A large geno-spatial cluster of multi-drug resistant tuberculosis outbreak in a western district of Thailand.

The growing issue of drug resistance, particularly multidrug-resistant TB (MDR-TB), has exacerbated this problem. The rise of drug resistance TB is a severe global health concern. In Thailand, a persistent community outbreak of primary MDR-TB has been confirmed in the Tha Maka district of Kanchanaburi province, with an increasing prevalence of MDR-TB among newly diagnosed pulmonary tuberculosis cases. It was the first site in Thailand where a cluster of MDR-TB, caused by the Asian African 3 Modern Beijing strain, and XDR-TB, caused by L2.1, outbreaks were reported. This study aims to assess the MDR-TB outbreak in detail by characterizing the genomic profiles of the prevalent MDR-TB strains and examining their geographical distribution within the affected district. Through whole-genome sequencing (WGS) and bioinformatic analysis of 188 MTB isolates, the study identified three major phylogenetic lineages: the East Asian lineage (L2, 92 %), the Indo-Oceanic lineage (L1, 5.9 %), and the Euro-American lineage (L4, 2.1 %). The detailed sub-lineage distribution offers valuable insights into the predominant genetic clusters of M. tuberculosis within the sampled population. Notably, Lineage 2, specifically the L2.2.M3 sub-lineage, stood out as the dominant strain of MDR-TB, accounting for 77.7 % of the isolates. This finding underscores the significant prevalence of the L2.2.M3 sub-lineage and its potential role in the local transmission dynamics of tuberculosis. The high proportion and genetic homogeneity of the L2.2.M3 cluster among MDR-TB patients may indicate the strain's adaptation for more effective transmission within the Thai population. The increasing prevalence of this pathogenic strain could significantly impact tuberculosis control programs. Early diagnosis and contact tracing with chemotherapeutic preventive therapy for MDR-TB will be essential in inhibiting the spread and reactivation of these strains. Additionally, further studies are needed to prospectively identify transmission routes through contact tracing and real-time genotypic methods. It will also be crucial to ensure that future vaccines and/or recommended chemoprophylaxis therapy for MDR-TB will provide protection against these emerging strains.