As far as public health officials know, the avian flu outbreak in dairy cows has so far only affected three farmworkers in the United States, all of whom have mostly mild symptoms.
But there's no guarantee that the virus, called H5N1, will remain harmless once it begins to spread among humans — in fact, accumulating evidence from the animal kingdom and data from other parts of the planet suggest the opposite.
Some dairy cows never recovered from H5N1 and died or were slaughtered due to it. Infected terns seemed disoriented and unable to fly. Elephant seal pups had difficulty breathing and began shivering after contracting the virus. Infected cats went blind and walked in circles, and two-thirds of them died.
“I don't think there's any room for complacency here,” said Annise Loewen, a virologist at Emory University.
“H5N1 is a highly pathogenic influenza virus and we should be of very high concern if it were to infect humans,” she said.
A report released Wednesday said that in ferrets that were experimentally inoculated with the virus through their eyes – the presumed route of infection for U.S. farm workers – the virus quickly spread to the airways, lungs, stomach and brain.
Other studies have found a similar pattern in mice fed contaminated milk, suggesting that entry through the eyes or digestive system may not reduce the virus' threat after all.
The H5N1 virus is omnivorous, rapidly adopting new hosts, including wild birds, poultry, rats, bears, cats and sea lions. Since it was discovered in Hong Kong in 1996, it has infected about 900 people.
An older version of the virus circulating in Asia killed about half of those infected.
Of the 15 people infected with the strain currently circulating among cattle, one has died and another has been hospitalized in China, two patients have become seriously ill in Chile and Ecuador, and four people in the United States have become mildly ill – one infected last year and three infected during this current outbreak.
The point is, no strain of the bird flu virus appears to be able to transmit efficiently from person to person, and there's no guarantee that H5N1 won't acquire that ability, said Yoshihiro Kawaoka, a virologist and bird flu expert at the University of Wisconsin-Madison.
“We haven't seen any outbreaks in cows, so we think the nature of the virus is clearly changing,” Dr. Kawaoka said. The main symptom seen in two of the three farm workers, conjunctivitis, also known as pink eye, is atypical of H5N1 infection. The appearance of the virus in the mammary glands of cows and even in non-lactating mice was also unexpected.
The current concern is that as H5N1 continues to infect mammals and evolve, it could acquire the mutations necessary to spread efficiently among humans and spark a new pandemic.
The incubation period for influenza is two to four days, meaning person-to-person transmission can occur long before a case is detected, said Erin Sorrell, a virologist and senior scholar at the Johns Hopkins University Center for Health Security.
“Once it spreads to the general public, it's too late,” she said. “We've missed our chance.”
Influenza typically hits older people and children under the age of 5 most seriously. (The 2009 swine flu epidemic, while not as devastating as feared, killed nearly 1,300 children.) The severity of the illness depends on how much and for how long an infected patient was exposed to the virus, as well as how they were infected, their genetic background, and their overall health.
Infected people typically develop fever and respiratory symptoms, but in some cases can rapidly progress to pneumonia and death. If the avian flu virus were to adapt to humans, the world would need billions of doses of vaccines and antiviral drugs to prevent this.
There are four flu antiviral drugs in the federal stockpile, but they must be taken within 48 hours of the onset of symptoms to be effective. One recent study found there was too little evidence to determine the effectiveness of three of the four drugs, including the common oseltamivir, sold as Tamiflu.
Some new versions of H5N1 have mutations that make them resistant to oseltamivir and two other drugs, but fortunately these mutations have not been widely transmitted in animal populations, and no mutations to the fourth drug, baloxavir, have been observed.
But there are only a few hundred thousand doses of that drug in the stockpile, according to David Boucher, infectious disease director at the federal Strategic Preparedness and Response Agency.
A vaccine would be a better option to stop a pandemic, but sufficient vaccines are unlikely to be in supply for at least many months: even if global production of seasonal influenza vaccines were completely switched to vaccines against H5N1, there would still not be enough vaccine for even 2 billion people, assuming two doses per person are needed.
The US has hundreds of thousands of doses of vaccine in the national stockpile that can be distributed to at-risk people, including children, and companies under government contract could manufacture more than 100 million doses in the first 130 days, Dr. Boucher said.
Officials recently announced they have taken steps to prepare 4.8 million doses of the vaccine that can be bottled without disrupting seasonal flu vaccine production.
But most of these plans will only help if the virus cooperates.
H5N1 has branched out into many different forms since it first emerged, so scientists have created a library of 40 so-called candidate vaccine viruses to match it. Developing a new candidate can take up to three months, so having one ready to go can save valuable time, said Todd Davis, a virologist at the Centers for Disease Control and Prevention.
So far, the virus has remained largely unchanged, particularly the part of the virus that binds to human cells, called hemagglutinin (HA), he said.
Some experts say that if the virus is to spread among people, it would first have to change significantly. “If this virus infects humans, it would have to change its HA, because right now it 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 candidate viruses in eggs or mammalian cells, both of which have potential problems: The viruses may not grow fast enough, or may mutate too much as they grow.
In 2009, the candidate virus grew well in eggs but evolved into one that was incompatible with wild H1N1 viruses, leading to a long delay in distribution to the public. “By the time vaccine stocks were manufactured and distributed, the first wave of the pandemic had already subsided,” Dr Hensley said.
CSL Sequilis, a leading manufacturer of seasonal influenza vaccines, already has a cell-based H5N1 vaccine approved by the Food and Drug Administration.
In the event of a pandemic, CSL executive director Mark Lacey said, if it had a vaccine candidate that matched the circulating strain, it could provide 150 million doses to the U.S. population within six months (the company also has agreements with 19 other countries).
But 150 million doses would only protect about one in five Americans. Federal officials are also studying mRNA avian flu vaccines, which could be produced very quickly to protect both cows and humans, as the COVID-19 pandemic has shown. Dr. Hensley's team is testing an mRNA vaccine in cows.
Experts say authorities are hesitant to vaccinate cattle due to trade concerns, and some countries have banned the import of vaccinated birds and animal products.
But immunizing cows could limit the risk to farm workers and other cows and limit the opportunity for the virus to continue spreading and evolving, experts say.
So far, federal officials have been reluctant to vaccinate farm workers, saying the risk remains low.
Emory's Dr. Loewen said the real danger would be if farmworkers were infected with both H5N1 and seasonal influenza viruses: Influenza viruses are good at swapping genes, so co-infection would give H5N1 a chance to pick up genes and spread between people as efficiently as seasonal influenza.
This possibility highlights the importance of vaccinating agricultural workers, Dr. Loewen said: “Anything we can do to limit seasonal infections in people who are occupationally exposed to H5N1 can really reduce the risk.”
