Dengue Virus Profile

The Dengue virus is a member of the virus family Flaviviridae and is transmitted to people through the bite of the mosquitos Aedes aegypti and Aedes albopictus. Dengue virus is now believed to be the most common arthropod-borne disease in the world. Dengue is mainly found in the tropics because the mosquitoes require a warm climate. A major fear of epidemiologists is that the mosquitoes will develop resistance to cooler climates and then be able to infect people in the United States and other temperate climates. The virus is transmitted when a mosquito of the Aedes genus bites an individual infected with dengue virus. The virus in the blood of the infected individual then infects the mosquito and travels from the mosquito's stomach to its salivary glands were the virus multiplies. The virus is then injected into another person when the mosquito injects anticoagulants that prevent blood clotting when the mosquito is feeding. The mosquito remains able to transmit dengue for its entire life.

Each year, 100 million people become infected with dengue virus. People first reported the existence of dengue-like disease in 1779 but it was most likely present long before in first appeared in literature. However, the majority of deaths that result from dengue infection result from Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS). People who develop DHF have a 5% chance of death but if they go on to develop DSS then the mortality rate can rise as high as 40%.
The General Distribution of Dengue and/or Dengue Haemorragic
Fever, 1975-1998

The incubation period of dengue fever is approximately four days. The person will come down with fever and present a discrete macular or maculopapular rash. It is difficult to distinguish dengue fever from other viral diseases and the person usually recovers in 5 days. In more severe cases, fever and rash are accompanied by headache, retroorbital pain, myalgia, backache, sore throat, and abdominal pain. The patients become lethargic and experience anorexia and nausea.

DHF has a similar incubation period as dengue fever and many of the same symptoms. However, the fever is more severe and the drowsiness and lethagry is more extreme. The patient has increased vascular permeablilty and abnormal hemostasis. This can cause the individual to lose blood volume, result in hypotension, go into shock (DSS) and die.

It is important to understand why an individual will develop DHF/DSS. The Dengue virus has been shown to have 4 subtypes. These 4 subtypes are different strains of dengue virus that have 60-80% homology between each other. The major difference for humans lies in subtle differences in the surface proteins of the different dengue subtypes. After a person is infected with dengue, they develop an immune response to that dengue subtype. The immune response produced specific antibodies to that subtype's surface proteins that prevents the virus from binding to macrophage cells (the target cell that dengue viruses infect) and gaining entry. However, if another subtype of dengue virus infects the individual, the virus will activate the immune system to attack it as if it was the first subtype. The immune system is tricked because the 4 subtypes have very similar surface antigens. The antibodies bind to the surface proteins but do not inactivate the virus. The immune response attracts numerous macrophages, which the virus proceeds to infect because it has not been inactivated. This situation is referred to as Antibody-Dependent Enhancement (ADE) of a viral infection. This makes the viral infection much more acute. The body releases cytokines that cause the endothelial tissue to become permeable which results in hemorrhagic fever and fluid loss from the blood vessels.

The most important aspect in treatment of DHF is to prevent further fluid loss. Drugs such as corticosteroids or carbazochrome sodium sulfonate are given to stabilize capillary permeability and avoid plasma leakage. As regards to prevention, a vaccine has proven rather difficult to produce. The reason for this stems from the 4 subtypes of dengue. If an individual develops immunity to one subtype and then tries to launch an immune response to another subtype then they will develop DHF/DSS. Work has been done on a tetravalent vaccine that will attempt to give the individual immunity to all four of the subtypes at the same time. Currently, the most effective prevention measures lie in mosquito control.

References:

Kautner, Ingrid PhD; Robinson, Max MD; Kuhnle, Ursula MD. "Dengue virus infection: Epidemiology, pathogenesis, clinical presentation, diagnosis, and prevention." The Journal of Pediatrics. Vol 131(4), October 1997, p 516-524.

Rigau-Perez, et al. "Dengue and dengue haemorrhagic fever" The Lancet. Vol 352, Sept. 1998, p 971-977.