Thawong Naphatcha, Srilohasin Prapaporn, Phelan Jody E, Phornsiricharoenphant Worawich, Tongsima Sissades, Suriyaphol Prapat, Prammananan Therdsak, Faksri Kiatichai, Sawaengdee Waritta, Wang Linfeng, Hinthong Woranich, Hibberd Martin L, Campino Susana, Wattanapokayakit Sukanya, Mahasirimongkol Surakameth, Chaiprasert Angkana, Clark Taane G
Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
Sci Rep. 2025 Aug 13;15(1):29617. doi: 10.1038/s41598-025-15093-7.
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 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.
泰国结核病负担沉重，耐药结核分枝杆菌（Mtb）阻碍了防控工作。Mtb全基因组测序（WGS）应用的增加为临床管理和公共卫生监测提供了有价值的见解。WGS可用于分析耐药性、识别流行的亚谱系以及追踪传播途径或疫情暴发。我们分析了1994年至2020年在泰国各地收集的2005株Mtb分离株的WGS数据，包括816株已检索样本和1189株新测序样本，大多数分离株为耐多药（MDR-TB）。大多数分离株是二线菌株（78.3%），主要是北京亚谱系（L2.2.1）。耐药性分析显示异烟肼和利福平耐药情况严重，67.3%的分离株被归类为MDR-TB。表型和基因型药敏试验显示高度一致（91.1%）。聚类分析确定了206个传播分支（最大规模为288株），主要为MDR-TB，尤其是在中部和东北部地区。一个分支（n = 22）含有与德拉马尼耐药相关的ddn Gly81Ser突变，一些成员在药物推出之前就已存在。在最大的分支（n = 288）中，包含跨越二十年的分离株，我们应用传播重建方法估计每年每个位点的突变率为1.1×10个替换。总体而言，本研究证明了WGS在揭示结核病传播和耐药性方面的价值，为泰国及其他地区制定更好的防控策略提供了关键数据。
