Avian flu may be more prevalent but less deadly than previously thought.

Would you estimate the percentage of movie fans in the world by polling at a cinema? Would you calculate the number of overweight Americans by taking a survey at Weight Watchers locations? Not if you were aiming for any sort of statistical accuracy; such methods would not give you samples at all representative of a larger population.

Regrettably, just this sort of sampling bias may have lead to huge errors in avian flu mortality numbers. While stony-faced newscasters somberly report that more than 50% of people infected with avian flu ultimately die, the death rate may be much lower.

A study published in the January 9th issue of Archives of Internal Medicine found that as many as 600 to 750 people in Vietnam may have come down with a mild variant of the avian flu—one that does not carry lethal consequences. This suggests that current mortality estimates, which are derived from only the most severely ill patients, are biased. We may be underestimating the virus’ transmission rate while overestimating the deadliness of avian flu.

“Our study suggests that this milder form may be more prevalent than the more deadly disease that we heard about earlier,” said Anna Thorson, a researcher at the Sweden’s Karolinska University Hospital and lead author of the study.

Thorson and colleagues examined data collected from April 1st to June 30th, 2004 as part of a demographic study in the Ha Tay province of Vietnam, where there is a confirmed epidemic of a highly-pathogenic H5N1 avian influenza in the poultry population. The researchers screened more than 45,000 randomly-selected individuals for health problems and exposure to sick poultry. Any individuals who reported flu-like symptoms, or possible exposure to the virus, were interviewed in person.

“Our results indicate a linkage between a mild flu-like illness and exposure to sick and dead poultry,” said Thorson. “That could suggest that there is a milder form of H5N1.” Thorson does warn that her theory needs to be confirmed by microbiological testing.

In January, 2004, the World Health Organization (WHO) confirmed H5N1 infection in 11 people in Thailand and Vietnam. Since then, human cases of H5N1 have been reported in Vietnam, Cambodia, China, Thailand, Indonesia and, most recently, Turkey. As of January 13th, the WHO reported 147 confirmed cases of H5N1 in humans and 78 fatalities due to the disease—equaling a mortality rate of 53%.

Thorson’s work suggests that the WHO statistics do not account for all cases of H5N1 infection in humans, because many cases go unreported by patients who do not seek medical assistance for milder symptoms.

Christian Sandrock, a physician and an assistant professor at the University of California Davis Health System, as well as a specialist in public health issues, says Thorson’s study brings public attention to a hotly-debated question in the medical community: Is there a mild or asymptomatic version of avian flu?

Sandrock explains that, without serology studies to confirm a patient’s infection with H5N1, Thorson’s study does not fully answer that question.

“It is not at all conclusive,” he said.

However, Sandrock thinks that the WHO’s 50% mortality figure will eventually be revised downward.

“There’s going to definitely be some people with the disease that were either asymptomatic or subclinical, that really didn’t come up on radar,” Sandrock said. “I think 50% is going to be the high end. How much it’s going to drop, I don’t know. What we’d like to see is that it goes from 50% to 3%. But, I think what we may see is that it goes from 50% to 40%, or 50% to 30%, which is still a phenomenally high mortality.”

Even if the mortality rate from H5N1 is much much lower than 50%—say as low as 5%—H5N1 could still kill millions of people if it mutates to a form communicable between humans. The “Spanish flu” of 1918 and 1919 had an estimated mortality rate of 2% to 5%. It killed an estimated 40- to 50-million people worldwide.

Avian flu is an infectious disease not usually found in species other than birds and pigs. Domestic poultry catch the disease from wild migratory waterfowl—who carry the virus but are relatively resistant to infection. Within poultry, the virus can mutate into a highly pathogenic form.

Avian flu is caused by a type A influenza virus. Type A influenza species can combine genetic material to create new subtypes, which are different from their parent viruses. A pandemic can result if the novel subtype has genes from human influenza viruses that make it transmissible between humans. At present, there have been no cases of human to human transmission of H5N1.

H5N1 was first isolated in human patients in Hong Kong in 1997. Eighteen people became infected after close contact with poultry suffering from the same strain of the virus. Six of the 18 died.

Originally published January 17, 2006

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