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Pandemics in perspective

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Police officers in Seattle wear face masks during the flu epidemic of 1918.

How bad can a flu epidemic get? The raw numbers indicate that over the past 90 years, far more people have been killed by relatively run-of-the-mill seasonal flu viruses than by the exotic bugs that have grabbed most of the headlines - such as bird flu or the current strain of swine flu.

But to get a more useful perspective on a flu epidemic's potential impact, you have to go back to the mother of all pandemics: the "Spanish flu" of 1918.

Newly published research supports the view that the H1N1 virus behind the current outbreak is a distant cousin of the virus that sparked the infamous 1918 epidemic. But all the signs so far indicate that the 1918 flu was much more lethal. In fact, some researchers report that today's headline-making microbe lacks some of the molecular machinery that made past versions of the virus deadlier.

Citing such reports, the Los Angeles Times noted today that the current outbreak "may not even do as much damage as the run-of-the-mill flu outbreaks that occur each winter without much fanfare."

So far, the raw numbers bear that out. Typically, about 36,000 Americans die each year due to flu complications, according to the Centers for Disease Control and Prevention. The worldwide toll is estimated at 250,000 to 500,000 annually. If you go back to the most recent officially recognized flu pandemic, the 1968-69 Hong Kong flu, the death toll is about the same: 34,000 in the U.S., 500,000 globally. The figures for the 1957-58 Asian flu pandemic are 70,000 U.S. deaths and 2 million deaths worldwide.

Even those figures pale in comparison with the 1918-19 flu pandemic: At least 550,000 people died in the United States alone. The worldwide death toll was estimated at 20 million to 40 million, or perhaps even as many as 100 million by some accounts. The flu killed more people than World War I (which may have contributed to its spread).

Compared to past pandemics, the current swine-flu outbreak is hardly a blip on the chart. (Speaking of charts, you can click onto a couple that show you mortality rates since 1900 and since 1950.) Last year, MIT researcher Peter Doshi pointed out that not all pandemics turn out to be as serious as the annual seasonal flu. And in its swine-flu FAQ, the Canadian government makes a similar point.

So does that mean the current outbreak is just a piddling pandemic? Not necessarily.

For one thing, it's far too early to assess how this outbreak will end up. For another thing, the pattern of the deaths so far is distressing. Both those caveats draw on the lessons learned from the 1918 flu.

The age factor
"The big difference between seasonal flu and pandemic flu is that when you move to pandemic flu, you get a pattern that the older people are not affected," said Lone Simonsen, an epidemiologist at George Washington University who is also the founder and president of SAGE Analytica. The age distribution curve for a typical seasonal flu looks like a "U," while the distribution pattern for the 1918 flu was more of a "W," as seen on this chart.

Experts worry that the distribution pattern for the current outbreak looks similar. Every death from the flu is a tragedy, but it's particularly tragic when a significant number of the fatalities come in the 20-to-50 age bracket rather than the over-85 bracket.

"That's a lot of life years lost," Simonsen said. "It has another flavor to it."

Simonsen and her colleagues are still trying to figure out why the 1918 flu hit people in the prime of their lives so hard. One hypothesis is that the virus could somehow push a healthy immune system into such a violent response that the body suffered irreparable damage. Another idea is that the older people had acquired immunity from a previous flu epidemic, while younger people missed out. Simonsen said a third possibility is that some sort of bacterial co-infection made the flu worse. Or it could have been a combination of factors.

Wave of the future
Even if the current outbreak turns out to be relatively mild, that's not necessarily the end of the story. "When you look at the past pandemics, you observe that they often come in waves," Simonsen said.

She said a review of the records from 1918 show that the year's first flu flare-up actually came in the spring and summer, in the form of a less lethal but highly transmissible infection. That appears to have been the precursor for the deadlier waves of influenza that swept across the world that fall.

If the current outbreak turns out to follow a similar pattern, that would be "good and bad news," Simonsen said. It's bad news because a worse outbreak could conceivably follow. But it's good news, she said, because we'd have "more time to defend ourselves," using all the defenses that have been developed since 1918.

Patrolling the pigs
In recent years, the biggest concern on the minds of epidemiologists has been avian flu, not swine flu - but the current outbreak is a sign that experts will have to pay attention to the pigs as well, said Juergen Richt, a veterinary researcher at Kansas State University.

He and his colleagues infected pigs with the 1918 "Spanish flu" virus, as well as a virus from 1930 that is thought to be a descendant of the 1918 strain, under Biosafety Level 4 lab conditions. The experiment, described in the May issue of the Journal of Virology, showed that the swine suffered mild respiratory disease but recovered from the infection.

"A virus which is lethal to monkeys, ferrets and mice, and was lethal to people [in 1918], is not lethal to pigs," Richt told me. That suggests that swine could have played a role in maintaining and spreading the 1918 flu, he said.

It also suggests that swine populations might have to be monitored more closely for evidence of potentially dangerous disease strains, perhaps through diagnostic screening. It's not enough to wait until pigs drop dead, he said.

Richt said swine-flu strains appear to be undergoing mutations more rapidly today than they did a decade ago. "Something happened 10 years ago, where the whole evolution of swine flu changed and became very dynamic," he said. Why? Richt said the reason is unknown, although it may have something to do with a genetic change enhancing the virus' ability to jump between pigs, birds and people. (You're free to offer your own speculation in the comment section below).

Richt is a big advocate for research that bridges the gap between human medicine and veterinary medicine, and he told me the current flap over flu viruses just underscores the point.

"It's not only bird flu and swine flu," he said. "There are lots of zoonotic diseases - tuberculosis, Rift Valley fever, Lyme disease. ... We have to realize that only together can we solve these problems."

Earlier postings on the swine flu epidemic: