History of Dengue

The first reported epidemics of dengue fever occurred in 1779-1780 in Asia, Africa, and North America; the near simultaneous occurrence of outbreaks on three continents indicates that these viruses and their mosquito vector have had a worldwide distribution in the tropics for more than 200 years. During most of this time, dengue fever was considered a benign, nonfatal disease of visitors to the tropics. Generally, there were long intervals (10-40 years) between major epidemics, mainly because the viruses and their mosquito vector could only be transported between population centers by sailing vessels.

A global pandemic of dengue began in Southeast Asia after World War II and has intensified during the last 15 years. Epidemics caused by multiple serotypes (hyperendemicity) are more frequent, the geographic distribution of dengue viruses and their mosquito vectors has expanded, and DHF has emerged in the Pacific region and the Americas. In Southeast Asia, epidemic DHF first appeared in the 1950s, but by 1975 it had become a leading cause of hospitalization and death among children in many countries in that region.

The World War II Phenomenon

World War II had a major effect not only on the spread of the disease but also on scientific understanding. The war caused massive demographic changes and ecologic disturbances in the Asia region. While these changes were disruptive for the human population, they provided ideal conditions for mosquito breeding and virus transmission. Key factors include the disruption to water supplies, an increase in the number of suitable breeding sites for mosquitoes (for example abandoned weaponry and equipment) and the increased mobility of people throughout the region. Following the war the region saw massive urbanization projects as people moved towards cities seeking work, food and shelter. With little time to plan for this massive influx of people, cities grew haphazardly with inadequate water supply and waste disposal systems, creating ideal breeding grounds for mosquitoes and the transmission of viruses.

Dengue was a cause of severe morbidity for troops deployed in the Asia region. This motivated scientific research by both the American and Japanese military. Both of these countries established commissions that were successful in isolating the virus, with the first strain (from Hawaii) labeled as Dengue 1. An antigenically distinct strain (from New Guinea) was also isolated and labeled as Dengue 2. Over a decade later, during an epidemic in the Philippines in 1956, the Dengue 3 and Dengue 4 serotypes were isolated, completing the serotype family. Thousands of dengue viruses have been isolated since then with all isolates fitting into one of the four serotypes.

Pathophysiology

Dengue viral infections frequently are not apparent. Classic dengue primarily occurs in nonimmune, nonindigenous adults and children. Symptoms begin after a 5- to 10-day incubation period. DHF/DSS usually occurs during a second dengue infection in persons with preexisting actively or passively (maternally) acquired immunity to a heterologous dengue virus serotype. Illness begins abruptly with a minor stage of 2-4 days’ duration followed by rapid deterioration. Increased vascular permeability, bleeding, and possible DIC may be mediated by circulating dengue antigen-antibody complexes, activation of complement, and release of vasoactive amines. In the process of immune elimination of infected cells, proteases and lymphokines may be released and activate complement coagulation cascades and vascular permeability.

Centers for Disease Control and Prevention

Dengue (DF) and dengue hemorrhagic fever (DHF) are caused by one of four closely related, but antigenically distinct, virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4), of the genus Flavivirus. Infection with one of these serotypes provides immunity to only that serotype for life, so persons living in a dengue-endemic area can have more than one dengue infection during their lifetime. DF and DHF are primarily diseases of tropical and sub tropical areas, and the four different dengue serotypes are maintained in a cycle that involves humans and the Aedes mosquito. However, Aedes aegypti, a domestic, day-biting mosquito that prefers to feed on humans, is the most common Aedes species. Infections produce a spectrum of clinical illness ranging from a nonspecific viral syndrome to severe and fatal hemorrhagic disease. Important risk factors for DHF include the strain of the infecting virus, as well as the age, and especially the prior dengue infection history of the patient.