Drought dynamics explain once in a century yellow fever virus outbreak in Brazil with implications for climate change.

While excess rainfall is associated with mosquito-borne disease because it supports mosquito breeding, drought may also counterintuitively increase disease transmission by altering mosquito and host behavior. This phenomenon is important to understand because climate change is projected to increase both extreme rainfall and drought. In this study, we investigated the extent to which seasonally-driven mosquito and primate behavior drove the first yellow fever virus (YFV) epidemic in an urban area in Brazil in nearly a century, coinciding with an equally rare drought, and to assess the role of interventions in ending the outbreak. We hypothesized that drought triggered the outbreak by driving the forest mosquitoes and non-human primates towards the city in search of water and that the mosquitoes were biting more frequently to avoid desiccation. A dynamical YFV model supports these hypotheses, showing that both behavioral changes were needed to explain the outbreak timing and incidence. Further, a combination of vector control, conservation measures, and vaccination contributed to ending the outbreak, with the strongest effects from vaccination. Together, these results suggest that drought, likely to become more frequent in this region in the coming decades, can significantly influence mosquito-borne disease transmission, and that sustained control will require multiple interventions.