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Whole Genome Sequence Analysis for Enhanced Contact Investigations of Tuberculosis Outbreaks in Chiang Rai

ภากร เอี้ยวสกุล; Pakorn Aiewsakun; สุรัคเมธ มหาศิริมงคล; Surakameth Mahasirimongkol;
Date: 2568-03
Abstract
Tuberculosis (TB) remains a global public health challenge, including in Thailand, where it is most commonly caused by Mycobacterium tuberculosis. While TB morbidity and mortality rates in Thailand have been steadily declining, the current “passive” approach to TB control has resulted in a reduction rate that remains too slow to achieve the national goal of "End TB" by 2030, in alignment with the Sustainable Development Goals. We believe that if large outbreak clusters can be identified and resources can be strategically allocated to target highly drug-resistant strains with prompt treatment or preventive measures in a more “proactive” manner, TB transmission could be more effectively reduced. This project aims to develop a bioinformatics pipeline for whole-genome sequencing (WGS) analysis of M. tuberculosis to detect large outbreak clusters, identify strains, and characterise drug resistance patterns. The findings will support targeted TB investigations, and prioritisation efforts, as well as capacity-building initiatives for healthcare professionals to enhance the efficiency and effectiveness of TB diagnosis, treatment, and outbreak investigations. Chiang Rai province, designated as a high-burden TB area with significant strain diversity, has been selected as the study site. The project has a total duration of two years. In year 1, the project collected and performed preliminary analyses on whole-genome sequences of M. tuberculosis isolates from Chiang Rai and other provinces in Thailand. The analysis identified four predominant lineages in Chiang Rai: L1, L2, L3, and L4. L2 exhibited a significantly higher overall drug resistance rate than L1. The spatial distribution of each lineage varied across Chiang Rai, but all regions faced comparable levels of drug-resistant TB. Over the past two decades (1999–2023), no significant increase or decrease was observed in the proportion of any particular lineage or drug-resistant strain. Data suggest that L1 is more frequently found among elderly patients, while L2 is more common in pediatric and working-age populations. Lineages L3 and L4 were detected across all age groups. Additionally, no significant association was found between drug resistance patterns and patient age. However, lineage distribution showed a significant correlation with patient nationality and ethnicity, as well as TB outcomes, whereas drug resistance patterns were only associated with nationality. Clustering and phylogenetic analyses indicate that TB outbreaks in Chiang Rai are linked to outbreaks in other Thai provinces. Notably, different drug-resistant strains were sometimes found within the same WGS cluster. Further analysis suggests that drug-resistant strains, particularly RR-TB and Pre-XDR-TB, tend to be able to sustain transmission more effectively compared to non-resistant strains, with transmission potential varying by drug resistance type and lineage. Specific lineages of interest include L2.2.M3MDR-TB, L2.2.M3Pre-XDR-TB, L2.2.AA3.2RR-TB, L4.4.2MDR-TB, L2.1Pre-XDR-TB, L2.2.M2.3MDR-TB, L2.2.M2.3Pre-XDR-TB, L2.2.M4.2HR-TB, L2.2.M4.2 Other DR type, and L2.2.M4.2Pre-XDR-TB, all of which exhibited an average of more than five WGS lineages at an SNP cut-off of 20. These findings have been shared with public health authorities to support targeted TB investigations in Chiang Rai and have been presented at multiple scientific conferences organised or attended by the project team. Currently, the project is developing a WGS data analysis pipeline for M. tuberculosis, which is expected to be completed in year 2. Once finalised, the tool will be publicly released for broader application and impact.
Copyright ผลงานวิชาการเหล่านี้เป็นลิขสิทธิ์ของสถาบันวิจัยระบบสาธารณสุข หากมีการนำไปใช้อ้างอิง โปรดอ้างถึงสถาบันวิจัยระบบสาธารณสุข ในฐานะเจ้าของลิขสิทธิ์ตามพระราชบัญญัติสงวนลิขสิทธิ์สำหรับการนำงานวิจัยไปใช้ประโยชน์ในเชิงพาณิชย์
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