Molecular Approaches to the Diagnosis of Tuberculosis

This chapter reviews the progress in developing new tools and procedures for the rapid and reliable diagnosis of tuberculosis. A definitive diagnosis of tuberculosis requires the identification of Mycobacterium tuberculosis bacilli in patient specimens. A definitive diagnosis of tuberculosis requires the identification of M. tuberculosis bacilli in patient specimens. In general, the commercially available assays display sensitivities and specificities approaching 100% for the detection and identification of these species and can usually be completed in a few hours. One easily detected component of M. tuberculosis is tuberculostearic acid, which can be detected in femtomole quantities by gas-liquid chromatography. Several diagnositic procedures have been described for use with M. tuberculosis and include strand displacement amplification (SDA), polymerase chain reaction (PCR) amplification, transcription-mediated amplification (TMA), reporter phage systems, oligonucleotide ligation amplification, and Q-beta replicase amplification. If one uses a physician’s diagnosis of tuberculosis as the gold standard, then the MTD test displayed 95% sensitivity and 96% specificity for correctly identifying persons as having tuberculosis. Given the importance of drug-resistant tuberculosis, it would be advantageous to determine drug susceptibilities directly from clinical specimens and avoid the time required for culture. The luciferase reporter technology has been used to develop simple and rapid screening procedures to identify new antituberculosis agents.