TY - JOUR
T1 - Discovery and validation of a personalized risk predictor for incident tuberculosis in low transmission settings
AU - Gupta, Rishi K.
AU - Calderwood, Claire J.
AU - Yavlinsky, Alexei
AU - Krutikov, Maria
AU - Quartagno, Matteo
AU - Aichelburg, Maximilian C.
AU - Altet, Neus
AU - Diel, Roland
AU - Dobler, Claudia C.
AU - Dominguez, Jose
AU - Doyle, Joseph S.
AU - Erkens, Connie
AU - Geis, Steffen
AU - Haldar, Pranabashis
AU - Hauri, Anja M.
AU - Hermansen, Thomas
AU - Johnston, James C.
AU - Lange, Christoph
AU - Lange, Berit
AU - van Leth, Frank
AU - Muñoz, Laura
AU - Roder, Christine
AU - Romanowski, Kamila
AU - Roth, David
AU - Sester, Martina
AU - Sloot, Rosa
AU - Sotgiu, Giovanni
AU - Woltmann, Gerrit
AU - Yoshiyama, Takashi
AU - Zellweger, Jean Pierre
AU - Zenner, Dominik
AU - Aldridge, Robert W.
AU - Copas, Andrew
AU - Rangaka, Molebogeng X.
AU - Lipman, Marc
AU - Noursadeghi, Mahdad
AU - Abubakar, Ibrahim
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85092704345&partnerID=8YFLogxK
U2 - 10.1038/s41591-020-1076-0
DO - 10.1038/s41591-020-1076-0
M3 - Article
C2 - 33077958
AN - SCOPUS:85092704345
SN - 1078-8956
VL - 26
SP - 1941
EP - 1949
JO - Nature Medicine
JF - Nature Medicine
IS - 12
ER -
