Influenza A H5N1
Avian influenza refers to disease in birds caused by infection with avian influenza Type A viruses. These viruses occur naturally among wild aquatic birds such as ducks, geese, swans, gulls, terns, storks, plovers, and sandpipers. They can infect domestic poultry and other bird and animal species.
Avian influenza A viruses are classified into two categories: low pathogenicity avian influenza (LPAI) A viruses, and highly pathogenic avian influenza (HPAI) A viruses. Most avian influenza A viruses are low pathogenic and cause few signs of disease in infected wild birds. Highly pathogenic avian influenza viruses cause severe disease and high mortality in infected poultry. Only some avian influenza A(H5) and A(H7) viruses are classified as HPAI A viruses.
Poultry may become infected with avian influenza A viruses through direct contact with infected wild birds or through contact with surfaces that have been contaminated with the viruses. H5N1 was first detected at a goose farm in Guangdong China in 1996 and then spread to poultry farms across China and Hong Kong in 1997. During that outbreak, 860 people became infected and half died.
Around 2005, the virus spilled over into migratory birds, which have since spread it across the world in several big waves. A new variant (H5N1 clade 2.3.4.4b) emerged in October 2020 in the Netherlands that was better adapted to infect all birds and spread faster and farther than any predecessor. The European Food Safety Authority reported that more than 58 million birds had died or been culled in 37 European countries since October 2021.
HPA1 H5N1 arrived in North America by December 2021. Since then, more than 1,100 outbreaks have been reported in 48 states. This was the first avian influenza outbreak in the U.S. since 2016. The previous avian flu pandemic lasted 6 months. The current outbreak has already lasted twice that time and killed many more animals.
The World Organization for Animal Health (WOAH) has raised concerns about the rapid spread of HPA1 H5N1 in Central and South America. Newly affected countries included Bolivia, Chile, Colombia, Costa Rica, Ecuador, Honduras, Panama, Peru, and Venezuela.
Infected birds shed avian influenza through their mucous, salvia, and feces. Other mammals can get sick by inhaling droplets or aerosols containing viral particles. The disease is not transmitted by eating poultry or eggs. Poultry to human transmission can occur by direct contact with contaminated fomites, inhalation of aerosols, or droplet contact with the eyes.
An outbreak of avian influenza H5N1 in October 2022 on a mink farm in Spain provided the strongest evidence so far that the H5N1 strain of flu could spread from one mammal to another. Genetic sequencing showed that the mink had been infected with a new variant of HPA1 H5N1 that had an increased ability to reproduce in mammals. Scientists believe the virus was spread from mink to mink by respiratory transmission. The weekly mortality rate reached 4.3% per week. Workers were forced to cull all 51,986 mink on the farm. Eleven farm workers had been in contact with the infected mink, but all tested negative for H5N1.
In the wild, mink are solitary animals that are unlikely to spread the virus to others. In mink farms, thousands of mink are forced to live together, creating ideal conditions for HPA1 H5N1 to adapt to other mammals including humans.
On February 6, 2024, Peru's National Agrarian Health Service (SENASA) announced it had detected HPA1 H5N1 virus in dead sea lions and one dolphin. SENASA said at least 585 sea lions and 55,000 wild birds in seven of the country's coastal nature preserves had died from avian influenza. Peru’s health ministry also announced that a zoo lion had died from an HPA1 H5N1 infection.
Over the past year, HPA1 H5N1 has shown an increasing ability to jump from birds to mammals. The H5N1 clade (2.3.4.4b) circulating in birds and poultry has gained a mutation that made the virus more recognizable by mammalian airway cells. The list of mammals with confirmed infections in Europe and the Americas now includes badgers, black bears, grizzly bears, bobcats, coyotes, dolphins, ferrets, fisher cats, foxes, leopards, lynxes, mink, opossums, otters, pigs, polecats, raccoons, raccoon dogs, sea lions, seals, and skunks.
In addition to the usual symptoms of influenza, some infected mammals have exhibited neurological symptoms. For example, grizzly bears have became disoriented and partially blind and seals have lost their ability to orient themselves and swim properly.
As of April 23, 2024, goats in Minnesota and 33 dairy cow herds in Texas, Michigan, Kansas, New Mexico, Ohio, Idaho, North Carolina, and South Dakota had tested positive for HPA1 H5N1. Genetic studies have suggested that H5N1 strain infecting cattle was first detected in Texas poultry in the middle of March. Cows were believed to have initially contracted the virus from infected wild birds, but the virus now appears to be spreading from cow to cow. HPA1 H5N1 is often fatal among birds, but so far has caused only mild illness in cows. The virus appears to be much more deadly in cats. Cats on the affected dairy farms have manifested serious neurologic symptoms that have lead to their rapid decline and death.
Cattle that appeared to be healthy when they left a Texas farm appear to infected cattle on a North Carolina farm. This suggests that many cattle are infected but asymptomatic and that cow to cow transmission is occurring. Other evidence suggests that avian influenza has spread from cattle back to poultry.
A farmhand working on one of these dairy farms in Texas tested positive for HPA1 H5N1 after developing conjunctivitis. He became the second known H5N1 infection of a human in the United States. In 2022, a poultry worker in Colorado was exposed to sick chickens and developed mild illness. Veterinarians have heard anecdotes about farm workers ho have developed pink eye, fever, cough, and lethargy but have refused to be tested or seen by physicians.
Genome sequencing of the HPAI H5N1 virus that infected the dairy worker detected a unique mutation (E67K) in the PB2 gene. This mutation enhances RNA polymerase activity and replication efficiency in mammalian cells. E67K was not detected in the PB2 genes of viruses circulating in wild birds, poultry or cattle, suggesting it emerged in the human patient during his infection.
On April 2, the Texas Department of Agriculture an outbreak of avian influenza in large poultry farm owned by Cal-Maine Foods, Inc. This outbreak resulted in the culling of 1.6 million hens and 337,00 pullets. The Michigan Department of Agriculture and Rural Development has also announced an outbreak at a commercial farm in Ionia County.
On April 5, 2024, the CDC issued a Health Advisory entitled: “Highly Pathogenic Avian Influenza A(H5N1) Virus: Identification of Human Infection and Recommendations for Investigations and Response.” The HAN included instructions for infection prevention and control measures, using personal protective equipment (PPE), testing, antiviral treatment, patient investigations, monitoring of exposed persons (including persons exposed to sick or dead wild and domesticated animals and livestock with suspected or confirmed infection with HPAI A(H5N1) viruses), and antiviral chemoprophylaxis of exposed persons.
On April 5, 2024, the United Nations Food and Agriculture Organization (FAO) announced that surveillance in Vietnam had detected a new H5N1 reassortant virus in chickens and mescovy ducks. The virus is a reassortant between the older H5N1 clade (2.3.2.1c) and the newer H5N1 clade (2.3.4.4b) that began circulating globally in 2021. The reassortant virus contains genes for the surface proteins of the older clade virus and genes for internal proteins from the newer clade. The FAO stated the reassortant virus posed a significant threat to animal and human health.
On April 23, the FDA reported that 20% of pasteurized commercially purchased milk tested positive for HPA1 H5N1 viral RNA by PCR. However, PCR cannot distinguish between live virus or fragments of viruses that could have been killed by the pasteurization process.
Veterinary epidemiologists at Ohio State University collected 150 commercial milk products from around the Midwest, representing dairy processing plants in 10 different states. They detected viral RNA in 58 samples. This finding indicates that H5N1 is more widespread among dairy herds than previously thought.
FDA is conducting further studies to determine if they can recover live virus from milk that tested positive for H5N1 viral RNA. So far, FDA has not changed its assessment that the nation’s pasteurized milk supply remains safe.
On April 24, the U.S. Department of Agriculture (USDA) announced that lactating dairy cows must be tested for H5N1 before interstate transport. Cows that test positive must be quarantined for 30 days before they can be moved. Laboratories and state veterinarians must report positive influenza nucleic acid test results and serology test results to USDA. Currently, the National Animal Health Laboratory Network has 50 laboratories that can perform the testing.
CDC has maintained that the risk of avian influenza for the general public remains low because there has been no evidence of human-to-human transmission. But with every new outbreak there is a heightened risk that the virus could mutate into a variant much more dangerous to humans.
The FDA is confident its stockpile of two candidate vaccine viruses are well matched against the HPA1 H5N1 virus. However, deployment of the first shots of the vaccines might require weeks to months.
References
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Sidik SM. Bird flu outbreak in mink sparks concern about spread in people. Nature News, January 24, 2023
Agüero, M. et al. Highly pathogenic avian influenza A(H5N1) virus infection in farmed minks, Spain, October 2022, Eurosurveillance 28, issue 3, Jan 19, 2023. https://doi.org/10.2807/1560-7917.ES.2023.28.3.2300001
Kupferschmidt, K. Bird flu spread between mink is a ‘warning bell’. Science, January 27, 2023. https://www.sciencemagazinedigital.org/sciencemagazine/library/item/27_january_2023/4074737/?Cust_No=60472896
Schnirring L, Peru confirms H5N1 avian flu in marine mammals, part of southward spread, CIDRAP, February 7, 2023.
Abbasi J. Bird Flu has begun to spread in mammals – Here’s what’s important to know. JAMA Published online February 8, 2023. doi:10.1001/jama.2023.1317
US Department of Agriculture Animal and Plant Health Inspection Service, 2022-2023 Detections of Highly Pathogenic Avian Influenza in Mammals. Feb 27, 2023, https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/animal-disease-information/avian/avian-influenza/hpai-2022/2022-hpai-mammals
CDC, Technical Update: Summary Analysis of Genetic Sequences of Highly Pathogenic Avian Influenza A(H5N1) Viruses in Texas, April 2, 2024, https://www.cdc.gov/flu/avianflu/spotlights/2023-2024/h5n1-analysis-texas.htm
Food and Agriculture Organization of the United Nations, Stay vigilant with Highly Pathogenic Avian Influenza A(H5N1), April 5, 2024
