Tracing drug‑resistant tuberculosis spread in Vietnam

Vietnam is among the top 20 countries burdened by multi-drug resistant/rifampicin-resistant tuberculosis (MDR/RR-TB), with nearly 10,000 cases each year. To better understand how rifampicin-resistant TB is spreading and what resistance looks like at the molecular level, Ori Solomon and colleagues studied bacterial samples collected through the VQUIN MDR trial. The team assembled cultured isolates from patients with confirmed RR-M. tuberculosis across 10 provinces, intentionally enriching for samples from outside the two major cities, Hanoi and Ho Chi Minh City, so they could capture regional patterns. They used a combination of newer diagnostic assays and genomic tools to map resistance: whole genome sequencing (WGS) and bioinformatic analysis on the cultured isolates, and phenotypic drug susceptibility testing (DST) on a subset to compare lab growth-based resistance with predictions from the genome. The new genome sequences were also placed into a wider Vietnamese context by comparing them to publicly-available M. tuberculosis genome sequences sampled in Vietnam from the National Center for Biotechnology Information (NCBI) Sequence Read Archives (SRA). This approach was designed to link specific resistance mutations and bacterial lineages to geographic spread and to test how well rapid diagnostics match genomic results.

Of the isolates studied, 252 rifampicin-resistant TB cases passed quality control and were included in the final analysis. Xpert MTB/RIF showed high concordance with WGS-based rifampicin-resistance prediction (PPV=96.8%). Of the 244 isolates confirmed to be rifampicin resistant, 235/244 (96.3%) carried mutations associated with resistance to at least one other first- or second-line antibiotic. Phenotypic DST for rifampicin, isoniazid, and levofloxacin was completed for 77 isolates and demonstrated high concordance between growth-based DST and genomic resistance predictions: 67/77, 87.0% RIF; 76/77, 98.7% INH; 73/77, 94.8% LFX. The team also compared genomic predictions with phenotypic results for newer and repurposed drugs and found high agreement: linezolid (100%, 60/60), pretomanid (100%, 60/60), and bedaquiline (56/60, 93.3%). When placed in the broader Vietnamese genomic context using NCBI SRA data, rifampicin-resistant strains were more likely to belong to lineage 2.2.1 compared with rifampicin-susceptible M. tuberculosis strains, a pattern particularly evident in the major cities.

These findings have several practical implications for controlling MDR/RR-TB in Vietnam. First, the very high rate of additional resistance among rifampicin-resistant isolates means that detecting RIF resistance alone is often not enough to guide treatment; most RIF-resistant strains carried resistance to at least one other drug. Second, the strong agreement between Xpert MTB/RIF, WGS-based predictions, and phenotypic DST for many drugs suggests that combining rapid molecular diagnostics with genomic analysis can give reliable information on resistance profiles, including for drugs like linezolid, pretomanid, and bedaquiline. Third, the dominance of lineage 2.2.1 across geographic regions points to the spread of a major bacterial lineage driving much of the MDR/RR-TB burden in Vietnam. Together, these results reinforce the importance of prompt and broad detection of drug-resistance to inform the timely initiation of effective drug regimens, and they highlight how genomic surveillance can help public health programs track and respond to resistant TB strains across the country.