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Published in: BMC Infectious Diseases 1/2018

Open Access 01-12-2018 | Research article

Prolonged persistence of IgM against dengue virus detected by commonly used commercial assays

Authors: Yu-Wen Chien, Zi-Hu Liu, Fan-Chen Tseng, Tzu-Chuan Ho, How-Ran Guo, Nai-Ying Ko, Wen-Chien Ko, Guey Chuen Perng

Published in: BMC Infectious Diseases | Issue 1/2018

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Abstract

Background

Initial symptoms of dengue fever are non-specific, and thus definite diagnosis requires laboratory confirmation. Detection of IgM against dengue virus (DENV) has become widely used for dengue diagnosis. Understanding the persistence of anti-DENV IgM in subjects after acute infection is essential in order to interpret test results correctly. Although the longevity of anti-DENV IgM has been vehemently investigated in symptomatic children, anti-DENV IgM persistence in adults and in asymptomatically infected people have seldom been reported.

Methods

We prospectively investigated 44 adults with detectable anti-DENV IgM in a serosurvey conducted in the 2015 dengue epidemic in Tainan, Taiwan. Among subjects within the cohort, 17 were classified to be symptomatic and 27 were asymptomatic. The enzyme-linked immunosorbent assay (ELISA) from Standard Diagnostic (SD) and Focus Diagnostic were used to detect anti-DENV IgM for specimens collected initially, at 6 and 12 months. Regression analyses were used to estimate the duration of anti-DENV IgM fell below the detectable level. Rapid dengue tests from Standard Diagnostics had been widely adopted to detect anti-DENV IgM in Taiwan during the 2015 dengue outbreak. As such, collected specimens were also evaluated with the SD rapid dengue test in parallel.

Results

Anti-DENV IgM was detectable in 70.5 and 46.2% of the 44 subjects at 6 months and 12 months by the SD ELISA, respectively, while 13.6 and 7.7%, respectively, by the Focus ELISA. There was no significant difference in anti-DENV IgM detection for the follow-up specimens between subjects with symptomatic and asymptomatic infections. The regression analysis estimated that anti-DENV IgM persistence fell to the undetectable level at 338.3 days (95% CI 279.7–446.9) by SD ELISA, while at 175.7 days (95% CI 121.9–221.1) by Focus ELISA. The detectable frequency of anti-DENV IgM by rapid tests was 86.4%, 68.2 and 35.9% at initial, 6 and 12 months, respectively.

Conclusion

Anti-DENV IgM was found to persist much longer than previously thought, suggesting a necessity of re-evaluation of the use of anti-DENV IgM for both the diagnosis of dengue and serological surveillance, especially when large outbreaks have occurred in the preceding year.
Literature
2.
go back to reference Brady OJ, Gething PW, Bhatt S, Messina JP, Brownstein JS, Hoen AG, Moyes CL, Farlow AW, Scott TW, Hay SI. Refining the global spatial limits of dengue virus transmission by evidence-based consensus. PLoS Negl Trop Dis. 2012;6:e1760.CrossRefPubMedPubMedCentral Brady OJ, Gething PW, Bhatt S, Messina JP, Brownstein JS, Hoen AG, Moyes CL, Farlow AW, Scott TW, Hay SI. Refining the global spatial limits of dengue virus transmission by evidence-based consensus. PLoS Negl Trop Dis. 2012;6:e1760.CrossRefPubMedPubMedCentral
3.
go back to reference Stanaway JD, Shepard DS, Undurraga EA, Halasa YA, Coffeng LE, Brady OJ, Hay SI, Bedi N, Bensenor IM, Castaneda-Orjuela CA, et al. The global burden of dengue: an analysis from the global burden of disease study 2013. Lancet Infect Dis. 2016;16:712–23.CrossRefPubMedPubMedCentral Stanaway JD, Shepard DS, Undurraga EA, Halasa YA, Coffeng LE, Brady OJ, Hay SI, Bedi N, Bensenor IM, Castaneda-Orjuela CA, et al. The global burden of dengue: an analysis from the global burden of disease study 2013. Lancet Infect Dis. 2016;16:712–23.CrossRefPubMedPubMedCentral
4.
go back to reference WHO: Dengue: Guidelines for Diagnosis, Treatment, Prevention, and Control. New edition. Geneva: World Health Organization; 2009. WHO: Dengue: Guidelines for Diagnosis, Treatment, Prevention, and Control. New edition. Geneva: World Health Organization; 2009.
5.
go back to reference Peeling RW, Artsob H, Pelegrino JL, Buchy P, Cardosa MJ, Devi S, Enria DA, Farrar J, Gubler DJ, Guzman MG, et al. Evaluation of diagnostic tests: dengue. Nat Rev Microbiol. 2010;8:S30–8.CrossRefPubMed Peeling RW, Artsob H, Pelegrino JL, Buchy P, Cardosa MJ, Devi S, Enria DA, Farrar J, Gubler DJ, Guzman MG, et al. Evaluation of diagnostic tests: dengue. Nat Rev Microbiol. 2010;8:S30–8.CrossRefPubMed
6.
7.
go back to reference Koraka P, Suharti C, Setiati TE, Mairuhu AT, Van Gorp E, Hack CE, Juffrie M, Sutaryo J, Van Der Meer GM, Groen J, et al. Kinetics of dengue virus-specific serum immunoglobulin classes and subclasses correlate with clinical outcome of infection. J Clin Microbiol. 2001;39:4332–8.CrossRefPubMedPubMedCentral Koraka P, Suharti C, Setiati TE, Mairuhu AT, Van Gorp E, Hack CE, Juffrie M, Sutaryo J, Van Der Meer GM, Groen J, et al. Kinetics of dengue virus-specific serum immunoglobulin classes and subclasses correlate with clinical outcome of infection. J Clin Microbiol. 2001;39:4332–8.CrossRefPubMedPubMedCentral
8.
go back to reference Innis BL, Nisalak A, Nimmannitya S, Kusalerdchariya S, Chongswasdi V, Suntayakorn S, Puttisri P, Hoke CH. An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis co-circulate. Am J Trop Med Hyg. 1989;40:418–27.CrossRefPubMed Innis BL, Nisalak A, Nimmannitya S, Kusalerdchariya S, Chongswasdi V, Suntayakorn S, Puttisri P, Hoke CH. An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis co-circulate. Am J Trop Med Hyg. 1989;40:418–27.CrossRefPubMed
9.
go back to reference Kuno G, Gomez I, Gubler DJ. An ELISA procedure for the diagnosis of dengue infections. J Virol Methods. 1991;33:101–13.CrossRefPubMed Kuno G, Gomez I, Gubler DJ. An ELISA procedure for the diagnosis of dengue infections. J Virol Methods. 1991;33:101–13.CrossRefPubMed
10.
go back to reference Nogueira RM, Miagostovich MP, Cavalcanti SM, Marzochi KB, Schatzmayr HG. Levels of IgM antibodies against dengue virus in Rio de Janeiro. Brazil Res Virol. 1992;143:423–7.CrossRefPubMed Nogueira RM, Miagostovich MP, Cavalcanti SM, Marzochi KB, Schatzmayr HG. Levels of IgM antibodies against dengue virus in Rio de Janeiro. Brazil Res Virol. 1992;143:423–7.CrossRefPubMed
11.
go back to reference Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, Rothman AL, Ennis FA, Nisalak A. Dengue in the early febrile phase: viremia and antibody responses. J Infect Dis. 1997;176:322–30.CrossRefPubMed Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, Rothman AL, Ennis FA, Nisalak A. Dengue in the early febrile phase: viremia and antibody responses. J Infect Dis. 1997;176:322–30.CrossRefPubMed
12.
go back to reference Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, Hunsperger E, Kroeger A, Margolis HS, Martinez E, et al. Dengue: a continuing global threat. Nat Rev Microbiol. 2010;8:S7–16.CrossRefPubMedPubMedCentral Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, Hunsperger E, Kroeger A, Margolis HS, Martinez E, et al. Dengue: a continuing global threat. Nat Rev Microbiol. 2010;8:S7–16.CrossRefPubMedPubMedCentral
13.
go back to reference PATHO. Dengue and Dengue Hemorrhagic Fever in The Americas: Guidelines for Prevention and Control. Wahshington, DC: Pan American Health Organization; 1994. (Scientific Publicaiton No. 548). PATHO. Dengue and Dengue Hemorrhagic Fever in The Americas: Guidelines for Prevention and Control. Wahshington, DC: Pan American Health Organization; 1994. (Scientific Publicaiton No. 548).
16.
go back to reference Hunsperger EA, Yoksan S, Buchy P, Nguyen VC, Sekaran SD, Enria DA, Vazquez S, Cartozian E, Pelegrino JL, Artsob H, et al. Evaluation of commercially available diagnostic tests for the detection of dengue virus NS1 antigen and anti-dengue virus IgM antibody. PLoS Negl Trop Dis. 2014;8:e3171.CrossRefPubMedPubMedCentral Hunsperger EA, Yoksan S, Buchy P, Nguyen VC, Sekaran SD, Enria DA, Vazquez S, Cartozian E, Pelegrino JL, Artsob H, et al. Evaluation of commercially available diagnostic tests for the detection of dengue virus NS1 antigen and anti-dengue virus IgM antibody. PLoS Negl Trop Dis. 2014;8:e3171.CrossRefPubMedPubMedCentral
17.
go back to reference Blacksell SD, Jarman RG, Bailey MS, Tanganuchitcharnchai A, Jenjaroen K, Gibbons RV, Paris DH, Premaratna R, de Silva HJ, Lalloo DG, 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.CrossRefPubMedPubMedCentral Blacksell SD, Jarman RG, Bailey MS, Tanganuchitcharnchai A, Jenjaroen K, Gibbons RV, Paris DH, Premaratna R, de Silva HJ, Lalloo DG, 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.CrossRefPubMedPubMedCentral
18.
go back to reference Chen CM, Kuo HW, Liu DP. Dengue fatal cases in Taiwan: a preliminary study for 2015 outbreak (in Chinese). Taiwan Epidemiol. Bull. 2015;31:605–7. Chen CM, Kuo HW, Liu DP. Dengue fatal cases in Taiwan: a preliminary study for 2015 outbreak (in Chinese). Taiwan Epidemiol. Bull. 2015;31:605–7.
19.
go back to reference Tsai HP, Tsai YY, Lin IT, Kuo PH, Chang KC, Chen JC, Ko WC, Wang JR. Validation and application of a commercial quantitative real-time reverse transcriptase-PCR assay in investigation of a large dengue virus outbreak in southern Taiwan. PLoS Negl Trop Dis. 2016;10:e0005036.CrossRefPubMedPubMedCentral Tsai HP, Tsai YY, Lin IT, Kuo PH, Chang KC, Chen JC, Ko WC, Wang JR. Validation and application of a commercial quantitative real-time reverse transcriptase-PCR assay in investigation of a large dengue virus outbreak in southern Taiwan. PLoS Negl Trop Dis. 2016;10:e0005036.CrossRefPubMedPubMedCentral
20.
go back to reference Kao JH, Chen CD, Tiger Li ZR, Chan TC, Tung TH, Chu YH, Cheng HY, Liu JW, Shih FY, Shu PY, et al. The critical role of early dengue surveillance and limitations of clinical reporting - implications for non-endemic countries. PLoS One. 2016;11:e0160230.CrossRefPubMedPubMedCentral Kao JH, Chen CD, Tiger Li ZR, Chan TC, Tung TH, Chu YH, Cheng HY, Liu JW, Shih FY, Shu PY, et al. The critical role of early dengue surveillance and limitations of clinical reporting - implications for non-endemic countries. PLoS One. 2016;11:e0160230.CrossRefPubMedPubMedCentral
21.
go back to reference Liao SY, Yen JJ, Huang CC. Quality of the dengue surveillance system in Taiwan (in Chinese). Taiwan Epidemiol. Bull. 2010;26:324–9. Liao SY, Yen JJ, Huang CC. Quality of the dengue surveillance system in Taiwan (in Chinese). Taiwan Epidemiol. Bull. 2010;26:324–9.
22.
go back to reference Shih HI, Hsu HC, Wu CJ, Lin CH, Chang CM, Tu YF, Hsieh CC, Chi CH, Sung TC. Applications of a rapid and sensitive dengue DUO rapid Immunochromatographic test kit as a diagnostic strategy during a dengue type 2 epidemic in an Urban City. PLoS One. 2016;11:e0158437.CrossRefPubMedPubMedCentral Shih HI, Hsu HC, Wu CJ, Lin CH, Chang CM, Tu YF, Hsieh CC, Chi CH, Sung TC. Applications of a rapid and sensitive dengue DUO rapid Immunochromatographic test kit as a diagnostic strategy during a dengue type 2 epidemic in an Urban City. PLoS One. 2016;11:e0158437.CrossRefPubMedPubMedCentral
23.
go back to reference Hunsperger EA, Yoksan S, Buchy P, Nguyen VC, Sekaran SD, Enria DA, Pelegrino JL, Vazquez S, Artsob H, Drebot M, et al. Evaluation of commercially available anti-dengue virus immunoglobulin M tests. Emerg Infect Dis. 2009;15:436–40.CrossRefPubMedPubMedCentral Hunsperger EA, Yoksan S, Buchy P, Nguyen VC, Sekaran SD, Enria DA, Pelegrino JL, Vazquez S, Artsob H, Drebot M, et al. Evaluation of commercially available anti-dengue virus immunoglobulin M tests. Emerg Infect Dis. 2009;15:436–40.CrossRefPubMedPubMedCentral
24.
go back to reference Domingo C, Alves MJ, de Ory F, Teichmann A, Schmitz H, Muller R, Niedrig M. International external quality control assessment for the serological diagnosis of dengue infections. BMC Infect Dis. 2015;15:167.CrossRefPubMedPubMedCentral Domingo C, Alves MJ, de Ory F, Teichmann A, Schmitz H, Muller R, Niedrig M. International external quality control assessment for the serological diagnosis of dengue infections. BMC Infect Dis. 2015;15:167.CrossRefPubMedPubMedCentral
25.
go back to reference Yip K. Malaria eradication: the Taiwan experience. Parassitologia. 2000;42:117–26.PubMed Yip K. Malaria eradication: the Taiwan experience. Parassitologia. 2000;42:117–26.PubMed
Metadata
Title
Prolonged persistence of IgM against dengue virus detected by commonly used commercial assays
Authors
Yu-Wen Chien
Zi-Hu Liu
Fan-Chen Tseng
Tzu-Chuan Ho
How-Ran Guo
Nai-Ying Ko
Wen-Chien Ko
Guey Chuen Perng
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2018
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-018-3058-0

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