Clinical Microbiology and Infection

Background: Colon capsule endoscopy (CCE) has been proposed as a non-invasive alternative to colonoscopy for colorectal cancer (CRC) screening, offering greater patient comfort and potentially reducing healthcare burden. However, its cost-effectiveness in population-based screening remains uncertain. Methods: This study used a state-transition (Markov) model to simulate lifetime outcomes of CRC screening in Denmark, Scotland, and Spain, comparing the standard pathway based on fecal immunochemical testing (FIT) followed by colonoscopy with an alternative pathway replacing colonoscopy with CCE after a positive FIT result. The model incorporated costs (2024 euros), quality-adjusted life-years (QALYs), and CRC cases avoided, applying a yearly discount rate of 3%. Deterministic sensitivity analyses explored uncertainty in capsule cost, adherence, and reinvestigation rates for non-advanced polyps. Results: Across all settings, CCE resulted in higher costs but slightly increased effectiveness and utility (mean QALYs 28.7 vs. 28.8; CRC detected 0.032-0.034 vs. 0.035-0.037 per person). Incremental cost-effectiveness ratios (ICER) ranged from 43,538EUR in Spain to 136,930EUR in Denmark per additional CRC detected. Capsule cost was the main driver of ICER variation, whereas adherence rates had minimal effect on cost-effectiveness. Changes in the prevalence of non-advanced polyps had a modest impact, except when capsule prices were high. Conclusions: Overall, replacing colonoscopy with CCE slightly increases detection and health gains at the expense of higher costs. Cost-effectiveness largely depends on capsule price and adherence. Artificial intelligence-assisted CCE interpretation may further improve diagnostic and economic performance, potentially supporting adoption in large-scale CRC screening programs.

Use of fungal mycelia, which has antiviral properties, constitutes a novel strategy for addressing existing and newly emerging viral diseases. We evaluated safety and feasibility of fungal mycelia (Fomitopsis officinalis and Trametes versicolor, FoTv) for treatment of COVID-19 and assessed its antiviral effects and potential to reduce symptoms. In a randomized, double-blind, placebo-controlled, dual site (UCSD/UCLA medical centers) clinical trial we examined non-hospitalized patients who contracted mild-to-moderate COVID-19 [≤] 96 hours, and experienced symptom onset [≤] nine days, before enrollment. FoTv was safe, well-tolerated, and feasible for COVID-19 treatment. Minor differences in biochemical markers were observed between groups (26 FoTv, 24 Placebo). FoTv significantly reduced the number and severity of symptoms, particularly sore throat/cough, and in vitro SARS-CoV-2 (pseudovirus) cellular infection. In conclusion, FoTv was safe and reduced COVID-19 symptoms and cellular viral infection. Future studies should investigate therapeutic benefits of fungal mycelia for SARS-CoV-2 and other viruses. Clinicaltrials.gov registration:NCT04667247.

Background and Aims SARS-CoV-2 infection is associated with an increased risk of cardiovascular, cerebrovascular and venous thromboembolism events. We aimed to assess the impact of COVID-19 vaccination prior to SARS-CoV-2 infection on the risk of these events post-infection. Methods Embase and MEDLINE were searched from January 2021 to 11 September 2025, supplemented by citation searching. Observational studies were included if they reported risks of cardiovascular, cerebrovascular, or venous thromboembolic events after SARS-CoV-2 infection between different vaccination groups (e.g. unvaccinated, vaccinated, or booster vaccinated), or reported risk of events after SARS-CoV-2 infection compared with no infection, stratified by vaccination status. Random-effects meta-analyses were conducted to estimate pooled hazard ratios (HRs) comparing vaccinated and unvaccinated individuals across prespecified outcomes. Results Twenty-three studies were included in the systematic review; most reported an association between vaccination and a reduced risk of post-infection vascular events. Ten studies were included across meta-analyses comparing vaccinated and unvaccinated individuals. Pre-infection vaccination was associated with significantly reduced risks of composite cardiovascular/cerebrovascular events (HR 0.60, 95% confidence intervals [CI] 0.51-0.69), stroke (HR 0.75, 95% CI 0.64-0.88), acute coronary syndrome (HR 0.70, 95% CI 0.52-0.95), arrhythmias (HR 0.82, 95% CI 0.69-0.98), and venous thromboembolism (HR 0.51, 95% CI 0.36-0.73). No statistically significant reduction was observed for heart failure (HR 0.72 [95% CI 0.47-1.10]). Conclusions Pre-infection COVID-19 vaccination is associated with lower risks of cardiovascular, cerebrovascular and venous thromboembolism events following SARS-CoV-2 infection in the pre- and post-Omicron eras, supporting its role within broader prevention strategies

Objectives In Quebec, Canada, vaccination against human papillomavirus (HPV) has been publicly-funded since January 2016 for gay, bisexual, and other men who have sex with men (GBM) aged [≤]26 years. The study aimed to analyze data collected in Greater Montreal (Engage study) to evaluate the HPV vaccination program for GBM in Quebec. Study Design Engage is a cohort of sexually active GBM aged [≥]16 recruited via respondent-driven-sampling (RDS) in Canada. Participants completed a questionnaire and tested for sexually transmitted infections. Methods RDS-II weights were applied to adjust for recruitment. Subgroups were compared using standardized mean differences. Odds ratios of HPV vaccination and prevalence ratios of anal HPV infection adjusted for potential confounders were estimated using robust regression models. Results Of 1179 participants, 309 were eligible for free HPV vaccination. Vaccine coverage among eligible GBM was 42%. Among those who disclosed same-sex sexual activity and discussed HPV vaccination with their healthcare provider, coverage reached 82%. Anal HPV prevalence among eligible GBM was 26.5% for [≥]1 HPV-6/11/16/18 genotypes without significant difference between vaccinated and unvaccinated individuals. Among unvaccinated GBM aged [≤]26 who were aware of the vaccine, 60% intended to get vaccinated within the next year. Conclusions One to two years after GBM aged [≤]26 were included in the Quebec HPV vaccination program, 42% of eligible GBM in Greater Montreal had been vaccinated. Anal HPV prevalence was high among GBM. Vaccinees were more likely to self-report a prior STI diagnosis. Offering vaccination to all preadolescents in schools appears essential to maximize vaccination benefits.

Nasopharyngeal (NP) swabs remain the dominant gold standard for respiratory infection diagnostics. While there has been increased use of alternative sample types since the COVID-19 pandemic, guidance on their use for detecting respiratory viruses is not yet definitive, especially for children. In this systematic review and meta-analysis, we aimed to compare the diagnostic accuracy and tolerability of multiple respiratory specimen types for detecting respiratory viruses in pediatric populations. Searches were conducted on July 17, 2025 in MEDLINE, Embase, Web of Science, and Scopus, with screening and data extraction performed in Covidence. English-language primary research articles published since 2000 comparing respiratory virus detection rates in children, using nucleic acid amplification tests between paired respiratory specimens, were included. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies criteria. We calculated pooled sensitivities and specificities of index specimens: nasopharyngeal aspirates (NPA), mid-turbinate swabs (MT), anterior nasal swabs (ANS), oropharyngeal swabs (OP), and bronchoalveolar lavage fluid (BAL), as compared to the reference, NP swabs, using random-effects modeling, firstly without discrimination by virus. Index specimens were then grouped by sample collection site as nasal, oral, and lower respiratory tract (LRT) specimens for virus-specific analyses. Overall performance and statistical validity were evaluated by hierarchical summary receiver operating characteristic (HSROC) analysis. Data regarding sampling tolerability was also assessed. We screened 2,448 studies and identified 36 publications (total N participants = 10,687) that reported diagnostic test accuracy using paired index-reference data in children. Of these, 18 (total N participants = 4,310) used NP specimens as the reference and were included in the diagnostic test accuracy analysis. Virus-agnostic pooled sensitivity estimates indicated that MT (0.92%) performed most similarly to NP, though sensitivities of ANS (0.79%) and OP (0.70%) were also moderately high for detection of any respiratory virus. BAL sensitivity was the lowest (0.37%). All sample types demonstrated high specificity (0.98%-0.99%). Group estimates and HSROC statistics found that nasal specimens, when grouped, had the highest sensitivity and accuracy for all examined viruses, including for influenza (92%) and RSV (90%). By comparison, oral and LRT specimens performed less well, with more variability, though both showed moderately high sensitivities for RSV (78%, 76%, respectively) and influenza (82%, 80%, respectively), and LRT samples showed high sensitivity for HMPV (82%). Analysis of sample tolerability found that NP swabs consistently ranked as the least comfortable and least preferred, while nasal swabs and saliva both performed well. Datasets for LRT and oral specimens were sparser than for nasal, and this contributed to greater variability, underscoring the need for further diagnostic accuracy studies on alternatives to NP sampling. These data support the viability of nasal and oral alternatives to NP swabs and affirm their application in pediatric care, particularly in outpatient settings. Such alternatives could greatly improve sampling tolerability and increase global access, including in resource-limited settings, to accurate diagnostic methods for respiratory infections.

Background: Isoniazid resistance is the most common form of drug-resistant tuberculosis (TB) globally. However, WHO-recommended molecular tests available to most TB patients worldwide detect rifampin resistance only, risking under-treatment of isoniazid-resistant, rifampin-susceptible TB (HR-TB) and subsequent emergence of rifampin resistance. Methods: This prospective study (2020-2024) aimed to collect and archive sputum specimens from all adults diagnosed with rifampin-susceptible pulmonary TB in Ho Chi Minh City, Vietnam. Cases were participants who developed rifampin-resistant recurrence; controls had rifampin-susceptible recurrence or no recurrence. Whole-genome sequencing of paired isolates distinguished acquired rifampin resistance from reinfection. The effect of pre-existing isoniazid resistance on rifampin resistance acquisition was estimated using inverse probability of treatment weighting, and the projected epidemiological impact of routine HR-TB testing was modelled. Results: 42,843 people were diagnosed with TB during the study period, from whom we archived 33,843 sputum samples. We enrolled 1,241 participants, 873 (70.4%) of whom had analysable data. 51/873 (5.8%) acquired rifampin resistance, of whom 49/51 (96.1%) had undetected isoniazid resistance. The weighted risk of acquired rifampin resistance was 2.98% (95% CI 2.08-4.50) with undetected isoniazid resistance, versus 0.03% (0.00-0.08) without (risk ratio105.42 (33.43-309.69)). Modelling projected that universal HR-TB diagnosis and treatment would reduce RR-TB incidence by 46% (35-61) over 10 years in Vietnam, with reductions of 26% (12-43) projected even where HR-TB prevalence was as low as 5%. Conclusions: Undetected, under-treated HR-TB confers a 100 fold increased risk of acquiring rifampin resistance. Routine isoniazid susceptibility testing combined with effective HR-TB treatment could substantially reduce the burden of RR-TB.

BackgroundBeef feedlots are increasing concerns that antibiotic use in beef cattle selects for antibiotic resistance, but limitations of primary studies and previous syntheses make it difficult to confirm a consistent effect. We conducted a rigorous systematic review and meta-analysis to summarise: 1) the effect during and after antibiotic administration; 2) its moderation by time since administration started/ended. MethodsEligible studies longitudinally compared beef cattle administered antibiotics to those that were not, measuring resistance determinants in faeces and/or environments. Information sources included Web of Science, CAB Abstracts, and Medline (last searches: 05/03/25). Risk of bias was assessed using RoB 2 and ROBINS-I. Meta-analysis was conducted where feasible, using individual participant data where necessary. ResultsThe 33 included studies were mostly small trials of North American feedlot cattle, all with high risks of bias. Meta-analysis of 11 studies of tylosin, ceftiofur, and chlortetracycline indicated positive effects on absolute abundance of resistance both during (SMDH = 0.4; 95% CI = 0.11 to 0.69, p = <0.01) and after (SMDH = 0.52; 95% CI = 0.33 to 0.71, p = <0.01) antibiotic administration. Log-transformed time was positively associated with effect size during (Slope = 0.63; 95% CI = 0.1 to 1.16, p = 0.02), and negatively associated after (Slope = -0.65; 95% CI = -1.24 to -0.06, p = 0.03) DiscussionAvailable evidence indicates time-dependent selection for antibiotic resistance in beef cattle, warranting further regulation to limit human health risks. Simultaneously, uncertainty about precise effect sizes warrants further research. FundingBBSRC Registrationhttps://doi.org/10.17605/OSF.IO/RXQHT

Background: Community-acquired pneumonia (CAP) remains a major global health burden disproportionately affecting older adults and people with comorbidities, with Streptococcus pneumoniae as one of the leading bacterial causes in Europe. The Hungarian Occurrence and Burden of PnEumonia (Hungarian-HOPE) study examined the incidence, hospitalization rates, and mortality of CAP between 2016 and 2020 in Hungary. Methods: The National Health Insurance Fund database was used to identify adult CAP patients (all-cause) based on ICD-10 codes J10-18. Outcomes included CAP incidence, 0-15-day hospitalization, and 0-30-day mortality after hospitalization, stratified by age, sex, and comorbidities (chronic obstructive pulmonary disease [COPD], asthma, cardiovascular disease [CVD], and type 1 and 2 diabetes [T1DM, T2DM]). Risk maps visualized relative risk gradients across population strata. Results: During the pre-pandemic period (2016-2019), over 100,000 CAP cases and more than 50,000 hospitalizations were recorded annually. In 2020, recorded cases fell to approximately 98,000, while hospitalizations increased to 66,200. Hospitalization rates increased from 25.1% in 2016 to 29.1% in 2019, then increased to 43.1% in 2020. The 30-day mortality among hospitalized patients rose from 22.7% in 2016 to 23.6% in 2019. Incidence, hospitalization, and mortality all increased with age. Relative to healthy males aged 30-39 years, CAP risk escalated steeply in the [&ge;]80 years cohort (incidence 5-15-fold; hospitalization >3-fold; mortality 11-24-fold) and was further amplified by COPD, CVD, or T2DM, with a lesser effect for T1DM. Conclusions: The results highlight the substantial age- and comorbidity-driven CAP burden in Hungary and support prioritization of preventive strategies including pneumococcal vaccination for older adults and high-risk groups.

Background Erythema nodosum leprosum (ENL) is a severe inflammatory complication of leprosy that often requires prolonged corticosteroid therapy which is associated with adverse effects. Methotrexate is an affordable immunomodulatory agent with limited evidence for its use in ENL treatment. We evaluated whether weekly oral methotrexate in additional to prednisolone reduces the need for additional prednisolone in adults with severe ENL. Methods and Findings We performed an international, multicentre, double-blind, randomised, placebo-controlled trial conducted at five leprosy referral centres in Ethiopia, India, Indonesia, and Nepal. Adults aged 18-60 years with severe ENL were randomised to receive oral methotrexate and prednisolone, or matching placebo and prednisolone. All participants received an identical prednisolone regime over 20 weeks and were followed for 60 weeks. The primary outcome was time to first ENL flare requiring additional prednisolone, assessed over 24 and 48 weeks. Between January 2023 and June 2024, 231 individuals were screened and 137 were randomised (68 methotrexate and prednisolone; 69 placebo and prednisolone). By 24 weeks, 85/137 (62.0%) participants experienced an ENL flare requiring additional prednisolone; the adjusted hazard ratio (HR) for methotrexate versus placebo was 0.98 (95% CI 0.62-1.54). By 48 weeks, 102/137 (74.5%) experienced an ENL flare; adjusted HR 0.95 (95% CI 0.62-1.43). Secondary outcomes were similar: methotrexate did not reduce ENL severity at first flare, flare frequency, or severity of subsequent flares. Health-related quality of life improved substantially in both groups with no evidence of a differential treatment effect. Methotrexate was generally well tolerated. The trial was registered at ClinicalTrials.gov (NCT03775460). Conclusions Oral methotrexate added to prednisolone did not reduce the requirement for additional prednisolone or delay ENL flares compared to placebo and prednisolone, and our study does not support the use of methotrexate for severe ENL.

Objective: To estimate the adjusted relative risk (RR) of administrative grant disruption faced by first-time and mechanism-first principal investigators (PIs) during the 2025 National Institutes of Health (NIH) grant disruptions. Design: Retrospective cohort study linking NIH RePORTER data to a publicly curated registry of grants disrupted in 2025. Setting: All NIH active research grants in fiscal years 2024 to 2025. Participants: 80,976 active projects: 4,961 disrupted during the wave that peaked in May 2025, 76,015 non-disrupted controls. Main outcome measures: Adjusted RR of disruption by two pre-specified first-time PI constructs: absolute first-time PI (no prior NIH grant) and mechanism-first PI (no prior NIH grant with the same activity code). Modified Poisson regression with institution-clustered standard errors adjusted for project, institutional, and geographic covariates. A pre-specified fiscal year 2024 common-anchor analysis addressed year-of-disruption confounding. Results: Of 4,961 disrupted grants, 237 (4.8%) had an absolute first-time PI and 396 (8.0%) had a mechanism-first PI. After adjustment, absolute first-time PIs faced 77% elevated risk of disruption (RR 1.77, 95% CI 1.34 to 2.32) and mechanism-first PIs faced 57% elevated risk (RR 1.57, 1.16 to 2.11). Under the common-anchor analysis, the absolute first-time effect attenuated to RR 1.22 (0.95 to 1.58); the mechanism-first effect persisted (RR 1.48, 1.07 to 2.06). The elevated risk was concentrated in research-mechanism grants (RR 1.78, 1.26 to 2.52) and was robust across 8 of 9 pre-specified sensitivity analyses. The Track A start-time construct, which asks whether the disrupted project was the PI's debut grant, yielded null estimates (RR 0.98, 0.93 to 1.04), with any effect concentrated entirely in newly started projects. Conclusions: First-time and mechanism-first PIs faced disproportionately elevated risk of disruption during the 2025 NIH wave, concentrated in research-mechanism grants and robust to year-confounding-free identification. The relevant exposure was being early-career at the moment of administrative action, not at project initiation. The findings have direct implications for workforce equity in US biomedical research.

BackgroundHigh-risk human papillomavirus (HPV) infection is necessary for cervical carcinogenesis, but HPV detection alone does not distinguish transient infection from lesions at greatest risk of progression. We evaluated whether HPV burden, vaginal microbiota structure, and host-context variables jointly characterize cervical intraepithelial neoplasia grade 3 (CIN3) in a Black/African American and White analytic cohort from the Vaginal Microbiome Health Project (VaMHP), integrating L1-based HPV typing, 16S rRNA vaginal microbiota profiling, and linked clinical metadata. ResultsAmong 1181 participants, 75 had CIN3. CIN3 was associated with HPV positivity (55/75, 73.3% vs 431/1106, 39.0%; odds ratio [OR] 4.31, 95% CI 2.55-7.29; Fisher exact p = 7.9 x 10^-9) and with multiple HPV infection among HPV-positive participants (35/55, 63.6% vs 176/431, 40.8%; OR 2.54, 95% CI 1.42-4.54; p = 0.0022). HPV communities in CIN3-positive samples showed higher Shannon diversity, greater observed strain richness, higher evenness, and significant beta-diversity separation. In vaginal microbiota analyses, alpha diversity did not differ by CIN3 status, but community composition did, and Lactobacillus crispatus was the only taxon depleted in CIN3 after multiple-testing correction. Race, age, and metronidazole exposure were central nodes in the host-factor network. In predictive modeling, a full integrated model combining metadata, HPV, and vaginal microbiota features (auROC = 0.745) outperformed both HPV + vaginal microbiota (auROC = 0.670) and HPV-only (auROC = 0.440) models. ConclusionsCIN3 in this cohort was associated with coordinated shifts in virologic burden, vaginal community structure, and host social-clinical context. The results support a structure-function interpretation in which loss of Lactobacillus crispatus-dominant states and enrichment of dysbiosis-associated communities define a host-microbiome context that is more permissive to HPV persistence and precancer. These findings move beyond descriptive omics by showing that microbiome and host-context features add nonredundant discriminatory signal beyond HPV-only models.

Background: Without tuberculosis preventive therapy (TPT), approximately 5% of individuals infected with M. tuberculosis progress to active tuberculosis (TB) disease. Recent studies have identified body mass index (BMI) < 25 kg/m2 as a predictor of TB progression, but additional markers are needed to better identify persons at increased risk. Methods: Close contacts of patients with culture-confirmed pulmonary TB were enrolled in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort from 2015 to 2019 and followed for up to 24 months. Analyses were restricted to interferon-{gamma} release assay (IGRA)-positive contacts who did not receive TPT or received <30 days of isoniazid. Prediction models to identify close contacts at increased TB risk were constructed using two complementary approaches: incremental models used BMI as the base predictor and evaluated whether baseline whole-blood transcriptomic signatures, human genetic polymorphism risk scores derived from low-pass whole-genome sequencing, and BMI-related plasma biomarkers improved model discrimination. Agnostic models did not impose BMI in the model and used penalized regression for predictor selection. Results: Among 285 close contacts, 15 (5%) progressed to TB. The model with BMI as unique predictor had a C-index of 0.66 (95% confidence interval [CI] 0.55; 0.77). Adding Rajan5 or Duffy9 transcriptomic signature scores to BMI improved discrimination compared with BMI alone, with C-indices of 0.78 (95% CI 0.62; 0.99) and 0.75 (95% CI 0.61; 0.89), respectively, but did not further improve discrimination after accounting for adiponectin. Adding adiponectin to BMI increased the C-index to 0.80 (95% CI 0.68; 0.91), while adiponectin alone captured most of the discriminatory performance in agnostic models (C-index, 0.80, 95% CI 0.69; 0.91). Genetic risk scores, leptin, and the adiponectin:leptin ratio did not improve model discrimination compared with the BMI-only model. In exploratory post hoc analyses, higher adiponectin was associated with increased risk of progression to TB, with each two-fold increase associated with a higher hazard of TB (HR 2.91, 95% CI 1.73; 4.91, p < 0.001). Conclusions: Baseline adiponectin strongly predicted progression to TB among close contacts and captured most of the discriminatory information contained in epidemiological and transcriptomic variables. Its consistent selection across modelling approaches supports adiponectin as a promising biomarker for TB risk stratification.

Background: Sexual and gender minorities (SGM), including men who have sex with men (MSM) and transgender women, often face stigma, legal constraints, and limited access to sexual and reproductive health services. These conditions restrict prevention and care, increasing vulnerability to HIV and human papillomavirus (HPV) infections. While strong HIV-HPV interaction is documented in high-income settings, evidence from low- and middle-income countries remains limited. This study examines the burden, co-infection dynamics, and progression of HPV infection and anal dysplasia among MSM and transgender women in Pakistan. Methods: A cross-sectional study was conducted between September 2015 and October 2016 among men who have sex with men (MSM) and transgender women recruited from sexual health and antiretroviral therapy centers in Karachi. Eligible participants were aged [&ge;]18 years and self-reported anal sex within the past 6 months (N=298). Two anal specimens were collected for HPV DNA detection and genotyping using PCR, and anal squamous intraepithelial lesions (ASIL) were assessed cytologically using the Bethesda classification. Associations were estimated using Cox proportional hazards regression algorithms to derive prevalence ratios (PRs). Results: Among participants, 44% (n=133) were living with HIV. Overall HPV prevalence was 65.1%, rising to 87% among HIV-positive individuals compared to 48% among those without HIV ({chi}{superscript 2}p[&le;]0.001). Likewise 28.9% of participants living with HIV were infected with two or more than two types of HPV as compared with 18.8% participants without HIV ({chi}{superscript 2}p[&le;]0.001). HIV infection was strongly associated with HPV acquisition (adjusted PR 2.81, 95% CI 2.16-3.82). Among HPV-positive participants (n=194), 58.8% were co-infected with HIV. High-risk HPV was highly prevalent among those living with HIV (83.2% vs. 35.3% ({chi}{superscript 2}p[&le;]0.001)), with HPV16 as the dominant oncogenic type. Multiple HPV infections were more common among HIV-positive individuals ({chi}{superscript 2}p[&le;]0.001), and HIV seropositivity was 3.43 (95% CI: 2.55-3.51) times higher among those with high-risk HPV. Co-infected participants demonstrated prolonged smoking, longer duration of sex work, high-intensity sex work with limited condom negotiation, and higher prevalence of anal warts (all p<0.05). Anal dysplasia (ASIL) was present in 35% of participants and was higher among HIV-positive individuals (42.4% vs. 28.1%, p<0.001). HIV-HPV co-infection was independently associated with ASIL (adjusted PR 1.75, 95% CI 1.07-2.88), while high-risk HPV further amplified this risk (PR 3.04, 95% CI 1.75-5.26). Conclusion: These findings demonstrate a biological continuum in HIV-positive MSM and transgender women, where HIV increases HPV acquisition, persistence, and multiplicity, accelerating progression to anal dysplasia. This reflects a syndemic shaped by biological interaction and structural vulnerability. Integrating HPV screening and vaccination within HIV services is essential to interrupt progression to cancer in this high-risk population.

ABSTRACT OBJECTIVES To examine whether psychological safety and power distance are associated with medical researchers' well-being, and whether these associations operate through team inclusiveness and conflict. DESIGN Cross-sectional survey study. SETTING A biomedical research institute at a major UK university. PARTICIPANTS 133 medical researchers from 17 teams, including 20 principal investigators and 113 team members. MAIN OUTCOME MEASURES Job satisfaction, life satisfaction, intrinsic motivation, and psychological detachment. Mediators were dimensions of team inclusiveness and team conflict. RESULTS Psychological safety had no significant direct associations with job satisfaction, life satisfaction, intrinsic motivation, or psychological detachment, but showed several indirect associations through researchers' team experiences. It was indirectly associated with higher job satisfaction, life satisfaction, and intrinsic motivation primarily through greater integration of differences, inclusion in decision making, or more constructive forms of conflict (bs=.23-.38, ps=.032-<.001).For psychological detachment, psychological safety showed conflicting indirect associations: it had the potential to support detachment through greater integration of differences and lower avoidant conflict (bs=.21-.56, ps=.054-.002), but to undermine detachment through greater inclusion in decision-making (b=-.26, p=.082). Power distance showed a different pattern. Most notably, it was positively associated with psychological detachment (b=.54, p=.062). However, power distance was indirectly associated with lower job satisfaction, life satisfaction, and intrinsic motivation, primarily through reduced integration of differences and greater dominating conflict (bs=-.14 to -.19, ps=.068-.020). CONCLUSIONS Common assumptions about psychological safety and power distance should be revisited. Psychological safety did not show strong direct benefits for researcher well-being, whereas power distance was not uniformly harmful and was positively associated with psychological detachment. A more nuanced understanding of both cultural dimensions is needed in medical research teams.

Trichophyton mentagrophytes genotype VII (TmVII) is an emerging sexually transmitted dermatophyte that causes skin infections characterized by inflammatory, erythematous-squamous, painful, and persistent lesions. This genotype is part of the T. interdigitale/T. mentagrophytes Species Complex (TiTmSC), which comprises 28 genotypes. To enable rapid and specific differentiation of TmVII from other genotypes, a real-time polymerase chain reaction (rt-PCR) assay was developed targeting three unique single-nucleotide polymorphisms in the ITS1 region of TmVII. Assay specificity was further improved by introducing an additional mismatch at the 3 ends of both forward and reverse primers. The rt-PCR assay demonstrated high sensitivity, with a detection limit of 0.0002 ng of TmVII genomic DNA. The assay was highly specific, with no cross-reactivity observed with either closely or distantly related fungal pathogens when a cycle threshold (Ct) cutoff of 37 was applied. Among 497 mold isolates tested, 47 were confirmed as TmVII by rt-PCR, and the results were fully concordant with conventional ITS-PCR/Sanger sequencing. The rt-PCR assay demonstrated high sensitivity, specificity, reproducibility, and speed, with a turnaround time of one day after DNA extraction, compared with seven to ten days for Sanger sequencing. The first rapid molecular assay developed using TaqMan chemistry for TmVII identification is expected to enhance patient care and support infection control measures.

Background Erythema nodosum leprosum (ENL) is a severe inflammatory complication of lepromatous leprosy characterised by recurrent inflammatory episodes often requiring prolonged immunosuppression. The severity of ENL can be quantified using the validated and reliable ENLIST ENL Severity Scale (EESS). The longitudinal course of ENL and how it is captured using standardised severity measures has not been well described. We prospectively evaluated the changes in ENL severity over time using the EESS in a randomised clinical trial. Methods We conducted a post-hoc analysis of participants enrolled in the Methotrexate and Prednisolone Study in ENL, an international multicentre randomised controlled trial conducted in Ethiopia, India, Indonesia, and Nepal. Adults with severe ENL (EESS score [&ge;]9) were followed for 60 weeks with repeated EESS assessments. Longitudinal trajectories were analysed using mixed-effects regression models. Item-level analyses characterised the clinical phenotype captured by the scale. Associations between EESS score, prednisolone exposure, and dermatology-specific health-related quality of life measured using the Dermatology Life Quality Index (DLQI) were examined. Findings A total of 135 participants contributed 1,958 EESS assessments. Mean EESS declined rapidly during the first four weeks of treatment (-2.10 points/week; 95% CI -2.36 to -1.84; p<0.001), increased modestly during reduction in corticosteroid dose (weeks 4-20), and gradually declined thereafter. Severe ENL (EESS score [&ge;]9) occurred in 20.6% of visits and was characterised primarily by pain and cutaneous inflammatory manifestations. Participants who required additional prednisolone had persistently higher EESS scores and showed limited improvement compared with those who did not receive additional prednisolone. Longitudinal EESS scores were strongly correlated with the DLQI score (Spearmans {rho}=0.75; p<0.001). Conclusion The EESS captures clinically meaningful changes in ENL severity, aligns with treatment decisions, and reflects patient-reported severity over time. These findings support the use of the EESS as a robust tool for monitoring ENL severity in both clinical research and routine care.

Background: Digital antimicrobial stewardship (AMS) interventions, such as clinical decision support systems, audit and feedback platforms, and electronic prescribing tools, have been increasingly adopted to improve antibiotic use. However, the effectiveness of these interventions across healthcare settings remains uncertain, and the certainty of the evidence has not been comprehensively evaluated. The objective of this study was to provide a comprehensive understanding of the role of digital interventions in optimizing antimicrobial use and improving clinical outcomes within a broad spectrum of healthcare settings. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials evaluating digital AMS interventions that followed PRISMA 2020 guidelines and registered in PROSPERO CRD420251178854 and funded by the Wellcome Trust CAMO Net programme. Searches were performed across major databases. Primary outcomes included the appropriateness of antibiotic prescriptions and the antibiotic prescription rate. Secondary outcomes included 30 day mortality, 30 day hospital readmission, and length of hospital stay (LOS). Random effects models were used to pool effect sizes. Risk of bias was assessed RoB 2, and certainty of evidence was rated using GRADE. A Summary of Findings table was prepared to present effect estimates, sample sizes, and evidence certainty. Results: Eleven RCTs met the inclusion criteria, and nine were included in the quantitative synthesis. Digital AMS interventions did not show a significant effect on appropriateness of antibiotic prescribing (RR 0.99, 95%CI 0.93 to 1.05; very low certainty). There was no reduction in antibiotic prescription (RR 0.98, 95%CI 0.88 to 1.09), with substantial statistical heterogeneity and very low certainty. Across clinical outcomes, digital AMS showed no effect on 30 day mortality (RR 0.91, 95%CI 0.77 to 1.09; very low certainty) or 30 day readmission (RR 0.95, 95%CI 0.79 to 1.14; very low certainty). For LOS, results were inconsistent across studies, and the pooled effect showed no clinically meaningful change (MD 0.17 days, 95%CI 0.01 to 0.35; very low certainty). Most trials had some concerns of bias due to deviations from intended interventions. Conclusion: Meta-analyses of digital AMS RCTs showed a lack of evidence with a high level of certainty on antibiotic prescribing or clinical outcomes due to high heterogeneity in interventions and study designs, as well as RCTs' limitations (no adoption/fidelity metrics).

Background Community-wide active case-finding (ACF) is being increasingly implemented as a tuberculosis (TB) elimination intervention. However, conventional site selection strategies may result in low yields from screening. We evaluated whether an artificial intelligence (AI) software guided targeting strategy could improve detection of TB during screening activities (called camps) relative to routine approaches to site selection in the programmatic setting in Pakistan. Methods We conducted a stepped-wedge cluster-randomised trial embedded within Global Fund supported ACF activities implemented by Pakistan s National TB Program and private sector partners. Thirty mobile X-ray van teams operating in 68 districts were randomly assigned to transition from routine site selection approaches (based on field-staff experience and historical data) to an AI-guided targeting strategy, using the software MATCH-AI. We assessed the effect of the intervention on the primary outcome, Camp Positivity Yield, defined as the number of individuals diagnosed with bacteriologically confirmed TB per camp, using generalised linear mixed models. The primary analysis was by intention to treat. Camps conducted within a 5-km radius of the AI selected locations were included in a validated per-protocol analysis. We conducted several district-level subgroup analyses. This trial is registered, number NCT06017843. Findings Between August 2023 and September 2024, 3,936 screening camps were conducted (2,046 control, 1,890 intervention), screening 269,254 individuals. In the intention-to-treat analysis, Camp Positivity Yield was 7% higher in the intervention group relative to the control group, however this difference was not statistically significant (adjusted risk ratio [RR] 1.07, 95% CI: 0.94 -1.22). In the validated per-protocol analysis, Camp Positivity Yield was 32% higher in the intervention group relative to the control group (adjusted RR 1.32, 95% CI: 1.12-1.54). Yields were highest in districts that had moderate baseline yields of 0.5-1% per population screened prior to the trial (adjusted RR: 1.57, 95% CI: 1.13 - 2.18) and in rural districts (adjusted RR 1.43, 95% CI: 1.23 -1.65). Interpretation The use of an AI-guided targeting strategy significantly increased detection of bacteriologically confirmed TB during active case-finding in the validated per-protocol analysis, relative to conventional site-selection approaches employed by field-staff. This software may be considered as a supportive tool to improve the efficiency of community-based TB case-finding interventions in other high burden countries.

Filoviruses pose a threat to individuals and the global community as pathogens of pandemic potential. The scientific community faces an ongoing challenge of developing effective vaccines with unpredictable outbreaks concentrated in countries with lower healthcare resources. Given these limitations, it is important to ensure that existing filovirus research is used as efficiently as possible. To enable rapid identification and use of this research, we have developed evidence maps of existing filovirus publications to enable further analysis and synthesis. We systematically identified and categorised existing immunological and clinical publications on Bundibugyo (BDBV), Marburg (MARV), Sudan (SUDV) and Ebola (EBOV) viruses. We captured studies that reported on animal or human immune responses to infection, outcome of infection, or human vaccine safety data. Initial searches of PubMed, Embase and Europe PMC were run between November 2024 and January 2025 and the MARV, SUDV and EBOV searches were updated on 1 August 2025. A BDBV search was conducted on 18 May 2026 in response to the WHO declaration of a Public Health Emergency on 17 May 2026. The initial searches retrieved 208, 1646, 534 and 3963 manuscripts for BDBV, MARV, SUDV and EBOV, respectively. After screening using an a priori exclusion criteria, 49 BDBV, 198 MARV, 149 SUDV and 850 EBOV publications were included on each evidence map. These maps provide a comprehensive, transparent and reproducible structure to categorise existing studies of filovirus vaccination and immunity. They allow rapid identification of the totality of available evidence and the existing experimental tools to support vaccine development for these priority pathogens.

ObjectivesListeria monocytogenes is an opportunistic pathogen, associated with foodborne infections that disproportionately affect newborns, elderly and immunocompromised patients. L. monocytogenes can be classified on the antigenic and related structural variation of cell-associated wall teichoic acid (WTA) molecules through conventional serotyping techniques. The WTA structure of serovars (SV) 1/2, 1/2*, 3 and 7 consists of a linear poly-ribitolphosphate (RboP) polymer either with or without decoration with rhamnose (Rha) and/or N-acetylglucosamine (GlcNAc). Of these four SVs, SV1/2 (WTA with GlcNAc and Rha) causes [~] 99% of all listeriosis cases. However, conventional serotyping cannot accurately discriminate between these four SVs, particularly SVs1/2* (WTA with Rha). MethodsHere we applied two identified monoclonal antibodies (mAb), with specificity for the RboP backbone or GlcNAc modification to develop a discriminatory serotyping scheme for SV1/2, 1/2*, 3 and 7. Isogenic mutants for the different SVs were created in L. monocytogenes SV1/2 strain EGD-e. The typing scheme was then adapted to an immnoblot assay and applied to a collection of 317 previously classified listeriosis isolates from the Netherlands Reference Laboratory for Bacterial Meningitis. ResultsBinding of the RboP-specific mAb was limited to EGD-e wild type (SV1/2), but increased significantly for isogenic EGD-e mutants representing SV1/2*, 3 and 7. In contrast, the GlcNAc-specific mAb only recognized EGD-e mutants representing SVs 1/2 and 3. The combined staining profiles of the two mAbs allowed accurate discrimination of the four SVs as verified on clinical isolates. Applying this typing scheme to 317 listeriosis isolates previously typed as SV1/2, we confirmed SV designation in >90% of isolates, but also identified SV1/2* (5.4%), SV3 (0.6%) and SV7 (0.3%) isolates. SV1/2* isolates were also identified among meningitis patients. ConclusionThe increased discriminatory capacity of L. monocytogenes serotyping provides a more detailed insight of the epidemiological landscape and the critical factors for L. monocytogenes infections.