Drug-Resistant Tuberculosis in Rural Eastern Cape: A Biosocial Pilot Study

Background: Drug-resistant tuberculosis (DR-TB) remains a major threat to global tuberculosis control, particularly in high-burden rural settings where transmission is driven by both biological and socio-structural determinants. Although genomic surveillance and mathematical transmission modelling have improved understanding of resistance evolution and transmission dynamics, these approaches often insufficiently incorporate community-level behavioral and social drivers of disease spread. This study integrated Community-Based Participatory Research (CBPR) within a genomic–epidemiological modelling framework to develop a biosocial understanding of DR-TB transmission dynamics in a rural South African setting. Methods: Whole-genome sequencing (WGS) was performed on 32 Mycobacterium tuberculosis isolates to identify resistance-associated mutations, phylogenetic lineages, and potential transmission clusters. A deterministic two-strain transmission model distinguishing drug-sensitive (DS) and drug-resistant (DR) tuberculosis was developed to simulate transmission dynamics. CBPR-informed mechanisms were incorporated into the model through modifications of key epidemiological parameters, including transmission rate (β), treatment initiation rate (γ), and resistance amplification rate (α), reflecting the influence of community engagement, treatment adherence, and health-seeking behavior. Scenario-based simulations evaluating varying levels of community-engaged interventions were conducted over a 10-year period. Results: A substantial burden of drug resistance was observed, with 84.4% of isolates resistant to at least one anti-tuberculosis drug. Multidrug-resistant tuberculosis (MDR-TB) accounted for 46.9% of isolates, while recurrent combinations of resistance-associated mutations suggested ongoing transmission of resistant strain lineages. Lineage 2 (Beijing genotype) and Lineage 4 predominated, with advanced resistance patterns occurring mainly within Lineage 2 isolates. Model simulations indicated that CBPR-informed interventions could reduce DS-TB transmission by approximately 40–60% and DR-TB transmission by 20–35%. Scenario-based estimates also indicated a higher transmission potential for DR-TB (R₀ ≈ 2.04) than for DS-TB (R₀ ≈ 1.29). Community-engaged interventions reduced transmission by improving treatment adherence, earlier diagnosis, and enhanced infection-prevention behaviors. Conclusions: Integrating CBPR into genomic and transmission modelling frameworks provides a novel biosocial approach for understanding tuberculosis dynamics in high-burden settings. The findings suggest that community-engaged interventions can substantially influence key epidemiological drivers of transmission and resistance amplification. Embedding community participation within TB surveillance and control strategies may strengthen efforts to reduce transmission, improve treatment continuity, and address the social determinants underpinning DR-TB persistence in rural settings.