H5N1 outbreak: route of mammalian transmission among cattle unclear

What started as a mystery disease in one cattle herd in Texas in March and quickly confirmed as Avian Influenza A H5N1 has now quickly grown to 36 herds across nine states in the U.S. With wider testing of cattle herds ongoing, this number is likely to go up significantly.

Two avian Influenza H5N1 lineages have been spreading across the world. The Influenza A H5N1 lineage 2.3.4.4.b that emerged in 2022 spread across all continents except Australia, affecting and decimating several avian species. The outbreak has pushed many avian species to the verge of extinction and has spilled over to over a hundred mammalian species to date.

It is important to note that the recent outbreak in the U.S. is not solely affecting cattle; farm cats have also been significantly impacted. A total of seven cats have been documented to be infected in the cattle farms. Unlike cattle, cats infected with the virus exhibited severe symptoms, including neurological ones. While there’s one documented case of a human with mild symptoms who had close contact with infected animals, the risk appears low.

A survey in affected regions in the U.S. found traces of the genetic material of the virus in nearly 20% of grocery milk samples using PCR testing, although further studies also confirmed the absence of live virus in the samples. However, this survey also suggests that the outbreak might be more widespread than reported cases. Despite this finding, pasteurisation, a standard milk treatment effectively destroys live viruses thus the public health risk is minimal.

Genomes and insights

Despite controversy surrounding limited metadata, the U.S. Department of Agriculture (USDA) has provided a large tranche of genomic data for the virus following the outbreak which has offered valuable insights into the outbreak. Most significantly, the data suggests that the virus had a single point of introduction in late 2023, and a potential undetected spread among cattle. A number of mammalian adaptation mutations have been identified in the genomes, consistent with the wider spread in cattle. The data also hints at the possibility of reverse spillover events — transmission from cattle back to poultry — which differs from previous avian-to-mammalian transmissions.

Unanswered questions

There are several unanswered questions about the outbreak that remain unanswered. Firstly, the route of mammalian transmission among cattle herds is unclear, while speculations for this include contaminated feed, milking equipment, or even airborne transmission. Secondly, the question of how the virus evaded detection among cattle populations remains open. Finally, the potential of reverse spillover events from cattle to poultry, as suggested by the genomic data, necessitates further research to assess the risk of transmission to humans and develop appropriate mitigation strategies.

Situation in India

India has seen avian influenza outbreaks in poultry this year across four states, Andhra Pradesh, Maharashtra, and more recently in Kerala, and Jharkhand. These outbreaks have largely been limited to poultry. However, the genome sequences from these outbreaks are not yet available in the public domain and therefore the lineages of the affecting virus are not known.

Given the fact that the genetic alterations currently occurring in the virus are not adequate enough to enable human-to-human transmission, the immediate risk of an outbreak in humans remains low. However, close contact with infected birds or animals significantly increases this risk. Though rare, human infections come with a significant mortality rate, and therefore handling of affected birds, animals or infected material should be done only with adequate personal protective equipment and caution. The transcontinental spread of avian Influenza reiterates the need for active surveillance and a much wider collaboration among countries and organizations sharing data and resources for understanding the virus and its transmission dynamics. As the world slowly crawls out of the SARS-CoV-2 pandemic, there has never been a better setting for the global pandemic treaty.

(Bani Jolly is a senior scientist at Karkinos Healthcare and Vinod Scaria is a senior consultant at Vishwanath Cancer Care Foundation)