Yellow fever and dengue—the interactions of virus, vector and host in the re-emergence of epidemic disease

Abstract

The incidence of the mosquito-borne flavivirus diseases, yellow fever, dengue and dengue hemorrhagic fever has increased dramatically in recent years. Both diseases are characterized by the emergence of explosive epidemics. Yellow fever outbreaks appear to have a periodicity dependent upon fluctuations in sylvatic (enzootic) transmission cycles and the ecological factors that influence these cycles. Spread of the virus from the sylvatic cycle to human settlements, ultimately with interhuman transmission by domestic Aedes aegypti is a repeating event in Africa, and presents a renewed threat in the Americas, where effective Ae. aegypti control collapsed in the 1970s. The incidence of dengue has also increased dramatically in recent years, with up to 80 million persons living in tropical regions of the world now affected annually—an attack rate of 4%. The severe form, dengue hemorrhagic fever (DHF) has become a leading health problem throughout Asia in the last 20 years and is emerging as an epidemic disease in the Americas. Unlike yellow fever, sylvatic dengue transmission cycles are not responsible for disease emergence. The major factors underlying dengue epidemics are changes in human ecology, increasing contact with Ae. aegypti, the co-circulation of multiple dengue serotypes, and a rising prevalence of immunity and immunopathological events that underlie the pathogenesis of DHF. In this review, the complex interplay of virus, host, vector, environment and weather in the ecology of yellow fever and dengue are explored.