Epidemiologic and Bacterial Factors Facilitating Long-Term Transmission of Multidrug-Resistant Tuberculosis in Shanghai, China

Abstract Background Long-term transmission of multidrug-resistant tuberculosis (MDR-TB) challenges TB control by generating new cases and enabling the emergence of extensively resistant strains. We investigated its epidemiologic and bacterial drivers in Shanghai, China. Methods We conducted a retrospective study of M. tuberculosis isolates and associated epidemiological data from individuals diagnosed with rifampicin-resistant TB in Shanghai over 14 years (2004–2018). Using whole-genome sequencing, Bayesian reconstruction of transmission trees, and multivariable regression analysis to identify epidemiological and bacterial factors associated with the transmission of MDR-TB. Results Between 2004 and 2018, 1,456 individuals in Shanghai were diagnosed with MDR or rifampicin-resistant TB, with whole-genome sequences available for 1,100 isolates. The overall genomic clustering rate was 55.3%, with large clusters (those containing ≥5 cases) accounting for 39.9% of the clustered strains. Risk factors for clustered MDR-TB transmission included local residency (aOR 2.28, 95% CI 1.67–3.11), diagnostic delays ≥2 months (aOR 1.75, 95% CI 1.24–2.47), specific M. tuberculosis sublineages (L2.3.3–L2.3.6), and the rpoB S450L mutation with compensatory mutations (aOR 2.14, 95% CI 1.64–2.78). Large MDR-TB clusters were significantly associated with long-term transmission (>5 years, p<0.001). Long-term transmission clusters correlated with same-street residence, local residency, and MDR-TB strains carrying katG315T, rpoB450L and compensatory mutations. Conclusions Despite ample healthcare resources, MDR-TB persists in urban areas due to both epidemiological and bacterial factors. The rpoB S450 mutation with compensatory mutations enhances transmission even in the absence of clear epidemiologic links. Effective control measures must address both epidemiological and bacterial factors.