Scientists believe it was roughly a year ago that an influenza virus sickening and killing birds happened upon a new and surprisingly hospitable host in the Texas Panhandle — dairy cattle.
That encounter was enough to set in motion today's cattle outbreak, which scientists who study influenza warn has the potential to become another pandemic.
The virus has already shuffled between hundreds of herds and repeatedly jumped into humans. And, in a troubling twist, several cases have emerged in North America without any known source of infection, most recently in a child living in the San Francisco Bay area and a teenager in British Columbia, who remains hospitalized in critical condition.
Genetic sequencing of that case in Canada suggests the culprit may have been a wild bird — and points to changes in the virus that could help it more efficiently latch on to human cells and replicate.
"This is exactly what we don't want to see," says Louise Moncla, a virologist at the University of Pennsylvania, "The case in British Columbia shows that flu is always going to surprise us. "
Luckily, Canadian health authorities have found no evidence the teen caught it from a person or spread it to others. And these sort of isolated cases are not unheard of in parts of the world where bird flu has long circulated.
But scientists are clear-eyed about the risk ahead.
With reservoirs of virus persisting in dairy cattle, poultry and wild birds, there are ample opportunities for spillover into humans. Meanwhile, the virus is turning up in raw milk on store shelves. And flu season is raising the troubling prospect that bird flu could commingle with seasonal influenza.
"This virus is not so easy to get rid of," says Dr. Jürgen Richt, a veterinary microbiologist at Kansas State University. "We will have to live with it for some years to come."
A Canadian case raises fears
There have been two reassuring constants since the first human infection tied to dairy cattle was detected in the spring.
There's still no compelling evidence people are spreading the virus to each other, and infections are largely leading to mild illness.
On that second point, however, the case in Canada represents a departure.
What began with conjunctivitis in early November progressed into fever and eventually full-blown acute respiratory distress syndrome, according to Canadian health officials.
The adolescent had no underlying medical conditions.
An exhaustive investigation failed to pinpoint how the teen, who is too sick to be interviewed, caught the virus. Repeated testing of the family dog turned up no signs of bird flu.
Based on genetic evidence, the best guess is that some encounter with a wild bird, or an intermediate species, seeded the infection, said Dr. Bonnie Henry with the British Columbia Ministry of Health.
"We may not ever know for certain exactly where they were exposed," she told reporters on Tuesday, during an update on the case.
While the virus sampled from the teen still belongs to the same "clade" of H5N1 circulating in cattle, Moncla says it descends from a "rare, genetically distinct cluster" of viruses that arrived from Asia several years ago. It's quite similar to the virus that infected poultry workers in nearby Washington state.
Particularly concerning, though, are signs the virus evolved while replicating inside the teenager.
Moncla says several mutations affecting the protein on the surface of the virus — what it uses to bind to receptors on cells — could help it more efficiently infect humans.
Canadian health officials are looking into whether any of these changes helped the virus more easily infect cells deep in the lungs, perhaps explaining why the teenager eventually developed such severe illness.
While more work needs to be done to understand the implications, it's an unsettling finding. Scientists are watching out for just these types of changes in the virus because it's seen as a key step in the path to bird flu sparking a pandemic.
So far, these concerning mutations that affect how the virus breaks into cells have not appeared in the version of bird flu moving through cattle.
Udders already have plenty of the receptors that avian-like viruses use — meaning, at least in those animals, there may not be much "pressure" for it to adapt in a way that makes it more dangerous to humans, says Richt.
But, he adds, "there are a lot of unknowns here."
An unchecked outbreak
For a time, Richt was optimistic the country could stamp out the dairy cattle outbreak.
His experiments involving infected cattle suggested bird flu was spreading primarily through virus-laden milk, not as a respiratory illness, which would be considerably more difficult to control.
"This was good news, I thought, you control your milk contamination and maybe you can control the outbreak," he recalls. "It didn't happen, apparently."
Instead, the virus eventually found its way into more than 670 dairy herds across fifteen states, with California now bearing the brunt of infections.
"I think it's fair to say that the control efforts have largely been a failure," says Michael Osterholm, who runs the Center for Infectious Disease Research and Policy at the University of Minnesota.
Without a new strategy and closer work with the industry, there's little indication that will change, given all the ways the virus "can move into a farm of susceptible dairy cattle and explode," says Gregory Gray, an epidemiologist at the University of Texas Medical Branch.
Milk with high concentrations of virus can easily spread in the milking parlor; rodents and other animals can ferry infectious material; humans can carry it on their clothing or via farm equipment.
"Short of a big vaccine campaign, I just don't see how we're going to control it," he says.
So far, there are more than fifty known human infections in the U.S., but the true number could be much higher.
"It's pretty clear we're probably missing a lot of cases," says Gray.
For example, a study conducted by the Centers for Disease Control and Prevention tested workers at farms in Michigan and Colorado after bird flu turned up in cattle there. About 7% of the people had evidence of a past infection and about half did not recall having symptoms at the time.
Right now, the country is repeating the "mistakes of COVID," says Dr. Deborah Birx, who helped oversee the pandemic response during the first Trump administration.
"The most important thing is to track where it is," says Birx, now a fellow at the George W. Bush Institute, "And what have we learned over the last five years? Well, a lot of viruses spread asymptomatically."
Unless there's more screening of cattle and testing for associated infections in humans, she says the true scale of the outbreak will remain murky. It will be hard to stay ahead of what could initially be relatively quiet human-to-human spread.
The several isolated humans cases in North America with no clear link to infected animals are unnerving, but Osterholm points out that, historically, this has happened in parts of the world where the virus has long circulated in wild birds.
"I'm not surprised," he says, noting that some kind of contact with migratory birds could "surely explain" the infections. "Could there be more of those cases occurring out there? Absolutely. Are there a lot of additional cases of severe illness? No."
Reassortment could change the virus
Scientists worry, under the right circumstance, a process known as reassortment — a genetic mixing of two viruses — could spawn a new version of bird flu that's better adapted to humans.
The prospect of this happening in pigs, which are seen as particularly dangerous "mixing vessels," has long concerned influenza researchers. So far, there's only one documented case of bird flu infection in that animal during the U.S. outbreak.
But it's entirely possible a human could incubate a virus in this way, too.
And flu seasons could set this in motion, says Kansas State's Richt.
The thinking goes: Some unlucky soul could simultaneously be infected with seasonal influenza and bird flu.
"We think every past pandemic virus that we've had for human influenza has been a reassortment event between a virus circulating in humans and a virus circulating in a different species," Moncla says. "Translating that into a probability that we are close to a pandemic or that a pandemic will happen now — I would say is impossible."
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