As bird flu spreads in cows, here are 4 big questions scientists are trying to answer

By Will Stone | NPR

On Friday, Colorado became the latest state to detect the bird flu virus spreading in dairy cattle. It follows revelations earlier in the week that viral fragments are turning up in retail milk.

Still, scientists don't view this as an immediate threat to human health.

Genetic material is not the same as infectious virus and pasteurization is expected to inactivate the virus in milk, but the findings speak to the broader uncertainty about the extent of the spread.

"There's so many critical things that we still need to know to get a better perspective on how bad this is, or maybe it's not so bad," says Dr. Rick Bright, a virologist and the former head of the Defense Advanced Research Projects Agency (DARPA).

Federal health agencies started sharing more details publicly this week, but Bright says there's still not enough transparency.

"It's the void that just leaves everyone nervous," he says

Other scientists say the reality is that there are still many unresolved questions about this outbreak, given how novel it is.

"There's a couple big unknowns at this point," says Louise Moncla, a virologist at the University of Pennsylvania School of Veterinary Medicine.

Here's what scientists who are tracking the virus still want to know:

How widespread is the virus in dairy cattle?

That's still far from clear.

While the official tally shows it's been detected in nine states and just over 30 herds, the actual number could be much larger.

First of all, there hasn't been widespread testing in cattle.

The fact that viral material is now being found in retail milk suggests "this virus is probably spread around quite a bit," says Richard Webby, a virologist at St. Jude Children's Research Hospital in Tennessee.

On Thursday, the FDA said that preliminary results from nationwide samples of retail milk indicate about one in five samples are positive for viral traces. A survey of retail milk in the Midwest found 58 out of 150 samples were positive, according to Andrew Bowman at the Ohio State University.

Webby discovered this himself when he went to the store to grab a carton of milk, which he intended to use as a negative control in his work on H5N1.

To his surprise, even that ended up being positive (unphased, he kept the milk).

Currently the virus has only been detected in a tiny fraction of dairy herds in the U.S., but it's hard to know the significance of that finding when you don't also have details on the overall number of cattle tested, says Dr. Tom Inglesby, director of the Johns Hopkins Centers for Health Security.

"Those are kind of basic questions that would really help get us more ground truth quickly," he says.

The USDA has just taken some new steps that could offer a better picture of the outbreak. There will be mandatory reporting of positive tests in cattle and a requirement that dairy cattle test negative for the virus before they move across state lines.

Potentially complicating the picture: Some unknown number of cattle could be shedding the virus without showing obvious symptoms. Federal health officials have confirmed this.

"We don't know how many animals have this," says Alexis Thompson, a veterinarian at Texas A&M Veterinary Medical Diagnostic Laboratory. "There has been very little sampling done. We don't know how many [sick] animals we have. We don't know how many asymptomatic animals we have. That testing has not been done."

Because milk from sick cows is supposed to be discarded, this could help explain how remnants of the virus entered the milk supply.

If it turns out there are lots of animals shedding the virus and not symptomatic, the outbreak could be "substantially larger" than we realize, says Inglesby. "To get to the bottom of that, we would need to do surveillance testing in places that don't already have clear outbreaks."

Does the milk testing positive on retail shelves contain infectious virus?

So far, it doesn't appear that way, but scientists who are studying this possibility acknowledge it's too soon to say that with absolute certainty.

The PCR testing that has found evidence of viral fragments in the milk on grocery store shelves doesn't actually tell you whether or not it's "live" virus, meaning whether it's capable of replicating.

This form of testing is extraordinarily sensitive and detects small pieces of genetic material, says Lee-Ann Jaykus, a food microbiologist at North Carolina State University.

"There's evidence that that milk at one point in time may have had virus associated with it, but there is no evidence that that virus would be infectious, at least with the information we currently have," she says.

Pasteurizing milk can knock out bacteria and viruses; however, it doesn't erase every trace of those germs.

Federal health officials have stressed that avian influenza doesn't stand up well to the high temperatures and past research on pasteurization indicates "it's very likely to effectively inactivate heat-sensitive viruses like H5N1 in milk from cows."

"We've seen nothing that would change our assessment that the commercial milk supply is safe," said Don Prater from the Food and Drug Administration.

Research on pasteurization in eggs, which happens at a lower temperature than milk, shows that the process inactivates the bird flu virus.

Jaykus and other scientists agree that finding viral material doesn't necessarily suggest an immediate threat to human health.

"It's really important to sort of not get out of control about fear of consuming milk," says Jaykus.

There is an important caveat though: There has been no direct research on how pasteurizing cow milk affects bird flu virus. Those studies are taking place right now.

Early experiments on a small number of samples suggest there is no viable virus in these positive samples, said Jeanne Marrazzo, who directs the National Institute of Allergy and Infectious Diseases.

Webby, who looked at samples of milk sent by Bowman, says they tried to grow the virus in cultured cells and embryonated chicken eggs — two places where flu loves to grow — and found that it did not reproduce.

"It's pretty good evidence," he says, "We could never say there's none, but we could say if it's there, it's at a very, very, very low level."

Jaykus says even if the milk did happen to have a small amount of infectious virus, "there just isn't evidence that that is a transmission route for flu."

Rick Bright, on the other hand, has more concerns about the milk.

"It's a small inconvenience for me not to drink milk until we have more data," he says, "It doesn't mean that I think everyone should stop drinking milk. It's a personal risk assessment."

He says the key question is how much virus is in the milk, and whether that changes if more cows get sick and more virus enters the milk supply.

"The higher the viral load in the milk, the more difficult it is for pasteurization to work completely," he says. "If they show at this point there's no viable virus in the milk, that's a point in time. And what's going to be really critical is that the FDA continues to monitor this."

How exactly is the virus spreading?

For weeks, the leading theory has been that the primary route of spread is through the milk. This is where high concentrations of the virus are being found.

This general idea was affirmed again this week by Mike Watson with the United States Department of Agriculture's Animal and Plant Health Inspection Service, who said the evidence still points to some form of "mechanical transmission."

Virus could be spread on "milking equipment," by "individuals moving from facility to facility," and via rodents that come in contact with milk and then move around, he said.

Federal health officials and scientists believe the virus has moved with lactating cattle from one herd to another. But how it's getting from one cow to another on a given farm "is a key missing piece of knowledge," says Webby.

Genetic sequencing indicates that there was likely a single introduction from birds into cattle, which then resulted in further spread among cattle, says Moncla, who has been analyzing the genomic data.

"A lot of these cattle sequences are quite similar to each other, suggesting that there's almost certainly some degree of cattle-to-cattle transmission going on," she says.

Moncla says it's hard to say exactly how long the virus has been spreading through dairy cattle, although some scientists have suggested it may have been circulating for many months, even earlier than February.

The USDA has also noted another concerning development — that there have been some instances of the virus moving from domesticated poultry to cattle.

"The degree of transmission, combined with the fact that we're likely missing cases in cattle, leads to a bit of concern," says Moncla.

What is the risk to humans as the virus keeps spreading?

First the reassuring news: Even with all these cows being infected, there has only been one documented human infection during the current outbreak in dairy cattle.

That person, a dairy worker in Texas, had conjunctivitis.

This week, federal health officials reiterated that the overall risk to the general public remains low, in part because "we have not observed changes to the virus's genetic makeup that would suggest an enhanced ability to spread to humans or among humans," said Dr. Nirav Shah, principal deputy director at the CDC.

So far, states have tested 23 people for avian flu and have monitored 44 people who were considered exposed and at risk for infection, he said.

Generally, cases of bird flu are rare in humans and it takes a big dose of virus — for example through direct contact while slaughtering poultry — to get infected. Since 2022, there have been 26 human cases of H5N1 virus infection reported worldwide.

Webby says it is possible that cows don't put that much "pressure on the virus to change," which could be one reason scientists haven't seen alarming mutations in the samples collected.

"I don't think the needle has moved at all" in terms of human risk, he says.

Of course, the perennial fear is that the virus could mutate while in cows, or an intermediary animal, and then find its way into humans.

Scientists have documented some mutations in bird flu when it has spread in other mammals. But previous research has shown there needs to be a host of changes — most of all, the virus would have to evolve a way to bind to receptors in the upper airway of humans — to become a pandemic threat.

When it comes to cattle, the CDC's Sanja Olsen says they still aren't sure if it's the exposure to raw milk on the farms that's the primary risk to humans. "We don't know if it's [surface] transmission. We don't know if there's aerosolization of the milk."

Dr. Bright says the CDC should be conducting antibody studies on dairy workers to see if human cases have escaped detection, rather than waiting for cases to show up in the emergency room.

"I am going to keep my radar up," he says. "If this were to get out of hand, we have to be prepared to respond really quickly. And I'm not quite sure we're fully ready to respond if we needed to."

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