PROJECT SUMMARY Tuberculosis (TB) caused 1.45 million deaths globally in 2018. Given that TB incidence is decreasing by only 2% annually, achieving the World Health Organization’s ENDTB goal of TB elimination by 2050 will require innovations in our TB control approach. Previous elimination strategies for other diseases were only successful once spatial variation in disease incidence was identified and locally relevant interventions implemented. TB elimination strategies require longitudinal TB cohorts that incorporate detailed spatial information. Ukraine is an ideal setting for our proposal with its high rifampin resistant (RR) TB burden (eighth highest globally), one third of Europe’s HIV/TB co-infected cases, centralized collection of demographic, laboratory, clinical and spatial data on all patients diagnosed with TB nationally (“eTB Manager”), and generalizability of results to other Former Soviet Union (FSU) countries. We will develop a six-year national TB cohort to track patients longitudinally and spatially including TB drug resistance and HIV status data, using eTB Manager. We hypothesize that eTB Manager data can be used to identify key metrics in the TB care cascade, at the district level, and evaluate the association between population movement and TB/RRTB care cascade gaps and burden. In aim 1a, we will compile a six-year cohort of ~180,000 TB patients diagnosed in Ukraine 2015-2020. In aim 1b, we will estimate key metrics in the TB care cascade and treatment pathways stratified by drug resistance profiles and HIV status. In aim 1c, we will examine the TB care cascade by district to identify spatial variation in care cascade metrics. In aim 2, we will map patient movements and understand the relationship between movements and key care cascade metrics and TB outcomes, stratified by drug resistance profile and HIV status. In aim 2, we will also quantify the association between population movement and TB/RRTB burden, allowing for development of targeted interventions to reduce TB morbidity and mortality. This contribution is significant because it will develop a national six-year cohort of TB patients tracking them longitudinally and spatially during treatment, enabling local public health professionals to develop locally appropriate interventions to close gaps in the TB care cascade and understand the impact of interventions and new TB diagnostics. The proposed work is innovative because it will provide the first cohort of this kind in a FSU country, with the longitudinal and spatial nature of these data allowing for unique assessment of TB care and the impact of interventions. This will allow policy makers to design locally-relevant interventions targeting specific gaps in TB care and migrant populations, preventing further spread and ultimately reducing disease and mortality due to TB. By using routinely collected data, our model adds minimal financial costs and can be adapted for similar settings with routinely-collected TB data. This work will lead to an R01 proposal to evaluate interventions that can close TB care cascade gaps, improve outcomes and mitigate the impact of population movement on the spread of TB and RRTB in Ukraine.

PROJECT NARRATIVE The proposed research is relevant to public health because it will provide a framework to use routinely collected data on all patients diagnosed with tuberculosis (TB) in Ukraine to define the TB care cascade nationally and by district. This work will be stratified by drug resistance profile and HIV status and will enable the targeting of these districts with locally appropriate interventions – directly relevant to the NIH’s mission of reducing morbidity and mortality due to TB. We will also evaluate the impact of population movement on care cascade gaps and district- level TB and drug-resistant TB “hot-spots”.