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Prenatal infection with the protozoan parasite Toxoplasma gondii can cause congenital toxoplasmosis (CT), an often fatal or lifelong-disabling condition. Several studies of human populations have reported temporal decreases in seroprevalence, suggesting declining CT incidence. However, the consistency of this trend among diverse populations remains unclear, as does its implication for prenatal screening programmes, the major intervention against CT. Using temporally resolved data on the seroprevalence of T. gondii in various countries, we discuss how the parasite's changing epidemiology may affect trends in CT incidence in varying and counterintuitive ways. We argue that parasite stage-specific serology could be helpful for understanding underlying causes of secular changes in seroprevalence. Furthermore, we highlight the importance of updating cost-effectiveness estimates of screening programmes, accounting for neuropsychiatric sequelae.

In children exposed to poor hygiene and sanitation, invasion of the gut by pathogenic microbes can result in a subclinical enteropathy termed “environmental enteric dysfunction” (EED) that contributes to undernutrition, growth faltering, and impaired organ development. EED may already be present by age 6–12 weeks; therefore, interventions that can be started early in life, and used alongside breastfeeding, are needed to prevent or ameliorate EED. A healthy gut microbiota is critical for intestinal development and repair, nutrient digestion and absorption, and resisting colonization or overgrowth by pathogens. However, its development can be impaired by several environmental factors. Dietary supplementation with pro-, pre-, or synbiotics may be a pragmatic and safe means of building the resilience of the developing gut microbiota against adverse environmental factors, thereby preventing EED.

Schistosomiasis is caused by dioecious helminths of the genus Schistosoma. Recent work indicated that unpaired female and male schistosomes can survive within their definitive host for at least 1 year, although the viability or fertility of these worms after subsequent pairing remained untested. We performed two experiments on laboratory mice, one with female Schistosoma japonicum exposure first and male schistosomes second and another vice versa. After surviving as single-sex unpaired forms for up to 1 year, 58.5% of male and 70% of female schistosomes were able to mate and produce viable eggs. This highlights an additional biological challenge in achieving elimination of schistosomiasis.

Schistosomiasis is a helminthiasis infecting approximately 250 million people worldwide. In 2001, the World Health Assembly (WHA) 54.19 resolution defined a new global strategy for control of schistosomiasis through preventive chemotherapy programmes. This resolution culminated in the 2006 WHO guidelines that recommended empirical treatment by mass drug administration with praziquantel, predominately to school-aged children in endemic settings at regular intervals. Since then, school-based and community-based preventive chemotherapy programmes have been scaled-up, reducing schistosomiasis-associated morbidity. Over the past 15 years, new scientific evidence-combined with a more ambitious goal of eliminating schistosomiasis and an increase in the global donated supply of praziquantel-has highlighted the need to update public health guidance worldwide. In February, 2022, WHO published new guidelines with six recommendations to update the global public health strategy against schistosomiasis, including expansion of preventive chemotherapy eligibility from the predominant group of school-aged children to all age groups (2 years and older), lowering the prevalence threshold for annual preventive chemotherapy, and increasing the frequency of treatment. This Review, written by the 2018-2022 Schistosomiasis Guidelines Development Group and its international partners, presents a summary of the new WHO guideline recommendations for schistosomiasis along with their historical context, supporting evidence, implications for public health implementation, and future research needs.

Schistosomiasis, a neglected tropical disease, is a widespread chronic helminthiasis reported in 78 countries, predominantly those within sub-Saharan Africa, as well as Latin America, Asia, and most recently, even Europe. Species of the causative blood fluke infect not only humans but also animals, and hybrids between previously assumed human-specific and animal-specific schistosomes are being increasingly reported. Existing control programs across Africa focus on humans and rely heavily on mass drug administration of praziquantel, the sole drug available against schistosomiasis. Praziquantel is safe and highly efficacious but could become ineffective if resistance emerges. To reach the revised World Health Organization goal of elimination of schistosomiasis as a public health problem, and interruption of transmission within selected regions, by 2030, new consideration of the role of animal reservoirs in human transmission in general, and whether to also treat livestock with praziquantel in particular, has been raised. However, whilst there are no dedicated control programs targeting animals outside of Asia, there are emerging reports of the use and misuse of praziquantel in livestock across Africa. Therefore, to effectively treat livestock in Africa and to help mitigate against the potential evolution of praziquantel resistance, structured control strategies are required. Here, using a transmission modelling approach, we evaluate the potential effectiveness of a theoretical test-and-treat (TnT) strategy to control bovine schistosomiasis using a currently available point-of-care diagnostic test (developed for human use) to detect circulating cathodic antigen (POC-CCA). We show that implementing TnT at herd-level from 2022 to 2030 could be highly effective in suppressing infection in cattle and even, in lower prevalence settings, reaching nominal ‘elimination’ targets. We highlight the importance of enhancing the specificity of POC-CCA for use in livestock to avoid unnecessary treatments and discuss the outstanding challenges associated with implementing TnT as part of a holistic One Health approach to tackling human and animal schistosomiasis.

As viral genomic imprints in host genomes, endogenous viral elements (EVEs) shed light on the deep evolutionary history of viruses, ancestral host ranges, and ancient viral-host interactions. In addition, they may provide crucial information for calibrating viral evolutionary timescales. In this study, we conducted a comprehensive in silico screening of a large data set of available mammalian genomes for EVEs deriving from members of the viral family Flaviviridae, an important group of viruses including well-known human pathogens, such as Zika, dengue, or hepatitis C viruses. We identified two novel pestivirus-like EVEs in the reference genome of the Indochinese shrew (Crocidura indochinensis). Homologs of these novel EVEs were subsequently detected in vivo by molecular detection and sequencing in 27 shrew species, including 26 species representing a wide distribution within the Crocidurinae subfamily and one in the Soricinae subfamily on different continents. Based on this wide distribution, we estimate that the integration event occurred before the last common ancestor of the subfamily, about 10.8 million years ago, attesting to an ancient origin of pestiviruses and Flaviviridae in general. Moreover, we provide the first description of Flaviviridae-derived EVEs in mammals even though the family encompasses numerous mammal-infecting members. This also suggests that shrews were past and perhaps also current natural reservoirs of pestiviruses. Taken together, our results expand the current known Pestivirus host range and provide novel insight into the ancient evolutionary history of pestiviruses and the Flaviviridae family in general. ispartof: MOLECULAR BIOLOGY AND EVOLUTION vol:39 issue:10 ispartof: location:United States status: published

Control and elimination of the parasitic disease schistosomiasis relies on mass administration of praziquantel. Whilst these programmes reduce infection prevalence and intensity, their impact on parasite transmission and evolution is poorly understood. Here we examine the genomic impact of repeated mass drug administration on Schistosoma mansoni populations with documented reduced praziquantel efficacy. We sequenced whole-genomes of 198 S. mansoni larvae from 34 Ugandan children from regions with contrasting praziquantel exposure. Parasites infecting children from Lake Victoria, a transmission hotspot, form a diverse panmictic population. A single round of treatment did not reduce this diversity with no apparent population contraction caused by long-term praziquantel use. We find evidence of positive selection acting on members of gene families previously implicated in praziquantel action, but detect no high frequency functionally impactful variants. As efforts to eliminate schistosomiasis intensify, our study provides a foundation for genomic surveillance of this major human parasite., Schistosomiasis control strategies rely on mass drug administration (MDA) using praziquantel. Here, Berger et al. perform whole-genome sequencing of larvae from infected children across Ugandan regions with differing MDA histories. They find extensive gene flow with limited positive selection suggesting minimal change post MDA.

Schistosomiasis is a major neglected tropical disease (NTD) affecting both humans and animals. The morbidity and mortality inflicted upon livestock in sub-Saharan Africa has been largely overlooked, in part due to a lack of validated sensitive and specific tests, which do not require specialist training or equipment to deliver and interpret. Inexpensive, non-invasive, and sensitive diagnostic tests for livestock-use would also facilitate both prevalence mapping and appropriate intervention programmes. The aim of this study was to assess the sensitivity and specificity of the currently available point-of-care circulating cathodic antigen test (POC-CCA), designed for Schistosoma mansoni detection in humans, for the detection of intestinal livestock schistosomiasis caused by Schistosoma bovis and Schistosoma curassoni. POC-CCA, together with the circulating anodic antigen (CAA) test, miracidial hatching technique (MHT) and organ and mesentery inspection (for animals from abattoirs only), were applied to samples collected from 195 animals (56 cattle and 139 small ruminants (goats and sheep) from abattoirs and living populations) from Senegal. POC-CCA sensitivity varied by ruminant group and by location/parasite species: sensitivity was greater in Barkedji (cattle: mean 81% (95% credible interval (CrI): 55%-98%); small ruminants: 49% (29%-87%), where livestock were primarily infected by S. curassoni, than in Richard Toll (cattle: 62% (41%-84%); small ruminants: 12% (1%-37%), where S. bovis was the main parasite species. Mean POC-CCA specificity across sites in small ruminants was 91% (77%-99%) with little variation between locations/parasites (Barkedji: 91% (73%-99%); Richard Toll: 88% (65% - 99%). Specificity could not be assessed in cattle owing to the low number of uninfected cattle surveyed. Overall, our results indicate that, whilst the current POC-CCA does represent a potential diagnostic tool for animal schistosomiasis, future work is needed to develop a livestock-specific affordable and field-applicable diagnostic tests to enable determination of the true extent of livestock schistosomiasis.Author summarySchistosomiasis is a debilitating neglected tropical and zoonotic disease, infecting over 230 million people and multiple millions of animals worldwide, most notably amongst the poorest regions and populations. The potential contribution of livestock schistosomiasis to disease transmission in human populations has implications for the design of effective disease management and elimination programmes. However, our understanding of the true prevalence, transmission and impact of animal schistosomiasis is severely limited, in part due to a lack of inexpensive, accessible, sensitive and specific diagnostic tools. As a point-of-care circulating cathodic antigen (POC-CCA) diagnostic test is now in widespread use to assess intestinal schistosomiasis caused by Schistosoma mansoni in humans, we hypothesised that the same test could be used to detect livestock intestinal schistosomiasis caused by Schistosoma bovis and Schistosoma curassoni. The aim of this study was thus to evaluate the sensitivity and specificity of the POC-CCA for the detection of intestinal livestock schistosomiasis in Senegal. POC-CCA sensitivity varied by ruminant group and by location/parasite species, while POC-CCA specificity in small ruminants, at least, did not vary across sites. We conclude that the currently-available POC-CCA does represent a potential diagnostic tool for animal schistosomiasis, but that the factors determining test performance warrant further investigation.

Schistosomiasis is a major neglected tropical disease mainly caused by Schistosoma haematobium, S. japonicum and S. mansoni, and results in the greatest disease burden. Mass drug administration (MDA) with praziquantel (PZQ), a single drug only available for the disease, has played a vital role in schistosomiasis control. Therefore, any possibility of selection of the parasites for PZQ resistance or low sensitivity may hamper the 2030's target of global disease elimination. We had experimentally demonstrated the long-term survival and reproductive potential of single-sex (of either sex) S. japonicum infections in definitive hosts mice. What has not yet been adequately addressed is whether the long live single-sex schistosomes remain sensitive to PZQ, and what reproduction potential for those schistosomes surviving treatment may have. We therefore performed experimental mice studies to explore the treatment effectiveness of PZQ (at total doses of 200 or 400 mg/kg, corresponding to the sub-standard or standard treatment doses in humans) for single-sex S. japonicum aged three months old. The results showed that no treatment efficiency was observed on female schistosomes, whereas on male schistosomes only at PZQ 400 mg/kg a significant higher efficiency in reducing worm burdens was observed. Moreover, either schistosome males or females surviving PZQ treatment remained their reproduction potential as normal. The results indicate that long (i.e., three months) live single-sex S. japonicum can easily survive the current treatment strategy, and moreover, any schistosomes, if with PZQ resistance or low sensitivity, could be easily transmitted in nature. Therefore, in order to realize the target for the national and the global schistosomiasis elimination, there is undoubtedly a great need for refining PZQ administration and dosage, looking for alternative therapies, and/or developing vaccines against schistosome.

Infection by the small liver fluke, Opisthorchis viverrini, causes serious public health problems, including cholangiocarcinoma, in Thailand and southeastern Asian countries. Previous studies have reported that O. viverrini represents a species complex with varying levels of genetic differentiation in Thailand and Lao PDR. In this study, we re-examined population genetic structure and genetic diversity of O. viverrini using extensive samples of the parasite collected over 15 years from 12 geographical localities in Thailand and eight localities in Lao PDR. Parasite life-cycle stages of 721 individuals of O. viverrini (91 cercariae, 230 metacercariae and 400 adult worms) were genotyped using 12 microsatellite loci. Metacercariae exhibited genetic diversity comparable with that of experimentally raised adults: metacercariae can therefore be used to represent O. viverrini populations without the need for laboratory definitive hosts. Data obtained from larval as well as adult worms identified two distinct genetic clusters of O. viverrini. Sequences of a portion of the mitochondrial cox1 gene strongly supported the existence of these two clusters. One, the widespread cluster, was found at all sampled sites. The second cluster occurred only in Phang Khon District, Sakon Nakhon Province (SPk), within the Songkram River wetland in Thailand. A striking feature of our data relates to the temporal dynamics of the SPk cluster, which was largely replaced by representatives of the widespread cluster over time. If the SPk cluster is excluded, no marked genetic differences were seen among O. viverrini populations from Thailand and Lao PDR. The underlying causes of the observed population structure and population dynamics of O. viverrini are not known.

Traditionally, the protozoan parasite Toxoplasma gondii has been thought of as relevant to public health primarily within the context of congenital toxoplasmosis or postnatally acquired disease in immunocompromised patients. However, latent T. gondii infection has been increasingly associated with a wide variety of neuropsychiatric disorders and, more recently, causal frameworks for these epidemiological associations have been proposed. We present assimilated evidence on the associations between T. gondii and various human neuropsychiatric disorders and outline how these may be explained within a unifying causal framework. We argue that the occult effects of latent T. gondii infection likely outweigh the recognised overt morbidity caused by toxoplasmosis, substantially raising the public health importance of this parasite.

The gut microbiome performs many important functions in mammalian hosts, with community composition shaping its functional role. However, the factors that drive individual microbiota variation in wild animals and to what extent these are predictable or idiosyncratic across populations remains poorly understood. Here, we use a multi-population dataset from a common rodent species (the wood mouse, Apodemus sylvaticus), to test whether a consistent “core” gut microbiota is identifiable in this species, and to what extent the predictors of microbiota variation are consistent across populations. Between 2014 and 2018 we used capture-mark-recapture and 16S rRNA profiling to intensively monitor two wild wood mouse populations and their gut microbiota, as well as characterising the microbiota from a laboratory-housed colony of the same species. Although the microbiota was broadly similar at high taxonomic levels, the two wild populations did not share a single bacterial amplicon sequence variant (ASV), despite being only 50km apart. Meanwhile, the laboratory-housed colony shared many ASVs with one of the wild populations from which it is thought to have been founded decades ago. Despite not sharing any ASVs, the two wild populations shared a phylogenetically more similar microbiota than either did with the colony, and the factors predicting compositional variation in each wild population were remarkably similar. We identified a strong and consistent pattern of seasonal microbiota restructuring that occurred at both sites, in all years, and within individual mice. While the microbiota was highly individualised, some seasonal convergence occurred in late winter/early spring. These findings reveal highly repeatable seasonal gut microbiota dynamics in multiple populations of this species, despite different taxa being involved. This provides a platform for future work to understand the drivers and functional implications of such predictable seasonal microbiome restructuring, including whether it might provide the host with adaptive seasonal phenotypic plasticity.

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.

Schistosoma mansoni, a snail-vectored, blood fluke that infects humans, was introduced into the Americas from Africa during the Trans-Atlantic slave trade. As this parasite shows strong specificity to the snail intermediate host, we expected that adaptation to S. American Biomphalaria spp. snails would result in population bottlenecks and strong signatures of selection. We scored 475,081 single nucleotide variants (SNVs) in 143 S. mansoni from the Americas (Brazil, Guadeloupe, and Puerto Rico) and Africa (Cameroon, Niger, Senegal, Tanzania, and Uganda), and used these data to ask: (i) Was there a population bottleneck during colonization? (ii) Can we identify signatures of selection associated with colonization? And (iii) what were the source populations for colonizing parasites? We found a 2.4-2.9-fold reduction in diversity and much slower decay in linkage disequilibrium (LD) in parasites from East to West Africa. However, we observed similar nuclear diversity and LD in West Africa and Brazil, suggesting no strong bottlenecks and limited barriers to colonization. We identified five genome regions showing selection in the Americas, compared with three in West Africa and none in East Africa, which we speculate may reflect adaptation during colonization. Finally, we infer that unsampled African populations from central African regions between Benin and Angola, with contributions from Niger, are likely the major source(s) for Brazilian S. mansoni. The absence of a bottleneck suggests that this is a rare case of a serendipitous invasion, where S. mansoni parasites were preadapted to the Americas and were able to establish with relative ease.

The Infectious Diseases Data Observatory (IDDO, https://www.iddo.org) has launched a clinical data platform for the collation, curation, standardisation and reuse of individual participant data (IPD) on treatments for two of the most globally important neglected tropical diseases (NTDs), schistosomiasis (SCH) and soil-transmitted helminthiases (STHs). This initiative aims to harness the power of data-sharing by facilitating collaborative joint analyses of pooled datasets to generate robust evidence on the efficacy and safety of anthelminthic treatment regimens. A crucial component of this endeavour has been the development of a Research Agenda to promote engagement with the SCH and STH research and disease control communities by highlighting key questions that could be tackled using data shared through the IDDO platform. Here, we give a contextual overview of the priority research themes articulated in the Research Agenda—a ‘living’ document hosted on the IDDO website—and describe the three-stage consultation process behind its development. We also discuss the sustainability and future directions of the platform, emphasising throughout the power and promise of ethical and equitable sharing and reuse of clinical data to support the elimination of NTDs.

Oxyurid nematodes (Syphacia spp.) from bank (Myodes glareolus) and field/common (Microtus spp.) voles, from disparate geographical sites in the British Isles, were examined morphologically and genetically. The genetic signatures of 118 new isolates are provided, based primarily on the rDNA internal transcribed spacers (ITS1-5.8S-ITS2) region and for representative isolates also on the small subunit 18S rDNA region and cytochrome c oxidase subunit 1 (cox-1) gene locus. Genetic data on worms recovered from Microtus spp. from the European mainland and from other rodent genera from the Palaearctic, North America and West Africa are also included. We test historical hypotheses indicating that S. nigeriana is a generalist species, infecting a range of different rodent genera. Our results establish that S. nigeriana is a parasite of both bank and field voles in the British Isles. An identical genotype was also recorded from Hubert's multimammate mouse (Mastomys huberti) from Senegal, but Mastomys spp. from West Africa were additionally parasitized by a related, although genetically distinct Syphacia species. We found no evidence for S. petrusewiczi in voles from the British Isles but isolates from Russia and North America were genetically distinct and formed their own separate deep branch in maximum likelihood molecular phylogenetic trees.

Background Reliable and field-applicable diagnosis of schistosome infections in non-human animals is important for surveillance, control, and verification of interruption of human schistosomiasis transmission. This study aimed to summarize uses of available diagnostic techniques through a systematic review and meta-analysis. Methodology and principal findings We systematically searched the literature and reports comparing two or more diagnostic tests in non-human animals for schistosome infection. Out of 4,909 articles and reports screened, 19 met our inclusion criteria, four of which were considered in the meta-analysis. A total of 14 techniques (parasitologic, immunologic, and molecular) and nine types of non-human animals were involved in the studies. Notably, four studies compared parasitologic tests (miracidium hatching test (MHT), Kato-Katz (KK), the Danish Bilharziasis Laboratory technique (DBL), and formalin-ethyl acetate sedimentation-digestion (FEA-SD)) with quantitative polymerase chain reaction (qPCR), and sensitivity estimates (using qPCR as the reference) were extracted and included in the meta-analyses, showing significant heterogeneity across studies and animal hosts. The pooled estimate of sensitivity was 0.21 (95% confidence interval (CI): 0.03–0.48) with FEA-SD showing highest sensitivity (0.89, 95% CI: 0.65–1.00). Conclusions/significance Our findings suggest that the parasitologic technique FEA-SD and the molecular technique qPCR are the most promising techniques for schistosome diagnosis in non-human animal hosts. Future studies are needed for validation and standardization of the techniques for real-world field applications.

The gut microbiome performs many important functions in mammalian hosts, with community composition shaping its functional role. However, what factors drive individual microbiota variation in wild animals and to what extent these are predictable or idiosyncratic across populations remains poorly understood.Here, we use a multi-population dataset from a common rodent species (the wood mouse,Apodemus sylvaticus), to test whether a consistent set of ‘core’ gut microbes is identifiable in this species, and to what extent the predictors of microbiota variation are consistent across populations.Between 2014 and 2018 we used capture-mark-recapture and 16S rRNA profiling to intensively monitor two wild UK mouse populations and their gut microbiota, as well as characterising the microbiota from a laboratory-housed colony of the same species.Although broadly similar at high taxonomic levels and despite being only 50km apart, the two wild populations did not share a single bacterial amplicon sequence variant (ASV). Meanwhile, the laboratory-housed colony shared many ASVs with one of the wild populations from which it is thought to have been founded decades ago. Despite strong taxonomic divergence in the microbiota, the factors predicting compositional variation in each wild population were remarkably similar. We identified a strong and consistent pattern of seasonal microbiota restructuring that occurred at both sites, in all years, and within individual mice. While the microbiota was highly individualised, seasonal convergence in the gut microbiota among individuals occurred in late winter/early spring.These findings reveal highly repeatable seasonal gut microbiota dynamics across distinct populations of this species, despite divergent taxa being involved. Providing a platform for future work to understand the drivers and functional implications of such predictable seasonal microbiome restructuring, including whether it might provide the host with adaptive seasonal phenotypic plasticity.

Oxyurid nematodes (Syphacia spp.) from bank (Myodes glareolus) and field/common (Microtus spp.) voles, from disparate geographical sites in the British Isles, were examined morphologically and genetically. The genetic signatures of 118 new isolates are provided, based primarily on the rDNA internal transcribed spacers (ITS1-5.8S-ITS2) region and for representative isolates also on the small subunit 18S rDNA region and cytochrome c oxidase subunit 1 (cox-1) gene locus. Genetic data on worms recovered from Microtus spp. from the European mainland and from other rodent genera from the Palaearctic, North America and West Africa are also included. We test historical hypotheses indicating that S. nigeriana is a generalist species, infecting a range of different rodent genera. Our results establish that S. nigeriana is a parasite of both bank and field voles in the British Isles. An identical genotype was also recorded from Hubert's multimammate mouse (Mastomys huberti) from Senegal, but Mastomys spp. from West Africa were additionally parasitized by a related, although genetically distinct Syphacia species. We found no evidence for S. petrusewiczi in voles from the British Isles but isolates from Russia and North America were genetically distinct and formed their own separate deep branch in maximum likelihood molecular phylogenetic trees.

Significance The threat to public health that is presented by zoonotic spillover of pathogens from animal reservoirs is predicted to increase with rapid anthropogenic changes and global trends such as migration and changing land use. Schistosomiasis currently infects more than 220 million people worldwide, and the multihost Schistosoma spp. system within Africa is a key example of where spillover of animal parasites into human populations has enabled the formation of viable hybrid parasite genotypes. Our study demonstrates how zoonotic spillover and complex interactions between pathogen species, such as parasite hybridization, may have implications such as resilience to current disease control strategies and may facilitate the spread of tropical diseases such as schistosomiasis beyond their original geographical boundaries., Zoonotic spillover and hybridization of parasites are major emerging public and veterinary health concerns at the interface of infectious disease biology, evolution, and control. Schistosomiasis is a neglected tropical disease of global importance caused by parasites of the Schistosoma genus, and the Schistosoma spp. system within Africa represents a key example of a system where spillover of animal parasites into human populations has enabled formation of hybrids. Combining model-based approaches and analyses of parasitological, molecular, and epidemiological data from northern Senegal, a region with a high prevalence of schistosome hybrids, we aimed to unravel the transmission dynamics of this complex multihost, multiparasite system. Using Bayesian methods and by estimating the basic reproduction number (R0), we evaluate the frequency of zoonotic spillover of Schistosoma bovis from livestock and the potential for onward transmission of hybrid S. bovis × S. haematobium offspring within human populations. We estimate R0 of hybrid schistosomes to be greater than the critical threshold of one (1.76; 95% CI 1.59 to 1.99), demonstrating the potential for hybridization to facilitate spread and establishment of schistosomiasis beyond its original geographical boundaries. We estimate R0 for S. bovis to be greater than one in cattle (1.43; 95% CI 1.24 to 1.85) but not in other ruminants, confirming cattle as the primary zoonotic reservoir. Through longitudinal simulations, we also show that where S. bovis and S. haematobium are coendemic (in livestock and humans respectively), the relative importance of zoonotic transmission is predicted to increase as the disease in humans nears elimination.

Hybridization of infectious agents is a major emerging public and veterinary health concern at the interface of evolution, epidemiology, and control. Whilst evidence of the extent of hybridization amongst parasites is increasing, their impact on morbidity remains largely unknown. This may be predicted to be particularly pertinent where parasites of animals with contrasting pathogenicity viably hybridize with human parasites. Recent research has revealed that viable zoonotic hybrids between human urogenital Schistosoma haematobium with intestinal Schistosoma species of livestock, notably Schistosoma bovis, can be highly prevalent across Africa and beyond. Examining human populations in Senegal, we found increased hepatic but decreased urogenital morbidity, and reduced improvement following treatment with praziquantel, in those infected with zoonotic hybrids compared to non-hybrids. Our results have implications for effective monitoring and evaluation of control programmes, and demonstrate for the first time the potential impact of parasite hybridizations on host morbidity.

Background: Schistosomiasis is a disease that poses major threats to human and animal health, as well as the economy, especially in sub-Saharan Africa (SSA). Furthermore, its zoonotic nature and the presence of hybrid species complicate efforts to achieve the new World Health Organization’s roadmap for neglected tropical diseases target of elimination. Whilst many studies have evaluated the economic impact of schistosomiasis in humans, only one has been performed to date in livestock in SSA and none in Senegal. The aim of this study was to estimate the financial impact of livestock schistosomiasis in selected regions of Senegal.Methods: Stochastic partial budget models were developed in RiskAmp add-in for Excel for a one-year period to estimate the disease costs on local traditional farmers in twelve villages from the Lac de Guiers and Barkedji regions, Senegal. Disease costs were the sum of disease losses and expenditures and included reduced income due to production losses (e.g. reduced milk yield), expenditures saved (e.g. concentrate feed saved due to disease), additional costs (e.g. testing and treatment, buying replacement animals), and additional income (e.g. selling of diseased animals). The models were parameterised using primary data from cross-sectional surveys and focus group discussions, as well as secondary data from scientific literature and available statistics. Two scenarios were defined based on the most common practices reported: scenario 1 modelled a situation in which the farmers tested and treated their livestock for schistosomiasis; whilst scenario 2 modelled a situation in which there was no tests nor treatment. The model was run with 10,000 iterations for a period of one year; results were expressed in XOF, i.e., the West African CFA franc (1 XOF is equivalent to 0.0014 GBP) with the median and 95% confidence range. Sensitivity analyses were conducted to assess the impact of uncertain variables on the output. Results: For scenario 1, the median disease costs per year and head of cattle, sheep, and goats, respectively, were estimated at XOF -13,408, XOF -27,227 and XOF -27,694. For scenario 2, the disease costs per year and head of cattle, sheep, and goats, respectively, were estimated at XOF -49,296 , XOF -70,072 and XOF -70,281. Sensitivity analyses indicated that the market prices for young and adult, healthy and sick animals had the biggest impact on the disease costs for all species.Conclusions: Our findings suggest that the financial impact of livestock schistosomiasis on traditional subsistence and transhumance farmers in North Senegal is substantial. Consequently, treating livestock schistosomiasis with an effective control strategy has the potential to generate substantial benefits to farmers and their families. Our results can also serve as a baseline for future cost-benefit and cost-effectiveness analyses for potential regional treatment campaigns for schistosomiasis in livestock.

The relevance of mustelids in SARS-CoV-2 transmission has become increasingly evident. Alongside experimental demonstration of airborne transmission among ferrets, the major animal model for human respiratory diseases, transmission of SARS-CoV-2 within and/or between commercial mink farms has occurred and continues to occur. The number of mink reared for the luxury fur trade is approximately 60.5 million, across 36 mustelid-farming countries. By July 2021, SARS-CoV-2 outbreaks have been reported in 12 of these countries, at 412 European and 20 North American mink farms. Reverse zoonotic transmission events (from humans to mink) have introduced the virus to farms with subsequent extensive mink-to-mink transmission as well as further zoonotic (mink-to-human) transmission events generating cases amongst both farm workers and the broader community. Overcrowded housing conditions inherent within intensive mink farms, often combined with poor sanitation and welfare, both guarantees spread of SARS-CoV-2 and facilitates opportunities for viral variants, thereby effectively representing biotic hubs for viral transmission and evolution of virulence. Adequate preventative, surveillance and control measures within the mink industry are imperative both for the control of the current global pandemic and to mitigate against future outbreaks.

Mass treatment with praziquantel (PZQ) monotherapy is the mainstay for schistosomiasis treatment. This drug shows imperfect cure rates in the field and parasites showing reduced PZQ response can be selected in the laboratory, but the extent of resistance in Schistosoma mansoni populations is unknown. We examined the genetic basis of variation in PZQ response in a S. mansoni population (SmLE-PZQ-R) selected with PZQ in the laboratory: 35% of these worms survive high dose (73 µg/mL) PZQ treatment. We used genome wide association to map loci underlying PZQ response. The major chr. 3 peak contains a transient receptor potential (Sm.TRPMPZQ) channel (Smp_246790), activated by nanomolar concentrations of PZQ. PZQ response shows recessive inheritance and marker-assisted selection of parasites at a single Sm.TRPMPZQ SNP enriched populations of PZQ-resistant (PZQ-ER) and sensitive (PZQ-ES) parasites showing >377 fold difference in PZQ response. The PZQ-ER parasites survived treatment in rodents better than PZQ-ES. Resistant parasites show 2.25-fold lower expression of Sm.TRPMPZQ than sensitive parasites. Specific chemical blockers of Sm.TRPMPZQ enhanced PZQ resistance, while Sm.TRPMPZQ activators increased sensitivity. A single SNP in Sm.TRPMPZQ differentiated PZQ-ER and PZQ-ES lines, but mutagenesis showed this was not involved in PZQ-response, suggesting linked regulatory changes. We surveyed Sm.TRPMPZQ sequence variation in 259 parasites from the New and Old World revealing one nonsense mutation that results in a truncated protein with no PZQ-binding site. Our results demonstrate that Sm.TRPMPZQ underlies variation in PZQ response in S. mansoni and provides an approach for monitoring emerging PZQ-resistance alleles in schistosome elimination programs.One Sentence SummaryA transient receptor potential channel determines variation in praziquantel-response in Schistosoma mansoni.