The outbreak of bird flu in dairy cattle has so far spread to just three farmers in the United States, as far as public health officials know. All of them had mostly mild symptoms.
But that doesn’t guarantee the virus, called H5N1, will remain benign if it starts spreading among people. Evidence from the animal world is piling up, and data from other parts of the planet, in fact, suggests the opposite.
Some dairy cows never recovered from H5N1 and died or were slaughtered because of it. Infected terns appeared disoriented and unable to fly. The elephant seal pups had trouble breathing and developed tremors after contracting the virus. Infected cats went blind, walking in circles. two-thirds of them died.
“I certainly don’t think there’s room for complacency here,” said Anice Lowen, a virologist at Emory University.
“H5N1 is a highly pathogenic type of influenza virus and we should have a high degree of concern around it if it spreads to humans,” he said.
In ferrets experimentally inoculated with the virus through their eyes — the presumed route of infection to U.S. farmers — the virus quickly spread to their airways, lungs, stomach and brain, according to a report published Wednesday.
Other studies have found similar patterns in mice fed contaminated milk. The findings suggest that entering through the eyes or digestive system may not make the virus any less threatening after all.
H5N1 has proven to be promiscuous, quickly acquiring new hosts — wild birds and poultry, mice and bears, cats and sea lions. Since its discovery in 1996 in Hong Kong, it has also infected nearly 900 people.
An earlier version of the virus circulating in Asia has killed about half of those infected.
Of the 15 people known to have been hit with the version now circulating in cattle, one in China died and another was hospitalized. Two patients in Chile and Ecuador had severe symptoms. Four Americans — one last year and the three infected in the latest outbreak — fared better.
Importantly, no form of the bird flu virus appears to have spread efficiently from person to person. That’s no guarantee that H5N1 won’t acquire that ability, said Yoshihiro Kawaoka, a virologist and avian flu expert at the University of Wisconsin-Madison.
“I think the virus is clearly changing its nature, because we have never seen outbreaks in cows,” Dr Kawaoka said. Conjunctivitis, also known as pink eye and the main symptom in two of the three farmers, is not typical of H5N1 infection. The appearance of the virus in the mammary glands – in cattle and even in non-lactating mice – was also unexpected.
The concern now is that as H5N1 continues to infect mammals and evolve, it may pick up the mutations needed to spread effectively among humans, sparking another pandemic.
The incubation period for the flu is two to four days, and the human-to-human version could spread long before cases are identified, said Erin Sorrell, a virologist and senior researcher at the Johns Hopkins Center for Health Security.
“If it goes to the general public, it’s too late,” he said. “We missed the boat.”
The flu is usually more serious in older adults and children under 5 years of age. (A swine flu outbreak in 2009 was not as devastating as feared, but it did kill nearly 1,300 children.) The severity of the disease also depends on what virus infected patients are exposed to and for how long, as well as the route of entry and genetic their background and general health.
Infected people generally have fever and respiratory symptoms. Some cases progress rapidly to pneumonia or death. If the bird flu virus adapted to humans, the world would need billions of doses of vaccines and antivirals to prevent these effects.
The federal stockpile contains four types of flu vaccines, but the drugs must be taken within 48 hours of the onset of symptoms to be effective. A recent review found too little evidence to measure the effectiveness of three of the four drugs, including the commonly used oseltamivir, sold as Tamiflu.
Some new versions of H5N1 have mutations that make the virus resistant to oseltamivir and the other two drugs, but these changes, fortunately, have not been widely spread in animal populations. No mutations have been observed in the fourth drug, baloxavir.
But there are only a few hundred thousand doses of this drug in stock, according to David Boucher, the federal agency’s director of infectious diseases for Strategic Preparedness and Response.
Vaccines are a better bet for stopping a pandemic, but enough doses aren’t likely to be available for many months, at least. Even if global production of seasonal flu vaccines shifted entirely to H5N1 vaccines, the number of doses that would be made would be enough for less than two billion people, assuming two doses were needed for each person.
In the United States, the national stockpile contains hundreds of thousands of doses of vaccine that could be made available to those at risk, including children. Companies contracting with the government could make more than 100 million doses in the first 130 days, Dr. Bowser said.
Officials recently announced that they had taken steps to prepare 4.8 million doses that could be bottled without disrupting seasonal flu vaccine production.
But most of these plans will only help if the virus cooperates.
Since H5N1 first appeared, it has branched out into many forms, and scientists have built a library of 40 so-called candidate vaccine viruses to match. Having them ready to go saves critical time because it can take three months to develop a new candidate, said Todd Davis, a virologist at the Centers for Disease Control and Prevention.
So far, he said, the virus has changed little, especially the part of the virus that binds to human cells, called hemagglutinin, or HA.
If the virus was to spread between humans, it would first have to change significantly, some experts noted. “If this virus jumps to humans, you can bet that the YA is going to change, because right now the YA of this virus doesn’t bind very effectively to human cells,” said Scott Hensley, an immunologist at the University of Pennsylvania.
Traditional flu vaccines are made by growing virus candidates in eggs or mammalian cells, which are fraught with potential problems: The virus may not grow fast enough or may mutate too much as it grows.
In 2009, the candidate virus grew well in eggs but evolved into a poor match to the wild H1N1 virus, introducing long delays in distribution to the public. “By the time vaccine stocks were created and distributed, the initial wave of the pandemic had already subsided,” Dr Hensley said.
CSL Seqirus, a leading manufacturer of seasonal influenza vaccines, has a cell-based H5N1 vaccine already approved by the Food and Drug Administration.
In the event of a pandemic, once CSL Seqirus obtains a candidate vaccine virus that matches the circulating virus, it could provide 150 million doses to Americans within six months, said Marc Lacey, the company’s chief executive. (The company also has contracts with 19 other countries.)
But 150 million doses would protect only about one in five Americans. Federal officials are also investigating mRNA vaccines for bird flu, which could be made very quickly, as seen by the Covid pandemic, to protect both cows and people. Dr. Hensley’s team is testing an mRNA vaccine in cows.
Officials have been reluctant to develop vaccines for cows because of trade concerns, experts said: Some countries ban imports of products from vaccinated birds and animals.
However, immunizing the cows would limit the risk to farm workers and other cows and limit opportunities for the virus to continue to spread and evolve, experts said.
So far, federal officials have also been reluctant to vaccinate farmers, saying the risk is still low.
The real risk, Emory’s Dr. Lowen said, is if a farmer becomes infected with both the H5N1 virus and the seasonal flu virus. Influenza viruses are adept at exchanging genes, so a coinfection would give H5N1 a chance to acquire genes that allow it to spread between humans as efficiently as seasonal flu.
The possibility underscores the importance of vaccinating farmers, Dr. Lowen said: “Anything we can do to limit seasonal infection in people occupationally exposed to H5N1 could really reduce the risk.”
