Cross-sectional Whole-genome Sequencing and Epidemiological Study of Multidrug-resistant Mycobacterium Tuberculosis in China

Overview

Journal Clin Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2018 Oct 16

PMID 30321294

Citations 27

Authors

Hairong Huang

Nan Ding

Tingting Yang

Cuidan Li

Xinmiao Jia

Guirong Wang

Jun Zhong

Ju Zhang

Guanglu Jiang

Shuqi Wang

Zhaojing Zong

Wei Jing

Yongliang Zhao

Shaofa Xu

Fei Chen

Affiliations

Soon will be listed here.

Abstract

Background: The increase in multidrug-resistant tuberculosis (MDR-TB) severely hampers tuberculosis prevention and control in China, a country with the second highest MDR-TB burden globally. The first nationwide drug-resistant tuberculosis surveillance program provides an opportunity to comprehensively investigate the epidemiological/drug-resistance characteristics, potential drug-resistance mutations, and effective population changes of Chinese MDR-TB.

Methods: We sequenced 357 MDR strains from 4600 representative tuberculosis-positive sputum samples collected during the survey (70 counties in 31 provinces). Drug-susceptibility testing was performed using 18 anti-tuberculosis drugs, representing the most comprehensive drug-resistance profile to date. We used 3 statistical and 1 machine-learning methods to identify drug-resistance genes/single-nucleotide polymorphisms (SNPs). We used Bayesian skyline analysis to investigate changes in effective population size.

Results: Epidemiological/drug-resistance characteristics showed different MDR profiles, co-resistance patterns, preferred drug combination/use, and recommended regimens among 7 Chinese administrative regions. These factors not only reflected the serious multidrug co-resistance and drug misuse but they were also potentially significant in facilitating the development of appropriate regimens for MDR-TB treatment in China. Further investigation identified 86 drug-resistance genes/intergenic regions/SNPs (58 new), providing potential targets for MDR-TB diagnosis and treatment. In addition, the effective population of Chinese MDR-TB displayed a strong expansion during 1993-2000, reflecting socioeconomic transition within the country. The phenomenon of expansion was restrained after 2000, likely attributable to the advances in diagnosis/treatment technologies and government support.

Conclusions: Our findings provide an important reference and improved understanding of MDR-TB in China, which are potentially significant in achieving the goal of precision medicine with respect to MDR-TB prevention and treatment.

Citing Articles

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Li Y, Shao Y, Li Y, Kong X, Tao N, Hou Y BMC Infect Dis. 2024; 24(1):1250.

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A Profile of Drug-Resistant Mutations in Isolates from Guangdong Province, China.

Zhang C, Wu Z, Huang X, Zhao Y, Sun Q, Chen Y Indian J Microbiol. 2024; 64(3):1044-1056.

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Association of mutations in Mycobacterium tuberculosis complex (MTBC) respiration chain genes with hyper-transmission.

Li Y, Li Y, Liu Y, Kong X, Tao N, Hou Y BMC Genomics. 2024; 25(1):810.

PMID: 39198760 PMC: 11350932. DOI: 10.1186/s12864-024-10726-z.

Toxin-antitoxin system gene mutations driving transmission revealed by whole genome sequencing.

Hou Y, Li Y, Tao N, Kong X, Li Y, Liu Y Front Microbiol. 2024; 15:1398886.

PMID: 39144214 PMC: 11322068. DOI: 10.3389/fmicb.2024.1398886.

Drug Resistance and Epidemiological Success of Modern Mycobacterium tuberculosis Lineages in Western India.

Dixit A, Ektefaie Y, Kagal A, Freschi L, Karyakarte R, Lokhande R J Infect Dis. 2024; 231(1):84-93.

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