Transmission of multidrug-resistant tuberculosis in Shimen community in Shanghai, China: a molecular epidemiology study

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) has become a major public health problem in China, with mounting evidence suggesting that recent transmission accounts for the majority of MDR-TB. Here we aimed to reveal the transmission pattern of an MDR-TB outbreak in the Jing'an District of Shanghai between 2010 and 2015. Methods We used whole-genome sequencing (WGS) to conduct genomic clustering analysis along with field epidemiological investigation to determine the transmission pattern and drug resistance profile of a cluster with ten MDR-TB patients in combining field epidemiological investigation. Results The ten MDR-TB patients with genotypically clustered Beijing lineage strains lived in a densely populated, old alley with direct or indirect contact history. The analysis of genomic data showed that the genetic distances of the ten strains (excluding drug-resistant mutations) were 0–20 single nucleotide polymorphisms (SNPs), with an average distance of 9 SNPs, suggesting that the ten MDR-TB patients were infected and developed the onset of illness by the recent transmission of M. tuberculosis. The genetic analysis confirmed definite epidemiological links between the clustered cases. Conclusions The integration of the genotyping tool in routine tuberculosis surveillance can play a substantial role in the detection of MDR-TB transmission events. The leverage of genomic analysis in combination with the epidemiological investigation could further elucidate transmission patterns. Whole-genome sequencing could be integrated into intensive case-finding strategies to identify missed cases of MDR-TB and strengthen efforts to interrupt transmission.

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A joint cross-border investigation of a cluster of multidrug-resistant tuberculosis in Austria, Romania and Germany in 2014 using classic, genotyping and whole genome sequencing methods: lessons learnt

Eurosurveillance ◽

10.2807/1560-7917.es.2017.22.2.30439 ◽

2017 ◽

Vol 22 (2) ◽

Cited By ~ 20

Author(s):

Lena Fiebig ◽

Thomas A Kohl ◽

Odette Popovici ◽

Margarita Mühlenfeld ◽

Alexander Indra ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Universal Access ◽

Multidrug Resistant ◽

Whole Genome ◽

The European Union ◽

Cross Border ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Molecular surveillance of multidrug-resistant tuberculosis (MDR-TB) using 24-loci MIRU-VNTR in the European Union suggests the occurrence of international transmission. In early 2014, Austria detected a molecular MDR-TB cluster of five isolates. Links to Romania and Germany prompted the three countries to investigate possible cross-border MDR-TB transmission jointly. We searched genotyping databases, genotyped additional isolates from Romania, used whole genome sequencing (WGS) to infer putative transmission links, and investigated pairwise epidemiological links and patient mobility. Ten isolates from 10 patients shared the same 24-loci MIRU-VNTR pattern. Within this cluster, WGS defined two subgroups of four patients each. The first comprised an MDR-TB patient from Romania who had sought medical care in Austria and two patients from Austria. The second comprised patients, two of them epidemiologically linked, who lived in three different countries but had the same city of provenance in Romania. Our findings strongly suggested that the two cases in Austrian citizens resulted from a newly introduced MDR-TB strain, followed by domestic transmission. For the other cases, transmission probably occurred in the same city of provenance. To prevent further MDR-TB transmission, we need to ensure universal access to early and adequate therapy and collaborate closely in tuberculosis care beyond administrative borders.

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Genetic Variation Putatively Associated with Mycobacterium tuberculosis Resistance to Perchlozone, a New Thiosemicarbazone: Clues from Whole Genome Sequencing and Implications for Treatment of Multidrug-Resistant Tuberculosis

Antibiotics ◽

10.3390/antibiotics9100669 ◽

2020 ◽

Vol 9 (10) ◽

pp. 669

Author(s):

Igor Mokrousov ◽

Anna Vyazovaya ◽

Gulnora Akhmedova ◽

Natalia Solovieva ◽

Eugeni Turkin ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Genetic Variation ◽

Whole Genome Sequencing ◽

Treatment Regimen ◽

Genome Sequencing ◽

Multidrug Resistant ◽

Whole Genome ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Perchlozone ([PCZ] 4-thioureido-iminomethylpyridinium perchlorate) is a new thiosemicarbazone approved for the treatment of multidrug-resistant tuberculosis (MDR-TB) in Russia and some other countries. The ethA and hadABC mutations may confer PCZ resistance. At the same time, ethA mutations are known to mediate resistance to ethionamide (ETH) and prothionamide (PTH). We aimed to study the genetic variation underlying Mycobacterium tuberculosis resistance to PCZ through whole genome sequencing (WGS) of consecutive isolates recovered during long-term treatment. This prospective study included patients admitted in 2018–2019 to the regional tuberculosis dispensary, Kaliningrad, Russia, whose treatment regimen included PCZ. Multiple M. tuberculosis isolates were recovered during PCZ treatment, and the bacterial DNA was subjected to WGS followed by bioinformatics analysis. We identified mutations in the genes putatively associated with PCZ resistance, ethA, and hadA. The most frequent one was a frameshift ethA 106 GA > G (seven of nine patients) and most of the other mutations were also likely present before PCZ treatment. In one patient, a frameshift mutation ethA 702 CT > C emerged after six months of PCZ treatment. A frequent presence of cross-resistance mutations to PCZ and ETH/PTH should be taken into consideration when PCZ is included in the treatment regimen of MDR-TB patients.

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Whole genome sequencing identifies bacterial factors affecting transmission of multidrug-resistant tuberculosis in a high-prevalence setting

Scientific Reports ◽

10.1038/s41598-019-41967-8 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 7

Author(s):

Avika Dixit ◽

Luca Freschi ◽

Roger Vargas ◽

Roger Calderon ◽

James Sacchettini ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Multidrug Resistant ◽

Whole Genome ◽

Factors Affecting ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

High Prevalence

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Lesion Heterogeneity and Long-Term Heteroresistance in Multidrug-Resistant Tuberculosis

The Journal of Infectious Diseases ◽

10.1093/infdis/jiab011 ◽

2021 ◽

Author(s):

Yiwang Chen ◽

Lecai Ji ◽

Qingyun Liu ◽

Jinli Li ◽

Chuangyue Hong ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Multidrug Resistant ◽

Whole Genome ◽

Drug Resistant ◽

Treatment Regimens ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis

Abstract Tuberculosis heteroresistance, in which only a fraction of the bacteria in a patient with tuberculosis contains drug-resistant mutations, has been a rising concern. However, its origins and prevalence remain elusive. Here, whole-genome sequencing was performed on 83 serial isolates from 31 patients with multidrug-resistant tuberculosis, and heteroresistance was detected in isolates from 21 patients (67.74%). Heteroresistance persisted in the host for long periods, spanning months to years, and was associated with having multiple tubercular lesions. Our findings indicate that heteroresistance is common and persistent in patients with multidrug-resistant tuberculosis and may affect the success of their treatment regimens.

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Clinical Application of Whole-Genome Sequencing To Inform Treatment for Multidrug-Resistant Tuberculosis Cases

Journal of Clinical Microbiology ◽

10.1128/jcm.02993-14 ◽

2015 ◽

Vol 53 (5) ◽

pp. 1473-1483 ◽

Cited By ~ 66

Author(s):

Adam A. Witney ◽

Katherine A. Gould ◽

Amber Arnold ◽

David Coleman ◽

Rachel Delgado ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Clinical Application ◽

Genome Sequencing ◽

Multidrug Resistant ◽

Whole Genome ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis

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Intercontinental translocation of latent multidrug‐resistant tuberculosis to Australia demonstrated by whole genome sequencing

The Medical Journal of Australia ◽

10.5694/mja2.50044 ◽

2019 ◽

Vol 210 (5) ◽

pp. 236

Author(s):

Sanjay S Gautam ◽

Greg Haug ◽

Louise A Cooley ◽

Micheál Mac Aogáin ◽

Ronan F O'Toole

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Multidrug Resistant ◽

Whole Genome ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis

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Individualized Treatment of Multidrug-resistant Tuberculosis Using Whole-Genome Sequencing and Expanded Drug-Susceptibility Testing

Clinical Infectious Diseases ◽

10.1093/cid/ciaa526 ◽

2020 ◽

Vol 71 (11) ◽

pp. 2981-2985

Author(s):

Navisha Dookie ◽

Nesri Padayatchi ◽

Richard J Lessells ◽

Cherise L Naicker ◽

Sunitha Chotoo ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Susceptibility Testing ◽

Drug Susceptibility ◽

Multidrug Resistant ◽

Drug Susceptibility Testing ◽

Individualized Treatment ◽

Whole Genome ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis

Abstract A case of multidrug-resistant tuberculosis is presented. It highlights the role of whole-genome sequencing, expanded phenotypic drug susceptibility testing, and enhanced case management, offering a more complete understanding of drug susceptibility to Mycobacterium tuberculosis. This approach guides an effective individualized treatment strategy that results in rapid sustained culture conversion.

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