Open forum infectious diseases · 2026
Extensive Endemic Transmission of Multidrug-Resistant Mycobacterium tuberculosis in Bhutan: A Retrospective Genomic-Epidemiological Study.
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Dorji Thinley, Tshering Karchung, Adhikari Lila, Jamtsho Thinley, Bhujel Pavitra, Lhaden Pema, Wangchuk Sonam, Wirth Wytamma, Horan Kristy, Denholm Justin T, Sherry Norelle L, Sait Michelle, Stinear Timothy P, Howden Benjamin P, Andersson Patiyan
Аннотация
BACKGROUND: The proportion of multidrug-resistant tuberculosis (MDR-TB) cases is increasing in Bhutan. We conducted the first retrospective genomic-epidemiological study to provide insights into the population structure, resistance patterns, and recent transmission in Bhutan.
METHODS: Whole genome sequencing was performed on randomly selected drug-resistant (DR-TB) and drug-sensitive TB (DS-TB) isolates from Bhutan, collected between 2018 and 2022 at the Microbiological Diagnostic Unit Public Health Laboratory in Melbourne, Australia. Bioinformatic analysis was performed to identify drug-resistance mutations and genomic clustering of cases.
RESULTS: Approximately 40% of DR-TB and 2.5% of DS-TB were sequenced each year. Of the 203 sequences that passed the quality control, 126 (62.1%) were MDR-TB and 15 (7.4%) were isoniazid-resistant TB. There were 4 different circulating lineages, with the majority belonging to lineage 2 (86.2%). Using a SNP-threshold of ≤12 SNPs, 71% of sequences formed 12 genomic clusters; the largest comprised 88% of all MDR-TB sequences and spanned the entire study period and the country. These cases were highly clonal, with a mean pairwise SNP distance of 10 (range 0-25). Phylogenetic analysis with publicly available international sequence data showed that this MDR-TB cluster formed a distinct clade.
CONCLUSIONS: Contrary to current assumptions of repeat importations, the major burden of MDR-TB in Bhutan appears to be due to recent local transmission resulting in a large endemic cluster, advocating for targeted and enhanced contact tracing and screening for this MDR-TB clade. This study highlights the significant value of investing in TB genomics in resource-limited settings to gain actionable insights to inform policy decisions.
METHODS: Whole genome sequencing was performed on randomly selected drug-resistant (DR-TB) and drug-sensitive TB (DS-TB) isolates from Bhutan, collected between 2018 and 2022 at the Microbiological Diagnostic Unit Public Health Laboratory in Melbourne, Australia. Bioinformatic analysis was performed to identify drug-resistance mutations and genomic clustering of cases.
RESULTS: Approximately 40% of DR-TB and 2.5% of DS-TB were sequenced each year. Of the 203 sequences that passed the quality control, 126 (62.1%) were MDR-TB and 15 (7.4%) were isoniazid-resistant TB. There were 4 different circulating lineages, with the majority belonging to lineage 2 (86.2%). Using a SNP-threshold of ≤12 SNPs, 71% of sequences formed 12 genomic clusters; the largest comprised 88% of all MDR-TB sequences and spanned the entire study period and the country. These cases were highly clonal, with a mean pairwise SNP distance of 10 (range 0-25). Phylogenetic analysis with publicly available international sequence data showed that this MDR-TB cluster formed a distinct clade.
CONCLUSIONS: Contrary to current assumptions of repeat importations, the major burden of MDR-TB in Bhutan appears to be due to recent local transmission resulting in a large endemic cluster, advocating for targeted and enhanced contact tracing and screening for this MDR-TB clade. This study highlights the significant value of investing in TB genomics in resource-limited settings to gain actionable insights to inform policy decisions.