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.
Highlights
Multidrug-resistant tuberculosis (MDR TB), pre-extensively drug-resistant tuberculosis, and extensively drug-resistant tuberculosis (XDR TB) complicate disease control
Phylogenetic Analysis Most of the M. tuberculosis isolates belonged to the East-Asian lineage (n = 482; 83.2%), followed by the Indo-Oceanic lineage (n = 67; 11.6%), the Euro-American lineage (n = 29; 5.0%), and the East African-Indian lineage
MDR TB and XDR TB are serious global problems, but few studies have focused on their transmission at a nationwide resolution
Summary
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). 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. In Thailand, despite the reducing incidence of TB, the reported number of MDR TB cases nearly doubled during 2014–2018 [1]; some are likely to be XDR TB. Analysis of M. tuberculosis WGS data from isolates across Thailand could provide much-needed insights into MDR/XDR TB transmission. Our aim was to investigate the clustering patterns and risk factors of possible MDR TB, pre-XDR TB, and XDR TB transmission clusters across Thailand using WGS data
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