City-wide study finds most rifampicin-resistant TB is spread, not newly caused

Rifampicin-resistant tuberculosis (RR-TB) is a major public health problem in Viet Nam, with nearly 10,000 incident cases estimated each year. To find out whether that burden comes mainly from people catching already-resistant strains or from resistance developing anew during treatment, a research team led by Ruan Spies carried out a dense, city-wide study in Ho Chi Minh City. Between March 2020 and April 2024 the team enrolled adults newly diagnosed with pulmonary RR-TB, collecting sputum for culture and whole-genome sequencing (WGS) and taking demographic and clinical histories at enrolment. By combining the genetic information from bacteria with patients’ treatment histories and where people lived and commuted, the researchers set out to untangle which cases reflected transmission of resistant strains and which reflected resistance that emerged during care. This design allowed the team to look at recent cases across the whole city and place them in historical and geographic context, giving a clearer picture of how rifampicin resistance is spreading in a large urban setting.

Of 2,319 RR-TB cases diagnosed during the study period, 1,491 (64%) isolates were successfully sequenced. The team used phylogenetic analyses together with individual clinical histories to decide whether rifampicin resistance had been transmitted or was acquired de novo during treatment. They corrected their estimates for incomplete sampling using simulation-extrapolation (SIMEX) and reconstructed the timing of resistance emergence by lineage with Bayesian phylogenetic dating. To understand spread across the city they used geocoded residential data and commute time-based analyses. After accounting for sampling and phylogenetic uncertainty, the study estimated that between 72% and 87% of RR-TB arose through transmission of already-resistant strains, with the remainder due to de novo acquired resistance. Bayesian dating showed resistance emergence events happened repeatedly from the 1980s to the present, seeding long-lived, city-wide transmission networks. Those networks were geographically dispersed with limited household clustering and only weak demographic structure, pointing to diffuse transmission across the city rather than tight local outbreaks.

The findings have clear implications for how to control RR-TB in Ho Chi Minh City and similar urban settings. Because most cases are driven by transmission, public health efforts should focus on interrupting spread through earlier diagnosis and rapid treatment initiation so people with resistant infections are identified and treated before they can pass them on. At the same time, the study highlights that a substantial minority of cases result from resistance emerging during care, so programs must also investigate and address the drivers of acquired resistance. The authors note that their dense sampling, integration of whole-genome sequencing (WGS), phylogenetic placement of resistance mutations, and correction for sampling uncertainty give robust population-level estimates. Together, these results argue for a dual approach: intensify measures that stop transmission city-wide while researching and removing factors that allow rifampicin resistance to arise during treatment.