Pediatric Infection and Vaccine

The Korean Society of Pediatric Infectious Diseases (대한소아감염학회)
권호 표지

Comparison of Results between Tuberculin Skin Test and QuantiFERON®-TB In-Tube Assay for Diagnosis of Latent Tuberculosis Infection in Children and Adolescents

소아청소년에서의 잠복결핵감염 진단을 위한 결핵 피부반응검사와 QuantiFERON®-TB Gold In-Tube 검사와의 결과 비교

  • Choi, Jong-Won (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Kim, Min-Sung (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Kim, Jong-Hyun (Department of Pediatrics, College of Medicine, The Catholic University of Korea)
  • 최종원 (가톨릭대학교 의과대학 소아과학교실) ;
  • 김민성 (가톨릭대학교 의과대학 소아과학교실) ;
  • 김종현 (가톨릭대학교 의과대학 소아과학교실)
  • Received : 2012.10.20
  • Accepted : 2012.10.24
  • Published : 2013.04.25
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: Recently, two tests are commercially available for the identification of latent tuberculosis infection (LTBI): tuberculin skin test (TST) and interferon-${\gamma}$ release assay (IGRA). Due to its false positiveness, TST tends to be preferred by IGRA until now. In our study, we simultaneously performed both TST and QuantiFERON$^{(R)}$-TB Gold In-Tube (QFT-GIT) and compared their results. Methods: TST and QFT-GIT were done for the diagnosis of LTBI among children who visited pediatric out-patient clinic at St. Vincent's Hospital, The Catholic University of Korea from February of 2007 to May of 2008. The study group was stratified into two groups in terms of whether there was intrafamilial contact or not. Results: Out of total 35 children, 29 were tuberculosis (TB)-exposed cases and the remainders were diagnosed as clinical pulmonary TB. Among these 29 children, TST was positive 38.9% (7/18) for the intrafamilial and 45.5% (5/11) for the nonintrafamilial, and at the same time, the result for QFT-GIT was positive 5.6% (1/18) and 9.1% (1/11), respectively which implies that TST was more sensitive than QFT-GIT. Among 29 TB-exposed cases, 26 initially went through TST and QFTGIT together on their first visit to out-patient clinic, and 15 continued the follow-up tests. Out of total 41 cases collected, the agreement (known as kappa value) was 0.063 which was relatively low. Including 6 cases with pulmonary TB who were all positive for TST and only 5 being positive for QFT-GIT, the final kappa value was 0.334. Conclusion: In our study, the agreement for TST and QFT-GIT was low, and the majorities were almost the cases of positive TST. In current situation with lacking a gold standard test and limited data on children to adolescents, this result is quite alarming that the recent trend tends to replace TST by QFT-GIT when diagnosing LTBI.

목 적 : 잠복결핵감염(LTBI)을 진단하는 방법은 결핵 피부반응검사(TST)와 interferon-${\gamma}$ releasing assay(IGRA)이다. 그런데 TST의 위양성 문제 때문에 TST 대신 IGRA로 대치하려는 경향이 있다. 이에 결핵 접촉자 조사를 시행함에 있어 TST와 QuantiFERON$^{(R)}$-TB Gold In-Tube (QFT-GIT) 검사를 동시에 시행하여 결과를 비교하였다. 방 법 : 2007년 2월부터 2008년 5월까지 가톨릭대학교 성빈센트병원 소아청소년과 외래에 LTBI 여부의 확인을 위해 방문한 소아를 대상으로 TST와 QFT-GIT 검사를 동시에 시행하였다. 연구대상은 감염원이 같은 집에 거주하는 경우를 동거 접촉, 아닌 경우를 비동거 접촉으로 구분하였다. 결 과 : 연구대상은 총 35명으로 폐결핵 노출 후 접촉자 조사 대상이 29명, 폐결핵으로 진단된 경우가 6명이었다. 접촉자 조사 대상에서 동거 접촉군은 18명(62.1%), 비동거 접촉군이 11명(37.9%)이었다. 최종 접촉자 조사 결과로 TST 양성은 동거 접촉군 38.9% (7/18), 비동거 접촉군 45.5% (5/11)이었고, QFT-GIT 검사 양성은 각각 5.6% (1/18), 9.1%(1/11)로 TST의 양성률이 더 높았다. 접촉자 조사에서 두 검사를 모두 시행한 경우는 1차 검사의 26건과 2차 추적검사의 15건을 합하여 총 41건으로 두 검사의 일치율(kappa값)은 0.063으로 매우 낮았다. 6명의 폐결핵 환자에서 TST는 모두 양성, QFT-GIT 검사는 5명이 양성으로, 이들까지를 포함했을 때의 일치율은 0.334이었다. 결 론 : 본 연구에서 TST와 QFT-GIT 검사 결과의 일치율은 낮았는데, 대부분이 TST 양성인 경우이었다. 두 검사 결과 중 어떤 것이 정확한 것인지 판단할 수 있는 표준 검사법이 없고, 소아청소년에 대한 자료가 충분치 않은 상황에서 민감도가 낮은 IGRA에 의한 결과만을 신뢰하여 LTBI 진단에 IGRA만 사용하는 것은 적절치 않다고 사료된다.

Keywords

References

  1. World Health Organization. Global tuberculosis control: WHO report 2011. Geneva : WHO, 2011:9-27.
  2. Kim HJ. Current status of tuberculosis in Korea. Korean J Med 2012;82:257-62. https://doi.org/10.3904/kjm.2012.82.3.257
  3. Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR Recomm Rep 2000;49(RR-6):1-51.
  4. 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;146:340-54. https://doi.org/10.7326/0003-4819-146-5-200703060-00006
  5. Pai M, Zwerling A, Menzies D. Systematic review: Tcell- based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med 2008;149:177-84. https://doi.org/10.7326/0003-4819-149-3-200808050-00241
  6. Centers for Disease Control and Prevention. Guidelines for using the QuantiFERON-TB Gold test for detecting Mycobacterium tuberculosis infection, United States. MMWR Morb Mortal Wkly Rep 2005;54:49–55.
  7. Farhat M, Greenaway C, Pai M, Menzies D. 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.
  8. Lewinsohn DA, Lobato MN, Jereb JA. Interferon-$\gamma$ release assays: new diagnostic tests for Mycobacterium tuberculosis infection, and their use in children. Curr Opin Pediatr 2010;22:71-6. https://doi.org/10.1097/MOP.0b013e3283350301
  9. Canadian Tuberculosis Committee (CTC). Recommendations on interferon gamma release assays for the diagnostic latent tuberculosis infection-2010 update. Canada Commun Dis Rep 2010;36(ACS-5):1-21.
  10. Starke JR. New concepts in childhood tuberculosis. Curr Opin Pediatr 2007;19:306-13. https://doi.org/10.1097/MOP.0b013e32814b164a
  11. Denkinger CM, Dheda K, Pai M. Guidelines on interferon- $\gamma$ release assays for tuberculosis infection: concordance, discordance or confusion? Clin Microbiol Infect 2011;17:806-14. https://doi.org/10.1111/j.1469-0691.2011.03555.x
  12. Ling DI, Zwerling AA, Steingart KR, Pai M. Immunebased diagnostics for TB in children: what is the evidence? Paediatr Resp Rev 2011;12:9-15. https://doi.org/10.1016/j.prrv.2010.09.009
  13. Machingaidze S, Wiysonge CS, Gonzalez-Angulo Y, Hatherill M, Moyo S, Hanekom W, et al. The utility of an interferon gamma release assay for diagnosis of latent tuberculosis infection and disease in children: a systematic review and meta-analysis. Pediatr Infect Dis J 2011;30:694-700. https://doi.org/10.1097/INF.0b013e318214b915
  14. Bouros D, Zeros G, Panaretos C, Vassilatos C, Siafakas N. Palpation vs pen method for the measurement of skin tuberculin reaction (Mantoux test). Chest 1991;99:416-9. https://doi.org/10.1378/chest.99.2.416
  15. Cellestis. QuantiFERONⓇ-TB Gold (in-tube method) package insert, document No. US05990301E, January 2009. Available at: http://www.cellestis.com. Accessed 12 September 2012.
  16. National Collaborating Centre for Chronic Conditions. Tuberculosis: clinical diagnosis and management of tuberculosis, and measures for its prevention and control. London : Royal College of Physicians, 2006:105-14.
  17. Marais BJ, Gie RP, Schaaf HS, Hesseling AC, Obihara CC, Starke JJ, et al. The natural history of childhood intra-thoracic tuberculosis: a critical review of literature from the pre-chemotherapy era. Int J Tuberc Lung Dis 2004;8:392–402.
  18. Marais BJ, Donald PR. The natural history of tuberculosis infection and disease in children. In : Schaar HS, Zulma AI, editors. Tuberculosis: a comprehensive clinical reference. Philadelphia : Elsevier Inc., 2009;133-45.
  19. Lighter J, Rigaud M, Eduardo R, Peng C, Pollack H. Latent tuberculosis diagnosis in children by using the QuantiFERON-TB Gold In-Tube test. Pediatrics 2009;123:30-7. https://doi.org/10.1542/peds.2007-3618
  20. O'Neal S, Hedberg K, Markum A, Schafer S. Discordant tuberculin skin and interferon-gamma tests during contact investigations: a dilemma for tuberculosis controllers. Int J Tuberc Lung Dis 2009;13:662-4.
  21. Herrera V, Perry S, Parsonnet J, Banaei N. Clinical application and limitations of interferon-gamma release assays for the diagnosis of latent tuberculosis infection. Clin Infect Dis 2011;52:1031-7. https://doi.org/10.1093/cid/cir068
  22. Chun JK, Kim CK, Kim HS, Jung GY, Lee TJ, Kim KH, et al. The role of a whole blood interferon-assay for the detection of latent tuberculosis infection in Bacille Calmette-Guerin vaccinated children. Diagn Microbiol Infect Dis 2008;62:389–94. https://doi.org/10.1016/j.diagmicrobio.2008.08.022
  23. Sung JY, Kim JH, Yang MA, Kim SH, Eun BW, Lee J, et al. Usefulness of interferon-$\gamma$ measurement following stimulation of tuberculosis-specific antigens for diagnosis of latent tuberculosis infection in children exposed to pulmonary tuberculosis. Korean J Pediatr Infect Dis 2008;15:50-7.
  24. Chun JK, Kim CK, Kim HS, Jung GY, Linton JA, Kim KH, et al. Comparison of a whole blood Interferongamma assay and A tuberculin skin test for detecting latent tuberculosis infection in children. Korean J Pediatr 2008;51:971-6. https://doi.org/10.3345/kjp.2008.51.9.971
  25. Kim YJ, Lee JS. Comparison of Interferon-gamma assays with the tuberculin skin test in children. Pediatr Allergy Respir Dis 2010;20:10-6.
  26. Soon EG, Lim BK, Kim HM, Namgoong MK, Cha BH, Uh Y, et al. A tapping the usefulness of whole blood interferon-gamma assay for diagnosing tuberculosis infection in children. Tuberc Respir Dis 2010;68:280-5. https://doi.org/10.4046/trd.2010.68.5.280
  27. Lee HW, Park HY, Ahn YM, Sohn KC. Clinical significance of interferon gamma release assay for diagnosis of tuberculosis in children. Korean J Pediatr Infect Dis 2010;17:137-47.
  28. Lee YJ, Chun P, We JH, Park SE. Accuracy of an interferon- gamma release assay to detect active tuberculosis in children: a pilot study. Korean J Pediatr Infect Dis 2011;18:48-53.
  29. Park YM, Chung S, Yoo KH. Relationship between asthma and latent tuberculosis infection in children. Korean J Asthma Allergy Clin Immunol 2012;32:101-6