Last Friday, a health alert from the Centers for Disease Control and Prevention pinged its way across the inboxes of clinicians and state health departments all over the US. The message described how a dairy farm worker in Texas had contracted H5N1, the highly infectious strain of avian influenza, or bird flu, that’s currently circling worldwide. The dairy worker had caught the virus, apparently, from cattle.
The CDC’s alert urged doctors to be vigilant and consider H5N1 a possibility in any patients presenting with acute respiratory symptoms or sore eyes who had recently been in contact with animals.
Around the world, virologists responded to the news with varying degrees of alarm. While this is the second confirmed human case of H5N1 infection in the US in the past two years—in 2022, a worker at a poultry farm in Colorado contracted it from infected birds—it appears to be the first known case of the virus jumping from another mammal to humans.
According to Raina MacIntyre, who heads the Biosecurity Program at the Kirby Institute in Sydney, the biggest concern is that as the virus adapts more and more to mammalian species, it will gain mutations that make it better equipped to spread between humans. So far, the public health threat from H5N1 has been minimal because it cannot easily enter the cells of the human nose and mouth, though when the virus does infect people, it can be deadly.
“The virus is not one that can transmit easily between humans,” says MacIntyre. “The key event that could result in a human pandemic is a mutation that switched the affinity of the virus to certain receptors in the human respiratory tract.”
H5N1 is not a new virus. It was first detected in chickens in Scotland way back in 1959, and between January 2003 and December 2023, 882 human cases were reported across 23 countries, with a case fatality rate of 52 percent. The subtype that infected the Texan farm worker, known as 2.3.4.4b, has been spreading in the wild on an unprecedented scale over the past four years. Reports suggest that it has killed hundreds of millions of domestic and wild birds since 2020, while at least 48 mammal species across 26 countries have also perished from the virus. This strain of H5N1 has already spread so far and wide that it has even reached Antarctica and infected species ranging from foxes to polar bears.
MacIntyre describes the spiraling infections in animals as being “unprecedented” and says that urgent surveillance is needed to monitor whether H5N1 begins spreading between pigs or ferrets, animals which have a similar receptor profile to humans.
“I have been following H5N1 since 1997, and the current situation is extremely worrying,” MacIntyre says. “In the past, H5N1 epidemics in birds were sporadic and would die down after culling of infected poultry. Since 2021 the pattern has changed, and it has not gone away but steadily increased.” In this time, many new mammalian species have been infected. “Some may be suitable genetic mixing vessels to create a human pandemic strain,” she says.
In recent weeks, health officials in the US have detected the presence of H5N1 in cows from 16 herds across six states, the biggest known outbreak in cattle. Research currently suggests, however, that the viral load is greatest in the animals’ milk, hinting that H5N1 may be spreading through contaminated equipment, such as milking machines, rather than through the air, a transmission pathway which would be harder to stop.
“I don’t think we need to panic; I think we just need to be alert,” says Nadav Davidovitz, an epidemiologist and public health expert at Ben-Gurion University of the Negev in Israel. “We need to invest in more routine animal surveillance and create a system of sharing data about this virus. But one of the problems is that there’s a lot of pandemic fatigue.”
If there is a human outbreak, MacIntyre says, the public health systems around the world are much better prepared to cope compared with a more novel virus, like SARS-CoV-2 was when it emerged. This is because influenza has been subject to decades of intensive research. The World Health Organization has a list of potential candidate vaccines for various subtypes of H5N1 that could be mass produced at short notice. The CDC has revealed that the strain isolated in the Texan farm worker is closely related to two H5N1 strains that can be targeted by existing vaccine candidates.
“The last human influenza pandemic was in 2009, and vaccines were available six months after the first cases,” says MacIntyre. “We now have many new vaccine technologies that can be made faster. We also have antivirals which work against all flu strains and do not need to be matched. Getting your seasonal flu shot can also confer a small amount of cross-protection.”
Other researchers point out that H5N1 remains a virus that is best adapted to birds, and the isolated infections of farm workers do not suggest that it will suddenly acquire the ability to spread rapidly between humans or even cows. “The virus sequence data still shows that the virus is an avian virus, so the likelihood of it persisting [long-term] in cattle will be low,” says Munir Iqbal, who leads an avian influenza research group at the Pirbright Institute in the UK.
Instead, a more pressing concern may be the impact H5N1 is already having on food security. Maurice Pitesky, a researcher at the UC Davis School of Veterinary Medicine, told WIRED that in the past week, two of the biggest commercial poultry facilities in the US have reported an H5N1 outbreak, resulting in the euthanasia of nearly 4 million laying hens. Last year, similar outbreaks cost the US government half a billion dollars in compensation payouts to poultry producers and caused a surge in the price of eggs.
“The impact on commercial poultry from a welfare, economic, and food security perspective is unprecedented,” says Pitesky. “We can’t seem to get this under control, and we’re kind of teetering a little in terms of how far this could potentially propagate and continue to spread in farm animals throughout the world.”
As a recent example of what may ensue, Pitesky points to the repeated African swine fever outbreaks across various Asian countries in the past decade, which decimated the pig farming industry to the extent that pork was briefly usurped by poultry as the most widely consumed animal protein on the planet. Pitesky argues, however, that the current model of governments heavily compensating farmers for their livestock losses in the wake of a viral outbreak is financially unsustainable, and more investment needs to be diverted toward AI-driven technologies that can prevent these infections in the first place.
“I work on predictive models, using a combination of weather radar, satellite imagery, and machine learning, to understand how waterfowl behavior around different farms is changing,” says Pitesky. “We can use this information to understand which of the 50,000 to 60,000 commercial poultry facilities in the US are at most risk, and form strategies to protect all the birds in those facilities.”
Technology may ultimately offer a path toward eliminating the virus in commercial poultry. In October, a team of researchers in the UK published a study in the journal Nature Communications demonstrating that it is possible to use the gene-editing tool Crispr to make chickens resistant to avian influenza. This was done through editing genes that make the proteins ANP32A, ANP32B, and ANP32E in chickens, which the virus uses to gain access to chicken cells.
Crispr has been shown to be capable of making livestock resistant to other infections such as the cancer-causing viral disease avian leukosis and porcine reproductive and respiratory syndrome, which is responsible for widespread economic losses in pig farms.
“The currently available methods are the use of strict farm biosecurity, poultry vaccinations in some countries, and massive depopulation of infected or exposed chicken flocks,” says Alewo Idoko-Akoh at the University of Bristol, the lead researcher on the Nature Communications study. “These methods have been partially successful but have so far failed to stop recurrent bird flu outbreaks around the world. Gene editing of chickens to introduce disease resistance should be considered as an additional tool for preventing or limiting the spread of bird flu.”
Pitesky described the paper as “really interesting” but pointed out that it would require widespread public acceptance toward consuming gene-edited chicken for it to become commercially viable. “I think that those technological solutions have a lot of potential, but the issue more than anything, especially in the United States, is sentiment toward chickens that have been genetically modified,” he says.
For now, Iqbal says that the best chance of keeping avian influenza under control is more active surveillance efforts in animal populations around the world, to understand how and where the H5N1 is spreading.
“The surveillance system has been improved, and any infection that appears unusual is thoroughly investigated,” he says of the situation in the US. “This has helped to identify unusual outbreaks, such as infections in goats and cattle.” However, he says, much more work is needed to detect the virus in animals that don’t show signs of disease.
