Frontiers in Cellular and Infection Microbiology

In primary healthcare centers lacking advanced imaging, community-based active tuberculosis (TB) case finding often relies on basic symptom screening. This approach often misses cases and leads to the inefficient allocation of rapid molecular testing (RMT). We aimed to develop and internally validate a simple clinical triage scorecard to improve TB detection and guide RMT use in resource-constrained settings. We conducted a retrospective cross-sectional study of 15,137 adults ([&ge;]18 years) evaluated within the Zero TB Yogyakarta program (2020-2025). Participants with complete clinical assessments and confirmatory GeneXpert results were included. Using multivariable logistic regression, we identified independent clinical predictors, which were subsequently transformed into an integer-based point scorecard. Model performance was evaluated via discrimination and calibration, utilizing bootstrap resampling (1,000 iterations) for internal validation. Among the 15,137 participants, 251 (1.7%) were GeneXpert-positive. The final multivariable model identified eight independent predictors: age, male sex, body mass index, prolonged cough, hemoptysis, unexplained weight loss, TB contact history, and diabetes mellitus. The model demonstrated strong predictive accuracy, with an optimism-adjusted AUROC of 0.836 and good calibration. When translated to the integer scorecard and compared directly to standard national symptom screening, the scorecard performed (AUROC 0.81 vs. 0.73; p<0.001). At a high sensitivity cut off score of [&ge;] 0, the tool achieved 93.63% sensitivity and 41.33% specificity. This point-of-care clinical scorecard provides higher diagnostic accuracy than standard symptom screening algorithms. By offering flexible operational thresholds, it empowers local health programs to dynamically balance the urgency of case detection with available diagnostic capacity, optimizing GeneXpert allocation where advanced radiological imaging is unavailable.

Background & Aims: Fatigue is a central symptom of chronic liver disease (CLD), substantially impacting health-related quality of life (HRQoL). This study aimed to further understand CLD symptomatology, including fatigue, and its impact on HRQoL from a patient perspective. Methods: Abbott Global Assessment of Patients unmet needs (aGAP) was a multinational, cross-sectional survey in adults with compensated CLD in China, India and Mexico, conducted between July and November 2024. Adult participants who self-reported that they had physician-diagnosed CLD and were experiencing fatigue completed a quantitative survey to assess symptom burden and included three HRQoL patient-reported outcome (PRO) questionnaires (Patient-Reported Outcomes Measurement Information System [PROMIS]-29+2, Work Productivity and Activity Impairment - Specific Health Problem version 2.0 [WPAI: SHP], Multidimensional Fatigue Inventory [MFI]). Results: Overall, 505 participants (China: 200; Mexico: 105; India: 200) completed the study. Participants reported that their CLD-related fatigue sometimes, often or always affected their self-esteem/confidence (45.1%) and ability to maintain or acquire new employment (38.6%). Most participants reported moderate (51.3%) or serious (26.9%) fatigue, with 33.5% experiencing fatigue every day or almost every day. Many participants felt their social life was negatively impacted by their fatigue (47.3%) and that there were related financial difficulties (53.9%). Use of validated PRO tools demonstrated severe fatigue (MFI: overall mean [SD] 13.9 [3.4] general fatigue and 13.4 [3.6] physical fatigue) as well as substantial levels of work and activity impairment (WPAI: SHP overall mean [SD] 53.0 [26.4]) and high levels of anxiety, pain interference, depression and sleep interference (PROMIS T-scores [&ge;]54). Conclusions: Fatigue has a substantial impact on HRQoL among adults with CLD across several countries, highlighting a global unmet need for targeted interventions to effectively identify and manage the condition.

Background: Oral dysbiosis has been associated with oral squamous cell carcinoma (OSCC); however, most microbiome studies rely on 16S ribosomal RNA (rRNA) gene sequencing, limiting species-level taxonomic resolution. Methods: Dental plaque, saliva, and tumor tissue samples from 10 patients with OSCC and dental plaque and saliva samples from 10 healthy controls were analyzed in this exploratory cross-sectional study. DNA was extracted and subjected to shotgun metagenomic sequencing using the Illumina MiSeq platform. Sequence reads were quality filtered with fastp, taxonomically classified using Kraken2 v2.1.3, and species-level abundances were re-estimated with Bracken v2.9 following the removal of human reads and low abundance taxa. Relative abundances were compared using the Mann Whitney U test with the Benjamini Hochberg false discovery rate correction, while the Bray Curtis principal coordinate analysis was used as an exploratory approach to visualize microbial community patterns. Results: Shotgun metagenomic sequencing revealed distinct bacterial community profiles across the oral microenvironment. Dental plaque exhibited the highest taxonomic diversity and relative abundance. The control plaque was enriched in Streptococcus koreensis, Capnocytophaga sp. oral taxon 878, Treponema sp. Marseille Q4132, and Leptotrichia sp. oral taxon 498, whereas the plaque from patients with OSCC showed a higher relative abundance of Pyramidobacter piscolens, Parvimonas parva, and Gemella sanguinis. Salivary samples displayed lower diversity and a more homogeneous composition, predominantly comprising Capnocytophaga endodontalis, Prevotella jejuni, Aggregatibacter aphrophilus, and Gemella sanguinis. The tumor tissue showed relatively higher abundance of Sellimonas catena, Escherichia coli, Solobacterium moorei, and Lacrimispora sp. HJ 01. Conclusions: This exploratory study provides species-level characterization of the oral microbiome across multiple oral microenvironments in OSCC and generates hypotheses for future integrative metagenomic and functional studies investigating the potential contribution of oral bacterial communities to OSCC pathogenesis.

Antimicrobial resistance is a public health challenge, driving the need for rapid, cost-effective diagnostic support tools. Artificial intelligence (AI) may enable prediction of susceptibility to untested antibiotics from known susceptibility results, but prospective clinical validation is required before routine use. We evaluated an AI-based decision support method, trained on invasive isolates from the European Surveillance System (TESSy), for prediction of antibiotic susceptibility in clinical Escherichia coli urine isolates. The evaluation included 99 E. coli isolates from urine samples with diversity in age, sex, and antibiotic susceptibility. Predictions were evaluated for 14 antibiotics using patient metadata and susceptibility results for 4-8 antibiotics as input. Prediction uncertainty was handled using conformal prediction, allowing abstention when confidence was insufficient. EUCAST disk diffusion test results were used as reference and genomic sequence data was used to explore mechanisms of the AI performance. Without conformal prediction, 84% of predictions were correct when susceptibility results of six antibiotics were used to predict susceptibility to eight additional antibiotics. Across all predictions generated using susceptibility results for six antibiotics as input, the major and very major error rates were 19% and 12%, respectively. Prediction errors varied between antibiotics and were associated with certain phenotypic and genotypic resistance patterns. Conformal prediction reduced errors but increased abstentions; at confidence levels of 90%, 95%, and 97.5%, the model abstained in 9.6%, 14%, and 22% of instances. The method showed promising performance, but its clinical use remains limited and may require diagnostic data beyond susceptibility test results and demographic variables.

Background: The condition of a patient with acute stroke often changes within hours of ICU admission. Prognostic work here targets fixed endpoints predicted from admission data, and trajectory phenotyping assigns one label per patient. We used longitudinal ICU data to identify interpretable dynamic clinical states, characterize transitions between them, and relate the current state to later events. Methods: Retrospective cohort study of 6368 adults with acute stroke in MIMIC IV v3.1. The first 72 h were divided into twelve 6-hour windows, and a hidden Markov model was fitted to 21 neurological, physiological and organ support variables. State number was chosen against criteria fixed before fitting: statistical fit, restart stability, state occupancy and clinical interpretability. Generalized estimating equations related the current state to new mechanical ventilation and vasopressor use within 12 h, and to ICU death within 72 h. Eleven sensitivity analyses assessed the robustness of the state solution. Results: Four states were selected: neurologically preserved-low support, neurological impairment low support, impairment renal dysfunction and impairment-respiratory support (63.3%, 7.8%, 11.8% and 17.1% of windows). Within 72 h, 40.3% of patients changed state at least once, and transitions ran in both directions rather than along a single severity gradient. States were identified without outcome data, yet ICU mortality by last state ranged from 2.9% to 43.9%. Adjusted for age, sex, subtype and Charlson index, the current state remained associated with organ-support escalation and death. State prevalence differed by at most 1.1 percentage points between training and test sets, and 10 of 11 sensitivity analyses gave a stable four-state solution (ARI 0.754 0.955). Conclusions: The early ICU course of acute stroke can be represented as movement among a small number of clinically interpretable states. The representation was reproducible in a held out set and across admission eras, but requires validation in an independent database before any clinical use.

Background. Urine-based testing offers a promising non-sputum approach for diagnosing paediatric tuberculosis. However, the currently available lipoarabinomannan (LAM) assay shows limited sensitivity in children and is primarily indicated for those living with HIV. Co-detection of LAM with Mycobacterium tuberculosis (Mtb) proteins in urine could provide complementary pathogen-derived biomarkers that improve diagnostic performance. Methods. We developed an ultrasensitive multiplex electrochemiluminescence (ECL) immunoassay to measure Ag85B, CFP-10, ESAT-6, MPT32, and MPT64 in urine. We determined the analytical limits of detection and evaluated the diagnostic performance of individual proteins and LAM using urine samples from children with Confirmed, Unconfirmed, and Unlikely pulmonary tuberculosis enrolled across five high-burden countries (The Gambia, India, Peru, South Africa, and Uganda). Performance was assessed overall, by HIV and nutritional status, and across biomarker combinations. Findings. Urine samples from 630 children were analysed (median age was 4 years [IQR 2-8]; 44% female, 15% living with HIV, 19% underweight, 24% with Confirmed tuberculosis). The ECL assay achieved femtomolar limits of detection (1.5 to 4.0 fM). The sensitivity and specificity of individual Mtb proteins were 12-33% and 98-100%, respectively. Ag85B had the highest sensitivity (33%, 95% CI 26-41) for Confirmed tuberculosis and was similar to LAM. A four-antigen signature (Ag85B, MPT64, MPT32, LAM) was 50% sensitive (95% CI 42-58) and 94% specific (95% CI 90-96), and was significantly more sensitive than LAM alone, in particular among those without HIV. An additional sixteen (10%) of children with Unconfirmed TB had at least one Mtb protein or LAM detected. Interpretation. Multiple Mtb proteins are detectable in paediatric urine with high specificity, and multi-antigen signatures can augment sensitivity versus LAM alone. These findings demonstrate the potential of multi-antigen urine detection for childhood TB and define analytical targets for the development of future point-of-care diagnostics. Funding. National Institutes of Health.

Introduction: Polyendocrine metabolic ovarian syndrome (PMOS), formerly known as polycystic ovary syndrome (PCOS), is a common endocrine disorder affecting women of reproductive age. Besides reproductive and metabolic disturbances, PMOS negatively impacts psychological well-being and quality of life. Despite available treatment options, there remains a need for safe and effective therapies that improve both clinical symptoms and fertility outcomes. Aim: To compare the efficacy of VAMHA and MYRHA tablet combination therapy with standard non-hormonal therapy in restoring regular menstruation. Secondary objectives included assessment of ovulation, menstrual symptoms, polycystic ovarian morphology, hormonal and metabolic parameters, anthropometric measures, and skin manifestations. Study Design: Open-label, randomized, multicentre, prospective comparative clinical study. Methods: Seventy-one women with PMOS were randomized to Group A (n=37) or Group B (n=34). Group A received VAMHA and MYRHA tablets (2 tablets each), while Group B received Metformin 500 mg plus Myoinositol 600 mg (1 tablet), twice daily for 180 days. Data were recorded in Case Report Forms. Statistical Analysis: Continuous variables were summarized using mean and standard deviation, while categorical variables were expressed as frequencies and percentages. Appropriate statistical tests, including Chi-square, were used. A p-value [&le;]0.05 was considered significant. Results: Significantly more participants in Group A achieved regular menstrual cycles than Group B (31 vs. 22; p<0.05). Ovulation occurred in 16 participants in Group A compared with 6 in Group B (p<0.05). Both groups showed significant improvement in menstrual irregularity and related symptoms. Significant reductions in Anti-Mullerian Hormone (AMH), fasting insulin, and body mass index (BMI) were observed in both groups (p<0.05). Resolution of polycystic ovarian morphology occurred in 13 participants (38.23%) in Group A and 10 (33.33%) in Group B. Both treatments were well tolerated with no major safety concerns. Conclusions: VAMHA and MYRHA combination therapy was superior to standard non-hormonal therapy in improving menstrual regularity and ovulation. It also produced favourable metabolic, hormonal, and ultrasonographic outcomes, suggesting its potential as a safe and effective option for comprehensive PMOS management and fertility enhancement.

The global prevalence of Extended-spectrum {beta}-lactamase-producing Enterobacterales (ESBL-E) colonization is increasing. However, it is unclear whether ESBL-E persist and if that is associated with an altered gut microbial ecology especially in early life where the developing microbiome may not provide the same colonization resistance as in adults. In this study, we collected longitudinal infant gut microbiome samples at delivery and in the nonclinical home setting in Chicago, Illinois, U.S.A, aiming to disentangle how genetic factors pertaining to the ESBL-E, as well as the surrounding gut ecology, influences persistence in the infant gut microbiome. We observed not only a higher-than-expected prevalence of ESBL-E in healthy infant gut microbiomes, but also a trend of ESBL-E persistence once colonized. Microbial communities showed higher dissimilarity between ESBL-E positive and negative infant gut microbiome at earlier time points. Although dissimilarity decreased over time, we present evidence that ESBL-E persist even when traditional detection methods are negative.

The distribution of fat-soluble compounds (including antioxidants) in follicular fluid (FF) remains sparsely documented in relation to in vitro fertilization (IVF) outcomes and existing studies have reported diverging associations. This study aimed to describe plasma and FF concentrations of fat-soluble micronutrients in women undergoing IVF and to analyze their adjusted associations with ovarian function, embryo development and pregnancy outcomes. In 2021-2022, plasma and FF samples were collected from 82 women (first IVF cycle) at oocyte puncture, along with lifestyle data covering the three preceding months. Eleven compounds (two tocopherols, three xanthophylls, five carotenes and retinol) were quantified. All compounds were detected in both compartments (lowest in FF) except phytoene, undetectable in FF. Plasma and FF -tocopherol concentrations were positively associated with plasma estradiol levels before oocyte puncture (both p<0.01) while FF -carotene and lycopene were inversely associated with plasma progesterone concentrations (p=0.01 and 0.02, respectively). Plasma phytofluene and phytoene were positively associated with mature oocyte rate (p=0.03 and p=0.01, respectively), while FF retinol was negatively associated (p=0.03). Carotenes, tocopherols and retinol were inversely associated with later IVF outcomes: fertilization rate (p<0.001 for plasma g-tocopherol, 0.02 for FF retinol), top-quality embryo (p=0.02 for plasma phytofluene), biochemical pregnancy at day 7 post-embryo transfer (p=0.05 for plasma -tocopherol, 0.02 for plasma -carotene), clinical pregnancy (p=0.03 for plasma -tocopherol, 0.01 for plasma phytoene) and live birth (p=0.04 for plasma -tocopherol, 0.02 for plasma phytoene). Plasma and FF g-tocopherol were positively associated with embryo fragmentation (both p<0.05). Finally, among xanthophylls, only plasma {beta}-cryptoxanthin was positively associated with plasma progesterone concentrations (p=0.02). Our findings of heterogeneous associations between tocopherols, carotenes, retinol and IVF outcomes across the stages of IVF suggest a beneficial effect limited to early outcomes and support a complex and context-dependent role of these compounds in female reproduction. This manuscript has been submitted to PlosOne on August 19, 2026.

H5N1 clade 2.3.4.4b avian influenza A viruses pose a significant threat to wild animal populations, domesticated animals, and potentially, the human population. For H5N1s to infect and transmit among mammalian species, mutations for improved utilization of mammalian receptors and enhanced replication at the lower temperatures of the upper respiratory tract need to be acquired. A human H1N1pdm09-like virus was compared to H5N1 genotypes B3.13 and D1.1 for replication at 33{o}C, 37{o}C, and 39{o}C - temperatures consistent with the upper and lower respiratory tract in humans, and dairy cow udder tissue. All H5N1 viruses had increased plaque sizes on MDCK cells at 37{o}C and 39{o}C compared to H1N1pdm09. In primary, differentiated human nasal and bronchial epithelial cultures, all H5N1 viruses show restricted infectious virus production compared to H1N1 at 33{o}C. While H5N1 D1.1 also showed restricted replication at 37{o}C and 39{o}C, the H5N1 B3.13 replicated to nearly equivalent titers as H1N1pdm09. All H5N1 viruses demonstrated similar cell tropism in cells from the upper and lower respiratory tract, infecting more ciliated than non-ciliated cells relative to H1N1pdm09. H1N1, H5N1 B3.13 D1.1 infection induced similar innate immune factors, with nasal epithelial cells producing higher levels compared to bronchial epithelial cells. These data suggest that genotype B3.13 and D1.1 H5N1 viruses show different temperature dependent replication patterns compared to H1N1pdm09.

Transmission-blocking vaccines (TBVs) are a promising strategy to reduce malaria transmission by targeting parasite stages within the mosquito. However, parasite genetic diversity may limit vaccine efficacy. We used next-generation amplicon deep sequencing to identify non-synonymous single nucleotide polymorphisms (SNPs) in Pfs25 from 184 Plasmodium falciparum isolates from Senegal, Tanzania, Ghana, and Burkina Faso. Prioritized SNPs were introduced into P. falciparum via CRISPR-Cas9. For the G116C variant, gametocyte development was evaluated by microscopy and qPCR, and mosquito infectivity was assessed by SMFAs. We identified 26 SNPs, including 24 novel variants. Functional assays showed that the Pfs25 G116C mutation did not affect gametocyte development or exflagellation. SMFA showed no significant differences in oocyst prevalence or intensity between mutant and WT parasites. These findings highlight the importance of integrating genetic surveillance with functional validation to guide the development of effective transmission blocking interventions

Background: Refractory and macrolide-resistant Mycoplasma pneumoniae pneumonia (MPP) has emerged as a major challenge in pediatric respiratory medicine, amplified by the post-2023 resurgence. However, a systematic overview of the research landscape specific to treatment-refractory and drugresistant disease in children remains lacking. Methods: Research articles and reviews on pediatric refractory or macrolide-resistant MPP published between 2000 and 2025 were retrieved from OpenAlex using Boolean searches. After screening, 2,286 records were quantitatively analyzed for annual output, contributing countries/institutions, thematic clusters, and citation-burst dynamics using Python. Results: Annual publications grew exponentially, with a pronounced surge after 2023 (n=378 in 2025). China produced the highest volume (45.1%) but recorded fewer citations per publication than the US, Japan, and Canada. The literature resolved into four clusters: macrolide resistance/molecular basis, epidemiology, etiology/co-infection, and refractory disease management. Burst analysis showed an evolution from earlier fronts like 23S rRNA mutations and azithromycin to recent emerging trends like pandemic-related co-circulation, genotype surveillance, and co-infection. Conclusions: Research on pediatric refractory and resistant MPP is expanding rapidly, shifting in emphasis from etiologic descriptions toward resistance mechanisms and clinical management. Standardizing the treatment of macrolide-unresponsive disease and post-pandemic epidemiological surveillance represent the principal directions for future work. Keywords: Mycoplasma pneumoniae; children; macrolide resistance; refractory pneumonia; bibliometric analysis; research trends

Abstract Background: Vaginal steaming has gained popularity among women for reasons known best to them. However, the effects of vaginal steaming on vaginal lactobacilli levels remain poorly understood and understudied. This study investigated the prevalence, assessed differences in the presence of bacterial vaginosis (BV) among women who practiced vaginal steaming and those who do not and determined the factors associated with vaginal steaming among women attending Mulago Sexually Transmitted Infections (STI) clinic in Uganda. Methods: This study utilized a cross-sectional design to enroll 181 women aged 18 to 49 years who were systematically sampled at Mulago STI clinic. Interviews were conducted to obtain the demographic characteristics of the participants. Vaginal swabbing and Gram staining were done to attain lactobacilli counts by microscopy which were categorized using the Nugent score. Data were analyzed using Stata. The potential confounding effects of other variables on the relation between vaginal steaming and the presence of bacterial vaginosis as well as factors associated with vaginal steaming were assessed using modified Poisson regression. Results: Prevalence of vaginal steaming was 40.3%, (95% confidence interval (CI) 33.0% - 48.0%). There were 41.1% women who practiced vaginal steaming occasionally, 53.4% who used hot water having herbs and 78.1% who practiced vaginal steaming for medical reasons. There was no difference in the presence of bacterial vaginosis when women who practiced vaginal steaming were compared to those who did not (p-value = 0.286). Factors that were significantly associated with vaginal steaming included having experienced vaginal issues (aPR = 0.07, 95% CI 0.01 - 0.12, p value = < 0.001) and contraceptive use (aPR= 0.52, 95% CI 0.37 - 0.72, p value = 0.001). Conclusions: About 2 in every 5 women at Mulago STI clinic reported to have indulged in vaginal steaming. There was no difference in the presence of bacterial vaginosis when women who practiced vaginal steaming were compared to those who did not. Having experienced vaginal issues and contraceptive use were significantly associated with vaginal steaming among women at Mulago STI clinic, Uganda. The Ministry of Health of Uganda should establish targeted screening and treatment for bacterial vaginosis alongside other sexually transmitted infections.

Post-acute infection syndromes (PAIS) follow viral syndromes including post-acute sequelae of COVID19 (PASC) which complicates 10-25% of SARS-CoV-2 infections. These syndromes lack precise explanatory mechanisms. We studied 173 human saliva proteomes during respiratory viral syndromes, seeking associations between 44 clinically-relevant protein expression patterns and subsequent sequelae counts. Exploratory models adjusted by extensive clinical annotations found interactions between 23 acutely-responsive proteins and SARS-CoV-2 infection that inversely predicted subsequent neurocognitive sequelae. An overlapping 19 acutely-responsive proteins during any acute respiratory viral syndrome inversely predicted general fatigue-related sequelae. Altogether, 29 proteins, derived from interferon stimulated genes (ISG), were uniformly beneficial, including 13 predictive of both neurocognitive and general sequelae. The proteins suggested both shared early pathobiology and virus-specific protective responses that shaped resolution of acute disease and different PAIS. Acutely elevated protective ISG proteins associated with reduced post-viral symptoms identify investigational starting points for novel mechanisms, diagnostics and therapeutics for PASC and PAIS.

Background: Seasonal influenza, commonly known as flu, is an acute respiratory, highly contagious illness caused by influenza viruses. A clear understanding of influenza seasonality is crucial for guiding prevention and treatment strategies, including decisions on vaccination timing to prevent outbreaks. While well documented in temperate regions, data on influenza epidemiology in tropical areas, particularly sub-Saharan Africa, remain limited. We described the types, subtypes and positivity rate of seasonal influenza in Uganda during 2019-2023. Methods: We abstracted data from the National Influenza database on positive seasonal influenza cases confirmed by Polymerase Chain Reaction. The cases were disaggregated by age group, sex, region, month and year of reporting. Using Microsoft excel, we calculated the influenza positivity rate and disaggregated it by strain, sex, age, region and time. Test positivity rate was computed as the number of positive cases as a percentage of the total samples tested. Results: Among 17,957 individuals tested, the overall positivity rate for seasonal influenza was 5% (936 cases). Positivity was higher among males compared to females (7% vs. 4%), with children aged 5-9 years having the highest positivity rate (16%), while individuals aged 50-54 years had the lowest (1%). The median positivity rate was 4%, with a range of 1-16%. Regionally, the central region reported a positivity rate of 5%, with rates across all regions ranging from 5% to 8%. Over time, there was a gradual decline in positivity rates, decreasing from 16.5% in 2019 to 5.3% in 2023. Seasonal influenza exhibited bimodal peaks, with the primary peak occurring between March and May and a secondary peak from October to December. Influenza A was the predominant strain, accounting for 70% of seasonal influenza cases (669/936). Among the Influenza A subtypes, H3N2 was most common, representing 63% of cases (425/669). Conclusions: The declining seasonal influenza positivity rates from 2019 to 2023 and the predominance of Influenza A and H3N2 highlight the need for sustained surveillance in Uganda. Given Influenza A's high genetic variability and potential for novel strain emergence, monitoring circulating strains, informing vaccine development, and implementing targeted interventions for high-risk groups and regions are critical to controlling and preventing outbreaks.

Background The COVID-19 pandemic substantially altered respiratory pathogen circulation worldwide. However, longitudinal analyses of changes in respiratory pathogen ecology across the pandemic and post-pandemic periods remain limited. Methods We analyzed 19,968 respiratory samples tested with the BioFire(R) FilmArray(R) Respiratory Panel at a hospital in Tokyo, Japan, between January 2020 and March 2026. We evaluated temporal changes in pathogen circulation, age-specific epidemiology, co-detection patterns, pairwise pathogen associations, and clinical parameters. Results At least one respiratory pathogen was detected in 27.8% of tests. Respiratory pathogens resurged asynchronously following the relaxation of COVID-19-related public health measures. Influenza virus circulation remained markedly suppressed until late 2022 before re-emerging in successive large seasonal epidemics, whereas other pathogens, including RSV, human metapneumovirus, and Mycoplasma pneumoniae, exhibited distinct resurgence patterns. Pathogen distributions also varied by age. Human rhinovirus/enterovirus remained predominant among young children, whereas SARS-CoV-2 predominated among older adults. Co-detection occurred in 14.0% of positive specimens and was significantly more frequent in younger patients. Pairwise analysis identified both positive and negative pathogen associations; however, the patterns varied across age groups and study periods. Conclusions Respiratory pathogen circulation changed substantially during the transition from the COVID-19 pandemic to the post-pandemic period, with pathogen-specific, age- and period-dependent patterns. Continued surveillance is warranted to determine how respiratory pathogen circulation will evolve and to inform infection control strategies in the post-pandemic era.

Background: Sexual and reproductive health (SRH) is essential for youth development, particularly in Sub-Saharan Africa where youth represent a significant proportion of the population. Despite global efforts to promote Sexual and Reproductive Health rights, many disadvantaged youths face barriers to accessing comprehensive information and services. Youth-friendly sexual and reproductive health (YFSRH) services are central to improving youth health outcomes. Despite national standards in Ethiopia, implementation challenges persist. Healthcare workers (HCWs) are key actors in promoting and delivering YFSRH services Method: A concurrent mixed-methods design was employed among youth (18-24 years) and health care workers in Guraghe Zone, Southern Ethiopia. Quantitative data were collected using self-administered questionnaires, while qualitative data were gathered through key informant interviews. Quantitative data were analyzed using SPSS version 29, and qualitative data were analyzed thematically. Result: Although youths showed strong interest in Sexual and Reproductive Health information, help-seeking was often delayed due to discomfort, secrecy, social pressure, and limited foresight. Utilization of youth-friendly Sexual and Reproductive Health services was constrained by distance, inconvenient service hours, limited privacy and confidentiality, perceived judgmental provider attitudes, and financial barriers, reducing trust and repeat use. Conclusion: Improving youth Sexual and Reproductive Health requires integrated actions across education, families, and health services. Strengthening multi-channel Sexual and Reproductive Health education with life skills and psychosocial support, alongside decentralized, affordable, confidential, and non-judgmental youth-friendly services, is essential.

The 17th Ebola outbreak in the Democratic Republic of the Congo, announced on 15 May 2026, was attributed to Bundibugyo ebolavirus (BDBV). Although case isolation is the main control strategy, its effectiveness is compromised when patients escape isolation facilities before recovery. Between 14 May and 17 June 2026, 175 individuals reportedly left isolation facilities without formal discharge across Ituri Province. We assessed how this "isolation leakage" affects community transmission. We refined the SEIHFR framework to distinguish undetected community infections, detected but not-yet-isolated cases, isolated individuals, leakage, funeral-associated transmission, and removals. Using Bayesian inference, we fitted the model to daily Ituri surveillance data, escapee counts, and isolation census records. We estimated the leakage rate, reporting and detection probabilities, and the transmission rate, while fixing other parameters based on the BDBV literature. The model reproduced confirmed cases, deaths, discharges, and escapees. We estimated R_0=3.67 (95% HDI: 2.0-5.7), a leakage rate of {rho} {approx} 0.034 day^-1 (0.022-0.051), and high contact-tracing-driven detection (p_d {approx} 0.91-0.99). Leakage increased the detection-dependent reproduction number [R](p_d) from approximately 3.2 to above 5. Eliminating leakage reduced cumulative infections by about one-third, from 1,120 to 764, while the minimum detection level required for control increased from p_d [&ge;] 0.73 without leakage to p_d [&ge;] 0.87 at the fitted leakage rate. Shortening time to isolation prevented the most infections (73.4%; 59-84), followed by reducing leakage (29.7%; 14-52) and re-isolating escapees (12.6%; 6-24). Delaying leakage reduction until week 4 reduced its benefit from about 27% to below 2%. Isolation leakage represents a major transmission pathway that has until now gone largely unmeasured. While rapid initiation of isolation is highly beneficial, it cannot compensate for permeable isolation; therefore, early, community-driven efforts to control leakage, embedded within a multilayered response, are critical.

Background Carbapenem-resistant bacteria are a major global public health threat, classified as critical priority pathogens by the WHO. In Indonesia, despite a national antimicrobial resistance control programme established by the Ministry of Health in 2015, resistance rates continue to rise, including increasing carbapenem resistance among clinically important bacteria. Strengthening approaches to directly interrupt transmission is essential, yet transmission pathways remain poorly understood with limited research and policy guidance within the Indonesian context. Methods and analysis The INTERCEPT study is a UK-Indonesia multidisciplinary collaboration aiming to identify transmission routes of carbapenem-resistant bacteria across healthcare and community settings, and the mechanisms of resistance gene transfer between bacteria and mobile genetic elementss. We will conduct genomic surveillance of hospital inpatients, healthcare workers, hospital environments, and surrounding communities, including wastewater systems, combined with genomic analyses and mathematical transmission modelling. A cohort of patients with bloodstream infections will be recruited to evaluate resistant bacteria, treatment practices, and clinical outcomes. Qualitative research will explore behavioural and system-level factors influencing transmission and intervention implementation. Findings will inform stakeholder workshops to co-design context-specific interventions, with pilot intervention over 9 months with pre- and post-intervention assessment to guide scalable strategies to reduce AMR transmission. Discussion The INTERCEPT study addresses carbapenem resistance in Indonesia using an integrated approach combining microbiological surveillance, genomics, modelling, and qualitative methods. Strengths include cross-sectoral analysis (patients, workers, environment) and participatory intervention design. Limitations include geographic scope restricted to Central Java, Indonesia.

Human deep-space missions face bone-kidney risks that cannot be extrapolated from six-month ISS data. We built a 12-state Ca-bone-urine-stone mechanistic ODE model and jointly calibrated its 11 physiological parameters on eight ISS targets by Bayesian identification (M0 base = 19-D; M1 extension adds a GCR-bone coupling term for parsimony testing only), then propagated the M0 posterior to four environments (ISS, Lunar subsurface, Lunar surface, Mars). Lumbar-lower BMD loss increases with mission duration and partial-gravity unloading (ISS 180 d -4.83% -> Mars 730 d -12.15%; 2^3 factorial: duration 82.9%, gravity 12.5%, GCR main effect ~ 0), whereas stone rate follows the opposite gradient (ISS 16.1 vs Mars 13.1 per 1000 person-years), reflecting weakened partial-gravity bone resorption alongside residual urinary chemistry changes. The dominant pathway thus shifts from bone-centric on the ISS to kidney-centric on Mars, where residual urinary-chemistry changes-not bone resorption-drive stone risk. The direct GCR-bone coupling term is unidentifiable at current ISS doses (DeltaWAIC = +0.0076 +/- 0.126 SE), so M0 is retained as the main inference model. Bisphosphonates provide >=84% BMD protection but leave a urinary-chemistry residual, so bisphosphonate monotherapy would underestimate Mars stone risk; potassium-magnesium-citrate combinations (RRR_RSS 51%) should therefore be added to deep-space countermeasures. A Lunar-surface 365-day mission is the earliest environment on the NASA roadmap to cross a composite RED threshold. That profile differs from the regolith-shielded 180-day case in both cumulative GCR (~69x) and duration (2x), so a shielding-specific effect cannot be isolated here; forcing the GCR coupling terms to zero leaves all four composite tiers unchanged (0/4, Supp S24), and the shielded 180-day profile is YELLOW rather than GREEN. Independent hold-out validation (Culliton 2025 60-day HDT-bedrest RCT, n=8 control arm of n=24 total) supports the M0 posterior predictive distribution on the lumbar-BMD sub-scope.