Correlates of immunity and the influence of co-infections on protection against infection with Mycobacterium tuberculosis following BCG immunisation at birth. (360G-Wellcome-086801_Z_08_Z)

This project will employ an established, Wellcome Trust-funded birth cohort to address new goals suggested by recent evidence of a protective effect of BCG against Mycobacterium tuberculosis infection. These goals are: First, to determine the prevalence of M. tuberculosis infection among 1000 five-year-olds who received BCG immunisation at birth, using an RD1-ELIspot assay to detect responses to M. tuberculosis-specific antigens. Within this goal we will explore interpretation of RD1-ELIspo t results for population studies by comparing responses to RD1 and latency antigens (presumed to characterise active and dormant mycobacteria, respectively), and by examining effects of prophylactic isoniazid therapy. Second, to determine BCG-induced profiles of cytokine response to mycobacterial antigens that are associated with subsequent M. tuberculosis infection, using results of whole blood assays conducted within the host cohort. Cytokine profiles at age one year will be compared betwe en children who are infected or uninfected at five years, as defined in goal one. Third, to determine the effects of co-infections on prevalence of M. tuberculosis infection at age five years and, if effects are observed, to explore whether these are mediated by effects on BCG-induced cytokine responses. Effects of helminths, malaria, maternal HIV infection and herpes virus infections will be examined.