Detection of I491F and V170F rpoB Mutations Associated with Misdiagnosis of Rifampicin Resistance Among Patients with Drug-susceptible Tuberculosis Treatment Failure, Myanmar, 2022.

Abstract

Detecting rifampicin resistance is crucial in selecting tuberculosis (TB) treatment. Recently, several studies reported that I491F and V170F rpoB mutations, previously designated as borderline rifampicin-resistance mutations, were found with a varying prevalence. Sputum specimens from first-line tuberculosis treatment failed patients attending Tuberculosis Centers in Yangon Region during 2022 were cultured in solid media. Phenotypic drug susceptibility testing (pDST) was conducted using Mycobacterial Growth Indicator Tube (MGIT) method. Whole genome or Deeplex targeted next-generation sequencing was performed using Illumina Miseq. Mutation analysis was done by PhyResSE and SAM-TB online platforms. A total of 32 culture-positive isolates with DNA qualified for genome sequencing were included in the study. Those were diagnosed as rifampicin-susceptible by routine GeneXpert and line probe assays. Rifampicin resistance conferring mutations were found in 17/32 (53.1%) M. tuberculosis isolates; 14 (43.7%) had mutations outside the RRDR (I491F and V170F), two (6.3%) were S450L, mutation within RRDR, and one isolate (3.1%) with interim resistance mutations S428T and S441A. This study highlighted the presence of rifampicin-resistant tuberculosis strains missed by current diagnostic strategies, and are circulating as treatment-failed patients. This demonstrates a gap in current WHO-endorsed algorithms for capturing all MDR-TB strains.