Infectious Diseases

BackgroundReliable identification of early predictors of adverse outcomes was essential during the pre-vaccination phase of the COVID-19 pandemic. Few studies have comprehensively integrated clinical presentation, laboratory parameters including arterial blood gas analysis, and chest computed tomography (CT) findings within a single well-characterized cohort, particularly in underrepresented regions of Brazil. MethodsThis retrospective cohort study included 482 consecutive adults (median age 61 years [IQR 49-73]; 64.3% men) with RT-PCR-confirmed SARS-CoV-2 infection hospitalized at a tertiary cardiac center in Central-West Brazil between March 2020 and January 2021. Demographic, clinical, laboratory (including arterial blood gas analysis), and chest CT data obtained within 48 hours of admission were analyzed. Univariable logistic regression was performed for 76 variables. Multivariable models were constructed using an a priori variable selection strategy based on clinical relevance, representation of distinct pathophysiological domains, and adherence to events-per-variable principles. Complete-case analyses were performed without imputation. ResultsIn-hospital mortality was 9.3% (45/482). Invasive mechanical ventilation was required in 74 patients (15.4%), with a mortality rate of 58.1% among those ventilated. In univariable analysis, 42 variables were associated with mortality (p < 0.05). In multivariable analysis (n = 438), five independent predictors of death were identified: age (adjusted OR 1.66 per 10 years; 95% CI 1.19-2.32; p = 0.003), arterial pH (adjusted OR 0.47 per 0.1-unit increase; 95% CI 0.25-0.89; p = 0.021), neutrophil-to-lymphocyte ratio (adjusted OR 1.30; 95% CI 1.18-1.44; p < 0.001), number of comorbidities (adjusted OR 1.59; 95% CI 1.25-2.02; p < 0.001), and serum creatinine (adjusted OR 1.37; 95% CI 1.05-1.77; p = 0.019). The model demonstrated good calibration (Hosmer-Lemeshow p > 0.05) and moderate-to-high explanatory power (Nagelkerke R{superscript 2} = 0.43). For the composite outcome of death or invasive mechanical ventilation (74 events; 15.4%), four predictors remained independently associated; serum creatinine showed a non-significant trend (p = 0.069). On chest CT (n = 424), analyzed descriptively and in univariable models only, pulmonary involvement > 50% was associated with increased odds of death (OR 2.87; 95% CI 1.42-5.79; p = 0.003). ConclusionsFive admission variables representing distinct pathophysiological domains--age, arterial pH, neutrophil-to-lymphocyte ratio, comorbidity burden, and serum creatinine--were independently associated with in-hospital mortality in this pre-vaccination cohort. Arterial pH provided independent prognostic information beyond inflammatory and renal markers. These findings support early risk stratification using routinely available clinical data.

Background: How post-COVID-19 condition (PCC) differs from post-acute infection syndromes (PAIS) caused by other respiratory viruses remains uncertain. Comparing these conditions may clarify whether post-acute symptoms reflect specific consequences of SARS-CoV-2 infection or broader post-viral mechanisms. Methods: We conducted a systematic review and meta-analysis of cohort studies comparing persistent symptoms or conditions in adults after SARS-CoV-2 infection with those following other acute respiratory viral infections. PubMed, Embase, and Scopus were searched. Random-effects models were used to estimate pooled risks. Results: Among 9,371 records screened, 22 studies were included and 14 contributed to the meta-analysis. Increased risk after SARS-CoV-2 infection was observed for pulmonary embolism, abnormal breathing, fatigue, hemorrhagic stroke, memory loss/brain fog, and palpitations; heart rate abnormalities showed borderline significance. For most other outcomes pooled estimates were inconclusive. Conclusions: Only a subset of outcomes appears more frequent after SARS-CoV-2 infection, suggesting many symptoms attributed to PCC may reflect broader post-viral syndromes.

BackgroundTuberculosis (TB) remains a major global health concern, posing a substantial burden in Pakistan. Genetic factors play a pivotal role in individual susceptibility to TB. Surfactant protein A and surfactant protein D are essential components of the innate immune system, contributing to pulmonary host defense against Mycobacterium tuberculosis (MTB). AimThis study aimed to investigate the association between single nucleotide polymorphisms (SNPs) in the SP-A1gene at rs1059047 (+1101 C/T) and the SP-D gene at rs3088308 (911 T/A) and TB susceptibility in the Pakistani population. MethodA case-control study was conducted, comprising 350 individuals, including 150 healthy controls, 100 TB patients, and 100 TB contacts. Genotyping was performed using tetra ARMS-PCR. GraphPad Prism v.10 was used for statistical analysis. ResultsOur results revealed no significant association between the SP-A1 gene polymorphism at rs1059047 (+1101 C/T) and SP-D gene polymorphism at rs3088308 (911 T/A) and TB susceptibility in the Pakistani population (p>0.5). Interestingly, concerning the rs3088308 polymorphism in the SP-D gene, a comparison between healthy controls and TB contacts indicated that the homozygous TT genotype was significantly associated with protection against LTBI (73.53% vs. 82.35%; p=0.00, OR=0.19, 95% CI=0.08-0.51).

Recent studies suggested that human cytomegalovirus (HCMV) exposure may increase tuberculosis (TB) disease risk. We assessed the association between active HCMV infection and recent HCMV exposure with tuberculosis (TB) disease among TB-presumptive South African adults. This was a nested case-control analysis that utilized stored plasma and serum samples collected from adults ([&ge;]18 years) with presumptive TB self-presenting to primary care clinics in in the Kraaifontein District in Cape Town, South Africa. Cases (n=98) and HIV status frequency matched controls (n=199) basing on mycobacterial culture and or GeneXpert Ultra were included in the study. HCMV DNAemia was detected by qPCR well as current HCMV reactivation or reinfection and recent HCMV infection, reactivation or reinfection were categorized using PCR and serology (IgM and IgG avidity ELISA) results. The median age of all participants was 37 years (IQR 29-47), 164 (55.2%) were male and 119 (40.1%) had previous TB treatment. Overall, 21 (7.1%) had HCMV DNAemia, 19 (6.4%) had positive HCMV IgM and 2 (0.7%) had low HCMV avidity. In a logistic regression model adjusting for age, gender, HIV status and BMI, TB disease was associated with current HCMV reactivation or reinfection [adjusted odds ratio (aOR) 4.88, 95%CI 1.59-16.31, p=0.007]. There was no association with recent HCMV infection, reactivation or reinfection. Unlike recent HCMV infection, reactivation or reinfection, active HCMV replication although not frequent was associated with TB disease which suggests that TB disease or an underlying common factor reactivates HCMV replication in this population.

BackgroundVariation in COVID-19 mortality rates by sex could have several explanations. We aimed to determine sex differences in infection and mortality patterns across different COVID-19 epidemics in Hong Kong, and to evaluate potential hypotheses. MethodsWe estimated age- and sex-specific incidence rates of cases, hospitalizations, and deaths per 100,000 population. Case-hospitalization, case-fatality risks (CFRs), and hospital-fatality risks of the COVID-19 pandemic were also estimated. Adjusted and unadjusted risks were estimated and compared to explore the relationships between mortality and health-related variables. We also explored the sex ratio of COVID-19 mortality rates of respiratory diseases from 2000 to 2019. ResultsHong Kong recorded 2876110 COVID-19 cases and 12737 deaths between January 2020 and January 2023, with 1317368 cases (45.8%) and 7523 (59.1%) fatal cases occurring in males. The incidence rate of cases was similar by sex across waves. The CFRs and hospital-fatality risks were higher in men across all waves. Males had a significantly higher mortality risk after adjusting for sex, COVID-19 vaccination status, and pre-existing chronic diseases. The ratio of COVID-19 mortality rates in men versus women from 2020 to 2023 was similar to the mortality ratio for other respiratory diseases in the pre-pandemic period. ConclusionsWhile infection rates were similar for males and females, males experienced higher mortality risks even after adjusting for differences in other known risk factors. COVID-19 shares a similar sex ratio of mortality with respiratory diseases excluding COVID-19.

Abstract Introduction: Streptococcus is the second genus involved in bone and joint infections (BJIs) after Staphylococcus. Streptococcus agalactiae is the predominant Streptococcus species implicated in BJIs. However, unlike Staphylococcus-related BJIs, data on S. agalactiae infections remain scarce. Methods: We conducted a retrospective cohort study from the West Region cohort of the CRIOAc registry among six university hospitals including all microbiologically confirmed streptococcal BJI in adults between 2014 and 2023. Results: 1454 patients were included, with a median age of 67 years and 65% male. S. agalactiae was the predominant streptococcal species involved 423/1454(29%). The most prevalent comorbidities identified were obesity (378/1454;26%) and diabetes mellitus (343/1454;24%). Prosthetic joint infections (PJIs) were the most common (653/1454;45%), although diabetic foot osteitis was less prevalent overall, it was significantly more associated with S. agalactiae infections (48/423;11% versus 70/1031;7%, p=0.05). S. agalactiae BJIs were more frequently lower-limb infections and chronic infections (240/423;57% versus 502/1031;49%, p=0.04). Half of the cohort had a polymicrobial infection and were slightly more frequent with S. agalactiae BJIs (235/423;56% versus 498/1031;48%, p=0.1). These results were consistent with a sensitivity analysis excluding diabetic foot related osteitis. Logistic regression analysis identified arteriopathy (OR: 4.16; IC95:1.64-11.24, p=0.003), and obesity (OR: 2.57; IC95: 1.41-4.78, p=0.002) as specific risk factors for S. agalactiae BJIs. Conclusion: S. agalactiae emerges as a prominent and distinct pathogen in complex streptococcal BJIs, with specific risk factors such as arteriopathy, obesity and diabetes mellitus, and more chronic infections.

The emergence of vaccine covered serotypes causing invasive pneumococcal disease (IPD) is a serious concern worldwide. We investigated the unexpected rise of serotype 4 causing IPD primarily in non-vaccinated young adults after the COVID-19 pandemic that further spread to adults [&ge;] 65 years in recent years. For this purpose, we conducted a retrospective study of serotype 4 IPD cases (n=827) reported in Spain between 2009 and 2024. Whole-genome sequencing was performed to assess clonal lineages and phylogenetic relationships. Clinical and epidemiological data were compared between serotype 4 and all other serotypes causing IPD. Epidemiological and genomic analysis confirmed that the rise started as an abrupt cluster of IPD cases in Seville (Andalusia) in the year 2022 due to the ST15063 within GPSC12 lineage. This outbreak initially caused pneumonia episodes that required hospitalization in young individuals associated with high rates of tobacco smoking, alcohol, and inhaled drugs such as cannabis and cocaine, followed by a general distribution pattern throughout the country in the following years, affecting the elderly population. Experimental studies to evaluate potential underlying mechanisms confirmed that ST15063 serotype 4 strains displayed enhanced infection rates of human lung cells that significantly increased in the presence of cigarette smoke exposure and by influenza H3N2 virus coinfection, but not with H1N1. These findings highlight the need for targeted vaccination strategies not only against pneumococcus but also against respiratory viruses such as influenza, RSV and COVID-19 and demonstrate the importance of molecular surveillance to establish effective interventions in high-risk populations.

BackgroundAlthough the impact of COVID-19 vaccination is widely documented in the general population, the evidence on its effectiveness in children under 5 years of age is still limited. In this context, the continuation of vaccination programs in this age group has been debated globally. Consequently, we estimated the effectiveness of the 3-dose series of BNT162b2 (Pfizer-BioNTech) in children aged 6 months to 4 years and the complete 2-dose series of CoronaVac (Sinovac) in children aged 3 to 4 in reducing the risk of hospitalizations due to COVID-19-attributed severe acute respiratory infection (SARI) in Brazil. MethodsWe conducted a retrospective cohort study in 24 Brazilian municipalities, using surveillance data. We evaluated vaccine effectiveness in reducing the incidence rate of COVID-19-attributed SARI hospitalizations from July 2023 to December 2024. Covariate adjustments, defined a priori based on a conceptual model represented by a directed acyclic graph (DAG), were implemented using random-effects Poisson regression models. We also analyzed alternative vaccination schedules and obtained age-specific estimates of effectiveness. ResultsThe cohort comprised 37.6 million person-months of follow-up and 1,384 COVID-19-attributed SARI hospitalizations, including 27 associated deaths. The 3-dose series of BNT162b2 vaccine had an effectiveness of 97% (IRR 0.03, 95%CI 0.01-0.10) in the group aged 6 months to 4 years, with no significant differences among age-specific estimates. No deaths occurred among children who completed the 3-dose series, whereas four deaths were observed among those with fewer doses. The effectiveness of CoronaVac was small and not statistically significant (IRR 0.96, 95%CI 0.57-1.62). However, no deaths were recorded among children who received any number of CoronaVac doses, and no COVID-19-attributed SARI hospitalizations were observed among those who received a third dose of this vaccine. ConclusionsThe 3-dose series of the mRNA vaccine (BNT162b2) had high and consistent effectiveness in protecting against severe COVID-19 in children aged 6 months to 4 years. These findings support the maintenance of routine COVID-19 vaccination in this age group.

BackgroundNumerous studies reporting utility of microbial blood biomarkers for diagnosis and treatment monitoring of M. tuberculosis (Mtb) infection and tuberculosis disease have been conducted, but up-to-date systematic reviews and meta-analyses of these data are lacking. We aimed to evaluate diagnostic accuracy of microbial blood biomarkers for detection of tuberculosis disease and to characterise their responses to antimicrobial therapy. MethodsFor this aggregate data meta-analysis, we searched MEDLINE, EMBASE and Scopus from 1st January, 1990, to 22 October, 2025, using terms for "tuberculosis", "microbial biomarker", and "human blood" to identify studies in which participants underwent blood sampling for detection of cell-free Mtb DNA, cell-associated Mtb DNA, protein/peptide Mtb antigens and lipid/glycolipid Mtb antigens before {+/-} after initiation of antimicrobial therapy. For bivariate analyses we used hierarchical summary receiver operating characteristic (HSROC) models to calculate areas under HSROC curves (AUC) for each analyte class to evaluate diagnostic accuracy for tuberculosis disease. For longitudinal analyses, we calculated risk differences to evaluate changes in proportions of biomarker-positive individuals after vs. before initiation of antimicrobial therapy, and pooled them using random-effects meta-analysis. Findings137 eligible articles were identified in the search, of which 109 vs. 13 contributed data to bivariate vs. longitudinal analyses, respectively. For cell-free Mtb DNA targets, AUC was 0.87 (95% CI 0.84 to 0.89), with sensitivity 61.5% (51.0 to 71.0) and specificity 93.0% (88.1 to 96.1); 4,878 samples from 34 unique study/setting/biomarker combinations (investigations). For cell-associated Mtb DNA targets, AUC was 0.93 (0.90 to 0.95), with sensitivity 43.9% (29.4 to 59.4) and specificity 97.1% (94.5 to 98.5); 3,589 samples, 32 investigations. For protein/peptide targets, AUC was 0.94 (0.92 to 0.96), with sensitivity 78.9% (73.2 to 83.6) and specificity 92.9% (90.7 to 94.5%); 10,260 samples, 61 investigations. For lipid/glycolipid targets, AUC was 0.96 (0.94 to 0.97), with sensitivity 68.6% (54.1 to 80.3) and specificity 97.0% (94.0 to 98.5); 3,287 samples, 22 investigations. Pooled risk differences for proportions of individuals biomarker-positive after vs. before initiation of antimicrobial therapy were -0.44 (-0.89 to 0.01; 68 samples, 5 investigations) for cell-free Mtb DNA; -0.46 (-0.88 to -0.03; 89 samples, 5 investigations) for cell-associated Mtb DNA, and -0.24 (-0.75 to 0.28; 160 samples, 4 investigations) for protein/peptide antigens. No studies investigating responses of lipid/glycolipid antigens to antimicrobial therapy were identified. Heterogeneity was moderate (I2 25-50%) for the majority of studies. 98/109 and 11/13 studies contributing data to bivariate vs. longitudinal analyses, respectively, were assessed as being at high risk of bias. InterpretationMolecular and biochemical microbial blood biomarkers exhibit similar accuracy for detection of tuberculosis disease, with specificity consistently exceeding sensitivity. Cell-associated Mtb DNA biomarkers exhibited a statistically significant response to antimicrobial therapy, with similar trends observed for cell-free Mtb DNA and protein/peptide antigens. These findings should be interpreted cautiously in the light of high risk of bias for many of the primary studies contributing data. Higher quality studies are needed to evaluate this emerging class of tuberculosis biomarkers. FundingBarts Charity, The Medical College of Saint Bartholomews Hospital Trust, Wellcome HARP Doctoral Fellowship Scheme. RESEARCH IN CONTEXT Evidence before this studyThe World Health Organisation (WHO) has identified high-priority biomarker needs for screening, diagnosis, evaluating likelihood of disease progression and treatment monitoring for tuberculosis. Numerous studies reporting utility of microbial blood biomarkers for diagnosis and treatment monitoring of M. tuberculosis (Mtb) infection and tuberculosis disease have been conducted, but up-to-date systematic reviews and meta-analyses of these data are lacking. We performed a systematic search of MEDLINE, EMBASE and Scopus from 1st January, 1990, to 22 October, 2025, using terms for "tuberculosis", "microbial biomarker", and "human blood" to identify studies in which participants underwent blood sampling for detection of cell-free Mtb DNA, cell-associated Mtb DNA, protein/peptide Mtb antigens and lipid/glycolipid Mtb antigens before {+/-} after initiation of antimicrobial therapy. Multiple studies have investigated utility of microbial blood biomarkers for detection of tuberculosis disease and monitoring responses to antimicrobial therapy, but only three relevant systematic reviews have been conducted to date, of which two (2007, 2021) report on detection of cell-free Mtb DNA, and one (2011) reports on antigen detection tests. Numerous primary studies have been published since these meta-analyses were conducted, but up-to-date syntheses incorporating the latest data for all classes of microbial blood biomarker for tuberculosis are lacking. Added value of this studyTo our knowledge, this study is the most comprehensive systematic review and meta-analysis of data from studies of microbial blood biomarkers of Mtb infection and tuberculosis disease conducted to date. It is also the first meta-analysis to synthesise data from studies investigating detection of cell-associated Mtb DNA in blood. Bivariate analysis of data from 109 studies revealed AUC values of 0.87 to 0.96 for the four microbial biomarker classes investigated, with sensitivity vs. specificity ranging from 43.9% to 80.2% vs. 87.9% to 97.1%, respectively. Cell-associated Mtb DNA biomarkers exhibited a statistically significant response to antimicrobial therapy, with similar trends observed for cell-free Mtb DNA and protein/peptide antigens. However, most primary studies were assessed as being at high risk of bias. Implications of all the available evidenceMolecular and biochemical microbial blood biomarkers exhibit similar accuracy for detection of tuberculosis disease, with specificity consistently exceeding sensitivity. Cell-associated Mtb DNA biomarkers exhibited a statistically significant response to antimicrobial therapy, with similar trends observed for cell-free Mtb DNA and protein/peptide antigens. These findings should be interpreted cautiously in the light of high risk of bias for many of the primary studies contributing data. Higher quality studies are needed to evaluate this emerging class of tuberculosis biomarkers.

Introduction Improved 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. Methods We 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. Results From 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. Conclusions The 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. TS high acceptability indicates it remains a promising sample for diagnostic algorithms.

BackgroundHigh-risk human papillomavirus (HR-HPV) infection is the necessary cause of cervical cancer, a leading cause of cancer mortality among women in sub-Saharan Africa. In Cameroon, there is a gap in synthetized evidence on HR-HPV epidemiology, limiting data-driven prevention strategies. This study provides the first comprehensive national synthesis of HR-HPV prevalence, genotype distribution, and HIV co-infection among HPV-infected individuals. MethodsA systematic review and meta-analysis were conducted following PRISMA guidelines and registered in PROSPERO (CRD420261282094). We systematically searched PubMed, Scopus, Web of Science, Embase, Cochrane Library, AJOL and local online publishers. Studies reporting the prevalence of HR-HPV among sexually active individuals were included. Pooled prevalence estimates were calculated using random-effects meta-analysis. Heterogeneity was assessed with I{superscript 2} statistics and explored through subgroup analyses. The methodological quality of included studies was evaluated using the Joanna Briggs Institute (JBI) critical appraisal tools. ResultsA total of 33 studies including 18,798 participants were included in this analysis. The overall pooled prevalence of HR-HPV was 28.95% (95% CI: 19.74-40.30; 33 studies; n = 18,798; I2 = 98.7%), with a notable decline from 53.34% before 2014 to 21.43% in 2021-2023. Prevalence varied substantially across populations, being highest among women with precancerous or cancerous lesions (90.69%; 95% CI: 78.48-96.30) and female sex workers (62.10%; 95% CI: 58.08-66.00) compared to women from the general population (21.09%; 95% CI: 15.16-28.55). Among HPV-positive women, HIV co-infection prevalence was 26.17% (95% CI: 13.48-44.65, 19 studies; n = 3,589; I2 = 97.9%), with higher rates in hospital-based studies (34.57%) compared to community-based studies (9.18%). Predominant HR-HPV genotypes included HPV16 (28.7%), HPV52 (23.6%), HPV6 6 (22.9%), HPV33 (22.8%), and HPV18 (20.2%). The pooled prevalence of abnormal cervical lesions among HPV-positive women was 35.15% (95% CI: 20.21-53.70; 12 studies; n = 2,186; I2 = 95.2%), comprising low-grade lesions (34.4%) and high-grade lesions (19.1%). ConclusionsHigh-risk human papillomavirus infection remains highly prevalent in Cameroon despite encouraging temporal declines. The substantial burden of HIV co-infection and circulation of multiple oncogenic genotypes underscore the need for integrated HPV-HIV prevention strategies, expanded screening, and consideration of broader-coverage vaccines to accelerate progress toward cervical cancer elimination targets.

The lack of a reliable chronic murine model limits drugs evaluation against Mycobacterium abscessus. Models show discrepancies, especially regarding host factors (mouse strain, sex and age). Using beads-model, we compared BALB/cJRJ and C57BL/6NCrl across sexes and ages. BALB/cJRJ showed more sustained infection and lower variability, with no significant sex- or age-related differences. Considering these results and the higher prevalence of NTM pulmonary infections in female patients, 5-6 weeks-old female BALB/cJRJ are appropriate for M. abscessus beads-model.

BACKGROUNDDiagnostic performance of tongue swab Mycobacterium tuberculosis PCR has been evaluated for facility-based triage of symptomatic tuberculosis (TB). It is unknown whether tongue swab performance differs for detection of asymptomatic TB in community-based screening. METHODSTongue swabs were collected from adult household contacts of TB patients (HHC Cohort), and symptomatic adults presenting to clinics with presumptive TB (Clinic Cohort), at eight South African sites. TB Cases were defined by positive sputum Xpert Ultra or liquid culture, performed in all participants; and matched [~]1:3 (HHC Cohort) or [~]1:2 (Clinic Cohort) to Controls without TB. Tongue swabs in both cohorts were tested by high-volume qPCR; and in the Clinic Cohort, also by sequence-specific magnetic capture (SSMaC) with qPCR. RESULTSThe Clinic Cohort included 217 TB Cases (100% symptomatic) and 437 Controls. The HHC Cohort included 44 TB Cases (84.1% asymptomatic) and 136 Controls. In the Clinic Cohort, sensitivity of SSMaC with qPCR was 73.2% (specificity 94.6%), but not significantly higher than high-volume qPCR (63.8%; p = 0.14) (specificity 94.4%). Sensitivity of high-volume qPCR in the Clinic Cohort (63.8%) was significantly higher than the HHC Cohort (34.1%; p = 0.0007) (specificity 91.9%). Among HHC, high-volume qPCR sensitivity was 35.1% for asymptomatic TB; 52.2% for TB with abnormal CXR; and 100% for TB with High sputum Xpert Ultra grade. CONCLUSIONSSensitivity of tongue swab high-volume qPCR for community-based, household screening for asymptomatic TB was low, approximately half that of facility-based triage for symptomatic TB, but increased with radiographic severity and sputum bacillary load. Key pointsSensitivity of tongue swab high-volume qPCR for community tuberculosis screening among primarily asymptomatic household contacts was low and approximately half that of facility-based triage for symptomatic tuberculosis. Sensitivity was lowest in individuals with normal chest radiography and low bacillary burden.

BACKGROUNDRespiratory viral infections can trigger acute myocardial infarction (AMI). However, the proportion of AMI events attributable to viral respiratory pathogens is unclear. METHODSThis ecological study used time-series and spatiotemporal analyses to examine population-level patterns in Victoria, Australia, from 2010 to 2022. Independent statewide admissions and laboratory datasets were obtained. Generalized additive modelling was used to analyze the temporal association between respiratory viral circulation captured by polymerase chain reaction (PCR) testing and weekly counts of AMI admissions. A Bayesian hierarchical model was used to explore spatiotemporal variation in AMI associated with respiratory viruses. RESULTSOur study included 164 283 AMI hospital admissions and 6 180 896 PCR-tested samples. An increase in any respiratory virus detection rate was significantly associated with an increased incidence of AMI (incidence rate ratio [IRR] 1.0041; 95% confidence interval 1.0015-1.0067), after adjusting for seasonality, cold temperature, and fine particulate matter air pollution. An estimated 8.7% of total AMI events may be attributable to respiratory viral triggers, constituting an average annual incidence of 16.2 per 100,000 population. Significant associations were found with specific respiratory viruses; the fractions of AMI attributable to enterovirus, influenza, and respiratory syncytial virus were 5.2%, 1.5%, and 0.9%, respectively, with figures increased during peak viral seasons. Spatiotemporal analysis revealed that the association was more pronounced in outer-metropolitan areas. CONCLUSIONSRespiratory viral triggers contribute to the incidence of AMI. Population-level infection prevention strategies, such as vaccination, may reduce the impact of respiratory viral outbreaks during peak seasons. CLINICAL PERSPECTIVEO_ST_ABSWhat Is New?C_ST_ABSO_LIUsing time-series analysis and modern spatiotemporal techniques, we analyzed data from Victoria, Australia, to model population-level associations between AMI and respiratory viral activity and found that a recent laboratory-confirmed respiratory viral infection is associated with a higher incidence of AMI. C_LIO_LIAn estimated 8.7% of total AMI events may be attributable to respiratory viral triggers, constituting an average annual incidence of 16.2 per 100,000 population. C_LI What Are the Clinical Implications?O_LISome respiratory viral infections temporarily increase the risk of acute MI. C_LIO_LIWith the existing vaccines available against influenza and respiratory syncytial virus (RSV), public health policy actions for influenza and RSV vaccination, particularly in high-growth urban areas, may help reduce the acute cardiovascular burden and health system strain. C_LI

Background: Our group previously reported that lung cancer (LC) screening history results and subsequent timing of diagnosis are associated with significant differences in survival outcomes. As a follow-up study, we sought to develop novel personalized risk models that considered screening history for incidence cancers, interval LCs, and prevalence LCs. Methods: Using data from the CT-arm of the NLST, four independent case-control analyses were conducted to develop parsimonious risk models. Controls (n=26,038) were those never diagnosed with LC. The four LC case groups were 270 prevalence LCs, 44 interval LCs, 206 screen-detected LCs (SDLCs) that had a baseline positive screen, and 164 SDLCs that had a baseline negative screen. For each case-control analysis, univariable analyses identified statistically significant covariates from 48 variables and then significant covariates were included into a stepwise backward selection approach to identify a model with the most informative covariates. Results: For prevalence LCs, the model (AUC=0.711) included age, pack-years smoked, BMI, smoking status, smoking onset age, personal history of cancer, family history of LC, alcohol consumption, and milling occupation. For interval LCs, the model (AUC=0.734) included age, smoking status, smoking onset age, cigar smoking, marital status, and asbestos occupation. For baseline positive SDLCs, the model (AUC=0.685) included age, pack-years smoked, BMI, emphysema, chemicals/plastics exposure, and milling occupation. For baseline negative SDLCs, the model (AUC=0.701) included age, pack-years smoked, BMI, smoking status, emphysema, sarcoidosis, and sandblasting occupation. Conclusions: Besides smoking and age, which are inclusion criteria for screening, these models identified other important risk factors which could be used to provide personalized LC risk assessment and screening management.

We genotyped 1189 multidrug-resistant Mycobacterium tuberculosis isolates identified during 2013-2022 in Argentina, through a mixed strategy using PCR-based methods and whole-genome sequencing. Epidemiological, geographic distribution and microbiological data were integrated. Most cases belonged to a cluster (75.7%). The proportion of orphan and clustered cases varied across regions. The Euro-American lineage4 was virtually predominant. The most important clusters, M, Ra, Rb and Callao2 strains, comprised 45.9% of the newly diagnosed cases, and their relative importance varied over time. A preliminary genomic analysis showed that several local transmission chains due to the Callao2 strain, imported from Peru, were active, including a superspreading event that occurred circa 2020. A good performance of the current second-line regimes can be expected for most of the cases. Heightening suspicion of drug-resistance and enhancing timely and active surveillance in specific risk groups could contribute to the tuberculosis management in Argentina, tackling transmission and resistance amplification. BiosketchBiochemist Federico Lorenzo is a professional of the Servicio de Micobacterias, Departamento de Bacteriologia, INEI, ANLIS "C. G. Malbran" and is specialized in the microbiological diagnosis of mycobacterial diseases using next-generation sequencing technologies. His research interests are drug-resistant tuberculosis, non-tuberculous mycobacteria and bioinformatic analysis applied to diagnostics. One-sentence summaryWe evaluated the genotypes associated with multidrug-resistant tuberculosis in Argentina, 2013-2022.

Background: Human papillomaviruses (HPVs) pose a severe threat to global public health by driving nonmelanoma skin cancer (NMSC) and cervical cancer, with NMSC being one of the most common cancers worldwide. Epidermodysplasia verruciformis (EV) is an inborn error of immunity characterized by an increased susceptibility to persistent infection of cutaneous HPV and a high risk of NMSC. The genetic basis remains unknown in many patients with EV. Methods: We collected four unrelated pedigrees with EV. Genetic analysis identified five variants in JAK1 encoding the Janus kinase 1. Ex vivo models and patient-derived tissue were employed to evaluate the functional effects of JAK1 variants and delineate the pathogenic mechanisms. Results: We identified different variants in JAK1 in four pedigrees with dominant EV. Genetic analysis revealed five novel variants in JAK1, three of which resulted in nonsense-mediated mRNA decay (NMD). Functional assays identified a decreased phosphorylation of the signal transducers and activators of transcription (STATs), impaired interferon responses, and defective T cell activation. Immune dysregulation in patients, characterized by a reduced CD4/CD8 T cell ratio, decreased CD8 naive T cell proportion, and accumulated memory T cells, implies impaired antiviral immunity against HPV. Conclusions: Our findings confirm that JAK1 loss-of-function (LOF) variants underlie susceptibility to cutaneous HPV infection. [Funded by the National Natural Science Foundation of China (81788101, 81230015, 82394420, and 82394423), the National Key Research and Development Program of China (2022YFC2703900), the CAMS Innovation Fund for Medical Sciences (2021-I2M-1-018), and the Regione Lombardia, Italy (Innovative Research Project 1137-2010)].

Background: Tuberculosis recurrence accounts for a substantial proportion of incident tuberculosis in many settings. Distinguishing between its mechanisms can inform public health interventions for prevention. Methods: We conducted a retrospective study of individuals with multiple culture-confirmed TB episodes and available sequential isolates from 2012 to 2023 in Dourados and Campo Grande, Mato Grosso do Sul state, Brazil. Patients were classified as having recurrent TB after treatment completion or retreatment following non-curative outcomes. Whole-genome sequencing was used to assess pairwise genetic distances between isolates, classifying relapse or persistent infection ([&le;]12 single-nucleotide polymorphisms [SNPs]) versus reinfection or retreatment with reinfection (>12 SNPs). Results: Among 9,293 individuals with TB, 772 recurrent or retreatment episodes were identified. Paired isolates from 82 individuals were available for comparisons. Among individuals who completed treatment, reinfection accounted for 74.1% (40/54) of recurrent episodes, while 25.9% (14/54) were classified as relapse. Among individuals with non-curative outcomes, persistent infection (53.6%, 15/28) and retreatment with reinfection (46.4%, 13/28) occurred at similar frequencies. Persistent infection and relapse occurred earlier after the initial episode, whereas reinfection and retreatment with reinfection predominated after two years. Incarceration history was strongly associated with reinfection after treatment completion (92.5%, p=0.012) and after non-curative outcomes (76.9%, p=0.016). Conclusions: In this high-burden setting, reinfection drives TB recurrence among individuals who complete treatment, particularly at longer intervals after initial disease, reflecting sustained exposure risk. Relapse and persistent infection remain clinically important, especially following non-curative outcomes. These findings underscore the need for integrated strategies combining adherence support to prevent treatment-related recurrence with interventions to reduce transmission, particularly in high-risk settings.

BackgroundCervical cancer, generally induced by human papillomavirus (HPV) infection remains one of the most prevalent and deadly female cancers in sub-Saharan Africa (SSA). In Cameroon, the impact of prevention strategies is limited by systemic challenges, and insufficient evidence base to guide effective interventions. This study aimed to synthesize available evidence on the prevalence and key determinants of HPV infection among Cameroonian women. MethodsA comprehensive search was conducted across PubMed, Scopus, Web of Science, Embase, Cochrane electronic databases and local online publishers. Quality assessment of included studies was performed using the Joanna Briggs Institute (JBI) critical appraisal tool. The random effect model was used to pooled the estimates. Heterogeneity was evaluated using the I2 statistics. Statistical significance was set at p <0.05 and all analyses were conducted using R Statistics version 4.5.2. The protocol was registered on PROSPERO (CRD420261279093). ResultsThirty-six studies (20,033 participants) were included. The pooled prevalence of HPV infection 36.10 (95% CI: 27.28-45.97) with high heterogeneity (I2 = 98.4%). Higher estimates were observed among female sex workers 62.10% (95% CI: 58.08-66.00%, 1 study, n = 599) and women with pre-cancerous genital lesions 85.53% (95% CI: 61.72-95.59%, 4 studies, n = 673). Significant determinants of HPV infection included age below 40 (OR = 1.31; 95% CI: 1.14-1.49; 7 reports), unmarried status (OR = 1.43; 95% CI: 1.24-1.64; 15 reports), having five or more sexual partners (OR = 1.26; 95% CI: 1.05-1.51; 2 reports), parity below four (OR = 1.29; 95% CI: 1.09-1.52; 2 reports), HIV infection (OR = 1.92; 95% CI: 1.24-2.98; 6 reports), CD4 count below 500 cells/mm3 (OR = 2.00; 95% CI: 1.02-3.95; 2 reports), and viral load below 1000 copies/mL (OR = 2.12; 95% CI: 1.27-3.53; 2 reports). ConclusionsOur study demonstrates a high and persistent burden of HPV infection in Cameroon, with a greater impact on younger women and women living with HIV. These findings highlight an urgent public health need to strengthen and expand prevention strategies to effectively reduce and eliminate cervical cancer incidence in the country.

Background: With the emergence of drug-resistant strains and an unprecedented threat to control initiatives, tuberculosis remains to be a major public health risk in Ethiopia. Resistance to rifampicin (RR) is an important indicator, since RR is an acceptable surrogate for multidrug-resistant TB (MDR-TB). Over 95% of RR is based on mutations in an 81base pair segment of the rpoB gene, detected using rapid molecular assays. Despite this, detailed molecular epidemiological information is scarce. This study characterized the specific rpoB gene mutation patterns among patients in Addis Ababa, Ethiopia. Methods: A cross-sectional study was conducted in 753 Mycobacterium tuberculosis complex (MTBC) clinical samples, corroborated as positive for MTBC from 2020 to 2024; respective probe mutation patterns were generated by the Xpert MTB/RIF platform. Demographic and clinical variables were also assessed for detecting the potential risk factors. Results: The overall RR-TB rate was 2.3% (17/753). Molecular analysis showed a distinct pattern of mutation, with codon 526 mutations being the most frequent, occurring in 54.3% of the resistance mechanisms. This was followed by those at codons 531 (21.7%) and 533 (15.2%). Most significant was the fact that 100% of RR-TB was observed among treatment-naive patients, providing unequivocal evidence that primary transmission is the exclusive cause of resistance in this population. Moreover, there were no statistically significant correlations between RR-TB and demographic factors, including sex, age, or HIV co-infection. Conclusion: The study demonstrates a steady, low-grade epidemic of RR-TB in Addis Ababa, dominated by a virulent bacterial strain with a distinctive mutation at codon 526. These observations highlight the imperative necessity for a strategic shift from a reactive, clinically-oriented model to proactive public health measures. To effectively break the chains of transmission, we recommend the universal application of drug susceptibility testing, enhanced and socially-directed contact tracing, and integrating molecular surveillance into the TB control program.