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Original Research |

Predictive Value of Interferon-γ Release Assays and Tuberculin Skin Testing for Progression From Latent TB Infection to Disease StatePredictive Value of Interferon-03B3 Release Assays: A Meta-analysis

Roland Diel, MD, MPH; Robert Loddenkemper, MD, FCCP; Albert Nienhaus, MD, MPH
Author and Funding Information

From the Department of Pulmonary Medicine (Dr Diel), Medical School Hannover (MHH), Hannover; The German Central Committee Against Tuberculosis (Dr Loddenkemper), Berlin; and University Medical Center Hamburg-Eppendorf (Dr Nienhaus), Institute for Health Service Research in Dermatology and Nursing, Hamburg, Germany.

Correspondence to: Roland Diel, MD, MPH, Department of Pulmonary Medicine, Medical School Hannover (MHH), Carl-Neuberg-Straße 1, 30625 Hannover, Germany; e-mail: Diel.Roland@mh-hannover.de

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Diel has received travel reimbursement and/or fees for speaking at symposia sponsored by Cellestis Ltd, Oxford Immunotec Ltd, and Pharmore Ltd (exclusive supplier of Tuberculin RT23 for Germany). 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.

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


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

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(1):63-75. doi:10.1378/chest.11-3157
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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.

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