Extensive transmission and variation in a functional receptor for praziquantel resistance in endemic Schistosoma mansoni.

Mass-drug administration (MDA) of human populations using praziquantel monotherapy has become the primary strategy for controlling and potentially eliminating the major neglected tropical disease schistosomiasis. To understand how long-term MDA impacts schistosome populations, we analysed whole-genome sequence data of 570 Schistosoma mansoni samples (and the closely related outgroup species, S. rodhaini) from eight countries incorporating both publicly-available sequence data and new parasite material. This revealed broad-scale genetic structure across countries but with extensive transmission over hundreds of kilometres. We characterised variation across the transient receptor potential melastatin ion channel, TRPMPZQ, a target of praziquantel, which has recently been found to influence praziquantel susceptibility. Functional profiling of TRPMPZQ variants found in endemic populations identified four mutations that reduced channel sensitivity to praziquantel, indicating standing variation for resistance. Analysis of parasite infrapopulations sampled from individuals pre- and post-treatment identified instances of treatment failure, further indicative of potential praziquantel resistance. As schistosomiasis is targeted for elimination as a public health problem by 2030 in all currently endemic countries, and even interruption of transmission in selected African regions, we provide an in-depth genomic characterisation of endemic populations and an approach to identify emerging praziquantel resistance alleles.

Genomic data reveal a north-south split and introgression history of blood fluke (Schistosoma haematobium) populations from across Africa.

The human parasitic fluke, Schistosoma haematobium hybridizes with the livestock parasite S. bovis in the laboratory, but the extent of hybridization in nature is unclear. We analyzed 34.6 million single nucleotide variants in 162 samples from 18 African countries, revealing a sharp genetic discontinuity between northern and southern S. haematobium. We found no evidence for recent hybridization. Instead the data reveal admixture events that occurred 257-879 generations ago in northern S. haematobium populations. Fifteen introgressed S. bovis genes are approaching fixation in northern S. haematobium with four genes potentially driving adaptation. We identified 19 regions that were resistant to introgression; these were enriched on the sex chromosomes. These results (i) demonstrate strong barriers to gene flow between these species, (ii) indicate that hybridization may be less common than currently envisaged, but (iii) reveal profound genomic consequences of interspecific hybridization between schistosomes of medical and veterinary importance.

Estimating the cost of young stock mortality in livestock systems-An application to sheep farming in Ethiopia.

Introduction: In sub-Saharan Africa, pre-weaning young stock mortality (YSM) is in the order of 20 to 30% across most livestock species and production systems. High YSM has significant economic implications for livestock keepers, but few studies provide estimates of the "cost of YSM." This study explores a bio-economic herd modeling approach to estimate the "cost of YSM" at farming/livestock system level. Methods: The static zero-growth version of DYNMOD was used to calculate the annual physical and monetary output of a sheep flock consisting of 100 breeding females at different levels of lamb mortality. Production parameter values and prices were taken from recently published research. Calculations were carried out for values of lamb mortality decreasing from 30% to 0% in 5% intervals, with 20% representing the "baseline" YSM. Calculations were repeated for a "high" fertility scenario (100% vs. 59% parturition rate) to gauge the sensitivity of the cost of YSM to another parameter determining flock productivity. Results: The relation of revenue per head and YSM is close to linear over the range of analyzed YSM with 1% decrease in YSM resulting in an increase in revenue per animal of approximately 1%. At the higher fertility rate, the absolute cost of YSM to sheep farmers is higher while the relative increase in revenue per animal resulting from YSM reduction is lower. The estimated difference in revenue of the 100-ewe flock between the 20% and 0% lamb mortality scenarios (at baseline fertility) amounts to approximately USD 90 per additionally surviving lamb, which is far above its market value. Discussion: Reduced lamb mortality ultimately impacts flock revenue through increased sales of "mature" animals, which embody the value of a lamb plus the revenue/profit from raising it to marketable age/weight. The modeling results suggest that foregone profit is an important component of the systemic "cost of YSM." Consequently, expected profit per animal, in addition to its current market value, is essential for estimating the absolute cost of YSM at farming system level.

Systematic map of recent evidence on reproductive performance of cattle in Africa.

Good cattle reproductive performance is essential for livestock productivity. Farmers are highly dependent on the success of productive outputs to support their livelihoods. In low- and middle-income countries (LMICs), however, optimal reproduction of cows and bulls is comparatively less well defined, with information on key reproductive parameters and reproductive management often not available. The aim of this study was to collate and synthesise the recent published evidence on cattle reproductive performance in selected sub-Saharan countries.Systematic mapping methodology was used, with searches conducted for both cow and bull reproductive performance in Eritrea, Ethiopia, Kenya, Nigeria, Somalia, South Sudan, Sudan, Tanzania and Uganda, for the period 2012-2022, in English language. Search returns were screened for relevance at title and abstract, and full-text levels, based on the research question criteria.A substantial number of studies were identified for cows (n = 133), but only very few for bulls (n = 11). A large proportion of reported studies have been conducted in Ethiopia, with relatively few from the other countries, and most studies published between 2014 and 2016, and in 2021. Certain reproductive parameters received more attention than others; calving interval was reported in 86 studies, while culling due to infertility was reported in eight studies.The study highlights where research is being conducted in this area, and importantly where there is a gap, in particular on bull reproductive performance. While there were a range of values reported for cow reproductive parameters, the values were reasonable, indicating that it is possible to have good reproductive performance in LMICs. The synthesis of studies in the map should help to inform farmers and their advisors, at farm and national levels.

Re-assessing thermal response of schistosomiasis transmission risk: evidence for a higher thermal optimum than previously predicted.

The geographical range of schistosomiasis is affected by the ecology of schistosome parasites and their obligate host snails, including their response to temperature. Previous models predicted schistosomiasis' thermal optimum at 21.7 °C, which is not compatible with the temperature in sub-Saharan Africa (SSA) regions where schistosomiasis is hyperendemic. We performed an extensive literature search for empirical data on the effect of temperature on physiological and epidemiological parameters regulating the free-living stages of S. mansoni and S. haematobium and their obligate host snails, i.e., Biomphalaria spp. and Bulinus spp., respectively. We derived nonlinear thermal responses fitted on these data to parameterize a mechanistic, process-based model of schistosomiasis. We then re-cast the basic reproduction number and the prevalence of schistosome infection as functions of temperature. We found that the thermal optima for transmission of S. mansoni and S. haematobium range between 23.1-27.3 °C and 23.6-27.9 °C (95 % CI) respectively. We also found that the thermal optimum shifts toward higher temperatures as the human water contact rate increases with temperature. Our findings align with an extensive dataset of schistosomiasis prevalence in SSA. The refined nonlinear thermal-response model developed here suggests a more suitable current climate and a greater risk of increased transmission with future warming for more than half of the schistosomiasis suitable regions with mean annual temperature below the thermal optimum.

Re-assessing thermal response of schistosomiasis transmission risk: Evidence for a higher thermal optimum than previously predicted.

The geographical range of schistosomiasis is affected by the ecology of schistosome parasites and their obligate host snails, including their response to temperature. Previous models predicted schistosomiasis' thermal optimum at 21.7°C, which is not compatible with the temperature in sub-Saharan Africa (SSA) regions where schistosomiasis is hyperendemic. We performed an extensive literature search for empirical data on the effect of temperature on physiological and epidemiological parameters regulating the free-living stages of S. mansoni and S. haematobium and their obligate host snails, i.e., Biomphalaria spp. and Bulinus spp., respectively. We derived nonlinear thermal responses fitted on these data to parameterize a mechanistic, process-based model of schistosomiasis. We then re-cast the basic reproduction number and the prevalence of schistosome infection as functions of temperature. We found that the thermal optima for transmission of S. mansoni and S. haematobium range between 23.1-27.3°C and 23.6-27.9°C (95% CI) respectively. We also found that the thermal optimum shifts toward higher temperatures as the human water contact rate increases with temperature. Our findings align with an extensive dataset of schistosomiasis prevalence in SSA. The refined nonlinear thermal-response model developed here suggests a more suitable current climate and a greater risk of increased transmission with future warming for more than half of the schistosomiasis suitable regions with mean annual temperature below the thermal optimum.

Integrating HIV Pre-Exposure Prophylaxis (PrEP) Education During Medical Residency: Training Outcomes and Suggestions for Learning Effectiveness.

Human immunodeficiency virus (HIV) infection is now preventable with pre-exposure prophylaxis (PrEP) drugs, however, barriers to PrEP implementation include primary-care physician (PCP) knowledge-gap and lack of comfort prescribing and managing PrEP. We hypothesized that integrating HIV-PrEP education during medical-residency would help address these problems and developed a 40-minute case-based lecture focused on the 2021 United States Preventative Services Taskforce (USPSTF) oral HIV-PrEP guidelines and integrated this into our residency's core curriculum. We analyzed data from physician-trainees who voluntarily completed a pre- and post-lecture survey measuring HIV-PrEP "knowledge" and "self-assessed readiness to independently initiate and manage PrEP." Independent group analysis was completed via the Mann-Whitney U and Pearson Chi-square 2-sided test with P-value <0.05 deemed significant. Of the total of 189 residents invited to the lecture, 130 (69%) completed the pre-survey while 107 (57%) completed the post-survey. Per knowledge-assessment: the median number of correctly answered questions rose from a pre-lecture baseline of 4/9 (44%) to 8/9 (89%) following the education intervention (P < .001). When asked about comfort initiating and managing HIV-PrEP on their own, 7/130 (5.4%) responded in agreement pre-lecture, but this rose to 55/107 (51.4%) post-lecture (P < .001). Our study revealed PrEP training during residency was effective per stated objectives and may be an important tool to increase PrEP delivery/uptake to achieve the target goals for the National HIV/AIDS Strategy.

Interventions to reduce camel and small ruminant young stock morbidity and mortality in Ethiopia.

Morbidity and mortality of young stock is a challenge for livestock producers globally. In Ethiopia, where camels and small ruminants (sheep and goats) are essential smallholder and pastoral livestock, young stock losses can cause severe consequences to livelihoods. This pilot study, part of a Government-led Young Stock Mortality Reduction Consortium project, was undertaken to identify and evaluate interventions to reduce young stock mortality in mixed crop-livestock and pastoral production systems in Ethiopia. Pastoralists and mixed crop-livestock farmers were enrolled by convenience sampling across four regions. Households were sampled with questionnaire surveys to establish baseline mortality risk and prevalence of diarrhoea and respiratory disease in animals younger than one year, and followed longitudinally over a one-year period, with final evaluations conducted from March to July 2020. Mortality risk and prevalence of diarrhoea and respiratory disease before and after implementation were compared using Poisson regression models including household as random effect. Prior to intervention, median camel mortality, prevalence of diarrhoea, and respiratory disease across production systems in the different households was 0.4, 0.44 and 0.2, respectively. This compared to median pastoralist small ruminant mortality risk and prevalence of diarrhoea and respiratory disease of 0.45, 0.32 and 0.18, respectively. Post-intervention, median camel mortality, prevalence of diarrhoea and respiratory disease dropped to 0.1, 0.08 and 0. Similarly, more than half of the small ruminant households reported no mortality, and no cases of diarrhoea or respiratory disease. In camels, rate ratios of mortality risk, prevalence of diarrhoea, and respiratory disease post-intervention compared to the baseline were 0.41, 0.41 and 0.37. In small ruminants, rate ratios were 0.33, 0.35 and 0.46. All reductions were statistically significant (p < 0.01). Generally, pastoralists experienced higher mortality and disease prevalence compared to mixed crop-livestock smallholders, and the effect of intervention was slightly higher in pastoralist households. The pilot study findings demonstrated highly significant reductions in mortality and risk of diarrhoea and respiratory disease post-interventions. However, not all households benefitted from the interventions, with a few households reporting increased mortality and morbidity. Many households had very few animals which made it challenging to measure impact and the study was conducted over a single year, without a control group, so between year effects could not be accounted for in the reductions observed. These findings should contribute to improved livestock productivity in Ethiopia.

The long road to schistosomiasis elimination in Zanzibar: A systematic review covering 100 years of research, interventions and control milestones.

Zanzibar is among the few places in sub-Saharan Africa where interruption of Schistosoma transmission seems an achievable goal. Our systematic review identifies and discusses milestones in schistosomiasis research, control and elimination efforts in Zanzibar over the past 100 years. The search in online databases, libraries, and the World Health Organization Archives revealed 153 records published between May 1928 and August 2022. The content of records was summarised to highlight the pivotal work leading towards urogenital schistosomiasis elimination and remaining research gaps. The greatest achievement following 100 years of schistosomiasis interventions and research is undoubtedly the improved health of Zanzibaris, exemplified by the reduction in Schistosoma haematobium prevalence from>50% historically down to<5% in 2020, and the absence of severe morbidities. Experiences from Zanzibar have contributed to global schistosomiasis guidelines, whilst also revealing challenges that impede progression towards elimination. Challenges include: transmission heterogeneity requiring micro-targeting of interventions, post-treatment recrudescence of infections in transmission hotspots, biological complexity of intermediate host snails, emergence of livestock Schistosoma species complicating surveillance whilst creating the risk for interspecies hybridisation, insufficient diagnostics performance for light intensity infections and female genital schistosomiasis, and a lack of acceptable sanitary alternatives to freshwater bodies. Our analysis of the past revealed that much can be achieved in the future with practical implementation of integrated interventions, alongside operational research. With continuing national and international commitments, interruption of S. haematobium transmission across both islands is within reach by 2030, signposting the future demise of urogenital schistosomiasis across other parts of sub-Saharan Africa.

Patterns of mortality in domesticated ruminants in Ethiopia.

Background: Premature death of livestock is a problem in all ruminant production systems. While the number of premature ruminant deaths in a country is a reasonable indicator for the nation's health, few data sources exist in a country like Ethiopia that can be used to generate valid estimates. The present study aimed to establish if three different data sets, each with imperfect information on ruminant mortality, including abortions, could be combined into improved estimates of nationwide mortality in Ethiopia. Methods: We combined information from a recent survey of ruminant mortality with information from the Living Standards Measurement Study and the Disease Outbreak and Vaccination Reporting dataset. Generalized linear mixed and hurdle models were used for data analysis, with results summarized using predicted outcomes. Results: Analyses indicated that most herds experienced zero mortality and reproductive losses, with rare occasions of larger losses. Diseases causing deaths varied greatly both geographically and over time. There was little agreement between the different datasets. While the models aid the understanding of patterns of mortality and reproductive losses, the degree of variation observed limited the predictive scope. Conclusions: The models revealed some insight into why mortality rates are variable over time and are therefore less useful in measuring production or health status, and it is suggested that alternative measures of productivity, such as number of offspring raised to 1 year old per dam, would be more stable over time and likely more indicative.

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.

Use of a cow-side oestrus detection test for fertility management in Kenyan smallholder dairy herds.

Background: The use of artificial insemination (AI) has great potential to improve smallholder dairy herds in Africa, however poor success and, in some situations, high costs in Kenya, have been discouraging.  Effective AI requires accurate oestrus detection and the measurement of progesterone (P4) can be used to indicate oestrus as well as non-pregnancy.  A cow-side progesterone lateral flow test, P4 Rapid, was evaluated as an aid to detect oestrus and non-pregnancy in Kenyan dairy cows, and assessed for association with AI efficiency.  Methods: A total of 527 cows were enrolled in the study, from two counties in central and southern Kenya.  Cattle in the test group (n = 308) were presented when suspected to be in oestrus and tested with the P4 Rapid (low P4 = oestrus, medium P4 = inconclusive, high P4 = not in oestrus/pregnant).  Cattle with low P4 were inseminated.  Cattle in the control group (n = 219) were inseminated when oestrus behaviour was detected i.e. standard practice. Results: Of the total P4 Rapid tests performed (n = 745), 1.5% were inconclusive, with the true accuracy of the test between 87-97%.  Conception rates were not significantly higher in the test group (83.9%) compared to the control group (77.9%). Abortion rates were not significantly different between the control (9.5%) and test groups (8.2%).  In the test group, 6.2% (19/308) cows showed a medium or high P4 level on day 0 and nine of these were subsequently found to have been already pregnant. Conclusions: The data indicated that the P4 Rapid test can be a useful tool to assist farmer decision-making in the confirmation of correct timing for AI, and importantly may avoid unnecessary inseminations in pregnant animals, thus reducing the risk of AI-induced abortion.

Genome-wide analysis of Schistosoma mansoni reveals limited population structure and possible praziquantel drug selection pressure within Ugandan hot-spot communities.

Populations within schistosomiasis control areas, especially those in Africa, are recommended to receive regular mass drug administration (MDA) with praziquantel (PZQ) as the main strategy for controlling the disease. The impact of PZQ treatment on schistosome genetics remains poorly understood, and is limited by a lack of high-resolution genetic data on the population structure of parasites within these control areas. We generated whole-genome sequence data from 174 individual miracidia collected from both children and adults from fishing communities on islands in Lake Victoria in Uganda that had received either annual or quarterly MDA with PZQ over four years, including samples collected immediately before and four weeks after treatment. Genome variation within and between samples was characterised and we investigated genomic signatures of natural selection acting on these populations that could be due to PZQ treatment. The parasite population on these islands was more diverse than found in nearby villages on the lake shore. We saw little or no genetic differentiation between villages, or between the groups of villages with different treatment intensity, but slightly higher genetic diversity within the pre-treatment compared to post-treatment parasite populations. We identified classes of genes significantly enriched within regions of the genome with evidence of recent positive selection among post-treatment and intensively treated parasite populations. The differential selection observed in post-treatment and pre-treatment parasite populations could be linked to any reduced susceptibility of parasites to praziquantel treatment.

Reducing Calf Mortality in Ethiopia.

Morbidity and mortality of young stock present economic and production challenges to livestock producers globally. In Ethiopia, calf morbidity and mortality rates, particularly due to diarrhea and respiratory disease, are high, limiting production, incomes, and the ability of farmers to improve their livelihoods. In this paper, we present findings from the combined experience of the Young Stock Mortality Reduction Consortium, which conducted epidemiological and intervention testing in calves across three production systems. This innovative alliance identified Cryptosporidium parvum and E. Coli K99 as the most common causes of diarrhea in pastoral and peri-urban calves; Strongyloides spp. as the most common fecal parasite in mixed crop-livestock and peri-urban calves; and bovine adenovirus, parainfluenza virus-3, and bovine respiratory syncytial virus as the most common respiratory pathogens in peri-urban calves. Furthermore, by improving producer knowledge with respect to fundamental livestock husbandry, feeding, housing, and neonatal care practices, calf mortality risk across production systems was reduced by 31.4 to 71.4% compared to baseline (between 10.5 and 32.1%), whereas risk of diarrhea was reduced by 52.6-75.3% (baseline between 11.4 and 30.4%) and risk of respiratory disease was reduced by 23.6-80.8% (baseline between 3.3 and 16.3%). These findings have informed scaling strategies and can potentially contribute to improved livestock productivity and human livelihoods in Ethiopia.

Genomic evidence of contemporary hybridization between Schistosoma species.

Hybridization between different species of parasites is increasingly being recognised as a major public and veterinary health concern at the interface of infectious diseases biology, evolution, epidemiology and ultimately control. Recent research has revealed that viable hybrids and introgressed lineages between Schistosoma spp. are prevalent across Africa and beyond, including those with zoonotic potential. However, it remains unclear whether these hybrid lineages represent recent hybridization events, suggesting hybridization is ongoing, and/or whether they represent introgressed lineages derived from ancient hybridization events. In human schistosomiasis, investigation is hampered by the inaccessibility of adult-stage worms due to their intravascular location, an issue which can be circumvented by post-mortem of livestock at abattoirs for Schistosoma spp. of known zoonotic potential. To characterise the composition of naturally-occurring schistosome hybrids, we performed whole-genome sequencing of 21 natural livestock infective schistosome isolates. To facilitate this, we also assembled a de novo chromosomal-scale draft assembly of Schistosoma curassoni. Genomic analyses identified isolates of S. bovis, S. curassoni and hybrids between the two species, all of which were early generation hybrids with multiple generations found within the same host. These results show that hybridization is an ongoing process within natural populations with the potential to further challenge elimination efforts against schistosomiasis.

A multi-stakeholder participatory pilot study of the data demands of the future Ethiopian dairy sector.

Background:  This paper describes a pilot study undertaken in 2018, to determine the key data needs of each of the different Ethiopian dairy sector stakeholder groups.  The study aimed to characterise the emerging trends of dairy product production, processing, retailing and consumption in Ethiopia, and to identify and characterise current and future data needs of different stakeholders. Methods:  The study undertook a mapping of the interactions between different stakeholders in the dairy sector, and an interactive evaluation of the institutional data repository and access options.  Focus group discussions and interviews were held in three regions of the country prior to a two-day workshop in the capital Addis Ababa.  Data needs were characterised by type, availability, format, level of detail, methods of dissemination, uptake and use, and the institutional arrangement, including the different roles of public and private sectors in decision making processes. Results:  The study highlighted the main data needs and identified several broader institutional issues constraining the further development of the Ethiopian dairy sector.  The stakeholder groups endorsed the reactivation of a national dairy board, independent of government but closely incorporating government, and with the buy-in and membership of private sector enterprises, including producers, processers, service providers and consumers, to provide clearer facilitative leadership on the dairy industry. Conclusions:  The study workshop provided a timely discussion between diverse stakeholders, including government, and several potential organisations were suggested to host and manage a national dairy database. Importantly, the reactivation of a national dairy board was strongly endorsed.  It was recommended that stakeholder links be established, sector-specific data needs be elevated to higher detail, and a national roll out of herd-specific data recording schemes was called for, to allow for effective evidence-based policies and decision making.

Specific Nucleic AcId Ligation for the detection of Schistosomes: SNAILS.

Schistosomiasis, also known as bilharzia or snail fever, is a debilitating neglected tropical disease (NTD), caused by parasitic trematode flatworms of the genus Schistosoma, that has an annual mortality rate of 280,000 people in sub-Saharan Africa alone. Schistosomiasis is transmitted via contact with water bodies that are home to the intermediate host snail which shed the infective cercariae into the water. Schistosome lifecycles are complex, and while not all schistosome species cause human disease, endemic regions also typically feature animal-infecting schistosomes that can have broader economic and/or food security implications. Therefore, the development of species-specific Schistosoma detection technologies may help to inform evidence-based local environmental, food security and health systems policy making. Crucially, schistosomiasis disproportionally affects low- and middle-income (LMIC) countries and for that reason, environmental screening of water bodies for schistosomes may aid with the targeting of water, sanitation, and hygiene (WASH) interventions and preventive chemotherapy to regions at highest risk of schistosomiasis transmission, and to monitor the effectiveness of such interventions at reducing the risk over time. To this end, we developed a DNA-based biosensor termed Specific Nucleic AcId Ligation for the detection of Schistosomes or 'SNAILS'. Here we show that 'SNAILS' enables species-specific detection from genomic DNA (gDNA) samples that were collected from the field in endemic areas.

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.

Cross-reactivity of glycan-reactive HIV-1 broadly neutralizing antibodies with parasite glycans.

The HIV-1 Envelope glycoprotein (Env) is the sole target for broadly neutralizing antibodies (bnAbs). Env is heavily glycosylated with host-derived N-glycans, and many bnAbs bind to, or are dependent upon, Env glycans for neutralization. Although glycan-binding bnAbs are frequently detected in HIV-infected individuals, attempts to elicit them have been unsuccessful because of the poor immunogenicity of Env N-glycans. Here, we report cross-reactivity of glycan-binding bnAbs with self- and non-self N-glycans and glycoprotein antigens from different life-stages of Schistosoma mansoni. Using the IAVI Protocol C HIV infection cohort, we examine the relationship between S. mansoni seropositivity and development of bnAbs targeting glycan-dependent epitopes. We show that the unmutated common ancestor of the N332/V3-specific bnAb lineage PCDN76, isolated from an HIV-infected donor with S. mansoni seropositivity, binds to S. mansoni cercariae while lacking reactivity to gp120. Overall, these results present a strategy for elicitation of glycan-reactive bnAbs which could be exploited in HIV-1 vaccine development.

Genomic analysis of a parasite invasion: Colonization of the Americas by the blood fluke Schistosoma mansoni.

Schistosoma mansoni, a snail-borne, 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 South American Biomphalaria spp. snails would result in population bottlenecks and strong signatures of selection. We scored 475,081 single nucleotide variants 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? (iii) What were the source populations for colonizing parasites? We found a 2.4- to 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 populations from central African regions between Benin and Angola, with contributions from Niger, are probably 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 pre-adapted to the Americas and able to establish with relative ease.