Bird flu can jump to mammals. Should we be worried?

An uncomfortable truth is that there is another flu pandemic in the future of mankind. No one knows if it will be a relative of the deadly strain of bird flu that is currently wreaking havoc on bird populations around the world.

Because the virus, called H5N1, can be deadly to birds, mammals and humans, researchers are closely monitoring reports of new cases. Worryingly, a new variant of H5N1 that appeared in 2020 has not only spread further than ever among the birdsbut has also spread to other animals, raising the specter of a human epidemic (SN: 12/12/22).

The variant was related to a seal death in Maine last summer. In October there was a H5N1 outbreak in a mink farm in Spainresearchers reported in January Eurosurveillance. (It’s unclear how the mink were exposed, but the animals were fed poultry byproducts.) Sea lions off the coast of Peru and wild bears, foxes and skunks, which hunt or retrieve the birds, in the United States and Europe have also tested positive for the virus.

Globally, hundreds of millions of domestic poultry have been culled or died due to the new variant. Millions of wild birds are also likely to have died, though few government agencies count, says Michelle Wille, a viral ecologist at the University of Sydney who studies bird flu. “This virus is catastrophic for bird populations.”

A handful of human cases have also been reported, although there is no evidence the virus is spreading among humans. Of seven cases, six people have recovered and one person from China has died. In February, health officials in China reported an eighth case in a woman whose current status is unknown.

Additionally, four of the reported human cases, including an American case from Colorado And two workers linked to Spanish mink farming – were in people who had no respiratory symptoms. This leaves open the possibility that these people were not really infected. Instead, tests may have detected viral contamination, for example in the nose, which people breathed in while handling infected birds.

The impossibility of predicting which bird flu viruses could spread to humans and trigger an epidemic is partly linked to knowledge gaps. These bird pathogens generally do not readily infect or circulate among mammals, including humans. And scientists don’t fully understand how these viruses might have to change for human transmission to occur.

So far, it’s encouraging that so few people have been infected amid such a large outbreak among birds and other animals, says Marie Culhane, a food animal veterinarian at the University of Minnesota at St. Paul. Still, experts around the world are diligently watching for any signs that the virus could evolve to spread more easily between people.

The good news is that flu drugs and vaccines that work against the virus already exist, Wille says. Compared to where the world was when the coronavirus causing the COVID-19 pandemic hit the scene, “we’re already ahead of the game.”

How the virus would need to change to spread among people is a big unknown

This new iteration of bird flu is what is known as highly pathogenic bird flu, which is particularly deadly to domestic and wild birds. Waterfowl such as ducks are natural carriers of bird flu with no or only minor signs of infection. But when flu viruses mix between poultry and waterfowl, variants with changes that make them deadly to birds can emerge and spread.

Avian viruses can be serious and even fatal for humans. Since 2003, there have been 873 human cases of H5N1 infections reported to the World Health Organization. Just under half of those people died. In February, an 11-year-old girl in Cambodia died after developing severe pneumonia from a bird flu virus, the first infection reported in the country since 2014. Her father was also infected with the virus – a different variant of the one causing the widespread outbreak among birds – although he has not developed any symptoms. It is not known how the two people were exposed.

Some of what scientists know about the pandemic potential of H5N1 comes from controversial ferret research made over a decade ago (SN: 06/21/13). Experiments have shown that certain changes to proteins that help the virus enter cells and replicate more could help the virus travel through the air to infect ferrets, a common laboratory surrogate for humans in research on influenza.

While researchers know these mutations are important in the lab, it’s still unclear how crucial these changes are in the real world, says Jonathan Runstadler, a disease ecologist and virologist at the University’s Cummings School of Veterinary Medicine. Tufts in North Grafton, Mass.

Viruses are constantly changing, but not all genetic adjustments work together. A change can help one version of the virus transmit better, while harming another variant and making it less likely to spread.

“We don’t know how critical or important these mutations are or how much to worry about these mutations when they occur in nature,” Runstadler says. “Or when they happen five years later, when there are other changes in the genetic makeup of the virus that impact those [original] mutations”.

That doesn’t stop researchers from trying to identify specific changes. Runstadler and his team are looking for viruses in nature that have spread to new animals and are working backwards to determine which mutations were crucial. And virologist Louise Moncla says her lab is trying to develop ways to scan entire genetic blueprints of viruses from past outbreaks to look for signatures of a virus that can hop between different animal species.

“There’s a ton we don’t know about bird flu viruses and host switching,” says Moncla, of the University of Pennsylvania.

Genetic analyzes of H5N1 circulating in mink farming in Spain, for example, have revealed a change known to help the virus infect mice and mammalian cells grown in the laboratory. Such a change could make it easier for the virus to spread among mammals, including humans. There may have been mink-to-mink transmission on the farm, the researchers concluded, but it’s still unclear what role this specific mutation played in the outbreak.

It’s a numbers game for when flu viruses with the ability to transmit between mammals might make the leap from birds, Runstadler says. “The more chances you give the virus to spread and adapt, the higher the risk that one of those adaptations will be effective. [at helping the virus spread among other animals] or take root and be a real problem.

The ongoing epidemic is still a big problem for birds

Regardless of our inability to predict the future of humans with H5N1, it is clear that many species of birds – and some other animals that eat them – are dying now. And more bird species are dying in this outbreak than previous ones, Culhane and Wille say.

“We saw huge outbreaks of raptors and seabirds, which had never really been affected before,” Wille says. It’s possible that genetic changes helped the virus spread more efficiently among birds than previous versions of H5N1, but that’s unknown. “There are a number of studies going on to try to figure it out,” Wille says.

Historically, these deadly bird flus haven’t been a persistent problem in the Americas, Moncla said. Sporadic outbreaks of H5N1 variants are generally limited to places such as parts of Asia, where the virus has circulated in birds since its emergence in the late 1990s, and North Africa.

The last major bird flu outbreak in North America dates back to 2015, when experts detected more than 200 cases of a different bird flu virus in commercial and backyard poultry throughout the United States. The poultry industry culled more than 45 million birds to stop the spread of this virus, Culhane says. “But it hasn’t disappeared from the rest of the world.”

The latest version of H5N1 arrived on North American shores from Europe in late 2021, first appearing in Canada in Newfoundland and Labrador. From there it spread south to the United States, where so far tens of millions of domestic poultry were culled to prevent transmission on farms where the virus was detected. By December 2022, the virus had reached South America. In Peru, tens of thousands of pelicans and more than 700 sea lions have been deceased since mid-January.

It’s important to understand exactly how animals other than birds are exposed, Culhane says. Highly pathogenic avian influenza infects all organs of a bird’s body. Thus, a fox that swallows an infected bird exposes its own mouth, nose and stomach to a lot of virus when it eats its meal.

For now, experts are keeping tabs on infected animals to provide early warning if H5N1 begins to spread among mammals.

“I think the mink outbreak, and then the sea lion outbreak, is a wake-up call,” Moncla says. “We should do our best to implement all the science we can to try to understand what is happening with these viruses so that if the situation changes we are better prepared.”