Last fall, a 26-year-old Thai woman spent the night holding her 11-year-old daughter in her arms. The little girl died after catching bird flu from an infected chicken. On Sept. 20, the mother died, too. She was the first known person to catch bird flu from another human being.

She may be far from the last. Officials at the World Health Organization (WHO) warn that millions of people, perhaps tens of millions, may die if the bird flu virus spreads among humans.

That isn't happening yet. It still takes very close contact with infected birds — or, it seems with another infected human – for a person to catch the bird flu virus. It's a rare event. There have been only 44 known cases. Why the worry? Those 44 human cases resulted in 32 deaths.

"The great concern is there is an incredibly virulent avian flu that shows ability to jump to humans," Jeremy Farrar, MD, DPhil, tells WebMD. "And when it gets to humans, it is clearly a very nasty disease with a high mortality rate."

Farrar should know. He's director of the Oxford University Clinical Research Unit at the Hospital for Infectious Diseases in Ho Chi Minh City, Vietnam. Farrar's team recently described 10 cases of humans infected with bird flu, officially known as type A H5N1 avian influenza virus.

In an editorial appearing in the Dec. 2 issue of The New England Journal of Medicine, Farrar argues that efforts to combat a worldwide flu outbreak — what public health officials refer to as pandemic influenza – should be top priority.

"The current situation is not a concern. There are not hundreds of people dying," Farrar says. "But this reminds us that avian influenza is not just a runny nose. It is a phenomenally destructive virus. If this came to be — if this virus developed a more efficient way to jump from human to human — you'd have a very virulent virus with high infectivity. It would be a very nasty global event."

The WHO is paying close attention, according to spokeswoman Maria Cheng.

"We are closer to a pandemic now than we were in the past," Cheng tells WebMD. "This is a virus that has the ability to jump to humans. As long as it circulates in animals, it will jump to humans. The more that happens, the greater the chance a human pandemic will occur. We think this is a very worrying situation. Now is the time to take action."

Bird Flu Virus Evolving

Why worry? In the 20th century, there have been three global flu pandemics. The first, the 1918 Spanish flu, was the worst. Coming on the heels of World War I, it killed between 20 million and 40 million people. Milder outbreaks in 1956 and 1968 killed about 1 million each.

All three times, a bird flu evolved a way to spread among humans. For decades, experts have predicted another outbreak. In 1976, for example, it looked as though swine flu would do the trick. But to the embarrassment of health officials of the time, it fizzled out almost before it began.

This time, the fears are based on more solid science. Modern genetic techniques have traced major flu outbreaks to birds. Birds can carry 15 known types of type A influenza, the most serious kind of flu virus. Humans — so far — get infected with only three of them.

There are two ways a flu virus can jump from birds to humans. One is evolution; the virus simply mutates into a form that infects humans.

The evidence so far isn't reassuring. Someone sold chickens that died of bird flu to a Bangkok zoo. Keepers fed the chickens to captive tigers. The virus not only infected the big cats, but also spread easily among them. So far, 147 of the zoo's 441 tigers have died.

The other way flu viruses figure out how to infect humans is reassortment. When two flu viruses infect the same person or animal, they swap DNA. So far, that hasn't happened. But pigs get infected with human flu viruses. And Chinese health officials report that the bird flu has been infecting pigs for more than a year.

Early hopes of eradicating the bird flu virus have evaporated. Now the virus is firmly entrenched in domestic and wild birds in Southeast Asia. Could it spread? Recently, officials in Belgium stopped a man getting off a plane from Thailand. They found that he was illegally carrying two hawk eagles. Both birds were infected with H5N1 bird flu. And the veterinarian who examined them came down with a suspicious eye infection, although swab tests were negative for bird flu.

Public Health Response Slow

The WHO last month convened an informal meeting of all 11 companies that make flu vaccines, regulatory authorities, and the health ministers of several nations. The bottom line: If and when bird flu breaks out in humans, there won't be a vaccine for at least several months.

"The most basic thing we are recommending is increased surveillance. It is important we have a global surveillance system in place," the WHO's Cheng says. "We are working with national authorities to accelerate the process of making a vaccine."

Surveillance means identifying human-to-human bird flu transmission in its earliest stages. That's not an easy task, given that bird flu is spreading in some of the most remote and rural areas of Asia. And people whose livelihood depends on small flocks of chickens are loath to report bird deaths when it means that public health officials will exterminate their only source of income.

Fortunately, there's hope that a worldwide pandemic could be contained. Ira Longini, PhD, professor of biostatistics at Rollins School of Public Health at Emory University in Atlanta, is part of an international team that's developing mathematical models of flu outbreaks. The models, nearing completion, predict exactly how far a flu outbreak will spread under different circumstances.

The models are sobering. For example, Longini's earlier work shows that if a flu outbreak were like the relatively mild 1957 Asian flu virus, it would infect 93 million Americans and cause 164,000 U.S. deaths.

Would a bird flu outbreak be worse? Probably. But Longini says it's highly unlikely that a bird flu would be as deadly as some people fear.

"Based on past experience, we don't have to panic," Longini tells WebMD. "It's clear that pandemic flu is inevitable. It is going to happen, and it could be a fairly pathogenic strain and could be a real problem. Right now, H5N1 bird influenza looks like it is fatal in 70 percent of cases. But this 70 percent figure is totally absurd. It has never been true of any human flu strain. I have never seen any evidence that human influenza is anywhere near that virulent. Case fatality of even highly virulent strains are a couple of deaths per 10,000 people infected."

It's also likely that human-to-human bird flu infections would spread slowly, at least at first. That would buy time. And since the bird flu bug is sensitive to Tamiflu, an oral flu drug, public health officials could buy even more time by giving the drug to all contacts of infected people.

"With good surveillance, with antivirals, and easy-to-implement public health methods — strategies such as closing schools and public places and limiting movement — we should be able to contain the pandemic at the source, wherever that may be," Longini says. "That would buy time to make vaccine to deal with it if it should spread. Emphasis should be on good surveillance everywhere, especially in Southeast Asia, and quick response with targeted use of antivirals."

By Daniel J. DeNoon, reviewed by Brunilda Nazario, MD

SOURCES: Farrar, J. The New England Journal of Medicine, Dec. 2, 2004; vol 351: pp 2363-2365. Jeremy Farrar, MD, DPhil, director, Oxford University Clinical Research Unit, Hospital for Infectious Diseases, Ho Chi Minh City, Vietnam. Maria Cheng, spokeswoman, World Health Organization, Geneva, Switzerland. Ira Longini, PhD, professor of biostatistics, Rollins School of Public Health, Emory University, Atlanta.