Is H5N1 bird flu pandemic brewing?

Five years since the highly pathogenic avian influenza (HPAI) H5N1 was detected in 2020, it continues to spread in wide geographic ranges, impacting poultry, wild birds and cattle.

As the panzootic event among the animals enters its sixth year, scientists warn the current strain of bird flu is increasingly infecting a large number of animals.

Globally, from January 1, 2003 to November 5, 2025, some 992 cases of human infections with avian influenza A (H5N1) virus were reported from 25 countries, according to the World Health Organization (WHO). Of these, nearly 48 per cent, or 476 out of 992 cases, were fatal.

“It’s now a global problem,” Ed Hutchinson, professor of molecular and cellular virology at the University of Glasgow, told BBC Science Focus in an interview, adding, “As a disease of wild animals, it’s completely out of control. It’s raging around the world, and there’s no feasible containment method other than just watching it infect huge populations of animals.” 

The current strain was first detected in Southern China in 1997 in poultry and since has evolved into newer sub-types and clades moving from poultry to wild birds in 2005, marine mammals in 2022 to cattle in 2024.

Over time, the hemagglutinin (HA) gene of the virus diversified into numerous genetic groups (clades). 

The HA gene which 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.

The new clade, 2.3.4.4b of H5N1, is known to have evolved between 2018 and 2020, spreading worldwide by 2021-2023. Since February 2022, over 285 million birds have been affected in the US alone.

By far, 71 cases of poultry or cattle to human transmission have been detected with two deaths in the US. 

Multiple studies indicate that the H5N1 virus now possesses a high pandemic risk. Though the virus has been successful in jumping across species, for it to become a pandemic threat, it should gain the ability to transfer between humans, which at present has no evidence of the same. 

However, some studies indicate that the virus is just one mutation away from achieving so.

Another study also indicates that the strain of the avian flu demonstrates higher ability to infect through air compared to its previous variants.

The genome reassortment is the key for the virus to trigger a pandemic and many experts fear that increasing and widespread transmissions among species may increase the ability of the virus to do the same.

Moreover, more research only throws light and indicates higher risks from the virus. A recent research by Cambridge and Glasgow universities suggest that bird flu viruses are resistant to fever, which means that human body temperatures when they rise during a seasonal human flu as a defence mechanism, may not function posing as a significant threat. 

It is due to a specific viral gene (PB1) that allows them to thrive at higher temperatures, similar to birds' body temperatures, which is why pandemic strains often involve avian genes, the scientists noted.

Scientists warn that the world is ignoring the threat from bird flu. In April 2025, scientists through a community Global Virus Network (GVN), which includes human and animal virologists from over 80 centres of excellence and affiliates in more than 40 countries. They urged countries to improve surveillance, implement biosecurity measures and prepare for potential human-to-human transmission.

The virus continues to mutate with increasing potential threats. On December 17, the National Veterinary Services Laboratories (NVSL) completed whole genome sequencing and confirmed that the virus is H5N1 clade 2.3.4.4b genotype D1.1. Analysis indicates that this detection is a new spillover event from wildlife into dairy cattle, separate from previous events, USDA said.

Recently, Indian scientists revealed how once a pandemic strain is unleashed, how a few 2-10 cases detected may still be too late for the virus to spread widely, making containment a challenging task.

Parallel to the ongoing threat, a new Influenza A (H3N2) virus is emerging as a threat to human population. First detected in 1968 among humans, causing one million deaths across the world and 100,000 deaths in the US alone, it is becoming a growing concern.

The flu is not related to bird flu but possesses has higher evolutionary traits compared to its counterparts causing more severe epidemics and higher mortality and morbidity.

The US, during the 2024 and 2025 influenza seasons, reported predominantly a mix of A(H3N2) and A(H1N1) viruses, causing severe impact across all age groups, including children. 

By July, the subclade K of the virus had been detected in patients in the UK, Australia, parts of Africa and Asia. 

WHO said that A(H3N2) subclade K viruses have genetically drifted from related J.2.4 viruses and have several amino acid changes in their HA in comparison. 

This new variant of seasonal influenza is not considered a pandemic strain, but has been reported in several parts of the world due to its ability to partially evade pre-existing immunity. 

From May through November 2025, the subclade K was responsible for 33 per cent of all A(H3N2) cases worldwide, according to Global Initiative on Sharing All Influenza Data, with Europe accounting for 47 per cent. 

Scientists admitted there is uncertainty as the virus has drifted from the subtype J to K. They called for surveillance and monitoring of the virus, while urging development of an effective vaccine.