Chest
Volume 142, Issue 1, July 2012, Pages 63-75
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Original Research
Chest Infections
Predictive Value of Interferon-γ Release Assays and Tuberculin Skin Testing for Progression From Latent TB Infection to Disease State

https://doi.org/10.1378/chest.11-3157Get rights and content

Background

Given the current lack of effective vaccines against TB, the accuracy of screening tests for determining or excluding latent TB infection (LTBI) is decisive in effective TB control. This meta-analysis critically appraises studies investigating the positive and the negative predictive value (PPV and NPV, respectively) from a test-determined LTBI state for progression to active TB of interferon-γ release assays (IGRAs) and the tuberculin skin test (TST).

Methods

We searched MEDLINE, EMBASE, and Cochrane bibliographies for relevant articles. After qualitative evaluation, the PPV and NPV for progression of commercial and “in-house” IGRAs and the TST for persons not receiving preventive treatment in the context of the respective IGRA studies were pooled using both a fixed and a random-effect model. Weighted rates were calculated for all study populations and for groups solely at high risk of TB development.

Results

The pooled PPV for progression for all studies using commercial IGRAs was 2.7% (95% CI, 2.3%–3.2%) compared with 1.5% (95% CI, 1.2%–1.7%) for the TST (P < .0001). PPV increased to 6.8% (95% CI, 5.6%–8.3%) and 2.4% (95% CI, 1.9%–2.9%) for the IGRAs and the TST, respectively, when only high-risk groups were considered (P < .0001). Pooled values of NPV for progression for both IGRAs and the TST were very high, at 99.7% (95% CI, 99.5%–99.8%) and 99.4% (95% CI, 99.2%–99.5%), respectively, although they were significantly higher for IGRAs (P < .01).

Conclusions

Commercial IGRAs have a higher PPV and NPV for progression to active TB compared with those of the TST, especially when performed in high-risk persons.

Section snippets

Search Methods for Identification of Studies

Original articles, letters to the editor, and published abstracts were identified by computerized searches of MEDLINE (up to October 10, 2011), EMBASE (up to October 10, 2011), and the Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane Library 2009, issue 3), combining the search terms used in a previous meta-analysis.5 No restrictions were made with respect to language or basic study design (prospective or retrospective), determination of predictive values not being the main

Results

As shown in Figure 1, a total of 241 papers were obtained through database searching and, of these, 28 publications were finally eligible for inclusion in this review: 18 for the TST, 23 for commercial, and five for “in-house” IGRAs (Table 1). In two studies,13, 14 more than one IGRA had been performed. Accordingly, results of both tests were analyzed. Five studies used “in-house” tests,15, 16, 17, 18, 19 four QFT-G,13, 20, 21, 22 14 QFT-GIT,14, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35

Discussion

In our meta-analysis, we included 28 studies with totals of 1,225, 5,194, and 8,479 subjects tested by “in-house” IGRAs, commercial IGRAs, and the TST, respectively, to calculate a pooled value for PPV for progression, and totals of 2,009, 12,154, and 8,618 subjects, respectively, to calculate an NPV. The IGRAs showed a significantly higher PPV than did the TST, especially when using commercially available IGRAs. PPV for progression largely depends on specificity, and only truly infected

Conclusions

In conclusion, positive test results of both commercial and “in-house” IGRAs have a higher PPV for progression to active TB than do those of the TST. Pooled NPVs for progression to exclude LTBI are very high for both IGRAs and TST, although the commercial IGRAs show a small, but statistically significant, superiority. Progression rates for commercial IGRAs are remarkably higher than those for the TST, but remain low in absolute numbers. Data suggest that IGRAs provide significant benefits over

Acknowledgments

Author contributions:Dr Diel: contributed to the article concept, statistical analysis, and drafting of the manuscript.

Dr Loddenkemper: contributed to the article concept, design of the study, and drafting of the manuscript.

Dr Nienhaus: contributed to the article concept, design of the study, acquisition and selection of data, and drafting of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Diel has received travel

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    Funding/Support: The authors have reported to CHEST that no funding was received for this study.

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