What is avian influenza?

Updated: Feb 12, 2020
  • Author: Nicholas John Bennett, MBBCh, PhD, MA(Cantab), FAAP; Chief Editor: Michael Stuart Bronze, MD  more...
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Avian influenza is a slightly misleading term, as influenza is among the natural infections found in birds. The term avian influenza used in this context refers to zoonotic human infection with an influenza strain that primarily affects birds.

Influenza virus is an orthomyxovirus—an enveloped, segmented, negative-sense RNA virus. Influenza virus has 3 strains—A, B, and C. (For additional information on influenza, see Medscape's Influenza Resource Center.) Avian influenza is caused by influenza A virus, which has 8 RNA segments. Avian influenza is a potential and unpredictable threat to humans because of the segmented nature of the genome.

The serotypes of influenza A virus are identified based on the hemagglutinin (H) and neuraminidase (N) proteins; 16 H serotypes and 9 N serotypes have been identified. For example, one currently circulating strain is designated as H3N2. The strain previously considered the greatest threat was H5N1, mostly because of the high associated mortality rate (up to 60%) in infected humans. H5N1 infections have decreased substantially in recent years, and the most recent avian influenza of note is H7N9, first described in China in 2013. [1]

These serotypic differences result in much of the species specificity due to differences in the receptor usage (specifically sialic acid, which binds to hemagglutinin and which is cleaved by neuraminidase when the virus exits the cell).

The immune response to these antigens is responsible for most host protection. The viral RNA polymerase lacks error-checking mechanisms and, as such, the antigenic drift from year to year is sufficient to ensure a significant susceptible host population. However, the segmented genome also has the potential to allow re-assortment of genome segments from different strains of influenza in a co-infected host.

Although all strains of influenza A virus naturally infect birds, certain strains can infect mammalian hosts such as pigs and humans. The re-assortment of an avian strain with a mammalian strain may produce a chimeric virus that is transmissible between mammals; such mutation products may contain hemagglutinin and/or neuraminidase proteins that are unrecognizable to the immune systems of mammals. This antigenic shift results in a much greater population of susceptible individuals in whom more severe disease is possible.

Such an antigenic shift can cause a pandemic, 4 of which have occurred in recorded history. The most striking pandemic occurred in 1918, when the Spanish influenza (H1N1) resulted in approximately 50 million deaths worldwide. Others included the pandemics of 1957 (H2N2) and 1968 (H3N2); smaller outbreaks occurred in 1947, 1976, and 1977. The fact that H3N2 is still circulating without causing an ongoing pandemic highlights the importance of herd immunity. The most recent pandemic was in 2009, caused by a swine-origin influenza of the H1N1 serotype.

Avian influenza has low-pathogenic (LPAI) and highly pathogenic (HPAI) strains. H5N1 is typically a highly pathogenic virus in birds, resulting in severe disease and death. This strain has drawn more attention than other HPAI strains because of ongoing reports of bird-to-human transmissions that result in severe disease in the human host. Recently, some evidence has indicated that H5N1 may cause fewer symptoms in ducks, making them a potential reservoir for infection and spread by migratory flocks. [2] A reassorted H5N1 virus has been reported in the United States among wild birds but is not considered a threat to humans.

Several confirmed cases of human infection with LPAI strains (H7N2 in the United Kingdom and the US states of Virginia and New York; H7N7 in the Netherlands, H9N2 in China and Hong Kong) have been reported. In 2004, one outbreak of an HPAI H7N3 in Canada resulted in mild human disease. [3] In early 2009, a recombinant H1N1 influenza consisting of a mix of swine, avian, and human gene segments spread rapidly around the world, but it was a low-pathogenicity strain.

H5N1 was first reported to cause severe human disease in 1997 in an outbreak among infected chickens on Hong Kong Island. The outbreak was successfully contained with the slaughter of the entire local chicken population (around 1.5 million birds). However, 18 human cases were reported, of which 6 resulted in death. [3] Since then, H5N1 has been found in chickens, ducks, and migratory fowl throughout Asia and is now spreading west through Europe and North Africa. Human cases are following the route of the avian spread, but H5N1 has also been found in dead birds in several countries without any reported human cases [4] (eg, the United Kingdom, Germany; see image below).

Global map of countries where avian influenza (bir Global map of countries where avian influenza (bird and human infections) has been reported. Image courtesy of PandemicFlu.gov.

The latest H7N9 outbreak started in China in 2013 and was initially described in 126 people. Smaller numbers of cases have been reported since, mostly involving direct contact with domestic birds. To date, the H7N9 has spread in the poultry population across China, resulting in more than 1500 reported human reported human infections. [5] One case was imported to Canada in January 2014.

To date, avian influenza remains a zoonosis, with no sustained human-to-human transmission. Family clusters have been reported but appear to be almost always related to common exposures; however, limited human-to-human spread through close proximity could not be officially ruled out. In September 2004, one case in Thailand probably involved daughter-to-mother transmission; the mother died. [6]

A 1996 case of suspected severe acute respiratory syndrome (SARS) was shown to be due to H5N1 influenza. [3, 7]

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