The bird flu that has killed millions of poultry in east Asia may be tougher and more dangerous to humans than previously suspected.

The avian influenza virus in question is the highly pathogenic (illness causing) A virus subtype H5N1. On some poultry farms it has killed 100 percent of infected birds.

Research from St. Jude Children´s Research Hospital in Memphis, Tennessee, revealed that domestic ducks infected with H5N1 shed large quantities of virus in feces as well as through the respiratory tract. The 2004 strain of H5N1 survives longer in the outside environment than those from earlier outbreaks. But most disturbing is the fact that ducks carrying the virus do not die or show any symptoms of disease.

The World Health Organization (WHO) released these results prior to publication of the St. Jude report because of their significance for public health.

"H5N1 is now circulating widely in Asia. It is becoming increasingly pathogenic and we are discovering it can infect more and more types of mammals," said Klaus St鰄r, who leads the Global Influenza Programme at the World Health Organization in Geneva, Switzerland.

In its most recent incarnation the virus has killed humans. To date there have been 44 confirmed human cases of H5N1 flu in Thailand and Vietnam. Of these, 32 people died梐 fatality rate of 75 percent. Survivors suffer from severe pneumonia.

"We believe we are closer than ever to the next pandemic [widespread outbreak]," St鰄r said. Statistically, pandemics tend to occur every 10 to 27 years. It has been 36 years since the last one struck, and St鰄r thinks the next is long overdue.

At present H5N1 cannot spread easily from person to person. There has been only one recorded instance of probable human-to-human transmission, although this cannot be confirmed experimentally, because scientists lack the appropriate biological specimens.

Superflu

Experts fear that the H5N1 virus could acquire genes from human influenza viruses that will transform it into a "superflu," allowing rapid spread among people. The more people H5N1 infects, the greater the chance these human and bird viruses will intermingle and produce a pandemic strain.

Scientists classify influenza viruses based on the hemagglutinin (H) and neuraminidase (N) proteins that cover the surface of every influenza virus.

There are 15 forms of H proteins that have been identified on influenza Type A viruses; all 15 viruses are found in birds. But only H1, H2, and H3 viruses circulate widely in humans.

Viruses of the H5 and H7 subtype are the "bad guys of the flu world," said Richard Webby, a virologist at St. Jude Children´s Research Hospital. "We don´t want H5 or H7 viruses in humans." These viruses have the capacity to become highly pathogenic and cause a much more pervasive disease than the influenza viruses currently circulating in the human population.

Until 1997 scientists believed that it was impossible for birds to directly infect humans with H5N1. But an outbreak in Hong Kong in 1997 that killed six of 18 people infected with the virus proved the contrary.

Though H1, H2, and H3 influenza viruses now circulate within the human population every flu season, each one triggered a pandemic upon its debut.

Three Pandemics

New viruses, to which the people have never been exposed, cause pandemics because humans lack immunity梬hich only results from exposure. This situation occurred three times in the last century. In 1918 an H1N1 virus triggered the notorious Spanish flu pandemic that killed at least 20 million worldwide, 500,000 in the U.S. alone. In 1957 and 1958 another new influenza virus, H2N2, dubbed the Asian flu, killed 70,000 Americans. In 1968 and 1969 the Hong Kong flu, H3N2, killed 34,000 in the U.S.

H5N1 is becoming more lethal and may be better suited to infect mammalian hosts. Studies in mice published earlier this year show that H5N1 is evolving rapidly. The H5N1 virus isolated from ducks in mainland China in 2002 was more deadly than that from 1999.

One approach to preventing a pandemic has been to eliminate the virus from its animal reservoir by killing millions of chickens. But this is economically devastating to countries like Thailand, which is the fourth largest producer and exporter of chickens. Almost a hundred million chickens have died or been culled since the 2004 outbreak.

In many places ducks and chickens mingle freely on family farms. They wander in and out of the home, and children are frequently the ones who tend the animals. Although no transmission of H5N1 from duck to human has been reported so far, this now merits consideration in light of human cases that cannot be tied to poultry outbreaks.

"How do you identify infected ducks? What cautionary measures do you recommend if you can´t tell if ducks are sick or not?" St鰄r said. "This is going to complicate our strategy in controlling this virus."

Virus Gets Tougher

Outbreaks of H5N1 in poultry have been reported in Laos, Cambodia, Vietnam, Thailand, Indonesia, Malaysia, and China. And new results from St. Jude suggest that the virus is getting tougher. The 2004 H5N1 can survive at 37 degrees Celsius (98 degrees Fahrenheit) for six days, compared with just two days for the H5N1 virus from the 1997 outbreak.

"We can´t eradicate this virus any time soon," said Tim Uyeki, a medical epidemiologist in the influenza branch of the Centers for Disease Control and Prevention in Atlanta, Georgia. "Even if infected poultry are culled, the virus persists in the feces and soil. Unless you could disinfect the entire farm, the virus will just infect healthy poultry.

"As H5N1 continues to circulate in people and evolve, the virus will become an increasing public health threat. It´s a ticking time bomb," Uyeki said.

Robert Cook, chief veterinarian at the Bronx-based Wildlife Conservation Society in New York, believes that a global surveillance program would be a vital early warning system for spotting new potential pandemics. Such a system should bring together disease data from wildlife, livestock, and humans.

The WHO will hold an informal meeting in Geneva on November 11 for vaccine makers and representatives from government and regulatory agencies to discuss a pandemic vaccine project.

There is currently no approved human vaccine for H5N1. One potential vaccine was "very effective in ferrets," said Webby, who co-developed and tested it at St. Jude. Webby´s vaccine is scheduled for clinical trials that will gauge safety and efficacy.

All pandemic viruses in the last century arose quickly and traveled around the world in less than a year. It takes about eight months of R&D before vaccine production can begin. "We now have a window of opportunity to get this done," St鰄r said.

Bijal P. Trivedi is a freelance science and health journalist based in Washington, D.C.