The first descriptions of DENV virulence differences came from epidemiologic and entomologic studies done in the South Pacific by Rosen and Gubler, in the 1970s (Gubler et al. 1978; Rosen 1977) . It was noted that some outbreaks in this region had fewer or no cases of DHF and the transmitted viruses were considered of low virulence; other outbreaks had many cases of DHF, after primary infection and these viruses were therefore more virulent. However, it took the development of RNA nucleotide sequencing techniques and the use of these sequences to generate phylogenetic trees of evolutionary relationships among viruses to discover that specific variant groups, or genotypes, were more frequently associated with dengue epidemics and severe disease (Chungue et al. 1995; Lanciotti et al. 1997; Lanciotti et al. 1994; Messer et al. 2003; Rico-Hesse 1990; Rico-Hesse et al. 1997 ). More recently it has been shown that some genotypes associated with DHF have been introduced and become established (endemic) in other continents, sometimes displacing the less-virulent DENV already being transmitted in those regions (causing DF only). "Virulent" genotypes have been described for serotypes 2 and 3 and it remains to be seen if further evolutionary studies will pinpoint similar groups in serotypes 1 and 4 (Rico-Hesse 2003) .