The Lancet

Introduction Acute lower respiratory tract disease (aLRTD) is a leading cause of hospitalisation and death, particularly in older adults and adults with comorbidities, with acute lower respiratory tract infection (aLRTI; pneumonia and non-pneumonic LRTI) being a major component. Non-pulmonary complications and functional decline after aLRTI are recognised, but their pathogen-specific burden is poorly described. We aimed to quantify renal, hepatic, thromboembolic and functional complications, and mortality, after aLRTI hospitalisation, by clinical phenotype and pathogen. Methods We conducted a cohort study of adults (>18 years) admitted with aLRTD to two hospitals in Bristol, UK (01 August 2022-31 July 2024). aLRTD was classified as pneumonia, non-pneumonic LRTI (NP-LRTI) or no diagnosis of aLRTI. Pathogens were identified from standard-of-care and research microbiology. Outcomes were acute kidney injury (AKI), acute liver dysfunction, venous thromboembolism (VTE), in-hospital falls, reduced mobility at discharge, increased care requirements, and 30-day and 1-year mortality. Analyses were descriptive. Results Among 246,797 adult admissions, 21,456 aLRTD hospitalisations were included: 10,239 (47.7%) pneumonia, 7,742 (36.1%) NP-LRTI and 3,475 (16.2%) with no evidence of aLRTI. Of 19,152 tested aLRTD admissions, 8,503 (44.4%) had a positive microbiological/virological test, yielding 9,204 pathogen detections; 1,194 (6.2%) had co-infections, and SARS-CoV-2 was most frequent, with influenza the second most common in pneumonia and NP-LRTI. Pneumonia had greater severity than NP-LRTI and no diagnosis of aLRTI (median length of stay 6 vs 4 vs 4 days; ICU admission 3.4% vs 0.7% vs 0.5%, respectively). Overall, 22.2% developed AKI, 6.1% acute liver dysfunction, 0.6% DVT and 2.4% PE; 1.8% had a fall, 11.5% reduced mobility, and 16.6% required increased care at discharge. 30-day and 1-year mortality were highest for pneumonia (14.0% and 32.0%, respectively). Pathogen-specific analyses showed longer stays and higher complications and mortality rates for SARS-CoV-2 and Streptococcus pneumoniae, and shorter stays with lower complication and mortality rates for influenza and Haemophilus influenzae. Conclusions Non-cardiovascular complications and functional decline after aLRTI were common, particularly in pneumonic and SARS-CoV-2 or pneumococcal disease. These findings support routine surveillance for renal, hepatic, thromboembolic events, early mobilisation and rehabilitation, and consideration of multi-system outcomes when evaluating public health and economic value of vaccines and therapies.

Introduction Aspiration events in hospitalized adults are common and linked to substantial morbidity, mortality, and healthcare burden. While antiemetics have been studied for aspiration prevention in specific settings, evidence for their broader preventive use in hospitalized adults is limited. We conducted a systematic review and meta-analysis to evaluate the effect of prophylactic scheduled antiemetics on aspiration events in adult inpatients. Methods: Ovid MEDLINE, Ovid Embase, CINAHL, and Cochrane Library (via Wiley) were searched in May 2025. We included randomized controlled trials (RCTs) and observational studies assessing prophylactic scheduled antiemetic use in hospitalized adults, with aspiration events as the primary outcome. Secondary outcomes were aspiration pneumonia, hospital length of stay, increased oxygen requirement, ICU admission, and mortality. Two investigators screened and independently extracted data in duplicate using standardized data collection forms. Extracted information included study characteristics, patient demographics and clinical characteristics, interventions, and outcomes. Results: Three RCTs met inclusion criteria (n = 515 patients; 237 antiemetic, 278 placebo). Pooled analysis of two RCTs demonstrated an 88% relative risk [RR] reduction of aspiration events; (2.8% [3/106] prophylactic antiemetic vs 27.9% [29/104] placebo; RR = 0.12, 95% confidence intervals [CI]: 0.02-0.73, p <0.0001, low certainty) in the antiemetic group. Pneumonia rates were also lower in the antiemetic group although they did not reach statistical significance (16.5% vs 32.4%; RR 0.44, 95% CI 0.15-1.28, P = 0.13, low certainty). ICU admission rates were lower in the antiemetic group (2.6% [2/76]) vs. placebo (23% [17/74]); RR = 0.11, 95% CI: 0.03-0.48, p=0.003, very low certainty). Mortality was similar between groups (35.0% vs 38.1%; RR 1.02, 95% CI: 0.84-1.24, P = 0.85, low certainty). No adverse events were reported among all studies. Conclusion: Prophylactic scheduled antiemetics were associated with a significant reduction in aspiration and ICU admission. There was a non-significant but favorable trend towards reduction of pneumonia among hospitalized adults. Larger, high-quality trials are needed to clarify their role in aspiration prevention.

Mpox has re-emerged as a public-health priority across Nigeria, and successive international public-health emergencies were declared in 2022 and 2024. Facility-level descriptions of admitted, clinically suspected cases from northeastern Nigeria remain sparse. We conducted a register-based descriptive study of all admissions to the infectious-diseases isolation ward of Modibbo Adama University Teaching Hospital, Yola, in which mpox was recorded as the working or a differential diagnosis between February 2022 and January 2025. Age, sex, month of admission, locality, recorded clinical impression, and outcome were abstracted and summarised, with proportions reported using Wilson 95% confidence intervals. Fifteen suspected mpox admissions were identified, representing 4.5% (95% confidence interval 2.8-7.4) of 330 isolation-ward admissions. The median age was 20 years (interquartile range 13-37; range 7-57); six patients (40.0%) were children under 18 years and 12 (80.0%) were male, giving a male-to-female ratio of 4:1. Admissions clustered in 2022 (9 of 15; 60.0%), with six in July 2022, including a probable household cluster of four children and adolescents aged 7-14 years from a single locality who presented within eight days of one another. Three deaths were recorded (case fatality 20.0%, 95% confidence interval 7.0-45.2), including one disseminated case complicated by acute respiratory distress syndrome. The demographic profile closely matches previously reported Adamawa State and national surveillance data, whereas the elevated case fatality reflects referral concentration and diagnostic uncertainty rather than true mpox-attributable mortality. Cases were clinically suspected rather than laboratory-confirmed, which is the principal limitation of this study. We recommend targeted strengthening of laboratory diagnosis at facility and sub-national level, including dual monkeypox-varicella testing algorithms, use of existing molecular platforms rather than new infrastructure, and mandatory recording of laboratory results within ward registers.

Introduction: Respiratory infections are a leading cause of morbidity. Newly available vaccines to prevent respiratory syncytial virus (RSV) disease and encouraging clinical progress on vaccines for human metapneumovirus (hMPV) and parainfluenza (PIV) could reduce the disease burden beyond existing influenza and SARS-CoV-2 immunisation programs. However, evidence on the contribution of these viruses to respiratory disease burden across the lifespan remains limited. Methods: We reviewed studies from 01/2002-11/2025 reporting age-stratified, medically attended cases of influenza, and at least one of RSV, hMPV, or PIV, in high-income countries, excluding periods substantially overlapping with the COVID-19 pandemic. Using only studies that tested for all four viruses, we estimated the age-specific proportion of cases that were non-influenza (total across RSV, hMPV and PIV) compared to influenza using a mixed-effects logistic regression model. Results: Following exclusions and screening, 61 studies were included in the primary analysis comprising >500,000 detections of the four viruses. We found that a substantial proportion of medically attended respiratory illness in infants and young children was due to PIV, hMPV and RSV, rather than influenza, with a non-influenza virus proportion of 90.2% (95% CI 85.9-93.2%) in young infants aged 0-6 months. The converse was true for school-aged children, with a non-influenza virus proportion of 34.8% (95% CI 26.5-44.2%) in children aged 5-18 years. In adults aged 65+ years, non-influenza causes of medically attended disease were common at 60.2% (95% CI 50.0-69.5%). Restricting to studies reporting hospitalised cases (n=19) produced broadly similar age-specific trends in relative virus burden contributions. Discussion: We highlight the significant burden of medically attended illness due to PIV, hMPV and RSV across ages, particularly in infant and preschool-aged children and older adults, supporting the need for effective vaccines targeting this burden.

Importance: Pharmacological targeting of host mechanisms that limit sepsis-induced organ dysfunction represents a new therapeutic approach. Preclinical studies showed that low-dose epirubicin enhances tissue damage control and attenuates sepsis severity independently of pathogen burden, thereby promoting disease tolerance to infection. Yet epirubicin can cause myelotoxicity when used in cancer therapy. Objective: To investigate whether low-dose epirubicin can safely be administered to patients with sepsis and septic shock. Design, Setting, and Participants: A randomized, double-blind, placebo-controlled clinical trial conducted in five German University hospitals. Patients with sepsis, defined by Sepsis-3 criteria, were eligible within 48 hours after diagnosis. The first patient was enrolled on October 19, 2022, and the last follow-up was conducted on May 21, 2025. Interventions: Eligible patients were randomized in a 4:1 ratio to receive either placebo or low-dose epirubicin in addition to standard care. There were three consecutive phases. Patients in the epirubicin group received a single dose of epirubicin (either 3.75 mg/m2, 7.5 mg/m2 or 15 mg/m2, depending on study phase). Main Outcomes and Measures: The primary endpoint of the trial was the 14-day myelotoxicity. Secondary and explorative outcomes included 90-day mortality, the degree of organ dysfunction as assessed by SOFA score, PK/PD modelling and cytokine release. Results: Of 854 patients assessed for eligibility, 32 were randomized and 31 were included in the primary analysis population. Six participants received placebo, nine participants received 3.75 mg/m2, nine received 7.5 mg/m2 and eight individuals received 15 mg/m2 epirubicin, respectively. There was no myelotoxicity in any group. Mortality at 90 days and SOFA-scores were not significantly different between groups. Two of 39 SAEs in the epirubicin group were assessed by the investigators as possibly related to epirubicin, Conclusions and Relevance Among patients with sepsis and septic shock, low dose epirubicin was not associated with increased myelotoxicity.

Septic shock caused by fungal organisms is characterized by high mortality and diagnostic complexity. We used the Premier Healthcare Database to characterize antifungal use and fungal diagnoses among adults with septic shock requiring vasopressors admitted between October 2022 through July 2024. Among 12.8 million admission at 886 hospitals, 554,948 met septic shock criteria and were included for analysis. A fungal diagnosis was established in 11,405 (2.1%) of encounters; of these, 3,565 (31.3%) received intravenous antifungal therapy within one day of vasopressor initiation. In the overall cohort, antifungal therapy was initiated in 29,824 (5.5%) within one day of vasopressor initiation; of these, 3,656 (12.2%) were ultimately diagnosed with a fungal infection. In the 116 hospitals reporting microbiological data, a subgroup of 489 encounters with septic shock and culture-confirmed candidemia was identified. In this subgroup, intravenous antifungal therapy was initiated in 43.8% within one day, 63.8% within three days, and 78.9% within seven days. These findings highlight a profound decoupling between fungal diagnosis and treatment--few patients receiving antifungals were diagnosed with an infection that would be treated by these agents, while less than half of patients with septic shock and candidemia received timely treatment. Strategies for greater precision in empiric antifungal use in septic shock are needed to improve safety, stewardship, and outcomes.

Seasonal influenza remains a major cause of morbidity and mortality worldwide. Although neuraminidase inhibitors improve outcomes, influenza-related deaths persist. We evaluated the impact of early aspirin (ASA) and non-aspirin nonsteroidal anti-inflammatory drug (NSAID) use on outcomes in adults hospitalized with influenza. This retrospective study included adults admitted to the University of Minnesota Medical Center from 2016 to 2018. Continuous variables were summarized as medians with interquartile ranges (IQRs) and categorical variables as counts and percentages. Group comparisons used Wilcoxon rank-sum, Chi-square, or Fishers exact tests. Analyses included case-control comparisons, assessments by vaccination status, and subgroup analyses by early ASA or NSAID use. Among 2,816 patients, 320 had laboratory-confirmed influenza, with vaccination less common among cases. Unvaccinated patients had higher rates of intensive care unit (ICU) admission (23.6% vs. 11.1%; P = 0.003) and ventilatory support (15.0% vs. 6.1%; P = 0.009). In vaccinated patients, early ASA use was associated with older age and higher in-hospital mortality, whereas early NSAID use was associated with no in-hospital deaths, better one- and three-year survival (P < 0.001), and fewer, though not statistically significant, cardiovascular complications. In unvaccinated patients, ASA use was associated with lower three-year survival (59.1% vs. 79.2%; P = 0.013), while NSAID use was associated with fewer ICU admissions and no cardiovascular or renal complications. In both vaccinated and unvaccinated adults hospitalized with influenza, early NSAID use was associated with improved survival and fewer complications, whereas ASA use was associated with worse outcomes.

Background In adults, cold-attributable mortality exceeds heat-attributable mortality roughly 17-fold. Child-specific evidence has begun to emerge only recently - a nationwide Brazilian case-crossover study located the minimum mortality temperature (MMT) for under-five deaths, and a 56-country survey-based analysis linked monthly temperature anomalies to under-five mortality - but no multi-country, climate-zone-resolved estimate of the childhood respiratory-infection MMT exists, and whether temperature variability is independently associated with childhood respiratory mortality at the global scale is unknown. We quantified both. Methods We combined Global Burden of Disease 2023 mortality estimates, lower respiratory infection (LRI) deaths at ages 0-19 years and asthma deaths at ages 0-24 years, 171 countries, 1990-2023 - with 0.5 deg monthly land temperature and diurnal temperature range (DTR) fields from C-LSAT/C-LDTR (1901-2023). Four exposure dimensions (annual mean, DTR, seasonal amplitude, interannual variability) entered two-way fixed-effects models with Driscoll-Kraay standard errors. A quadratic term in mean temperature located the MMT, with percentile confidence intervals from a 300-replication country-cluster bootstrap. Future-exposure leads, country-level detrending, and permutation tests assessed contemporaneous causality, applied to both the linear coefficients and the quadratic term generating the MMT; national pneumococcal conjugate vaccine (PCV3) coverage and ambient PM2.5 exposure series were added as time-varying mechanistic covariates. Results The childhood LRI MMT was 17.1 C (95% CI 14.7-19.8), the 36th percentile of the annual-temperature distribution; zone estimates were 24.7 C in tropical and 15.8 C in subtropical countries, with weak temperate and no subarctic identification. The quadratic term underpinning the MMT, however, failed both falsification checks - future temperatures reproduced the U-shape and country-level detrending erased it - so these MMT values describe a trend-level geographic pattern of the annual construct rather than a contemporaneous dose-response. Interannual temperature variability was positively associated with LRI (+0.278, 95% CI 0.102-0.454; p = 0.002) and asthma mortality (+0.836, 95% CI 0.447-1.226; p = 2.6 x 10^-5) per 1 C, but future-exposure models returned nearly identical significant coefficients and detrending erased significance, supporting only a trend-level association; adjustment for national PCV3 coverage and PM2.5 exposure left these estimates essentially unchanged. Annual mean temperature was likewise inversely associated with both outcomes at the trend level; DTR and seasonal amplitude showed no independent within-country effects. Conclusions This study provides the first multi-country, climate-zone-resolved geography of the optimal temperature for childhood respiratory survival, spanning 171 countries; because the underlying quadratic association is trend-level, the estimates are directional. The observed variability-mortality associations are trend-level signals rather than contemporaneous causal evidence; daily-scale, child-specific designs are required to determine whether short-term thermal variability affects paediatric respiratory mortality.

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

Objectives: To compare the effectiveness of povidone-iodine ear wash compared to no ear wash and oral cotrimoxazole compared to placebo given in addition to standard topical antibiotic treatment (ciprofloxacin drops) for chronic suppurative otitis media (CSOM) in Australian Aboriginal children. Methods: A randomised, parallel, 2 x 2 factorial design, assessor-blinded clinical trial in the remote Northern Territory of Australia. Aboriginal children with confirmed CSOM were eligible to be randomised into four treatment groups, allowing two primary treatment comparisons in a 2-in-1 trial approach. Participants received standard treatment (twice daily cleaning and topical ciprofloxacin drops) plus: i) either 16 weeks of pre-treatment povidone-iodine ear wash or no povidone-iodine ear wash; and ii) either 16 weeks of oral cotrimoxazole or placebo. Central randomisation with allocation concealment and triple-blinding of the oral antibiotic treatment arms was used. The relative risk (RR) and risk difference (RD) were estimated after adjustment for age, community, and the other intervention. The primary outcome was the proportion of children with any otorrhoea (clinical failure) after 16 weeks of treatment. Secondary outcomes included size of tympanic membrane (TM) perforation and amount of discharge, time to cessation of discharge, proportion of children with respiratory and other pathogens in ear discharge (at baseline and 16 weeks) and hearing levels (at 12 months). Findings: 280 children with CSOM were randomised and 270 had their primary outcome assessed. Clinical failure (presence of any ear discharge) after 16 weeks of treatment was 66/134 (49%) in the povidone-iodine group versus 69/136 (51%) in the no povidone-iodine group (RD= -1% (-12,11), p= 0.93) and 56/134 (42%) in the cotrimoxazole group versus 79/136 (58%) in the placebo group (RD=-16% (-28,-4), p=0.007). The amount of discharge, TM perforation size, the level of hearing impairment, and serious adverse events were not significantly different in both treatment comparisons. Anaerobic growth (24%), Pseudomonas aeruginosa (21%) and Haemophilus influenzae (17%) were the most common pathogens found in the ear discharge before treatment. Fungi or yeast (24%), Staphylococcus aureus (15%), and anaerobic growth (10%) were the common pathogens after 16 weeks of treatment, with no significant differences between groups. At 12 months post-randomisation, 55-60% of children had at least one discharging ear and there was no difference between treatment groups. Interpretation: Povidone-iodine ear washes did not contribute to better ear outcomes in this study. Cotrimoxazole for 16 weeks resulted in more children with clinical improvement to dry ears. Oral cotrimoxazole may play a role in reducing the burden of CSOM in populations with high rates of persistent disease.

Background: The World Health Organization has expanded its recommendations for prophylactic Ebola vaccination for at-risk populations. Durable vaccine-induced immunity is important for sustaining outbreak preparedness in regions with recurrent Ebola virus disease (EVD). We assessed five-year persistence of vaccine-induced immune responses in adults and children from the PREVAC trial. Methods: Two large randomised phase 2 trials (NCT02876328), in adults and children aged [&ge;]1 year, were conducted in four west African countries. Participants were randomly assigned to placebo or to one of three Ebola vaccine strategies: Ad26.ZEBOV followed by MVA-BN-Filo at 56 days; rVSV{Delta}G-ZEBOV-GP followed by placebo; or rVSV{Delta}G-ZEBOV-GP followed by a homologous booster dose at 56 days. After 12 months of follow-up, the primary results were published, participants unblinded to their vaccine assignment, and follow-up continued for 60 months. After Month 24, placebo group recipients were offered active vaccination. Anti Ebola virus glycoprotein Immunoglobulin G (IgG) concentrations were measured for 5 years. Findings: 1401 adults and 1401 children were initially randomized, and 1315 (93.9%) adults and 1322 (94.4%) children attended at least one long-term visit. Retention was high, with 95% followed beyond 1 year and 83% completion at 5-year follow-up. For the three vaccine strategies, antibody geometric mean concentrations (GMC) declined modestly between Months 12 and 24, followed by a stable plateau from Months 24 to 60. At Month 60, antibody GMC were higher in the rVSV-based groups (1099 and 1216 EU/ml for adults; 1982 and 2347 EU/ml for children) than in the Ad26.ZEBOV, MVA-BN-Filo group (252 adults and 645 EU/ml children). Antibody persistence at Month 60 was heterogeneous, varying by age, sex, country, and baseline IgG concentration. Interpretation: Licensed Ebola vaccines induced sustained antibody responses in adults and children for up to 5 years. While the protective antibody level is unknown, these data demonstrate long-lasting immune responses from currently employed vaccine strategies.

Each year, over 50 million children receive preventive malaria treatment. However, to date there has been no consensus on the most effective antimalarial drugs to use, especially given geographic differences in drug resistance. Here, we conduct a systematic review comparing the effectiveness of the most commonly used antimalarial chemopreventive regimen, sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ), with other antimalarial drugs in preventing new infections. We searched MEDLINE, Embase, Global Health, PubMed and WWARN clinical trial databases until 06 December 2025 for studies satisfying the inclusion criteria. Studies were included if they were peer-reviewed, randomised-controlled studies in Africa, measuring incidence of infection or clinical episodes of Plasmodium falciparum malaria for at least 28 days post-treatment. We also compiled data on the prevalence of markers of resistance in the parasite dhfr, dhps and mdr1 genes in the study areas. We conducted meta-analyses of incidence rates, with subgroup analyses by drug resistance levels. This review is registered on PROSPERO (CRD42024577149). We identified 27 studies representing 38,252 participants in 32 sites across 13 countries. In pooled analysis, SP+AQ reduced incidence of malaria by 54.6% (95% CI: 33.8-68.8%) compared to SP alone, including significantly outperforming SP even in areas with low SP resistance. These findings suggest that countries currently using SP alone for chemoprevention should consider switching to SP+AQ. Where AQ resistance remains low, available evidence suggests SP+AQ remains efficacious for malaria chemoprevention. SP+AQ was comparable to the artemisinin-based treatment, dihydroartemisinin-piperaquine across all studies (incidence rate ratio 0.93; 95% CI 0.78-1.11). By resistance levels, SP+AQ had slightly higher efficacy in areas with low SP and AQ resistance but had comparable or slightly lower efficacy in areas with higher resistance. Using artemisinin-based treatments for chemoprevention must be balanced against the risk of worsening artemisinin resistance in Eastern and Southern Africa. This study was funded by the UK Royal Society.

Background Sequencing capacity in Africa greatly expanded during the COVID-19 pandemic. However, the availability of sequence data for non-SARS-CoV-2 respiratory viruses in the region remains uncertain. We systematically analysed sequence data from GenBank, GISAID and Pathoplexus for 12 non-SARS-CoV-2 respiratory virus groups from Africa and compared Africa's genomic record availability with global genomic datasets. We further examined global genomic sequences to identify virus-specific patterns that could inform respiratory virus monitoring efforts in Africa. Results In Africa, the most sequenced virus was respiratory syncytial virus (RSV) (n=15,452), followed by influenza A virus (IAV) (n=10,900) and rhinovirus (n=4,774), when all sequences, including partial ones, were considered. Kenya and South Africa together contributed more than 60% of African respiratory virus sequences, while 30% of African countries submitted none. Within the global dataset of near-complete genomes, IAV was the most sequenced virus in Africa, consistent with global trends. However, Africa contributed the second-lowest number of genomes per million population among all world regions, exceeding only Asia. Substantial differences in relative genetic diversity were observed across viruses. Cytomegalovirus (94%) and parechovirus (38%) showed high sequence retention after clustering, with their clusters typically comprising sequences from a single region. In contrast, influenza viruses and RSV exhibited lower retention, with most clusters circulating across world regions. Additionally, sequences generated through next-generation sequencing were generally more complete than those obtained using Sanger sequencing. Conclusions Our analysis revealed substantial regional disparities in respiratory virus sequence availability across Africa, along with differences in diversity and geographical distribution patterns observed among viruses. This indicates the need for tailored and virus-specific surveillance strategies. Expanding sequencing capacity in more African nations is crucial for a clearer understanding of respiratory viruses circulating in Africa. Ultimately, this can guide vaccine and diagnostic development as well as performance assessment, aiding pandemic preparedness through the timely detection of emerging respiratory viruses.

Introduction: Respiratory syncytial virus (RSV) causes significant disease in older and comorbid adults. Current UK vaccination recommendations restrict eligibility to adults [&ge;]75-years, 65-74-years with chronic respiratory disease or immunosuppression, and those in care homes, but evidence on clinical burden in adults <75-years with comorbidities is limited. This study assessed patient characteristics, healthcare resource utilisation (HCRU), and mortality in adults hospitalised with RSV in England. Methods: Population-based retrospective cohort study using linked Clinical Practice Research Datalink Aurum and Hospital Episode Statistics. Adults [&ge;]60-years hospitalised with RSV between October 2014-March 2019 were included. RSV episodes defined as 90-days post diagnosis. Case definitions were created using diagnosis codes related to confirmed RSV (RSV-specific) or acute lower respiratory tract infection where other causative pathogens were excluded (RSV-possible). All-cause HCRU (hospitalisations, critical care admissions, outpatient attendance, primary care consultations, and prescriptions) and case fatality rates were assessed. Results were stratified by age (60-74 and [&ge;]75-years), case definitions (RSV-specific, RSV-possible) and comorbidity profiles (chronic respiratory disease, immunocompromised, cardiovascular disease). Results: A total of 97,712 hospitalised episodes in those aged [&ge;]60-years were included in the analysis, where 785 (0.8%) were RSV-specific cases (n=338 aged 60-74-years, n=447 aged [&ge;]75-years). In RSV-specific cases, median (IQR) cumulative length of stay (LoS) for those [&ge;]75-years was 10.00 (6.00-22.00) days which was equivalent to or lower than each comorbidity sub-group in those aged 60-74-years, with longest LoS in those immunocompromised (11.50 [7.00-26.00] days). Critical care admissions were more often observed across comorbidity stratifications (13.85%-22.34%) compared to those [&ge;]75-years (5.03%). All-cause and RSV-related case fatality rates for RSV-specific cases were highest among those [&ge;]75-years (all-cause: 19.3%; RSV-related: 10.3%). Conclusion: HCRU within RSV episodes in those aged 60-74-years across comorbidity profiles was equal to or greater compared to those aged [&ge;]75-years. These findings highlight the need to prioritise consideration of comorbidity groups that could benefit from RSV vaccination. Key words: Respiratory syncytial virus; vaccine; chronic obstructive pulmonary disease; diabetes mellitus; immunocompromised; asthma; chronic kidney disease; cardiovascular disease; healthcare resource utilisation.

Background Risk stratification tools for childhood pneumonia have been proposed to improve identification of children at highest risk of death, particularly in low-resource settings. However, their added value over the WHO Integrated Management of Childhood Illness (IMCI) criteria and danger signs remains uncertain. Methods We conducted a secondary analysis of a multi-country randomised controlled trial of children without HIV hospitalised with pneumonia in Mozambique, South Africa, Uganda, Zambia, and Zimbabwe. We evaluated the performance of five published risk scores alongside WHO IMCI severity classification and danger signs. Discrimination for (1) in-hospital mortality, (2) 28-day mortality, and (3) 28-day readmission or death was assessed using area under the receiver operating characteristic curve (AUC). Comparative performance and clinical utility were examined. Results Of the 1010 participants, 18 (1.8%) died in hospital, 22 (2.2%) died in hospital or in the 7 days post-discharge, and 63 (6.2%) died or were readmitted by day 28. Univariate case-fatality rates were highest for variables associated with malnutrition, convulsions, and hypoxaemia. All risk scores demonstrated moderate discrimination for in-hospital and in-hospital+7-day mortality (AUC range approximately 0.75-0.84), with no meaningful differences between models, and performed similarly to the WHO danger signs and IMCI severity classification. In contrast, all approaches performed poorly in predicting 28-day readmission or death (AUC approximately 0.54-0.58). No risk score consistently outperformed simple clinical criteria. Conclusions In this multi-country dataset, we found no evidence that published paediatric pneumonia risk scores meaningfully outperform WHO IMCI-based clinical assessment for predicting mortality. The relatively small number of mortality events limits precision, and modest differences cannot be excluded. These findings suggest that, in low-resource settings, strengthening implementation of existing WHO clinical criteria may be more effective than adopting more complex prediction tools.

Background: Group A streptococcal (GAS) pharyngitis drives substantial antibiotic prescribing in children. The 10-day standard burdens adherence and prolongs exposure, increasing selective pressure for resistance. Yet, whether shorter courses achieve comparable outcomes remains unresolved. Purpose: To address how the duration of oral antibiotics affects clinical outcomes in children and adolescents with suspected or confirmed GAS pharyngitis. Data Sources: MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL from inception to July 2025. Reviewers also searched reference lists of eligible trials and relevant systematic reviews. Study Selection: Randomized trials enrolling children and adolescents [&le;]18 years with suspected or confirmed GAS pharyngitis comparing different durations of oral antibiotics, or oral antibiotics against placebo or no treatment. Data Extraction: Paired reviewers independently screened records, extracted data, and assessed risk of bias. Data Synthesis: We performed random-effects dose-response meta-analyses with restricted cubic splines and rated the certainty of evidence using GRADE. Forty-five trials enrolling 22,636 participants met eligibility criteria. Across outcomes, low to moderate certainty evidence suggests that 3, 5, and 10 days of antibiotic treatment may produce little to no difference. Moderate certainty evidence supports similar effects of 5 and 10 days on clinical cure, relapse, and adverse events. Evidence comparing 3 and 10 days carries lower certainty. Serious adverse events were rare: no deaths, 4 cases of acute rheumatic fever, and 4 cases of post-streptococcal glomerulonephritis among 776, 8,818, and 9,096 participants, respectively, making clinically important differences across treatment durations unlikely. Limitations: Evidence on 3-day courses came almost exclusively from trials of azithromycin, limiting inference about shorter penicillin regimens. Findings apply most directly to high-income settings. Conclusion: These findings challenge the long-standing 10-day standard for pediatric GAS pharyngitis and show that 5 days of oral antibiotics are likely as effective and safe as 10 days.

Rationale. Guidelines disagree on antibacterial treatment for adults with community-acquired pneumonia and a positive respiratory viral test, particularly hospitalized patients and outpatients with comorbidities. Objectives. To estimate associations between antibacterial treatment selected for community-acquired pneumonia and outcomes in adults with virus-positive, imaging-evaluated nonsevere pneumonia. Methods. We conducted a retrospective multicenter study using Epic Cosmos data from 2016-2025. Hospitalized patients treated empirically by 24 hours were compared by continuation during hours 24-48; outpatients were compared by prescription at emergency-department discharge. Analyses were stratified by guideline-defined comorbidity and used propensity-score overlap weighting with source-cluster bootstrap confidence intervals. Exploratory analyses assessed respiratory virus, antiviral treatment, antibacterial class, and outpatient timing. Measurements and Main Results. The cohort included 376,320 adults: 275,604 inpatients and 100,716 outpatients. Inpatients who continued treatment had higher 30-day adverse-event risk without guideline comorbidity (adjusted risk difference, 1.70 percentage points; 95% confidence interval, 0.80-2.39) and with guideline comorbidity (2.56; 1.88-3.14), and longer post-landmark stay (adjusted mean ratios, 1.14 and 1.08). Exploratory class-specific analyses showed the largest adverse-event and mortality associations with broad therapy targeting resistant staphylococci or Pseudomonas; macrolide-containing and other atypical coverage showed no consistent adverse signal. Outpatient prescribing was associated with lower risks, but care-transition and residual confounding remained. Conclusions. Continued inpatient therapy after the empiric period showed no evidence of benefit and was associated with worse observed outcomes. Outpatient associations favored prescribing but remained vulnerable to care-transition and residual confounding.

Background: Nontuberculous mycobacteria (NTM) are environmental pathogens causing pulmonary and extrapulmonary infections. First Nations people in Australia experience higher burdens of communicable diseases, comorbidities, and systemic barriers to care, increasing NTM risk. This study examined the incidence and spatial distribution of NTM infections in First Nations people in Queensland. Methods: A retrospective longitudinal analysis was conducted using NTM notifications from the Queensland Health Notifiable Conditions Database, stratified by Indigenous status. Incidence was calculated using population denominators and Indigenous Region boundaries, with direct rate comparisons between 2011 and 2024. Results: Between 2001 and 2024, 717 NTM notifications were recorded from 606 First Nations people, with a significant male predominance among those aged 30-44 years ({chi}^2=21.63, P<0.0001). NTM incidence was higher in 2024 than in 2011, increasing from 4.6 to 26.3 per 100,000 (incidence rate ratio (IRR): 5.74, 95% confidence interval (CI): 2.97-11.08, P<0.0001). Although incidence in 2024 was lower than in the non-Indigenous population (35.81 per 100 000), the rate of increase was 4.4 times greater. Pulmonary infections predominated (569/717, 79.36%) and were more frequent in 2024 than in 2011 (IRR: 6.95, 95% CI: 3.00-19.75, P<0.0001). Extrapulmonary incidence increased by 140% from 2020 primarily due to an outbreak of Mycobacterium abscessus infections among incarcerated First Nations males. Marked geospatial heterogeneity was observed, with the greatest increases in incidence in the Brisbane, Rockhampton, Townsville-Mackay, and Cairns-Atherton Indigenous Regions (P<0.001). Conclusions: NTM incidence among First Nations people in Queensland has increased substantially, with a faster rate of rise than in the non-Indigenous population despite lower absolute incidence, consistent with under-ascertainment. These findings highlight gaps in detection and diagnostic access, alongside heterogeneous geographic and outbreak-associated transmission dynamics. Strengthening culturally appropriate surveillance and improving access to timely diagnosis are required to better define disease burden and inform targeted clinical and public health responses in First Nations and other underserved populations.

Public genomic repositories can support antimicrobial resistance (AMR) surveillance, but unequal sampling can bias interpretation. We characterised AMR determinants, multicountry genomic cluster overlap and surveillance gaps across Africa using an NCBI Pathogen Detection snapshot retrieved on 24 August 2026 for 55 African Union member states. Records were validated and deduplicated by BioSample, and complete AMRFinderPlus calls were summarised across five United Nations M49 subregions and eight overlapping regional economic communities (RECs). Country-pair cluster overlap was assessed using the Jaccard index, while project-based and composition-standardised sensitivity analyses evaluated repository bias. The dataset contained 86,829 unique BioSamples from 51 states; South Africa, Malawi and Kenya contributed 55.8%. Complete extended-spectrum {beta}-lactamase calls were detected in 21,513 isolates and carbapenemase calls in 4,642. blaCTX-M-15 dominated the ESBL profile, while NDM and OXA types predominated. Seventy clusters contained carbapenemase-positive isolates from at least two countries. A shared REC covered all participating countries in 38 clusters, while 32 crossed REC boundaries. Normalised country-pair overlap was low, with a maximum Jaccard index of 9.5%. Project balancing reduced the Northern African carbapenemase estimate from 32.3% to 17.9% and the Eastern African ESBL estimate from 36.9% to 12.5%. Public repositories identify determinants and clusters for investigation but do not estimate prevalence or transmission. AMR surveillance should combine national confirmation, regional institution-led investigation where countries share an REC, and continent-wide coordination through Africa CDC for cross-REC signals, supported by representative One Health sampling, standardised metadata and sustained African sequencing capacity.

Background Early recognition of presentations consistent with the deliberate release of a Category A bioterrorism agent is essential for rapid isolation, public health notification, and containment. The ability of UK clinicians-in-training to recognise these syndromes is unstudied. This pilot assessed final-year UK medical students' ability to recognise these syndromes. Methods A pilot cross-sectional online survey of final-year UK medical students used single-best-answer clinical vignettes depicting syndromes associated with Category A bioterrorism agents (BT vignettes) and clinically overlapping non-bioterrorism syndromes (NBT vignettes). Performance was summarised as the proportion of vignettes correctly identified, with primary analysis comparing within-participant BT and NBT performance. Results Twenty-five participants completed the survey. Participants performed worse on BT vignettes (M = 0.55) than on NBT vignettes (M = 0.81), with a within-participant difference of -0.26 (95% CI [-0.35, -0.18]; t(24) = -6.33, p < 0.001; Cohen's dz = -1.27). Botulism (96.0%) and Ebola virus disease (88.0%) were recognised by most participants, while anthrax (40.0%), pneumonic plague (28.0%), and smallpox (24.0%) were recognised by fewer than half. Conclusion This pilot provides the first UK evidence of a substantial diagnostic deficit in final-year medical students' recognition of Category A bioterrorism agent syndromes.