Standard Genotyping Overestimates Transmission of Mycobacterium tuberculosis among Immigrants in a Low-Incidence Country

Stucki, David; Ballif, Marie; Egger, Matthias; Furrer, Hansjakob; Altpeter, Ekkehardt; Battegay, Manuel; Droz, Sara; Bruderer, Thomas; Coscollá, Mireia; Borrell, Sònia; Zürcher, Kathrin; Janssens, Jean–Paul; Calmy, Alexandra; Mazza-Stalder, Jesica; Jaton, Katia; Rieder, Hans L.; Pfyffer, Gaby E.; Siegrist, Hans H.; Hoffmann, Matthias; Fehr, Jan; Dolina, Marisa; Frei, Reno; Schrenzel, Jacques; Böttger, Erik C.; Gagneux, Sébastien; Fenner, Lukas

doi:10.1128/jcm.00126-16

Cited by 95 publications

(81 citation statements)

References 41 publications

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“…Since 2015, Public Health England has been undertaking a phased introduction of routine whole genome sequencing (WGS) for all mycobacterial cultures. 8 This has meant the relatedness of isolates could be simultaneously compared using both single nucleotide variants (SNV) and by MIRU-VNTR typing, and has provided a novel opportunity to compare the added value of whole genome sequencing ( 9-14 ;Table 1) in an unselected population, at scale.…”

Section: Introductionmentioning

confidence: 99%

A quantitative evaluation of MIRU-VNTR typing against whole-genome sequencing for identifying Mycobacterium tuberculosis transmission: A prospective observational cohort study

Wyllie

Davidson

Walker

et al. 2018

Preprint

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SummaryBackgroundMycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR) typing is widely used in high-income countries for Mycobacterium tuberculosis typing. Whole-genome sequencing (WGS) is known to deliver greater specificity, but no quantitative prospective comparison has yet been undertaken.MethodsWe studied isolates from the English Midlands, sampled consecutively between 1 January 2012 and 31 December 2015. In addition to routinely performed MIRU-VNTR typing, DNA was extracted from liquid cultures and sequenced using Illumina technology. Demographic and epidemiological data were extracted from the Enhanced Tuberculosis Surveillance system maintained by Public Health England. Closely related samples, defined using a threshold of five single nucleotide variants (SNVs), were compared to samples with identical MIRU-VNTR profiles, with shared epidemiological risk factors, and to those with both characteristics.Findings1,999 patients were identified for whom at least one M. tuberculosis isolate had been MIRU-VNTR typed and sequenced. Comparing epidemiological risk factors with close genetic relatedness, only coresidence had a positive predictive value of over 5%. Excluding co-resident individuals, 18.6% of patients with identical MIRU-VNTR profiles were within 5 SNVs. Where patients also shared social risk factors and ethnic group, this rose to 48%. Only 8% of MIRU-VNTR linked pairs in lineage 1 were within 5 SNV, compared to 31% in lineage 4.InterpretationIn the setting studied, MIRU-VNTR typing and epidemiological risk factors are poorly predictive of close genomic relatedness, assessed by SNV. MIRU-VNTR performance varies markedly by lineage.FundingPublic Health England, National Institute of Health Research Oxford Biomedical Research Centre.

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Section: Introductionmentioning

confidence: 99%

A quantitative evaluation of MIRU-VNTR typing against whole-genome sequencing for identifying Mycobacterium tuberculosis transmission: A prospective observational cohort study

Wyllie

Davidson

Walker

et al. 2018

Preprint

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“…Similarly, areas with a high burden of multidrug (MDR) resistant TB might also show different patterns. Due to the selection of drug resistance mutations, we can expect a higher number of mutations between epidemiologically linked strains as a result of genetic hitchhiking effects (further discussed in the following section) (Sun et al 2012;Eldholm et al 2014;Liu et al 2015). For example, by looking at serial isolates of a single patient _Eldholm et al (2015) identifies more SNPs separating the isolates than the number expected between two transmission cases.…”

Section: Population Scale Analysis Of Tb Transmission Using Wgsmentioning

confidence: 99%

Genomic Epidemiology of Tuberculosis

Comas

2017

Advances in Experimental Medicine and Biology

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The application of next generation sequencing technologies has opened the door to a new molecular epidemiology of tuberculosis, in which we can now look at transmission at a resolution not possible before. At the same time, new technical and analytical challenges have appeared, and we are still exploring the wider potential of this new technology. Whole genome sequencing in tuberculosis still requires bacterial cultures. Thus, although whole genome sequencing has revolutionized the interpretation of transmission patterns, it is not yet ready to be applied at the point-of-care. In this chapter, I will review the promises and challenges of genomic epidemiology, as well as some of the new questions that have arisen from the use of this new technology. In addition, I will examine the role of molecular epidemiology within the general frame of global tuberculosis control and how genomic epidemiology can contribute towards the elimination of the disease.

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“…Then, NGS could enter the routine laboratories through whole genome sequencing (WGS). Indeed, WGS has been shown to be a promising tool for assessing the relationships between strains, [6,7] the detection of ARGs (in case of suspicion of multidrug-resistant bacteria such as those producing carbapenemase) [8] or even the antibiotic susceptibility inference for fastidious-growing bacteria such as Mycobacterium tuberculosis. [9] The use of NGS in clinical practice was extensively addressed during the Swiss MedLab 2016 in Bern (organized by the Swiss Union of Laboratory Medicine) and will be further discussed in the first International Conference on Clinical Metagenomics (October 13-14, 2016 in Geneva).…”

Section: Clinical Microbiologymentioning

confidence: 99%