DOI QR코드

DOI QR Code

Usefulness of interferon-γ release assay for the diagnosis of latent tuberculosis infection in young children

  • Yun, Ki Wook (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Young Kwang (Department of Pediatrics, Chung-Ang University College of Medicine) ;
  • Kim, Hae Ryun (Department of Laboratory Medicine, Chung-Ang University College of Medicine) ;
  • Lee, Mi Kyung (Department of Laboratory Medicine, Chung-Ang University College of Medicine) ;
  • Lim, In Seok (Department of Pediatrics, Chung-Ang University College of Medicine)
  • Received : 2015.10.15
  • Accepted : 2016.03.13
  • Published : 2016.06.15

Abstract

Purpose: Latent tuberculosis infection (LTBI) in young children may progress to severe active tuberculosis (TB) disease and serve as a reservoir for future transmission of TB disease. There are limited data on interferon-${\gamma}$ release assay (IGRA) performance in young children, which our research aims to address by investigating the usefulness of IGRA for the diagnosis of LTBI. Methods: We performed a tuberculin skin test (TST) and IGRA on children who were younger than 18 years and were admitted to Chung-Ang University Hospital during May 2011-June 2015. Blood samples for IGRA were collected, processed, and interpreted according to manufacturer protocol. Results: Among 149 children, 31 (20.8%) and 10 (6.7%) were diagnosed with LTBI and active pulmonary TB, respectively. In subjects lacking contact history with active TB patients, TST and IGRA results were positive in 41.4% (29 of 70) and 12.9% (9 of 70) subjects, respectively. The agreement (kappa) of TST and IGRA was 0.123. The control group, consisting of non-TB-infected subjects, showed no correlation between age and changes in interferon-${\gamma}$ concentration after nil antigen, TB-specific antigen, or mitogen stimulation in IGRAs (P=0.384, P=0.176, and P=0.077, respectively). In serial IGRAs, interferon-${\gamma}$ response to TB antigen increased in IGRA-positive LTBI subjects, but did not change considerably in initially IGRA-negative LTBI or control subjects. Conclusion: The lack of decrease in interferon-${\gamma}$ response in young children indicates that IGRA could be considered for this age group. Serial IGRA tests might accurately diagnose LTBI in children lacking contact history with active TB patients.

Acknowledgement

Supported by : Korean Pediatric Society

References

  1. Ellner JJ. Review: the immune response in human tuberculosis: implications for tuberculosis control. J Infect Dis 1997;176:1351-9. https://doi.org/10.1086/514132
  2. Getahun H, Matteelli A, Chaisson RE, Raviglione M. Latent Mycobacterium tuberculosis infection. N Engl J Med 2015;372:2127-35. https://doi.org/10.1056/NEJMra1405427
  3. Kim JH. Treatment of latent tuberculous infection in children and adolescent. Korean J Pediatr 2009;52:519-28. https://doi.org/10.3345/kjp.2009.52.5.519
  4. Perez-Velez CM, Marais BJ. Tuberculosis in children. N Engl J Med 2012;367:348-61. https://doi.org/10.1056/NEJMra1008049
  5. 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
  6. Choi JW, Kim MS, Kim JH. Comparison of results between tuberculin skin test and QuantiFERON(R)-TB in-tube assay for diagnosis of latent tuberculosis infection in children and adolescents. Korean J Pediatr Infect Dis 2013;20:17-27. https://doi.org/10.14776/kjpid.2013.20.1.17
  7. 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.
  8. 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;15:51-7. https://doi.org/10.14776/kjpid.2008.15.1.51
  9. Kim YJ, Lee JS. Comparison of interferon-gamma assays with the tuberculin skin test in children. Pediatr Allergy Respir Dis 2010;20:10-6.
  10. Dogra S, Narang P, Mendiratta DK, Chaturvedi P, Reingold AL, Colford JM Jr, et al. Comparison of a whole blood interferongamma assay with tuberculin skin testing for the detection of tuberculosis infection in hospitalized children in rural India. J Infect 2007;54:267-76. https://doi.org/10.1016/j.jinf.2006.04.007
  11. Lalvani A, Millington KA. T cell-based diagnosis of childhood tuberculosis infection. Curr Opin Infect Dis 2007;20:264-71. https://doi.org/10.1097/QCO.0b013e32813e3fd8
  12. Tieu HV, Suntarattiwong P, Puthanakit T, Chotpitayasunondh T, Chokephaibulkit K, Sirivichayakul S, et al. Comparing interferongamma release assays to tuberculin skin test in Thai children with tuberculosis exposure. PLoS One 2014;9:e105003. https://doi.org/10.1371/journal.pone.0105003
  13. Lewinsohn DA, Zalwango S, Stein CM, Mayanja-Kizza H, Okwera A, Boom WH, et al. Whole blood interferon-gamma responses to mycobacterium tuberculosis antigens in young household contacts of persons with tuberculosis in Uganda. PLoS One 2008;3:e3407. https://doi.org/10.1371/journal.pone.0003407
  14. 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
  15. Garazzino S, Galli L, Chiappini E, Pinon M, Bergamini BM, Cazzato S, et al. Performance of interferon-${\gamma}$ release assay for the diagnosis of active or latent tuberculosis in children in the first 2 years of age: a multicenter study of the Italian Society of Pediatric Infectious Diseases. Pediatr Infect Dis J 2014;33:e226-31. https://doi.org/10.1097/INF.0000000000000353
  16. Chiappini E, Bonsignori F, Accetta G, Boddi V, Galli L, Biggeri A, et al. Interferon-${\gamma}$ release assays for the diagnosis of Mycobacterium tuberculosis infection in children: a literature review. Int J Immunopathol Pharmacol 2012;25:335-43. https://doi.org/10.1177/039463201202500203
  17. Pavic I, Topic RZ, Raos M, Aberle N, Dodig S. Interferon-${\gamma}$ release assay for the diagnosis of latent tuberculosis in children younger than 5 years of age. Pediatr Infect Dis J 2011;30:866-70. https://doi.org/10.1097/INF.0b013e318220c52a
  18. Starke JR; Committee On Infectious Diseases. Interferon-${\gamma}$ release assays for diagnosis of tuberculosis infection and disease in children. Pediatrics 2014;134:e1763-73. https://doi.org/10.1542/peds.2014-2983
  19. 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.
  20. Mazurek GH, Jereb J, Vernon A, LoBue P, Goldberg S, Castro K, et al. Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection - United States, 2010. MMWR Recomm Rep 2010;59(RR-5):1-25.
  21. Howley MM, Painter JA, Katz DJ, Graviss EA, Reves R, Beavers SF, et al. Evaluation of QuantiFERON-TB gold in-tube and tuberculin skin tests among immigrant children being screened for latent tuberculosis infection. Pediatr Infect Dis J 2015;34:35-9. https://doi.org/10.1097/INF.0000000000000494
  22. Haustein T, Ridout DA, Hartley JC, Thaker U, Shingadia D, Klein NJ, et al. The likelihood of an indeterminate test result from a whole-blood interferon-gamma release assay for the diagnosis of Mycobacterium tuberculosis infection in children correlates with age and immune status. Pediatr Infect Dis J 2009;28:669-73. https://doi.org/10.1097/INF.0b013e3181a16394
  23. Ferrara G, Losi M, D'Amico R, Roversi P, Piro R, Meacci M, 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. https://doi.org/10.1016/S0140-6736(06)68579-6
  24. Connell TG, Curtis N, Ranganathan SC, Buttery JP. Performance of a whole blood interferon gamma assay for detecting latent infection with Mycobacterium tuberculosis in children. Thorax 2006;61:616-20. https://doi.org/10.1136/thx.2005.048033
  25. Smart JM, Kemp AS. Ontogeny of T-helper 1 and T-helper 2 cytokine production in childhood. Pediatr Allergy Immunol 2001;12:181-7. https://doi.org/10.1034/j.1399-3038.2001.012004181.x
  26. Diagnostic Standards and Classification of Tuberculosis in Adults and Children. This official statement of the American Thoracic Society and the Centers for Disease Control and Prevention was adopted by the ATS Board of Directors, July 1999. This statement was endorsed by the Council of the Infectious Disease Society of America, September 1999. Am J Respir Crit Care Med 2000;161(4 Pt 1):1376-95. https://doi.org/10.1164/ajrccm.161.4.16141
  27. Connell T, Bar-Zeev N, Curtis N. Early detection of perinatal tuberculosis using a whole blood interferon-gamma release assay. Clin Infect Dis 2006;42:e82-5. https://doi.org/10.1086/503910
  28. Bianchi L, Galli L, Moriondo M, Veneruso G, Becciolini L, Azzari C, et al. Interferon-gamma release assay improves the diagnosis of tuberculosis in children. Pediatr Infect Dis J 2009;28:510-4. https://doi.org/10.1097/INF.0b013e31819abf6b