Molecular diagnostics for tuberculosis.

The phenotypic methods of smear microscopy, culture and indirect drug susceptibility testing (DST) remain the 'gold standard' diagnostics for tuberculosis (TB) in 2015. However, this review demonstrates that genotypic methods are in the ascendancy. Current-generation nucleic acid amplification tests (NAATs) are important supplementary tests for the rapid direct detection of (multidrug-resistant) TB in specific clinical settings. Genotypic detection is already the preferred method of detecting rifampicin and pyrazinamide resistance. Next-generation NAATs able to detect about 10 colony forming units/mL of sputum could replace culture as the initial test for detecting TB. Whole genome sequencing could also plausibly replace phenotypic DST but much work is required in method standardisation, database development and elucidation of all resistance gene determinants. The challenge then will be to rollout these increasingly complex and expensive diagnostics in the low-income countries where TB is prevalent.