The Lancet Respiratory Medicine

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 [≥]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[≥]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 [≥]60-year-olds with chronic medical conditions, e.g., COPD and asthma.

BackgroundIn extensively drug-resistant and pre-extensively drug-resistant TB, bacteriology-based monitoring often fails to capture structural lung recovery and patient-reported functional health. We aimed to characterize multidomain treatment response and examine host inflammatory and transcriptional features associated with incomplete recovery. MethodsWe conducted an ancillary analysis of a prospective, open-label, pilot study evaluating adjunctive ibuprofen in XDR-TB (NCT02781909). Participants were assessed at baseline and during treatment using TBS, chest radiography, sputum culture, SGRQ, blood cell indices, plasma cytokines, and whole-blood transcriptomic profiling. Clinical and laboratory measures were compared across outcome groups, and blood transcriptional profiles were analyzed in relation to treatment outcomes. ResultsHere we show that microbiological and symptomatic improvement occurred earlier than radiological and functional recovery. Higher baseline systemic inflammation, including elevated NLR, SII, and IL-6, as well as increased expression of interferon-related genes such as CD274 and GBP5, were associated with poorer radiological and SGRQ outcomes at 6 months. In contrast, transient elevations of IL-8 and IL-4 were associated with early bacteriological clearance. IL-8 was the only plasma biomarker consistently correlated with symptom severity, radiological findings, and functional health. ConclusionsTreatment response in drug-resistant TB is asynchronous across biological domains. Integrated host profiling identifies inflammatory and transcriptional features associated with incomplete structural and functional recovery, supporting the use of multidimensional endpoints to better capture long-term outcomes and inform individualized patient management. Plain Language SummaryPeople with highly drug-resistant tuberculosis can clear the infection but still experience lung damage and reduced quality of life after treatment. In this study, we examined recovery using several measures, including symptoms, chest X-rays, blood markers of inflammation, and gene activity, in addition to tests for tuberculosis bacteria. We analyzed data and stored samples from a small clinical trial to see how these measures changed over time. We found that lung structure and quality of life improved more slowly than bacterial clearance. People with higher levels of inflammation before treatment were more likely to have ongoing lung changes and poorer quality of life later. These results suggest that tuberculosis care should look beyond bacterial clearance and include monitoring inflammation to better support long-term recovery.

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

Long COVID is a disabling chronic illness with no proven treatments. Persistence of SARS-CoV-2 has been proposed as a biological driver of the disease. We conducted a placebo-controlled, double-blind, 2:1 randomized mechanistic trial of the SARS-CoV-2-specific monoclonal antibody AER002 in 36 participants who met the World Health Organization case definition of Long COVID. After baseline characterization, participants received a single infusion and were followed for 360 days. The primary endpoint was the PROMIS-29 Physical Health Summary Score (PHSS) at 90 days; secondary and exploratory endpoints included patient-reported and objective measures of physical, cognitive, and neurologic function as well as blood-, imaging-, and tissue-based biomarkers. While AER002 was safe and well tolerated, no significant differences in physical health, quality of life, objective measures of physical function or cognition, or blood-based biomarkers were demonstrated between the treatment and control arms. In a post-hoc analysis, participants with a lower baseline SARS-CoV-2 antibody level and higher drug exposure were more likely to express a perceived treatment benefit based on the Patient Global Impression of Change scale (p<0.05 for anti-S, S1, and RBD). Although AER002 was not efficacious in this proof-of-concept study of people with broadly defined Long COVID, our findings could inform recruitment or dosing strategies employed in future trials using monoclonal antibodies to target viral persistence as a driver of Long COVID.

BackgroundPost-tuberculosis (TB) lung disease (PTLD) affects approximately 50% of persons with pulmonary TB. We recently discovered whole blood transcriptional signatures associated with PTLD. We examined whether a minimum gene signature predicts PTLD as a clinically useful biomarker. MethodsWe prospectively enrolled 301 treatment naive adults with newly diagnosed pulmonary TB (PTB) (cohort A). We collected whole blood at 0 and 6-month visits, isolated RNA, and measured a modified MTB Host Response (HR) signature (mHR) based on expression of DUSP3, GBP5, and TMBIM6. We recorded spirometry at 6 (n=216) and 12 months (n=210) after treatment initiation and examined the association of the mHR score with PTLD and Mtb aerosolization. We recruited household contacts of cohort A to compare mHR score with non-PTB participants (cohort B). FindingsmHR was associated with TB (p=4.15e-66) when compared to HHCs, treatment response (p=1.07e-53), and characteristics including CD4 count (p=0.003), bacillary load (p=3.02e-05), lung cavities (p=1.59e-04), and lung quadrants involved (p=3.87e-06). The mHR score was not associated with Mtb aerosolization. In total, 105 (50%) participants had PTLD at 12 months including 61 with restriction, 26 with obstruction, and 18 with mixed obstruction and restriction. Baseline mHR was associated with obstructive PTLD at both 6 (p=0.003) and 12 months (p=0.012) in bivariate and multivariate analyses. The mHR score was not associated with restrictive lung disease. InterpretationBaseline mHR was associated with obstructive PTLD at 6 and 12 months and may have applications in targeting treatment and prognostication.

BackgroundCold chain requirements limit vaccine accessibility and deployment. SPVX02 (Stablepharma Ltd), is a lyophilised, fridge-free version of Tetadif (BB-NCIPD EAD) tetanus-diphtheria vaccine, stable for at least 18 months at temperatures up to 30{degrees}C. MethodsA multicentre, first-in-human phase 1, blinded, randomised clinical trial to evaluate the safety and tolerability of SPVX02 compared to existing approved tetanus-diphtheria (Td) vaccines was conducted. Healthy adults aged 18-55 (BMI <=32 kg/m2) who had received Td vaccination >=10 years previously were randomly assigned (1:1:1) to receive SPVX02, Tetadif, or diTeBooster (AJ Vaccines A/S). Participants and all investigatory staff were blinded to treatment allocation. Primary outcomes were incidence of adverse events during the trial period including incidence of adverse events reported in participant diaries for 7 days post-dose. Secondary outcomes were day 28 seroprotection rates. Analyses were descriptive. The trial is registered with ISRCTN (98920861). FindingsBetween April 1st and September 22nd, 2025, 120 healthy volunteers were screened and sixty participants enrolled at two of three sites. The demographic characteristics of participants were equivalent between groups. No serious adverse reactions, suspected unexpected adverse reactions, or serious adverse events occurred. Fifty-four participants experienced mild or moderate adverse events (AEs); none were severe (grade 3 or higher) AEs. Reactogenicity and tolerability profiles were similar across all groups. All participants had anti-tetanus toxoid (TT) levels >=1{middle dot}0 IU/ml at Day 28. All participants in both the SPVX02 and Tetadif groups and 19 (95%) in the diTeBooster group had anti-diphtheria (DT) toxoid levels >=0{middle dot}1 IU/ml at Day 28. InterpretationSPVX02 is safe, well tolerated, with TT and DT immunogenicity similar to approved Td vaccines. This trial provides first-in-human evidence that StablevaX (Stablepharma, UK) technology can safely reformulate an aluminium-adjuvanted vaccine stable up to 30{degrees}C for 18 months. FundingFunded by Innovate UK Smart Grant project #10083165 and Stablepharma Ltd. Research In ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for randomised controlled trials with thermostable vaccines between database inception and June 2024 using the terms ("temperature stable") OR ("thermostable") AND ("vaccin*") OR ("thermostable vaccine") with no language restrictions. We identified 33 publications which described various in vitro and in vivo studies that have been performed by researchers as part of their efforts to develop thermostable vaccines. We also identified 2 publications which described randomised, controlled clinical trials that were conducted with thermostable vaccines; (1) a phase 2 clinical trial with ROTASIL, an oral rotavirus vaccine (Isanaka et al, NEJM, 2017) which is now licenced and distributed as a refrigerated product that must be stored but must be stored at 2-8{degrees}C; and (2) a phase 1 clinical trial with a current unapproved TB vaccine candidate, ID93+GLE-SE (Sagawa et al, Nature Comms, 2023) where there is no current public information regarding vaccine tolerance to freezing. Added value of this studyThis first in human study demonstrates that the reformulated thermostable aluminium hydroxide adjuvanted tetanus-diphtheria vaccine, SPVX02, is safe, well tolerated, and can boost immune responses to tetanus and diphtheria to similar levels as approved comparator vaccines. This vaccine can be stored and distributed at room temperature and is not affected by freezing. A larger Phase 2/3 trial is now planned to confirm these findings prior to consideration for market authorisation. Implications of all the available evidenceThe evidence presented here demonstrates that StablevaX technology can be successfully utilised to reformulate a vaccine to be thermostable at room temperature for an extended period of time, without compromising reactogenicity or immunogenicity. While we present data pertaining to a single vaccine, the reformulation and lyophilisation technology underpinning SPVX02 can be applied to many liquid vaccines and biological products. The WHO Immunization Agenda 2030 sets out the global strategy to improve vaccine access in resource-limited settings, prevent vaccine wastage and to reduce the logistical, financial and environmental impact of cold chain requirements. If proven successful across a broader range of vaccine products this technology has potential to significantly benefit global health.

A number of vaccines and long-acting monoclonal antibodies have been shown to be effective in the prevention of respiratory syncytial virus (RSV) disease. However, an immune correlate of protection for RSV has not yet been identified. We conducted a systematic review to identify published reports of immunogenicity and/or efficacy in vaccines and long-acting monoclonal antibodies against RSV and performed a meta-analysis on extracted data to identify any relationship between antibody increase and protection against RSV disease. We identified 130 relevant reports which we classified into an open access evidence map of RSV immunisation products. We found a strong correlation between the immunisation induced rise in neutralising antibody titres and efficacy ({rho}>0.7 for all comparisons, Spearman). For infants, we estimated that each 10-fold increase in neutralising antibody titre rise provides an additional 31% [95% CI 10%-47%], 47% [95% CI 36%-56%] and 57% [95% CI 45%-66%] reduction in the relative risk of symptomatic, moderate and severe disease respectively. For older adults, a 10-fold rise in antibody levels was associated with a 34% [95% CI -2%-57%], 50% [95% CI 22%-67%] and 63% [95% CI 36%-79%] reduction in the relative risk of RSV disease with 1, 2 and 3 symptoms respectively. These results align extremely well with findings from natural history studies and individual-based analysis of correlates of protection studies. This work paves the way for use of neutralising antibodies as a correlate of protection to guide the development, approval, and deployment of RSV vaccines and monoclonal antibodies.

BackgroundThe SARS-CoV-2 LP.8.1 subvariant was incorporated into the 2025-2026 U.S. COVID-19 vaccines (mRNA-1273.251 and mRNA-1283.251). We evaluated immunogenicity and safety of these vaccines against vaccine-matched and emerging variants in individuals aged [&ge;]65 and those aged 12-64 years at high-risk of severe COVID-19. MethodsData were generated from: (1) two independent, ongoing, phase 3b/4, open-label, single-arm studies in which participants received a single dose of 50-{micro}g mRNA-1273.251 (n=103; median age, 64.0 years) or 10-{micro}g mRNA-1283.251 (n=172, median age, 59.0 years) and followed through Day 29 post-vaccination; neutralizing antibodies (nAb) were measured at baseline (Day 1) and Day 29 using a pseudovirus neutralization assay against the vaccine-matched LP.8.1 variant; (2) Day 29 immunogenicity against circulating variants (BA.3.2.2, XFG, and NB.1.8.1) was assessed in a randomly selected subset; and (3) immune-escape potential was estimated using predictive modeling. Unsolicited adverse events (AEs), including serious AEs, leading to study withdrawal, and those of special interest, were monitored. ResultsBoth vaccines elicited robust nAbs at Day 29 against LP.8.1 (geometric mean fold-rise from baseline: 12-64 years, mRNA-1273.251, 26.3; mRNA-1283.251, 53.0; [&ge;]65 years, mRNA-1273.251, 15.4; mRNA-1283.251, 36.7) and circulating variants. Model-based estimates with mRNA-1273.251 were consistent with clinical data and indicated the highest responses against LP.8.1 and lower responses against BA.3.2.2. No vaccine-related AEs were reported in either study. ConclusionsmRNA-1273.251 and mRNA-1283.251 were well tolerated through Day 29 and elicited robust nAbs against vaccine-matched and circulating variants. In predictive models, BA.3.2.2 had the highest relative risk of immune escape following mRNA-1273.251 vaccination. SUMMARYLP.8.1-containing mRNA-1273.251 and mRNA-1283.251 vaccines given as a single dose were well tolerated and induced robust Day 29 neutralizing antibodies against LP.8.1 and circulating variants.

We evaluated 2024/25 KP.2 vaccine effectiveness (VE) against COVID-19 hospitalization among adults >60 years old eligible for publicly-funded vaccination during fall and/or spring campaigns in the province of Quebec, Canada. We included Quebec residents tested for COVID-19-compatible symptoms in an acute-care hospital between October 13, 2024 (epi-week 2024-42) and August 23, 2025 (2025-34), linking vaccine, hospital, chronic diseases and laboratory administrative records to assess VE through test-negative design. We compared the odds of being COVID-19 test-positive versus test-negative among vaccinated versus non-vaccinated participants, adjusting for sex, age, comorbidities, place of residence, and epidemiological week. Overall, 49,949 (43%) participants were vaccinated. Over an analysis period spanning up to ten months, including median time since vaccination of 16 weeks (interquartile range 9-24 weeks), VE was 34% overall, declining from 43% <8 weeks to negligible by the 32nd week post-vaccination. Findings confirm meaningful but short-lived COVID-19 vaccine protection against hospitalization in older adults.

Background Rifampicin-resistant tuberculosis (RR-TB) is a major threat to public health in Viet Nam, with nearly 10,000 incident cases estimated annually. It is uncertain whether these cases are driven by transmission of resistant strains or de novo resistance acquisition during treatment. Methods We undertook dense, city-wide sampling of adults newly diagnosed with pulmonary RR-TB in Ho Chi Minh City, Viet Nam's largest city, between March 2020 and April 2024. Participants provided sputum for culture and whole-genome sequencing (WGS), and demographic and clinical data were collected at enrolment. Phylogenetic analyses were combined with clinical histories to infer transmitted versus acquired rifampicin resistance. Estimates were corrected for sampling coverage using simulation-extrapolation (SIMEX). Temporal emergence of rifampicin resistance was reconstructed by lineage using Bayesian phylogenetic dating, and the geographic and demographic structure of transmission networks was assessed using geocoded residential data and commute time-based analyses. Findings Among 2,319 RR-TB cases diagnosed during the study period, 1,491 (64%) isolates were successfully sequenced. After accounting for sampling and phylogenetic uncertainty, we estimated that between 72% and 87% of all RR-TB arose through transmission of already-resistant strains with the remainder due to de novo acquired resistance. Bayesian dating analyses revealed that resistance emergence events occurred repeatedly from the 1980s to the present, with early events seeding long-lived, city-wide transmission networks. Transmission networks were geographically dispersed across the city, with limited household clustering, and only weakly structured by host demographics, consistent with diffuse, city-wide transmission rather than localised or assortative spread. Interpretation RR-TB in Ho Chi Minh City is driven predominantly by ongoing transmission, but a substantial minority of cases arise from newly acquired resistance. Alongside promoting early diagnosis and treatment to interrupt transmission, the main drivers of acquired resistance need to be identified to control RR-TB.

BackgroundHousehold contact investigation for tuberculosis (TB) is limited by referral for clinic-based testing services. We evaluated the performance of in-home tongue swab (TS) testing among symptom-agnostic household contacts (HHC) to inform HCI screening strategies. MethodsWe conducted a prospective cohort study among HHC of TB patients in Eastern Cape, South Africa. In-home testing of sputum and TSs, with TSs pooled from up to three HHCs, was performed using Xpert Ultra on portable GeneExpert devices. Outcomes included diagnostic performance of TS testing relative to sputum and linkage-to-care outcomes. FindingsBetween June 2021 and October 2024, 909 HHC were enrolled; 99{middle dot}1% provided s TS, 31{middle dot}6% provided sputum. Overall sensitivity and specificity of TS testing was 61{middle dot}9% (95% CI: 38{middle dot}4%-81{middle dot}9%) and 100% (98{middle dot}9%-100%), respectively; sensitivity was 100% (47{middle dot}8%-100%) for individually tested swabs. Among two-swab and three-swab pools where 21 individual was sputum positive, 55{middle dot}6% (21{middle dot}2%-86{middle dot}3%) and 42{middle dot}9% (9{middle dot}9%-81{middle dot}6%) tested positive, respectively; TS sensitivity declined with decreasing sputum Ultra semi-quantitative category. 27 of 439 (6{middle dot}2%) households had an indictation of secondary TB; 13 (3{middle dot}0%) by sputum and TS, 11 (2{middle dot}5%) by sputum only, 3 (0{middle dot}7%) by TS only. Sputum testing identified 29 HHC with TB (yield=3{middle dot}2%); 25/29 (86{middle dot}2%) linked to care (median 1 day [IQR 1-2]). InterpretationWhile in-home molecular testing of sputum supported rapid linkage-to-care, and TSs enabled near-universal testing of symptom-agnostic HHCs, efficiency gains through pooled TS testing must be balance against sensitivity trade-offs. FundingU.S. NIH; Australian Department of Foreign Affairs and Trade; UK Foreign, Commonwealth and Development Office RESEARCH IN CONTEXTO_ST_ABSEvidence Before This StudyC_ST_ABSHousehold contacts (HHCs) of people with TB are prioritized for active case-finding (ACF) strategies due to their increased risk of developing TB disease. Household contact investigation (HCI), a widely recommended ACF strategy, is constrained by attrition from referral-based cascades and sputum-based testing. We searched PubMed and Embase for studies published in English from January 1, 2010 to January 31, 2026, using combinations of the terms "tuberculosis" or "TB" with "household contact," "contact tracing," "contact investigation," "screening," "triage," "in-home testing," "molecular testing," and "tongue swab." We also reviewed references listed in relevant articles. There are limited data describing microbiological testing strategies targeting HHCs conducted outside clinic settings, and fewer still that explore the integration of HCI and in-home molecular TB testing. Tongue swabs have emerged as a promising non-invasive, non-sputum specimen type for molecular TB diagnosis. However, most tongue swab performance data have been generated in clinic-based or symptom-prompted populations, with a marked paucity of data generated in populations at high risk for asymptomatic or paucibacillary TB, including HHC. Before this study, published work exploring the use of tongue swabs within in-home TB testing strategies was limited to two papers, both from our group, which focused on acceptability, feasibility, and preliminary costing and modeling analyses. To date, no published studies have assessed the diagnostic performance of tongue swab-based molecular testing relative to sputum-based testing among HHC, the use of tongue swab specimens as part of in-home testing strategies, nor the implication of pooled tongue swab testing to inform household-level screening and diagnostic escalation strategies. In addition, evidence describing verified linkage to TB treatment services following in-home sputum molecular testing was limited to one pilot study paper. Added Value of This StudyThis study is the first to evaluate in-home molecular TB testing using tongue swab specimens, and to incorporate household-level pooling of tongue swabs from multiple household members as a primary screening strategy. Near-universal swab collection substantially expanded access to microbiological testing in a population with limited sputum production. Although pooled swab testing exhibited reduced sensitivity compared with individual-level sputum testing, stratified analyses of tongue swab tests by sputum Xpert Ultra semi-quantitative categories demonstrate that this reduction reflects a biological gradient associated with low mycobacterial burden. Importantly, pooled swab testing identified TB among contacts unable to produce sputum, increasing diagnostic yield beyond sputum-dependent approaches. The study also documents the increase in diagnostic yield when implementing a symptom-agnostic testing strategy among HHC, and rapid, verified linkage to clinic-based TB treatment services following in-home sputum testing. Implications of All the Available EvidenceCollectively, the available evidence supports reframing TB household contact investigation from individual-level referral for clinic-based testing toward in-home testing models, including the use of household-level screening with diagnostic escalation. Near-universal, in-home collection of tongue swab specimens enables substantially broader microbiological assessment than sputum-dependent strategies and facilitates detection of TB among asymptomatic and sputum-scarce HHCs, individuals frequently missed by referral-based approaches for clinic-based sputum collection and testing. Our findings show that the reduced sensitivity associated with pooled tongue swab testing follows a predictable biological gradient related to mycobacterial burden rather than a technical failure of pooling. Pooled swab testing should therefore be understood as a household-level screening strategy within a sequential diagnostic algorithm, not a replacement for individual diagnosis. For TB programs, efficiency gains and expanded coverage achieved through pooling must be balance against sensitivity trade-offs. Household-level screening using pooled specimens can focus downstream referrals and may improve programmatic efficiency without requiring universal individual testing. Future research should evaluate optimized diagnostic algorithms that integrate pooled, non-sputum testing with diagnostic escalation, assess impact on linkage-to-care and prevention outcomes, and define the role of pooled testing within scalable, community-based TB case-finding strategies.

Background: Extreme-phenotype comparisons allowed the discovery of novel asthma genetic risk loci. However, this approach remains unexplored in epigenome-wide association studies (EWAS). We aimed to identify bulk and cell-specific methylation markers of asthma with severe exacerbations across diverse ancestry groups. Methods: We conducted a meta-EWAS of 739,543 CpGs in whole blood among 1,192 African American and Latino pediatric populations, comparing non-asthmatics and asthma exacerbators. Genome-wide CpGs were followed up for replication in a meta-analysis across 1,516 ethnically diverse participants and in a cross-tissue evaluation of 393 nasal samples. We conducted differentially methylated region (DMRs), cell-type-deconvoluted, and quantitative trait loci analyses (whole-genome sequencing n=1,668; RNA-seq n=1,209). We examined enrichment in traits, pathways, and druggable genes, and analyzed DNAm predictors of plasma proteins and aging. Results: DNAm at 505 CpGs and 119 DMRs in whole blood were associated with asthma exacerbations (p<9x10-8, {lambda}=1.05). We replicated 25 CpGs in blood cells, cross-validated 7 in nasal samples, and detected 42 cell-specific DNAm markers mainly driven by T cells. DNAm at 134 CpGs was associated with gene expression in whole blood, including 118 associations with T-cell receptor genes, and 446 CpGs were regulated by [&ge;]1 genetic variant. We found enrichment for previous associations with environmental exposures, immune disorders, immune and inflammatory pathways, and druggable genes by developmental drugs. 21 methylation-predicted plasma proteins, involved in host defense, and one lung aging clock were associated with asthma exacerbations. Conclusions: The first meta-EWAS of extreme asthma phenotypes identified hundreds of novel DNAm markers, suggesting novel methylation biomarkers and candidate drugs for asthma and supporting the role of T cells.

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.

ObjectiveThis study explored the recovery experiences of individuals who report having (largely) recovered from long covid and who attributed their improvement to mind-body approaches. Design, setting and participantsWe conducted an explorative qualitative study using purposive recruitment through social media and snowball sampling. Eighteen adult women (aged 37-62 years), who self-identified as having had long covid and having substantially recovered through mind-body approaches participated in semi-structured interviews. Data were analysed using Saunders practical thematic analysis. ResultsDespite variation in personal narratives, a common trajectory emerged: participants moved away from a biomedical explanatory model towards one centred on nervous system dysregulation. This shift, sometimes following initial scepticism, was often described as a turning point, sparking hope and motivation to engage in self-directed strategies. Recovery was not linear but an iterative process, involving cycles of practice, reflection (especially when progress stagnated) and adaptation of mind-body techniques. Over time, participants gained insights into contributing factors and, in many cases, made intentional life changes to support ongoing recovery. These patterns echo findings from previous research on mind-body approaches in chronic pain and chronic fatigue, and align with neuroscientific perspectives on symptom generation. Most participants navigated this process without formal clinical support, relying instead on online communities and actively avoiding sources of (biomedical) information that conflicted with their new understanding. ConclusionsWhile causal inferences cannot be drawn from qualitative data, this study highlights potential mechanisms that may underpin recovery for people with long covid using mind-body approaches. Further research is needed to develop structured interventions, and to evaluate their efficacy and safety. Future research should also explore how prevailing narratives within healthcare and society influence treatment engagement and recovery trajectories. STRENGTHS AND LIMITATIONS OF THIS STUDYO_LIThis is the first study exploring experiences of recovery from long covid using mind-body approaches. C_LIO_LIIn-depth, real-world accounts capture the lived-experiences over time and allow in-depth exploration if the recovery process, while the semi-structured design facilitates the emergence of themes rarely captured in clinical research. C_LIO_LIGeneralisability is limited due to self-identified long covid status, lack of formal diagnostic verification, absence of strict definitions of mind-body approaches and recovery, and a relatively homogenous sample (mostly highly educated women). C_LI

BackgroundIn England, the burden of respiratory infections varies by ethnicity, contributing to health inequalities, but the role of additional demographic factors remains underexplored. We quantified how differences in social mixing and demographic characteristics between ethnic groups cause inequalities in transmission dynamics. MethodsWe analysed the association between the ethnicity and the number of contacts of 12,484 participants in the 2024-2025 Reconnect social contact survey, using a negative binomial regression model. We simulated respiratory pathogen epidemics using a compartmental model stratified by age, ethnicity, and contact levels, at a national level and in major cities in England. FindingsAfter adjusting for demographic variables, participants of Black and Mixed ethnicities had more contacts than those of White ethnicity (rate ratios (RR): 1.18 [95% Credible Interval (CI): 1.11-1.26], and 1.31 [95% CI: 1.14-1.52]). Participants of Asian ethnicity had fewer contacts (RR: 0.85 [95% CI: 0.79-0.91]). In national-level simulations, individuals of White ethnicity had the lowest attack rates due to demographic differences and mixing patterns. Local demographic structures changed simulated dynamics: attack rates in individuals of Black and Mixed ethnicities were approximately double those of White ethnicity in Birmingham, but less than 60% higher in Liverpool. InterpretationDemographic characteristics and mixing patterns create inequalities in transmission dynamics between ethnicities, while local demographic characteristics and pathogen infectiousness change the expected relative burden. To ensure mitigation strategies are effective and equitable, their evaluation must explicitly account for inequalities arising from local context. FundingMedical Research Council, National Institute for Health and Care Research, Wellcome Trust Research in context Evidence before this studyWe searched PubMed for population-based studies quantifying differences in respiratory infections between ethnic groups, up to 1 April 2026, with no language restrictions. Keywords included: (respiratory pathogens OR influenza OR COVID-19) AND (ethnic* OR race) AND (inequ*) AND (compartmental model OR incidence rate ratio OR hazard ratio). We excluded studies that focused on non-respiratory pathogens (e.g. looking at consequences of COVID-19 on incidence of other pathogens). A population-based cohort study showed that influenza infection risk was higher in South Asian, Black, and Mixed ethnic groups compared to White ethnicity in England. Another population-based cohort study highlighted that during the first wave of COVID-19 in England, the South Asian, Black, and Mixed ethnic groups were more likely to test positive and to be hospitalised than the White ethnic group. Census data in England showed that the distributions of age, household size, household income and employment status differed between ethnic groups, and the recent Reconnect social contact surveys highlighted the impact of each demographic factor on the participants number of contacts. Added value of this studyOur study shows that social contact patterns, mixing, and demographic structure all lead to unequal infection risk between ethnic groups in respiratory pathogen epidemics. Using the largest available social contact survey in England, we show that both the average number of contacts and the proportion of high-contact individuals varied by ethnic group, even after adjusting for participants demographics. These differences, together with mixing patterns and age structure, led to lower expected incidence among individuals of White ethnicity than in all other ethnic groups in simulated outbreaks. The level of inequality between ethnic groups changed when we used different values of pathogen transmissibility. Finally, as ethnic composition and population structure differ between cities in England, our results show differences in expected inequalities at a local level. Implications of all the available evidenceInequalities in infection risk between ethnic groups are context- and pathogen-dependent. They arise from both local population structure and contact patterns. Detailed information on mixing between groups and population structure is needed to accurately measure group-specific infection risk. These findings indicate that public health interventions based only on national-level estimates conceal regional variation in risk and may ultimately increase inequalities. Public health interventions need to be tailored to local contexts to be equitable and effective. Finally, our findings provide a foundation for understanding the progression from infection-risk inequalities to disparities in disease presentation and clinical outcomes.

Background: The 2025/2026 COVID-19 vaccine season introduced updated formulations targeting the LP.8.1 lineage. This study assessed the absolute vaccine effectiveness (aVE) of mRNA-1283 and BNT162b2 on COVID-19 outcomes in adults aged [&ge;]65 years. Methods: Background: The 2025/2026 COVID-19 vaccine season introduced updated formulations targeting the LP.8.1 lineage. This study assessed the absolute vaccine effectiveness (aVE) of mRNA-1283 and BNT162b2 on COVID-19 outcomes in adults aged [&ge;]65 years. Methods: This retrospective study used linked electronic health record and administrative claims data through Jan 31, 2026. Adults [&ge;]65 years who received the mRNA-1283 or BNT162b2 2025/2026 COVID-19 vaccine were matched to unvaccinated individuals. Inverse probability of treatment weighting was applied to matched cohorts of each vaccine to balance covariates. Each vaccine was evaluated independently against its own unvaccinated comparator group. aVE against COVID-19 related hospitalization and medically-attended COVID-19 was estimated using Cox proportional hazards models; aVE = 100 x (1 - hazard ratio [HR]). Results: We identified 233,072 mRNA-1283 recipients and 422,610 BNT162b2 recipients [&ge;]65 years. The aVE (95% confidence interval) of mRNA-1283 against COVID-19 related hospitalization and medically-attended COVID-19 was 59.3% (39.0%, 72.9%) and 42.0% (35.0%, 48.3%) among adults [&ge;]65 years and 66.9% (45.9%, 79.8%) and 50.2% (42.1%, 57.2%) in [&ge;]75 years, respectively. The aVE of BNT162b2 against COVID-19 related hospitalization and medically-attended COVID-19 was 48.3% (32.4%, 60.5%) and 41.2% (36.2%, 45.8%) in [&ge;]65 years and 45.9% (26.0%, 60.4%) and 44.0% (37.8%, 49.6%) in [&ge;]75 years, respectively. Conclusions: This is the first real-world evidence showing that mRNA-1283 prevents COVID-19-related hospitalizations and medically attended events in vulnerable older adults at highest risk of severe disease. These findings support mRNA-1283 as an important public health tool for reducing the ongoing burden of COVID-19.Results: We identified 233,072 mRNA-1283 recipients and 422,610 BNT162b2 recipients [&ge;]65 years. The aVE (95% confidence interval) of mRNA-1283 against COVID-19 related hospitalization and medically-attended COVID-19 was 59.3% (39.0%, 72.9%) and 42.0% (35.0%, 48.3%) among adults [&ge;]65 years and 66.9% (45.9 %, 79.8%) and 50.2% (42.1%, 57.2%) in [&ge;]75 years, respectively. The aVE of BNT162b2 against COVID-19 related hospitalization and medically-attended COVID-19 was 48.3% (32.4%, 60.5%) and 41.2% (36.2%, 45.8%) in [&ge;]65 years and 45.9% (26.0%, 60.4%) and 44.0% (37.8%, 49.6%) in [&ge;]75 years, respectively. Conclusions: This is the first real-world evidence showing that mRNA-1283 prevents COVID-19-related hospitalizations and medically attended events in vulnerable older adults at highest risk of severe disease. These findings support mRNA-1283 as an important public health tool for reducing the ongoing burden of COVID-19.

BackgroundTuberculosis (TB) and human immunodeficiency virus (HIV) are leading causes of infectious disease deaths, with disproportionate impact in low- and middle-income countries (LMICs). Despite well-established biological relationships between these diseases, there is limited information on how TB prevalence differs between people living with and without HIV. MethodsWe conducted a systematic review and meta-analysis of TB prevalence surveys conducted in LMICs and published during January 1st 1993-October 13th 2025 (PROSPERO CRD42024503853). We extracted bacteriologically-confirmed TB prevalence estimates stratified by participant HIV status. Surveys that offered HIV testing to all, sputum-collection-eligible, or TB-positive participants were included in the primary analysis. We applied Bayesian meta-regression to estimate pooled risk ratios (RR) of bacteriologically-confirmed TB prevalence among participants living with versus without HIV. Additionally, we estimated country-level and overall TB notification-to-prevalence (N:P) ratios by HIV status. FindingsOf 10,211 potentially relevant publications, 12 TB prevalence surveys--representing 264,530 participants within nine countries in Southern and Eastern Africa--were used in the primary analysis. Reported TB prevalence was higher among participants living with versus without HIV in 11/12 surveys, with an overall pooled RR of 3{middle dot}86 (95% credible interval: 2{middle dot}41-5{middle dot}53). N:P ratios were higher among participants living with HIV in all examined countries. The overall pooled N:P ratios were 1{middle dot}74 (0{middle dot}59-4{middle dot}56) and 0{middle dot}48 (0{middle dot}17-1{middle dot}20) among participants living with versus without HIV, respectively. InterpretationIn Southern and Eastern Africa, bacteriologically-confirmed TB prevalence is three- to six-times higher among people living with HIV. Comparison of prevalence and notification data suggest higher rates of TB diagnosis for people living with versus without HIV, but also indicates substantial delays in the detection of untreated TB cases for both populations. FundingWellcome Trust, UK National Institute for Health and Care Research, UK Foreign, Commonwealth and Development Office, NIH. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThere is limited systematic evidence on how the prevalence of TB disease differs between people living with HIV and without HIV. Multiple observational cohorts have described substantially elevated TB incidence among populations with HIV, but disease prevalence will also be affected by differences in mortality and treatment uptake rates. We searched PubMed from inception through January 21, 2026 using the search string ((HIV AND TB) OR HIV/TB) AND (prevalence AND (systematic review OR meta-analysis)) without any restrictions on language. We also reviewed investigators personal libraries. This search yielded 506 publications; however few of these included prevalence data. An analysis conducted in 2020 synthesized HIV status-stratified data from seven national TB prevalence surveys in Africa and found that HIV prevalence was lower among prevalent TB cases than among notified cases. This study did not include subnational surveys and did not distinguish between survey participants with self-reported or test-confirmed HIV status. Added value of this studyThis study synthesized TB prevalence data, stratified by participant HIV status, from national and subnational surveys conducted in LMICs and published between January 1st 1993 and October 13th, 2025. Collated data represented 681,402 survey participants across ten countries. All but one study were conducted in Southern and Eastern Africa. We limited our primary analysis to surveys that systematically tested participants for HIV and bacteriologically-confirmed TB. The prevalence of bacteriologically-confirmed TB was estimated to be three to six times higher than among people living with versus without HIV. Ratios of TB notifications to TB prevalence were higher for people living with HIV compared to people without HIV, suggesting higher rates of TB case detection (and likely shorter duration of disease) for people living with HIV and untreated TB than those without HIV. Implications of all available evidenceFew estimates of community-representative TB prevalence stratified by participant HIV status exist. These surveys have been concentrated in Southern and Eastern Africa, despite TB-HIV burden being distributed globally. Our findings highlight the elevated burden of TB among people living with HIV in these settings, as well as the limited data on the intersection of TB and HIV epidemiology in other world regions. Furthermore, our comparison of notification and prevalence data demonstrate substantial shortfalls in TB case detection, regardless of an individuals HIV status.

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.

Abstract Objective: The objective of this study was to compare hospital length of stay and other clinical outcomes between intact fish skin graft (IFSG; Graftguide, Kerecis, Arlington, VA) and synthetic/biosynthetic dermal substitutes (SSS; Integra Dermal Regeneration Template and NovoSorb Biodegradable Temporizing Matrix) in propensity score matched burn patients using the American Burn Association Burn Care Quality Platform. Methods: This retrospective cohort study identified adult patients treated with a single dermal substitute product during hospitalization for acute burn injury. Patients receiving IFSG (n = 93) were matched 1:4 to patients receiving SSS (n = 372) using nearest neighbor propensity score matching on the logit scale. Matching covariates included total body surface area burned (TBSA), patient age, sex), burn severity classification, inhalation injury, and trauma diagnosis. The primary outcome was hospital length of stay (LOS), analyzed using a gamma generalized linear mixed model (GLMM). Secondary outcomes included the incidences of sepsis, graft loss, venous thromboembolism (VTE), and hospital acquired pressure injury (HAPI). A prespecified sensitivity analysis was performed using a broader mixed product cohort. Results: A total of 93 IFSG treated patients from 17 burn centers admitted between the years 2019 and 2025 were matched 1:4 to 372 SSS treated patients from 44 centers. Unadjusted mean LOS was 24.1 days (median 20, IQR 11 to 32) in the IFSG treated group and 36.7 days (median 31, IQR 17 to 52) in the SSS treated group representing a 12.6 day reduction. GLMM-adjusted estimated marginal mean LOS was 24.2 days (95% CI, 20.0 to 29.4) for IFSG versus 33.5 days (95% CI, 30.0 to 37.6) for SSS (ratio 0.723; p = 0.00245), representing a 9.3 day reduction. Sepsis (1.1% vs 4.6%), graft loss (3.2% vs 8.3%), VTE (2.2% vs 2.7%), and HAPI (2.2% vs 3.8%) were all numerically lower in the IFSG treated arm; although GLMM-adjusted odds ratios were not statistically significant for any individual complication. The mixed cohort sensitivity analysis (n = 229 IFSG vs 458 SSS across 67 centers) confirmed the primary finding with GLMM adjusted LOS ratio 0.716 (p = 0.0001). Conclusions: In this propensity score matched analysis of the ABA registry, IFSG was associated with a statistically significant and clinically meaningful reduction in hospital length of stay compared with synthetic/biosynthetic dermal substitutes, in requiring dermal substitution and autografting, with all complication rates, sepsis, graft loss, VTE, and HAPI, numerically lower in the IFSG-treated arm. The shorter hospitalization was not achieved at the expense of safety. These findings support IFSG as a viable alternative to synthetic dermal substitutes in burns requiring dermal substitution and autografting. Prospective studies are warranted particularly in larger burns requiring staged reconstruction.

An efficacious blood-stage malaria vaccine would serve as a highly useful public health tool alongside licensed vaccines targeting the pre-erythrocytic life cycle stage of the Plasmodium falciparum parasite. RH5 is the leading blood-stage malaria vaccine candidate antigen due to its highly-conserved sequence and non-redundant role in merozoite invasion of red blood cells. Following encouraging immunogenicity data in UK and Tanzanian Phase Ia/b vaccine trials, RH5-based vaccines have progressed to Phase IIb evaluation in Burkina Faso in recent years. Here, we report a Phase Ia clinical trial in malaria-naive UK adults to assess the safety and immunogenicity of the malaria vaccine candidate RH5.1 soluble protein with Matrix-M adjuvant using two different booster dosing regimens: 10-10-10 micrograms versus 50-50-10 micrograms RH5.1, both delivered in a 0-1-6-month schedule with 50 micrograms Matrix-M adjuvant per dose (ClinicalTrials.gov NCT06141057). A total of n=24 participants were recruited to this study, with n=23 completing all follow-up visits through to 1 year following final vaccination. The RH5.1/Matrix-M formulation was well-tolerated in this population, with injection site pain, myalgia and fatigue being the most commonly reported symptoms up to 7 days post-vaccination. There were no serious adverse events, adverse events of special interest, or suspected unexpected serious adverse reactions reported over the course of the trial. Both vaccination regimens were similarly immunogenic; no differences were observed in peak anti-RH5.1 serum IgG concentrations, in vitro functional anti-parasitic activity, avidity, or durability. Our findings build on other observations from clinical trials of adjuvanted RH5.1 indicating that humoral immunogenicity can be enhanced by delaying the final booster vaccination, but that there is limited impact of fractionation of the final dose. These insights can help to guide the next steps of multi-antigen, multi-stage malaria vaccine development in malaria-endemic settings.