Subtype of influenza A virus
Influenza A virus subtype H5N1 (A/H5N1) is a subtype of the influenza A virus, which causes the disease avian influenza (often referred to as "bird flu"). It is enzootic (maintained in the population) in many bird populations, and also panzootic (affecting animals of many species over a wide area). 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.
A/H5N1 virus is shed in the saliva, mucus, and feces of infected birds; other infected animals may shed bird flu viruses in respiratory secretions and other body fluids (such as milk). The virus can spread rapidly through poultry flocks and among wild birds. An estimated half billion farmed birds have been slaughtered in efforts to contain the virus.
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. Classification as either Low Pathogenic Avian Influenza (LPAI) or High Pathogenic Avian Influenza (HPAI) is based on the severity of symptoms in domestic chickens and does not predict the severity of symptoms in other species. Chickens infected with LPAI A/H5N1 virus display mild symptoms or are asymptomatic, whereas HPAI A/H5N1 causes serious breathing difficulties, a significant drop in egg production, and sudden death.
In mammals, including humans, A/H5N1 influenza (whether LPAI or HPAI) is rare. Symptoms of infection vary from mild to severe, including fever, diarrhea, and cough. 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. 
A/H5N1 influenza virus was first identified in farmed birds in southern China in 1996. 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. Some strains of A/H5N1 which are highly pathogenic to chickens have adapted to cause mild symptoms in ducks and geese, and are able to spread rapidly through bird migration. Mammal species in addition to humans that have been recorded with H5N1 infection include cattle, seals, goats, and skunks.
Due to the high lethality and virulence of HPAI A(H5N1), its worldwide presence, its increasingly diverse host reservoir, and its significant ongoing mutations, the H5N1 virus is regarded as the world's largest pandemic threat. Domestic poultry may potentially be protected from specific strains of the virus by vaccination. 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.
Signs and symptoms.
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. 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. All subtypes of avian Influenza A have potential to cross the species barrier, with H5N1 and H7N9 considered the biggest threats. In December 2024, researchers showed one mutation could allow the virus to switch its specificity to human receptors, 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.
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. 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.
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 been in contact with multiple sick and dead birds from their backyard flock.
Virology.
Influenza virus nomenclature.
To unambiguously describe a specific isolate of virus, researchers use the internationally accepted "Influenza virus nomenclature," 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):
Other examples include: A/duck/Hong Kong/308/78(H5N3), and A/shoveler/Egypt/03(H5N2).
Genetic structure.
H5N1 is a subtype of Influenza A virus. Like all subtypes it is an enveloped negative-sense RNA virus, with a segmented genome. 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. 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.
Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses. 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. 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.
Prevention and treatment.
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. Some governments have prepared strategic stockpiles of vaccines against the H5N1 subtype which is considered the biggest risk among subtypes. 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.
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. In many countries, it is routine to vaccinate poultry against H5N1. 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.
Treatment.
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.
Epidemiology.
History.
Influenza A/H5N1 was first detected in 1959 after an outbreak of highly pathogenic avian influenza in Scotland, which infected two flocks of chickens. 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.
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.
Pandemic potential.
Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses. 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. 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.
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. A/H5N1 in particular has infected a wide range of mammals and may be adapting to mammalian hosts.
Surveillance.
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. 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.
Transmission and prevention.
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. 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. 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. 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. 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. 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.
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. 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