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

David Wyllie, Jennifer Davidson, Tim Walker, Preeti Rathod, Derrick Crook, Tim Peto, Esther Robinson, Grace Smith, Colin Campbell
doi: https://doi.org/10.1101/252734
David Wyllie
1Nuffield Department of Medicine, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
2Public Health England Academic Collaborating Centre, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
3The National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at University of Oxford
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Jennifer Davidson
4Tuberculosis Section, National Infection Service, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK
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Tim Walker
1Nuffield Department of Medicine, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
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Preeti Rathod
5Public Health England National Regional Mycobacteriology Laboratory North and Midlands, Heartlands Hospital, Birmingham BS9 5SS
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Derrick Crook
1Nuffield Department of Medicine, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
3The National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at University of Oxford
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Tim Peto
1Nuffield Department of Medicine, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
3The National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at University of Oxford
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Esther Robinson
5Public Health England National Regional Mycobacteriology Laboratory North and Midlands, Heartlands Hospital, Birmingham BS9 5SS
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Grace Smith
5Public Health England National Regional Mycobacteriology Laboratory North and Midlands, Heartlands Hospital, Birmingham BS9 5SS
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Colin Campbell
4Tuberculosis Section, National Infection Service, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK
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Summary

Background Mycobacterial 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.

Methods We 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.

Findings 1,999 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.

Interpretation In 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.

Funding Public Health England, National Institute of Health Research Oxford Biomedical Research Centre.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted January 24, 2018.
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A quantitative evaluation of MIRU-VNTR typing against whole-genome sequencing for identifying Mycobacterium tuberculosis transmission: A prospective observational cohort study
David Wyllie, Jennifer Davidson, Tim Walker, Preeti Rathod, Derrick Crook, Tim Peto, Esther Robinson, Grace Smith, Colin Campbell
bioRxiv 252734; doi: https://doi.org/10.1101/252734
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A quantitative evaluation of MIRU-VNTR typing against whole-genome sequencing for identifying Mycobacterium tuberculosis transmission: A prospective observational cohort study
David Wyllie, Jennifer Davidson, Tim Walker, Preeti Rathod, Derrick Crook, Tim Peto, Esther Robinson, Grace Smith, Colin Campbell
bioRxiv 252734; doi: https://doi.org/10.1101/252734

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