Mysteries of the Flu

Influenza is a common virus with a long history. Then why do we know so little about it?

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There is a joke among flu researchers: “If you’ve seen one flu season, you’ve seen…one flu season.” The translation, for those not up on epidemiological humor: the joke is wry commentary on the unpredictable nature of the flu virus. Every year it looks different, and every strain follows its own pattern. This is not just a quirk that frustrates scientists—it’s the reason new strains like H1N1 are impossible to anticipate and fully prepare for.

“I know less about influenza today than I did 10 years ago,” quips Dr. Michael Osterholm, director of the Minnesota Center of Excellence for Influenza Research and Surveillance and a former adviser to the U.S. Department of Health and Human Services. “Every stone we’ve turned over, we get more questions than we do answers.”

The flu returns every season and the world periodically experiences catastrophic pandemics, but epidemiologists still do not understand why some strains evolve to infect people and others do not; they are not entirely sure about how the flu is transmitted; nor do they understand why some patients become fatally ill while others develop minimal symptoms. As a result, when a new strain shows up—like H1N1—they often have little information to fall back on, and the lessons of previous pandemics are only somewhat helpful. While epidemiologists are still putting together a complete picture of H1N1, for example, its most striking difference with the seasonal flu is that the elderly are not the most vulnerable population. And when H1N1 does cause serious illness, patients develop different complications (that are more difficult to treat) than those with seasonal flu. “It’s a very different death,” says Osterholm.

The Centers for Disease Control currently maintains six different categories of flu-surveillance programs, but has rolled out new measures this year in order to monitor H1N1’s most worrying features. The backbone of its routine surveillance systems is not designed to count individual flu cases, but rather to get general indicators of how widespread the flu is and which strains are in circulation. Uncertainty about the fast-moving H1N1 prompted the CDC to begin asking state health departments to report the number of hospitalizations and deaths caused by influenza, and it is still adjusting the methods for calculating the disease’s impact. Even the methods for counting the number of those who died of H1N1 is uncertain: on Tuesday, The New York Times reported that the CDC will revise its estimates of H1N1 deaths to 4,000 from 1,200. This revised figure is the result of a new calculation that encompasses fatal cases confirmed via lab tests to have been caused by H1N1, as well as hospital reports of deaths that “appear to have been brought on” by the flu.

Influenza’s chimerical nature makes it a moving target for researchers, says Dr. Allison Aiello, assistant professor of epidemiology at the University of Michigan. (NEWSWEEK reached Aiello by phone at home, where she and her husband are both recovering from H1N1 under self-imposed quarantine to protect their infant child.) “Even if we had [complete] seasonal flu data from the past, it wouldn’t necessary be helpful for a new strain” of influenza, she explains.

Aiello identifies three areas where additional research would be most useful. First, the exact mechanism of flu transmission is unclear. If it is primarily transmitted through the air, how large must infectious particles be in order to pose a threat? What role does hand-to-hand contact play in transmitting the virus, if any? This is an area where it is especially hard to study the flu on its own, because it can be expensive to perform the lab tests on sick patients to separate influenza from other “flulike” illnesses that cause similar symptoms but may be transmitted differently. A cough and a fever could be caused by influenza, but it also could be the common-cold virus or many other bugs. Understanding how the flu spreads will help fill in gaps in a second area: how can face masks and hygiene measures effectively protect against transmission?

Finally, we need more information on the immune response and why certain patients fare far better than others once they become infected. One of the most alarming things about H1N1 is the high rate of serious illness among otherwise healthy adults as compared with the seasonal flu, which takes its heaviest toll mostly on the elderly. (In fact, some studies have suggested, the populations hardest hit by the H1N1 pandemic resemble those targeted by the catastrophic 1918 outbreak, though the overall number of deaths is so far much lower.)

Though influenza might be hard to pin down under the best of circumstances, researchers say the epidemiological community may be behind because the flu was a low priority until recently. “The flu was—if not ignored—not as studied as it need to be,” comments Dr. Arthur Reingold of the UC Berkeley School of Public Health. “That’s been true for decades.” This situation began to change around 2005, when 43 people died in Asia from avian flu. Though this never turned into a catastrophic pandemic, it prompted governments to step up their flu-preparation efforts, including the United States, which that year launched a national strategy for pandemic influenza.

While epidemiologists are frustrated by the holes in their knowledge, they say, however, that the public-health community is generally doing a very good job responding to H1N1 with the information that does exist. Studying influenza, says Osterholm, is “like looking through the windows of a house you can’t get into because the door is locked.” Piecing together the data epidemiologists do have is like “looking through the windows…[to] get a pretty good picture of what the inside looks like.”

One thing researchers do know for sure: the best way for Americans to protect against H1N1 is to get the vaccine once it becomes available to them.


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