Study Shows Immediate Treatment Needed for Bird Flu Cases

(Sep. 12, 2006) Avian flu kills in much the same way the global flu pandemic of 1918 did, by drowning victims in fluid produced in their own lungs, a new study has found. The study also suggests that immediate treatment with antiviral drugs is crucial, because the virus reproduces so quickly that, if not suppressed within the first 48 hours, it tends to push victims into a rapid decline to death.

“The paradigm ‘hit hard and hit early’ probably is very true for H5N1 influenza,” said Dr. Menno D. de Jong, an Oxford University virologist and the study’s lead author. However, he added, because the body’s own immune response does part of the damage, doctors should consider giving anti-inflammatory drugs along with antivirals like Tamiflu.

Although the results of the relatively small study are precisely what flu experts had predicted from laboratory work, Dr. Anne Moscona, a professor of pediatrics and immunology at the Weill Cornell Medical College, called it a “major advance,” because so little clinical information had previously been gleaned from the 241 known cases of the disease.

Many of those cases have been in rural villages in Asia, where victims pick it up from backyard chickens and are buried before the virus that killed them is even identified. Provincial hospitals have done few autopsies and little genetic analysis.

This study, which appears in the October issue of Nature Medicine, was led by an Oxford research team in Ho Chi Minh City, Vietnam, and compared 18 people with the A(H5N1) avian flu in 2004 and 2005 to 8 people infected with seasonal human flus.

It found that the avian flu patients, and particularly the 13 who died from it, had unusually high levels of the virus in their bodies. Consequently, they also had high levels of the chemicals, known as cytokines and chemokines, that set off the immune system’s inflammatory response.

Those chemicals, some of which are produced in cells lining the narrowest passages in the lungs, draw in white blood cells to attack invaders. But doing so too vigorously can flood the lungs, causing deadly pneumonia.

The effect, known as the “cytokine storm” is the leading theory as to why so many young, previously healthy people died in the 1918-19 pandemic, known as the Spanish flu, which killed tens of millions of people. Seasonal flus tend to kill the very old and very young, who usually die from bacterial infections that develop days after the milder flu virus has irritated their lung tissue.

The avian flu virus was easier to detect in throat swabs than in nasal swabs, Dr. de Jong said, which is the opposite of how seasonal flu is detected, and useful for doctors doing flu tests. And the virus was found in rectal swabs, which is important for hospitals to know because it means diarrhea, common among flu patients, can also spread the disease.

Flu experts were surprised that such high concentrations of the virus were found in nose and throat swabs. Earlier studies had suggested that the avian flu is not easily transmitted between humans because, unlike seasonal flu, it attaches primarily to receptors found deep in the lungs.

Dr. de Jong said there could be several explanations: the throat swabs could have picked up virus coughed up from the lungs. Different receptors are spread up and down the breathing tract. And it is possible — though unproved — that some people may simply be born with receptors more amenable to the virus. That theory has been offered by epidemiologists who note that, even in villages where all the chickens are sick, human outbreaks tend to cluster in families.

The study also showed that some of the flu strains isolated in Vietnam had particular genetic changes that virologists have been watching for, fearing that these changes would make them more lethal.

But those changes appeared in only some patients, and in those who died as well as those who lived, “so I wouldn’t make too much of it,” Dr. Moscona said.

Henry L. Niman, a Pittsburgh biochemist who has been tracking viral changes and raised earlier alarms about E627K, agreed.

“Lethality in the virus may rely on several changes,” he said. “But it’s got several different paths to the same end. That’s what makes it so efficient.” (from The New York Times)


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