Many influenza authorities are suffering sleepless nights, eyes trained on Asia where they fear a viral monster is readying itself to unleash a perfect storm of flu on the world.

Should that happen, what will follow will be a public health disaster that will make SARS seem like child's play, they believe. Between a quarter and a third of the world's population will fall ill, according to new World Health Organization estimates, and one per cent of the sick will die.

Do the math and the numbers defy credulity; between 16 million and 21 million people would die in a matter of mere months. In Canada, 80,000 to 106,000 people would be expected to succumb.

Armed with that math, think of the consequences. Panic. Crippled health-care systems. Economic disruption on a global scale. Grounded airlines. Distribution networks that will grind to a halt. Social instability.

Or, "three years of a given hell," as a leading U.S. epidemiologist, Michael Osterholm, puts it: "I can't think of any other risk, terrorism or Mother Nature included, that could potentially pose any greater risk to society than this."

Until recently, official guesstimates of the expected death toll of a new pandemic have been modest. Using mathematical models devised by the U.S. Centers for Disease Control, Canada's public health agency estimates between 11,000 to 58,000 here people might die.

The CDC models point to between two million and seven million deaths worldwide.

Many question those figures and say they're far too rosy. And many believe the WHO's new numbers are overly optimistic as well.

Osterholm is one of them. He's done age-adjusted calculations based on the experience of the 1918 Spanish flu, the worst pandemic in known history.

Laying 1918 fatality rates over the world's current population, Osterholm suggests between 36 million and 177 million people would die if a pandemic of similar severity hit again. (The top figure is based on half the world's population becoming infected.)

But public discussion of numbers like those makes many in the flu world nervous, fearing the figures are so impossibly large they take on the mantle of science fiction.

"None of these models can 100 per cent predict what's going to be happening. And it would be wrong in my view to always play the worst case scenario," cautions Dr. Klaus Stohr, head of the WHO's global influenza program.

"Irrespective of what type of model we are talking about, the figures are certainly not comforting," he continues. "None of these estimates would suggest that we should let down our efforts in pandemic preparedness."

But Osterholm and others around the globe are extremely concerned those efforts are moving at a snail's pace. They fear governments and vaccine companies are dismissing the potential disaster as too hypothetical, too apocryphal.

"This to me is akin to living in Iowa . . . and seeing the tornado 35 miles away coming. And it's coming. And it's coming. And it's coming. And it keeps coming," says Osterholm, who is a special adviser to U.S. Health Secretary Tommy Thompson and associate director of Homeland Security's National Center for Food Protection and Defence.

"You just see it. And we're largely ignoring it."

The "it" Osterholm refers to is a nasty strain of influenza A known as H5N1, so named because of the hemagglutinin (H) and neuraminidase (N) proteins on the virus's outer shell. Though flu is notoriously unpredictable, H5N1 is currently considered the leading candidate to spark the next pandemic.

With 500 years of history to guide them, experts say flu pandemics are inevitable.

The highly unstable RNA viruses are constantly recombining (mutating) and reassorting (swapping genes with each other). The result: new forms of flu are always finding ways to slip past the immune system's sentries to pick the lock of the human respiratory tract.

When an entirely new version appears, one to which no one has any immunity, a pandemic occurs. And with 36 years having elapsed since the last pandemic, experts warn another could come at any time.

The thought of an H5N1 pandemic chills the hearts of those who've been following the virus's evolution since it was first known to have infected humans, in Hong Kong in 1997.

Dr. Keiji Fukuda of the CDC's flu branch investigated the Hong Kong outbreak and others since. He sighs softly when asked whether the prospect of an H5N1 pandemic robs him of sleep.

"More nights than I like," admits Fukuda, head of epidemiology for the branch.

Fukuda chooses his words with care. He often describes H5N1 developments as "spooky," the closest he gets to hyperbole.

"When a pandemic will occur and what the agent might be is completely unknowable," he says.

"Nonetheless I think that all of us are definitely working under an increased sense of urgency because of all of the events that have gone on in Asia. . . .

"We know that we're not adequately prepared. And to that extent we are pushing things pretty urgently."

Since the beginning of the year H5N1 has killed millions of chickens and forced the culling of tens of millions more in at least nine Southeast Asian countries.

It has defied longstanding flu dogma by directly infecting and killing mammals previously thought to be immune to an avian virus, house cats, leopards and tigers among them.

It's also killed 32 of the 42 people - mainly children and young adults - known to have caught it in Vietnam and Thailand. There is much suspicion in the flu world that other deaths elsewhere have gone unreported.

Efforts to eradicate the virus from chicken stocks have so far failed. Some believe the virus has become endemic in a region where dense human populations live cheek by jowl with animals that can be a mixing bowl for virus reassortment.

Factor in the inadequacy of the international vaccine system, which under current regulatory rules could only produce enough pandemic vaccine for a fraction of the world's people, add the lack of surge capacity in hospitals the world over and the picture looks bleak, says Osterholm, who is also director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

"You keep adding all these things up and you see - we are talking about a perfect storm."

More worrisome still is the fact that H5N1 is currently behaving much like the dreaded Spanish flu, which had the astonishing capacity to swiftly kill people in the prime of life.

Flu generally kills the old and the very young; it weakens their systems, making them prey to secondary infections like pneumonias which they can't fight.

But the Spanish flu was different. It's believed that virus sparked what's called a cytokine storm - a cascading hyper-reaction of the immune system so severe that attacking the invader actually killed the host.

"Everything that we're seeing in the virus-host interaction in Southeast Asia says cytokine storm," Osterholm says.

If H5N1 becomes a pandemic strain and retains that fearsome feature, in addition to the very young and the very old - flu's normal targets - young, healthy people with robust immune systems would be at great risk.

© The Canadian Press, 2004

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