Abstract
Tuberculosis (TB) remains a critical public health issue in Johannesburg, South Africa, driven by a complex interplay of individual, social, and structural factors. This study assessed the syndemic relationship between these determinants to understand their collective impact on TB burden and treatment outcomes. A cross-sectional survey was conducted among TB patients attending selected clinics, examining behavioural risks (e.g., smoking, alcohol use, HIV co-infection), social conditions (poverty, overcrowding, stigma), and structural challenges (access to healthcare, migration status). The results revealed a significant co-occurrence of TB and HIV (56.1%), alongside high rates of smoking (33.1%) and alcohol use (45.2%). Unemployment (50.2%), inadequate housing, and limited healthcare access, particularly for undocumented migrants (26.2%), were also prominent. Factor analysis demonstrated a syndemic interaction between behavioural and social determinants, underscoring the compounded vulnerability of affected populations. The findings highlight the necessity of integrating medical interventions with social and structural reforms. Recommendations include TB-HIV co-management, substance abuse programmes, improved housing, and inclusive healthcare access. A multisectoral approach addressing both health and socioeconomic inequalities is critical for comprehensive TB control in urban South African contexts.