Clusters of Drug-Resistant Mycobacterium tuberculosis Detected by Whole-Genome Sequence Analysis of Nationwide Sample, Thailand, 2014–2017

Abstract

Multidrug-resistant tuberculosis (MDR TB), pre-extensively drug-resistant tuberculosis (pre-XDR TB), and extensively drug-resistant tuberculosis (XDR TB) complicate disease control. We analyzed whole-genome sequence data for 579 phenotypically drug-resistant M. tuberculosis isolates (28% of available MDR/pre-XDR and all culturable XDR TB isolates collected in Thailand during 2014–2017). Most isolates were from lineage 2 (n = 482; 83.2%). Cluster analysis revealed that 281/579 isolates (48.5%) formed 89 clusters, including 205 MDR TB, 46 pre-XDR TB, 19 XDR TB, and 11 poly–drug-resistant TB isolates based on genotypic drug resistance. Members of most clusters had the same subset of drug resistance-associated mutations, supporting potential primary resistance in MDR TB (n = 176/205; 85.9%), pre-XDR TB (n = 29/46; 63.0%), and XDR TB (n = 14/19; 73.7%). Thirteen major clades were significantly associated with geography (p<0.001). Clusters of clonal origin contribute greatly to the high prevalence of drug-resistant TB in Thailand.

Drug-Resistant Characteristics, Genetic Diversity, and Transmission Dynamics of Rifampicin-Resistant Mycobacterium tuberculosis in Hunan, China, Revealed by Whole-Genome Sequencing

“…Further study is needed to clarify this issue, especially from a molecular evolutionary perspective. Some studies reported that lineage 2 has higher transmissibility than lineage 4 ( 19 , 20 ). However, the present study found no association between the genotype and clustering rates of RR-TB strains.…”

“…Our study found 75.0% of isolates within a cluster were collected from the same county, indicating that the recent transmission mainly occurred in local area. In some clusters, isolates exhibited different drug-resistant types in relation to chronology, suggesting the progression and accumulation of mutations linked to drug resistance ( 19 ). Interestingly, some clusters included isolates of different drug-resistant types and ancestral isolates carried more drug-resistant mutations than their descendants.…”

“…This result could be partially explained by the different durations of latent phase after transmission events, resulting in cases infected with more troublesome isolates (e.g., XDR-TB) emerging earlier than those with less troublesome strains (e.g., MDR-TB) ( 49 ). Another possible explanation is that not all cases from the potential cluster were enrolled in this study, and some index cases with primary resistance may have been missed in the selected population ( 19 ).…”

Molecular Epidemiology of Drug-Resistant Mycobacterium Tuberculosis in Japan

“…There are few studies of MDR M. tuberculosis based on whole-genome sequencing at the nationwide scale in Asian countries ( 10 , 11 ). MDR M. tuberculosis belonging to lineage 2 caused an ongoing MDR M. tuberculosis epidemic throughout Central Asia ( 10 ).…”

“…MDR M. tuberculosis belonging to lineage 2 caused an ongoing MDR M. tuberculosis epidemic throughout Central Asia ( 10 ). Of drug-resistant M. tuberculosis isolates, 83.2% belonged to lineage 2 in Thailand, and clusters of these isolates contributed to the high prevalence of drug-resistant TB in that country ( 11 ). Those results are consistent with the findings of the present study.…”