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Influenza A viruses are significant for their potential for disease and death in humans and other animals. Influenza A virus subtypes that have been confirmed in humans, in order of the number of known human pandemic deaths that they have caused, include:
H1N1, which caused "Spanish Flu" and currently causes seasonal human flu
H2N2, which caused "Asian Flu"
H3N2, which caused "Hong Kong Flu" and currently causes seasonal human flu
H5N1, the world's major current pandemic threat
H7N7, which has unusual zoonotic potential and killed one person
H1N2, which is currently endemic in humans and pigs and causes seasonal human flu
H9N2, which has infected three people
H7N2, which has infected two people
H7N3, which has infected two people
H10N7, which has infected two people
Infectivity
Highly pathogenic H5N1
→ Countries with poultry or wild birds killed by H5N1.
→ Countries with humans, poultry and wild birds killed by H5N1.
H5N1 is easily transmissible between birds facilitating a potential global spread of H5N1. While H5N1 undergoes specific mutations and reassorting creating variations which infect species not previously known to carry the virus, not all of these variant forms can infect humans. H5N1, as an avian virus preferentially bind to what are known as α2,3 galactose receptors, which populate the avian respiratory tract from the nose to the lungs. These receptors are virtually absent in humans, occurring only in and around the alveoli, 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.
H5N1 is mainly spread by domestic poultry, 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. Migrating waterfowl (wild ducks, geese and swans) carry H5N1, often without themselves becoming sick. 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.
Virulence
H5N1 has mutated into a variety of strains with 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. Through antigenic drift, H5N1 has mutated into dozens of highly pathogenic varieties divided into genetic clades which are known from specific isolates, but all currently belonging to genotype Z of avian influenza virus H5N1, now the dominant genotype. H5N1 isolates found in Hong Kong in 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 in ducks. This was the first reported case of lethal influenza virus infection in wild aquatic birds since 1961. Genotype Z emerged in 2002 through reassortment from earlier highly pathogenic genotypes of H5N1 that first infected birds in China in 1996, and first infected humans in Hong Kong in 1997. 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 are occurring within this genotype that are increasing their pathogenicity. Birds are also able to shed the virus for longer periods of time before their death, increasing the transmissibility of the virus.
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