Dengue hemorrhagic fever (DHF) is a severe manifestation of mosquito-borne dengue virus (DV) infection that is characterized by plasma leakage. Several factors are believed to be important in the pathogenesis of DHF, including host factors (e.g. HLA, pre-existing memory B and T cell responses), viral factors and entomologic factors. The goal of this project is to better define the mechanisms of disease pathogenesis and control utilizing three distinct clinical studies in Thailand to address the following specific aims: * Aim 1 conducts a prospective study of symptomatic children in the early phase of suspected dengue infection to quantitate the DV-specific T cell responses, plasma and cellular viremia levels and markers of immune activation, as well as shifts in body fluid compartments, to better define predictors and outcome measures of disease severity. * Aim 2 focuses on the characterization of virus infection and localized cellular immune responses in skin compared to that seen in blood in a cohort of DV-infected adults with skin rash. * Aim 3 conducts a prospective, school-based study of children to determine correlations of disease severity with pre-existing memory T and B cell responses, immunogenetic factors, and serotype of the infecting virus. Case-based cluster investigations, in conjunction with Project 3, will characterize DV transmission in the home to define relationships between disease burden, illness severity, vector density and activity, and quantitative measures of virus in both host and vector. The long-term objectives of this Project are to better understand the pathophysiology of DHF for improved early diagnosis and novel therapeutics. An improved understanding of the correlations between host immune response and subsequent risk of DHF will help guide future vaccine trials in areas where dengue is endemic. The knowledge gained from these unique clinical studies will also improve our understanding of the roles human immune response genes and cross-reactive T and B cells may play in other emerging flavivirus infections such as West Nile Virus and in developing safe and effective vaccines against dengue and WNV.