The Indispensability of Snail Control for Accelerating Schistosomiasis Elimination: Evidence from Zanzibar.

Schistosomiasis is a serious and neglected global tropical disease, affecting upwards of 230 million people, with more than 95% of infections concentrated in Africa. For many years, the main schistosomiasis control strategy in Africa focused on mass drug administration (MDA). The aim of this study was to compare the difference between MDA alone and alongside another intervention, namely snail control, by exploring effective measures for eliminating schistosomiasis. Retrospective data of human prevalence on Schistosoma haematobium and major control measures were collected from the China-Zanzibar-WHO Cooperation Project for Schistosomiasis Elimination (CZW) and the Zanzibar Elimination of Schistosomiasis Transmission (ZEST) project since 2012. The optimal order polynomial regression fitting model and joinpoint regression model (JRM) were used to analyze trends in schistosomiasis prevalence and the consistency of change points with strengthening of the control measures. In Unguja Island, the main control measure was MDA, and prevalence decreased to a nadir in 2019, and then rebounded. The R2 value of the optimal fitting model was 0.6641. There was a single JRM changepoint in 2019, the annual percent change (APC) was −19.3% (p < 0.05) from 2012 to 2019, and the APC was 59.7% (p > 0.05) from 2019 to 2021. In Pemba Island, the main control measures until 2016 was MDA, while integrated measures of MDA and snail control were implemented from 2017, the prevalence continuously decreased, and the R2 value was 0.8673. There was also a single JRM changepoint in 2017, the APC was −22.2% (p < 0.05) from 2012 to 2017, and was maintained at −8.6% (p > 0.05) from 2017 to 2021. Our data indicate that, while it is challenging to eliminate schistosomiasis by MDA alone, integrated measures, including both MDA and snail control, can prevent reinfection and help to eliminate the diseases in Africa.

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.

Transmission and diversity of Schistosoma haematobium and S. bovis and their freshwater intermediate snail hosts Bulinus globosus and B. nasutus in the Zanzibar Archipelago, United Republic of Tanzania.

BACKGROUND: The Zanzibar Archipelago (Pemba and Unguja islands) is targeted for the elimination of human urogenital schistosomiasis caused by infection with Schistosoma haematobium where the intermediate snail host is Bulinus globosus. Following multiple studies, it has remained unclear if B. nasutus (a snail species that occupies geographically distinct regions on the Archipelago) is involved in S. haematobium transmission on Zanzibar. Additionally, S. haematobium was thought to be the only Schistosoma species present on the Zanzibar Archipelago until the sympatric transmission of S. bovis, a parasite of ruminants, was recently identified. Here we re-assess the epidemiology of schistosomiasis on Pemba and Unguja together with the role and genetic diversity of the Bulinus spp. involved in transmission. METHODOLOGY/PRINCIPAL FINDINGS: Malacological and parasitological surveys were conducted between 2016 and 2019. In total, 11,116 Bulinus spp. snails were collected from 65 of 112 freshwater bodies surveyed. Bulinus species identification were determined using mitochondrial cox1 sequences for a representative subset of collected Bulinus (n = 504) and together with archived museum specimens (n = 6), 433 B. globosus and 77 B. nasutus were identified. Phylogenetic analysis of cox1 haplotypes revealed three distinct populations of B. globosus, two with an overlapping distribution on Pemba and one on Unguja. For B. nasutus, only a single clade with matching haplotypes was observed across the islands and included reference sequences from Kenya. Schistosoma haematobium cercariae (n = 158) were identified from 12 infected B. globosus and one B. nasutus collected between 2016 and 2019 in Pemba, and cercariae originating from 69 Bulinus spp. archived in museum collections. Schistosoma bovis cercariae (n = 21) were identified from seven additional B. globosus collected between 2016 and 2019 in Pemba. By analysing a partial mitochondrial cox1 region and the nuclear ITS (1-5.8S-2) rDNA region of Schistosoma cercariae, we identified 18 S. haematobium and three S. bovis haplotypes representing populations associated with mainland Africa and the Indian Ocean Islands (Zanzibar, Madagascar, Mauritius and Mafia). CONCLUSIONS/SIGNIFICANCE: The individual B. nasutus on Pemba infected with S. haematobium demonstrates that B. nasutus could also play a role in the local transmission of S. haematobium. We provide preliminary evidence that intraspecific variability of S. haematobium on Pemba may increase the transmission potential of S. haematobium locally due to the expanded intermediate host range, and that the presence of S. bovis complicates the environmental surveillance of schistosome infections.

Potential risk of colonization of Bulinus globosus in the mainland of China under climate change.

BACKGROUND: Bulinus globosus, the main intermediate snail host of Schistosoma haematobium. The increased contacts between Africa and China could even lead to large-scale dissemination of B. globosus in China. Temperature is the key factor affecting fresh-water snail transmission. This study predicted potential risk of colonization of B. globosus in the mainland of China under climate change. METHODS: We investigated minimum and maximum temperatures for B. globosus eggs, juveniles and adult snails kept under laboratory conditions to find the most suitable range by pinpointing the median effective temperatures (ET50). We also assessed the influence of temperature on spawning and estimated the accumulated temperature (AT). The average air temperatures between 1955 and 2019 in January and July, the coldest and hottest months in China, respectively, were collected from national meteorological monitoring stations and investigated in a geographic information system (GIS) using empirical Bayesian Kriging to evaluate the theoretical possibility for distribution of B. globosus in southern China based on temperature. RESULTS: The effective minimum temperature (ET50min) for eggs, juveniles, adult snails and spawning were 8.5, 7.0, 7.0, 14.9 °C, respectively, with the corresponding maximum values (ET50max) of 36.6, 40.5, 40.2 and 38.1 °C. The AT was calculated at 712.1 ± 64.9 °C·d. In 1955, the potential B. globosus distribution would have had a northern boundary stretching from the coastal areas of Guangdong Province and Guangxi Autonomous Region to southern Yunnan Province. Since then, this line has gradually moved northward. CONCLUSIONS: Annual regeneration of B. globosus can be supported by the current climate conditions in the mainland of China, and a gradual expansion trend from south to north is shown in the study from 2015 to 2019. Thus, there is a potential risk of colonization of B. globosus in the mainland of China under climate change.

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 .