Genomic epidemiology sheds light on the recent spatio-temporal dynamics of Yellow Fever virus and the spatial corridor that fueled its ongoing emergence in southern Brazil.

Despite the considerable morbidity and mortality of Yellow fever virus (YFV) infections in Brazil, as well as its widespread presence in non-human primate host, our understanding of disease outbreaks is hampered by limited viral genomic data. Determining the timing and spatial corridors of YFV spread, as well as the geographic hotspots that link the endemic north of the country with epidemic extra-Amazonian regions, are central to predicting and preventing future outbreak events and epidemics. Here, we tracked the recent spread of the virus by integrating genome sequences of new YFV infections sampled from infected non-human primates and humans with both epidemiological and vector data. Through a combination of phylogenetic and epidemiological models we reconstructed the recent transmission history of YFV within different epidemic seasons in Brazil. A suitability index based on the highly domesticated Aedes aegypti was able to capture the seasonality of reported human infections. Spatial modelling revealed spatial hotspots with both past reporting and low vaccination coverage, which coincided with many of the largest urban centres in the Southeast. Phylodynamic analysis unravelled the circulation of three distinct YFV lineages, and provided proof of the directionality of a known spatial corridor of viral spread that connects the endemic North with the extra-Amazonian basin. This study illustrates that genomics linked with field sampling of animals and humans within a One Health framework can provide new insights into the landscape of YFV transmission, augmenting traditional approaches to infectious disease surveillance and control.