Tuberculosis Risk and Prevention: Findings from Domestic and Global Cohorts

Tuberculosis is a highly infectious disease, leading to disproportionate morbidity and mortality amongst vulnerable populations such as immigrants, adolescents and young adults (AYA), and people living with HIV (PLWHIV). Approximately one quarter of the global population is infected with TB, which can develop into TB disease due to a myriad of factors. There has been an increasing proportion of TB cases in the U.S. attributed to non-U.S. born individuals, particularly among individuals from countries with high TB burden. Individuals who are immunocompromised, such as PLWHIV, are particularly susceptible to TB disease due to the weakened status of their immune system. Additionally heightened risk of TB during the adolescent and young adult period (age 10-24) has been linked to changes in environmental and physiological factors. There have been changes in approaches to TB screening in the U.S; however, new screening recommendations do not account for variations of TB risk by country of origin. Additionally, gaps in knowledge persist regarding TB risk particularly among adolescents and young adults with HIV (YWHIV). TB diagnosis is particularly difficult among children and knowledge of TB risk among YWHIV has been further hampered by dichotomized data reporting among children (less than 15) and adults (15 years of age and older). TB prevention therapy (TPT) can significantly decrease TB, especially among PLHIV on ART. TPT should be available to all PLHIV, however reporting has been prone to missingness and overlooked among YWHIV. Understanding other factors associated with TPT use and TB disease among YWHIV is of utmost importance to achieving global TB targets. In this dissertation, we evaluate TB risk among non-U.S. born individuals, quantify TPT use among YWHIV, and evaluate TPT utilization and TB risk among YWHIV to address the current gaps in research. In Chapter 2, we estimated TB risk among non-U.S. born individuals in Washington state utilizing region of origin, World Health Organization (WHO) incidence categories, and time since entry into the U.S. In Chapters 3, we conducted the largest retrospective cohort analyses among 10,000 YWHIV in our study cohort. We estimated the TPT cascade of care, quantifying the number of YWHIV who initiated and completed TPT during our study period. We also evaluated clinic level and individuals level co-factors associated with TPT initiation and completion. Lastly in Chapter 4, we estimated the TB risk among YWHIV in Kenya and calculated TB incidence among individuals newly initated on ART and those previously on ART and evaluated co-factors for TB. Cumulatively these findings emphasize the continued need for tailored screening guidelines for non-U.S. born individuals and identified deficiencies in TPT utilization and the particularly high risk of TB among YWHIV in Kenya.