What Will the Next Influenza Pandemic Look Like?

Features | Health

Predicting pandemics might still be impossible, but with millions of lives at stake, researchers are using the latest science and lessons from history to best prepare for the next big one

By Katherine Harmon ?| September 19, 2011?|

Planning for the unpredictable: The only thing scientists are certain about the next influenza pandemic is that it will happen--sometime, somewhere. Image: flickr/trendscout

MALTA?Contagion, a film released earlier this month, depicts a gruesome outbreak of an exotic and deadly new virus. In the real world, a not-so foreign infection is circulating among animals every day of every year. If it picks up just a handful of certain mutations, it could start spreading among people, with a mortality rate as high as 60 percent. What is this potent virus? The flu.

Although the 2009 pandemic of influenza A H1N1 ended up being relatively mild?killing about one in 10,000 people who came down with it?it still claimed more than 14,000 lives across the globe. The relatively low mortality rate was a relief to forecasters because the outbreak's origin in Mexico and type had taken many by surprise.

Such surprises have turned out to be one of the few constants in the virus world: "Expect the unexpected," Ab Osterhaus, a professor of virology at the Erasmus Medical Center in Rotterdam, said here Tuesday at the fourth European Scientific Working Group on Influenza (ESWI) conference.

The uncertainty factor makes global preparedness particularly challenging. And given the basic questions that remain to be answered?such as why some healthy people die of the flu and others do not?researchers are using new technologies to look for leads in victims as well as in the virus itself.

Because, as scientists and public health experts seemed to agree: "What is clear is that it is when, not if," Frederick Hayden, of the University of Virginia School of Medicine, said here on Tuesday, referring to the next influenza pandemic?one of many proclamations of coming plague during the meeting that was tinged with just enough urgency to generate attention (and research funding) but not ignite an all-out panic.

Ongoing research is providing some new clues about what type of virus might become pandemic, where it might emerge and who it is most likely to kill.

Mysterious mutations
Topping the worst-case scenario list for most flu experts is a pandemic of H5N1, the "bird flu" which has killed about six in 10 people who have gotten it?a total of at least 550 people since 2003?and has laid to waste hundreds of millions of domestic fowl and wild birds.

Fortunately, so far, it has not been transferred from human to human and has passed to us only via direct contact with animals. But any flu can change rapidly, mutating in each new host. So researchers wonder: Could the dreaded H5N1 ever morph into a disease that could spread among people, via a cough or sneeze, to attach to nasal or tracheal membranes, as the seasonal flu does every year?

To help answer this question, Ron Fouchier, also of Erasmus Medical Center, and his team "mutated the hell out of H5N1" and looked at how readily it would bind with cells in the respiratory tract. What they found is that with as few as five single mutations it gained the ability to latch onto cells in the nasal and tracheal passageways, which, Fouchier added as understated emphasis, "seemed to be very bad news."

The variety that they had created, however, when tested in ferrets (the best animal model for influenza research) still did not transmit very easily just through close contact. It wasn't until "someone finally convinced me to do something really, really stupid," Fouchier said, that they observed the deadly H5N1 become a viable aerosol virus. In the derided experiment, they let the virus itself evolve to gain that killer capacity. To do that, they put the mutated virus in the nose of one ferret; after that ferret got sick, they put infected material from the first ferret into the nose of a second. After repeating this 10 times, H5N1 became as easily transmissible as the seasonal flu.

The lesson from these admittedly high-risk experiments is that "the H5N1 virus can become airborne," Fouchier concluded?and that "re-assortment with mammalian viruses is not needed" for it to evolve to spread through the air. And each of these mutations has already been observed in animals. "The mutations are out there, but they have not gotten together yet," Osterhaus said.

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