When mink on a large farm in Galicia, a region of northwestern Spain, began dying off in October 2022, vets initially thought the culprit might be SARS-CoV-2, which has affected mink farms in several other countries. But laboratory tests soon revealed something more terrifying: a deadly avian influenza virus called H5N1. Authorities immediately placed the workers at the farm under quarantine restrictions. The more than 50,000 mink at the facility were killed and their carcasses destroyed.
None of the farmworkers became infected. But the episode, described in an article in Eurosurveillance last week, has reignited simmering fears that H5N1 could trigger a human pandemic. The virus is not known to spread well among mammals; people almost always get it from infected birds, not each other. But now, H5N1 appears to have spread through a densely packed mammalian population and gained at least one mutation that favors mammal-to-mammal spread. Virologists warn that H5N1, now ravaging birds around the world, could invade other mink farms and become even more transmissible.
“This is incredibly worrying,” says Tom Peacock, a virologist at Imperial College London. “This is a clear mechanism for an H5 pandemic to start.” Isabella Monne, a veterinary researcher at the European Union Reference Laboratory for Avian Influenza in Italy, where the samples from Spain were sequenced, calls the finding “a warning bell.”
H5N1 was first detected on a goose farm in China in 1996. A large poultry outbreak in Hong Kong in 1997 caused the first documented human deaths and raised the first pandemic fears. Around 2005, the virus spread to migratory birds, which have since spread it around the world in several large waves. A new variant called 126.96.36.199b that emerged in 2020 has spread faster and farther than any predecessor, dealing big blows to the poultry industry in Europe and North America before hitting Central and South America in the fall of 2022. “It seems that this is simply the virus is more adapted to all birds than any other,” says Richard Webby, an influenza researcher at St. Jude Children’s Research Hospital.
Because the receptors to which the virus binds in the upper respiratory tract of birds are less common in the upper respiratory tract of mammals, H5N1 does not greatly affect mammals. But this time, many species of mammals have been infected, including foxes, cats, ferrets, seals, and dolphins, presumably through contact with infected birds. On January 17, Montana authorities said three young grizzly bears euthanized in the fall after becoming seriously ill were also infected with H5N1. People have also been infected. So far there have been six confirmed human infections in the current global wave, including one death.
There are some signs that 188.8.131.52b is less pathogenic in humans than earlier versions, which killed about half of those infected, says Thomas Mettenleiter, director of the Friedrich Loeffler Institute. “Of course, that can also be bad news, because it could make it easier for the virus to start spreading under the radar, giving it a better chance to evolve,” he says. The more often the virus infects mammals, the greater the risk, Webby says. “It’s a numbers game”.
There have been some previous reports of avian influenza outbreaks on mink farms in China, but there is no clear evidence that the virus spreads between animals. In the Spanish outbreak, there seems little doubt that it did. In theory, all sick animals could have acquired the virus from their feed, which included poultry by-products, but no H5N1 outbreaks have been reported in the region where the poultry farms and slaughterhouses that supply the feed are located. And the virus spread from pen to pen as expected if it were transmitted between mink. The chain of infections could have started after an animal caught a sick bird and put it in its cage, says Thijs Kuiken, a veterinary pathologist at the Erasmus University Medical Center.
It is unknown how easily the virus found in Spain could infect or spread between humans. Virus samples sequenced from four mink show several changes compared to the bird virus, including T271A, a mutation in the gene for an enzyme, polymerase. The change, also seen in viral samples from other infected mammals, is known to help H5N1 replicate better in mammalian tissues. However, E627K, another worrisome mutation in the polymerase gene, hasn’t emerged and the gene for hemagglutinin, a protein on the viral surface that binds to the host receptor, hasn’t changed, Peacock says. “We may still have had luck with this one.”
Monne says his team and others are now studying the properties of the mink virus and the effects of the mutations it has accumulated. Among other things, they want to study how well the virus is transmitted through close contact between animals. “We are planning to do aerosol transmission studies as well,” she says.
The outbreak once again highlights the risks of mink farming. SARS-CoV-2, introduced to farms by humans, spread like wildfire among animals but was also transmitted to their keepers, and researchers feared the mink industry could become a permanent source of the virus. infections and a breeding ground for genetic variants. The Netherlands, which had already decided to phase out mink farming by 2024 for ethical reasons, closed all remaining farms in 2021. Denmark culled all of the country’s mink in 2020, but the mink farming ban expired earlier this year. .
Farms pose just as big a threat when it comes to H5N1, Kuiken says. Most of the mammalian species infected with the virus so far are wild predators and scavengers that feed on infected birds: “solitary animals or animals that live in small families,” she says. They are unlikely to spread the virus far or infect humans. On mink farms, thousands of these solitary carnivores are forced to live together, creating the ideal conditions for the avian virus to adapt to mammals. “It’s a human construction,” says Kuiken.
At the very least, biosecurity measures on mink farms should be tightened, Monne says. Farmworkers must wear masks and take other measures to prevent infection, and farms must reduce the risk of accidental introductions of H5N1. “They should keep the animals very carefully away from wild birds.” PeaCock says that maybe it’s time to end mink farming. “That this is happening in Europe today, and after COVID-19, it’s getting to my head,” he says. “It’s a bit of an existential threat.”