Detection, treatment and prevention of tuberculosis

Mycobacteria tuberculosis (Mtb) infects millions yearly in many countries. Numerous multi-generational genetic factors have been identified that account for high host susceptibility to Mtb. Diagnostic tests based on quantification of interferon-γ generation by Mtb antigen-stimulated blood mononuclear leukocytes detect infection accurately and show far lower false-positive and false-negative results than Mtb antigen skin tests. Antibiotic resistance of Mtb has limited effective treatment. Now new tests for antibiotic resistance of Mtb based on genetic mutations characteristic of resistance to individual antibiotics report more accurately and rapidly than prior assays of resistance of cultured Mtb growth to antibiotics. The Bacillus Calmette-Guerin vaccine given to babies protects them against serious Mtb manifestations, such as Mtb meningitis, but does not prevent childhood or adult Mtb disease. Development of human Mtb vaccines has succeeded recently with antigens composed of mRNAs encoding Mtb polypeptides or recombinant peptides fused to proven adjuvant systems. Two of these vaccines have completed phase IIb or III trials and have prevented > 50% of individuals with inactive pulmonary Mtb from progressing to active disease over three years.