Inflammasome Genetics and Tuberculosis Treatment Outcomes

Dr. Amita Gupta is a Co-PI on this study.

STUDY DESIGN

We will conduct a retrospective case-cohort study nested within the CTRIUMPH and EDOTS cohorts to address our study objectives. This will enable us to measure the association of polymorphisms with multiple clinical outcomes simultaneously and efficiently, while also enabling us to estimate polymorphism prevalence. From the 889 participants in the CTRIUMPH and EDOTS cohort, we will select a random sub-cohort of 290 participants (33% of full cohort) at initiation of TB therapy using a random number generator. While we expect approximately 44 (15%) participants from the sub-cohort to have experienced an unfavorable TB treatment outcome, our sampling strategy for the sub-cohort will proceed through random selection at initiation of TB therapy as appropriate for a case-cohort study. Next, we will select the remainder of predicted 110 participants who experienced an unfavorable TB treatment outcome but were not previously included in the sub-cohort. Overall, we will include all 154 participants from CTRIUMPH and EDOTS cohorts who experienced an unfavorable treatment outcome, hereafter referred to as cases. The sub-cohort and cases will together (n=400) comprise the analytic cohort for  

OBJECTIVES

1. To determine the association between single nucleotide polymorphisms (SNPs) in candidate genes related to inflammasomes and microbiologic treatment outcomes in adults being treated for drug-susceptible pulmonary TB.
2. To determine the association between SNPs in candidate genes related to inflammasomes and pulmonary involvement in adults who successfully complete treatment for a new diagnosis of drug-susceptible pulmonary TB.