Although we have not detected increases in replication fitness for any given genotype, some of the evolutionary events leading to more virulent strains seem to have already occurred and by the time these viruses rapidly spread from Southeast Asia to other areas of the world (1940s), they were already virulent or replicatively fit (Gubler 2002) . We have yet to measure any specific genetic changes that are fixed in the viral population as virulent genotypes are successfully dispersed to other continents and we do not know whether there have been any changes imposed by selection in their new environments (e.g., for serotype 2, Southeast Asian genotype introduced into the Americas; for serotype 3, Sri Lankan genotype III introduced to the Americas). That is, these viruses had increased fitness at their origin, in that they are directly linked to the appearance of DHF and they are transmitted more efficiently by mosquitoes. However, some researchers believe differences in clinical presentation and severity of epidemics are a function of only immunologic and genetic differences between the human populations in both continents (Southeast Asia and Americas) (Halstead 2006) or that nonneutralizing antibodies formed during DENV infection play a role in gradually selecting for more pathogenic viruses in humans (Morens and Fauci 2008) .