Understanding the persistence of Dengue epidemic and associated risk factors in Urban Bamako Mali - Summary Dengue fever disease (DFD) is an growing public health threat in Mali and in the West African Region, particularly in urban Bamako, which has recently experienced significant epidemics with a case fatality rate of 2.8%. Despite the historic presence and recent outbreaks in the region there is limited knowledge on the dynamic of DENV transmission and the severity of the disease because of limited diagnoses capacity and misdiagnoses with other febril illnesses. The overall aim of this study is to assess burden and risk factor associated with DFD its severity by conducting hospital-and community health facility-based fever surveillance to characterize clinical profile of DFD in relation with DENV genomic profile, and population based serological surveys to determine the seroconversion rate of exposure to DENV. We hypothesis is that genetic variations in dengue virus strains, coupled with host immune response are associated with the incidence and severity of DFD. Aim 1 will determine hospital and community health facility-based prevalence of DFD among febrile patients and risk factors for severe dengue in Urban Bamako and rural setting in Mali. Aim 2: will determine the prevalence and annual incidence of seroconversion to DENV infection in the general population around study sites; and Aim 3: Investigate the genomic diversity and evolutionary dynamics of DENV in relation with illness. By integrating hospital and community health facility-based fever surveillance, we will characterize the clinical profile of DFD and identify risk factors for severe disease. Population-based serological surveys will be conducted to determine the seroconversion rates and identify factors associated with asymptomatic DENV infections. Utilizing advanced genomic techniques such as virome capture sequencing (VirCapSeq-VERT), we will investigate genetic variations in DENV strains and their correlation with disease severity and transmission dynamics. We hypothesize that genetic variations in DENV strains, coupled with host immune responses, influence the incidence and severity of DFD. The study will provide valuable information the burden and risk factors associated with DFD that can contribute to refine the clinical guide for dengue classification and treatement based on combination of clinical symptoms and laboratory testing. The outcomes will inform the design of effective public health interventions and vaccine development.