PT  - JOURNAL ARTICLE
AU  - David Wyllie
AU  - Jennifer Davidson
AU  - Tim Walker
AU  - Preeti Rathod
AU  - Derrick Crook
AU  - Tim Peto
AU  - Esther Robinson
AU  - Grace Smith
AU  - Colin Campbell
TI  - A quantitative evaluation of MIRU-VNTR typing against whole-genome sequencing for identifying <em>Mycobacterium tuberculosis</em> transmission: A prospective observational cohort study
AID  - 10.1101/252734
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 252734
4099  - http://biorxiv.org/content/early/2018/01/24/252734.short
4100  - http://biorxiv.org/content/early/2018/01/24/252734.full
AB  - 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.