Investigating Mycobacterium tuberculosis transmission in rural Malawi

Current control strategies are failing to contain the tuberculosis (TB) epidemic and are limited by our lack of understanding of Mycobacterium tuberculosis (M.tb) transmission dynamics, especially in high HIV prevalence settings. M.tb infection in children aged under 5 years of age indicates recent transmission, acting as a sentinel for infectious (typically adult) TB and highlights recent failures in community control measures. The overall aim of this research, which was based in a high HIV prevalence rural community in northern Malawi, was to delineate M.tb transmission events occurring within the context of a wellimplemented TB control programme, and thereby elucidate factors driving transmission that are not being addressed by current control strategies. This thesis presents findings from a series of linked studies, including a longitudinal tuberculin skin-test (TST) study of pre-school children in an area under demographic surveillance, and a household contact study of smear-positive TB cases. Estimates of the average annual risk of M.tb infection (ARTI) in this population of young BCG-vaccinated children varied widely depending on the method used to estimate infection prevalence. A previously overlooked ... (continues)