title: Analysis for a limited number of gene codons can predict drug resistance of Mycobacterium tuberculosis in a high-incidence community.
abstract: 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.
authors.affiliation: Department of Pediatrics and Child Health, University of Stellenbosch, Stellenbosch, South Africa.
authors.forename: A
authors.initials: A
authors.lastname: Van Rie
authors.forename: R
authors.initials: R
authors.lastname: Warren
authors.forename: I
authors.initials: I
authors.lastname: Mshanga
authors.forename: A M
authors.initials: AM
authors.lastname: Jordaan
authors.forename: G D
authors.initials: GD
authors.lastname: van der Spuy
authors.forename: M
authors.initials: M
authors.lastname: Richardson
authors.forename: J
authors.initials: J
authors.lastname: Simpson
authors.forename: R P
authors.initials: RP
authors.lastname: Gie
authors.forename: D A
authors.initials: DA
authors.lastname: Enarson
authors.forename: N
authors.initials: N
authors.lastname: Beyers
authors.forename: P D
authors.initials: PD
authors.lastname: van Helden
authors.forename: T C
authors.initials: TC
authors.lastname: Victor
mesh_terms: D001426:Bacterial Proteins; D016000:Cluster Analysis; D003062:Codon; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D018432:Drug Resistance, Multiple; D005838:Genotype; D006801:Humans; D015994:Incidence; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D010544:Peroxidases / Q000235:genetics; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D013019:South Africa / Q000453:epidemiology; D013183:Sputum / Q000382:microbiology; D014376:Tuberculosis / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins; D003062:Codon; D010544:Peroxidases; C076136:catalase HPI; D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit