The outbreak of avian flu in dairy cattle has so far spread to only three farm workers in the United States, as far as public health authorities are aware. All experienced mostly mild symptoms.
But that doesn’t guarantee that the virus, called H5N1, will remain benign if it begins to spread among humans. Accumulating evidence from the animal world and data from other parts of the globe actually suggests the opposite.
Some dairy cows never recovered from H5N1 and died or were put down due to this virus. The infected terns appeared disoriented and unable to fly. The baby elephant seals had difficulty breathing and developed tremors after catching the virus. Infected cats became blind and walked in circles; two thirds of them died.
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“I absolutely don’t think there’s any room for complacency here,” said Anice Lowen, a virologist at Emory University.
“H5N1 is a highly pathogenic type of influenza virus, and we should be concerned if it spreads to humans,” she said.
In ferrets experimentally inoculated with the virus through the eyes — the suspected route of infection among U.S. farmworkers — the virus quickly spread to the respiratory tract, lungs, stomach and brain, according to a published report Wednesday.
Other studies have found similar trends in mice fed contaminated milk. The results suggest that entry through the eyes or digestive system does not make the virus less threatening.
H5N1 turned out to be a promiscuous virus, quickly gaining 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 older version of the virus circulating in Asia killed about half of those infected.
Of the 15 people known to have been affected by the variant currently circulating in cattle, one in China has died and another has been hospitalized. Two patients in Chile and Ecuador had serious symptoms. Four Americans – one last year and the three infected in the latest outbreak – are faring better.
Importantly, no form of the avian flu virus appears to have spread effectively from person to person. That doesn’t guarantee that H5N1 won’t gain 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 properties, because we have never seen an outbreak in cows,” Kawaoka said. Conjunctivitis, also known as pink eye and the main symptom in two of the three farm workers, is not typical of H5N1 virus infection. The appearance of the virus in mammary glands – in cattle and even in non-lactating mice – was also unexpected.
The worry now is that as H5N1 continues to infect mammals and evolve, it could pick up the mutations needed to spread effectively among humans, triggering another pandemic.
The incubation period for the flu is two to four days, and a human-to-human version could spread well before cases are detected, said Erin Sorrell, a virologist and senior researcher at the Johns Hopkins Center for Health Security.
“If this gets out to the general public, it’s too late,” she said. “We missed the boat.”
The flu is usually more serious in older people and children under 5 years old. (A swine flu outbreak in 2009 was not as devastating as feared, but it killed nearly 1,300 children.) The severity of the disease also depends on how much virus is present in infected patients. are exposed and for how long, as well as the route of entry, their genetic background and their general health.
Infected people usually have fever and respiratory symptoms; some cases progress quickly to pneumonia or death. If the avian flu virus were to adapt to humans, the world would need billions of doses of vaccines and antivirals to avoid these consequences.
The federal stockpile contains four types of flu antivirals, but the drugs must be taken within 48 hours of symptoms appearing to be effective. A recent review found too little evidence to assess the effectiveness of three of the four drugs, including the commonly used oseltamivir, sold under the name 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 transmitted in animal populations. No mutations were observed against the fourth drug, baloxavir.
But there are only a few hundred thousand doses of the drug in stock, according to David Boucher, director of infectious diseases for the federal Strategic Preparedness and Response Administration.
Vaccines are a better solution to stemming a pandemic, but sufficient doses are unlikely to be available for at least several months. Even if global production of seasonal flu vaccines were shifted entirely to H5N1 vaccines, the number of doses manufactured would be enough for fewer than 2 billion people, assuming two doses are needed for each person.
In the United States, the national stockpile contains hundreds of thousands of vaccine doses that could be administered to people at risk, including children. Companies contracting with the government could make more than 100 million doses in the first 130 days, Boucher said.
Authorities recently announced they had taken steps to prepare 4.8 million doses that could be bottled without disrupting production of seasonal flu vaccines.
But most of these plans will only be useful if the virus cooperates.
Since its first appearance, the H5N1 virus has diversified into many forms, and scientists have created a library of 40 corresponding candidate vaccine viruses. Having them ready to go saves crucial time because creating a new candidate can take three months, said Todd Davis, a virologist at the Centers for Disease Control and Prevention.
So far, he said, the virus has changed very little, particularly the part of the virus that binds to human cells, called hemagglutinin, or HA.
If the virus were to spread among humans, it would first have to change significantly, some experts note. “If this virus attacks humans, you can be sure that the HA will change, because at the moment the HA in this virus does not bind to human cells very effectively,” said Scott Hensley, an immunologist at the University of Pennsylvania.
Traditional flu vaccines are made by growing candidate viruses in eggs or in mammalian cells, two methods that have many potential problems: The virus may not grow fast enough or mutate too much as it develops. his growth.
In 2009, the candidate virus grew well in eggs but evolved into a poor match for the wild H5N1 virus, leading to long delays in distribution to the public. “By the time vaccine stocks were built and distributed, the first wave of the pandemic had already subsided,” Hensley said.
CSL Sequiris, a leading manufacturer of seasonal flu vaccines, has a cellular H5N1 vaccine that is already approved by the Food and Drug Administration.
In the event of a pandemic, once CSL receives 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 executive director. (The company also has contracts with 19 other countries.)
But 150 million doses would only protect about 1 in 5 Americans. Federal officials are also studying mRNA avian flu vaccines, which could be made very quickly, as the COVID pandemic has illustrated, to protect against both cows and humans. Hensley’s team is testing an mRNA vaccine in cows.
Authorities have been reluctant to roll out vaccines for cows due to trade concerns, experts said: Some countries ban imports of products from vaccinated birds and animals.
But vaccinating cows would reduce the risk to farmworkers and other cows, and limit the possibilities for the virus to spread and evolve, experts said.
So far, federal officials have also been reluctant to vaccinate farmworkers, saying the risk is still low.
The real danger, Lowen of Emory said, is that a farmworker becomes infected with both H5N1 and the seasonal flu virus. Influenza viruses are capable of exchanging genes, so co-infection would give H5N1 the opportunity to acquire genes that would allow it to spread among people as effectively as seasonal flu does.
This possibility underscores the importance of vaccinating farmworkers, Lowen said: “Anything we can do to limit seasonal infection in people occupationally exposed to H5N1 could really reduce the risk. »
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