Ecologic Factors Contributing to West Nile Virus Hyperendemicity in Central South Carolina: An Integrated Vector–Human–Environmental Study

West Nile virus (WNV) is an endemic arboviral infection in the United States that has undergone phylogenetic evolution since its introduction 25 years ago. An integrated vector-human-pathogen study was conducted in the summer of 2023 to unearth contemporary Culex quinquefasciatus habitat patterns and human transmission spillover foci in South Carolina, a state with historically little WNV data. A serosurvey revealed WNV seroprevalence 10 times the national average (22% versus 2%, respectively), with unusual epidemiologic risk factors. Female Culex quinquefasciatus WNV positivity was low (2.7%), with viral phylogenetics 100% homologous to the WN02 clade. Mosquito vectors clustered in affluent urban neighborhoods with greater tree canopy cover and abundant waterbodies. Culex quinquefasciatus abundance was greatest when climate variance was nominal in the 72 hours preceding collection. An unusual bimodal mosquito temporal pattern was observed, reflecting changing climate patterns. The present comprehensive WNV study reveals emerging transmission factors as WNV continues to evolve and persist in the southeastern United States.