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genotype 111, which had been present In the Caribbean since at least 1969.Similarity between the Caribbean E- genotyelll strains and DEN-2 strains isolatedin the South Pacific between 1971 and 1976 indicated a potential route of spread.More than two decades ago, DEN-3 which was prevalent in the Caribbean, belongedto subtype IV but during 1996-1998 epidemic in Guatemala, DEN-3 isolatesbelonged to sub type IIIwhich was reported to be imported from Asia or Africa orfrom a Pacific island where this subtype was recovered in 1994. (Usuku et al.,2001). The DEN-4 circulating in endemic/epidemic pattems in the Americas since1981 is closely related to the strains from Niue Island and the Gilbert Islands, againindicating virus transfer between the Americas and the Oceania (Monath and Heinz,1996). Comparisons of DEN-2 strains isolated in the 1980sin Africa demonstratedthat enzootic strains associated with sylvatic vectors and nonhuman primates inWest Africa were genetically distinct from strains causing human epidemics. TheWest African epidemic strains were genetically related to isolates from Indonesia,Sri Lanka, the Seychelles Islands and Somalia, suggesting a route of spread acrossthe Indian Ocean to East Africa and thence to West Africa. The epidemics thus aroseby introduction of viremic travelers rather than from a local jungle cycle (Gubler andTrent, 1994; Rico- Hesse, 1990).2.3.7 THE PATHOGENESIS OF DENGUE FEVERNeuroadapted DEN produces typical encephalitic lesions, predominantly inthe rhinencephalus of infant, weanling, and adult mice (Monath and Heinz, 1996).Viral antigen is detectable by immunofluorescence in reticuloendothelial cells ofliver, lymph nodes and spleens of intraperineally-infected mice (Boonpucknavig et.al., 1981). DEN antigens are detectable by Western blotting in suckling mousebrain or liver examined 7 days after intracerebral inoculation (Chardboonchart et al.,1990). A thymic nude mice peripherally infected with adapted DEN developes fatalencephalitis and viral antigens in neurons, skeletal muscles, and myocardi urn andKupffer cells In experimentally infected non - human primates, the role ofmononuclear phagocytes as principal sites of DEN replication has been establishedby tissue titration and IF staining of cells in the skin. spleen, lymph nodes, liver,lung, and thymus (Monath and Heinz, 1996) Classical DF produces self-limitedinfection in humans. Biopsies of skin lesions have shown swelling of endothelial.,.,33