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.

Genome-wide insights into adaptive hybridisation across the Schistosoma haematobium group in West and Central Africa.

Schistosomiasis remains a public health concern across sub-Saharan Africa; current control programmes rely on accurate mapping and high mass drug administration (MDA) coverage to attempt disease elimination. Inter-species hybridisation can occur between certain species, changing epidemiological dynamics within endemic regions, which has the potential to confound control interventions. The impact of hybridisation on disease dynamics is well illustrated in areas of Cameroon where urogenital schistosomiasis, primarily due to Schistosoma haematobium and hybrid infections, now predominate over intestinal schistosomiasis caused by Schistosoma guineensis. Genetic markers have shown the ability to identify hybrids, however the underlying genomic architecture of divergence and introgression between these species has yet to be established. In this study, restriction site associated DNA sequencing (RADseq) was used on archived adult worms initially identified as; Schistosoma bovis (n = 4), S. haematobium (n = 9), S. guineensis (n = 3) and S. guineensis x S. haematobium hybrids (n = 4) from Mali, Senegal, Niger, São Tomé and Cameroon. Genome-wide evidence supports the existence of S. guineensis and S. haematobium hybrid populations across Cameroon. The hybridisation of S. guineensis x S. haematobium has not been demonstrated on the island of São Tomé, where all samples showed no introgression with S. haematobium. Additionally, all S. haematobium isolates from Nigeria, Mali and Cameroon indicated signatures of genomic introgression from S. bovis. Adaptive loci across the S. haematobium group showed that voltage-gated calcium ion channels (Cav) could play a key role in the ability to increase the survivability of species, particularly in host systems. Where admixture has occurred between S. guineensis and S. haematobium, the excess introgressive influx of tegumental (outer helminth body) and antigenic genes from S. haematobium has increased the adaptive response in hybrids, leading to increased hybrid population fitness and viability.

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.

Abyssal fauna of the UK-1 polymetallic nodule exploration area, Clarion-Clipperton Zone, central Pacific Ocean: Mollusca.

We present the first DNA taxonomy publication on abyssal Mollusca from the Clarion-Clipperton Zone (CCZ), central Pacific ocean, using material collected as part of the Abyssal Baseline (ABYSSLINE) environmental survey cruise 'AB01' to the UK Seabed Resources Ltd (UKSRL) polymetallic-nodule exploration area 'UK-1' in the eastern CCZ. This is the third paper in a series to provide regional taxonomic data for a region that is undergoing intense deep-sea mineral exploration for high-grade polymetallic nodules. Taxonomic data are presented for 21 species from 42 records identified by a combination of morphological and genetic data, including molecular phylogenetic analyses. These included 3 heterodont bivalves, 5 protobranch bivalves, 4 pteriomorph bivalves, 1 caudofoveate, 1 monoplacophoran, 1 polyplacophoran, 4 scaphopods and 2 solenogastres. Gastropoda were recovered but will be the subject of a future study. Seven taxa matched published morphological descriptions for species with deep Pacific type localities, and our sequences provide the first genetic data for these taxa. One taxon morphologically matched a known cosmopolitan species but with a type locality in a different ocean basin and was assigned the open nomenclature 'cf' as a precautionary approach in taxon assignments to avoid over-estimating species ranges. One taxon is here described as a new species, Ledella knudseni sp. n. For the remaining 12 taxa, we have determined them to be potentially new species, for which we make the raw data, imagery and vouchers available for future taxonomic study. The Clarion-Clipperton Zone is a region undergoing intense exploration for potential deep-sea mineral extraction. We present these data to facilitate future taxonomic and environmental impact study by making both data and voucher materials available through curated and accessible biological collections.

Praziquantel coverage in schools and communities targeted for the elimination of urogenital schistosomiasis in Zanzibar: a cross-sectional survey.

BACKGROUND: Biannual mass drug administration (MDA) with praziquantel and additional interventions to eliminate urogenital schistosomiasis has been implemented on the Zanzibar islands, United Republic of Tanzania, since 2012. We aimed to assess the coverage of school-based treatment (SBT) and community-wide treatment (CWT), to validate the coverage reported by the Zanzibar Ministry of Health (MoH) and to identify reasons for non-compliance. METHODS: We conducted a post-MDA cross-sectional survey in 93 schools and 92 communities on Pemba and Unguja islands in early 2014, 3-5 months after the last MDA round. Pupils and adults were asked whether they had received and taken the praziquantel treatment provided in the last SBT or CWT, respectively, and the observed and reported coverage were compared. Reasons for non-compliance were recorded in a pretested questionnaire and assessed in qualitative interviews. Urine samples of participants were examined for Schistosoma haematobium eggs with a single urine filtration. RESULTS: Around 8000 pupils and 4000 adults were included in the analysis. Our survey revealed a SBT coverage of 85.2% in Pemba and of 86.9% in Unguja, which was in line with MoH reports from Pemba (84.3%) and higher than reports from Unguja (63.9%). However, 15 among the 48 schools surveyed in Unguja had not received SBT. Among the interviewed adults, 53.6% in Pemba and 64.9% in Unguja had received praziquantel during CWT, which was less than the 59.0% and 67.7%, respectively, indicated by MoH reports. Moreover, only 43.8% and 54.0% of adults in Pemba and Unguja, respectively, had taken all the tablets as recommended. The main reasons for not receiving or taking praziquantel were absence during CWT, no drug distributor coming, being busy, fear of adverse events, pregnancy, breastfeeding or feeling healthy. CONCLUSION: To increase coverage and compliance in Zanzibar, SBT should target all schools and mobilization, sensitization and implementation of the CWT need to be improved. To reach elimination of urogenital schistosomiasis transmission in Zanzibar and elsewhere, a very high treatment coverage and compliance at national and local level is key and additional control measures such as snail control and behaviour change interventions will need to be implemented area wide. TRIAL REGISTRATION: ISRCTN48837681.