Avian influenza, also known as avian fluorbird flu, is a disease caused by the influenza A virus (IAV) which primarily affects birds but can sometimes affect mammals including humans.[1] Wild aquatic birds are the primary host of Influenza A virus (IAV), which is endemic in many bird populations.[2][3]
Symptoms of avian influenza vary according to both the strain of virus underlying the infection, and on the species of bird or mammal affected. Classification of a virus strain 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 severity of symptoms in other species.[4] Chickens infected with LPAI display mild symptoms or are asymptomatic, whereas HPAI causes serious breathing difficulties, significant drop in egg production, and sudden death.[5] Domestic poultry may potentially be protected from specific strains of the virus by vaccination.[6]
Humans and other mammals can only become infected with avian influenza after prolonged close contact with infected birds.[7] In mammals including humans, infection with avian influenza (whether LPAI or HPAI) is rare. Symptoms of infection vary from mild to severe, including fever, diarrhoea, and cough.[8]
Influenza A 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 (e.g., cow milk).[9] The virus can spread rapidly through poultry flocks and among wild birds.[9] A particularly virulent strain, Influenza A virus subtype H5N1 (A/H5N1) has the potential to decimate domesticated poultry stocks and an estimated half a billion farmed birds have been slaughtered in efforts to contain the virus.[10]
Because of the impact of avian influenza on economically important chicken farms, a classification system was devised in 1981 which divided avian virus strains as either highly pathogenic (and therefore potentially requiring vigorous control measures) or low pathogenic. The test for this is based solely on the effect on chickens - a virus strain is highly pathogenic avian influenza (HPAI) if 75% or more of chickens die after being deliberately infected with it. The alternative classification is low pathogenic avian influenza (LPAI).[11] This classification system has since been modified to take into account the structure of the virus' haemagglutinin protein.[12] Other species of birds, especially water birds, can become infected with HPAI virus without experiencing severe symptoms and can spread the infection over large distances; the exact symptoms depend on the species of bird and the strain of virus.[11] Classification of an avian virus strain as HPAI or LPAI does not predict how serious the disease might be if it infects humans or other mammals.[11][13]
Avian influenza is caused by the Influenza A virus which principally affects birds but can also infect humans and other mammals.[15][16] Influenza A is an RNA virus with a genome comprising a negative-sense, RNA segmented genome that encodes for 11 viral genes.[17] The virus particle (also called the virion) is 80–120 nanometers in diameter and elliptical or filamentous in shape.[18][19] There is evidence that the virus can survive for long periods in freshwater after being excreted in feces by its avian host, and can withstand prolonged freezing.[20]
There are two proteins on the surface of the viral envelope; hemagglutinin and neuraminidase.[4] These are the major antigens of the virus against which neutralizing antibodies are produced. Influenza virus epidemics and epizootics are associated with changes in their antigenic structure.[21]
Hemagglutinin (H), is an antigenic glycoprotein which allows the virus to bind to and enter the host cell. Neuraminidase (N) is an antigenic glycosylated enzyme which facilitates the release of progeny viruses from infected cells.[22] There are 18 known types of hemagglutinin, of which H1 thru H16 have been found in birds, and 11 types of neuraminidase.[15]
Subtypes of Influenza A are defined by the combination of H and N proteins in the viral envelope; for example, "H5N1" designates an influenza A subtype that has a type-5 hemagglutinin (H) protein and a type-1 neuraminidase (N) protein.[7] The subtyping scheme only takes into account the two envelope proteins, not the other proteins coded by the virus' RNA. Almost all possible combinations of H (1 thru 16) and N (1 thru 11) have been isolated from wild birds.[23] Further variations exist within the subtypes and can lead to very significant differences in the virus's ability to infect and cause disease.[24]
Influenza viruses are constantly changing as small genetic mutations accumulate, a process known as antigenic drift. Over time, mutation may lead to a change in antigenic properties such that host antibodies (acquired through vaccination or prior infection) do not provide effective protection, causing a fresh outbreak of disease.[25]
To unambiguously describe a specific isolate of virus, researchers use the internationally accepted Influenza virus nomenclature,[26] which describes, among other things, the species of animal from which the virus was isolated, and the place and year of collection. As an example - A/chicken/Nakorn-Patom/Thailand/CU-K2/04(H5N1):
Other examples include: A/duck/Hong Kong/308/78(H5N3), A/avian/NY/01(H5N2), A/chicken/Mexico/31381-3/94(H5N2), and A/shoveler/Egypt/03(H5N2).[27]
Analysis of the virus' genome enables researchers to determine the order of its nucleotides. Comparison of the genome of a virus with that of a different virus can reveal differences between the two viruses.[15][28] Genetic variations are important because they can change amino acids that make up the influenza virus’ proteins, resulting in structural changes to the proteins, and thereby altering properties of the virus. Some of these properties include the ability to evade immunity and the ability to cause severe disease.[28]
Genetic sequencing enables influenza strains to be further characterised by their cladeorsubclade, revealing links between different samples of virus and tracing the evolution of the virus over time.[28]
Rarely, humans can become infected by avian flu if they are in close contact with infected birds. Symptoms vary from mild to severe (including death) but these instances have not sustained transmission from one person to another. Five subtypes (H5, H6, H7, H9, and H10) are known to have caused disease in humans,[4][16]
There are a number of factors which generally prevent avian flu from causing epidemics in humans or other mammals.[29][30] One of them is that the HA protein of avian influenza binds to alpha-2,3 sialic acid receptors, present in the intestines of avian species, while human influenza HA binds to alpha-2,6 sialic acid receptors which are present in the human upper respiratory tract.[31] Other factors include the ability to replicate the viral RNA genome within the host cell nucleus, to evade host immune responses and to transmit between individuals.[32]
The segmented genome of influenza viruses facilitates genetic reassortment. This can occur if a host is infected simultaneously with two different strains of influenza virus; then it is possible for the viruses to interchange genetic material as they reproduce in the host cells.[33] Thus an avian influenza virus can acquire characteristics, such as the ability to infect humans, from a different virus strain. The presence of both alpha 2,3 and alpha 2,6 sialic acid receptors in pig tissues allows for co-infection by avian influenza and human influenza viruses. This susceptibility makes pigs a potential "melting pot" for the reassortment of influenza A viruses.[34]
Avian influenza (historically known as fowl plague) is caused by bird-adapted strains of the influenza type A virus.[4] The disease was first identified by Edoardo Perroncito in 1878 when it was differentiated from other diseases that caused high mortality rates in birds; in 1955 it was established that the fowl plague virus was closely related to human influenza. In 1972 it became evident that many subtypes of avian flu were endemic in wild bird populations.[11]
Between 1959 and 1995, there were 15 recorded outbreaks of highly pathogenic avian influenza (HPAI) in poultry, with losses varying from a few birds on a single farm to many millions. Between 1996 and 2008, HPAI outbreaks in poultry have been recorded at least 11 times and 4 of these outbreaks have resulted in the death or culling of millions of birds.[11] Since then, several virus strains (both LPAI and HPAI) have become endemic among wild birds with increasingly frequent outbreaks among domestic poultry, especially of the H5 and H7 subtypes.
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. 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.[35] 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.[36] 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.[37][38] 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. [36]
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.[39][38] 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.[40] All subtypes of avian Influenza A have potential to cross the species barrier, with H5N1 and H7N9 considered the biggest threats.[41][42]
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.[43]
Other animals - a wide range of other animals have been affected by avian flu, generally due to eating birds which had been infected.[44] There have been instances where transmission of the disease between mammals, including seals and cows, may have occurred.[45][46]
Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses.[47] 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.[48][49] 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.[35] It is thought that all influenza A viruses causing outbreaks or pandemics among humans since the 1900s originated from strains circulating in wild aquatic birds through reassortment with other influenza strains.[50][51] It is possible (though not certain) that pigs may act as an intermediate host for reassortment.[52]
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.[53] Several millions of specimens are tested by the GISRS network annually through a network of laboratories in 127 countries.[54] As well as human viruses, GISRS monitors avian, swine, and other potentially zoonotic influenza viruses.
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.[55][56]
Humans - Several "candidate vaccines" are available in case of an avian virus acquires the ability to infect and transmit among humans. There are strategic stockpiles of vaccines against the H5N1 subtype which is considered the biggest risk.[57][58][59] A vaccine against the H7N9 subtype, which has also infected humans, has undergone a limited amount of testing.[60] 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.
The highly pathogenic influenza A virus subtype H5N1 is an emerging avian influenza virus that is causing global concern as a potential pandemic threat. It is often referred to simply as "bird flu" or "avian influenza", even though it is only one of many subtypes.
H5N1 has killed millions of poultry in a growing number of countries throughout Asia, Europe, and Africa. Health experts are concerned that the coexistence of human flu viruses and avian flu viruses (especially H5N1) will provide an opportunity for genetic material to be exchanged between species-specific viruses, possibly creating a new virulent influenza strain that is easily transmissible and lethal to humans. The mortality rate for humans with H5N1 is 60%.[61]
Since the first human H5N1 outbreak occurred in 1997, there has been an increasing number of HPAI H5N1 bird-to-human transmissions, leading to clinically severe and fatal human infections. Because a significant species barrier exists between birds and humans, the virus does not easily spread to humans. Some cases of infection were researched to discern whether human-to-human transmission occurred.[62] More research is necessary to understand the pathogenesis and epidemiology of the H5N1 virus in humans. Exposure routes and other disease transmission characteristics, such as genetic and immunological factors that may increase the likelihood of infection, are not clearly understood.[63]
The first known transmission of H5N1 to a human occurred in Hong Kong in 1997, when there was an outbreak of 18 human cases; 6 deaths were confirmed. None of the infected people worked with poultry. After culling all of the poultry in the area, no more cases were diagnosed.[64] In 2006, the first human-to-human transmission likely occurred when seven members of a family in Sumatra became infected after contact with a family member who had worked with infected poultry.[65]
Although millions of birds have become infected with the virus since its discovery, 359 people have died from H5N1 in twelve countries according to World Health Organization reports as of August 10, 2012.[66]
The H5N1 outbreak in Thailand caused massive economic losses, especially among poultry workers. Infected birds were culled and slaughtered. The public lost confidence with the poultry products, thus decreasing the consumption of chicken products. This also elicited a ban from importing countries. Several factors enhanced the virality, including bird migration, cool temperature (increases virus survival) and several festivals at that time.[67]
A mutation in the virus was discovered in two Guangdong patients in February 2017 which rendered it more deadly to chickens, inasmuch as it could infect every organ; the risk to humans was not increased.[68]
Influenza A virus subtype H7N9 is a novel avian influenza virus first reported to have infected humans in 2013 in China.[69] Most of the reported cases of human infection have resulted in severe respiratory illness.[70] In the month following the report of the first case, more than 100 people had been infected, an unusually high rate for a new infection; a fifth of those patients had died, a fifth had recovered, and the rest remained critically ill.[71] The WHO has identified H7N9 as "...an unusually dangerous virus for humans."[72] As of June 30, 133 cases have been reported, resulting in the deaths of 43.
Research regarding background and transmission is ongoing.[73] It has been established that many of the human cases of H7N9 appear to have a link to live bird markets.[74] As of July 2013, there is no evidence of sustained human-to-human transmission. A study group headed by one of the world's leading experts on avian flu reported that several instances of human-to-human infection were suspected.[75] It has been reported that H7N9 virus does not kill poultry, which will make surveillance much more difficult. Researchers have commented on the unusual prevalence of older males among H7N9-infected patients.[76] While several environmental, behavioral, and biological explanations for this pattern have been proposed,[77] as yet, the reason is unknown.[78] Currently no vaccine exists, but the use of influenza antiviral drugs known as neuraminidase inhibitors in cases of early infection may be effective.[79]
The number of cases detected after April fell abruptly. The decrease in the number of new human H7N9 cases may have resulted from containment measures taken by Chinese authorities, including closing live bird markets, or from a change in seasons, or possibly a combination of both factors. Studies indicate that avian influenza viruses have a seasonal pattern, thus it is thought that infections may pick up again when the weather turns cooler in China.[80]
In the four years from early 2013 to early 2017, 916 lab-confirmed human cases of H7N9 were reported to the WHO.[81]
On 9 January 2017, the National Health and Family Planning Commission of China reported to the WHO 106 cases which occurred from late November through December. 29, 2016. The cases are reported from Jiangsu (52), Zhejiang (21), Anhui (14), Guangdong (14), Shanghai (2), Fujian (2) and Hunan (1). 80 of these 106 persons have visited live poultry markets. Of these cases, there have been 35 deaths. In two of the 106 cases, human-to-human transmission could not be ruled out.[81]
Affected prefectures in Jiangsu province closed live poultry markets in late December 2016, whereas Zhejiang, Guangdong and Anhui provinces went the route of strengthening live poultry market regulations. Travellers to affected regions are recommended to avoid poultry farms, live bird markets, and surfaces which appear to be contaminated with poultry feces. Similar sudden increases in the number of human cases of H7N9 have occurred in previous years during December and January.[81]
Several domestic species have been infected with and shown symptoms of H5N1 viral infection, including cats, dogs, ferrets, pigs, and birds.[82]
Attempts are made in the United States to minimize the presence of HPAI in poultry through routine surveillance of poultry flocks in commercial poultry operations. Detection of a HPAI virus may result in immediate culling of the flock. Less pathogenic viruses are controlled by vaccination[83]
Avian influenza was detected in dairy cows in several US states during April 2024. In late April 2024, the United States FDA, or Food and Drug Administration, announced that fragments of Highly Pathogenic Avian Influenza (HPAI) have been found in pasteurized milk. However, these fragments cannot cause disease in humans.[87]
In 2005, the formation of the International Partnership on Avian and Pandemic Influenza was announced in order to elevate the importance of avian flu, coordinate efforts, and improve disease reporting and surveillance in order to better respond to future pandemics. New networks of laboratories have emerged to detect and respond to avian flu, such as the Crisis Management Center for Animal Health, the Global Avian Influenza Network for Surveillance, OFFLU, and the Global Early Warning System for major animal diseases. After the 2003 outbreak, WHO member states have also recognized the need for more transparent and equitable sharing of vaccines and other benefits from these networks.[88] Cooperative measures created in response to HPAI have served as a basis for programs related to other emerging and re-emerging infectious diseases.
HPAI control has also been used for political ends. In Indonesia, negotiations with global response networks were used to recentralize power and funding to the Ministry of Health.[89] In Vietnam policymakers, with the support of the Food and Agriculture Organization of the United Nations (FAO), used HPAI control to accelerate the industrialization of livestock production for export by proposing to increase the portion of large-scale commercial farms and reducing the number of poultry keepers from 8 to 2 million by 2010.[90]
In 2023, report by the Royal Society for the Protection of Birds (RSPB) and the British Trust for Ornithology 75% decrease in the Great Skua and a 25% reduction in Northern Gannets.[citation needed]
Backyard poultry production was viewed as "traditional Asian" agricultural practices that contrasted with modern commercial poultry production and seen as a threat to biosecurity. Backyard production appeared to hold greater risk than commercial production due to lack of biosecurity and close contact with humans, though HPAI spread in intensively raised flocks was greater due to high density rearing and genetic homogeneity.[91][92] Asian culture itself was blamed as the reason why certain interventions, such as those that only looked at placed-based interventions, would fail without looking for multifaceted solutions.[90]
Approximately 20% of the protein consumed in developing countries come from poultry.[91] A report by the FAO totalled economic losses caused by avian influenza in South East Asia up to 2005 around US$10 billion. This had the greatest impact on small scale commercial and backyard producers.[93]
As poultry serves as a source of food security and liquid assets, the most vulnerable populations were poor small scale farmers.[90] The loss of birds due to HPAI and culling in Vietnam led to an average loss of 2.3 months of production and US$69–108 for households where many have an income of $2 a day or less.[93] The loss of food security for vulnerable households can be seen in the stunting of children under five in Egypt. Women are another population at risk as in most regions of the world, small flocks are tended to by women. Widespread culling also resulted in the decreased enrollment of girls in school in Turkey.[91]
This Memorandum was drafted by the signatories listed on page 590 on the occasion of a meeting held in Geneva in February 1980.
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.
If an avian virus mutates or reassorts and gains the ability to bind to α2,6 linked sialic acids, it might cross the species barrier and infect humans. Swine tissues express both forms of sialic acid and can be coinfected with human and avian viruses. Thus pigs serve as a melting vessel for human, avian and swine influenza strains.
World Health Organisation (WHO)
Food and Agriculture Organization of the UN (FAO)
World Organisation for Animal Health (OIE)
United States
Europe