCSs) and the presence of S. haematobium-infected and uninfected Bulinus globosus, as well as safe water sources (SWSs) and their reliability in terms of water availability were determined and mapped. RESULTS: We found no major difference in the treatment coverage between persistent hot-spot and low-prevalence shehias. On average, there were considerably more HWCSs containing B. globosus in hot-spot than in low-prevalence shehias (n = 8 vs n = 2) and also more HWCSs containing infected B. globosus (n = 2 vs n = 0). There was no striking difference in the average abundance of SWSs in hot-spot and low-prevalence shehias (n = 45 vs n = 38) and also no difference when considering SWSs with a constant water supply (average: 62 % vs 62 %). The average number of taps with a constant water supply, however, was lower in hot-spot shehias (n = 7 vs n = 14). Average distances from schools to the nearest HWCS were considerably shorter in hot-spot shehias (n = 229 m vs n = 722 m). CONCLUSION: The number of HWCSs, their infestation with B. globosus and their distance to schools seem to play a major role for a persistently high S. haematobium prevalence in children. In addition to treatment, increasing access to reliably working taps, targeted snail control at HWCSs near schools and enhanced behaviour change measures are needed to reduce prevalences in hot-spot areas and to finally reach elimination. TRIAL REGISTRATION: ISRCTN48837681 .