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.

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.

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.

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.

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.

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.

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.

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.

High prevalence of urinary schistosomiasis in a desert population: results from an exploratory study around the Ounianga lakes in Chad.

BACKGROUND: Researching a water-borne disease in the middle of the Sahara desert might not seem the most relevant concern. However, nomadic Sahelian pastoralists health concerns regarding their livestock and anecdotal reports about trematode infections of Fasciola spp. and Schistosoma spp. in desert-raised animals justified an exploratory study focusing on the lakes of Ounianga in Northern Chad. The aim was to test whether trematode parasites such as Schistosoma spp. occur in human populations living around the Sahara desert lakes of Ounianga Kebir and Ounianga Serir in northern Chad. METHODS: The study was carried out in January 2019 and comprised of three components. First, a cross sectional survey based on a random sample drawn from the population to detect infections with S. haematobium and S. mansoni; second, focus group discussions exploring disease priorities, access to health and health seeking behaviour; and third, surveying water contact sites for intermediate host snails. Samples of trematode parasites and snails were confirmed on species level by molecular genetic methods. For parasitological and malacological surveys descriptive statistics were performed. Qualitative data analysis included the full review of all transcripts, followed by a descriptive and explorative thematic analysis. RESULTS: Among 258 participants, the overall S. haematobium prevalence using urine filtration was 39.2% [95% confidence interval (CI): 33.5-45.1%], with 51.5% of the infected suffering from heavy infection. The intermediate host snail of S. haematobium (Bulinus truncatus) occurred at water contact sites near both study villages, revealing the potential for local transmission. Although a positive S. mansoni point-of-care circulating cathodic antigen (POC-CCA) test result was obtained from 8.6% (95% CI 5.7-12.8%) of the samples, no intermediate host snails of S. mansoni were found, and the relevance of S. mansoni remains uncertain. Qualitative findings underline the importance of morbidity caused by urinary schistosomiasis, and the lack of access to diagnostics and treatment as a major health concern. CONCLUSIONS: This research revealed a high prevalence of urinary schistosomiasis in the population living around the lakes of Ounianga in the Sahara, a United Nations Educational, Scientific and Cultural Organization (UNESCO) world heritage site in Chad. Despite the high public health importance of the associated morbidity expressed by the population, there is no access to diagnostics and treatment. Further work is needed to develop and test a context-adapted intervention.

Genetic analysis of praziquantel response in schistosome parasites implicates a transient receptor potential channel.

Mass drug administration with praziquantel (PZQ) monotherapy is considered the mainstay for control and elimination of the parasites causing schistosomiasis in humans. 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 the variation in response in a PZQ-selected S. mansoni population (SmLE-PZQ-R) in which 35% of the parasitic worms survive high-dose PZQ (73 micrograms per milliliter) treatment. We used genome-wide association to map loci underlying PZQ response and identified a transient receptor potential (Sm.TRPMPZQ) channel (Smp_246790) within the major chromosome 3 peak that is activated by nanomolar concentrations of PZQ. The PZQ response showed recessive inheritance and marker-assisted selection of parasites at a single Sm.TRPMPZQ SNP that produced populations of PZQ-enriched resistant (PZQ-ER) and PZQ-enriched sensitive (PZQ-ES) parasites, exhibiting >377-fold difference in PZQ response. The PZQ-ER parasites survived treatment in rodents at higher frequencies compared with PZQ-ES, and resistant parasites exhibited 2.25-fold lower expression of Sm.TRPMPZQ relative to sensitive parasites. Specific chemical blockers of Sm.TRPMPZQ enhanced PZQ resistance, whereas Sm.TRPMPZQ activators increased sensitivity. We surveyed Sm.TRPMPZQ sequence variations in 259 parasites from different global sites and identified one nonsense mutation that resulted in a truncated protein with no PZQ binding site. Our results demonstrate that Sm.TRPMPZQ underlies variation in PZQ responses in S. mansoni and provides an approach for monitoring emerging PZQ-resistant alleles in schistosome elimination programs.

Safety and Efficacy of the East Coast Fever Muguga Cocktail Vaccine: A Systematic Review.

Immunisation of livestock with high quality vaccines is considered an essential approach to controlling many animal diseases. The only currently available commercial vaccine to protect cattle from East Coast fever (ECF), a tick-borne disease caused by Theileria parva, is an unconventional "infection and treatment method" (ITM) involving administration of a combination of live T. parva isolates, referred to as the "Muguga cocktail", and simultaneous treatment with long-acting oxytetracycline. Veterinary vaccine research and development typically involves studies designed to demonstrate vaccine quality, safety, and efficacy; however, as there were no such purpose-designed registration studies conducted for the Muguga cocktail, evidence for safety and efficacy is solely based on that which is available in the clinical literature. An extensive systematic review was conducted to analyse the evidence available in the literature in order to establish the safety and efficacy of the Muguga cocktail vaccine. A combination of meta-analyses and narrative summaries was conducted. A total of 61 studies met the criteria to be included in the systematic review. The majority of studies demonstrated or reported in favour of the vaccine with regards to safety and efficacy of the Muguga cocktail vaccine. Proximity to buffalo often resulted in reduced vaccine efficacy, and reports of shed and transmission of vaccine components affected the overall interpretation of safety. Better understanding of control options for this devastating livestock disease is important for policymakers and livestock keepers, enabling them to make informed decisions with regards to the health of their animals and their livelihoods.

A cross-sectional survey to establish Theileria parva prevalence and vector control at the wildlife-livestock interface, Northern Tanzania.

East Coast fever (ECF) in cattle is caused by the protozoan parasite Theileria parva, transmitted by Rhipicephalus appendiculatus ticks. In cattle ECF is often fatal, causing annual losses >$500 million across its range. The African buffalo (Syncerus caffer) is the natural host for T. parva but the transmission dynamics between wild hosts and livestock are poorly understood. This study aimed to determine the prevalence of T. parva in cattle, in a 30 km zone adjacent to the Serengeti National Park, Tanzania where livestock and buffalo co-exist, and to ascertain how livestock keepers controlled ECF and other vector-borne diseases of cattle. A randomised cross-sectional cattle survey and questionnaire of vector control practices were conducted. Blood samples were collected from 770 cattle from 48 herds and analysed by PCR to establish T. parva prevalence. Half body tick counts were recorded on every animal. Farmers were interviewed (n = 120; including the blood sampled herds) using a standardised questionnaire to obtain data on vector control practices. Local workshops were held to discuss findings and validate results. Overall prevalence of T. parva in cattle was 5.07% (CI: 3.70-7.00%), with significantly higher prevalence in older animals. Although all farmers reported seeing ticks on their cattle, tick counts were very low with 78% cattle having none. Questionnaire analysis indicated significant acaricide use with 79% and 41% of farmers reporting spraying or dipping with cypermethrin-based insecticides, respectively. Some farmers reported very frequent spraying, as often as every four days. However, doses per animal were often insufficient. These data indicate high levels of acaricide use, which may be responsible for the low observed tick burdens and low ECF prevalence. This vector control is farmer-led and aimed at both tick- and tsetse-borne diseases of livestock. The levels of acaricide use raise concerns regarding sustainability; resistance development is a risk, particularly in ticks. Integrating vaccination as part of this community-based disease control may alleviate acaricide dependence, but increased understanding of the Theileria strains circulating in wildlife-livestock interface areas is required to establish the potential benefits of vaccination.

Whole-genome sequencing of Schistosoma mansoni reveals extensive diversity with limited selection despite mass drug administration.

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.