Article

Brief Communication

Ann Lab Med 2019; 39(6): 566-571

Published online November 1, 2019 https://doi.org/10.3343/alm.2019.39.6.566

Copyright © Korean Society for Laboratory Medicine.

Comparison of Six Commercial Diagnostic Tests for the Detection of Dengue Virus Non-Structural-1 Antigen and IgM/IgG Antibodies

Hyeyoung Lee , M.D.1,2 , Ji Hyeong Ryu , B.S.3 , Hye-Sun Park , M.S.3 , Ki Hyun Park , M.S.3 , Hyunjoo Bae , B.S.3, Sojeong Yun , B.S.3 , Ae-Ran Choi , B.S.1 , Sung-Yeon Cho , M.D.4,5 , Chulmin Park , Ph.D.5 , Dong-Gun Lee , M.D.4,5 , Jihyang Lim , M.D.6 , Jehoon Lee , M.D.6 , Seungok Lee , M.D.7 , Soyoung Shin , M.D.8 , Haeil Park , M.D.9 , and Eun-Jee Oh , M.D.1

1Department of Laboratory Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea Seoul, Korea; 2Department of Laboratory Medicine, Catholic Kwandong University International St. Mary’s Hospital, Incheon, Korea; 3Department of Convergence Medical Science, Graduate School, The Catholic University of Korea, Seoul, Korea; 4Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea; 5Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea; 6Department of Laboratory Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea Seoul, Korea; 7Department of Laboratory Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea Seoul, Korea; 8Department of Laboratory Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea Seoul, Korea; 9Department of Laboratory Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea Seoul, Korea

Correspondence to: Eun-Jee Oh, M.D., Ph.D.
Department of Laboratory Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea
Tel: +82-2-2258-1641 Fax: +82-2-2258-1719 E-mail: ejoh@catholic.ac.kr

Received: January 3, 2019; Revised: March 29, 2019; Accepted: June 9, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

ELISAs and rapid diagnostic tests (RDTs) are widely used for diagnosing dengue virus (DENV) infection. Using 138 single blood samples, we compared the ability to detect non-structural (NS)-1 antigen and anti-DENV IgM/IgG antibodies among (1) DENV Detect NS1 ELISA, DENV Detect IgM capture ELISA and DENV Detect IgG ELISA (InBios International, Inc.); (2) Anti-Dengue virus IgM Human ELISA and Anti-Dengue virus IgG Human ELISA (Abcam); (3) Dengue virus NS1 ELISA, Anti-Dengue virus ELISA (IgM) and Anti-Dengue virus ELISA (IgG) (Euroimmun); (4) Asan Easy Test Dengue NS1 Ag 100 and Asan Easy Test Dengue IgG/IgM (Asan Pharm); (5) SD BIOLINE Dengue Duo (Standard Diagnostics); and (6) Ichroma Dengue NS1 and Ichroma Dengue IgG/IgM (Boditech Med). For NS1 antigen detection, InBios and Euroimmun showed higher sensitivities (100%) than the RDTs (42.9–64.3%). All tests demonstrated variable sensitivities for IgM (38.1–90.5%) and IgG (65.7–100.0%). InBios and Boditech Med demonstrated higher sensitivity (95.6% and 88.2%, respectively) than the other tests for combined NS1 antigen and IgM antibody. Five NS1 antigen tests had good agreement (92.8–98.6%) without showing positivity for chikungunya. However, all IgG tests demonstrated potential false-positivity with variable ranges. Clinical laboratories should note performance variations across tests and potential cross-reactivity.

Keywords: Dengue virus, Diagnosis, Rapid diagnostic tests, ELISA, Performance

Characteristics of six commercial tests for diagnosing DENV infection

ManufacturerTest principleProduct nameAnalyteSample typeSample volume (µL)Time to result (min)
InBiosELISADENV Detect NS1 ELISANS1S50110
DENV Detect IgM capture ELISAIgMS4196
DENV Detect IgG ELISAIgGS4136
AbcamELISAAnti-Dengue virus IgM Human ELISA kitIgMS, P10105
Anti-Dengue virus IgG Human ELISA kitIgGS, P10105
EuroimmunELISADengue virus NS1 ELISANS1S, P50135
Anti-Dengue virus ELISA (IgM)IgMS, P1075
Anti-Dengue virus ELISA (IgG)IgGS, P1075
AsanLateral flowAsan Easy Test Dengue NS1 Ag 100NS1S, P, W90–12015–20
Asan Easy Test Dengue IgG/IgMIgM, IgGS, P, W10015–20
Standard DiagnosticsLateral flowSD BIOLINE Dengue DuoNS1, IgM, IgGS, P, W10015–20
Boditech MedLateral flowichroma Dengue NS1NS1S, P, W7515–20
ichroma Dengue IgG/IgMIgM, IgGS, P, W1015–20

Performance of six commercial tests for detecting NS1 antigen and anti-dengue IgM and IgG antibodies

TestsTPFPFNTNSensitivity % (95% CI)Specificity % (95% CI)PPV % (95% CI)NPV % (95% CI)
NS1ELISAInBios1410123100.0 (76.8–100.0)99.2 (95.6–99.9)93.3 (66.6–98.9)100.0 (97.7–100.0)
Euroimmun1410123100.0 (76.8–100.0)99.2 (95.6–99.9)93.3 (66.6–98.9)100.0 (97.7–100.0)
RDTAsan61812342.9 (17.7–71.1)99.2 (95.6–99.9)85.7 (43.7–97.9)93.9 (90.7–96.0)
SD80612457.1 (28.9–82.3)100.0 (97.1–100.0)100.0 (63.6–100.0)95.4 (91.9–97.4)
Boditech Med90512464.3 (35.1–87.2)100.0 (97.1–100.0)100.0 (67.2–100.0)96.1 (92.5–98.0)
IgMELISAInBios57267390.5 (80.4–96.4)97.3 (90.7–99.7)96.6 (87.9–99.1)92.4 (85.0–96.3)
Abcam511127481.0 (69.1–89.8)98.7 (92.8–99.9)98.1 (87.9–99.7)86.1 (78.7–91.1)
Euroimmun240397538.1 (26.1–51.2)100.0 (95.2–100.0)100.0 (84.1–100.0)65.8 (61.3–70.0)
RDTAsan260377541.3 (29.0–54.4)100.0 (95.2–100.0)100.0 (85.2–100.0)66.9 (62.2–71.4)
SD311327449.2 (36.4–62.1)98.7 (92.8–99.9)96.9 (81.3–99.5)69.8 (64.4–74.7)
Boditech Med54696985.7 (74.6–93.3)92.0 (83.4–97.0)90.0 (80.6–95.1)88.5 (80.7–93.4)
IgGELISAInBios68126797.1 (90.1–99.7)97.7 (87.9–99.9)98.6 (90.7–99.8)97.1 (89.5–99.2)
Abcam707061100.0 (94.9–100.0)89.7 (79.9–95.8)90.9 (83.2–95.3)100.0 (94.1–100.0)
Euroimmun66146794.3 (86.0–98.4)98.5 (92.1–99.9)98.5 (90.4–99.8)94.4 (86.6–97.7)
RDTAsan460246865.7 (53.4–76.6)100.0 (94.7–100.0)100.0 (91.5–100.0)73.9 (67.2–79.7)
SD500206871.4 (59.4–81.6)100.0 (94.7–100.0)100.0 (92.2–100.0)77.3 (70.1–83.1)
Boditech Med66146794.3 (86.0–98.4)98.5 (92.1–99.9)98.5 (90.4–99.8)94.3 (86.6–97.7)
NS1+IgMELISAInBios65236895.6 (87.6–99.1)97.1 (90.1–99.6)97.0 (89.2–99.2)95.8 (88.2–98.6)
Euroimmun320367047.1 (34.8–59.6)100 (94.9–100.0)100.0 (87.8–100.0)66.0 (60.9–70.9)
RDTAsan301386944.1 (32.1–56.7)98.6 (92.3–99.9)96.8 (80.8–99.5)64.5 (59.5–69.2)
SD351336951.5 (39.0–63.8)98.6 (92.3–99.9)97.2 (83.1–99.6)67.6 (62.0–72.8)
Boditech Med60586588.2 (78.1–94.8)92.9 (84.1–97.6)92.3 (83.7–96.6)89.0 (80.9–93.9)
NS1+IgG+ IgMELISAInBios753060100.0 (95.2–100.0)95.2 (86.7–99.0)96.2 (89.2–98.7)100.0 (94.5–100.0)
Abcam71745694.7 (86.9–98.5)88.9 (78.4–95.4)91.0 (83.4–95.3)93.3 (84.3–97.3)
Euroimmun74116298.7 (92.8–99.9)98.4 (91.5–99.9)98.7 (91.4–99.8)93.4 (89.8–99.8)
RDTAsan581176277.3 (66.3–86.2)98.4 (91.5–99.9)98.3 (89.2–99.8)78.5 (70.6–84.7)
SD620136382.7 (72.2–90.4)100.0 (94.3–100.0)100.0 (93.9–100.0)82.9 (74.7–88.8)
Boditech Med74615798.7 (92.8–99.9)90.5 (80.4–96.4)92.5 (85.2–96.4)98.3 (89.0–99.8)

Agreement between the dengue virus NS1 antigen and IgM/IgG antibody detection results of available tests

AbcamEuroimmunAsanSDBoditech Med
NS1
 InBios-98.6*, 0.93 (0.82–1.00)92.8, 0.51 (0.25–0.77)94.9, 0.67 (0.45–0.90)95.7, 0.73 (0.52–0.93)
 Euroimmun--92.8, 0.51 (0.25–0.77)94.9, 0.67 (0.45–0.90)95.7, 0.73 (0.52–0.93)
 Asan---97.8, 0.79 (0.56–1.00)97.1, 0.73 (0.49–0.98)
 SD----97.8, 0.82 (0.60–1.00)
IgM
 InBios86.2, 0.71 (0.60–0.83)70.3, 0.34 (0.21–0.48)74.6, 0.44 (0.31–0.58)73.2, 0.42 (0.27–0.56)84.8, 0.69 (0.57–0.81)
 Abcam-79.7, 0.52 (0.38–0.66)81.2, 0.55 (0.42–0.69)82.6, 0.60 (0.46–0.74)81.2, 0.61 (0.48–0.74)
 Euroimmun--91.3, 0.71 (0.55–0.86)89.9, 0.69 (0.54–0.84)69.6, 0.33 (0.20–0.47)
 Asan---91.3, 0.74 (0.60–0.88)73.9, 0.43 (0.30–0.57)
 SD----72.5, 0.41 (0.27–0.55)
IgG
 InBios92.8, 0.86 (0.77–0.94)97.1, 0.94 (0.89–0.99)83.3, 0.67 (0.55–0.78)84.8, 0.70 (0.58–0.81)95.7, 0.91 (0.85–0.98)
 Abcam-92.8, 0.86 (0.77–0.94)77.5, 0.57 (0.45–0.69)80.4, 0.62 (0.50–0.74)91.3, 0.83 (0.73–0.92)
 Euroimmun--84.8, 0.69 (0.58–0.81)86.2, 0.72 (0.61–0.83)95.7, 0.91 (0.84–0.98)
 Asan---94.2, 0.87 (0.79–0.96)83.3, 0.66 (0.54–0.78)
 SD----86.2, 0.72 (0.61–0.83)

  1. World Health Organization, Dengue guidelines for diagnosis, treatment, prevention and control: new edition. World Health Organization. http://www.who.int/iris/handle/10665/44188 (Updated on Jan 2009).
  2. Suleman M, Faryal R, Alam MM, Sharif S, Shaukat S, Aamir UB, et al. Dengue virus serotypes circulating in Khyber Pakhtunkhwa Province, Pakistan, 2013-2015. Ann Lab Med 2017;37:151-154.
    Pubmed
  3. 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;18:2095-2101.
    Pubmed
  4. Fatima A, Wang J. Review: progress in the diagnosis of dengue virus infections and importance of point of care test: a review. Pak J Pharm Sci 2015;28:271-280.
    Pubmed
  5. Dussart P, Labeau B, Lagathu G, Louis P, Nunes MR, Rodrigues SG, et al. Evaluation of an enzyme immunoassay for detection of dengue virus NS1 antigen in human serum. Clin Vaccine Immunol 2006;13:1185-1189.
    Pubmed
  6. Andries AC, Duong V, Ong S, Ros S, Sakuntabhai A, Horwood P, et al. Evaluation of the performances of six commercial kits designed for dengue NS1 and anti-dengue IgM, IgG and IgA detection in urine and saliva clinical specimens. BMC Infect Dis 2016;16:201.
    Pubmed
  7. Murugananthan K, Coonghe PAD, Ketheesan N, Noordeen F. Comparison of a rapid immuno-chromatography assay with a standard ELISA for the detection of IgM and IgG antibodies against dengue viruses. Virusdisease 2018;29:199-202.
    Pubmed
  8. Blacksell SD, Jarman RG, Gibbons RV, Tanganuchitcharnchai A, Mammen MP, 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;19:804-810.
    Pubmed
  9. Pang J, Chia PY, Lye DC, Leo YS. Progress and challenges towards point-of-care diagnostic development for dengue. J Clin Microbiol 2017;55:3339-3349.
    Pubmed
  10. Vickers IE, Harvey KM, Brown MG, Nelson K, DuCasse MB, Lindo JF. The performance of the SD BIOLINE Dengue DUO&reg rapid immunochromatographic test kit for the detection of NS1 antigen, IgM and IgG antibodies during a dengue type 1 epidemic in Jamaica. J Biomed Sci 2015;22:55.
    Pubmed
  11. Vickers I, Harvey K, Nelson K, Brown M, Bullock-DuCasse M, Lindo J. Evaluation of OneStep Dengue NS1 RapiDip™ InstaTest and OneStep Dengue Fever IgG/IgM RapiCard™ InstaTest during the course of a dengue type 1 epidemic. Diagn Microbiol Infect Dis 2017;89:271-275.
    Pubmed
  12. Hunsperger EA, Yoksan S, Buchy P, Nguyen VC, Sekaran SD, Enria DA, 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.
    Pubmed
  13. Anand AM, Sistla S, Dhodapkar R, Hamide A, Biswal N, Srinivasan B. Evaluation of NS1 antigen detection for early diagnosis of dengue in a tertiary hospital in Southern India. J Clin Diagn Res 2016;10:DC01-DC04.
  14. Allwinn R, Doerr HW, Emmerich P, Schmitz H, Preiser W. Cross-reactivity in flavivirus serology: new implications of an old finding?. Med Microbiol Immunol 2002;190:199-202.
    Pubmed
  15. Hunsperger EA, Yoksan S, Buchy P, Nguyen VC, Sekaran SD, Enria DA, et al. Evaluation of commercially available anti-dengue virus immunoglobulin M tests. Emerg Infect Dis 2009;15:436-440.
    Pubmed
  16. Hage DS. Development of immunochromatographic assays for the selective detection of zika virus or dengue virus serotypes in serum. Clin Chem 2018;64:991-993.
    Pubmed
  17. Park JH, Lee DW. Dengue fever in South Korea, 2006-2010. Emerg Infect Dis 2012;18:1525-1527.
    Pubmed