Analyzing Spatial Movement Patterns and Transmission Hotspots to Inform Targeted Case-Finding Interventions in KwaZulu-Natal, South Africa

PROJECT SUMMARY/ABSTRACT Background. Global tuberculosis (TB) incidence has only decreased incrementally – despite concerted efforts to understand TB transmission patterns in high-prevalence settings. As TB exhibits pronounced spatial heterogeneity in high-incidence settings like South Africa, spatially targeted case-finding approaches may be effective. Although the underlying processes giving rise to spatial heterogeneity remain unclear, individual mobility and assortative patterns likely underlie areas of heightened TB transmission. Understanding spatial mobility patterns may provide insights into the mechanisms that generate and interconnect hotspots within a community, guiding future active case-finding approaches. Aims. In line with NIAID Strategic Priorities for Tuberculosis Research, this study will 1) characterize forms of spatial mobility and their association with recent transmission and 2) examine the relationship between spatial mobility subclasses and community-based TB transmission hotspots. Elucidating these gaps will advance our understanding of local transmission and inform the development of targeted case-finding interventions to curb ongoing TB transmission in endemic settings. Approach. Since there is a limited understanding of the mobility patterns of TB patients, this research will use detailed mobility data (i.e., the frequency, duration, and spatial dimensions) from TARGET-TB, an ongoing population-based epidemiologic study that enrolls all incident TB cases identified in a peri-urban community in KwaZulu-Natal, South Africa, to identify individuals, groups, and places where control efforts may be targeted. Furthermore, advances in genomic statistical modeling have greatly enhanced our understanding of transmission linkages at various spatial scales. This contextual setting presents a unique opportunity to combine detailed spatial mobility data with bacterial whole genome sequencing data to understand the relationship between spatial mobility and recent transmission and identify transmission hotspots. The overarching goal is to provide insights into local transmission mechanisms to inform targeted case-finding strategies. Training. Ms. Bezuidenhout’s training plan leverages her quantitative abilities and TB research experience to advance her skills and launch her career as an independent investigator focused on spatial mobility and TB transmission. Her training goals are to develop in-depth knowledge of spatial mobility, advance her expertise in molecular epidemiology and TB transmission inference, learn advanced epidemiologic techniques for missing data, and build capacity for effective research dissemination. Under the guidance of her Primary Sponsor, Ms. Bezuidenhout will receive tailored mentorship from a team of experienced TB researchers who work with the parent study, conduct spatial- and molecular-focused research, and have tremendous expertise in the requisite quantitative methods. Training will take place at Columbia University, a high-caliber institution with specialized research programs in population health, infectious disease, and spatial and social epidemiology.