Review highlights failures in global control strategies for bird flu transmission

A review of sustained mammal-to-mammal bird flu transmission in diverse species, led by The Pirbright Institute, shows global control strategies are not working.

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

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

"Influenza A viruses (IAV) have caused more documented global pandemics in human history than any other pathogen. Historically, swine are considered optimal intermediary hosts that help avian influenza viruses adapt to mammals before jumping to humans," said Dr Peacock, who investigates the drivers of the current H5N1 avian influenza panzootic. "However, the altered ecology of H5N1 has opened the door to new evolutionary pathways."

The review highlights potential gaps in control mechanisms, including a reluctance to engage with modern vaccine and surveillance technologies and a dearth of data collection around the transmission of H5N1 between cows and to humans on US dairy farms.

Whilst previous generations of US cattle producers had eradicated foot-and-mouth disease by rapidly sharing epidemiological data, the authors say months of missing data is leaving researchers, veterinarians, and policy makers in the dark.

H5N1 is a reportable disease in poultry, but not mammals, in the US. The US Department of Agriculture requires H5N1 testing only in lactating cattle prior to interstate movement."

Dr. Thomas Peacock, zoonotic influenza specialist

Current practices for H5N1 testing in wildlife focus on carcasses, not monitoring animals whilst alive, the paper notes, providing opportunities for variants of H5N1 to spread silently undetected.

"What keeps scientists up at night is the possibility of unseen chains of transmission silently spreading through farm worker barracks, swine barns, or developing countries, evolving under the radar because testing criteria are narrow, government authorities are feared, or resources are thin."

An evolutionary process of "genomic reassortment" in viruses with segmented genomes is driving the global panzootic outbreak. When two or more viruses co-infect a single host, they can swap entire segments during genome replication to create novel hybrids.

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

The writers say the prospect of H5N1 becoming continually present in Europe and the Americas is a turning point for High Pathogenicity Avian Influenza (HPAI).

"New control strategies are needed, including vaccination. Influenza vaccines are licensed for poultry that reduce disease burden, but do not prevent infection and have varying degrees of success."

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

"The severity of a future H5N1 pandemic remains unclear. Recent human infections with H5N1 have a substantially lower case fatality rate compared to prior H5N1 outbreak 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 through viral pneumonia in the lung."

Older people appear to have partial immunity to H5N1 due to childhood exposure, whereas younger people born since the 1968 H3N2 pandemic may be more susceptible to severe disease in a H5N1 pandemic.

Dr Peacock's work is funded by UKRI Biotechnology and Biological Sciences Research Council (BBSRC) via the Pirbright Institute's Strategic Programme Grants (ISPGs) and the UK Medical Research Council / Department for Environment, Food and Rural Affairs FluTrailMap One Health consortium, and the BBSRC/DEFRA 'FluTrailMap' consortium.