Avian Flu Threat Still Hovering

HOUSTON, Dec. 22 -- The threat of a pandemic flu originating in birds can be summed up in a phrase: The eagle has not landed.

After a plaque of scary headlines early this year, the pandemic flu threat has fallen off the front pages. But experts fear it is merely waiting in the wings.

Mainly because the H5N1 variant of influenza is still circulating in wild birds and flaring up from time to time among domestic poultry, they have not let down their guard. South Korea, for instance, had three outbreaks in a month, the last two weeks ago.

"The epizootic (epidemic among animals) doesn't appear to be dwindling, although the media coverage is dwindling," according to Paul Glezen, M.D., a respiratory diseases expert at Baylor College of Medicine here.

The virus is "certainly uncontrolled in Africa and Indonesia," he said, and the outbreaks in South Korea, while reportedly controlled, may have spread to North Korea where very little is known about control measures."

The H5N1 virus, so far, shows little sign of being able to transmit itself efficiently from human to human, but when it does infect people it is deadly. Of the 111 human cases reported this year - most thought to originate in birds rather than other people - 76 have been fatal.

Indeed, Indonesia reported two cases - both fatal - in November.

It would take only small mutations - of the type for which influenza is notorious - to make the virus easily transmissible, Dr. Glezen said. "The longer this smolders on and the more humans are exposed and infected, the greater is the possibility that we'll have a new pandemic," he said.

But controlling the virus is not easy. Its natural reservoir is wild, migratory birds, which are not usually seriously affected, but which spread the virus to domestic flocks. Once domestic flocks are infected, the usual recourse is to destroy the birds.

In relatively well-off countries, such a strategy appears to work, but in poorer nations, where there is little money to compensate farmers for the loss of their flocks, it is more difficult.

The World Bank says an extra .2 billion is needed to pay for surveillance, control, and compensation - on top of .9 billion pledged at a meeting in Beijing in January.

At a meeting in the west African nation of Mali early this month, international donors promised an additional million, including million from the U.S., on top of the million the nation promised in Beijing.

The meeting was held in Mali to highlight Africa's avian flu problems, which include a weak public health and veterinary infrastructures, poor disease surveillance, and populations with high levels of other diseases, including HIV/AIDS, malaria and tuberculosis.

African nations are particularly vulnerable to emerging diseases, including avian influenza, and "the possibility of a human pandemic hangs over us," said Alexander Muller, assistant director-general of the UN's Food and Agriculture Organization. "Failure by any one country to contain the disease could lead to ? a domino effect, undoing all the good that we have achieved so far."

Eight African countries have reported finding the virus in birds, meaning that Asia, Europe, and Africa have now seen the epizootic take root. So far, North and South America have been spared.

But there's evidence that the H5N1 virus - like its human counterparts - spreads best during the cooler months, according to Robert Webster, Ph.D., and Elena Govorkova, M.D., Ph.D., of St. Jude Children's Research Hospital in Memphis, Tenn.

Writing in the New England Journal of Medicine, Drs. Webster and Govorkova said that raises the possibility that the virus could spread from Eurasia to the Americas this winter and take root in domestic flocks here.

While the virus has vanished from the front pages, it has been a top of mind issue for federal health officials, according to Roland Levandowski, M.D., of the respiratory diseases branch of the National Institute for Allergy and Infectious Diseases (NIAID).

"Infectious diseases don't fall off the radar screen in the public health service," Dr. Levandowski said. While the glare of publicity has turned elsewhere, he said, researchers have continued tracking the virus and developing vaccines against a potential pandemic version.

Specifically, he said, researchers are trying to modify test vaccines that were based on an H5 strain isolated in Vietnam several years ago so they'll take into account more recent changes in the virus - so-called antigenic drift.

Also, researchers are trying to improve diagnosis. In a cluster of cases in Turkey this summer, the standard testing procedure using nasal swabs did not identify the virus, because its preferred receptor - the ?2-3 sialic acid receptor - is found deep in the respiratory tract of humans.

Two research teams - one at the University of Colorado and the other at New York's Columbia University - reported this fall they've been able to adapt gene microarray technology to the hunt for influenza.

The chips are able to identify with remarkable precision the strain and subtype of virus that's present in a sample.

But the best line of defense against a flu pandemic - whether it arises from the current avian flu or some other strain - is a vaccine, according to Baylor's Dr. Glezen. But it's hard to create and stockpile a vaccine against a disease that doesn't yet exist, he said.

For that reason, he said, it's important to develop new ways of creating vaccines - in tissue cultures, for example, or using recombinant genetic methods - as well as to maintain the capacity of manufacturing large amounts in times of need.

NIAID's Dr. Levandowski echoed that view: "The more vaccine we use now (to combat the seasonal human flu), the more supply we will have if a pandemic comes," he said.

"The message is: We have excellent vaccines, let's use them," he said.