London School of Hygiene & Tropical Medicine

Pre-viva seminar

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 HIV-prevalent 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 an HIV-prevalent rural community in northern Malawi, as part of a long-term population-based study of tuberculosis, was to delineate M.tb transmission events occurring within the context of a well-implemented TB control programme, and thereby elucidate factors driving transmission that are not being addressed by current prevention 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 tuberculosis 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 method of estimating M.tb infection prevalence, initially published by Rust and Thomas in 1975, appeared to be only method to appropriately adjust for the marked effect of BCG-attributable induration in the youngest children (aged <2 years).

Marked differences in the estimates of the risk of M.tb infection when using cross-sectional data compared to using longitudinal data are also highlighted. Age, distance to known smear-positive TB case and community M.tb exposure were risk factors for prevalent and incident M.tb infection in children.  Being HIV-exposed in utero was the strongest risk factor for prevalent infection, whilst having an HIV-positive father was strongly associated with incident infection.  Additional risk factors for incident infection included church attendance and travel on mini-buses.  No evidence was found in the household contact study that smear-positive tuberculosis patients on ART were more likely to transmit M.tb infection to household child contacts (as inferred from TST positivity) compared to smear-positive tuberculosis patients not on ART. 

However, child contacts of HIV-negative individuals had nearly three times the odds of having a positive TST compared to child contacts of HIV-positive TB patients not on ART; this was partly explained by differences in the degree of smear positivity. HIV-related risk factors for prevalent and incident M.tb infection in pre-school children highlight that interventions, such as screening for HIV and TB with implementation of isoniazid preventive therapy where indicated within the household of HIV-positive individuals may further reduce the burden of TB at a community level in the longer term. Findings from this research also highlight the need for better infection control practices (improved ventilation) in congregate settings such as churches and mini-buses.