Since 2020, outbreaks of avian influenzasubtype H5N1 have been occurring, with cases reported from every continent except Australia as of November 2024.[1][2][3][4] Some species of wild aquatic birds act as natural asymptomatic carriers of a large variety of influenza A viruses, which can infect poultry, other bird species, mammals and humans if they come into close contact with infected feces or contaminated material, or by eating infected birds.[5] In late 2023, H5N1 was discovered in the Antarctic for the first time, raising fears of imminent spread throughout the region, potentially leading to a "catastrophic breeding failure" among animals that had not previously been exposed to avian influenza viruses.[6] The main virus involved in the global outbreak is classified as H5N1 clade 2.3.4.4b, however genetic diversification with other clades such as 2.3.2.1c has seen the virus evolve in ability to cause significant outbreaks in a broader range of species including mammals.[7][8][9]
H5N6 and H5N8 viruses with the H5-2.3.4.4b hemagglutinin (HA) gene became prominent globally in 2018–2020.[8][10] In 2020, reassortment (genetic "swapping") between these H5-2.3.4.4b viruses and other strains of avian influenza led to the emergence of a H5N1 strain with a H5-2.3.4.4b gene.[8] The virus then spread across Europe, detected there in autumn, before spreading to Africa and Asia.[1] It continues to swap genes with local flu viruses as it travels the globe.[11]: (fig.1)
Timeline
2020 and prior
Genetic reassortment of several influenza A strains culminates in the emergence of a highly pathogenic H5N1 subtype bearing the clade 2.3.4.4b hemagglutinin (HA) gene.[13][12]
In January 2022, an infection in an eighty-year-old man was reported, who raised ducks in England.[1] Also in January, infections were reported from the United States in wild birds.[1] In February, infections were reported from commercial poultry centres in the U.S., and Peru reported infections in sea lions.[1][16] The virus continued to spread further, infecting additional species of mammals. In October, a mink farm in northwest Spain was affected.[1] In December, a HPAI H5N1 subtype of clade 2.3.4.4b was found in a captive Asian black bear and in wild and captive birds in a wildlife park in France.[17]
A human case of H5N1 was reported in the U.S. in April, "though this detection may have been the result of contamination of the nasal passages with the virus rather than actual infection."[1][18] In September, Spain reported a human case; this was followed by a second case in November, in a person who worked at the same poultry farm as the first. Both were asymptomatic.[1][19] In November, China reported a human case, infected due to contact with poultry. The case died from their infection.[1]
A mass Caspian seal die-off in December 2022, with 700 infected seals found dead along the Caspian Sea coastline of Russia's Dagestanrepublic, worried researchers regarding the possibility that wild mammal-to-mammal spread had begun.[20]
2023
Antarctic islands
H5N1 was first detected in the islands of the Antarctic region in October 2023, via a brown skua on Bird Island, near South Georgia. Within several months, hundreds of elephant seals were found dead, as well as fur seals, kelp gulls and further brown skua.[21]
Arctic
In December 2023, conservation officials confirmed that a polar bear had died of H5N1 near Alaska's northernmost city, Utqiagvik.[21]
Brazil
On May 22, Brazil declared an 180-day "animal health emergency" in response to eight cases of H5N1 found in wild birds. Although Brazil's major poultry-producing regions are in the country's south and the infections were found in Espirito Santo state and Rio de Janeiro state, Brazil, as the world's largest exporter of chicken meat, created an emergency operations center to plan for and mitigate potential further spread of H5N1.[22]
Canada
On April 1st of 2023 a domestic dog in Oshawa, Canada was tested positive for H5N1.[23]
Cambodia
In February 2023, Cambodia reported the death of a girl due to H5N1 infection after developing symptoms on 16 February.[24][25] The girl's father also tested positive for the virus. The World Health Organization (WHO) described the situation as "worrying" and urged "heightened vigilance".[26][27][28] Further sequencing determined that at least one of the two cases was from an older H5N1 clade, 2.3.2.1c, which had circulated as a common H5N1 strain in Cambodia for many years, rather than the more recent clade 2.3.4.4b, which had caused mass poultry deaths since 2020. This older clade had jumped to humans in the past yet hadn't previously resulted in any known human-to-human transmission.[29]
On March 1, 2023, as Taiwan raised its travel alert for Cambodia, the WHO and the U.S. Center for Disease and Control and Prevention (CDC), in concert with Cambodian authorities, determined that both of the individuals had been infected through direct contact with poultry.[30][31]
South America
In late February 2023, Argentina confirmed a case of H5N1 in industrial poultry, in the Rio Negro province. Avian product exports were suspended as a result.[32]
In late March 2023, Chile detected H5N1 in a 53-year-old man who had severe symptoms.[35] The patient survived but had to stay on a ventilator. The virus was determined to be in the 2.3.4.4b lineage.[36]
In September 2023, Uruguay reported upwards of 400 seals and sea lions found dead of H5N1 on the nation's Atlantic coastline and along the River Plate.[37] Between January and October 2023, at least 24,000 South American sea lions died from H5N1 flu, with the outbreak starting on the Pacific coast of Peru, moving down the coast to Chile and then up the Atlantic coast of Argentina.[38]
According to a 2024 paper, a large outbreak of H5N1 killed 70% of Southern elephant seal pups born in the 2023 breeding season. In surveyed areas of Península Valdés, Argentina, seal mortality rates exceed 96%.[7] A February 2024 article reports that the outbreak in South America has, since 2022, killed at least 600,000 wild birds and 50,000 mammals.[7]
2024
Southeast Asia
A cluster of five human infections of H5N1 occurred in Cambodia in late January and early February; one patient died. All patients had recent contact with sick poultry. Genetic sequencing revealed that they were infected by clade 2.3.2.1c, a different lineage from the 2.3.4.4b clade that is causing global outbreaks.[39] A person in Vietnam died of H5N1 infection around the same time, clade unknown.[40]
In April 2024 the FAO reported that recent reassortment in the Greater Mekong Subregion has produced viruses that carry internal genes from the 2.3.4.4b lineage but the H5 gene from the older 2.3.2.1c lineage. These viruses have been implicated in human cases.[41]
On April 5, the Philippines reported a H5N1 outbreak on a poultry farm in Leyte, which killed 4,475 birds. Earlier in the year, the Philippines Department of Agriculture temporarily banned poultry exports from several countries including Japan, Belgium, and France.[42]
On July 6, it was reported that two Cambodian children became sick with H5N1 infections after handling dead chickens.[43]
India
On April 18, a H5N1 outbreak was detected in ducks in two parts in Alappuzha district, Kerala. The District Collector has decided to initiate the process of culling domestic birds within a 1 kilometre radius from the epicentre of the outbreak.[44] As of May 9, district officials have culled 60,232 birds in Alappuzha. Farmers were compensated ₹100 per ducklings and chicks, ₹200 per older bird, and ₹5 per egg destroyed.[45]
On April 2, a dairy worker in Texas became infected, and strong indications of cow-to-cow spread were evident as cow herds in five different states became ill.[51] A few days later, on April 4, H5N1 was confirmed to have spread to several additional dairy herds in six US states, including Texas, along with Idaho, Kansas, New Mexico, Ohio and Michigan. Scientists deemed these to be either cow-to-cow transmission or spillover from wild birds.[52][53][54] On April 11, H5N1 was found in dairy cattle herds in North Carolina and South Dakota.[55][56]
On April 10, researchers found several cases of HPAI H5N1 in animals in New York City, including three Canada geese, a red-tailed hawk, a peregrine falcon, and a chicken.[57][58] Scientists have also found cases of H5N1 of clade 2.3.4.4b in common bottlenose dolphins from Florida.[59]
On April 26, the FDA reported the virus had spread to cow herds in nine states, including Colorado, with one in five U.S. commercial milk samples testing positive for traces of bird flu.[60][61] H5N1 was found to be present at high levels in the mammary glands of affected cows, and cats that consumed unpasteurized milk from symptomatic cows displayed a high mortality rate from a severe systemic influenza infection.[62] More than half the cats on one farm died after drinking raw milk from infected cows.[63]
On May 16, the US Department of Agriculture's National Veterinary Services Laboratories confirmed positive tests for the virus in alpacas on a farm in Idaho, who had to be culled.[65]
On May 22, a farm worker in Michigan was infected with the bird flu due to their regular exposure to infected dairy cows. The person had mild symptoms and recovered.[66] It was shown that H5N1 can persist on milking equipment, which provides a probable transmission route for cow-to-cow and cow-to-human spread.[67] On May 30, it was announced that a second Michigan farm worker from a different dairy farm had been diagnosed with bird flu after exhibiting respiratory symptoms.[68][69]
In early June, a flock of 4.2 million egg-laying chickens and a flock of 103,000 turkeys were infected in Iowa.[70] It was also that reported that HPAI H5N1 had spread to dairy herds in Iowa,[71] as well as Minnesota, Wyoming and Oklahoma,[72] increasing the number of states with infected dairy herds to thirteen.[73][74][75] As of June 6, infected dairy cows in five states, South Dakota, Michigan, Texas, Ohio, and Colorado, had died from the H5N1 avian flu, with an estimated mortality rate of up to 10%.[76]
Beginning in late June, the USDA launched voluntary pilot programs to test bulk milk tanks on dairy farms in four states: Kansas, Nebraska, New Mexico, and Texas. Farmers who volunteer for the program were allowed to move their herds across state lines without additional testing if their bulk milk tanks were found negative for H5N1 for three consecutive weeks.[77]
By the end of July, it had become apparent that Weld County, Colorado had become the centre of the unprecedented multi-species outbreak of H5N1 in the United States. Outbreaks in multiple large poultry facilities and intensive dairy farms led to ten human farm-worker cases being reported in and around the county.[78] Research conducted in this region showed H5N1 as having the ability to replicate copiously in bovine mammary glands leading to multi-directional intra- and inter-species transmission between cows, humans, cats, birds and a raccoon. It was also shown that asymptomatic cows could spread the disease.[79]
In response, the Colorado authorities brought in mandatory milk tank testing (excluding raw milk producers) and an on-line data tracker for human cases in the state.[80]
In late August, H5N1 had spread to dairy cow herds in California.[81]
In September 2024, the CDC confirms that two dairy workers in California have contracted bird flu, marking the 15th and 16th human cases in this year’s ongoing outbreak, which has impacted dairy cows nationwide.[82] The cases occurred in California’s Central Valley, where over 50 herds have been affected since August. Both workers, who had contact with infected cattle, developed mild symptoms, including conjunctivitis. The CDC confirmed the positive test results on Thursday, while state health officials noted that the workers were employed at separate farms, indicating the infections likely resulted from animal exposure rather than human transmission.
In October 2024, a third farmworker in California has tested positive for bird flu, according to the state’s health department, marking the 17th potential human case of H5N1 in the U.S. since March.[83] Like the previous two cases, this farmworker had contact with infected dairy cattle, and investigators believe the transmission occurred from animals rather than between people.
By late October, California had reported that 133 of its 1,100 dairy herds were infected, with a bovine mortality rate of around 15%. The business interests of the heavily corporatised dairy and livestock industries being prioritised over public health and animal welfare was stipulated as the main cause of the failure to control the novel outbreak.[84] Meanwhile, human cases of H5N1 in the USA increased to near forty for the year with infections being reported in six states. H5N1 was also detected in a pig in Oregon, the first ever reported case in the USA.[85]
In May 2024, H5N1 was detected for the first time in Australia after a human child who had returned to the country from India tested positive. The child was infected with the South Asian 2.3.2.1a clade of H5N1 and had severe symptoms but recovered.[88][89]
Control
H5-2.3.4.4b can be prevented by vaccination in chickens. The H5-Re14 (2.3.4.4b) strain used in updated vaccines since 2022 is a reasonably good match for the new virus.[11]
In 2024, Penn Medicine announced it had created a human avian flu vaccine on the same platform as its COVID-19 vaccine. As of May, the experimental mRNA vaccine utilizing lipid nanoparticles (LNPs) has worked to protect lab animals from severe illness and death for at least one year prior to the announcement. The vaccine was tested in mice and ferrets, and all vaccinated animals were found to survive H5N1 infections.[90][91][92]
^European Food Safety Authority, European Centre for Disease Prevention, Control, European Union Reference Laboratory for Avian Influenza; Adlhoch C, Fusaro A, Gonzales JL, Kuiken T, Marangon S, Niqueux É, Staubach C, Terregino C, Aznar I, Muñoz Guajardo I, Baldinelli F (December 2021). "Avian influenza overview September - December 2021". EFSA J. 19 (12): e07108. doi:10.2903/j.efsa.2021.7108. PMC8698678. PMID34987626.