Body Mass Index and Incident Tuberculosis in Close Tuberculosis Contacts

Abstract Background Approximately 95% of people 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 patients were enrolled in a prospective multi-center cohort study (RePORT-Brazil) from 2015-2019 and followed for 24 months. Empirical review and LASSO regression, using baseline clinical and laboratory information, were used as dimension reduction techniques 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 patients, 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)=16.55, 95% confidence interval (CI): 2.22-124.45]. Internal validation with all contacts yielded an area under the ROC curve of 0.80 [95%CI: 0.72-0.86]. 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=0.89, 95%CI: 0.80-0.99). IGRA-positive contacts with BMI <25 kg/m2 had a 4.14-fold (95%CI: 1.17-14.67) higher risk of progression to TB than IGRA-positive contacts with BMI ≥25 kg/m2: 8.4% vs. 2.1%, respectively. Conclusions BMI <25 kg/m2, a readily available biomarker, identified IGRA-positive close TB contacts at high risk of progressing to TB disease. Prioritizing this high-risk group for TB preventive therapy could improve TB prevention efforts.