Evaluation of diagnostic tests: dengue

Abstract

Dengue is an arthropod-borne flavivirus that comprises four distinct serotypes (DEN-1, DEN-2, DEN-3 and DEN-4) that constitute an antigenic complex of the genus flavivirus, family Flaviviridae. Infection by one serotype induces life-long immunity against reinfection by the same serotype, but only transient and partial protection against infection with the other serotypes1,2. Dengue virus infections can result in a range of clinical manifestations from asymp tomatic infection to dengue fever (DF) and the severe disease dengue haemorrhagic fever/dengue shock syndrome (DHF/ DSS). Most dengue infections are asymptomatic or cause mild symptoms, which are characterized by undifferentiated fever with or without rash. Typical DF is characterized by high fever, severe headache, myalgia, arthralgia, retro-orbital pain and maculopapular rash. Some patients show petechiae, bruising or thrombocytopenia. The clinical presentation of acute dengue infection is non-specific but 5–10% of patients progress to severe DHF/DSS, which can result in death if it is not managed appropriately. Plasma extravasation is the main pathophysiological finding of DHF/ DSS, which differentiates it from DF. DHF/ DSS is characterized by high fever, bleeding, thrombocytopenia and haemoconcentration (an increase in the concentration of blood cells as a result of fluid loss). Approximately 3–4 days after the onset of fever, patients can present with petechiae, rash, epistaxis, and gingival and gastrointestinal bleeding. Pleural effusion and ascites are common. Some patients develop circulatory failure (DSS), presenting with a weak and fast pulse, narrowing of pulse pressure or hypotension, cold and moist skin and altered mental state. Although there are no specific antiviral treatments for dengue infection, patients usually recover when the need for fluid management is identified early and electrolytes are administered3. It has been proposed that the classification of dengue disease should be simplified as severe and non-severe dengue. This simplified classification would make patient management and surveillance easier4. There is a need for specific, inexpensive dengue diagnostic tests that can be used for clinical management, surveillance and outbreak investigations and would permit early intervention to treat patients and prevent or control epidemics. Progress is being made in primary prevention, with several candidate dengue vaccines in late phases of development as well as improved vector control measures. Additionally, new techniques for the early detection of severe disease such as the use of biomarkers have the potential to decrease morbidity and