Dengue Virus

Dengue is a RNA virus that is a member of the Flavivirus genus. Infection with dengue virus is usually asymptomatic but can cause a spectrum of disease including nonspecific febrile illness, classic dengue fever, dengue hemorrhage fever and dengue hypovolemic shock.

Dengue is a major health problem in tropical and subtropical countries, where an estimated 50 million cases occur annually. During the past 20 years, dengue has reemerged in Mexico, Central and South America and the Caribbean. Dengue is endemic in some U.S. territories including Puerto Rico, US Virgin Islands and American Samoa. Dengue is not endemic in the continental United States, but local outbreaks have occurred in Texas, Hawaii and Florida. Most cases are associated with travelers returning from dengue endemic areas.

There are four related dengue viruses, designated DENV-1, -2, -3, and -4. Infection with one DENV produces lifelong immunity against that DENV type and short-term immunity (<2 months) against infection the other three DENVs. An individual has a lifetime risk of up to four DENV infections.

Dengue fever (DF) is characterized by an acute high fever plus two or more of the following: headache, retro-orbital pain, joint pain, muscle or bone pain, rash, mild hemorrhagic manifestations (e.g., nose or gum bleed, petechiae, or easy bruising), and leukopenia. Most DF cases are self-limited and can be treated with bed rest, acetaminophen, and oral fluids.

A small proportion of patients develop dengue hemorrhagic fever (DHF), which is characterized by a fever lasting 2 to 7 days, any hemorrhagic manifestation, thrombocytopenia (platelet count <100,000/mm³), and increasedl vascular permeability manifested by hemoconcentration, hypoalbuminemia, or abdominal or pleural effusions. DHF can result in circulatory instability or shock, and the risk for these complications may be increased among persons with prior dengue infection. Adequate management of DHF patients generally requires hospitalization and fluid replacement.

A clinical management tool can be downloaded from:

 http://www.cdc.gov/dengue/resources/Dengue&DHF%20Information%20for%20Health%20Care%20Practitioners_2009.pdf

DENVs are transmitted from person to person through the bite of an infected Aedes aegypti mosquito. Humans are the main amplifying host for DENV. The mosquito remains infectious during its lifespan of approximately one month. Following a mosquito bite, the incubation period in humans ranges from 3 to 14 days, but is typically about one week. Infected persons can transmit DENV to mosquitos as early as 1 to 2 days before symptoms develop and throughout the 7 day viremic period. Infected persons, even those who remain asymptomatic, have high viral loads, approximating 10⁷ viral RNA copies per milliliter of blood.

During the viremic period, DENV can be transmitted by transfusion and organ or tissue transplantation. The true incidence of transfusion transmitted dengue is unknown. Risk may be high in endemic areas because infections are asymptomatic and viral load is high and the viremic period lasts up to 7 days. The only approach to prevent transfusion of DENV positive blood would be screening of blood donors with a sensitive nucleic acid amplification test. Blood and organ donors are currently not screened for dengue virus. 

An anti-DENV IgM immunoassay has been approved by the FDA. Unfortunately, dengue IgM does not become detectable until at least 4 days after symptom onset. DENV RNA can be detected in plasma by a number of nucleic acid amplification methods, including real time PCR. A commercially available PCR test is not available at this time.