The mosquito-borne dengue viruses (serotype 1-4) cause dengue fever, a severe flu-like illness. The disease is prevalent in Third World tropical regions and spreading to sub-tropical developed countries - including the United States. WHO estimates that 50-80 million cases of dengue fever occur worldwide each year, including a potentially deadly form of the disease called dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Primary infection with dengue virus results in a self-limiting disease characterized by mild to high fever lasting 3 to 7 days, severe headache with pain behind the eyes, muscle and joint pain, rash and vomiting. Secondary infection is the more common form of the disease in many parts of Southeast Asia and South America. This form of the disease is more serious and can result in DHF and DSS. The major clinical symptoms can include high fever, hemorrhagic events, and circulatory failure, and the fatality rate can be as high as 40%. Early diagnosis of DSS is particularly important, as patients may die within 12 to 24 h if appropriate treatment is not administered. Primary dengue virus infection is characterized by elevations in specific IgM antibody levels 3 to 5 days after the onset of symptoms; this generally persists for 30 to 60 days. IgG levels also become elevated after 10 to 14 days and remain detectable for life. During secondary infection, IgM levels generally rise more slowly and reach lower levels than in primary infection, while IgG levels rise rapidly from 1 to 2 days after the onset of symptoms.