M-tuberculosis: immunology and vaccination

Tuberculosis is increasing. Current treatment regimens require at least 6 m onths, because latent or stationary phase organisms are difficult to kill. Such regimens do not achieve full compliance, and "directly observed therap y short course" (DOTS) is having less impact than expected. This worrying s ituation is aggravated by coinfection with human immunodeficiency virus (HI V), and by the increase in drug-resistant strains. We need new insights that lead to more rapid therapies and immunotherapies, and more reliable vaccines. Recent insights have come from: understanding of the relationship between M ycobacterium tuberculosis and macrophages; the multiple T cell types that r ecognise mycobacterial peptides, lipids and glycolipids; the critical role of interferon-gamma (IFN gamma) and interleukin-12 (IL,-12) in human mycoba cterial infection revealed by genetically defective children; quantitation of the presence and importance of Th2 lymphocyte activation in human tuberc ulosis; the role of local conversion of inactive cortisone to active cortis ol in the lesions; the recognition that some effective prophylactic vaccine s also work as immumotherapeutics whereas others do not. In the longer term the recent sequencing of the M. tuberculosis genome will lead to further a dvances. In the short term, effective immunotherapy remains the most accessible brea kthrough in the management of tuberculosis. The types of practical advance that will result from sequencing the genome are discussed speculatively, bu t cannot yet be predicted with certainty.