Dengue virus serotype-4 during the 2015-2017 epidemic: emergence of a novel genotype IIa of DENV-4 in the Philippines.

Dengue remains a major public health problem in the Philippines. Here, we determined the circulating serotypes in the Philippines during the 2015-2017 outbreaks by using a total of 678 serum samples that were collected from 537 individual dengue patients. Following an increase in the percentage of DENV-4 patients in recent years, we conducted a comprehensive molecular epidemiology analysis on the DENV-4 strains isolated recently in the Philippines. While two genotypes of DENV-4 have been isolated in the Philippines since 1956, the GI and GIIa which were the DENV-4 strains isolated in this study were closely related to a distinct group of GIIa strains that were isolated from the Philippines since 2004. A majority of the isolates of this sub-group has been identified in the Philippines, suggesting that the lineage may have been introduced and evolved in the Philippines to form the distinct sub-group within GIIa strains. The increase in DENV-4 activity also coincided with the appearance of GIIa sub-group and the phasing-out of GI lineage in the Philippines. Overall, our study demonstrates a shift in DENV-4 genotype and epidemic dynamics in a hyperendemic region, suggesting the importance of DENV genetic evolution in establishing and sustaining transmission.