Clusters of Drug-Resistant <i>Mycobacterium tuberculosis</i> Detected by Whole-Genome Sequence Analysis of Nationwide Sample, Thailand, 2014–2017
Ditthawat Nonghanphithak, Angkana Chaiprasert, Saijai Smithtikarn, Phalin Kamolwat, Petchawan Pungrassami, Virasakdi Chongsuvivatwong, Surakameth Mahasirimongkol, Wipa Reechaipichitkul, Chaniya Leepiyasakulchai, Jody Phelan, David Blair, Taane G. Clark, Kiatichai Faksri
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.