Vaccines against dengue: a review of current candidate vaccines at advanced development stages.

Dengue is a viral disease transmitted by the Aedes aegypti mosquito vector, and is caused by four antigenically related flaviviruses (dengue virus serotypes one through four (DENV-1-4)). Dengue is endemic throughout large parts of the Americas and Asia, and is increasingly reported in Africa. More than 2.5 billion people are at high risk of infection in more than 100 endemic countries throughout the tropical and subtropical climate zones (1). Unplanned urbanization, population migration , and the breakdown of vector control efforts have contributed to the spread of the vector. There is an increase of dengue in its more severe forms, such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), for reasons that are not fully understood. The severe forms, when not properly treated, have become an increasing cause of morbidity and mortality, and are straining the health care systems of many en-demic countries (2). Current treatment of severe disease essentially involves the restoration of fluid, colloid, and electrolyte balances. The disease is mainly observed in children and is a leading cause of pediatric hospitalization. However, in recent years, severe dengue has been increasingly reported in adults as well. Dengue is the most common arthropod-borne disease in humans, and its control represents a high public health priority for many endemic countries. From a public health perspective, emphasis should be put on the prevention of the disease, which today is essentially confined to vector control measures. Vector control can be successful if implemented in a sustainable and systematic manner. Efforts to develop vaccines began in the 1920s, with inactivated extracts from infected Aedes mosquitoes. During World War II, more systematic studies, using passaged viruses, were undertaken by United States military scientists, including Al-bert Sabin. The systematic development of a dengue vaccine has been hampered and delayed by the complex pathology of the disease, the need to control four viruses simultaneously, and insufficient investment by vaccine developers, due to low commercial interest. However, over the past few years, the continuing spread and increasing intensity of the disease, combined with new funding mechanisms for the development and use of vaccines for the developing world, have triggered renewed interest and investment in dengue vaccine research.