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

Tananchai Petnak; Dararat Eksombatchai; Supavit Chesdachai; Ploypin Lertjitbanjong; Pahnwat Taweesedt; Angsupat Pornchai; Charat Thongprayoon; Larry J Prokop; Zhen Wang

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

BMC Pulm Med. 2022 Jun 6;22(1):219. doi: 10.1186/s12890-022-02013-y.

Authors

Affiliations

¹ Division of Pulmonary and Pulmonary Critical Care Medicine, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Ramathibodi Hospital, Rama VI Road, Ratchathewi, Bangkok, 10400, Thailand.
² Division of Pulmonary and Pulmonary Critical Care Medicine, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Ramathibodi Hospital, Rama VI Road, Ratchathewi, Bangkok, 10400, Thailand. Dararat.eks@mahidol.ac.th.
³ Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
⁴ Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
⁵ Department of Pulmonary Medicine, Corpus Christi Medical Center, Corpus Christi, TX, USA.
⁶ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
⁷ Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
⁸ Mayo Clinic Libraries, Mayo Clinic, Rochester, MN, USA.
⁹ The Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA.
¹⁰ Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN, USA.

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.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Humans
Interferon-gamma Release Tests / methods
ROC Curve
Sensitivity and Specificity
Tuberculin Test
Tuberculosis* / diagnosis
Tuberculosis, Pulmonary* / diagnosis