The unpleasant truth is that another flu pandemic awaits humanity in the future. Whether it will be a relative of the deadly bird flu strain now wreaking havoc on bird populations around the world is anyone’s guess.
Because the virus, called H5N1, can be deadly to birds, mammals and humans, researchers are closely monitoring reports of new cases. Worryingly, the new H5N1 variant that emerged in 2020 has not only spread further than ever before in birds, but has also spread to other animals, raising the specter of a human outbreak.
This variant was linked to the death of seals in Maine last summer. In October, an outbreak of H5N1 occurred on a mink farm in Spain, researchers reported in January in Eurosurveillance . (It’s unclear how the minks were exposed, but the animals were fed poultry offal.) Sea lions off the coast of Peru and wild bears, foxes and skunks that hunt birds or scavenge in the United States and Europe have also tested positive for the virus.
Worldwide, hundreds of millions of poultry have been culled or died from the new variant. It’s also likely that millions of wild birds have died, although few government agencies are counting, says Michelle Ville, a viral ecologist at the University of Sydney who studies bird flu. “This virus is catastrophic for bird populations.”
A few human cases have also been reported, although there is no evidence that the virus is spreading among humans. Of the 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 condition is unknown.
Moreover, four of the reported human cases — including the US case in Colorado and two workers linked to a Spanish mink farm — were in people who had no respiratory symptoms. This leaves open the possibility that these people were not actually infected. Instead, the tests could detect viral contamination in, say, the nose that people inhaled while handling infected birds.
The impossibility of predicting which bird flu viruses might enter humans and cause an outbreak is partly due to gaps in knowledge. These avian pathogens usually do not easily infect or spread to mammals, including humans. And scientists don’t have a complete picture of how these viruses might change to allow human-to-human transmission.
So far, it’s encouraging that so few people have become infected amid such a large outbreak among birds and other animals, says Marie Culhane, a food animal veterinarian at the University of Minnesota in St. Paul. Still, experts around the world are watching closely for any signs that the virus may be spreading 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 that caused the COVID-19 pandemic hit the scene, “we’re already ahead of the game.”
It is not known how the virus must change to spread among humans
This new iteration of avian flu is the so-called highly pathogenic avian flu, which is particularly deadly to both domestic and wild birds. Waterfowl, such as ducks, naturally carry bird flu with little or no signs of infection. But when flu viruses move between poultry and waterfowl, variants with changes that make them lethal to birds can emerge and spread.
Avian viruses can be severe or even fatal to humans. Since 2003, the World Health Organization has reported 873 cases of human infection with H5N1. A little less than half of them died. In February, an 11-year-old girl in Cambodia died after developing severe pneumonia caused by the bird flu virus, the country’s first reported infection since 2014. Her father was also infected with the virus—a different variant than the one causing the widespread outbreak in birds—although he did not develop symptoms. It is not known how the two people were exposed.
Part of what scientists know about H5N1’s pandemic potential comes from controversial research on ferrets more than a decade ago. Experiments have shown that some changes in proteins that help the virus enter cells and make more copies of itself can help the virus travel through the air to infect ferrets, a common laboratory substitute for humans in flu research.
While researchers know these mutations are important in the lab, it’s still unclear how important these changes are in the real world, says Jonathan Runstadler, an ecologist and virologist at the Tufts University Cummings School of Veterinary Medicine in North Grafton, Massachusetts.
Infected mammals
A variety of mammal species have tested positive for bird flu in the United States. Each symbol represents counties in which cases have been reported. The state colors represent the routes that the birds use, called flyways, as they migrate south in the winter or north in the summer.
Detection of a new H5N1 avian influenza variant in US mammals, 2022–2023.
Viruses are constantly changing, but not all genetic changes work together. The changes can help one version of the virus transmit better, while harming another version and making it less likely to spread.
“We’re not sure how critical or big the difference is, or whether we should be concerned about these mutations when they occur in the wild,” Runstadler says. “Or when they occur five years later, when there are other changes in the genetic background of the virus that affect these [початкові] mutations”.
This does not prevent researchers from trying to identify specific changes. Ranstadler and his team look in nature for viruses that have entered new animals and work backwards to find out which mutations were crucial. And virologist Louise Moncla says her lab is trying to develop ways to scan the complete genetic patterns of viruses from past outbreaks to find signatures of a virus that can move between different animal species.
“There’s a lot we don’t know about avian flu viruses and host switching,” says Monkla of the University of Pennsylvania.
Genetic analysis of H5N1 circulating on mink farms in Spain, for example, revealed a change known to help the virus infect mice and mammalian cells grown in the lab. Such a change could make it easier for the virus to spread among mammals, including humans. The researchers concluded that there may have been mink-to-mink transmission on the farm, but it remains unclear what role this particular mutation played in the outbreak.
Runstadler says it’s a numbers game when flu viruses that can be transmitted among mammals can jump from birds. “The more chances you give a virus to spread and adapt, the higher the risk that one of those adaptations will be effective [допомагаючи поширенню вірусу серед інших тварин] or will take root and become a real problem.”
The ongoing outbreak is still a major problem for birds
Despite our inability to predict the human future with H5N1, it is clear that many species of birds—and some of the other animals that eat them—are now dying. And more bird species are dying in this outbreak than in previous ones, Culhane and Wille say.
“We’ve seen huge outbreaks in raptors and seabirds that have never been affected before,” says Ville. It is possible that genetic changes helped the virus spread among birds more efficiently than earlier versions of H5N1, but this is not known. “There’s a lot of research going on to try to understand that,” says Ville.
Historically, these deadly bird flus have not been a persistent problem in America, Moncla says. Sporadic outbreaks of H5N1 variants are usually confined to places like parts of Asia, where the virus has been circulating among birds since it emerged in the late 1990s, and North Africa.
The last major outbreak of bird flu in North America was in 2015, when experts found more than 200 cases of another bird flu virus in commercial and domestic birds across the United States. According to Culhane, the poultry industry has culled more than 45 million birds to stop the spread of the virus. “But it hasn’t gone away 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 into the United States, where tens of millions of poultry have so far been culled to prevent transmission on farms where the virus has been found. By December 2022, the virus had reached South America. Tens of thousands of pelicans and more than 700 sea lions have died in Peru since mid-January.
It’s important to understand exactly how animals other than birds are affected, Culhane says. Highly pathogenic avian influenza affects all organs of birds. So a fox that chews on an infected bird exposes its own mouth, nose and stomach to large amounts of the virus when it eats its food.
Experts are currently monitoring infected animals to provide an early warning if H5N1 starts to spread among mammals.
“I really think the mink outbreak and then the sea lion outbreak is a wake-up call,” Monkla says. “We have to do everything we can to apply all the science we can to try to understand what’s going on with these viruses so that if things change, we’re better prepared.”
