Transmission of multidrug-resistant Mycobacterium tuberculosis in Shanghai, China: a retrospective observational study using whole-genome sequencing and epidemiological investigation

Chongguang Yang, Tao Luo, Xin Shen, Jie Wu, Mingyu Gan, Peng Xu, Zheyuan Wu, Senlin Lin, Jiyun Tian, Qingyun Liu, Zheng An Yuan, Jian Mei, Kathryn DeRiemer, Qian Gao

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Abstract

Background Multidrug-resistance is a substantial threat to global elimination of tuberculosis. Understanding transmission patterns is crucial for control of the disease. We used a genomic and epidemiological approach to assess recent transmission of multidrug-resistant (MDR) tuberculosis and identify potential risk factors for transmission. Methods We did a population-based, retrospective study of patients who tested positive for tuberculosis between Jan 1, 2009, and Dec 31, 2012, in Shanghai, China. We did variable-number-of-tandem-repeat genotyping and whole-genome sequencing of isolates. We measured strain diversity within and between genomically clustered isolates. Genomic and epidemiological 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 tuberculosis strains, with increasing drug-resistance, drives the MDR tuberculosis epidemic in Shanghai, China. Whole-genome sequencing can measure of the heterogeneity of drug-resistant mutations within and between hosts and help to determine the transmission patterns of MDR tuberculosis. Funding National Science and Technology Major Project, National Natural Science Foundation of China, and US National Insitutes of Health.

Original languageEnglish (US)
Pages (from-to)275-284
Number of pages10
JournalThe Lancet Infectious Diseases
Volume17
Issue number3
DOIs
StatePublished - Mar 1 2017

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Multidrug-Resistant Tuberculosis
Mycobacterium tuberculosis
Observational Studies
China
Retrospective Studies
Genome
Mutation
Tuberculosis
Drug Resistance
Natural Science Disciplines
Minisatellite Repeats
Delayed Diagnosis
Multiple Drug Resistance
Rifampin
Single Nucleotide Polymorphism
Technology
Health
Pharmaceutical Preparations
Population

ASJC Scopus subject areas

  • Infectious Diseases

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Transmission of multidrug-resistant Mycobacterium tuberculosis in Shanghai, China : a retrospective observational study using whole-genome sequencing and epidemiological investigation. / Yang, Chongguang; Luo, Tao; Shen, Xin; Wu, Jie; Gan, Mingyu; Xu, Peng; Wu, Zheyuan; Lin, Senlin; Tian, Jiyun; Liu, Qingyun; Yuan, Zheng An; Mei, Jian; DeRiemer, Kathryn; Gao, Qian.

In: The Lancet Infectious Diseases, Vol. 17, No. 3, 01.03.2017, p. 275-284.

Research output: Contribution to journalArticle

Yang, Chongguang ; Luo, Tao ; Shen, Xin ; Wu, Jie ; Gan, Mingyu ; Xu, Peng ; Wu, Zheyuan ; Lin, Senlin ; Tian, Jiyun ; Liu, Qingyun ; Yuan, Zheng An ; Mei, Jian ; DeRiemer, Kathryn ; Gao, Qian. / Transmission of multidrug-resistant Mycobacterium tuberculosis in Shanghai, China : a retrospective observational study using whole-genome sequencing and epidemiological investigation. In: The Lancet Infectious Diseases. 2017 ; Vol. 17, No. 3. pp. 275-284.
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T1 - Transmission of multidrug-resistant Mycobacterium tuberculosis in Shanghai, China

T2 - a retrospective observational study using whole-genome sequencing and epidemiological investigation

AU - Yang, Chongguang

AU - Luo, Tao

AU - Shen, Xin

AU - Wu, Jie

AU - Gan, Mingyu

AU - Xu, Peng

AU - Wu, Zheyuan

AU - Lin, Senlin

AU - Tian, Jiyun

AU - Liu, Qingyun

AU - Yuan, Zheng An

AU - Mei, Jian

AU - DeRiemer, Kathryn

AU - Gao, Qian

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Background Multidrug-resistance is a substantial threat to global elimination of tuberculosis. Understanding transmission patterns is crucial for control of the disease. We used a genomic and epidemiological approach to assess recent transmission of multidrug-resistant (MDR) tuberculosis and identify potential risk factors for transmission. Methods We did a population-based, retrospective study of patients who tested positive for tuberculosis between Jan 1, 2009, and Dec 31, 2012, in Shanghai, China. We did variable-number-of-tandem-repeat genotyping and whole-genome sequencing of isolates. We measured strain diversity within and between genomically clustered isolates. Genomic and epidemiological 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 tuberculosis strains, with increasing drug-resistance, drives the MDR tuberculosis epidemic in Shanghai, China. Whole-genome sequencing can measure of the heterogeneity of drug-resistant mutations within and between hosts and help to determine the transmission patterns of MDR tuberculosis. Funding National Science and Technology Major Project, National Natural Science Foundation of China, and US National Insitutes of Health.

AB - Background Multidrug-resistance is a substantial threat to global elimination of tuberculosis. Understanding transmission patterns is crucial for control of the disease. We used a genomic and epidemiological approach to assess recent transmission of multidrug-resistant (MDR) tuberculosis and identify potential risk factors for transmission. Methods We did a population-based, retrospective study of patients who tested positive for tuberculosis between Jan 1, 2009, and Dec 31, 2012, in Shanghai, China. We did variable-number-of-tandem-repeat genotyping and whole-genome sequencing of isolates. We measured strain diversity within and between genomically clustered isolates. Genomic and epidemiological 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 tuberculosis strains, with increasing drug-resistance, drives the MDR tuberculosis epidemic in Shanghai, China. Whole-genome sequencing can measure of the heterogeneity of drug-resistant mutations within and between hosts and help to determine the transmission patterns of MDR tuberculosis. Funding National Science and Technology Major Project, National Natural Science Foundation of China, and US National Insitutes of Health.

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