Large local spread of multidrug-resistant TB found in Bhutan

Tuberculosis remains a public health concern in Bhutan even as overall case notifications fall, because the proportion of multidrug-resistant tuberculosis (MDR-TB) is rising. Thinley Dorji and colleagues set out to understand whether these drug-resistant cases represent repeated introductions from outside the country or ongoing local spread. Traditional diagnostic tests used in the country cannot reliably tell the difference. To fill that gap, the team carried out a retrospective genomic-epidemiological study using bacterial samples collected from 2018 to 2022. Samples were analyzed offsite at the Microbiological Diagnostic Unit Public Health Laboratory in Melbourne, Australia. The goal was to map the population structure of Mycobacterium tuberculosis in Bhutan, identify genotypic resistance patterns, and look for signs of recent transmission. By combining patient isolates with genomic methods, the researchers could look beyond routine lab results and trace how closely related individual infections were, helping to distinguish between imported cases and chains of local transmission.

The researchers performed Whole genome sequencing on randomly selected drug-resistant and drug-sensitive TB isolates collected between 2018 and 2022 at the Microbiological Diagnostic Unit Public Health Laboratory in Melbourne, Australia. They investigated drug resistance mutations and examined genomic clustering using different single nucleotide polymorphisms (SNPs) thresholds. Of 203 sequences that passed quality control, 126 (62.1%) were classified as MDR-TB and 15 (7.4%) were isoniazid-resistant TB. The isolates represented four 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. Strikingly, the largest cluster contained 88% of all MDR-TB sequences and persisted across the entire study period. These cases were highly clonal, with a mean pairwise SNP-distance of 10 and a range of 0–25. Phylogenetic analysis that included publicly available international sequence data showed that this MDR-TB cluster formed a distinct clade.

The study’s main finding is that the major burden of MDR-TB in Bhutan appears to come from recent local transmission that has produced a large, single endemic cluster. This means that many MDR-TB cases are not separate importations but are linked in chains of spread within the country. The authors highlight that this genomic picture is immediately useful for public health action: the national TB control program can focus on enhanced contact tracing targeted at the members of this MDR-TB clade. The genomic data are also valuable regionally, because neighbouring countries can use these sequences to watch for any spread beyond Bhutan’s borders. Finally, the work underscores the significant value of investing in TB genomics in resource-limited settings to produce actionable insights into transmission dynamics and to guide more effective interventions.