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System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis
Published on: April 5, 2017
Screening of tuberculosis before biologics
N Mrozek1, B Pereira, M Soubrier
1Service maladies infectieuses, hôpital G Montpied, Clermont-Ferrand, France.
Using anti-TNF has significantly improved the management of chronic inflammatory rheumatism. However, there is clear evidence that this treatment increases the risk of reactivating tuberculosis. The intradermal tuberculin skin test (ITT) and interferon-γ-release assays (IGRAs) are currently used to detect latent tuberculosis infection. The results of ITT are difficult to analyze in patients vaccinated with Bacille Calmette-Guérin (BCG) and because of variation in test administration and reading. Numerous authors have compared the sensitivity and specificity of IGRA and ITT, including in two recent meta-analyses and one literature review. These authors, however, compared different populations with different ITT positive thresholds (5, 10, and 15mm). We performed a meta-analysis of studies in which the threshold was 15mm, the recommended level in France. The sensitivity of QuantiFERON, T-spot, and ITT was 79% (IC 76%-83%), 84% (IC 75%-95%), and 69% (IC 65%-73%), respectively. In France, it is recommended to detect latent tuberculosis infection on the basis of history taking, physical examination, 5-unit ITT, and lung X-ray. This screening leads to treating 20%-30% of patients, with considerable adverse-effects. Because of the sensitivity and specificity of IGRAs, it is no longer justified to systematically perform TST for detection of tuberculosis before initiating anti-TNF treatment.
Using anti-TNF has significantly improved the management of chronic inflammatory rheumatism. However, there is clear evidence that this treatment increases the risk of reactivating tuberculosis. The intradermal tuberculin skin test (ITT) and interferon-γ-release assays (IGRAs) are currently used to detect latent tuberculosis infection. The results of ITT are difficult to analyze in patients vaccinated with Bacille Calmette-Guérin (BCG) and because of variation in test administration and reading. Numerous authors have compared the sensitivity and specificity of IGRA and ITT, including in two recent meta-analyses and one literature review. These authors, however, compared different populations with different ITT positive thresholds (5, 10, and 15mm). We performed a meta-analysis of studies in which the threshold was 15mm, the recommended level in France. The sensitivity of QuantiFERON, T-spot, and ITT was 79% (IC 76%-83%), 84% (IC 75%-95%), and 69% (IC 65%-73%), respectively. In France, it is recommended to detect latent tuberculosis infection on the basis of history taking, physical examination, 5-unit ITT, and lung X-ray. This screening leads to treating 20%-30% of patients, with considerable adverse-effects. Because of the sensitivity and specificity of IGRAs, it is no longer justified to systematically perform TST for detection of tuberculosis before initiating anti-TNF treatment.
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