Kinetics of non-structural protein 1, IgM and IgG antibodies in dengue type 1 primary infection

BackgroundEarly and accurate diagnosis of dengue infection is essential for control of disease outbreaks. Recently, the dengue virus non-structural antigen 1 (NS1), a conserved and secreted glycoprotein, has been used as a marker for early diagnosis of dengue with convenience and cost-effectiveness. Serological tests of dengue IgM and IgG antibodies are still the most widely used for diagnosis of dengue. In order to assess combined diagnostic value of these tests, we study the kinetic profiles of circulating NS1, dengue IgM and IgG antibodies over the course of the disease by using an in-house dengue type 1 (DENV1) specific NS1 capture ELISA and the commercial Panbio Dengue IgM and IgG capture ELISAs.ResultsA panel of 313 acute-and early convalescent-phase serum specimens from 140 DENV1 primary infected patients during an outbreak of dengue in Guangzhou, China, in 2006 were studied. Dengue NS1 presented high levels in acute-phase serum samples. It was detectable as early as day 1 of illness, and up to 14 day after onset. The sensitivity of NS1 detection was ranged from 81.8% to 91.1% with samples taken during the first 7 days. Anti-dengue IgM antibody was detectable on the third day of onset with the positive rate of 42.9%, and rapidly increasing to 100% by day 8 of illness. Anti-dengue IgG antibody was detectable on the fifth day of onset with low level at the first week of onset, and slowly increasing to 100% by day 15 of illness. Combining the results of NS1 and IgM antibody detection allowed positive diagnosis in 96.9% -100% for samples taken after day 3 of onset.ConclusionsDengue NS1 detection might shorten the window period by first few days of illness. A combination of dengue NS1 antigen and IgM antibody testing facilitates enhanced diagnosis rates. The procedures should be suitable for developing countries where dengue is endemic.

[1]  Gagandeep Singh,et al.  NS1 antigen as an early diagnostic marker in dengue: report from India. , 2010, Diagnostic microbiology and infectious disease.

[2]  V. Deubel,et al.  Enzyme-Linked Immunosorbent Assay Specific to Dengue Virus Type 1 Nonstructural Protein NS1 Reveals Circulation of the Antigen in the Blood during the Acute Phase of Disease in Patients Experiencing Primary or Secondary Infections , 2002, Journal of Clinical Microbiology.

[3]  J. L. Lima-Filho,et al.  Trends in dengue diagnosis , 2005, Reviews in medical virology.

[4]  M. Guzmán,et al.  Evaluation of immunoglobulin M and G capture enzyme-linked immunosorbent assay Panbio kits for diagnostic dengue infections. , 2007, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[5]  S. Sekaran,et al.  Evaluation of a Commercial SD Dengue Virus NS1 Antigen Capture Enzyme-Linked Immunosorbent Assay Kit for Early Diagnosis of Dengue Virus Infection , 2010, Journal of Clinical Microbiology.

[6]  Yanqing Ding,et al.  Development of an Antigen Capture Immunoassay Based on Monoclonal Antibodies Specific for Dengue Virus Serotype 2 Nonstructural Protein 1 for Early and Rapid Identification of Dengue Virus Serotype 2 Infections , 2008, Clinical and Vaccine Immunology.

[7]  K. Chua,et al.  Evaluating the sensitivity of a commercial dengue NS1 antigen-capture ELISA for early diagnosis of acute dengue virus infection. , 2007, Singapore medical journal.

[8]  K. Yuen,et al.  Serotype 1-Specific Monoclonal Antibody-Based Antigen Capture Immunoassay for Detection of Circulating Nonstructural Protein NS1: Implications for Early Diagnosis and Serotyping of Dengue Virus Infections , 2006, Journal of Clinical Microbiology.

[9]  E. Hunsperger,et al.  Comparison of Two Commercially Available Dengue Virus (DENV) NS1 Capture Enzyme-Linked Immunosorbent Assays Using a Single Clinical Sample for Diagnosis of Acute DENV Infection , 2008, Clinical and Vaccine Immunology.

[10]  Cameron P. Simmons,et al.  Diagnostic Accuracy of NS1 ELISA and Lateral Flow Rapid Tests for Dengue Sensitivity, Specificity and Relationship to Viraemia and Antibody Responses , 2009, PLoS neglected tropical diseases.

[11]  O. Vapalahti,et al.  Early diagnosis of dengue in travelers: comparison of a novel real-time RT-PCR, NS1 antigen detection and serology. , 2010, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[12]  Jinhua Liu,et al.  Real-time PCR for detecting circulating dengue virus in the Guangdong Province of China in 2006. , 2008, Journal of medical microbiology.

[13]  I. Kurane,et al.  Molecular characterization of the E gene of dengue virus type 1 isolated in Guangdong province, China, in 2006 , 2008, Epidemiology and Infection.

[14]  Chwan-Chuen King,et al.  Laboratory diagnosis of dengue virus infection: current and future perspectives in clinical diagnosis and public health. , 2005, Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi.

[15]  C. Hsieh,et al.  The commercial dengue NS1 antigen-capture ELISA may be superior to IgM detection, virus isolation and RT-PCR for rapid laboratory diagnosis of acute dengue infection based on a single serum sample. , 2009, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[16]  M. Guzmán,et al.  Dengue: an update. , 2002, The Lancet. Infectious diseases.

[17]  C. Pannuti,et al.  Sensitivity and specificity of three ELISA-based assays for discriminating primary from secondary acute dengue virus infection. , 2007, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[18]  S. Schilling,et al.  Laboratory diagnosis of primary and secondary dengue infection. , 2004, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[19]  P. Shu,et al.  Current Advances in Dengue Diagnosis , 2004, Clinical Diagnostic Laboratory Immunology.