Laboratory diagnosis of dengue virus infection: current and future perspectives in clinical diagnosis and public health

Chuan-Liang Kao^1,2, Chwan-Chuen King², Day-Yu Chao², Hui-Lin Wu³, Gwong-Jen J. Chang^4
1Department and Graduate Institute of Medical Technology, College of Medicine, National Taiwan University, Taipei; ²Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei; ³Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; and ⁴Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC), Fort Collins, Colorado, 80522, USA

Received: October 8, 2004 Revised: November 9, 2004 Accepted: December 6, 2004

Corresponding author: Chuan-Liang Kao, Associate Professor, Department and Graduate Institute of Medical Technology, College of Medicine, National Taiwan University, 1, Chang-Te Street, , Taiwan. E-mail:

Since no protective vaccine or specific treatments are available for dengue fever/dengue hemorrhagic fever (DHF), accurate diagnosis is critical for the early initiation of specific preventive health measures to curtail epidemic spread and reduce economic losses. Commonly used diagnosis methods for confirming dengue infection involve virus isolation, detection of virus antigen or RNA in plasma or serum or tissues, and the presence of dengue virus-specific antibodies in serum and other body fluids. Recently, several techniques have been developed for rapid laboratory diagnosis of dengue virus, including centrifugation amplification to enhance virus isolation rate, the flow cytometry method for early detection of cultured virus, detecting viral nucleic acid e.g., by nested reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative RT-PCR, nucleic acid sequence-based amplification, and real-time PCR, detecting free viral non-structure antigens, anti-dengue virus immunoglobulin M (IgM) or IgG antibodies by enzyme-linked immunosorbent assay, and differentiation of primary versus secondary dengue virus infection. Newly established methods must be standardized to maintain high quality laboratory performance. Laboratory diagnostics must be tailored to a specific laboratory environment, the objectives of clinical needs and the availability of clinical specimens. Speed and accuracy of diagnosis must be balanced against test cost and availability. Future challenges in the study of dengue and DHF include the application of modern techniques, such as nucleic acid chips, protein chips and new biomarkers to avoid cross-reactivity among different serotypes of dengue viruses and other flaviviruses, plus development of internationally standardized guidelines to improve quality assurance of these advanced laboratory tests.

Key words: Dengue virus, diagnosis, epidemiology, laboratory techniques and procedures, serologic tests, viral hemorrhagic fevers

J Microbiol Immunol Infect 2005;38:5-16.