Influenza and Other Respiratory Viruses

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

BackgroundWe assessed associations between antibody concentrations within 7 days of symptom onset and testing positive for influenza virus infection among outpatients enrolled in a test-negative study. MethodsFrom November 2018[boxh]May 2019, study sites in five states obtained serum and respiratory specimens from outpatients aged [&ge;]18 years presenting with acute respiratory illness. Respiratory specimens were tested for influenza virus, and viral clades were identified by genomic sequencing. We measured influenza antibody titers against vaccine and circulating viruses by hemagglutination inhibition (HI), microneutralization (MN) and neuraminidase inhibition (NAI) assays. Percent of patients with HI, MN and NAI titers [&ge;]10 and [&ge;]40 were compared among patients with and without influenza-associated illness, and reduction in odds of confirmed influenza at increasing HI, MN and NAI antibody titers was estimated using logistic regression adjusting for influenza vaccination status and time since beginning of influenza season. ResultsAmong 175 patients with confirmed influenza virus infection, including 112 with influenza A(H1N1)pdm09 and 63 with A(H3N2) (44 clade 3C.3a), and 130 test-negative control patients, higher antibody titers against influenza hemagglutinin or neuraminidase proteins at enrollment were associated with lower odds of influenza virus infection. HI and MN antibody titers against circulating viruses were more strongly associated with protection than titers against vaccine reference viruses. Odds of A(H1N1)pdm09 infection were 44% and 54% lower for each two-fold increase in A(H1N1)pdm09 HI or NAI titer, respectively. Odds of A(H3N2) infection were 46% and 30% lower, respectively, for each two-fold increase in MN or NAI titer against circulating A(H3N2) virus clade. NAI titers were independently associated with lower odds of influenza A(H1N1)pdm09 and A(H3N2) after controlling for HI titer. ConclusionHigher influenza antibody titers against circulating viruses were associated with lower likelihood of influenza virus infection among adult patients with acute respiratory illness. SUMMARYFrom November 2018[boxh]May 2019, we assessed the association between antibody concentrations during acute illness and laboratory-confirmed influenza among adult patients enrolled in a test-negative study in five US states. We found that higher influenza antibody titers were associated with lower likelihood of symptomatic influenza virus infection.

BackgroundInfluenza A(H1N1)pdm09 and A(H3N2) viruses predominated during the 2024-25 U.S. influenza season. We estimated influenza vaccine effectiveness (VE) in the United States against mild-to-moderate outpatient influenza illness by influenza type and subtype in the 2024-25 season. MethodsWe enrolled outpatients aged [&ge;]8 months with acute respiratory illness symptoms including cough in 7 states. Upper respiratory specimens were tested for influenza type/subtype by reverse-transcriptase polymerase chain reaction (RT-PCR). Influenza VE was estimated with a test-negative design comparing odds of testing positive for influenza among vaccinated versus unvaccinated participants controlling for age, study site, underlying health status, and month of illness onset. We also estimated VE of current season vaccination among adults stratified by prior season vaccination status. ResultsAmong 6,793 enrolled patients, 2,016 (30%) tested positive for influenza including 961 A(H3N2), 770 A(H1N1)pdm09, and 183 B/Victoria. Overall vaccine effectiveness against any influenza illness was 33% (95% Confidence Interval [CI]: 24 to 41): 27% (95% CI: 14 to 39) against influenza A(H3N2), 37% (95% CI: 24 to 48) against A(H1N1)pdm09, and 40% (95% CI: 12 to 59) against B/Victoria. VE did not differ based on whether or not participants had received influenza vaccine the previous season. ConclusionsInfluenza vaccination during the 2024-25 season protected against circulating influenza viruses, reducing the risk of outpatient medically attended influenza overall by approximately one-third among people who were vaccinated. Key PointsInfluenza vaccine reduced the risk of outpatient acute respiratory illness due to laboratory-confirmed influenza during the 2024-25 season by a third.

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

Background/ObjectivesThe trajectory of influenza hospitalization burden from pre-pandemic baseline through post-pandemic recovery remains poorly characterized at the national level. This study characterized phase-stratified burden and seasonal structure, quantified racial and ethnic disparities, and assessed whether post-pandemic seasons represent anomalous departures from pre-pandemic expectations. MethodsSixteen seasons of FluSurv-NET surveillance data (2009-2010 through 2024-2025; 509 observation weeks) were analyzed across pre-pandemic, disruption, and recovery phases using OLS regression with effect-size estimation, bootstrapped age-adjusted rate ratios, seasonal-trend decomposition (STL), Prophet time-series forecasting, and Isolation Forest anomaly detection. ResultsMean peak weekly hospitalization rate nearly doubled from pre-pandemic to recovery (5.1 to 11.1 per 100,000), cumulative seasonal burden increased from 46.3 to 87.0 per 100,000, and median peak timing advanced from MMWR week 9 to week 50. STL decomposition revealed a marked shift from weak pre-pandemic seasonality (Fs = 0.14) to substantially stronger annual regularity (Fs = 0.98) across three recovery seasons, with threefold amplitude increase. Non-Hispanic Black persons had rate ratios of 1.72, 2.16, and 1.99 relative to White persons across phases; American Indian and Alaska Native persons showed the highest disruption-phase ratio (2.24, 95% CI 1.90-3.53), based on two contributing seasons. A flat-growth Prophet model detected first exceedance in February 2020, outperforming a linear-growth specification on held-out validation. Isolation Forest identified 2017-2018, 2023-2024, and 2024-2025 as robust anomalies across all contamination thresholds. ConclusionsPost-pandemic influenza recovery is characterized by intensified and restructured seasonality, persistent racial and ethnic disparities, and anomalous burden exceeding pre-pandemic projections, identified independently by time-series forecasting and unsupervised anomaly detection.

IntroductionModeling when influenza epidemics typically occur can help countries optimize surveillance, time clinical and public health interventions, and reduce the burden of influenza. MethodsWe used influenza virus detections reported during 2011-2024 by 180 countries to the Global Influenza Surveillance and Response System, excluding COVID-19 pandemic impacted years (2020-2023). We analyzed data by calendar year (week 1-52) or shifted year (week 30-29) time windows, based on when most influenza detections occurred in each country. For countries with sufficient data, we computed generalized additive models (GAMs) of each countrys weekly influenza-positive tests to smooth and impute time series distributions. From these GAMs, we calculated each countrys normalized weekly influenza burden. Country-specific normalized time series were grouped using hierarchical k-means clustering reducing the Euclidean distance between time series within clusters. We calculated cluster-specific GAMs to estimate average seasonal timing. Countries without sufficient data were assigned to a cluster based on population-weighted latitudinal distance to a clusters mean latitude. ResultsWe identified five clusters, or epidemic zones, from 111 countries with sufficient data. The influenza burden in epidemic zones A and B was consistent with a northern hemisphere pattern, with most influenza detections occurring during October-April (A) and September-March (B), while epidemic zones D and E were characterized by southern hemisphere-like seasonal timing, with most influenza burden occurring during May-November. Epidemic zone C had most influenza burden occurring during September-March; most countries assigned to this cluster were in the tropics. ConclusionEpidemic zones may serve as a useful tool to strengthen and optimize influenza surveillance for global health decision-making (e.g., during vaccine strain composition discussions) and to guide country preparedness efforts for seasonal influenza epidemics, including the timing of enhanced surveillance, as well as the procurement and delivery of vaccines and antivirals. What is already known on this topicPrevious initiatives to provide a framework for describing global influenza patterns and to support national and regional prevention and control strategies have classified countries into influenza transmission zones, based primarily on geographic proximity. Many countries have improved their surveillance systems for respiratory viruses, providing an opportunity to re-assess patterns of influenza dynamics using analytic approaches focused on influenza detection data and maximizing global coverage. What this study addsOptimal clustering of influenza surveillance data from 111 countries and proximal assignment by latitude of countries lacking sufficient data grouped countries into five epidemic zones. How this study might affect research, practice or policyBy providing improved resolution on the temporal and geographical dynamics of influenza activity, this study offers an evidence base to aid national and global decision-making on enhanced surveillance strategies, vaccine strain selection, seasonal epidemic preparedness, and resource allocation, thereby strengthening efforts to prevent and control influenza worldwide. This data-driven framework for characterizing global patterns of influenza virus circulation can be leveraged to reexamine patterns as new data become available.

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

BackgroundThe 2024-25 influenza season was the most severe in the United States (US) since 2017-18, with co-circulation of both influenza A virus subtypes (H1N1 and H3N2). Influenza vaccine effectiveness (VE) has varied by season, setting, and patient characteristics. MethodsUsing electronic healthcare encounter data from eight US states, we evaluated influenza vaccine effectiveness (VE) against influenza-associated hospitalizations and emergency department or urgent care (ED/UC) encounters from October 2024-April 2025 among children aged 6 months-17 years and adults aged [&ge;]18 years. Using a test-negative, case-control design, we compared the odds of influenza vaccination between acute respiratory illness (ARI) encounters with a positive (cases) versus negative (controls) test for influenza by molecular assay, adjusting for confounders. ResultsAnalyses included 108,618 encounters (5,764 hospitalizations and 102,854 ED/UC encounters) among children and 309,483 encounters (76,072 hospitalizations and 233,411 ED/UC encounters) among adults. Among children across care settings, 17.0% (6,097/35,765) of cases versus 29.4% (21,449/72,853) of controls were vaccinated. Among adults, 28.2% (21,832/77,477) of cases versus 44.2% (102,560/232,006) of controls were vaccinated. VE was 51% (95% confidence interval [95% CI]: 41-60%) against influenza-associated hospitalizations and 54% (95% CI: 52-55%) against influenza-associated ED/UC encounters among children. VE was 43% (95% CI: 41-46%) against influenza-associated hospitalizations and 49% (95% CI: 47-50%) against influenza-associated ED/UC encounters among adults. ConclusionsInfluenza vaccination provided protection against influenza-associated hospitalizations and ED/UC encounters among children and adults in the US during the severe 2024-25 influenza season. These findings support influenza vaccination as an important tool to reduce influenza-associated disease. Brief SummaryDuring the 2024-25 influenza season, influenza vaccination provided protection against influenza-associated hospitalizations (43-51%) and emergency department or urgent care encounters (49-54%) among children and adults in the United States.

The panzootic caused by high pathogenicity avian influenza (HPAI) H5N1 clade 2.3.4.4b has been devastating for animals, globally. Despite global spread, the virus remains absent in Oceania. Herein we report the results of our fourth year of enhanced migratory bird surveillance, coinciding with the spring migration of wild birds in 2025; none of the 847 migratory wild birds or 38 marine mammals were positive for HPAI H5N1, although we did detect LPAI. Surveillance remains a critical tool for HPAI H5N1 response, with early detection and rapid response being critical to mitigate the impacts of this virus on animal, environment and human health.

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.

BackgroundBacterial co-infection contributes substantially to influenza-associated morbidity and mortality. Patterns of viral circulation, diagnostic testing and antimicrobial use changed markedly during the COVID-19 pandemic, yet contemporary estimates of bacterial co-infection and antimicrobial use in influenza have not been synthesised. ObjectivesTo estimate the pooled prevalence of microbiologically confirmed bacterial co-infection among hospital-attended patients with laboratory-confirmed influenza. Secondary objectives were to characterise co-infecting bacterial pathogens, quantify antimicrobial prescribing overall and across key subgroups. This study was registered with PROSPERO (CRD420251072782). Data sources and eligibilityWe searched Embase (Ovid), MEDLINE, PubMed, Scopus, and Web of Science to 15th June 2025 for English-language studies including [&ge;]50 hospital-attended patients with laboratory-confirmed influenza and reporting bacterial co-infection. MethodsPooled prevalence estimates and antimicrobial prescription proportions were calculated using a generalised linear mixed model with logit link. Subgroup analyses included age group, clinical setting, and seasonal vs. pandemic influenza. Risk of bias was assessed using ROBINS-E and certainty of evidence using GRADE. ResultsNinety-three studies from 30 countries, comprising 111,889 patients with influenza, met inclusion criteria; 9,899 had confirmed bacterial co-infection. The pooled prevalence was 17.3% (95%CI 13.6-21.7%; I2=99.2%). Prevalence was higher in ICU compared to non-ICU settings (28.3% vs. 13.6%). The most frequently identified bacterial pathogens were Streptococcus pneumoniae (35.7%) and Staphylococcus aureus (30.3%). Antimicrobial use, reported in 38 studies, was high (pooled prevalence 88.1%, 95%CI 76.0-94.5%; I2=99.9%), and was more common in adults than children (97.8% vs 65.0%), and in ICU compared with non-ICU settings (96% vs 81%). ConclusionsBacterial co-infection was identified in approximately one in six hospital-attended influenza cases, yet antimicrobial prescribing is near-universal. Substantial heterogeneity and diagnostic variability constraint interpretation but underscore persistent challenges in clinical decision-making. These findings support strengthened diagnostic capacity and antimicrobial stewardship to optimise management of suspected influenza-associated bacterial co-infection.

BackgroundThe World Health Organization has developed several global template protocols for epidemiological investigations, including for household transmission investigations (HHTIs). These investigations facilitate rapid characterisation of novel or re-emerging respiratory pathogens and support evidence-based public health actions. Beyond technical readiness, community buy-in is central to the feasibility and acceptability of HHTIs. Research is needed to determine the perceived legitimacy among the community to inform local protocol adaptation and development of implementation plans that consider community attitudes and needs. MethodsIn 2025, we conducted a convenience survey of community members living in Victoria, Australia to explore: their understanding of emerging respiratory diseases; their willingness to take part in public health surveillance activities such as HHTIs; the acceptability of clinical and epidemiological data collection and respiratory/blood sample collection as main components of HHTIs, and; participant comfort towards including their companion animals in HHTIs. ResultsWe received 282 survey responses, of which 235 were included in the analysis dataset. Compared to the general Victorian population, our participants included a higher proportion of participants who reported being female, tertiary-educated, of Aboriginal and/or Torres Strait Islander heritage, born in Australia and speaking only English at home. Participants indicated overall high levels of comfort and acceptability towards participation in HHTIs, particularly in relation to clinical and epidemiological data collection, with lesser but still high levels of comfort with providing multiple respiratory specimens in a 14-day period. Participants were least comfortable with other specimens such as urine and blood. Involving companion animals in HHTIs was similarly acceptable as human-focused components. ConclusionsDespite our survey population being non-representative of the general Victorian population, our findings provide valuable descriptive insights into the acceptability of HHTIs in Victoria, Australia from which to benchmark future local and international surveys and community engagement activities.

Background Pediatric immunizations for Respiratory Syncytial Virus (RSV), including monoclonal antibodies for infants and vaccines for pregnant people, have become broadly available and can prevent severe RSV outcomes in infants. However, quantifying the impact of RSV immunization in prevention of severe pediatric illness at the population-level is limited by lack of RSV case surveillance data. The Massachusetts Department of Public Health (DPH) conducted a modeling analysis using routine public health surveillance data to estimate the state-level impact of new RSV immunization products on Emergency Department (ED) visits and hospitalizations in Massachusetts for highest risk pediatric groups. Methods A scenario projection tool, called R.Scenario.Vax, was utilized to simulate RSV-associated ED hospital encounters by age group in the context of newly available immunizations. ED visit and hospitalization data from the National Syndromic Surveillance Program (NSSP) during the time period 10/08/2017--10/19/2024 were analyzed, scaled to account for changes in RSV testing practices over time and missing encounter volume in historic data, and utilized to inform model fit of a "typical" RSV season. RSV immunization data from the Massachusetts Immunization Information System (MIIS) for the 2023--2024 and 2024--2025 RSV seasons informed high and moderate pediatric RSV immunization coverage scenarios and their impact was compared to a counterfactual reference scenario of no new immunizations. Median projections were quantitatively and qualitatively compared to observed 2024--2025 season data. Percent reduction in hospital encounters and encounters averted per 10,000 population were calculated for each scenario as compared to the reference. Results Projections for the youngest at-risk age groups showed significantly lower RSV-associated ED visits and hospitalizations during the 2024--2025 season for both high and moderate immunization coverage scenarios. Median projections for infants under 6 months old in the highest coverage scenario, wherein nearly all infants were immunized, showed 72.6% lower ED visits and 73.4% lower hospitalizations when compared to the reference scenario, equating to 262 ED visits and 85 hospitalizations averted per 10,000 population. Conclusions Our results support the use of modeling methods for public health insights and suggest that RSV immunizations for infant populations result in significantly lower RSV-related ED encounters in Massachusetts.

BackgroundIn World War 1 (WW1) outbreaks of measles were associated with high case fatality rates amongst soldiers. Recent studies have shown that survivors of acute measles can also develop immune amnesia, increasing their susceptibility to other infections. However, the impact of prior measles infection on infectious diseases during WWI remains unclear. MethodsHere, we create a searchable database documenting the medical history of 1,569 individuals from the Australian, New Zealand, and Canadian forces during WW1. ResultsWe use this novel database to show that a recent measles hospitalisation was associated with a higher chance of death for infectious diseases (excluding pandemic influenza like illness), consistent with immune amnesia. Surprisingly, a prior measles infection was associated with a significant reduction in hospitalisations duration from pandemic influenza like illness. ConclusionThese findings highlight the unique interaction between measles and pandemic influenza, contrasting with other infectious diseases, and underscore the significant health burden measles placed on young adults during WW1.

Global efforts to prevent and mitigate the impacts of high pathogenicity avian influenza (HPAI) H5 on domestic animals, humans, and wildlife rely on timely and transparent information that is both accurate and interpretable across countries and sectors. International epidemiological and genomic databases, such as the World Animal Health Information System (WAHIS), the Global Animal Disease Information System (EMPRES-i+), the Global Initiative on Sharing All Influenza Data (GISAID), and the National Center for Technological Bioinformation Virus Portal (NCBI) provide essential information for surveillance, research, and decision-making. To evaluate how well these resources capture recent wildlife impacts, we consolidated information from these databases and complementary public sources including government reports, scientific literature, and news articles, on wildlife mortality associated with HPAI H5 in the Americas from November 2021 to July 2024. The consolidated dataset comprised 615,883 wild birds (287 spp.) and 63,409 wild mammals (39 spp.). In comparison, WAHIS represented 16,902 wild birds (261 spp.) and 6,323 wild mammals (31 spp.) while EMPRES-i+ captured a substantially smaller portion of affected host diversity for both wild birds (105 spp.) and wild mammals (27 spp.). Genomic databases (GISAID and NCBI) represented 7,027 whole genome equivalents of H5 viruses from wild birds (175 spp.) and 371 from wild mammals (26 spp.). These discrepancies indicate that international databases, while essential, provide an incomplete picture of HPAI impacts on wildlife, with significant geographic and taxonomic asymmetries attributable to differences in surveillance capacity, reporting practices, sequencing effort, and data-sharing pathways. Studies and management strategies relying on these resources without complementary validation may therefore mistake data gaps for real-world epidemiological patterns. Strengthening data reporting standards, improving validation procedures, and integrating international databases with national reports, scientific publications, and other sources will enhance the reliability of epidemiological analyses and support more effective One Health surveillance, risk assessment, and conservation action. Author summaryHigh pathogenicity avian influenza (HPAI) H5 viruses, often called bird flu viruses, can cause severe disease in birds and mammals, including humans. Because of their relevance for human health, livestock production, and wildlife conservation, international databases were established to share information on when and where these viruses are detected, which species are affected, and what virus strains are found. These databases are essential tools for governments, scientists, and conservation practitioners working to track outbreaks, understand how these viruses spread and evolve, and guide surveillance and response. In this study, we compiled and compared information on recent HPAI H5 events in wildlife in the Americas available in international databases with information from other public sources, including reports from governments, scientific literature, and news articles. We found important discrepancies in how countries and species affected were represented across sources. As a result, international databases might not fully capture the actual distribution or conservation impact of HPAI H5 on wildlife. Our findings also show why decision-makers and scientists should interpret database-derived patterns carefully. We provide recommendations to improve international databases to address these gaps and better inform One Health risk assessment and wildlife conservation actions.

Background: The annual respiratory season in Europe is marked by the co-circulation of multiple respiratory pathogens, such as influenza viruses, rhinoviruses, and coronaviruses. Effective surveillance is necessary but hampered by heterogeneity of case definitions and limited pathogen specificity in existing systems. This study aims to detect pathogen-specific signals in the participatory surveillance of the Netherlands using a sub-set of samples with virological detection. Additionally, we explore a method to use the findings in the Netherlands to enhance the virological interpretation of participatory surveillance data in Italy. Methods: We analyzed symptom data collected through a participatory surveillance platform in the Netherlands and Italy over five years (2020-2025). Symptom-by-week matrices from the Dutch cohort were aggregated into syndromes and their associated time series using Non-negative Matrix Factorization (NMF). We compared the respective time series of the syndromes with influenza virus, SARS-CoV-2, seasonal coronaviruses, RSV, and rhinovirus incidence estimated from nose- and throat swabs of a subsample of symptomatic participants of the participatory surveillance platform in the Netherlands. We tested the transferability of these components by applying the Dutch-derived components to describe Italian symptom data and extract respective incidences. Results: NMF identified eight symptom clusters in the Dutch cohort, one aligning with SARS-CoV-2, one aligning with rhinovirus and a third component aligning with influenza virus, RSV and seasonal incidences estimated from collected nose- and throat swabs. Transferring Dutch-derived symptom clusters to Italian data showed consistency in key components between Dutch and Italian cohorts, particularly those associated with SARS-CoV-2. Conclusion: This study demonstrates that unsupervised symptom decomposition can identify co-circulating respiratory pathogens trends from syndromic surveillance data, providing timely pathogen circulation insights.

Background: Human metapneumovirus (hMPV) is commonly associated with respiratory tract infections (RTIs) in young children. Methods: We estimated the annual hospital incidence of hMPV RTIs in children under 5 years in Scotland from 2017 to 2023 using national hospital and laboratory data. Incidence outside Lothian, where testing practices were uncertain, was extrapolated from Lothian laboratory data, where hMPV testing was advised for all RTI admissions. We also examined the severity and mortality of laboratory-confirmed hMPV cases. We developed similar estimates for RSV and Influenza A for comparison. Results: This analysis included 1,462 laboratory-confirmed hMPV hospitalisations in children aged under 5 years. The extrapolated hMPV hospital incidence ranged from 19 per 100,000 to 537 per 100,000 in children aged under 5 years. The extrapolated incidence was two to three times higher than that based on laboratory-confirmed data. Hospital incidence was higher in infants than in toddlers. hMPV incidence dropped substantially during the 2020/21 season, followed by a rebound during the 2021/22 season. About 10% of hMPV RTI hospital admissions required hospital stay [&ge;]5 days, but <1% required intensive care unit admissions or resulted in in-hospital death. RSV hospital incidence appeared substantially higher than the hMPV hospital incidence in this population. Conclusions: hMPV RTIs contribute to a substantial hospital burden in young children in Scotland. However, the RSV RTI burden is likely to be higher in the population unvaccinated against both viruses. Improved surveillance and diagnosis strategies are required to develop robust hospital burden estimates.

Background Human challenge trials provide a unique opportunity to quantify pathogen infectivity in terms of the probability of infection given an inoculated dose. However, between-pathogen comparisons are often distorted by individual heterogeneity in host susceptibility and by differences in background immunity across trial populations. We examined how dose-dependent infection risks differ across common respiratory viruses when such heterogeneity is explicitly incorporated. Methods We conducted a systematic review of human challenge trials for four respiratory viruses: respiratory syncytial virus (RSV), influenza virus, rhinovirus, and adenovirus. Using the extracted data, we fitted dose-response models under different distributional assumptions, allowing both continuous susceptibility variation and discrete immune fractions. We compared alternative heterogeneity models and evaluated pathogen-specific dose-response patterns using original and scaled dose metrics. Results All four viruses showed substantial heterogeneity in host susceptibility, and models assuming homogeneous susceptibility were unsupported. RSV and influenza were best described by models with a distinct immune or effectively non-susceptible subgroup, and the estimated immune proportions were approximately 40% and 25%, respectively. In contrast, rhinovirus and adenovirus were better explained by continuously distributed susceptibility, with little evidence of a fully immune subgroup. On a scaled dose axis, rhinovirus and adenovirus showed steeper increases in infection risk with dose than RSV and influenza. Conclusions The structure of susceptibility heterogeneity differs across common respiratory viruses, which in turn shapes dose-dependent infection risks. Incorporating this heterogeneity is essential for valid cross-pathogen comparison and for interpreting human challenge data in epidemiologic and public health contexts.

Background: The 2026 FIFA World Cup may bring over one million visitors to North America from around the globe to participate in mass gathering events. The nature of the event and recent news have raised concerns for some that the tournament could lead to infectious disease outbreaks or fuel existing epidemics. Objective: To systematically assess the infectious disease threat posed to the United States by the tournament. Design: A multi-institutional team evaluated pathogen-specific risk across three dimensions: importation, outbreak potential, and impact to identify a priority pathogen list. A systematic screening protocol ensured common criteria and that pathogen information was collected when necessary to inform inclusion. Results: Increased risk from the World Cup is near zero for 63 of 77 evaluated pathogens. Pathogens were predominantly excluded as threats due to low excess importation risk and low outbreak potential if introduced. The remaining priority pathogens fall into five categories: (a) mosquito borne pathogens with the potential for sustained transmission in some host cities, (b) seasonal respiratory viruses, (c) chronic infections with high prevalence outside the United States, (d) pathogens present in the United States with likely increased transmission at World Cup activities, and (e) high-consequence infectious threats. Limitations: Data availability is variable across diseases. Impact calculations may not reflect actual costs to host cities. Disease incidence in World Cup travelers may differ from national incidence rates. Conclusion: While infectious disease outbreaks at the 2026 FIFA World Cup are possible, in an already highly connected world where large gatherings are frequent, the elevated risk from the tournament is not as extreme as it first may seem.

Currently circulating swine influenza viruses (SIVs) mainly include H1N1, H1N2, and H3N2 subtypes. In this study, two G4 genotype Eurasian avian-like (EA) H1N1 SIVs were isolated from 556 samples collected between 2023 and 2026. A systematic analysis was conducted on the two EA H1N1 isolates (FYD30 and YZF69) to assess their pandemic potential. The hemagglutinin (HA) proteins of both H1N1 viruses possessed residues 225E and 228S, indicating enhanced affinity for human-like -2,6-linked sialic acid receptors, which was confirmed by receptor-binding assays. Polymerase activity tests demonstrated that the two SIVs exhibited significantly higher activity in mammalian cells, relative to avian cells, which is consistent with the efficient replication in mammalian cells. Challenge experiments revealed that both H1N1 caused significant pathogenicity in mice and pigs, with YZF69 exhibited higher virulence than FYD30. The higher virulence of YZF69 may be attributed to its molecular features, including the NP Q357K mutation, and an additional glycosylation site in HA. In conclusion, currently circulating EA H1N1 SIVs have acquired key molecular signatures of mammalian adaptation, exhibit enhanced virulence in mammals, and continue to undergo extensive reassortment driven by international swine trade. These findings highlight the potential pandemic risk of SIVs and underscore the urgent need for strengthened surveillance.