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Published: Sunday, 2/1/2004

Mating of bird flu, human virus feared

BY MIKE WOODS
BLADE SCIENCE EDITOR

Influenza experts last week pressed ahead with efforts to make a “pandemic vaccine,” a special potion used only once before in history to shield humanity from offspring of a marriage made in hell.

Dr. Klaus Stohr, chief of the World Health Organization Global Influenza Program, described consequences of a “mating” between a human flu virus and avian influenza virus, the “bird flu” now wreaking havoc with poultry flocks in Asia.

To the union, bird flu brings genes that cause serious illness in humans. But it lacks genes needed to spread from one infected person to another. Without those “transmissibility” genes, bird flu menaces only people in close contact with diseased chickens.

As its bride, bird flu picks an ordinary human flu virus, with genes enabling it to spread among people.

The two swap genes when a person with human flu catches the bird virus. Their offspring is a brand new flu virus, with the worst of both parents: It is highly lethal and spreads among people like wildfire.

“The offspring would have the transmissibility of the normal human virus as well as the pathogenicity of the chicken virus,” Dr. Stohr explained. “What I m trying to say is that this avian virus merges with the human influenza virus and the resulting new strain will travel very quickly around the world.”

It would spread, he explained, because people have no natural immunity to a hybrid virus that never existed. Existing flu vaccines do not target the virus and offer little or no protection.

High-profile, new flu viruses appear an average of three times a century and create pandemics, worldwide epidemics.

During the 20th century, a 1918-1919 pandemic killed 40 million to 50 million people. Smaller ones hit in 1957–1958 and 1968–1969.

In briefings at WHO headquarters in Geneva, flu experts noted two facts sometimes lost in the furor about bird flu virus, known as H5N1, as it decimated poultry flocks in South Korea, Japan, Thailand, China, and Cambodia.

So far, only a handful of people have gotten sick with bird flu. By late last week, the toll stood at 11 human cases in Vietnam and Thailand and 10 deaths. Most were in children.

Second, the plague-producing marriage has not taken place.

“I have to emphasize that currently there is no indication that there is human to human transmission of this strain,” Dr. Stohr said. “There is no indication that this virus has already acquired genes from human influenza virus.”

The H5N1 virus has plenty of time to do so, he added.

Various flu viruses infect birds, pigs, horses, and other animals. Avian flu was first identified about 100 years ago in Italy. More than a dozen bird flu viruses exist, in addition to the highly dangerous H5N1 strain.

H5N1 has been circulating inside people since at least 1997, when H5N1 caused the first known human outbreak. It killed six of the 18 victims in Hong Kong. Eighty-three people in contact with infected chickens in The Netherlands became infected last year and one died.

How would the world fare if bird flu and human flu do swap those genes?

“The world will be in deep trouble,” Dr. Robert G. Webster said, “if the impending influenza pandemic strikes this week, this month, or even this year.” A virologist at St. Jude Children s Research Hospital in Memphis, Dr. Webster investigated the H5N1 outbreak in 1997. He analyzed international preparedness for a flu pandemic late last year in the journal Science.

But the world would not be helpless.

Prescription anti-viral drugs such as Tamiflu and Relenza, used to prevent and treat ordinary flu, also work against bird flu in people.

Dr. Stohr noted antiviral drugs have protected poultry workers involved in slaughtering thousands of infected chickens. The 2003 death in The Netherlands, for instance, involved a person who refused to take an antiviral drug.

“In a pandemic situation where the virus is transmitted very quickly and widely, many people will want to have these antivirals,” Dr. Stohr noted.

The drugs, however, are expensive - a big barrier to use in poor countries. Amantadine, an inexpensive antiviral drug, does not work against bird flu, WHO said. And demand may outstrip supply.

“The stocks of antiviral drugs are too low to cope with an epidemic and would be quickly depleted,” predicted Dr. Webster. He has urged establishment of emergency stockpiles that could be tapped in an epidemic.

A vaccine would be the No. 1 weapon in a pandemic, and an emergency program to develop a pandemic vaccine shifted into high gear last week.

WHO on Wednesday held talks with a dozen drug companies interested in making a bird flu vaccine and drug licensing agencies that would approve it.

Drug companies are awaiting results of research under way at the U.S. Centers for Disease Control and Prevention in Atlanta, St. Jude s in Memphis, and a British national laboratory in London. Those labs are in a network of centers that work with WHO s influenza program.

They are making a “vaccine prototype virus,” a custom-tailored form of H5N1 that would become the basis of a vaccine. Natural H5N1 won t work. One problem is its tendency to kill chickens. It would kill the chicken embryos used to make flu vaccine. So researchers must come up with a nonlethal virus.

Dr. Stohr estimated that the prototype virus would be ready in two to three months. WHO then would hand it over to drug companies, which would use it to begin developing and testing bird flu vaccines.

If bird flu becomes a human health threat, batches of the anti-pandemic vaccine could be ready by autumn, according to Dr. Stohr s estimates.

The United States rolled out its last pandemic vaccine in September, 1976, to combat “swine flu,” then believed to be a reincarnation of the deadly 1918-19 virus.

Swine flu never proved a major problem in unvaccinated people.

Public health experts from around the world will meet Feb. 11 to discuss composition of the 2004-5 vaccine, and WHO will not recommend that it target H5N1. “We have no human to human transmission,” Dr. Stohr noted. “We will proceed with things as usual.”

No changes are expected, he said unless bird flu starts spreading rapidly from one person to another.



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