Updated joint FAO/WHO/WOAH public health #assessment of recent #influenza #H5 virus #events in #animals and #people, based on data as of 1 March '26 (18 May 2026)

Key points 

    -- Based on currently available information, Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) / World Organisation for Animal Health (WOAH) assess the global public health risk posed by Gs/Gd-like high pathogenicity avian influenza (HPAI) A(H5) viruses as low. 

    -- The risk of infection for occupationally or frequently exposed persons (e.g., with backyard poultry) is assessed as low to moderate depending on local epidemiologic conditions and the risk mitigation and hygiene measures in place. 

    -- Transmission among animals continues and sporadic human infections at the human-animal-environment interface continue to be reported. 

    -- While additional human infections associated with exposure to infected animals or contaminated environments are expected, the overall global public health impact of such infections is currently considered minor. 

    -- The assessment may change rapidly as new epidemiological or virological information becomes available. 

    -- This joint FAO/WHO/WOAH risk assessment updates the transmission risk using new global information available since the previous assessment of 28 July 2025. 

    -- Given the potential risk to human health and the wide-ranging impacts on wild birds and mammals, poultry, livestock and other animal populations, timely notification to global authorities and the application of a One Health approach remain essential to monitor and characterize virus circulation, limit transmission within species and between species, reduce spread among animals, and prevent human infections. 

Infections in animals  

    -- To date, HPAI A(H5) viruses have been detected in birds and/or mammals across all continents except Oceania. 

    -- The predominant H5 virus clades currently circulating worldwide derive from clades 2.3.2.1 and 2.3.4.4. 

    -- Between 1 July 2025 and 1 March 2026, an additional 185 A(H5N1) events{i} in animals (including birds and bovines) have been reported to WOAH. 

    -- Of these, 1204 outbreaks occurred in poultry (of any farming system), 6326 outbreaks in wild birds and nine outbreaks occurred in bovines.  

H5 clade 2.3.2.1 viruses 

    -- Between 1 July 2025 and 1 March 2026, A(H5N1) clade 2.3.2.1a viruses were detected in poultry in Bangladesh and India, while A(H5N1) clade 2.3.2.1e viruses were detected in poultry in Cambodia 

H5 clade 2.3.4.4b viruses 

    -- Detections of A(H5) in wild and domestic mammals and wild and domestic birds continued to be reported in many countries worldwide. 

    -- During the period of September-November 2025, Europe experienced an exceptional and early season and a high incidence of HPAI A(H5) activity in wild birds, with more than 3200 detections reported across 28 countries. 

    -- This represents a ten-fold increase compared to the same period in 2024. 

    -- Based on genetic data available so far, the A(H5N1) HPAI viruses identified in Europe all fall into clade 2.3.4.4b, and the majority belong to the genotype EA-2024.DI2.12,{3} 

    -- This surge has disproportionately affected migratory waterfowl and colonial species, with widespread A(H5N1) virus infections confirmed in key migratory hosts (e.g., Eurasian wigeons, Northern pintails, Mute swans, Greylag geese) and severe mass mortality events in Eurasian cranes (Grus grus).{4}  

    -- In Africa, poultry outbreaks of A(H5N1) clade 2.3.4.4b viruses have been reported in Nigeria and South Africa since September 2025. 

    -- Several other countries in sub-Saharan Africa consider HPAI to be present in their territories. 

    -- Detections of A(H5N1) were also made in wild birds in Namibia and South Africa. 

    -- A(H5N1) clade 2.3.4.4b viruses are considered endemic in Egypt’s poultry populations.   

    -- In Asia, clade 2.3.4.4b viruses have been reported in several countries. 

    -- In India, recent poultry outbreaks have involved A(H5N1), while in Kazakhstan, A(H5N1) was detected in wild birds. 

    -- In the Republic of Korea, detections include A(H5N1), A(H5N6), and A(H5N9), while in Japan A(H5N1) and A(H5N5) viruses have been reported. 

    -- In North America, substantial activity of clade 2.3.4.4b A(H5) viruses has continued since the last assessment. 

    -- In the United States of America, more than 3700 A(H5) detections in wild birds and over 400 A(H5) HPAI outbreaks in poultry were reported, while Canada reported nearly 500 A(H5N1) detections in wild birds and over 80 A(H5) HPAI outbreaks in poultry.{5,6} 

    -- A(H5N1) detections in terrestrial and marine mammals have also been reported. 

    -- Notably, A(H5N1) clade 2.3.4.4b was detected for the first time in northern elephant seals in February 2026 in California, involving a virus of the A3 genotype.{7} 

    -- In central America, Mexico reported H5N1 outbreaks in backyard poultry in October 2025 and A(H5N1) detections in wild birds in November. 

    -- A(H5N1) detections of American genotype D1.1 viruses were reported in domestic birds in the Cayman Islands and Guatemala during the second half of 2025. Genotype D1.1 was the most frequently detected A(H5N1) genotype in North America in 2025, affecting wild birds, poultry and multiple mammalian species, including wild and domestic felids and marine mammals. 

    -- A(H5N2) clade 2.3.4.4b viruses belonging to the K.5 genotype were detected in poultry in Mexico.  

    -- In South America, A(H5N1) has continued to spread, with detections in both poultry and wild birds across multiple countries. 

    -- In late 2025, A(H5N1) outbreaks were reported from Argentina, Brazil and Colombia. 

    -- Where sequence data are available, viruses belong to clade 2.3.4.4b.{8} 

    -- In 2026, additional outbreaks occurred across the region. HPAI A(H5) outbreaks occurred in Peru in backyard poultry and in Uruguay in wild birds, although detailed genetic information for these events is not yet available. 

    -- Between 1 February and 1 March 2026, Argentina detected at least 12 A(H5N1) events across domestic and wild birds, while further A(H5N1) outbreaks occurred in backyard and wild birds in Brazil, and in backyard birds in Colombia and Peru.  

    -- Although the full extent of ongoing circulation and establishment in wild bird populations across South America remains uncertain, evidence suggests that A(H5N1) viruses circulating have continued to diversify through reassortment. 

    -- Viruses detected in Brazil in mid- to late 2025 belonged to two distinct genotypes, K.8 and N.1. 

    -- The K.8 genotype is related to “triple reassortant” viruses{9} identified in Argentina in early 2025, combining North American B3.6- and B3.13-like genomes but with multiple internal gene segments derived from South American low pathogenicity avian influenza viruses (LPAIVs).{10,11} 

    -- Its continued presence is consistent with sustained regional spread. 

    -- In contrast, the N.1 genotype clusters with recent North American B3.2 viruses but contains a PB2 segment derived from South American low pathogenicity avian influenza viruses. 

    -- This suggests a separate, more recent introduction of A(H5N1) viruses to South America, followed by reassortment with locally circulating viruses.{12} 

    -- In the Antarctic peninsula and sub-Antarctic islands, A(H5N1) clade 2.3.4.4b viruses have been repeatedly detected in the region, including in sea birds such as skuas and penguins, following their introduction during the 2023–2024 austral summer.{13} 

    -- Detections in wild birds and mammals in the region have continued through 2025–2026. This includes outbreaks in additional sub-Antarctic territories, such as Heard Island, where A(H5N1) was detected in Antarctic fur seals, gentoo penguins and southern elephant seals.{14,15} 

    -- This follows initial detections in southern elephant seals on an earlier voyage in October 2025. 

    -- There was no further evidence of ongoing mass mortality detected on this second voyage in January 2026. 

    -- Further sequencing and phylogenetic analysis are being undertaken. 

    -- The extensive circulation of clade 2.3.4.4b A(H5) viruses in wild and domestic bird populations has resulted in multiple spillover events into wild terrestrial mammals, both carnivorous and omnivorous, wild marine mammals, and domestic cats and dogs.{16} 

    -- Amino acid changes potentially associated with increased virulence, transmission, or adaptation to mammalian hosts have been sporadically identified.{17,18,19}  

    -- Since 2024 and as of 1 March 2026, 1088 dairy herds in 19 states of the United States of America have tested positive for A(H5N1). 

    -- Since the last assessment of 28 July 2025, 14 additional A(H5N1) detections have been reported in the country, with the latest detection confirmed in December 2025 in Wisconsin.{20} 

    -- Analyses of virus sequence data suggest that there have been at least four independent spillovers of A(H5N1) into dairy cattle with the most recent occurring in December 2025.{21} 

    -- In January 2026, Netherlands (Kingdom of the) reported the detection of A(H5N1) HPAI antibodies in the milk of a dairy cow at a dairy farm in Friesland Province, following the investigation of a cat living on that dairy farm that died from an A(H5N1) infection.{22} 

    -- The virus detected in the cat belonged to clade 2.3.4.4b genotype EA-2024.DI2.1—which is distinct from the B3.13 and D1.1 genotypes detected in dairy cattle in the United States of America. No evidence of active infection was found in  the herd, but antibodies were later detected in four additional cows on the same farm, therefore, they do not constitute a case according to the WOAH case definition.  

    -- Mammalian detections of A(H5N5) clade 2.3.4.4b viruses have also been reported in recent years, particularly those belonging to the A6 genotype. 

    -- Since 2023, detections have been reported in terrestrial carnivora (northern racoon, striped skunk, red fox, Eurasian lynx, Eurasian Otter, American mink, Arctic fox and domestic cats) across North America and Europe and in marine mammals. 

    -- 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 July 2025 and as of 1 March 2026, nine additional human cases of A(H5N1) virus infections, and single cases of A(H5), A(H5N2), A(H5N5) virus infections have been detected (based on date of reporting) in Bangladesh, Mexico and the United States of America. 

    -- Eight A(H5N1) cases were detected in Cambodia, and one was detected in Bangladesh. 

    -- All cases reported direct or indirect exposure to domestic birds or contaminated environments. 

    -- No human-to-human transmission was suspected associated with these confirmed cases. 

    -- The viruses from two cases in Bangladesh belong to clade 2.3.2.1a viruses, viruses from six of the cases from Cambodia belong to clade 2.3.2.1e, and viruses from the cases in Mexico and the United States of America belong to clade 2.3.4.4b.  

Virus characteristics  

    -- Routine monitoring and screening of viral sequences from birds have rarely identified markers of mammalian adaptation in A(H5) viruses, and when detected, these have primarily involved the polymerase proteins. 

    -- Such mutations have been observed more frequently in viruses isolated from mammals. 

    -- The PB2 D701N amino acid mutation has been identified in genotype D1.1 viruses detected in poultry (including chickens and turkeys), wild birds, cats, dairy cattle and wild mammals such as red foxes.{23} 

    -- The PB2 E627K mutation has been detected in some B3.13 viruses identified in dairy cattle and in clade 2.3.2.1 and 2.3.4.4 A(H5) viruses detected in poultry, cats and wild birds across multiple regions. 

    -- Some genetic markers in A(H5N1) virus sequences from human cases have been linked to potentially lower lab-based susceptibility to common antivirals like oseltamivir or baloxavir marboxil; the clinical significance of some of these markers remains uncertain.{24} 

    -- Experimental studies with A(H5N1) clade 2.3.4.4b viruses have generally not demonstrated efficient transmission via respiratory droplets.{25,26,27,28,29,30,31} 

    -- Ferret studies conducted by the US CDC using a D1.1 A(H5N1) virus (A/Washington/239/2024) did not show respiratory droplet transmission.{32} 

    -- Overall, currently circulating A(H5N1) viruses would require additional genetic changes to acquire efficient human-to-human transmission via respiratory droplets, consistent with the current low public health risk. 

    -- 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.{33}  

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), continue to evaluate candidate vaccine viruses for pandemic preparedness purposes both biannually 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 2026 following the WHO Consultation on the Composition of Influenza Virus Vaccines for Use in the 2026-2027 Northern Hemisphere Influenza Season.  

 

Assessment of current public health risk posed by influenza A(H5N1) viruses{34} 

    -- Despite continued detections of A(H5) viruses in animals and ongoing human exposure at the human-animal-environment interface, relatively few human infections have been reported to date. 

    -- Since the beginning of 2021, the vast majority of reported human A(H5) infections have been associated with direct or indirect exposure to infected animals such as milking cows on an infected dairy farm or participating in mass culling and disposal events at poultry farms, or contaminated environments, such as live poultry markets, or beaches with sick and dying wild birds and marine mammals.{35,36} 

    -- Illness severity has ranged from mild to fatal. 

    -- To date, no human-to-human transmission has been identified through epidemiologic, virologic and serologic investigations, although investigations for some of cases are ongoing. 

    -- Current evidence indicates that these viruses remain avian-adapted, without established mammalian adaptive mutations or the capacity for sustained human-to-human transmission.  

    -- Based on currently available information, FAO/WHO/WOAH assess the global public health risk posed by currently circulating influenza A(H5) viruses as low and unchanged from the previous risk assessment, while the risk of infection for occupationally or frequently exposed persons remains low to moderate depending on local epidemiological conditions and mitigation measures in place. 

    -- However, as influenza viruses are constantly evolving and spreading in animal populations, zoonotic influenza risk assessments require continuous review and may change rapidly. 

    -- WHO, together with FAO and WOAH, continues to evaluate A(H5) viruses closely and will re-assess 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, and assess the risk 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, using such methods as active case finding and molecular and serologic methods; 

        • reduce the risk among occupationally exposed persons by reducing environmental exposures and providing adequate and appropriate personal protective equipment; and 

        • conduct epidemiological investigations including case finding around suspected and confirmed human cases to determine if there are additional cases or indications of humanto-human transmission.  

    -- Under the International Health Regulations (IHR) (2005),{37} 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.{38} 

    -- WHO has published the case definition for human infections with avian influenza A(H5) virus requiring notification under IHR (2005).{39}  

    -- Avian influenza is a WOAH-listed disease. Based on Chapter 10.440 of the Terrestrial Animal Health Code, three categories of avian influenza should be notified to WOAH by national Veterinary Authorities through WAHIS. It includes infection with HPAI in poultryii, infection of birds other than poultry including wild birds, and infection of domestic and captive wild birds with low pathogenicity avian influenza (LPAI) viruses having proven natural transmission to humans associated with severe consequences. 

    -- Member States and national authorities are also recommended to: 

        • conduct joint epidemiological investigations in and around suspected and confirmed outbreak areas in animals to determine the extent of spillover; 

        • increase surveillance, including joint/collaborative genomic surveillance, and sharing surveillance data applying One Health principles;  

        • timely reporting efforts for the early detection of A(H5) influenza viruses in domestic birds, wild birds and wild mammals{41}; 

        • 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{42,43}; 

        • promptly report high pathogenicity avian influenza (HPAI) events in all animal species, including cattle (according to the WOAH case definition{44}) 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 in a timely manner; 

        • 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; and 

        • 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: 

        • FAO and WOAH Global strategy for the prevention and control of high pathogenicity avian influenza (2024–2033) 

        • Recommendations from the FAO Global Dialogue - Tackling high pathogenicity avian influenza together. Foz do Iguaçu, Brazil – 11 September 2025 

        • FAO recommendations for Global Avian Influenza Viruses with Zoonotic Potential 

        • FAO Recommendations for the surveillance of influenza A(H5N1) in cattle. With broader application to other farmed mammals 

        • WOAH Surveillance of High Pathogenicity Avian Influenza for Smallholder Poultry Systems in Resource-Limited Settings 

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

        • WHO Surveillance for human infections with avian influenza A(H5) viruses: objectives, case definitions, testing and reporting 

        • WHO Considerations for the use of human A(H5) influenza vaccines during non-pandemic period 

        • WHO guidance on the use of licensed human influenza A(H5) vaccines for the interpandemic and emergence periods 

    -- 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(H5) 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 health care facilities according to WHO guidance.{45}  

    -- 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.{46} 

    -- 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. 

    -- 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.{47} 

    -- 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.{48} 

    -- Some manufacturers have initiated production of an A(H5) human vaccine that matches current circulating strains. 

    -- Updated WHO guidance on the use of licensed human influenza A(H5) vaccines for the interpandemic and emergence periods were published in December 2025.{49} 

    -- FAO, WHO and WOAH advise consuming pasteurized milk, instead of raw/unpasteurized milk. Due to the potential health risks from many dangerous zoonotic pathogens, raw/unpasteurized milk consumption should be avoided.{50} 

    -- If pasteurized milk is not available, heating raw milk until it boils makes it safer for consumption.{51}  

___

{i} An event includes all related epidemiologically related outbreaks reported from the time of the immediate notification through to the final report. Separately the total number of outbreaks is also stated. 

{ii} All birds reared or kept in captivity for the production of any commercial animal products or for breeding for this purpose, fighting cocks used for any purpose, and all birds used for restocking supplies of game or for breeding for this purpose, until they are released from captivity. Birds that are kept in a single household, the products of which are used within the same household exclusively, are not considered poultry, provided that they have no direct or indirect contact with poultry or poultry facilities. Birds that are kept in captivity for other reasons, including those that are kept for shows, racing, exhibitions, zoological collections and competitions, and for breeding or selling for these purposes, as well as pet birds, are not considered poultry, provided that they have no direct or indirect contact with poultry or poultry facilities. 

References 

{1} WHO. Genetic and antigenic characteristics of zoonotic influenza A viruses and development of candidate vaccine viruses for pandemic preparedness. February 2026 (https://cdn.who.int/media/docs/default-source/vcm-northern-hemisphere-recommendation-20262027/c.-27-feb-2026_zoonotic_vaccinvirus-update.pdf?sfvrsn=8532151e_5). 

{2} European Food Safety Authority (EFSA), European Union Reference Laboratory (EURL) for Avian Influenza, Ducatez M, Fusaro A, Gonzales J L, Kuiken T, et al. Unprecedented high level of highly pathogenic avian influenza in wild birds in Europe during the 2025 autumn migration. EFSA Journal 2025;23(11):9811, 9 pp (https://doi.org/10.2903/j.efsa.2025.9811). 

{3} EURL. Avian flu data portal. 2026 (eurlaidata.izsvenezie.it/epidemio.php). 

{4} EFSA, European Centre for Disease Prevention and Control (ECDC), EURL for Avian Influenza; Buczkowski H, Ducatez M, Fusaro A, et al. Avian influenza overview September-November 2025. EFSA J. 2025 Dec 18;23(12):e9834 (efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2025.9834).  

{5} United States Department of Agriculture (USDA). 2026. Highly Pathogenic Avian Influenza (HPAI) Detections in Wild Birds (www.aphis.usda.gov/livestock-poultry-disease/avian/avian-influenza/hpai-detections/wild-birds?page=1). 

{6} Canada Food Inspection Agency (CFIA). 2026. National Avian Influenza dashboard (cfiancr.maps.arcgis.com/apps/dashboards/89c779e98cdf492c899df23e1c38fdbc). 

{7} GISAID: EPI_ISL_20420880, EPI_ISL_20420879, EPI_ISL_20420878. 

{8} FAO. FAO alert on avian influenza – risk of upsurge and regional spread through wild birds in Latin America and the Caribbean, 8 April 2026 (https://openknowledge.fao.org/server/api/core/bitstreams/02a3ab2c-0f8d-427f-a71a-3f378a6474bd/content). 

{9} GISAID: EPI_ISL_19752381 and EPI_ISL_19823059–68. 

{10} Vanstreels R, Nelson MI, Artuso MC, Marchione VD, Piccini LE, Benedetti E, et al. Novel Highly Pathogenic Avian Influenza A(H5N1) Virus, Argentina, 2025. Emerg Infect Dis. 2025;31(12):2279-2283 (https://doi.org/10.3201/eid3112.250783).  

{11} Benedetti, E, Artuso, MC, Byrne, AMP, Garibotto, MDB, Avaro, M, Piccini, LE et al.  Emergence and Evolution of Triple Reassortant Highly Pathogenic Avian Influenza A(H5N1) Virus, Argentina, 2025. Preprint (https://doi.org/10.20944/preprints202512.0962.v1). 

{12} Rivetti AV Jr, Reischak D, Carnegie L, Otaka JNP, Domingues CS, Cardoso FG et al. Genomic diversity and reassortment of highly pathogenic avian influenza A/H5N1 virus (clade 2.3.4.4b) in Brazil: Evidence of multiple introductions and intra-epidemic reassortment in 2025. Virology. 2026 Feb;615:110751 (https://doi.org/10.1016/j.virol.2025.110751). 

{13} Steinfurth A, Lynton-Jenkins JG, Cleeland J, Mollett BC, Coombes HA, Moores A et al. Investigating high pathogenicity avian influenza virus incursions to remote islands: detection of H5N1 on Gough Island in the South Atlantic Ocean. Emerg Microbes Infect. 2026 Dec;15(1):2627076 (https://doi.org/10.1080/22221751.2026.2627076). 

{14} WOAH. World Animal Health Information System (WAHIS). Heard and McDonald Islands - Influenza A viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification [FINAL] ( https://wahis.woah.org/#/inreview/7261?fromPage=event-dashboard-url). 

{15} WOAH. Sharing other important animal health information with WOAH (https://www.woah.org/en/what-we-do/animal-health-andwelfare/disease-data-collection/sharing-other-important-animal-health-information-with-woah/). 

{16} OFFLU. Beyond poultry: Rethinking monitoring and control of HPAI H5Nx anticipating spillover risks for mammals. 2026 (https://offlu.org/publications/beyond-poultry-rethinking-monitoring-and-control-of-hpai-h5nx-anticipating-spilloverrisks-for-mammals/). 

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

{18} Uhart MM, Vanstreels RET, Nelson MI, Olivera V, Campagna J, Zavattieri V 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) (https://doi.org/10.1038/s41467024-53766-5). 

{19} OFFLU. Beyond poultry: Rethinking monitoring and control of HPAI H5Nx anticipating spillover risks for mammals. 2026 (https://offlu.org/publications/beyond-poultry-rethinking-monitoring-and-control-of-hpai-h5nx-anticipating-spilloverrisks-for-mammals/). 

{20} USDA. Highly Pathogenic Avian Influenza (HPAI) Detections in Livestock. 2026 (www.aphis.usda.gov/livestock-poultrydisease/avian/avian-influenza/hpai-detections/livestock). 

{21} USDA. Update: Genetic sequencing results for Wisconsin dairy herd detection of highly pathogenic avian influenza. 19 December 2025 (www.aphis.usda.gov/news/agency-announcements/update-genetic-sequencing-results-wisconsin-dairy-herd-detection-highly). 

{22} Rijksoverheid (Government of the Netherlands). Antibodies Against the Avian Influenza Virus Found in Dairy Cow. News, 23 January 2026 (www.rijksoverheid.nl/actueel/nieuws/2026/01/23/antistoffen-vogelgriepvirus-gevonden-bij-melkkoe). 

{23} GISAID. 

{24} US CDC. CDC A(H5N1) Bird Flu Response Update November 18, 2024 (www.cdc.gov/bird-flu/spotlights/h5n1-response-11152024.html). 

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

{26} Pulit-Penaloza JA, Brock N, Belser JA, Sun X, Pappas C, Kieran TJ et al. 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 (https://doi.org/10.1080/22221751.2024.2332667). 

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

{28} 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) (https://doi.org/10.1038/s41467-024-48475-y). 

{29} Pulit-Penaloza JA, Belser JA, Brock N, Kieran TJ, Sun X, Pappas C et al. Transmission of a human isolate of clade 2.3.4.4b A(H5N1) virus in ferrets. Nature. Published online October 28, 2024. (https://doi.org/10.1038/s41586-024-08246-7). 

{30} 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). (https://doi.org/10.1038/s41586-024-08254-7). 

{31} Brock N, Pulit-Penaloza JA, Belser JA, Pappas C, Sun X, Kieran TJ, et al. Avian Influenza A(H5N1) Isolated from Dairy Farm Worker, Michigan, USA. Emerg Infect Dis. 2025;31(6):1253-1256 (https://doi.org/10.3201/eid3106.250386). 

{32} US CDC. Influenza Risk Assessment Tool (IRAT) - Virus Report. Highly pathogenic avian influenza A(H5N1) virus; clade 2.3.4.4b Viruses: A/California/147/2024 and A/Washington/239/2024. Date of Evaluation: March 14, 2025 (www.cdc.gov/pandemicflu/media/pdfs/2025/IRATA-California-Washington.pdf). 

{33} 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):168-171 (https://doi.org/10.3201/eid3001.230756). 

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

{35} Garg S, Reinhart K, Couture A, Kniss K, Davis CT, Kirby MK et al. Highly Pathogenic Avian Influenza A(H5N1) Virus Infections in Humans. N Engl J Med. 2025 Feb 27;392(9):843-854 (https://doi.org/10.1056/nejmoa2414610). 

{36} Pardo-Roa, C., Nelson, M.I., Ariyama, N. et al. Cross-species and mammal-to-mammal transmission of clade 2.3.4.4b highly pathogenic avian influenza A/H5N1 with PB2 adaptations. Nat Commun 16, 2232 (2025) (https://doi.org/10.1038/s41467-025-57338-z). 

{37} WHO. International Health Regulations (2005), as amended through resolutions WHA67.13 (2014), WHA75.12 (2022), and WHA77.17 (2024) (https://apps.who.int/gb/bd/pdf_files/IHR_2014-2022-2024-en.pdf). 

{38} WHO. Case definitions for the four diseases requiring notification to WHO in all circumstances under the IHR (2005). 2009 (www.who.int/publications/m/item/case-definitions-for-the-four-diseases-requiring-notification-to-who-in-all-circumstances-under-theihr-(2005)). 

{39} WHO. WHO case definition for human infections with avian influenza A(H5) virus requiring notification under IHR (2005). 2024 (www.who.int/teams/global-influenza-programme/avian-influenza/case-definitions). 

{40} WOAH. Terrestrial Animal Health Code Chapter 10.4 Infection with high pathogenicity avian influenza viruses (https://www.woah.org/en/what-we-do/standards/codes-and-manuals/, cited on 05/05/2026). 

{41} 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 (https://doi.org/10.4060/cd3422en). 

{42} OFFLU. OFFLU Avian Influenza Vaccine Matching (AIM) for poultry vaccines: H5Nx executive summary, September 2025 (https://offlu.org/publications/offlu-aim-technical-report-september-2025/). 

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

{44} WOAH. Case definition for infection of bovines with influenza a viruses of high pathogenicity in poultry (high pathogenicity avian influenza in cattle), 29 October 2025 (https://www.woah.org/app/uploads/2025/03/2025-10-case-definiton-hpai-cattle-2.pdf). 

{45} 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. 2024 (https://iris.who.int/handle/10665/379678). 

{46} WHO. Tool for influenza pandemic risk assessment. 2026 (www.who.int/teams/global-influenza-programme/avian-influenza/tool-forinfluenza-pandemic-risk-assessment-(tipra)). 

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

{48} WHO. Guidelines for the clinical management of severe illness from influenza virus infections. 2022 (https://apps.who.int/iris/handle/10665/352453). 

{49} WHO. WHO guidance on the use of licensed human influenza A(H5) vaccines for the interpandemic and emergence periods. Weekly Epidemiological Record, 100(51), 643 - 660 (https://iris.who.int/handle/10665/384548). 

{50} FAO. Preliminary rapid risk assessment of foodborne avian influenza A (H5N1) virus. 14 June 2024 (https://openknowledge.fao.org/server/api/core/bitstreams/ca83524e-b3f9-4abe-b52b-dea213227fcf/content). 

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

DISCLAIMER 

The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO) or of the World Organisation for Animal Health (WOAH) concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. All reasonable precautions have been taken by WHO, FAO and WOAH to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall WHO, FAO and WOAH be liable for damages arising from its use. 

© FAO, WHO, WOAH, 2026 

Source: 

Link: https://www.who.int/publications/m/item/updated-joint-fao-who-woah-public-health-assessment-of-recent-high-pathogenicity-avian-influenza-a(h5)-virus-events-in-animals-and-people

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Avian #Influenza #Report, May 10 - 16 '26 (Wk 20) (HK CHP, May 19, 2026): One new #human case with #H9N2 virus

 

{Excerpt}

-- Avian influenza A(H9N2): 

    ° Sichuan Province: 

        - 1) A three-year-old girl with onset on April 25, 2026. 

(...)

Source: 

Link: https://www.chp.gov.hk/files/pdf/2026_avian_influenza_report_vol22_wk20.pdf

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Imported case of avian #influenza #H9N2 virus #infection in a patient with miliary #tuberculosis, #Italy, March 2026

 

Abstract

On 21 March 2026, avian influenza A(H9N2) virus was confirmed in Italy in a patient with miliary tuberculosis. The patient had recently travelled to West Africa. Following the detection of an unsubtypable influenza A virus, rapid molecular confirmation and full genome sequencing were performed. Phylogenetic analysis revealed that the virus belonged to subclade G5.5 and was closely related to African strains. Epidemiological investigations identified no additional cases, suggesting there was no evidence of onward transmission at the time of reporting.

Source: 

Link: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2026.31.15.2600285#abstract_content

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Concurrent #Detection of #Swine-Origin #Influenza #H1N1 Virus in #Pigs and #Farmer, #Switzerland

 

Abstract

We report zoonotic transmission of Eurasian avian-like swine influenza A(H1N1) virus from pigs to a farmer. The pigs and farmer experienced influenza-like illness. Whole-genome sequencing revealed >99.9% isolate sequence identity between hosts. Our findings highlight the risk posed by enzootic swine influenza A virus and the need for genomic and epidemiologic surveillance.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/6/25-1487_article

____

Avian #Influenza #Report - May 3 – 9 '26 (Wk 19) (#HK PRC SAR CHP, May 12 '26): 1 new #human #fatal case of #H5N6 virus in #Chongqing, #China

 

{Excerpt}

(...)

Avian influenza A(H5N6): 

-- Chongqing Municipality: 

- The case involved a 55-year-old woman with symptom onset on April 16, 2026. 

- She was hospitalised on April 23 with severe pneumonia but died on May 3.   

- She had purchased lived poultry, slaughtered and consumed them. 

- Environmental samples taken from a chopping board from her home tested positive for avian influenza A(H5). 

- All close contacts tested negative and developed no symptoms.  

(...)

Source: 

Link: https://www.chp.gov.hk/files/pdf/2026_avian_influenza_report_vol22_wk19.pdf

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Computational Structural Analysis Predicts #Host-Range Promiscuity and #Antiviral #Resistance in North #American #H5N1 Lineages

 

Abstract

Influenza A virus has been circulating in birds in Eurasia for more than 146 years, but human infection has been sporadic. H5N1 (clade 2.3.4.4b) has recently infected hundreds of species of wild and domestic birds and mammals in North America. Infections include 71 people in the United States. There have been 2 human fatalities (United States and Mexico). We have integrated time-series analysis, molecular phylogenetics, and structural biology to understand how H5N1 is circulating in North America and adapting to new hosts. Our time-series analysis reveals that the circulation of H5N1 follows a distinct seasonal pattern, with cases in the United States increasing November to April. We also document an increase in the number of cases reported since 2021. We show that H5N1 spreads in North America as 2 distinct lineages. These viral lineages have achieved a vast host range by efficiently binding the viral surface protein hemagglutinin to both mammalian and avian cell surface receptors. This novel host-range promiscuity is concomitant with the strengthening of the viral polymerase basic 2 protein binding for mammalian and avian immune proteins. Once bound, the immune proteins have diminished ability to fight the virus, thus allowing for efficient replication. Our analyses predict that while most antivirals remain effective, a fatal human isolate showed reduced binding to multiple drugs from different classes. The H5N1 virus is causing an animal pandemic through promiscuity of host range and strengthening ability to evade the innate immune systems of both mammalian and avian cells.

Source: 

Link: https://spj.science.org/doi/10.34133/csbj.0066

____

A single PA-X #mutation in #bovine-origin #H5N1 #influenza virus reduces #pathogenicity in mice

 

Abstract

Dairy cows have emerged as a reservoir for human infection with highly pathogenic avian influenza (HPAI) H5N1. At the bovine-human interface, H5N1 strains may acquire adaptive mutations that influence their zoonotic potential. Sequence analysis identified a K142E substitution (bovine to human) in the PA and PA-X proteins, with the potential to affect both polymerase activity and host shutoff. Here, we used a loss-of-function approach to investigate how the bovine substitution (E142K) in PA/PA-X impacts viral replication, host shutoff activity, and pathogenicity in the human H5N1 background. Viral growth kinetics demonstrated that the virus containing the E142K substitution is attenuated, with reduced replication compared to wild-type (WT) virus. Consistently, PA-X-mediated host shutoff activity was reduced, resulting in increased induction of interferon (IFN) responses relative to WT. In vivo, mice infected with the E142K mutant virus survived, whereas infection with the WT virus was uniformly lethal. Despite comparable viral titers and inflammation score in mouse lungs, cytokine and chemokine profiling revealed distinct immune responses, with reduced CCL2 and increased CCL5 and IFN-γ in mice infected with the E142K mutant virus compared to mice infected with the WT virus. These findings indicate that increased virulence of the human-adapted strain is driven by a PA-X mutation that modulates inflammatory responses, producing distinct immune signatures linked to host survival or viral lethality rather than changes in polymerase activity by PA. Collectively, these results highlight PA-X as a key determinant of pathogenicity of H5N1 and a potential target for the rational design of antiviral strategies.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.05.09.724031v1

____

Variable #transmission efficiency of #mammalian origin #HPAI D1.1 #H5N1 strains in #ferrets

 

Abstract

Highly pathogenic avian influenza H5N1 2.3.4.4b genotype D1.1 lineage continues to predominate in the United States wild bird population and has spilled over into dairy cattle three independent times. To assess the transmission risk of this sublineage, we performed direct-contact transmission experiments for three distinct D1.1 strains in ferrets. Two of these strains were isolated from humans and one from a lethal cat infection. We found that only one human isolate (A/NV/10/2025) was able to transmit efficiently between ferrets. Compared to the other strains, this isolate harbored the mammalian adaptive PB2 D701N mutation, suggesting this mutation may be critical for D1.1 transmission as opposed to the PB2 E627K substitution present in the lethal cat isolate. Based on these data we conclude that the transmission fitness of D1.1 strains is modest but that special attention should be paid to emergence of adaptation at the PB2 701 position.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

National Institute of Allergy and Infectious Diseases, https://ror.org/043z4tv69, 75N93021C00015, 75N93021C00017

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.05.07.722809v1

____

#USA, One #human #infection with influenza #H1N2 #variant virus was reported by #Nebraska (US CDC, May 8 '26)

 

{Excerpt}

(...)

The patient, who is <18 years of age, initially developed respiratory illness during the week ending April 4, 2026 (Week 13). 

The patient sought healthcare during the week ending April 18, 2026 (Week 15) with worsening symptoms, was not hospitalized, and has recovered from their illness. 

An investigation by local and state public health officials did not identify direct or indirect swine contact by the patient. 

Additional investigation identified that a close contact developed mild respiratory illness on the same day as the case, but no cases of human infection with A(H1N2)v virus associated with this case have been identified.

This is the second human infection with a variant influenza virus reported in the 2025-2026 season, and the first reported in 2026; both have been influenza A(H1N2)v viruses.

When an influenza virus that normally circulates in swine (but not people) is detected in a person, it is called a "variant" influenza virus. 

Most human infections with variant influenza viruses occur following exposure to swine, but limited, non-sustained, human-to-human transmission has occurred. 

It is important to note that in most cases, variant influenza viruses have not shown the ability to spread easily and sustainably from person to person.

Notification to WHO of this case was completed according to International Health Regulations (IHR). More information regarding IHR can be found at http://www.who.int/topics/international_health_regulations/en/.

(...)

Source: 

Link: https://www.cdc.gov/fluview/surveillance/2026-week-17.html

____

#Fatal #Human Case of #Influenza #H5N5 in a Backyard Flock Owner — #Washington {State}, November 2025

 

Summary

-- What is already known about this topic?

- Since 2022, highly pathogenic avian influenza (HPAI) A(H5) viruses have circulated among wild birds in the United States. Seventy human cases of influenza A(H5), most with mild illness, have been reported in the United States since 2024; 14 human influenza A(H5N1) cases were previously identified in Washington.

-- What is added by this report?

- In November 2025, Washington reported the first human case of HPAI A(H5N5) infection worldwide. A positive laboratory result was obtained from a lower respiratory sample after multiple negative upper respiratory sample results; the patient experienced respiratory failure and died 28 days after symptom onset. The public health investigation identified approximately 135 exposed persons.

-- What are the implications for public health practice?

- Symptom management and testing of exposed persons are critical to monitoring for human-to-human transmission of novel influenza infection. Environmental and animal investigations, including genomic analysis, can identify epidemiologic risk factors.

Abstract

Clade 2.3.4.4b influenza A(H5N1) viruses have circulated across migratory bird flyways in the United States since 2022, including in Washington, where backyard flock detections have been reported annually. In November 2025, a Washington resident died from acute respiratory failure after receiving a positive influenza A(H5) test result at a hospital laboratory. Washington Public Health Laboratories confirmed influenza A(H5), and genomic sequencing identified influenza A(H5N5) virus (A6 genotype). Polymerase chain reaction testing detected highly pathogenic avian influenza A(H5) virus clade 2.3.4.4b from an apparently healthy backyard flock of ducks and sediment from a watering basin on the patient’s property. Six of eight gene segments from the environmental sample and one duck sample (partial neuraminidase segment) were highly genetically similar to the patient’s virus sequence. Although existing wild bird surveillance had not detected influenza A(H5N5) virus (A6) in the U.S. Pacific Flyway, introduction via wild birds into the environment of the backyard flock was likely the source of the patient’s exposure. The public health investigation identified approximately 135 exposed persons; symptom monitoring and influenza testing detected no additional cases. The overall risk for avian influenza A remains low among the general U.S. population; however, novel avian influenza A virus infection should be considered in persons with symptoms of influenza and potential exposures.

Source: 

Link: https://www.cdc.gov/mmwr/volumes/75/wr/mm7517a2.htm?s_cid=OS_mm7517a2_e&ACSTrackingID=USCDC_921-DM155047&ACSTrackingLabel=Week%20in%20MMWR%3A%20Vol.%2075%2C%20May%207%2C%202026&deliveryName=USCDC_921-DM155047

____

Serologic #Evidence of #Influenza #H5N1 Virus #Infection in a #Veterinary Professional Exposed to an Infected #Cat — Los Angeles County, #California, Dec. '24–Jan. '25

 

Summary

-- What is already known about this topic?

- Transmission of influenza A(H5N1) viruses from domestic cats to humans has not been documented.

-- What is added by this report?

- During November 2024–January 2025, a total of 139 persons exposed to 19 A(H5N1)-infected domestic cats that consumed raw animal products were identified in Los Angeles County, California. Among 25 exposed persons who received serologic testing, one asymptomatic veterinary professional had serologic evidence of A(H5N1) infection after occupational exposure to an A(H5N1)-infected cat.

-- What are the implications for public health practice?

- These findings provide evidence of zoonotic transmission of influenza A(H5N1) virus from domestic cats to humans. Pet owners are advised not to feed raw animal products to cats. Veterinary professionals should be aware of infection risks, use appropriate personal protective equipment, and adhere to recommended infection control practices to reduce the risk for zoonotic transmission of influenza A(H5N1).

Abstract

Since 2021, avian influenza A(H5N1) clade 2.3.4.4b viruses have spread widely among wild birds and domesticated poultry in the United States, with sporadic spillover into mammals. During November 2024–January 2025, 19 domestic cats in Los Angeles County, California, became ill after consumption of commercially purchased raw milk, raw meat, or raw pet food; nine cats tested positive for influenza A(H5N1) virus (clade 2.3.4.4b genotype B3.13). Overall, 139 persons were exposed to the 19 infected cats, and all were monitored for symptoms. Although 30 persons reported influenza-like illness symptoms, none received a positive influenza A(H5) reverse transcription–polymerase chain reaction (RT-PCR) test result. In April 2025, the Los Angeles County Department of Public Health and CDC invited all exposed persons to participate in an influenza A(H5N1) serosurvey to determine whether transmission of influenza A(H5N1) virus occurred, including in those without symptoms. Sera from 25 (18%) of the 139 exposed persons were tested. Among these, antibodies specific to A(H5N1) clade 2.3.4.4.b (antigenically similar to the clade 2.3.4.4.b influenza A[H5N1] virus isolated from the infected cats) were detected in serum from one veterinary professional, who was asymptomatic. This person did not use respiratory or eye protection during the exposure, did not report influenza-like illness after the exposure, and reported no other known risk factors for A(H5N1) infection. These findings represent serologic evidence of possible transmission of influenza A(H5N1) clade 2.3.4.4.b virus from a domestic cat to a human, highlighting concerns about potential cat-to-human transmission of influenza A(H5N1) virus and the importance of infection control practices in veterinary settings.

Source: 

Link: https://www.cdc.gov/mmwr/volumes/75/wr/mm7517a1.htm?s_cid=OS_mm7517a1_e&ACSTrackingID=USCDC_921-DM155047&ACSTrackingLabel=Week%20in%20MMWR%3A%20Vol.%2075%2C%20May%207%2C%202026&deliveryName=USCDC_921-DM155047

____

Computational #design of an ultrapotent #deltacoronavirus miniprotein #inhibitor

 

Significance

Multiple porcine deltacoronavirus (PDCoV) spillovers occurred in Haiti and there are currently no vaccines or therapeutics approved for use in humans. We computationally designed PDCoV miniprotein inhibitors and identified one (MB11) that potently and broadly neutralizes distantly related delta-coronaviruses. MB11 is resistant to multiple biochemical stresses, an ideal property for easy storage and delivery. These data pave the way for developing therapeutics to prepare for possible future PDCoV outbreaks.

Abstract

Multiple spillovers of porcine deltacoronavirus (PDCoV) into humans in Haiti highlight its zoonotic potential and the need for targeted interventions. No approved vaccines or therapeutics are available for use in humans against any DCoVs. Here, we report the de novo design of PDCoV miniprotein inhibitors (aka minibinders, MBs) and show that one of them, MB11, binds with picomolar affinity to the PDCoV receptor-binding domain (RBD). MB11 potently inhibits PDCoV, outcompeting monoclonal antibodies, and cross-reacts with and broadly neutralizes a panel of distantly related DCoVs. We determined a cryoelectron microscopy structure of MB11 bound to the PDCoV RBD which reveals the molecular basis of broad DCoV neutralization through interference with host receptor engagement. Deep mutational scanning of the PDCoV RBD reveals that MB11 has a high barrier to viral escape with only few mutations mediating escape without dampening APN receptor binding. MB11 resists stringent biochemical stresses, including high temperature, low pH, and proteolysis, which may enable delivery to various tissues for viral inhibition. This work delineates a prime candidate for clinical evaluation against PDCoV infection and for pandemic preparedness.

Source: 

Link: https://www.pnas.org/doi/abs/10.1073/pnas.2533456123?af=R

____