Drug-Resistant Tuberculosis in Rural Eastern Cape: Integrating Whole-Genome Sequencing, Conceptual Transmission Modelling and Community-Based Participatory Research

Background: Drug-resistant tuberculosis (DR-TB) remains a major challenge in high-burden rural settings where biological, health-system, and social determinants interact. This study integrated whole-genome sequencing (WGS), mathematical modelling and Community-Based Participatory Research (CBPR)-informed principles to examine DR-TB within a conceptual biosocial framework. Methods: WGS data from 32 Mycobacterium tuberculosis isolates were analysed for resistance-associated mutations, phylogenetic lineages and genomic relatedness. A deterministic two-strain model explored drug-susceptible (DS) and DR-TB transmission. Hypothetical CBPR-informed scenarios modified transmission (β), treatment initiation (γ) and resistance amplification (α) parameters over 10 years. Results: Twenty-seven isolates (84.4%) showed resistance to at least one anti-TB drug, and 15 (46.9%) met MDR-TB criteria. Lineages 2 and 4 predominated. Under predefined assumptions, community-informed scenarios produced approximately 40–60% reductions in modelled DS-TB transmission and 20–35% reductions in DR-TB transmission relative to baseline. Conclusions: Integrating genomic evidence with transmission modelling and community-informed assumptions provides a useful hypothesis-generating framework for examining DR-TB. However, the modelled scenarios are exploratory and do not demonstrate the effectiveness of the CBPR intervention. Prospective studies using larger genomic datasets, longitudinal epidemiological data, and empirically measured community-level parameters are required.