Genetic diversity and evolution within the genus Bulinus and species-level interactions with the transmission of Schistosoma haematobium group parasites

Schistosomiasis is a Neglected Tropical Disease (NTD) prevalent across much of Africa, and also regions in South America, Asia, the Middle East and parts of Southern Europe. Caused by infections with dioecious parasitic flatworms of the Schistosoma genus, schistosomiasis results in an undue degree of suffering for humans and animals, particularly in Sub-Sharan Africa. Transmission occurs in freshwater containing specific intermediate host snails that act as vectors for the parasites; hosts becoming infected when the larval stages, released (shed) from the snails, burrow through the skin of the mammalian hosts that come into contact with the freshwater. Therefore, in humans this is a preventable water borne disease disproportionately affecting those that do not have access to safe water sources and good sanitation infrastructures. Mass drug administration (MDA) for the control of human schistosomiasis, which can occur in both intestinal and urogenital forms, is the recommended strategy by the World Health Organization (WHO), however, various factors contribute to the maintenance of schistosomiasis transmission in endemic areas of Africa. Potentially the biggest cause for persistence is the reservoir of infection that remains in freshwater intermediate host snails. Establishing the geographical distribution of intermediate host species in endemic regions and determining their associations with different schistosome species is paramount during schistosomiasis control programmes. Following years of neglect, a resurgence of interest in snail focussed surveillance and control is currently underway, with the WHO even recognising it as a critical action point in their 2020 road map for schistosomiasis control and elimination goals by 2030. However, rigorously tested and refined tools necessary for incorporating snails into schistosomiasis control programmes and the fundamental knowledge about the diversity of the snails and schistosomes underpinning such developments, are not available. Focusing on two endemic regions for urogenital schistosomiasis: the Niger River Valley, and the elimination setting of the Zanzibar Archipelago, this study provides new insights into the genetic diversity of Bulinus spp. and importantly, the associations they have with multiple S. haematobium group species in these regions. Furthermore, the first largescale approach for snail surveillance protocols are tested, showing the advantages that this approach will provide in certifying future elimination and in monitoring disease endemicity. Additionally, novel mitogenome data produced for Bulinus spp. from across Sub-Saharan Africa and the Indian Ocean islands are analysed, which sheds light on the evolutionary radiation of this important genus and the cryptic species diversity that has traditionally confounded taxonomy. The findings can be applied to implement new policies on snail surveillance in schistosomiasis control, whilst also providing a valuable resource for future research investigating the Bulinus genus

St. Thomas Aquinas and John Locke on Natural Law

John Locke’s natural law theory has frequently been conceived as a continuation of the Thomistic tradition and as sound basis for human rights as universally binding. This paper concludes that this is not the case. Unlike Aquinas’ metaphysical realism, Locke’s empiricism and nominalism make it impossible for us to know our human nature, our exclusively human goods, and telos—thereby undermining the sound foundations of the exceptionless moral precepts of natural law. Whereas Aquinas defines the good as that which is perfective and fulfilling of human nature, Locke identifies the good with pleasure, which leads to subjectivism. While both Aquinas and Locke argue that God is the origin and foundation of the binding force of natural law, Locke’s voluntarism is incompatible with the ruling nature of law. Consequently, unlike Aquinas, Locke’s theory lacks the metaphysical foundations for universal human rights

Development of novel multiplex microsatellite polymerase chain reactions to enable high-throughput population genetic studies of Schistosoma haematobium

© 2015 Webster et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article

Parasite Population Genetic Contributions to the Schistosomiasis Consortium for Operational Research and Evaluation within Sub-Saharan Africa

Analyses of the population genetic structure of schistosomes under the “Schistosomiasis Consortium for Operational Research and Evaluation” (SCORE) contrasting treatment pressure scenarios in Tanzania, Niger, and Zanzibar were performed to provide supplementary critical information with which to evaluate the impact of these large-scale control activities and guide how activities could be adjusted. We predicted that population genetic analyses would reveal information on a range of important parameters including, but not exclusive to, recruitment and transmission of genotypes, occurrence of hybridization events, differences in reproductive mode, and degrees of inbreeding, and hence, the evolutionary potential, and responses of parasite populations under contrasting treatment pressures. Key findings revealed that naturally high levels of gene flow and mixing of the parasite populations between neighboring sites were likely to dilute any effects imposed by the SCORE treatment arms. Furthermore, significant inherent differences in parasite fecundity were observed, independent of current treatment arm, but potentially of major impact in terms of maintaining high levels of ongoing transmission in persistent “biological hotspot” sites. Within Niger, naturally occurring Schistosoma haematobium/Schistosoma bovis viable hybrids were found to be abundant, often occurring in significantly higher proportions than that of single-species S. haematobium infections. By examining parasite population genetic structures across hosts, treatment regimens, and the spatial landscape, our results to date illustrate key transmission processes over and above that which could be achieved through standard parasitological monitoring of prevalence and intensity alone, as well as adding to our understanding of Schistosoma spp. life history strategies in general

The detection of Schistosoma bovis in livestock on Pemba Island, Zanzibar: a preliminary study

Schistosoma bovis is a parasitic trematode of ungulates transmitted by freshwater snails in Sub-Saharan Africa causing bovine intestinal schistosomiasis that leads to chronic morbidity and significant agricultural economic losses. The recently reported occurrence of Bulinus globosus infected with S. bovis for the first time on Pemba Island (Zanzibar, United Republic of Tanzania) is a cause of concern for livestock/wildlife health and complicates the surveillance of Schistosoma haematobium. To confirm that local cattle are infected with S. bovis, fresh faecal samples were collected from six adult cows surrounding two schistosomiasis transmission sites in Kinyasini, Pemba Island. Schistosome eggs were concentrated, egg hatching stimulated and miracidia were individually captured and identified by analysis of the partial mitochondrial cytochrome c oxidase subunit 1 (cox1) and the partial nuclear internal transcribed spacer region (ITS1+5.8S+ITS2). Two S. bovis miracidia were collected from one faecal sample with two cox1 haplotypes, one matching cox1 data obtained from S. bovis cercariae, collected previously at the same site in Pemba, the other matching S. bovis cox1 data originating from coastal Tanzania. The findings conclude that S. bovis transmission has been established on Pemba Island and is likely to have been imported through livestock trade with East Africa. Increasing the sensitivity of non-invasive diagnostics for bovine schistosomiasis, together with wider sampling, will enable a better assessment on the epidemiology of S. bovis on Pemba Island

Development of a Molecular Snail Xenomonitoring Assay to Detect Schistosoma haematobium and Schistosoma bovis Infections in their Bulinus Snail Hosts.

Schistosomiasis, a neglected tropical disease of medical and veterinary importance, transmitted through specific freshwater snail intermediate hosts, is targeted for elimination in several endemic regions in sub-Saharan Africa. Multi-disciplinary methods are required for both human and environmental diagnostics to certify schistosomiasis elimination when eventually reached. Molecular xenomonitoring protocols, a DNA-based detection method for screening disease vectors, have been developed and trialed for parasites transmitted by hematophagous insects, such as filarial worms and trypanosomes, yet few have been extensively trialed or proven reliable for the intermediate host snails transmitting schistosomes. Here, previously published universal and Schistosoma-specific internal transcribed spacer (ITS) rDNA primers were adapted into a triplex PCR primer assay that allowed for simple, robust, and rapid detection of Schistosoma haematobium and Schistosoma bovis in Bulinus snails. We showed this two-step protocol could sensitively detect DNA of a single larval schistosome from experimentally infected snails and demonstrate its functionality for detecting S. haematobium infections in wild-caught snails from Zanzibar. Such surveillance tools are a necessity for succeeding in and certifying the 2030 control and elimination goals set by the World Health Organization

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