Preventive Veterinary Medicine

Objectives: Research on mental health in agriculture has increased in recent years; however, it remains largely focused on farmers themselves and is predominantly male-oriented. The mental health of farm wives and partners, many of whom play integral roles in farm operations, business management, and family life, remains difficult to characterise. This study therefore aims to explore the prevalence and causes of mental health challenges among farm wives and partners, and to investigate their use of, and barriers to, mental health support services. Methods: Quantitative data was collected using over 450 structured questionnaire responses that assessed mental health prevalence, contributing stressors and support service utilisation. Results: Findings indicate that there is a high prevalence of mental ill health amongst farm wives, seemingly due to industry stressors and support role overwhelm. Interpersonal relationships played a significant role in the types of mental distress experienced and highlighted the toll that farm life can take on farm wives' social and emotional connections. Despite a range of formal and informal support services being available, and effective when used, significant barriers to accessing these services were identified, including both practical difficulties and self-stigmatisation due to cultural beliefs. Conclusions: Farm wives and partners experience substantial mental health burdens linked to their diverse and often underrecognized roles within agricultural systems. In future, targeted interventions are needed to reduce stigma, improve service accessibility, and recognize women's contributions within farm enterprises. Further research and dedicated investment are also essential to better understand and help improve the mental health of this overlooked population within agricultural industries.

Background Nipah virus (NiV) is a priority zoonotic pathogen causing high-fatality outbreaks. Early NiV outbreaks in Malaysia and Singapore had limited transmission beyond spillover events. However, since 2001, NiV outbreaks with person-to-person transmission have occurred in Bangladesh and India, driven by the NiV-Bangladesh genotype and NiV-India genotype. Our study aims to estimate the reproduction number, offspring dispersion, and serial interval governing NiV transmission in Bangladesh and India during 2001-2026. Methods We conducted a systematic review of NiV outbreak investigations in Bangladesh and India, searching PubMed, Embase, Web of Science, and grey literature through 28 February 2026. Case-level offspring counts from 27 eligible sources (323 cases across 67 outbreaks) were used as input to a hierarchical Bayesian negative binomial offspring distribution model. The serial interval was estimated by parametric distribution fitting to 137 transmission pairs. Country-stratified and sensitivity analyses were performed to evaluate the robustness of estimates. Results Pooling across 67 outbreaks, we estimated a median reproduction number of 0.46 (95% CrI: 0.28-0.73), an offspring dispersion parameter of 0.07 (0.05-0.10), and a serial interval of 13.3 days (95% CI: 12.8-13.8). Country-stratified median reproduction numbers were 0.48 (0.23-0.97) for India and 0.35 (0.19-0.59) for Bangladesh, and dispersion parameters were 0.04 (0.02-0.07) and 0.11 (0.06-0.18), respectively, indicating marked overdispersion in both settings. Conclusion NiV transmission is self-limiting on average and highly overdispersed, suggesting that a disproportionate share of onward transmission arises from a small number of cases. This epidemiological profile supports targeted containment measures, including contact tracing and quarantine, for effective NiV outbreak control.

Background: Vaccine hesitancy and logistical barriers continue to limit influenza vaccination uptake among healthcare personnel. The STRENGTH initiative evaluated employee drivers of influenza vaccine acceptance in healthcare workgroups with lower vaccination compliance. Methods: This mixed-methods program evaluation used a custom Epic electronic medical record dashboard to identify workgroups with lower influenza vaccination rates, followed by focus groups, targeted worksite vaccination clinics, and an anonymous survey. Survey data from 73 respondents were analyzed using descriptive statistics, Mann-Whitney U tests, Kruskal-Wallis tests, chi-square or Fisher exact tests, and Spearman rank correlations. Results: Respondents had a mean age of 44.8 years (SD 11.3); 36 of 70 respondents reporting binary gender were male. Convenience of worksite vaccination received the highest importance ratings (mean 4.72/5), followed by protection from influenza (mean 4.38/5). Both were rated significantly above the neutral midpoint of 3 (Wilcoxon p<0.001). The strongest observed Spearman correlations were between peer pressure and leadership participation (rho=0.47) and between protection from influenza and willingness to receive a future combined influenza/COVID-19 vaccine (rho=0.42). Conclusions: Convenience and perceived protection were the most important vaccination drivers. Employer-sponsored workplace vaccination programs can reduce logistical barriers while providing opportunities for targeted education and trust-building. Keywords: influenza vaccination; healthcare workers; vaccine hesitancy; occupational health; workplace vaccination; employer-sponsored vaccination

Background: Cholera outbreaks can spread rapidly, which means that the optimal decision-making window for a large, coordinated response is very narrow. Alerts for triggering interventions need to balance tradeoffs between wasting resources on false positives and delaying decisions until they lose effectiveness. A systematic evaluation of such tradeoffs across settings is needed to understand which alerts may have the greatest public health utility and where. Methods: Using weekly suspected cholera surveillance across 4,081 subnational administrative units across 34 countries in Africa from 2010-2023, we evaluated 24 alert definitions (4 alert types with different numeric thresholds) over a 1-year post-alert period on five utility dimensions - potential health impact, potential intervention efficiency, positive predictive value (PPV) for large outbreaks, proportion of missed outbreaks, and timeliness of alert trigger. The dimensions were combined into a utility score, which was used to identify the best alert across the continent and by country. For top-performing alerts, we estimated the reduction in potential health impact for additional delays in response using Bayesian hierarchical models. Results: Fifty suspected cases for three consecutive weeks was the definition with the highest utility score across most contexts. In administrative units with 50,000 to 500,000 people, the year following such an alert experienced a mean of 376 suspected cases (standard deviation: 618.3) and 2 cases per 1000 population (SD: 4.1). Forty percent of such alerts (N alerts: 265) were followed by a 1-year period with over 300 cases, yet the definition missed 40% of outbreaks with over 300 cases (N outbreaks: 278) and was triggered 5.3 weeks (SD: 5) after outbreak start. Each week of delay was estimated to result in an additional 20% reduction (95% CrI: -23 to -17) of potential health impact in the outbreak response. One hundred cases over a three-week period was another definition that had high utility, particularly in administrative units with smaller populations and country-specific evaluations. Conclusion: We present a decision analytic framework that can be deployed in a short decision-making window using case-based surveillance to trigger large-scale cholera response activities with moderately high utility across most African transmission contexts. Future work should consider adaptations based on local data availability and priorities and examine the generalizability of early case-based signals outside Africa.

Background: Zoonotic infectious disease risk arises at human-animal-environment interfaces where pathogen spillover can occur. Rural communities living in biodiverse settings may experience frequent contact with wildlife and shared environments through livelihoods, food practices, and economic activities. Reducing spillover risk and strengthening pandemic prevention requires both structural and individual-level change. Community-based interventions that promote awareness, risk perception, self-efficacy, pro-environmental behaviour, and safe coexistence with wildlife may support prevention by shifting behavioural determinants of zoonotic disease risk. The Saan Suk intervention was co-developed with rural communities in Thailand using a Human-Centred Design approach and is grounded in the Health Belief Model and One Health principles. The intervention is intended to be feasible, acceptable, and deliverable through Thailands established Village Health Volunteer (VHV) system. Methods: This protocol describes a parallel-arm, cluster-randomised controlled superiority trial that will be conducted during July - October 2026, in Chanthaburi Province, Thailand. 24 villages will be equally randomised to the Saan Suk intervention or the current practice (control). In intervention villages, trained VHVs will deliver, once a week over four weeks, a multimodal One Health educational intervention designed to improve knowledge of zoonotic spillover, promote protective behaviours, reduce risky wildlife-related contacts, and support respectful coexistence with wildlife. Trained outcome assessment teams will conduct structured interviews with 42 adult participants per village, yielding a total sample size of 1,008 participants. The sample size was calculated for the primary outcome, accounting for clustering, with 90% power to detect a medium effect size (6 points on the 0-100 knowledge scale) at a significance level of 0.05, accounting for a design effect with an ICC of 0.028. The primary outcome is knowledge of zoonotic spillover, transmission pathways, risk factors, protective and risky behaviours, and safe coexistence with wildlife. Secondary outcomes include attitudes, self-efficacy, preventive and risky behaviours, and reported contacts with major local reservoir hosts. A structured questionnaire was developed, expert-reviewed, and piloted for the outcome assessment. Outcomes will be analysed using mixed-effects regression models with random effects for village and adjustment for relevant pre-specified confounders. Primary analyses will follow the intention-to-treat principle. Discussion: This trial will evaluate whether a co-designed, VHV-delivered One Health educational programme can improve knowledge of zoonotic disease prevention and behavioural determinants in rural communities living in close contact with wildlife and shared ecosystems. If effective and feasible, Saan Suk could inform integration into routine VHV training and community-based zoonotic disease and pandemic prevention strategies. Trial Registration: The Saan Suk trial is registered with the German Clinical Trials Register (DRKS). Registration ID: DRKS00038582; date of registration: 11 May 2026.

Background. In 2026, the Democratic Republic of the Congo (DRC) experienced the largest recorded outbreak of Ebola disease caused by Bundibugyo virus, with epidemiologically linked importations and secondary transmission in Uganda. This study analysed the publicly reported trajectory and assessed the risk of introduction and onward transmission in North Africa and Europe. Methods. Public surveillance reports from the World Health Organization (WHO), European Centre for Disease Prevention and Control (ECDC), Africa CDC, national ministries of health, and peer-reviewed sources were synthesised through 15-17 July 2026. Headline counts and crude case-fatality ratios were restricted to laboratory-confirmed cases. Average notification rates were calculated from cumulative DRC counts. Exact Poisson intervals used the Garwood method, and the June-July rate ratio was estimated on the log scale. Risk was assessed across introduction likelihood, conditional onward-transmission likelihood, impact, and confidence. Results. By 15 July, the DRC had reported 2,124 confirmed cases and 828 deaths (crude confirmed-case fatality ratio, 39.0%) across 46 health zones in five provinces. Uganda had reported 20 confirmed cases and two confirmed deaths: 15 imported infections and five secondary cases, with no documented community transmission. DRC notifications averaged 47.4 per day during 1-15 July versus 35.9 per day during 2-29 June (rate ratio 1.32; counting-model 95% interval 1.20-1.46). WHO reported that more than 80% of new cases were detected outside known contact lists, while 119 confirmed healthcare-worker infections and 36 deaths had occurred. Introduction likelihood was assessed as very low to low for North Africa and very low for the general European population; delayed recognition in routine healthcare was the principal scenario for limited secondary transmission. Interpretation. Available indicators were inconsistent with effective control in eastern DRC at the data cut-off. Public reporting-date series cannot separate transmission from changing ascertainment, but they showed no sustained decline. Preparedness in North Africa and Europe should prioritise complete exposure histories, rapid isolation, validated diagnostics, protected clinical care, and contact management rather than reliance on border screening. Keywords: Bundibugyo virus; Ebola disease; outbreak surveillance; rapid risk assessment; importation; North Africa; Europe; Algeria; International Health Regulations.

Background. The 2026 Bundibugyo virus disease (BVD) epidemic in the Democratic Republic of the Congo (DRC) was declared on 15 May 2026 and determined a public health emergency of international concern on 17 May 2026. Public surveillance reporting consists of cumulative counts by report date; no line list with symptom-onset dates is available. Widely circulated characterisations - that this is the fastest-growing Ebola outbreak on record, that reported cases are doubling every 22 days, and that the case fatality ratio (CFR) is 37.5% - rest on these aggregates. We examined what the published data actually support. Methods. We assembled twelve published anchor points from 15 May to 13 July 2026 from WHO, WHO AFRO, NICD and the DRC National Institute of Public Health; one was recovered by back-calculation and checked against the directly reported subsequent total. We computed mean daily incidence between anchors and the within-interval death-to-case ratio. We reconstructed symptom-onset dates by Richardson-Lucy deconvolution with right-truncation correction under assumed onset-to-report delays with means of 5, 7 and 9 days, estimated the instantaneous reproduction number using the Cori method, and computed three CFR estimators: crude, resolved-case and outcome-delay-adjusted. Provincial CFRs used exact binomial intervals. Results. Confirmed cases plateaued at 40-52 per day for eighteen days, from 25 June to 13 July. Over the same period, the within-interval death-to-case ratio rose from 0.28 to 0.58. Reconstructed Rt was 1.28, with a 95% credible interval of 1.15-1.41, on 7 July, having fallen from approximately 2.9 in mid-May. Growth on the reconstructed onset curve corresponded to a doubling time of approximately 90 days, compared with 22 days computed from cumulative counts. CFR estimates were 37.5% for the crude estimator, 50.2% for the outcome-delay-adjusted estimator and 67.3% for the resolved-case estimator. Crude provincial CFR was 34.9% with a 95% confidence interval of 32.7-37.1 in Ituri, 58.2% with a 95% confidence interval of 50.7-65.5 in North Kivu, and 81.0% with a 95% confidence interval of 58.1-94.6 in newly affected provinces. Conclusions. A flat case count accompanied by a rising death-to-case ratio is difficult to reconcile with a transmission plateau and is consistent with saturated case detection. Reported case counts appear to have substantially decoupled from transmission and cannot presently distinguish control from detection failure. Doubling times computed from cumulative totals are artefacts. Test volume and positivity by health zone are the critical missing denominators.

Diarrheal disease remains a leading cause of morbidity and mortality among children under five globally, with poor sanitation and hygiene accounting for over 88% of diarrhea and malnutrition burden. In Kenya, diarrhea ranks third in under-five mortality, particularly affecting arid and semi-arid regions. School-Led Total Sanitation (SLTS), adapted from Community-Led Total Sanitation (CLTS), uses pupils as change agents for household hygiene knowledge transfer. However, SLTS effectiveness in addressing diarrhea and malnutrition has not been evaluated in Kenya. This study assessed SLTS effects on diarrheal disease and nutritional outcomes among children aged 5-59 months in Baringo County. A pre- and post-test quasi-experimental design with nonequivalent control groups was employed in Mogotio (intervention) and Baringo South (control) sub-counties. Using multistage sampling, 440 children aged 6-59 months were enrolled. The six-month SLTS intervention included capacity building, school health club formation, triggering activities using Participatory Rural Appraisal tools, Information, Education, and Communication materials distribution, continuous sensitization, and household monitoring. Data were collected at baseline and three months post-intervention using electronic questionnaires and anthropometric measurements. Nutritional status was assessed using WHO Anthro software z-scores for length/height-for-weight (HWZ), and weight-for-age (WAZ) to determine wasting, and underweight prevalence. Chi-square analysis assessed intervention-control differences. Baseline and endline socio-demographic characteristics were comparable between groups. At endline, no significant nutritional outcome differences were observed: wasting prevalence was at 15.0% versus 16.4% ({chi}{superscript 2}=0.155, df=1, p=0.694) while underweight was 12.3% versus 13.6% ({chi}{superscript 2}=0.181, df=1, p=0.670). However, diarrheal disease prevalence significantly reduced in intervention versus control groups: 5.9% versus 13.2% ({chi}{superscript 2}=6.738, df=1, p=0.009), representing a 53% reduction. SLTS intervention showed no significant effect on nutritional outcomes but demonstrated a significant reduction in diarrheal disease among children aged 6-59 months. These findings provide strong evidence for integrating school-based sanitation and hygiene approaches into broader public health strategies addressing diarrheal diseases.

Background & aims of study: Current measles outbreaks around the world have highlighted the evolving immunity landscape of some vaccine-preventable diseases (VPDs). In Canada, there have been approximately 1,100 reported measles cases between January and June 2026 alone. This far exceeds the previous average annual case count of <200. This significant outbreak has underscored the need to better understand the present state of population immunity to measles in Canada, an essential input parameter for outbreak response models. Most population immunity in this setting is derived from routine childhood vaccination, but vaccine coverage data is available heterogeneously across the country and is typically collected cross-sectionally to monitor population adherence to immunization schedules rather than to inform population-level susceptibility. This study developed statistical methods to adapt available measles vaccine coverage estimates into more complete estimates of present-day immunity in Canada by age and province/territory (PT). Methods & results: First, a standardized dataset for vaccine coverage by PT was curated from existing publicly-available datasets and reports. A significant number of vaccine coverage estimates were missing by PT, dose, and year. We used Gaussian Process models to impute current coverage with at least one dose of a measles vaccine, to create a complete "modelled dataset" by PT and age. Our modelling framework was also tested against data for England, which was much more complete, to gauge model accuracy. Implications: We developed methodology for estimating vaccine coverage in the absence of detailed population immunity data, to support ongoing measles outbreak modelling response work. While this project focused on measles, we built the associated code/tools such that the methodology can be applied to other vaccine-preventable diseases in future outbreak settings.

Introduction Adolescent idiopathic scoliosis (AIS) requires frequent x-rays for management, exposing young patients to cumulative radiation risks. While radiation-sparing imaging modalities exist, access across the National Health Service (NHS) remains uneven and information given to patients is variable. This qualitative study investigated the systemic, geographic, and interpersonal dynamics of AIS imaging in England. Design This qualitative study employed in-depth semi-structured interviews with healthcare professionals (HCPs) from NHS paediatric spinal centres, patients aged 13 to 25 years old with AIS and parents/carers of young people with AIS. Setting England. Participants A total of 22 HCPs from 13/24 NHS paediatric spinal centres in England, 19 10-25 years with AIS and 11 parents/carers. Results Conventional x-ray remains the main imaging modality. Significant geographic inequality exists. The most commonly available radiation-sparing imaging modality available is the EOS system, which uses slot-scanning technology, is available at 7 centres in England, primarily in London imaging networks. Acquisition of EOS systems is currently driven by local charitable funding rather than a centralised strategy, with high capital and installation costs cited as primary barriers. Inconsistent knowledge of imaging within primary care and a lack of specialist expertise in local secondary care services led to diagnostic redundancy, gatekeeping, and low value inconsistent imaging. These systemic delays frequently closed the window for conservative treatments like bracing. A professional balancing act exists between the duty to inform and the desire to minimise patient anxiety. HCPs often use selective communication regarding radiation risks. Conversely, families demonstrate high relational trust with HCPs and low baseline knowledge of cumulative exposure, often viewing frequent imaging as a reassuring marker of clinical progress. In centres with EOS systems, clinicians felt empowered to lead proactive, transparent risk discussions. In standard X-ray settings, dialogue remains reactive and infrequent, leading to a reliance on implied rather than truly informed consent. Conclusions AIS imaging in England is variable. Geographic location dictates access to low-dose radiation technology and the quality of informed consent. Systemic inefficiencies and fragmented referral pathways contribute to diagnostic redundancy and delayed specialist care. National standardisation of clinical pathways, information provision and a centralised strategy for low-dose technology procurement are essential to eliminate structural inequalities and ensure equitable, transparent care for all patients.

Background: Monoclonal antibodies have emerged as a prophylactic strategy to prevent symptomatic SARS-CoV-2 infection in immunocompromised individuals. However, the evolutionary and clinical implications of breakthrough infections under this regime remain unclear. Methods: A male in their 80s with a haematological/oncological diagnosis received a 2000 mg intravenous infusion of sotrovimab in March 2023 and was diagnosed with COVID-19 by RT-qPCR from a nasopharyngeal swab in August 2023. Weekly samples (n=24) were collected through February 2024 (171 days). All samples underwent whole-genome sequencing, with select mutations subjected to functional assessment. Findings: Sequencing identified the GE.1 lineage at all timepoints. An intra-host recombination event in ORF1ab (positions 8942-12458) was detected prior to 23 weeks post-detection, followed by a 14-fold increase in viral load (7.42e+06 to 1.00e+08 RNA copies/mL) and a marked shift in the viral population. E340D, a sotrovimab resistance mutation, was detected at low abundance (46%) within the first week post-infection, fluctuated over time, and was nearly fixed by week 15 (107 days) post-detection. We assessed five spike mutations - V36M, S98F, and V213G in the N-terminal domain, Y505P in the receptor-binding domain, and P681Q near the S1/S2 cleavage site - and additionally evaluated the impact of E340D. V36M conferred the highest infectivity across all cell lines, with the most significant effect in low-TMPRSS2 cells. While all mutations showed enhanced infectivity with the addition of E340D, the effect was most pronounced in mutations with lower baseline infectivity. The addition of E340D significantly decreased relative neutralizing titres for V36M, S98F, and V213G, enabling escape from neutralizing antibodies in XBB-responsive individuals, illustrating an enhanced phenotypic advantage. Patient neutralizing activity was absent pre-sotrovimab, and sotrovimab-induced neutralization was further compromised by selection of E340D. Interpretation: Sotrovimab pre-exposure prophylaxis in an immunocompromised patient did not prevent SARS-CoV-2 infection, and selected for resistant mutation E340D, with unexpected fitness consequences across non-receptor binding domain spike regions.

Background and Aims The optimal treatment for first episodes and first recurrences of Clostridioides difficile infections (CDI) is unknown and there is emerging evidence for pulse and taper (P-T) regimens. Therefore, we sought to estimate the relative efficacy of treatment options. Methods MEDLINE and CENTRAL were searched from database inception to May 21, 2025 and unpublished conference abstracts were searched from recent infectious disease conferences. RCTs on the treatment of first episodes or first recurrences of CDI comparing fixed-dose or P-T regimens of fidaxomicin or vancomycin were included. The primary and secondary outcomes were 40- and 56-day CDI recurrence, respectively. A random-effects network meta-analysis on the risk ratio (RR) scale was conducted using a standard regimen (10-14 days) of vancomycin as the comparator. Treatments were ranked using the surface under the cumulative ranking curve (SUCRA). Results 8 RCTs were included comprising a total of 2181 patients. For 40-day recurrence, fidaxomicin P-T had the highest probability of ranking best (RR=0.10, 95%Confidence Interval [95%CI]=0.10-0.49, SUCRA=1.00), followed by vancomycin P-T (RR=0.49, 95%CI=0.32-0.76, SUCRA=0.61), fixed-dose fidaxomicin (RR=0.61, 95%CI=0.49-0.76, SUCRA=0.39), and, finally, fixed-dose of vancomycin (SUCRA=0.00). The treatments ranked in the same order for 56-day recurrence, though only 3 RCTs reported on this timepoint. Conclusion Vancomycin P-T, fidaxomicin P-T, and fixed-dose fidaxomicin were all superior to a fixed-dose vancomycin. Head-to-head comparative effectiveness RCTs are needed to quantify their relative effect sizes of and impact on long-term prevention of recurrent CDI.

Background The 2022-2023 global mpox outbreak highlighted the critical need for robust genomic surveillance capabilities to track mpox virus (MPXV) evolution and transmission dynamics. Methods Building upon our established SARS-CoV-2 sequencing infrastructure, we implemented a Molecular Loop probe-based long-read sequencing approach using Pacific Biosciences Sequel II technology for comprehensive MPXV genomic surveillance across the United States (US). From August 2024 to June 2025, we generated 326 high-quality whole genome sequences from residual mpox-positive clinical specimens collected by Labcorp across all 10 US Department of Health and Human Services regions. Results Our analysis identified two samples containing clade Ib MPXV in January and June 2025 and captured shifting trends in clade IIb diversity, with 13 distinct lineages observed. We also identified multiple instances of large (~1.6-17.6kb) deletions proximal to the inverted terminal repeats in clade IIb genomes. APOBEC3 mutation analysis indicated substantial evidence of human-to-human transmission among both clades. Further, we observed significantly higher APOBEC3-associated SNPs per kilobase (P<0.001) in clade IIb genomic variable regions relative to their central conserved region. Our assay exhibited strong reproducibility across biological replicates from individual patients and accuracy was confirmed via parallel sequencing of select specimens by US Centers for Disease Control and Prevention (CDC) using metagenomic sequencing. We also demonstrated via custom simulation that our assay discriminates all known MPXV clades and lineages, including those we have not observed in the US. Conclusions Our integrated nationwide surveillance system facilitates real-time genomic tracking of outbreak evolution, with demonstrated capacity across SARS-CoV-2 and MPXV, positioning this platform for rapid deployment during future pathogen emergence.

The World Health Organization (WHO) validated Sri Lanka had eliminated lymphatic filariasis as a public health problem in 2016, the second country in Southeast Asia to attain this status. However, post-validation surveillance has identified sporadic cases of brugian filariasis. The reemergence of Brugia malayi infections in Sri Lanka warrants urgent investigations. Recent studies have shown that the parasite responsible for the reemergence is a novel zoonotic Brugia sp. maintained among dogs that is closely related but distinct to the human-infecting B. malayi species. The current study employed morphological and morphometric assessments, revealing that this novel zoonotic Brugia sp. is within the B. malayi morphological range. Molecular characterization of three genomic regions, the nuclear genomic region SLXI, the non-coding region HhaI, and the mitochondrial genomic region COXI confirmed it as a genetic variant more closely related to B. malayi than to B. pahangi. Phylogenetic analysis further indicated it as a distinct genomic variant, closely related to a B. malayi-like parasite reported from India. Notably, that same parasite was identified in infected humans, animals, and potential vector mosquitoes. This, together with the detection of both human and animal blood within the same brugian infective mosquitoes, and delineating the canine origin of the parasites in human infections, provides compelling evidence supporting zoonotic transmission of this parasite. To our knowledge, this is the first report demonstrating the presence of the same brugian parasite in humans, domestic animals, and potentially infective mosquitoes in Sri Lanka, supported by multi-genomic evidence. The recent identification of multiple potential mosquito vector species suggests that this parasite may have undergone adaptive changes, facilitating its ability to overcome the species barrier. These findings substantiate the long-held hypothesis of zoonotic transmission of the reemerged brugian parasite, highlighting significant implications for ongoing surveillance and control strategies.

Background: Opioid use disorder (OUD) is heritable, yet most genome-wide association studies (GWAS) have focused on European populations, leaving the genetic architecture of OUD in non-European populations underexplored. Methods: We conducted GWAS of OUD across three ancestries using electronic health records and genomic data from 52,357 All of Us Research Program participants (8,912 cases; 43,445 matched opioid-exposed controls; 48.5% female). Participants were stratified into European (EUR), African (AFR), and Admixed American (AMR) ancestry groups for logistic regression GWAS, with independent replication in the Million Veteran Program. We then applied the deep-learning model AlphaGenome to predict the tissue-specific transcriptomic and splicing consequences of top risk variants across 13 reward-pathway brain regions. Results: We identified and replicated a novel DDX6 risk locus, alongside established OPRM1 and FURIN signals. AlphaGenome predicted the DDX6 regulatory allele downregulates the stress-resistance gene FOXR1 in the nucleus accumbens, while the protective OPRM1 variant (rs1799971) upregulates OPRM1 expression across reward networks. Other signals of interest included IL6R and SHISA9 (EUR); GHR (AFR); and ASTN2 (AMR). Conclusions: This study identifies DDX6 as a novel OUD risk locus, replicates associations with OPRM1 and FURIN, and highlights biologically plausible ancestry-specific signals in AFR and AMR populations. We also replicated top variants in an independent population. Finally, integrating GWAS with deep-learning annotations provides specific, localized biological hypotheses to guide future experimental validation and targeted therapeutics.

Stochastic epidemic models are a cornerstone of infectious disease epidemiology and are often used to study intervention scenarios. However, large run-to-run variability can make intervention effects difficult to estimate precisely. We revisit the epidemic Sellke construction, which assigns each individual an infection threshold for the cumulative infection hazard such that, conditional on the thresholds, the epidemic trajectory becomes deterministic. This enables coupling of simulations with and without an intervention, yielding low-variance effect estimates even when outcomes such as final size or peak incidence vary widely between runs. We develop an exact, event-driven implementation that maintains infection and recovery events in priority queues. Cumulative infection-hazard updates require O(log N) time per event, yielding overall complexity O(Elog N) for E events in a population of size N. The implementation achieves computational performance comparable to the classical Gillespie algorithm while naturally accommodating non-Markovian infectious periods and complex infectiousness profiles. We illustrate the approach using distance-dependent spread of avian influenza between poultry farms in the Netherlands and a multilayer population with households, schools, and workplaces. In both examples, coupling enables efficient within-run comparisons of intervention scenarios across stochastic realisations.

Purpose: Nonresponse to routinely collected patient-reported outcome measures (PROMs) threatens the representativeness of aggregated data. We characterized patient-, provider-, and clinic-level factors associated with PROMIS Global-10 nonresponse in routine radiation oncology care. Methods: In this retrospective cohort study, all adults seen at five Mass General Brigham radiation oncology clinics over one year were included. The primary outcome was patient-level nonresponse, defined as never completing the portal-administered Global-10 versus completing it at least once. Using iterative mixed-effects logistic regression, we modeled patient-, provider-, and clinic-level factors. Results: Among 12,214 patients, 71 providers, and five clinics, patient- and appointment-level response rates were 35.4% and 10.9%, with patient-level response ranging nearly fivefold across clinics (12.8% to 66.2%). In Model 1, male sex, lower education, not working, and recent surgery had higher odds of nonresponse, and longer time since diagnosis lower odds. After provider- and clinic-level factors were added, patient sex, education, and employment became nonsignificant, whereas recent surgery (adjusted odds ratio [aOR] 1.97) and longer time since diagnosis (aOR 0.46 for >12 months) persisted. A provider's historical collection rate was protective but attenuated at the clinic level. There, a later program launch (aOR 0.29) and higher historical collection rate (aOR 0.79) correlated with lower nonresponse, whereas academic versus community setting did not. Conclusions: Nonresponse to routinely collected PROMs is a multilevel phenomenon driven substantially by clinic-level implementation factors, not patient characteristics alone. Because response rate is only a proxy for representativeness, PROMs programs and PRO-based performance measures should prioritize representative collection over volume.

Estimating dengue force of infection (FOI) is essential for understanding transmission dynamics and targeting intervention programmes, yet surveillance data in endemic settings required for estimations are often incomplete, with varying formats. We developed a Bayesian hierarchical catalytic model that jointly fits age-stratified case data, aggregate case data, and seroprevalence surveys within a single framework, incorporating external covariates to improve parameter identifiability. Synthetic validation showed that covariates alone recovered accurate FOI point estimates even when most districts contributed only aggregate data, but did so with poorly calibrated uncertainty; anchoring the model with a single seroprevalence survey was necessary to bring credible interval coverage close to nominal. Applied to 128 districts across Java and Bali, Indonesia (2016-2024), the model revealed substantial spatial heterogeneity in FOI and reporting rates. Many districts in Java exceeded the WHO-suggested seroprevalence threshold for vaccine introduction, yet were classified as low-priority when using reported incidence as prioritisation criterion, particularly in areas with weak surveillance. Model-based seroprevalence estimation, integrating multiple data sources, offers a more consistent basis for identifying high-priority districts for vaccine introduction, and is less susceptible to surveillance bias than reported incidence.

Background: Children born prematurely (before 37 weeks) or admitted to the neonatal unit (NNU) are at increased risk of adverse long-term physical health outcomes. It is also recognised that there is an association with later academic performance and special educational needs, however it is not clear whether these broad risk factors could be used as stand-alone heuristics to identify children who may benefit from additional support in educational settings. We aimed to examine the associations between neonatal unit (NNU) admission and educational attainment in mid-childhood. Methods and Findings: Pregnancy data from a prospective birth cohort (Pregnancy Outcome Prediction Study, Cambridge, United Kingdom, 2008-2012) were linked to national educational outcomes (Department for Education, United Kingdom). Multivariable regression models adjusted for maternal, child, and socioeconomic factors were used to evaluate associations between (i) all NNU admissions, (ii) at term NNU admissions >48 hours, (iii) preterm birth without ongoing physical health needs, and educational outcomes at ages 5-11 years. Children who required any NNU care were more likely not to meet expected educational standards across multiple ages and domains in early and mid-childhood: age 5 early year foundation (aOR 1.64, 95% CI 1.19-2.27, p=0.003), phonics at age 6 (aOR 2.43, 95% CI 1.72-3.57, p<0.001), and at age 7 (here assessments were divided into multiple domains): reading (aOR 1.67, 95% CI 1.18-2.38, p=0.004), writing (aOR 1.72, 95% CI 1.25-2.38, p<0.001), mathematics (aOR 1.56, 95% CI 1.09-2.22, p=0.020), and science (aOR 1.85, 95% CI 1.22-2.78, p=0.003). Similar patterns were observed among both at term-born infants who stayed >48hrs in NNU (phonics assessment at age 6 aOR 2.26, 95% CI 1.51-3.36, p<0.001) and in children born preterm without long-term physical health sequelae (phonics assessment at age 6 aOR 3.07, 95% CI 1.96-4.81, p<0.001). These associations were robust to adjustment for demographic, perinatal, and socio-economic factors. By age 11, differences in academic attainment were attenuated and no longer clearly distinguishable across all exposure groups. However, there was an increased likelihood of special educational needs (SEN) at age 11 associated with any NNU admission (aOR 1.78, 95% CI 1.15-2.73, p=0.009), at term NNU admission for >48hrs (aOR 1.88, 95% CI 1.19-3.00, p=0.007), and children born preterm without long-term physical health sequelae (aOR 1.50, 95% CI 1.00-2.25, p=0.049). Predictive performance of any NNU admission for SEN at age 11 was moderate (AUC 0.70, 95% CI: 1.14-2.65, p=0.010), with balanced sensitivity and specificity and high negative predictive value. Conclusions: NNU admission, for both term and preterm infants, is associated with poorer educational outcomes and an increased likelihood of special educational needs in mid-childhood.

Background Post-infection conditions (PICs), such as Long Covid, are associated with heterogeneous, fluctuating symptoms that profoundly affect daily functioning. Despite moderate-certainty evidence from the NIHR-funded LISTEN trial (COV-LT2-0009) that personalised self management support improves outcomes and may reduce societal and economic impacts of Long Covid, many people living with PICs still receive condition-specific services, generic advice, or stand-alone digital tools that do not address their complex needs. Aim To map care approaches in general practice and synthesise UK evidence for PIC management. Design and setting Scoping review and online survey. Method A two-phase study was conducted: (1) a scoping review of UK evidence on PIC management in general practice; and (2) a supplementary online survey of practitioners working in UK general practice to provide contextual insights. Results The scoping review identified 32 studies focused on Long Covid. One study included a comparator group (ME/CFS). Study populations were predominantly white ethnicity and female. Evidence for non-Covid PICs in UK general practice was largely absent. The supplementary survey (n=46) provided preliminary practice-level insights. Healthcare practitioners reported varied PIC presentations, diagnostic uncertainty, limited referral pathways, inequitable access, and low confidence in managing PICs. Conclusion Evidence informing PIC management in UK general practice remains predominantly Long Covid-focused and may not reflect the range of PICs encountered in practice. While survey findings are preliminary and require confirmation in larger samples, they highlight uncertainty around PIC management. Further research is needed to evaluate whether existing Long Covid pathways should be expanded or complemented by broader PIC models. Keywords general practice; Long Covid; self-management; post-viral syndromes