Avian influenza
Avian influenza, also known as avian flu or bird flu, is a disease caused by the influenza A virus, which primarily affects birds but can sometimes affect mammals including humans. Wild aquatic birds are the primary host of the influenza A virus, which is enzootic in many bird populations.
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 or high pathogenic avian influenza is based on the severity of symptoms in domestic chickens and does not predict severity of symptoms in other species. Chickens infected with LPAI display mild symptoms or are asymptomatic, whereas HPAI causes serious breathing difficulties, significant drop in egg production, and sudden death. Domestic poultry may potentially be protected from specific strains of the virus by vaccination.
Humans typically become infected with avian influenza after prolonged close contact with infected birds or non-human mammals. However, cases have also been linked to consumption of improperly prepared animal byproducts, contact with contaminated surfaces, and, in rare cases, limited human-to-human spread. Symptoms of infection vary from mild to severe, including fever, diarrhea, and cough.
The influenza A 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. The virus can spread rapidly through poultry flocks and among wild birds. A particularly virulent strain, influenza A virus subtype H5N1 has the potential to devastate domesticated poultry stocks and an estimated half a billion farmed birds have been slaughtered in efforts to contain the virus.
Highly pathogenic avian influenza
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 or low pathogenic. The test for this is based solely on the effect on chickens – a virus strain is highly pathogenic avian influenza if 75% or more of chickens die after being deliberately infected with it. The alternative classification is low pathogenic avian influenza. This classification system has since been modified to take into account the structure of the virus' haemagglutinin protein. 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. 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.Since 2006, the World Organization for Animal Health requires all LPAI H5 and H7 detections to be reported because of their potential to mutate into highly pathogenic strains.
Virology
Avian influenza is caused by the influenza A virus which principally affects birds but can also infect humans and other mammals. Influenza A is an RNA virus with a genome comprising a negative-sense, RNA segmented genome that encodes 11 viral genes. The virus particle is 80–120 nanometers in diameter and elliptical or filamentous in shape. 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.There are two proteins on the surface of the viral envelope; hemagglutinin and neuraminidase. 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.
Hemagglutinin is an antigenic glycoprotein which binds to sialic acid receptors on the surface of the host cell, thereby mediating the entry of the virus into the host cell. Neuraminidase is an antigenic glycosylated enzyme which facilitates the release of progeny viruses from infected cells. There are 18 known types of hemagglutinin, of which H1 thru H16 have been found in birds, and 11 types of neuraminidase.
Subtypes
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 protein and a type-1 neuraminidase protein. 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 and N have been isolated from wild birds. Further variations exist within the subtypes and can lead to very significant differences in the virus's ability to infect and cause disease.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. As an example, A/chicken/Nakorn-Patom/Thailand/CU-K2/04:- A stands for the genus of influenza
- chicken is the animal species the isolate was found in
- 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.
Genetic characterization
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. 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.Genetic sequencing enables influenza strains to be further characterised by their clade or subclade, revealing links between different samples of virus and tracing the evolution of the virus over time.
Species barrier
Humans can become infected by the avian flu if they are in close contact with infected birds. Symptoms vary from mild to severe, but as of December 2024 there have been no observed instances of sustained human-human transmission.There are a number of factors that generally prevent avian influenza viruses from causing epidemics in humans or other mammals.
- The viral HA protein of avian influenza binds to alpha-2,3 sialic acid receptors, which are present in the respiratory tract and 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.
- The myxovirus resistance protein is an important antiviral restriction factor that inhibits the replication of avian influenza viruses in particular. Human-adapted strains of IAV display reduced sensitivity to human Mx1 compared with avian strains.
- Other factors include the ability to replicate the viral RNA genome within the host cell nucleus, and to transmit between individuals.
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. 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.
Epidemiology
History
Avian influenza is caused by bird-adapted strains of the influenza type A virus. 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.Between 1959 and 1995, there were 15 recorded outbreaks of highly pathogenic avian influenza 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. Since then, several virus strains have become endemic among wild birds with increasingly frequent outbreaks among domestic poultry, especially of the H5 and H7 subtypes.
Transmission and prevention
Birds – Influenza A viruses of various subtypes have a large reservoir in wild waterbirds of the orders Anseriformes and Charadriiformes 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 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.In 2024, the clade 2.3.4.4b H5N1 was documented causing high mortality in migratory shorebirds, particularly in sanderlings along the Atlantic coast of the United States. Affected birds exhibited severe brain and pancreatic damage, highlighting the vulnerability of some shorebird species to HPAI during migration stopovers.
Avian influenza outbreaks in domesticated birds are of concern for several reasons. There is potential for low pathogenic avian influenza viruses to evolve into strains which are high pathogenic to poultry, 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 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.
Other animals – a wide range of other animals have been affected by avian flu, generally due to eating birds which had been infected. There have been instances where transmission of the disease between mammals, including seals and cows, may have occurred.