Tropical Medicine & International Health

Background Antibiotic pricing is a key determinant of access and stewardship in low- and middle-income countries (LMICs), yet empirical evidence on how prices are formed within pharmaceutical markets remains limited. However, there is little longitudinal evidence on how antibiotic prices behave within national pharmaceutical supply systems. This study evaluated the patterns and determinants of systemic antibiotic pricing in Tanzania using national regulatory import permit data. Methods We conducted a retrospective analysis of antibiotic importation records from the Tanzania Medicines and Medical Devices Authority for 2010-2016. Systemic antibiotics for human use imported via oral or parenteral routes were included. Unit prices (USD per smallest unit of measure) were summarized using the median and interquartile range (IQR). Prices were compared by route of administration, supplier country, and product naming practice (INN-named versus brand-named) using Mann-Whitney U and Kruskal-Wallis tests with false discovery rate adjustment. Results Of the 14,301 records, 10,894 (76.2%) met the inclusion criteria. Oral antibiotics predominated (89.6%). Although the median oral antibiotic prices declined over time, substantial price dispersion persisted across all study years. Parenteral antibiotics were consistently more expensive (USD 0.755-3.370) and more variable than oral antibiotics. Importation was concentrated in a few medicines, with amoxicillin-clavulanate (16.7%) and amoxicillin (11.4%) accounting for over one-quarter of records, and in a few supplier countries, with India representing 44.9% of the records. Significant price differences between INN-named and branded products were observed for amoxicillin (adjusted p<0.001) and ciprofloxacin (adjusted p=0.018), whereas prices differed significantly by supplier country across major medicines (adjusted p<0.05). Across medicines and years, wide within-product price distributions indicate persistent market segmentation rather than price convergence. Conclusions Antibiotic import prices in Tanzania exhibit systematic and reproducible variations associated with formulation type, supplier origin, and product naming practices. The findings indicate that procurement structure and supplier participation strongly influence pricing in the import-dependent pharmaceutical market. Monitoring import-level prices can serve as an upstream indicator of market conditions and support evidence-informed procurement, pricing regulations, and antimicrobial stewardship policies in LMIC settings.

Because of its recent regulatory approval in southern and eastern Africa, CAB PrEP represents a scientific advancement with unknown implementation costs in most African countries. To our knowledge, this paper is the first study comparing PrEP costs in health facilities where clients had a choice between three PrEP methods. We collected and analyzed the direct service delivery costs for each method using the same costing approach and assumptions at three facilities in Lesotho and six facilities in Zimbabwe. On average, in Lesotho, the direct costs of providing CAB PrEP were $57.22 for an initiation visit and $54.20 for a refill visit (same PrEP product dose dispensed in both visit types), while the direct costs of oral PrEP were $22.47 (initiation visit with one month of PrEP dispensed) and $31.98 (refill visit dispensing a three-month dose of medication), and the direct costs of the dapivirine ring were $34.27 (initiation visit with one month of PrEP dispensed) and $50.70 (refill visit dispensing a three-month supply). In Zimbabwe, the average per-visit direct costs to provide CAB PrEP were $48.26 (initiation visit) and $47.40 (refill visit), to provide oral PrEP were $13.47 (initiation visit with one month of PrEP dispensed) and $21.78 (refill visit dispensing a three-month dose), and to provide the dapivirine ring were $42.56 (refill visit dispensing a three-month supply). Initiation visits for the dapivirine ring were not observed in Zimbabwe. At a time when national governments are creating budgets for the HIV response with decreased financial support from bilateral and multilateral partners, this paper will inform HIV prevention planning by providing critical client-level data from the healthcare provider perspective.

Background: Schistosoma mansoni is a leading cause of hepatosplenic disease in sub-Saharan Africa. Yet, associations with current Schistosoma mansoni infections and hepatosplenic organometry remain unclear in the context of widespread mass drug administration and co-endemic infections. Methods: From January to February 2024, we conducted a community-based, cross-sectional study nested within the SchistoTrack cohort in three districts of Uganda. Liver and spleen dimensions were assessed via point-of-care B-mode ultrasound for 3121 individuals. Organ dimensions were classified using the standard deviations from height-standardized internal reference values derived from an infection-free population. Multinomial logistic regressions were run for children (5-17 years) and adults (18+ years) separately. Population attributable fractions (PAFs) were used to estimate the proportion of abnormal organometry statistically attributable to each infection. Key exposures were S. mansoni, malaria, human immunodeficiency virus (HIV), and hepatitis B virus (HBV) alongside a comprehensive set of social, biomedical, and other covariates controlled for. Results: Moderate-to-severe splenic enlargement was observed in 29.1% (438/1507) of children and 23.3% (376/1614) of adults. Among adults, 20.9% (337/1614) had left liver lobe enlargement and 18.8% (303/1614) had right liver lobe shrinkage. In children, severe splenic enlargement was statistically attributable to malaria (PAF 46.7%; Relative Risk Ratio (RRR) 3.96, 95% CI 2.64-5.92) and S. mansoni infection intensity (PAF 23.6%; RRR 1.12, 95% CI 1.04-1.20). In adults, S. mansoni intensity was associated with moderate left liver lobe enlargement (PAF 12.4%; RRR 1.11, 95% CI 1.04-1.18). In adults, HIV was associated with severe left liver lobe shrinkage (RRR 4.50, 95% CI 1.19-17.00) and severe splenomegaly (RRR 3.62, 95% CI 1.58-8.33), while HBV was associated only with severe left liver lobe shrinkage (RRR 2.54, 95% CI 1.07-6.03). Praziquantel treatment in the past year showed inconsistent associations and no clear protective pattern. Conclusion: Current S. mansoni infection intensity remains associated with splenomegaly in children despite controlling for concurrent malaria positivity, and with hepatomegaly in adults despite HIV and HBV associations.

Background The microbial aetiology of early childhood caries (ECC) in sub-Saharan African populations remains poorly characterised, with most studies focusing on conventional cariogenic pathogens like Streptococcus mutans. This study aimed to characterise the salivary microbial profile of children with ECC in urban Kano, northern Nigeria. Methods In this cross-sectional study of 162 children aged 3-5 years in urban Kano, unstimulated saliva samples were collected and analysed using standard bacteriological culture methods. Caries status was assessed using decayed, missing, and filled teeth (dmft) index and International Caries Detection and Assessment System (ICDAS). Microbial isolates were identified through Gram staining, colony morphology, and biochemical tests (catalase, coagulase, oxidase). Results Of 32 microbial isolates obtained, Staphylococcus aureus was the most prevalent (43.8%, n=14), followed by Streptococcus species (28.1%, n=9), Klebsiella species (12.5%, n=4), non-aureus staphylococci (6.3%, n=2), yeast (6.3%, n=2), and Pseudomonas species (3.1%, n=1). Only one isolate demonstrated direct association with dmft-detectable caries. Polymicrobial colonisation occurred in four cases (12.5%), predominantly featuring S. aureus-yeast combinations (n=2). White spot lesions (ICDAS 1-2) were associated with S. aureus and Klebsiella species in two separate cases. Conclusion This study reveals an unexpected predominance of S. aureus in the salivary microbiome of children in northern Nigeria, challenging conventional paradigms of ECC microbiology. The low correlation between microbial isolates and clinical caries suggests complex, multifactorial aetiology. These findings highlight the need for molecular characterisation of oral microbiomes in African populations and reconsideration of caries pathogenesis models in this unique epidemiological context.

Despite the relevance of spatial mapping in analyzing the health situation and understanding the risk factors and determinants of leptospirosis, peripheral urban communities often remain invisible on maps, which tend to use data and methods that do not express community contribution nor promote local participation. Furthermore, in the implementation of sanitation interventions, the same happens: there is limited user participation, and a lack of identification of intervention needs based on the perception of community residents, failing the interventions. We conducted a cross-sectional study through collaborative mapping from February to October 2022 with 213 residents and self-declared heads-of-household in two peripheral urban communities. We analyzed the perception of sanitation needs indicated by residents and their relationship with the risk of leptospirosis in these communities. Based on community perception, sewage (NS: 87.1%; JSI/ME: 84.9%) and urban cleaning and solid waste management (NS: 25.9%; JSI/ME: 32.6%) were the sanitation needs. In NS, most participants indicated that the necessary interventions for sewage improvement were actions of sewer cleaning and sealing (26.5%), sewer cleaning and piping (23.5%), and implementation/installation/construction of a sanitary sewage network (41.4%). In JSI/ME, interventions included sewage sealing (48.7%) and piping (25.6%), in addition to actions to maintain sewage cleaning (93.3%). The removal of solid waste (trash) in the square (NS: 22.2%) and on the streets (JSI/ME: 69.2%), as well as community awareness (JSI/ME: 15.4%), were indicated as interventions to meet the needs of urban cleaning and solid waste management. Respondents agreed on where interventions should occur, which congregated around the local river. We found a negative correlation between the predicted leptospirosis seropositivity and perceived intervention needs in both study areas. The prevention of diseases such as leptospirosis in peripheral urban communities requires integrated basic sanitation interventions, encompassing different components and aligned with the local needs perceived by residents.

The spread of Anopheles stephensi into the Horn of Africa represents one of the main challenges for malaria control, given the species ecological plasticity and resistance to multiple insecticides. In response to the World Health Organizations 2022 vector alert, an adaptive, model-based spatial surveillance framework was developed and evaluated to improve detection, mapping accuracy, and operational responsiveness during invasion. Adaptive surveillance utilises initial observations to guide subsequent surveillance, linking the surveillance design to the underlying geographical characteristics of Anopheles stephensi distribution through observed data. This dynamic approach targets areas of high uncertainty and/or abundance, making the design responsive rather than predetermined. Focusing on Djibouti and selected regions of Ethiopia and Kenya, the adaptive surveillance was designed on previous in-country Anopheles stephensi surveillance data integrated with assembled open-source environmental, epidemiological, and demographic covariates. Key driver factors of the average monthly Anopheles stephensi catches varied geographically, although seasonality was universally important. Adaptive site allocation was optimised using a multicriteria target function which combines the trapping probability and uncertainty from previous surveys, with a simulation based on peaks-over-threshold (generalized Pareto) modelling of exceedances and Bayes factor-guided prioritisation. The selected adaptive surveillance design is the one that minimise the uncertainty in Anopheles stephensi trapping probability in hotspot areas. Optimal adaptive designs required between 50 to 59 sites per country, with uncertainty reductions in the probability of trapping projected up to 36% in Djibouti and more than 60% in Ethiopia and Kenya, with more than 60% site implementation halving uncertainty in Djibouti and Kenya and reducing it by up to 75% in Ethiopia. The proposed adaptive surveillance framework operationalises WHO guidance, accelerates hotspot identification, and inform targeted ecological studies and control interventions. It is extensible to other urban vectors (e.g., Aedes aegypti), enabling integrated, cross-border surveillance essential to contain Anopheles stephensi during ongoing invasion.

Background: In low- and middle-income countries, the burden of hypertension is increasing. Medication adherence is a critical component of reducing hypertension-related cardiovascular disease (CVD) risk and death. There are many barriers to hypertension medication adherence, including challenges with access to and possession of medication. To address these challenges, we aim to implement a strategy in rural western Kenya that combines peer delivery of medications and health information technology to improve hypertension medication possession and adherence. Recognizing that stakeholder experience and knowledge can be useful to optimize successful implementation, we sought to assess micro- and macro-level stakeholder perceptions of the planned implementation strategy. Methods: Focus group discussions in both English and Kiswahili were conducted among people living with hypertension, community members, and health workers. In addition, key informant interviews were conducted with public sector health administrators including the program/policy planners for non-communicable diseases at the national and county levels. Content analysis of all transcripts was conducted. A codebook containing deductive codes was generated based on a priori themes identified from the interview guide. These included the perceptions of peers being involved in health service provision, medication delivery, psychosocial support, and the use of health information technology. Emerging themes were also identified and integrated into the results. The investigator team pooled codes according to conceptual alignment and integrated them into common themes after joint review and discussion. NVIVO 12 was used for the data analysis. Results:The PT4A implementation strategy was perceived to have both benefits and potential challenges. Major themes included the importance of trust resulting from a safe space to share experiences with peers, increased access to medications, improved hypertension management at the facility and community levels, and anticipated improved health outcomes for people living with hypertension. The success of the program was felt to rely heavily on the peers competency and how well they communicated, which was viewed as a potential challenge by some stakeholders. Areas of consensus expressed across all participant groups were mostly focused on patient psychosocial support and access to medications. Conclusion: This study was able to identify key perceptions elicited for an implementation strategy that combines peer medication delivery and health information technology to improve hypertension medication adherence. Pre-implementation stakeholder engagement can unearth unique perspectives around perceived benefits and challenges that can be used to refine strategies to increase the success of implementing evidence-based interventions in new contexts.

Background The Hump-nosed pit viper is a recognized but neglected medically significant species causing morbidity and mortality, with non-availability of a specific antivenom. There are many gaps in our understanding of its envenomation, including burden, clinical syndrome, complications and management. Methodology The study is a retrospective sub analysis of the Prospective VENOMS registry and hospital records of Hump Nosed Pit Viper envenomation from a single tertiary care center in coastal Karnataka from May 2018 to March 2024. Epidemiology, syndrome, complications and treatment strategies have been described. A linear mixed model analysis was conducted to study the effect of different therapeutic interventions in combating venom induced consumptive coagulopathy (VICC) Principal Findings Of 46 cases, 24 patients had VICC. The most common complications were AKI (21.7%), TMA (10.9%) and stroke (4.4%). Anaphylaxis to ASV (23.9%) was the most common therapeutic complication. Therapeutic interventions included ASV, administration of blood products and therapeutic plasma exchange along with supportive care. The linear mixed model revealed that administration of blood products (p=<0.001) had the strongest influence on the INR value, however, often resulting in a transient decline in INR value. ASV (p=0.052) caused only marginally significant change in INR. The role of TPE could not be statistically inferred, however, individual cases with severe VICC improved without complications, therefore it required further study but can be considered in critical cases. Conclusions/Significance This study describes the syndrome of hump-nosed pit viper envenomation, while highlighting the urgent need for a species-specific antivenom, recommends treatment strategies that can be used in the interim. Additionally, geo-spatial mapping draws attention to hotspots and the hypothesis that HNPV in coastal Karnataka have regionally distinct toxicity trends.

Introduction Glomerular filtration rate (GFR) is invasive to measure. Therefore, in clinical care, estimated GFR is derived from serum levels of endogenous filtration markers such as creatinine and cystatin C. Multiple studies from high income countries showed differences between estimated glomerular filtration rate based on cystatin C (eGFRcys) and creatinine (eGFRcr). This study aimed to assess the agreement between eGFRcys and eGFRcr in Ethiopian children and identify factors influencing higher eGFRcys and eGFRcr. Method We studied 350 Ethiopian children who were part of the iABC birth cohort study. At the recent follow-up (average age 10 years), serum cystatin C and creatinine were measured. Formulas by Berg (2015) and Hoste (2014) were used to estimate eGFRcys and eGFRcr, respectively, and Bland-Altman plots assessed their agreement. The difference in eGFR (eGFRdiff) was calculated and categorized as less than -15 mL/min/1.73 m2 (higher eGFRcr), between -15 and <15 mL/min/1.73 m2 (concordant), and greater than or equal to 15 mL/min/1.73 m2 (higher eGFRcys). Multinomial logistic regression was used to identify factors associated with higher eGFRcr and higher eGFRcys. Result Estimated glomerular filtration rate (eGFR) showed significant variation based on the estimation formula used. When using formulas by Berg (2015) and Hoste (2014), the median (IQR) eGFRcys and eGFRcr were 99.4 (90.0; 114.1), and 123.2 (110.3; 143.8) mL/min/1.73 m2, respectively. Overall, we observed a poor agreement between eGFRcys and eGFRcr, with only 94 (27.6%) children having concordant results compared to 220 (64.7%) with higher eGFRcr and 26 (7.6%) with higher eGFRcys. If the eGFRcys results are considered reliable, 27.5% of the children had eGFR below 90 mL/min/1.73 m2. Conclusion There was very marked variation in the distributions of estimated eGFRs depending on which formulas for children were used. Agreement between eGFR estimated using cystatin C and creatinine was poor among Ethiopian children. Relative to eGFRcys, kidney function may be overestimated by creatinine-based equation as up to 30ml/min in Ethiopia. Ideally, a validation study with GFR measured by gold standard methods (Inlulin clearance) among children is required. However, because of its invasive nature and financial concerns, Iohexol clearance studies are recommended.

From 2021 to 2025, MRSA emerged as a major multidrug-resistant pathogen in the study area. Among 545 S. aureus isolates, 67.2% were MRSA, disproportionately affecting children under five (26.5%) and males (55.5%). Case incidence more than doubled by 2025, suggesting rising transmission or resistance. Most isolates were hospital-associated (85.2%), predominantly from outpatients (88.5%), with middle ear discharge as the main source (67%). Gentamicin showed the highest susceptibility (72.1%), while penicillin G resistance was nearly universal (96.7%). The majority (93.4%) were multidrug-resistant, with high MARI values indicating widespread and likely inappropriate antibiotic use. These findings reflect a complex interplay between pathogen behavior, antimicrobial use, and healthcare practices. Increasing MRSA burden may stem from inadequate infection control, poor stewardship, or enhanced community transmission. Incorporating molecular typing could deepen understanding of strain diversity and resistance mechanisms to guide targeted interventions

Background: Type 2 diabetes is a growing challenge in low- and middle-income countries, where health systems face major capacity gaps. Participatory learning and action (PLA) has shown effectiveness in preventing type 2 diabetes in Bangladesh, but little is known about its use in other LMICs for diabetes. The EMPOWER-D (Engagement of community through Participatory learning and action for cOntrol and prevention of type 2 diabetes) trial is testing PLA for diabetes prevention in communities in Pakistan and Afghanistan. This protocol describes the plans for the embedded process evaluation (PE). Methods: The PE will use a mixed-methods design across three sites, following the UK Medical Research Council framework for PE, examining implementation, mechanisms of impact and context. Implementation will be assessed using adaptation reports, fidelity checklists, attendance data, and supervisor reports. Mechanisms of impact will be explored through interviews, focus group discussions and photovoice. Contextual factors will be examined through interviews with participants, community mobilisers, supervisors, and key stakeholders. Quantitative data will be analysed descriptively, while qualitative data will undergo thematic analysis using a theory of change framework. Comparative analysis will identify common and context-specific influences. Discussion: This is the first multi-country PE of a PLA intervention for diabetes prevention to our knowledge, and the first in Afghanistan and Pakistan. The study will provide insights into how the intervention was delivered, how and why it worked (or did not work), and the contextual factors shaping outcomes. Findings will inform the adaptation and scale-up of participatory approaches for non-communicable disease prevention in resource strained setting health systems.

Abstract Background: Urinary tract infections (UTIs) are common health issue during pregnancy, often lead to adverse maternal and neonatal outcomes if left untreated, low knowledge contribute to high UTI rates, particularly in resource-limited settings like Jordan. To assess the knowledge levels about UTIs among pregnant women in Jordan and its association with socio-demographic characteristics. Methods: A descriptive cross-sectional study was conducted among 500 pregnant women attending antenatal clinics in four major governmental hospitals across Jordan. Data were collected using a validated questionnaire based on the Theory of Planned Behavior (TPB) comprising 25 questions, including 5 socio-demographic questions and 20 knowledge questions, scores were categorized as "adequate" or "inadequate" based on the median score. Results: Among participants, 51.4% had inadequate knowledge, while 48.6% demonstrated adequate knowledge. Higher knowledge levels were significantly associated with younger age (21-30 years), urban residence, higher education (university and postgraduate), and employment status. Conclusion: The findings highlight a knowledge gap among pregnant women regarding UTIs. Integrating targeted health education and addressing socio-demographic disparities into antenatal care, especially for women with low education and rural residence, may improve maternal outcomes. Keywords: Urinary tract infection, Knowledge, Pregnancy, Antenatal care, Jordan, Maternal health.

Background Acute malnutrition remains a major public health challenge among children under five in Malawi due to undetected and untreated cases. While several policies and programmes are in place, they face significant resource input and implementation constraints. In this study, we evaluate the potential health impact and cost-effectiveness of three interventions designed to address constraints along the care pathway in childhood acute malnutrition management. These include improving early recognition of symptoms by caregivers, increasing attendance at routine growth monitoring visits through community outreach, and scaling up the availability of therapeutic food supplements. Methods and Findings We use a newly developed model representing the natural history and management of acute malnutrition, implemented within the Thanzi La Onse (TLO) dynamic individual-based simulation framework, which captures the public health system in Malawi. Each of the three interventions is assessed both individually and in combination, translated into seven scenarios which we evaluate in comparison to the status quo. The optimal strategy combines two interventions, improved caregiver awareness of early symptoms with increased availability of therapeutic food supplements. Over five years, this strategy is predicted to avert 840,470 (95% CI: 682,057-998,883) DALYs with total incremental costs of $34 million. This corresponds to an annual health expenditure increase of $0.32 per capita. At a cost-effectiveness threshold of $76 per DALY averted, the strategy results in an incremental net health benefit of 394,252 (95% CI: 235,839-552,665) DALYs averted. Conclusions The cost-effective strategy for addressing constraints in childhood acute malnutrition management is simultaneously improving caregiver recognition of early symptoms and expanding therapeutic food supplement availability. Out of the seven scenarios evaluated, this integrated approach was found to be the optimal strategy within the Malawian public health system, yielding substantial health at modest costs. These findings provide critical evidence to inform national policy and guide investment prioritisation for the management of childhood acute malnutrition.

Objective To test the effectiveness of a postpartum behavioural intervention delivered by automated text messaging in reducing weight. Design Two parallel group, multicentre, randomised controlled trial. Setting Recruitment from five areas across the United Kingdom (Belfast, Bradford, Stirling, London and Cardiff) through healthcare and community pathways, including social media. Participants A diverse sample of 892 women between 6 weeks and 24 months postpartum, aged 18 years or more and with a body mass index of 25 kg/m2 or more, enrolled between May 2022 and May 2023: 445 were randomised to the intervention and 447 to an active control (comparator). Interventions Twelve months of fully automated text messages with embedded behaviour change techniques and two-way messaging components to support weight loss and maintenance of weight loss in the postpartum period by targeting dietary, physical activity and weight management behaviours. The comparator group received 12 months of text messages on child health and development tailored to child age. Main outcome measures Primary outcome: weight in kilograms at 12 months (end of intervention). Secondary outcomes recorded at 6 and 12 months were changes in weight (at 6 months), body mass index, proportions of women with weight gain or loss of 5 kg or more, waist circumference, self-reported dietary intake, physical activity and infant feeding practices. Results 674 (75.6%) participants were included in the primary analysis. There was no statistically significant difference found in the adjusted mean weight change between the intervention and active control groups (-0.1 kg (95% confidence interval -1.0 to 0.8, P= 0.84). Sensitivity analyses did not change these results. There was a small statistically significant improvement in Fat and Fibre Barometer scores at 12 months in the intervention compared with control group (adjusted mean difference 0.09, 95% CI: 0.04 to 0.14; P <0.001) and a statistically significant increase in physical activity scores (International Physical Activity Questionnaire Short Form) at 12 months in the intervention group compared with the control group (adjusted mean difference 405.3 total MET minutes/week, 95% CI: 141.3 to 669.3; P= 0.003). Conclusions A 12 month automated, interactive behavioural weight management intervention delivered by text message did not support weight loss for postpartum women but did have a positive impact on diet and physical activity behaviours.

Introduction Heat waves are increasingly frequent and linked to higher mortality risks in Hong Kong. However, estimates of total excess mortality associated with heat waves remain unavailable. This study quantifies excess deaths associated with heat waves in Hong Kong from 2014 to 2023. Methods Daily age- and sex-specific mortality rates and population data were obtained from the Hong Kong Life Tables and Census and Statistics Department. Temperature data came from the Hong Kong Observatory, and relative risks were derived from local research. A Monte Carlo simulation was used to estimate heat-attributable deaths under different heat wave definitions, calculating total excess deaths and annualized death rates per 100,000 population. Results Between 2014 and 2023, heat exposure resulted in an estimated 1,455 (95% CI: 1,098-1,812) to 3,238 (95% CI: 3,234-3,242) excess deaths. In 2023, annualized excess death rates ranged from 2.95 (95% CI: 2.41-3.50) to 5.09 (95% CI: 5.07-5.12) per 100,000 people. Males and individuals aged 65 or older were disproportionately affected. Conclusion Over the 10-year study period, 1,455 to 3,238 excess deaths in Hong Kong were attributed to extreme heat. Heat waves now rank among the top ten causes of death in Hong Kong, with mortality rates comparable to diabetes. These findings underscore the need for urgent public health interventions to mitigate the impact of extreme heat.

Understanding host susceptibility to Mycobacterium tuberculosis (Mtb) is critical for the development of new vaccines. Certain individuals "resist" becoming infected with Mtb despite intensive exposure; however, it is unknown whether there is a genetic basis for "resistance" to Mtb infection across populations. Here we conducted a genome-wide association study (GWAS) of resistance to Mtb infection by carefully characterizing exposure to TB patients among 4,058 close contacts in India, Brazil, and South Africa. 476 (12%) "resisters" remained free of Mtb infection despite substantial exposure to highly infectious TB patients. GWAS identified a novel chromosome 13 locus (rs1295104126) associated with resistance across the multi-ancestry meta-analysis. Comparing Mtb-infection to all uninfected contacts, irrespective of exposure, yielded a different locus on chromosome 6 (rs28752534), near the HLA-II region. These findings demonstrate a common genetic basis for resistance to Mtb infection across multi-ancestral cohorts with potential to elucidate novel mechanisms of protection from Mtb infection.

Background Persistent inequities in immunisation coverage, particularly among zero-dose and under-immunised children, continue to challenge Pakistan's Expanded Programme on Immunization. Weak feedback loop, inconsistent data quality, and limited real-time monitoring impede effective decision-making. This Implementation Research was conducted under the MAINSTREAM Initiative funded by Alliance for Health Policy and Systems Research (AHPSR) and supported by the Aga Khan Community Health Services Department and National Institutes of Health Pakistan to design, implement, and evaluate a digital monitoring and action planning tool to strengthen data-driven decision-making within routine immunisation systems. Methodology/Principal Findings A co-creation approach was employed to design a digital monitoring solution through inclusive consultations, key informant interviews, and focus group discussions with EPI Punjab at provincial and district levels. The solution included a customised mobile application for data collection and a Power BI visualisation dashboard to map low-coverage areas, identify drivers of dropouts and zero-dose children, and capture caregivers' information sources to inform targeted communication. The intervention was piloted in 60 households across six clusters of a Union Council of District Lahore. Advanced analytics identified reasons for non-vaccination and missed opportunities, generating tailored recommendations and practical plans for program managers. The analysis assessed acceptability, adoption, fidelity, and perceived scalability through field observations, system use, and stakeholder feedback. The co-developed digital tool enhanced visibility of coverage gaps through UC-level mapping, real-time dashboards, and structured action planning. Pilot testing in Lahore showed strong acceptability, ease of use, fidelity, and adaptability among managers, supervisors, and vaccinators. Scalability and sustainability potential were demonstrated, though barriers included leadership turnover, system fragmentation, workload pressures, and resource constraints. Conclusion The tool demonstrated feasibility to strengthen immunisation equity, accountability, and responsiveness. Co-creation with stakeholders enhanced ownership, operational relevance, and adoption, while complementing existing platforms. Sustainability will depend on effective integration, local ownership, capacity building, and accountability, while scalability requires interoperability, resource commitment, policy support, and alignment with existing workflows.

The use of semaglutide (SE), a glucagon-like peptide-1 receptor agonist (GLP-1RA) with glucose-lowering and weight-loss effects, has risen rapidly, particularly among women of reproductive age. While preclinical studies suggest benefits for ovarian function via the hypothalamic-pituitary-ovarian axis, its impact on the endometrial-embryo interface remains unclear. Here, we show that GLP-1R is dynamically expressed in fertile human endometrium, restricted to epithelial cells and markedly upregulated during the mid-secretory phase of the menstrual cycle. In a preclinical model of endometrial epithelial organoids, SE at physiological concentrations activates intracellular cAMP signaling, enhances epithelial metabolism, and upregulates receptivity markers without steroid hormone priming, whereas higher concentrations modestly reduce expression of a key receptivity marker PAEP/glycodelin and shift metabolism towards oxidative phosphorylation. By contrast, in stromal cells lacking detectable GLP-1R, SE disrupts decidualization, induces endoplasmic reticulum stress and suppresses cell-cycle at G2/M phase. Human embryo models, blastoids, expressed GLP-1R and underwent concordant SE-mediated transcriptional remodeling in epiblast and trophectoderm lineages, encompassing changes in metabolism and epigenetic regulation, but without shifts in lineage proportions. Notably, SE increased blastoid attachment to the endometrial epithelium in the absence of exogenous steroid hormones, suggesting enhanced epithelial-embryo interaction. Together, these findings reveal a compartment-specific mismatch, as SE augments epithelial and embryonic metabolic activity but compromises stromal support for implantation, with potential consequences for implantation due to stromal dysfunction.

Background: Quadriceps weakness may reduce sagittal plane shock absorption during landing, shifting load toward the frontal plane and increasing knee abduction moment (KAM), a biomechanical risk factor for anterior cruciate ligament (ACL) injuries. Purpose: The purpose of this study was to evaluate the association between isokinetic quadriceps strength and peak KAM during drop vertical jump landing in adolescent athletes. Study Design: Secondary analysis of previously collected data. Methods: Healthy adolescent athletes completed quadriceps strength testing using an isokinetic dynamometer and a biomechanical assessment during a drop vertical jump task. Quadriceps strength was quantified as peak concentric torque and the peak external KAM was calculated during the landing phase on the dominant limb. Both strength and KAM were normalized to body mass. Linear regression was used to examine the association between normalized quadriceps strength and peak external KAM on the dominant limb. Results: The association between quadriceps strength and peak normalized KAM on the dominant limb was not statistically significant ({beta} = -0.053 (95% CI [-0.137 to 0.030]), F(1,119) = 1.62, R2 = 0.013, p = 0.206). Quadriceps strength explained only 1.3% of the variance in peak KAM, indicating a negligible association between these variables in this cohort. Discussion: Quadriceps strength was not associated with peak normalized KAM during landing, suggesting that frontal-plane knee loading during a drop vertical jump is not meaningfully explained by maximal concentric quadriceps strength alone. KAM appears to be driven more by multi-joint movement strategy and neuromuscular coordination than by the capacity of a single muscle group.

Objectives: Compare Anterior Cruciate Ligament (ACL) Return to Sport after Injury (ACL-RSI) scores over time following ACL reconstruction (ACLR) between male and female patients aged 15 to 25 years with primary ACL injuries and ACL reinjuries. Design: Retrospective cohort design. Setting: Sports physical therapy clinics. Participants: 332 patients aged 15-25 years who underwent ACLR following either primary ACL injury or ACL reinjury, either contralateral or ipsilateral graft reinjury, and had at least one observation of the ACL-RSI. Main Outcome Measures: ACL-RSI score. Results: ACL-RSI scores significantly increased over time post- ACLR (p < .001), males reported significantly higher scores compared to females (p < .001), and patients with contralateral ACL reinjury demonstrated higher scores than those with ipsilateral ACL graft reinjury (p = .006), though there was no difference in scores between patients with primary ACL injury and ACL reinjury. A significant interaction effect of sex and injury status was also observed (p = .009), generally demonstrating that females had lower psychological readiness compared to males across injury statuses. Conclusions: ACL-RSI following ACLR varies based on biological sex and time post-ACLR, though ACL reinjury, independent of the reinjured leg, does not appear to effect scores compared to primary ACL injury.