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Tagmouti S.,McGill University | Slater M.,Stanford University | Benedetti A.,ll International Tuberculosis Center | Benedetti A.,Montreal Chest Institute | And 11 more authors.
Annals of the American Thoracic Society | Year: 2014

Rationale: Interferon gamma (IFN-γ) release assays for latent tuberculosis infection result in a larger-than-expected number of conversions and reversions in occupational screening programs, and reproducibility of test results is a concern. Objectives: Knowledge of the relative contribution and extent of the individual sources of variability (immunological, preanalytical, or analytical) could help optimize testing protocols. Methods: We performed a systematic review of studies published by October 2013 on all potential sources of variability of commercial IFN-γ release assays (QuantiFERON-TB Gold In-Tube and T-SPOT.TB). The included studies assessed test variability under identical conditions and under different conditions (the latter both overall and stratified by individual sources of variability). Linear mixed effects models were used to estimate within-subject SD. Measurements and Main Results: We identified a total of 26 articles, including 7 studies analyzing variability under the same conditions, 10 studies analyzing variability with repeat testing over time under different conditions, and 19 studies reporting individual sources of variability. Most data were on QuantiFERON (only three studies on T-SPOT.TB). A considerable number of conversions and reversions were seen around the manufacturer-recommended cut-point. The estimated range of variability of IFN-γ response in QuantiFERON under identical conditions was ±0.47 IU/ml (coefficient of variation, 13%) and ±0.26 IU/ml (30%) for individuals with an initial IFN-γ response in the borderline range (0.25-0.80 IU/ml). The estimated range of variability in noncontrolled settings was substantially larger (±1.4 IU/ml; 60%). Blood volume inoculated into QuantiFERON tubes and preanalytic delay were identified as key sources of variability. Conclusions: This systematic review shows substantial variability with repeat IFN-γ release assays testing even under identical conditions, suggesting that reversions and conversions around the existing cut-point should be interpreted with caution. Copyright © 2014 by the American Thoracic Society


Fox G.J.,McGill University | Fox G.J.,ll International Tuberculosis Center | Lee R.S.,ll International Tuberculosis Center | Lee R.S.,McGill University | And 12 more authors.
Annals of the American Thoracic Society | Year: 2015

Background: Tuberculosis predominantly affects socioeconomically disadvantaged communities. The extent to which specific dietary and lifestyle factors contribute to tuberculosis susceptibility has not been established. Methods: A total of 200 residents of a village in Northern Quebec were investigated during a tuberculosis outbreak and identified to have active tuberculosis, latent tuberculosis infection, or neither. Participants completed questionnaires about their intake of food from traditional and commercial sources, and provided blood samples. Adults were asked about recent smoking and drug and alcohol intake. Nutritional adequacy was evaluated with reference to North American standards. Multiple dietary, lifestyle, andhousing factorswere combinedina logistic regression model evaluating the contributions of each to disease and infection. Findings: After adjusting for potential confounding, new infection was associated with inadequate intake of fruit and vegetables (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.03-4.3), carbohydrates (OR, 4.4; 95% CI, 1.2-16.3), and certain vitamins and minerals. A multivariable model, combining nutrition, housing, and lifestyle factors, found associations between new infection and inadequate fruit and vegetable intake (OR, 2.3; 95% CI, 1.0-5.1), living in the same house as a person with smear-positive tuberculosis (OR, 14.7; 95% CI, 1.6-137.3), and visiting a community gathering house (OR, 3.7; 95% CI, 1.7-8.3). Current smoking was associated with new infection (OR, 9.4; 95% CI, 1.2-72) among adults completing a detailed lifestyle survey. Interpretation: Inadequate nutrition was associated with increased susceptibility to infection, but not active tuberculosis. Interventions addressed at improving nutrition may reduce susceptibility to infection in settings where access to healthy foods is limited. Copyright © 2015 by the American Thoracic Society.

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