Influenza and Other Respiratory Viruses

BackgroundContinued serosurvey for SARS-CoV-2 population immunity is critical for vaccine strain selection and identification of susceptible groups such as young children. We aim to evaluate the use of a high-throughput, low-volume assay to describe strain-specific IgG measurement in a longitudinally followed community-based cohort. MethodsThe longitudinal Household Influenza Vaccine Evaluation study has observed around 300 households annually for acute respiratory illness. SARS-CoV-2 variant-specific IgG (including original, delta, beta, and omicron variants) concentrations were measured using multiplex electrochemiluminescence (ECL), pseudoviral neutralization (PN), and ACE2 inhibition assays in participants who had serum samples drawn between July 1 and December 31, 2021. Spearmans rank correlation coefficient assessed correlation within and between ECL, ACE2, and PN assays. Receiver operating characteristic (ROC) analysis evaluated the performance of ECL and ACE2 assays. Generalized Additive Mixed Models estimated population immunity by age against SARS-CoV-2 variants. ResultsA total of 156 serum samples from 117 participants were selected for this study. Most were from adults and a majority received vaccination during the analysis period. High correlations were observed within ECL (0.99-1.0), ACE2 (0.87-0.99), and between panels: ECL vs. PN (0.95-1.00), ACE2 vs. PN (0.85-0.96). ROC analysis showed medium to high areas under the curve, sensitivity, and specificity for ECL (0.85-0.87; 0.89-0.90; 0.87-0.88) and ACE2 (0.85-0.96; 0.94-1.0; 0.42-0.92). SARS-CoV-2 IgG concentrations are higher in older individuals, plateauing at age 20. ConclusionWe found a high correlation between ECL, ACE2, and PN across variants. Age-specific IgG quantities reflected behavior and infection histories collected by active surveillance.

BackgroundSeasonal human influenza viruses can escape from antibody-mediated neutralization when amino acid changes occur in the hemagglutinin protein. Routine surveillance identified circulation of an A(H3N2) virus variant in the Netherlands with amino acid substitutions at hemagglutinin positions 158 and 189. These amino acid positions were previously responsible for antigenic change of influenza A(H3N2) viruses and potentially lead to escape of this variant from vaccine-mediated immunity. AimTo characterize the emergence and antigenic properties of N158K and K189R double substitution virus variants. MethodsWe analyzed the geographical and temporal dynamics of the double-substitution variant using a phylogeographic approach and used hemagglutination inhibition assays and antigenic cartography methods to map its antigenic properties. ResultsA(H3N2) viruses carrying K189R were first detected in Guatemala in June 2024, before subsequently gaining the N158K substitution, which was intially detected in Colombia in November 2024, followed by detection in the Netherlands in December 2024. However, detections within Europe remained almost entirely confined to the Netherlands. The proportion of viruses carrying the N158K and K189R substitutions increased to 16% - 24% per collection week of sequenced Dutch viruses during the peak of the epidemic of the 2024-2025 respiratory season. Antigenic characterization of viruses with N158K and K189R substitutions indicated that these are antigenically distinct from the A(H3N2) components of 2025-2026 Northern Hemisphere vaccines, showing 8-192-fold reduction in hemagglutination inhibition titers with antisera against the vaccine strain compared to antisera against the homologous virus. ConclusionsInfluenza A(H3N2) viruses with N158K and K189R escaped recognition by antibodies raised against the 2024-2025 and 2025/2026 Northern Hemipshere vaccine strains in hemagglutination inhibition assays. These variants circulated widely in the Netherlands during the 2024-2025 influenza season, raising concerns about reduced vaccine-mediated protection if such variants would spread more broadly during 2025-2026 Northern Hemipshere season.

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 [≥]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 [≥]10 and [≥]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.

Between 2022 and 2025, highly pathogenic avian influenza viruses (HPAIVs) of clade 2.3.4.4b, including four distinct H5 Eurasian (EA) genotypes, were detected in wild birds and mammals in the Svalbard Archipelago and on the island of Jan Mayen. We describe their epidemiology and genomic characteristics to improve understanding of HPAIV occurrence and transmission in the High Arctic. The initial cases in 2022 occurred during summer and involved a glaucous gull (Larus hyperboreus) and great skuas (Stercorarius skua) on Svalbard and Jan Mayen, representing the first detections of HPAIVs in the High Arctic. Three HPAIV genotypes were identified: EA-2020-C (H5N1), EA-2021-AB (H5N1), and EA-2021-I (H5N5). In 2023, HPAIVs were detected in a broader range of bird species, and retrospectively in an Atlantic walrus reported by another research group (Odobenus rosmarus rosmarus). Genotypes identified in 2023 were EA-2020-C (H5N1), EA-2021-I (H5N5), and EA-2022-BB (H5N1). No cases were reported in 2024. In 2025, EA-2021-I (H5N5) was detected in Arctic foxes (Vulpes lagopus) on Svalbard, without preceding detections in wild birds. The foxes exhibited neurological symptoms, and necropsy of one individual revealed the presence of feathers in its stomach. All sequenced viruses from the Arctic foxes uniquely carried the combination of PB2-E627K and PB1-H115Q, which is associated with mammalian adaptation. The detection of multiple genotypes indicates repeated and independent introductions of HPAIVs into these regions. The co-circulation of genetically distinct virus strains in areas of high bird density further suggests that Arctic breeding grounds may facilitate local viral amplification, reassortment, and subsequent dissemination along migratory flyways, including transcontinental spread. Data summaryThe authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files. Influenza A whole genome sequences generated through this study are available under the GISAID accession numbers found in Table 1. All genome sequences and associated metadata supporting the findings of this study can be accessed through the persistent digital object identifier https://doi.org/10.55876/gis8.260211rq. O_TBL View this table: org.highwire.dtl.DTLVardef@15e1921org.highwire.dtl.DTLVardef@c3e91borg.highwire.dtl.DTLVardef@1fcfe78org.highwire.dtl.DTLVardef@a69606org.highwire.dtl.DTLVardef@c36c74_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 1.C_FLOATNO O_TABLECAPTIONDetections of highly pathogenic avian influenza virus (HPAIV) in wild birds and mammals sampled in the Svalbard Archipelago and on Jan Mayen from January 1st, 2022, to August 31st, 2025. C_TABLECAPTION C_TBL

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

Accurate vaccination status ascertainment is fundamental to valid vaccine effectiveness (VE) estimation. We evaluated the accuracy of current and prior seasons self-reported influenza vaccination status among outpatients with acute respiratory illness recruited by the Canadian Sentinel Practitioner Surveillance Network (SPSN) during the 2023-2024 season in Quebec, Canada. Vaccination status was self-reported at specimen collection for influenza virus testing and compared to the provincial vaccination registry. Self-report showed high registry agreement, including sensitivity, specificity, accuracy and kappa statistics for current (91%, 98%, 96%, 0.89) and prior (85%, 95%, 92%, 0.78) seasons vaccination status. Metrics were similar by influenza case status, age, sex and comorbidity with more variation for sensitivity than specificity. Test-negative design estimates of the crude association between influenza case status and current seasons self-reported or registry-based vaccination status did not meaningfully differ, with absolute difference of 2% overall. Findings support self-reported influenza vaccination for timely and valid VE estimation.

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.

BACKGROUND AND OBJECTIVESSeasonal influenza vaccination has been shown to reduce the risk of influenza and severe complications among children 6 months and older. Since 2010, reported numbers of influenza-associated pediatric deaths among children aged <18 years have ranged from 37 during the 2011-2012 season to 289 during 2024-2025. We estimated influenza vaccine effectiveness (VE) against pediatric death from 2016-2017 through 2024-2025. METHODSWe conducted a case-cohort analysis comparing current season influenza vaccination status among reported influenza-associated pediatric deaths with survey estimates of influenza vaccination coverage in pediatric age groups. Underlying medical conditions and current seasonal influenza vaccination were obtained from surveillance case reports. We estimated vaccination odds ratios (OR) and 95% confidence intervals (CI) from logistic regression comparing influenza vaccination among children who died with vaccination coverage in comparison cohorts. VE was calculated as (1 - OR) x 100. RESULTSFrom August 2016 through July 2025, 1234 laboratory-confirmed influenza-associated pediatric deaths were reported among children aged 6 months--17 years. Of 1086 reported deaths including influenza vaccination information, 124 (23%) of 530 children with underlying medical conditions and 70 (13%) of 556 children without known conditions were fully vaccinated against influenza. Average influenza vaccination coverage in survey cohorts was 49%. VE was 80% (95% CI, 75% to 84%) overall, 77% (95% CI, 71% to 82%) among children with underlying medical conditions and 87% (95% CI, 84% to 89%) among children without known conditions. CONCLUSIONSInfluenza vaccination reduced risk of fatal influenza among children with or without known underlying medical conditions.

Introduction: Modeling when influenza epidemics typically occur can help countries optimize surveillance, time clinical and public health interventions, and reduce the burden of influenza. Methods: We 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 country's weekly influenza-positive tests to smooth and impute time series distributions. From these GAMs, we calculated each country's 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 cluster's mean latitude. Results: We 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. Conclusion: Epidemic 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.

Background: The 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. Methods: Using 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 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. Results: Analyses 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. Conclusions: Influenza 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.

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 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.

The emergence and spread of highly pathogenic avian influenza H5N1 subtypes have raised global concerns due to their ability to cross species barriers and occasional spillover to humans. The viruses primarily infect wild birds and poultry, which have caused significant, sporadic outbreaks in mammals including dairy cattle. Influenza D virus is a recently identified influenza virus that mainly affects cattle with frequent spillover to other species such as swine. Despite the availability of poultry vaccines, there are no H5N1 and Influenza D vaccines for cattle or other potentially affected livestock. Given a history of frequent influenza pandemics originating from avian and mammalian hosts, there is an urgent need for enhanced surveillance, biosecurity, and the development of antivirals and vaccines. Here we describe the development of a novel hybrid alphavirus-influenza pseudovirion (Ha-IV), which is a non-replicating influenza virus-like particle composed of viral structural proteins and an RNA genome derived from a fast-expressing alphaviral vector. As a proof-of-concept, we assembled Ha-IV pseudoviruses based on influenza D and influenza A and B subtypes, and demonstrated their infectivity. In addition, we validated an influenza A pseudovirus based on the H5N1 clade 2.3.4.4b strain, A/Texas/37/2024, for rapid quantification of neutralization antibodies within 4 to 18 hours. Furthermore, we used the pseudovirus to quantify infected cow sera and performed a correlation study with the classic hemagglutinin inhibition assay (HIA). We demonstrate that the Ha-IAV pseudovirus-based assay is consistent with HIA in identifying protective antibody responses. Our results demonstrate that this new Ha-IV pseudovirus provides a rapid tool for quantifying the infectivity of emerging HA mutants and for assessing neutralizing antibody responses.

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.

BackgroundThe emergence of the highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in North America, beginning in February 2022, has highlighted the dynamic, unpredictable, and regionally variable risk of infections. Studies are needed to assess the spatiotemporal clustering of HPAI H5 at the interface between wild waterfowl and commercial poultry to better understand and mitigate this risk. MethodsPublicly available data on HPAI H5 detections in wild birds and commercial poultry from January 2022 to January 2026 were analyzed at the county level. Retrospective space-time permutation models were used to identify and scan for clusters with higher than expected detection rates. ResultsA total of 17,091 HPAI H5 detections were reported in wild birds across 1,467 county-level locations. Four species, Mallard (Anas platyrhynchos) (2,848 detections, 16.66%), Canada goose (Branta canadensis) (1,496, 8.75%), Green-winged teal (Anas carolinensis) (1,364, 7.98%), and Snow goose (Anser caerulescens) (1,084, 6.34%), accounted for 39.73% of detections. In commercial poultry, 532 outbreaks in turkey operations, 148 outbreaks in table-egg layer operations, 99 outbreaks in broiler chicken operations, and 89 outbreaks in commercial duck operations were reported, respectively. Several spillover events followed an east-to-west expansion. In early 2022, mallard detections preceded outbreaks in Northeast egg-layer and duck farms, while snow goose detections in the Upper Midwest coincided with turkey farm outbreaks. In the Pacific and Mountain West during summer 2022, detections in Canada geese overlapped with turkey farm outbreaks. A resurgence occurred in the Midwest (2025), with snow and Canada goose detections overlapping severe outbreaks in turkey and layer flocks. Additionally, in the Upper Midwest, Canada goose and mallard detections overlapped with outbreaks in commercial duck farms during fall-winter 2025. ConclusionsThe study findings demonstrate distinct vector-based transmission dynamics of HPAI H5 at the wild waterfowl-poultry interface. Farm biosecurity strategies must adapt to these recurrent, vector-specific risks.

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.

ObjectiveTo quantify the seasonal burden of acute respiratory viral infections among healthcare workers (HCWs), characterize virologic etiologies, and identify predictors of symptomatic illness and sick leave. MethodsWe conducted a prospective cohort study of HCWs during winter 2024-2025, with weekly surveys capturing acute respiratory infections (ARI) and sick leave. Nasal-throat multiplex PCR swabs were self-collected during symptomatic episodes. Incidence rate ratios (IRRs) for symptomatic episodes and sick days were estimated using Poisson regression; presenteeism was assessed among febrile episodes. ResultsAmong 655 HCWs, 400 (61.1%) reported [&ge;]1 symptomatic episode. Over 70,861 person-days, incidence rates were 1.34 symptomatic episodes and 0.82 sick days per 100 person-days. Among PCR-confirmed episodes (n=112), rhinovirus (45.5%) and influenza (23.2%) predominated. Female sex was associated with higher rates of symptomatic episodes (IRR 1.38, 95% CI 1.11-1.72) and sick days (IRR 2.55, 95% CI 1.62-4.00), while age >56 years was associated with lower rates of both. During febrile episodes, 38.8% (95% CI 31.5%-46.6%) reported working despite fever. ConclusionsARIs were common among HCWs and frequently resulted in sick leave, yet febrile presenteeism remained substantial, underscoring the need for strengthened respiratory virus prevention and occupational health policies.