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

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

Association between current smoking of people with TB and the same in their household members.

Association between current smoking of people with TB and the same in their household members.</p

Association between alcohol drinking of people with TB and the same in their household members.

Association between alcohol drinking of people with TB and the same in their household members.</p

BMI in members of households with TB compared to those without TB.

BMI in members of households with TB compared to those without TB.</p

Sensitivity analysis- the association between any alcohol drinking and TB status.

Sensitivity analysis- the association between any alcohol drinking and TB status.</p

Alcohol drinking twice per week or more in members of households with TB compared to those without TB.

Alcohol drinking twice per week or more in members of households with TB compared to those without TB.</p

Sensitivity analysis- prevalence of NCD/NCD risk factors in members of households with TB compared to those without TB.

Sensitivity analysis- prevalence of NCD/NCD risk factors in members of households with TB compared to those without TB.</p

Sensitivity analysis-impact of misclassification of diabetes on its association with members of households with TB.

Sensitivity analysis-impact of misclassification of diabetes on its association with members of households with TB.</p

Association between hypertension of people with TB and the same in their household members.

Association between hypertension of people with TB and the same in their household members.</p

PRISMA-IPD checklist of items to include when reporting a systematic review and meta-analysis of individual participant data (IPD).

PRISMA-IPD checklist of items to include when reporting a systematic review and meta-analysis of individual participant data (IPD).</p