Skip to main content
SpringerLink
Log in

Evaluation of a Tuberculosis Whole-Blood Interferon-γ Chemiluminescent Immunoassay among Chinese Military Recruits

  • Original Research Article
  • Published:
Molecular Diagnosis & Therapy Aims and scope Submit manuscript

Abstract

Background and Objective: China is a country with a high prevalence of latent tuberculosis (TB) infection (LTBI) and has a policy of routine bacillus Calmette-Guérin (BCG) vaccination. The purified protein derivative (PPD) skin test cannot distinguish TB infection from BCG vaccination, and the diagnosis of LTBI lacks an accepted standard method. The primary objective of this study was to assess the potential of a highly sensitive whole-blood interferon (IFN)-γ release assay that uses recombinant culture filtrate protein (CFP)-10/early secretory antigenic target (ESAT)-6 fusion protein (rCFP-10/ESAT-6) as a stimulus for diagnosis of LTBI.

Methods: Between December 2009 and March 2010, a total of 892 new recruits to the army in Beijing, China, were interviewed and routinely examined by chest radiographs. IFNγ released from whole blood in response to stimulation with rCFP-10/ESAT-6 was detected with an enzyme-linked chemiluminescent immunoassay. The recruits were also intradermally injected with PPD to assess 72-hour skin induration (the PPD skin test).

Results: Of the 892 participants, 450 (50.4%) had a positive PPD skin test and 244 (27.4%) had a positive whole-blood IFNγ release assay. Of 442 PPD-negative subjects, 88 (19.9%) had a positive whole-blood IFNγ test. Of 450 PPD-positive subjects, 156 (34.7%) had a positive whole-blood IFNγ test. Of 132 strongly PPD- positive subjects, 62 (47.0%) had a positive whole-blood IFNγ test. The agreement between the two tests was 57.2%. Of the 892 participants, 579 (64.9%) had clear vaccination scars on their arms, and of these, 382 (66.0%) had positive PPD skin responses and 162 (28.0%) were positive for the whole-blood IFNγ test.

Conclusion: The new whole-blood IFNγ release assay might be a better indicator of LTBI than the PPD test in China.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Fig. 1
Table II

Similar content being viewed by others

References

  1. National Technical Steering Group of the Epidemiological Sampling Survey for Tuberculosis. Report on Fourth National Epidemiological Sampling Survey of Tuberculosis [in Chinese]. Chin J Tuberc Respir Dis 2002; 25: 3–7

    Google Scholar 

  2. Kang YA, Lee HW, Yoon HI, et al. Discrepancy between the tuberculin skin test and the whole-blood interferon gamma assay for the diagnosis of latent tuberculosis infection in an intermediate tuberculosis-burden country. JAMA 2005; 293: 2756–61

    Article  PubMed  CAS  Google Scholar 

  3. Lee JY, Choi HJ, Park IN, et al. Comparison of two commercial interferon-γ assays for diagnosing Mycobacterium tuberculosis infection. Eur Respir J 2006; 28: 24–30

    Article  PubMed  CAS  Google Scholar 

  4. Ferrara G, Losi M, D'Amico R, et al. Use in routine clinical practice of two commercial blood tests for diagnosis of infection with Mycobacterium tuberculosis: a prospective study. Lancet 2006; 367: 1328–34

    Article  PubMed  CAS  Google Scholar 

  5. Mazurek GH, Weis SE, Moonan PK, et al. Prospective comparison of the tuberculin skin test and 2 whole-blood interferon-γ release assays in persons with suspected tuberculosis. Clin Infect Dis 2007; 45: 837–45

    Article  PubMed  CAS  Google Scholar 

  6. Behr MA, Wilson MA, Gill WP, et al. Comparative genomics of BCG vaccines by whole genome DNA microarray. Science 1999; 284: 1520–3

    Article  PubMed  CAS  Google Scholar 

  7. Behr MA. Comparative genomics of BCG vaccines. Tuberculosis 2001; 81: 165–8

    Article  PubMed  CAS  Google Scholar 

  8. Harboe M, Oettinger T, Wiker HG, et al. Evidence for occurrence of the ESAT6 protein in Mycobacterium tuberculosis and virulent Mycobacterium bovis and for its absence in Mycobacterium bovis BCG. Infect Immun 1996; 64: 16–22

    PubMed  CAS  Google Scholar 

  9. Porsa E, Cheng L, Graviss EA. Comparison of an ESAT-6/CFP-10 peptide-based enzyme-linked immunospot assay to a tuberculin skin test for screening of a population at moderate risk of contracting tuberculosis. Clin Vaccine Immunol 2007; 14: 714–9

    Article  PubMed  CAS  Google Scholar 

  10. Mori T, Sakatani M, Yamagishi F, et al. Specific detection of tuberculosis infection: an interferon-γ-based assay using new antigens. Am J Respir Crit Care Med 2004; 170: 59–64

    Article  PubMed  Google Scholar 

  11. Goletti D, Vincenti D, Carrara S, et al. Selected RD1 peptides for active tuberculosis diagnosis: comparison of a gamma interferon whole-blood enzyme-linked immunosorbent assay and an enzyme-linked immunospot assay. Clin Diagn Lab Immun 2005; 12: 1311–6

    CAS  Google Scholar 

  12. Brock I, Munk ME, Kok-Jensen A, et al. Performance of whole blood IFN-γ test for tuberculosis diagnosis based on PPD or the specific antigens ESAT-6 and CFP-10. Int J Tuberc Lung Dis 2001; 5: 462–7

    PubMed  CAS  Google Scholar 

  13. Brock I, Weldingh K, Lillebaek T, et al. Comparison of tuberculin skin test and new specific blood test in tuberculosis contacts. Am J Respir Crit Care Med 2004; 170: 65–9

    Article  PubMed  Google Scholar 

  14. Wu X, Li Q, Yang Y, et al. Latent tuberculosis infection among new soldiers in Chinese army: comparison of ELISPOT assay and tuberculin skin test. Clinica Chimica Acta 2009; 405: 110–3

    Article  CAS  Google Scholar 

  15. Alkana S, Akdisa C, Towbina H. Immuno assays for sensitive detection of human IFN-γ. J Immunoass Immunoch 1994; 15: 217–38

    Article  Google Scholar 

  16. Olesen CEM, Voyta JC, Bronstein I. Chemiluminescent immunoassay for the detection of chloramphenicol acetyltransferase and human growth hormone reporter proteins. Method Mol Biol 1997; 63: 71–6

    CAS  Google Scholar 

  17. Singh AK. Evaluation of solid-phase chemiluminescent enzyme immunoassay, enzyme-linked immunosorbent assay, and latex agglutination tests for screening toxoplasma IgG in samples obtained from cats and pigs. J Vet Diagn Invest 2000; 12: 136–41

    Article  PubMed  CAS  Google Scholar 

  18. Basso D, Guariso G, Fasolo M, et al. A new indirect chemiluminescent immunoassay to measure anti-tissue transglutaminase antibodies. J Pediatr Gastr Nutr 2006; 43: 613–8

    Article  Google Scholar 

  19. Pai M, Riley LW, Colford Jr JM. Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review. Lancet Infect Dis 2004; 4: 761–76

    Article  PubMed  CAS  Google Scholar 

  20. Pai M, Kalantri S, Dheda K. New tools and emerging technologies for the diagnosis of tuberculosis: part I. Latent tuberculosis. Expert Rev Mol Diagn 2006; 6: 413–22

    Article  PubMed  CAS  Google Scholar 

  21. Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection. An update. Ann Intern 2008; 149: 177–84

    Google Scholar 

  22. Kang YA, Lee HW, Yoon HI, et al. Discrepancy between the tuberculin skin test and the whole-blood interferon-γ assay for the diagnosis of latent tuberculosis infection in an intermediate tuberculosis-burden country. JAMA 2005; 293: 2756–61

    Article  PubMed  CAS  Google Scholar 

  23. Kimura M, Converse PJ, Astemborski J, et al. Comparison between a whole blood interferon-γ release assay and tuberculin skin testing for the detection of tuberculosis infection among patients at risk for tuberculosis exposure. J Infect Dis 1999; 179: 1297–300

    Article  PubMed  CAS  Google Scholar 

  24. Ewer K, Deeks J, Alvarez L, et al. Comparison of T-cell-based assay with tuberculin skin test for diagnosis of Mycobacterium tuberculosis infection in a school tuberculosis outbreak. Lancet 2003; 361: 1168–73

    Article  PubMed  Google Scholar 

  25. Farhat M, Greenaway C, Pai M, et al. False-positive tuberculin skin tests: what is the absolute effect of BCG and non-tuberculous mycobacteria? Int J Tuberc Lung Dis 2006; 10: 1192–204

    PubMed  CAS  Google Scholar 

  26. Van Pinxteren LA, Ravn P, Agger EM, et al. Diagnosis of tuberculosis based on the two specific antigens ESAT-6 and CFP10. Clin Diagn Lab Immunol 2000; 7: 155–60

    Google Scholar 

  27. Hill PC, Jackson-Sillah D, Fox A, et al. ESAT-6/CFP-10 fusion protein and peptides for optimal diagnosis of Mycobacterium tuberculosis infection by ex vivo enzyme-linked immunospot assay in the Gambia. J Clin Microbiol 2005; 43: 2070–4

    Article  PubMed  CAS  Google Scholar 

  28. Mori T, Harada N, Higuchi K, et al. Waning of the specific interferon-gamma response after years of tuberculosis infection. Int J Tuberc Lung Dis 2007; 11: 1021–5

    PubMed  CAS  Google Scholar 

  29. Dheda K, Udwadia ZF, Huggett JF, et al. Utility of the antigen-specific interferon-gamma assay for the management of tuberculosis. Curr Opin Pulm Med 2005; 11: 195–202

    Article  PubMed  CAS  Google Scholar 

  30. Diel R, Nienhaus A, Lange C, et al. Tuberculosis contact investigation with a new, specific blood test in a low-incidence population containing a high proportion of BCG-vaccinated persons. Respir Res 2006; 7: 77

    Article  PubMed  CAS  Google Scholar 

  31. Andersen P, Doherty TM, Pai M, et al. The prognosis of latent tuberculosis: can disease be predicted? Trends Mol Med 2007; 13: 175–82

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Serious Infectious Diseases Special Foundation of China (grant no. 2008ZX-10003-001) and the National Nature and Science Foundation of China (grant no. 30471648). The authors have no conflicts of interest that are directly relevant to the content of this study.

Author information

Authors and Affiliations

  1. Army Tuberculosis Prevention and Control Key Laboratory, Institute of Tuberculosis Research, 309th Hospital of the Chinese PLA, Beijing, 100091, China

    Xueqiong Wu, Ying Hou, Yan Liang, Junxian Zhang, Yourong Yang, Lan Wang & Chuiying Zhang

Authors
  1. Xueqiong Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ying Hou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yan Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Junxian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yourong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chuiying Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xueqiong Wu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wu, X., Hou, Y., Liang, Y. et al. Evaluation of a Tuberculosis Whole-Blood Interferon-γ Chemiluminescent Immunoassay among Chinese Military Recruits. Mol Diag Ther 15, 341–346 (2011). https://doi.org/10.1007/BF03256469

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03256469

Keywords

Search

Navigation