Mapping genes & genomes: A molecular approach for epidemiological insight and targeted dengue control in Singapore

Abstract

Background: Dengue control rides solely on the suppression of vector populations as there is no alternative way to occlude Dengue virus (DENV) infection at present. In-depth understanding of virus-host interactions, vector biology and ecology facilitates such an indirect approach that targets to minimize the disease burden in endemic regions. Based on this fundamental, dengue control in Singapore utilizes an evidence-based decision support system inclusive of major elements of the disease cycle: host (case and entomological surveillance), pathogen (virus surveillance) and environment (ecological information). Methods: Aedes breeding data is collected routinely as part of vector control operations by the National Environment Agency whereas case surveillance is spearheaded by the Ministry of Health. At the Environmental Health Institute, DENVs isolated from human sera obtained through an island wide network are routinely subjected to serotyping and genome sequencing. While circulating viruses are compared with a global pool for potential introductions, their spatial distribution is mapped in the local landscape of Aedes and dengue clusters to target enhanced vector control. In parallel, genetically diverse viruses are tested for fitness in mosquitoes and mammaliansystems in order to determine their outbreak potential. Results: From 2005-2011, 454 full length and 10 nearly complete envelope genes belonging to all 4 DENV serotypes (DENV-1 = 78, DENV-2 = 285, DENV-3 = 81, DENV-4 = 20) have been characterized. Data revealed a switch in the predominant serotype in two occasions in 2005 and 2007, both of which were associated with unprecedented outbreaks. Phylogenetic analyses revealed multiple introductions and alternating genotype/clade changes of all 4 DENV serotypes. One of the noteworthy was the clade change in DENV-2 cosmopolitan genotype in 2007. Post-2006 clade viruses showed higher transmission potential in Ae. aegypti, which may explain the outbreak in 2007 despite a low Aedes house index. Conclusion: Utilizing the serotype switch combined with spatial analysis of cases and vector density as a major warning sign to alert control operations and monitoring virus evolution as ameans of disease transmission have presumably contributed to avert a major dengue outbreak in Singapore since 2007.