Diagnostic value of T-SPOT.TB and QuantiFERON-TB in adult active tuberculosis: a systematic review_Chinese Journal of Evidence-Based Medicine

Authors：

ZOU Xiaoqing ¹ , YANG Zhengrong ² , ZHANG Lifan ^3,4,5,6 ,  ZHANG Yuelun ^4,6 ,  LIU Xiaoqing ^1,3,4,5,6

1. School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P. R. China;
2. Department of Infectious Diseases, Capital Medical University, Beijing Friendship Hospital, Beijing 100050, P. R. China;
3. Division of Infectious Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, P. R. China;
4. Clinical Epidemiology Unit, International Epidemiology Network, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, P. R. China;
5. Centre for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P. R. China;
6. Medical Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P. R. China;

Corresponding author：

ZHANG Yuelun, Email: yuelunzhang@outlook.com; LIU Xiaoqing, Email: liuxq@pumch.cn

Keywords：

Active tuberculosis; T-SPOT.TB; QFT-GIT; QFT-Plus; Diagnostic accuracy; Systematic review; Meta-analysis

DOI：

10.7507/1672-2531.202208133

Video：

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Objective To systematically review the diagnostic value of T-SPOT.TB and QuantiFERON-TB (QFT-GIT/QFT-Plus) in active tuberculosis (ATB). Methods The PubMed, Web of Science, Cochrane Library, EMbase, CNKI, WanFang Data, and CBM databases were electronically searched to collect diagnostic accuracy studies comparing QFT-GIT/QFT-Plus and T-SPOT.TB for diagnosing ATB from inception to February 8, 2022. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies, then, meta-analysis was performed by using Stata 16.0 software. Results A total of 20 studies were included. The results of meta-analysis showed that the pooled sensitivity of T-SPOT.TB and QFT-GIT were 0.89 (95%CI 0.85 to 0.92) and 0.84 (95%CI 0.79 to 0.89), the pooled specificity were 0.85 (95%CI 0.68 to 0.93) and 0.86 (95%CI 0.72 to 0.94), the area under the curve (AUC) of summary receiver operating characteristic (SROC) were 0.93 (95%CI 0.84 to 0.97) and 0.90 (95%CI 0.56 to 0.99), respectively. The pooled sensitivity of T-SPOT.TB and QFT-Plus were 0.93 (95%CI 0.81 to 0.97) and 0.93 (95%CI 0.89 to 0.96), specificity were 0.99 (95%CI 0.39 to 1.00) and 0.94 (95%CI 0.67 to 0.99), the AUC of SROC were 0.99 (95%CI 0.67 to 1.00) and 0.98 (95%CI 0.65 to 1.00), respectively. Conclusion Both T-SPOT.TB and QFT have high diagnostic accuracy for ATB, and the diagnostic sensitivity of T-SPOT.TB is better than QFT-GIT. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.

Citation： ZOU Xiaoqing, YANG Zhengrong, ZHANG Lifan, ZHANG Yuelun, LIU Xiaoqing. Diagnostic value of T-SPOT.TB and QuantiFERON-TB in adult active tuberculosis: a systematic review. Chinese Journal of Evidence-Based Medicine, 2023, 23(4): 404-409. doi: 10.7507/1672-2531.202208133 Copy

1.	WHO. Global tuberculosis report 2020. Geneva: WHO, 2020.
2.	崔晓敬, 魏栋, 王春雷, 等. 分子生物学和液体培养方法提高综合医院结核病病原学诊断能力的价值. 中国防痨杂志, 2021, 43(2): 143-146.
3.	Zhang L, Zhang Y, Shi X, et al. Utility of T-cell interferon-γ release assays for diagnosing tuberculous serositis: a prospective study in Beijing, China. PLoS One, 2014, 9(1): e85030.
4.	Takwoingi Y, Whitworth H, Rees-Roberts M, et al. Interferon gamma release assays for Diagnostic Evaluation of Active tuberculosis (IDEA): test accuracy study and economic evaluation. Health Technol Assess, 2019, 23(23): 1-152.
5.	Kang WL, Wang GR, Wu MY, et al. Interferon-gamma release assay is not appropriate for the diagnosis of active tuberculosis in high-burden tuberculosis settings: a retrospective multicenter investigation. Chin Med J (Engl), 2018, 131(3): 268-275.
6.	Petruccioli E, Vanini V, Chiacchio T, et al. Analytical evaluation of QuantiFERON- Plus and QuantiFERON- Gold In-tube assays in subjects with or without tuberculosis. Tuberculosis (Edinb), 2017, 106: 38-43.
7.	Shen Y, Qi X, Wu J, et al. Effect of adjusted cut-offs of interferon-γ release assays on diagnosis of tuberculosis in patients with fever of unknown origin. J Clin Tuberc Other Mycobact Dis, 2021, 26: 100290.
8.	Takeda K, Nagai H, Suzukawa M, et al. Comparison of QuantiFERON-TB Gold Plus, QuantiFERON-TB Gold In-Tube, and T-SPOT. TB among patients with tuberculosis. J Infect Chemother, 2020, 26(11): 1205-1212.
9.	曲艳吉, 杨智荣, 孙凤, 等. 偏倚风险评估系列: (六)诊断试验. 中华流行病学杂志, 2018, 39(4): 524-531.
10.	Whitworth HS, Badhan A, Boakye AA, et al. Clinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort study. Lancet Infect Dis, 2019, 19(2): 193-202.
11.	Du F, Xie L, Zhang Y, et al. Prospective comparison of QFT-GIT and T-SPOT. TB assays for diagnosis of active tuberculosis. Sci Rep, 2018, 8(1): 5882.
12.	Takasaki J, Manabe T, Morino E, et al. Sensitivity and specificity of QuantiFERON-TB Gold Plus compared with QuantiFERON-TB Gold In-Tube and T-SPOT. TB on active tuberculosis in Japan. J Infect Chemother, 2018, 24(3): 188-192.
13.	Kobashi Y, Abe M, Mouri K, et al. Usefulness of tuberculin skin test and three interferon-gamma release assays for the differential diagnosis of pulmonary tuberculosis. Intern Med, 2012, 51(10): 1199-1205.
14.	Lai CC, Wang HC. Diagnostic performance of enzyme-linked immunospot assay and whole-blood interferon-γ assay for the diagnosis of extrapulmonary tuberculosis. J Microbiol Immunol Infect, 2011, 44(5): 406-407.
15.	Domínguez J, De Souza-Galvão M, Ruiz-Manzano J, et al. T-cell responses to the Mycobacterium tuberculosis-specific antigens in active tuberculosis patients at the beginning, during, and after antituberculosis treatment. Diagn Microbiol Infect Dis, 2009, 63(1): 43-51.
16.	Chee CB, Gan SH, Khinmar KW, et al. Comparison of sensitivities of two commercial gamma interferon release assays for pulmonary tuberculosis. J Clin Microbiol, 2008, 46(6): 1935-1940.
17.	Domínguez J, Ruiz-Manzano J, De Souza-Galvão M, et al. Comparison of two commercially available gamma interferon blood tests for immunodiagnosis of tuberculosis. Clin Vaccine Immunol, 2008, 15(1): 168-171.
18.	Goletti D, Carrara S, Butera O, et al. Accuracy of immunodiagnostic tests for active tuberculosis using single and combined results: a multicenter TBNET-Study. PLoS One, 2008, 3(10): e3417.
19.	Fukushima K, Kubo T, Akagi K, et al. Clinical evaluation of QuantiFERON®-TB Gold Plus directly compared with QuantiFERON®-TB Gold In-Tube and T-Spot®. TB for active pulmonary tuberculosis in the elderly. J Infect Chemother, 2021, 27(12): 1716-1722.
20.	Theron G, Pooran A, Peter J, et al. Do adjunct tuberculosis tests, when combined with Xpert MTB/RIF, improve accuracy and the cost of diagnosis in a resource-poor setting. Eur Respir J, 2012, 40(1): 161-168.
21.	Kobashi Y. Clinical evaluation of IP-10 and MIG for the diagnosis of active tuberculosis disease. Mycobact Dis, 2015, 5(3): 1-6.
22.	Matsumoto T, Yamazaki T. The evaluation of the utility of QuantiFERON TB-Gold In-Tube; QFT-GIT. Kekkaku: Tuberculosis, 2014, 89(9): 743-755.
23.	Dheda K, van Zyl-Smit RN, Sechi LA, et al. Utility of quantitative T-cell responses versus unstimulated interferon-gamma for the diagnosis of pleural tuberculosis. Eur Respir J, 2009, 34(5): 1118-1126.
24.	Markova YR, Drenska TR. Usefulness of interferon-gamma release assays in the diagnosis of tuberculosis infection in HIV infected patients in Bulgaria. Biotech Equip, 2009, 23(1): 1103-1108.
25.	美朗曲措, 陈民, 黄丽萍, 等. 三种干扰素γ释放试验在不同年龄结核病患者中的应用比较. 医学信息, 2020, 33(18): 164-167.
26.	贾红彦, 潘丽萍, 杨新婷, 等. 两种γ-干扰素释放试验在结核性胸膜炎中的辅助诊断价值. 北京医学, 2018, 40(4): 297-300,385.
27.	Zhang L, Yang Z, Bao X, et al. Comparison of diagnostic accuracy of QuantiFERON-TB Gold Plus and T-SPOT. TB in the diagnosis of active tuberculosis in febrile patients. J Evid Based Med, 2022, 15(2): 97-105.
28.	Qiagen. QuantiFERONw-TB Gold Plus (QFT-Plus) ELISA package insert. Hilden: Qiagen, 2015.
29.	Sester M, Sotgiu G, Lange C, et al. Interferon-γ release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis. Eur Respir J, 2011, 37(1): 100-111.
30.	Chen H, Nakagawa A, Takamori M, et al. Diagnostic accuracy of the interferon-gamma release assay in acquired immunodeficiency syndrome patients with suspected tuberculosis infection: a meta-analysis. Infection, 2022, 50(3): 597-606.
31.	Glas AS, Lijmer JG, Prins MH, et al. The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol, 2003, 56(11): 1129-1135.
32.	Ahn SS, Kim HW, Park Y. Frequency and factors of indeterminate QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold PLUS test results in rheumatic diseases. J Clin Med, 2021, 10(19): 4357.
33.	Pai M, Denkinger CM, Kik SV, et al. Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clin Microbiol Rev, 2014, 27(1): 3-20.
34.	罗卫红, 曹刚, 田斌. 年龄因素对肺结核患者T-SPOT. TB试验灵敏度的影响. 国际检验医学杂志, 2017, 38(18): 2638-2639.
35.	Luo Y, Xue Y, Mao L, et al. Diagnostic value of T-SPOT. TB assay for tuberculous peritonitis: a meta-analysis. Front Med (Lausanne), 2020, 7: 585180.
36.	Huo ZY, Peng L. Accuracy of the interferon-γ release assay for the diagnosis of active tuberculosis among HIV-seropositive individuals: a systematic review and meta-analysis. BMC Infect Dis, 2016, 16: 350.
37.	Sotgiu G, Saderi L, Petruccioli E, et al. QuantiFERON TB Gold Plus for the diagnosis of tuberculosis: a systematic review and meta-analysis. J Infect, 2019, 79(5): 444-453.

1. WHO. Global tuberculosis report 2020. Geneva: WHO, 2020.
2. 崔晓敬, 魏栋, 王春雷, 等. 分子生物学和液体培养方法提高综合医院结核病病原学诊断能力的价值. 中国防痨杂志, 2021, 43(2): 143-146.
3. Zhang L, Zhang Y, Shi X, et al. Utility of T-cell interferon-γ release assays for diagnosing tuberculous serositis: a prospective study in Beijing, China. PLoS One, 2014, 9(1): e85030.
4. Takwoingi Y, Whitworth H, Rees-Roberts M, et al. Interferon gamma release assays for Diagnostic Evaluation of Active tuberculosis (IDEA): test accuracy study and economic evaluation. Health Technol Assess, 2019, 23(23): 1-152.
5. Kang WL, Wang GR, Wu MY, et al. Interferon-gamma release assay is not appropriate for the diagnosis of active tuberculosis in high-burden tuberculosis settings: a retrospective multicenter investigation. Chin Med J (Engl), 2018, 131(3): 268-275.
6. Petruccioli E, Vanini V, Chiacchio T, et al. Analytical evaluation of QuantiFERON- Plus and QuantiFERON- Gold In-tube assays in subjects with or without tuberculosis. Tuberculosis (Edinb), 2017, 106: 38-43.
7. Shen Y, Qi X, Wu J, et al. Effect of adjusted cut-offs of interferon-γ release assays on diagnosis of tuberculosis in patients with fever of unknown origin. J Clin Tuberc Other Mycobact Dis, 2021, 26: 100290.
8. Takeda K, Nagai H, Suzukawa M, et al. Comparison of QuantiFERON-TB Gold Plus, QuantiFERON-TB Gold In-Tube, and T-SPOT. TB among patients with tuberculosis. J Infect Chemother, 2020, 26(11): 1205-1212.
9. 曲艳吉, 杨智荣, 孙凤, 等. 偏倚风险评估系列: (六)诊断试验. 中华流行病学杂志, 2018, 39(4): 524-531.
10. Whitworth HS, Badhan A, Boakye AA, et al. Clinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort study. Lancet Infect Dis, 2019, 19(2): 193-202.
11. Du F, Xie L, Zhang Y, et al. Prospective comparison of QFT-GIT and T-SPOT. TB assays for diagnosis of active tuberculosis. Sci Rep, 2018, 8(1): 5882.
12. Takasaki J, Manabe T, Morino E, et al. Sensitivity and specificity of QuantiFERON-TB Gold Plus compared with QuantiFERON-TB Gold In-Tube and T-SPOT. TB on active tuberculosis in Japan. J Infect Chemother, 2018, 24(3): 188-192.
13. Kobashi Y, Abe M, Mouri K, et al. Usefulness of tuberculin skin test and three interferon-gamma release assays for the differential diagnosis of pulmonary tuberculosis. Intern Med, 2012, 51(10): 1199-1205.
14. Lai CC, Wang HC. Diagnostic performance of enzyme-linked immunospot assay and whole-blood interferon-γ assay for the diagnosis of extrapulmonary tuberculosis. J Microbiol Immunol Infect, 2011, 44(5): 406-407.
15. Domínguez J, De Souza-Galvão M, Ruiz-Manzano J, et al. T-cell responses to the Mycobacterium tuberculosis-specific antigens in active tuberculosis patients at the beginning, during, and after antituberculosis treatment. Diagn Microbiol Infect Dis, 2009, 63(1): 43-51.
16. Chee CB, Gan SH, Khinmar KW, et al. Comparison of sensitivities of two commercial gamma interferon release assays for pulmonary tuberculosis. J Clin Microbiol, 2008, 46(6): 1935-1940.
17. Domínguez J, Ruiz-Manzano J, De Souza-Galvão M, et al. Comparison of two commercially available gamma interferon blood tests for immunodiagnosis of tuberculosis. Clin Vaccine Immunol, 2008, 15(1): 168-171.
18. Goletti D, Carrara S, Butera O, et al. Accuracy of immunodiagnostic tests for active tuberculosis using single and combined results: a multicenter TBNET-Study. PLoS One, 2008, 3(10): e3417.
19. Fukushima K, Kubo T, Akagi K, et al. Clinical evaluation of QuantiFERON®-TB Gold Plus directly compared with QuantiFERON®-TB Gold In-Tube and T-Spot®. TB for active pulmonary tuberculosis in the elderly. J Infect Chemother, 2021, 27(12): 1716-1722.
20. Theron G, Pooran A, Peter J, et al. Do adjunct tuberculosis tests, when combined with Xpert MTB/RIF, improve accuracy and the cost of diagnosis in a resource-poor setting. Eur Respir J, 2012, 40(1): 161-168.
21. Kobashi Y. Clinical evaluation of IP-10 and MIG for the diagnosis of active tuberculosis disease. Mycobact Dis, 2015, 5(3): 1-6.
22. Matsumoto T, Yamazaki T. The evaluation of the utility of QuantiFERON TB-Gold In-Tube; QFT-GIT. Kekkaku: Tuberculosis, 2014, 89(9): 743-755.
23. Dheda K, van Zyl-Smit RN, Sechi LA, et al. Utility of quantitative T-cell responses versus unstimulated interferon-gamma for the diagnosis of pleural tuberculosis. Eur Respir J, 2009, 34(5): 1118-1126.
24. Markova YR, Drenska TR. Usefulness of interferon-gamma release assays in the diagnosis of tuberculosis infection in HIV infected patients in Bulgaria. Biotech Equip, 2009, 23(1): 1103-1108.
25. 美朗曲措, 陈民, 黄丽萍, 等. 三种干扰素γ释放试验在不同年龄结核病患者中的应用比较. 医学信息, 2020, 33(18): 164-167.
26. 贾红彦, 潘丽萍, 杨新婷, 等. 两种γ-干扰素释放试验在结核性胸膜炎中的辅助诊断价值. 北京医学, 2018, 40(4): 297-300,385.
27. Zhang L, Yang Z, Bao X, et al. Comparison of diagnostic accuracy of QuantiFERON-TB Gold Plus and T-SPOT. TB in the diagnosis of active tuberculosis in febrile patients. J Evid Based Med, 2022, 15(2): 97-105.
28. Qiagen. QuantiFERONw-TB Gold Plus (QFT-Plus) ELISA package insert. Hilden: Qiagen, 2015.
29. Sester M, Sotgiu G, Lange C, et al. Interferon-γ release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis. Eur Respir J, 2011, 37(1): 100-111.
30. Chen H, Nakagawa A, Takamori M, et al. Diagnostic accuracy of the interferon-gamma release assay in acquired immunodeficiency syndrome patients with suspected tuberculosis infection: a meta-analysis. Infection, 2022, 50(3): 597-606.
31. Glas AS, Lijmer JG, Prins MH, et al. The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol, 2003, 56(11): 1129-1135.
32. Ahn SS, Kim HW, Park Y. Frequency and factors of indeterminate QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold PLUS test results in rheumatic diseases. J Clin Med, 2021, 10(19): 4357.
33. Pai M, Denkinger CM, Kik SV, et al. Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clin Microbiol Rev, 2014, 27(1): 3-20.
34. 罗卫红, 曹刚, 田斌. 年龄因素对肺结核患者T-SPOT. TB试验灵敏度的影响. 国际检验医学杂志, 2017, 38(18): 2638-2639.
35. Luo Y, Xue Y, Mao L, et al. Diagnostic value of T-SPOT. TB assay for tuberculous peritonitis: a meta-analysis. Front Med (Lausanne), 2020, 7: 585180.
36. Huo ZY, Peng L. Accuracy of the interferon-γ release assay for the diagnosis of active tuberculosis among HIV-seropositive individuals: a systematic review and meta-analysis. BMC Infect Dis, 2016, 16: 350.
37. Sotgiu G, Saderi L, Petruccioli E, et al. QuantiFERON TB Gold Plus for the diagnosis of tuberculosis: a systematic review and meta-analysis. J Infect, 2019, 79(5): 444-453.

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Diagnostic value of T-SPOT.TB and QuantiFERON-TB in adult active tuberculosis: a systematic review

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