Dataset Information

Transmission of multidrug-resistant tuberculosis in Beijing, China: An epidemiological and genomic analysis.

ABSTRACT:

Background

Understanding multidrug-resistant tuberculosis (MDR-TB) transmission patterns is crucial for controlling the disease. We aimed to identify high-risk populations and geographic settings of MDR-TB transmission.

Methods

We conducted a population-based retrospective study of MDR-TB patients in Beijing from 2018 to 2020, and assessed MDR-TB recent transmission using whole-genome sequencing of isolates. Geospatial analysis was conducted with kernel density estimation. We combined TransPhylo software with epidemiological investigation data to construct transmission networks. Logistic regression analysis was utilized to identify risk factors for recent transmission.

Results

We included 241 MDR-TB patients, of which 146 (60.58%) were available for genomic analysis. Drug resistance prediction showed that resistance to fluoroquinolones (FQs) was as high as 39.74% among new cases. 36 (24.66%) of the 146 MDR strains were grouped into 12 genome clusters, suggesting recent transmission of MDR strains. 44.82% (13/29) of the clustered patients lived in the same residential community, adjacent residential community or the same street as other cases. The inferred transmission chain found a total of 6 transmission events in 3 clusters; of these, 4 transmission events occurred in residential areas and nearby public places. Logistic regression analysis revealed that being aged 25-34 years-old was a risk factor for recent transmission.

Conclusions

The recent transmission of MDR-TB in Beijing is severe, and residential areas are common sites of transmission; high levels of FQs drug resistance suggest that FQs should be used with caution unless resistance can be ruled out by laboratory testing.

SUBMITTER: Yin J

PROVIDER: S-EPMC9672842 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Transmission of multidrug-resistant tuberculosis in Beijing, China: An epidemiological and genomic analysis.

Yin Jinfeng J Zhang Hongwei H Gao Zhidong Z Jiang Hui H Qin Liyi L Zhu Chendi C Gao Qian Q He Xiaoxin X Li Weimin W

Frontiers in public health 20221104

<h4>Background</h4>Understanding multidrug-resistant tuberculosis (MDR-TB) transmission patterns is crucial for controlling the disease. We aimed to identify high-risk populations and geographic settings of MDR-TB transmission.<h4>Methods</h4>We conducted a population-based retrospective study of MDR-TB patients in Beijing from 2018 to 2020, and assessed MDR-TB recent transmission using whole-genome sequencing of isolates. Geospatial analysis was conducted with kernel density estimation. We comb ...[more]

PMID: 36408017

Similar Datasets

Project description:BackgroundPopulation movement could extend multidrug-resistant tuberculosis (MDR-TB) transmission and complicate its global prevalence. We sought to identify the high-risk populations and geographic sites of MDR-TB transmission in Shenzhen, the most common destination for internal migrants in China.MethodsWe performed a population-based, retrospective study in patients diagnosed with MDR-TB in Shenzhen during 2013-2017. By defining genomic clusters with a threshold of 12-single-nucleotide polymorphism distance based on whole-genome sequencing of their clinical strains, the clustering rate was calculated to evaluate the level of recent transmission. Risk factors were identified by multivariable logistic regression. To further delineate the epidemiological links, we invited the genomic-clustered patients to an in-depth social network investigation.ResultsIn total, 105 (25.2%) of the 417 enrolled patients with MDR-TB were grouped into 40 genome clusters, suggesting recent transmission of MDR strains. The adjusted risk for student to have a clustered strain was 4.05 (95% confidence interval, 1.06-17.0) times greater than other patients. The majority (70%, 28/40) of the genomic clusters involved patients who lived in different districts, with residences separated by an average of 8.76 kilometers. Other than household members, confirmed epidemiological links were also identified among classmates and workplace colleagues.ConclusionsThese findings demonstrate that local transmission of MDR-TB is a serious problem in Shenzhen. While most transmission occurred between people who lived distant from each other, there was clear evidence that transmission occurred in schools and workplaces, which should be included as targeted sites for active case finding.The average residential distance between genomic-clustered cases was more than 8 kilometers, while schools and workplaces, identified as sites of transmission in this study, deserve increased vigilance for targeted case finding of multidrug-resistant tuberculosis.

Project description:BackgroundMassive internal migration from rural to urban areas poses new challenges for tuberculosis control in China. We aimed to combine genomic, spatial, and epidemiological data to describe the dynamics of tuberculosis in an urban setting with large numbers of migrants.MethodsWe did a population-based study of culture-positive Mycobacterium tuberculosis isolates in Songjiang, Shanghai. We used whole-genome sequencing to discriminate apparent genetic clusters of M tuberculosis sharing identical variable-number-tandem-repeat (VNTR) patterns, and analysed the relations between proximity of residence and the risk of genomically clustered M tuberculosis. Finally, we used genomic, spatial, and epidemiological data to estimate time of infection and transmission links among migrants and residents.FindingsBetween Jan 1, 2009, and Dec 31, 2015, 1620 cases of culture-positive tuberculosis were recorded, 1211 (75%) of which occurred among internal migrants. 150 (69%) of 218 people sharing identical VNTR patterns had isolates within ten single-nucleotide polymorphisms (SNPs) of at least one other strain, consistent with recent transmission of M tuberculosis. Pairs of strains collected from individuals living in close proximity were more likely to be genetically similar than those from individuals who lived far away-for every additional km of distance between patients' homes, the odds that genotypically matched strains were within ten SNPs of each other decreased by about 10% (OR 0·89 [95% CI 0·87-0·91]; p<0·0001). We inferred that transmission from residents to migrants occurs as commonly as transmission from migrants to residents, and we estimated that more than two-thirds of migrants in genomic clusters were infected locally after migration.InterpretationThe primary mechanism driving local incidence of tuberculosis in urban centres is local transmission between both migrants and residents. Combined analysis of epidemiological, genomic, and spatial data contributes to a richer understanding of local transmission dynamics and should inform the design of more effective interventions.FundingNational Natural Science Foundation of China, National Science and Technology Major Project of China, and US National Institutes of Health.

Project description:BackgroundMultidrug-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.MethodsWe 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.Findings367 (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.InterpretationRecent 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.FundingNational Science and Technology Major Project, National Natural Science Foundation of China, and US National Insitutes of Health.

Project description:BackgroundThe 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.MethodsWe 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.ResultsEpidemiological/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.ConclusionsOur 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.

Dataset Information

Transmission of multidrug-resistant tuberculosis in Beijing, China: An epidemiological and genomic analysis.

Background

Methods

Results

Conclusions

Publications

Transmission of multidrug-resistant tuberculosis in Beijing, China: An epidemiological and genomic analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets