H5N1 bird flu outbreak in cows is likely widespread, milk tests show

AAndrew Bowman, a veterinary epidemiologist at Ohio State University, had a hunch. He had been struck by the huge amounts of H5N1 virus he had seen in the milk of cows infected with bird flu and believed that at least some of the virus was leaving farms and making its way downstream to store shelves.

He knew the Food and Drug Administration was working on its own national investigation into the milk supply. But he was impatient. So he and a graduate student took a road trip: They collected 150 commercial dairy products from across the Midwest, representing dairy processing plants in 10 different states, including some where herds tested positive for H5N1. Genetic testing revealed the presence of viral RNA in 58 samples, he told STAT.

Researchers expect that additional ongoing laboratory studies will show that these samples do not contain live viruses capable of causing infections in humans, meaning that the risk of pasteurized milk to consumers’ health is still very weak. But the prevalence of viral genetic material in the products sampled suggests that the H5N1 outbreak is likely much more widespread among dairy cows than official figures indicate. So far, the U.S. Department of Agriculture has reported that 33 herds across eight states have tested positive for H5N1.

“The fact that you can go to a supermarket and 30 to 40 percent of those samples are positive, that suggests there is more virus around than is currently recognized,” said Richard Webby, a virologist of influenza who analyzed the samples. at St. Jude’s Children’s Research Hospital in Memphis, Tennessee, where he directs the WHO Collaborating Center for Animal Influenza Ecology Studies.

Earlier this week, the FDA announced that its efforts had found evidence of the H5N1 virus in samples of milk purchased on store shelves, but it provided no detailed results. On Thursday, during an online symposium hosted by the Association of State and Territorial Health Officials, the FDA disclosed a high-level finding from the agency’s investigation. Results returned Thursday morning showed PCR-positive milk in 20% of samples, “perhaps with some preponderance in areas with known herds,” said Donald Prater, acting director of the Center for Food Safety and FDA Applied Nutrition. He did not say how many samples the FDA analyzed or in what geographic area.

PCR – polymerase chain reaction – tests have only revealed genetic traces of the virus, not proof that it is alive or infectious. The FDA has insisted that H5N1, which is sensitive to heat, is most likely killed by the pasteurization process.

The agency is still evaluating the viral viability of these samples by attempting to culture the virus from milk containing H5N1 RNA. The FDA plans to release the results of these studies in the coming days. On Wednesday, Jeanne Marrazzo, the new director of the National Institute of Allergy and Infectious Diseases, told reporters that a team of NIAID-funded researchers had early data suggesting that pasteurization appeared to be effective.

The team that produced this data — the St. Jude and OSU groups — told STAT that they have so far analyzed four samples of store-bought milk that tested positive by PCR for H5N1 genetic material. “We’ve done viral growth testing to see if we can recover any virus from it and we can’t,” Webby said.

These four samples came from an initial collection of 22 commercial dairy products purchased in the Columbus, Ohio area. “Basically it was just me visiting the five grocery stores between campus and my house,” Bowman said.

PCR testing at OSU revealed that three of these 22 products were positive for viral RNA. Bowman sent them to Webby to inject them into plates of mammalian cells and embryonated chicken eggs and look for any signs of active viral replication. To do this, Webby needed a negative control, so he went to buy milk at a store near his lab in Memphis. But PCR testing also found H5N1 RNA in this sample, making it useless as a negative control but as an additional data point showing the absence of live virus.

This sample is still in Webby’s refrigerator at home. He used it to make dinner earlier this week. “All this doesn’t worry me,” he said.

Although the risk of infection from dairy products is very low, the concern is that the more H5N1 spreads among cows, the more opportunities the virus has to adapt to transmit effectively among mammalian hosts. It also increases the chances that H5N1 could enter pigs, where it could swap genes and form hybrids with other flu viruses. Viruses that mutate so they can spread easily across a mammalian species might have an easier time infecting humans.

The St. Jude group is now repeating its analyzes with the additional samples that Bowman and his graduate student purchased in the Midwest. Their initial findings provide further evidence that H5N1 is spreading widely among dairy cows in the United States.

This week, researchers examining viral genome sequences released Sunday by the USDA found that the outbreak has likely been going on for months longer than previously thought. “These two data – the milk data and the genetic data which shows this has been around since December of last year – suggest that the outbreak is probably much larger than we think,” said Angie Rasmussen, a virologist who studies emerging zoonotic pathogens at the Vaccines and Infectious Diseases Organization at the University of Saskatchewan in Canada.

It may also indicate that herds may be contagious with only mild symptoms or no symptoms, which would complicate the response and make containment much more difficult.

“This tells us that we are probably already seeing that milk from asymptomatically infected cows contains virus,” said Andrew Pekosz, a molecular microbiologist who studies respiratory viruses at the Johns Hopkins Bloomberg School of Public Health.

So far, there has been only one report of H5N1 infection in a cattle herd without symptoms – in North Carolina. But USDA officials have not released any further details, other than that milk from infected but asymptomatic cows appears unchanged.

In cows infected with H5N1, the first thing that happens is that their appetite disappears and their activity decreases. Then their milk production dries up. In some animals, the milk they produce turns yellow and thick. “It’s a strange thing that seems to be unique to this particular virus,” said Keith Poulsen, director of the Wisconsin Veterinary Diagnostic Laboratory. And it’s one of the main red flags that dairy farmers are supposed to watch for when deciding whether or not to test their herds. If milk from asymptomatic or presymptomatic cows appears normal but may carry the virus, this would mask the need for testing.

To truly understand the extent of the spread as well as possible mechanisms of viral transmission, widespread testing of animals with and without symptoms is necessary, said Jennifer Nuzzo, an epidemiologist and director of the University’s Pandemic Center. Brown. “If we only test cows with outward symptoms, we miss infections in those that don’t.”

Until this week, USDA policy did not require any animal testing and only recommended it for dairy cows over 3 years old that had been nursing for at least 150 days and had serious clinical symptoms such as fever, lethargy, abnormal milk. production and loose stools.

On Wednesday, the agency issued a federal order requiring an animal to test negative for the virus before it can be transported across state lines. It also requires state laboratories and veterinarians to report to the USDA any animals that test positive for H5N1 or any other influenza A virus. But outside of interstate travel, testing remains voluntary and encouraged only for visibly ill animals. .

Public health experts told STAT that such narrow testing criteria likely distort the true extent of the outbreak. “I haven’t seen any evidence that makes me want to dismiss the concern that testing practices absolutely shape what we think we know about this virus,” Nuzzo said. “We just don’t have the right data at the moment to tell us what’s going on.”

The situation is reminiscent, she says, of the Covid-19 pandemic. In the early weeks of this outbreak, testing policies were narrow: limited to symptomatic people who had traveled to China. Meanwhile, the SARS-CoV-2 virus was spreading undetected across the United States, genomic analyzes would later show. Later, when at-home testing became widely available, official counts became unreliable, leaving state and local health departments in the dark.

“At least with Covid, wastewater monitoring has finally stepped in to complete our picture,” Nuzzo said. “With H5N1, we don’t have that.”

On Wednesday, the Centers for Disease Control and Prevention said it was studying the possibility of testing wastewater for H5N1, but pointed to significant obstacles, including the fact that farms are not connected to municipal sewer systems and the possibility of infected wild birds disrupting water testing around farms.

Requiring dairy farms to regularly test all of their animals, including asymptomatic ones, is not logistically feasible given the current capacity of the state’s veterinary diagnostic laboratories, Poulsen said. He and other lab directors are already preparing for the massive ramp-up of testing they plan to begin when the USDA order takes effect Monday. But he thinks more needs to be done at the federal level to encourage farmers to test their herds.

“At this point, farms just aren’t offering samples because there’s no incentive to raise their hands,” Poulsen said. This lack of information makes it much more difficult for epidemiologists to trace the virus and understand how it spreads, the exact mechanisms of which still remain unclear.


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