Journal List > Tuberc Respir Dis > v.68(3) > 1001481

Bae, Kim, and Wang: An Usefulness of In Vitro Interferon Gamma Assay for the Diagnosis of Latent Tuberculosis Infection in Middle- and High-School Students in Jeju-Shi, Korea



The tuberculin skin test (TST) has limitations in diagnosing a latent tuberculosis infection (LTBI). The interferon-gamma release assay (IGRA) was introduced to middle- and high-school students since 2009 by the Korea Centers for Disease Control and Prevention. The aim was to evaluate the utility of IGRA in diagnosing LTBI in middle- and high-school students.


From August 2007 to July 2009, among suspected LTBI students showing TST induration with a 10 mm diameter and over with a normal chest x-ray in school students of Jeju city, 341 students underwent a Quanti FERON-TB Gold In-Tube (QFT-IT) test to confirm LTBI.


From 348 students showing a positive TST, a QFT-IT test was carried out on 341 students. The positive QFT-IT rate was 52.8% (=180/341). The positive QFT-IT rate was higher in high-school boys with a 15~19 mm diameter of induration in TST.


With the introduction of IGRA for diagnosing LTBI in middle- and high-school students, approximately 47% of students who show a TST induration with a 10 mm diameter and over can avoid taking unnecessary preventive chemotherapy. These results suggest that IGRA is useful for diagnosing and controlling LTBI in Korean students.

Figures and Tables

Figure 1
The guideline for diagnosis of latent tuberculosis infection in school students, Korea. BCG: bacilli Chalmette-Guerin vaccine; TST: tuberculin skin test; IGRA: Interferon gamma release assay) [cited from Reference 2].
Table 1
Proportional rate of postive tuberculin skin test (TST) and in vitro interferon-gamma assay (QFT-IT) in subjects by events of outbreaks

LTBI: latent tuberculosis infection; CI: confidence interval.

Table 2
The proportional rate of positive tuberculin skin test (TST) and in vitro interferon-gamma assay (QFT-IT) in subjects in 3 high schools

LTBI: latent tuberculosis infection; CI: confidence interval.

Table 3
Characteristics of subjects (n=341) in positive tuberculin skin test (TST) by results of in vitro interferon-gamma assay (QFT-IT)

PTB: pulmonary tuberculosis infection; BCG: bacilli Chalmette-Guerin vaccine.

*p-value by chi-square test.

Table 4
Adjusted odds ratios (aOR) in results of in vitro interferon-gamma assay (QFT-IT) for age, sex and size of induration

CI: confidence interval.


1. Global tuberculosis control: epidemiology, strategy, financing. Global report 2009 [Internet]. World Health Organization. 2009. cited 2010 Feb 15. Geneva: World Health Organization;Available from:
2. Tuberculosis [Internet]. Korea Centers for Diseases Control and Prevention. 2010. cited 2010 Feb 15. Seoul: Korea Centers for Diseases Control and Prevention;Available from:
3. Shim TS, Koh WJ, Yim JJ, Lew WJ. Diagnosis and treatment of latent tuberculosis infection in Korea. Tuberc Respir Dis. 2004. 57:101–108.
4. Swindells JE, Aliyu SH, Enoch DA, Abubakar I. Role of interferon-gamma release assays in healthcare workers. J Hosp Infect. 2009. 73:101–108.
5. Lee JY, Shim TS. Diagnosis of Mycobacterium tuberculosis infection using ex-vivo interferon-gamma assay. Tuberc Respir Dis. 2006. 60:497–509.
6. 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. 6:413–422.
7. Madariaga MG, Jalali Z, Swindells S. Clinical utility of interferon gamma assay in the diagnosis of tuberculosis. J Am Board Fam Med. 2007. 20:540–547.
8. Pai M, Gokhale K, Joshi R, Dogra S, Kalantri S, Mendiratta DK, et al. Mycobacterium tuberculosis infection in health care workers in rural India: comparison of a whole-blood interferon gamma assay with tuberculin skin testing. JAMA. 2005. 293:2746–2755.
9. Pai M, Riley LW, Colford JM Jr. Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review. Lancet Infect Dis. 2004. 4:761–776.
10. Fine PE. Variation in protection by BCG: implications of and for heterologous immunity. Lancet. 1995. 346:1339–1345.
11. Brock I, Weldingh K, Lillebaek T, Follmann F, Andersen P. Comparison of tuberculin skin test and new specific blood test in tuberculosis contacts. Am J Respir Crit Care Med. 2004. 170:65–69.
12. Menzies D, Pai M, Comstock G. Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research. Ann Intern Med. 2007. 146:340–354.
13. Shalabi NM, Houssen ME. Discrepancy between the tuberculin skin test and the levels of serum interferon-gamma in the diagnosis of tubercular infection in contacts. Clin Biochem. 2009. 42:1596–1601.
14. Machado A Jr, Emodi K, Takenami I, Finkmoore BC, Barbosa T, Carvalho J, et al. Analysis of discordance between the tuberculin skin test and the interferon-gamma release assay. Int J Tuberc Lung Dis. 2009. 13:446–453.
15. Tsara V, Serasli E, Christaki P. Problems in diagnosis and treatment of tuberculosis infection. Hippokratia. 2009. 13:20–22.
16. Andersen P, Munk ME, Pollock JM, Doherty TM. Specific immune-based diagnosis of tuberculosis. Lancet. 2000. 356:1099–1104.
17. Lalvani A. Spotting latent infection: the path to better tuberculosis control. Thorax. 2003. 58:916–918.
18. QuantiFERON technology [Internet]. Cellestis. 2010. cited 2010 Feb 15. Valencia: Cellestis Inc.;Available from:
19. Dye C, Scheele S, Dolin P, Pathania V, Raviglione MC. Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA. 1999. 282:677–686.
20. Styblo K. Recent advances in epidemiological research in tuberculosis. Adv Tuberc Res. 1980. 20:1–63.
21. Huebner RE, Schein MF, Bass JB Jr. The tuberculin skin test. Clin Infect Dis. 1993. 17:968–975.
22. Reid JK, Ward H, Marciniuk D, Hudson S, Smith P, Hoeppner V. The effect of neonatal bacille Calmette-Guerin vaccination on purified protein derivative skin test results in Canadian aboriginal children. Chest. 2007. 131:1806–1810.
23. Richeldi L. An update on the diagnosis of tuberculosis infection. Am J Respir Crit Care Med. 2006. 174:736–742.
24. Eum SY, Lee YJ, Kwak HK, Min JH, Hwang SH, Via LE, et al. Evaluation of the diagnostic utility of a whole-blood interferon-gamma assay for determining the risk of exposure to Mycobacterium tuberculosis in Bacille Calmette-Guerin (BCG)-vaccinated individuals. Diagn Microbiol Infect Dis. 2008. 61:181–186.
25. Pathan AA, Wilkinson KA, Klenerman P, McShane H, Davidson RN, Pasvol G, et al. Direct ex vivo analysis of antigen-specific IFN-gamma-secreting CD4 T cells in Mycobacterium tuberculosis-infected individuals: associations with clinical disease state and effect of treatment. J Immunol. 2001. 167:5217–5225.
26. Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med. 2008. 149:177–184.
27. Kang YA, Lee HW, Yoon HI, Cho B, Han SK, Shim YS, 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. 293:2756–2761.
28. Dheda K, Udwadia ZF, Huggett JF, Johnson MA, Rook GA. Utility of the antigen-specific interferon-gamma assay for the management of tuberculosis. Curr Opin Pulm Med. 2005. 11:195–202.
29. Lee JY, Choi HJ, Park IN, Hong SB, Oh YM, Lim CM, et al. Comparison of two commercial interferon-gamma assays for diagnosing Mycobacterium tuberculosis infection. Eur Respir J. 2006. 28:24–30.
30. Mazurek GH, Jereb J, Lobue P, Iademarco MF, Metchock B, Vernon A. Guidelines for using the Quanti FERON-TB Gold test for detecting Mycobacterium tuberculosis infection, United States. MMWR Recomm Rep. 2005. 54:49–55.
31. Canadian Tuberculosis Committee. Interferon gamma release assays for latent tuberculosis infection: an Advisory Committee Statement (ACS). Can Commun Dis Rep. 2007. 33:1–18.
32. Mori T, Sakatani M, Yamagishi F, Takashima T, Kawabe Y, Nagao K, et al. Specific detection of tuberculosis infection: an interferon-gamma-based assay using new antigens. Am J Respir Crit Care Med. 2004. 170:59–64.
33. Nienhaus A, Schablon A, Bacle CL, Siano B, Diel R. Evaluation of the interferon-gamma release assay in healthcare workers. Int Arch Occup Environ Health. 2008. 81:295–300.
34. Harada N, Nakajima Y, Higuchi K, Sekiya Y, Rothel J, Mori T. Screening for tuberculosis infection using whole-blood interferon-gamma and Mantoux testing among Japanese healthcare workers. Infect Control Hosp Epidemiol. 2006. 27:442–448.
35. Lalvani A, Pathan AA, McShane H, Wilkinson RJ, Latif M, Conlon CP, et al. Rapid detection of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells. Am J Respir Crit Care Med. 2001. 163:824–828.
36. Fietta A, Meloni F, Cascina A, Morosini M, Marena C, Troupioti P, et al. Comparison of a whole-blood interferon-gamma assay and tuberculin skin testing in patients with active tuberculosis and individuals at high or low risk of Mycobacterium tuberculosis infection. Am J Infect Control. 2003. 31:347–353.
37. Choi JC, Shin JW, Kim JY, Park IW, Choi BW, Lee MK. The effect of previous tuberculin skin test on the follow-up examination of whole-blood interferon-gamma assay in the screening for latent tuberculosis infection. Chest. 2008. 133:1415–1420.
38. Hotta K, Ogura T, Nishii K, Kodani T, Onishi M, Shimizu Y, et al. Whole blood interferon-gamma assay for baseline tuberculosis screening among Japanese healthcare students. PLoS One. 2007. 2:e803.
39. Lee JY, Choi HJ, Cho SN, Park IN, Oh YM, Lee SD, et al. Effect of tuberculin skin test on ex-vivo interferon-gamma assay for latent tuberculosis infection. Tuberc Respir Dis. 2005. 59:406–412.
40. Richeldi L, Ewer K, Losi M, Bergamini BM, Roversi P, Deeks J, et al. T cell-based tracking of multidrug resistant tuberculosis infection after brief exposure. Am J Respir Crit Care Med. 2004. 170:288–295.
Similar articles