Dengue

CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY, July 2004, p. 642–650 1071-412X/04/$08.00 0 DOI: 10.1128/CDLI.11.4.642–650.2004 Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Vol. 11, No. 4

Current Advances in Dengue Diagnosis
Pei-Yun Shu and Jyh-Hsiung Huang*
Division of Laboratory Research and Development, Center for Disease Control, Department of Health,Taipei, Taiwan, Republic of China Dengue is an endemic viral disease affecting tropical and subtropical regions around the world, predominantly in urban and semiurban areas. Dengue fever (DF) and its more serious forms, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), are becoming important public health problems and were formally included within the disease portfolio of the UnitedNations Development Programme/World Bank/ World Health Organization Special Programme for Research and Training in Tropical Diseases by the Joint Coordination Board in June 1999 (100). The global prevalence of dengue has grown dramatically in recent decades. The disease is now endemic in more than 100 countries in Africa, the Americas, the eastern Mediterranean, Southeast Asia, and the Western Pacific,threatening more than 2.5 billion people (33). The World Health Organization estimates that there may be 50 million to 100 million cases of dengue virus infections worldwide every year, which result in 250,000 to 500,000 cases of DHF and 24,000 deaths each year (25, 99) Dengue virus is a mosquito-borne flavivirus and the most prevalent arbovirus in tropical and subtropical regions of the world(32). Dengue virus is a positive-stranded encapsulated RNA virus. The genomic RNA is approximately 11 kb in length and is composed of three structural protein genes that encode the nucleocapsid or core protein (C), a membraneassociated protein (M), an envelope protein (E), and seven nonstructural (NS) protein genes. The gene order is 5 -CprM(M)-E-NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5-3 , as for otherflaviviruses (11, 18, 60, 74). The proteins are synthesized as a polyprotein of about 3,000 amino acids that is processed cotranslationally and posttranslationally by viral and host proteases. There are four distinct serotypes, serotypes 1 to 4. Infection induces a life-long protective immunity to the homologous serotype but confers only partial and transient protection against subsequent infections by theother three serotypes. Instead, it has generally been accepted that secondary infection or infection with secondary or multiple infections with various dengue virus serotypes is a major risk factor for DHFDSS due to antibody-dependent enhancement (8, 34, 37, 38). Other factors have been postulated to be important in the pathogenesis of DHF, including viral virulence (29, 76), host geneticbackground (4), T-cell activation (26, 54), the viral burden (93), and autoantibodies (59, 61). As attempts to eradicate Aedes aegypti, the most efficient mosquito vector of dengue virus, are not successful in countries where dengue is endemic, the control of dengue will be possible only after an
* Corresponding author. Mailing address: Division of Laboratory Research and Development, Center for DiseaseControl, Department of Health, 161, Kun-Yang St., Taipei, Taiwan, Republic of China. Phone: 886-2-26531374. Fax: 886-2-27883992. E-mail: jhhuang @cdc.gov.tw. 642

efficient vaccine has been developed. At present, no dengue vaccine has been licensed. The development of an efficient dengue vaccine is difficult because the vaccine must be tetravalent so that it includes all four serotypes. Inaddition, there is no acceptable animal model for DHF. Although several candidate vaccines are in clinical trials, an efficient, safe, low-cost vaccine will not be available in the near future. Dengue virus causes a broad spectrum of illnesses, ranging from inapparent infection, flu-like mild undifferentiated fever, and classical DF to the more severe form, DHF-DSS, from which rates of morbidity and...