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Bird flu snapshot: This is the latest installment in a series of regular updates on H5N1 avian flu that STAT is publishing on Monday mornings. To read future updates, you can also subscribe to STAT’s Morning Rounds newsletter.

Public health experts who’ve been following the surprising spillover of H5N1 bird flu into America’s dairy cattle herds now have all eyes on Colorado, waiting to see if a cluster of human cases there might balloon into something bigger.

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On July 14, Colorado officials announced that five workers involved in the culling of 1.8 million chickens at a large H5N1-infected egg farm in Weld County had tested positive for the virus. And the strain infecting the workers appears to be closely related to the virus infecting cows in Colorado and at least 12 other states.

On Friday, the Centers for Disease Control and Prevention confirmed a sixth case among the Colorado poultry workers. Almost 70 individuals involved in the “depopulation” operation were tested for H5N1 after showing symptoms of the disease, according to a spokesperson for the Colorado Department of Public Health and the Environment. On Saturday, the state announced it had found a possible seventh human case; the CDC, which must conduct confirmatory testing, is expected to receive the sample on Tuesday.

The six Colorado cases were all mild, with some experiencing the more traditional flu signs of fever and cough, and others having conjunctivitis, a symptom that’s been seen with some of the dairy workers who’ve been infected during the outbreak. But it’s the first time multiple human cases have been reported on a single farm in the U.S., raising questions about whether the virus has changed or the environmental factors presented unique opportunities for it to spread.

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A recent study led by noted flu virologist Yoshihiro Kawaoka of the University of Wisconsin-Madison found evidence that the virus now circulating inside cows has acquired some ability to bind to receptors found in the upper respiratory tracts of humans, though other labs have produced conflicting data. The concern with a large cluster of human cases is the increased potential for those people to pass on the virus to others, particularly immunocompromised individuals.

But Michael Osterholm, director of the University of Minnesota’s Center for Infectious Disease Research and Policy, said without more data, it’s too soon to say what the risk is with the situation in Colorado. “If we get 7, or even 70 more cases of conjunctivitis, what does that mean? Could this be a precursor to a respiratory infection, to influenza being transmitted people to people? No one knows.”

He pointed to the situation in Michigan earlier this summer, where 54 farmworkers who had been exposed to infected cows and experienced some flu-like symptoms were tested by state public health officials. Only two of those individuals tested positive for H5N1.

Results from a serological study of farmworkers in Michigan released by the CDC Friday provide additional reassurance that asymptomatic human infections are not going undetected. None of the blood samples collected from people who had been exposed to infected dairy cows on two farms but showed no symptoms were found to contain H5N1 antibodies, meaning they had not been infected.

Further back in time was an outbreak of a different strain of avian influenza that struck commercial poultry farms in the Netherlands in February of 2003. Nearly 500 farmworkers registered health complaints, and while some complained of flu-like symptoms, and one veterinarian died, the majority experienced only conjunctivitis. Eighty-nine of those people tested positive for the bird flu virus, and all the cases were linked to direct contact with poultry. But the outbreak never spread more widely; by the next year it had largely burned out.

“Clearly we’re vulnerable to H5N1 when it’s floating in the air,” Osterholm said. “Our bare eyeballs are a perfect landing spot for it. But there’s a big difference between that and the virus taking hold in the human respiratory tract.”

During a news briefing Tuesday, federal officials said Weld County workers faced challenging conditions inside the poultry facilities. Temperatures that exceeded 104 degrees and high-powered fans made it difficult to wear the protective equipment, including full-body suits and N95 masks, meant to protect them from the virus, particularly if it becomes aerosolized.

“The workers were finding it hard to maintain a good seal or a good fit, either between the mask or with eye protection,” said Nirav Shah, the CDC principal deputy director. “This confluence of factors may play a role in explaining why this outbreak occurred, where it did, and when it did.”

Initial genetic analyses have indicated that the virus sickening the poultry workers is related to the version that’s spreading among cows, but it’s still unclear which dairy farm it came from. The state is in the early stages of conducting an investigation to understand those linkages, and has requested additional epidemiology support from the U.S. Department of Agriculture. The CDC on Friday said genetic sequencing of the virus infecting one of the poultry workers showed it was closely related to the first Michigan case and does not have changes associated with antiviral resistance.

Weld County, just northeast of Denver, is home to 350,000 people and the largest concentration of dairies in the state. So it’s no surprise it’s been especially hard-hit by H5N1, Colorado State Veterinarian Maggie Baldwin told STAT in an interview last week. “Geography is a really big factor,” she said. “The fact that most of our dairies in Colorado are in the same region is going to lead to more transmission of this virus.”

Colorado has been dealing with H5N1 on its poultry farms since early 2022, but until this summer, those outbreaks were sporadic and linked to wild birds. “What we have now is sustained mammal-to-mammal transmission of H5N1 in dairy cows, which is leading to a potential source of continued spillovers into our poultry operations,” Baldwin said. “So this is even riskier than what we have been seeing for the last two and a half years.”

Since its first reported case of bird flu in dairy cattle in late April, Colorado has registered 41 additional H5N1-positive herds, with six in the past week alone. That means infections have been reported in 40% of Colorado’s herds. It now leads the nation, making up nearly a quarter of the 163 livestock outbreaks in the USDA’s official tally.

Correction: An earlier version of this story had an incorrect number of people who tested positive for bird flu during the 2003 outbreak in the Netherlands.

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