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Seasonal Flu Outbreaks Start in Asia: Study

Knowing the source should lead to more effective vaccines, researchers say

WEDNESDAY, April 16 (HealthDay News) -- Each year, new strains of virus that produce seasonal flu epidemics start in East Asia and Southeast Asia and then spread around rest of the world, researchers report.

And by focusing on new flu strains emerging in Asia, scientists may be able to improve their forecast of seasonal flu strains and develop better vaccines, the researchers said.

"For over 60 years, the global migration pattern of influenza has been a mystery," lead researcher Colin Russell, of the University of Cambridge in England, said during a Wednesday teleconference.

Conventional wisdom has held that flu viruses migrate between the northern and southern hemispheres after the flu season. Other theories contend that the viruses surface in the tropics and circulate continuously, or start out in China, Russell said.

"We found solid evidence that influenza H3N2 viruses [the most common viruses] have migrated out of what we call the East and Southeast Asian circulation network, which includes tropical, subtropical and temperate countries," Russell said.

Virus strains begin in East and Southeast Asia and take about nine months to reach Europe and North America. They arrive in South America several months later because of South America's isolation in terms of travel from East and Southeast Asia, Russell explained.

Currently, the decision about which strains to include in the yearly flu vaccine are made almost a year before the flu hits the United States, co-author Derek Smith, also from the University of Cambridge, said during the teleconference. Knowing where flu patterns begin will be invaluable in helping to develop more effective vaccines earlier, he added.

"The ultimate goal is to increase our ability to predict the evolution of influenza virus, and this study is one step along that path," Smith said. "This may help us get a step ahead of the virus, because we now know where to look."

Russell said flu viruses rarely return to their place of origin and usually become extinct after a flu epidemic has run its course. "When these viruses leave East and Southeast Asia, they rarely return," he said. "The regions outside East and Southeast Asia are essentially the evolutionary graveyard of influenza virus."

Also, Russell said, flu viruses don't circulate continuously in any one region of the world. "They don't survive at the end of an epidemic in both temperate and tropical countries," he said. However, because East and Southeast Asia are made up of both temperate and tropical areas, flu virus is able to circulate year-round in those areas, he explained.

"It is this year-round circulation, combined with a substantial volume of air traffic amongst East and Southeast Asian countries, that allows East and Southeast Asia to serve as the source of influenza epidemics to the rest of the world," Russell said.

The findings are published in the April 18 issue of the journal Science.

For the study, researchers analyzed 13,000 samples of flu virus collected by the World Health Organization Global Influenza Surveillance Network from six continents from 2002 to 2007.

The researchers compared the differences between the strains in a surface protein called hemagglutinin. Hemagglutinin is the main target of the immune response to the flu, and even small changes can enable the virus to fool immune systems. The researchers also compared the genetic codes for hemagglutinin in a number of the flu strain samples.

Although there are sometimes mismatches between strains of circulating flu virus in the vaccine, the vaccine usually works very well and protects about 300 million people each year from getting the flu, Russell said. Even in years when the flu vaccine is a mismatch, getting vaccinated still offers protection, he said.

According to the World Health Organization, yearly flu epidemics cause some 3 million to 5 million cases of severe illness, and 250,000 to 500,000 deaths every year.

In a separate study published in the April 17 issue of the journal Nature, Edward Holmes, a professor of biology at Pennsylvania State University, and colleagues analyzed 1,302 samples of flu collected over 12 years from around the world.

Because of the limited sample size, Holmes said he can't tell where flu viruses start. But he agrees that East and Southeast Asia is the likely source. "That's a really big finding," he said.

Holmes's team analyzed the entire gene sequence of their flu samples. Using the entire genetic sequence, rather than just one gene such as the one for hemagglutinin, will make it possible to create even more effective vaccines, Holmes said.

"Focusing on that one gene alone, you're not getting the complete picture," Holmes said. "That may have a major bearing on why the vaccine fails sometimes."

To make a more effective vaccine, the first thing you need to do is look in the right place -- East and Southeast Asia, Holmes said. "You also have to look at the whole genome rather than just one gene alone."

More information

To learn more about the flu, visit the U.S. Centers for Disease Control and Prevention.

SOURCES: April 16, 2008, teleconference with Colin Russell, Ph.D., Derek Smith, Ph.D., University of Cambridge, U.K.; April 18, 2008, Science; Edward Holmes, Ph.D., professor of biology, Pennsylvania State University, University Park; April 17, 2008, Nature

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