Summary Background Multidrug-resistant tuberculosis (MDR-TB) is a significant threat to tuberculosis elimination worldwide. Understanding the transmission pattern is crucial for its control. We used a genomic epidemiological approach to assess the recent transmission of MDR-TB and potential risk factors for transmission. Methods In a population-based retrospective study, we performed variable-number-of-tandem-repeat (VNTR) genotyping, followed by whole-genome sequencing (WGS) of isolates from all MDR-TB patients in Shanghai, China, 2009-2012. We measured strain diversity within and between genomically clustered patients. Genomic and epidemiologic data were combined to construct transmission networks. Findings 367 (5%) of 7982 patients with tuberculosis had MDR tuberculosis and 324 (88%) of these had isolates available for genomic analysis. 103 (32%) of the 324 MDR strains were in 38 genomic clusters that differed by 12 or fewer single nucleotide polymorphisms (SNPs), indicating recent transmission of MDR strains. Patients who had delayed diagnosis or were older than 45 years had high risk of recent transmission. 235 (73%) patients with MDR tuberculosis probably had transmission of MDR strains. Transmission network analysis showed that 33 (87%) of the 38 clusters accumulated additional drug-resistance mutations through emergence or fixation of mutations during transmission. 68 (66%) of 103 clustered MDR strains had compensatory mutations of rifampicin resistance. Interpretation Recent transmission of MDR strains, with increasing drug-resistance, helps drive the MDR-TB epidemic in Shanghai, China. WGS provides a measure of the heterogeneity of drug-resistant mutations within and between hosts and enhances our ability to determine the transmission patterns of MDR-TB. Funding National Science and Technology Major Project, National Natural Science Foundation of China, and US National Insitutes of Health.

National Natural Science Foundation of China, National Science and Technology Major Project of China, and US National Institutes of Health.

Recent transmission of M. tuberculosis, including MDR strains, contributes substantially to tuberculosis disease in China. Sputum smear-negative cases were responsible for at least 30% of the secondary cases. Interventions to reduce the transmission of M. tuberculosis should be implemented in China.

To determine the factors contributing to tuberculosis incidence in the U.S.-born and foreign-born populations in San Francisco, California, and to assess the effectiveness of tuberculosis control efforts in these populations, we performed a population-based molecular epidemiologic study using 367 patients with strains of Mycobacterium tuberculosis recently introduced into the city. IS6110-based and PGRS-based restriction fragment length polymorphism (RFLP) analyses were performed on M. tuberculosis isolates. Patients whose isolates had identical RFLP patterns were considered a cluster. Review of public health and medical records, plus patient interviews, were used to determine the likelihood of transmission between clustered patients. None of the 252 foreign-born cases was recently infected (within 2 yr) in the city. Nineteen (17%) of 115 U. S.-born cases occurred after recent infection in the city; only two were infected by a foreign-born patient. Disease from recent infection in the city involved either a source or a secondary case with human immunodeficiency virus (HIV) infection, homelessness, or drug abuse. Failure to identify contacts accounted for the majority of secondary cases. In San Francisco, disease from recent transmission of M. tuberculosis has been virtually eliminated from the foreign-born but not from the U.S.-born population. An intensification of contact tracing and screening activities among HIV-infected, homeless, and drug-abusing persons is needed to further control tuberculosis in the U.S.-born population. Elimination of tuberculosis in both the foreign-born and the U.S. -born populations will require widespread use of preventive therapy.