Evolution of dengue virus type 2 during two consecutive outbreaks with an increase in severity in southern Taiwan in 2001-2002.

To investigate viral determinants and evolution linked to outbreak with increased severity, we examined dengue virus type 2 (DENV-2) sequences from plasma of 31 patients (14 dengue fever, 17 dengue hemorrhagic fever, DHF) continuously during the 2001 and 2002 outbreaks in southern Taiwan, in which both the total cases and proportion of DHF cases increased. Analysis of envelope (E) and full-genome sequences between viruses of the two outbreaks revealed 5 nucleotide changes in E, NS1, NS4A, and NS5 genes. None was identical to those reported in the DENV-2 outbreak in Cuba in 1997, suggesting viral determinants linked to severe outbreak are genotype dependent. Compared with previous reports of lineage turnover years apart, our findings that the 2002 viruses descended from a minor variant of the 2001 viruses in less than 6 months was novel, and may represent a mechanism of evolution of DENV from one outbreak to another.