Silence of the cats: Should we worry about deadly bird flu outbreaks in mammals?

An outbreak of highly pathogenic H5N1 influenza among domestic cats in Poland has rekindled concerns about the risk of the virus spilling over into humans. Scientists have also expressed anxieties about recent bird flu outbreaks in farmed mink and foxes. Yet, although some human infections have occurred, there is currently no evidence of sustained human-to-human transmission.

The good news is that none of the 70 people who had been in contact with the infected cats have reported symptoms.

Meanwhile, a growing understanding of the obstacles these viruses must overcome to infect humans could bolster surveillance efforts and help to keep us protected.

Bird flu

The reason scientists worry about avian influenza or, ‘bird flu’, is because in all four influenza pandemics in recorded history, starting with 1918 ‘Spanish Flu’, the influenza viruses responsible contained at least one genomic segment that was derived from a bird virus.

Another reason for concern is that the H5N1 influenza viruses that are behind recent outbreaks in birds and mammals are associated with a high death rate if they do manage to infect humans. Thankfully, such infections are rare. Globally, between 2003 and April 2023, the World Health Organization (WHO) received 873 reports of human infections with H5N1 and 458 deaths – a case fatality rate of 52%.

“Of course, every death is a tragedy, but in the context of a global health scenario, that is still a very small number,” said Prof Massimo Palmarini, director of the MRC-University of Glasgow Centre for Virus Research in Glasgow, UK.

Infected mammals

H5N1 viruses have been circulating among birds and poultry since the late 1990s, but a current form of the virus called 2.3.4.4b is particularly good at transmitting between wild birds and poultry, resulting in an unprecedented number of deaths in many parts of the world. It is also increasingly triggering outbreaks in mammals, including mink, foxes, seals, otters and cats.

Since 2020, 12 human cases involving the 2.3.4.4b virus have also been reported  four of which were severe. Most of these infections resulted from direct or indirect contact with infected poultry.

Dr Gregorio Torres, head of science at the World Organisation for Animal Health, described recent events as a “paradigm change in the ecology and epidemiology of avian influenza, which has heightened global concern”.

The outbreak in cats in Poland is particularly unusual because, although sporadic H5N1 infections have been reported before in cats, “this is the first report of a high numbers of infected cats over a wide geographical area within a country,” WHO said.

As of 11 July 2023, 29 cats had tested positive for H5N1 from 13 different regions, with genomic sequencing indicating that they all belonged to the 2.3.4.4b group. Fourteen of the infected cats were euthanised and a further 11 died of their illness.

Investigations into the source of these infections continues, with possibilities including direct or indirect contact with infected birds or eating infected birds/food contaminated with the virus.

The good news is that none of the 70 people who had been in contact with the infected cats have reported symptoms. Because of this, the risk is currently assessed as low to moderate for people living with infected cats, and low for the general population. There is also no evidence of cat-to-cat transmission at the current time.

According to Palmarini, there are several barriers that avian influenza viruses must overcome before they pose a substantial threat to humans. Jumping from birds to mammals is one of them, but evolving the ability to easily pass from mammal to mammal could increase the chances of human-to-human transmission.

Mink link

Cats are relatively solitary species, meaning they don’t tend to spend prolonged periods in close contact with many other cats. However, farmed mink do live close to one another, and they are highly susceptible to infection with several viruses that also infect humans – including influenza.

Writing in the latest issue of the Proceedings of the National Academy of Sciences, flu experts Prof Wendy Barclay and Dr Tom Peacock at Imperial College London, UK, warned of the risk mink farming poses for the emergence of future pandemics. “Any situation in which an RNA virus [such as influenza] is allowed to transmit among multiple densely housed animals may lead to the evolution of virus with altered phenotypes, including those with enhanced pandemic potential,” they said.

Also, because mink are susceptible to both human and avian influenza viruses, if animals became infected with both types at once, they could serve as “mixing vessels” for the exchange of genetic material, which could help them further adapt to mammals.

Human adaptation

Even so, to trigger a human pandemic, avian influenza viruses have a further step to overcome. These viruses find it particularly difficult to gain a foothold inside human airways.

Once inside our lung cells, a protein called MX1 stops them from getting into the cell nucleus and replicating, and Palmarini and his team recently discovered a second protein called BTN3A3 that further inhibits their replication. This protein isn’t found in cats, mink, or even some monkeys – it has only evolved in primates.

“All these different barriers slow the virus, and while any of them could be overcome by mutation, when you have a lot of them it is much harder for the virus to be transmitted efficiently,” Palmarini said.

The identification of such factors is important, because it could help scientists to identify the emergence of flu viruses with pandemic potential sooner, and target efforts to contain them, such as by culling or vaccinating infected birds or animals, which would reduce the chances of human infections.

As highly pathogenic H5N1 influenza continues to circulate, global surveillance for any signs that it is adapting to humans are more important than ever.