Update on Dengue: Epidemiology, Virus Evolution, Antiviral Drugs, and Vaccine Development Annelies Wilder-Smith & Eng-Eong Ooi & Subhash G. Vasudevan & Duane J. Gubler Published online: 30 March 2010 # Springer Science+Business Media, LLC 2010 Abstract Dengue virus is the most widespread geograph- ically of the arboviruses and a major public health threat in the tropics and subtropics. Scientific advances in recent years have provided new insights about the pathogenesis of more severe disease and novel approaches into the development of antiviral compounds and dengue vaccines. Phylogenetic studies show an association between specific subtypes (within serotypes) and severity of dengue. The lack of association between maternal antibodies and development of severe dengue in infants in a recent study has called for the rethinking or refinement of the current antibody-dependent enhancement theory of dengue hemor- rhagic syndrome in infancy. Such studies should stimulate new directions of research into mechanisms responsible for the development of severe dengue. The life cycle of dengue virus readily shows that virus entry and replication can be targeted by small molecules. Advances in a mouse model (AG 129 mice) have made it easier to test such antiviral compounds. The efforts to find specific dengue inhibitors are intensifying and the tools to evaluate the efficacy of new drugs are now in place for rapid translation into trials in humans. Furthermore, several dengue vaccine candidates are in development, of which the chimeric dengue/yellow fever vaccine has now entered phase 3 trials. Until the availability of a licensed vaccine, disease surveillance and vector population control remain the mainstay of dengue prevention. Keywords Dengue . Expansion of dengue . Dengue serotypes . Dengue genotypes . Dengue vaccines . Dengue antiviral compounds . Dengue antiviral therapy . Epidemiology of dengue Introduction Dengue viruses are the most widespread geographically of the arboviruses and are found in tropical and subtropical areas where 2.5 billion to 3 billion people are at risk of infection [1]. Dengue viruses are transmitted by mosquitoes of the genus Aedes, subgenus Stegomyia (eg, Aedes aegypti and A. albopictus). A. aegypti is well established in much of the tropical and subtropical world [1]. As a peridomiciliary mosquito, A. aegypti is well adapted to urban life and typically breeds in clean, stagnant water (eg, rain water) and thrives on human proximity. Coupled with the epidemic potential of its blood meal–seeking behavior through feeding on multiple human hosts during a single blood meal, A. aegypti is the main epidemic vector of dengue virus [2]. A. albopictus, often regarded as a secondary vector although it has been implicated in several dengue outbreaks such as that in Hawaii in 2001 [3], is continuing its geographic expansion into tropical and temperate climates. However, the scale of epidemic mediated by A. albopictus has been much smaller relative to A. aegypti [1]. Dengue is also the most rapidly spreading mosquito- borne viral disease in the world. In the past 50 years, the incidence of dengue has increased 30-fold with increasing geographic expansion to new countries and, in the present A. Wilder-Smith (*) Department of Medicine, National University of Singapore, 5 Lower Kent Ridge, Singapore 119074, Singapore e-mail: epvws@pacific.net.sg A. Wilder-Smith : E.-E. Ooi : S. G. Vasudevan : D. J. Gubler Emerging Infectious Diseases Program, Duke-NUS, Singapore, Singapore Curr Infect Dis Rep (2010) 12:157–164 DOI 10.1007/s11908-010-0102-7