Bird flu may kill millions, or it may fizzle out among the chickens. But if it does spread among humans, the legacies of earlier flu pandemics...

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WASHINGTON — Bird flu may kill millions, or it may fizzle out among the chickens. But if it does spread among humans, the legacies of earlier flu pandemics offer at least two lessons on what to expect:

• There will probably be a warning. An early “smoldering” phase of relatively few deaths might offer a grace period to get started on a vaccine or reduce large shortages of treatment drugs.

• If the flu does catch fire, a large proportion of the dead will be healthy young adults, either because they don’t have immunity to the flu strain or because their defense systems go into dangerous overdrive.

Those likelihoods, based on recent studies of the catastrophic 1918-19 Spanish flu and two later pandemics, may figure prominently into the federal government’s long-awaited blueprint to prepare for and respond to a flu calamity.

President Bush today will announce his strategy on how to prepare for the next flu pandemic. Knowing a pandemic might kill large numbers of working-age adults would be vital background for health authorities deciding which Americans would get scarce supplies of flu vaccines and treatment.

“The healthy, the young are critical members of society,” said Shelley Hearne, executive director of Trust for America’s Health, a Washington group that tracks public-health issues. “They keep the lights on, the water running, they are the first responders. These are the people needed the most in a major health crisis.”

In a typical flu season, the elderly account for about 90 percent of fatalities. But in a flu pandemic, “you have about half the deaths or more in people under 65,” said Lone Simonsen, an epidemiologist at the National Institute of Allergy and Infectious Diseases.

In 1918-19, deaths soared among the young, while mortality among the elderly didn’t even suggest a severe season.

Young adults’ vulnerability in a pandemic may be linked to the fatal overreaction of their strong immune systems. With a serious flu, the lungs may be flooded by too many immune cells, leading to inflamed tissues, clogged air passages and cells unable to properly absorb oxygen.

Or, younger people may not have immunity. Studies have shown that people who were 77 or older in 1968-69 carried effective antibodies from being exposed to a similar flu virus around 1892.

“There was some benefit from having those old antibodies hanging around from childhood,” Simonsen said.

The U.S. has experienced three flu pandemics since 1900; all told different stories.

Still, all three flus had this in common: They qualified as pandemics not because of their large death tolls, but because they were “novel” viruses — new strains unrecognized by contemporary immune systems.

The two most recent pandemics — the Asian flu of 1957-58 and the Hong Kong flu of 1968-69 — shared an important characteristic: Each virus became novel through a genetic process called “reassortment.”

Viruses survive by entering healthy cells, hijacking their hosts to replicate before spreading. Sometimes two viruses enter the same cell. If a human virus and a bird virus meet, they might swap genes — reassort — and create a novel strain.

The final product can be nasty. Hong Kong flu killed 40,000 more people in the U.S. than a routine flu. Asian flu killed 60,000 more.

“The concern is, you get the virulence from the avian flu, but the contagiousness from the human strain,” said Dr. James Campbell, a researcher at the Center for Vaccine Development at the University of Maryland School of Medicine.

The 1918-19 Spanish flu pandemic, on the other hand, was a bird virus that mutated differently. Somehow it spread among humans without picking up human genes. That mysterious jump, along with its awesome death toll — 500,000 Americans — is why experts fear the current bird flu could be devastating.

“We have no idea how many [mutations] it would take before it takes off in humans,” said researcher Richard Webby, a flu specialist at St. Jude Children’s Research Hospital in Memphis, Tenn. “It could be it needs to change two amino acids. It could be it needs to change 20 to 30.”

Health experts once assumed pandemics acted like tornadoes, arriving with almost no warning and spreading with little interruption. But recent research found early waves sometimes are mild and account for few deaths.

One study of New York City showed the Spanish flu caused modest death in spring 1918 before blooming into a full-blown crisis in the fall.

The 1968-69 pandemic, initially mild in many countries, caused most of its deaths in the second season.

On the other hand, the 1957-58 pandemic spread aggressively in its first season. With only three pandemics to study, experts are unable to predict how the next pandemic might unfold.