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A commonly held theory says that flu virus persists in Southeast and Eastern Asia, making this region the source of seasonal flu epidemics in other parts of the world.

However, researchers at Duke-NUS Graduate Medical School in Singapore have found that influenza A virus doesn't persist in those tropical regions as the only global source of annual epidemics. The international team of scientists involved in the work found that any one of the urban centers they studied could act as a source for an epidemic in any other locality.

"We found that these regions are just one node in a network of urban centers connected by air travel, through which flu virus circulates and causes a series of local epidemics that overlap in time," said Gavin Smith, PhD, senior author and associate professor in the Program in Emerging Infectious Diseases at Duke-NUS.

The study was published the week of Nov. 14, 2011 in the online Proceedings of the National Academy of Sciences Early Edition.

The research team chose to study influenza A because it is much more prevalent than both influenza B and C. Influenza is a significant cause of human illness and death worldwide -- the World Health Organization estimates that 250,000 to 500,000 influenza A related deaths occur per year worldwide, and about 49,000 deaths occur in the United States.

The team obtained RNA sequences of virus samples from 2003 to 2006 in Australia, Europe, Japan, New York, New Zealand, and Southeast Asia, as well as some more recently sequenced viruses from Hong Kong.

The analysis used time and space parameters to reveal high rates of viral migration among the urban centers tested. Although the virus population that migrated between Southeast Asia and Hong Kong persisted through time, the pattern of infections also depended on virus input from temperate regions that have distinct seasons.

None of the seven temperate and tropical regions they examined was the source of all of the new flu strains in a given year. The migration pattern was more complex: viral strains moved from one region to several others in a year, and flu outbreaks were traced back to more than one source.

The scientists showed that multiple lineages of a virus could seed annual flu epidemics, and that each region could function as a potential source population.

Current strategies for controlling flu virus through vaccination are based on biannual selection of vaccine candidates for the Northern and Southern hemispheres, and these plans require an understanding of circulating viruses.

"While current vaccine-strain selection strategies are generally effective, the results of our study could potentially be used to improve this process by incorporating knowledge of virus migration and connections between regions," said lead author Justin Bahl, PhD, assistant professor in the Duke-NUS Program in Emerging Infectious Diseases.

Many examples of the global movement of viruses facilitated by air travel exist, including the SARS epidemic and the H1N1 pandemic in 2009. Because air travel by large groups of people has been common for some time, today there is not any increased risk from air travel, Smith said. "Larger regions with greater connectedness may potentially contribute more to the global diversity of influenza viruses circulating."

The researchers plan to build on this study by generating new data from areas where there is currently little or no genetic information available. This work forms part of a larger effort to understand the patterns and mechanisms of transmission of respiratory viruses in humans, using influenza as a model system, Bahl said.

Other authors were from Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Department of Community Medicine and School of Public Health, Li Ka Shing Faculty of Medicine, and Hong Kong University-Pasteur Research Centre, University of Hong Kong, Pokfulam, in the Hong Kong Special Administrative Region; Laboratory of Virus Evolution, Program in Emerging Infectious Diseases, Duke–National University of Singapore Graduate Medical School; Fogarty International Center, National Institutes of Health, Bethesda, Md.; University of Texas Medical Branch, Galveston; J. Craig Venter Institute, Rockville, Md.; Center for Vaccine Research, Department of Computational and Systems Biology, University of Pittsburgh School of Medicine; Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College, London; Institute of Evolutionary Biology, University of Edinburgh; and the Center for Infectious Disease Dynamics, Department of Biology, Pennsylvania State University.

The study was supported by contracts for the Influenza Genome Sequencing Project of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health; the Area of Excellence Scheme of the University Grants Committee of the Hong Kong Special Administrative Region Government; the RAPIDD program of the Science and Technology Directorate, U.S. Department of Homeland Security and the Fogarty International Center, National Institutes of Health; a career development award under National Institute of Allergy and Infectious Diseases Contract and the Duke–National University of Singapore Signature Research Program funded by the Agency for Science, Technology and Research, Singapore; and the Ministry of Health, Singapore.