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Meta-Analysis
. 2022 Jun 6;22(1):219.
doi: 10.1186/s12890-022-02013-y.

Diagnostic accuracy of interferon-gamma release assays for diagnosis of smear-negative pulmonary tuberculosis: a systematic review and meta-analysis

Affiliations
Meta-Analysis

Diagnostic accuracy of interferon-gamma release assays for diagnosis of smear-negative pulmonary tuberculosis: a systematic review and meta-analysis

Tananchai Petnak et al. BMC Pulm Med. .

Abstract

Introduction: The diagnosis of smear-negative pulmonary tuberculosis (SNPTB) is challenging. Interferon gamma-release assays (IGRAs) may be helpful in early diagnosis among these patients resulting in prompt treatment and favorable outcomes.

Methods: We performed a comprehensive search from each databases' inception to April 5, 2021. The studies that provided sufficient data regarding the sensitivity and specificity of IGRAs included QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB, or QuantiFERON-TB Gold Plus for diagnosis of SNPTB were included.

Results: Of 1,312 studies screened, 16 studies were included; 11 QFT-GIT, 2 T-SPOT.TB, and 3 QFT-GIT and T-SPOT.TB. For diagnosis of SNPTB, QFT-GIT had sensitivity of 0.77 (95% CI 0.71-0.82), specificity of 0.70 (95% CI 0.58-0.80), diagnostic odds ratio (DOR) of 8.03 (95% CI 4.51-14.31), positive likelihood ratio (LR) of 2.61 (95% CI 1.80-3.80), negative LR of 0.33 (95% CI 0.25-0.42), and area under receiver operating characteristic (AUROC) of 0.81 (95% CI 0.77-0.84). T-SPOT.TB had sensitivity of 0.74 (95% CI 0.71-0.78), specificity of 0.71 (95% CI 0.49-0.86), DOR of 6.96 (95% CI 2.31-20.98), positive LR of 2.53 (95% CI 1.26-5.07), negative LR of 0.36 (95% CI 0.24-0.55), and AUROC of 0.77 (95% CI 0.73-0.80). The specificity seemed lower in the subgroup analyses of studies from high tuberculosis burden counties compared to the studies from low tuberculosis burden.

Conclusion: IGRAs do have insufficient diagnostic performance for SNPTB. However, the tests are still helpful to exclude tuberculosis among patients with low pre-test probability. Registry: PROSPERO: CRD42021274653.

Keywords: Diagnosis; Interferon-gamma release assays; Meta-analysis; Sensitivity; Smear-negative; Specificity; Tuberculosis.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study selection
Fig. 2
Fig. 2
Summary of assessment of study quality using QUADAS-2 tool stratified by each QUADAS-2 item
Fig. 3
Fig. 3
Hierarchical summary receiver operating characteristic (HSROC) plots demonstrate summary operating point (red square), 95% confidence interval (yellow dash line) and HSROC curve (green solid line) of A QuantiFERON-TB Gold In-Tube and B T-SPOT.TB for diagnosis of smear-negative pulmonary tuberculosis. Open circles represent individual study included in the meta-analysis, with circle size representing the sample size in each study

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References

    1. Global tuberculosis report 2021. https://www.who.int/teams/global-tuberculosis-programme/tb-reports/globa....
    1. Cattamanchi A, Ssewenyana I, Davis JL, Huang L, Worodria W, den Boon S, Yoo S, Andama A, Hopewell PC, Cao H. Role of interferon-gamma release assays in the diagnosis of pulmonary tuberculosis in patients with advanced HIV infection. BMC Infect Dis. 2010;10:75. doi: 10.1186/1471-2334-10-75. - DOI - PMC - PubMed
    1. Syed Ahamed Kabeer B, Raman B, Thomas A, Perumal V, Raja A. Role of QuantiFERON-TB gold, interferon gamma inducible protein-10 and tuberculin skin test in active tuberculosis diagnosis. PLoS ONE. 2010;5(2):e9051. doi: 10.1371/journal.pone.0009051. - DOI - PMC - PubMed
    1. Lui G, Lee N, Cheung SW, Lam JSY, Wong BCK, Choi KW, Wong KT, Wong RYK, Cockram CS, Hui DSC, et al. Interferon gamma release assay for differentiating tuberculosis among pneumonia cases in acute healthcare setting. J Infect. 2011;62(6):440–447. doi: 10.1016/j.jinf.2011.04.011. - DOI - PubMed
    1. Taki-Eddin L, Monem F. Utility of an interferon-gamma release assay as a potential diagnostic aid for active pulmonary tuberculosis. J Infect Dev Ctries. 2012;6(1):67–72. doi: 10.3855/jidc.2098. - DOI - PubMed