Avian flu was once limited to poultry — here’s how it evolved as a potential trigger for another pandemic

Highly Pathogenic Avian Influenza (HPAI) was first detected in poultry in 1996, but its newer sub-types and clades, particularly since 2021, have transformed it into a major threat capable of triggering a flu pandemic.

Since 2021, the virus has affected at least 485 species from 25 avian groups and 48 new mammal species. By June this year, 142 outbreaks of HPAI had been reported in animals globally, including penguins and polar bears.

These outbreaks have spanned five geographical regions and involved various strains, including HxNx (1), H5Nx (48), H5N1 (85), H5N5 (2), H7N5 (1) and H7N8 (5). Together, these strains pose a growing threat of a potential pandemic.

Previously considered a significant danger to poultry, HPAI has evolved to infect wild birds and mammals, raising concerns from the World Health Organization (WHO) that it could potentially trigger a global pandemic.

The H5N1 strain was first discovered in domestic waterfowl in southern China, causing six human deaths during its outbreak in China and Hong Kong in 1997. Since then, the virus has infected 860 people, with a mortality rate exceeding 50 per cent, according to the United States Centers for Disease Control and Prevention (CDC).

Since its initial detection, the virus has become a recognised public health concern, according to the United Nations.

In 2003, it re-emerged in China and other parts of Asia, leading to widespread poultry outbreaks. By 2005, the virus was detected in wild birds, which then spread it across continents, reaching Africa, the Middle East and Europe.

Over time, the hemagglutinin (HA) gene of the virus diversified into numerous genetic groups (clades). Between 2014 and 2016, multiple genetic lineages (genotypes) were detected and gene swapping led to the emergence of new H5N6 and H5N8 subtypes.

The HA gene further diversified into clade 2.3.4.4 across Asia, Africa, Europe, the Middle East and North America, with H5 viruses combining with different neuraminidase (NA) genes detected in wild birds and poultry.

However, a new clade, 2.3.4.4b of H5N1, evolved between 2018 and 2020, spreading worldwide by 2021-2023.

Studies show that millions of birds have died either from direct infection or have been culled to control outbreaks globally.

In 2022, this clade killed thousands of marine mammals in South America alone. A pre-print study titled Massive Outbreak of Influenza A H5N1 in Elephant Seals at Península Valdés, Argentina: Increased Evidence for Mammal-to-Mammal Transmission reported unprecedented mass mortality of around 17,000 southern elephant seals in October 2023.

This year alone, H5N1 has spread to 191 cattle herds across 13 states in the US, infecting over 100 million animals across 48 states. The virus, now detected in the remotest parts of the world, including Antarctica, is feared to soon reach the Pacific Islands and New Zealand — regions that have so far remained untouched.

According to the Food and Agriculture Organization of the United Nations, the clade 2.3.4.4b A (H5N1) viruses have resulted in a limited number of human cases but have caused significant outbreaks in mammalian species, including aquatic mammals.

Among humans, officials have reported 15 new cases of the virus contracted from poultry and dairy cows. Between 2003 and 2023, 878 people have tested positive for the H5N1 virus, resulting in 458 fatalities, representing a mortality rate of 52 per cent.

The CDC has expressed concern over mutations found in diverse mammal species, especially in the current panzootic, considering them a significant threat.

A study published in The Lancet in May 2024 warned that the pandemic risk from this virus remains high. For avian influenza viruses to become pandemics, they must become transmissible between humans and be able to replicate efficiently. The study noted that “this usually requires reassortment with human influenza viruses, or the virus could undergo adaptation — a process that can take a long time but could be expedited by frequent infection of mammals and humans.”

In an email interview in April 2024, professor Suresh Kuchipudi, chair of the department of infectious diseases and microbiology at the Center for Vaccine Research, University of Pittsburgh School of Public Health, US, said, “While we cannot accurately predict the severity of the virus after it gains the ability to transmit between humans, it is prudent to assume — based on current data — that it is likely to cause more severe disease in humans than COVID-19 and we must prepare for this potential global health emergency.”