Dengue is a vector-borne viral disease affecting humans that is endemic in tropical and subtropical areas worldwide. As a re-emerging disease, a growing body of literature is dedicated to the dynamic, clinico-epidemiology of dengue, complicated by the co-existence of several Dengue virus serotypes and an increase in the range and seasonality of mosquito vectors. A spatiotemporal model was developed using an extended version of the Ross-Macdonald theory to calculate a Relative Global Dengue Basic Reproductive Model (R0). It included temperature, rainfall, Aedes aegypti vector distribution, and geolocalized economic factors to evaluate disease transmission dynamics. A literature review identified the comprehensive factors that determine the severity and determinants of the disease, the characteristics of non-traditional high-risk populations with repeated and/or prolonged exposures, and mitigation and control measures. The impact of new vaccines on the potential for limiting travel-related cases was explored through a cost-benefit analysis of a vaccine implementation program in a special population with high-risk exposures, using United States Peace Corps volunteers as a population-case study. The mechanistic model predicts a global relative dengue outbreak risk profile and demonstrates its spatiotemporal heterogeneity by identifying areas at risk of high virus transmission throughout the various months of the year. It shows an increase in the geographic spread of the risk area during summer temperatures, demonstrating an optimal temperature and precipitation range for the genesis and proliferation of a dengue disease outbreak. A comprehensive, One Health approach should be employed to fight the spread of dengue. A tailored pre-travel health assessment and focus on primary prevention can reduce disease risk. After establishing previous infection through a serum study, administering vaccines for travelers to endemic and hyperendemic areas should be considered. The cost-benefit analysis revealed that no comprehensive vaccination program should be started for Peace Corps volunteers--the benefits achieved through vaccine efficacy against the risk of severe clinical disease is too low for a blanket recommendation. Dengue is and will continue to be a threat to global health; control and mitigation strategies targeting specific high-risk populations and understanding the true risk of the disease will be paramount to curb the spread.
