# Genomic decoding of drug-resistant tuberculosis transmission in Thailand over three decades

## TL;DR

This study uses whole-genome sequencing to track drug-resistant tuberculosis transmission in Thailand over 26 years, revealing key patterns and mutations.

## Contribution

The study provides a comprehensive genomic analysis of MDR-TB transmission in Thailand using a large dataset spanning three decades.

## Key findings

- Most isolates are lineage two strains, primarily the Beijing sub-lineage, with high rates of isoniazid and rifampicin resistance.
- Clustering analysis identified 206 transmission clades, predominantly with MDR-TB in Central and Northeastern regions.
- A large transmission cluster showed a mutation rate of 1.1 × 10–7 substitutions per site per year.

## Abstract

Thailand has a high burden of tuberculosis, with control efforts hindered by drug-resistant Mycobacterium tuberculosis (Mtb). The increasing use of whole-genome sequencing (WGS) of Mtb offers valuable insights for clinical management and public health surveillance. WGS can be used to profile drug resistance, identify circulating sub-lineages, and trace transmission pathways or outbreaks. We analysed WGS data from 2,005 Mtb isolates collected across Thailand from 1994–2020, including 816 retrieved and 1,189 newly sequenced samples, with most isolates being multidrug-resistant (MDR-TB). Most isolates are lineage two strains (78·3%), primarily the Beijing sub-lineage (L2.2.1). Drug resistance profiling revealed substantial isoniazid and rifampicin resistance, and 67·3% classified as MDR-TB. Phenotypic and genotypic drug susceptibility testing showed high concordance (91·1%). Clustering analysis identified 206 transmission clades (maximum size 288), predominantly with MDR-TB, especially in Central and Northeastern regions. One cluster (n = 22) contains the ddn Gly81Ser mutation, linked to delamanid resistance, with some members pre-dating drug roll-out. In the largest cluster (n = 288), containing isolates spanning two decades, we applied transmission reconstruction methods to estimate a mutation rate of 1·1 × 10–7 substitutions per site per year. Overall, this study demonstrates the value of WGS in uncovering TB transmission and drug resistance, offering key data to inform better control strategies in Thailand and elsewhere.