The significant outbreak of dengue fever in Singapore in 2005 was likely triggered by environmental factors, as opposed to mutation or other genetic changes in the dengue virus itself, according to an extensive collaborative genomic study led by researchers from the Genome Institute of Singapore and Institute for High Performance Computing of A*STAR. The results of the study have important implications for future research, surveillance and control of dengue fever epidemics.
Dengue fever is the world’s most common, insect-borne (Fig. 1), viral infection of humans with about 100 million cases reported worldwide each year that result in about 2.5 million deaths. Nearly 40% of the world’s population living in the tropics and subtropics is at risk of contracting the disease. It is caused by four closely related flaviviruses (DENV-1 to -4) known as serotypes because they stimulate different immunological responses. At present there are no vaccines or cures for dengue fever.
The researchers from the two A*STAR institutes joined forces with colleagues from several important medical research institutes in Singapore and the USA to determine and analyze whole-genome sequence data for more than 100 viruses isolated from patients during the outbreak. They compared these data with those of viruses sampled prior to the 2005 epidemic.
The team found that the DENV-1 and DENV-3 serotypes were responsible for the bulk of the outbreak, and demonstrated that they showed simultaneous patterns of increase and decrease during the epidemic. Further analysis of samples of these two serotypes collected during the outbreak revealed that, in both cases, they were most closely related genetically to viruses collected locally prior to 2005. This suggests that the outbreak was not triggered by the arrival on the island of an exotic strain.
In addition, although the genomic analysis detected that numerous mutations had occurred within each serotype during the outbreak, few could be detected by 2006. Thus, the genetic variations appeared to have conferred no particular advantage, because neither serotype was able to withstand the change in environmental factors that caused a rapid decline in dengue fever cases in 2006.
Based on this work, the researchers conclude that the outbreak of 2005 was caused by viruses already circulating in Singapore, and most likely triggered by environmental and not genetic factors, which challenges the traditional view of epidemiologists. They also suggest measures that could be added to the surveillance programs designed to predict outbreaks of dengue fever in Singapore.