The recent emergence and spread of dengue hemorrhagic fever in the Ame
ricas have been a major source of concern. Efforts to control this dis
ease are dependent on understanding the pathogenicity of dengue viruse
s and their transmission dynamics. Pathogenicity studies have been ham
pered by the lack of in vitro or in vivo models of severe dengue disea
se. Alternatively, molecular epidemiologic studies which associate cer
tain dengue Virus genetic types with severe dengue outbreaks may point
to strains with increased pathogenicity. The comparison of nucleotide
sequences (240 bp) from the E/NS1 gene region of the dengue virus gen
ome has been shown to reflect evolutionary relationships and geographi
c origins of dengue virus strains. This approach was used to demonstra
te an association between the introduction of two distinct genotypes o
f dengue type 2 virus and the appearance of dengue hemorrhagic fever i
n the Americas. Phylogenetic analyses suggest that these genotypes ori
ginated in Southeast Asia and that they displaced the native, American
genotype in at least four countries. Vaccination and other control ef
forts should therefore be directed at decreasing the transmission of t
hese ''virulent'' genotypes. (C) 1997 Academic Press.