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Discovery and validation of a personalised risk predictor for incident tuberculosis in low transmission settings

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posted on 17.09.2020, 13:54 by Pranabashis Haldar, Claire J. Calderwood, Alexei YavlinskyAlexei Yavlinsky, Maria KrutikovMaria Krutikov, Matteo QuartagnoMatteo Quartagno, Maximilian C. Aichelburg, Neus Altet, Roland Diel, Claudia C. Dobler, Jose Domínguez, Joseph S. Doyle, Connie Erkens, Steffen Geis, Anja M. Hauri, Thomas Hermansen, James C. Johnston, Christoph Lange, Berit Lange, Frank van LethFrank van Leth, Laura Muñoz, Christine Roder, Kamila Romanowski, David Roth, Martina Sester, Rosa Sloot, Giovanni Sotgiu, Gerrit Woltmann, Takashi Yoshiyama, Jean-Pierre Zellweger, Dominik Zenner, Robert W. Aldridge, Andrew CopasAndrew Copas, Molebogeng X. Rangaka, Marc LipmanMarc Lipman, Mahdad NoursadeghiMahdad Noursadeghi, Ibrahim AbubakarIbrahim Abubakar
The risk of tuberculosis (TB) is variable among individuals with latent Mycobacterium tuberculosis infection (LTBI), but validated estimates of personalized risk are lacking. In pooled data from 18 systematically identified cohort studies from 20 countries, including 80,468 individuals tested for LTBI, 5-year cumulative incident TB risk among people with untreated LTBI was 15.6% (95% confidence interval (CI), 8.0–29.2%) among child contacts, 4.8% (95% CI, 3.0–7.7%) among adult contacts, 5.0% (95% CI, 1.6–14.5%) among migrants and 4.8% (95% CI, 1.5–14.3%) among immunocompromised groups. We confirmed highly variable estimates within risk groups, necessitating an individualized approach to risk stratification. Therefore, we developed a personalized risk predictor for incident TB (PERISKOPE-TB) that combines a quantitative measure of T cell sensitization and clinical covariates. Internal–external cross-validation of the model demonstrated a random effects meta-analysis C-statistic of 0.88 (95% CI, 0.82–0.93) for incident TB. In decision curve analysis, the model demonstrated clinical utility for targeting preventative treatment, compared to treating all, or no, people with LTBI. We challenge the current crude approach to TB risk estimation among people with LTBI in favor of our evidence-based and patient-centered method, in settings aiming for pre-elimination worldwide.



Nature Medicine, volume 26, pages 1941–1949 (2020)

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Respiratory Biomedical Research Centre, Institute for Lung Health, Department of Respiratory 54 Sciences, University of Leicester


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