Saturday, April 19, 2025

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, April 19 '25)

 


    Am J Med

  1. BILC M, Cramer H
    Use of Complementary Medicine Among US Adults with Post-COVID-19: Results from the 2022 National Health Interview Survey.
    Am J Med. 2025;138:862-869.
    PubMed         Abstract available

  2. MAURO M, Cegolon L, Bestiaco N, Zulian E, et al
    Heart Rate Variability Modulation Through Slow-Paced Breathing in Health Care Workers with Long COVID: A Case-Control Study.
    Am J Med. 2025;138:870-883.
    PubMed         Abstract available

  3. NAIK H, Wilton J, Tran KC, Janjua NZ, et al
    Long-Term Health-Related Quality of Life in Working-Age COVID-19 Survivors: A Cross-Sectional Study.
    Am J Med. 2025;138:850-861.
    PubMed         Abstract available

  4. PALACIO A, Bast E, Klimas N, Tamariz L, et al
    Lessons Learned in Implementing a Multidisciplinary Long COVID Clinic.
    Am J Med. 2025;138:843-849.
    PubMed         Abstract available

  5. KRUMHOLZ HM, Sawano M, Bhattacharjee B, Caraballo C, et al
    The PAX LC Trial: A Decentralized, Phase 2, Randomized, Double-blind Study of Nirmatrelvir/Ritonavir Compared with Placebo/Ritonavir for Long COVID.
    Am J Med. 2024 May 10:S0002-9343(24)00271-7. doi: 10.1016/j.amjmed.2024.
    PubMed         Abstract available

  6. SANAL-HAYES NEM, Hayes LD, Mclaughlin M, Berry ECJ, et al
    People with Long COVID and ME/CFS Exhibit Similarly Impaired Dexterity and Bimanual Coordination: A Case-Case-Control Study.
    Am J Med. 2025;138:893-900.
    PubMed         Abstract available


    BMC Pediatr

  7. SINAEI R, Hosseininasab A, Abbaslou P, Zeinali M, et al
    Gastrointestinal and hepatic manifestations among hospitalized COVID-19 children.
    BMC Pediatr. 2025;25:308.
    PubMed         Abstract available


    Epidemiol Infect

  8. ABUCAR EAM, Kern M, Kurth T, Meierkord A, et al
    Health-related quality of life up to 2 years after SARS-CoV-2 infection: a descriptive cohort study.
    Epidemiol Infect. 2025;153:e60.
    PubMed         Abstract available


    J Exp Med

  9. SAIDOUNE F, Lee D, Di Domizio J, Le Floc'h C, et al
    Enhanced TLR7-dependent production of type I interferon by pDCs underlies pandemic chilblains.
    J Exp Med. 2025;222:e20231467.
    PubMed         Abstract available


    J Immunol

  10. MADRID DMC, Gu W, Karim SJI, Lowke MT, et al
    Single-cell analysis of pig lung leukocytes and their response to influenza infection and oseltamivir therapy.
    J Immunol. 2025 Apr 15:vkaf032. doi: 10.1093.
    PubMed         Abstract available


    J Infect Dis

  11. MORRIS SE, Mathis SM, Reeves E, Chung JR, et al
    Modeling the Potential Impacts of Outpatient Antiviral Treatment in Reducing Influenza-Associated Hospitalizations in the United States.
    J Infect Dis. 2025 Apr 12:jiaf061. doi: 10.1093.
    PubMed         Abstract available

  12. CORTIER T, Gilboa M, Layan M, Joseph G, et al
    Factors Associated With the Transmission of the Delta Severe Acute Respiratory Syndrome Coronavirus 2 Variant in Households: The Israeli COVID-19 Family Study (ICoFS).
    J Infect Dis. 2025;231:e734-e742.
    PubMed         Abstract available

  13. KOZANLI E, Winkel AMAM, Han AX, van den Brink S, et al
    Shortened SARS-CoV-2 Viral RNA Shedding in Saliva During Early Omicron Compared to Wild-Type Pandemic Phase.
    J Infect Dis. 2025;231:940-945.
    PubMed         Abstract available

  14. CHALKIAS S, Pragalos A, Akinsola A, Berman G, et al
    Safety and Immunogenicity of SARS-CoV-2 Spike Receptor-Binding Domain andN-Terminal Domain mRNA Vaccine.
    J Infect Dis. 2025 Jan 10:jiaf022. doi: 10.1093.
    PubMed         Abstract available

  15. FELDSTEIN LR, Ruffin J, Wiegand RE, Borkowf CB, et al
    Effectiveness of mRNA COVID-19 vaccines and hybrid immunity in preventing SARS-CoV-2 infection and symptomatic COVID-19 among adults in the United States.
    J Infect Dis. 2025 Jan 8:jiaf007. doi: 10.1093.
    PubMed         Abstract available

  16. DOLANGE V, Slamanig S, Abdeljawad A, Lai TY, et al
    A Surrogate Enzyme-Linked Immunosorbent Assay to Select High-Titer Human Convalescent Plasma for Treating Immunocompromised Patients Infected With Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern.
    J Infect Dis. 2025;231:e723-e733.
    PubMed         Abstract available

  17. ALESSANDRINI J, Smith BT, Fitzpatrick T, Buchan SA, et al
    Socioeconomic Inequities in the Age-Specific Burden of Severe Respiratory Syncytial Virus in Canada, 2016-2019.
    J Infect Dis. 2025;231:e626-e637.
    PubMed         Abstract available

  18. JACOBS MB, Clark AE, Goldhaber NH, Valentine HD, et al
    Antibody Levels From High-Throughput Variant-Specific SARS-CoV-2 Anti-Spike Immunoglobulin G and Angiotensin-Converting Enzyme 2 Neutralization Assays Correlate With COVID-19 Infection Risk in a Large Population.
    J Infect Dis. 2025;231:921-930.
    PubMed         Abstract available

  19. SANKARANARAYANAN R, Ha B, Sun H, Liu K, et al
    Evaluation of Immunoglobulin A Enzyme Immunoassays to Detect Primary Respiratory Syncytial Virus Infection in Infants and Young Children.
    J Infect Dis. 2025;231:1060-1068.
    PubMed         Abstract available

  20. CHO HK, Frivold C, Chu HY
    Maternal Immunization.
    J Infect Dis. 2025;231:830-836.
    PubMed         Abstract available


    J Virol

  21. HU H, Zhang Y, Zheng H, Zhao X, et al
    Thymic stromal lymphopoietin improves protective immunity of the SARS-CoV-2 subunit vaccine by inducing dendritic cell-dependent germinal center response.
    J Virol. 2025 Mar 4:e0232324. doi: 10.1128/jvi.02323.
    PubMed         Abstract available

  22. KARL V, Hofmann M, Thimme R
    Role of antiviral CD8+ T cell immunity to SARS-CoV-2 infection and vaccination.
    J Virol. 2025 Mar 3:e0135024. doi: 10.1128/jvi.01350.
    PubMed         Abstract available

  23. LOWEN AC, Baker AL, Bowman AS, Garcia-Sastre A, et al
    Pandemic risk stemming from the bovine H5N1 outbreak: an account of the knowns and unknowns.
    J Virol. 2025;99:e0005225.
    PubMed         Abstract available

  24. SIMS A, Weir DJ, Cole SJ, Hutchinson E, et al
    SARS-CoV-2 cellular coinfection is limited by superinfection exclusion.
    J Virol. 2025 Mar 21:e0207724. doi: 10.1128/jvi.02077.
    PubMed         Abstract available

  25. DADONAITE B, Burrell AR, Logue J, Chu HY, et al
    SARS-CoV-2 neutralizing antibody specificities differ dramatically between recently infected infants and immune-imprinted individuals.
    J Virol. 2025 Mar 25:e0010925. doi: 10.1128/jvi.00109.
    PubMed         Abstract available

  26. JOHN K, Huntress I, Smith E, Chou H, et al
    Human long noncoding RNA VILMIR is induced by major respiratory viral infections and modulates the host interferon response.
    J Virol. 2025 Mar 25:e0014125. doi: 10.1128/jvi.00141.
    PubMed         Abstract available

  27. LI P, Faraone JN, Hsu CC, Chamblee M, et al
    Role of glycosylation mutations at the N-terminal domain of SARS-CoV-2 XEC variant in immune evasion, cell-cell fusion, and spike stability.
    J Virol. 2025 Mar 26:e0024225. doi: 10.1128/jvi.00242.
    PubMed         Abstract available

  28. JANA ID, Kanjo K, Roy S, Bhasin M, et al
    Early 2022 breakthrough infection sera from India target the conserved cryptic class 5 epitope to counteract immune escape by SARS-CoV-2 variants.
    J Virol. 2025 Mar 26:e0005125. doi: 10.1128/jvi.00051.
    PubMed         Abstract available


    J Virol Methods

  29. CHANG C, Li L, Guo Y, Ji L, et al
    The potential application of digital PCR in detecting different SARS-CoV-2 viral loads.
    J Virol Methods. 2025;335:115151.
    PubMed         Abstract available

  30. DE BEER C, Vanmali HD
    Genotypic analysis of rhinovirus and human respiratory syncytial virus in sudden unexpected death in infancy cases at Tygerberg Hospital, Cape Town, South Africa.
    J Virol Methods. 2025;335:115150.
    PubMed         Abstract available

  31. ZARGAR B, Sattar SA, McKinney J, Ijaz MK, et al
    The stability and elimination of mammalian enveloped and non-enveloped respiratory and enteric viruses in indoor air: Testing using a room-sized aerobiology chamber.
    J Virol Methods. 2025;335:115144.
    PubMed         Abstract available

  32. REYNA RA, Walker J, Viveros A, Mitchell B, et al
    Optimization of a panel of behavioral tests for use in containment using a golden Syrian hamster model.
    J Virol Methods. 2025;335:115132.
    PubMed         Abstract available


    Minerva Pediatr (Torino)

  33. PECORARO L, Castagnoli R, Salemi C, Piacentini G, et al
    The "stay at home" COVID-19 lockdown restriction may have prevented asthma exacerbations in children affected by pollen allergy: a single center experience.
    Minerva Pediatr (Torino). 2025;77:139-142.
    PubMed         Abstract available

  34. SODERO G, Talloa D, Cipolla C
    GH therapy in children and adolescents with growth hormone deficiency during the first phase of COVID-19 lockdown: a survey in an Italian center.
    Minerva Pediatr (Torino). 2025;77:148-153.
    PubMed         Abstract available

  35. TESARI CRNKOVIC H, Bendelja K, Gjergja Juraski R, Turkalj M, et al
    Respiratory syncytial virus specific immunoglobulin G4 antibodies and atopic diseases in children.
    Minerva Pediatr (Torino). 2025;77:130-138.
    PubMed         Abstract available


    PLoS Comput Biol

  36. POZZATI G, Flores SC
    Combining flipped-classroom and spaced-repetition learning in a master-level bioinformatics course.
    PLoS Comput Biol. 2025;21:e1012863.
    PubMed         Abstract available


    PLoS One

  37. IWU CD, Shrestha P, Littman AJ, Hood JE, et al
    The association between healthcare access and shingles vaccination among older adults in Virginia, United States.
    PLoS One. 2025;20:e0316429.
    PubMed         Abstract available

  38. STRICKLING M, Zarif N, Nguyen H, Moradi Khalaj S, et al
    A comparison of fit, heat stress, oxygen saturation and comfort between a novel reusable mask and disposable N95 respirator.
    PLoS One. 2025;20:e0321538.
    PubMed         Abstract available

  39. AGUIRRE-MILACHAY E, Leon-Figueroa DA, Diaz-Velez C, Valladares-Garrido MJ, et al
    Factors associated with the survival of adults with COVID-19 using a high-flow nasal cannula in a tertiary hospital in northern Peru during the second wave of the pandemic.
    PLoS One. 2025;20:e0309855.
    PubMed         Abstract available

  40. VILLOTA SD, Veloz-Villavicencio E, Garcia-Iturralde S, Arevalo JV, et al
    Validation of new equipment for SARS-CoV-2 diagnosis in Ecuador: Detection of the virus and antibodies generated by disease and vaccines with one POC device.
    PLoS One. 2025;20:e0321794.
    PubMed         Abstract available

  41. PARKINSON C, Shen X, MacDonald M, Logan SW, et al
    Outdoor recreation's association with mental health and well-being during the COVID-19 pandemic.
    PLoS One. 2025;20:e0321278.
    PubMed         Abstract available

  42. SUSLOW A, Schlossler K, Chikhradze N, Lauer R, et al
    Should I stay or should I go-Medical assistants experiences and coping with patient demand and lack of appreciation during the Covid-19 pandemic.
    PLoS One. 2025;20:e0320953.
    PubMed         Abstract available

  43. LEISER R, McLeod J, Mapp F, Stirrup O, et al
    Insights into the implementation of a whole genome sequencing report form (SRF) to reduce nosocomial SARS-CoV-2 in UK hospitals within an unfolding pandemic: A qualitative process evaluation using normalisation process theory.
    PLoS One. 2025;20:e0321534.
    PubMed         Abstract available

  44. CILOVIC-LAGARIJA S, Eitze S, Skocibusic S, Musa S, et al
    Behavioral insights during the COVID-19 pandemic in the Federation of Bosnia and Herzegovina: the role of trust, health literacy, risk and fairness perceptions in compliance with public health and social measures.
    PLoS One. 2025;20:e0320433.
    PubMed         Abstract available

  45. QUINTERO-RINCON A, Di-Pasquale R, Quintero-Rodriguez K, Batatia H, et al
    Computer-based quantitative image texture analysis using multi-collinearity diagnosis in chest X-ray images.
    PLoS One. 2025;20:e0320706.
    PubMed         Abstract available


    Proc Natl Acad Sci U S A

  46. RIOS CARRASCO M, Lin TH, Zhu X, Gabarroca Garcia A, et al
    The Q226L mutation can convert a highly pathogenic H5 2.3.4.4e virus to bind human-type receptors.
    Proc Natl Acad Sci U S A. 2025;122:e2419800122.
    PubMed         Abstract available

  47. HUANG QJ, Kim R, Song K, Grigorieff N, et al
    Virion-associated influenza hemagglutinin clusters upon sialic acid binding visualized by cryoelectron tomography.
    Proc Natl Acad Sci U S A. 2025;122:e2426427122.
    PubMed         Abstract available


    Vaccine

  48. TONG F, Zhou T, Tang L, Wu X, et al
    Evaluating the impact of influenza vaccine on preventing stroke hospitalization and death in Chinese elderly hypertensive patients: A retrospective cohort study.
    Vaccine. 2025;54:127004.
    PubMed         Abstract available


    Virology

  49. BEAUDOIN-BUSSIERES G, Tauzin A, Dionne K, El Ferri O, et al
    Multiple exposures to SARS-CoV-2 Spike enhance cross-reactive antibody-dependent cellular cytotoxicity against SARS-CoV-1.
    Virology. 2025;607:110512.
    PubMed         Abstract available

  50. ANDERSON M, Lopez J, Wyr M, Ramirez PW, et al
    Defining diverse spike-receptor interactions involved in SARS-CoV-2 entry: Mechanisms and therapeutic opportunities.
    Virology. 2025;607:110507.
    PubMed         Abstract available

  51. CHAKRABORTY C, Bhattacharya M, Abdelhameed AS
    Recent SARS-CoV-2 evolution trajectories indicate the emergence of Omicron's several subvariants and the current rise of KP.3.1.1 and XEC.
    Virology. 2025;607:110508.
    PubMed         Abstract available


    Virus Res

  52. ZHAO X, Zhu X, Wang J, Ye C, et al
    The epidemiological analysis of respiratory virus infections in Children in Hangzhou from 2019 to 2023.
    Virus Res. 2025;355:199558.
    PubMed         Abstract available

  53. ZADEH VR, Lew JM, Zahoor MA, Santer D, et al
    Combination therapy enhances the antiviral activity of IFN-lambda against SARS-CoV-2 and MERS-CoV.
    Virus Res. 2025;355:199560.
    PubMed         Abstract available

  54. YAN J, Liu F, Hu S, Pan J, et al
    Regional dynamics and mechanisms behind SARS-CoV-2 XDV.1 prevalence in Chongqing via genomic surveillance and molecular insights.
    Virus Res. 2025;355:199562.
    PubMed         Abstract available

  55. YANG W, Tao T, Zhang J, Yao Y, et al
    The association of cycle threshold value with clinical features in patients infected with Omicron variant.
    Virus Res. 2025;355:199565.
    PubMed         Abstract available

Emerging #zoonotic potential of #H4N1 avian #influenza virus: enhanced #human #receptor binding and #replication via novel mutations

Abstract

Background

Avian influenza virus (AIV), a zoonotic pathogen found worldwide, includes multiple subtypes, one of which is the H4 subtype frequently detected in wild birds and poultry. Despite its prevalence, research on H4 subtype AIV has been scarce, with a focus predominantly on the H4N2 and H4N6 subtypes. The zoonotic potential of H4N1 has not been investigated to date.

Methods

In this study, we used gene sequencing in conjunction with bioinformatics methodologies to analyze wild-type H4N1 AIV strain and mutant strains emerging from serial passaging in cell culture. Furthermore, we assessed the zoonotic potential of H4N1 and the alterations caused by mutations via a series of phenotype assays, including evaluation of receptor binding affinity, immunofluorescence assays, analyses of growth kinetics across different animal cell cultures, and in vivo pathogenicity studies.

Results

Our research reveals that H4N1 AIV can bind to human receptors and exhibits an affinity for human lung and tracheal tissues. In vitro experiments demonstrate that H4N1 replicates efficiently in human cell lines. Furthermore, animal studies demonstrate that H4N1 can induce pneumonia in mice without the need for prior adaptation to the host. Notably, during passage in cell culture, H4N1 rapidly acquired two previously unreported mutations. These mutations significantly enhanced the virus’s ability to attach to human receptors and its capacity for replication.

Conclusions

In summary, our study provides preliminary experimental evidence for the emerging zoonotic potential of H4N1 AIV. These findings expand our knowledge of the H4 subtype AIV and reinforce the critical need for continued surveillance of AIV to prevent and prepare for potential outbreaks affecting human health.

Source: Virology Journal, https://virologyj.biomedcentral.com/articles/10.1186/s12985-025-02736-4

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Sustained cross-species #transmission of #gammacoronavirus in wild #birds reveled by viral characterization in #China

Abstract

Gammacoronavirus (γ-CoV) primarily infects poultry, wild birds, and marine mammals. The widespread distribution and circulation of γ-CoV in the ecological environment may lead to sustained transmission and economic loss. To better understand the diversity of γ-CoV in wild birds, we collect 482 wild-bird fecal samples from Yunnan, encompassing fourteen bird species. We detected twelve γ-CoV positive samples in five bird species, with the characterization of five complete genomes - HNU5-1, HNU5-2, HNU5-3, HNU6-1, and HNU6-2-indicating that these genomes represent two viral species. The HNU5 strains were derived from Black-headed gull (Chroicocephalus ridibundus), while the HNU6 strains were came from Mallard (Anas platyrhynchos), and both of those were recombinant. The HNU5 strain exhibited the highest sequence identity (95.45%) with a γ-CoV strain isolated from Numenius phaeopus (GenBank accession: PP845452). Similarly, the HNU6 strain showed 95.18% nucleotide identity with a γ-CoV strain (GenBank accession: PP845437) derived from Anas platyrhynchos. Taxonomic analysis confirmed that HNU6s belong to the Gammacoronavirus anatis species, while HNU5s attributed to a new species. Cross-species analysis revealed active host-switching events among γ-CoVs, indicating potential transmission of γ-CoVs from marine mammals to wild bird, from wild bird to poultry, and inter-wild bird and inter-poultry transmission. In summary, we report five new γ-CoV strains in wild birds and outline the cross-species transmission of γ-CoVs. Our findings link γ-CoV hosts across different natural environments and provide new insights for exploring γ-CoVs.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.04.17.648926v1

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Friday, April 18, 2025

Detection of Avian #Influenza Virus in #Pigeons

Abstract

Pigeons (Columba livia) are usually kept as free-ranging or racing birds, and they have direct contact with livestock, poultry, and humans. Therefore, they may have an important role in the ecology of influenza virus among various species. In the present study, we bring together all available sequence data of pigeon avian influenza virus (AIV) from public databases to address the current understanding of the genomic characteristics and emergence of each subtype of AIV in pigeons. Collectively, we identified 658 pigeon AIV strains in 21 countries across the world, which were mainly distributed in Europe, Asia, and North America. H1 (2), H2 (1), H3 (8), H5 (71), H6 (16), H7 (16), H9 (543), and H11 (1) AIV subtypes have been identified in pigeons. In addition, we interrogate features of the H5, H6, H7, and H9 subtypes of pigeon AIV, which are relatively common in pigeons. It is particularly noteworthy that the H5 AIV strains identified in pigeons are all classified as HPAIV. For the first time, this study presents a complete overview of the multiple AIV subtypes that have been circulating in pigeons, providing information on their distribution and genomic characteristics. This study will help to understand the molecular evolution of AIV in pigeons.

Source: Viruses, https://www.mdpi.com/1999-4915/17/4/585

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#Liberia - High pathogenicity avian #influenza #H5N1 viruses (poultry) (Inf. with) - Immediate notification

 


A poultry farm in Totota, right behind the Lutheran football field in Bong County.

Source: WOAH, https://wahis.woah.org/#/in-review/6432

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#USA, Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater (as of April 18 '25)



{Excerpt}

Time Period: April 06, 2025 - April 12, 2025

-- H5 Detection3 sites (0.9%)

-- No Detection348 sites (99.1%)

-- No samples in last week243 sites

(...)




Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/h5-monitoring/index.html?cove-tab=0

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#Chikungunya virus virus-like particle #vaccine #safety and immunogenicity in adults older than 65 years: a phase 3, randomised, double-blind, placebo-controlled trial

Summary

Background

Adults older than 65 years are at increased risk for atypical presentations of chikungunya disease, as well as for severe outcomes including death.

Methods

In this phase 3, randomised, double-blind, placebo-controlled, parallel-group trial, adults aged 65 years and older received a single intramuscular dose of Vimkunya (previously chikungunya virus virus-like particle vaccine) or placebo at ten sites in the USA. Participants, clinical site personnel, and the sponsor were masked to individual treatment assignments until all participants had completed their involvement in the trial and the database was cleaned and locked. Baseline and postvaccination chikungunya virus serum neutralising antibody (SNA) titres (NT80) were assessed at selected timepoints. Safety was assessed up to 183 days after dose administration in all participants from the exposed population who provided safety assessment data. This trial is registered with ClinicalTrials.gov, NCT05349617, and is completed.

Findings

Between May 12 and Dec 2, 2022, 413 participants were recruited and randomly assigned (1:1) to receive the Vimkunya vaccine (n=206) or placebo (n=207). The coprimary endpoints of immunologic superiority of chikungunya virus SNA titres compared with placebo and geometric mean titre at day 22 were met. Vimkunya induced a protective seroresponse (SNA NT80≥100, considered the presumptive seroprotective antibody response) in 149 (82%) of 181 participants (95% CI 76·1–87·2) at day 15, in 165 (87%) of 189 participants (81·8–91·3) at day 22, and in 139 (76%) of 184 participants (68·9–81·2) at day 183. Although there was a slightly higher early immune response in the 65–74 years age group at day 15 compared with the 75 years and older age group, the seroresponse rates at day 22 and day 183 were similar. There were no notable differences in adverse event rates between groups, and most adverse events were grade 1 or 2 in severity and of short duration. No vaccine-related serious adverse events or deaths occurred.

Interpretation

We provide robust data from adults aged 65 years and older showing that Vimkunya is well tolerated and can provide a high rate of protection within 2 weeks postvaccination and during 6 months of follow-up.

Source: The Lancet, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00372-1/abstract?rss=yes

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Estimates of #epidemiological #parameters for #H5N1 #influenza in #humans: a rapid review

Abstract

Background 

The ongoing H5N1 panzootic in mammals has amplified zoonotic pathways to facilitate human infection. Characterising key epidemiological parameters for H5N1 is critical should it become widespread. 

Aim 

To identify and estimate critical epidemiological parameters for H5N1 from past and current outbreaks, and to compare their characteristics with human influenza subtypes and the 2003 Netherlands H7N7 outbreak . 

Methods 

We searched PubMed, Embase, and Cochrane Library for systematic reviews reporting parameter estimates from primary data or meta-analyses. To address gaps, we searched PubMed and Google Scholar for studies of any design providing relevant estimates. We estimated the basic reproduction number for the outbreak in the US and the 2003 Netherlands H7N7 outbreak. In addition we estimated the serial interval for H5N1 using data from previous household clusters in Indonesia. We also applied a branching process model to simulate transmission chain size and duration to assess if simulated transmission patterns align with observed dynamics. 

Results 

From 46 articles, we identified H5N1s epidemiological profile as having lower transmissibility (R0 < 0.2) but higher severity compared to human subtypes. Evidence suggests H5N1 has a longer incubation (~4 days vs ~2 days) and serial intervals (~6 days vs ~3 days) than human subtypes, impacting transmission dynamics. The epidemiology of the US H5 outbreak is similar to the 2003 Netherlands H7N7 outbreak. Key gaps remain regarding latent and infectious periods. 

Conclusions 

We characterised critical epidemiological parameters for H5N1 infection. The current U.S. outbreak shows lower pathogenicity but similar transmissibility compared to prior outbreaks. Longer incubation and serial intervals may enhance contact tracing feasibility. These estimates offer a baseline for monitoring changes in H5N1 epidemiology.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2024.12.11.24318702v3

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Thursday, April 17, 2025

Towards #diagnostic #preparedness: detection of #HPAI A(#H5N1) in contrived nasal #swab #specimens using rapid #antigen and point-of-care molecular tests

Abstract

Highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b was first detected in birds in the United States in 2021 and an ongoing outbreak in dairy cattle began in early 2024. At least 70 U.S. cases have been identified in humans with exposure to infected cattle, poultry, and wild birds. No human-to-human transmission has been documented. However, as part of diagnostic preparedness, we evaluated the ability of currently available influenza tests to detect 2024 U.S. H5N1 strains. Contrived nasal swab samples were prepared using live or inactivated 2024 H5N1 and used to test twelve rapid antigen tests (lateral flow assays, or LFA), including 10 commercially-available influenza A LFAs and two H5-specific LFAs. Five point-of-care (POC) molecular assays were also tested. An inclusivity testing protocol was used, wherein a predetermined dilution series is used to evaluate each assay, enabling head-to-head comparison of assay performance. All lateral flow assays and POC molecular tests were able to detect bovine 2024 H5N1 (genotype B3.13). Sensitivity for the POC molecular tests (heat-inactivated virus) ranged from 1.55 to 7.75 TCID50/swab. For 11/12 LFAs, including 10 commercial influenza A tests and an RUO H5 assay, sensitivity (live virus) ranged from 78-1550 TCID50/swab. Testing of four LFAs confirmed inclusivity for a genotype D1.1 strain. Available rapid antigen and point-of-care molecular influenza tests can detect 2024 U.S. H5N1 strains in contrived samples, with a wide range of analytical sensitivity. In the event of human-to-human transmission, clinical performance and optimal sample types would need to be established.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.04.15.25325613v1

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Updated joint #FAO / #WHO / #WOAH public health #assessment of recent #influenza A(#H5) virus events in #animals and people - Assessment based on data as of 1 March 2025



Key points 

-- At the present time, based on available information, FAO-WHO-WOAH assess the global public health risk of influenza A(H5) viruses to be low, while the risk of infection for occupationally exposed persons is low to moderate depending on the risk mitigation measures in place and the local avian influenza epidemiological situation. 

-- Transmission between animals continues to occur and, to date, a growing yet still limited number of human infections are being reported. Although additional human infections associated with exposure to infected animals or contaminated environments are expected to occur, the overall public health impact of such infections at a global level, at the present time, is considered minor

-- The assessment could change if and when additional epidemiological or virological information becomes available. 

-- This risk assessment from FAO, WHO and WOAH updates the assessment of the risk of zoonotic transmission (for example, animal to human) considering additional information made available since the previous assessment from 20 December 2024. 

-- This update is limited to the inclusion of additional information being made available globally. 

-- Due to the potential risk to human health and the far-reaching implications of the disease on the health of wild birds, poultry, livestock and other animal populations, the use of a One Health approach is essential to tackle avian influenza effectively, to monitor and characterize virus circulation, to prevent transmission within species and to new species  to reduce spread among animals, and to prevent human infections from exposure to animals. 


Infections in animals  

In March 2024, a clade 2.3.4.4b influenza A(H5N1) virus of the B3.13 genotype was detected in unpasteurized milk samples and oropharyngeal swabs from dairy cattle for the first time in the USA.{1,2} 

Since then, influenza A(H5N1) virus detections have continued to be reported through the testing of dairy cattle and bulk milk samples.{3} 

Until January 2025, analyses of virus sequence data from infected dairy cattle in the USA indicated that the detections in dairy herds since January 2024 were linked to a single wild bird-to-dairy cow transmission event of a B3.13 genotype clade 2.3.4.4b A(H5N1) virus that occurred in late 2023 or early 2024.{4}  

On 31 January 2025, the USDA APHIS National Veterinary Services Laboratories (NVSL) confirmed the first detection of clade 2.3.4.4b A(H5N1) virus of the D1.1 genotype in dairy cattle in the state of Nevada, indicating a second bird-to-dairy cow transmission event.{5, 6} 

Shortly after, on 13 February 2025, clade 2.3.4.4b A(H5N1) virus, also of the D1.1 genotype, was detected in dairy cattle in the state of Arizona. Phylogenetic analysis indicated that this was another, distinct transmission event marking the third bird-to-cow transmission event reported.{7} 

The genotype D1.1 is currently the most frequently detected genotype across North America and has affected wild birds, poultry and been detected in mammals, including wild and domestic felids and a marine mammal. 

Presently, to our knowledge, viruses from clade 2.3.4.4b A(H5N1) and  genotypes B3.13 and D1.1 have not been detected outside of North America in field conditions. 

As of 1 March 2025, 979 dairy cattle herds in 15 states of the USA have tested positive for A(H5N1), with a significant surge of confirmed outbreaks in dairy  cattle in the State of California reaching 383 herds since the first detection in California in late August 2024.{8} 

The average incidence of clinical disease on affected farms ranges between 10 and 20% with the predominant clinical signs including decreased milk production with abnormal milk, decreased feed intake, fever, dehydration, altered faecal consistency, respiratory distress and abortions.{9,10,11} 

Studies have shown that commercial milk pasteurization inactivates the virus making it safe for human consumption.{12,13,14} 

The routes and modes of transmission between cattle, the duration of virus shedding as well as the infectious period remain under investigation. A preliminary modelling study indicates the duration of infectiousness could range from 2.8 to 13.1 days with a median of 6.2 days.{15} 

Transmission between farms and states in the USA has been linked to cattle movements or possibly through feed and manure handling equipment, or on clothing or footwear of people working or visiting farms.{16} 

While there have been advancements in our understanding, transmission dynamics remain poorly understood.{17}  Experimental studies of lactating dairy cattle and non-lactating heifers have been published and have provided some insight into receptor distribution, viral replication kinetics, and infection routes (see the previous assessment from 20 December 2024). 

No further detections in swine have been reported in the USA since October 2024, which marked the first detection of H5N1 virus in swine in the USA.{18} 

A preliminary experimental study in swine indicated limited replication of a bovine-derived B3.13 genotype A(H5N1) virus and no transmission via direct contact from infected pigs to naĂ¯ve pigs. Experimental infections studies conducted in pigs with other genotype A(H5N1) clade 2.3.4.4b viruses showed that mammalian-derived A(H5N1) virus strains demonstrated higher potential for replication, pathogenicity, and transmissibility as compared to avian-derived A(H5N1) virus strains.{19,20} This warrants vigilance and testing for avian influenza virus in pigs due to the genetic diversity and extent of avian influenza virus circulation as pigs  act as "mixing vessels" for genetic reassortment of avian and human influenza viruses, potentially creating new strains with pandemic potential. 

Detections of A(H5) in mammals, other than dairy cattle, and wild and domestic birds continue to be reported in the USA and in other countries worldwide. Clade 2.3.4.4b A(H5) viruses are circulating in wild and domestic birds, have been involved in multiple spillover events affecting wild carnivorous and marine mammals as well as domestic cats and dogs. Clade 2.3.4.4b virus infections reported in mammals in the Americas, Asia and Europe have resulted in severe clinical presentation (e.g., pneumonia, myocardial necrosis), with neurological signs (e.g., meningoencephalitis) in some species. {21, 22} 

Amino acid changes potentially associated with increased virulence, transmission, or adaptation to mammalian hosts have been sporadically identified.{23,24} 

Since 2022, at least 88 cases of A(H5N1) infections in domestic cats have been reported in the USA. Some of these domestic cat infections have been linked to the consumption of raw, unpasteurized milk from affected dairy farms as well as contaminated raw pet food.{25,26,27} 

Ingestion of wild birds while hunting or scavenging on carcasses is another possible route of infection, as observed in wild animal species (predators and scavengers). However, humans can carry the virus on contaminated clothing, equipment, or fomites and infect other animals such as cats. Similarly, cats may become infected from wild birds and could carry contaminated materials to their household, such as those originating from an infected wild bird, and expose people indirectly to the virus. 

Influenza A(H5N1) virus was detected in two indoor domestic cats with respiratory and neurologic illness that lived in homes of dairy workers but had no known direct exposure to influenza A(H5N1)-affected farms.{28} 

Domestic and wild felids have been reported infected with influenza A(H5) virus belonging to other clades as well. In 2024, avian influenza outbreaks were reported in captive wild felines in two zoos in southern Viet Nam. These led to the death of at least 47 tigers, three lions and a leopard, and were confirmed to be caused by clade 2.3.2.1e A(H5N1) viruses, previously classified as a 2.3.2.1c clade A(H5) viruses.{29,30} 

Additional influenza A(H5N1) infections in felids were reported in January 2025 in a wildlife rescue centre in Maharashtra State, India, causing the death of one leopard and three tigers.{31} 

Influenza A(H5N1) clade 2.3.2.1a infections were reported in domestic cats in January 2025 in Madhya Pradesh, India.{32} 

Previous A(H5N1) outbreaks in captive felines, characterized by severe pneumonia and high mortality, have been associated with the feeding of infected poultry and likely tiger-to-tiger transmission.{33,34} 

Whilst limited cat-to-human transmission has previously been reported in the USA with A(H7N2) viruses{35}, studies have not yet shown that the currently circulating H5N1 viruses have gained the ability to effectively transmit between humans and cats.  

Other A(H5) virus clades such as 2.3.2.1e and 2.3.2.1a continue to circulate and evolve in poultry in geographically restricted regions. For the latest information on avian influenza situation in animals worldwide, see the FAO Global Avian Influenza Viruses with Zoonotic Potential situation update and the WOAH situation reports on HPAI, as well as WOAH’s World Animal Health Information System. 


Detections in humans 

Since the last joint assessment of December 2024 and as of 1 March 2025, an additional 17 human cases of infection with A(H5) viruses have been reported. Of these, 12 were reported from the USA: six in persons with exposure to A(H5N1)-infected dairy cattle in California (five) and Nevada (one), three in persons with exposure while working at or involved in depopulation of A(H5N1)-infected commercial poultry farms. In Iowa, Ohio and Wisconsin, two in persons with exposure to sick and dead backyard poultry in Louisiana and Wyoming,  and one in a person from California with unknown exposure at the time of reporting. 

Samples from three cases related to exposure to dairy cattle in California were confirmed to be clade 2.3.4.4b A(H5N1) viruses of the genotype B3.13. Viruses from two cases with exposure to poultry in Louisiana and Wyoming were confirmed to be clade 2.3.4.4b A(H5N1) viruses of the D1.1 genotype, while one virus from the case in Nevada with exposure to dairy cattle was also of the D1.1 genotype. All but three of the detected cases in the USA have reported mild symptoms, including conjunctivitis and mild respiratory symptoms, and recovered without hospitalization. 

The cases detected in Wyoming and Ohio were hospitalized but have recovered while the case detected in Louisiana died.  

A serological study in 115 persons in Colorado and Michigan working on dairy farms during A(H5N1) outbreaks among dairy cattle found that eight (7.0%) had serologic evidence of recent infection (seropositive, ≥40 antibody titres to H5 2.3.4.4b by both micro-neutralization and hemagglutination inhibition assays). These seropositive individuals reporting working with dairy cattle or in the milking parlour, and four reported being ill when A(H5) was detected among the dairy cattle.{36} 

Another serosurvey conducted in September 2024 among 150 bovine veterinary practitioners found three (2%; 95% CI = 0.7%–5.7%) survey participants with antibodies to HPAI A(H5). {37}  

Two human cases of clade 2.3.2.1e{38} A(H5N1) virus infection were reported from Cambodia since the last update of December 2024. Both cases were fatal and had exposure to sick or dead backyard poultry. 

One detection of A(H5) was reported by the United Kingdom of Great Britain and Northern Ireland in January 2025. The detection was in a specimen from an individual recruited to a zoonotic influenza surveillance study while working at farms where birds were infected with A(H5N1) viruses. The individual had mild symptoms, and the virus was determined via whole genome sequencing to be an A(H5N1) virus belonging to the clade 2.3.4.4b of A(H5) viruses and the DI.2 genotype which was predominant in Europe in the 2024/25 winter season. This genotype is distinct from the genotypes of A(H5) 2.3.4.b detected in North America.{39} 

One case of A(H5) infection was reported in an individual in Viet Nam in November 2024. The individual had contact with sick and dead poultry and developed severe disease but recovered. Further information on the virus from this case is not available. 


Virus characteristics  

Regular monitoring and screening of viral sequences from birds has rarely found markers of mammalian adaptation in clade 2.3.4.4b viruses. Those that have been detected are mainly in the polymerase proteins of the virus. Sporadic events of changes in polymerase proteins have been observed more frequently detected in viruses from mammals. 

As of 1 March 2025, none of the virus sequences from dairy cattle in the USA have well-recognized markers in the HA gene associated with increased human receptor binding.  

Additional studies on some B3.13 A(H5N1) viruses indicate no differences in receptor binding, pH fusion or thermostability compared to other non-B3.13 avian A(H5N1) viruses, and that these viruses retain their avian influenza virus phenotype.{40} 

Some of the D1.1 viruses detected in dairy cattle have the change D701N in the PB2 protein, which has been associated with increased activity in mammalian cells. This change was also observed in the genetic sequence of the virus isolated from a patient infected with A(H5N1) clade 2.3.4.4b D1.1 genotype virus in Nevada.{41} 

As of 1 March 2025, this change had not been observed in D1.1 viruses detected in  wild birds nor poultry. The virus from the patient in Wyoming infected with A(H5N1) clade 2.3.4.4b genotype D1.1 had the E627K mutation in the PB2 protein which is associated with efficient virus replication in people and mammals.{42} This change has not been observed in any D1.1 viruses which have been detected in dairy cattle. 

Available virus sequences from human cases have shown some genetic markers that may reduce susceptibility to neuraminidase inhibitors (antiviral medicines such as oseltamivir) or endonuclease inhibitors (such as baloxavir marboxil). While these changes may reduce antiviral susceptibility in laboratory testing the clinical impact of these genetic changes requires further studies.{43}  

Experimental studies with A(H5N1) clade 2.3.4.4b viruses, including a B3.13 virus from the human case in Texas, have shown variable transmission between ferrets by direct contact, but no or inefficient transmission via respiratory droplets in most studies. {44,45,46,47,48,49} 

Ferrets infected with a non-B3.13 A(H5N1) clade 2.3.4.4b virus via the ocular route did experience severe disease and were able to transmit the virus to other ferrets via direct contact; these contact animals also developed severe disease.{50} 

Currently circulating A(H5N1) viruses would need further genetic changes to gain the ability to spread efficiently among humans via respiratory droplets, consistent with the current level of risk to public health, which is low. 

Based on limited seroprevalence information available on A(H5) viruses, human population immunity against the HA of A(H5) viruses is expected to be minimal; human population immunity targeting the N1 neuraminidase is found to be present although the impact of this immunity is yet to be understood.{51} 

Experimental studies suggest prior A(H1N1) immunity reduced virus replication and disease severity of bovine-derived B3.13 genotype A(H5N1) virus in ferrets and that ferrets with this pre-existing immunity expressed A(H5N1) cross-reacting antibodies to the neuraminidase protein.{52} 


Candidate vaccine viruses (CVV) 

The WHO Global Influenza Surveillance and Response System (GISRS), in collaboration with animal health partners (FAO, WOAH, OFFLU (Joint WOAH-FAO network of expertise on animal influenza) and others), continue to evaluate candidate vaccine viruses for pandemic preparedness purposes both bi-annually and on an ad hoc basis. 

Regular genetic and antigenic characterization of contemporary zoonotic influenza viruses are published here with the most recent update on A(H5) CVVs published in February 2025 following the WHO Consultation on the Composition of Influenza Virus Vaccines for Use in the 2025-2026 Northern Hemisphere Influenza Season.  

The majority of circulating clade 2.3.4.4b viruses reacted well to at least one of the post-infection ferret antisera raised against the existing CVVs. The majority of the clade 2.3.2.1e viruses characterized antigenically reacted well to ferret antisera raised against the existing and CVV proposed in September 2024. Clade 2.3.2.1a viruses detected recently in poultry and felines in India were not characterized antigenically but had HA genes similar to that of the A(H5N1) virus detected in a traveller returning to Australia from India. This virus reacted poorly with ferret antisera raised again available CVVs, thus a new clade 2.3.2.1a CVV was proposed. A new clade 2.3.4.4h CVV was also proposed due to the ongoing detections of this clade of viruses in poultry in China and continued genetic evolution leading to reduced reactivity to existing CVVs. 

The updated list of available zoonotic influenza candidate vaccine viruses (CVVs) which include A(H5N1) viruses and potency testing reagents is updated on the WHO website. Data which has not yet been peer reviewed revealed that vaccination of 39 persons with two doses of an adjuvanted inactivated A/Astrakhan/3212/2020 H5N8 virus elicited functional antibodies against European and North American A(H5N1) clade 2.3.4.4b viruses.{53} 


Assessment of current public health risk posed by influenza A(H5N1) viruses{54} 

1. What is the global public health risk of additional human cases of infection with avian influenza A(H5) viruses? 

-- Despite the continued detections of A(H5) clade 2.3.4.4b in animals and  increasing human exposures to the virus at the human-animal-environment  interface, there have been relatively few human infections reported to date.  Of  the human cases of A(H5) detections reported since the beginning of 2021, the  vast majority were infections in people associated with exposure to A(H5) viruses  through direct or indirect contact with infected animals, or contaminated  environments, such as live poultry markets or other premises with infected  animals. Severity of illness has ranged from mild to fatal, with the majority of  recent cases reported by the USA had mild illness. Thus far, among these cases,  there has been no reported or identified human-to-human transmission through  follow up epidemiologic, virologic and serologic investigations. Investigations for  some of the cases continue. Current virologic and epidemiologic information  indicates that these viruses remain avian influenza viruses without established  adaptations to mammalian hosts and have not acquired the capacity for sustained  transmission between humans.  The epidemiological situation has changed with  the ongoing spread of A(H5) virus in the USA dairy cattle population and two  additional spillover events from birds to dairy cattle identified. Persons exposed to  affected dairy cattle and other infected animals may be in prolonged and close  contact with potentially contaminated surfaces and animal products. As long as  A(H5) viruses continue to be detected in wild and domestic birds and mammals,  including dairy cattle, and related environments, including in unpasteurized/raw  milk, further human cases are expected, particularly amongst exposed individuals  not wearing appropriate personal protective equipment and/or in environments  where mitigation measures are not in place.  Based on currently available  information, FAO-WHO-WOAH assesses the global public health risk of influenza  A(H5) viruses as low. Although additional human infections  associated with exposure to infected animals or contaminated environments are  expected to occur, they remain limited in the general population and the overall  current public health impact of such infections at a global level is minor,  considering the surveillance, response, mitigation and control measures in place.  However, while the risk of infection to the general public is low, among persons  with exposure to infected birds or mammals or contaminated environments, the  risk of infection can range from low to moderate, depending on nature of the  exposure, the duration of exposure, the consistent and appropriate use of  personal protective equipment, and the use of other response, mitigation and  control measures particularly in environments where animals are kept.  The  pandemic potential of these viruses requires enhanced vigilance, especially  in animal populations where animal to animal transmission is known to  occur (poultry and dairy cattle), and close monitoring in animals and humans. It  remains essential that, while farmers enhance biosecurity on their farms,  governments focus efforts on strengthening surveillance in susceptible animal  populations and in persons exposed to infected animals, to prevention and  mitigation efforts to reduce and/or stop animal to animal transmission and reduce  environmental contamination, to prevention efforts to stop animals to human  transmission and to improve communication with at risk persons and provide  occupationally exposed persons with and train in the use of personal protective  equipment. 

2. What is the likelihood of human-to-human transmission of avian  influenza A(H5) viruses?  

There has been no reported human-to-human transmission of A(H5) viruses since  2007, although there may be knowledge gaps in investigations around identified  human infections. In 2007 and the years prior, small clusters of A(H5) virus  infections in humans were reported, including limited human to human  transmission from patients to health care workers. At the present time sustained  human-to-human transmission has not been reported of A(H5) viruses.55  The  A(H5) viruses currently detected in mammals, including in human cases, largely  retain genomic and biological characteristics of avian influenza viruses and remain  well-adapted to spread among birds. Except for within-host obtained  amino acid mutations in polymerase proteins, there is still limited evidence for  adaptation to mammals and humans even when transmission in mammals has  been suspected.{56} No changes in receptor binding tropism have been  consistently observed that would increase binding to receptors in the human  upper respiratory tract which would increase the probability of transmission to and  among people. In addition, available preliminary sero-studies and sero- investigations have not identified humanto-human transmission of A(H5N1) in the  USA. Therefore, sustained human-to-human transmission of the currently  circulating A(H5N1) viruses is considered unlikely without further genetic changes  in the virus. This is actively being assessed by agencies in affected Member  States, FAO, WHO, WOAH and partners. WHO, together with FAO and WOAH,  continues to evaluate A(H5) viruses closely and will reassess the risk associated  with the currently circulating A(H5) viruses as more information becomes  available.  Further antigenic characterization of A(H5) viruses, including in relation  to the existing CVVs, and development of specific reagents are being  prioritized at the WHO Collaborating Centres and essential Regulatory Laboratories  of GISRS in collaboration with public health, animal health, and  veterinary sector colleagues.  


Recommended actions  

It is recommended that Member States and national authorities: 

• increase surveillance and vigilance, in human populations, especially amongst  occupationally exposed persons, for the possibility of zoonotic infections,  particularly through National Influenza Centres (NICs) and other influenza  laboratories associated with GISRS; 

• assess and reduce the risk among  occupationally exposed persons using  methods such as active case finding and molecular and serologic methods, reducing environmental exposures, providing adequate and appropriate personal protective equipment; 

• conduct active case finding around suspected and confirmed human cases to determine if there are additional cases or indications of human-to-human transmission; and   

• work with national agencies and partners to better understand the exposure to and risk from raw/unpasteurized milk and milk products.  

Under the International Health Regulations (IHR) (2005),{57} States Parties are required to notify WHO within 24 hours of any laboratory-confirmed case of human influenza caused by a new subtype according to the WHO case definition.{58} WHO has published the case definition for human infections with avian influenza A(H5) virus requiring notification under IHR (2005).{59}  

Member States and national authorities are also recommended to: 

• increase surveillance and timely reporting efforts for the early detection of A(H5) influenza viruses in domestic birds, wild birds and mammals{60}; 

• include infection with an A(H5) influenza virus as a differential diagnosis, in non-avian species, including cattle, swine and other livestock and farmed domestic and wild animal populations, with high likelihood of exposure to A(H5) viruses; 

• implement preventive and early response measures to break the chain of infection among domestic animals (for example, poultry and dairy cattle), including considering the use of vaccination to reduce circulation in poultry as per national policies and according to guidance provided by animal health organizations{61,62}; 

• promptly report high pathogenicity avian influenza (HPAI) events in all animal species, including cattle (according to the WOAH case definition{63}) and other domestic and wild mammals, to WOAH and other international organizations such as FAO;  

• conduct genetic sequencing and share genetic sequences of influenza viruses and associated metadata in publicly available databases; 

• protect animals by mitigating the risk of introduction and spread of the disease through implementation and/or strengthening biosecurity in livestock holdings/premises and along the value chain; 

• protect persons by employing good production and hygiene practices when handling animals and animal products;  

• protect persons in contact with suspected/infected animals by providing appropriate personal protective equipment and communicating and educating on the importance and proper use of personal protective equipment and providing information and access to testing. 

Additional sets of recommendations related to avian influenza viruses with zoonotic potential can be found here: 

• Global strategy for the prevention and control of high pathogenicity avian influenza (2024) 

• WOAH Statement on High Pathogenicity Avian Influenza in Cattle, updated 6 December 2024 

• FAO Recommendations for the surveillance of influenza A(H5N1) in cattle with broader application to other farmed mammals, published 27 November 2024 

• FAO alert on avian influenza: Risk of upsurge and regional spread through wild birds in Latin America and the Caribbean in English and Spanish 

• FAO recommendations for Global Avian Influenza Viruses with Zoonotic Potential 

• FAO EMPRES Watch entitled ‘A(H5N1) influenza in dairy cattle in the United States of America’ 

• WHO Practical interim guidance to reduce the risk of infection in people exposed to avian influenza viruses 

• CDC Information for Workers Exposed to H5N1 Bird Flu 


Additional studies/surveillance, applying One Health principles are warranted, which could provide information to enhance confidence in the risk assessment. These may include serological studies in high-risk animal populations, in high-risk human populations, and epidemiological investigations.  Anyone who may have been exposed to infected or potentially infected animals or contaminated environments should be advised to promptly seek health care if they feel unwell, and to inform their health care provider of their possible exposure. 

Following prompt testing, early and appropriate clinical management should be initiated, and precautionary measures put in place to assess and prevent potential further spread among humans and animals.  

Clinicians should also be alerted to potential zoonotic infection in patients with an exposure history to birds or animals especially in areas where A(H5N1) viruses are known or suspected to be circulating in animals but also in areas where surveillance in animals may be limited.  

Routine epidemiologic and virologic surveillance for influenza should be conducted ideally yearround using a standard case definition in healthcare facilities according to WHO guidance.{64}  

Timely sharing of information and sequence data from both the human and animal health sectors from all regions should continue to be strongly recommended and is critical for rapid and robust joint risk assessment. The rapid sharing of virus materials with WHO Collaborating Centres of GISRS continues to be essential to conduct a thorough risk assessment and develop or adjust targeted response measures. 

The Tool for Influenza Pandemic Risk Assessment (TIPRA) provides an in-depth  assessment of risk associated with some zoonotic influenza viruses – notably the likelihood of the virus gaining human-to-human transmissibility, and the impact should the virus gain such transmissibility. TIPRA maps relative risk amongst viruses assessed using multiple elements.{65} 

Data pertaining to the risk elements within TIPRA should be generated and shared with WHO.  

Efforts to reduce human exposure to birds, livestock, and other mammals infected with or potentially infected with avian and other animal influenza viruses should be implemented and enhanced to minimize the risk of zoonotic infections. Individuals with activities that involve exposure to infected animals and/or contaminated environments are at higher risk and should take necessary precautions to prevent infection.{66} 

Those who are exposed to potentially infected animals should have access to, be trained in their use under different environmental conditions, and wear personal protective equipment including eye protection.{67} If they develop respiratory symptoms or conjunctivitis, they should be rapidly tested, and precautionary infection control measures should be put in place to prevent potential further spread among humans and to animals. 

For detailed guidance on treatment, refer to relevant global and national guidance.{68} 

Some manufacturers have initiated production of an A(H5) human vaccine that matches current circulating strains. Although a few countries are procuring vaccine to vaccinate occupationally exposed persons, this is not currently being recommended as a global strategy considering the limited number of human infections with A(H5N1) 2.3.4.4b viruses.  

Investigations are ongoing to understand the risk to humans from consuming raw/unpasteurized milk contaminated with A(H5N1) virus. FAO, WHO and WOAH advise consuming pasteurized milk. Due to the potential health risks from many dangerous zoonotic pathogens, raw/unpasteurized milk consumption should be avoided.{69} 

If pasteurized milk is not available, heating raw milk until it boils makes it safer for consumption.{70}  

More information will be available as investigations are actively ongoing in the USA and elsewhere. WHO and GISRS, jointly with FAO, WOAH and OFFLU are working closely together to continuously assess the avian influenza situation. This includes increased surveillance and testing to monitor the evolution and geographic spread of avian influenza viruses, including A(H5N1) viruses, to provide timely and updated joint risk assessments.  


References 

1} Lee D, Bahl J, Torchetti M, Killian M, Ip HS, DeLiberto TJ, et al. Highly Pathogenic Avian Influenza Viruses and Generation of Novel Reassortants, United States, 2014–2015. Emerg Infect Dis. 2016;22(7):1283-1285. doi.org/10.3201/eid2207.160048.  

2} United States Department of Agriculture (USDA). Federal and State Veterinary, Public Health Agencies Share Update on HPAI Detection in Kansas, Texas Dairy Herds. 25 March 2024. www.aphis.usda.gov/news/agencyannouncements/federal-state-veterinary-public-health-agencies-share-update-hpai. 

3} USDA. Highly Pathogenic Avian Influenza (HPAI) Detections in Livestock. www.aphis.usda.gov/livestockpoultry-disease/avian/avian-influenza/hpai-detections/livestock. 

4} Nguyen T-Q, Hutter C, Markin A, Thomas M, Lantz K, Killian ML et al. Emergence and interstate spread of highly pathogenic avian influenza A(H5N1) in dairy cattle. bioRxiv 2024.05.01.591751; doi.org/10.1101/2024.05.01.591751. 

5} USDA. APHIS Confirms D1.1 Genotype in Dairy Cattle in Nevada. www.aphis.usda.gov/news/programupdate/aphis-confirms-d11-genotype-dairy-cattle-nevada-0   

6} USDA. The Occurrence of Another Highly Pathogenic Avian Influenza (HPAI) Spillover from Wild Birds into Dairy Cattle. www.aphis.usda.gov/sites/default/files/dairy-cattle-hpai-tech-brief.pdf   

7} USDA. APHIS Identifies Third HPAI Spillover in Dairy Cattle. www.aphis.usda.gov/news/programupdate/aphis-identifies-third-hpai-spillover-dairy-cattle. 

8} USDA. Highly Pathogenic Avian Influenza (HPAI) Detections in Livestock. www.aphis.usda.gov/livestockpoultry-disease/avian/avian-influenza/hpai-detections/livestock. 

9} Burrough ER, Magstadt DR, Petersen B, Timmermans SJ, Gauger PC, Zhang J, Siepker C, Mainenti M, Li G, Thompson AC, Gorden PJ, Plummer PJ, Main R. Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Domestic Dairy Cattle and Cats, United States, 2024. Emerg Infect Dis. 2024 Jul;30(7):1335-1343. doi: 10.3201/eid3007.240508. 

10} Caserta, L.C., Frye, E.A., Butt, S.L. et al. Spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle. Nature 634, 669–676 (2024). doi.org/10.1038/s41586-024-07849-4. 

11}  Animal and Plant Health Inspection Service, USDA, 24 Sept 2024. Highly Pathogenic Avian Influenza H5N1 Genotype B3.13 in Dairy Cattle: National Epidemiologic Brief. www.aphis.usda.gov/sites/default/files/highlypathogenic-avian-influenza-national-epidemiological-brief-09-24-2024.pdf. 

12} United States Food and Drug Administration. Updates on Highly Pathogenic Avian Influenza (HPAI). Ongoing Work to Ensure Continued Effectiveness of the Federal-State Milk Safety System. 28 June 2024. www.fda.gov/food/alerts-advisories-safety-information/updates-highly-pathogenic-avian-influenzahpai?utm_medium=email&utm_source=govdelivery. 

13} Spackman E, Jones DR, McCoig AM, Colonius TJ, Goraichuk I, Suarez DL. Characterization of highly pathogenic avian influenza virus in retail dairy products in the US. medRxiv 2024.05.21.24307706; doi.org/10.1101/2024.05.21.24307706. 

14} Spackman E, Anderson N, Walker S, Suarez DL, Jones DR, McCoig A et al. Inactivation of Highly Pathogenic Avian Influenza Virus with High-temperature Short Time Continuous Flow Pasteurization and Virus Detection in Bulk Milk Tanks, Journal of Food Protection, Volume 87, Issue 10, 2024, 100349, ISSN 0362-028X, doi.org/10.1016/j.jfp.2024.100349. 

15} Eales O, McCaw JM, Shearer FM. Viral kinetics of H5N1 infections in dairy cattle. bioRxiv 2025.02.01.636082; doi.org/10.1101/2025.02.01.636082. 

16} Animal and Plant Health Inspection Service, USDA, 24 Sept 2024. Highly Pathogenic Avian Influenza H5N1 Genotype B3.13 in Dairy Cattle: National Epidemiologic Brief. www.aphis.usda.gov/sites/default/files/highlypathogenic-avian-influenza-national-epidemiological-brief-09-24-2024.pdf. 

17} Campbell AJ, Brizuela K, Lakdawala SS. mGem: Transmission and exposure risks of dairy cow H5N1 influenza virus. mBio. 2025 Feb 11;16(3):e02944-24. doi.org/10.1128/mbio.02944-24. 

18} USDA. Federal and State Veterinary Agencies Share Update on HPAI Detections in Oregon Backyard Farm, Including First H5N1 Detections in Swine. www.aphis.usda.gov/news/agency-announcements/federal-stateveterinary-agencies-share-update-hpai-detections-oregon. 

19} Kwon T, Trujillo JD, Carossino M, et al. Pigs are highly susceptible to but do not transmit mink-derived highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b. Emerg Microbes Infect. 2024;13(1):2353292. doi.org/10.1080/22221751.2024.2353292. 

20} Graaf A, Piesche R, Sehl-Ewert J, Grund C, Pohlmann A, Beer M, et al. Low Susceptibility of Pigs against Experimental Infection with HPAI Virus H5N1 Clade 2.3.4.4b. Emerg Infect Dis. 2023 Jul;29(7):1492–5. doi.org/10.3201/eid2907.230296. 

21} Elsmo EJ, WĂ¼nschmann A, Beckmen KB, et al. Highly Pathogenic Avian Influenza A(H5N1) Virus Clade 2.3.4.4b Infections in Wild Terrestrial Mammals, United States, 2022. Emerg Infect Dis. 2023;29(12):2451-2460. doi:10.3201/eid2912.230464. 

22} Plaza PI, Gamarra-Toledo V, EuguĂ­ J, Lambertucci SA. Recent Changes in Patterns of Mammal Infection with Highly Pathogenic Avian Influenza A(H5N1) Virus Worldwide. Emerg Infect Dis. 2024;30(3):444-452. doi.org/10.3201/eid3003.231098. 

23} Puryear W, Sawatzki K, Hill N, et al. Highly Pathogenic Avian Influenza A(H5N1) Virus Outbreak in New England Seals, United States. Emerg Infect Dis. 2023;29(4):786-791. 10.3201/eid2904.221538. doi.org/10.3201/eid2904.221538. 

24} Uhart, M.M., Vanstreels, R.E.T., Nelson, M.I. et al. Epidemiological data of an influenza A/H5N1 outbreak in elephant seals in Argentina indicates mammal-to-mammal transmission. Nat Commun 15, 9516 (2024). doi.org/10.1038/s41467-024-53766-5. 

25} Mainenti M, Siepker C, Magstadt DR, et al. Distribution of lesions and detection of influenza A(H5N1) virus, clade 2.3.4.4b, in ante- and postmortem samples from naturally infected domestic cats on U.S. dairy farms. J Vet Diagn Invest. 2025;37(1):27-35. doi:10.1177/10406387241300464. 

26} Washington State Department of Agriculture. Raw pet food identified as source of bird flu infection to house cats. agr.wa.gov/about-wsda/news-and-media-relations/news-releases?article=42075 

27} USDA. Detections of Highly Pathogenic Avian Influenza in Mammals. www.aphis.usda.gov/livestock-poultrydisease/avian/avian-influenza/hpai-detections/mammals. 

28} Naraharisetti R, Weinberg M, Stoddard B, et al. Highly Pathogenic Avian Influenza A(H5N1) Virus Infection of Indoor Domestic Cats Within Dairy Industry Worker Households — Michigan, May 2024. MMWR Morb Mortal Wkly Rep 2025;74:61–65. dx.doi.org/10.15585/mmwr.mm7405a2. 

29} WOAH. 2024. Report from World Animal Health Information System (WAHIS). https://wahis.woah.org/#/inreview/5944?fromPage=event-dashboard-url. 

30} Formerly classified as A(H5) clade 2.3.2.1c. Ort JT, Zolnoski SA, Lam TT, Neher R, Moncla LH. Development of avian influenza A(H5) virus datasets for Nextclade enables rapid and accurate clade assignment. bioRxiv [Preprint]. 2025 Feb 3:2025.01.07.631789. doi: 10.1101/2025.01.07.631789. 

31} WOAH. Report from World Animal Health Information System (WAHIS). wahis.woah.org/#/inreview/6218?reportId=171807&fromPage=event-dashboard-url. 

32} Raut AA, Aasdev A, Kumar N, Pathak A, Mishra A, Sehgal P et al. Highly Pathogenic Avian Influenza A (H5N1) Clade 2.3.2.1a virus infection in domestic cats, India, 2025. bioRxiv 2025.02.23.638954; doi: https://doi.org/10.1101/2025.02.23.638954. biorxiv.org/content/10.1101/2025.02.23.638954v1.full.pdf. 

33} Thanawongnuwech R, Amonsin A, Tantilertcharoen R, et al. Probable tiger-to-tiger transmission of avian influenza H5N1 [published correction appears in Emerg Infect Dis. 2005 Jun;11(6):976]. Emerg Infect Dis. 2005;11(5):699-701. doi.org/10.3201/eid1105.050007. 

34} Keawcharoen J, Oraveerakul K, Kuiken T, et al. Avian influenza H5N1 in tigers and leopards. Emerg Infect Dis. 2004;10(12):2189-2191. doi.org/10.3201/eid1012.040759. 

35} Lee CT, Slavinski S, Schiff C, Merlino M, Daskalakis D, Liu D et al. Outbreak of Influenza A(H7N2) Among Cats in an Animal Shelter With Cat-to-Human Transmission—New York City, 2016, Clinical Infectious Diseases, Volume 65, Issue 11, 1 December 2017, Pages 1927–1929,  doi.org/10.1093/cid/cix668. 

36} Mellis AM, Coyle J, Marshall KE, Frutos AM, Singleton J, Drehoff C et al. Serologic Evidence of Recent Infection with Highly Pathogenic Avian Influenza A(H5) Virus Among Dairy Workers — Michigan and Colorado, June–August 2024. MMWR Morb Mortal Wkly Rep 2024;73:1004–1009. dx.doi.org/10.15585/mmwr.mm7344a3. 

37} Leonard J, Harker EJ, Szablewski CM, Margrey SF, Gingrich II KF, Crossley K et al. Notes from the Field: Seroprevalence of Highly Pathogenic Avian Influenza A(H5) Virus Infections Among Bovine Veterinary Practitioners — United States, September 2024. MMWR Morb Mortal Wkly Rep 2025;74:50–52. www.cdc.gov/mmwr/volumes/74/wr/mm7404a2.htm?s_cid=mm7404a2_w. 

38} Formerly classified as A(H5) clade 2.3.2.1c. Ort JT, Zolnoski SA, Lam TT, Neher R, Moncla LH. Development of avian influenza A(H5) virus datasets for Nextclade enables rapid and accurate clade assignment. bioRxiv [Preprint]. 2025 Feb 3:2025.01.07.631789. doi: 10.1101/2025.01.07.631789. PMID: 39829835; PMCID: PMC11741357. 

39} UK Health Security Agency. Human case of avian flu detected in England, 27 January 2025. www.gov.uk/government/news/human-case-of-avian-flu-detected-in-england. 

40} Yang J, Qureshi M, Kolli R, Peacock TP, Sadeyen J-R, Carter T et al. The Haemagglutinin Gene of Bovine Origin H5N1 Influenza Viruses Currently Retains an Avian Influenza Virus phenotype.  bioRxiv 2024.09.27.615407; doi.org/10.1101/2024.09.27.615407. 

41} US CDC. CDC A(H5N1) Bird Flu Response Update February 26, 2025. www.cdc.gov/bird-flu/spotlights/h5n1response-02262025.html. 

42} US CDC. CDC A(H5N1) Bird Flu Response Update February 26, 2025. www.cdc.gov/bird-flu/spotlights/h5n1response-02262025.html. 

43} US CDC. CDC A(H5N1) Bird Flu Response Update November 18, 2024. www.cdc.gov/bird-flu/spotlights/h5n1response-11152024.html. 

44} US CDC. CDC Reports A(H5N1) Ferret Study Results. 7 June 2024. www.cdc.gov/bird-flu/spotlights/ferretstudy-results.html. 

45} Pulit-Penaloza JA, Brock N, Belser JA, Sun X, Pappas C, Kieran TJ, Thakur PB, Zeng H, Cui D, Frederick J, Fasce R, Tumpey TM, Maines TR. Highly pathogenic avian influenza A(H5N1) virus of clade 2.3.4.4b isolated from a human case in Chile causes fatal disease and transmits between co-housed ferrets. Emerg Microbes Infect. 2024 Mar 17:2332667. doi.org/10.1080/22221751.2024.2332667. 

46} Eisfeld AJ, Biswas A, Guan L, Gu C, Maemura T, Trifkovic S et al. Pathogenicity and transmissibility of bovine H5N1 influenza virus. Nature (2024). doi.org/10.1038/s41586-024-07766-6. 

47} Restori KH, Septer KM, Field CJ, Patel DR, VanInsberghe D, Raghunathan V et al. Risk assessment of a highly pathogenic H5N1 influenza virus from mink. Nat Commun 15, 4112 (2024). doi.org/10.1038/s41467-02448475-y. 

48} Pulit-Penaloza JA, Belser JA, Brock N, et al. Transmission of a human isolate of clade 2.3.4.4b A(H5N1) virus in ferrets. Nature. Published online October 28, 2024. doi.org/10.1038/s41586-024-08246-7. 

49} Gu C, Maemura T, Guan L, Eisfeld AJ, Biswas A, Kiso M et al. A human isolate of bovine H5N1 is transmissible and lethal in animal models. Nature (2024). doi.org/10.1038/s41586-024-08254-7. 

50} Belser JA, Sun X, Pulit-Penaloza JA, Maines TR. Fatal Infection in Ferrets after Ocular Inoculation with Highly Pathogenic Avian Influenza A(H5N1) Virus. Emerg Infect Dis. 2024;30(7):1484-1487. doi.org/10.3201/eid3007.240520. 

51} Daulagala P, Cheng S, Chin A, Luk L, Leung K, Wu JT, et al. Avian Influenza A(H5N1) Neuraminidase Inhibition Antibodies in Healthy Adults after Exposure to Influenza A(H1N1)pdm09. Emerg Infect Dis. 2024;30(1):168171. doi.org/10.3201/eid3001.230756. 

52} Le Sage V, Werner BD, Merrbach GA, Petnuch SE, O'Connell AK, Simmons HC, McCarthy KR, Reed DS, Moncla LH, Bhavsar D, Krammer F, Crossland NA, McElroy AK, Duprex WP, Lakdawala SS. Pre-existing H1N1 immunity reduces severe disease with bovine H5N1 influenza virus. bioRxiv [Preprint]. 2024 Oct 23:2024.10.23.619881. doi: 10.1101/2024.10.23.619881. 

53} Liedes O, Ekström N, Haveri A, Solastie A, Vara S, Rijnink WF et al. Inactivated Zoonotic Influenza A(H5N8) Vaccine Induces Robust Antibody Responses Against Recent Highly Pathogenic Avian Influenza Clade 2.3.4.4b A(H5N1) Viruses [Internet]. medRxiv; 2025. www.medrxiv.org/content/10.1101/2025.02.12.25322044v1. 

54} WHO. (2012). Rapid risk assessment of acute public health events. https://iris.who.int/handle/10665/70810.  

55} US CDC. Past Examples of Probable Limited, Non-Sustained, Person-to-Person Spread of Avian Influenza A Viruses. www.cdc.gov/bird-flu/php/avian-flu-summary/h5n1-humaninfections.html?CDC_AAref_Val=https://www.cdc.gov/flu/avianflu/h5n1-human-infections.htm. 

56} US CDC. Technical Update: Summary Analysis of Genetic Sequences of Highly Pathogenic Avian Influenza A(H5N1) Viruses in Texas, 2 April 2024. www.cdc.gov/bird-flu/spotlights/h5n1-analysis-texas.html.  

57} International Health Regulations (2005). Third edition. Geneva: World Health Organization; 2016. https://iris.who.int/handle/10665/246107. 

58} Case definitions for the four diseases requiring notification to WHO in all circumstances under the IHR (2005). Geneva: World Health Organization; 2009. www.who.int/publications/m/item/case-definitions-for-thefour-diseases-requiring-notification-to-who-in-all-circumstances-under-the-ihr-(2005). 

59} WHO case definition for human infections with avian influenza A(H5) virus requiring notification under IHR (2005). Geneva: World Health Organization; 2024. www.who.int/teams/global-influenza-programme/avianinfluenza/case-definitions. 

60} El Masry I, Delgado AH, Silva GOD, Dhingra M, Lyons NA. 2024. Recommendations for the surveillance of influenza A(H5N1) in cattle – With broader application to other farmed mammals. FAO Animal Production and Health Guidelines, No. 37. Rome, FAO. doi.org/10.4060/cd3422en 

61} OFFLU Avian Influenza Vaccine Matching (AIM) for poultry vaccines: H5Nx executive summary, October 2024. https://www.offlu.org/wp-content/uploads/2024/11/OFFLU-Avian-Influenza-Vaccine-Matching-finalclean.pdf. 

62} WOAH. Avian influenza vaccination: why it should not be a barrier to safe trade, December 2023. https://www.woah.org/app/uploads/2023/12/en-woah-policybrief-avianinfluenzavaccinationandtrade.pdf. 

63} WOAH. Case definition for infection of bovines with influenza a viruses of high pathogenicity in poultry (high pathogenicity avian influenza in cattle), 26 March 2025. https://www.woah.org/en/document/case-definition-hpai-cattle/. 

64} WHO. Implementing the integrated sentinel surveillance of influenza and other respiratory viruses of epidemic and pandemic potential by the Global Influenza Surveillance and Response System: standards and operational guidance. Geneva: World Health Organization; 2024. https://iris.who.int/handle/10665/379678.  

65} WHO. Tool for influenza pandemic risk assessment. www.who.int/teams/global-influenzaprogramme/avian-influenza/tool-for-influenza-pandemic-risk-assessment-(tipra). 

66} US CDC. Highly Pathogenic Avian Influenza A(H5N1) Virus in Animals: Interim Recommendations for Prevention, Monitoring, and Public Health Investigations. www.cdc.gov/bird-flu/prevention/hpai-interimrecommendations.html. 

67} Animal and Plant Health Inspection Service, USDA (12 April 2024). APHIS Recommendations for Highly Pathogenic Avian Influenza (HPAI) H5N1 Virus in Livestock For Workers. www.aphis.usda.gov/sites/default/files/recommendations-workers-hpai-livestock.pdf. 

68} Guidelines for the clinical management of severe illness from influenza virus infections. Geneva: World Health Organization; 2022. https://apps.who.int/iris/handle/10665/352453. 

69} FAO. Preliminary rapid risk assessment of foodborne avian influenza A (H5N1) virus. https://openknowledge.fao.org/server/api/core/bitstreams/ca83524e-b3f9-4abe-b52b-dea213227fcf/content. 

70} Joint FAO/WHO Codex Alimentarius Commission. Codex Alimentarius: Code of hygienic practice for milk and milk products. www.fao.org/fileadmin/user_upload/livestockgov/documents/CXP_057e.pdf. 

Source: World Health Organization, https://www.who.int/publications/m/item/updated-joint-fao-who-woah-public-health-assessment-of-recent-influenza-a(h5)-virus-events-in-animals-and-people_apr2025

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