4 July 2011
Tuberculosis (TB) is a major health problem especially in the developing world. It has been estimated that one third of the global population is latently infected with Mycobacterium tuberculosis. Despite years of effort we currently have no reliable biomarkers for identifying protective immunity against TB and for the various disease states, or for predicting response to intervention. In this component of the TB Grand Challenge Projects, we will establish TB case contact cohorts to facilitate the identification of biomarkers and signature profiles of protective immunity and TB disease. Biomarkers may become important tools to facilitate the design and the monitoring of novel TB interventions, including TB vaccines and new anti-mycobacterial drugs. These case contact cohorts will form a central component of our TB case contact study platform and enable the use of molecular and immunological tools to study the host response to recent M. tuberculosis infection, dormancy and progression to disease.
We will perform cross-sectional analyses of immune responses in healthy TB case contacts with and without HIV-1 co-infection. We will conduct immunological studies during a 2 year follow up of household contacts of sputum smear positive TB index cases, in order to observe longitudinal changes in candidate biomarkers in relation to acquisition of new infection with M. tuberculosis, dormancy, reactivation and disease progression. The study of disease progression will benefit from combining data from multiple African sites as part of the Gates Grand Challenge Biomarkers consortium.