title: Sensitivities and specificities of spoligotyping and mycobacterial interspersed repetitive unit-variable-number tandem repeat typing methods for studying molecular epidemiology of tuberculosis.
abstract: The development of PCR-based genotyping modalities (spoligotyping and mycobacterial interspersed repetitive unit-variable-number tandem repeat [MIRU-VNTR] typing) offers promise for real-time molecular epidemiological studies of tuberculosis (TB). However, the utility of these methods depends on their capacity to appropriately classify isolates. To determine the operating parameters of spoligotyping and MIRU-VNTR typing, we have compared results generated by these newer tests to the standard typing method, IS6110 restriction fragment length polymorphism, in analyses restricted to high-copy-number IS6110 isolates. Sensitivities of the newer tests were estimated as the percentages of isolates with identical IS6110 fingerprints that had identical spoligotypes and MIRU-VNTR types. The specificities of these tests were estimated as the percentages of isolates with unique IS6110 fingerprints that had unique spoligotypes and MIRU-VNTR types. The sensitivity of MIRU-VNTR typing was 52% (95% confidence interval [CI], 31 to 72%), and the sensitivity of spoligotyping was 83% (95% CI, 63 to 95%). The specificity of MIRU-VNTR typing was 56% (95% CI, 51 to 62%), and the specificity of spoligotyping was 40% (95% CI, 35 to 46%). The proportion of isolates estimated to be due to recent transmission was 4% by identical IS6110 patterns, 19% by near-identical IS6110 patterns, 33% by MIRU-VNTR typing, and 53% by spoligotyping. The low calculated specificities of spoligotyping and MIRU-VNTR typing led to misclassification of cases, inflated estimates of TB transmission, and low positive predictive values, suggesting that these techniques have unsuitable operating parameters for population-based molecular epidemiology studies.
authors.affiliation: Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada.
authors.forename: Allison N
authors.initials: AN
authors.lastname: Scott
authors.forename: Dick
authors.initials: D
authors.lastname: Menzies
authors.forename: Terry-Nan
authors.initials: TN
authors.lastname: Tannenbaum
authors.forename: Louise
authors.initials: L
authors.lastname: Thibert
authors.forename: Robert
authors.initials: R
authors.lastname: Kozak
authors.forename: Lawrence
authors.initials: L
authors.lastname: Joseph
authors.forename: Kevin
authors.initials: K
authors.lastname: Schwartzman
authors.forename: Marcel A
authors.initials: MA
authors.lastname: Behr
mesh_terms: D015373:Bacterial Typing Techniques; D004251:DNA Transposable Elements; D006801:Humans; D020071:Interspersed Repetitive Sequences / Q000235:genetics*; D018598:Minisatellite Repeats / Q000235:genetics*; D017720:Molecular Epidemiology; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000235:genetics; D009841:Oligonucleotides / Q000032:analysis*; D012150:Polymorphism, Restriction Fragment Length; D012680:Sensitivity and Specificity; D014376:Tuberculosis / Q000453:epidemiology* / Q000382:microbiology
chemical_list: D004251:DNA Transposable Elements; D009841:Oligonucleotides