Interferon-γ release assays for active pulmonary tuberculosis diagnosis in adults in low- and middle-income countries: systematic review and meta-analysis

Abstract

Background: The diagnostic value of interferon-γ release assays (IGRAs) for active tuberculosis in low- and middle-income countries is unclear.

Methods: We searched multiple databases for studies published through May 2010 that evaluated the diagnostic performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB (T-SPOT) among adults with suspected active pulmonary tuberculosis or patients with confirmed cases in low- and middle-income countries. We summarized test performance characteristics with use of forest plots, hierarchical summary receiver operating characteristic (HSROC) curves, and bivariate random effects models.

Results: Our search identified 789 citations, of which 27 observational studies (17 QFT-GIT and 10 T-SPOT) evaluating 590 human immunodeficiency virus (HIV)-uninfected and 844 HIV-infected individuals met inclusion criteria. Among HIV-infected patients, HSROC/bivariate pooled sensitivity estimates (highest quality data) were 76% (95% confidence interval [CI], 45%-92%) for T-SPOT and 60% (95% CI, 34%-82%) for QFT-GIT. HSROC/bivariate pooled specificity estimates were low for both IGRA platforms among all participants (T-SPOT, 61% [95% CI, 40%-79%]; QFT-GIT, 52% [95% CI, 41%-62%]) and among HIV-infected persons (T-SPOT, 52% [95% CI, 40%-63%]; QFT-GIT, 50% [95% CI, 35%-65%]). There was no consistent evidence that either IGRA was more sensitive than the tuberculin skin test for active tuberculosis diagnosis.

Conclusions: In low- and middle-income countries, neither the tuberculin skin test nor IGRAs have value for active tuberculosis diagnosis in adults, especially in the context of HIV coinfection.

Figure 1.

Study selection. IGRA, interferon-γ release assay; LTBI, latent tuberculosis infection.

Figure 2.

Assessment of study quality with use of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. For each QUADAS item, 2 reviewers independently determined whether a study met the quality criterion or whether it was unclear.

Figure 3.

A and B, Hierarchical summary receiver operating characteristic (HSROC) plot of studies that reported both sensitivity and specificity among persons with suspected active tuberculosis. The summary curves from the HSROC model contain a summary operating point (red square) representing summarized sensitivity and specificity point estimates for individual study estimates (open circles). The 95% confidence region is delineated by the area in the orange dashed line.

Figure 4.

Sensitivity of QuantiFERON-TB Gold In-Tube and T-SPOT.TB in human immunodeficiency virus (HIV)–infected persons with confirmed active tuberculosis in low- and middle-income countries. The forest plots display the sensitivity estimates obtained from individual studies and pooled estimates derived from random effects (DerSimonian–Laird) modeling.

Figure 5.

Sensitivity of QuantiFERON-TB Gold In-Tube and T-SPOT.TB among human immunodeficiency virus (HIV)–uninfected persons with confirmed active tuberculosis in low- and middle-income countries. The forest plots show the sensitivity estimates obtained from individual studies and pooled estimates derived from random effects (DerSimonian–Laird) modeling.

Figure 6.

Sensitivity difference between interferon-γ release assay (IGRA) and tuberculin skin test (TST) results. The forest plots display percent differences (IGRA sensitivity–TST sensitivity) for confirmed active pulmonary tuberculosis in individual studies and pooled estimates derived from random effects (DerSimonian–Laird) modeling. *Studies involving human immunodeficiency virus (HIV)–infected patients.