INTRODUCTION — Since the early 20th century there have been four influenza pandemics; each has been caused by the emergence of a novel virus which included genes of avian influenza viruses. (See "Influenza: Epidemiology and pathogenesis", section on 'Pandemic and emerging viruses'.)
The epidemiology and transmission of avian influenza will be reviewed here. The clinical manifestations, diagnosis, treatment, and prevention of avian influenza are discussed separately. (See "Avian influenza: Clinical manifestations and diagnosis" and "Avian influenza vaccines" and "Avian influenza: Treatment and prevention".)
VIROLOGY — Sixteen hemagglutinin (H1-H16) and nine neuraminidase (N1-N9) virus subtypes occur in the natural reservoir of aquatic birds. Only three hemagglutinin subtypes (H1, H2, and H3) have caused widespread human respiratory infection. Influenza B viruses are very rarely carried by birds. Issues related to the virology of influenza, including the nature of surface proteins and discussions of antigenic drift and shift, are discussed separately. (See "Influenza: Epidemiology and pathogenesis", section on 'Virology'.)
Pathogenic avian influenza viruses are of concern to humans because they pose potential pandemic risk ; potential mechanisms include:
●Spontaneous mutations could arise in an avian influenza virus that could facilitate airborne transmission to humans.
●Simultaneous infection of a cell by two influenza viruses (such as an avian H5N1 influenza virus and an H3N2 or H1N1 influenza virus) may allow recombination of RNA segments, resulting in a new "reassorted" virus with novel surface proteins to which there is little population immunity.
●Pigs may also play an important role in the evolution of human pandemic strains. Pig tracheal epithelial cells contain receptors for both avian and human influenza viruses, and domestic pigs thus can support simultaneous replication of viruses of both human and avian origin. Therefore, it has been proposed that genetic reassortment between avian and human virus may occur in pigs, leading to a novel strain.
Newly shifted influenza strains have historically emerged in Southeast Asia, where agricultural practices and the close proximity of humans, birds, and swine facilitate virus reassortment and spread.
To date, two avian influenza H subtypes, H5 and H7, have repeatedly emerged as highly pathogenic; this usually occurs when low-pathogenic viruses cross from wild birds into poultry, where changes in the H protein increase their pathogenicity, causing severe disease, substantial outbreaks, and high mortality in chickens .
GLOBAL SPREAD — The mechanism of avian influenza introduction appears to vary by region. Introduction into Asia countries appears to occur mainly via domestic poultry, while introduction into Europe and North America appears to occur via bird migration; in Africa both mechanisms have occurred. These findings are based on analysis of virus phylogenetic relationships, migratory bird movements, and poultry trade patterns .
●Bird to human − Infected birds shed viruses in secretions and excretions. Transmission can occur if virus gets into a person’s eyes, nose, or mouth, or is inhaled.
•H5N1 − Individuals at increased risk of H5N1 infection include those with close or prolonged contact with infected birds or fomites contaminated with bird secretions or excretions, in the absence of protective equipment (including gown, gloves, mask, and eye protection) [3-5]. Exposure to sick or dead poultry during the week before illness is the most common risk factor for human H5N1 infection [6,7].
•H7N9 − Avian influenza A H7N9 viruses have been isolated from poultry (including ducks and chickens) and pigeons and their environment in some areas of China; most samples have been detected in live-poultry markets [8,9]. More than 90 percent of human cases have been associated with exposure to these markets .
It is likely that avian influenza A H7N9 transmission to humans has occurred via secretions or excretions of infected poultry [11-13]. In one study including 131 patients with avian influenza A H7N9 infection, 82 percent had a history of recent exposure to animals (82 percent to chickens, 22 percent to ducks, and 6 percent to swine) . These exposures occurred while visiting or working at a live-animal market.
Wild and domestic songbirds (finches, sparrows, parakeets) have the potential to serve as intermediate hosts, since avian influenza A H7N9 can replicate in and be shed by these birds .
●Other animals − The host range for H5N1 includes birds, cats, dogs, and minks [16-19]. Infection may be transmitted between cats or from birds to cats via consumption of infected poultry or wild birds.
An outbreak of H5N1 virus infection was reported on a mink farm in Spain in October 2022 . This event was notable for mink-to-mink transmission and the presence of an uncommon mutation in the PB2 gene of the isolated virus which may be associated with increased transmissibility.
●Human to human
•H5N1 − Limited, nonsustained human-to-human transmission of H5N1 has occurred [20-22]. Vertical transmission has also been observed; in one pregnant woman with H5N1 infection who died, autopsy demonstrated virus genomic sequences in the placenta and in the fetus .
One study of 26 cluster outbreaks and 113 sporadic cases of H5N1 influenza infection in Indonesia described risk factors for secondary transmission; these included being between 5 and 30 years of age and being a first-degree relative to an index case .
•H7N9 − Several small clusters of human infections have been reported; however, there is no evidence of sustained human-to-human transmission [14,25,26].
In one study including 2675 close contacts of 139 confirmed cases, respiratory symptoms developed in 1 percent of individuals during the seven-day surveillance period . In another study including 330 close contacts of 14 patients who died from avian influenza A H7N9 infection, none developed infection within seven days of monitoring .
●Environmental transmission − Potential environmental modes of transmission of H5N1 influenza include ingestion of contaminated water while swimming, intranasal or conjunctival inoculation during water exposure, contamination of hands from infected fomites, and exposure to untreated poultry stool used as fertilizer [20,21].
AVIAN INFLUENZA H5N1
General principles — Highly pathogenic avian H5N1 influenza viruses are endemic among wild bird and poultry populations in Asian countries [28,29]. From 2003 to the present, more than 880 human cases in 19 countries have been reported to the World Health Organization .
Since 2021, waves of avian influenza H5N1 activity in wild birds and poultry have occurred throughout Eurasia, Africa, and North America . Wild birds, including seagulls, have reintroduced H5N1 into North American poultry flocks, causing significant economic damage to poultry production.
Sporadic human-to-human transmission has raised concern that the H5N1 virus may mutate or combine with genetic material from coinfecting human influenza viruses to generate a novel strain capable of sustained human-to-human transmission with pandemic potential. The World Health Organization has described the threat from H5N1 as a potential public health crisis.
●1997 − The first association of avian influenza H5N1 with human respiratory disease occurred in 1997 in Hong Kong, when 18 cases occurred during a poultry outbreak of highly pathogenic H5N1 influenza in live-bird markets [31,32]. The outbreak was associated with a high mortality rate (33 percent), a high incidence of pneumonia (61 percent), and a high rate of intensive care (51 percent). All virus genes were of avian origin, suggesting that H5N1 had jumped the species barrier without adaptation . Serologic surveillance revealed little evidence of human-to-human transmission, and no further cases were reported following mass culling of poultry [32,34,35].
●2003 − H5N1 re-emerged in humans in 2003 when two culture-confirmed cases occurred in a family group returning to Hong Kong from China . Since 2003, highly pathogenic H5N1 has caused extensive and unprecedented outbreaks among poultry across Eurasia and appears to have become established as an endemic virus in poultry and ducks [37,38].
●2005-2006 − Poultry outbreaks of H5N1 in western China, Mongolia, Kazakhstan, and Russia in 2005 were associated with deaths of wild waterbirds in local lakes. Molecular analysis of H5N1 isolates from Russian outbreaks revealed antigenic similarity to viruses isolated in China, suggesting capability of spread among migratory birds .
In October 2005, when large outbreaks of H5N1 affected poultry in eastern Turkey; outbreaks in multiple provinces were reported, despite culling of domestic and agricultural flocks. The first fatal human cases outside southeastern Asia were detected in early 2006 among Turkish poultry farmers and young children with poultry exposure .
Since 2006, rapid geographic spread of H5N1 virus in wild and domestic birds has been reported in Iraq, Nigeria, Azerbaijan, Bulgaria, Greece, Italy, Slovenia, Iran, Austria, Germany, Egypt, India, France, and Israel. The virus has been isolated in migratory wild birds, and concurrent poultry farm outbreaks in several European Union countries suggest multiple introductions.
●2014 − The first reported human case of H5N1 infection in North America was in 2014; a fatal case occurred in a woman in Canada, following return from a trip to Beijing, China . H5N1 viruses were detected in wild and domestic birds in the United States and Canada in late 2014 and 2015 [41,42].
●2021-2023 – In December 2021, an asymptomatic human H5N1 virus infection was identified in the United Kingdom as part of routine surveillance, in an individual who kept domestic birds .
In April 2022, the first human case of H5N1 in the United States was reported . The case occurred in a person in Colorado with direct exposure to poultry who was involved in culling of poultry with presumptive H5N1 virus infection. The patient reported fatigue and recovered after treatment with oseltamivir .
In September 2022, two asymptomatic poultry workers involved with outbreak control on a farm in Spain had H5N1 detected from nasal samples .
Antigenic drift — Influenza H5N1 has undergone antigenic drift since its emergence in humans in 1997; significant antigenic differences have been observed between hemagglutinin genes in viruses isolated in 1997 and viruses isolated between 2003 and 2010 .
●Clade 1 − Clade 1 viruses caused disease in humans in Cambodia, Thailand, and Vietnam in 2004 and 2005, in Thailand in 2006, and continue to circulate among poultry in Cambodia, with sporadic human infections in Vietnam [7,30,48,49].
●Clade 2 − Clade 2 viruses have been circulating in birds in China and Indonesia since 2003, and spread to the Middle East, Europe, and Africa in 2005. This clade caused human infections between 2005 and 2010, principally in Egypt and Indonesia. Clade 2 has been divided into three subclades, which differ in their geographic distribution; all have been implicated in human infections [35,49,50].
Clade 126.96.36.199b H5N1 viruses have become predominant in 2021-2023 outbreaks in North America, Europe, and Africa.
In one registry including 215 patients from 10 countries with H5N1 influenza infection treated with oseltamivir, mortality was higher among patients infected with a clade 2.1 virus than patients who were infected with other clades .
Seroprevalence — Some studies suggest that subclinical H5N1 infection is relatively uncommon; in a 2020 systematic review including 66 studies of H5N1 seroprevalence among more than 19,000 close contacts of confirmed H5N1 cases or poultry-exposed individuals, seroprevalence rates up to 1.8 percent were observed .
In contrast, other studies suggest a higher prevalence of asymptomatic infection than previously recognized. In a 2014 seroprevalence study among 101 poultry market workers in Indonesia, the seroprevalence of avian H5 influenza was 84 percent; no individuals recalled a severe acute respiratory illness .
Risk factors for H5N1 seropositivity in a 2011 study from Thailand included advanced age, lack of an indoor water source, and chronic pulmonary disease; surprisingly, poultry exposure was not a risk factor for seropositivity .
●2013 to 2017 − In 2013, human cases of novel avian influenza A H7N9 infection were reported to the World Health Organization (WHO); the earliest cases occurred in eastern China [14,55,59,60]. Between 2013 and 2017, annual epidemics of avian influenza A H7N9 resulted in more 1560 reported cases [61-63].
During the 2015-2016 and 2016-2017 seasons, a higher proportion of cases in China occurred in semiurban and rural areas than during earlier waves, when most cases occurred in urban area .
●2017 to present − Since the fall of 2017, relatively few cases of H7N9 infection have been reported . Possible explanations for this observation include aggressive surveillance measures, closures of live-bird markets and farms in affected provinces, culling of infected birds, and bird vaccination [66-68]. Under-reporting may also be a factor.
Geographic distribution — The majority of reported cases have occurred in mainland China. Additional cases have been reported in Hong Kong, Macau, Taiwan, Malaysia, and Canada [62,69,70].
OTHER AVIAN INFLUENZA STRAINS
●Avian influenza H5N6 − Since 2014, avian influenza H5N6 viruses have been isolated from several individuals in China presenting with disease ranging from mild self-limiting respiratory symptoms to severe pneumonia and death [71-74]. Avian influenza H5N6 viruses have also been detected among wild birds in England but no virologically proven human infections have been identified .
●Avian influenza H7 – Issues related to avian influenza H7N9 are discussed above. (See 'Avian influenza H7N9' above.)
Other avian influenza H7 viruses have also been linked to human disease [76-78]:
•H7N7 − Extensive outbreaks of H7N7 infection occurred in poultry in the Netherlands in 2003 [77,79,80]. Among workers involved in the control of these outbreaks, including culling of poultry, there were 83 virologically confirmed cases of H7N7 conjunctivitis (of which five had influenza-like illness) and two cases of isolated respiratory illness . All genes from the human viruses were avian in origin.
•H7N2 − A case of H7N2 infection was described in an immunocompromised patient in New York who was hospitalized with a respiratory illness; no exposure was identified .
A veterinarian in New York developed H7N2 infection after collecting deep oropharyngeal aspirates from cats with H7N2 infection as part of an outbreak investigation at an animal shelter . A second case was identified by serologic analysis in an animal shelter worker who had multiple direct cat exposures .
•H7N4 − Avian influenza H7N4 was isolated from a 68-year-old Chinese woman hospitalized with severe respiratory illness; the same virus was also isolated from her backyard poultry flock .
●Avian influenza H6N1 − In 2013, a previously healthy 20-year-old woman in Taiwan presented to a hospital with pneumonia. She was found to be infected with avian influenza A H6N1, an influenza subtype known to circulate in wild and domestic avian species; this was the first known human case . The patient had no exposure to live animals or raw animal products; no source was identified.
●Avian influenza H9N2 − Avian influenza H9N2 is a virus of low pathogenicity that has become endemic in poultry in Asia, the Middle East, and Africa; it has also been isolated from pigs [85-87]. In Hong Kong between 1999 and 2009, influenza H9N2 viruses were first isolated mainly from children with mild, self-limited respiratory infection [3,88]. More than 70 human infections have been identified, mainly in children in China and subsequently in Cambodia [30,89,90].
Cocirculation and reassortment of H9N2 and H7N9 viruses among poultry have generated genetically diverse H7N9 viruses containing the internal genes of H9N2 viruses, suggesting that H9N2 viruses are important sources for novel viruses of pandemic potential and have contributed to the ongoing evolution of human H7N9 infections .
●Avian influenza H10
•H10N8 − In 2013, the first human infection with avian influenza H10N8 was detected in a 73-year-old woman in China with multiple comorbidities . The patient had visited a live-bird market four days prior to onset of illness. She developed severe pneumonia and died several days after being hospitalized. A second case in China was detected in a 55-year-old woman with severe pneumonia who had also visited a live-bird market.
Avian influenza A H10N8 has been detected in wild and domestic birds in China as well as in South Korea, Japan, the United States, Canada, Italy, and Sweden. The genes of the virus detected from the first human case were all of avian origin, with six internal genes deriving from avian influenza A H9N2 viruses that circulate in poultry in China; the internal genes were substantially different from H10 and H8 viruses previously detected in birds .
•H10N7 − Mild human infections with avian influenza A H10N7 have been reported in Egypt and Australia among individuals with poultry exposure [93,94].
•H10N3 − Avian influenza A H10N3 viruses have been circulating among wildfowl and poultry in south Asia for some years. It can infect healthy adults, with homology suggesting sporadic transmission from poultry:
-In 2021, influenza H10N3 was isolated from a 41-year-old man in Jiangsu Province, China, with diabetes and hypertension; he developed severe pneumonia and recovered after prolonged extracorporeal membrane oxygenation . He had exposure to a live-poultry market within one week before the onset of illness. No infections among close contacts were detected.
-In 2022, influenza H10N3 was isolated from a 32-year-old man in Zhejiang Province, China, with history of fatty liver disease; he developed severe pneumonia and recovered with intensive care . He raised chickens and ducks at home and worked in a slaughterhouse that processed sheep. He had not been in contact with others with respiratory symptoms.
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Bird flu (avian influenza) (The Basics)")
●Virology − Avian influenza viruses are of concern to humans because they pose potential pandemic risk. To date, two avian influenza H subtypes, H5 and H7, have repeatedly emerged as highly pathogenic; this usually occurs when low-pathogenic viruses cross from wild birds into poultry, where changes in the H protein increase their pathogenicity, causing severe disease, substantial outbreaks, and high mortality in chickens. (See 'Virology' above.)
●Global spread − The mechanism of avian influenza introduction appears to vary by region. Introduction into Asia countries appears to occur mainly via domestic poultry, while introduction into Europe appears to occur via bird migration; in Africa, both mechanisms have occurred. (See 'Global spread' above.)
●Avian influenza H5N1 − Pathogenic avian H5N1 influenza viruses are endemic among bird and poultry populations in Asian countries. From 2003 to the present, more than 800 human cases in 19 countries have been reported to the World Health Organization. Since 2021, new waves of avian influenza H5N1 activity in wild birds and poultry have occurred throughout Eurasia, Africa, and North America. The first human case of H5N1 in the United States was reported in April 2022. (See 'Avian influenza H5N1' above.)
●Avian influenza H7N9 − Pathogenic avian H7N9 influenza viruses appeared initially in eastern China. Between 2013 and 2017, annual epidemics of avian influenza A H7N9 resulted in more 1560 reported cases. Since the fall of 2017, relatively few cases have been reported. Possible explanations for this observation include aggressive surveillance measures, closures of live-bird markets and farms in affected provinces, culling of infected birds, and bird vaccination; under-reporting may also be a factor. (See 'Avian influenza H7N9' above.)
●Transmission (see 'Transmission' above):
•Bird to human − Transmission of avian influenza from birds to humans can occur if virus shed in bird secretions or excretions gets into a person’s eyes, nose, or mouth, or is inhaled. Individuals at increased risk of avian influenza infection include those with close or prolonged contact with infected birds or fomites contaminated with bird secretions or excretions, in the absence of protective equipment (including gown, gloves, mask, and eye protection). Exposure to sick or dead poultry during the week before illness is the most common risk factor for human infection with avian influenza.
•Human to human − Limited, nonsustained human-to-human transmission of avian influenza H5N1 and H7N9 has occurred; thus far, there is no evidence of sustained human-to-human transmission.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟