The state of H5N1 infections and research as 2025 approaches

In March 2024, US federal agencies announced a multistate outbreak of H5N1 avian influenza in dairy cows. Since then, the virus has infected at least 876 cattle herds in 16 states and 65 people have tested positive for H5N1. The majority of human bird flu cases—typically reported in workers exposed to infected dairy cows or poultry—have been mild.

But on Dec. 18, the US Centers for Disease Control and Prevention (CDC) confirmed the country’s first severe case of H5N1, in a person in Louisiana who was exposed to sick or dead birds in a backyard flock. The version of the virus that infected this person is not the one currently infecting US dairy cows but the version circulating in wild birds and poultry. “A sporadic case of severe H5N1 bird flu illness in a person is not unexpected,” the CDC said in a statement.

In November, a teenager in Canada also had a severe H5N1 infection, which resulted in acute respiratory distress. The genetic sequence of the virus isolated from the teen closely matched that of H5N1 circulating in wild birds in British Columbia. But the virus that made this teenager critically ill had two mutations that could make it easier for the pathogen to infect humans.

These mutations have Richard Webby, an influenza virologist at St. Jude Children’s Research Hospital, feeling concerned. “I’m not in the ‘run to the hills’ camp yet,” he says. “But I am a little more uneasy about [the H5N1 situation] now than I was prior to the case in Canada.”

Webby’s concerns are compounded by a recent experimental study that identified a single mutation that would make it easier for the version of H5N1 currently spreading in US dairy cows to infect humans. “Before that study, I would have said we’re probably two or three changes away from a switch,” he says. But this find “brings us a little bit closer to a virus that may have the potential to switch [from a cow or bird virus to a human virus].”

So far, there’s no evidence of human-to-human transmission of H5N1, and the CDC maintains that the risk of infection for the general public remains low. Recent guidelines have called for expanding bird flu virus testing among farmworkers and in raw (unpasteurized) milk at dairy-processing facilities. Those transmission concerns are among many issues related to H5N1 that researchers and public health officials will monitor in 2025.

Mutations

As more cows get infected with H5N1 bird flu, and more people get exposed to infected animals, there’s increased opportunity for the virus to evolve into a version that’s more capable of spreading between people, says virologist Ed Hutchinson at the University of Glasgow. The process could result in the virus accumulating mutations that allow for better replication and transmission, including between people.

Virologists are also concerned about a situation where a person simultaneously gets infected with H5N1 and human influenza virus H3N2 or H1N1, each of which is currently circulating as flu activity gains pace. But it’s hard to predict whether genetic reassortment between those viruses would create a version of H5N1 that’s more adept at spreading in humans, Webby says.

Signs of severe illness

Influenza researchers are surprised that the majority of human H5N1 cases in the US have been mild. Farmworkers have reported conjunctivitis, and some experienced mild respiratory symptoms. In contrast, the infection has been lethal in some animals experimentally infected with the bovine H5N1 virus or exposed to it in the wild. Also, 52% of the human H5N1 cases reported between 1997 and April 2024 from 23 countries (not linked to dairy cows) have been fatal.

For now, Webby is keeping track of instances of severe disease in humans, particularly cases that might be associated with changes in the virus.

Better understanding of how the virus spreads

In 2024, California reported the most cases of H5N1 infections in cattle and humans. That’s not surprising, says Brinkley Raynor Bellotti, an infectious disease epidemiologist and veterinarian at the Wake Forest University School of Medicine. The state has the highest number of dairy cows in the country, according to the most recent US Department of Agriculture Census of Agriculture report.

Last week, Governor Gavin Newsom declared a state of emergency in response to the rising H5N1 outbreaks in California. And at a press briefing on Dec. 20, state veterinarian Annette Jones told reporters that it’s unclear how the virus was spreading between herds.

Public health officials have detected “high concentrations” of H5N1 in raw milk from infected cows. They think that shared milking equipment could spread H5N1 to other cows on the same farm. People working on these farms may also get infected (and not all infections may be symptomatic) during the milking process or while caring for sick animals. But how the virus is spreading from farm to farm is a complicated question to answer, Bellotti says.

In the press call, Jones mentioned that 40 H5N1-related research projects are under way, some of which aim to understand virus spread.

Infections linked to raw milk consumption

Earlier this year, 12 barn cats on a Texas farm died after drinking H5N1-infected raw milk. Last week, Los Angeles County confirmed the death of four house cats infected with H5N1 that had consumed recalled raw dairy milk.

So far, no human case has been linked to consuming infected unpasteurized milk. According to the CDC, the risk of acquiring an infection through this route is unknown, but the concern remains high. It’s a risk people shouldn’t be taking, University of Glasgow’s Hutchinson argues. “You shouldn’t be giving the virus a chance to use you as a foothold to becoming a pandemic virus.”

Virus clues in wastewater

For public health officials, wastewater surveillance continues to be an important tool for early detection of H5N1. “The wastewater is lighting up before the infected herds are identified,” says Alexandria Boehm, program director at WastewaterSCAN, a sewage surveillance initiative that monitors influenza A—including its subtype H5N1—and 10 other pathogens at 190 wastewater treatment plants across the US.

But it’s hard to tell whether this virus lurking in wastewater is coming from humans, animals, or infected milk. Nonetheless, such surveillance could continue to help public health officials prepare for potential H5N1 outbreaks in 2025.