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 Table of Contents  
LETTER TO THE EDITOR
Year : 2015  |  Volume : 2  |  Issue : 3  |  Page : 147-148

Nonstructural protein 1: A tool for early dengue diagnosis


Department of Microbiology, Mahatma Gandhi Medical College, Jaipur, Rajasthan, India

Date of Web Publication3-Sep-2015

Correspondence Address:
Ekadashi Rajni Sabharwal
202, Rajkiya Awaas, Malviya Nagar, Jaipur - 302 017, Rajasthan
India
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DOI: 10.4103/2384-5147.164425

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How to cite this article:
Sabharwal ER. Nonstructural protein 1: A tool for early dengue diagnosis. Sub-Saharan Afr J Med 2015;2:147-8

How to cite this URL:
Sabharwal ER. Nonstructural protein 1: A tool for early dengue diagnosis. Sub-Saharan Afr J Med [serial online] 2015 [cited 2020 Apr 9];2:147-8. Available from: http://www.ssajm.org/text.asp?2015/2/3/147/164425

Sir,

Dengue is an endemic viral disease transmitted to humans by the Aedes mosquito and affects tropical and subtropical regions around the world. Dengue fever and its more serious counterparts, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are becoming important public health problems. The global prevalence of dengue has grown dramatically in recent years. It affects up to 100 million people each year, with 500,000 cases of DHF and DSS and around 30,000 deaths, mostly among children. [1] In order to reduce the immense global disease burden, and to reduce the high mortality rate, there is urgent needs to have a rapid and sensitive laboratory assay for the early detection of the disease.

The major diagnostic methods currently available for dengue fever are viral culture, viral ribonucleic acid detection by reverse transcription polymerase chain reaction, and serological tests such as an immunoglobulin M (IgM) and IgG capture enzyme-linked immunosorbent assay. However, these procedures are of limited utility in routine clinical use. The antibody detection tests, despite being extremely useful, are limited by low sensitivity in the early phase of the infection. [1],[2] The requirement of paired sera at acute and convalescent phase, which improves the accuracy of diagnosis, further delays the results. [2],[3]

A simplified method of diagnosis during the acute phase of dengue infection compared with virus isolation, or nucleic acid detection is the detection of viral antigens in the bloodstream. Nonstructural protein 1 (NS1) is a highly conserved glycoprotein, that is, essential for the viability of dengue virus (DENV), and is produced both in membrane-associated and secretory forms by the virus. The NS1 is expressed on the surface of infected cells, and is a target of human antibody responses to DENV infection. NS1 Ag circulates uniformly in all serotypes of DENV and it circulates at high levels during the first few days of illness. [4] The previous studies by Alcon et al., Gubler et al., and Singh et al. have reported that the NS1 Ag were detectable from the 1 st day after the onset of fever up to day 9. [4],[5],[6] Some studies have reported varying sensitivities of 50-70% for diagnosis of acute dengue infection, with specificity above 95%. [7],[8] However, NS1 does not identify the specific virus serotype or quantitative measurement of soluble NS1 protein levels.

In this study, carried out in the Department of Microbiology of a tertiary care hospital in Jaipur, Northern India, we have evaluated the role of NS1 Ag assay in dengue IgM negative sera for early diagnosis of infection. In this prospective study, covering a period of 4 months (August 2012-November 2012), a total of 510 serum samples from clinically suspected cases of dengue, as per World Health Organization criteria were received for detection of anti-dengue IgM and IgG antibodies. Of these, 78 randomly selected serum samples, clinically suspected of DENV infection, which were found to be seronegative for anti-dengue IgM antibodies using a rapid immunochromatographic test by Standard Diagnostics, Inc., Korea, formed the study group. These 78 IgM seronegative samples were subjected to a rapid immunochromatographic test for detection of dengue NS1 Ag (Standard Diagnostics Inc, Korea). All the tests were performed in strict adherence to the manufacturer's instructions provided in the kit literature.

Of the 510 samples received, 152 (29.8%) were positive for anti-dengue antibodies, while 358 (70.2). Of the 152 positive samples, 74 (48.6%) were positive for IgM anti-dengue antibodies, 33 (21.7%) were positive for IgG anti-DEN antibodies and 26 (29.7%) showed the presence of both. Of 358 seronegative samples, 78 samples were randomly selected for detection of dengue NS1 Ag. It was observed that 38 (48.7%) out of 78 samples were positive for the presence of dengue NS1 Ag while 40 (51.3%) were negative.

A thorough analysis of the results has shown a high sensitivity of dengue NS1 Ag in dengue IgM and IgG seronegative samples. This result has highlighted our handicap in recognizing early cases of dengue fever if only antibody-based detection tests are used. It is an established fact that IgM antibody response takes 5-10 days to develop in cases of primary DENV infection, and 4-5 days in cases of secondary DENV infection. [5],[9] Hence, at a particular time postinfection, there is a high likelihood of missing the diagnosis. The requirement of a paired serum in such cases would only delay the results. In such a scenario, availability of a simple, rapid and an inexpensive test, such as the NS1, to clinch the diagnosis would be nothing lesser than a boon. High positivity of dengue NS1 Ag in the seronegative samples seems like a very promising option for making a timely diagnosis. Other current studies have also revealed similar results and provided strong evidence of the value of combining DENV antigen and antibody-based test results for diagnosis of acute dengue infection. [6],[9],[10],[11],[12] Especially in underdeveloped areas, NS1 Ag detection test, if used in conjunction with the IgM and IgG antibody detection assays, can help avert a lot of casualties and can significantly reduce disease burden. The test is very simple to perform, with no need for any sophisticated equipment or highly trained personnel. Combined with the facts that NS1 is seen in circulation from day 1 of fever and also that it is highly specific, makes it an ideal assay for early and timely diagnosis of dengue fever. Newer immunochromatographic tests are also available that permit the simultaneous detection of both DENV NS1 Ag and IgM/IgG antibodies, which has further simplified the diagnostic algorithm. [8],[12],[13]

 
  References Top

1.
Murray NE, Quam MB, Wilder-Smith A. Epidemiology of dengue: Past, present and future prospects. Clin Epidemiol 2013;5:299-309.  Back to cited text no. 1
    
2.
Chakravarti A, Kumaria R, Batra VV, Verma V. Improved detection of dengue virus serotypes from serum samples-evaluation of single tube multiplex RT-PCR with cell culture. Dengue Bull 2006;30:133-40.  Back to cited text no. 2
    
3.
Shu PY, Huang JH. Current advances in dengue diagnosis. Clin Diagn Lab Immunol 2004;11:642-50.  Back to cited text no. 3
    
4.
Alcon S, Talarmin A, Debruyne M, Falconar A, Deubel V, Flamand M. 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. J Clin Microbiol 2002;40:376-81.  Back to cited text no. 4
    
5.
Gubler DJ, Suharyono W, Tan R, Abidin M, Sie A. Viraemia in patients with naturally acquired dengue infection. Bull World Health Organ 1981;59:623-30.  Back to cited text no. 5
    
6.
Singh MP, Majumdar M, Singh G, Goyal K, Preet K, Sarwal A, et al. NS1 antigen as an early diagnostic marker in dengue: Report from India. Diagn Microbiol Infect Dis 2010;68:50-4.  Back to cited text no. 6
    
7.
Guzman MG, Jaenisch T, Gaczkowski R, Ty Hang VT, Sekaran SD, Kroeger A, et al. Multi-country evaluation of the sensitivity and specificity of two commercially-available NS1 ELISA assays for dengue diagnosis. PLoS Negl Trop Dis 2010;4. pii: e811.  Back to cited text no. 7
    
8.
Blacksell SD, Jarman RG, Gibbons RV, Tanganuchitcharnchai A, Mammen MP Jr, Nisalak A, et al. Comparison of seven commercial antigen and antibody enzyme-linked immunosorbent assays for detection of acute dengue infection. Clin Vaccine Immunol 2012;19:804-10.  Back to cited text no. 8
    
9.
Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, et al. Dengue in the early febrile phase: Viremia and antibody responses. J Infect Dis 1997;176:322-30.  Back to cited text no. 9
    
10.
Sheemar S, Mahajan G, Chopra S, Kaur J. Non-structural protein 1 antigen capture kit as an early dengue diagnostic tool. J Med Soc 2012;26:154-5.  Back to cited text no. 10
  Medknow Journal  
11.
World Health Organization. Epidemiology, burden of disease and transmission. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control. 1 st ed. Geneva, Switzerland: WHO; 2009. p. 3.  Back to cited text no. 11
    
12.
Blacksell SD, Jarman RG, Bailey MS, Tanganuchitcharnchai A, Jenjaroen K, Gibbons RV, et al. Evaluation of six commercial point-of-care tests for diagnosis of acute dengue infections: The need for combining NS1 antigen and IgM/IgG antibody detection to achieve acceptable levels of accuracy. Clin Vaccine Immunol 2011;18:2095-101.  Back to cited text no. 12
    
13.
Arya SC, Agarwal N, Parikh SC, Agarwal S. Simultaneous detection of dengue NS1 antigen, IgM plus IgG and platelet enumeration during an outbreak. Sultan Qaboos Univ Med J 2011;11:470-6.  Back to cited text no. 13
    




 

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