With one small genetic adjustment in Influenza A, or H5N1, millions of people could die, warned World Health Organization Regional Director for the Western Pacific Shigeru Omi.

Omi, speaking at the regional WHO meeting in Noumea, New Caledonia, in the South Pacific, called for health ministers and representatives to launch an all-out war on the deadly strain, which has killed at least 57 people.

"While we still have a window of opportunity, we must do everything we can to avert an influenza pandemic as we simultaneously prepare for a worse-case scenario," Omi said in his address.

If the virus acquires sufficient human genes, allowing transmission from one person to another, an estimated 2 million to 7.4 million people around the world could die, the WHO estimates.

Others put the figure in the tens of millions.

In Jakarta yesterday, authorities closed down the popular Ragunan Zoo and had workers tested after rare eagles, peacocks and other birds were infected by the virus.

Three children suspected of contracting the disease were being treated at the Indonesian capital's infectious diseases hospital. Two of the children are in serious condition.

Nine days ago, a 37-year-old woman became the fourth fatality in Indonesia, where the virus has become endemic in chicken flocks across island nation.

According to the WHO, the Ministry of Health in Vietnam confirmed an additional fatal case of H5N1 infection that dates back to July, a 35-year-old male farmer from Ben Tre Province.

Since mid-December, 21 have died in Vietnam in 64 cases.

Worst case

The worst-case scenario, the New York Times reported, would be if person-to-person transmission spawned successive generations of severe disease with high mortality – the situation during the great influenza pandemic of 1918-1919, which killed an estimated 40 to 50 million people.

The early 20th century disaster resulted from the emergence of a completely new influenza virus subtype that spread worldwide in four to six months, causing several waves of infection over two years.

The H5N1 virus, which spreads through migratory birds, has plagued poultry populations in Asia since 2003, exposing more humans.

More than 140 million birds have died, and half of the 112 people infected have succumbed to the virus.

Russia is the most recent of 10 countries where the virus has turned up, and it now is threatening Europe, according to WHO officials.

The U.S. Centers for Disease Control says the world's defenses against flu are improving but remain inadequate, the Financial Times reports.

There is no pre-existing human immunity to the H5N1 virus.

"We've never seen so much influenza in so many birds in such close proximity to humans in so many places," said CDC Director Julie Gerberding. "If ever there was a time when the risk [of a pandemic] was higher than usual it is now."

At the United Nations last week, President Bush proposed an "international partnership" to combat the disease, requiring members facing an outbreak to share information immediately.

Already Vietnam, Japan, Cambodia, Thailand, Nigeria and Canada have indicated interest in the partnership.

"We cannot afford to face the pandemic unprepared," WHO Director Lee Jong Wook said Thursday at the United Nations.

To shore up its drug stockpile, the U.S. has awarded more than $100 million to two European pharmaceuticals, France's Sanofi pasteur of Sanofi-Aventis and Britain's GlaxoSmithKline.

"These countermeasures provide us with tools that we have never had prior to previous influenza pandemics," said Mike Leavitt, secretary of Health and Human Services, last week.

But WHO officials acknowledge that because the new virus has not changed in a way that would enable human-to-human transmission, they don't know precisely how they would combat it.

"We know we're overdue for an influenza pandemic strain, and we know it will occur, but we don't know when or even exactly what virus will cause it," Dick Thompson, a WHO spokesman, told the New York Times. "It is possible that the virus won't be H5N1 at all or that this virus will change in a way so that the vaccine under development doesn't work against it."

Gerberding, according to the Financial Times, agreed the laws of probability suggest a pandemic is due, noting the world has gone an unusual number of years since the last one in 1968, when the Hong Kong flu killed an estimated 1 million people.

The CDC director said the pharmaceuticals industry had the capacity to produce about 900 million doses of human vaccine against bird flu within several months.

But she pointed out this would meet only a fraction of the need in the event of a pandemic.