article

01.14.13

Flu Fears: The Race Between Pandemic Viruses and a Universal Vaccine

John M. Barry, author of The Great Influenza: The Story of the Deadliest Pandemic in History, on this year’s epidemic.

The recent upsurge of influenza has officially crossed the line– although so far just barely—into epidemic status, and it looks like it will be a bad year. It’s too early to tell exactly how lethal the disease will be: there is tremendous variation year to year, with an annual death toll from ordinary seasonal influenza in the U.S. ranging from 4,000 to as high as 40,000, according to the Centers for Disease Control and Prevention. And the vaccine this year has been only moderately effective, with those taking it 62 percent less likely to get the disease than those who don’t. (In a good year the vaccine is over 80 percent effective.)

There is good news. The virus causing the overwhelming majority of disease this year is the regular “season flu,” or H3N2, not the “swine flu,” or the H1N1 pandemic virus of 2009 that jumped to humans from pigs. There is no sign of viral resistance this year to the two drugs (oseltamivir, sold as Tamiflu, and zanamivir, sold as Relenza) that can shorten the illness and moderate its severity if taken in the first 48 hours after symptoms appear. And promising work continues toward a universal influenza vaccine, one that would work at a high level of effectiveness against all such viruses, including any new pandemic ones.

But there’s no time to spare in developing that vaccine: H1N1 is still out there, likely to return in force in the next few years, and the threat of the far more lethal H5N1 bird-flu virus persists.

All these viruses play a perpetual game of hide-and-seek with the human immune system. Influenza is one of the fastest-mutating viruses in existence—which explains why a new vaccine has to be produced each year (and why a given year’s batch sometimes misses the target) and the year-to-year variations in lethality.

In good influenza years, when the virus doesn’t “drift” too much from prior years, natural immunity tends to be high and the vaccine hits its target. In bad years, the drift is more pronounced and vaccine doesn’t work as well, so more people get sick and die. Worse, influenza viruses can jump species from animals to the human population, creating new viruses that people have little natural immunity to and for which no vaccines exist. These can become the pandemics that cause widespread disease, as happened in 1918—when the “Spanish flu” killed as many as 100 million people—1957, 1968, and, of course, 2009.

But normal year-to-year variation in the virus can be lethal too. The deadliest year since the 1918–19 pandemic was not 1957, 1968, or 2009; it was 1951, when the seemingly run-of-the-mill virus turned especially virulent.

And then there’s “bird flu,” an H5N1 virus that has occasionally jumped from birds to people and has killed 60 percent (345 of 584 people) of those its infected.

In 2009 nearly all influenza cases were caused by the pandemic H1N1 virus, driving the previously dominant H3N2 underground. Since then H3N2 has roared back, this year in a huge way: right now it’s responsible for 98.9 percent of illness caused by influenza A viruses, with only 1.1 percent caused by H1N1. While influenza B also causes illness, it is not considered a major threat, and the present vaccine provides some protection against all three.

The 2009 “swine flu” outbreak was far more serious than is generally recognized with a much higher actual death toll than reported.

But in the future, those numbers could again swing dramatically. Many people consider the 2009 pandemic an overhyped nonevent, partly because the world feared a much more lethal bird-flu pandemic and partly because the media routinely but mistakenly cited a worldwide death toll of 18,000. In fact, that number includes only “laboratory confirmed” pandemic deaths—but only a tiny fraction of the victims were tested. So the 2009 outbreak was far more serious than is generally recognized; its actual total death toll was much higher: an estimated 9,000 to 18,000 in the U.S., pretty close to the number of AIDS deaths here, and 150,000 to 575,000 worldwide.

But even those numbers mask the pig flu’s real impact. Normally, the overwhelming majority of influenza deaths are in the elderly and fragile. But in 2009, 80 percent of the deaths were in people younger than 65, including many young adults.

This year influenza looks serious, but it’s still nothing like what a really lethal influenza season can be. What this year and 2009 both show us is the urgent need for the universal vaccine. According to Gary Nabel and Anthony Fauci, two outstanding infectious-disease experts generally not given to over-optimism, that goal is finally within sight. That would be a very good thing, for if they are wrong, we still could face a global calamity.

H5N1 is still out there, infecting people and threatening to become the next human pandemic—and in Indonesia in 2012, it killed 100 percent of those known to have gotten sick from it.