What are the unknowns in latent TB infection?
Although some 90\;% of individuals infected with tuberculosis (TB) never develop clinical disease, the possible progression from infection to disease is not standard. Of those who are infected and do develop overt clinical disease, about 50\;% are diagnosed as fast progressors, being diagnosed with TB within 2 years of infection. The other half develop clinical disease later; such cases are described as 'reactivation' or post-primary TB. Immunisation with the Mycobacterium bovis–derived Bacillus Calmette-Guerin (BCG) vaccine can provide protection against childhood TB, but is relatively useless in protecting older children and adults from contracting the disease. Thus, infected individuals carry with them a life-long risk of reactivation, which is intensified when the immune system is weakened, as in the case of HIV infection. The 'Host and microbial molecular dissection of pathogenesis and immunity in tuberculosis' (HOMITB) project is investigating the interactions between mycobacteria and host cells. Since such interactions can lead to infection, examining their regulation by cellular immune responses is also a part of the study. Both targeted and genome-wide explorations are being employed to identify genes involved in the immunological control or development of primary Mycobacterium tuberculosis infection in children and secondary pulmonary TB in adults. HOMITB is also using various mouse models and human patients to investigate the role that key intracellular signalling molecules play in the immune response and outcomes of mycobacterial infection.
