Monday, November 27, 2006

Outbreaks Show Bird Flu Virus Is Changing

(HealthDay News) -- Detailed data on clustered human cases of avian flu have experts agreeing that the H5N1 virus is evolving -- but in what direction?

"The virus is always changing, and the mutations that make it more compatible with human transmission may occur at any time," warn Drs. Robert Webster and Elena Govorkova, both virologists at St Jude's Children's Research Hospital in Memphis, Tenn.

Their commentary accompanies reports from Indonesia and Turkey, both published in the Nov. 23 issue of the New England Journal of Medicine.

However, another expert believes that, so far, H5N1 has given no indication it is mutating toward human-to-human transmission.

"It's far from a certainty," said Dr. Marc Siegel, a clinical associate professor of medicine at New York University School of Medicine, and author of Bird Flu: Everything You Need to Know About the Next Pandemic. "The virus could move closer to human-to-human transmission, and it could move farther away. I don't think that you can conclude from these articles in the NEJM that the thing is becoming easier to transmit."

The two studies' most basic data is not new. They focus on three clusters of H5N1 infection in Indonesia in mid-to-late 2005, involving four deaths, and an eight-patient cluster treated in the first weeks of 2006 at a hospital in far-eastern Turkey. Four of the Turkish patients died.

Details published in the journal do point to some intriguing trends, however.

As noted in other cases, almost all infections were linked to close handling of domestic fowl. More troubling was the fact that the Turkish group, led by Dr. Ahmet Oner, of Yuzuncu Yil University, in Van, found it very difficult to diagnose H5N1 in humans at its earliest stages.

Two standard tests turned up negative for the virus, and only a high-tech "polymerase-chain-reaction assay" confirmed H5N1 as the culprit. Infection also "causes a wide spectrum of illnesses in humans," the study authors wrote, with symptoms varying widely among patients.

In the Indonesian report, led by epidemiologist Dr. Timothy Uyeki of the U.S. Centers for Disease Control and Prevention, researchers found that H5N1 affected some patients more severely than others, suggesting that there are genetic factors influencing patient vulnerability.

They also noted that certain drugs, such as oseltamivir (Tamiflu), could help fight the predominant Indonesian strain, but these drugs are only effective when given a day or two after infection. That's probably too early for most patients, however.

"In the countries that have reported human H5N1 cases, patients generally do not seek medical care early in their illness," Uyeki explained. "They usually present for medical care when their illness is advanced, e.g., they have pneumonia, and therefore they are not able to receive early oseltamivir treatment."

In their commentary, Webster and Govorkova noted that the number of documented human cases of H5N1 infection is rising worldwide. A total of 251 cases have been recorded globally since 1997, they said, and "by mid-August, 97 humans had been infected in 2006 -- the same number as in all of 2005."

No definite case of human-to-human transmission has yet been reported, suggesting that "the current H5N1 virus is apparently not well 'fitted' to replication in humans," the two experts wrote. However, "the intermittent spread to humans will continue, and the virus will continue to evolve," they added. "Clearly, we must prepare for the possibility of an influenza epidemic."
Siegel believes this kind of language can be misleading.

"We don't know enough about H5N1, and the science hasn't evolved to the point where we can predict when an epizoonotic problem -- a disease that has killed a lot of birds -- is going to start killing a lot of humans," he said.

And, while reports do suggest a rise in human cases over time, Siegel noted that, prior to 1997, no one was keeping close tabs on the epidemiology of H5N1. "I think there may have been previous clusters that might have gone unreported because of a lack of attention -- they may have been misdiagnosed as other kinds of flu," he explained.

Underreporting of prior outbreaks means it also impossible to say that the avian flu is mutating in any one direction, Siegel said. "There's just no way of telling from these clusters that this virus is evolving in the direction of easier transmission -- we can't tell if these clusters are anything new, or if there was a precedent for them," he said.

Finally, he said, H5N1's genetic "leap" to human-to-human transmission -- if it ever happens -- will be much tougher than media reports have let on.

"I've talked to a top expert at the U.S. National Institutes of Health," Siegel said. "He has tried [in the lab] to manipulate H5N1 to make it transmit more easily human-to-human, and he hasn't been able to do it. He's tried different mutations, including using proteins from the 1918 Spanish flu."

While that doesn't mean the right combination of random mutations won't happen in the natural world, it suggests that a bird flu pandemic is a possibility -- but not a certainty. "There's no sense of 'imminence' here," Siegel said.

All of the experts agreed that more needs to be done to curb the spread of the virus among birds, however.

"H5N1 viruses are a 'moving target' and are evolving globally," Uyeki said. "Therefore, what is needed is ongoing, expanded surveillance of highly pathogenic avian influenza A (H5N1) viruses in animals (including poultry and wild birds) and humans in many countries."

Webster and Govorkova noted that countries that have implemented tough, bird-focused interventions did reduce the threat. But with winter approaching, they worry that H5N1 will finally make its way from Eurasia to the Americas via migrating flocks.

However, Siegel said, vaccinating every bird in the United States does not make sense right now. That's because the virus would simply go "underground," infecting fowl but not producing outward symptoms.

"You want to vaccinate susceptible populations, and then control outbreaks by killing affected birds," Siegel said.

But he also stressed that, "here, in the U.S., we as yet have no birds that have this virus. We don't even have a problem yet, except for fear."

More information
There's more on bird flu at the U.S. Centers for Disease Control and Prevention.

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