Version July 2025
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 —
Eighteen hemagglutinin (H1-H18) and 11 neuraminidase (N1-N11) virus subtypes occur in the natural reservoir of aquatic birds and mammals. 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 a potential pandemic risk [1]; 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 ribonucleic acid (RNA) segments, resulting in a new "reassorted" virus with novel surface proteins to which there is little population immunity.
●Genetic reassortment between avian and human influenza viruses can occur following dual infection in mammal hosts. Historically, pigs have been considered to play an important role in the evolution of human pandemic strains. Pig tracheal epithelial cells contain receptors for both avian and human influenza viruses, so they can support simultaneous replication of viruses with human or avian origin. Therefore, it has been proposed that genetic reassortment between human and avian viruses 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 [1]. Enhanced surveillance and awareness have led to the isolation of other avian influenza virus subtypes from humans, highlighting the pandemic potential of these viruses.
GLOBAL SPREAD —
The mechanism of avian influenza introduction appears to vary by region. Introduction into countries of Asia 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 [2].
TRANSMISSION —
Virus transmission to humans may occur in the setting of exposure to infected birds and, more recently, dairy cows [3]:
Between birds and humans — Infected birds shed viruses in secretions and excretions. Transmission can occur if the 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) [4-6]. Exposure to sick or dead poultry during the week before illness is the most common risk factor for human H5N1 infection [7,8]. Potential transmission routes include inhalation, mucosal contact (conjunctival or oral), and consumption of raw or undercooked eggs.
●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 [9,10]. 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) [14]. 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 [15].
Between cows and humans
●H5N1 – In 2024, H5N1 virus infections were confirmed among dairy cattle herds in the United States and have been confirmed in at least 17 states [16]. Affected cows may display decreased lactation and low appetite. The isolated H5N1 viruses have been similar in lineage to circulating clade 2.3.4.4b viruses in wild birds and poultry, with no changes that would make them more transmissible to humans [17]. Milking procedures may be a primary route of H5N1 transmission among cattle [18,19] and between cattle and humans [20,21]. Detection of H5N1 virus in high concentrations in milk samples from infected dairy cattle raises the potential for onward transmission following consumption of unpasteurized infected milk. Ingestion of infected milk by cats has resulted in cross-species transmission [21]; thus far, virus transmission via human ingestion of infected milk has not been confirmed.
Transmission among other animals — The mammalian host range for H5N1 includes swine, cats, dogs, minks, and rats [22-26].
Historically, pigs have been considered likely intermediary hosts, as these animals can be infected with both avian and human influenza A viruses – raising concern for the possibility of genetic reassortment, making the virus more easily transmissible to humans.
However, widespread circulation of clade 2.3.4.4b H5N1 viruses among wild bird populations since 2021 has increased spillover events with sustained mammal-to-mammal H5N1 transmission on mink fur farms [25] and among marine mammals (including elephant seals) [27], raising the possibility of the emergence of adapted, more human-like strains from other infected animals.
Infection may be transmitted between cats or from birds to cats via consumption of wild birds or undercooked infected poultry [28,29]. In addition, H5N1 virus has been detected in two indoor domestic cats with respiratory and neurologic illness that lived in homes of dairy workers but had no known direct exposure to H5N1–affected farms [30].
Human-to-human transmission
●H5N1 − Limited, nonsustained human-to-human transmission of H5N1 has occurred [31-33]. 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 [34].
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 [35].
●H7N9 − Several small clusters of human infections have been reported; however, there is no evidence of sustained human-to-human transmission [14,36,37].
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 [14]. 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 [38].
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 [31,32].
AVIAN INFLUENZA H5N1 —
Highly pathogenic avian H5N1 influenza viruses are endemic among wild bird and poultry populations in Asian countries [39,40] (table 1). Between 2003 and 2025, more than 954 human cases from 24 countries were reported to the World Health Organization (WHO) [41].
Since 2021, waves of avian influenza H5N1 activity in wild birds and poultry have occurred throughout Eurasia, Africa, and North America [1]. Wild birds, including seagulls, have reintroduced H5N1 into North American poultry flocks, causing significant economic damage to poultry production. Since 2024, H5N1 outbreaks have occurred among dairy cattle in the United States.
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. (See 'Virology' above.)
Epidemiologic timeline
●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 [42,43]. 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 [44]. Serologic surveillance revealed little evidence of human-to-human transmission, and no further cases were reported following mass culling of poultry [43,45,46].
●2003 − H5N1 re-emerged in humans in 2003 when two culture-confirmed cases occurred in a family group returning to Hong Kong from China [47]. 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 [48,49].
●2005 to 2020 − 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, demonstrating spread among migratory birds [50].
In October 2005, when large outbreaks of H5N1 affected poultry in eastern Turkey, outbreaks in multiple provinces were reported, despite the 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 [4].
Since 2006, rapid geographic spread of H5N1 viruses 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 viruses were isolated in migratory wild birds and concurrent poultry farm outbreaks in several European Union countries, suggesting multiple introductions from wild birds. The accumulation of mutations in the H5 hemagglutinin has allowed evolution of phylogenetically distinct genetic groups or clades of circulating H5 viruses, with clade 2.3.3.4b viruses causing frequent outbreaks among wild birds and poultry in Eurasia.
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 [51]. The first H5 viruses detected in wild and domestic birds in the United States and Canada occurred during late 2014 and 2015 [52,53]. These viruses caused multiple poultry farm outbreaks but were not sustained within wild bird populations.
●2021 to 2023 – In 2021, the clade 2.3.4.4b H5 viruses circulating among birds in Europe underwent genetic reassortment, generating new genotypes of avian H5N1 viruses highly adapted to avian spread, resulting in sustained virus activity and outbreaks among wild birds [54]. Since late 2021, these clade 2.3.4.4b H5N1 viruses have been introduced into North America, resulting in large outbreaks among wild birds and poultry, with spillover events into mammals – often with close human proximity [55].
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 [56]. In May 2023, a further three asymptomatic poultry cullers exposed to infected birds had H5N1 viruses isolated during enhanced surveillance [57].
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 [58].
In September 2022, two asymptomatic poultry workers involved with outbreak control on a farm in Spain had H5N1 detected from nasal samples [25].
In 2023, the first human H5N1 cases in South America were reported. In Ecuador during January 2023, a nine-year-old girl was hospitalized with respiratory symptoms following exposure to infected backyard poultry [59]. In Chile, March 2023, a 53-year-old man developed severe pneumonia and respiratory failure requiring ventilation following exposure to infected aquatic wildlife [60].
●2024
•United States – Clade 2.3.4.4b H5N1 viruses have been associated with ongoing multistate dairy cattle outbreaks following introduction from wild birds, with sustained cow-to-cow transmission. At least 70 cases of H5N1 were reported in a variety of farm workers from several states [61-69]. Mild conjunctivitis and/or upper respiratory syndromes have been described.
In September 2024, a case of avian influenza in Missouri was identified through the state's seasonal influenza surveillance system; the illness developed in the absence of known animal exposure [70,71].
•Worldwide – Globally, 72 human cases of H5N1 were reported in 2024 [72].
●2025 – The first H5N1 death in the United States was reported in Louisiana in a woman who had exposure to infected backyard poultry flocks [73]. Additional updates may be found on the United States Centers of Disease Control & Prevention (CDC) website.
Seroprevalence — In April 2024, sampling from two dairy cattle farms in Texas detected H5N1 in 9 of 14 milk specimens (64 percent); in addition, serologic evidence of H5N1 infection was detected among 2 of 14 farm workers (14 percent) [74].
Between June and August 2024, a serologic study was conducted in Michigan and Colorado among 115 dairy worker volunteers [20]. Serologic evidence of H5 infection was observed in eight individuals (7 percent); all reported cleaning milk parlors and/or milking cows. Four of the eight workers reported symptomatic illness shortly before seropositivity was detected; of these, three had ocular manifestations suggestive of conjunctivitis. Approximately 50 percent reported no symptoms.
In September 2024, the CDC conducted an HPAI A(H5) serosurvey among 150 veterinary practitioners in 46 states with cattle exposure in the previous three months [75]. Serologic evidence of recent infection with HPAI A(H5) virus was observed in three individuals (2 percent), including two without exposures to animals with known or suspected HPAI A(H5) virus infections, and one who did not practice in a state with known HPAI A(H5) virus–infected cattle.
Historically, 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 [76].
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 [77].
Antigenic drift — Influenza H5N1 has undergone genetic evolution and antigenic drift since its emergence in humans in 1997; significant antigenic differences have been observed between hemagglutinin genes in viruses isolated in 1997, viruses isolated between 2003 and 2010 [78,79], and those emerging after 2021.
●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 [8,80-82].
●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 [46,80,83].
Since undergoing genetic reassortment, increasing transmissibility among birds in 2021, clade 2.3.4.4b H5N1 viruses have become endemic in wild birds and continue to cause intense outbreaks in North and South America, Europe, and Africa. Clade 2.3.2.1a H5N1 viruses also continue to circulate in South Asia.
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 among patients infected with other clades [84].
AVIAN INFLUENZA H7N9 —
Avian influenza A H7N9 virus appears to have derived from multiple reassortment events of several avian influenza viruses (figure 1) [85-88].
Epidemiologic timeline — Some reported human influenza cases are summarized in the table (table 1).
●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 [14,85,89,90]. Between 2013 and 2017, annual epidemics of avian influenza A H7N9 resulted in more than 1560 reported cases [91].
During the 2015 to 2016 and 2016 to 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 areas [92].
●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 [93-95]. 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 [96,97].
OTHER AVIAN INFLUENZA STRAINS —
Some reported human influenza cases are summarized in the table (table 1).
●Avian influenza H3N8 – Since 2022, avian influenza H3N8 viruses have been isolated from three individuals in China, ranging from mild respiratory symptoms to severe fatal pneumonia in an immunocompromised patient with multiple myeloma [98-100].
●Avian influenza H5N2 – In May 2024, avian influenza H5N2 was isolated in Mexico from a 59-year-old man with multiple medical comorbidities [101]. He presented with acute shortness of breath and diarrhea, and died after hospitalization. Avian influenza H5N2 viruses of both low and high pathogenicity circulate among poultry and wild birds in Mexico [102].
●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 [103-107]. Avian influenza H5N6 viruses have also been detected among wild birds in England, but no virologically proven human infections have been identified [108].
●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 [109-111]:
•H7N7 – Extensive outbreaks of H7N7 infection occurred in poultry in the Netherlands in 2003 [110,112,113]. Among workers involved in the control of these outbreaks, including the 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 [112]. All genes from the human viruses were avian in origin.
•H7N3 – In 2004, an outbreak of highly pathogenic avian influenza H7N3 occurred in poultry in British Columbia, Canada [114,115].
•H7N2 – A case of H7N2 infection was described in an immunocompromised patient in New York, United States, in 2004 who was hospitalized with a respiratory illness; no exposure was identified [116,117].
An outbreak of H7N2 was described in the United Kingdom in 2007 [118].
A veterinarian in New York, United States, developed an H7N2 infection in 2016 after collecting deep oropharyngeal aspirates from cats with H7N2 infection as part of an outbreak investigation at an animal shelter [111]. A second case was identified by serologic analysis in an animal shelter worker who had multiple direct cat exposures [119].
•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 [120].
●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 [121]. 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 [122-124]. In Hong Kong between 1999 and 2009, influenza H9N2 viruses were first isolated mainly from children with mild, self-limited respiratory infections [4,125]. More than 115 human infections have been identified, mainly in children in China and subsequently in Cambodia [81,126,127], India [128], and Vietnam [129].
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 [130].
●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 [131]. The patient had visited a live-bird market four days prior to the 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 [132]. 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 [131].
•H10N7 − Mild human infections with avian influenza A H10N7 have been reported in Egypt and Australia among individuals with poultry exposure [133,134].
•H10N5 – In December 2024, influenza H10N5 was isolated from a 63-year-old woman in Anhui, China, with underlying chronic medical conditions; she developed severe respiratory failure and died in the hospital. Molecular analysis suggests reassortment between avian influenza viruses from different migratory bird flyways [135].
•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 [136]. 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 steatotic liver disease; he developed severe pneumonia and recovered with intensive care [19]. 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 —
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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)")
SUMMARY AND RECOMMENDATIONS
●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 countries in Asia appears to occur mainly via domestic poultry, while introduction into Europe and the Americas appears to occur via wild bird migration; in Africa, both mechanisms have occurred. Some reported human influenza cases are summarized in the table (table 1). (See 'Global spread' above.)
●Transmission (see 'Transmission' above):
•Between birds and humans – 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.
•Between cows and humans – In 2024, H5N1 virus infections were confirmed among dairy cattle herds in several states in the United States. Milking procedures may be a primary route of H5N1 transmission among cattle and between cattle and humans.
•Human-to-human transmission – 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.
●Avian influenza H5N1 − Pathogenic avian H5N1 influenza viruses have spread to all continents. Since 2003, more than 950 human cases in 24 countries have been reported to the World Health Organization (WHO). Since 2021, new waves of avian influenza H5N1 activity in wild birds and poultry have occurred throughout Eurasia, Africa, and North and South America. The first human case of H5N1 in the United States was reported in 2022, with the first death in 2024. During 2024, extensive H5N1 outbreaks have occurred among United States dairy herds, with more than 60 human cases. (See 'Avian influenza H5N1' above.)
●Avian influenza H7N9 − Pathogenic avian H7N9 influenza viruses appeared initially in eastern China. Between 2013 and 2017, annual avian influenza A H7N9 epidemics resulted in more than 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.)
