NEW YORK — As bad as this year's flu season is, it hasn't brought the worldwide outbreak known as a pandemic. But experts warn that a pandemic is coming, it's just a question of when.

"It's going to happen," said Dr. Greg Poland of the Mayo Clinic. "For the American public in particular, I think it will be horrific."

Many Americans haven't experienced the overwhelming crush of patients at hospitals and doctors' offices and the widespread fear a flu pandemic could bring. And by historical pattern, Poland said it's about time for the next one.

There have been three in the past 100 years, igniting in 1918, 1957 and 1968. There's no way to predict when the next one will appear, but the pattern does give experts pause.

It's all up to a virus that is variable and fickle, constantly changing its genetic makeup, and the time when it hits upon a combination that lets it take off worldwide is a "roll of the genetic dice," said Dr. William Schaffner of Vanderbilt University.

So the lack of a pandemic in the past 35 years basically means "the genetic dice haven't been rolled that way," Schaffner said. "While we're grateful for that, it makes us nervous."

There's plenty to be nervous about. It's estimated that in the industrialized nations alone, the next pandemic is likely to send 1 million to 2.3 million people to the hospital and kill 280,000 to 650,000, according to the World Health Organization. Its impact will probably be greatest in developing countries.

As a practical matter, flu shots probably could not be counted on to prevent a pandemic. For one thing, pandemic virus strains emerge unexpectedly, and there would probably not be enough time to recognize the threat and then provide vaccines that target them, Schaffner said. What's more, many countries outside the United States wouldn't have the means to give enough flu shots to stop the spread, Poland said.

Dr. Robert Couch of the Baylor College of Medicine noted that health authorities are making major efforts to prepare for controlling a pandemic, including putting an emphasis on developing and manufacturing vaccines faster and in greater quantities.

The pandemic of 1918-19, known as the Spanish flu, sickened an estimated 20 percent to 40 percent of the worldwide population, with a death toll believed to exceed 20 million. In the United States alone, some 500,000 people died. An ordinary flu epidemic kills an average of 36,000 Americans.

The next pandemic, the Asian flu of 1957-58, killed about 70,000 in the United States. The 1968-69 Hong Kong flu led to about 34,000 deaths in the United States. Scientists suggest several reasons why this rate was lower than in previous pandemics, including that the illness did not gain momentum until near the school holidays in December, when children were home rather than infecting each other at school.

New strains of the flu virus, and so potential pandemics, get their start in rural Asia, where the various strains that infect chickens and other birds, pigs and humans can mingle. That gives them a chance to swap genetic information as well as mutate on their own.

The potential spark for a pandemic occurs when that environment produces a new virus that infects people and bears surface proteins that people's bodies have never seen before. That means people have no natural defense against it.

In contrast, ordinary outbreaks like this year's come from a virus that has changed only slightly from previous ones, so that the population it enters still has some natural immunity from encounters with the previous germs.

But the genetic shift alone is not enough to launch a pandemic. In addition, the new virus must acquire the ability to pass easily from person to person, either by random genetic change or by picking up genetic material from a previous human flu virus.

The world has had some close calls in the past few years, says Richard Webby of St. Jude's Children's Research Hospital in Memphis. In 1997, a bird flu in Hong Kong jumped to people, killing six. But the virus never developed the ability to pass easily from person to person, Webby said. Hong Kong authorities slaughtered 1.4 million chickens to end the threat.

Just this year, authorities became alarmed when a father and son in Hong Kong were hospitalized because of a bird flu virus, and when flu virus infected some workers in the Netherlands who had slaughtered infected chickens. The Netherlands outbreak was contained by anti-flu drugs and fast vaccination, and slaughter of the poultry, Webby said.

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Scientists have been noticing a lot of flu virus in chickens and pigs globally, and a lot of variety in the strains, which is worrisome, Webby said. It's impractical to develop vaccines against all the animal strains in case they jump to humans, and there's no reliable way to identify the most hazardous ones, he said.

When the next pandemic shows up, experts say, it will find a population with many more vulnerable people like the elderly, infirm and those with weakened natural defenses than were living 35 years ago. It will also find a trimmed-down hospital system with fewer beds to handle a surge of patients. And while today's anti-flu drugs will probably attack the new strain, that's not yet clear. Supplies of the drugs and vaccines would be strained.

But still, with the improvements in health care since the last pandemic, might the next one be less serious?

"I want to believe that," Poland said, "but we won't know until it happens."

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