Despite effective treatment being available since the 1940s, tuberculosis (TB) remains a leading cause of death by a single infectious agent. Continued transmission is one of the driving factors of the TB epidemic. In high TB and HIV prevalent settings Mycobacterium tuberculosis transmission dynamics are still poorly understood. Throughout adolescence, individuals have increasing social contacts with the wider community. Thus, understanding M. tuberculosis infection among adolescents has potential for understanding M. tuberculosis infection in the population. This thesis reports findings from a cross-sectional study among adolescents in a high TB and HIV prevalence setting. A sample of adolescents (aged 10-19 years) resident in the southern part of the Africa Health Research Institute(AHRI) demographic surveillance area (DSA) was enrolled from their homes. Blood samples were obtained, and M. tuberculosis infection was measured using the QuantiFERON-TB Gold-plus assay. A total, 1,094 adolescents were enrolled, and the prevalence of M. tuberculosis infection was 22.8% (95% confidence interval [CI]: 20.4-25.3%). Older age, history of lifetime household TB contact and living in communities with high HIV prevalence were associated with increased odds of M. tuberculosis infection. There was no evidence of association between M. tuberculosis infection and Bacillus Calmette-Guérin (BCG) vaccination, household socioeconomic status, and increased cumulative monthly contact hours with either adult males or females. The spatial distribution of M. tuberculosis infection showed geographical variation. Communities with increased M. tuberculosis infection prevalence were observed on the south eastern part of the study area where population density and HIV prevalence are higher than other parts of the study area. The findings in this research show that household contacts of individuals with TB disease and individuals from communities with high HIV prevalence remain at risk of infection and should be prioritised for TB prevention and care activities.