title: Three-year population-based evaluation of standardized mycobacterial interspersed repetitive-unit-variable-number tandem-repeat typing of Mycobacterium tuberculosis.
abstract: Standardized mycobacterial interspersed repetitive-unit-variable-number tandem repeat (MIRU-VNTR) typing based on 15 and 24 loci recently has been proposed for Mycobacterium tuberculosis genotyping. So far, this optimized system has been assessed in a single, 1-year population-based study performed in Germany (M. C. Oelemann, R. Diel, V. Vatin, W. Haas, S. Rusch-Gerdes, C. Locht, S. Niemann, and P. Supply, J. Clin. Microbiol. 45:691-697, 2007). Here, we evaluated these optimized formats in a much larger population-based study conducted during 39 months in the Brussels capital region of Belgium. Isolates from 807 patients were genotyped. The resolution power, cluster, and lineage identification by the standardized MIRU-VNTR sets were compared to those obtained using standardized IS6110-restriction fragment length polymorphism (RFLP), spoligotyping, and a previous 12-MIRU-VNTR-locus set. On a subset representing 77% of the cases during a 16-month period, a high concordance was observed between unique isolates or strain clusters as defined by standardized MIRU-VNTR and IS6110-RFLP (i.e., more than five IS6110 bands). When extended to the entire population-based collection, the discriminatory subset of 15 loci decreased the strain-clustering rate by almost twofold compared to that of the old 12-locus set. The addition of the nine ancillary MIRU-VNTR loci and/or spoligotyping only slightly further decreased this strain-clustering rate. Familial, social, and/or geographic proximity links were found in 48% of the clusters identified, and well-known risk factors for tuberculosis transmission were identified. Finally, an excellent correspondence was determined between our MIRU-VNTR-spoligotyping strain identifications and external reference strain lineages included in the MIRU-VNTRplus database and identified by, e.g., large sequence polymorphisms. Our results reinforce the proposal of standardized MIRU-VNTR typing as a new reference genotyping method for the epidemiological and phylogenetic screening of M. tuberculosis strains.
authors.affiliation: Molecular Mechanisms of Bacterial Pathogenesis, INSERM U629, Institut de Biologie de Lille/Institut Pasteur de Lille, 1 rue du Professeur Calmette, F-59021 Lille Cedex, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Allix-Béguec
authors.forename: Maryse
authors.initials: M
authors.lastname: Fauville-Dufaux
authors.forename: Philip
authors.initials: P
authors.lastname: Supply
mesh_terms: D015373:Bacterial Typing Techniques; D016000:Cluster Analysis; D015342:DNA Probes; D004251:DNA Transposable Elements; D004269:DNA, Bacterial / Q000032:analysis; D005838:Genotype; D006801:Humans; D020071:Interspersed Repetitive Sequences / Q000235:genetics*; D018598:Minisatellite Repeats / Q000235:genetics*; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000235:genetics*; D009841:Oligonucleotides / Q000032:analysis; D012150:Polymorphism, Restriction Fragment Length; D011933:Reagent Kits, Diagnostic; D014376:Tuberculosis / Q000453:epidemiology* / Q000382:microbiology
chemical_list: D015342:DNA Probes; D004251:DNA Transposable Elements; D004269:DNA, Bacterial; D009841:Oligonucleotides; D011933:Reagent Kits, Diagnostic