Abstract
BACKGROUND: Yellow fever virus (YFV) is transmitted by mosquitoes among humans and non-human primates (NHPs) in South America. The 2024-25 yellow fever (YF) outbreak was notable for its spread into new areas, including the department of Tolima in Colombia's Andean region. We investigated the eco-epidemiology of human and NHP YF cases to understand the patterns and drivers of the Tolima outbreak. METHODS: We collected spatiotemporal, sociodemographic, and mortality data on human YF cases in Tolima, as well as the locations of deceased NHPs with YF. We then conducted exploratory, descriptive, and spatial statistical analyses to identify risk factors and hotspots for YF. We then used inferential spatiotemporal modelling to compare ecological and sociodemographic drivers. FINDINGS: From September 2024 to October 2025, 116 human and 53 non-human primate YF cases were detected in Tolima. Among the human cases, 77% were male (89/116), and the median age was 47 (interquartile range 34-63). Of these cases, 45 (39%) died, and older age was associated with increased odds of death (adjusted odds ratio, 1.34 per 10 years; 95% confidence interval, 1.10-1.65). There was significant clustering among human and NHP cases. Higher rainfall and poverty/deprivation were associated with increased YF incidence at the neighborhood level, and rainfall during the outbreak was above average due to La Niña. INTERPRETATION: These findings demonstrate significant mortality from YF, which re-emerged in Tolima after nearly a century. Rural populations with greater ecological risk and poverty/deprivation could benefit from targeted vaccination strategies for YF. FUNDING: National Institutes of Health.