Interferon-Gamma Release Assay in the Diagnosis of Tuberculosis

cocukgogus-4-3-2023-kapak

Fatih ERCANa , Hanife Tuğçe ÇAĞLARa , Sevgi PEKCANa
aNecmettin Erbakan University Meram Faculty of Medicine, Department of Pediatric Chest Diseases, Konya, Türkiye

ABSTRACT
Tuberculosis (TB) is a communicable disease caused by Mycobacterium tuberculosis complex. The World Health Organization (WHO) recommends preventive treatment for populations at risk of developing TB. Recommended tests to identify patients who may benefit from anti-tuberculosis treatment include tuberculin skin testing (TST) and interferon-gamma release assays (IGRAs). Both TST and IGRA results indicate the presence or absence of possible infection. Because they measure immunologic susceptibility to mycobacterial antigens and therefore cannot differentiate current TB infection from past infection or actual disease from infection, neither test can be considered the “gold standard” for TB infection. In conclusion, there is a need for broader and prolonged research on IGRAs that encompasses all patient groups. It should be emphasized that a negative outcome from either IGRA or TST does not completely eliminate the possibility of active disease; thus, therapeutic intervention must be considered if deemed clinically necessary.

Keywords: Tuberculosis; interferon-gamma release tests

Referanslar

  1. Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin Infect Dis. 2017;64(2):111-5. [Crossref]
  2. World Health Organization. Global Tuberculosis Report 2020. Geneva: World Health Organization, 2019. Available from: [Link]
  3. World Health Organization. Global Tuberculosis Report 2022. Available at: [Link]
  4. Statistics of the Ministry of Health, General Directorate of Public Health, Department of Tuberculosis.Available from: [Link]
  5. World Health Organization. WHO consolidated guidelines on tuberculosis: module 1: prevention: tuberculosis preventive treatment. Geneva, Switzerland: WHO; 2020. [Crossref]
  6. American Academy of Pediatrics, Pediatric Tuberculosis Collaborative Group. Targeted tuberculin skin testing and treatment of latent tuberculosis infection in children and adolescents. Pediatrics. 2004;114(Suppl 4). [Crossref]
  7. Bergamini BM, Losi M, Vaienti F, D'Amico R, Meccugni B, et al. Performance of commercial blood tests for the diagnosis of latent tuberculosis infection in children and adolescents. Pediatrics. 2009;123:e419-24. [Crossref]  [PubMed]
  8. Mack U, Migliori GB, Sester M, et al. LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis. A TBNET consensus statement. Eur Respir J. 2009;33(5):956-73. [Crossref]  [PubMed]
  9. Hamada Y, Gupta RK, Quartagno M, Izzard A, Acuna-Villaorduna C, Altet N, et al. Predictive performance of interferon-gamma release assays and the tuberculin skin test for incident tuberculosis: an individual participant data meta-analysis. EClinicalMedicine. 2023;56:101815. [Crossref]  [PubMed]  [PMC]
  10. Kara F. Ministry of Health Tuberculosis Diagnosis and Treatment Guide. 2nd ed. Ankara: 2019.
  11. Wilmott R, Deterding R, Li A, Ratjen F, Sly P, Zar H, et al, eds. Kendig's Disorders of the Respiratory Tract in Children. 9th ed. Philadelphia: Elsevier; 2019.
  12. Plourde A. Interferon Gamma Release Assays. Trainee Council in 2019, English.
  13. Pai M, Behr M. Latent Mycobacterium tuberculosis Infection and Interferon-Gamma Release Assays. Microbiol Spectr. 2016;4(5). [Crossref]  [PubMed]
  14. The Texmax Co Ltd. (Cited: 27 Aug 2023) Available from: [Link]
  15. Available from: (Cited: 27 Aug 2023). [Link]
  16. T-SPOT.TB. Package insert. Oxford Immunotec Inc; 2017. Accessed September 20, 2022. [Link]
  17. Slater M, Parsonnet J, Banaei N. Investigation of false-positive results given by the QuantiFERON-TB Gold In-Tube assay. J Clin Microbiol. 2012;50:3105-7. [Crossref]  [PubMed]  [PMC]
  18. Doberne D, Gaur RL, Banaei N. Preanalytical delay reduces sensitivity of QuantiFERON-TB gold in-tube assay for detection of latent tuberculosis infection. J. Clin. Microbiol. 2011;49:3061-4. [Crossref]  [PubMed]  [PMC]
  19. 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. [Crossref]  [PubMed]
  20. Shanaube K, De Haas P, Schaap A, Moyo M, Kosloff B, et al. Intra-assay reliability and robustness of QuantiFERON(R)-TB Gold In-Tube test in Zambia. Int J Tuberc Lung Dis. 2010;14:828-33.
  21. Gaur R, Pai M, Banaei N. Impact of blood volume, tube shaking, and incubation time on reproducibility of QuantiFERON-TB Gold InTube assay. J Clin Microbiol. 2013;51:3521-6. [Crossref]  [PubMed]  [PMC]
  22. Mazurek GH, Whitworth WC, Goodwin DJ. Effect of blood collection time on QuantiFERON-TB Gold In-Tube test variability, p A4735, C61. In Immunodiagnostics for latent tuberculosis infection and tuberculosis. New York, NY: American Thoracic Society; 2012. [Crossref]
  23. Pai M, Denkinger CM, Kik SV, Rangaka MX, Zwerling A, Oxlade O, et al. Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clin Microbiol Rev. 2014;27(1):3-20. [Crossref]  [PubMed]  [PMC]
  24. Franken WP, Thijsen S, Wolterbeek R, Bouwman JJ, el Bannoudi H, et al. 2009. Variation in T-SPOT.TB spot interpretation between independent observers from different laboratories. Clin. Vaccine Immunol. 2009;16:1439-42. [Crossref]  [PubMed]  [PMC]
  25. van Zyl-Smit RN, Pai M, Peprah K, Meldau R, Kieck J, et al. Within-subject variability and boosting of T-cell interferon-gamma responses after tuberculin skin testing. Am J Respir Crit Care Med. 2009;180:49-58. [Crossref]  [PubMed]
  26. Vilaplana C, Ruiz-Manzano J, Gil O, Cuchillo F, Montane E, et al. The tuberculin skin test increases the responses measured by T cell interferon-gamma release assays. Scand J Immunol. 2008;67:610-7. [Crossref]  [PubMed]
  27. Naseer A, Naqvi S, Kampmann B. Evidence for boosting Mycobacterium tuberculosis-specific IFN-gamma responses at 6 weeks following tuberculin skin testing. Eur Respir J. 2007;29:1282-3. [Crossref]  [PubMed]
  28. Choi JC, Shin JW, Kim JY, Park IW, Choi BW, et al. 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;133:1415-20. [Crossref]  [PubMed]
  29. Igari H, Watanabe A, Sato T. Booster phenomenon of QuantiFERON-TB Gold after prior intradermal PPD injection. Int J Tuberc Lung Dis. 2007;11:788-91.
  30. WHO consolidated guidelines on tuberculosis. Module 1: prevention-tuberculosis preventive treatment. 2020
  31. Clifford V, He Y, Zufferey C, Connell T, Curtis N. Interferon gamma release assays for monitoring the response to treatment for tuberculosis: A systematic review. Tuberculosis (Edinb). 2015;95(6):639-50. [Crossref]  [PubMed]
  32. Primaturia C, Reniarti L, Nataprawira HMN. Comparison between the Interferon γ Release Assay-QuantiFERON Gold Plus (QFT-Plus)-and Tuberculin Skin Test (TST) in the Detection of Tuberculosis Infection in Immunocompromised Children. Pulm Med. 2020;2020:7159485. [Crossref]  [PubMed]  [PMC]
  33. Tabatneck ME, He W, Lamb GS, Sun M, Goldmann D, Sabharwal V, et al. Interferon Gamma Release Assay Results and Testing Trends Among Patients Younger Than 2 Years Old at Two US Health Centers. The Pediatric Infectious Disease Journal. 2023;42(3):189-94. [Crossref]  [PubMed]  [PMC]
  34. Turner NA, Ahmed A, Haley CA, Starke JR, Stout JE. Use of Interferon-Gamma Release Assays in Children <2 Years Old. J Pediatric Infect Dis Soc. 2023;12(8):481-5. [Crossref]  [PubMed]
  35. Eber E, Midulla F. ERS Handbook: Pediatric Respiratory Medicine. 2nd ed. 2021. [Crossref]
  36. Kay AW, Islam SM, Wendorf K, Westenhouse J, Barry PM. Interferon-γ Release Assay Performance for Tuberculosis in Childhood. Pediatrics. 2018;141(6):e20173918. [Crossref]  [PubMed]
  37. Gaensbauer J, Gonzales B, Belknap R, Wilson ML, O'Connor ME. Interferon-Gamma Release Assay-Based Screening for Pediatric Latent Tuberculosis Infection in an Urban Primary Care Network. J Pediatr. 2018;200:202-9. [Crossref]  [PubMed]