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Dengue Virus Spread in Asia Appears Aided By Airline Hubs

NEW YORK (GenomeWeb) – The dengue fever virus appears to have gained a toehold in parts of the world where it did not previously produce infections with the help of human air travel, according to a study published online today in PLOS Neglected Tropical Diseases.

In an effort to begin untangling the origins of dengue fever infections in East and Southeast Asia in recent years, investigators from China, the UK, and France brought together available gene and/or genome sequences for more than 2,200 dengue viruses collected in Asia over nearly six decades.

When the team considered the phylogenetic patterns for these viruses in the context of human socioeconomic patterns, migration, and travel by sea and air, one factor stood out most in the spread of the dengue virus serotypes considered: air traffic hubs.

"Our analyses suggest the network centrality of air traffic hubs such as Thailand and India contribute to seeding dengue epidemics, whilst China, Cambodia, Indonesia, and Singapore may establish viral diffusion links with multiple countries in Asia," corresponding authors Bing Xu, a researcher affiliated with Tsinghua University and Beijing Normal University, Oliver Pybus of the University of Oxford, and their co-authors wrote.

Dengue virus infections characteristically occur in tropical and subtropical regions, but increasingly produce disease in other parts of the world, as well, the team explained. An outbreak took place in a temperate region of Japan in 2014, for example, and global rates of dengue fever infections have jumped significantly over the past 50 years or so. According to the World Health Organization, the number of countries with a history of severe dengue epidemics jumped from nine prior to 1970 to more than 100 today.

Although some dengue cases are marked by relatively mild fever symptoms, the virus can cause potentially life-threatening complications such as dengue hemorrhagic fever and dengue shock syndrome. Consequently, investigators are keen to get a closer look at factors promoting the virus' spread.

For their new analyses, researchers brought together sequence data for 2,202 isolates collected at 20 sites in Asia between 1956 and 2015. The collection included representatives from three dengue virus serotypes: DENV-1, DENV-2, and DENV-3.

From there, the team considered dengue virus phylogeny — based largely on dengue virus "E gene" sequences — in parts of Asia within a statistical framework that took several potential disease-spreading factors into consideration.

Along with analyses to retrace divergence times for Asian genotypes within DENV-1, -2, and -3, for example, the researchers used joint modeling to uncover apparent ties between dengue virus spread and airline hubs. They also identified instances of dengue virus movement that seemed to be helped along by other forms of human migration between nearby countries.

"The spatial dynamics of dengue virus in Asia inferred here suggests that dengue virus genetic diversity in Asia is dynamic yet spatially structured, with frequent virus lineage movement among countries, and frequent co-circulation of dengue virus lineages," the authors concluded, noting that air transportation networks appear to have contributed to the current serotype distribution in the region.

The investigators cautioned that a clearer view of dengue virus spread will likely be achieved as more epidemiological data — combined with large sets of whole-genome sequences for dengue isolates and vector mosquitoes — become available.