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v »infected cells. Also, lysis or immune clearance of these cells led to the release ofvasoactive mediators and procoagulants, which results in increased capillarypermeability. Consequently the blood cells cripple, and bleeding develops in thegum, the skin, and the intestinal tract. Eventually the blood vessels do not workquite right and the blood pressure drops precipitously; as a result the blood fails tomeet the metabolic demands of the cells in the body -which is shock (Halstead andDeen, 2002). Host immune factors, such as cytokines, interferon and acti vatedcomplement have been suggested to increase the capillary permeability, the hallmarkofDHF (Kurane et al., 1994, Annstrong and Ricco-Hesse, 2001). Loke et al., (2001)observed that there seems to be a genetic component that places certain individualsat high risk of severe disease during secondary dengue infection. For two decadesADE has served as an explanatory hypothesis (Halstead and Deen, 2002). It hasbeen demonstrated that severity is correlated with peak virus titers early in theillness with children with secondary dengue infections (Vaughn et al., 1999).Halstead and Deen, (2002) therefore, suggested that with ADE as an explanation fordisease severity, proposed vaccines need to be capable of producing protectiveneutralizing antibodies to all the four-dengue viruses.2.3.5 Epidemiology ofDHFNearly 3 million cases of DHF have been officially reported worldwide withmost cases occurring in Asia. In Thailand alone, 874,207 cases of DHF werereported between 1958 and 1990, with a case-fatality rate of 1.57% (Monath andHeinz, 1996) and the disease ranks fifth as a cause of morbidity, third as a cause ofdeath, and fifth as a cause of years of productive life lost (Grats, 1993). Factorsresponsible for the emergence of DHF as an epidemic disease in Asia in the 1950sand 1960s and for the dramatic rise in incidence in the last decade include:1. Demographic changes (human population growth and urbanization)favoring contact with the domestic mosquito vector, Aedes aegypti.; ..2. Ecologic changes linked to urbanization (poor sanitation, inadequatepiped water necessitating domestic water storage) favoring Aedesaegypti breeding;3. The rapid rise in air travel, providing the means for movement ofviremic human beings and dissemination of multiple dengue serotypes.27