Update on Dengue: Epidemiology, Virus Evolution, Antiviral Drugs, and Vaccine Development

Abstract

Dengue virus is the most widespread geographically 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 hemorrhagic 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.

Persistence of Th1/Tc1 responses one year after tetravalent dengue vaccination in adults and adolescents in Singapore

“…Over the past two decades, the number of dengue infections has continued to increase in the endemic areas of South-east Asia, Central and South America and the South Pacific regions. 1,2 Immune responses to natural infection are thought to provide lifelong protection against homoserotypic strains, but limited cross-protection between serotypes. 3 Secondary infections with a different serotype have been associated with a higher risk of developing severe disease due to inappropriate heterologous humoral and cellular immune responses.…”

Metodología para la elaboración de canales endémicos y tendencia de la notificación del dengue, Valle del Cauca, Colombia, 2009-2013

“…Según el reporte del Ministerio de Salud titulado "La situación actual del dengue", en el que se analiza el periodo de 2008 a 2013, en la semana 12 del 2013 se detectaron situaciones de epidemia en 32 municipios del país, 18 de los cuales eran capitales de departamento (13,14). El Valle del Cauca es el departamento con más casos de dengue en el país (19,8 %) (2,15); en Cali, la prevalencia de la enfermedad ha aumentado hasta ubicarlo como el municipio con mayor número de casos en Colombia (15,5 % del total nacional) (16,17), lo que se explica, en parte, porque tiene las condiciones necesarias para que el vector se reproduzca adecuadamente.…”

Antiviral Activity of Thiazolide Derivatives Against Dengue Virus in Huh-7 Cell Line

“…Dengue was seen a 30-fold upsurge worldwide between 1960 and 2010 due to increased population growth rate, global warming, unplanned urbanization, inefficient mosquito control, frequent air travel, and lack of health care facilities (2)(3)(4)(5). Two and a half billion people reside in dengue-endemic regions and 400 million infections roughly occur per year, with a mortality rate surpassing 5% -20% in some areas (6,7). Dengue infection affects more than 100 countries, including European countries and the United States (USA) (7).…”

“…Two and a half billion people reside in dengue-endemic regions and 400 million infections roughly occur per year, with a mortality rate surpassing 5% -20% in some areas (6,7). Dengue infection affects more than 100 countries, including European countries and the United States (USA) (7). In Pakistan, all the serotypes of dengue virus are reported to present especially during the monsoon period, making it a dengue hyper endemic region (8,9).…”