Spillover risk for yellow fever virus is amplified by forest-urban interface in the Amazon

Zoonotic spillover from wildlife to humans is a growing concern under rapid environmental change. Land use change is a major driver, altering habitats and creating new environments and opportunities for species interactions. Such changes can shift community composition, increase contact between humans and wildlife and provide susceptible hosts for pathogens, potentially leading to human transmission. In the Amazon, we examined how land use change affects spillover of yellow fever virus (YFV), a mosquito-transmitted virus with a primarily sylvatic cycle. Using two decades of municipality-level case data from Brazil, Peru and Colombia, along with high-resolution annual land cover data, we modelled the relationship between forest loss, fragmentation and YFV spillover using panel regression models. We found that forest fragmentation metrics previously linked to sylvatic YFV dynamics were not consistent predictors of spillover to humans. Instead, proximity of forests to urban areas-forest-urban interface-was a consistent and significant positive predictor of human YFV infection. While forest fragmentation and edge density may promote epizootic transmission among wildlife hosts, expansion of urban land use at forest frontiers increases spillover risk. In the Amazon, ongoing forest fragmentation and urban encroachment are raising the likelihood of YFV transmission to people.