Flaviviruses are single-stranded positive sense RNA viruses that include Dengue virus (DENV). Composed of 4 serotypes that are genetically and antigenically distinct thus allowing up to 4 infections in a lifetime, DENV is transmitted by Aedes species of mosquitos, which limits its presence to tropical and sub-tropical regions of the world. Over half of the world’s population are now at risk of dengue, and this is forecasted to increase with continued urbanisation and climate change. DENV shows strong evidence of seasonality, peaking in case numbers when weather conditions are favourable to the propagation and survival of the insect vector. Yet, outside of these transmission seasons, reporting case numbers can drop to very low levels. This thesis investigated the immunological and viral risk factors for dengue outbreaks. Using patient data collected as part of an index case led household study in Vietnam that enrolled 1,650 participants with 838 dengue positive index cases and their household contacts (HHCs). Initially, DENV whole genome sequencing approaches were developed and contrasted. This allowed sample appropriate techniques to be deployed on patient and HHC samples, which resulted in 511 whole genomes from 701 qPCR positive subjects. Predictors of transmissibility were then considered with little difference observed between serotypes and prior immune status (although without serotype specific information). Analysis of serological and viral marker data collected from enrolled participants revealed that sub-clinical disease from HHCs had similar viral RNA blood levels to index cases. Analysis of the sequenced DENV whole genomes showed long-term viral clade persistence in the study area despite fluctuations in reported case numbers. 90 transmission clusters were identified using genomic, epidemiological and serological data, revealing that within household transmissions were relatively rare. Together, the findings indicate the importance of underreported sub-clinical disease in maintaining disease transmission and that human movement is an important driver of outbreaks.