Omics and single molecule detection: The future of TB diagnostics

The diagnosis of tuberculosis (TB) depends on sputum-smear examination, mycobacterial culture and tuberculin skin testing (TST). Future diagnosis requires near-patient tests and early recognition of drug-resistant (DR) TB. Nucleic acid amplification techniques (NAAT) can detect approximately 100 bacilli?mL-1 and have moved from the laboratory into the field. Sensitivity can be improved by detecting proteins, using mass spectrometry, and their function, using reporter enzymes. Ultimately, microfluidics will permit reactions in restricted spaces with the potential to measure single molecules or sequence strains of Mycobacterium tuberculosis directly. Metabolic products released by TB and the human response to infection can be described by a characteristic metabolome and volatome of exhaled air. Interferon-γ release assays (IGRA) are blood tests that indicate the immune response to the few bacilli responsible for latent TB infection (LTBI). Their sensitivity may be improved by cytokines released by activated macrophages (inducible protein-10). The pattern of the immune response to many or all TB antigens, the immunome, may in future distinguish between active disease and latent infection.