Chest
Volume 137, Issue 4, April 2010, Pages 952-968
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Special Feature
Evidence-Based Comparison of Commercial Interferon-γ Release Assays for Detecting Active TB: A Metaanalysis

https://doi.org/10.1378/chest.09-2350Get rights and content

Test accuracy of interferon-γ release assays (IGRAs) for diagnosing TB differs when using older or precommercial tools and inconsistent diagnostic criteria. This metaanalysis critically appraises studies investigating sensitivity and specificity of the commercial T-Spot.TB and the QuantiFERON-TB Gold In-Tube Assay (QFT-IT) among definitely confirmed TB cases. We searched Medline, EMBASE, and Cochrane bibliographies of relevant articles. Sensitivities, specificities, and indeterminate rates were pooled using a fixed effect model. Sensitivity of the tuberculin skin test (TST) was evaluated in the context of IGRA studies. In addition, the rates of indeterminates of both IGRAs were assessed. The pooled sensitivity of TST was 70% (95% CI, 0.67-0.72) compared with 81% (95% CI, 0.78-0.83) for the QFT-IT and 88% (95% CI, 0.85-0.90) for the T-Spot.TB. Sensitivity increased to 84% (95%CI, 0.81-0.87) and 89% (95% CI, 0.86-0.91) for the QFT-IT and T-Spot.TB, respectively, when restricted to performance in developed countries. In contrast, specificity of the QFT-IT was 99% (95% CI, 0.98-1.00) vs 86% for the T-Spot.TB (95% CI, 0.81-0.90). The pooled rate of indeterminate results was low, 2.1% (95% CI, 0.02-0.023) for the QFT-IT and 3.8% (95% CI, 0.035-0.042) for the T-Spot.TB, increasing to 4.4% (95% CI, 0.039-0.05) and 6.1% (95% CI, 0.052-0.071), respectively, among immunosuppressed hosts. The newest commercial IGRAs are superior, in comparison with the TST, for detecting confirmed active TB disease, especially when performed in developed countries.

Section snippets

Inclusion and Exclusion Criteria

Search methods for identification of studies, data collection and analysis, as well as statistical analysis were performed as described in the online supplement. Studies were identified as potentially relevant as outlined in the “Search Methods” section. From these, original articles or letters to the editor were selected if they met the following selection criteria:

  • Studies had to present original data and to have followed a study design allowing data comparison; case reports,

Results

As shown in Figure 1, a total of 679 English and non-English articles were obtained through database searching, and of these, 124 publications were eligible for inclusion. Of the 124 studies, 40 reported sensitivity of any of the three screening tests, a further seven (of these five also included in the studies reporting sensitivity) investigated specificity of IGRAs, and a total of 116 studies (of these 82 additional studies unrelated to sensitivity or specificity) provided data on

Discussion

Until new biomarkers are found to establish a gold standard for latent TB, active TB has to be used as a surrogate for latent TB infection (LTBI). Although the superiority of IGRAs over TST for detecting LTBI seems likely,132 conclusions made to date have not been based on a rigorous comparison of confirmed TB cases. The early metaanalysis of Pai and colleagues1 took in studies from the limited literature available at that time that used different definitions of the presence of active TB

Conclusions

Our metaanalysis of the existing literature has produced results showing that IGRAs are superior to the TST for detecting confirmed active TB disease, irrespective of the degree of economic resources of the particular setting. This advantage appeared even greater for both QFT-IT and the T-Spot.TB when they were performed in developed countries. Although basic sensitivity of the T-Spot is consistently higher than that of the QFT-IT, its specificity is comparatively very low. Our review

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Diel received €1,000 for speaking at a conference sponsored by Cellestis and €750 for speaking at a conference sponsored by Oxford Immunotec. Drs Loddenkemper and Nienhaus have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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