Rapid Molecular Diagnostics of Tuberculosis: What Do We Have, What Do We Need?

Smear microscopy and culture are conventional methods of tuberculosis (TB) diagnostics. Microscopy is fast and inexpensive but has low sensitivity, whereas culture is highly sensitive but may take several weeks. Molecular diagnostic (MDx) methods were widely introduced into TB diagnostics much later, in the early 2010s, when the GeneXpert system was launched. MDx methods combine the benefits of the conventional methods. Furthermore, significant developments have occurred in recent years. The current selection of available rapid MDx methods covers the full range of TB diagnostics: detection of pulmonary and extrapulmonary TB, narrow- to broad-range rapid drug susceptibility testing, mycobacterial species identification, and Mycobacterium tuberculosis (MTB) strain typing. Several issues-often focusing on high assay costs-have still prevented the complete roll-out of MDx methods over conventional methods in both low-resource, high-incidence settings and high-resource, low-incidence settings. This review covers topics related to molecular detection of MTB and MTB drug resistance directly from clinical specimens. The aim of the review is to describe currently available methods, how they perform, and what key issues must be addressed for more optimal implementation. Overall, MDx methods currently represent an essential but often accessory tool in the detection of TB and MTB drug resistance. At present, several limitations-including diagnostic equivalence with the reference method, breadth of drug resistance testing, treatment monitoring, and accessibility due to analysis costs and assay complexity-still hinder efficient replacement of the conventional smear microscopy and culture methods. However, new advances in testing methods and strategies are continuously being made.