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Journal of Clinical Microbiology, February 2001, p. 636-641, Vol. 39, No. 2
0095-1137/01/$04.00+0   DOI: 10.1128/JCM.39.2.636-641.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Analysis for a Limited Number of Gene Codons Can Predict Drug Resistance of Mycobacterium tuberculosis in a High-Incidence Community

Annelies Van Rie,1,2 Robin Warren,2 Idris Mshanga,3 Annemarie M Jordaan,2 Gian D. van der Spuy,2 Madalene Richardson,2 John Simpson,4 Robert P. Gie,1 Donald A. Enarson,5 Nulda Beyers,1 Paul D. van Helden,2 and Thomas C. Victor2,*

MRC Center for Molecular and Cellular Biology, Department of Medical Biochemistry,2 and Department of Pediatrics and Child Health,1 University of Stellenbosch, Stellenbosch, and South African Institute for Medical Research, Cape Town,4 South Africa; Department Biochemistry, Muhimbili Medical Center, Faculty of Medicine, Dar Es Salaam, Tanzania3; and International Union Against Tuberculosis and Lung Disease, Paris, France5

Received 14 June 2000/Returned for modification 28 August 2000/Accepted 4 November 2000

Correct and rapid diagnosis is essential in the management of multidrug-resistant tuberculosis (MDR-TB). In this population-based study of 61 patients with drug-resistant tuberculosis, we evaluated the frequency of mutations and compared the performance of genotypic (mutation analysis by dot blot hybridization) and phenotypic (indirect proportion method) drug resistance tests. Three selected codons (rpoB531, rpoB526, and katG315) allowed identification of 90% of MDR-TB cases. Ninety percent of rifampin, streptomycin, and ethambutol resistance and 75% of isoniazid resistance were detected by screening for six codons: rpoB531, rpoB526, rrs-513, rpsL43, embB306, and katG315. The performance (reproducibility, sensitivity, and specificity) of the genotypic method was superior to that of the routine phenotypic method, with the exception of sensitivity for isoniazid resistance. A commercialized molecular genetic test for a limited number of target loci might be a good alternative for a drug resistance screening test in the context of an MDR "DOTS-plus" strategy.

* Corresponding author. Mailing address: Department of Medical Biochemistry, University of Stellenbosch, Stellenbosch, South Africa. Phone: 27-21-9389251. Fax: 27-21-9317810. E-mail: TV{at}gerga.sun.ac.za.

Journal of Clinical Microbiology, February 2001, p. 636-641, Vol. 39, No. 2
0095-1137/01/$04.00+0   DOI: 10.1128/JCM.39.2.636-641.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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