The history and evolution of human dengue emergence

Dengue viruses (DENV) are the most important human arboviral pathogens. Transmission in tropical and subtropical regions of the world includes a sylvatic, enzootic cycle between nonhuman primates and arboreal mosquitoes of the genus Aedes, and an urban, endemic/epidemic cycle principally between Aedes aegypti, a mosquito that exploits peridomestic water containers as its larval habitats, and human reservoir hosts that are preferred for blood feeding. Genetic studies suggest that all four serotypes of endemic/epidemic DENV evolved independently from ancestral, sylvatic viruses and subsequently became both ecologically and evolutionarily distinct. The independent evolution of these four serotypes was accompanied by the expansion of the sylvatic progenitors' host range in Asia to new vectors and hosts, which probably occurred gradually over a period of several hundred years. Although many emerging viral pathogens adapt to human replication and transmission, the available evidence indicates that adaptation to humans is probably not a necessary component of sylvatic DENV emergence. These findings imply that the sylvatic DENV cycles in Asia and West Africa will remain a potential source of re-emergence. Sustained urban vector control programs and/or human vaccination will be required to control DEN because the enzootic vectors and primate reservoir hosts are not amenable to interventions.