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

Zhao, Bing; Liu, Chunfa; Fan, Jiale; Ma, Aijing; He, Wencong; Hu, Yan; Zhao, Yanlin

doi:10.1128/spectrum.02405-21

Cited by 9 publications

(10 citation statements)

References 41 publications

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“…Only 9.6% reported in Guangxi 32 and 5.35% reported in Thailand 33 were found in other areas of China and neighboring countries of Hainan Island, which indicated Molecular evolution studies have suggested that lineage 2 (East Asian) has a higher propensity for propagation compared to lineage 4 (Euro-American). 34,35 However, despite no significant association between MDR-MTB genotypes 27 it can be inferred that 75 (37.1%) MDR-TB patients on Hainan Island potentially transmitted MDR-MTB strains during the study period, consistent with findings from other studies where more than one-third of MDR-TB cases were suspected to be transmission events. 20 Several factors, including sample size, study duration, and different genomic cluster thresholds, may contribute to variations in these results.…”

Section: Discussionsupporting

confidence: 87%

“…However, WGS can aid in identifying transmission events in patients even without epidemiological data. 26,27 In this study, WGS was employed to detect drug resistance patterns, assess genetic diversity, and analyze the drug resistance of potential MDR-MTB strains, thereby shedding light on the molecular epidemiology of MDR-MTB on Hainan Island, China. Consistent with previous reports from various regions in China, 6,27-29 lineage 2 (East Asian) was found to be the predominant genotype among MDR-MTB strains on Hainan Island, followed by lineage 4 (Euro-American).…”

Section: Discussionmentioning

confidence: 99%

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Analysis of Drug-Resistance Characteristics and Genetic Diversity of Multidrug-Resistant Tuberculosis Based on Whole-Genome Sequencing on the Hainan Island, China

Wang,

Yu,

et al. 2023

IDR

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Given the high burden of Tuberculosis (TB) in China, the prevalence of multidrug-resistant tuberculosis (MDR-TB) is significant. Whole-genome sequencing (WGS) of Mycobacterium tuberculosis (MTB) enables the identification of lineages, drugresistant mutations, and transmission patterns, offering valuable insights for TB control, clinical diagnosis, and treatment. Methods: We collected 202 MDR-MTB strains from 3519 suspected pulmonary TB patients treated at The Second Affiliated Hospital of Hainan Medical University between July 2019 and June 2021. Proportional drug-susceptibility testing was performed using 8 common anti-tuberculosis drugs. Subsequently, the genotypic drug resistance and genetic characteristics were analyzed by the WGS. Results: Lineages are identified by TB-profiler revealed 202 MDR-MTB strains, showcasing three predominant lineages, with lineage 2 being the most prevalent. Close genomic relatedness analysis and evidence of MTB transmission led to the formation of 15 clusters comprising 42 isolates, resulting in a clustering rate of 20.8%. Novelty, lineage 2.1 (non-Beijing) accounted for 27.2% of the MDR-MTB strains, which is rare in China and Neighboring countries. Regarding first-line anti-TB drugs, genes associated with rifampicin resistance, primarily the rpoB gene, were detected in 200 strains (99.0%). Genes conferring resistance to isoniazid, ethambutol, and streptomycin were identified in 191 (94.5%), 125 (61.9%), and 100 (49.5%) strains, respectively. Among the second-line drugs, 97 (48.0%) strains exhibited genes encoding resistance to fluoroquinolones. Comparing the results to phenotypic drug susceptibility-based testing, the sensitivity of WGS for detecting resistance to each of the six drugs (rifampicin, isoniazid, ethambutol, ofloxacin, kanamycin, capreomycin) was 90% or higher. With the exception of ethambutol, the specificity of WGS prediction for the remaining drugs exceeded 88%. Conclusion:Our study provides crucial insights into genetic mutation types, genetic diversity, and transmission of MDR-MTB on Hainan Island, serving as a significant reference for MDR-MTB surveillance and clinical decision-making.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Analysis of Drug-Resistance Characteristics and Genetic Diversity of Multidrug-Resistant Tuberculosis Based on Whole-Genome Sequencing on the Hainan Island, China

Wang,

Yu,

et al. 2023

IDR

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“… 27 In addition, low fluoroquinolone resistance rate was detected in this study, which is inconsistent with reports from other provinces in China. 17 , 22 , 27 The conflicting result might be due to the frequency and dosage of fluoroquinolone antibiotics used in different regions or the strains selected for the research. However, this finding favors future applications of fluoroquinolones in TB treatment regimens of shorter duration.…”

Section: Discussionmentioning

confidence: 99%

“…According to previous studies, the isolates sharing less than 12 allelic differences are classed into a cluster, suggesting the occurrence of recent transmission. 21 , 22 …”

Section: Methodsmentioning

confidence: 99%

The Recent Transmission and Associated Risk Factor of Mycobacterium tuberculosis in Golmud City, China

Song,

He,

Cao

et al. 2024

IDR

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Background Tuberculosis (TB) remains a severe public health problem globally, and it is essential to comprehend the transmission pattern to control tuberculosis. Herein, we evaluated the drug-resistant characteristics, recent transmission, and associated risk factors of TB in Golmud, Qinghai, China. Methods In this study, we performed a population-based study of patients diagnosed with TB in Golmud from 2013 to 2018. Drug-susceptibility testing and whole-genome sequencing were performed on 133 Mycobacterium tuberculosis strains. The genomic clustering rate was calculated to evaluate the level of recent transmission. Risk factors were identified by logistic regression analysis. Results Our results showed that 46.97% (62/132) of strains were phylogenetically clustered and formed into 23 transmission clusters, suggesting a high recent transmission of TB in the area. 12.78% (17/133) strains were multidrug-resistant/rifampicin tuberculosis (MDR/RR-TB), with a high drug-resistant burden. Based on drug resistance gene analysis, we found 23 strains belonging to genotype MDR/RR-TB, where some strains may have borderline mutations. Among these strains, 65.2% (15/23) were found within putative transmission clusters. Additionally, risk factor analysis showed that recent transmission of TB happened more in patients with Tibetan nationality or older age. Conclusion Overall our study indicates that the recent transmissions of MTB strains, especially genotypic MDR/RR strains, drive the tuberculosis epidemic in Golmud, which could contribute to developing effective TB prevention and control strategies.

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“…In this study, 300 MDR-TB isolates (phenotypically resistant to rifampicin and isoniazid) were randomly selected from the National Tuberculosis Reference Laboratory (NTRL) in China, and 298 isolates were recovered successfully for follow-up studies. Subsequently, we included the 248 phenotypic MDR-TB isolates from the Hunan and Chongqing regions of our previous study to expand the sample size of the study ( 11 , 13 ). The remaining 546 MDR-TB isolates were selected for in-depth analysis ( Table S1 ), which collected from diverse geographic locations in China ( Fig.…”

Section: Methodsmentioning

confidence: 99%

Insight into the drug-resistant characteristics and genetic diversity of multidrug-resistant Mycobacterium tuberculosis in China

Song,

Liu,

et al. 2023

Microbiol Spectr

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Multidrug-resistant tuberculosis (MDR-TB) has a severe impact on public health. To investigate the drug-resistant profile, compensatory mutations and genetic variations among MDR-TB isolates, a total of 546 MDR-TB isolates from China underwent drug-susceptibility testing and whole genome sequencing for further analysis. The results showed that our isolates have a high rate of fluoroquinolone resistance (45.60%, 249/546) and a low proportion of conferring resistance to bedaquiline, clofazimine, linezolid, and delamanid. The majority of MDR-TB isolates (77.66%, 424/546) belong to Lineage 2.2.1, followed by Lineage 4.5 (6.41%, 35/546), and the Lineage 2 isolates have a strong association with pre-XDR/XDR-TB ( P < 0.05) in our study. Epidemic success analysis using time-scaled haplotypic density (THD) showed that clustered isolates outperformed non-clustered isolates. Compensatory mutations happened in rpoA , rpoC, and non-RRDR of rpoB genes, which were found more frequently in clusters and were associated with the increase of THD index, suggesting that increased bacterial fitness was associated with MDR-TB transmission. In addition, the variants in resistance associated genes in MDR isolates are mainly focused on single nucleotide polymorphism mutations, and only a few genes have indel variants, such as katG , ethA . We also found some genes underwent indel variation correlated with the lineage and sub-lineage of isolates, suggesting the selective evolution of different lineage isolates. Thus, this analysis of the characterization and genetic diversity of MDR isolates would be helpful in developing effective strategies for treatment regimens and tailoring public interventions. IMPORTANCE Multidrug-resistant tuberculosis (MDR-TB) is a serious obstacle to tuberculosis prevention and control in China. This study provides insight into the drug-resistant characteristics of MDR combined with phenotypic drug-susceptibility testing and whole genome sequencing. The compensatory mutations and epidemic success analysis were analyzed by time-scaled haplotypic density (THD) method, suggesting clustered isolates and compensatory mutations are associated with MDR-TB transmission. In addition, the insertion and deletion variants happened in some genes, which are associated with the lineage and sub-lineage of isolates, such as the mpt64 gene. This study offered a valuable reference and increased understanding of MDR-TB in China, which could be crucial for achieving the objective of precision medicine in the prevention and treatment of MDR-TB.

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

Cited by 9 publications

References 41 publications

Analysis of Drug-Resistance Characteristics and Genetic Diversity of Multidrug-Resistant Tuberculosis Based on Whole-Genome Sequencing on the Hainan Island, China

Analysis of Drug-Resistance Characteristics and Genetic Diversity of Multidrug-Resistant Tuberculosis Based on Whole-Genome Sequencing on the Hainan Island, China

The Recent Transmission and Associated Risk Factor of Mycobacterium tuberculosis in Golmud City, China

Insight into the drug-resistant characteristics and genetic diversity of multidrug-resistant Mycobacterium tuberculosis in China

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