Abstract

Drug-resistant tuberculosis (TB) is a major health threat in Myanmar. An initial study was conducted to explore the potential utility of whole-genome sequencing (WGS) for the diagnosis and management of drug-resistant TB in Myanmar. Fourteen multidrug-resistant Mycobacterium tuberculosis isolates were sequenced. Known resistance genes for a total of nine antibiotics commonly used in the treatment of drug-susceptible and multidrug-resistant TB (MDR-TB) in Myanmar were interrogated through WGS. All 14 isolates were MDR-TB, consistent with the results of phenotypic drug susceptibility testing (DST), and the Beijing lineage predominated. Based on the results of WGS, 9 of the 14 isolates were potentially resistant to at least one of the drugs used in the standard MDR-TB regimen but for which phenotypic DST is not conducted in Myanmar. This study highlights a need for the introduction of second-line DST as part of routine TB diagnosis in Myanmar as well as new classes of TB drugs to construct effective regimens.

Highlights

  • Myanmar is one of the 22 high-burden tuberculosis (TB) countries, with a high prevalence of multidrug-resistant TB (MDRTB) [1]

  • The Whole-genome sequencing (WGS) results for rpoB, inhA and katG were in full agreement with the results of the MTBDRplus (Table 2)

  • Two katG mutations were detected in isoniazid-resistant strains that cannot be detected with the MTBDRplus: G299C in M00011, which is known to be associated with isoniazid resistance; and a frameshift in M00020, which should result in high-level isoniazid resistance [9]

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Summary

Introduction

Myanmar is one of the 22 high-burden tuberculosis (TB) countries, with a high prevalence of multidrug-resistant TB (MDRTB) [1]. Molecular DST using the Hain GenoType MTBDRplus v.2.0 (Hain Lifescience GmbH, Nehren, Germany) and, more recently, the Cepheid GeneXpert MTB/RIF (Cepheid, Sunnyvale, CA) has been established in Myanmar. These assays only interrogate the most frequent resistance mutations for a limited number of antibiotics. Whilst WGS is being considered for routine diagnosis and management of drug-resistant TB in well-resourced, low-TB burden settings, currently there are no plans for routine implementation in resource-limited, high-TB burden countries. Since it is important that new tools with the potential to improve TB control are adopted as early as possible especially in countries where these tools are needed the most, a preliminary evaluation of the utility of WGS in the diagnosis and management of drugresistant TB in Myanmar was conducted

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