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Twice a year, influenza experts from 10 institutions around the world meet at the World Health Organization’s Geneva headquarters to pore over mounds of data. At the end of the weeklong meetings, they make decisions that affect people around the world: namely, which variants of the flu virus should be used for vaccinations the following season.

While the selections don’t always hit the mark — influenza is notoriously hard to predict — it’s the best process health officials have to keep flu vaccines up to date and try to protect people from the annual scourge.

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Now, with the pending withdrawal of the United States from the WHO, the future of the process — or at least America’s involvement in it — is in question. President Trump has criticized the global health agency’s handling of the Covid-19 pandemic, and other earlier health crises; he has cited that as his rationale for withdrawing from the WHO, which was established more than 60 years ago.

Currently, the flu strain selection group includes three seats for institutions from the United States, which uses more flu vaccine than any other country in the world. It’s unclear how the U.S. officials might try to preserve its role in the process, or whether it could.

Without access to the intelligence coming from other institutions at the table, the U.S. would be “flying blind,” said Nancy Cox, who retired from the Centers for Disease Prevention and Control in 2014 after leading the agency’s influenza division for 22 years.

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For one thing, new flu variants don’t typically emerge in the Americas; they often are first spotted in Asia. For another, countries that are reluctant to share viruses on a bilateral basis — because of fears others will profit from them — will often only share viruses with the WHO.

The risk to the U.S. wouldn’t simply relate to season flu vaccine. Participants at the meetings share important intelligence on animal flu viruses — avian and swine influenza — that could pose pandemic threats. (Viruses that jump from animals to humans are called zoonoses.)

“You won’t know what’s coming. You won’t be aware of what’s going on with respect to zoonotic flu cases,” said Cox. “It would be a really difficult position to be in at CDC as head of the influenza division and not have access to the information to be able to keep people within the U.S. informed about the global threats that exist out there.”

Richard Webby is the director of one of the 10 institutions involved in the strain selection process, the WHO Collaborating Center for Studies on the Ecology of Influenza in Animals, located at St. Jude Children’s Research Hospital in Memphis. It’s one of six WHO collaborating centers for flu research. The CDC also is a WHO collaborating center, with the others located in Australia, Britain, Japan, and China.

He, too, sees real problems if the U.S. can no longer take part in the strain selection process.

“I think if the U.S. collaborating centers are not at the table, you know, actually hearing the discussions, seeing the in-depth analyses from the other collaborating centers, I think that that would be a blow,” said Webby.

Four key regulatory agencies are also at the table — the Food and Drug Administration, and counterparts from Australia, Britain, and Japan.

Representatives of the collaborating centers arrive at the WHO meetings armed with data submitted to them from national influenza laboratories in 125 countries around the world. In the months leading up to the meetings, scientists in the collaborating centers chart the genetic sequences of the thousands of flu viruses but also test them to see how different they are from known circulating strains.

The sequence of a virus may show mutations that might change the way the virus behaves. But it’s only when the testing is done that one can see if the new variant appears to be able to evade the protection of the viruses selected for inclusion in the previous year’s vaccine. If a variant that is sufficiently different seems to be gaining momentum and appears poised to become the dominating variant of its strain — H1N1 or H3N2, say — the experts will recommend flu vaccine manufacturers swap out the old version and replace it with the new variant.

This process is done for four types of flu — the two influenza A viruses, H1N1 and H3N2, and the two influenza B viruses, known as B/Victoria and B/Yamagata. And it happens twice a year: the group looks for variants that are likely to cause the most problems in the coming Northern Hemisphere winter (the February meeting) and the Southern Hemisphere winter (the September meeting).

Once the Northern Hemisphere selections are made, committees in the United States that advise the CDC and the FDA review the decisions. While they have the power to ask for changes for vaccines destined to the U.S. market — and they sometimes do — they are working from the data shared at the WHO meeting.

Malik Peiris, a leading influenza expert at Hong Kong University, said the flu surveillance network — Global Influenza Surveillance and Response System — would suffer if the U.S. partners can’t participate because they are no longer part of the WHO. But the bigger loser, he suggested, might be the United States.

“How on earth can the United States do proper global vaccine selection for flu if they are working on their own? It’s completely impossible,” he said. “Basically, they’ll be forced to copy whatever is decided. Because how can they get the data from the rest of the world?”

Webby said that wouldn’t be in the interest of the U.S. It is often unclear which variants are likely to become dominant in the coming months. What looks important to one region may not seem like the best choice to another.

“So, I think, losing three votes for what is the best decision for the Americas, although it’s a global decision, certainly the [other] collaborating centers have an intrinsic bias from what’s circulating in their own regions,” he said.

He is also concerned about the U.S. capacity to stay on top of pandemic flu threats if it’s not at the table for the strain selection meetings. As part of its pandemic flu preparedness work, the U.S. makes and stores in the Strategic National Stockpile doses of the vaccines against the animal flu viruses deemed to be the highest pandemic risks.

“Being inside that circle that are making these frontline decisions and getting access to the frontline data as it comes off is so vital,” said Webby. “You have to have that global picture to make sure you have the best vaccines.”

Of the roughly 500 million doses of flu vaccine made each year, the United States uses upward of 170 million doses, Cox said.

The WHO, which has said little about the threatened U.S. withdrawal, lauded the country’s contribution to global influenza surveillance. Among the projects U.S. voluntary contributions to the WHO support is the flu surveillance program. (Cox fears jobs in that department may be lost with the withdrawal of U.S. funding.)

“WHO hopes that the technical institutions such as CDC will continue their technical collaboration within the [surveillance] network,” spokesman Tarik Jasarevic said via email.

The Trump administration has said it is reviewing the programs on which it collaborates with the WHO, looking for alternative organizations to support the same kind of work. It has been reported that the United States may continue to interact with the WHO, but only on issues that are deemed to be in the country’s national security interests.

The Department of Health and Human Services would not say if flu vaccine strain selection will be one such exception.

“There are many areas and issues where the United States and WHO have collaborated, and as part of the withdrawal process all of these are being examined to ensure that as we move forward the health and safety of the American people remain in the forefront,” a spokesperson said.

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