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Journal of Clinical Microbiology, January 2005, p. 89-94, Vol. 43, No. 1
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.1.89-94.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Sensitivities and Specificities of Spoligotyping and Mycobacterial Interspersed Repetitive Unit-Variable-Number Tandem Repeat Typing Methods for Studying Molecular Epidemiology of Tuberculosis

Allison N. Scott,1 Dick Menzies,1,2 Terry-Nan Tannenbaum,1,3 Louise Thibert,4 Robert Kozak,2 Lawrence Joseph,1 Kevin Schwartzman,1,2 and Marcel A. Behr1,5*

Department of Epidemiology and Biostatistics,1 Respiratory Epidemiology Unit, McGill University,2 Direction de la Santé Publique, Montréal-Centre,3 Laboratoire de Santé Publique du Québec,4 Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada5

Received 11 June 2004/ Returned for modification 13 August 2004/ Accepted 15 September 2004

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.

* Corresponding author. Mailing address: Division of Infectious Diseases and Microbiology, A5.156, Montreal General Hospital, 1650 Cedar Ave., Montreal, H3G 1A4, Quebec, Canada. Phone: (514) 934-1934, ext. 42815. Fax: (514) 934-8423. E-mail: marcel.behr{at}mcgill.ca.

Journal of Clinical Microbiology, January 2005, p. 89-94, Vol. 43, No. 1
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.1.89-94.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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