Characterizing Socio-Demographic Tuberculosis Disparities and their Underlying Drivers across Subpopulations in both Low and High Burden Settings

Abstract

Tuberculosis (TB) continues to be one of the leading infectious killers, despite its long history as a human disease. In many high burden countries (HBCs), the TB epidemic is exacerbated by the overlapping HIV epidemic as HIV infection substantially increases the risk of primary TB infection, reinfection, and reactivation of LTBI. While the burden of TB is widespread among the general public in HBCs, in low incidence countries the TB epidemic often concentrates among socially and historically marginalized subpopulations. In this dissertation, I characterized the racial/ethnic disparities in TB incidence in Arkansas, United States (U.S.), a low incidence state for TB. By applying an analytical framework that disaggregates TB surveillance data by detailed racial/ethnic categorizations, not widely used in previous state TB reports and studies, I found the risk of TB among Native Hawaiian/Pacific Islander (NHPI) persons to be highest (RR= 174, 95% CI: 140.6, 214.2), followed by Asian, Hispanic and non-Hispanic (NH) Black persons, compared to NH White persons after adjusting for age and sex. I also found that the risk of advanced TB disease at diagnosis was significantly higher for all racial/ethnic minorities, suggesting that the observed racial disparities may be driven by inequitable access to TB diagnosis. The mere quantification of racial disparities is inconsequential without understanding the underlying mechanisms that drive racial disparities, as each mechanism requires a specialized TB mitigation strategy. By integrating genotyping of Mycobacterium tuberculosis clinical isolates of TB incident cases with traditional surveillance data, I quantified the relative contribution of recent transmission and reactivation of LTBI across racial groups in Arkansas during 2010-2021 using time restricted genotypic clusters as a proxy for recent transmission. Approximately, 1/3rd of the TB cases in the state were clustered, and NHPI (RR=218.7, 95% CI: 150.6, 317.4) and NH Black (RR=7.4, 95% CI: 5.3, 10.2) persons were at a higher risk of clustered TB compared to NH White persons, suggesting a particular need to disrupt ongoing transmission among NHPI and NH Black communities. The risk of clustered TB among ≥65 year NH White persons was 6.5 times (95% CI: 1.52, 27.8) the risk among 15-24 year old NH White persons, demonstrating that previously recognized risk factors for clustered TB may have evolved over time and may not ubiquitously apply to all racial groups. Taken together, Arkansas needs a pro-equity and two-pronged approach for TB elimination, which considers the role of reactivation along with ongoing transmission despite its low overall burden. This dissertation also characterized gender disparities in a TB-HIV syndemic setting, Zimbabwe. The large TB surveillance dataset (N=24 277) provided sufficient sample size to study the association of gender with TB across granular categorizations of TB anatomic sites, often unavailable in resource limited settings. Women of childbearing age were found to be at an increased risk of TB-HIV coinfection, which may result in increased antenatal transmission. When resolved by TB anatomic sites, women were found to have increased likelihood of severe forms of TB including abdominal TB (male/female odds ratio= 0.51, 95% CI: 0.39, 0.68) and TB of the bones/joints/spine (male/female odds ratio= 0.63, 95% CI: 0.45, 0.90). To summarize, this dissertation generates new knowledge related to local epidemiological factors that differentially drive TB epidemics across subpopulations in low and high burden settings, highlighting why a one-for-all approach fails to address the local drivers of TB epidemics.