With ∼8 million new infections each year and 2 million deaths, tuberculosis is a serious problem; this problem is compounded by the 2 billion people who have been infected and now carry latent infection that might reactivate later in life.Evidence for persistent infection.Epidemiological evidence of persistent infection shows that reactivation occurs where there is a low risk of reinfection and is related to both age and immune status; in endemic areas both reactivation and reinfection occur. Autopsy studies have detected viable bacteria in asymptomatic individuals, and provide evidence that bacteria can be found where there are no visible lesions. Animal models of persistence, particularly mice, provide a means of dissecting the interaction between host and bacteria. The murine model provides evidence that, during the persistent plateau phase of infection, mycobacteria are dividing very slowly or not at all. Mycobacterial mutants with persistence phenotypes have been constructed by inactivating a wide range of genes, providing clues to the mechanisms that mycobacteria use.The immune response.Having controlled initial infection, why does the immune response not clear the bacteria? Having coped with persistent infection, what triggers breakdown to active disease? Containment uses both the adaptive and innate immune responses, including macrophages and dendritic cells signalling through several receptors. CD4+ T cells and cytokines have a central role in containment, with other cell types (including CD8+ T cells) being involved in the control of persistence.Targeting persistent infection.Present therapies seek to break transmission by treating patients with active disease — an intervention that prevents the progression of patients with latent infection to active disease. This could be achieved by targeted drugs against persistent bacteria, or by post-exposure vaccination.
