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Influenza A virus subtype H5N1

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Influenza A virus
Colorized transmission electron micrograph of Avian influenza A H5N1 viruses (seen in gold) grown in MDCK cells (seen in green)
Virus classificationEdit this classification
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Negarnaviricota
Class: Insthoviricetes
Order: Articulavirales
Family: Orthomyxoviridae
Genus: Alphainfluenzavirus
Species:
Influenza A virus
Notable strains

Influenza A virus subtype H5N1(A/H5N1) is a subtype of theinfluenza A virus,which causesinfluenza(flu), predominantly in birds. It isenzootic(maintained in the population) in many bird populations, and alsopanzootic(affecting animals of many species over a wide area).[1]A/H5N1 virus can also infect mammals (including humans) that have been exposed to infected birds; in these cases, symptoms are frequently severe or fatal.[2]

A/H5N1 virus is shed in the saliva, mucous, and feces of infected birds; other infected animals may shed bird flu viruses in respiratory secretions and other body fluids (such as milk).[3]The virus can spread rapidly through poultry flocks and among wild birds.[3]An estimated half a billion farmed birds have been slaughtered in efforts to contain the virus.[2]

Symptoms of A/H5N1 influenza vary according to both the strain of virus underlying the infection and on the species of bird or mammal affected.[4][5]Classification as either Low Pathogenic Avian Influenza (LPAI) or High Pathogenic Avian Influenza (HPAI) is based on the severity of symptoms in domesticchickensand does not predict the severity of symptoms in other species.[6]Chickens infected with LPAI A/H5N1 virus display mild symptoms or areasymptomatic,whereas HPAI A/H5N1 causes serious breathing difficulties, a significant drop in egg production, and sudden death.[7]

In mammals, including humans, A/H5N1 influenza (whether LPAI or HPAI) is rare. Symptoms of infection vary from mild to severe, including fever, diarrhoea, and cough.[5]Human infections with A/H5N1 virus have been reported in 23 countries since 1997, resulting in severe pneumonia and death in about 50% of cases.[8]As of May 2024, 889 human cases had been identified worldwide, with 463 fatalities, giving acase fatality rateof around 50%;[9]however, it is likely that this may be an overestimate given that mild infections can go undetected and under-reported.[10]

A/H5N1 influenza virus was first identified in farmed birds in southern China in 1996.[11]Between 1996 and 2018, A/H5N1 coexisted in bird populations with other subtypes of the virus, but since then, the highly pathogenic subtype HPAI A(H5N1) has become the dominant strain in bird populations worldwide.[12]Some strains of A/H5N1 which are highly pathogenic to chickens have adapted to cause mild symptoms in ducks and geese,[13][6]and are able to spread rapidly through bird migration.[14]Mammal species that have been recorded with H5N1 infection include cows, seals, goats, and skunks.[15]

Due to the high lethality andvirulenceof HPAI A(H5N1), its worldwide presence, its increasingly diversehostreservoir,and its significant ongoing mutations, the H5N1 virus is regarded as the world's largestpandemicthreat.[16]Domestic poultry may potentially be protected from specific strains of the virus by vaccination.[17]In the event of a serious outbreak of H5N1 flu among humans, health agencies have prepared "candidate" vaccines that may be used to prevent infection and control the outbreak; however, it could take several months to ramp up mass production.[3][18][19]

Signs and symptoms[edit]

This section is an excerpt fromInfluenza A virus § Birds.[edit]
Some species of wildaquatic birdsact as naturalasymptomatic carriersof a large variety of influenza A viruses.[20]Symptoms of avian influenza vary according to both the strain of virus underlying the infection, and on the species of bird affected. Symptoms of influenza in wild birds may include swollen head, watery eyes, unresponsiveness, lack of coordination, respiratory distress such as sneezing or gurgling.[21]

Humans[edit]

Further information: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.[22][23]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.[24]All subtypes of avian Influenza A have potential to cross the species barrier, withH5N1andH7N9considered the biggest threats.[25][26]

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.[27]

The avian influenzahemagglutininprefers to bind to Alpha -2,3sialic acidreceptors, while the human influenza hemagglutinin prefers to bind to Alpha -2,6 sialic acid receptors.[28][29]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 causeviral pneumonia.[30][31]

Between 2003 and May 2024, theWorld Health Organizationhas recorded 892 cases of confirmed H5N1 influenza, leading to 463 deaths.[32]The true fatality rate may be lower because some cases with mild symptoms may not have been identified as H5N1.[33]

Virology[edit]

Influenza virus nomenclature[edit]

Diagram of influenza nomenclature

To unambiguously describe a specificisolateof virus, researchers use the internationally acceptedInfluenza virus nomenclature,[34]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):

  • Astands for the genus of influenza (A,BorC).
  • chickenis 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/Thailandis the place this specific virus was isolated
  • CU-K2is the laboratory reference number that identifies it from other influenza viruses isolated at the same place and year
  • 04represents the year of isolation 2004
  • H5stands for the fifth of several known types of the proteinhemagglutinin.
  • N1stands for the first of several known types of the proteinneuraminidase.

Other examples include: A/duck/Hong Kong/308/78(H5N3), and A/shoveler/Egypt/03(H5N2).[35]

Genetic structure[edit]

TheNin H5N1 stands for "Neuraminidase",the protein depicted in this ribbon diagram.

H5N1 is a subtype of Influenza A virus, like all subtypes it is anenvelopednegative-senseRNA virus,with a segmented genome.[36]Subtypes of IAV are defined by the combination of the antigenichemagglutininandneuraminidaseproteins in theviral envelope."H5N1" designates an IAV subtype that has a type 5 hemagglutinin (H) protein and a type-1 neuraminidase (N) protein.[37]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.[38][39]

Influenza viruses have a relatively high mutation rate that is characteristic ofRNA viruses.[40]The segmentation of itsgenomefacilitatesgenetic recombinationby segmentreassortmentin hosts infected with two different strains of influenza viruses at the same time.[41][42]Through a combination ofmutationand geneticreassortmentthe virus can evolve to acquire new characteristics, enabling it to evade host immunity and occasionally to jump from one species of host to another.[43][44]

Prevention and treatment[edit]

Vaccine[edit]

There are several H5N1vaccinesfor several of the avian H5N1 varieties, but the continual mutation of H5N1 renders them of limited use to date: while vaccines can sometimes provide cross-protection against related flu strains, the best protection would be from a vaccine specifically produced for any future pandemic flu virus strain.Daniel R. Lucey,co-director of the Biohazardous Threats and Emerging Diseases graduate program atGeorgetown Universityhas made this point, "There is no H5N1pandemicso there can be no pandemicvaccine".[45]However, "pre-pandemic vaccines" have been created; are being refined and tested; and do have some promise both in furthering research and preparedness for the next pandemic.[46][47][48]Vaccine manufacturing companies are being encouraged to increase capacity so that if a pandemic vaccine is needed, facilities will be available for rapid production of large amounts of a vaccine specific to a new pandemic strain.

Public health[edit]

Further information:Influenza pandemic

"TheUnited Statesis collaborating closely with eight international organizations, including theWorld Health Organization(WHO), theFood and Agriculture Organization of the United Nations(FAO), theWorld Organization for Animal Health(OIE), and 88 foreign governments to address the situation through planning, greater monitoring, and full transparency in reporting and investigating avian influenza occurrences. The United States and these international partners have led global efforts to encourage countries to heighten surveillance for outbreaks in poultry and significant numbers of deaths in migratory birds and to rapidly introduce containment measures. TheU.S. Agency for International Development(USAID) and theU.S. Department of State,theU.S. Department of Health and Human Services(HHS), andAgriculture(USDA) are coordinating future international response measures on behalf of the White House with departments and agencies across the federal government ".[49]

Together steps are being taken to "minimize the risk of further spread in animal populations", "reduce the risk of human infections", and "further support pandemic planning and preparedness".[49]

Ongoing detailed mutually coordinated onsite surveillance and analysis of human and animal H5N1 avian flu outbreaks are being conducted and reported by theUSGSNational Wildlife Health Center, theCenters for Disease Control and Prevention,theWorld Health Organization,theEuropean Commission,and others.[50]

Treatment[edit]

Further information:Flu research

There is no highly effective treatment for H5N1 flu, butoseltamivir(commercially marketed byRocheas Tamiflu) can sometimes inhibit the influenza virus from spreading inside the user's body. This drug has become a focus for some governments and organizations trying to prepare for a possible H5N1 pandemic.[51]On April 20, 2006, Roche AG announced that astockpileof three million treatment courses ofTamifluare waiting at the disposal of theWorld Health Organizationto be used in case of a flu pandemic; separately Roche donated two million courses to the WHO for use indeveloping nationsthat may be affected by such a pandemic but lack the ability to purchase large quantities of the drug.[52]

However, WHO expert Hassan al-Bushra has said:[53]

Even now, we remain unsure about Tamiflu's real effectiveness. As for avaccine,work cannot start on it until the emergence of a new virus, and we predict it would take six to nine months to develop it. For the moment, we cannot by any means count on a potential vaccine to prevent the spread of a contagious influenza virus, whose various precedents in the past 90 years have been highly pathogenic.

Animal and lab studies suggest that Relenza (zanamivir), which is in the same class of drugs as Tamiflu, may also be effective against H5N1. In a study performed on mice in 2000, "zanamivir was shown to be efficacious in treating avian influenza viruses H9N2,H6N1,and H5N1 transmissible to mammals ".[54]In addition, mice studies suggest the combination of zanamivir, celecoxib and mesalazine looks promising producing a 50% survival rate compared to no survival in the placebo arm.[55]While no one knows if zanamivir will be useful or not on a yet to exist pandemic strain of H5N1, it might be useful to stockpile zanamivir as well as oseltamivir in the event of an H5N1 influenza pandemic. Neither oseltamivir nor zanamivir can be manufactured in quantities that would be meaningful once efficient human transmission starts.[56]In September, 2006, a WHO scientist announced that studies had confirmed cases of H5N1 strains resistant to Tamiflu and Amantadine.[57]Tamiflu-resistant strains have also appeared in theEU,which remain sensitive to Relenza.[58][59]

Epidemiology[edit]

Further information:Transmission and infection of H5N1andGlobal spread of H5N1

History[edit]

Influenza A/H5N1 was first detected in 1959 after an outbreak of highly pathogenic avian influenza in Scotland, which infected two flocks of chickens.[60][61]The next detection, and the earliest infection of humans by H5N1, was anepizootic(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.[62][63]

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.[64][65]

Contagiousness[edit]

Highly pathogenic H5N1
Countries with humans, poultry and wild birds killed by H5N1
Countries with poultry or wild birds killed by H5N1 and has reported human cases of H5N1
Countries with poultry or wild birds killed by H5N1

H5N1 is easily transmissible between birds, facilitating a potentialglobal spread of H5N1.While H5N1 undergoes mutation and reassortment, creating variations which can infect species not previously known to carry the virus, not all of these variant forms can infect humans. H5N1 as an avian virus preferentially binds to a type ofgalactosereceptors that populate the avian respiratory tract from the nose to the lungs and are virtually absent in humans, occurring only in and around thealveoli,structures deep in the lungs where oxygen is passed to the blood. Therefore, the virus is not easily expelled by coughing and sneezing, the usual route of transmission.[29][30][66]

H5N1 is mainly spread by domesticpoultry,both through the movements of infected birds and poultry products and through the use of infected poultry manure as fertilizer or feed. Humans with H5N1 have typically caught it from chickens, which were in turn infected by other poultry or waterfowl. Migratingwaterfowl(wildducks,geeseandswans) carry H5N1, often without becoming sick.[67][68]Many species of birds and mammals can be infected with HPAI A(H5N1), but the role of animals other than poultry and waterfowl as disease-spreading hosts is unknown.[69]

According to a report by theWorld Health Organization,H5N1 may be spread indirectly. The report stated the virus may sometimes stick to surfaces or get kicked up in fertilizer dust to infect people.[70]

Virulence[edit]

H5N1 hasmutatedinto a variety ofstrainswith differing pathogenic profiles, some pathogenic to one species but not others, some pathogenic to multiple species. Each specific known genetic variation is traceable to a virus isolate of a specific case of infection. Throughantigenic drift,H5N1 has mutated into dozens of highly pathogenic varieties divided into genetic clades which are known from specific isolates, but all belong to genotype Z of avian influenza virus H5N1, now the dominant genotype.[42][41]H5N1 isolates found inHong Kongin 1997 and 2001 were not consistently transmitted efficiently among birds and did not cause significant disease in these animals. In 2002, new isolates of H5N1 were appearing within the bird population of Hong Kong. These new isolates caused acute disease, including severe neurological dysfunction and death inducks.This was the first reported case of lethal influenza virus infection in wild aquatic birds since 1961.[71]

Genotype Z emerged in 2002 throughreassortmentfrom earlier highly pathogenic genotypes of H5N1[72]that first infected birds in China in 1996, and first infected humans inHong Kongin 1997.[41][42][73]Genotype Z is endemic in birds in Southeast Asia, has created at least two clades that can infect humans, and is spreading across the globe in bird populations. Mutations occurring within this genotype are increasing their pathogenicity.[74]Birds are also able to shed the virus for longer periods of time before their death, increasing the transmissibility of the virus.

Pandemic potential[edit]

Influenza viruses have a relatively high mutation rate that is characteristic ofRNA viruses.[75]The segmentation of the influenza A virusgenomefacilitatesgenetic recombinationby segmentreassortmentin hosts who become infected with two different strains of influenza viruses at the same time.[76][77]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 - azoonoticevent.[78]

As of June 2024, there is concern about two subtypes of avian influenza which are circulating in wild bird populations worldwide, A/H5N1 andA/H7N9.Both of these have potential to devastate poultry stocks, and both have jumped to humans with relatively highcase fatality rates.[79]A/H5N1 in particular has infected awide range of mammalsand may be adapting to mammalian hosts.[80]

Surveillance[edit]

TheGlobal Influenza Surveillance and Response System(GISRS)is a global network of laboratories that monitor the spread ofinfluenzawith the aim to provide theWorld Health Organizationwith influenza control information and to inform vaccine development.[81]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 potentiallyzoonoticinfluenza viruses as well as human viruses.[82]

Transmission and host range[edit]

Transmission electronmicrograph(TEM) of negatively stainedInfluenza A virusparticles (small and white) attached to host cells (large and irregular) (late passage).Source: Dr. Erskine Palmer, Centers for Disease Control and Prevention Public Health Image Library

Infected birds transmit H5N1 through theirsaliva,nasal secretions,fecesandblood.Other animals may become infected with the virus through direct contact with these bodily fluids or through contact with surfaces contaminated with them. H5N1 remains infectious after over 30 days at 0 °C (32 °F) (over one month at freezing temperature) or 6 days at 37 °C (99 °F) (one week at human body temperature); at ordinary temperatures it lasts in the environment for weeks. In Arctic temperatures, it does not degrade at all.[citation needed]

Because migratory birds are among the carriers of the highly pathogenic H5N1 virus, it is spreading to all parts of the world. H5N1 is different from all previously known highly pathogenic avian flu viruses in its ability to be spread by animals other than poultry.

In October 2004, researchers discovered H5N1 is far more dangerous than was previously believed.Waterfowlwere revealed to be directly spreading this highly pathogenic strain tochickens,crows,pigeons,and other birds, and the virus was increasing its ability to infect mammals, as well. From this point on, avian flu experts increasingly referred to containment as a strategy that can delay, but not ultimately prevent, a future avian flu pandemic.[citation needed]

"Since 1997, studies of influenza A (H5N1) indicate that these viruses continue to evolve, with changes in antigenicity and internal gene constellations; an expanded host range in avian species and the ability to infect felids; enhanced pathogenicity in experimentally infected mice and ferrets, in which they cause systemic infections; and increased environmental stability."[83]

The New York Times,in an article on transmission of H5N1 through smuggled birds, reports Wade Hagemeijer of Wetlands International stating, "We believe it is spread by both bird migration and trade, but that trade, particularly illegal trade, is more important".[84]

On September 29, 2007, researchers reported the H5N1 bird flu virus can also pass through a pregnant woman's placenta to infect the fetus. They also found evidence of what doctors had long suspected—the virus not only affects the lungs, but also passes throughout the body into the gastrointestinal tract, the brain, liver, and blood cells.[85]

In May 2013,North Koreaconfirmed a H5N1 bird flu outbreak that forced authorities to kill over 160,000 ducks inPyongyang.[86]


Confirmed human cases andmortality rateofavian influenza(H5N1) 2003–2024
Country
Australia
Azerbaijan
Bangladesh
Cambodia
Canada
Chile
China
Djibouti
Ecuador
Egypt
India
Indonesia
Iraq
Laos
Myanmar
Nepal
Nigeria
Pakistan
Spain
Thailand
Turkey
United Kingdom
United States
Vietnam
Total
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 Total
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
cases
deaths
CFR
1 0 0% 1 0 0%
8 5 62.5% 8 5 62.5%
1 0 0% 2 0 0% 3 0 0% 1 1 100% 1 0 0% 8 1 12.5%
4 4 100% 2 2 100% 1 1 100% 1 0 0% 1 0 0% 1 1 100% 8 8 100% 3 3 100% 26 14 53.8% 9 4 44.4% 6 4 66.7% 7 1 14.0% 69 42 60.9%
1 1 100% 1 1 100%
1 0 0% 1 0 0%
1 1 100% 8 5 62.5% 13 8 61.5% 5 3 60.0% 4 4 100% 7 4 57.1% 2 1 50.0% 1 1 100% 2 1 50.0% 2 2 100% 2 0 0% 6 1 16.7% 1 1 100% 1 0 0% 55 32 58.2%
1 0 0% 1 0 0%
1 0 0% 1 0 0%
18 10 55.6% 25 9 36.0% 8 4 50.0% 39 4 10.3% 29 13 44.8% 39 15 38.5% 11 5 45.5% 4 3 75.0% 37 14 37.8% 136 39 28.7% 10 3 30.0% 3 1 33.3% 359 120 33.4%
1 1 100% 1 1 100%
20 13 65.0% 55 45 81.8% 42 37 88.1% 24 20 83.3% 21 19 90.5% 9 7 77.8% 12 10 83.3% 9 9 100% 3 3 100% 2 2 100% 2 2 100% 1 1 100% 200 168 84.0%
3 2 66.6% 3 2 66.6%
2 2 100% 1 0 0% 3 2 66.7%
1 0 0% 1 0 0%
1 1 100% 1 1 100%
1 1 100% 1 1 100%
3 1 33.3% 3 1 33.3%
2 0 0% 2 0 0%
17 12 70.6% 5 2 40.0% 3 3 100% 25 17 68.0%
12 4 33.3% 12 4 33.3%
1 0 0% 4 0 0% 5 0 0%
1 0 0% 7 0 0% 8 0 0%
3 3 100% 29 20 69.0% 61 19 31.1% 8 5 62.5% 6 5 83.3% 5 5 100% 7 2 28.6% 4 2 50.0% 2 1 50.0% 2 2 100% 1 0 0% 1 1 100% 129 65 50.0%
4 4 100% 46 32 69.6% 98 43 43.9% 115 79 68.7% 88 59 67.0% 44 33 75.0% 73 32 43.8% 48 24 50.0% 62 34 54.8% 32 20 62.5% 39 25 64.1% 52 22 42.3% 145 42 29.0% 10 3 30.0% 4 2 50.0% 0 0 0% 1 1 100% 1 0 0% 2 1 50.0% 6 1 16.7% 12 4 33.3% 16 2 12.5% 898 463 51.6%
Updated 14 July 2024
Source:World Health OrganizationGlobal Influenza ProgramCumulative Cases Report·edit this table


2020–2024 global H5N1 outbreak[edit]

Main article:2020–2024 H5N1 outbreak

Europe[edit]

A major outbreak of a new strain of H5N1 in wild birds and poultry appeared in Russia in August 2020 and quickly spread to other parts of Europe by October.[87]

Over the winter of 2021 and 2022, avian flu spread among the population ofbarnacle geeseon the Solway Firth, UK, with estimates of up to a third of the Svalbard population being lost;[88][89]pink-footed geesewere also affected there and it seems carried the virus to new sites in northern Scotland. The disease was confirmed insandwich ternsin South Africa in April 2022.[90]In late spring 2022 avian flu outbreaks affected many species of wild bird in the United Kingdom, with heavy losses reported among seabirds returning to breed at colonies in the Northern Isles and Outer Hebrides,[91]includinggreat skuas(bonxie) for which outbreaks had initially been reported in 2021[92](Scotland hosts c. 60% of the world's breeding population) – the 2022 census onSt Kildashowed a 64% decline on 2019 with 106 dead birds recorded so far (to 6 June),[93]gannets(1000+ birds reported dead at the Shetlands'Hermanesscolony alone,[91]where there are around 26,000 breeding pairs), with many more gannets being reported dead at other colonies (Troup Head,Bass Rock,andSt Kilda);[94]the range of species also seems to be expanding, with reports for many species of wildfowl, seabirds (auks, terns and gulls) and scavenging species (corvids and raptors).[95][96]

Elsewhere in Europe the virus killed hundreds (574+) ofDalmatian pelicansin Greece,[97][98]and in Israel around 6000common craneswere found dead at Hula in December 2021.[99]A report by Scientific Task Force on Avian Influenza and Wild Birds on: "H5N1 Highly Pathogenic Avian Influenza in poultry and wild birds: Winter of 2021/2022 with focus on mass mortality of wild birds in UK and Israel" summarises the situation up to 24 January 2022 and mentions that "H5N8 HPAI is still responsible for poultry and wild bird cases mainly in Asia, H5N1 has now in effect replaced this subtype in Africa and Eurasia in both poultry and wild birds".[100]

The 2022–2023 season was also the worst recorded outbreak in the United Kingdom, with the British government requiring a so-called "poultry lockdown" which required that farmers keep their birds indoors.[101]Meanwhile, an outbreak of H5N1 on a Spanish mink farm led researchers to believe that they had observed the first case of mammal-to-mammal transmission of H5N1.[102]Human cases were reported in Spain in November 2022, and in the UK in May 2023.[87]

Asia[edit]

By November 2020, large outbreaks of the new strain of H5N1 had started to spread into wild birds and farmed poultry across Asia. In February 2023, human cases were reported in Cambodia.[87]

Africa[edit]

Large losses of poultry and wild birds to H5N1 started to occur in Africa in November 2021 and continued through 2022.[87]

Americas[edit]

Similar to 2021 reports, outbreaks were noted fromgannetcolonies in Canada, with thousands of birds dead in June 2022,[103]as well ascommon eidersandgreat black-backed gulls.[104]Prior to that there were reports of spread in wild birds in over 30 states in the US, including major mortalities in adouble-crested cormorantcolony inBarrington, Illinois,[105][106]the virus also spreading to scavengers including threebald eaglesin Georgia.[107]Mass die-offs of both birds and mammals were noted in Peru during the 2022–2023 season.[108]In particular, the Peruvian government reported the deaths of approximately 63,000 birds as well as 716sea lions,with the WHO noting that mammalian spillovers needed to be "monitored closely".[101][109]In the United States, the 2022–2023 avian outbreak was the worst since H5N1 was first detected.[101]

Ecuadorentered into a three-month "animal-health emergency" on 29 November 2022, just days after its first case was reported, whereasArgentinaandUruguayboth declared "national sanitary emergencies" on 15 February 2023, after their respective first cases were discovered.[110]On 22 May 2023, Brazil, as the world's largest exporter of chicken meat, declared a 180-day emergency following several cases detected in wild birds and created an emergency operations center to plan for and mitigate potential further spread of H5N1.[111]Human cases were reported in Ecuador and Chile.[87]

In March 2024, H5N1 infections were recorded for the first time in deceased and sick livestock located in the United States.Goatsand cows in three states became ill after exposure to wild birds and culled poultry.[112]In early April, H5N1 was reported to have spread amongstdairy cowherds in multiple states of the USA, indicating cow-to-cow spread, possibly occurring while the animals were being milked.[113]A dairy worker in Texas also became infected, withconjunctivitisbeing the main symptom.[114]

On 22 May 2024, a farm worker in Michigan was infected with the H5N1 virus due to their regular exposure to infected dairy cows. The person had mild symptoms and recovered.[115]On 30 May, it was announced that a second Michigan farm worker from a different dairy farm had been diagnosed with H5N1 after exhibiting respiratory symptoms.[116][117]By mid July, seven human cases in the USA were reported in workers at both dairy and poultry farms.[118]

Antarctica[edit]

H5N1 was detected in dead birds on the Antarctic mainland for the first time in February 2024.[119]

Arctic[edit]

In December 2023, conservation officials confirmed that apolar bearhad died of H5N1 near Alaska's northernmost city,Utqiagvik.[120]

Australia[edit]

In May 2024, H5N1 was detected for the first time in Australia after a human child who had returned to the country from India tested positive. The child had a severe infection but recovered.[121]

Mammalian infections[edit]

Main article:List of mammals that can get H5N1

H5N1 transmission studies in ferrets (2011)[edit]

Novel,contagiousstrains of H5N1 were created by Ron Fouchier of theErasmus Medical Centerin 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 infectedferretsto the noses of uninfected ones, which was repeated 10 times.[122]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 journalScience,the USNational 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.[123]However, then theDutch governmentdeclared 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.[note 1]After much controversy surrounding the publishing of his research, Fouchier complied (under formal protest) with Dutch government demands to obtain a special permit[124]for submitting his manuscript, and his research appeared in a special issue of the journalSciencedevoted to H5N1.[125][126][127]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.[128]

In May 2013, it was reported that scientists at theHarbin Veterinary Research InstituteinHarbin,China, had created H5N1 strains which passed betweenguinea pigs.[129]

In response to Fouchier and Kawaoka's work, a number of scientists expressed concerns with therisksof creating novel potential pandemic pathogens, culminating in the formation ofthe Cambridge Working Group,a consensus statement calling for an assessment of the risks and benefits of such research.[130][131]

Mammal-to-mammal transmission (2022–2024)[edit]

Although mammals, including humans, had become infected with H5N1 bird flu strains in the past, these cases had ostensibly been caused by direct exposure to infected birds, such as through consumption of birds by wildlife or exposure to infected poultry by farmers. In contrast, the October 2022 mammalian 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.[102][132]The mink respiratory tract is particularly well suited to act as a pathway of viral transmission into humans, which has concerned public health professionals due to the production of all but one approved human vaccine requiring the eggs of chickens, which H5N1 kills at a 90–100 percent fatality rate.[133]Infected mink in Spain were also found to have exhibited the "PB2" viral mutation found when H5N1 jumped into pigs over a decade prior, adding to fears that farms could be acting as incubators and/orreservoirsof the virus, similar to the role of minks inSARS-CoV-2.[102]

As of January 2023, fifteen species of wild and captive mammals had become infected with H5N1 throughout the United States.[134]A massCaspian sealdie-off in December 2022, with 700 infected seals found dead along the Caspian Sea coastline of Russia'sDagestanrepublic,worried researchers regarding the possibility that wild mammal-to-mammal spread had begun.[135]A similar mass die-off of 95% ofsouthern elephant sealpups in 2023 also raised concerns of mammal-to-mammal spread, as nursing pups would have had less exposure to birds.[136]

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.[113][137]Although mortality in bovines infected with H5N1 is rare, abundant virus shedding in the milk is evident.[113]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.[138]

Society and culture[edit]

Main article:Social impact of H5N1

H5N1 has had a significant effect onhumansociety,especially thefinancial,political,social,and personal responses to both actual and predicteddeathsinbirds,humans,and otheranimals.Billions of dollars are being raised and spent to research H5N1 and prepare for a potentialavian influenzapandemic.Over $10 billion have been spent and over 200 million birds have been killed to try to contain H5N1.[139][140][141][142][143][144][145][146][147]

People have reacted by buying less chicken, causing poultry sales and prices to fall.[148]Many individuals have stockpiled supplies for a possible flu pandemic. International health officials and other experts have pointed out that many unknown questions still hover around the disease.[149]

Dr.David Nabarro,Chief Avian Flu Coordinator for the United Nations, and former Chief of Crisis Response for the World Health Organization has described himself as "quite scared" about H5N1's potential impact on humans. Nabarro has been accused of being alarmist before, and on his first day in his role for the United Nations, he proclaimed the avian flu could kill 150 million people. In an interview with theInternational Herald Tribune,Nabarro compares avian flu toAIDSin Africa, warning that underestimations led to inappropriate focus for research and intervention.[150]

See also[edit]

Notes[edit]

  1. ^The World Intellectual Property Organization (WIPO) listsstrategic goodswith 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.

References[edit]

Citations[edit]

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Sources[edit]

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

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

External links[edit]

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