Tuberc Respir Dis.  2018 Jan;81(1):59-72. 10.4046/trd.2017.0072.

Comparison of Interferon-γ Release Assays and the Tuberculin Skin Test for Diagnosis of Tuberculosis in Human Immunodeficiency Virus: A Systematic Review

• Overton K
• Varma R
• Post JJ

• KMID: 2420592
• DOI: http://doi.org/10.4046/trd.2017.0072

Abstract

BACKGROUND
It remains uncertain if interferon-γ release assays (IGRAs) are superior to the tuberculin skin test (TST) for the diagnosis of active tuberculosis (TB) or latent tuberculosis infection (LTBI) in immunosuppressed populations including people with human immunodeficiency virus (HIV) infection. The purpose of this study was to systematically review the performance of IGRAs and the TST in people with HIV with active TB or LTBI in low and high prevalence TB countries.
METHODS
We searched the MEDLINE database from 1966 through to January 2017 for studies that compared results of the TST with either the commercial QuantiFERON-TB Gold in Tube (QFTGT) assay or previous assay versions, the T-SPOT.TB assay or in-house IGRAs. Data were summarized by TB prevalence. Tests for concordance and differences in proportions were undertaken as appropriate. The variation in study methodology was appraised.
RESULTS
Thirty-two studies including 4,856 HIV subjects met the search criteria. Fourteen studies compared the tests in subjects with LTBI in low TB prevalence settings. The QFTGT had a similar rate of reactivity to the TST, although the first-generation version of that assay was reactive more commonly. IGRAs were more frequently positive than the TST in HIV infected subjects with active TB. There was considerable study methodology and population heterogeneity, and generally low concordance between tests. Both the TST and IGRAs were affected by CD4 T-cell immunodeficiency.
CONCLUSION
Our review of comparative data does not provide robust evidence to support the assertion that the IGRAs are superior to the TST when used in HIV infected subjects to diagnose either active TB or LTBI.

Keyword

Interferon-Gamma Release Assays; Tuberculin Test; HIV Infection; Latent Tuberculosis; Review, Systematic

MeSH Terms

Diagnosis*
HIV Infections
HIV*
Humans*
Interferon-gamma Release Tests
Latent Tuberculosis
Population Characteristics
Prevalence
Skin Tests*
Skin*
T-Lymphocytes
Tuberculin Test
Tuberculin*
Tuberculosis*
Tuberculin

Figure

• 

  Figure 1 Selection and assessment of articles for inclusion in review.

Reference

1. World Health Organization. Global tuberculosis control: WHO report 2011. Geneva: World Health Organization;2011.

2. Targeted tuberculin testing and treatment of latent tuberculosis infection. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. This is a Joint Statement of the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC). This statement was endorsed by the Council of the Infectious Diseases Society of America. (IDSA), September 1999, and the sections of this statement. Am J Respir Crit Care Med. 2000; 161(4 Pt 2):S221–S247. PMID: 10764341.

3. Wang L, Turner MO, Elwood RK, Schulzer M, FitzGerald JM. A meta-analysis of the effect of Bacille Calmette Guerin vaccination on tuberculin skin test measurements. Thorax. 2002; 57:804–809. PMID: 12200526.

4. Telisinghe L, Amofa-Sekyi M, Maluzi K, Kaluba-Milimo D, Cheeba-Lengwe M, Chiwele K, et al. The sensitivity of the QuantiFERON(R)-TB Gold Plus assay in Zambian adults with active tuberculosis. Int J Tuberc Lung Dis. 2017; 21:690–696. PMID: 28482964.

5. Richeldi L. An update on the diagnosis of tuberculosis infection. Am J Respir Crit Care Med. 2006; 174:736–742. PMID: 16799073.

6. Brock I, Ruhwald M, Lundgren B, Westh H, Mathiesen LR, Ravn P. Latent tuberculosis in HIV positive, diagnosed by the M. tuberculosis specific interferon-gamma test. Respir Res. 2006; 7:56. PMID: 16579856.

7. Dheda K, van Zyl Smit R, Badri M, Pai M. T-cell interferon-gamma release assays for the rapid immunodiagnosis of tuberculosis: clinical utility in high-burden vs. low-burden settings. Curr Opin Pulm Med. 2009; 15:188–200. PMID: 19387262.

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; 7:428–438. PMID: 17521596.

9. Mori T. Usefulness of interferon-gamma release assays for diagnosing TB infection and problems with these assays. J Infect Chemother. 2009; 15:143–155. PMID: 19554399.

10. Andersen P, Munk ME, Pollock JM, Doherty TM. Specific immune-based diagnosis of tuberculosis. Lancet. 2000; 356:1099–1104. PMID: 11009160.

11. 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. PMID: 17339619.

12. Diel R, Loddenkemper R, Meywald-Walter K, Niemann S, Nienhaus A. Predictive value of a whole blood IFN-gamma assay for the development of active tuberculosis disease after recent infection with Mycobacterium tuberculosis. Am J Respir Crit Care Med. 2008; 177:1164–1170. PMID: 18276940.

13. Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009; 6:e1000097. PMID: 19621072.

14. Stavri H, Ene L, Popa GL, Duiculescu D, Murgoci G, Marica C, et al. Comparison of tuberculin skin test with a whole-blood interferon gamma assay and ELISA, in HIV positive children and adolescents with TB. Roum Arch Microbiol Immunol. 2009; 68:14–19. PMID: 19507622.

15. Vincenti D, Carrara S, Butera O, Bizzoni F, Casetti R, Girardi E, et al. Response to region of difference 1 (RD1) epitopes in human immunodeficiency virus (HIV)-infected individuals enrolled with suspected active tuberculosis: a pilot study. Clin Exp Immunol. 2007; 150:91–98. PMID: 17680823.

16. Syed Ahamed Kabeer B, Sikhamani R, Swaminathan S, Perumal V, Paramasivam P, Raja A. Role of interferon gamma release assay in active TB diagnosis among HIV infected individuals. PLoS One. 2009; 4:e5718. PMID: 19479058.

17. Idh J, Abate E, Westman A, Elias D, Janols H, Gelaw A, et al. Kinetics of the QuantiFERON-TB Gold In-Tube test during treatment of patients with sputum smear-positive tuberculosis in relation to initial TST result and severity of disease. Scand J Infect Dis. 2010; 42:650–657. PMID: 20465490.

18. Tsiouris SJ, Coetzee D, Toro PL, Austin J, Stein Z, El-Sadr W. Sensitivity analysis and potential uses of a novel gamma interferon release assay for diagnosis of tuberculosis. J Clin Microbiol. 2006; 44:2844–2850. PMID: 16891501.

19. Raby E, Moyo M, Devendra A, Banda J, De Haas P, Ayles H, et al. The effects of HIV on the sensitivity of a whole blood IFN-gamma release assay in Zambian adults with active tuberculosis. PLoS One. 2008; 3:e2489. PMID: 18560573.

20. 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; 364:2196–2203. PMID: 15610806.

21. Jiang W, Shao L, Zhang Y, Zhang S, Meng C, Xu Y, et al. High-sensitive and rapid detection of Mycobacterium tuberculosis infection by IFN-gamma release assay among HIV-infected individuals in BCG-vaccinated area. BMC Immunol. 2009; 10:31. PMID: 19476627.

22. Davies MA, Connell T, Johannisen C, Wood K, Pienaar S, Wilkinson KA, et al. Detection of tuberculosis in HIV-infected children using an enzyme-linked immunospot assay. AIDS. 2009; 23:961–969. PMID: 19287300.

23. Bourgarit A, Baron G, Breton G, Tattevin P, Katlama C, Allavena C, et al. Latent tuberculosis infection screening and 2-year outcome in antiretroviral-naive HIV-infected patients in a low-prevalence country. Ann Am Thorac Soc. 2015; 12:1138–1145. PMID: 26213798.

24. Luetkemeyer AF, Charlebois ED, Flores LL, Bangsberg DR, Deeks SG, Martin JN, et al. Comparison of an interferon-gamma release assay with tuberculin skin testing in HIV-infected individuals. Am J Respir Crit Care Med. 2007; 175:737–742. PMID: 17218620.

25. Jones S, de Gijsel D, Wallach FR, Gurtman AC, Shi Q, Sacks H. Utility of QuantiFERON-TB Gold in-tube testing for latent TB infection in HIV-infected individuals. Int J Tuberc Lung Dis. 2007; 11:1190–1195. PMID: 17958980.

26. Weinfurter P, Blumberg HM, Goldbaum G, Royce R, Pang J, Tapia J, et al. Predictors of discordant tuberculin skin test and QuantiFERON(R)-TB Gold In-Tube results in various high-risk groups. Int J Tuberc Lung Dis. 2011; 15:1056–1061. PMID: 21740668.

27. Talati NJ, Seybold U, Humphrey B, Aina A, Tapia J, Weinfurter P, et al. Poor concordance between interferon-gamma release assays and tuberculin skin tests in diagnosis of latent tuberculosis infection among HIV-infected individuals. BMC Infect Dis. 2009; 9:15. PMID: 19208218.

28. Richeldi L, Losi M, D'Amico R, Luppi M, Ferrari A, Mussini C, et al. Performance of tests for latent tuberculosis in different groups of immunocompromised patients. Chest. 2009; 136:198–204. PMID: 19318676.

29. Latorre I, Martinez-Lacasa X, Font R, Lacoma A, Puig J, Tural C, et al. IFN-gamma response on T-cell based assays in HIV-infected patients for detection of tuberculosis infection. BMC Infect Dis. 2010; 10:348. PMID: 21143955.

30. Santin M, Casas S, Saumoy M, Andreu A, Moure R, Alcaide F, et al. Detection of latent tuberculosis by the tuberculin skin test and a whole-blood interferon-gamma release assay, and the development of active tuberculosis in HIV-seropositive persons. Diagn Microbiol Infect Dis. 2011; 69:59–65. PMID: 21146715.

31. Balcells ME, Perez CM, Chanqueo L, Lasso M, Villanueva M, Espinoza M, et al. A comparative study of two different methods for the detection of latent tuberculosis in HIV-positive individuals in Chile. Int J Infect Dis. 2008; 12:645–652. PMID: 18534887.

32. Stephan C, Wolf T, Goetsch U, Bellinger O, Nisius G, Oremek G, et al. Comparing QuantiFERON-tuberculosis gold, T-SPOT tuberculosis and tuberculin skin test in HIV-infected individuals from a low prevalence tuberculosis country. AIDS. 2008; 22:2471–2479. PMID: 19005270.

33. Hoffmann M, Reichmuth M, Fantelli K, Schoch OD, Fierz W, Furrer H, et al. Conventional tuberculin skin testing versus T-cell-based assays in the diagnosis of latent tuberculosis infection in HIV-positive patients. AIDS. 2007; 21:390–392. PMID: 17255757.

34. Kimura M, Converse PJ, Astemborski J, Rothel JS, Vlahov D, Comstock GW, et al. Comparison between a whole blood interferon-gamma release assay and tuberculin skin testing for the detection of tuberculosis infection among patients at risk for tuberculosis exposure. J Infect Dis. 1999; 179:1297–1300. PMID: 10191241.

35. Converse PJ, Jones SL, Astemborski J, Vlahov D, Graham NM. Comparison of a tuberculin interferon-gamma assay with the tuberculin skin test in high-risk adults: effect of human immunodeficiency virus infection. J Infect Dis. 1997; 176:144–150. PMID: 9207360.

36. Mathad JS, Bhosale R, Balasubramanian U, Kanade S, Mave V, Suryavanshi N, et al. Quantitative IFN-gamma and IL-2 response associated with latent tuberculosis test discordance in HIV-infected pregnant women. Am J Respir Crit Care Med. 2016; 193:1421–1428. PMID: 26765255.

37. Mandalakas AM, Kirchner HL, Walzl G, Gie RP, Schaaf HS, Cotton MF, et al. Optimizing the detection of recent tuberculosis infection in children in a high tuberculosis-HIV burden setting. Am J Respir Crit Care Med. 2015; 191:820–830. PMID: 25622087.

38. Leidl L, Mayanja-Kizza H, Sotgiu G, Baseke J, Ernst M, Hirsch C, et al. Relationship of immunodiagnostic assays for tuberculosis and numbers of circulating CD4+ T-cells in HIV infection. Eur Respir J. 2010; 35:619–626. PMID: 19608590.

39. Rangaka MX, Wilkinson KA, Seldon R, Van Cutsem G, Meintjes GA, Morroni C, et al. Effect of HIV-1 infection on T-Cell-based and skin test detection of tuberculosis infection. Am J Respir Crit Care Med. 2007; 175:514–520. PMID: 17158278.

40. Mandalakas AM, Hesseling AC, Chegou NN, Kirchner HL, Zhu X, Marais BJ, et al. High level of discordant IGRA results in HIV-infected adults and children. Int J Tuberc Lung Dis. 2008; 12:417–423. PMID: 18371268.

41. Baboolal S, Ramoutar D, Akpaka PE. Comparison of the QuantiFERON(R)-TB Gold assay and tuberculin skin test to detect latent tuberculosis infection among target groups in Trinidad & Tobago. Rev Panam Salud Publica. 2010; 28:36–42. PMID: 20857019.

42. Zhang M, Wang H, Liao M, Chen X, Graner M, Zhu X, et al. Diagnosis of latent tuberculosis infection in bacille Calmette-Guerin vaccinated subjects in China by interferon-gamma ELISpot assay. Int J Tuberc Lung Dis. 2010; 14:1556–1563. PMID: 21144240.

43. Mutsvangwa J, Millington KA, Chaka K, Mavhudzi T, Cheung YB, Mason PR, et al. Identifying recent Mycobacterium tuberculosis transmission in the setting of high HIV and TB burden. Thorax. 2010; 65:315–320. PMID: 20388756.

44. Chapman AL, Munkanta M, Wilkinson KA, Pathan AA, Ewer K, Ayles H, et al. Rapid detection of active and latent tuberculosis infection in HIV-positive individuals by enumeration of Mycobacterium tuberculosis-specific T cells. AIDS. 2002; 16:2285–2293. PMID: 12441800.

45. Karam F, Mbow F, Fletcher H, Senghor CS, Coulibaly KD, LeFevre AM, et al. Sensitivity of IFN-gamma release assay to detect latent tuberculosis infection is retained in HIV-infected patients but dependent on HIV/AIDS progression. PLoS One. 2008; 3:e1441. PMID: 18197251.

46. Huang L, Crothers K. HIV-associated opportunistic pneumonias. Respirology. 2009; 14:474–485. PMID: 19645867.

47. Lee MP, Chan JW, Ng KK, Li PC. Clinical manifestations of tuberculosis in HIV-infected patients. Respirology. 2000; 5:423–426. PMID: 11192558.

48. Hill PC, Jackson-Sillah DJ, Fox A, Brookes RH, de Jong BC, Lugos MD, et al. Incidence of tuberculosis and the predictive value of ELISPOT and Mantoux tests in Gambian case contacts. PLoS One. 2008; 3:e1379. PMID: 18167540.

49. Bosshard V, Roux-Lombard P, Perneger T, Metzger M, Vivien R, Rochat T, et al. Do results of the T-SPOT.TB interferon-gamma release assay change after treatment of tuberculosis? Respir Med. 2009; 103:30–34. PMID: 18977647.

50. Ribeiro S, Dooley K, Hackman J, Loredo C, Efron A, Chaisson RE, et al. T-SPOT.TB responses during treatment of pulmonary tuberculosis. BMC Infect Dis. 2009; 9:23. PMID: 19250549.

51. Cobelens F, Borgdorff M. Boosting, BCG, and time of reading in tuberculin skin testing. Lancet. 2001; 358:2014.

52. van Zyl-Smit RN, Zwerling A, Dheda K, Pai M. Within-subject variability of interferon-g assay results for tuberculosis and boosting effect of tuberculin skin testing: a systematic review. PLoS One. 2009; 4:e8517. PMID: 20041113.

53. Cattamanchi A, Ssewenyana I, Davis JL, Huang L, Worodria W, den Boon S, et al. Role of interferon-gamma release assays in the diagnosis of pulmonary tuberculosis in patients with advanced HIV infection. BMC Infect Dis. 2010; 10:75. PMID: 20302657.

54. Dheda K, Chang JS, Breen RA, Haddock JA, Lipman MC, Kim LU, et al. Expression of a novel cytokine, IL-4delta2, in HIV and HIV-tuberculosis co-infection. AIDS. 2005; 19:1601–1606. PMID: 16184029.

55. Chen J, Zhang R, Wang J, Liu L, Zheng Y, Shen Y, et al. Interferon-gamma release assays for the diagnosis of active tuberculosis in HIV-infected patients: a systematic review and metaanalysis. PLoS One. 2011; 6:e26827. PMID: 22069472.

56. Cattamanchi A, Smith R, Steingart KR, Metcalfe JZ, Date A, Coleman C, et al. Interferon-gamma release assays for the diagnosis of latent tuberculosis infection in HIV-infected individuals: a systematic review and meta-analysis. J Acquir Immune Defic Syndr. 2011; 56:230–238. PMID: 21239993.

57. Santin M, Munoz L, Rigau D. Interferon-gamma release assays for the diagnosis of tuberculosis and tuberculosis infection in HIV-infected adults: a systematic review and meta-analysis. PLoS One. 2012; 7:e32482. PMID: 22403663.

58. Ayubi E, Doosti-Irani A, Sanjari Moghaddam A, Sani M, Nazarzadeh M, Mostafavi E. The clinical usefulness of tuberculin skin test versus interferon-gamma release assays for diagnosis of latent tuberculosis in HIV patients: a meta-analysis. PLoS One. 2016; 11:e0161983. PMID: 27622293.