Gaps in the data highlight the potential for silent spread

A review of ongoing mammal-to-mammal transmission of avian flu in several species, led by the Pirbright Institute, shows that global control strategies are not working.

To write Natureresearchers analyzed whether outbreaks in European fur farms, South American marine mammals and dairy cattle in the United States raise questions about whether humans are next. Led by zoonotic flu specialist Dr. Thomas Peacock, the scientists evaluated how recent changes in the ecology and molecular evolution of H5N1 in wild and domestic birds increase the chances of spillover to mammals.

They also weighed several evolutionary pathways that could turn the global H5N1 flu panzootic into a human pandemic virus.

“Influenza A viruses (IAV) have caused more documented global pandemics in human history than any other pathogen. Historically, pigs have been considered optimal intermediate hosts that help avian flu viruses adapt to mammals before jumping to humans,” said Dr. Peacock, who is investigating the drivers of the current panzootic bird flu H5N1.

“However, the changed ecology of H5N1 has opened the door to new evolutionary pathways.”

The research points to potential gaps in control mechanisms, including a reluctance to engage with modern vaccine and surveillance technologies and a lack of data collection surrounding H5N1 transmission between cows and humans on U.S. dairy farms.

While previous generations of American livestock farmers had eradicated foot-and-mouth disease by quickly sharing epidemiological data, the authors say months of missing data are leaving researchers, veterinarians and policymakers in the dark.

“H5N1 is a reportable disease in poultry, but not mammals, in the US. The US Department of Agriculture only requires H5N1 testing in lactating livestock prior to interstate movement,” said Dr. Peacock.

Current practices for H5N1 testing in wildlife focus on carcasses rather than monitoring animals while they are still alive, the paper notes, allowing variants of H5N1 to spread silently and undetected.

“What keeps scientists awake at night is the possibility that invisible chains of transmission are spreading silently through farm worker barracks, piggeries or developing countries, developing under the radar because testing criteria are limited, government is feared or resources are scarce.”

An evolutionary process of ‘genomic rearrangement’ in viruses with segmented genomes is driving the global panzootic outbreak. When two or more viruses simultaneously infect a single host, they can swap entire segments during genome replication to create new hybrids.

The reassortment between H5N8 and low pathogenic avian influenza viruses (LPAI), which generated the panzootic H5N1 virus in the Americas, is believed to have occurred in Europe or Central Asia around 2020 and infected South American marine mammals and American dairy cattle.

The authors say the prospect of H5N1’s continued presence in Europe and America is a turning point for highly pathogenic avian influenza (HPAI).

“New control strategies are needed, including vaccination. Influenza vaccines for poultry have been approved that reduce the burden of disease but do not prevent infections and with varying degrees of success.”

Supplies of H5 vaccine that are antigenically related to circulating viruses are available and could be produced at scale using mRNA platforms if H5N1 begins to spread among humans, the authors note.

“The severity of a future H5N1 pandemic remains unclear. Recent human infections with H5N1 have had a significantly lower mortality rate compared to previous H5N1 outbreaks in Asia, where half of people with reported infections died. The lack of severity in US cases may be due to infection through the eye, rather than viral pneumonia in the lungs.”

Older people appear to be partially immune to H5N1 due to childhood exposure, while younger people born since the 1968 H3N2 pandemic may be more susceptible to severe illness in an H5N1 pandemic.

Provided by the Pirbright Institute