When mink at a big farm in Galicia, a region in northwestern Spain, started to die in October 2022, veterinarians initially thought the culprit might be SARS-CoV-2, which has struck mink farms in several other countries. But lab tests soon revealed something scarier: a deadly avian influenza virus named H5N1. Authorities immediately placed workers on the farm under quarantine restrictions. The more than 50,000 mink at the facility were killed and their carcasses destroyed.
None of the farm workers became infected. But the episode, described in a paper in Eurosurveillance last week, has reignited long-smoldering fears that H5N1 could trigger a human pandemic. The virus is not known to spread well between mammals; people almost always catch it from infected birds, not one another. 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 rampaging through birds around the world, could invade other mink farms and become still more transmissible.
“This is incredibly concerning,” 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’s Reference Laboratory for Avian Influenza in Italy, where the samples from Spain were sequenced, calls the finding “a warning bell.”
H5N1 was first detected at a goose farm in China in 1996. A big poultry outbreak in Hong Kong in 1997 led to the first documented human deaths and sparked the first pandemic fears. Around 2005, the virus spilled over into migratory birds, which have since spread it across the world in several big waves. A new variant named 220.127.116.11b that emerged in 2020 has spread faster and farther than any predecessor, dealing huge blows to the poultry industry in Europe and North America before arriving in Central and South America in the fall of 2022. “It seems this virus is just more adapted to all birds than any others have been,” says Richard Webby, an influenza researcher at St. Jude Children’s Research Hospital.
Because the receptors the virus binds to in the upper airways of birds are less common in mammalian upper airways, H5N1 largely spares mammals. But this time around many mammalian species have become infected, including foxes, cats, ferrets, seals, and dolphins, presumably through contact with infected birds. On 17 January, Montana authorities said three juvenile grizzly bears euthanized in the fall after becoming very sick were infected with H5N1 as well. People have caught it, too. So far there have been six confirmed human infections in the current global wave, including one death.
There are some signs that 18.104.22.168b is less pathogenic in humans than earlier versions, which killed roughly half of those infected, says Thomas Mettenleiter, head of the Friedrich Loeffler Institute. “Of course that can be bad news, too, because it might make it easier for the virus to start spreading under the radar, giving it more opportunity 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 past reports of avian influenza outbreaks on mink farms in China, but no clear evidence that the virus spread between the animals. In the Spanish outbreak, there seems to be little doubt it did. In theory, all of the sick animals could have picked up the virus from their feed, which included poultry byproducts, but H5N1 outbreaks have not been reported in the region where the poultry farms and slaughterhouses supplying the feed are located. And the virus spread from pen to pen as expected if it was transmitted between mink. The chain of infections might have begun after one animal caught a sick bird and pulled it into its cage, says Thijs Kuiken, a veterinary pathologist at Erasmus University Medical Center.
How readily the virus found in Spain might infect humans—or spread between them—is unknown. Sequenced virus samples from four mink show several changes compared with 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 better replicate in mammalian tissues. E627K, another worrisome mutation in the polymerase gene, has not emerged, however, and the gene for hemagglutinin—a protein on the viral surface that latches on to the host receptor—has not changed, Peacock says. “We may still have been lucky with this one.”
Monne says her 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 transmits through close contact between animals. “We are planning to also do aerosol transmission studies,” she says.
The outbreak again puts the spotlight on the risks of mink farming. SARS-CoV-2, introduced at farms by humans, spread like wildfire among the animals but was also passed back to their caretakers, and researchers worried the mink industry might become a permanent source of 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 mink in the country in 2020, but a ban on mink farming expired at the beginning of this year.
The farms pose just as big of 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 feeding on infected birds—“solitary animals, or animals that live in small families,” he says. They are unlikely to spread the virus far or infect humans. At mink farms, thousands of such solitary carnivores are forced to live together, creating ideal conditions for the avian virus to adapt to mammals. “It’s a human construct,” Kuiken says.
At the very least, biosafety measures on mink farms need to be tightened, Monne says. Farm workers should wear masks and take other measures to prevent infection, and the farms should reduce the risk of accidental H5N1 introductions. “They should be really carefully keeping the animals far away from wild birds.” Peacock says perhaps it’s time to just end mink farming. “That this is happening in Europe in this day and age, and after COVID-19, is doing my head in,” he says. “It’s a bit of an existential threat.”