With U.S. bird flu outbreak out of control, scientists see growing risks

For nearly four months, the spread of bird flu in the country’s dairy herd has fuelled fears that, if left unchecked, the virus could eventually trigger a pandemic.

The recent string of human cases linked to poultry farms in Colorado only underscores that the threat remains real.

Genetic sequencing of the virus collected from sick poultry farmers closely resembles that circulating in dairy herds, suggesting that cattle somehow introduced the virus into the poultry flock.

In a huge poultry farm, workers were slaughtering birds in particularly dangerous conditions.

As health officials describe it, they struggled to properly wear protective gear over their mouths, noses and eyes as they handled thousands of sick birds in a sweltering barn, with industrial fans blowing feathers and other potentially virus-laden material into the air.

Under these conditions, it’s not surprising that people are catching the virus themselves, says Jennifer Nuzzo, an epidemiologist at Brown University.

“It’s like playing with people’s lives,” she said. “There’s no other way to describe it.”

Federal and state health officials are still investigating the extent of the outbreak, although so far everyone who has tested positive has had only mild, flu-like symptoms.

Nuzzo says the spread on poultry farms highlights the risks of having a viral reservoir in dairy herds that provides ample opportunity for the virus to jump between species and potentially adapt to mammals.

“Any time you give an avian virus a chance to infect a human, it’s like buying a lottery ticket you don’t want to win,” says Troy Sutton, a virologist at Penn State University who studies bird flu transmission.

Based on the latest research, here’s what scientists are learning — and what worries them — as they study the virus.

Some mutations could make the virus more dangerous

Fortunately, there is no indication that we have drawn the dreaded “winning ticket”. At least not yet.

The virus that is spreading in dairy cows is still fundamentally well adapted to infecting birds, not humans; however, there are clearly some mutations that help it maintain a presence in mammals, says Thomas Peacock, a virologist at the Pirbright Institute in the UK who studies bird flu.

““I wouldn’t be surprised if the virus was much more infectious at the same doses than a purely avian virus that was seen last year in poultry,” Peacock says, adding that this could give it an advantage when it comes to infecting humans as well.

Scientists are still trying to better understand the exact effects of these changes in the bovine version of the H5N1 virus. Some samples of the virus indicate that certain mutations improve its ability to replicate in mammalian cells, he explains.

The most worrying possibility would be if the virus evolved to use the type of receptors found in the human upper respiratory tract. Such a change could allow bird flu to spread easily through the air between people, much like seasonal flu viruses that typically infect humans.

Peacock and other scientists are closely monitoring changes in hemagglutinin proteins on the surface of the virus that may be driving this development.

A new study suggests the virus may be more effective at infecting mammals than other types of bird flu

There are still many questions about exactly how humans catch the virus.

Federal health officials say milk splashing into the eyes may explain some infections among dairy workers whose only symptoms were conjunctivitis. There is also speculation that aerosolized milk may be another source of infection.

Although the virus still cannot find a home in the upper respiratory tract of humans, Peacock says, it is clear that viral replication is occurring there, because nasal swabs are positive for low amounts of viral genetic material, at least in some people.

Research on bird flu prior to the dairy cow outbreak showed that with just a few artificially inserted mutations, airborne transmission can occur between ferrets, which are used as a model of human infection.

Since the outbreak began in dairy cows, scientists have begun to analyze the behavior of this version of the virus in hopes of understanding the threat it poses to humans.

The latest research, led by the University of Wisconsin-Madison, shows that the virus can be transmitted through respiratory droplets in ferrets, but inefficiently.

Amie Eisfeld, an author of the study, says her lab has not observed this type of transmission event with any other version of highly pathogenic avian influenza that they have isolated from the natural world and tested in ferrets.

“This virus has some concerning characteristics,” says Eisfeld, a virologist at the University of Wisconsin-Madison. “It’s important to monitor what’s happening here and limit infections in cows and exposure in humans.”

The infected ferrets had no virus in nasal swabs, but there were antibodies in their blood showing they had been exposed.

Sutton notes that just because ferrets in the lab caught the virus this way doesn’t necessarily mean humans will, too.

In another troubling finding from the study, the team found that the virus can bind to the type of receptors found in the upper respiratory tract of humans, suggesting that it has “characteristics that may facilitate infection and transmission in mammals,” the authors write.

To figure this out, Eisfeld says they artificially generated these receptors and attached them to a piece of plastic, then added the virus to see if it would stick.

Since the experiment was not conducted on real people, she says the results should be interpreted with caution: “I wouldn’t want to sound the alarm and suggest that this phenomenon is transmissible between humans.”

Peacock, who was not involved in the work, says the findings suggest the virus is “more infectious” in mammals than previous avian viruses. And while it doesn’t yet appear to be spreading between humans, he worries that could change. “It’s a flu virus, if it’s pressured to do something, it’s going to learn to do it.”

This type of finding is certainly disconcerting, but Sutton says it needs to be put into context: Lab experiments essentially create an “infection-friendly environment” that may not reflect what happens outside the lab.

“It’s not exactly what the human nose looks like in the real world,” he explains. “There’s snot, bacteria, and all sorts of other things that interfere with its functioning.”

The virus can spread among cattle through respiratory transmission.

It is well established that infected cattle shed high levels of virus in milk for days to weeks before eventually recovering.

These results support the hypothesis that the virus is spread primarily from cow to cow during the milking process and through other shared equipment in dairy barns rather than through the respiratory route.

However, some research suggests that respiratory transmission cannot be ruled out.

In a recent study, a small number of non-lactating cows were deliberately infected with aerosols containing avian influenza virus collected from cow’s milk. Only one of the four animals consistently had viral genetic material in nasal swabs, while the others only tested positive on certain days. Necropsies showed signs of viral replication in their lungs, although none of the cattle developed severe symptoms.

In contrast, lactating cows that were deliberately infected at the teat level quickly showed signs of disease and an increased viral load.

Taken together, these findings strengthen the hypothesis that contact with infected milk is a key source of infection, but they also suggest that the respiratory route may still have a role to play, said Dr. Amy Baker, lead author of the preliminary study and a research veterinarian at the National Animal Disease Center in Ames, Iowa.

“It doesn’t really tell us whether or not that’s the primary mode of transmission on these dairy farms, but it does highlight the fact that we need to at least keep an open mind that respiratory infection and transmission could occur,” she said.

The risks of a hands-off approach to stopping the epidemic

Let’s be clear: There is no evidence yet that humans who have caught the virus have spread it to others, which is why the CDC still considers the risk to the general public to be low. Additionally, a recent study of workers at two Michigan dairy farms affected by outbreaks analyzed blood samples and found no antibodies suggesting undetected past infections.

The human infections that have been reported all appear to have occurred in “highly contaminated and high-dose virus environments,” which is reassuring because it means steps can be taken to minimize spread, Sutton says.

“If you started seeing people getting infected with low doses of the virus, that would be alarming,” he said.

Federal health officials maintain that it is still possible to stop the outbreak in dairy cows.

Nuzzo is skeptical. She has yet to find a clearly defined and viable strategy to stop the spread. New cases are still appearing every week in dairy herds.

As a scientist following the situation from outside the United States, Peacock struggles to understand how the government has failed to curb the spread of a virus that has genuine pandemic potential, even after months of mobilizing for a response.

“I feel that if even moderate efforts had been made to stop this phenomenon, it would have been stopped by now,” he said.