#Baloxavir and #molnupiravir protect against severe #influenza #H5N1 #infection in immunosuppressed hamsters

 

Abstract

Highly pathogenic avian influenza A(H5N1) viruses continue to expand their geographic and host range, raising concerns about zoonotic transmission and pandemic preparedness. Immunocompromised individuals often develop severe and prolonged disease, yet evidence guiding antiviral therapy remains limited. Here, we characterized the pathogenesis and assessed direct-contact transmission of an influenza A(H5N1) clade 2.3.4.4b genotype D1.1 virus recently isolated from a human case in British Columbia, Canada, in cyclophosphamide-immunosuppressed hamsters, with normal hamsters included for comparison of infection outcomes and viral shedding kinetics. We also evaluated the antiviral efficacy of oseltamivir (20 mg/kg twice daily for 5 days), baloxavir (50 mg/kg, 2 doses), and molnupiravir (50 or 200 mg/kg twice daily) as monotherapies or in combination (oseltamivir with low-dose molnupiravir) in immunosuppressed hamsters. While normal hamsters showed no mortality and achieved viral clearance, infection in immunosuppressed hamsters caused severe disease characterized by prolonged viral replication, neuroinvasion, and 75% mortality, with no direct-contact transmission detected. In the antiviral efficacy experiment, placebo-treated hamsters exhibited 50% mortality. Baloxavir resulted in 100% survival, shortened viral shedding, reduced viral replication and pulmonary inflammatory responses, and prevented neuroinvasion. High-dose molnupiravir also prevented mortality and achieved viral clearance in lung and brain tissues. Combination therapy resulted in 75% survival and similarly achieved viral clearance in both tissues, with reduced morbidity compared with oseltamivir and low-dose molnupiravir monotherapies. Oseltamivir resulted in 75% survival but failed to prevent severe clinical signs or reduce tissue viral titers, whereas low-dose molnupiravir showed outcomes comparable to placebo. These findings demonstrate the high pathogenicity of a human A(H5N1) isolate in immunosuppressed hamsters, support baloxavir as an effective therapeutic option, and identify molnupiravir-based regimens as promising strategies for severe influenza A(H5N1) infection.

Source: PLoS Pathogens, https://doi.org/10.1371/journal.ppat.1014796

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#Japan - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

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A Wild Whooper Swan in the Hokkaido Region.

A Wild Large-Billed Crow in the Akita Region.

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Source: World Animal Health Organization, https://wahis.woah.org/#/in-review/7940

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Cross #Protection against #Influenza #H5 Clade 2.3.4.4b Viruses after #H1N1pdm09 Infection

 

Abstract

We challenged ferrets previously infected with influenza A(H1N1)pdm09 virus with H5N1 or H5N5 clade 2.3.4.4b viruses to assess cross-protection. Results show that previous A(H1N1)pdm09 virus immunity conferred partial protection against both viruses, with slightly reduced protection against H5N5 compared with H5N1, potentially reflecting the absence of cross-reactive N5 neuraminidase antibodies.

Source: Emerging Infectious Diseases Journal, https://doi.org/10.3201/eid3212.261032

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

 

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A poultry farm (geese (20), ducks (40), chicken (30)) in the Brandenburg Region.

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Source: World Animal Health Organization, https://wahis.woah.org/#/in-review/7972

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#Finland - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

{Click on Image to Enlarge}

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By Martin Mecnarowski (http://www.photomecan.eu/) - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=12814916

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A Wild Eurasian Eagle-Owl in the Länsi- ja Sisä-Suomen aluehallintovirasto Region.

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Source: World Animal Health Organization, https://wahis.woah.org/#/in-review/7970

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Rare recovery of #reassortants between contemporary clade 2.3.4.4b #H5N1 viruses and #human #influenza A viruses in vitro

 

Abstract

Influenza A virus (IAV) pandemics can arise when animal-derived and human-adapted IAVs exchange genome segments; however, whether contemporary clade 2.3.4.4b H5N1 viruses can generate viable reassortants with human IAVs is unclear. Here, we tested the reassortment potential of two clade 2.3.4.4b H5N1 viruses with human-adapted H1N1 and H3N2 IAVs using a biosafe reassortment system. Across multiple coinfection conditions, we genotyped 2,698 plaque-purified viral clones and recovered 20 reassortants (0.74%). Polymerase assays identified human IAV subunits, particularly H1N1 PA or H3N2 PB2, that increased H5N1 polymerase activity. Thus, contemporary clade 2.3.4.4b H5N1 viruses can reassort with human IAVs, but factors beyond polymerase compatibility may limit their recovery.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://doi.org/10.1073/pnas.2631654123

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

 

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{England}

    Poultry premises 67,000 duck meat farm with birds of 35 weeks of age. 

    Samples taken were positive for HPAI H5N1. 

    Birds presented clinical signs prior to testing.

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Source: World Animal Health Organization, https://wahis.woah.org/#/in-review/7964

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Broad #vaccine #protection against globally diverse #influenza #H5Nx viruses

 

Summary

Influenza A/H5Nx viruses continue to diversify and undergo gene reassortment as they infect avian and mammalian hosts worldwide. The severity of human infections varies substantially between different H5 clades and neuraminidase (NA) reassortants, creating unpredictable pandemic risk. Existing H5 vaccines, typically based on a single hemagglutinin (HA) strain, cannot keep pace with this natural variation. To address this problem, we computationally engineer HA, NA, and M2 antigens representing the global antigenic space of circulating H5Nx viruses, prioritizing N1 and N6 subtypes associated with the highest threat in humans. The resulting digitally immune-optimized mRNA vaccine, DVX-panH5Nx, elicits broad HA neutralization and NA inhibition across divergent clades in mice and ferrets. Compared to WHO candidate vaccine viruses (CVVs), DVX-panH5Nx confers superior protection against antigenically distinct H5N1 challenges spanning two decades of viral evolution, demonstrating that computationally designed multivalent antigen vaccines can overcome natural influenza diversification and provide a scalable strategy for pre-pandemic preparedness.

Source: Cell Reports Medicine Journal, https://doi.org/10.1016/j.xcrm.2026.103131

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

 

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A Turkeys for Fatteing Farm in the Mecklenburg-Vorpommern Region.

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Source: World Animal Health Organization, https://wahis.woah.org/#/in-review/7963

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Weekly #US #Influenza #Surveillance #Report: Key Updates for Week 43, ending October 31, 2026 (CDC, Summary): #H1N1pdm09 vastly predominated

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Key Points

    ° Multiple seasonal influenza surveillance indicators continue to increase in many parts of the country.

    ° This early-season influenza activity is currently higher than typically observed at this time of year, but an earlier increase in activity does not necessarily lead to a higher seasonal peak or greater overall severity.

    ° During Week 43 (the week ending October 31, 2026), of the 513 influenza viruses reported by public health laboratories, 502 were influenza A and 11 were influenza B. Of the 388 influenza A viruses subtyped during Week 43, 379 (97.7%) were influenza A(H1N1)pdm09, 7 (1.8%) were A(H3N2) and 2 (0.5%) were influenza A(H5).

    ° Since Week 21 (the week ending May 30, 2026), 83.4% of the influenza A viruses reported have been A(H1N1)pdm09 and among these, the majority have been D.3.1.1 HA subclade.

    ° The influenza A(H1N1) viruses detected this season are still A(H1N1)pdm09 viruses, which emerged in 2009 and have caused seasonal epidemics globally since then. Influenza viruses are constantly changing, often requiring updates to influenza vaccine viruses each season.

    ° Historically, influenza A(H1N1)pdm09 viruses have changed less often than A(H3N2) viruses. Recently circulating influenza A(H1N1)pdm09 viruses (which are in an HA subclade called "D.3.1.1") have divided into distinct groups with different genetic changes in their HA genes. We are seeing more genetic diversity among co-circulating A(H1N1)pdm09 viruses than we have before.

    ° It is too early to know what viruses may predominate or to say whether there might be implications on flu vaccine effectiveness this season.

    ° Two pediatric deaths associated with season influenza virus infection and occurring during the 2026-27 influenza season were reported to CDC this week.

    ° Because case investigation takes time, flu-associated deaths in children may be reported to CDC weeks after they occur; counts are preliminary and may increase. All reported cases meet the influenza-associated pediatric mortality case definition.

    ° The preliminary in-season severity assessment has classified the severity of influenza activity at this point in the season as low across all ages and for children (0-17years), adults (18-64 years) and older adults (65+ years). The severity assessment for the season may change as flu activity is currently increasing.

    ° CDC estimates that there have been at least 1,700,000 illnesses, 25,000 hospitalizations, and 1,400 deaths from flu so far this season.

    ° CDC’s FluSight forecasts predict a likely increase nationally in both flu hospital admissions and the percentage of emergency department visits due to flu for the week ending November 21. The number of new flu hospital admissions is forecast to range from 6,900 to 30,100 admissions, while the national percentage of emergency department visits due to flu is forecast to range from 1.6% to 6.7%.

    ° Annual seasonal influenza (flu) vaccination is recommended. Influenza vaccines are available for persons aged 6 months and older. People who are recommended for influenza vaccination but have not been vaccinated yet this season are encouraged to be vaccinated now.

    ° There are prescription flu antiviral drugs that can treat flu illness; those should be started as early as possible and are especially important for patients at higher risk for influenza complications.1

    ° Two confirmed cases of avian influenza A(H5) virus infection were reported to CDC this week, including one death. To date, human-to-human transmission of avian influenza A(H5) virus (H5 bird flu) has not been identified in the United States.

    ° Influenza viruses are among several viruses contributing to respiratory disease activity. CDC is providing updated, integrated information about COVID-19, flu, and respiratory syncytial virus (RSV) activity on a weekly basis.

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Novel Influenza A Virus Infections

    ° Two confirmed human infections with avian influenza A(H5) virus were reported to CDC this week, including one death. To date, human-to-human transmission of avian influenza A(H5) virus has not been identified in the United States.

    ° Both cases were reported by the Washington State Department of Health and occurred in adults aged ≥18 years who worked at commercial dairy cattle farms where highly pathogenic avian influenza (HPAI) A(H5N1) virus has been detected in cows.

    ° One individual developed respiratory symptoms during the week ending October 24, 2026 (Week 42). The patient presented to an emergency department the following week, was hospitalized, and has died. A respiratory specimen collected at the healthcare facility tested positive for influenza A and was presumptive positive for influenza A(H5) at the University of Washington. The specimen was sent to the Washington State Public Health Laboratory where influenza A(H5) was confirmed using the CDC influenza A(H5) assay. Additional testing conducted by the University of Washington determined this was an avian influenza A(H5N1) virus.

    ° The second individual developed conjunctivitis and sought healthcare. Specimens were collected from the individual and tested at the state public health laboratory using the CDC influenza A(H5) assay during the week ending October 31, 2026 (Week 43). Influenza A(H5) virus was confirmed by the state public health laboratory. The specimen has been shipped to CDC for additional testing.

    ° There has been a total of three influenza A(H5) cases in dairy workers in Washington.

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Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/fluview/surveillance/2026-week-43.html

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

 

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{Yucatán State}

    As part of efforts to promote reporting, a suspicion of avian influenza at a commercial poultry production facility in the state of Yucatán was reported. 

    Laboratory results confirmed the presence of the high pathogenicity influenza A H5N1 virus through sequencing. 

    The production facility was placed under quarantine to carry out anti-epidemic measures and epidemiological surveillance of poultry and wild birds in the area.

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Source: World Animal Health Organization, https://wahis.woah.org/#/in-review/7960

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#USA, #H5 Avian #Influenza: Current #Situation (CDC, Nov. 5 '26): 2 new Human Cases, 1 fatal

 

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National situation summary since 2024

    ° Person-to-person spread: None

        § There is no known person-to-person spread at this time.

    ° Current public health risk: Low

        § The current public health risk is Low.

    ° Cases in the U.S.:

        § 74 cases {+2, Washington State}

    ° Deaths in U.S.: 

        § 3 deaths {+1, Washington State}

    Footnote: 

        Of the 74 total reported human cases of A(H5) bird flu reported in the United States since February 2024, seven were detected through national flu surveillance and 67 were detected through human monitoring.

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Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/situation-summary/?CDC_AAref_Val=https://www.cdc.gov/flu/avianflu/avian-flu-summary.htm

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#Serologic Evidence of Avian #Influenza Virus Exposure in #Livestock, #Egypt, 2024–2026

 

Abstract

Spillover of influenza A(H5N1) virus to cattle in the United States sparked global concern. We investigated whether endemic avian influenza viruses are potentially spilling over into domestic livestock in Egypt. We detected influenza H9N2 antibodies in 2.5% and H5N1 antibodies in 2.9%–4.5% of tested animals. Additional surveillance will elucidate host infection dynamics.

Source: Emerging Infectious Diseases Journal, https://doi.org/10.3201/eid3212.260869

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

 

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A Poultry Farm in the Rogaland Region.

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Source: World Animal Health Organization, https://wahis.woah.org/#/in-review/7956

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

 

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{Scotland}

    Poultry premises with 64,000 free-range laying hens (102 weeks old). 

    Samples taken were positive for HPAI H5N1. 

    Birds presented clinical signs prior to testing.

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Source: World Animal Health Organization, https://wahis.woah.org/#/in-review/7952

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

 

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A Poultry Farm in the Niedersachsen Region.

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Source: World Animal Health Organization (WOAH), https://wahis.woah.org/#/in-review/7950

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#Austria - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

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A wild Mute Swan in the Niederösterreich Region.

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Source: World Animal Health Organization (WOAH), https://wahis.woah.org/#/in-review/7951

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Avian #Influenza #Report: October 25 - 31 '26 (Wk 44) (HK CHP, November 3, 2026): 2 New Human Infections with #H5N1 virus in #USA & 2 cases with #H9N2 virus in #China

 

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Avian influenza A(H5N1)

    ° Washington State:

        § The Washington State Department of Health reported the second and  third human infection with avian influenza A(H5N1) from Yakima County.

        § The second case, who had underlying health conditions, was  hospitalised with severe illness and passed away on November 1, 2026.

        § The third case has not experienced severe illness or been hospitalised.

        § Both cases had exposure to dairy cattle infected with avian influenza  A(H5N1) virus at local dairy farms.

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Avian influenza A(H9N2):

    ° Hubei Province:

        § A two-year-old boy with onset on September 22, 2026.

    ° Jiangxi Province:

        § A 77-year-old woman with onset on September 16, 2026.

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Source: Centre for Health Protection, Hong Kong PRC SAR, https://www.chp.gov.hk/files/pdf/2026_avian_influenza_report_vol22_wk44.pdf

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#USA, #Washington State: Avian #Influenza in #Humans - Current #Situation and Data (DoH, Nov. 2 '26): 2 new cases of which 1 fatal [18 cases in total since 2024]

 

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Human Bird Flu Cases in Washington State Residents

[Case - Classification - Known Exposure - 2024 - 2025 - 2026 - Total]

    ° Confirmed - Commercial Poultry - 11* - 0- 0 - 11

    ° Confirmed - Backyard Flock - 0 - 1 - 0 - 1

    ° Confirmed - Dairy - 0 - 0 - 3 - 3 {+2}

    ° Probable - Commercial Poultry - 3 - 0 - 0 - 3

        § Total - 14 - 1 - 3 - 18

    {*} Washington residency not confirmed for one case in 2024.

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Source: US State of Washington Department of Health, https://doh.wa.gov/you-and-your-family/illness-and-disease-z/bird-flu/current-situation-and-data

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#Germany - #Influenza A #H5N5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

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A wild Laridae species bird in the Schleswig-Holstein Region.

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Source: WOAH, https://wahis.woah.org/#/in-review/7945

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