influenza A virus subtype H5N1

{{Excerpt|Influenza A virus|Birds}}

{{further|Influenza}}

Avian flu viruses, both HPAI and LPAI, can infect humans who are in close, unprotected contact with infected poultry. Incidents of cross-species transmission are rare, with symptoms ranging in severity from no symptoms or mild illness, to severe disease that resulted in death.{{Cite web |last=CDC |date=2024-05-30 |title=Avian Influenza A Virus Infections in Humans |url=https://www.cdc.gov/flu/avianflu/avian-in-humans.htm |access-date=2024-06-11 |website=Centers for Disease Control and Prevention |language=en-us}}{{Cite web |date=11 June 2024 |title=Questions and Answers on Avian Influenza |url=https://ec.europa.eu/commission/presscorner/detail/en/qanda_24_3169 |access-date=2024-06-11 |website=An official website of the European Commission}} As of February 2024 there have been very few instances of human-to-human transmission, and each outbreak has been limited to a few people.{{Cite web |date=2024-02-01 |title=Reported Human Infections with Avian Influenza A Viruses {{!}} Avian Influenza (Flu) |url=https://www.cdc.gov/flu/avianflu/reported-human-infections.htm |access-date=2024-06-11 |website=Centers for Disease Control and Prevention |language=en-us}} All subtypes of avian Influenza A have potential to cross the species barrier, with H5N1 and H7N9 considered the biggest threats.{{Cite web |title=Zoonotic influenza |url=https://www.who.int/news-room/spotlight/influenza-are-we-ready/zoonotic-influenza |access-date=2024-06-16 |website=World Health Organization |language=en}}{{Cite web |title=The next pandemic: H5N1 and H7N9 influenza? |url=https://www.gavi.org/vaccineswork/next-pandemic/h5n1-and-h7n9-influenza |access-date=2024-06-16 |website=Gavi, the Vaccine Alliance |language=en}} In December 2024, researchers showed one mutation could allow the virus to switch its specificity to human receptors,{{Cite journal |last1=Lin |first1=Ting-Hui |last2=Zhu |first2=Xueyong |last3=Wang |first3=Shengyang |last4=Zhang |first4=Ding |last5=McBride |first5=Ryan |last6=Yu |first6=Wenli |last7=Babarinde |first7=Simeon |last8=Paulson |first8=James C. |last9=Wilson |first9=Ian A. |date=2024-12-06 |title=A single mutation in bovine influenza H5N1 hemagglutinin switches specificity to human receptors |journal=Science |volume=386 |issue=6726 |pages=1128–1134 |doi=10.1126/science.adt0180|doi-access=free |pmid=39636969 |bibcode=2024Sci...386.1128L }} increasing the risk of human-to-human transmission.

In order to avoid infection, the general public are advised to avoid contact with sick birds or potentially contaminated material such as carcasses or feces. People working with birds, such as conservationists or poultry workers, are advised to wear appropriate personal protection equipment.{{Cite web |last= |date=2024-06-05 |title=Highly Pathogenic Avian Influenza A(H5N1) Virus in Animals: Interim Recommendations for Prevention, Monitoring, and Public Health Investigations |url=https://www.cdc.gov/bird-flu/prevention/hpai-interim-recommendations.html |access-date=2024-06-13 |website=Centers for Disease Control |language=en-us}}

The avian influenza hemagglutinin prefers to bind to alpha-2,3 sialic acid receptors, while the human influenza hemagglutinin prefers to bind to alpha-2,6 sialic acid receptors.{{cite journal |vauthors= Bertram S, Glowacka I, Steffen I, Kühl A, Pöhlmann S |title=Novel insights into proteolytic cleavage of influenza virus hemagglutinin |journal=Reviews in Medical Virology |volume=20 |issue=5 |display-authors =3| pages=298–310 |date= September 2010 |pmid=20629046 |pmc=7169116 |doi=10.1002/rmv.657 |quote= The influenza virus HA binds to alpha 2–3 linked (avian viruses) or alpha 2–6 linked (human viruses) sialic acids presented by proteins or lipids on the host cell surface.}}{{cite journal |vauthors= Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y | display-authors =3| title=Avian flu: influenza virus receptors in the human airway |journal=Nature |volume=440 |issue= 7083 |pages=435–436 |date= March 2006 |pmid=16554799 |doi= 10.1038/440435a| bibcode= 2006Natur.440..435S |s2cid=9472264 }} This means that when the H5N1 strain infects humans, it will replicate in the lower respiratory tract (where alpha-2,3 sialic acid receptors are more plentiful in humans) and consequently cause viral pneumonia.{{cite journal |vauthors=van Riel D, Munster VJ, de Wit E, Rimmelzwaan GF, Fouchier RA, Osterhaus AD, Kuiken T |year=2006 |title=H5N1 Virus Attachment to Lower Respiratory Tract |journal=Science |volume=312 |issue=5772 |page=399 |doi=10.1126/science.1125548 |pmid=16556800 |s2cid=33294327 |doi-access=}}

{{cite journal |last=Bennett |first=Nicholas John |title= Avian Influenza (Bird Flu): Background, Pathophysiology, Epidemiology |website= Medscape Reference |date=13 October 2021 |url=https://emedicine.medscape.com/article/2500029-overview |access-date=28 April 2024 |quote= Avian influenza is still primarily a respiratory infection but involves more of the lower airways than human influenza typically does. This is likely due to differences in the hemagglutinin protein and the types of sialic acid residues to which the protein binds. Avian viruses tend to prefer sialic acid alpha(2-3) galactose, which, in humans, is found in the terminal bronchi and alveoli. Conversely, human viruses prefer sialic acid alpha(2-6) galactose, which is found on epithelial cells in the upper respiratory tract.}}

{{#section:Human mortality from H5N1|H5N1_WHO}}

On January 6, 2025, the first death from avian influenza in the United States was recorded. This was the first case considered to officially link transmission of avian influenza to backyard flocks. The individual was reported to have been older than 65, had underlying medical problems as well as being in contact with multiple sick and dead birds from their backyard flock.{{Cite web |last=Stobbe |first=Mike |date=2025-01-06 |title=Louisiana person is the first US bird flu death, health officials say |url=https://apnews.com/article/bird-flu-death-louisiana-82e4d00876e62cb2b13bb621826c84f9 |access-date=2025-01-06 |website=AP News |language=en}}

File:InfluenzaNomenclatureDiagram.svg

To unambiguously describe a specific isolate of virus, researchers use the internationally accepted Influenza virus nomenclature,{{Cite journal |date=1980 |title=A revision of the system of nomenclature for influenza viruses: a WHO Memorandum |journal=Bull World Health Organ |volume=58 |issue=4 |pages=585–591 |pmc=2395936 |pmid=6969132 |quote=This Memorandum was drafted by the signatories listed on page 590 on the occasion of a meeting held in Geneva in February 1980.}} which describes, among other things, the species of animal from which the virus was isolated, and the place and year of collection. For example, A/chicken/Nakorn-Patom/Thailand/CU-K2/04(H5N1):

• A stands for the genus of influenza (A, B or C)
• chicken is the animal species the isolate was found in (note: human isolates lack this component term and are thus identified as human isolates by default)
• Nakorn-Patom/Thailand is the place this specific virus was isolated
• CU-K2 is the laboratory reference number that identifies it from other influenza viruses isolated at the same place and year
• 04 represents the year of isolation 2004
• H5 stands for the fifth of several known types of the protein hemagglutinin
• N1 stands for the first of several known types of the protein neuraminidase.

Other examples include: A/duck/Hong Kong/308/78(H5N3), and A/shoveler/Egypt/03(H5N2).{{cite journal|vauthors=Payungporn S, Chutinimitkul S, Chaisingh A, Damrongwantanapokin S, Nuansrichay B, Pinyochon W, Amonsin A, Donis RO, Theamboonlers A, Poovorawan T | title=Discrimination between Highly Pathogenic and Low Pathogenic H5 Avian Influenza A Viruses | journal=Emerging Infectious Diseases | year=2006 | volume=12 | issue=4 | pmid=16715581| pages=700–701 | pmc=3294708 | doi=10.3201/eid1204.051427}}

{{Main|H5N1 genetic structure}}

File:Neuraminidase Ribbon Diagram.jpg", the protein depicted in this ribbon diagram.]]

H5N1 is a subtype of Influenza A virus. Like all subtypes it is an enveloped negative-sense RNA virus, with a segmented genome.{{Cite web |date=2024-05-13 |title=Influenza A Subtypes and the Species Affected {{!}} Seasonal Influenza (Flu) {{!}} CDC |url=https://www.cdc.gov/flu/other/animal-flu.html |access-date=2024-06-17 |website=Centers for Disease Control and Prevention |language=en-us}} Subtypes of IAV are defined by the combination of the antigenic hemagglutinin and neuraminidase proteins in the viral envelope. "H5N1" designates an IAV subtype that has a type 5 hemagglutinin (H) protein and a type-1 neuraminidase (N) protein.{{Cite web |last=CDC |date=2024-02-01 |title=Influenza Type A Viruses |url=https://www.cdc.gov/flu/avianflu/influenza-a-virus-subtypes.htm |access-date=2024-05-03 |website=Centers for Disease Control and Prevention |language=en-us}} Further variations exist within the subtypes and can lead to very significant differences in the virus's ability to infect and cause disease, as well as to the severity of symptoms.{{Cite web |last=CDC |date=2023-03-30 |title=Types of Influenza Viruses |url=https://www.cdc.gov/flu/about/viruses/types.htm |access-date=2024-06-17 |website=Centers for Disease Control and Prevention |language=en-us}}{{Cite web |last=CDC |date=2024-06-11 |title=Avian Influenza Type A Viruses |url=https://www.cdc.gov/bird-flu/about/index.html |access-date=2024-06-17 |website=Avian Influenza (Bird Flu) |language=en-us}}

Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses.{{cite journal |vauthors=Márquez Domínguez L, Márquez Matla K, Reyes Leyva J, Vallejo Ruíz V, Santos López G |title=Antiviral resistance in influenza viruses |journal=Cellular and Molecular Biology (Noisy-le-Grand, France) |volume=69 |issue=13 |pages=16–23 |date=December 2023 |pmid=38158694 |doi=10.14715/cmb/2023.69.13.3 |url=|doi-access=free }} The segmentation of its genome facilitates genetic recombination by segment reassortment in hosts infected with two different strains of influenza viruses at the same time.{{cite journal |vauthors=Kou Z, Lei FM, Yu J, Fan ZJ, Yin ZH, Jia CX, Xiong KJ, Sun YH, Zhang XW, Wu XM, Gao XB, Li TX |year=2005 |title=New Genotype of Avian Influenza H5N1 Viruses Isolated from Tree Sparrows in China |journal=J. Virol. |volume=79 |issue=24 |pages=15460–15466 |doi=10.1128/JVI.79.24.15460-15466.2005 |pmc=1316012 |pmid=16306617}}{{cite journal |author=The World Health Organization Global Influenza Program Surveillance Network. |year=2005 |title=Evolution of H5N1 avian influenza viruses in Asia |journal=Emerging Infectious Diseases |volume=11 |issue=10 |pages=1515–1521 |doi=10.3201/eid1110.050644 |pmc=3366754 |pmid=16318689}}

Figure 1 shows a diagramatic representation of the genetic relatedness of Asian H5N1 hemagglutinin genes from various isolates of the virus

Through a combination of mutation and genetic reassortment the virus can evolve to acquire new characteristics, enabling it to evade host immunity and occasionally to jump from one species of host to another.{{Cite journal |last1=Shao |first1=Wenhan |last2=Li |first2=Xinxin |last3=Goraya |first3=Mohsan Ullah |last4=Wang |first4=Song |last5=Chen |first5=Ji-Long |date=2017-08-07 |title=Evolution of Influenza A Virus by Mutation and Re-Assortment |journal=International Journal of Molecular Sciences |volume=18 |issue=8 |pages=1650 |doi=10.3390/ijms18081650 |issn=1422-0067 |pmc=5578040 |pmid=28783091 |doi-access=free}}{{cite journal |vauthors=Eisfeld AJ, Neumann G, Kawaoka Y |date=January 2015 |title=At the centre: influenza A virus ribonucleoproteins |journal=Nature Reviews. Microbiology |language=En |volume=13 |issue=1 |pages=28–41 |doi=10.1038/nrmicro3367 |pmc=5619696 |pmid=25417656}}

{{Main|H5N1 vaccine}}

Humans – Several "candidate" (unproved) vaccines are available in case an avian virus acquires the ability to infect and transmit among humans; as of July 2024 these include Aflunov, Celldemic and Seqirus/Audenz.{{Cite web |title=Vaccines for pandemic influenza |url=https://www.ema.europa.eu/en/human-regulatory-overview/public-health-threats/pandemic-influenza/vaccines-pandemic-influenza |access-date=30 July 2024 |website=European Medicines Agency |language=en}}{{cite web |date=January 31, 2020 |title=Audenz |url=http://www.fda.gov/vaccines-blood-biologics/audenz |url-status=live |archive-url=https://web.archive.org/web/20200806022227/https://www.fda.gov/vaccines-blood-biologics/audenz |archive-date=August 6, 2020 |access-date=February 5, 2020 |publisher=U.S. Food and Drug Administration (FDA) |id=STN: 125692}} {{PD-notice}} Some governments have prepared strategic stockpiles of vaccines against the H5N1 subtype which is considered the biggest risk among subtypes.{{Cite web |title=Vaccines for pandemic influenza |url=https://www.ema.europa.eu/en/human-regulatory-overview/public-health-threats/pandemic-influenza/vaccines-pandemic-influenza |access-date=2024-06-15 |website=European Medicines Agency}}{{cite web |date=February 4, 2020 |title=FDA Approves Seqirus' Audenz as Vaccine Against Potential Flu Pandemic |url=https://www.biospace.com/article/seqirus-wins-fda-approval-of-vaccine-for-potential-flu-pandemic/ |url-status=live |archive-url=https://web.archive.org/web/20200205184348/https://www.biospace.com/article/seqirus-wins-fda-approval-of-vaccine-for-potential-flu-pandemic/ |archive-date=February 5, 2020 |access-date=February 5, 2020 |website=BioSpace |vauthors=Keown A}} However, because the influenza virus is highly variable, any vaccine needs to be specifically targeted against the particular strain of virus which is causing concern. Existing influenza vaccine technologies can be adapted to a H5N1 strain causing the pandemic; in the event of an outbreak, the candidate vaccine would be rapidly tested for safety as well as efficacy against the zoonotic strain, and then authorised and distributed to vaccine manufacturers.{{Cite web |date=2024-06-03 |title=Making a Candidate Vaccine Virus (CVV) for a HPAI (Bird Flu) Virus |url=https://www.cdc.gov/bird-flu/php/severe-potential/candidate-vaccine-virus.html |access-date=2024-06-22 |work=U.S. Centers for Disease Control and Prevention (CDC) |language=en-us}}

Poultry – it is possible to vaccinate poultry against specific strains of HPAI influenza. Vaccination should be combined with other control measures such as infection monitoring, early detection and biosecurity.{{Cite web |date=2023-10-10 |title=Vaccination of poultry against highly pathogenic avian influenza – Available vaccines and vaccination strategies |url=https://www.efsa.europa.eu/en/news/vaccination-poultry-against-highly-pathogenic-avian-influenza-available-vaccines-and |access-date=2024-05-09 |website=efsa.europa.eu |publisher= |language=en}}{{Cite web |date=2024-06-03 |title=Making a Candidate Vaccine Virus (CVV) for a HPAI (Bird Flu) Virus |url=https://www.cdc.gov/bird-flu/php/severe-potential/candidate-vaccine-virus.html |access-date=2024-06-15 |work=U.S. Centers for Disease Control and Prevention (CDC) |language=en-us}} In many countries, it is routine to vaccinate poultry against H5N1.{{Cite news |date=17 February 2023 |title=Bird flu vaccination policies by country |url=https://www.reuters.com/business/healthcare-pharmaceuticals/bird-flu-vaccination-policies-by-country-2023-02-17/ |access-date=30 July 2024 |work=Reuters}} In China, the world's biggest poultry producer, there has been is a mandatory vaccination requirement since 2017; the vaccine is bivalent or trivalent, targeting the H5 and H7 subtypes of influenza A virus. It is manufactured using recombinant influenza virus.{{Cite journal |last1=Wu |first1=Jie |last2=Ke |first2=Changwen |last3=Lau |first3=Eric H.Y. |last4=Song |first4=Yingchao |last5=Cheng |first5=Kit Ling |last6=Zou |first6=Lirong |last7=Kang |first7=Min |last8=Song |first8=Tie |last9=Peiris |first9=Malik |last10=Yen |first10=Hui-Ling |date=January 2019 |title=Influenza H5/H7 Virus Vaccination in Poultry and Reduction of Zoonotic Infections, Guangdong Province, China, 2017–18 |journal=Emerging Infectious Diseases |volume=25 |issue=1 |pages=116–118 |doi=10.3201/eid2501.181259 |issn=1080-6040 |pmc=6302570 |pmid=30355435}}

{{Main|Treatment of influenza}}

In the event of an outbreak of human H5N1, the main antiviral drugs recommended are neuraminidase inhibitors, such as zanamivir (Relenza) and oseltamivir (Tamiflu). These drugs can reduce the severity of symptoms if taken soon after infection and can also be taken as prophylaxis to decrease the risk of infection.{{cite journal |vauthors=Peteranderl C, Herold S, Schmoldt C |date=August 2016 |title=Human Influenza Virus Infections |journal=Seminars in Respiratory and Critical Care Medicine |volume=37 |issue=4 |pages=487–500 |doi=10.1055/s-0036-1584801 |pmc=7174870 |pmid=27486731}}{{Cite web |date=2017-10-19 |title=Bird flu |url=https://www.nhs.uk/conditions/bird-flu/ |access-date=2024-07-30 |website=National Health Service (NHS) UK |language=en}}{{Cite web |last=CDC |date=2024-07-29 |title=Avian Influenza (Bird Flu) – Emergency Use Instructions (EUI) for Oseltamivir |url=https://www.cdc.gov/bird-flu/hcp/emergency-use-oseltamivir/index.html |access-date=2024-07-30 |website=Centers for Disease Control and Prevention |language=en-us}}{{Cite journal |last=Stiver |first=Grant |date=2003 |title=The treatment of influenza with antiviral drugs |journal=Canadian Medical Association Journal |volume=168 |issue=1 |pages=49–57 |pmc=139319 |pmid=12515786 |via=Pub Med}}

{{Further|Transmission and infection of H5N1|Global spread of H5N1}}

Influenza A/H5N1 was first detected in 1959 after an outbreak of highly pathogenic avian influenza in Scotland, which infected two flocks of chickens.{{Cite journal |last1=Charostad |first1=Javad |last2=Rezaei Zadeh Rukerd |first2=Mohammad |last3=Mahmoudvand |first3=Shahab |last4=Bashash |first4=Davood |last5=Hashemi |first5=Seyed Mohammad Ali |last6=Nakhaie |first6=Mohsen |last7=Zandi |first7=Keivan |date=September 2023 |title=A comprehensive review of highly pathogenic avian influenza (HPAI) H5N1: An imminent threat at doorstep |journal=Travel Medicine and Infectious Disease |volume=55 |pages=102638 |doi=10.1016/j.tmaid.2023.102638 |issn=1477-8939|doi-access=free |pmid=37652253 }}{{Cite web |last=CDC |date=2024-06-10 |title=1880-1959 Highlights in the History of Avian Influenza (Bird Flu) Timeline |url=https://www.cdc.gov/bird-flu/avian-timeline/1880-1959.html |access-date=2024-07-08 |website=Avian Influenza (Bird Flu) |language=en-us}} The next detection, and the earliest infection of humans by H5N1, was an epizootic (an epidemic in nonhumans) of H5N1 influenza in Hong Kong's poultry population in 1997. This outbreak was stopped by the killing of the entire domestic poultry population within the territory. Human infection was confirmed in 18 individuals who had been in close contact with poultry, 6 of whom died.{{Cite web |last=CDC |date=2024-06-10 |title=1960-1999 Highlights in the History of Avian Influenza (Bird Flu) Timeline |url=https://www.cdc.gov/bird-flu/avian-timeline/1960-1999.html |access-date=2024-07-08 |website=Avian Influenza (Bird Flu) |language=en-us}}{{Cite journal |last=Chan |first=Paul K. S. |date=2002-05-01 |title=Outbreak of Avian Influenza A(H5N1) Virus Infection in Hong Kong in 1997 |url=https://doi.org/10.1086/338820 |journal=Clinical Infectious Diseases |volume=34 |issue=Supplement_2 |pages=S58–S64 |doi=10.1086/338820 |pmid=11938498 |issn=1537-6591}}

Since then, avian A/H5N1 bird flu has become widespread in wild birds worldwide, with numerous outbreaks among both domestic and wild birds. An estimated half a billion farmed birds have been slaughtered in efforts to contain the virus.{{Cite web |last=Bourk |first=India |date=26 April 2024 |title='Unprecedented': How bird flu became an animal pandemic |url=https://www.bbc.com/future/article/20240425-how-dangerous-is-bird-flu-spread-to-wildlife-and-humans |access-date=2024-05-08 |website=www.bbc.com |language=en-GB}}{{Cite web |last=CDC |date=2024-07-05 |title=H5N1 Bird Flu: Current Situation |url=https://www.cdc.gov/bird-flu/situation-summary/index.html |access-date=2024-07-08 |website=Avian Influenza (Bird Flu) |language=en-us}}

Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses.{{cite journal |vauthors=Sanjuán R, Nebot MR, Chirico N, Mansky LM, Belshaw R |date=October 2010 |title=Viral mutation rates |journal=Journal of Virology |volume=84 |issue=19 |pages=9733–48 |doi=10.1128/JVI.00694-10 |pmc=2937809 |pmid=20660197}} The segmentation of the influenza A virus genome facilitates genetic recombination by segment reassortment in hosts who become infected with two different strains of influenza viruses at the same time.{{cite journal |author=The World Health Organization Global Influenza Program Surveillance Network. |year=2005 |title=Evolution of H5N1 avian influenza viruses in Asia |journal=Emerging Infectious Diseases |volume=11 |issue=10 |pages=1515–1521 |doi=10.3201/eid1110.050644 |pmc=3366754 |pmid=16318689}} Figure 1 shows a diagramatic representation of the genetic relatedness of Asian H5N1 hemagglutinin genes from various isolates of the virus With reassortment between strains, an avian strain which does not affect humans may acquire characteristics from a different strain which enable it to infect and pass between humans – a zoonotic event.{{Cite web |last=CDC |date=2024-05-15 |title=Transmission of Bird Flu Viruses Between Animals and People |url=https://www.cdc.gov/flu/avianflu/virus-transmission.htm |access-date=2024-06-10 |website=Centers for Disease Control and Prevention |language=en-us}}

As of June 2024, there is concern about two subtypes of avian influenza which are circulating in wild bird populations worldwide, A/H5N1 and A/H7N9. Both of these have potential to devastate poultry stocks, and both have jumped to humans with relatively high case fatality rates.{{Cite web |date=29 July 2020 |title=Global AIV with Zoonotic Potential |url=https://www.fao.org/animal-health/situation-updates/global-aiv-with-zoonotic-potential/en |access-date=2024-06-24 |website=The Food and Agriculture Organization (FAO) of the United Nations |language=en}} A/H5N1 in particular has infected a wide range of mammals and may be adapting to mammalian hosts.{{Cite journal |last1=Plaza |first1=Pablo I. |last2=Gamarra-Toledo |first2=Víctor |last3=Euguí |first3=Juan Rodríguez |last4=Lambertucci |first4=Sergio A. |date=2024 |title=Recent Changes in Patterns of Mammal Infection with Highly Pathogenic Avian Influenza A(H5N1) Virus Worldwide |url=https://wwwnc.cdc.gov/eid/article/30/3/23-1098_article |journal=Emerging Infectious Diseases |language=en-us |volume=30 |issue=3 |pages=444–452 |doi=10.3201/eid3003.231098 |pmc=10902543 |pmid=38407173}}

The Global Influenza Surveillance and Response System (GISRS) is a global network of laboratories that monitor the spread of influenza with the aim to provide the World Health Organization with influenza control information and to inform vaccine development.{{cite book |last1=Lee |first1=Kelley |url=https://books.google.com/books?id=9zCEmpopjG0C&dq=%22WHO%22+%22GISRS+is+a%22&pg=PA163 |title=Historical Dictionary of the World Health Organization |last2=Fang |first2=Jennifer |publisher=Rowman & Littlefield |year=2013 |isbn=9780810878587}} Several millions of specimens are tested by the GISRS network annually through a network of laboratories in 127 countries. GISRS monitors avian, swine, and other potentially zoonotic influenza viruses as well as human viruses.{{Cite web |date=19 September 2022 |title=70 years of GISRS – the Global Influenza Surveillance & Response System |url=https://www.who.int/news-room/feature-stories/detail/seventy-years-of-gisrs---the-global-influenza-surveillance---response-system |access-date=2024-06-13 |website=World Health Organization |language=en}}

[[File:Main international flyways - bird migration-fr.svg|thumb|upright=1.4|The eight major flyways used by shorebirds (waders) on migration{{Cite book |last1=Thompson |first1=Des |title=Shorebirds |last2=Byrkjedal |first2=Ingvar |publisher=Colin Baxter Photography Ltd |year=2001 |isbn=978-1841070759}}

{{Legend|#54A1FF|Pacific}}

{{Legend|#EEDCD0|Mississippi}}

{{Legend|#CDDBC3|West Atlantic}}

{{Legend|#EAD27A|East Atlantic}}

{{Legend|#ff187a|Mediterranean and Black Sea}}

{{Legend|#D7C6D9|West Asia and Africa}}

{{Legend|#FFC6C6|Central Asia and India}}

{{Legend|#53F05A|East Asia and Australasia}}

]]

Birds – Influenza A viruses of various subtypes have a large reservoir in wild waterfowl, which can infect the respiratory and gastrointestinal tract without affecting the health of the host. They can then be carried by the bird over large distances especially during annual migration. Infected birds can shed avian influenza A viruses in their saliva, nasal secretions, and feces; susceptible birds become infected when they have contact with the virus as it is shed by infected birds.{{Cite web |date=2024-05-15 |title=Transmission of Bird Flu Viruses Between Animals and People |url=https://www.cdc.gov/flu/avianflu/virus-transmission.htm |access-date=2024-06-10 |work=U.S. Centers for Disease Control and Prevention (CDC) |language=en-us}} The virus can survive for long periods in water and at low temperatures, and can be spread from one farm to another on farm equipment.{{Cite web |title=Avian Influenza |url=https://www.woah.org/en/disease/avian-influenza/ |access-date=2024-06-10 |website=WOAH – World Organisation for Animal Health |language=en-GB}} Domesticated birds (chickens, turkeys, ducks, etc.) may become infected with avian influenza A viruses through direct contact with infected waterfowl or other infected poultry, or through contact with contaminated feces or surfaces.

Avian influenza outbreaks in domesticated birds are of concern for several reasons. There is potential for low pathogenic avian influenza viruses (LPAI) to evolve into strains which are high pathogenic to poultry (HPAI), and subsequent potential for significant illness and death among poultry during outbreaks. Because of this, international regulations state that any detection of H5 or H7 subtypes (regardless of their pathogenicity) must be notified to the appropriate authority.{{Cite web |date=August 2020 |title=Prevention and Control of H5 and H7 Avian Influenza in the Live Bird Marketing System |url=https://www.aphis.usda.gov/media/document/309/file |access-date=15 June 2024 |website=United States Department of Agriculture}} It is also possible that avian influenza viruses could be transmitted to humans and other animals which have been exposed to infected birds, causing infection with unpredictable but sometimes fatal consequences.

When an HPAI infection is detected in poultry, it is normal to cull infected animals and those nearby in an effort to rapidly contain, control and eradicate the disease. This is done together with movement restrictions, improved hygiene and biosecurity, and enhanced surveillance.

Humans – Avian flu viruses, both HPAI and LPAI, can infect humans who are in close, unprotected contact with infected poultry. Incidents of cross-species transmission are rare, with symptoms ranging in severity from no symptoms or mild illness, to severe disease that resulted in death.{{Cite web |date=2024-05-30 |title=Avian Influenza A Virus Infections in Humans |url=https://www.cdc.gov/flu/avianflu/avian-in-humans.htm |access-date=2024-06-11 |work=U.S. Centers for Disease Control and Prevention (CDC) |language=en-us}} As of February 2024, there have been very few instances of human-to-human transmission, and each outbreak has been limited to a few people.{{Cite web |date=2024-02-01 |title=Reported Human Infections with Avian Influenza A Viruses |url=https://www.cdc.gov/bird-flu/php/avian-flu-summary/reported-human-infections.html?CDC_AAref_Val=https://www.cdc.gov/flu/avianflu/reported-human-infections.htm |access-date=2024-06-11 |website=Centers for Disease Control and Prevention |language=en-us}} All subtypes of avian Influenza A have potential to cross the species barrier, with H5N1 and H7N9 considered the biggest threats.

In order to avoid infection, the general public are advised to avoid contact with sick birds or potentially contaminated material such as carcasses or feces. People working with birds, such as conservationists or poultry workers, are advised to wear appropriate personal protection equipment.{{Cite web |date=2024-06-05 |title=Highly Pathogenic Avian Influenza A(H5N1) Virus in Animals: Interim Recommendations for Prevention, Monitoring, and Public Health Investigations |url=https://www.cdc.gov/bird-flu/prevention/hpai-interim-recommendations.html |access-date=2024-06-13 |work=U.S. Centers for Disease Control and Prevention |language=en-us}}

Cattle – The H5N1 avian flu variant had first been identified in cattle around March 25, 2024. Since then the variant has been identified in 845 individual cases across 16 states as of early December, 2024.{{Cite web |title=HPAI Confirmed Cases in Livestock {{!}} Animal and Plant Health Inspection Service |url=https://www.aphis.usda.gov/livestock-poultry-disease/avian/avian-influenza/hpai-detections/hpai-confirmed-cases-livestock |access-date=2024-12-13 |website=www.aphis.usda.gov |language=en}} Recent tests have shown that the most common clade of the H5N1 variant found in cattle has been Eurasian lineage goose/Guangdong clade 2.3.4.4b which is also commonly found in commercial poultry and wild birds. According to the American Veterinary Medical Association, common clinical signs of H5N1 infection in dairy cattle include symptoms such as a reduced appetite, lower milk production, and abnormal milk appearance (e.g., thickened or discolored). While lactating cows are the most affected, illness is still often only reported in less than 10% of a herd, with a low mortality or culling rate of 2% or less. The United States Department of Agriculture (USDA) has started to require testing of lactating dairy cattle before interstate movement or travel and now mandates reporting of positive test results to the Animal and Plant Health Inspection Service (APHIS).{{Cite web |title=HPAI in Livestock {{!}} Animal and Plant Health Inspection Service |url=https://www.aphis.usda.gov/livestock-poultry-disease/avian/avian-influenza/hpai-livestock |access-date=2024-12-13 |website=www.aphis.usda.gov |language=en}} Internationally, Canada tightened import rules for U.S. dairy cattle as a response.{{Cite web |date=May 3, 2024 |title=Canada toughens import requirements on US breeding cattle over bird flu concerns |url=https://www.reuters.com/business/healthcare-pharmaceuticals/canada-toughens-import-requirements-us-breeding-cattle-over-bird-flu-concerns-2024-05-03/ |access-date=December 13, 2024 |website=Reuters}} The USDA then introduced various forms of financial support for producers to bolster biosecurity and offset losses from production disruptions as a result of the spread. As for the future, the American Association of Bovine Practitioners (AABP) and the AVMA are coordinating with federal and state officials to provide further biosecurity guidance.{{Cite web |title=Avian influenza virus type A (H5N1) in U.S. dairy cattle {{!}} American Veterinary Medical Association |url=https://www.avma.org/resources-tools/animal-health-and-welfare/animal-health/avian-influenza/avian-influenza-virus-type-h5n1-us-dairy-cattle |access-date=2024-12-13 |website=www.avma.org |language=en}}

The commercial milk supply has not been affected, as milk from H5N1-affected animals is almost always diverted or destroyed before entering the food supply, and then as milk goes through pasteurization the virus becomes effectively inactivated. Testing of retail dairy products, including milk, butter, cheese, and ice cream, has found no live, infectious H5N1 virus which further supports the FDA's position that pasteurized milk is safe for consumption. The USDA's Food Safety and Inspection Service (FSIS) has also tested ground beef and muscle samples from culled dairy cows, with the results also confirming the absence of H5N1 in meat products. Any meat from condemned cows is prohibited from entering the human food supply. Beginning in September 2024, the FSIS has expanded testing of dairy cows that are going to be slaughtered to further safeguard the meat supply. For states permitting raw milk sales, the FDA has advised halting such sales if the milk may contain viable H5N1 virus. In December, a California dairy recalled raw milk and cream after multiple samples tested positive for the virus, which underscored the risks of consuming unpasteurized dairy products.{{Cite web |last=Gutierrez |first=Kassandra |date=December 4, 2024 |title=Sales paused for Fresno County dairy farm after raw milk recalled for bird flu |url=https://abc30.com/post/sales-paused-fresno-county-dairy-farm-after-raw-milk-recalled-bird-flu/15623213/ |access-date=December 13, 2024 |website=ABC 30 Action News}} The FDA recommended heat-treating milk intended for calf feeding to eliminate harmful pathogens. Consumers were also advised by the FDA to avoid raw milk, properly handle raw meat, and cook meat to an internal temperature of at least 165 °F, including meat used for pet food.{{Cite journal |last=Program |first=Human Foods |date=2024-12-12 |title=Investigation of Avian Influenza A (H5N1) Virus in Dairy Cattle |url=https://www.fda.gov/food/alerts-advisories-safety-information/investigation-avian-influenza-h5n1-virus-dairy-cattle |journal=FDA |language=en}}

Other animals – a wide range of other animals have been affected by avian flu, generally due to eating birds which had been infected.{{Cite news |date=2023-02-02 |title=Bird flu 'spills over' to otters and foxes in UK |url=https://www.bbc.com/news/science-environment-64474594 |access-date=2024-06-11 |work=BBC News |language=en-GB}} There have been instances where transmission of the disease between mammals, including seals and cattle, may have occurred.{{Cite web |date=2023-03-15 |title=Study of H5N1 avian flu seal deaths reveals multiple lineages |url=https://www.cidrap.umn.edu/avian-influenza-bird-flu/study-h5n1-avian-flu-seal-deaths-reveals-multiple-lineages |access-date=2024-06-13 |website=Center for Infectious Disease Research and Policy |language=en}}{{cite journal |vauthors=Kozlov M |date=June 2024 |title=Huge amounts of bird-flu virus found in raw milk of infected cows |journal=Nature |doi=10.1038/d41586-024-01624-1 |pmid=38840011}}

{{H5N1 cases}}

{{See also|Global spread of H5N1|2020–2025 H5N1 outbreak}}

• A highly pathogenic strain of H5N1 caused flu outbreaks in 1959 in Scotland in chickens.{{Cite journal |last1=Charostad |first1=Javad |last2=Rezaei Zadeh Rukerd |first2=Mohammad |last3=Mahmoudvand |first3=Shahab |last4=Bashash |first4=Davood |last5=Hashemi |first5=Seyed Mohammad Ali |last6=Nakhaie |first6=Mohsen |last7=Zandi |first7=Keivan |date=2023-09-01 |title=A comprehensive review of highly pathogenic avian influenza (HPAI) H5N1: An imminent threat at doorstep |journal=Travel Medicine and Infectious Disease |volume=55 |pages=102638 |doi=10.1016/j.tmaid.2023.102638 |issn=1477-8939|doi-access=free |pmid=37652253 }}
• In 1997, in Hong Kong, 18 humans were infected and 6 died in the first known case of H5N1 infecting humans.{{cite web |author=WHO |date=October 28, 2005 |title=H5N1 avian influenza: timeline |url=https://www.who.int/csr/disease/avian_influenza/Timeline_28_10a.pdf |url-status=dead |archive-url=https://web.archive.org/web/20051129155319/http://www.who.int/csr/disease/avian_influenza/Timeline_28_10a.pdf |archive-date=November 29, 2005}} Subsequently 1.3 million chickens were culled in the territory of Hong Kong. The government also suspended the import of chickens from mainland China.{{cite web |title=香港禽流感大事记 |url=http://www.yangtse.com/epaper/yzwb/2007-06/28/content_9354072.htm |url-status=dead |archive-url=https://web.archive.org/web/20081007173436/http://www.yangtse.com/epaper/yzwb/2007-06/28/content_9354072.htm |archive-date=October 7, 2008 |access-date=June 12, 2008}}

• In 2003 the first cases in humans since 1997 were diagnosed. Three people in one family were infected after visiting Fujian province in mainland China and 2 died.{{cite journal |last1=Peiris |first1=J. S. |last2=Yu |first2=W. C. |last3=Leung |first3=C. W. |last4=Cheung |first4=C. Y. |last5=Ng |first5=W. F. |last6=Nicholls |first6=J. M. |last7=Ng |first7=T. K. |last8=Chan |first8=K. H. |last9=Lai |first9=S. T. |last10=Lim |first10=W. L. |last11=Yuen |first11=K. Y. |last12=Guan |first12=Y. |date=February 21, 2004 |title=Re-emergence of fatal human influenza A subtype H5N1 disease |journal=Lancet |volume=363 |issue=9409 |pages=617–9 |doi=10.1016/S0140-6736(04)15595-5 |pmc=7112424 |pmid=14987888}}{{cite web |date=6 June 2023 |title=Emergence and Evolution of H5N1 Bird Flu {{!}} Avian Influenza (Flu) |url=https://www.cdc.gov/flu/avianflu/communication-resources/bird-flu-origin-infographic.html |url-status=live |archive-url=https://web.archive.org/web/20240307155551/https://www.cdc.gov/flu/avianflu/communication-resources/bird-flu-origin-infographic.html |archive-date=7 March 2024 |access-date=10 March 2024 |website=Centers for Disease Control and Prevention |language=en-us}}
• By midyear of 2003 outbreaks of poultry disease caused by H5N1 occurred in Asia, but were not recognized as such. In December animals in a Thai zoo died after eating infected chicken carcasses. Later that month H5N1 infection was detected in 3 flocks in the Republic of Korea.{{cite web |author=WHO |title=Confirmed Human Cases of Avian Influenza A(H5N1) |url=https://www.who.int/csr/disease/avian_influenza/country/en/ |url-status=dead |archive-url=https://web.archive.org/web/20060423065725/http://www.who.int/csr/disease/avian_influenza/country/en/ |archive-date=April 23, 2006}}

• In January 2004 a major new outbreak of H5N1 surfaced in Vietnam and Thailand's poultry industry, and within weeks spread to ten countries and regions in Asia, including Indonesia, South Korea, Japan and China.{{Citation needed|date=July 2024}}
• Variants have been found in a number of domestic cats, leopards, and tigers in Thailand, with high lethality.{{cite journal |author1=T. Tiensin |author2=P. Chaitaweesub |author3=T. Songserm |author4=A. Chaisingh |author5=W. Hoonsuwan |author6=C. Buranathai |author7=T. Parakamawongsa |author8=S. Premashthira |author9=A. Amonsin |author10=M. Gilbert |author11=M. Nielen |author12=A. Stegeman |date=November 2005 |title=Highly pathogenic avian influenza H5N1, Thailand, 2004 |journal=Emerg Infect Dis |volume=11 |issue=11 |pages=1664–72 |doi=10.3201/eid1111.050608 |pmc=3367332 |pmid=16318716}} "The Thailand Zoo tiger outbreak killed more than 140 tigers, causing health officials to make the decision to cull all the sick tigers in an effort to stop the zoo from becoming a reservoir for H5N1 influenza.{{cite web |author=Henry L Niman |date=October 22, 2004 |title=Thailand: Up to 100 Tigers in Sri Racha Zoo Now Affected by Avian Influenza |url=http://www.promedmail.org/pls/otn/f?p=2400:1202:45722282341019::NO::F2400_P1202_CHECK_DISPLAY,F2400_P1202_PUB_MAIL_ID:X,26990 |url-status=dead |archive-url=https://web.archive.org/web/20090422193601/http://www.promedmail.org/pls/otn/f?p=2400:1202:45722282341019::NO::F2400_P1202_CHECK_DISPLAY,F2400_P1202_PUB_MAIL_ID:X,26990 |archive-date=April 22, 2009 |access-date=February 19, 2008}}

• In January 2005 an outbreak of avian influenza affected thirty three out of sixty four cities and provinces in Vietnam, leading to the forced killing of nearly 1.2 million poultry.{{Citation needed|date=July 2024}}
• In April 2005 there begins an unprecedented die-off of over 6,000 migratory birds at Qinghai Lake in central China over three months. Later in the year H5N1 was detected in Kazakhstan, Mongolia and Russia, Turkey, Romania, Croatia and Kuwait.{{Citation needed|date=April 2024}}
• H5N1 was found to be infecting pigs in Indonesia, but without causing symptoms.[http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/may2705avflu.html CIDRAP] article Indonesian pigs have avian flu virus; bird cases double in China published May 27, 2005

• In the first two months of 2006 H5N1 spread to India, north Africa, and Europe in wild bird populations.{{Citation needed|date=April 2024}}
• February/March 2006 – A dead cat infected with the H5N1 bird flu virus was found in Germany.{{cite news |date=February 28, 2006 |title=German cat gets deadly bird flu |url=http://news.bbc.co.uk/2/hi/europe/4758632.stm |access-date=October 8, 2006 |work=BBC News}}

• Significant outbreaks recorded in Japan, Hungary, Russia, United Kingdom, Pakistan, Turkey, Afghanistan, Myanmar, Bangladesh, Saudi Arabia, Ghana, Malaysia, Germany, Czech Republic, Togo, France and India.{{Citation needed|date=July 2024}}

Many more outbreaks are recorded, in almost every country in the world, affecting both wild birds and poultry, with occasional spillover events infecting humans.

{{Excerpt|2020–2024 H5N1 outbreak|paragraphs=1,2}}In March 2025, India reported eight outbreaks of H5N1 avian influenza in farms and backyard poultry in the southeastern state of Andhra Pradesh. The outbreaks resulted in the death or culling of 602,000 poultry, according to the World Organisation for Animal Health.{{Cite web |title=India reports eight outbreaks of bird flu in Andhra Pradesh |url=https://www.reuters.com/business/healthcare-pharmaceuticals/india-reports-eight-outbreaks-bird-flu-andhra-pradesh-2025-03-28/}}

{{main|List of mammals that can get H5N1}}

In October 2022 an outbreak of H5N1 on a Spanish mink farm showed evidence of being the first recorded case of mammal-to-mammal transmission, with 4 percent of the farm's mink population dying from H5N1-related haemorrhagic pneumonia. This coincided with H5N1 detections in the area among gulls and other seabirds, which are the presumed source of the outbreak.{{cite news |last1=Nuki |first1=Paul |title=How worried should we be about avian flu? |url=https://www.telegraph.co.uk/global-health/science-and-disease/avian-flu-jumping-mammals-experts-fear-humans-will-next/ |access-date=5 February 2023 |publisher=The Telegraph |date=2 February 2023 |archive-url=https://web.archive.org/web/20230202100423/https://www.telegraph.co.uk/global-health/science-and-disease/avian-flu-jumping-mammals-experts-fear-humans-will-next/ |archive-date=2 February 2023}}{{cite news |last1=Pelley |first1=Lauren |title=Bird flu keeps spreading beyond birds. Scientists worry it signals a growing threat to humans, too |url=https://www.cbc.ca/news/health/bird-flu-keeps-spreading-beyond-birds-scientists-worry-it-signals-a-growing-threat-to-humans-too-1.6732287 |access-date=5 February 2023 |publisher=CBC News |date=2 February 2023 |archive-url=https://web.archive.org/web/20230202120256/https://www.cbc.ca/news/health/bird-flu-keeps-spreading-beyond-birds-scientists-worry-it-signals-a-growing-threat-to-humans-too-1.6732287 |archive-date=2 February 2023}}

A mass Caspian seal die-off in December 2022, with 700 infected seals found dead along the Caspian Sea coastline of Russia's Dagestan republic, worried researchers regarding the possibility that wild mammal-to-mammal spread had begun.{{cite news |last1=Merrick |first1=Jane |title=Mass death of seals raises fears bird flu is jumping between mammals, threatening new pandemic |url=https://inews.co.uk/news/politics/mass-death-of-seals-raises-fears-bird-flu-is-jumping-between-mammals-threatening-new-pandemic-2121376 |access-date=15 February 2023 |publisher=The i newspaper |date=1 February 2023 |archive-url=https://web.archive.org/web/20230203230815/https://inews.co.uk/news/politics/mass-death-of-seals-raises-fears-bird-flu-is-jumping-between-mammals-threatening-new-pandemic-2121376 |archive-date=3 February 2023}} A similar mass die-off of 95% of southern elephant seal pups in 2023 also raised concerns of mammal-to-mammal spread, as nursing pups would have had less exposure to birds.{{cite news |last1=Kwan |first1=Jacklin |title=Bird flu wipes out over 95% of southern elephant seal pups in 'catastrophic' mass death |url=https://www.livescience.com/animals/seals/bird-flu-wipes-out-over-95-of-southern-elephant-seal-pups-in-catastrophic-mass-death |access-date=23 January 2024 |work=livescience.com |date=22 January 2024 |language=en}} Between January and October 2023, at least 24,000 South American sea lions died from H5N1 flu, with the outbreak starting on the Pacific coast of Peru, moving down the coast to Chile and then up the Atlantic coast of Argentina.{{Cite journal |last1=Plaza |first1=Pablo I. |last2=Gamarra-Toledo |first2=Víctor |last3=Rodríguez Euguí |first3=Juan |last4=Rosciano |first4=Natalia |last5=Lambertucci |first5=Sergio A. |date=2024-05-01 |title=Pacific and Atlantic sea lion mortality caused by highly pathogenic Avian Influenza A(H5N1) in South America |journal=Travel Medicine and Infectious Disease |volume=59 |pages=102712 |doi=10.1016/j.tmaid.2024.102712 |issn=1477-8939|doi-access=free }}

In April 2024, spread of H5N1 amongst dairy cow herds in nine states of the USA strongly indicated the presence of cow-to-cow transmission possibly occurring while the animals were being milked.{{Cite journal |last=Kozlov |first=Max |date=2024-06-05 |title=Huge amounts of bird-flu virus found in raw milk of infected cows |url=https://www.nature.com/articles/d41586-024-01624-1 |journal=Nature |language=en |doi=10.1038/d41586-024-01624-1 |issn=0028-0836 |pmid=38840011}}{{Cite journal |last=Mallapaty |first=Smriti |date=2024-04-27 |title=Bird flu virus has been spreading in US cows for months, RNA reveals |url=https://www.nature.com/articles/d41586-024-01256-5 |journal=Nature |language=en |doi=10.1038/d41586-024-01256-5|pmid=38678111 }} Although mortality in bovines infected with H5N1 is rare, viable virus can be shed in the milk. Around 50% of cats that lived on the affected dairy farms and were fed unpasteurised milk from symptomatic cows died within a few days from severe systemic influenza infection, raising significant concerns of cross-species mammal-to-mammal transmission.{{cite journal |last1=Burrough |first1=Eric |last2=Magstadt |first2=Drew |last3=Main |first3=Rodger |title=Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Domestic Dairy Cattle and Cats, United States, 2024 |journal=Emerging Infectious Diseases |date=29 April 2024 |volume=30 |issue=7 |pages=1335–1343 |doi=10.3201/eid3007.240508 |pmid=38683888 |pmc=11210653 |url=https://wwwnc.cdc.gov/eid/article/30/7/24-0508_article |access-date=30 April 2024}}

In March 2025 a sheep was found in Yorkshire, UK, infected with H5N1; it was culled. Extensive testing suggests that it was the sole non-avian victim locally, with, for example, its own lambs testing negative.{{cite news |title=First case of bird flu in sheep found on Yorkshire farm |url=https://www.bbc.com/news/articles/c3w1jj0jzl2o |access-date=24 March 2025 |work=www.bbc.com |date=24 March 2025}}

Novel, contagious strains of H5N1 were created by Ron Fouchier of the Erasmus Medical Center in Rotterdam, the Netherlands, who first presented his work to the public at an influenza conference in Malta in September 2011. Three mutations were introduced into the H5N1 virus genome, and the virus was then passed from the noses of infected ferrets to the noses of uninfected ones, which was repeated 10 times.

{{cite magazine |last=Harmon |first=Katherine |date=2011-09-19 |title=What Will the Next Influenza Pandemic Look Like? |url=http://www.scientificamerican.com/article.cfm?id=next-influenza-pandemic |url-status=live |archive-url=https://web.archive.org/web/20120302235202/http://www.scientificamerican.com/article.cfm?id=next-influenza-pandemic |archive-date=2012-03-02 |access-date=2012-01-23 |magazine=Scientific American}} After these 10 passages the H5N1 virus had acquired the ability of transmission between ferrets via aerosols or respiratory droplets.

After Fouchier offered an article describing this work to the leading academic journal Science, the US National Science Advisory Board for Biosecurity (NSABB) recommended against publication of the full details of the study, and the one submitted to Nature by Yoshihiro Kawaoka of the University of Wisconsin describing related work. However, after additional consultations at the World Health Organization and by the NSABB, the NSABB reversed its position and recommended publication of revised versions of the two papers.{{cite news |author=Malakoff |first=David |date=March 30, 2012 |title=Breaking News: NSABB Reverses Position on Flu Papers |url=http://news.sciencemag.org/scienceinsider/2012/03/breaking-news-nsabb-reverses-pos.html |url-status=dead |archive-url=https://web.archive.org/web/20120630154419/http://news.sciencemag.org/scienceinsider/2012/03/breaking-news-nsabb-reverses-pos.html |archive-date=June 30, 2012 |access-date=June 23, 2012 |journal=Science Insider}} However, then the Dutch government declared that this type of manuscripts required Fouchier to apply for an export permit in the light of EU directive 428/2009 on dual use goods.{{efn-lr|The World Intellectual Property Organization (WIPO) lists strategic goods with prohibited goods or goods that require a special permit for import and export without which the carrier faces pecuniary punishment or up to 5 years' imprisonment.}} After much controversy surrounding the publishing of his research, Fouchier complied (under formal protest) with Dutch government demands to obtain a special permit{{cite news |author=Nell Greenfieldboyce |date=April 24, 2012 |title=Bird Flu Scientist has Applied for Permit to Export Research |url=https://www.npr.org/blogs/health/2012/04/24/151292681/bird-flu-scientist-has-applied-for-permit-to-export-research |url-status=live |archive-url=https://web.archive.org/web/20120622123109/http://www.npr.org/blogs/health/2012/04/24/151292681/bird-flu-scientist-has-applied-for-permit-to-export-research |archive-date=June 22, 2012 |access-date=June 23, 2012 |newspaper=NPR}} for submitting his manuscript, and his research appeared in a special issue of the journal Science devoted to H5N1.{{cite news |author=Greenfieldboyce |first=Nell |date=June 21, 2012 |title=Journal Publishes Details on Contagious Bird Flu Created in Lab |url=https://www.npr.org/blogs/health/2012/06/21/155504336/journal-publishes-details-on-controversial-bird-flu-experiments |url-status=live |archive-url=https://web.archive.org/web/20120622181156/http://www.npr.org/blogs/health/2012/06/21/155504336/journal-publishes-details-on-controversial-bird-flu-experiments |archive-date=June 22, 2012 |access-date=June 23, 2012 |publisher=National Public Radio (NPR)}}{{cite journal |date=June 21, 2012 |title=H5N1 |url=https://www.science.org/toc/science/336/6088 |url-status=live |format=Special Issue |journal=Science |archive-url=https://web.archive.org/web/20120625000009/http://www.sciencemag.org/site/special/h5n1/ |archive-date=June 25, 2012 |access-date=June 23, 2012}}{{cite journal |last1=Herfst |first1=S. |last2=Schrauwen |first2=E. J. A. |last3=Linster |first3=M. |last4=Chutinimitkul |first4=S. |last5=De Wit |first5=E. |last6=Munster |first6=V. J. |last7=Sorrell |first7=E. M. |last8=Bestebroer |first8=T. M. |last9=Burke |first9=D. F. |last10=Smith |first10=D. J. |last11=Rimmelzwaan |first11=G. F. |last12=Osterhaus |first12=A. D. M. E. |last13=Fouchier |first13=R. A. M. |year=2012 |title=Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets |journal=Science |volume=336 |issue=6088 |pages=1534–1541 |bibcode=2012Sci...336.1534H |doi=10.1126/science.1213362 |pmc=4810786 |pmid=22723413}} The papers by Fouchier and Kawaoka conclude that it is entirely possible that a natural chain of mutations could lead to an H5N1 virus acquiring the capability of airborne transmission between mammals, and that a H5N1 influenza pandemic would not be impossible.{{cite news |last=Brown |first=Eryn |date=June 21, 2012 |title=Scientists create bird flu that spreads easily among mammals |url=https://www.latimes.com/science/la-xpm-2012-jun-21-la-sci-h5n1-bird-flu-20120622-story.html |url-status=live |archive-url=https://web.archive.org/web/20120623022726/http://www.latimes.com/news/science/la-sci-h5n1-bird-flu-20120622,0,4539172.story |archive-date=June 23, 2012 |access-date=June 23, 2012 |newspaper=Los Angeles Times}}

In May 2013, it was reported that scientists at the Harbin Veterinary Research Institute in Harbin, China, had created H5N1 strains which passed between guinea pigs.{{Cite magazine |last=Keim |first=Brandon |date=2013-05-02 |title=Chinese Scientists Create New Mutant Bird-Flu Virus |url=https://www.wired.com/2013/05/h5n1-h1n1-reassortment/ |access-date=2023-02-07 |magazine=Wired |language=en-US |issn=1059-1028}}

In response to Fouchier and Kawaoka's work, a number of scientists expressed concerns with the risks of creating novel potential pandemic pathogens, culminating in the formation of the Cambridge Working Group, a consensus statement calling for an assessment of the risks and benefits of such research.{{Cite web |title=Scientists Resume Efforts to Create Deadly Flu Virus, with US Government's Blessing |url=https://www.forbes.com/sites/stevensalzberg/2019/03/04/scientists-restart-research-on-creating-deadly-bird-flu-with-nihs-blessing/ |website=Forbes |date=2019-03-04 |access-date=2025-03-24}}{{Cite web |date=18 July 2014 |title=From anthrax to bird flu – the dangers of lax security in disease-control labs |url=https://www.theguardian.com/world/2014/jul/18/anthrax-bird-flu-dangers-lax-security-disease-control-labs |website=TheGuardian.com |access-date=2025-03-24}}

• Antigenic shift
• Avian influenza virus
• Favipiravir
• Fujian flu
• H5N1 clinical trials
• H7N9
• Influenzavirus A
• International Conference on Emerging Infectious Diseases
• National Influenza Centers
• Swine influenza
• Zoonosis

{{notelist-lr}}

{{Reflist}}

{{refbegin}}

• Analysis of the efficacy of an adjuvant-based inactivated pandemic H5N1 influenza virus vaccine. https://link.springer.com/article/10.1007%2Fs00705-019-04147-7 Ainur NurpeisovaEmail authorMarkhabat KassenovNurkuisa RametovKaissar TabynovGourapura J. RenukaradhyaYevgeniy VolginAltynay SagymbayAmanzhol MakbuzAbylay SansyzbayBerik Khairullin

Research Institute for Biological Safety Problems (RIBSP), Zhambyl Region, Republic of Kazakhstan.

{{refend}}

{{Commons|H5N1}}

{{wikinews category|Avian Flu}}

• [http://www.fludb.org/ Influenza Research Database] – Database of influenza genomic sequences and related information.
• WHO World Health Organization
• [https://web.archive.org/web/20060206210909/http://www.who.int/csr/disease/avian_influenza/avianinfluenza_factsheetJan2006/en/index.html WHO's Avian Flu Facts Sheet for 2006]
• [https://web.archive.org/web/20030216050054/http://www.who.int/csr/en/ Epidemic and Pandemic Alert and Response] Guide to WHO's H5N1 pages
• [https://web.archive.org/web/20040201212659/http://www.who.int/csr/disease/avian_influenza/en/ Avian Influenza Resources (updated)] – tracks human cases and deaths
• [https://web.archive.org/web/20050427093205/http://www.who.int/csr/disease/influenza/nationalpandemic/en/index.html National Influenza Pandemic Plans]
• [https://web.archive.org/web/20031226024855/http://www.who.int/csr/disease/influenza/collabcentres/en/ WHO Collaborating Centres and Reference Laboratories] Centers, names, locations, and phone numbers
• [http://www.fao.org/ag/avian.html FAO Avian Influenza portal] {{Webarchive|url=https://web.archive.org/web/20120126123910/http://www.fao.org/ag/avian.html |date=2012-01-26 }} Information resources, animations, videos, photos
• [http://www.fao.org/ag/againfo/programmes/en/empres/maps.html FAO] Food and Agriculture Organisation – Bi-weekly Avian Influenza Maps – tracks animal cases and deaths
• [http://www.fao.org/ag/againfo/subjects/en/health/diseases-cards/avian.html FAO Bird Flu disease card]
• [https://web.archive.org/web/20060923101709/http://www.fao.org/ag/againfo/subjects/en/economics.html FAO Socio-Economic impact of AI] Projects, Information resources
• OIE World Organisation for Animal Health – tracks animal cases and deaths
• [http://www.oie.int/downld/AVIAN%20INFLUENZA/A_AI-Asia.htm Official outbreak reports by country] {{Webarchive|url=https://web.archive.org/web/20121213055030/http://www.oie.int/downld/avian%20influenza/A_AI-Asia.htm |date=2012-12-13 }}
• [https://web.archive.org/web/20060927164029/http://www.oie.int/eng/info/hebdo/a_isum.htm Official outbreak reports by week]
• [http://www.oie.int/downld/AVIAN%20INFLUENZA/graph%20HPAI%2010112005.pdf Chart of outbreaks by country] {{Webarchive|url=https://web.archive.org/web/20120419050634/http://www.oie.int/downld/AVIAN%20INFLUENZA/graph%20HPAI%2010112005.pdf |date=2012-04-19 }}

;European Union

• [http://ec.europa.eu/health-eu/health_problems/avian_influenza/index_en.htm Health-EU Portal] EU response to Avian Influenza.
• {{ECDC|avian_influenza/qa.aspx|Avian influenza – Q & A's}}

;United Kingdom

• [http://news.bbc.co.uk/1/shared/bsp/hi/pdfs/23_02_06_defra_plan.pdf Exotic Animal Disease Generic Contingency Plan] – DEFRA generic contingency plan for controlling and eradicating an outbreak of an exotic animal disease. PDF hosted by BBC.
• [http://news.bbc.co.uk/1/shared/bsp/hi/pdfs/19_10_05_bird_flu.pdf UK Influenza Pandemic Contingency Plan] by the National Health Service – a government entity. PDF hosted by BBC
• [http://www.dh.gov.uk/en/Aboutus/MinistersandDepartmentLeaders/ChiefMedicalOfficer/Features/DH_4102997 UK Department of Health]. {{Webarchive|url=https://web.archive.org/web/20090709154350/http://www.dh.gov.uk/en/AboutUs/MinistersAndDepartmentLeaders/ChiefMedicalOfficer/Features/DH_4102997 |date=2009-07-09 }}

;United States

• [http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/biofacts/avflu_human.html Center for Infectious Disease Research and Policy]. {{Webarchive|url=https://web.archive.org/web/20130617170122/http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/biofacts/avflu_human.html |date=2013-06-17 }} Avian Influenza (Bird Flu): Implications for Human Disease – An overview of Avian Influenza
• [http://www.pandemicflu.gov/ PandemicFlu.Gov] U.S. Government's avian flu information site
• [https://web.archive.org/web/20051025231157/http://www.usaid.gov/our_work/global_health/home/News/news_items/avian_influenza.html USAID] U.S. Agency for International Development – Avian Influenza Response
• [https://www.cdc.gov/flu/avian/gen-info/facts.htm CDC], Centers for Disease Control and Prevention – responsible agency for avian influenza in humans in US – Facts About Avian Influenza (Bird Flu) and Avian Influenza A (H5N1) Virus
• [https://web.archive.org/web/20121025013240/http://www.nwhc.usgs.gov/disease_information/avian_influenza/ USGS – NWHC] National Wildlife Health Center – responsible agency for avian influenza in animals in US
• [https://web.archive.org/web/20090115222738/http://wildlifedisease.nbii.gov/diseasehome.jsp?disease=Avian%20Influenza&pagemode=submit Wildlife Disease Information Node] A part of the National Biological Information Infrastructure and partner of the NWHC, this agency collects and distributes news and information about wildlife diseases such as avian influenza and coordinates collaborative information sharing efforts
• [https://web.archive.org/web/20120302132121/http://www.hhs.gov/pandemicflu/plan/ HHS] U.S. Department of Health & Human Services's Pandemic Influenza Plan

{{Influenza}}

{{Portal bar|Viruses}}

{{Taxonbar|from=Q160122}}

{{DEFAULTSORT:Influenza A Virus Subtype H5n1}}

Category:Bird diseases

H5N1