Scientists Race To Head Off Lethal Potential Of Avian Flu

The other way avian flu viruses can adapt to become human viruses is by slowly acquiring mutations. As small changes pile up, the virus's behavior can evolve. One trait that can appear is the capacity to enter human cells easily. That, and the ability to replicate efficiently once inside, are the two requirements for contagiousness.

Evolution of flu viruses is inevitable because the microbe is prone to making mistakes as it copies its genes. The more times a virus replicates, the more opportunity there is for a new mutation to arise that allows easy person-to-person transmission. For that reason, suppressing H5N1 outbreaks in birds -- where the microbe is replicating trillions of times a day -- is a crucial tool in preventing a human outbreak. China and Indonesia have vaccinated poultry flocks against H5N1, and Vietnam this month is starting a two-year, $35 million campaign to do so, too.

The highly lethal H5N1 viruses isolated from last year's human cases of avian flu were genetically 99 percent identical to each other. The slightly less lethal -- but perhaps more transmissible -- virus taken from patients in northern Vietnam early this year is only 98 percent identical to last year's; more important, it isn't completely inhibited by antibodies to last year's strain. It may be on its way to becoming a new, human-adapted strain.

But H5N1 flu isn't evolving just in human hosts. It's also changing in birds in a dangerous way.

Decades ago, Webster demonstrated that waterfowl are the true "home range" of influenza A viruses -- another of his key scientific contributions. For nearly 30 years, he and his colleagues have annually sampled wild ducks in the birds' nesting grounds in Alberta, looking for new flu strains. Since 1985, they have also sampled the feces of more than 5,000 migrating shorebirds along Delaware Bay.

H5N1 strains with slightly different traits have appeared several times in East Asia since the first one emerged in southern China in 1996. Last fall, while analyzing a strain circulating after an outbreak in Hong Kong in 2002, one of Webster's post-doctoral researchers, Diane Hulse, made an unusually important observation.

Many ducks experimentally infected with thevirus didn't die, even though the strain was highly lethal to chickens. But one of the duck viruses was highly lethal to ferrets, the animal whose susceptibility mirrors that of people. This meant that killing infected chickens wasn't going to be enough to stop the spread of the microbe. Ducks could serve as a permanent reservoir of H5N1 virus.

Webster immediately informed officials at the WHO, who in turn sounded the alarm. They announced that ducks -- there are 2 billion domestic ones in East Asia -- might be "silent carriers" of H5N1 influenza strains potentially fatal to people.

The discovery by Hulse and Webster led, in part, to an extreme program Thailand mounted last November. About 70,000 investigators went into every village in the country looking for sick ducks and sampling the feces of healthy-looking ones. Flocks carrying H5N1 influenza virus were killed.

The strategy appears to have worked. Last year, Thailand had 12 human deaths from H5N1 flu. So far this year, it has had none.

Stretching out before Webster and public health experts is a long list chores the world must complete if it is to abort the bird-to-man transfer of disease he long ago proved could happen.

Last month, two teams of scientists based in China, one assisted by Webster, proved that H5N1 is now circulating in several species of migratory birds capable of carrying the virus to India, Australia and Central Asia. Tests announced last week suggest that some of those long-distance fliers have already carried H5N1 into Mongolia, where it hadn't been seen before.

A task equal in importance to charting the spread of H5N1 is developing and distributing a good duck vaccine for the billions of those birds in East Asia.

Those countries, which collectively are the likely ground zero of pandemic flu, also need to improve their disease surveillance. In particular, they need to develop laboratories capable of safely isolating and testing influenza viruses.

And while they are doing that, they -- and the rest of the world, Webster believes -- would be well advised to draw up a plan to limit human movement and distribute vaccine and antiviral drugs should a pandemic flu strain emerge despite the efforts to prevent it.

It's a long list with an uncertain deadline, and it's enough to keep Rob Webster at work.

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http://www.washingtonpost.com/wp-dyn/content/article/2005/08 /22/AR2005082201365_3.html