Molecular Diagnosis of Drug-Resistant Tuberculosis; A Literature Review

Abstract

Drug-resistant tuberculosis is a global health problem that hinders the progress of tuberculosis eradication programs. Accurate and early detection of drug-resistant tuberculosis is essential for effective patient care, for preventing tuberculosis spread, and for limiting the development of drug-resistant strains. Culture-based drug susceptibility tests are the gold standard method for the detection of drug-resistant tuberculosis, but they are time-consuming and technically challenging, especially in low- and middle-income countries. Nowadays, different nucleic acid-based assays that detect gene mutations associated with resistance to drugs used to treat tuberculosis are available. These tests vary in type and number of targets and in sensitivity and specificity. In this review, we will describe the available molecular tests for drug-resistant tuberculosis detection and discuss their advantages and limitations.

Keywords: challenges; diagnosis; drug resistance; molecular markers; mutations; tuberculosis.

Figure 1

Diagnostic flowchart for presumptive multi-drug resistant tuberculosis in Vietnam (Vietnam’s Ministry of Health) and perspectives. MTB, Mycobacterium tuberculosis; RIF, rifampicin; Hain 2, GenoType MTBDRsl (Hain Lifescience, Germany); MDR, multi-drug resistance; XDR, extensively drug resistance; NGS, next generation sequencing; TGS, targeted gene sequencing; DST, drug susceptibility testing; ^∗If the result of consultation is non-TB, non-tuberculosis mycobacteria identification by culture is recommended; ^∗∗Culture and culture DST are performed when the patient is still suspected of having second-line drug resistant TB.