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Bird flu, the poultry disease that health experts fear could morph into a globe-spanning epidemic of severe human illness, has reappeared in Southeast Asia, sweeping through four countries in the past two weeks.

More than 15,000 chickens, ducks and other birds have died in China, Indonesia, Thailand and Vietnam, and 78,000 others have been slaughtered in an attempt to halt the spread of the disease, technically known as avian influenza H5N1.

Flu authorities, who nervously tracked last winter's six-country outbreak ? which sickened 34 people, killing 23, as well as causing the slaughter or disease deaths of millions of birds ? are alarmed by the flu's rapid recurrence only four months after it finally subsided in March.

Is it too late?

Heightening their concern is a sense that it may already be too late. In interviews, several government and private scientists expressed the same thought: Avian flu's transformation into a virulent human disease is no longer a matter of "if," but "when."

"In my almost 30 years in public health, I have seen nothing else that could bring us closer to the edge of a major international catastrophe, including HIV," said Dr. Michael Osterholm, founder of the Center for Infectious Disease Research and Policy at the University of Minnesota and an adviser to Health and Human Services Secretary Tommy Thompson. "This could do to the world in a few months what has taken HIV 30 years." HIV is the virus that causes AIDS.

H5N1 is the most virulent of several strains of influenza that primarily affect and rapidly kill birds. For years, it was believed that H5N1 could not affect humans. A 1997 outbreak in Hong Kong proved that assumption wrong: The disease infected 18 residents of the city, killing six of them.

Several times every century, the influenza viruses that usually affect humans change sharply enough to evade the human immune system and cause rapidly moving global epidemics of severe disease, called pandemics. The worst known flu pandemic was in 1918, when approximately 675,000 Americans and at least 40 million people around the world died in less than a year.

Infectious disease experts fear H5N1 because humans have no natural protection against it, leading to worry that the virus could spark another pandemic. For that to happen, the virus would need to change in ways that would allow it to infect humans more easily and also spread from person to person.

Such changes could occur either via mutation ? small changes that the virus makes to adapt to its host as it reproduces ? or by the virus' infecting a human already suffering from a common human flu strain and swapping genes with that other strain.

Two scientific papers published in the past 10 days, in the journals Nature and Proceedings of the National Academy of Sciences, say the H5N1 virus is already mutating in bird populations ? a surprise to investigators, who expected it to be stable ? and is spreading more widely in wild birds such as ducks, which are suspected of spreading it across Asia.

It is now flu season in Asia. With millions of birds in backyard flocks and at huge commercial farms, chance favors the possibility that a human flu and an avian flu will combine.

"This is a huge rural expanse, with 30 percent of the world's population in it, and a huge proportion of them have backyard poultry," said Dr. Scott Dowell, who directs the Bangkok, Thailand, office of the International Emerging Infections Program of the U.S. Centers for Disease Control and Prevention.

Thailand vulnerable

Influenza surveillance done by the CDC in two provinces in Thailand has found in the past two weeks that 35 percent of people tested for flu have the disease. Those provinces share borders with two of the 15 Thai provinces where H5N1 was recently found.

With domesticated poultry distributed so widely across Asia, researchers fear that controlling H5N1 will prove impossibly challenging. It would require changes in backyard agriculture and urban markets ? both of which cater to a cultural preference for obtaining live poultry ? as well as slowing the growth ofAsian agriculture. Thailand is the world's fourth-largest exporter of chicken.

Last winter, millions of chickens and other birds were slaughtered in eight countries to curb the spread of the virus, a strategy that appears not to have worked. Hong Kong has halted the spread of H5N1 within its borders by severely restricting live-bird markets, but those measures may not work in larger areas.

"You can change things in a highly organized city like Hong Kong, but it will be awfully difficult to make similar changes in the countryside, or even in a country such as Thailand that is newly industrialized," said Dr. Arnold Monto, an influenza researcher at the University of Michigan-Ann Arbor.

With control at the source difficult to achieve, researchers are exploring defensive measures. Those, however, have their limits. The one existing drug, oseltamivir, or Tamiflu, prevents infection after exposure to flu virus, but it is made by only one company, so supplies are limited.

There is no existing vaccine for H5N1, and development of one has been slow because the traditional method for producing flu vaccine ? growing it in chicken embryos ? doesn't work for a virus that is lethal to chickens. In April, virologists at a British government laboratory and at St. Jude Children's Research Hospital in Memphis achieved vaccine seed viruses using an alternative method. The strains have been given to the National Institutes of Health, which plans preliminary human trials this year.

However, the worldwide production capacity of flu vaccine manufacturers currently stands at about 250 million doses per year ? not enough to protect even the U.S. population.

Experts say the outlook can be improved only if nations make combating H5N1, and planning for pandemics, a global priority.