Accuracy of an Interferon-gamma Release Assay to Detect Active Tuberculosis in Children: A Pilot Study

소아 결핵 진단에서의 인터페론감마 분비 검사의 유용성

  • Lee, Young Jin (Department of Pediatrics, School of Medicine, Pusan National University) ;
  • Chun, Peter (Department of Pediatrics, School of Medicine, Pusan National University) ;
  • We, Ju Hee (Department of Pediatrics, School of Medicine, Pusan National University) ;
  • Park, Su Eun (Department of Pediatrics, School of Medicine, Pusan National University)
  • 이영진 (부산대학교 의학전문대학원 소아과학교실) ;
  • 천베드로 (부산대학교 의학전문대학원 소아과학교실) ;
  • 위주희 (부산대학교 의학전문대학원 소아과학교실) ;
  • 박수은 (부산대학교 의학전문대학원 소아과학교실)
  • Received : 2010.09.15
  • Accepted : 2010.10.20
  • Published : 2011.06.25

Abstract

Purpose : Early diagnosis of active tuberculosis (TB) in children is difficult. The widely used tuberculin skin test has low sensitivity and cross reactivity with non-tuberculous mycobacteria or Bacille Calmette-Gu$\acute{e}$rin vaccination. Interferon gamma release assays have been shown good diagnostic accuracy for active in adults. But studies in children were limited. The purpose of this study was to examine the performance of enzyme-linked immunospot assay (ELISpot) as an initial test in the diagnosis of active tuberculosis in children. Methods : In a hospital-based study, we prospectively examined the performance of ELISPot in 33 children suspected of active TB. TB was confirmed bacteriologically or histologically. Results : Among 33 patients, 9 had active tuberculosis. When tested, they all had a positive test result from the ELISpot. The sensitivity and specificity of the assay were 100% (95% CI, 66.4-100%) and 95.8% (95% CI, 78.9-99.9%) respectively. Conclusion : ELISpot might be an useful and improved clinical diagnostic method for the detection of active TB in children.

목 적 : 활동성 결핵의 진단으로 투베르쿨린 피부반응 검사(TST)가 널리 사용되어 왔으나 민감도가 낮고 BCG 예방접종을 한 경우 교차반응이 일어날 수 있는 한계가 있어 이를 극복하기 위해 인터페론감마검사(IGRA)에 대한 연구가 보고되고 있다. 이에 본 연구는 소아 활동성 결핵을 진단하는 초기검사로서 IGRA의 유용성에 대해 알아보았다. 방 법: 2007년 4월부터 2008년 8월까지 부산대학교병원 소아청소년과에서 활동성결핵이 의심되어 입원한 18세 이하의 환자 33명을 대상으로 성별, 나이, BCG 접종력, 임상양상과 IGRA 검사결과를 분석하였다. 결 과:총 33명의 환아 중 9명이 활동성 결핵으로 진단되었고 ELISpot에 양성은 10명, 음성은 23명이었다. 활동성 결핵이었던 환아는 모두 양성이었다. 검사의 민감도는 활동성 결핵 환자에서 100%이었다. 23명의 환아가 ELISpot에 음성 반응을 보였는데 이들은 모두 임상적으로 결핵이 아닌 것으로 확진되었고 검사의 특이도는 95.8%였다. 결 론:소아의 활동성 결핵 진단에 있어 ELISpot은 유용한 것으로 생각된다.

Keywords

References

  1. World Health Organization. 2007. Tuberculosis, fact sheet no. 104. World Health Organization, Geneva, Switzerland. http://www.who.int/mediacentre/factsheets/fs104/en/
  2. Chan ED, Heifets L, Iseman MD. Immunologic diagnosis of tuberculosis: a review. Tuber Lung Dis 2000;80:131-40. https://doi.org/10.1054/tuld.2000.0243
  3. Keeler E, Perkins MD, Small P, Hanson C, Reed S, Cunningham J et al. Reducing the global burden of tuberculosis: the contribution of improved diagnostics. Nature 2006;444:49-57.
  4. Hesseling AC, Schaaf HS, Gie RP, Starke JR, Beyers N. A critical review of diagnostic approaches used in the diagnosis of childhood tuberculosis. Int J Tuberc Lung Dis 2002;6:1038-45.
  5. Shingadia D, Novelli V. Diagnosis and treatment of tuberculosis in children. Lancet Infect Dis 2003;3:624-32. https://doi.org/10.1016/S1473-3099(03)00771-0
  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;6:413-22. https://doi.org/10.1586/14737159.6.3.413
  7. Richeldi L. An update on the diagnosis of tuberculosis infection. Am J Respir Crit Care Med 2006;174:736-42. https://doi.org/10.1164/rccm.200509-1516PP
  8. Pai M, Dheda K, Cunningham J, Scano F, O'Brien R. T-cell assays for the diagnosis of latent tuberculosis infection: moving the research agenda forward. Lancet Infect Dis 2007;7:428-38. https://doi.org/10.1016/S1473-3099(07)70086-5
  9. Detjen AK, Keil T, Roll S, Hauer B, Mauch H, Wahn U et al. Interferon-γ release assays improve the diagnosis of tuberculosis and nontuberculous mycobacterial disease in children in a country with a low incidence of tuberculosis. Clin Infec Dis 2007;45:322-8. https://doi.org/10.1086/519266
  10. Kampmann B, Whittaker E, Williams A, Walters S, Gordon A, Martinez-Alier N et al. Interferon-gamma release assays do not identify more children with active tuberculosis than tuberculin skin test. Eur Respir J 2009;33:1374-82. https://doi.org/10.1183/09031936.00153408
  11. Pai M, Menzies D. Interferon-gamma release assays: what is their role in the diagnosis of active tuberculosis? Clin Infect Dis 2007;44:74-7. https://doi.org/10.1086/509927
  12. Nishimura T, Hasegawa N. Mori M, Takebayashi T, Harada N, Higuchi K et al. Accuracy of an interferongamma release assay to detect active pulmonary and extra-pulmonary tuberculosis. Int J Tuberc Lung Dis 2008;12:269-74.
  13. Dosanjh DP, Hinks TS, Innes JA, Deeks JJ, Pasvol G, Hackforth S et al. Improved diagnostic evaluation of suspected tuberculosis. Ann Intern Med 2008;148:325-36. https://doi.org/10.7326/0003-4819-148-5-200803040-00003
  14. Liebeschuetz S, Bamber S, Ewer K, Deeks J, Pathan AA, Lalvani A. Diagnosis of tuberculosis in South African children with a T-cell-based assay: a prospective cohort study. Lancet 2004; 364:2196-203. https://doi.org/10.1016/S0140-6736(04)17592-2