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Phylogenetic Analysis Indicates Dengue May Be Endemic in Southern China

NEW YORK (GenomeWeb) – A phylogenetic analysis of dengue viruses circulating in southern China has found that the virus may in fact be endemic there, according to a pair of researchers from the US and China.

Whether or not the virus circulates in southern Chinese provinces between outbreaks has been a point of debate, though the region's climate, dense population, and widespread distribution of mosquito vectors make it perfect for the spread and maintenance of the disease. A recent outbreak in 2014 in Guangdong sickened more than 40,000 people in two months.

The University of Texas Medical Branch's Rubing Chen and Nanjing Normal University's Guan-Zhu Han analyzed dengue virus gene sequences housed in GenBank through June 2015, a total of more than 2,300 sequences. As they reported yesterday in the American Journal of Tropical Medicine and Hygiene, the researchers found some 50 clades of dengue virus serotype-1 there as well as clades of viruses belonging to other serotypes. Some of these strains were present year after year, the researchers said.

"We now have compelling evidence that dengue can persist in China — in some cases up to six to eight years," Chen, an evolutionary virologist, said in a statement. "Further, we found a surprisingly complex and diverse mix of viral subtypes represented in China, a factor that can mean greater risk of epidemic dengue in the future."

Chen and Han downloaded all sequences for each dengue virus serotype from GenBank. They focused on the complete E gene region, and after filtering they had 687 DENV-1, 526 DENV-2, 660 DENV-3, and 478 DENV-4 sequences for analysis.

Using these sequences, the researchers constructed phylogenetic trees through different maximum likelihood approaches.

Their phylogenetic trees indicated that there are some 50 individual clades of DENV-1 in mainland China as well as more than 20 DENV-2 and a handful each of the DENV-3 and DENV-4 serotypes.

Viruses from multiple clades, though, appeared to be circulating at the same time, the researchers reported. During the 2014 Guangdong outbreak, both DENV-1 and DENV-2 viruses, each involving two lineages with two and three origins, respectively, were present.

Further, in 2013, all four serotypes were present with a greater number of lineages present, representing some 20 different origins, the researchers added.

This genetic diversity is surprisingly high, Chen and Han said, noting that recent dengue outbreaks in South American and African countries generally had a single origin.

And this diversity has consequences for public health. "Even within the same year, a person can catch dengue more than once if distantly related variants are circulating in the same region," said Chen. "That's why we become concerned about public health when many variants are found, as was the case in our study."

She and Han also noted that frequent lineage replacement could reflect the genetic diversity of the source strains as well as the establishment of herd immunity.

Based on their clustering, these source strains, the researchers reported, seemed to come mostly from southeast Asian counties with occasional influxes from Latin America, south Pacific Islands, and Somalia.

In Guangdong, dengue viral strains from consecutive years grouped together, indicating that the virus persisted and could be endemic. For DENV-1, they noted groupings ranging from 2006 to 2014, 2009 to 2014, 2010 to 2013, and 2002 to 2004.

Some of these clusters, though, included strains from other countries, muddying the picture. Two possible scenarios, the researchers said, could explain this pattern. First, the dengue viral lineages are persisting endemically in Guangdong, and those picked up in other countries were actually exports from Guangdong. Alternatively, the dengue viruses were imported from other areas of Southeast Asia each year from the same source lineage, but those sources weren't always sampled and are thus missing from their phylogenetic tree.

Based on this, Chen and Han argued that the likelihood that dengue is endemic in southern China should be considered. Even if it is not endemic, they said that China still should be viewed as a key piece of the dengue transmission cycle in Southeast Asia.

"[T]he complicated DENV genetic diversity, long-term local persistence of DENV-1 in Guangdong province, and the rapid movement of DENVs as well as its widespread vector Ae. albopictus suggest that China is facing a substantial dengue threat with potential invasion into broader areas," Chen and Han wrote in their paper.