Whole genome sequencing of Mycobacterium tuberculosis for detection of recent transmission and tracing outbreaks: A systematic review

Tuberculosis (TB) control programs use whole-genome sequencing (WGS) of Mycobacterium tuberculosis (Mtb) for detecting and investigating TB case clusters. Existence of few genomic differences between Mtb isolates might indicate TB cases are the result of recent transmission. However, the variable and sometimes long duration of latent infection, combined with uncertainty in the Mtb mutation rate during latency, can complicate interpretation of WGS results. To estimate the association between infection duration and single nucleotide polymorphism (SNP) accumulation in the Mtb genome, we first analyzed pairwise SNP differences among TB cases from Los Angeles County, California, with strong epidemiologic links. We found that SNP distance alone was insufficient for concluding that cases are linked through recent transmission. Second, we describe a well-characterized cluster of TB cases in California to illustrate the role of genomic data in conclusions regarding recent transmission. Longer presumed latent periods were inconsistently associated with larger SNP differences. Our analyses suggest that WGS alone cannot be used to definitively determine that a case is attributable to recent transmission. Methods for integrating clinical, epidemiologic, and genomic data can guide conclusions regarding the likelihood of recent transmission, providing local public health practitioners with better tools for monitoring and investigating TB transmission.

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Whole genome sequencing of Mycobacterium tuberculosis for detection of drug resistance: a systematic review

Clinical Microbiology and Infection ◽

10.1016/j.cmi.2016.09.008 ◽

2017 ◽

Vol 23 (2) ◽

pp. 61-68 ◽

Cited By ~ 39

Author(s):

D. Papaventsis ◽

N. Casali ◽

I. Kontsevaya ◽

F. Drobniewski ◽

D.M. Cirillo ◽

...

Keyword(s):

Systematic Review ◽

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome

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Genetic Diversity of Multi- and Extensively Drug-Resistant Mycobacterium tuberculosis Isolates in the Capital of Iran, Revealed by Whole-Genome Sequencing

Journal of Clinical Microbiology ◽

10.1128/jcm.01477-18 ◽

2018 ◽

Vol 57 (1) ◽

Cited By ~ 4

Author(s):

Farzam Vaziri ◽

Thomas A. Kohl ◽

Hasan Ghajavand ◽

Mansour Kargarpour Kamakoli ◽

Matthias Merker ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome ◽

Drug Resistant ◽

Content Type ◽

Extensively Drug Resistant ◽

Recent Transmission ◽

Mdr Tb ◽

Lineage 2

ABSTRACT The emergence and spread of multidrug resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains is a critical global health problem. Between 2014 and 2018, 606 MTBC strains were isolated from 13,892 suspected pulmonary tuberculosis (TB) patients in Tehran, Iran, including 16 (2.6%) MDR-TB cases. A combination of phenotypic and genotypic methods (whole-genome sequencing) was employed for the identification of additional drug resistances and strain-to-strain genetic distances as a marker for recent transmission events. MDR and extensively drug-resistant (XDR) TB cases were almost exclusively infected by lineage 2/Beijing strains (14/16, P < 0.001). We further showed that recent transmission and/or recent introduction of lineage 2/Beijing strains contribute to high XDR-TB rates among all MDR-TB cases and should be considered an emerging threat for TB control in Tehran. In addition, the extensive pre-existing drug resistance profiles of MDR/XDR strains will further challenge TB diagnostics in the region.

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Impact of Whole-Genome Sequencing of Mycobacterium Tuberculosis On Treatment Outcomes for MDR-TB/ XDR-TB: A Systematic Review Protocol

10.21203/rs.3.rs-1046897/v1 ◽

2021 ◽

Author(s):

Druti Hazra ◽

Connie Lam ◽

Vijay Shree Dhyani ◽

Bhumika T V ◽

Kiran Chawla ◽

...

Keyword(s):

Systematic Review ◽

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Whole Genome Sequencing ◽

Treatment Outcomes ◽

Genome Sequencing ◽

Meta Analysis ◽

Cochrane Library ◽

Whole Genome ◽

Mdr Tb

Abstract Background The emergence of drug-resistant tuberculosis (DR-TB) is a persistent threat to public health. The detection of DR-TB requires culture-based drug susceptibility testing (DST) or rapid molecular assays for targeted genes. The recent advances in Whole-genome sequencing (WGS) technology have offered a new capacity to identify resistance-conferring mutations in Mycobacterium tuberculosis (MTB). This study reviews and quantifies the emerging evidence on the association between genomic markers of drug resistance in MTB identified by WGS and treatment outcomes for DR-TB. Methods A literature search will be conducted in NCBI PubMed, Scopus, Cochrane Library, Web of Science, and CINAHL (Ebsco) to retrieve all the relevant original reports from 2000 onwards. Clinical trials and observational studies describing different applications of WGS to genotypic resistance testing for TB and detection of MDR-TB/ XDR-TB as well as treatment outcomes of the patients will be included. Two primary reviewers will separately screen and select papers for data extraction, risk of bias, and assess the quality. Any disagreement between the reviewers' will be clarified by a third reviewer. The I2 statistics will be used to assess the heterogeneity of the included studies and if the data are sufficiently homogenous, a meta-analysis will be performed. The Egger's test and visual representation of the funnel plot will be used to monitor for publication bias. Narrative data synthesis will be conducted for all the included studies if performing meta-analysis is not possible. Discussion This systematic review will examine the evidence on the feasibility and added value of WGS in improving treatment outcomes in DR-TB patients. The rapid detection of drug-resistance conferring mutations and selection of appropriate drug regimens is likely to improve the cure rates while minimizing adverse events and treatment costs. Hence, the outcome of this systematic review will inform policy-making and will guide clinical laboratory practice to improve drug resistance diagnostic capacity and treatment outcomes. Systematic review registration: PROSPERO CRD42020197099.

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Whole-Genome Sequencing Reveals Recent Transmission of Multidrug-Resistant Mycobacterium tuberculosis CAS1-Kili Strains in Lusaka, Zambia

Antibiotics ◽

10.3390/antibiotics11010029 ◽

2021 ◽

Vol 11 (1) ◽

pp. 29

Author(s):

Joseph Yamweka Chizimu ◽

Eddie Samuneti Solo ◽

Precious Bwalya ◽

Wimonrat Tanomsridachchai ◽

Herman Chambaro ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Regulatory Region ◽

Multidrug Resistant ◽

Epidemiological Methods ◽

Whole Genome ◽

Recent Transmission ◽

Mdr Tb

Globally, tuberculosis (TB) is a major cause of death due to antimicrobial resistance. Mycobacterium tuberculosis CAS1-Kili strains that belong to lineage 3 (Central Asian Strain, CAS) were previously implicated in the spread of multidrug-resistant (MDR)-TB in Lusaka, Zambia. Thus, we investigated recent transmission of those strains by whole-genome sequencing (WGS) with Illumina MiSeq platform. Twelve MDR CAS1-Kili isolates clustered by traditional methods (MIRU-VNTR and spoligotyping) were used. A total of 92% (11/12) of isolates belonged to a cluster (≤12 SNPs) while 50% (6/12) were involved in recent transmission events, as they differed by ≤5 SNPs. All the isolates had KatG Ser315Thr (isoniazid resistance), EmbB Met306 substitutions (ethambutol resistance) and several kinds of rpoB mutations (rifampicin resistance). WGS also revealed compensatory mutations including a novel deletion in embA regulatory region (−35A > del). Several strains shared the same combinations of drug-resistance-associated mutations indicating transmission of MDR strains. Zambian strains belonged to the same clade as Tanzanian, Malawian and European strains, although most of those were pan-drug-susceptible. Hence, complimentary use of WGS to traditional epidemiological methods provides an in-depth insight on transmission and drug resistance patterns which can guide targeted control measures to stop the spread of MDR-TB.

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Whole-genome sequencing to detect recent transmission of Mycobacterium tuberculosis in settings with a high burden of tuberculosis

Tuberculosis ◽

10.1016/j.tube.2014.04.005 ◽

2014 ◽

Vol 94 (4) ◽

pp. 434-440 ◽

Cited By ~ 52

Author(s):

Tao Luo ◽

Chongguang Yang ◽

Ying Peng ◽

Liping Lu ◽

Guomei Sun ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome ◽

High Burden ◽

Recent Transmission

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Faculty Opinions recommendation of Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13431956.14806056 ◽

2011 ◽

Author(s):

Bruce Levin

Keyword(s):

Mycobacterium Tuberculosis ◽

Rna Polymerase ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome ◽

Compensatory Mutations

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Clinical and public health utility of Mycobacterium tuberculosis whole genome sequencing

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2021.02.114 ◽

2021 ◽

Author(s):

Alice Kizny Gordon ◽

Ben Marais ◽

Timothy M. Walker ◽

Vitali Sintchenko

Keyword(s):

Public Health ◽

Mycobacterium Tuberculosis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Health Utility ◽

Whole Genome

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Whole genome sequencing data of 1110 Mycobacterium tuberculosis isolates identifies insertions and deletions associated with drug resistance

BMC Genomics ◽

10.1186/s12864-018-4734-6 ◽

2018 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Xi Zeng ◽

Jamie Sui-Lam Kwok ◽

Kevin Yi Yang ◽

Kenneth Siu-Sing Leung ◽

Mai Shi ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome Sequencing Data ◽

Whole Genome ◽

Sequencing Data ◽

Insertions And Deletions

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Transmission of Multidrug/Rifampicin-Resistant Mycobacterium Tuberculosis in Chongqing, China: A Retrospective Observational Study Using Whole-Genome Sequencing

10.21203/rs.3.rs-717466/v1 ◽

2021 ◽

Author(s):

Bing Zhao ◽

Chunfa Liu ◽

Jiale Fan ◽

Aijing Ma ◽

Wencong He ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome ◽

Nucleotide Polymorphisms ◽

Resistance Mutations ◽

Treatment Information ◽

Recent Transmission ◽

Drugs Analysis ◽

Lineage 2 ◽

And Cluster Analysis

Abstract Background: Multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) is a global barrel for ‘Stop TB plan’. China has the second highest MDR/RR-TB burden in whole world wide. Understanding the transmission dynamic is facilitated for disease control. Methods: Whole genome sequencing (WGS) data from patients of Chongqing tuberculosis control institute were used for phylogenetic classifications, resistance predictions, and cluster analysis as indicator for recent transmission (RT). Factors associated with MDR/RR-TB were defined by a logistic regression model. Results: A total of 223 cases of MDR/RR-TB were recorded between Jan 1, 2018 and Dec 31, 2020, and 200 cases obtained relevant treatment information. The patients who are older than 55 year old were more likely to suffering from death. 178 MDR/RR strains were obtained WGS data, 152 were classified as lineage 2 strains. 80 (44.9%, 80 of 178) strains were in 20 genomic clusters that differed by 12 or fewer single nucleotide polymorphisms (SNPs), indicating RT. Patients who were infected with lineage 2 strains is a significant factor driving the epidemic towards MDR/RR-TB. Resistance mutations of first-line tuberculosis drugs analysis found that 79 (98.8%) of all 80 strains defined as RT have same mutations among each clusters totally. 55% (44 of 80) of the MDR/RR-TB strains accumulated additional drug resistance mutations along the transmission chain, especially fluoroquinolones (FQs) (63.6%, 28 of 44). Conclusions: The age is the most significant factor that causes death of MDR/RR-TB patients. RT of MDR/RR strains is not only drove the MDR/RR-TB epidemic, but also accumulated more serious resistance along the transmission chains.

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