An international team of scientists has determined the itinerary of the seasonal flu, paving the way for better monitoring and more effective vaccines.

The researchers report in Science that they sussed out the bug's travel plans by studying 13,000 samples of the virus collected from every continent (except Antarctica) over the past five years. Among their findings: seasonal flu originates in eastern and Southeast Asia. The result broadens previous hypotheses that such viruses emerged in China or exclusively in tropical regions.

"For over 60 years the global travel patterns of the influenza virus have been a mystery," study co-author Colin Russell, an epidemiologist specializing in pathogen evolution at the University of Cambridge in England said during a teleconference today. Russell said that he and his colleagues found that each year since 2002 new strains of influenza A (H3N2), the most infectious variety of seasonal flu, originated in "the east and Southeast Asian circulation network," which spans from Malaysia and western Indonesia to Korea and Japan. The virus showed up in Europe and North America six to nine months later—and then continued on to South America.

The finding will allow researchers to refine their search for new influenza strains and manufacture a yearly vaccine designed to give recipients resistance to the right ones. "Flu evolves quickly and in complex ways," so this will help the World Health Organization (WHO) track and aim at the right strains with annual vaccines, says co-author Derek Smith, a Cambridge epidemiologist and member of the WHO committee tasked with planning WHO's annual flu shot regimen.

Smith says the team traced the source of influenza by homing in on hemagglutinin, a protein on the surface of the virus that triggers an immune response in our bodies. (Flu shots, which are actually a weakened form of the virus used to prime the immune system, are essentially based on this protein.)  If a flu virus evolves—and it's hemagglutinin changes—it can elude the vaccine because this protein is altered, allowing the bug to slip into the body undetected by immune system sentries.

The researchers speculate that the broad range of climates in eastern Asia allows epidemics to arise in crowded areas at different times of the year. The flu typically strikes in temperate climes (like those in China) in winter months and in tropical areas, such as those in Vietnam, during their rainy seasons. "There is a lot of variability like this in east and Southeast Asia, so [there is] lots of opportunity for an epidemic in one country to seed an epidemic in another nearby country and then flow out of the region," Smith says.

According to WHO statistics, 300 million people are vaccinated against the flu each year, receiving an immunization with a cocktail of weakened strains of influenza A (varieties H3N2 and H1N1), along with the influenza B virus to protect against a full infection. Smith says the vaccination provides good protection to the population as a whole, although flu epidemics still cause three million to five million people to become seriously ill and claims 250,000 to 500,000 lives annually. .If they bottle the wrong strain, however, and the virus evolves, it can leave those who have been vaccinated as vulnerable as an unimmunized population.

"Because these flu viruses change so quickly, we have to update the vaccine fairly regularly," Smith says. "The more we know about how flu viruses change and how they spread around the world, the more that this process can be changed and improved."

Eddie Holmes, a biologist at Pennsylvania State University, agrees. In a study appearing in tomorrow's Nature, he reports how the genome of the influenza virus evolves. "We hypothesize that there must be a source population, that it might be in the tropics," he says, "and that's where you should concentrate monitoring and surveillance."

He notes, however, that researchers should also keep an eye out for proteins other than hemagglutinin and the genes that carry the recipes for them. "A couple of other genes are also evolving rapidly and we know nothing about them," he says, adding that they may affect the behavior of hemagglutinin. "You cannot say that the virus is hemagglutinin; that is just one protein."