Transmission and Drug Resistance Genotype of Multidrug-Resistant or Rifampicin-Resistant Mycobacterium tuberculosis in Chongqing, China

ABSTRACT Multidrug-resistant or rifampicin-resistant tuberculosis (MDR/RR-TB) is a global barrier for the Stop TB plan. To identify risk factors for treatment outcome and cluster transmission of MDR/RR-TB, whole-genome sequencing (WGS) data of isolates from patients of the Chongqing Tuberculosis Con...

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Main Authors: Bing Zhao, Chunfa Liu, Jiale Fan, Aijing Ma, Wencong He, Yan Hu, Yanlin Zhao
Format: Article
Language:English
Published: American Society for Microbiology 2022-10-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/spectrum.02405-21
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author Bing Zhao
Chunfa Liu
Jiale Fan
Aijing Ma
Wencong He
Yan Hu
Yanlin Zhao
author_facet Bing Zhao
Chunfa Liu
Jiale Fan
Aijing Ma
Wencong He
Yan Hu
Yanlin Zhao
author_sort Bing Zhao
collection DOAJ
description ABSTRACT Multidrug-resistant or rifampicin-resistant tuberculosis (MDR/RR-TB) is a global barrier for the Stop TB plan. To identify risk factors for treatment outcome and cluster transmission of MDR/RR-TB, whole-genome sequencing (WGS) data of isolates from patients of the Chongqing Tuberculosis Control Institute were used for phylogenetic classifications, resistance predictions, and cluster analysis. A total of 223 MDR/RR-TB cases were recorded between 1 January 2018 and 31 December 2020. Elderly patients and those with lung cavitation are at increased risk of death due to MDR/RR-TB. A total of 187 MDR/RR strains were obtained from WGS data; 152 were classified as lineage 2 strains. Eighty (42.8%) strains differing by a distance of 12 or fewer single nucleotide polymorphisms were classified as 20 genomic clusters, indicating recent transmission. Patients infected with lineage 2 strains or those with occupations listed as “other” are significantly associated with a transmission cluster of MDR/RR-TB. Analysis of resistant mutations against first-line tuberculosis drugs found that 76 (95.0%) of all 80 strains had the same mutations within each cluster. A total of 55.0% (44 of 80) of the MDR/RR-TB strains accumulated additional drug resistance mutations along the transmission chain, especially against fluoroquinolones (63.6% [28 of 44]). Recent transmission of MDR/RR strains is driving the MDR/RR-TB epidemics, leading to the accumulation of more serious resistance along the transmission chains. IMPORTANCE The drug resistance molecular characteristics of MDR/RR-TB were elucidated by genome-wide analysis, and risk factors for death by MDR/RR-TB were identified in combination with patient information. Cluster characteristics of MDR/RR-TB in the region were analyzed by genome-wide analysis, and risk factors for cluster transmission (recent transmission) were analyzed. These analyses provide reference for the prevention and treatment of MDR/RR-TB in Chongqing.
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spelling doaj.art-5ecf5831cb994b1a8298072e0bb50f012022-12-22T03:54:08ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-10-0110510.1128/spectrum.02405-21Transmission and Drug Resistance Genotype of Multidrug-Resistant or Rifampicin-Resistant Mycobacterium tuberculosis in Chongqing, ChinaBing Zhao0Chunfa Liu1Jiale Fan2Aijing Ma3Wencong He4Yan Hu5Yanlin Zhao6National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Changping, Beijing, ChinaNational Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Changping, Beijing, ChinaNational Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Changping, Beijing, ChinaNational Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Changping, Beijing, ChinaNational Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changping, Beijing, ChinaTuberculosis Reference Laboratory, Chongqing Tuberculosis Control Institute, Jiulongpo, Chongqing, ChinaNational Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Changping, Beijing, ChinaABSTRACT Multidrug-resistant or rifampicin-resistant tuberculosis (MDR/RR-TB) is a global barrier for the Stop TB plan. To identify risk factors for treatment outcome and cluster transmission of MDR/RR-TB, whole-genome sequencing (WGS) data of isolates from patients of the Chongqing Tuberculosis Control Institute were used for phylogenetic classifications, resistance predictions, and cluster analysis. A total of 223 MDR/RR-TB cases were recorded between 1 January 2018 and 31 December 2020. Elderly patients and those with lung cavitation are at increased risk of death due to MDR/RR-TB. A total of 187 MDR/RR strains were obtained from WGS data; 152 were classified as lineage 2 strains. Eighty (42.8%) strains differing by a distance of 12 or fewer single nucleotide polymorphisms were classified as 20 genomic clusters, indicating recent transmission. Patients infected with lineage 2 strains or those with occupations listed as “other” are significantly associated with a transmission cluster of MDR/RR-TB. Analysis of resistant mutations against first-line tuberculosis drugs found that 76 (95.0%) of all 80 strains had the same mutations within each cluster. A total of 55.0% (44 of 80) of the MDR/RR-TB strains accumulated additional drug resistance mutations along the transmission chain, especially against fluoroquinolones (63.6% [28 of 44]). Recent transmission of MDR/RR strains is driving the MDR/RR-TB epidemics, leading to the accumulation of more serious resistance along the transmission chains. IMPORTANCE The drug resistance molecular characteristics of MDR/RR-TB were elucidated by genome-wide analysis, and risk factors for death by MDR/RR-TB were identified in combination with patient information. Cluster characteristics of MDR/RR-TB in the region were analyzed by genome-wide analysis, and risk factors for cluster transmission (recent transmission) were analyzed. These analyses provide reference for the prevention and treatment of MDR/RR-TB in Chongqing.https://journals.asm.org/doi/10.1128/spectrum.02405-21MDR/RR-TBrecent transmissiondrug resistanceWGS
spellingShingle Bing Zhao
Chunfa Liu
Jiale Fan
Aijing Ma
Wencong He
Yan Hu
Yanlin Zhao
Transmission and Drug Resistance Genotype of Multidrug-Resistant or Rifampicin-Resistant Mycobacterium tuberculosis in Chongqing, China
Microbiology Spectrum
MDR/RR-TB
recent transmission
drug resistance
WGS
title Transmission and Drug Resistance Genotype of Multidrug-Resistant or Rifampicin-Resistant Mycobacterium tuberculosis in Chongqing, China
title_full Transmission and Drug Resistance Genotype of Multidrug-Resistant or Rifampicin-Resistant Mycobacterium tuberculosis in Chongqing, China
title_fullStr Transmission and Drug Resistance Genotype of Multidrug-Resistant or Rifampicin-Resistant Mycobacterium tuberculosis in Chongqing, China
title_full_unstemmed Transmission and Drug Resistance Genotype of Multidrug-Resistant or Rifampicin-Resistant Mycobacterium tuberculosis in Chongqing, China
title_short Transmission and Drug Resistance Genotype of Multidrug-Resistant or Rifampicin-Resistant Mycobacterium tuberculosis in Chongqing, China
title_sort transmission and drug resistance genotype of multidrug resistant or rifampicin resistant mycobacterium tuberculosis in chongqing china
topic MDR/RR-TB
recent transmission
drug resistance
WGS
url https://journals.asm.org/doi/10.1128/spectrum.02405-21
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