If one can point to anything good about the H5N1 bird flu outbreak in dairy cattle — to be honest, there’s nothing good about this situation — it’s the timing. Transmission of the virus through U.S. dairy herds took off when last winter’s flu season was effectively over, making the job of looking for people infected with H5N1 an easier task in theory, though there have been plenty of human hurdles impeding those efforts.
But in the months since the outbreak was first detected, the spread of the virus in cows has not been contained, with infections reported in 339 herds in 14 states so far. Now, with cold and flu season looming, it is likely to become significantly more difficult for the country’s public health departments to track the virus.
In the weeks and months to come, when dairy farmworkers or others culling infected poultry flocks develop influenza-like symptoms, what ails them could be a common cold, Covid-19, regular influenza, or a bird flu virus. Spotting a new flu virus before it starts to transmit more easily among humans and stopping that spread — if it’s possible — could make the difference between a close call and something no one wants, another pandemic.
Trying to do this surveillance at any point in the year is devilishly tough. Doing it in flu season will be next-level hard, experts warn.
“It’s going to be more challenging. You’re going to have more viruses that are in circulation, more cases coming forward. The labs are going to have much more to do,” said Maria Van Kerkhove, the World Health Organization’s acting director of epidemic and pandemic preparedness and prevention.
Carrie Reed, chief of the epidemiology and prevention branch in the influenza division at the Centers for Disease Control and Prevention, agreed that things are going to get harder in the months ahead.
“It’s certainly going to get harder to tease out what’s unusual versus the usual signal in the fall,” Reed told STAT in a recent interview. “Looking at unusual trends in flu activity is going to mean something different in the winter when the usual increases in flu activity [occur].”
You may be wondering: Can wastewater testing help in what’s going to be a more challenging situation? Long used elsewhere to detect transmission of polio viruses, it is proving to be a useful tool to detect levels of a number of pathogens such as SARS-CoV-2, the cause of Covid-19. And it can detect H5N1, differentiating it from seasonal flu viruses, said Marlene Wolfe, an assistant professor of environmental health at Emory University and program director for WastewaterSCAN. But if wastewater testing turns up H5N1 virus in a community’s sewage system, it cannot say if the virus came from a person, a cow, or discarded contaminated milk.
Here are three ways in which H5N1 surveillance is about to get more difficult.
The risk of more infections and maybe worse, co-infections
There’s a reason why influenza attacks more commonly in winter in northern and southern climes. (It transmits year-round in the tropics.)
“We have flu seasons because there are environmental conditions that make transmission more favorable,” said Marion Koopmans, who heads the department of viroscience at the Erasmus Medical Center in Rotterdam, the Netherlands. Those conditions could also give H5N1 more of a transmission edge, she said.
So come winter, there could be an uptick in human H5N1 infections, each of which gives the virus a chance to mutate in ways that could allow it to more easily infect people.
Perhaps a bigger concern about the coming flu season, though, is the possibility that we could see what’s known as a reassortment event. That’s when a human flu A virus — H3N2 or H1N1 — could swap genes with H5N1, giving rise to a hybrid virus that might be better able to spread from person to person, something H5N1 has so far lacked the ability to do. That could happen if a person becomes co-infected, contracting both a human flu virus and H5N1. Reassortment could also occur in a cow, if it were co-infected with two different strains of flu A viruses. (The 2009 H1N1 pandemic was triggered by reassortment of several flu viruses in pigs.)
Reassortment is something flu virologist Florian Krammer worries about. “By reassorting with seasonal influenza viruses, [H5N1] could get a replication machinery that just does much better in human cells,’’ said Krammer, who teaches at Mount Sinai’s Icahn School of Medicine in New York. “That could get hairy.”
“Over the summer and in spring, it’s much easier to see things like that, and the risk of reassortment is much lower. I mean, it’s not like there is no human influenza out there. There are sporadic cases. But the chances are not very high. And it’s a numbers game in the end,” he said.
In an effort to lower the risk of a reassortment event, the CDC is calling for farmworkers who might be exposed to H5N1 to be vaccinated against seasonal flu. Knowing that many do not have health care coverage — and may be unlikely to prioritize getting a flu shot they have to pay for — the CDC is providing 100,000 doses for farmworkers in 12 of the states where H5N1 has been seen to circulate in cows. (Wyoming and Oklahoma, where the virus has also been detected in cows, declined to take part in the program, a CDC spokesperson said.)
The approach, however, is far from perfect. For starters, 100,000 doses divided by 12 states isn’t a lot of vaccine. California, for instance, is the country’s largest milk producer, with over 1,100 dairy herds in the state, and an estimated dairy farm workforce of between 17,000 and 18,000 workers. It is getting 5,000 doses of flu vaccine through the CDC program — in effect 4.5 doses per farm.
“It’s not a huge amount, but it’s certainly helpful,” Erica Pan, California state’s chief epidemiologist, told STAT. “In general our local health departments are working to figure out how to provide more vaccinations in that community.”
“I think we’re working on and thinking about other creative solutions, especially if there are workers in smaller farms, etc., that don’t have other health care access,” Pan said. “It will be interesting to see what the uptake is.”
The other limitation of the approach centers on the vaccines themselves. Flu vaccination does not offer complete protection against infection; these vaccines cannot totally block infection or transmission of the virus. Instead, they lessen the severity of illness, if infection occurs. This reality — which is not well understood by the public — is reflected in a campaign slogan the CDC has used for the past couple of flu seasons to promote flu shots, saying they can turn flu infection “from wild to mild.”
Seema Lakdawala, an associate professor of microbiology and immunology at Emory University, suggested the CDC’s plan to try to increase seasonal flu vaccination in dairy farmworkers could create a false sense of security. “The communication around that is inaccurate,” she said. “It does not block infection. None of our vaccines are targeted for infection. And I don’t think we’re communicating that this does not reduce the risk of these dairy farmworkers from getting H5N1, the cattle virus.”
Thomas Peacock, an influenza virologist at Britain’s Pirbright Institute, which focuses on controlling viral illnesses in animals, is also dubious of how much impact the seasonal flu vaccination program can or will have. He’d rather see U.S. authorities focused on tracking the spread of the virus by widespread bulk tank testing on dairy farms. “But there still doesn’t seem to be any political appetite to do any sort of nationwide testing in a coordinated way, and actually try and work out where this [virus] is,” Peacock said.
Getting exposed people to get tested
Mild H5N1 cases — virtually all of the 34 cases reported in the United States this year have been mild — could be especially hard to find in winter, given that there is no culture of widespread flu testing in this country.
People rarely seek medical care when they have what seems like a garden variety influenza-like illness, known among health care providers as an ILI. Doctors typically only test for flu when someone is severely ill, at high risk of becoming seriously ill from flu because of age or underlying health conditions, or has been admitted to hospital.
Although home tests for influenza and Covid-19 are coming onto the market, those don’t differentiate between bird flu and regular flu, and positive results don’t get reported to any authority. How often home tests will be used this season remains to be seen. There is a sense that many people have stopped testing themselves for Covid, because they either no longer fear the virus or don’t want to know the answer. The same could very well be true for influenza, especially among farmworkers without paid sick leave who may be told to stay home if they test positive for flu. If an answer is inconvenient to arrive at, why go looking for it?
Dairy farms in some states rely heavily on undocumented workers who may well be nervous about their immigration standing, especially in these turbulent political times. Take Wisconsin, for example. In the nation’s second biggest dairy-producing state, more than 10,000 undocumented workers hold down 70% of the dairy jobs, according to a survey released in April 2023 by the School for Workers at the University of Wisconsin-Madison. State law bars them from driving legally, which can limit what they can do outside of work, a ProPublica report from August 2023 explained.
How realistic is it to expect workers in this situation, people who would be docked wages if they were told not to work, to seek and potentially have to pay for a test if they develop conjunctivitis or cold-like symptoms? Even if the testing is offered for free — near the farm gate, by local public health workers — what is the upside for farmworkers? For their bosses?
“I think a lot of it is about actually encouraging people to test who might not normally seek health care to get tested,” Pan said in an interview.
Most affected states aren’t looking for illnesses among dairy farmworkers or workers who are culling chickens on poultry farms that get hit by bird flu. But California is, and it has been reporting new cases weekly this fall. Still, Pan told a workshop on H5N1 research priorities held last week by the National Academies of Science, Engineering, and Medicine that even in her state there are plenty of barriers for dairy farmworkers to report symptoms and to gain access to testing and treatment.
Access to farmworkers has been variable, with some farms being more cooperative than others, she told STAT. That’s not unique to California.
“We’ve heard that from a number of states where there is reluctance,” Reed said. “There’s great cooperation by many farms and also reluctance by others — by farms and by workers to either report illness or seek out testing. So, yeah, it has run the spectrum across the states.”
Koopmans said widespread testing with a very low bar should be the norm this flu season.
“You would like to see a very low-level threshold for testing in people working with animals. I don’t think that’s happening. That need will continue as long as this situation in cattle continues,” Koopmans said, noting that this goes against the grain of the way health care providers — and even the public — view the significance of mild ILIs. “You don’t do that with very mild complaints. Why would you?”
If farmworkers become sick enough that they do interact with the health care system, there should be a low threshold for testing there too, Koopmans said. “And … if you have a flu positive, immediately making sure which [flu virus] is it.”
She likened this effort to looking for a needle in a haystack and said she’s worried about public health systems trying to do this when there are more needles and more haystacks.
The workload on labs
Frontline tests typically will tell you if a person is infected with flu, and if so, whether the virus is influenza A or B. (It is believed that only influenza A viruses can trigger flu pandemics.) H5N1 is an influenza A virus, as are the H3N2 and H1N1 viruses that circulate every winter. To spot H5N1 cases — or in fact any novel flu virus that could cause a pandemic — additional testing needs to be done to tease out which flu A virus was responsible for the positive test result.
Only a portion of positive flu A tests are subtyped in this way. The CDC’s Reed said that after the 2009 H1N1 pandemic, a lot of work went into determining what percentage of tests should undergo subtyping, in order to be able to detect spread of a new flu virus before it becomes a significant public health problem. The CDC called the effort “right sizing” testing. In partnership with public health laboratories, state and local health departments, and statisticians, guidance for individual jurisdictions was developed and published in 2013. It’s been updated since then, Reed said.
Targets vary depending on a state’s population and change based on the time of the year. The portion of positive flu A tests that should be sent for subtyping is lower in the summer, for example, rising as flu season approaches.
It is this system, by the way, that led to the detection of a still-unexplained H5N1 case in Missouri that occurred in August in a person who had no known exposure to infected animals and who lived in a state that has reported no infections in dairy herds and no recent infections in poultry flocks.
State laboratories have to report on how much of this testing they are doing. They even get an annual report card on how well they’ve done. Reed said most manage to get a representative mix of viruses to test from across their state and drawn from people in different age groups. “A common theme that we hear from those health care facilities is that it’s extra work for them in a period where they’re running a lot of clinical testing for flu to then identify flu positive specimens, set them aside, get them over to the health department [for subtyping],” Reed said. “So it does happen, but it is a burden that they’ve identified and are sometimes reluctant to do.”
But it’s a lot of work — work that’s going to be more crucial this winter.
“It is going to be very intense in terms of influenza surveillance,” Lakdawala said. “So individuals who work on influenza surveillance are going to have a very likely busy flu season, because we really need to capture what subtypes of the virus are circulating.”