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Robert Edelman, Dengue and Dengue Vaccines, The Journal of Infectious Diseases, Volume 191, Issue 5, 1 March 2005, Pages 650–653, https://doi.org/10.1086/427784
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Dengue fever (DF) is rapidly evolving into one of the world’s major infectious diseases [1]. DF is an acute flavivirus infection transmitted by several species of Aedes mosquitoes. Dengue virus has 4 antigenically related serotypes: DEN-1, DEN-2, DEN-3, and DEN-4. Infection with any 1 of the 4 serotypes can produce a broad spectrum of effects, including asymptomatic infection, mild febrile illness, classic DF, and the lethal dengue hemorrhagic fever/shock syndrome (DHF/DSS). Dengue virus has become impossible to eradicate and difficult to control, because of massive urbanization, overpopulation, ever-increasing regional and international travel, and failure to sustain Aedes aegypti control programs. Moreover, there is no specific treatment for DHF/DSS. Mortality rates vary from <1% to >30%, depending on diagnostic acumen and availability of intravenous fluids and blood for treatment of the hypovolemic shock caused by massive hemorrhage and capillary plasma leak [2]
An estimated 50–100 million dengue infections and 500,000 DHF/DSS cases occur annually in the tropics, and DF is well known in North American and European travelers and military personnel [3]. In tropical areas where dengue virus is highly endemic, DHF/DSS is typically confined to children younger than age 15 years, with a mean age of 5–10 years. Dengue infection has spread progressively to most tropical countries during the past 40 years, particularly to countries in Southeast Asia, the western Pacific, and Latin America [1]. To illustrate, the number of cases of DF and DHF/DSS in the Philippines has increased 700% between the 1970s and the early 1990s. In Indonesia, dengue infection was recognized in only 2 cities in 1968; by 2001, it was reported in all of the nation’s provinces and in 93% of its 310 districts. DHF is the second-most-frequent cause of pediatric admissions at Jakarta’s largest public hospital, after acute respiratory infections. The spread of dengue virus from cities to rural areas has impeded the diagnosis and management of DHF/DSS; this, in turn, has resulted in higher case fatality rates, which may be as high as 30% in rural areas, compared with 1% in cities. The disease now occurs throughout most months of the year and is no longer confined to the 4–6-month rainy season. Prominent media attention and the fact that DHF/DSS affects poor and rich children alike have contributed to its notoriety. Dengue epidemics cause the population to panic and to overwhelm hospitals and outpatient clinics. There is near-universal agreement among policy makers in Southeast Asian countries that a dengue vaccine is urgently needed [4]. This sense of urgency is shared by the US military and the World Health Organization [5]
