Advice on treating bird flu: Hit it hard and early

Advice on treating bird flu: Hit it hard and early
By Donald McNeil The New York Times
SUNDAY, SEPTEMBER 10, 2006

Avian flu kills in much the same way the 1918 flu 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 H5N1 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 Menno 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, Anne Moscona, a professor of pediatrics and immunology at the Weill Medical College of Cornell University, 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 get the virus 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 H5N1 avian flu in 2004 and 2005 to eight people infected with seasonal human flus.

It found that bird flu patients, and particularly the 13 who died from it, had unusually high levels of virus in their bodies. Consequently, they also had high levels of the chemicals, known as cytokines and chemokines, that trigger 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. Young adults have stronger immune systems, and accounts of the deaths of recruits in World War I military camps describe whole rows of men turning blue-black as they struggled for breath.

The virus was also found in the blood of most patients who died. It probably leaked in from their lungs, de Jong said, which showed that the disease has the same potential to reach and destroy other organs in humans as it does in birds.

It was easier to detect in throat swabs than in nasal swabs, de Jong said, which is the opposite of seasonal flu and useful for doctors doing flu tests. And it 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 viral loads 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 primarily attaches to receptors found deep in the lungs.

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.

It is also possible, although unproven, that some people might simply be born with receptors more amenable to the virus. That theory has been offered before by epidemiologists noting 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 they would make them more lethal.

One, known as an E627K substitution on the PB2 gene, has been much discussed on Web sites devoted to the flu because, in laboratory tests, it lets the virus reproduce 20 times faster at the lower temperatures found in mammals' cool noses as compared to those found in birds' hot intestines.

But those changes appeared in only some patients, and in patients who died and those who lived "so I wouldn't make too much of it," Moscona said.

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