Scientists from around the world have teamed up to track the way the seasonal flu virus travels from its origins in East and Southeast Asia to where it fizzles out in South America. They hope the discovery will help to improve flu vaccines by making it easier to anticipate how the virus evolves.

The discovery is to be published in the 18 April 2008 edition of Science and is the work of scientists at the University of Cambridge and the World Health Organisation (WHO) Global Influenza Surveillance Network. The Network comprises 100 labs in 80 countries around the world.

Scientists have established that since 2002, new “seed strains” of the the common type A (H3N2) human flu virus arise every year in what the study authors describe as the “East and Southeast Asian circulation network”, which includes countries in tropical, subtropical, and temperate zones, spanning Malaysia, western Indonesia, Korea and Japan.

According to the World Health Organization (WHO), around 5 to 15 per cent of the world’s population catches the flu every year, resulting in 3 to 5 million serious cases and between quarter and half a million deaths. Some 300 million people are vaccinated every year against seasonal flu.

In February and September each year, WHO specialists, many of whom co-authored this study, meet to select the strains of flu to use in preparing the coming season’s vaccine. They base their selection on what they consider to be the strains that are most likely to pose the greatest threat.

A significant challenge in making this selection is not knowing exactly what migration pattern the flu virus strains follow, which until now has been somewhat of a mystery. There have been several theories, such as the virus follows the seasons, or it circulates continuously in the tropics and breaks out now and again, or that it migrates out of China.

Cambridge epidemiologist and study co-author Colin Russell and colleagues examined 13,000 global samples of the type A (H3N2) virus that were collected between 2002 and 2007 by the WHO Global Influenza Surveillance Network.

By analysing the samples they identified which strains in A (H3N2) caused the most disease in each of the five years at each point of their journey around the world. They also determined the path of that journey, which starts in East and Southeast Asia, then six to nine months later reaches Europe and North America. A few months after that the virus strains travel to South America, and rarely return to their origins in Asia, said the authors.

Scientists don’t know why, but flu epidemics typically occur during winter in temperate regions in the northern and southern hemispheres, and in tropical regions they mostly break out during the rainy season. These two different types of region overlap in East and Southeast Asia, which the authors suggest give the flu virus the chance to keep circulating all year round, giving rise to new strains that break out and travel around the world.

Corresponding author Derek Smith, also from the University of Cambridge said:

“Flu epidemics appear to be driven by seasonal factors such as winter, or rainy seasons. So there can be cities that are only 700 miles away from each other, such as Bangkok and Kuala Lumpur, which have epidemics six months apart.”

“There is a lot of variability like this in East and Southeast Asia, so lots of opportunity for an epidemic in one country to seed an epidemic to another nearby country, like a baton passed by runners in a relay race,” he added.

On the whole, said the authors, the seasonal flu vaccine is effective at protecting the 300 million people that are vaccinated every year, because the vaccine selection specialists hit on the right combination of subtypes. But every now and again a new strain emerges after the selection is made.

Smith said the goal of the collaborative effort is to increase the ability to predict the new strains every year, and this study was another step in that direction, and particulary:

“Highlights the importance of ongoing collaborations and surveillance in East and Southeast Asia, and expanding these collaborations in the future,” said Smith.

A key method used in the study was the analysis of genetic and “antigenic” data. The first comes from studying the genetics of the virus itself, and the second comes from studying immune system reactions to the virus, and how both change as the virus evolves on its journey around the world.

To map the evolutionary trajectory of the virus, the authors used an innovative computer based quantitative technique called “antigenic cartography”, created by researchers at Erasmus Medical Center, Los Alamos National Laboratory and the University of Cambridge.

Using this method scientists can compare thousands of viruses at a time and map the differences between them in such a way that they can trace their evolutionary path over time.

Dr Elias A Zerhouni, director of the US National Institutes of Health, whose Pioneer Award programme co-sponsored the study, said:

“By applying an innovative strategy to map differences in seasonal influenza strains worldwide, Smith and his colleagues have offered important insights into patterns of influenza virus spread that could greatly improve surveillance and vaccine strain selection.”

Zerhouni added that this research showed the value of “supporting exceptionally creative approaches to major challenges in biomedical and behavioural research”.

The importance of worldwide timely colloboration among the many scientists in the WHO Global Influenza Surveillance Network cannot be under-emphasized. The flu virus evolves so quickly that the scientists are essentially “tracking its evolution in real time”, said Smith.

“Because flu evolves so quickly, flu science and public health necessarily go hand in hand,” he added.

“The global circulation of seasonal influenza A(H3N2) viruses.”
Science, To be published early online on 18 April 2008.

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Click here to learn more about seasonal flu (WHO factsheet).

Source: University of Cambridge press release, WHO.

Written by: Catharine Paddock, PhD