Abstract
Mycobacterium tuberculosis drug resistance is a threat to global tuberculosis (TB) control. Comprehensive and timely drug susceptibility determination is critical to inform appropriate treatment of drug-resistant tuberculosis (DR-TB). Phenotypic drug susceptibility testing (DST) is the gold standard for M. tuberculosis drug resistance determination. M. tuberculosis whole genome sequencing (WGS) has the potential to be a one-stop method for both comprehensive DST and epidemiological investigations. We discuss in this review the tremendous opportunities that next-generation WGS presents in terms of understanding the molecular epidemiology of tuberculosis and mechanisms of drug resistance. The potential clinical value and public health impact in the areas of DST for patient management and tracing of transmission chains for timely public health intervention are also discussed. We present the current challenges for the implementation of WGS in low and middle-income settings. WGS analysis has already been adapted routinely in laboratories to inform patient management and public health interventions in low burden high-income settings such as the United Kingdom. We predict that the technology will be adapted similarly in high burden settings where the impact on the epidemic will be greatest.
Highlights
To curb the emergence and spread of tuberculosis (TB) drug resistance, early detection and effective treatment informed by comprehensive drug susceptibility testing (DST) are vital
Mycobacterium tuberculosis whole genome sequencing (WGS) is an attractive method for both DST to inform treatment decisions and surveillance of drug resistance in high burden settings where capacity for routine resistance testing for everyone with TB is inadequate
We look at challenges or barriers to application of M. tuberculosis WGS analysis for routine clinical use especially in resource limited TB high burden countries
Summary
To curb the emergence and spread of tuberculosis (TB) drug resistance, early detection and effective treatment informed by comprehensive drug susceptibility testing (DST) are vital. It is important to monitor and understand the development, evolution, biology, and epidemiology of TB drug resistance to inform community level or public health interventions Molecular methods such as Xpert MTB/RIF (Cepheid, Inc. Sunnyvale, CA, USA) and the line probe assays GenoType MTBDRplus/sl (Hain lifescience, GmbH, Nehren, Germany) have considerably increased access to DST and shortened turnaround time to results. CA, USA) and the line probe assays GenoType MTBDRplus/sl (Hain lifescience, GmbH, Nehren, Germany) have considerably increased access to DST and shortened turnaround time to results These methods provide resistance information for a limited number of drugs. We highlight how analysis of M. tuberculosis whole genome sequence data could routinely provide guidance for individual treatment, tracing of transmission chains and continuous drug resistance surveillance for public health interventions. We look at challenges or barriers to application of M. tuberculosis WGS analysis for routine clinical use especially in resource limited TB high burden countries
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