Open Forum Infectious Diseases

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

BackgroundHigh workload among healthcare workers has increasingly been correlated with poor patient outcomes, inefficient operational and financial outcomes, and burnout. Despite growing literature exploring causes of attending physician workload, there is limited understanding of trainee-specific measures. ObjectiveWe aimed to characterize elements contributing to trainee workload and perceived challenges and satisfiers to the trainee workday as a foundation for better understanding and measuring trainee work experience. MethodsInternal Medicine and Medicine-Pediatrics residents at an academic medical center were invited to participate in focus groups discussing contributors to inpatient workload and work experience between March and April 2024. A qualitative content analysis identified key metrics of trainee workload and work experience, which were then consolidated into overarching domains. A structured, multi-round rating process ranked the perceived relevance of each metric. ResultsTwenty residents participated across six focus groups. Analysis of focus groups yielded 297 workload metrics across 28 unique domains. Seventeen domains had metrics identified as highly relevant (median 6-7; IQR < 1) including autonomy, communication, disruptions, task switching, documentation, emotional burden, patient factors, professional fulfillment, rounding, teaming, and work-life balance. ConclusionsResident physicians highlighted complex interactions between clinical factors, work design, and psychosocial dynamics that contribute to their sense of workload. This creates opportunities to develop unique measures of workload to understand the trainee experience better. Further studies are needed to capture the generalizability of these findings and the relationship between these workload domains and patient, organizational, and trainee outcomes with the aim of implementing evidence-based work design.

Background: Oseltamivir is an antiviral medication for influenza that can reduce the duration of symptoms and may lower the risk of some complications. Recommendations for use of oseltamivir include in the outpatient setting for individuals at higher risk of developing influenza complications. Objectives: To describe oseltamivir initiation and treatment completion among influenza-positive outpatients and identify factors associated with each. Methods: In a U.S. outpatient household transmission study, index participants with laboratory-confirmed influenza provided up to 12 days of detailed information on medication use. We described oseltamivir initiation among index cases and treatment course completion of [&ge;] 10 doses among cases who initiated oseltamivir. We used unadjusted and adjusted logistic regression to identify factors associated with initiation and course completion. Results: Among 823 enrolled index cases, 324 (39%) initiated oseltamivir treatment. Of 406 persons at higher risk for influenza complications, 172 (42%) initiated treatment. Oseltamivir initiation was lowest among children aged 2 to < 5 years (19%) compared to all other age groups. Among 313 cases who initiated oseltamivir, 42% completed the recommended treatment course of [&ge;] 10 doses. Among 163 individuals at higher risk of influenza complications, 69 (42%) completed the recommended treatment course of [&ge;] 10 doses. Children < 2 years were significantly less likely to complete treatment compared to adults aged 18-50 years (aOR: 0.21, 95% CI: 0.04, 0.78, p= 0.030); reasons for discontinuation could not be determined. Conclusions: These findings reveal differences in oseltamivir treatment in an outpatient setting among groups at higher risk for influenza complications.

Tuberculosis (TB) is a significant cause of morbidity and mortality in children and adolescents, causing 172,000 deaths in 2024 in children and adolescents worldwide. Diagnostic challenges are pronounced in pediatrics, in which collecting respiratory specimens is challenging and TB is often paucibacillary, leading to delayed diagnosis and increased mortality. We describe the protocol and methodology of the Pediatric TB Diagnostic (PDTBDx) cohort, a study with the primary aim of evaluating non-sputum-based TB diagnostics for diagnosis and treatment response in children. This is a prospective observational cohort study of >400 children recruited from inpatient and outpatient clinical sites in Nairobi, Kenya. Children <15 years presenting to study clinical sites with TB symptoms will be considered for enrollment as symptomatic participants. Enrolled participants will undergo rigorous clinical assessment and longitudinal follow-up to ensure appropriate diagnostic classification by NIH consensus statement guidelines for pediatric TB. Baseline evaluation includes symptom assessment, chest x-ray, HIV testing, respiratory TB culture and GeneXpert Ultra, and urine LAM. Subsequent visits occur at week 2, months 1, 2, 4, 6,12 and 24. Blood and urine specimens will be collected at baseline and at follow-up visits for storage for evaluation of novel diagnostic assays, including exosome-based and CRISPR-based TB biomarkers. This large, prospective cohort of pediatric participants with and without TB follows a consistent and rigorous protocol for diagnosing childhood TB, in concordance with internationally recognized guidelines. Assays evaluated in PDTBDx will guide improved diagnostic strategies for pediatric TB.

The A(H1N1)pdm09 virus remains a major global health threat. This study examined the burden of ICU admission, mortality, and associated predictors among patients with A(H1N1)pdm09 pneumonia in a leading center for infectious diseases in Vietnam. Information on demographic, clinical, and laboratory characteristics, and outcomes was retrieved from medical records of adults admitted with influenza A(H1N1)pdm09 during 2009-2019. Among 729 cases, 21.7% (158/729) developed pneumonia. Among 158 pneumonia cases, 36.7% (58/158) developed moderate-to-severe acute respiratory distress syndrome (ARDS), and 15.2% (24/158) received invasive ventilation. ICU admission and mortality rates were 48.7% (77/158, 95%CI 41.1-56.5%) and 8.2% (13/158, 95%CI 4.9-13.6%), respectively. Predictors of ICU admission included being >60 years old (adjusted OR [AOR] 13.864, 95%CI 2.185-87.956, P=0.005), comorbidities (AOR 6.527, 95%CI 1.710-24.915, P=0.006), AST (AOR 1.013, 95%CI 1.001-1.025, P=0.029), and moderate-to-severe ARDS (AOR 14.027, 95%CI 4.220-46.627, P<0.001). Predictors of mortality were invasive ventilation (AOR 55.355, 95%CI 1.486-2062.375, P=0.030) and double-dose oseltamivir or combination therapy (AOR 32.625, 95%CI 1.594-667.661, P=0.024). In conclusion, mortality is not rare in A(H1N1)pdm09 infection. Monitoring of older patients and those with comorbidities, liver enzyme elevation, or moderate-to-severe ARDS is essential for the timely detection of complications requiring intensive care.

Background: Induction of HIV envelope (Env)-specific broadly neutralizing antibodies (bnAbs) is considered a key objective for HIV-1 vaccine development. One approach is to vaccinate with HIV Env immunogens that initially target the naive B cell receptors of a bnAb type and boost with a series of HIV Env variants. We chose a priming immunogen, the CH505 transmitted/founder Env with high affinity for the naive B cell receptor of the prototype CD4 binding site (bs) bnAb lineage, CH103, as a candidate priming immunogen to induce the initial critical step in CD4bs bnAb development. Methods: HVTN 300 is a first-in-human, open-label Phase 1 study evaluating the safety and immunogenicity of a CH505 TF chimeric (ch) Trimer adjuvanted with 3M-052-AF (a TLR7/8 agonist) + Alum. The immunogen is a recombinant, stabilized chimeric Env trimer protein with the N-terminal sequence of CH505 TF gp120 Env transplanted into the BG505 SOSIP sequence. Participants received the adjuvanted protein administered in both deltoid muscles at months 0, 2, 4, 8, and 12. Results: Adults (n=18) aged 18 to 55 were screened at a single site in Boston, USA, and 13 were enrolled. Local and systemic reactogenicity was typically mild to moderate. One participant had severe pain/tenderness, and five participants reported transient severe systemic symptoms at least once. Five participants chose to stop further vaccination due to reactogenicity. No vaccine-related SAEs occurred. Vaccine-specific B-cell response rates reached 100% two weeks post third and fifth vaccinations. Antibody blocking experiments with monoclonal antibodies demonstrated that most participants had antibodies directed to the CD4bs. Four out of 11 participants had serum neutralization signatures for CD4bs bnAb precursors. Conclusions: No safety concerns were identified. The adjuvanted CH505 TF chTrimer elicited serum antibodies capable of CD4bs-mediated neutralization against strains designed to detect early precursors of the CD4bs B-cell lineages. Trial Registration: NCT04915768 Disclosure: Presented in part at HIVR4P 2024, Lima, Peru, October 6-10, 2024

Background: The U.S. 2024-2025 influenza season was characterized by sustained elevated activity from November 2024 to April 2025, with circulation of both influenza A(H1N1)pdm09 and A(H3N2), the latter of which included some antigenically drifted viruses. Methods: From October 1, 2024, to April 30, 2025, a multistate respiratory virus surveillance network enrolled adults hospitalized with acute respiratory illness in 26 U.S. medical centers. Influenza vaccine effectiveness (VE) against influenza-associated hospitalization and severe in-hospital outcomes was estimated using a test-negative study. The odds of influenza vaccination among influenza-positive case patients and influenza-negative control patients were compared using multivariable logistic regression; VE was calculated as (1-adjusted odds ratio for vaccination) x 100, expressed as a percent. Results: The 2024-2025 seasonal influenza vaccine was effective against influenza-associated hospitalization (VE: 40% [95% confidence interval (CI): 32%-47%]), consistent across age group and influenza A subtypes. Influenza vaccination also reduced the overall risk of all severe in-hospital outcomes evaluated, including standard oxygen therapy (VE: 41% [95% CI: 31%-50%]), non-invasive advanced respiratory support (VE: 38% [95% CI: 19%-52%]), invasive organ support (VE: 58% [95% CI: 44%-69%]), ICU admission (VE: 58% [95% CI: 47%-67%]), and death (VE: 52% [95% CI: 18%-71%]) with effectiveness varying by influenza A subtype and age. Conclusions: Influenza vaccination reduced the risk of influenza-related hospitalization and severe in-hospital outcomes in adults during the severe 2024-2025 influenza season compared to those not vaccinated.

Background Five-biomarker-defined hypervirulent Klebsiella pneumoniae (hvKp) causes invasive infections, but its burden in bloodstream infections versus classical K. pneumoniae (cKp) is unclear. Methods This retrospective cohort study at a tertiary hospital in Japan included K. pneumoniae bloodstream infection episodes from January 2022-December 2024. hvKp was defined by the presence of all 5 genotypic biomarkers (rmpA, rmpA2, iucA, iroB, and peg-344). The primary outcome was abscess complications, and secondary outcomes were length of stay and antibiotic duration. Whole-genome sequencing was performed for 164 isolates. Results Among the 207 episodes, 28 (14%) were of hvKp. Abscess complication occurred in 17 (61%) hvKp versus 23 (13%) cKp episodes (adjusted odds ratio 10.7; 95% CI, 4.36-26.2). Median length of stay in hvKp versus cKp was 28 versus 14 days (adjusted ratio 1.60; 95% CI, 1.18-2.16) and median antibiotic duration was 43 versus 14 days (adjusted ratio 2.13; 95% CI, 1.64-2.77). These associations were attenuated after adjusting for abscess-related complications. No significant difference in 30-day mortality was observed, although the study was underpowered. Multidrug resistance was less frequent in hvKp strains than in cKp strains (11% vs. 30%; P = .040). Among the sequenced hvKp episodes, abscess rates varied across lineages, from 9 of 10 in ST23 to 1 of 4 in ST412. Conclusions Five biomarker-defined hvKp strains delineated a bloodstream infection subgroup with frequent abscess complications and prolonged care. hvKp and cKp present distinct clinical challenges; diagnostic tools distinguishing these subgroups may aid abscess evaluation and source control.

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

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

1.Etiological diagnosis of lower respiratory tract infections (LRTIs) relies on sputum or bronchoalveolar lavage (BAL), which may be difficult to obtain or invasive. Exhaled breath aerosol (XBA) sampling offers a non-invasive alternative for pathogen detection. We evaluated the performance of the AveloMask, a face mask-based device designed to capture XBAs for molecular testing. In this prospective paired-sample study, hospitalized adults with pneumonia at three hospitals in Switzerland and Georgia provided an XBA sample using the AveloMask and a lower respiratory tract (LRT) specimen (sputum or BAL). XBA samples were analyzed by multiplex PCR using the Roche LightMix(R) panel and LRT samples were tested using the BioFire(R) FilmArray(R) Pneumonia Panel. Concordance between XBA and LRT samples was assessed using positive percent agreement (PPA), negative percent agreement (NPA), and overall percent agreement (OPA). Ninety-three participants were enrolled and 63 participants provided paired samples. AveloMask sampling identified the dominant pathogen (lowest Ct value in the LRT sample) in 40/47 LRT-positive cases (85.1%). Across all targets, PPA was 61% (95%CI, 50-72%), NPA was 100% (95%CI, 99-100%), and OPA was 95% (95% CI, 92-96%). PPA was higher for bacteria than for viruses and lower PPA was largely driven by reduced detection of low-abundance or co-infecting pathogens. In a subset analysis, AveloMask results showed substantial overlap with standard-of-care testing and could have supported antimicrobial de-escalation. Breath aerosol sampling using the AveloMask enabled non-invasive molecular detection of LRT pathogens in pneumonia cases and may complement conventional standard-of-care testing, particularly when sputum is unavailable.

Improving diversity in U.S. Alzheimers disease (AD) research is a pressing need. By 2050, Hispanic and Latino Americans will comprise 30% of the population. Hispanics are 1.5 times more likely and Blacks are twice as likely to develop AD compared to Whites, yet both remain vastly underrepresented in clinical trials research. Aging and AD research mentorship of underrepresented STEM undergraduates is designed to promote entry into related professions by students committed to decreasing disparities in AD research participation and clinical care. The NIA-funded MADURA program recruited 93 students from backgrounds historically underrepresented in STEM majors and/or from NIH-defined disadvantaged backgrounds. Trainees were placed in aging/AD research labs and received weekly training and mentorship from faculty research PIs and other types of supervisors (postdoctoral researchers, graduate students, research assistant staff...) Our study examined student ratings of the program and mentor behaviors, using a program-specific survey and the Mentoring Competency Assessment-21 (MCA-21). Trainees were highly satisfied with both mentoring relationships and the overall program. Student rated MCA-21 competency areas were quite high for both P.I.s and other types of research mentors. However, there were striking differences in associations between competencies and relationship and program satisfaction, by mentor type. For PI mentors, no MCA-21 competencies were associated with relationship satisfaction, but five of six competencies were associated with relationship satisfaction for other mentor types. Similarly, no PI mentor competencies were significantly correlated with overall placement satisfaction, but all six competencies were correlated with overall placement satisfaction for other mentor types. The authors discuss the likelihood of differing student expectations of faculty PI versus other types of research mentors, recommendations for assessing role-specific student expectations (including functions primarily possible only for senior faculty PIs), and utilizing nearer-peer plus PI faculty mentors to comprehensively address the gamut of mentee needs.

Introduction: Antibiotic misuse is a major driver of antimicrobial resistance (AMR), contributing to an estimated 1.27 million deaths globally. In Kenya, inappropriate antibiotic use is shaped by health-seeking behaviors and sociodemographic factors. However, little is known about how adults with productive coughs seek and use antibiotics, or how sociodemographic factors underpin these practices. This study explored antibiotic-seeking pathways, usage patterns, and the sociodemographic factors influencing these practices among adults with productive coughs attending selected chest and tuberculosis clinics in Nairobi County, Kenya. Methodology: A facility-based cross-sectional study was conducted among 400 adults ([&ge;]18 years) with productive coughs. Data were collected using a structured questionnaire on sociodemographic characteristics, antibiotic-seeking pathways, and use patterns. Results: Most participants were male (65.0%) and employed (67.0%), with 68.3% earning below Ksh 10,000 (approximately USD 80) monthly and 35.8% having basic education. A history of smoking (37.3%), tuberculosis (32.0%), or other comorbidities (29.8%) was common. Among 347 (86.7%) antibiotic users, 46.4% obtained antibiotics through general practitioners (GP) only, 31.4% via both GP and over-the-counter (OTC) sources, 15.3% from OTC only, and 6.9% through self-medication. Females were more likely to self-medicate (13.3% vs. 3.2%) and had higher odds of antibiotic use (cOR: 2.00; 95% CI: 1.04-4.10). Tuberculosis history was linked to greater GP reliance (61.7% vs. 37.4%). Low-income participants mainly used GP-only sources, while higher-income earners favored GP plus OTC routes (RRR: 2.67; 95% CI: 1.41-5.05). Empirical use was common (71.1%), dominated by Amoxicillin (90.8%), with multiple antibiotic use reported by 67.2% of the participants. Conclusion: Antibiotic use among adults with productive coughs in Nairobi was widespread and largely empirical, dominated by Amoxicillin and Amoxicillin/Clavulanic acid. Self-medication, unregulated antibiotic access, and inappropriate use highlight the urgent need for stricter prescription enforcement and strengthened stewardship programs to promote rational antibiotic use and curb AMR.

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.

BackgroundWe explored the efficacy of AS01E-adjuvanted respiratory syncytial virus prefusion F protein-based vaccine (adjuvanted RSVPreF3) in subpopulations of participants with underlying medical conditions in the multi-country, phase 3 AReSVi-006 trial (conducted May/2021-May/2024). MethodsMedically stable [&ge;]60-year-olds were 1:1-randomised to receive one adjuvanted RSVPreF3 or placebo dose pre-RSV season 1. In exploratory post-hoc analyses in subgroups of participants with underlying conditions (including COPD, asthma, diabetes, obesity [BMI[&ge;]30 kg/m2]), we evaluated efficacy of one vaccine dose against RSV-related lower respiratory tract disease (RSV-LRTD), acute respiratory illness (RSV-ARI), and RSV-ARI-related complications (e.g., pneumonia, COPD/asthma exacerbation, cardiovascular events). We also evaluated (post-hoc) RSV-ARI-related systemic corticosteroid and antibiotics use in participants with COPD or asthma. ResultsThe efficacy analyses comprised 12,468 vaccine and 12,498 placebo recipients. Efficacy against RSV-LRTD over three RSV seasons was similar among participants with COPD (75.1%, 95% CI: 40.2-91.4), asthma (65.8%, 31.0-84.7), diabetes (69.8%, 37.5-87.1), and obesity (74.1%, 56.4-85.5) as in the overall study population (62.9%, 97.5% CI: 46.7-74.8). Efficacy was also observed against RSV-ARI in these subgroups. Efficacy against RSV-ARI-related complications was 74.4% (95% CI: 11.2-95.2) in participants with COPD and 60.8% (-9.9-88.7) in those with asthma. Among participants with COPD, 15.4% (1.9-45.4) of RSV-ARI episodes in vaccine vs 22.4% (12.5-35.3) in placebo recipients were treated with systemic corticosteroids, and 46.2% (19.2-74.9) vs 56.9% (43.2-69.8) with antibiotics. ConclusionsPost-hoc analyses of the AReSVi-006 trial suggest that adjuvanted RSVPreF3 may help prevent RSV-ARI, RSV-LRTD, and RSV-related complications in medically stable older adults with underlying medical conditions like COPD and asthma. Trial registrationClinicalTrials.gov: NCT04886596 SummaryPost-hoc analyses of the AReSVi-006 trial suggest that 1 dose of adjuvanted RSVPreF3 may help prevent RSV-related illness and complications over 3 consecutive RSV seasons in subgroups of [&ge;]60-year-olds with chronic medical conditions, e.g., COPD and asthma.

Background: Although the hemagglutination inhibition (HAI) titer remains the gold standard correlate of protection against influenza, it does not fully capture the broader antibody responses that contribute to immunity. Methods: We analyzed immune responses in paired pre-infection and convalescent sera from 306 RT-PCR-confirmed A/H3N2 infections from two household studies (2014-18) in Managua, Nicaragua. Antibody responses were measured by HAI and enzyme-linked immunosorbent assays (ELISAs) against full-length hemagglutinin (HA), the HA stalk, and neuraminidase (NA). Participants were classified as HAI responders ([&ge;]4-fold HAI rise), alternate responders (no HAI rise but [&ge;]4-fold boost in [&ge;]1 ELISA), or no-response individuals (no [&ge;]4-fold rise in any assay). We compared demographic, clinical, and pre-infection antibody characteristics across these groups. We also analyzed predictors of an NA response. Results: Overall, 77% of participants had HAI seroconversion or a 4-fold rise. Among the 23% HAI non-responders, 62% had alternate antibody responses. No-response individuals had the highest pre-infection HAI and full-length HA titers (p < 0.0001), the lowest viral loads, and the fewest fever or influenza like illness (ILI) symptoms (p < 0.01). An NA response was more common among symptomatic individuals (p = 0.0483) and those with low or high baseline NA titers. Conclusions: High baseline HAI titers can limit detectable 4-fold rises and are associated with milder illness. Evaluating additional immune responses may capture a more complete picture of the host response to infection, thereby improving surveillance and informing vaccine development. Keywords: Influenza A/H3N2; Hemagglutination inhibition (HAI); Neuraminidase antibodies; symptomatic vs asymptomatic infection; correlates of protection.

Background: In Rwanda, genomic surveillance identified a dominant multidrug-resistant tuberculosis (MDR-TB) strain, the R3clone, responsible for approximately 70% of rifampicin-resistant TB cases. Its presence beyond Rwanda remains unexplored. Methods: Unique genetic signatures of the R3clone were defined using whole-genome sequencing of MDR-TB isolates from Rwanda. We developed a targeted qPCR assay detecting a clone-specific single-nucleotide polymorphism. With these tools, we screened isolates from neighbouring countries and public genomic repositories. Results: We identified 375 R3clone isolates, including 264 from historical Rwandan collections (1991-2021), 49 from recent Rwandan diagnostic routine (2021-2024), 25 from historical Burundi isolates (2002-2013), and 37 among public repositories from several countries. The R3clone-specific qPCR showed 100% specificity in distinguishing the R3clone from other MTBC (sub-)lineages. Transmission analysis revealed cross-border transmission of the R3clone within the Great Lakes Region. Conclusion: This study comprehensively assesses cross-border transmission of a dominant MDR-TB strain, highlighting the need for coordinated international surveillance.

Objectives: To better define the clinical features of Acinetobacter spp. infection in Northern Thailand, including a comparison of hospital- and community-acquired infections (HAIs and CAIs). Methods: A prospective clinical study of Acinetobacter spp. infections at two Northern Thailand hospitals from 2019 to 2022, collecting data on sample sources, patient demographics, comorbidities, antimicrobial resistance profiles, and outcomes. Results: Of 129 enrolled patients, 81.4% had Acinetobacter spp. isolated from a respiratory sample. A significant minority (25.6%) of infections were CAIs, 33.3% of which were admitted to ITU within 24 hours of admission. Compared to HAIs, CAIs were significantly more likely to be caused by blood (15.2%, p=0.0258), wound (21.2%, p=0.0120), or urine infections (12.1%, p=0.0370). Acinetobacter spp. HAIs mainly occurred after admission to ITU (87.7%, p<0.0001) and were more likely to be multidrug-resistant than CAIs (76.3% vs. 34.4%, p<0.0001). Overall, the median length of hospital stay was 27 days and there was a 27.1% in-hospital mortality, which was increased in patients with CVA/brain (p=0.005), and multidrug-resistant (p=0.010) or carbapenem-resistant infections (p=0.003). Conclusions: These data define the clinical profile of Acinetobacter spp. infections in Northern Thailand, confirming their high mortality and demonstrating CAIs are a significant proportion of all cases.

Abstract Background Timely 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. Methods We conducted a laboratory-based evaluation of two multiplex real-time PCR assays (MTBc/NTM R-Gene and MTB-RIF/INH R-Gene) 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. Results The analytical performance for detecting MTBc demonstrated 100% sensitivity and specificity (150/150). NTM detection showed 70.0% sensitivity (35/50) and a specificity of 100%, highlighting limitations in coverage of NTM species. Rifampicin resistance was detected with a sensitivity of 96.0% (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}=0.76-1.00) within this analytical context. Interpretation This 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

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.