Current strategies in TB immunotherapy

Currently available chemotherapy for the treatment of pulmonary tuberculosis (TB) is far from ideal, requiring multiple anti-tuberculous drugs to be taken in combination for extended time periods. This long duration of therapy, coupled with the side effects of current regimens, often results in poor patient adherence, treatment failure and the associated emergence of drug resistance with major financial implications. Thus, the development of novel, shorter treatment regimens is an urgent objective of anti-tuberculous drug discovery. Immunotherapy is an area that merits more consideration than it has previously received, not least, as it could potentially avoid the problem of pathogen resistance. However, this must be undertaken with caution, as at least part of the disease pathology is a consequence of the host immune response. Thus, the protective, and not the harmful, aspects of immunity must be stimulated. Various attempts at utilizing immunotherapy as an adjunct to chemotherapy are reviewed with particular emphasis on the evidence from human studies, including the modulation of cytokine levels, administration of environmental mycobacteria and antibody therapy, in order to modulate or enhance the host immune response to Mycobacterium tuberculosis.