Abstract

Abstract : The overall objective of this proposal is to examine the evolutionary consequences of introducing a tetravalent live-attenuated dengue virus vaccine into children in Northern Thailand on naturally occurring endemic wild-type dengue virus. Dengue is considered an emerged global public health problem. It is the most common arbovirus causing human disease in subtropical and tropical regions of the world and estimated that over 50 million DV infections occur each year and over 20,000 deaths. In this grant, an interdisciplinary team of university and military investigators are conducting coordinated studies to determine the effect vaccination with a candidate tetravalent vaccine will have on vaccine related genetic changes on wild-type dengue virus and how these changes will determine risk for severe dengue and serotype-specific dengue virus transmission. Coordinated studies are being performed during the vaccine trial in Kamphaeng Phet Province, Northern Thailand, to isolate wild-type dengue virus and examine genetic diversity in the population, in hospitalized children with severe dengue illness and cluster investigation of their neighborhoods, and by using sophisticated Global Positioning Systems (GPS) technology of isolated viruses and genetic characterization, spatial and temporal analysis are being performed in detail. This study offers a unique opportunity to study the evolutionary consequences of this vaccine on wild-type dengue virus with findings that will have long-term impact on the design of future dengue vaccines and conduct of dengue vaccine efficacy trials.

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