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Identification of the relative importance of within- and between-host variability in infectiousness and the impact of these heterogeneities on the transmission dynamics of infectious agents can enable efficient targeting of control measures. Cattle, a major reservoir host for the zoonotic pathogen Escherichia coli O157, are known to exhibit a high degree of heterogeneity in bacterial shedding densities. By relating bacterial count to infectiousness and fitting dynamic epidemiological models to prevalence data from a cross-sectional survey of cattle farms in Scotland, we identify a robust pattern: ~80% of the transmission arises from the 20% most infectious individuals. We examine potential control options under a range of assumptions about within- and between-host variability in infection dynamics. Our results show that the within-herd basic reproduction ratio, [R.sub.0], could be reduced to bacterial count | core groups | super shedder | superspreading | targeted control

Reasons for performing study A significant effect of gender, experience and background, i.e. an evaluator's relationship with horses as equine anaesthetists, orthopaedic surgeons, practitioners or owners, on perceptions of recovery quality after anaesthesia would reduce the validity of recovery quality scoring systems. Objectives To determine the effects of evaluator background, experience and gender on their perceptions of recovery quality; and questionnaire response rate as a function of background. Study design Cross-sectional survey. Methods A total of 440 potential evaluators were invited to evaluate the video-recorded recoveries of 24 horses using a visual analogue scale ( VAS) in which 0 = worst, 100 = best possible recovery. A mean score was generated for each of the 1-24 recoveries within each background group. These were compared using Spearman's rank correlation. The effect of gender and experience on VAS scores were analysed using an ordinal logistic regression after scores were categorised into 'intermediate, 'worst' and 'best' recovery categories based on median, 25th and 75th percentile VAS scores, respectively. Results The overall response rate was 35%. The greatest was from the anaesthetists (78%) followed by surgeons (43%). The response rate among owners and practitioners was 26%. Correlation among VAS scores across all background groups was high ( Spearman rank >0.90; P<0.001). Among the combined veterinarians, there was no significant gender (P = 0.551) or experience (P = 0.103) effect. Among horse owners, the effect of experience was not significant (P = 0.116) although gender was (P = 0.027). Male horse owners awarded significantly greater scores than females. Conclusions When VAS are used to grade recovery quality, neither the background nor the gender of veterinary evaluators affects quality perception. Male owners awarded greater scores than female owners, implying that they are less critical of recovery quality and a gender effect among horse owners must be considered when VAS are used to score recovery quality. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate epidemiological risk factors for porcine non-specific colitis (NSC). Forty-seven Scottish pig farms, with and without a clinical history of diarrhoea during the growing period (15-40 kg), were selected. The study included farm visits, clinical inspection of pigs, completion of farm management questionnaires, pathological tests into the cause of the diarrhoea and analysis of the non-starch polysaccharide (NSP) content of feeds. The results from 17 farms designated as NSC and 10 control farms suggest dietary associations with NSC. Farms with NSC fed diets with significantly higher levels of NSPs, especially containing the sugars glucose, arabinose and xylose. Few management factors were identified, although the high prevalence of infectious colitis reduced the power of the study. [ABSTRACT FROM AUTHOR]

Abstract Background Escherichia coli O157 is an important cause of acute diarrhoea, haemorrhagic colitis and, especially in children, haemolytic uraemic syndrome (HUS). Incidence rates for human E. coli O157 infection in Scotland are higher than most other United Kingdom, European and North American countries. Cattle are considered the main reservoir for E. coli O157. Significant associations between livestock related exposures and human infection have been identified in a number of studies. Results Animal Studies: There were no statistically significant differences (P = 0.831) in the mean farm-level prevalence between the two studies (SEERAD: 0.218 (95%CI: 0.141-0.32); IPRAVE: 0.205 (95%CI: 0.135-0.296)). However, the mean pat-level prevalence decreased from 0.089 (95%CI: 0.075-0.105) to 0.040 (95%CI: 0.028-0.053) between the SEERAD and IPRAVE studies respectively (P < 0.001). Highly significant (P < 0.001) reductions in mean pat-level prevalence were also observed in the spring, in the North East and Central Scotland, and in the shedding of phage type (PT) 21/28. Human Cases: Contrasting the same time periods, there was a decline in the overall comparative annual reported incidence of human cases as well as in all the major PT groups except 'Other' PTs. For both cattle and humans, the predominant phage type between 1998 and 2004 was PT21/28 comprising over 50% of the positive cattle isolates and reported human cases respectively. The proportion of PT32, however, was represented by few (P = 0.002). Conclusion There was no significant decrease in the mean farm-level prevalence of E. coli O157 between 1998 and 2004 in Scotland, despite significant declines in mean pat-level prevalence. Although there were declines in the number of human cases between the two study periods, there is no statistically significant evidence that the overall rate (per 100,000 population) of human E. coli O157 infections in Scotland over the last 10 years has altered. Comparable patterns in the distribution of PTs 21/28 and 32 between cattle and humans support a hypothesized link between the bovine reservoir and human infections. This emphasizes the need to apply and improve methods to reduce bovine shedding of E. coli O157 in Scotland where rates appear higher in both cattle and human populations, than in other countries.

Abstract Background E. coli O157 is a bacterial pathogen that is shed by cattle and can cause severe disease in humans. Phage type (PT) 21/28 is a subtype of E. coli O157 that is found across Scotland and is associated with particularly severe human morbidity. Methods A cross-sectional survey of Scottish cattle farms was conducted in the period Feb 2002-Feb 2004 to determine the prevalence of E. coli O157 in cattle herds. Data from 88 farms on which E. coli O157 was present were analysed using generalised linear mixed models to identify risk factors for the presence of PT 21/28 specifically. Results The analysis identified private water supply, and northerly farm location as risk factors for PT 21/28 presence. There was a significant association between the presence of PT 21/28 and an increased number of E. coli O157 positive pat samples from a farm, and PT 21/28 was significantly associated with larger E. coli O157 counts than non-PT 21/28 E. coli O157. Conclusion PT 21/28 has significant risk factors that distinguish it from other phage types of E. coli O157. This finding has implications for the control of E. coli O157 as a whole and suggests that control could be tailored to target the locally dominant PT.

Abstract Background Epidemiological analyses indicate that the age distribution of natural cases of transmissible spongiform encephalopathies (TSEs) reflect age-related risk of infection, however, the underlying mechanisms remain poorly understood. Using a comparative approach, we tested the hypothesis that, there is a significant correlation between risk of infection for scrapie, bovine spongiform encephalopathy (BSE) and variant CJD (vCJD), and the development of lymphoid tissue in the gut. Methods Using anatomical data and estimates of risk of infection in mathematical models (which included results from previously published studies) for sheep, cattle and humans, we calculated the Spearman's rank correlation coefficient, rs, between available measures of Peyer's patch (PP) development and the estimated risk of infection for an individual of the corresponding age. Results There was a significant correlation between the measures of PP development and the estimated risk of TSE infection; the two age-related distributions peaked in the same age groups. This result was obtained for each of the three host species: for sheep, surface area of ileal PP tissue vs risk of infection, rs = 0.913 (n = 19, P < 0.001), and lymphoid follicle density vs risk of infection, rs = 0.933 (n = 19, P < 0.001); for cattle, weight of PP tissue vs risk of infection, rs = 0.693 (n = 94, P < 0.001); and for humans, number of PPs vs risk of infection, rs = 0.384 (n = 46, P = 0.008). In addition, when changes in exposure associated with BSE-contaminated meat were accounted for, the two age-related patterns for humans remained concordant: rs = 0.360 (n = 46, P = 0.014). Conclusion Our findings suggest that, for sheep, cattle and humans alike there is an association between PP development (or a correlate of PP development) and susceptibility to natural TSE infection. This association may explain changes in susceptibility with host age, and differences in the age-susceptibility relationship between host species.

This study compared three subjective scoring systems used to assess lameness associated with equine laminitis: (1) visual analogue scale, (2) Obel score and (3) clinical grading system (CGS). Two groups of 12 observers, consisting of equine veterinarians and final-year veterinary students, scored lameness severity after watching video footage of 14 horses on two occasions. Generalizability theory was used to investigate the reliability of the three systems and the effects of observer experience. Overall reliability across all times and observers was high. Intra-observer reliability was higher than inter-observer reliability for all scoring systems, with student reliability being consistently lower than veterinarians, especially for Obel and CGS. All three methods were reasonably reliable tools for assessing lameness, but they were more limited in the hands of inexperienced observers. [ABSTRACT FROM AUTHOR]

Neutropenia is a common chemotherapy-associated adverse event (AE) in dogs and a significant cause of decreased relative dose intensity. Dose reductions (DRs) and treatment delays (TDs) are frequently applied to decrease the risk of further neutropenic events (NEs) and AEs, but there is no standardised approach. The two main objectives of this retrospective study were to determine: (1) the failure rate of a 10% DR to prevent a subsequent inadequate absolute neutrophil count (ANC), defined as a nadir ANC <0.75 × 10 9 /L or pretreatment ANC <1.5 × 10 9 /L; and (2) if the duration of TDs due to pretreatment neutropenia affects the occurrence of subsequent NEs. A total of 1056 chemotherapy treatments were recorded for 128 dogs that developed at least one NE. In 75 of 124 (60.5%, 95% CI: 51.2%-69%) evaluable NEs, a nadir ANC of ≥0.75 × 10 9 /L and pretreatment ANC of ≥1.5 × 10 9 /L were achieved after a single 10% chemotherapy DR, while a 10% DR failed to prevent a subsequent inadequate ANC in the remaining 49/124 (39.5%, 95% CI: 30.1%-48.3%). The only variable associated with failure was the drug prescribed. DR failure occurred in 22/39 (56.4%, 95% CI: 40.9%-70.6%) lomustine DRs, 14/27 (51.9%, 95% CI: 33.9%-69.2%) cyclophosphamide DRs, but only 2/22 (9.1%, 95% CI: 2.5%-27.8%) doxorubicin DRs and 2/24 (8.3%, 95% CI: 2.3%-25.8%) vincristine DRs. Seventy-three evaluable TDs (mean: 5 days, SD ± 2.2 days) were prescribed. There was no association between TD duration and subsequent NEs (p = 0.11)., (© 2024 The Author(s). Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

Transmissibility, the ability to spread within host populations, is a prerequisite for a pathogen to have epidemic or pandemic potential. Here, we estimate the phylogenies of human infectivity and transmissibility using 1,408 genome sequences from 743 distinct RNA virus species/types in 59 genera. By repeating this analysis using data sets censored by virus discovery date, we explore how temporal changes in the known diversity of RNA viruses-especially recent increases in recognized nonhuman viruses-have altered these phylogenies. Over time, we find significant increases in the proportion of RNA virus genera estimated to have a nonhuman-infective ancestral state, in the fraction of distinct human virus lineages that are purely human-transmissible or strictly zoonotic (compared to mixed lineages), and in the number of human viruses with nearest relatives known not to infect humans. Our results are consistent with viruses that are capable of spreading in human populations commonly emerging from a nonhuman reservoir. This is more likely in lineages that already contain human-transmissible viruses but is rare in lineages that contain only strictly zoonotic viruses., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Background: Sars-CoV-2, the causative agent of COVID-19, has led to more than 226,000 deaths in the UK and multiple risk factors for mortality including age, sex and deprivation have been identified. This study aimed to identify which individual indicators of the Scottish Index of Multiple Deprivation (SIMD), an area-based deprivation index, were predictive of mortality., Methods: This was a prospective cohort study of anonymised electronic health records of 710 consecutive patients hospitalised with Covid-19 disease between March and June 2020 in the Lothian Region of Southeast Scotland. Data sources included automatically extracted data from national electronic platforms and manually extracted data from individual admission records. Exposure variables of interest were SIMD quintiles and 12 indicators of deprivation deemed clinically relevant selected from the SIMD. Our primary outcome was mortality. Age and sex adjusted univariable and multivariable analyses were used to determine measures of association between exposures of interest and the primary outcome., Results: After adjusting for age and sex, we found an increased risk of mortality in the more deprived SIMD quintiles 1 and 3 (OR 1.75, CI 0.99-3.08, p = 0.053 and OR 2.17, CI 1.22-3.86, p = 0.009, respectively), but this association was not upheld in our multivariable model containing age, sex, Performance Status and clinical parameters of severity at admission. Of the 12 pre-selected indicators of deprivation, two were associated with greater mortality in our multivariable analysis: income deprivation rate categorised by quartile (Q4 (most deprived): 2.11 (1.20-3.77) p = 0.011)) and greater than expected hospitalisations due to alcohol per SIMD data zone (1.96 (1.28-3.00) p = 0.002))., Conclusions: SIMD as an aggregate measure of deprivation was not predictive of mortality in our cohort when other exposure measures were accounted for. However, we identified a two-fold increased risk of mortality in patients residing in areas with greater income-deprivation and/or number of hospitalisations due to alcohol. In areas where aggregate measures fail to capture pockets of deprivation, exploring the impact of specific SIMD indicators may be helpful in targeting resources to residents at risk of poorer outcomes from Covid-19., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Shiga toxin-producing E. coli (STEC) infections associated with wildlife are increasing globally, highlighting many 'spillover' species as important reservoirs for these zoonotic pathogens. A human outbreak of STEC serogroup O157 in 2015 in Scotland, associated with the consumption of venison meat products, highlighted several knowledge gaps, including the prevalence of STEC O157 in Scottish wild deer and the potential risk to humans from wild deer isolates. In this study, we undertook a nationwide survey of wild deer in Scotland and determined that the prevalence of STEC O157 in wild deer is low 0.28% (95% confidence interval = 0.06-0.80). Despite the low prevalence of STEC O157 in Scottish wild deer, identified isolates were present in deer faeces at high levels (>10 4 colony forming units/g faeces) and had high human pathogenic potential based on whole genome sequencing and virulence gene profiling. A retrospective epidemiological investigation also identified one wild deer isolate from this study as a possible source of a Scottish human outbreak in 2017. These results emphasise the importance of food hygiene practices during the processing of wild deer carcasses for human consumption.

For the last two decades, the human infection frequency of Escherichia coli O157 (O157) in Scotland has been 2.5-fold higher than in England and Wales. Results from national cattle surveys conducted in Scotland and England and Wales in 2014/2015 were combined with data on reported human clinical cases from the same time frame to determine if strain differences in national populations of O157 in cattle could be associated with higher human infection rates in Scotland. Shiga toxin subtype (Stx) and phage type (PT) were examined within and between host (cattle vs human) and nation (Scotland vs England and Wales). For a subset of the strains, whole genome sequencing (WGS) provided further insights into geographical and host association. All three major O157 lineages (I, II, I/II) and most sub-lineages (Ia, Ib, Ic, IIa, IIb, IIc) were represented in cattle and humans in both nations. While the relative contribution of different reservoir hosts to human infection is unknown, WGS analysis indicated that the majority of O157 diversity in human cases was captured by isolates from cattle. Despite comparable cattle O157 prevalence between nations, strain types were localized. PT21/28 (sub-lineage Ic, Stx2a+) was significantly more prevalent in Scottish cattle [odds ratio (OR) 8.7 (2.3-33.7; P <0.001] and humans [OR 2.2 (1.5-3.2); P <0.001]. In England and Wales, cattle had a significantly higher association with sub-lineage IIa strains [PT54, Stx2c; OR 5.6 (1.27-33.3); P =0.011] while humans were significantly more closely associated with sub-lineage IIb [PT8, Stx1 and Stx2c; OR 29 (4.9-1161); P <0.001]. Therefore, cattle farms in Scotland were more likely to harbour Stx2a+O157 strains compared to farms in E and W ( P <0.001). There was evidence of limited cattle strain migration between nations and clinical isolates from one nation were more similar to cattle isolates from the same nation, with sub-lineage Ic (mainly PT21/28) exhibiting clear national association and evidence of local transmission in Scotland. While we propose the higher rate of O157 clinical cases in Scotland, compared to England and Wales, is a consequence of the nationally higher level of Stx2a+O157 strains in Scottish cattle, we discuss the multiple additional factors that may also contribute to the different infection rates between these nations.

Background: Porcine reproductive and respiratory syndrome (PRRS) remains one of the most important infectious diseases for the pig industry. A novel small-scale transmission experiment was designed to assess whether the WUR0000125 (WUR for Wageningen University and Research) PRRS resilience single nucleotide polymorphism (SNP) confers lower susceptibility and infectivity to pigs under natural porcine reproductive and respiratory syndrome virus (PRRSV-2) transmission., Methods: Commercial full- and half-sib piglets (n = 164) were assigned as either Inoculation, Shedder, or Contact pigs. Pigs were grouped according to their relatedness structure and WUR genotype, with R- and R+ referring to pigs with zero and one copy of the dominant WUR resilience allele, respectively. Barcoding of the PRRSV-2 strain (SD09-200) was applied to track pig genotype-specific transmission. Blood and nasal swab samples were collected and concentrations of PRRSV-2 were determined by quantitative (q)-PCR and cell culture and expressed in units of median tissue culture infectious dose (TCID 50 ). The Log 10 TCID 50 at each sampling event, derived infection status, and area under the curve (AUC) were response variables in linear and generalized linear mixed models to infer WUR genotype differences in Contact pig susceptibility and Shedder pig infectivity., Results: All Shedder and Contact pigs, except one, became infected through natural transmission. There was no significant (p > 0.05) effect of Contact pig genotype on any virus measures that would indicate WUR genotype differences in susceptibility. Contact pigs tended to have higher serum AUC (p = 0.017) and log 10 TCID 50 (p = 0.034) when infected by an R+ shedder, potentially due to more infectious R+ shedders at the early stages of the transmission trial. However, no significant Shedder genotype effect was found in serum (p = 0.274) or nasal secretion (p = 0.951) that would indicate genotype differences in infectivity., Conclusions: The novel design demonstrated that it is possible to estimate genotype effects on Shedder pig infectivity and Contact pig susceptibility that are not confounded by family effects. The study, however, provided no supportive evidence that genetic selection on WUR genotype would affect PRRSV-2 transmission. The results of this study need to be independently validated in a larger trial using different PRRSV strains before dismissing the effects of the WUR marker or the previously detected GBP5 gene on PRRSV transmission., (© 2023. The Author(s).)

Antimicrobial resistance (AMR) is a recognised threat to global health. Obtaining data on the prevalence of AMR in environmental bacteria is key to understanding drivers and routes of transmission. Here, 325 Shiga toxin negative deer faecal samples-gathered from across the Scottish mainland-were screened for the presence of AMR Escherichia coli and investigated for potential risk factors associated with AMR occurrence. E. coli with resistance to antimicrobials of clinical health concern, including carbapenems and 3rd generation cephalosporins, were targeted. Ninety-nine percent of samples yielded E. coli, and the prevalence of resistant E. coli at the level of faecal samples was 21.8% (n = 71) for tetracycline, 6.5% (n = 21) for cefpodoxime, 0.3% for ciprofloxacin (n = 1), with no recorded resistance to meropenem. Potential risk factors for tetracycline and cefpodoxime resistance were investigated. The presence of broadleaved woodlands was significantly associated with both AMR phenotypes, which may relate to land use within or around such woodlands. Associated risk factors varied across resistance phenotype and deer species, with proximity or density of horses an indicator of significantly decreased and increased risk, respectively, or tetracycline and cefpodoxime resistance in E. coli from roe deer, but not from red deer. Distance from wastewater treatment plants was a significant risk factor for tetracycline resistance in E. coli from red deer but not from roe deer. Data indicated that AMR E. coli can occur in wild deer populations that are not directly exposed to the selective pressure exerted by antimicrobial treatment. Overall, resistance to critically important antimicrobials was found to be low in the studied population, suggesting no immediate cause for concern regarding human health. Utilising existing culling frameworks, wild deer in Scotland could function well as a sentinel species for the surveillance of AMR in the Scottish environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Wild deer hunting is necessary in Scotland to control deer population density, with most carcasses being processed for human consumption. As limited information is available on the microbial condition of Scottish venison, we studied the variation of total coliforms and Escherichia coli (E. coli) on 214 wild deer carcasses collected from six approved establishments. Samples were collected from the hide, body cavity and external surface of each carcass and mean values were determined following bacterial plate counts. The mean log 10 /cm 2 coliforms were 5.78 (hide), 6.80 (body cavity) and 6.36 (external surface). The mean log 10 /cm 2 E. coli were 1.82 (hide), 2.27 (body cavity) and 2.17 (external carcass). Significantly higher coliforms counts were associated with storage-to-dressing times above 6 days and with longer transport distances. Risk factors that increased E. coli were red deer species, ambient temperature above 7 °C during hunting, dirty hides, faecal contamination and moisture or slimy film on the carcass. Although the bacterial counts obtained in this study indicated some hygienic processing, for around half of the carcasses, the E. coli counts were above 2 log 10 /cm 2 . Therefore, the above risk factors suggest a few handling hygiene practices that should be further improved to enhance quality and safety., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The variation in the pathogen type as well as the spatial heterogeneity of predictors make the generality of any associations with pathogen discovery debatable. Our previous work confirmed that the association of a group of predictors differed across different types of RNA viruses, yet there have been no previous comparisons of the specific predictors for RNA virus discovery in different regions. The aim of the current study was to close the gap by investigating whether predictors of discovery rates within three regions-the United States, China, and Africa-differ from one another and from those at the global level., Methods: Based on a comprehensive list of human-infective RNA viruses, we collated published data on first discovery of each species in each region. We used a Poisson boosted regression tree (BRT) model to examine the relationship between virus discovery and 33 predictors representing climate, socio-economics, land use, and biodiversity across each region separately. The discovery probability in three regions in 2010-2019 was mapped using the fitted models and historical predictors., Results: The numbers of human-infective virus species discovered in the United States, China, and Africa up to 2019 were 95, 80, and 107 respectively, with China lagging behind the other two regions. In each region, discoveries were clustered in hotspots. BRT modelling suggested that in all three regions RNA virus discovery was better predicted by land use and socio-economic variables than climatic variables and biodiversity, although the relative importance of these predictors varied by region. Map of virus discovery probability in 2010-2019 indicated several new hotspots outside historical high-risk areas. Most new virus species since 2010 in each region (6/6 in the United States, 19/19 in China, 12/19 in Africa) were discovered in high-risk areas as predicted by our model., Conclusions: The drivers of spatiotemporal variation in virus discovery rates vary in different regions of the world. Within regions virus discovery is driven mainly by land-use and socio-economic variables; climate and biodiversity variables are consistently less important predictors than at a global scale. Potential new discovery hotspots in 2010-2019 are identified. Results from the study could guide active surveillance for new human-infective viruses in local high-risk areas., Funding: FFZ is funded by the Darwin Trust of Edinburgh (https://darwintrust.bio.ed.ac.uk/). MEJW has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 874735 (VEO) (https://www.veo-europe.eu/)., Competing Interests: FZ, MC, CG, MW No competing interests declared, (© 2022, Zhang et al.)

Countries of the World Health Organization (WHO) African Region have experienced a wide range of coronavirus disease 2019 (COVID-19) epidemics. This study aimed to identify predictors of the timing of the first COVID-19 case and the per capita mortality in WHO African Region countries during the first and second pandemic waves and to test for associations with the preparedness of health systems and government pandemic responses. Using a region-wide, country-based observational study, we found that the first case was detected earlier in countries with more urban populations, higher international connectivity and greater COVID-19 test capacity but later in island nations. Predictors of a high first wave per capita mortality rate included a more urban population, higher pre-pandemic international connectivity and a higher prevalence of HIV. Countries rated as better prepared and having more resilient health systems were worst affected by the disease, the imposition of restrictions or both, making any benefit of more stringent countermeasures difficult to detect. Predictors for the second wave were similar to the first. Second wave per capita mortality could be predicted from that of the first wave. The COVID-19 pandemic highlights unanticipated vulnerabilities to infectious disease in Africa that should be taken into account in future pandemic preparedness planning., (© 2021. The Author(s).)

Background: The antihelminthic drug praziquantel has been used as the drug of choice for treating schistosome infection for more than 40 years. Although some epidemiological studies have reported low praziquantel efficacy in cure rate (CR) and/or egg reduction rate (ERR), there is no consistent robust evidence of the development of schistosome resistance to praziquantel (PZQ). There is need to determine factors that lead to variable treatment CR and/or ERR. Therefore, we conducted a systematic review and meta-analysis to review CR and ERR as well as identify their predictors., Methodology/principal Findings: In this systematic review and meta-analysis, a literature review was conducted using Biosis Citation Index, Data Citation Index, MEDLINE, and Web of Science Core Collection all of which were provided through Web of Science. Alongside these, EMBASE, and CAB abstracts were searched to identify relevant articles. Random effect meta-regression models were used to identify the factors that influence CR and/or ERR by considering differences in host characteristics and drug dose. In total, 12,127 potential articles were screened and 146 eligible articles (published from 1979 to 2020) were identified and included for the meta-analysis. We found that there has been no significant reduction in CR or ERR over the study period. The results showed more variability in CR, compared with ERR which was more consistent and remained high. The results showed a positive effect of "PZQ treatment dose" with the current recommended dose of 40 mg/kg body weight achieving 57% to 88% CR depending on schistosome species, age of participants, and number of parasitological samples used for diagnosis, and ERR of 95%., Conclusions/significance: Based on a review of over 40 years of research there is no evidence to support concerns about schistosomes developing resistance to PZQ. These results indicate that PZQ remains effective in treating schistosomiasis., Competing Interests: The authors have declared that no competing interests exist.

RNA viruses are a leading cause of human infectious diseases and the prediction of where new RNA viruses are likely to be discovered is a significant public health concern. Here, we geocoded the first peer-reviewed reports of 223 human RNA viruses. Using a boosted regression tree model, we matched these virus data with 33 explanatory factors related to natural virus distribution and research effort to predict the probability of virus discovery across the globe in 2010-2019. Stratified analyses by virus transmissibility and transmission mode were also performed. The historical discovery of human RNA viruses has been concentrated in eastern North America, Europe, central Africa, eastern Australia, and north-eastern South America. The virus discovery can be predicted by a combination of socio-economic, land use, climate, and biodiversity variables. Remarkably, vector-borne viruses and strictly zoonotic viruses are more associated with climate and biodiversity whereas non-vector-borne viruses and human transmissible viruses are more associated with GDP and urbanization. The areas with the highest predicted probability for 2010-2019 include three new regions including East and Southeast Asia, India, and Central America, which likely reflect both increasing surveillance and diversity of their virome. Our findings can inform priority regions for investment in surveillance systems for new human RNA viruses., Competing Interests: The authors disclose no conflicts of interest.

In 2012, the World Health Organisation (WHO) set out a roadmap for eliminating schistosomiasis as a public health problem by 2025. To achieve this target, preschool-aged children (PSAC; aged 6 years and below) will need to be included in schistosomiasis treatment programmes. As the global community discusses the tools and approaches for treating this group, one of the main questions that remains unanswered is how to quantify infection in this age group to inform treatment strategies. The aim of this study was thus to determine whether a relationship exists between levels of schistosome infection in PSAC and school-aged children (SAC), that can be used to determine unknown schistosome infection prevalence levels in PSAC. A systematic search of publications reporting schistosomiasis prevalence in African PSAC and SAC was conducted. The search strategy was formulated using the PRISMA guidelines and SPIDER search strategy tool. The published data was subjected to regression analysis to determine if a relationship exists between infection levels in PSAC and SAC. The interaction between SAC and community treatment history was also entered in the regression model to determine if treatment history significantly affected the relationship between PSAC and SAC prevalence. The results showed that a significant positive relationship exists between infection prevalence levels in PSAC and SAC for Schistosoma mansoni (r = 0.812, df (88, 1), p = <0.0001) and S. haematobium (r = 0.786, df (53, 1), p = <0.0001). The relationship was still significant after allowing for diagnostic method, treatment history, and the African sub-region where the study was conducted (S. mansoni: F = 25.63, df (88, 9), p = <0.0001; S. haematobium: F = 10.20, df (53, 10), p = <0.0001). Using the regression equation for PSAC and SAC prevalence, over 90% of the PSAC prevalence studies were placed in the correct WHO classifications category based on the SAC levels, regardless of treatment history. The study indicated that schistosome prevalence in SAC can be extended as a proxy for infection levels in PSAC, extending on its current use in the adult population. SAC prevalence data could identify where there is a need to accelerate and facilitate the treatment of PSAC for schistosomiasis in Africa., Competing Interests: The authors have declared that no competing interests exist.

Vaccination is the main tool for controlling infectious diseases in livestock. Yet current vaccines only provide partial protection raising concerns about vaccine effectiveness in the field. Two successive transmission trials were performed involving 52 pigs to evaluate the effectiveness of a Porcine Reproductive and Respiratory Syndrome (PRRS) vaccinal strain candidate against horizontal transmission of a virulent heterologous strain. PRRS virus, above the specified limit of detection, was observed in serum and nasal secretions for all but one pig (the exception only tested positive for serum), indicating that vaccination did not protect pigs from becoming infected and shedding the heterologous strain. However, vaccination delayed the onset of viraemia, reduced the duration of shedding and significantly decreased viral load throughout infection. Serum antibody profiles indicated that 4 out of 13 (31%) vaccinates in one trial had no serological response (NSR). A Bayesian epidemiological model was fitted to the data to assess the impact of vaccination and presence of NSRs on PRRS virus transmission dynamics. Despite little evidence for reduction in the transmission rate, vaccinated animals were on average slower to become infectious, experienced a shorter infectious period and recovered faster. The overall PRRSV transmission potential, represented by the reproductive ratio R 0 was lower for the vaccinated animals, although there was substantial overlap in the credibility intervals for both groups. Model selection suggests that transmission parameters of vaccinated pigs with NSR were more similar to those of unvaccinated animals. The presence of NSRs in a population, however, seemed to only marginally affect the transmission dynamics. The results suggest that even when vaccination can't prevent infection, it can still have beneficial impacts on the transmission dynamics and contribute to reducing a herd's R 0 . However, biosecurity and other measures need to be considered to decrease contact rates and lower R 0 below 1., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Competing interests SG is employed by the Virbac pharmaceutical group. The authors HN, JX, IT, CB and KR performed studies on the efficacy of the vaccinal strain with the Virbac pharmaceutical group. The authors did not receive any salary or receive any personal economic compensation for those studies. The remaining authors have no conflict of interest in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Many livestock and human vaccines are leaky because they block symptoms but do not prevent infection or onward transmission. This leakiness is concerning because it increases vaccination coverage required to prevent disease spread and can promote evolution of increased pathogen virulence. Despite leakiness, vaccination may reduce pathogen load, affecting disease transmission dynamics. However, the impacts on post-transmission disease development and infectiousness in contact individuals are unknown. Here, we use transmission experiments involving Marek disease virus (MDV) in chickens to show that vaccination with a leaky vaccine substantially reduces viral load in both vaccinated individuals and unvaccinated contact individuals they infect. Consequently, contact birds are less likely to develop disease symptoms or die, show less severe symptoms, and shed less infectious virus themselves, when infected by vaccinated birds. These results highlight that even partial vaccination with a leaky vaccine can have unforeseen positive consequences in controlling the spread and symptoms of disease., Competing Interests: The authors declare no competing interests.