Maggie Fox, Yahoo News 16 Mar 08;
Flu viruses evolve freshly somewhere in east or southeast Asia every year, spreading around the world over the next nine months before dying out, researchers reported on Wednesday.
Genetic analysis by two teams of international researchers show that there are just a few initial sources of annual, seasonal influenza epidemics. The viruses spread around the world from these before dying.
Then every year, new strains emerge to infect people, according to the studies published in the journals Nature and Science.
One team led by Edward Holmes of Pennsylvania State University could not pinpoint the source but said that both H3N2 and H1N1 strains of influenza appear to arise every year from a "reservoir," perhaps in the tropics.
A second team led by Colin Russell and Derek Smith of the University of Cambridge in Britain analyzed 13,000 samples of H3N2 flu taken since 2002 to demonstrate this source must be in east and southeast Asia, perhaps a different place every year.
"For over 60 years the global migration pattern of influenza viruses has been a mystery," Russell told reporters in a telephone briefing.
Many experts have long believed Asia, and specifically China, to be the source of most influenza viruses.
Others hypothesized that flu viruses migrated back and forth between the northern and southern hemispheres, or that they cooked year-round in the tropics, to pop out every once in a while to the rest of the world, Russell said.
"We find that viruses come out of east and southeast Asia as a region each year and it is not any one particular country that is the continual source of influenza viruses. So it is not as simple as saying out of China, because out of China is not the whole story," Russell said.
RAINY SEASONS
In tropical regions, flu tends to break out in the rainy season. "In east and southeast Asia there is a there a lot of variability in the timing of the rainy season and the timing of the epidemic," Russell said.
"Bangkok and Kuala Lumpur are only 700 miles apart but they have their flu epidemics at completely different times of year." This means flu epidemics can be occurring almost year-round in Asia, he said.
Then the viruses die out every year in the Americas, Europe, Australia and the rest of Oceania, making these areas "evolutionary graveyards," Russell said.
Even if travelers carry the flu viruses back from the Americas to Asia, for example, people living in Asia are already immune to those particular variants.
The World Health Organization estimates that annual influenza epidemics infect between 5 percent and 15 percent of the world population each year, cause 3 million to 5 million cases of severe illness, and between 250,000 and 500,000 deaths,
About 300 million people get the flu vaccine each year. Without it, said Smith, a person can expect to catch the flu about once every 10 years.
Smith said the findings are important for the experts who formulate the new flu vaccine each year. It typically includes a cocktail of three strains, and the scientists try to predict which strains will cause the most trouble each year.
"If we are trying to predict what will happen a year from now we should be paying attention to what is happening in east and southeast Asia," he said.
The researchers said their study does not have any bearing on what might happen in a pandemic of a new source of flu, such as the H5N1 virus now circulating mostly among birds in Asia, Europe and Africa.
(Editing by Will Dunham and Cynthia Osterman)
Flu Viruses Originate in Asia, Hitch Across Globe
Ker Than, National Geographic News 16 Apr 08;
The densely packed cities of East and Southeast Asia act as incubators for new strains of deadly influenza viruses that get exported around the globe, new research shows.
Two new studies show that the virus spreads in waves through cities such as Hong Kong and Bangkok before hitching rides upon human hosts to other regions.
"For over 60 years, the global migration of influenza viruses has been a mystery," said study author Colin Russell of the University of Cambridge in the United Kingdom.
Now the new findings will help scientists better predict the evolution of the most common type of influenza virus, A (H3N2), which could in turn lead to improved flu vaccines, the authors said.
(See photos of people fighting the spread of influenza.)
Evolutionary Graveyards
Russell and colleagues analyzed 13,000 samples of influenza A (H3N2) virus gathered across six continents from 2002 to 2007. Their findings appear in this week's issue of the journal Science.
The team used a new technique called antigenic cartography to make fine-grained measurements of genetic differences between strains.
They focused on the gene that encodes for hemagglutinin, a protein on the virus's protective shell that plays an important role in infection.
The team's analysis allowed them to identify different viral strains as they traveled around the world.
New strains first appeared in East and Southeast Asia and reached Europe and North America about six to nine months later.
Several months after that the viruses arrived in South America.
South America was the last to be infected because people travel less between that continent and East and Southeast Asia than they do between other parts of the world.
A key point, the authors say, is that once the strains leave their points of origin, they rarely return.
"Regions outside of East and Southeast Asia are essentially evolutionary graveyards of influenza viruses," Russell said.
The team speculates that East and Southeast Asia are good breeding grounds for the virus because of the densely packed and well-connected cities of the region.
Also, unlike in North America and Europe, where flu is a seasonal occurrence that spikes in winter, influenza has a yearlong presence in the tropics.
Perfect Sense
Edward Holmes, a biologist at Pennsylvania State University, said that the team's reasoning is sound.
"To me, it makes perfect sense," Holmes said.
Holmes led a separate study, detailed in tomorrow's issue of the journal Nature, that reached similar conclusions.
Rather than comparing a single gene, Holmes' team compared the full genomic sequences of influenza viruses gathered from New York State and New Zealand.
Their results also suggested a common source of influenza viruses located somewhere in the tropics, but due to the study's limited geographic sampling, the scientists could not pinpoint it to a specific region.
The work by Holmes' team could help solve another influenza mystery, however.
For years, scientists have wondered how some influenza strains gain resistance to drugs that are not widely used, such as Tamiflu.
By sequencing the virus's full genome, the team showed that genes are linked in a complicated way.
"We show in our paper that you can't think of the evolution of [hemagglutinin] alone," Holmes said. "The whole genome evolves. It all links up."
Thus, one way influenza might be acquiring resistance to new drugs is by linking together mutations on different genes.
Kathryn Edwards is an influenza researcher at Vanderbilt University in Tennessee, who was not involved in either study.
"These are really fascinating molecular stories," Edwards said. "It's really beautiful science."
Better Forecasts
The findings could lead to improved forecasts of which strains to target when creating flu vaccines, experts say.
Currently, flu experts meet twice a year to pinpoint strains they think will pose the greatest threat the following season.
Now that scientists know the virus's Asian origins, they can better focus their energies and resources.
"There's no point in going to New York or Seattle or Buenos Aires," Holmes of Penn State said.
"The viruses are dying in those places. We need to go to the source."
