Transmission of rifampicin-resistant tuberculosis in Ho Chi Minh City, Viet Nam: a prospective genomic epidemiology study.
Spies R., Hanh NH., Phu PT., Lan LK., Lan K., Hue NN., Le Quang N., Anh Thu DD., Le Huong NT., Le Thi Ngoc Thao T., Bich Tram TT., Ngoc Ha VT., Minh Ha DT., Hai NP., Thuan NH., Kim Quy TT., Lan NH., Dreyer V., Niemann S., Crook D., Van LH., Thwaites G., Thuong Thuong NT., Choisy M., Watson JA., Walker TM.
BACKGROUND: Rifampicin-resistant tuberculosis (RR-TB) is a major threat to public health in Viet Nam, with nearly 10,000 incident cases estimated annually. It is uncertain whether these cases are driven by transmission of resistant strains or de novo resistance acquisition during treatment. METHODS: We undertook dense, city-wide sampling of adults newly diagnosed with pulmonary RR-TB in Ho Chi Minh City, Viet Nam's largest city, between March 2020 and April 2024. Participants provided sputum for culture and whole-genome sequencing (WGS), and demographic and clinical data were collected at enrolment. Phylogenetic analyses were combined with clinical histories to infer transmitted versus acquired rifampicin resistance. Estimates were corrected for sampling coverage using simulation-extrapolation (SIMEX). Temporal emergence of rifampicin resistance was reconstructed by lineage using Bayesian phylogenetic dating, and the geographic and demographic structure of transmission clades was assessed using geocoded residential data and commute time-based analyses. FINDINGS: Among 2319 RR-TB cases diagnosed during the study period, 1491 (64%) isolates were successfully sequenced. Among these, 1320 (89%) were Lineage 2. After accounting for sampling and phylogenetic uncertainty, we estimated that 72-87% of RR-TB was attributable to transmission of already-resistant strains, with the remainder reflecting de novo acquired resistance. Bayesian dating analyses revealed that resistance emergence events occurred repeatedly from the 1980s to the present, with early events seeding long-lived, city-wide transmission clades. Transmission clades were geographically dispersed across the city, with limited household clustering, and only weakly structured by host demographics, consistent with diffuse, city-wide transmission rather than localised or assortative spread. INTERPRETATION: RR-TB in Ho Chi Minh City is driven predominantly by ongoing transmission, but a substantial minority of cases arise from newly acquired resistance. Alongside promoting early diagnosis and treatment to interrupt transmission, the main drivers of acquired resistance need to be identified to control RR-TB. FUNDING: The Rhodes Trust, Wellcome.