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Journal of Clinical Microbiology, May 2002, p. 1705-1708, Vol. 40, No. 5
0095-1137/02/$04.00+0     DOI: 10.1128/JCM.40.5.1705-1708.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Calculation of the Stability of the IS6110 Banding Pattern in Patients with Persistent Mycobacterium tuberculosis Disease

R. M. Warren,1 G. D. van der Spuy,1 M. Richardson,1 N. Beyers,2 M. W. Borgdorff,3 M. A. Behr,4 and P. D. van Helden1*

MRC Centre for Molecular and Cellular Biology, Department of Medical Biochemistry,1 Department of Pediatrics and Child Health, Faculty of Health Sciences, University of Stellenbosch, Tygerberg 7505, South Africa,2 Royal Netherlands Tuberculosis Association, 2510 CC The Hague, The Netherlands,3 Department of Medicine, McGill University Health Centre, Montreal H3G 1A4, Canada4

Received 3 December 2001/ Returned for modification 4 January 2002/ Accepted 30 January 2002

The interpretation of molecular epidemiologic data of Mycobacterium tuberculosis infection is dependent on the understanding of the stability and evolutionary characteristics of the DNA fingerprinting marker used to classify clinical isolates. This study investigated the stability of the IS6110 banding pattern in serial tuberculosis isolates collected from patients resident in an area with a high incidence of tuberculosis. Evolutionary changes were observed in 4% of the strains, and a half-life (t1/2) of 8.74 years was calculated, assuming a constant rate of change over time. This rate may be composed of a high rate of change seen during the early disease phase (t1/2 = 0.57 years) and a low rate of change seen in the late disease phase (t1/2 = 10.69 years). The early rate probably reflects change occurring during active growth prior to therapy, while the low late rate may reflect change occurring during or after treatment. We demonstrate that the calculation of these rates is strongly influenced by the time interval between onset of disease and sputum sampling. These calculations are further complicated by partial replacement of the original strain population, resulting in the sporadic appearance of clonal variants in sputum specimens. Therefore, the true extent of genetic diversity may be underestimated within each host, thereby influencing molecular epidemiological data used to establish transmission chains.

* Corresponding author. Mailing address: MRC Centre for Molecular and Cellular Biology, Department of Medical Biochemistry, University of Stellenbosch, P.O. Box 19063, Tygerberg 7505, South Africa. Phone: 27-21-9389401. Fax: 27-21-9317810. E-mail: PVH{at}SUN.AC.ZA.

Journal of Clinical Microbiology, May 2002, p. 1705-1708, Vol. 40, No. 5
0095-1137/02/$04.00+0     DOI: 10.1128/JCM.40.5.1705-1708.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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