Molecular epidemiology of rifampicin resistant Mycobacterium tuberculosis in Vietnam
Abstract
Background: Vietnam is a top 20 burden country for multi-drug resistant/rifampicin-resistant tuberculosis (MDR/RR-TB), with nearly 10,000 cases a year. With the emergence of new diagnostic assays for M. tuberculosis and resistance, along with new drugs for both treatment and prevention, we sought to better understand the molecular epidemiology of RR-TB in this high-burden setting, through the study of clinical trial isolates from the VQUIN MDR trial.
Methods: We assembled a sample of cultured isolates, collected from patients with confirmed RR- M. tuberculosis within 10 provinces, enriching for isolates from outside of the 2 major cities, Hanoi and Ho Chi Minh City. We subjected these isolates whole genome sequencing (WGS) and bioinformatic analysis, with a subset subject to phenotypic drug susceptibility testing to evaluate phenotypic/genotypic concordance. New genome sequences were phylogenetically contextualised to publicly-available M. tuberculosis genome sequences sampled in Vietnam from National Center for Biotechnology Information (NCBI) Sequence Read Archives (SRA).
Results: Isolates from 252 RR-TB cases passed quality controls and were available for analysis. Xpert MTB/RIF had a high concordance with WGS-based rifampicin-resistance prediction (PPV=96.8%). Of the 244 isolates confirmed to be rifampicin resistant, a high proportion (235/244 = 96.3%) had mutations associated with resistance to at least one other first- or second-line antibiotic. Phenotypic drug…
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