Abstract
BACKGROUND: Approximately 95% of persons infected with M. tuberculosis do not progress to tuberculosis (TB) disease. Identifying key determinants of TB progression could focus prevention efforts. METHODS: Contacts of pulmonary TB cases were enrolled in a prospective multi-center cohort study (RePORT-Brazil) from 2015-2019 and followed for 24 months. Dimension reduction techniques included empirical review and LASSO regression, using clinical and laboratory information at baseline, to determine factors for inclusion in prediction models. Models were created for: 1) all contacts, 2) contacts IGRA-positive at baseline, and 3) IGRA-positive contacts who did not receive TB preventive therapy (TPT; <30 days isoniazid). Internal validation was performed using bootstrapping. RESULTS: Among 1846 contacts of 619 TB index cases, 25 (1.4%) progressed to TB. No TPT was a risk factor for progression to TB among all contacts [mixed-effects adjusted hazard ratio (aHR): 11.79 (95% confidence interval (CI): 1.55-89.77). Internal validation of the model with all contacts estimated an area under the ROC curve: 0.85 [95%CI: 0.78-0.91]. Body mass index (BMI) was inversely associated with increased risk of progressing to active TB among IGRA-positive contacts who did not receive TPT (aHR): 0.87 (95%CI:0.78-0.98); IGRA-positive contacts with BMI<25 kg/m (2) had 4.14-fold (95%CI:1.17-14.67) higher risk of progression to TB than IGRA-positive contacts with BMI ≥25 kg/m (2) ; TB risk was 8.4% vs. 2.1%, respectively. CONCLUSIONS: BMI<25 kg/m (2) , an easily obtained biomarker, identified IGRA-positive close TB contacts at high risk of progressing to TB disease. TPT should be targeted to this high-risk group to maximize TB prevention.