[2] Symptoms of A/H5N1 influenza vary according to both the strain of virus underlying the infection and on the species of bird or mammal affected.

[6] Chickens infected with LPAI A/H5N1 virus display mild symptoms or are asymptomatic, whereas HPAI A/H5N1 causes serious breathing difficulties, a significant drop in egg production, and sudden death.

[12] Some strains of A/H5N1 which are highly pathogenic to chickens have adapted to cause mild symptoms in ducks and geese,[13][6] and are able to spread rapidly through bird migration.

[14] Mammal species in addition to humans that have been recorded with H5N1 infection include cattle, seals, goats, and skunks.

[15] Due to the high lethality and virulence of HPAI A(H5N1), its worldwide presence, its increasingly diverse host reservoir, and its significant ongoing mutations, the H5N1 virus is regarded as the world's largest pandemic threat.

[25][26] In December 2024, researchers showed one mutation could allow the virus to switch its specificity to human receptors,[27] increasing the risk of human-to-human transmission.

People working with birds, such as conservationists or poultry workers, are advised to wear appropriate personal protection equipment.

The individual was reported to have been older than 65, had underlying medical problems as well as being in contact with multiple sick and dead birds from their backyard flock.

[38] Further variations exist within the subtypes and can lead to very significant differences in the virus's ability to infect and cause disease, as well as to the severity of symptoms.

[54] In the event of an outbreak of human H5N1, the main antiviral drugs recommended are neuraminidase inhibitors, such as zanamivir (Relenza) and oseltamivir (Tamiflu).

[59][60] The next detection, and the earliest infection of humans by H5N1, was an epizootic (an epidemic in nonhumans) of H5N1 influenza in Hong Kong's poultry population in 1997.

Both of these have potential to devastate poultry stocks, and both have jumped to humans with relatively high case fatality rates.

[71] Birds – Influenza A viruses of various subtypes have a large reservoir in wild waterfowl, which can infect the respiratory and gastrointestinal tract without affecting the health of the host.

People working with birds, such as conservationists or poultry workers, are advised to wear appropriate personal protection equipment.

[81] The USDA then introduced various forms of financial support for producers to bolster biosecurity and offset losses from production disruptions as a result of the spread.

As for the future, the American Association of Bovine Practitioners (AABP) and the AVMA are coordinating with federal and state officials to provide further biosecurity guidance.

The USDA's Food Safety and Inspection Service (FSIS) has also tested ground beef and muscle samples from culled dairy cows, with the results also confirming the absence of H5N1 in meat products.

Beginning in September 2024, the FSIS has expanded testing of dairy cows that are going to be slaughtered to further safeguard the meat supply.

Many more outbreaks are recorded, in almost every country in the world, affecting both wild birds and poultry, with occasional spillover events infecting humans.

[102] 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.

[113] In April 2024, spread of H5N1 amongst dairy cow herds in nine states of the USA strongly indicated the presence of cow-to-cow transmission possibly occurring while the animals were being milked.

[114] Around 50% of cats that lived on the affected dairy farms and were fed unpasteurised milk from symptomatic cows died within a few days from severe systemic influenza infection, raising significant concerns of cross-species mammal-to-mammal transmission.

[116] Novel, contagious strains of H5N1 were created by Ron Fouchier of the Erasmus Medical Center in Rotterdam, the Netherlands, who first presented his work to the public at an influenza conference in Malta in September 2011.

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.

[118] 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.

[120][121][122] The papers by Fouchier and Kawaoka conclude that it is entirely possible that a natural chain of mutations could lead to an H5N1 virus acquiring the capability of airborne transmission between mammals, and that a H5N1 influenza pandemic would not be impossible.