PROJECT SUMMARY The intersection of tuberculosis (TB) disease with non-communicable diseases (NCDs), including diabetes mellitus, pulmonary disease, and cardiovascular disease, has emerged as a critical public health concern. Rapidly expanding NCD epidemics threaten TB control in low- and middle-income countries, where preventing and treating TB disease remains a great burden. However, to date, the notion that TB disease may increase the risk of chronic NCDs has not been well explored. Using two large healthcare databases, we will determine the extent that TB increases the risk of post-TB diabetes, pulmonary disease, and cardiovascular disease. This secondary data analysis research study will advance understanding of dual burdens of TB and NCD multimorbidity and build a knowledge base for integrated care and prevention of NCDs. The overall objective of this study is to improve understanding of the relationship between TB disease and subsequent risks of diabetes, pulmonary disease, and cardiovascular disease, and to identify targets for preventing these NCDs among TB patients. The specific aims of this proposal are to: (1) determine the extent to which TB disease increases the risk of future development of diabetes mellitus, pulmonary disease (asthma and COPD) and cardiovascular disease (ischemic stroke, coronary artery disease, peripheral vascular disease, and transient ischemic attack TIA), (2) determine the extent to biologic sex, BMI, HIV, race/ethnicity, and age at time of TB disease modify and mediate the relationships between TB and incidence of diabetes, pulmonary disease, and CVD, and (3) explore TB clinical characteristics that predict early NCD incidence (a first diagnosis of diabetes, pulmonary diseases, or CVD within 5 years after TB cure) among patients with previous TB disease. To meet the study’s objectives and aims, we will leverage two well-characterized and comprehensive health care databases. First, we will use electronic health records from the US Veterans Affairs Medical Care Centers to assemble comparable data on diagnostic codes, prescription medication use, hospitalization, and vital status. Second, we will use the Clinical Practice Research Datalink, a database of primary care patients in the United Kingdom that is nationally representative and linked to hospital admissions and mortality data. The proposed approach will allow us to assemble a cohort of >16,000 TB survivors and follow them for an average of 6.5 years. We will then compare NCD incidence among TB survivors to >64,000 age, sex, and race/ethnicity matched controls without previous TB. The proposed study will importantly characterize the extent to which TB contributes to post-TB NCD multimorbidity. The comparison of post-TB outcomes across two large health care will greatly strengthen the validity of our results and increase the ability to suggest causal inferences based on our findings. A long-term goal of the proposed work is to prepare for prospective interventional studies that evaluate NCD prevention approaches during TB treatment and determine their efficacy several years after TB treatment.

PROJECT NARRATIVE Increasingly non-communicable disease multimorbidity impedes tuberculosis control in high-, middle-, and low- income countries. However, studies have not evaluated the extent to which tuberculosis disease may increase the risk of non-communicable disease after tuberculosis treatment is completed. The goal of this study is to elucidate the relationship between tuberculosis disease and risk of diabetes, pulmonary disease, and cardiovascular disease among tuberculosis survivors.