Evolutionary and ecological factors underlying the tempo and distribution of yellow fever virus activity

Yellow fever virus (YFV) is historically one of the most important viruses to affect human populations. Despite the existence of highly effective vaccines for over 70 years, yellow fever remains a significant and re-emerging cause of morbidity and mortality in endemic and high-risk regions of South America and Africa. The virus may be maintained in sylvatic enzootic/epizootic, transitional and urban epidemic transmission cycles with geographic variation in terms of levels of genetic diversity, the nature of transmission cycles and patterns of outbreak activity. In this review we consider evolutionary and ecological factors underlying YFV emergence, maintenance and spread, geographic distribution and patterns of epizootic/epidemic activity.