Tropical Medicine and Infectious Disease

Background/aims The World Health Organization (WHO) aims to eliminate schistosomiasis as a public health problem (EPHP) across 78 endemic countries by 2030. However, for low-prevalence settings that reach EPHP, guidance on managing transmission to maintain EPHP or move towards Interruption of Transmission (IoT) is limited, partly due to insufficient evidence on drivers of resurgence. In Uganda, some communities inland from Lake Victoria have achieved EPHP for Schistosoma mansoni but not progressed to IoT. This study explored whether routine, short-range travel to the highly endemic lake could sustain transmission in these settings. Methods We conducted a cross-sectional study in five Ugandan villages ~5 km from Lake Victoria. Parasitological data were collected using Kato-Katz and Point-of-Care Circulating Cathodic Antigen tests, alongside questionnaires on lake travel from 585 individuals aged 1-91 years. A structural causal model estimated the total and direct effects of travel frequency, activity type, water contact duration, and drug treatment history on infection. Bayesian regression models and counterfactual simulations predicted infection under hypothetical interventions. Results Reaching IoT in low-risk villages may be undermined by habitual, short-range travel to high-risk sites, driven by the nature and duration of lake contact. Daily lake travel caused a 1.7-fold increase in odds of infection, while occupational activities caused a 3.4-fold increase compared with no lake activity. Counterfactual analysis showed that removing lake contact duration most reduced infection risk among moderate-frequency travellers, while daily travellers showed smaller changes, and some transmission persisted among individuals with little or no lake contact. Simulations demonstrated that modifying lake contact behaviours could reduce individual infection risk but had limited population-level impact. Conclusion These findings indicate that targeting only high-risk villages or individual behaviours is unlikely to achieve sustained, wide-spread IoT, underscoring the need for integrated control strategies that account for mobility, behaviour, and local transmission ecology.

Background: Since September 2024, France has implemented a national reform allowing prescription-free access (PFA) to sexually transmitted infection (STI) screening in medical biological laboratories (MBLs). This study aims to characterize the populations undergoing STI testing according to their access modality and evaluate the probability of test positivity in relation to testing pathway, sex, and age groups. Methods: We conducted a cross-sectional analysis of all individuals screened for Chlamydia trachomatis, Gonorrhoea, human immunodeficiency virus (HIV), hepatitis B virus (HBV), and syphilis by treponemal-specific immunoassay (TSI) in Cerballiance MBLs between Mars 2025 and February 2026. Multivariable logistic regression models stratified by sex and adjusted for age and region assessed associations between screening modality and STI positivity. Results: Among 1,008,737 individuals included, 27.8% were under PFA and 72.2 under prescription-based access (PBA). PFA users were more frequently male (47.4% vs. 36.3%, p<0.001) and aged 20-39 years (34.0%, p<0.001). Overall positivity rates differed by modality: PFA was associated with higher detection of Chlamydia (4.6% vs. 3.6%). PBA group showed more positive cases of syphilis (3.4% vs. 1.2%), HBV (1.3% vs. 0.4%), and HIV infections (0.3% vs. 0.2%, all p<0.001). Co-infection and gonorrhoea proportions did not significantly differ between modalities. Conclusions: PFA substantially increased STI screening uptake, particularly among young adults and men, and enhanced detection of bacterial STIs. PBA remains essential for diagnosing viral and chronic infections. These findings highlight the complementary roles of both access strategies and support PFA screening as an effective public health intervention to broaden STI detection and reduce transmission.

BackgroundAnimal bites represent a significant public health concern due to the risk of injuries and transmission of zoonotic diseases such as Rabies, particularly in low and lower- middle-income countries (LMICs). Understanding the epidemiological characteristics of animal bite incidents is essential for improving the prevention and control strategies. This study aimed to characterize the epidemiological patterns and characteristics of animal bite cases in Sylhet, Bangladesh. Methodology/Principal findingsWe conducted a retrospective analysis of 6,565 animal bite cases reported between January 1 and December 31, 2024, in Sylhet, Bangladesh. Data on demographic characteristics, type of biting animal, site of bite, and exposure category were collected and analyzed to determine associations using correlation analyses and chi-square tests. Among the victims, 3,917 (60%) were male and 2,648 (40%) were female and young adults aged 20-39 years comprised the largest group (39% of cases). The majority of cases (88.1%) originated from urban areas within Sylhet City Corporation. Cats were the leading cause of bites (56.6%), followed by dogs (35.0%) and monkeys (7.5%), suggesting a shift from the traditional dog-dominated pattern. The most frequently affected anatomical sites were the legs (50.3%) and hands (40.9%). Most exposures were classified as World Health Organization (WHO) Category II (98.2%). Bite incidents showed moderate seasonal variation, with peaks in spring and early autumn. A significant declining temporal trend was observed for monkey bites (R = -0.59, p = 0.044), whereas cat and dog bite patterns remained relatively stable throughout the year. Significant associations were identified between bite site and age group, as well as between biting animal and demographic characteristics (p < 0.05). Conclusion/SignificanceThese findings highlight the epidemiological patterns of animal bites in Sylhet and emphasize the need for strengthened public awareness, surveillance, and preventive strategies to reduce animal bite incidents and associated zoonotic disease risks. SynnopsisO_LIA large-scale retrospective analysis of 6,565 animal bite cases revealed a cat-dominant bite pattern (56.6%), contrasting with the traditional dog-dominant paradigm in South Asia. C_LIO_LIYoung adults (20-39 years) and males (60%) were disproportionately affected, reflecting occupational and behavioral exposure risks. C_LIO_LIUrban residents (88.1%) accounted for the majority of cases, highlighting the growing public health burden of animal bites in rapidly urbanizing settings. C_LIO_LIThe most frequently affected anatomical sites were the legs (50.3%) and hands (40.9%). Bite incidents showed moderate seasonal variation, with peaks in spring and early autumn. C_LIO_LICategory II exposures (98.2%) predominated, indicating a high burden of seemingly minor injuries that may be underestimated in rabies prevention strategies. C_LI

Objectives: In Latin America, up-to-date information to monitor UNAIDS 95-95-95 HIV targets in key populations, such as men who have sex with men, is limited. Elsewhere, structural homophobia restricts access to ART. Conceptual frameworks suggest that intersecting forms of violence and discrimination may negatively influence HIV care outcomes through psychosocial and structural pathways, although empirical evidence remains limited. The study aimed to assess whether sexual orientation outness and recent homophobic violence are associated with not being on ART among Latin American MSM living with HIV. Methods: This cross-sectional study is a secondary analysis of data from LAMIS-2018, including 7,609 MSM aged 18+ with an HIV diagnosis [&ge;]1 year prior from 18 Latin American countries. Participants self-reported ART status, sociodemographic characteristics, homophobic violence, and sexual orientation outness. Bivariate and multivariate logistic regressions identified those factors associated with not being on ART. Results: Nine percent of MSM with HIV were not on ART, 18% reported low sexual orientation outness, and 27% experienced homophobic violence, especially in Andean and Central American countries. Not being on ART was associated with recent homophobic violence (aPR=1.25), low outness (aPR=1.22), unemployment (aPR=1.27), and residence in the Andean subregion (aPR=1.87), Mexico (aPR=1.28), or the Southern Cone (aPR=1.45) versus Brazil. Protective factors included being older (25-39: aPR=0.72; >39: aPR=0.49), living in large cities (aPR=0.72), having a stable partner (aPR=0.78), and university education (aPR=0.74). Conclusions: Recent homophobic violence and low sexual orientation outness were associated with not being on ART among MSM in Latin America. While access varies across countries, structural factors such as stigma and violence may limit engagement in care. Addressing these barriers alongside strengthening health systems may be key to improving ART uptake and advancing progress toward the 95-95-95 targets.

Background: HIV/AIDS remains a major public health challenge in Tanzania, where viral load suppression among adults on ART stands at 78% and HVL testing uptake among eligible patients is approximately 22%. Since the introduction of the National HVL Testing Guideline in 2015, little has been done to systematically evaluate its implementation. Objective: To evaluate adherence to the National HVL Testing Guideline across CTC clinics in Dar es Salaam Region, covering ART monitoring, documentation, turnaround time, and factors affecting implementation. Methods: A cross-sectional study was conducted in 2021 across 15 public health facilities with CTC clinics in all five Dar es Salaam districts. A total of 330 PLHIV on ART for more than six months were selected through systematic random sampling with proportional to size allocation, and 45 healthcare providers through convenient sampling. Data were collected via abstraction forms and self-administered questionnaires, and analysed using SPSS Version 23 with descriptive statistics, bivariate analysis, and binary logistic regression. Results: Only 25.1% of patients had their first HVL sample taken at six months as per guideline, with 68.8% delayed beyond six months. Second and third samples were similarly delayed. MoHCDGEC sample tracking forms were absent in 96.7% of facilities and incomplete in 99.1%, and no facility captured specimen acceptance or rejection as site feedback. Turnaround time exceeded the 14-day guideline threshold in 64.5%, 66.7%, and 69.4% of first, second, and third results respectively. Patient negligence (AOR=9.84; 95% CI: 1.83-52.77) and storage (AOR=5.72; 95% CI: 0.94-35.0) were independently associated with guideline adherence. Conclusion: Adherence to the National HVL Testing Guideline in Dar es Salaam is suboptimal across testing timelines, documentation, and turnaround time, with patient negligence and storage capacity as significant determinants. Targeted interventions are needed to strengthen patient education, improve storage infrastructure, enhance documentation systems, and support providers in adhering to guideline-specified timelines.

Introduction: The need to collaborate with community partners has long been considered essential for achieving sustainable HIV prevention and treatment. While the level of youth engagement in research varies by project, it is important that youth collaboration and partnership is meaningful and measurable. We previously conducted a survey that aimed to assess the acceptability of providing SRH/HIV services for young women at hair salons in Lesotho. The survey relied on participatory research with several community partners who were fundamental to its implementation. This study reports on the lessons learned from these participatory processes. Methods: The Hair SALON survey was conducted in Lesotho between December 2023 and August 2024. For the present study, we used the Report of Engagement in Community Research (REACH) tool to systematically define the various depths of engagement of stakeholders at different stages of the research. In addition, we conducted semi-structured individual interviews with the four young community partners who were involved as the Hair Salon Expert Group (HSEG) throughout the project, and a subset of six stylists who helped enroll clients to fill in the questionnaires. The audio-recorded interviews were transcribed, translated, and coded using thematic analysis. Results: Challenges to engagement with the research project included the lack of full understanding of the project team's expectations (for the HSEG), and difficulty engaging potential participants due to mistrust and the sensitive content of the project (for the stylists). As possible mitigation strategies, interviewees suggested developing better community dissemination efforts prior to the project start, and providing more training to the community partners. Facilitators for engagement included multiple altruistic, professional development, and material incentives. Conclusions: Our findings highlight that a participatory approach across all research phases is feasible and that various facilitators - beyond material incentives - motivate youth community partners to be part of such a project. However, some barriers remain. It is important to increase efforts to clarify community partners' roles and responsibilities beyond written agreements, which in turn improves their perceived ownership of the research.

BackgroundLymphatic filariasis remains a public health concern in many endemic regions, where chronic disease persists despite substantial reductions in transmission. In Ghana, more than two decades of mass drug administration have significantly reduced disease prevalence and transmission; however, chronic manifestations and gaps in community understanding continue to be reported in parts of the north. This study assessed infection status, chronic morbidity burden, and community knowledge in a rural setting in northern Ghana approaching elimination. Methodology/Principal FindingsA community-based cross-sectional study was conducted in Birifor, northern Ghana, from October 2024 to January 2025. A total of 261 residents aged ten years and above were selected using random sampling. Data collection included structured questionnaires, clinical examination for chronic disease, and night blood microscopy for the detection of infection. No microfilariae were detected (0/261; 0%). However, chronic lymphoedema was identified in five individuals (1.9%), all aged over 40 years. Awareness of the disease was high (95.8%), yet only 39.5% of participants demonstrated good community knowledge and perceptions and self-reported preventive practices. Misconceptions regarding transmission, particularly beliefs that the disease is hereditary or caused by spiritual factors, were common. Participation in mass drug administration was high (93.1%). Despite this, chronic disease imposed a notable socioeconomic burden: all affected individuals reported loss of income, and 60% reported additional household income loss due to caregiving. Conclusions/SignificanceThese findings suggest that transmission in the study area is likely very low, although residual infection cannot be excluded; however, chronic disease and gaps in community knowledge persist. Strengthening morbidity management, improving community education, and providing support for affected households are essential. Sustained surveillance and integrated approaches will be critical to prevent resurgence and support long-term elimination efforts. Author SummaryLymphatic filariasis, also known as elephantiasis, is a mosquito-borne disease that can cause long-term swelling of the legs, arms, or genitals. Global efforts have greatly reduced its occurrence, especially through repeated mass drug administration to afflicted communities. However, many people continue to live with chronic swelling caused by past infections, which can affect their ability to work and participate fully in daily life. In this study, we examined the current situation of lymphatic filariasis in a rural community in northern Ghana that has received many years of treatment. We tested people for active infection, assessed signs of chronic disease, and explored what community members know and believe about the disease. We found no evidence of active infection, suggesting that transmission is now very low. However, some individuals were still living with chronic swelling and reported loss of income, while households also experienced financial strain due to caregiving. Although most people had heard of the disease, many did not fully understand how it is transmitted. Our findings show that reducing transmission alone is not enough. Continued education, community support, and access to care are needed to address the long-term impact of the disease and support ongoing elimination efforts.

Background Nepal has set a goal to eliminate lymphatic filariasis (LF) by 2030. As of 2024, Nepal has stopped the mass drug administration (MDA) in 56 of the 64 endemic districts and completed two rounds of MDA in six districts with persistent LF ([&ge;]2% antigen prevalence) using the three-drug regimen of Ivermectin, Diethylcarbamazine, and Albendazole (IDA), exceeding 65% coverage. We subsequently conducted an Epidemiological Monitoring Survey (EMS) to assess the impact of the MDA in reduction of LF infection prevalence below the transmission threshold and examine the factors associated with it. Methods We conducted a cross-sectional EMS nine months after MDA in 12 evaluation units (EUs) across six districts, with two sites per EU. We recruited a total of 7,343 individuals aged [&ge;]20 years, sampled using multi-stage sampling, ensuring at least 300 blood samples collected per site. We collected data on demographics and MDA participation. We performed the LF antigen testing for all participants, followed by night blood microfilariae testing in antigen-positive individuals. Statistical analyses included non-parametric tests, Chi-square and Fishers Exact tests, and multivariable logistic regression to assess outcomes after adjusting for potential confounders. Results Nine of 12 evaluation units (EUs) recorded <1% microfilaremia, meeting the WHO threshold for passing EMS, while three EUs failed with [&ge;]1% prevalence in at least one site. Antigen and MF prevalence were 4.47% and 0.34%, respectively (ratio 13:1). Both Antigen and MF prevalences were significantly associated with female sex (AOR= 0.564, 95% CI: 0.441-0.721 and AOR = 0.326, 95% CI: 0.129-0.826 respectively) and participation in the most recent MDA round (AOR = 0.477; 95% CI: 0.385-0.591 and AOR = 0.089; 95% CI: 0.017-0.464 respectively). MDA uptake was influenced by age (<40 years, AOR = 0.72; 95% CI: 0.653-0.793), sex (female, AOR = 1.438; 95% CI: 1.29-1.603), cross-border residence (AOR = 0.616; 95% CI: 0.558-0.681), and occupation (agriculture and housewife, AOR = 1.144; 95% CI: 1.008-1.298). MF prevalence was also associated with younger age (<40 years, AOR = 0.211; 95% CI: 0.071-0.626). Conclusion The survey indicates progress toward LF elimination, with nine of twelve EUs achieving WHOs <1% microfilaremia threshold after two rounds of IDA-MDA. However, transmission persists in three sites, likely linked to poor MDA participation among specific subgroups--particularly males, younger adults, and cross-border populations. Strengthening MDA coverage and compliance across all demographic and occupational groups, with special focus on border areas, is essential to achieve LF elimination in Nepal.

Background: In sub-Saharan Africa where both tuberculosis (TB) and HIV are prevalent, empiric TB treatment in people living with HIV (PLHIV) persists due to limited sensitivity of sputum-based TB tests. We evaluated mortality among molecular test-negative presumptive TB adult PLHIV in a population where the majority are or have been on antiretroviral therapy (ART), comparing mortality between those who received empiric TB treatment and those who did not. Materials and Methods: From November 2017 to December 2020, Xpert-negative presumptive TB adult PLHIV were recruited at Mulago Referral Hospital and Kisenyi Health Centre-IV in Kampala, Uganda. Clinical data including TB symptoms, chest X-ray, and empiric TB treatment decision were collected. Laboratory investigations included CD4 cell count, serum cryptococcal antigen (CrAg), urine TB-lipoarabinomannan (TB-LAM), microbiological blood cultures, and sputum mycobacterial growth indicator tube (MGIT) cultures. Participants were followed monthly for 12 months to ascertain vital status. Results: Overall, 300 participants were enrolled; 61.3% inpatients, 55.7% female, median age 37 (IQR 29-45) years, 82.3% on ART, median CD4 206 cells/mm3 (IQR 36-507). Of the 300 participants, 68 (22.7%) received empiric TB treatment, of which 53 (77.9%) were inpatients. 12-month mortality was 31.0% (93/300); 91.4% among inpatients, 72% within three months post-enrolment. Mortality was higher among those who received empiric TB treatment (51.5 vs. 30.2 per 1,000 person-months; p=0.013) compared to those who did not. TB cultures were positive in 5.0% (15/300), of whom seven (46.7%) were also TB-LAM positive. CrAg was positive in 12.3% and 3.7% had positive blood culture. Conclusion: We found high mortality among Xpert-negative PLHIV, particularly those who received empiric TB treatment, despite high ART coverage. Cryptococcal antigenemia and bacteremia were not uncommon. In presence of negative Xpert results in PLHIV, clinicians should perform extensive laboratory evaluations to identify possible comorbidities or alternative non-TB diagnosis.

BackgroundTuberculosis (TB) remains a leading cause of morbidity and mortality among people living with HIV (PLHIV), who face a 12-fold higher risk of active TB reactivation than HIV-negative individuals. TB preventive therapy (TPT) is an effective intervention, yet TB/HIV co-infection persists at 40-45%, raising questions about the durability of a single course of TPT. This study assessed the time from TPT completion to TB diagnosis and predictors of early TB reactivation. MethodsWe conducted a retrospective case-only cohort study using routine data from Ugandas electronic medical record system, TB registers, and patient files at three TASO Centres of Excellence (Soroti, Mbale, Tororo). PLHIV on antiretroviral therapy (ART) diagnosed with TB after completing TPT between 2022-2024 were included. Participant characteristics and time to TB diagnosis were summarised descriptively; predictors of early TB were identified using logistic regression. ResultsAmong 670 participants, most were female (464, 69.3%) with mean age 51.6 years (SD 14.5). Newly diagnosed TB accounted for 638 (95.2%), including bacteriologically confirmed pulmonary TB (535, 79.9%), clinically diagnosed TB (123, 18.4%), and extrapulmonary TB (12, 1.8%). Overall, 548 (82.8%) participants were virally suppressed, with most on Dolutegravir-based regimens (641, 95.7%). Early TB occurred in 144 (21.5%), with average time to diagnosis 2.6 years. Multivariable analysis showed care at TASO Soroti was protective (aOR = 0.104, p < 0.001), while clinically diagnosed TB (aOR = 1.91, p = 0.007), shorter ART duration (<5 years: aOR = 3.07, p = 0.001; 5-10 years: aOR = 1.74, p = 0.018), and viral suppression (aOR = 1.87, p = 0.014) increased odds of early TB. ConclusionsTB can occur soon after TPT completion, with one in five PLHIV developing early disease particularly those with shorter ART duration despite viral suppression. Strengthening TB screening, continuous monitoring, and repeat TPT for high-risk groups may improve prevention.

The global ambition to end the human immunodeficiency virus (HIV) epidemic requires understanding which system-level policy levers, enacted under the framework of Universal Health Coverage (UHC), are most effective in achieving both transmission reduction and diagnostic coverage. This study addresses an important evidence gap by quantifying the within-country association between measurable UHC policy indicators and the estimated rate of new HIV infections across nine Southeast Asian countries between 2013 and 2022. Employing a Fixed-Effects panel data methodology, the analysis controls for time-invariant national heterogeneity, ensuring reliable estimates of policy impact. We found that marginal changes in total current health expenditure (CHE) as a percentage of gross domestic product (GDP) were not statistically significantly associated with changes in HIV incidence. However, increases in the UHC Infectious Disease Service Coverage Index were statistically significantly associated with concurrent reductions in HIV incidence (p < 0.001), suggesting the efficacy of targeted service implementation as the principal driver of curbing new HIV infections. In addition, the UHC Reproductive, Maternal, Newborn, and Child Health Service Coverage Index exhibited a statistically significant positive association with changes in HIV incidence (p < 0.01), which is interpreted as a vital surveillance artefact resulting from expanded detection and reporting of previously undiagnosed HIV cases. Furthermore, out-of-pocket (OOP) health expenditure as a percentage of CHE showed a counter-intuitive negative association with changes in HIV incidence (p < 0.01), suggesting this metric primarily shows ongoing indirect cost burdens on the established patient cohort, or, alternatively, presents a diagnostic access barrier that results in lower case finding. These findings suggest that policymakers should prioritise investment in targeted infectious disease service efficacy over aggregate fiscal commitment and utilise integrated sexual health platforms for strengthened HIV surveillance and case identification.

BackgroundDelayed tuberculosis (TB) treatment remains a major challenge to TB control and is associated with increased mortality, drug resistance, and onward transmission. Food insecurity may contribute to delayed TB treatment through economic, physical, and psychosocial pathways. Depression and anxiety are also associated with delayed TB treatment and may mediate the relationship between food insecurity and delayed TB treatment. This study examined the association between food insecurity and delayed TB treatment initiation and assessed the mediation roles of depression and anxiety for this relationship among people newly diagnosed with TB. MethodsWe recruited 180 participants newly diagnosed with TB in Gaborone, Botswana. Food insecurity, depression, and anxiety were measured using the Household Food Insecurity Access Scale, PHQ-9, and Zung Self-Rating Anxiety Scale, respectively. Delayed TB treatment was defined as > 2 months since first TB symptoms. Logistic regression was used to examine the association between food insecurity and delayed TB treatment. Causal mediation analysis was conducted to assess the mediating roles of depression and anxiety. ResultsAmong the 180 participants, 45 (25%) experienced delayed TB treatment initiation. Participants with delayed TB treatment had slightly higher median scores for food insecurity (2 vs. 1, p = 0.11), depression (9 vs. 6, p = 0.001), and anxiety (37 vs. 34, p = 0.05). There was insufficient evidence of an overall association between food insecurity and delayed TB treatment initiation (OR = 1.04, 95% CI 0.98-1.11, p = 0.20). Mediation analysis found insufficient evidence of total and direct effects through depression and anxiety. However, there was evidence of significant indirect effect through depression (OR = 1.04, 95% CI 1.01-1.08, p < 0.001) and a borderline indirect effect through anxiety (OR = 1.02, 95% CI 1.00-1.04, p = 0.05). ConclusionMediation analysis revealed associations between food insecurity and delayed TB treatment initiation mediated by depression and anxiety which were not evident in total effects analysis. These findings highlight the importance of considering both socioeconomic and psychological factors in addressing delayed TB treatment. Further studies are needed to confirm these pathways.

BackgroundTuberculosis (TB) remains a leading cause of infectious disease mortality worldwide, and treatment failure contributes to ongoing transmission, drug resistance, and poor clinical outcomes. Artificial intelligence and machine learning approaches have attracted growing interest for predicting tuberculosis treatment outcomes, but the literature is heterogeneous and lacks a comprehensive synthesis. MethodsWe conducted a systematic review and meta-analysis of studies that developed or validated machine learning models to predict TB treatment failure. We searched PubMed/MEDLINE and Embase from January 2000 to October 2025. Studies were eligible if they developed, validated, or implemented an artificial intelligence or machine learning model for the prediction of TB treatment failure or a closely related poor outcome in patients receiving anti-TB treatment. Risk of bias was assessed using the Prediction model Risk Of Bias Assessment Tool. Random-effects meta-analysis was performed to pool area under the curve values, with subgroup analyses and meta-regression to explore heterogeneity. ResultsThirty-four studies were included in the systematic review, of which 19 reported area under the curve values suitable for meta-analysis (total participants, 100,790). Studies were published between 2014 and 2025, with 91% published from 2019 onward. Tree-based methods were the most common algorithm family (52.9%), and multimodal models integrating three or more data types were used in 41.2% of studies. The pooled area under the curve was 0.836 (95% confidence interval 0.799-0.868), with substantial heterogeneity (I{superscript 2} = 97.9%). In subgroup analyses, studies including HIV-positive participants showed lower discrimination (pooled area under the curve 0.748) compared to those excluding them (0.924). Only eight studies (23.5%) performed external validation, and only one study (2.9%) was rated as low risk of bias overall, primarily due to methodological concerns in the analysis domain. Eggers test suggested publication bias (p = 0.024). Major evidence gaps included underrepresentation of high-burden countries, HIV-affected populations, social determinants, pediatric TB, and extrapulmonary disease. ConclusionsMachine learning models for predicting TB treatment failure show promising discrimination but are not yet ready for routine clinical implementation. Performance varies substantially across populations and settings, and methodological limitations, including inadequate validation, poor calibration assessment, and high risk of bias, limit confidence in current estimates. Future research should prioritize rigorous external validation, calibration assessment, and development in underrepresented populations, particularly HIV-affected and high-burden settings. Author SummaryTB kills over a million people annually. While curable, treatment failure remains common and drives ongoing transmission and drug resistance. Researchers increasingly use artificial intelligence and machine learning to predict which patients will fail treatment, but it is unclear if these models are ready for clinical use. We reviewed 34 studies including nearly 1.1 million participants from 22 countries. On average, models correctly distinguished patients who would fail treatment from those who would not 84% of the time, a performance generally considered good. However, this average hid enormous variation. Models developed in populations including HIV-positive people performed substantially worse, suggesting prediction is harder with HIV co-infection. Worryingly, only one study used high-quality methods; 97% had serious flaws in handling missing data, checking calibration, or testing in new populations. Only eight studies validated their models in different settings. To conclude, we found that machine learning is promising in predicting TB treatment failure, but it is not ready for clinical use. Researchers should prioritize validation in high-burden settings, include social determinants, and improve methodological rigor before these tools can help patients.

Background In clinical trials for alopecia areata (AA) the treatment effect (percentage of hair loss) is estimated using the Severity of Alopecia Tool (SALT) score. Trials in patients with severe AA (>=50% hair loss) employed a local rating of the SALT score performed at trial sites by different investigators. However, in mild-to-moderate AA (<= 50% hair loss) where SALT scores are lower, potential inter rater variability and margin of error may compromise the results. Objectives To compare Centralised and Local measurement of hair loss in mild moderate AA. Methods In a Phase 2 clinical trial a centralised measurement of hair loss was performed from photographic images taken using a standardised protocol and professional camera equipment. Local scoring was also undertaken at screening/baseline for eligibility. We assessed: the repeatability of the central system (screening vs baseline values), the reproducibility of the central versus the local rating system and the potential impact of each method on the endpoints using a Monte-Carlo simulation method. Results There was good agreement and consistency of scoring with Central rating. This provided much smaller margins of error, 50% lower than Local rating. The simulations demonstrated that substituting Local rating for Central rating would result in a reduction of the likelihood of a statistically significant outcome by at least 50% depending on the SALT score defined clinical response endpoint. Conclusions Central rating is most appropriate in the Phase 2 learning stage of clinical development and provides an accurate representation of the quantity of hair loss, minimising error and ensuring consistency in measurements.

Women living with HIV face about a six-fold higher risk of cervical cancer, yet screening uptake remains low in many sub-Saharan African settings. We explored factors influencing repeated decisions to decline cervical cancer screening during routine HIV care among women living with HIV at a large HIV clinic in Jos, Nigeria. Between September and December 2024, we conducted an exploratory qualitative study at the AIDS Prevention Initiative in Nigeria Clinic in Jos, Nigeria. We purposively recruited 27 women living with HIV aged 21 to 65 years who had never undergone cervical cancer screening and had repeatedly declined screening offers during routine HIV care, including at the current clinic visit. Semi-structured in-depth interviews were conducted in English or Hausa, audio-recorded, transcribed verbatim, and translated into English where needed. Data were analyzed thematically using theory-informed coding based on the Health Belief Model and Social Ecological Model. Among 27 women living with HIV who had repeatedly declined screening, perceived susceptibility was often low or uncertain despite recognition of cervical cancer severity. Perceived benefits were acknowledged but were frequently outweighed by overlapping barriers, including knowledge gaps and misinformation, indirect and downstream costs, emotional barriers, logistical constraints, clinic-flow and service-delivery barriers, and anticipated stigma. Education, reminders, and supportive clinic processes acted as cues to action, and most participants expressed willingness to screen in future. Among women living with HIV at this clinic who repeatedly declined screening when it was offered, perceived benefits were often outweighed by multilevel barriers. Screening programs may integrate fear-reduction and stigma-sensitive counseling with practical service delivery improvements, including shorter waiting times, reduced indirect costs, predictable and streamlined clinic flow, and consistent provider invitations and reminders, while addressing misinformation through community-embedded, culturally tailored messaging. These strategies may improve screening uptake and support more equitable cervical cancer prevention for women living with HIV in similar HIV-care settings.

BackgroundSchistosomiasis remains a major public health challenge in sub-Saharan Africa. Recent World Health Organization (WHO) guidance calls for community-wide treatment and fine-scale data to optimise preventive chemotherapy (PC) strategies, yet the practical implications for resource allocation by health ministries are unclear. MethodsWe analysed epidemiological and cost data from Ethiopia and Zimbabwe to compare survey designs and five implementation scenarios. Scenarios varied by data source, administrative unit of implementation, WHO guidance on PC strategies. Outcomes were target population, praziquantel needs, and delivery costs. ResultsGeostatistical surveys reduced sample size by up to 90% and survey costs by [&ge;]72% compared with a design-based approach, while increasing spatial coverage. Applying updated WHO guidance expanded eligibility to pre-school-aged children and adults, and in one scenario increased treatment needs by 72% in Ethiopia and 262% in Zimbabwe. Correspondingly, praziquantel requirements and delivery costs were driven primarily by expanded age eligibility rather than geographic coverage. ConclusionsGeostatistical surveys provide substantial efficiency gains for impact assessments, enabling cost-efficient, granular targeting. However, implementing 2022 WHO guidance was the dominant driver of increases in programme scope and resource needs, underscoring the importance of accurate fine-scale data to guide efficient planning and budgeting toward elimination goals. Author summarySchistosomiasis control programmes are required to use finer-scale data and updated World Health Organization (WHO) guidance to decide where and how often to deliver praziquantel. We analysed national schistosomiasis data and programme costs from Ethiopia and Zimbabwe to compare different approaches to impact assessment surveys and to estimate how treatment needs change under alternative decision rules.We found that model-based geostatistical surveys can reduce the number of people that need to be sampled and the cost of surveys while providing more detailed information for planning at sub-district level. However, when we applied the 2022 WHO schistosomiasis guidance, expanded eligibility (including adults and pre-school-age children and a lower threshold for community-wide treatment) substantially increased the number of people needing treatment. In our scenarios, expanded eligibility drove much larger increases in praziquantel requirements and delivery costs than changes in geographic coverage. Our findings help health ministries to anticipate the operational and budget implications of updated guidance and highlight why accurate fine-scale data are essential for equitable and realistic planning toward elimination.

Background There are no licensed treatments for patients with mild to moderate patchy alopecia areata (AA). Objectives To evaluate the efficacy, safety and dose response of STS01, a novel nanoparticle controlled release, topical formulation of dithranol/Prosilic. Methods In a phase 2, double blind study, adult patients with mild to moderate AA (guideline 10% to 50% of scalp hair loss) were randomly assigned to STS01 at doses of 0.25%, 0.5%, 1%, 2% or placebo, daily for 6 months. The primary endpoints included the proportion of patients achieving a >=30% improvement in Severity of Alopecia Tool (SALT) score, and percentage change from baseline in SALT score. This minimum level of improvement is generally accepted as an indicator of the population likely to progress to complete regrowth Results A total of 155 patients were randomized and treated (placebo, n=32; STS01 groups, n=30 to 31). STS01 1% met the primary efficacy endpoint of >=30% SALT score improvement compared to placebo: 75.9% (95% CI, 60.3 to 91.4%) vs 36.7% (95% CI, 19.4 to 53.9%) at 6 months; p=0.0037. The least squares (LS) mean percentage change in SALT score from baseline to end of treatment showed a clear dose response relationship; STS01 0.5% was the minimally effective dose and 2% the maximum tolerated dose, and there was a statistically significant improvement in the STS01 1% group (minus 55.0% vs +0.6% with placebo; p<0.01). Significant improvements (p<0.05) in LS mean percentage changes from baseline in SALT scores were demonstrated in the STS01 1% group at 2 months (-28.6% vs 12.8%), 4 months (-57.2% vs 1.5%), and 6 months (minus 67.0% vs 0.6%). Clinical Global Impression improvement was reported in 72.0% of patients with STS01 1% vs 41.7% with placebo (p<0.05). The most commonly reported treatment emergent adverse events were skin irritation reactions, but were mostly mild (STS01: 56.7% to 71.0%; placebo: 21.9%) or moderate (STS01:13.3% to 35.5%; placebo: 0%) and manageable by reduced frequency of application. There were 15 skin-related discontinuations with STS01 (12.2%) and 2 (6.3%) with placebo. Conclusions STS01 demonstrated a clear dose response, with STS01 1% dose optimally more effective than placebo for hair regrowth with minimal tolerance concerns in mild to moderate patchy AA. Skin irritation reactions were generally manageable and there were no new safety signals. Further characterisation of the STS01 1% dose is planned in a phase 3 study. Chief Investigator AGM reports fees from Soterios Ltd. Chief Statistician DMF is an employee of Soterios Ltd. All other authors were Principal Investigators in the trial and their clinics were reimbursed for the work involved. Most also had sponsorship in the form of consultancies, investigational roles or lecturing roles on behalf of other Dermatological pharmaceutical companies

Background: The WHO End TB strategy targets 80% and 90% reductions in TB incidence and mortality, respectively, between 2015 and 2030. Objective: We assess which epidemiologic factors, including existing and new interventions, are most critical to reducing future TB in South Africa. Methods: We adapted an existing mathematical model of TB and HIV in South Africa. Prior distributions were specified to represent uncertainty ranges for 27 model parameters that are highly uncertain and potentially important in driving future TB dynamics. Latin Hypercube Sampling was used to sample 1000 parameter combinations from these distributions, and the model was projected to 2040 for each. Partial rank correlation coefficients (PRCCs) were calculated to assess correlation between each parameter and average adult TB incidence and mortality rates over 2025-2040. Results: Adult TB incidence and mortality rates in South Africa are projected to decline by 46% (95% CI: 17-69%) and 54% (95% CI: 21-84%) respectively by 2030, relative to 2015. The parameters most strongly associated with future TB incidence are the increase in microbiological testing in symptomatic individuals due to near-point-of-care/tongue swab (NPOC/TS) testing (PRCC=-0.67), reductions in social contact rates post-COVID (PRCC=-0.61), the probability of sputum testing in symptomatic individuals in the absence of NPOC/TS testing (PRCC=-0.39), and the efficacy of TB preventive therapy (PRCC=-0.35). TB mortality predictors are similar. Conclusions: Increasing testing among people with TB symptoms, including through new NPOC/TS technologies, is likely to have the largest impact on progress towards End TB goals in South Africa, though attainment by 2030 is unlikely.

Objectives: A pooled testing algorithm for tuberculosis (TB), in which sputum specimens from multiple individuals are tested in pools with individual testing of positive pools, can optimise diagnostic resources. This study evaluated the diagnostic accuracy and cartridge savings of pooled testing with the Xpert MTB/RIF Ultra assay (Xpert Ultra) relative to individual Xpert Ultra testing. Methods: We conducted a cross sectional study among 2,396 adults (aged above 15 years) with presumptive TB enrolled between July 2024 and February 2025, through facility based case finding (FBCF) and community based case finding (CBCF). Participants submitted two sputum specimens. The first underwent individual Xpert Ultra testing; remnant specimens were combined into four specimen pools and tested again with Xpert-Ultra. The second specimen was used to inoculate liquid culture (BACTEC MGIT). Data were used to simulate an up-front pooled testing strategy; sensitivity and specificity of this approach was estimated against culture, and cartridge use was compared with individual Xpert-Ultra testing. Results: Of 2,396 participants, 395 (16.5%) had a positive Xpert Ultra and/or culture, including 360/912 (39.5%) in FBCF and 35/1484 (2.4%) in CBCF. The pooled testing approach had sensitivity of 82.4% (95% confidence interval [CI], 77.9; 86.3) and specificity of 98.5% (97.8; 99.0) compared to culture, with lower sensitivity than individual Xpert-Ultra testing (86.5%, 82.4; 89.9) but high specificity (98.1%, 97.4; 98.7). Sensitivity of pooled testing was lower in CBCF (59.1%, 36.4; 79.3) than in FBCF (84.0%, 79.5;87%), whereas cartridge savings were greater in CBCF (69.1% vs 9.6%). The pooling strategy reduced Xpert-Ultra cartridge use by 46.5%, saving USD 14,447. Conclusions: Pooled Xpert-Ultra testing among adults appears resource-efficient for TB screening in Vietnam. As sensitivity is lower compared to individual Xpert Ultra testing, particularly for paucibacillary disease, these losses should be carefully weighed against gains in affordability and expand access to molecular testing. Careful, context-specific implementation is essential to maximise programmatic benefit while minimising missed persons with TB.

Red Mark Syndrome (RMS) is a widespread skin disease affecting rainbow trout (Onchorhynchus mykiss). It provokes substantial economic losses in aquaculture, and is putatively caused by a Rickettsiales bacterium named Midichloria-like organism (RMS-MLO), which is strongly associated with RMS lesions. However, RMS-MLO ecology and epidemiology in aquaculture systems remain poorly understood. In this study, we analysed environmental DNA to monitor the presence of RMS-MLO and its putative vector Ichthyophthirius multifiliis in a trout farm in Northern Italy over one year. Water and sediment samples were monthly collected from multiple water tanks. RMS-MLO was consistently detected by PCR throughout the study in all trout-containing tanks, both in water and sediment samples, but never in the trout-free inflow tank. We did not observe an increase in RMS-MLO abundance during the single RMS outbreak recorded nor in relation with the co-occurrence of I. multifiliis. Our findings indicate a long-term persistence of RMS-MLO in the aquaculture, possibly as a consequence of infections with low prevalence or abundance, rather than its entry from the external environment at the time of RMS outbreaks. Additionally, hints were recorded for a potential role of free-living aquatic microeukaryotes as additional occasional reservoirs. In contrast, I. multifiliis was negatively related with RMS-MLO, while it significantly increased in abundance during the RMS outbreak, particularly in the inflow tank. This supports that, rather than a stable reservoir, I. multifiliis may act as a facilitator of RMS outbreaks, which might indeed be triggered by the entry of this parasite in trout farms.