Clinical Microbiology and Infection

BackgroundHuman papillomavirus (HPV) infection is a major public health concern in Cameroon, where cervical cancer remains the second leading cause of cancer-related morbidity and mortality among women. Despite the availability of effective preventive measures, their uptake remains suboptimal and is influenced by population-level knowledge and awareness. This study aimed to synthesize existing evidence on HPV-related knowledge and its associated factors in Cameroon. MethodsThis review included studies assessing knowledge of HPV as a sexually transmitted infection (STI), its causal role in cervical cancer, and overall good HPV knowledge. A comprehensive and systematic search was conducted across PubMed, Scopus, Web of Science, Embase, the Cochrane Library, and local online databases. Study quality was appraised using the Joanna Briggs Institute critical appraisal tool. Pooled prevalence estimates were calculated using random-effects models (DerSimonian and Laird). Heterogeneity was assessed using the I{superscript 2} statistic and explored through subgroup analyses. ResultsA total of 32 studies involving 13,{square}457 participants were included. The pooled prevalence of overall good HPV knowledge was 27.4% (95% CI: 7.6-63.2; 7 studies; n = 3,312), with considerable heterogeneity (I{superscript 2} = 99.3%). Knowledge of HPV as a cause of cervical cancer was 27.9% (95% CI: 15.8-44.4; 26 studies; n = 8,688), while knowledge of HPV as an STI was 47.1% (95% CI: 31.4-63.5; 18 studies; n = 9,040). Healthcare workers demonstrated the highest levels of knowledge (80.2% for HPV as an STI; 78.7% for HPV as a cause of cervical cancer), whereas students (43.4% and 10.2%, respectively) and women from the general population (30.6% and 19.9%, respectively) showed substantially lower levels. Factors associated with poor knowledge included Christian affiliation (OR = 1.46; 95% CI: 0.08-26.06) and secondary level education (OR = 1.32; 95% CI: 0.66-2.63), although these associations were non-significant. ConclusionsThis study reveals that, HPV-related knowledge in Cameroon remains low, particularly regarding the causal link between HPV and cervical cancer. These findings highlight the urgent need for targeted, context-specific educational interventions and strengthened public health strategies to improve awareness and uptake of HPV prevention measures. Systematic review registrationPROSPERO CRD420261283152.

BackgroundSince 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. MethodsWe 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. ResultsAmong 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. ConclusionsPFA 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.

BackgroundHuman papillomavirus (HPV) vaccination is a key strategy for cervical cancer elimination. In Cameroon, HPV vaccine was introduced into the expanded program on immunization in 2020. However, synthesized evidence on vaccine acceptability is needed to guide policy. This systematic review and meta-analysis aimed to estimate the pooled prevalence of HPV vaccine awareness, willingness to vaccinate, recommendation practices, and actual uptake in Cameroon, and to identify determinants of vaccine hesitancy. MethodsWe searched PubMed, Scopus, Web of Science, Embase, Cochrane Library, and African Journals Online from studies to January 2025. Studies reporting willingness to vaccinate, awareness, recommendation, and uptake of HPV vaccine were included. Pooled prevalence estimates and odds ratios were calculated using random-effects models. Heterogeneity was assessed using the I{superscript 2} statistic. The study was reported following PRISMA 2020 guidelines and registered in PROSPERO ID: CRD420261301213. ResultsThirty-three studies were included. The pooled prevalence of willingness to vaccinate was 68.1% (95% CI: 57.4-77.2; 12 studies; n = 4,993; I{superscript 2} = 98%), while HPV vaccine awareness was 41.3% (95% CI: 28.7-55.1; 33 studies; n = 8,175 participants; I{superscript 2} = 98%). Two-thirds of participants (67.7%; 95% CI: 50.7-81.0; 8 studies; n = 1,617) reported recommending the vaccine, but actual uptake was only 22.9% (95% CI: 6.9-54.5; 9 studies; n = 9,686). Willingness significantly declined from 74.2% before 2014 to 57.5% after 2021. Healthcare workers had the highest awareness (74.5%) and willingness (77.8%). Lack of HPV knowledge was associated with nearly three-fold higher hesitancy (OR: 2.58; 95% CI: 2.06-3.22). ConclusionsDespite moderate willingness, HPV vaccine awareness and uptake remain low in Cameroon, with marked disparities across regions and populations. Addressing knowledge gaps and strengthening context-specific vaccination strategies are needed to improve coverage.

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.

BackgroundVietnam is a top 20 burden country for multi-drug resistant/rifampicin-resistant tuberculosis (MDR/RR-TB), with nearly 10,000 cases a year. With the emergence of new diagnostic assays for M. tuberculosis and resistance, along with new drugs for both treatment and prevention, we sought to better understand the molecular epidemiology of RR-TB in this high-burden setting, through the study of clinical trial isolates from the VQUIN MDR trial. MethodsWe assembled a sample of cultured isolates, collected from patients with confirmed RR-M. tuberculosis within 10 provinces, enriching for isolates from outside of the 2 major cities, Hanoi and Ho Chi Minh City. We subjected these isolates whole genome sequencing (WGS) and bioinformatic analysis, with a subset subject to phenotypic drug susceptibility testing to evaluate phenotypic/genotypic concordance. New genome sequences were phylogenetically contextualised to publicly-available M. tuberculosis genome sequences sampled in Vietnam from National Center for Biotechnology Information (NCBI) Sequence Read Archives (SRA). ResultsIsolates from 252 RR-TB cases passed quality controls and were available for analysis. Xpert MTB/RIF had a high concordance with WGS-based rifampicin-resistance prediction (PPV=96.8%). Of the 244 isolates confirmed to be rifampicin resistant, a high proportion (235/244 = 96.3%) had mutations associated with resistance to at least one other first- or second-line antibiotic. Phenotypic drug susceptibility testing (DST) for rifampicin, isoniazid, and levofloxacin was completed for 77 isolates with a high concordance demonstrated between DST and genomic-based resistance predictions (67/77, 87.0% RIF; 76/77, 98.7% INH; 73/77, 94.8%LFX). High concordance was also observed with new and repurposed antibiotics linezolid (100%, 60/60), pretomanid (100%, 60/60), and bedaquiline (56/60, 93.3%). Rifampicin-resistant strains were more likely to be lineage 2.2.1, compared to rifampicin-susceptible M. tuberculosis strains in Vietnam, particularly in the major cities. ConclusionsThe high prevalence of secondary drug-resistance beyond RIF and INH, along with the dominance of one major lineage across geographic regions, provides insights on the spread of MDR/RR-TB in Vietnam and reinforces the importance of prompt and broad detection of drug-resistance to inform the timely initiation of effective drug regimens.

ObjectivesTo identifiy risk factors for antimicrobial resistance (AMR) in seven pathogen-antimicrobial combinations in patients with cancer and cancer survivors. MethodsUsing data from patients with recent or past cancer diagnostic codes in Oxfordshire, UK, we examined associations between 22 potential risk-factors and AMR in blood culture isolates, collected between 1-April-2015 and 31-March-2025. ResultsAmong 5,975 bacteraemias in 4,365 adults, we analysed 3,141 (52.6%) due to Enterobacterales and 620 (10.4%) due to Enterococcus faecalis/faecium in 2,752 patients. Fourteen risk-factors for antimicrobial-resistant bacteraemia were identified, varying across pathogen-antimicrobial combinations. Compared with no previous antimicrobial susceptibility test result, prior resistance to the same antibiotic in any culture in the last year was strongly associated with AMR across all pathogen-antimicrobial combinations (all p[&le;]0.001). Prior antibiotic exposure and younger age were also positively associated with AMR in four and five combinations, respectively. Cancer type showed modest effects; lymphoid/haematopoietic malignancies were associated with higher odds (vs colorectal cancer) of trimethoprim-sulfamethoxazole-resistant Enterobacterales (aOR=2.07 95%CI 1.40-3.06) and vancomycin-resistant Enterococcus bacteraemia (aOR=6.68, 1.21-36.91). ConclusionsPrevious resistance was the greatest risk factor for bacteraemia with AMR in cancer patients and survivors, with prior antibiotic exposure and age also contributing. Lymphoid/haematopoietic malignancies increased risk of resistance to specific antimicrobials. Keywords: antimicrobial resistance, bacteraemia, cancer, risk factors

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 [&le;] 96 hours, and experienced symptom onset [&le;] 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.

Objectives: To assess the availability of key clinical trial registration data and compliance with legal reporting requirements for all Phase 2-4 drug trials registered on the new European Clinical Trial Information System (CTIS) registry. This study is the first ever assessment of data quality and legal compliance with reporting requirements on CTIS. Design: Cross-sectional observational study of CTIS registry data combined with manual review of results documents. Setting: Cohort of all 7,547 Phase II-IV clinical trials registered on CTIS as of November 2025. Main outcome measures: Number and proportion of missing data points in CTIS registration data. Proportion of completed clinical trials that are compliant with regulatory reporting requirements. Results: Trial registration data quality was high overall with more than 99% of expected data present. Of 234 clinical trials legally required to report results, fewer than half (49.6%) fully reported results within the required timeframe, 20 trials (8.5%) fully reported results late, and 98 trials (41.9%) failed to fully report results. Legal compliance was similar for adult trials (79/158) and paediatric trials (37/76). Conclusions: Sponsor compliance with legal reporting requirements is weak. Current efforts by European regulators to monitor and enforce compliance appear to be insufficient. New results reporting functions currently being set up by trial registries worldwide will require quality assurance processes. Trial registration: Study protocol prospectively registered on OSF: https://osf.io/sn4j2/overview

IntroductionImproved diagnostics are needed for people at risk of tuberculosis, especially adolescents. Tongue swab (TS) molecular testing has emerged as a promising strategy for tuberculosis diagnosis. We evaluated diagnostic accuracy and acceptability of Xpert MTB/RIF Ultra (Xpert) using TS samples for tuberculosis detection among adolescents. MethodsWe conducted a cross-sectional diagnostic accuracy study with consecutive recruitment in Vietnam. Adolescents aged 10-19 who were recommended to undergo investigation for tuberculosis and had not received tuberculosis treatment in the past years were eligible. Participants provided TS and sputum samples and completed a structured survey regarding sampling experiences. TS was tested on Xpert, with sputum tested on Xpert and liquid culture. We utilised a composite reference standard of a positive result on sputum Xpert or sputum culture to define disease status. Sensitivity, specificity, and diagnostic yield were calculated for TS Xpert. ResultsFrom July to December 2025, we enrolled 225 adolescents from Can Tho and An Giang provinces in southern Vietnam. Fewer than half (96/225, 43%) the participants exhibited a tuberculosis -like symptom, and the majority (157/225, 70%) were close contacts of a person recently diagnosed with tuberculosis. TS were collected from all adolescents, while 116 (52%) could provide mucopurulent sputum. Tuberculosis prevalence was relatively low (12/225, 5.3%). TS Xpert sensitivity (90% CI) and specificity (90% CI) were 58.3% (35.6, 78.0) and 99.5% (97.9, 99.9), respectively. Diagnostic yield among all diagnosed was 58.3% (7/12). TS sampling was highly acceptable to adolescents; the short time and simplicity of collecting TS were considered favourably. ConclusionsThe sensitivity and diagnostic yield of TS Xpert was relatively low among adolescents recommended for tuberculosis investigation, which includes asymptomatic individuals who may not provide high quality sputum. Specificity was excellent, and everyone could provide a TS. TSs high acceptability indicates it remains a promising sample for diagnostic algorithms.

BackgroundAccess to tuberculosis (TB) diagnostics remains limited in high-burden countries, partly due to centralised and complex testing. We evaluated MiniDock MTB, a low-complexity near point-of-care (nPOC) assay, in sputum for diagnostic accuracy and agreement with Xpert MTB/RIF Ultra (Xpert). MethodsFrom September 2024 to April 2025, presumptive pulmonary TB cases aged >28 days were consecutively enrolled at 15 community health centres, a lung clinic, and a lung hospital in Bandung, Indonesia. Sputum was tested with MiniDock MTB on sputum swab, Xpert, and liquid culture. We assessed diagnostic accuracy against microbiological and composite reference standards (CRS) and agreement with Xpert. ResultsFrom 3051 individuals screened, 671 were eligible and included; 533 were adults (aged [&ge;]15 years), 138 were children. Overall, 126 were Xpert-positive and 132 culture-positive. In adults, MiniDock MTB sensitivity was 86.2% (110/116; 95% CI 78.8 - 91.3) and 55.8% (110/197; 95% CI 48.9 - 62.6) against liquid culture and CRS, respectively; small numbers of positive results precluded estimation in children. Specificity ranged from 96.8% to 98.8%. Overall agreement between MiniDock MTB and Xpert (excluding trace positive) was 94.8% (95% CI 92.6 - 96.3; K = 0.84). Positive percent agreement was 82.8% (95% CI 75.1 - 88.4) and 25% (95% CI 4.6 - 69.9) in adults and children, respectively, and reduced with lower bacillary burden (p = 0.004). ConclusionsSensitivity of MiniDock MTB in sputum against liquid culture exceeded the WHO threshold for a sputum-based nPOC TB test in adults. There was high agreement with Xpert but reduced sensitivity in low-bacillary burden TB disease.

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

Human papillomavirus (HPV) testing is the primary method for cervical cancer screening, and a negative HPV test is associated with a very low subsequent risk of invasive cancer. Nevertheless, a small number of cervical cancers are diagnosed following an HPV-negative testing result, posing challenges within HPV-based screening pathways. Using nationwide Swedish registry data of HPV testing, we identified women diagnosed with invasive cervical cancer between 2019 and 2024 and reconstructed HPV testing histories from the National Cervical Screening Registry (NKCx). The most recent HPV test prior to diagnosis was defined as the index test, and longitudinal HPV testing trajectories were classified among women with an HPV-negative index test. Of 3,000 women diagnosed with invasive cancer, 243 (8.1%) had an HPV-negative index test. These women were older at diagnosis and more frequently diagnosed at advanced stages compared with women with an HPV-positive index test. Most HPV-negative index tests (66.3%) were performed in the peri-diagnostic period (+/- 30 days). Among women with an HPV-negative index test, 52.7% (128/243) had no prior HPV testing recorded, while the remainder had consistently HPV-negative histories (33.3%, 83/243) or evidence of prior HPV positivity before the index negative test (14%, 32/243). Possible recurrent HPV positivity following an intervening negative test was rare (0.4%, 1/243). HPV-negative screening results preceding invasive cancer reflect heterogeneous screening histories and cannot be explained solely by test failure. Findings highlighting the importance of reaching women earlier in screening programs and show that fluctuating HPV detectability is rare. Novelty and impactHPV-negative results preceding cervical cancer are interpreted as test failures, yet underlying screening histories have not been systematically described. Using nationwide registry data, this study reconstructs HPV testing trajectories. HPV-negative cancers occur in older women with limited screening and advanced-stage disease, but also in women with consistently HPV-negative or previously HPV-positive histories. Findings indicate that such cancers cannot be explained solely by test failure and highlight the importance of earlier screening and rare HPV fluctuation.

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 [&le;]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 [&ge;]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 [&ge;]1 HPV-6/11/16/18 genotypes without significant difference between vaccinated and unvaccinated individuals. Among unvaccinated GBM aged [&le;]26 who were aware of the vaccine, 60% intended to get vaccinated within the next year. Conclusions One to two years after GBM aged [&le;]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.

BackgroundTimely diagnosis of tuberculosis and drug resistance remains a cornerstone of effective disease control. Multiplex open molecular platforms capable of simultaneously detecting Mycobacterium tuberculosis complex (MTBc), non-tuberculous mycobacteria (NTM), and resistance to first-line anti-tuberculosis drugs could streamline diagnostic pathways. MethodsWe conducted a laboratory-based evaluation of two multiplex real-time PCR assays (MTBc/NTM R-Gene(R) and MTB-RIF/INH R-Gene(R)) using 300 well-characterized samples, including 150 MTBc-positive culture isolates (including rifampicin-resistant, isoniazid-resistant, and drug-susceptible strains) and 150 MTBc-negative samples (50 NTM isolates and 100 mycobacteria-negative specimens). Composite reference standards included culture, MPT64 antigen testing, and line probe assay corroborated by phenotypic drug susceptibility testing for resistance profiling, with NTM speciation performed using a dedicated line probe assay. DNA extraction was performed using the QIAamp DNA Mini Kit (QIAGEN, Germany), followed by amplification on a real-time PCR platform according to manufacturer instructions. The diagnostic performance was assessed against composite reference standards. ResultsThe analytical performance for detecting MTBc demonstrated 100% sensitivity and specificity (150/150). NTM detection showed 70{middle dot}0% sensitivity (35/50) and a specificity of 100%, highlighting limitations in coverage of NTM species. Rifampicin resistance was detected with a sensitivity of 96{middle dot}0% (48/50) and specificity of 100%, whereas isoniazid resistance detection was 100% sensitive and specific (50/50). Agreement with established reference standards was high ({kappa}=0{middle dot}76-1{middle dot}00) within this analytical context. InterpretationThis analytical validation demonstrates that multiplex open real-time PCR assays can accurately and simultaneously detect MTBc, NTM, and rifampicin and isoniazid resistance using culture isolates. While these platforms offer potential advantages in flexibility and expanded resistance profiling, additional studies on clinical diagnostic accuracy, cost-effectiveness analyses, and operational feasibility are required to determine their practical utility and programmatic impact in high-burden settings

BackgroundIncomplete dissemination of clinical trial results remains an important challenge for research transparency and evidence synthesis. Although prior studies have quantified the overall extent of non-dissemination, less is known about whether trial characteristics observable at registration are associated with subsequent dissemination within sponsor portfolios. Methods and findingsWe conducted a retrospective cohort study of 17,537 completed interventional clinical trials registered on ClinicalTrials.gov between 2007 and 2024 across the 20 largest global pharmaceutical companies. We developed the Operational Complexity Index (OCI), a composite measure derived from planned enrollment, facility count, and geographic scope, and examined its association with trial dissemination using multivariable logistic regression and time-to-event analyses. Higher OCI was associated with greater odds of dissemination (adjusted odds ratio [aOR] = 2.40, 95% CI 2.23-2.60; p < 0.001), with dissemination increasing from 47% in the lowest OCI decile to 95% in the highest. Higher operational complexity was also associated with earlier dissemination; over a 1,095-day horizon, high-OCI trials were disseminated a mean of 310.88 days earlier than low-OCI trials (RMST difference, 310.88 days; 95% CI 300.59-320.96; p < 0.001). This pattern was observed across sponsors, clinical phases, and therapeutic areas. In predictive analyses using registration-time variables, the structural model achieved a cross- validated AUC of 0.816 and a holdout AUC of 0.814, whereas the full model, including sponsor identity, achieved a cross-validated AUC of 0.858 and a holdout AUC of 0.857. Using benchmark phase-based costing assumptions, the 5,019 non-disseminated trials corresponded to an estimated US$10.94-15.26 billion in sunk research investment. ConclusionsAmong trials conducted by the 20 largest pharmaceutical sponsors, greater operational complexity at registration was associated with a higher likelihood of dissemination and earlier dissemination. These findings suggest that aggregate sponsor-level transparency metrics may mask important heterogeneity within sponsor portfolios. Future work should assess whether registration-time trial characteristics can help identify trial subgroups at higher risk of non-dissemination. AUTHOR SUMMARYO_ST_ABSWhy was this study done?C_ST_ABSO_LIIncomplete dissemination of clinical trial results reduces the completeness of the medical evidence base and the public value of research participation. C_LIO_LIPrevious studies have described overall rates of trial non-dissemination, but less is known about whether dissemination varies systematically across different types of trials within sponsor portfolios. C_LIO_LIWe examined whether trial characteristics available at registration were associated with later dissemination of results among large pharmaceutical sponsors. C_LI What did the researchers do and find?O_LIWe analyzed 17,537 completed interventional clinical trials sponsored by the 20 largest pharmaceutical companies and registered on ClinicalTrials.gov between 2007 and 2024. C_LIO_LIWe developed an Operational Complexity Index (OCI) based on planned enrollment, number of facilities, and geographic scope to measure trial operational scale at registration. C_LIO_LIHigher OCI was associated with a greater likelihood of dissemination and earlier dissemination. Dissemination ranged from 47% in the lowest OCI decile to 95% in the highest. C_LIO_LIThis pattern was observed across sponsor portfolios, clinical phases, and therapeutic areas, with an average within-sponsor dissemination gap of 40 percentage points between lower- and higher-complexity trials. C_LIO_LIIn manual validation of 344 sampled trials, the automated dissemination-classification pipeline achieved 92.1% accuracy. C_LIO_LIUsing benchmark phase-based costing assumptions, the 5,019 non-disseminated trials corresponded to an estimated US$10.9-15.3 billion in sunk research investment. C_LI What do these findings mean?O_LIDissemination was not uniform across trial types within sponsor portfolios; trials with lower operational complexity were less likely to be disseminated than trials with higher operational complexity. C_LIO_LIAggregate sponsor-level transparency measures may therefore miss important differences within portfolios. C_LIO_LIRegistration-time trial characteristics showed predictive signal for non-dissemination, but whether such information could support monitoring strategies would require prospective validation. C_LIO_LIMore complete dissemination of trial results would strengthen the scientific record and improve the public value of clinical research. C_LI

BackgroundPeripheral neuropathy frequently leads to linezolid dose reductions or interruptions during multidrug- or rifampicin-resistant tuberculosis treatment. The effect of these modifications to linezolid on treatment success is uncertain. MethodsWe conducted a target trial emulation using the endTB Observational Study among individuals who developed mild or moderate peripheral neuropathy while receiving linezolid 600 mg daily within 6 months of initiating an individualized regimen. We examined three linezolid management strategies: immediate change (suspension or dose reduction) during Weeks 1-7, deferred change during Weeks 8-26, and no change (i.e., continuing linezolid 600 mg daily) during Weeks 1-26. We used a clone-censor-weight approach to estimate the observational analog of the per-protocol effect on treatment success. ResultsAmong 303 eligible participants from 12 countries, peripheral neuropathy occurred a median (interquartile range) of 11 (4-18) weeks after treatment initiation. Weighted, standardized probabilities of treatment success were 85.8% (95% CI: 72.7%, 93.9%) for immediate change, 78.8% (95% CI: 66.1%, 87.1%) for deferred change, and 85.2% (95% CI: 80.5%, 89.1%) for no change. Compared with no change, treatment success ratios were 1.01 for immediate change (95% CI: 0.86, 1.11) and 0.93 for deferred change (95% CI: 0.78, 1.01) strategies. ConclusionsWe did not find evidence of a substantial negative impact of immediate modification to linezolid among people who developed mild or moderate peripheral neuropathy in the first six months of an individualized regimen. Our results support the clinical practice of cautiously adjusting linezolid when needed to manage non-severe peripheral neuropathy. Key pointsIn this target trial emulation, we found that immediate modifications to linezolid (dose reduction or suspension) in response to mild or moderate peripheral neuropathy during the first six months of MDR/RR-TB treatment did not substantially compromise MDR/RR-TB treatment success.

Background: Correctional facilities are vital venues for expanding testing and treatment for hepatitis C virus (HCV) infections, essential components of national hepatitis C elimination plans. Objective: This study characterizes HCV testing and treatment outcomes among individuals entering incarceration into California state prisons, overall, by year, and by key individual-level characteristics. Methods: We analyzed individual-level electronic health record data from all adults entering California prisons ('entrants') between July 1, 2016 and June 30, 2023. We quantified the percentages of entrants receiving an HCV antibody test within four weeks of entry, the percentage antibody positive among tested, the percentage RNA positive among antibody positive, and the percentage initiating direct acting antiviral (DAA) treatment within one year among RNA positive. Results: Of entrants, 133,639 (76%) were tested for HCV antibody, 25,455 (19% of tested) were ever HCV-infected, and 16,738 (66% of ever infected) were currently infected. Among individuals currently infected, 7,479 (45%) initiated DAA treatment within one year. Individuals with identified SUD had 3.2 times higher antibody positivity and 1.3 times higher proportions initiating DAA, compared to individuals not having an identified SUD. Discussion: We show that HCV testing and treatment in California prisons, a central component of national hepatitis C elimination efforts, supported effective and equitable increases in access to hepatitis C treatment, particularly for those with SUD.

Urinary tract infections (UTIs) are among the most common infectious diseases worldwide, with Escherichia coli being the predominant uropathogen. The increasing prevalence of extended-spectrum beta-lactamase (ESBL)-producing strains and their association with fluoroquinolone resistance pose a significant challenge to empirical therapy, particularly in community settings. The aim of this study was to determine the epidemiology and predictive factors associated with ESBL-producing E. coli and its concomitant fluoroquinolone resistance in community-acquired clinical isolates. A retrospective cross-sectional study was conducted analyzing 244 clinical E. coli isolates. Demographic and microbiological data were collected, including age, sex, sample type, and antibiotic susceptibility. Associations between variables and ESBL production were assessed using Pearsons chi-squared test, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Of the isolates, 165 (68%) were ESBL-producing. A significant association was observed between age group and ESBL production (p < 0.001), with the highest frequency in the 20-39 age group. Most ESBL-positive isolates were obtained from women (73%), although odds ratio (OR) analysis suggested a non-significant trend toward a higher probability in men (OR = 1.29; 95% CI: 0.72-2.31). High rates of fluoroquinolone resistance were identified among the ESBL-producing isolates, with 30% resistance to levofloxacin and 35% to ciprofloxacin (p < 0.001). Urine samples showed the highest concentration of ESBL-positive isolates, with a significant association between sample type and resistance (p < 0.001). The high prevalence of ESBL-producing E. coli and its concomitant resistance to fluoroquinolones highlight a critical challenge for the empirical treatment of urinary tract infections in Mexico, underscoring the need to strengthen antimicrobial use management and local surveillance strategies.

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.