Researchers from the Indian Institute of Science’s department of biochemistry have cautioned about a new threat on the horizon that requires urgent attention from the central and state health authorities. They have discovered that the currently circulating and dominant 2.3.4.4b variant of the H5N1 avian influenza virus has undergone genomic mutations that significantly increase the threat of humans getting infected with bird flu. It poses the threat of an outbreak that could be much more challenging to prevent or manage than the Covid pandemic.
The IISc team analysed 7,000 protein sequences of the 2.3.4.4b H5N1 variant found in birds, 820 sequences from non-human mammals, and 35,000 human H1N1 (swine flu virus) and H3N2 (seasonal influenza virus) sequences. They identified rapidly changing amino acids in the sequences, used multiple tools to identify similar regions in various proteins, constructed an evolutionary trend to understand how the viral species diverged from their common ancestor over time, and detailed specific variations in all the proteins of H5N1 infecting non-human mammals and humans to conclude that the 2.3.4.4b variant is much more harmful to humans than its predecessors.
The researchers also cautioned that foxes, as intermediary hosts, harboured the H5N1 strain with the highest human adaptive potential. Indian foxes are spread widely across the subcontinent, mainly in agricultural areas near human settlements, although in low densities. Rural populations can potentially be more exposed to infected birds and non-human mammals, monitoring of which would be a Herculean challenge. According to Wildlife SOS, about 370 species of migratory birds from 29 countries visit India every year.
The challenges of managing a highly infectious bird flu outbreak would be vastly different from those posed by the Covid pandemic, which could be controlled at human entry points. The World Health Organization has recorded 972 cases of confirmed H5N1 influenza leading to 468 deaths globally between 2003 and February 2025. India has reported two deaths in 2021 and 2025 from Haryana and Andhra Pradesh, although these were caused by the 2.3.2.1b H5N1 variant. The virus commonly spreads from infected birds and non-human mammals to humans, rarely from humans to humans, rendering India’s vast rural hinterland vulnerable to its influx and spread. It’s time for the authorities to prepare to tackle this steep challenge and inform the nation about the steps.