The earliest infections of humans by<unk>  coincided with an epizootic (an epidemic in nonhumans) of<unk> <unk>  in Hong Kong's poultry population in 1997. This panzootic (a disease affecting animals of many species, especially over a wide area) outbreak was stopped by the killing of the entire domestic poultry population within the territory. However, the disease has continued to spread; outbreaks were reported in Asia again in 2003. On December 21, 2009 the WHO announced a total of 447 cases which resulted in the deaths of 263. Contagiousness Highly pathogenic<unk> <unk>  is easily transmissible between birds, facilitating a potential global spread of<unk> . While<unk>  undergoes mutation and reassortment, creating variations which can infect species not previously known to carry the virus, not all of these variant forms can infect humans.<unk>  as an avian virus preferentially binds to a type of galactose receptors that populate the avian respiratory tract from the nose to the lungs and 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.<unk>  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<unk>  have typically caught it from chickens, which were in turn infected by other poultry or waterfowl. Migrating waterfowl (wild ducks, geese and swans) carry<unk> , often without becoming sick. Many species of birds and mammals can be infected with HPAI A<unk> , but the role of animals other than poultry and waterfowl as disease-spreading hosts is unknown. According to a report by the World Health Organization,<unk>  may be spread indirectly. The report stated the virus may sometimes stick to surfaces or get kicked up in fertilizer dust to infect people. Virulence<unk>  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,<unk>  has mutated into dozens of highly pathogenic varieties divided into genetic clades which are known from specific isolates, but all belong to genotype Z of avian<unk>  virus<unk> , now the dominant genotype. Figure 1 shows a diagramatic representation of the genetic relatedness of Asian<unk>  hemagglutinin genes from various isolates of the virus<unk>  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<unk>  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<unk>  virus infection in wild aquatic birds since 1961. Genotype Z emerged in 2002 through reassortment from earlier highly pathogenic genotypes of<unk>  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 occurring within this genotype 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. Transmission and host range Transmission electron micrograph (TEM) of negatively stained<unk>  A virus particles (small and white) attached to host cells (large and irregular) (late passage). (Source: Dr. Erskine Palmer, Centers for Disease Control and Prevention Public Health Image Library) Infected birds transmit<unk>  through their saliva, nasal secretions, feces and blood. Other animals may become infected with the virus through direct contact with these bodily fluids or through contact with surfaces contaminated with them.<unk>  remains infectious after over 30 days at (over one month at freezing temperature) or 6 days at (one week at human body temperature); at ordinary temperatures it lasts in the environment for weeks. In Arctic temperatures, it does not degrade at all. Because migratory birds are among the carriers of the highly pathogenic<unk>  virus, it is spreading to all parts of the world.<unk>  is different from all previously known highly pathogenic avian flu viruses in its ability to be spread by animals other than poultry. In October 2004, researchers discovered<unk>  is far more dangerous than was previously believed. Waterfowl were revealed to be directly spreading this highly pathogenic strain to chickens, crows, pigeons, and other birds, and the virus was increasing its ability to infect mammals, as well. From this point on, avian flu experts increasingly referred to containment as a strategy that can delay, but not ultimately prevent, a future avian flu pandemic. "Since 1997, studies of<unk>  A <unk>  indicate that these viruses continue to evolve, with changes in antigenicity and internal gene constellations; an expanded host range in avian species and the ability to infect felids; enhanced pathogenicity in experimentally infected mice and ferrets, in which they cause systemic infections; and increased environmental stability." The New York Times, in an article on transmission of<unk>  through smuggled birds, reports Wade Hagemeijer of Wetlands International stating, "We believe it is spread by both bird migration and trade, but that trade, particularly illegal trade, is more important". On September 29, 2007, researchers reported the<unk>  bird flu virus can also pass through a pregnant woman's placenta to infect the fetus. They also found evidence of what doctors had long suspected—the virus not only affects the lungs, but also passes throughout the body into the gastrointestinal tract, the brain, liver, and blood cells. In May 2013, North Korea confirmed a<unk>  bird flu outbreak that forced authorities to kill over 160,000 ducks in Pyongyang.<unk>  transmission studies in ferrets (2011) Novel, contagious strains of<unk>  were created by Ron Fouchier of the Erasmus Medical Center in Rotterdam, the Netherlands, who first presented his work to the public at an<unk>  conference in Malta in September 2011. Three mutations were introduced into the<unk>  virus genome, and the virus was then passed from the noses of infected ferrets to the noses of uninfected ones, which was repeated 10 times. After these 10 passages the<unk>  virus had acquired the ability of transmission between ferrets via aerosols or respiratory droplets. After Fouchier offered an article describing this work to the leading academic journal Science, the US National Science Advisory Board for Biosecurity (NSABB) recommended against publication of the full details of the study, and the one submitted to Nature by Yoshihiro Kawaoka of the University of Wisconsin describing related work. However, after additional consultations at the World Health Organization and by the NSABB, the NSABB reversed its position and recommended publication of revised versions of the two papers. However, then the Dutch government declared that this type of manuscripts required Fouchier to apply for an export permit in the light of EU directive 428/2009 on dual use goods. After much controversy surrounding the publishing of his research, Fouchier complied (under formal protest) with Dutch government demands to obtain a special permit for submitting his manuscript, and his research appeared in a special issue of the journal Science devoted to<unk> . The papers by Fouchier and Kawaoka conclude that it is entirely possible that a natural chain of mutations could lead to an<unk>  virus acquiring the capability of airborne transmission between mammals, and that a<unk> <unk>  pandemic would not be impossible. In May 2013, it was reported that scientists at the Harbin Veterinary Research Institute in Harbin, China had created<unk>  strains which passed between guinea pigs. In response to Fouchier and Kawaoka's work, a number of scientists expressed concerns with the risks of creating novel potential pandemic pathogens, culminating in the formation of The Cambridge Working Group, a Consensus Statement calling for an assessment of the risks and benefits of such research.
Influenza A virus subtype H5N1
Influenza A virus subtype H6N1
Influenza A virus subtype H3N8
Influenza A virus subtype H5N6
Influenza A virus subtype H1N1
Influenza A virus subtype H10N3
SARS-CoV-2 Iota variant
SARS-CoV-2 Alpha variant