Bird flu has been behaving very strangely lately. A strain of the highly pathogenic avian influenza virus (H5N1) has been spreading in dairy cows in at least nine U.S. states. Infected cows have very high levels of virus in their milk, and early reports indicate that it is being spread by contaminated milking equipment, although other methods of transmission are also possible. Several cats that drank raw milk from infected cows developed neurological symptoms and died. Pasteurizing milk appears to effectively neutralize the H5N1 virus.
In recent weeks, three human infections with the virus have been confirmed—all in dairy workers who had contact with sick cows. All three developed symptoms of eye infections known as conjunctivitis. The latest case, reported in Michigan this week, also involved respiratory symptoms more typical of a flu infection. The workers were most likely exposed to the virus in contaminated milk—by getting it on their hands and then touching their eyes, for example, or via milk droplets (or even microscopic particles called aerosols) from a cow’s udder or milking equipment.
“It is really surprising how widespread this thing got over a few months’ time and how this virus seems to be spreading through the milking machines from udder to udder,”says Ron Fouchier, deputy head of the viroscience department at Erasmus University Medical Center Rotterdam in the Netherlands. “This is a completely new situation for all of us, and it’s surprising and a little bit worrying because of the enormous amounts of virus that can be in raw milk.”
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But why is H5N1 causing eye infections in humans? And is there a risk the virus could spread more widely and potentially cause a pandemic?
In fact, cases of avian flu causing conjunctivitis are not that rare. There was a large outbreak of H7N7 avian flu in poultry in the Netherlands in 2003, which led to 89 confirmed human cases. Of these, 78 people had conjunctivitis; five had both conjunctivitis and flulike illness and two had only flulike illness. One person developed pneumonia and respiratory distress and died, according to a 2004 study by Fouchier and his colleagues.
“We’ve seen this [conjunctivitis] also before with ... H7N7 viruses quite a lot and a little bit less with H5 bird flu viruses,” Fouchier says. (The latter is the type now spreading in cows.) “But we know that these bird flu viruses can cause conjunctivitis rather easily.”
In the recent H5N1 outbreak in cows and infections in humans, viruses that got into workers’ eyes may have bound to receptors in the conjunctiva, the clear membrane that covers the inside of the eyelid and the white of the eye and protects the eye. Influenza viruses bind to what are called sialic acid receptors. The accepted wisdom suggests that avian flu viruses preferentially bind to one type of sialic acid receptor predominant in birds, whereas human seasonal flu viruses bind to another type of sialic acid receptor predominant in the human respiratory tract, says Patrik Ellström, an infection medicine researcher at Sweden’s Uppsala University. But recent research suggests the picture is more complicated; both receptor types have now been found in the respiratory tracts of humans and birds. So it’s not clear that the virus would need to bind to the “human” receptor to cause infection, Ellström says. In the human eye, however, the “bird” receptor is the one most frequently found, and this could explain why the virus in cows is causing eye infections in humans.
An H5N1 eye infection could conceivably spread to a person’s respiratory system via the sinuses and possibly cause a more severe, systemic infection, Fouchier says. That’s likely what happened with the one person known to have died in the 2003 outbreak in the Netherlands. So far, there is little evidence that the currently circulating strain of H5N1 is spreading person to person, although that could change. The more the virus spreads from cows to people and the more people who become infected, the higher its chances of evolving to become better at infecting and spreading among humans.
“Given the amount of virus detected in milk from H5N1 virus-infected cows, I am concerned about its spillover to humans, poultry and other animals,”says Yoshihiro Kawaoka, a professor of virology at the University of Wisconsin–Madison’s School of Veterinary Medicine.
Conditions in many milking parlors can be especially conducive to spreading the virus among workers via milk, according to Seema Lakdawala, an associate professor of microbiology and immunology at Emory University School of Medicine and an expert in influenza virus transmission. Lakdawala says she recently visited a parlor to observe the milking process. “It was eye-opening to me, and I, of course, got splattered on my face with milk because that’s what happens,” she says.
The cows were on a platform that put their udder roughly at eye level so humans could access it easily, she says. The first step in milking was “forestripping,” in which a worker very briefly milks the animal by hand to start lactation. When Lakdawala was watching this process, “these animals were just leaking,” she says, comparing the effect to that of water misters in a plant nursery.
Next, the cow’s udder was disinfected, and the workers attached a tube capped by a cup to each teat with a liner that inflates to exert pressure: “basically a breast pump for a cow teat,” Lakdawala says. As anyone who has breastfed a child knows, the breast pump gets totally coated with milk, Lakdawala says. And although workers disinfect the udder, they don’t always do so to the milking equipment between animals, she says, so it’s easy to see how an infected cow could transmit the bird flu virus to another cow via the milking pump and how workers could be infected by splashing milk droplets.
The U.S. Centers for Disease Control and Prevention currently recommends that workers on farms where H5N1 has been detected have access to personal protective equipment, or PPE, such as N95 respirators, face masks, goggles and face shields. But it’s only a recommendation, Lakdawala says.
In order to prevent bird flu from causing more infections in humans, Lakdawala thinks dairy workers on all farms should have access to and use proper PPE—especially face shields to protect their eyes. Getting workers to wear N95 masks while working all day in hot barns is unlikely, she notes, but a face shield would provide at least some protection. Additionally, all dairy workers and veterinarians visiting those farms should be offered H5N1 vaccines, she says.
Lakdawala says it is crucial to get farm owners, workers and state public health officials to come together and figure out how to stop the spread of this virus. “No farm owner wants their working staff out sick,” she says, and “none of us in public health want those workers to get sick.”
It’s a daunting problem, she admits. But there is still a chance to act before any potential sustained human-to-human transmission of the virus.
In addition to providing every farmworker with PPE, Lakdawala believes the CDC should issue a “stay-at-farm” order for all cows “to get an assessment of what is happening and the extent of what has happened.” Tens of thousands of cows are transported across the country every week, she says. The U.S. Department of Agriculture now requires lactating cows from farms with known H5N1 infections to be tested before they can be transported to other states. But Lakdawala thinks the industry should temporarily stop moving all cows around.
Finally, she says that experts and officials need to talk with farmers about how to reduce contamination of milking equipment and about how to safely dispose of milk from infected animals.
“Nobody, no one, absolutely nobody, wants another pandemic,” Lakdawala says. “We really need to take a moment and do everything we possibly can right now to prevent it.”