The recent emergence and spread of dengue hemorrhagic fever in the Americas have been a major source of concern. Efforts to control this disease are dependent on understanding the pathogenicity of dengue viruses and their transmission dynamics. Pathogenicity studies have been hampered by the lack of in vitro or in vivo models of severe dengue disease. Alternatively, molecular epidemiologic studies which associate certain 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 genome has been shown to reflect evolutionary relationships and geographic origins of dengue virus strains. This approach was used to demonstrate an association between the introduction of two distinct genotypes of dengue type 2 virus and the appearance of dengue hemorrhagic fever in the Americas. Phylogenetic analyses suggest that these genotypes originated in Southeast Asia and that they displaced the native, American genotype in at least four countries. Vaccination and other control efforts should therefore be directed at decreasing the transmission of these "virulent" genotypes.

Venezuelan equine encephalitis virus (VEEV) remains a naturally emerging disease threat as well as a highly developed biological weapon. Recently, progress has been made in understanding the complex ecological and viral genetic mechanisms that coincide in time and space to generate outbreaks. Enzootic, equine avirulent, serotype ID VEEV strains appear to alter their serotype to IAB or IC, and their vertebrate and mosquito host range, to mediate repeated VEE emergence via mutations in the E2 envelope glycoprotein that represent convergent evolution. Adaptation to equines results in highly efficient amplification, which results in human disease. Although epizootic VEEV strains are opportunistic in their use of mosquito vectors, the most widespread outbreaks appear to involve specific adaptation to Ochlerotatus taeniorhynchus, the most common vector in many coastal areas. In contrast, enzootic VEEV strains are highly specialized and appear to utilize vectors exclusively in the Spissipes section of the Culex (Melanoconion) subgenus.

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