title: Rapid molecular screening for multidrug-resistant tuberculosis in a high-volume public health laboratory in South Africa.
abstract: BACKGROUND
  The dual challenges to tuberculosis (TB) control of HIV infection and multidrug resistance are particularly pressing in South Africa. Conventional methods for detecting Mycobacterium tuberculosis drug resistance take weeks to months to produce results. Rapid molecular testing for drug resistance is available but has not been implemented in high-TB-burden settings.
  
  
  OBJECTIVE
  To assess the performance and feasibility of implementation of a commercially available molecular line-probe assay for rapid detection of rifampicin and isoniazid resistance.
  
  
  METHODS
  We performed the assay directly on 536 consecutive smear-positive sputum specimens from patients at increased risk of multidrug-resistant (MDR) TB in a busy routine diagnostic laboratory in Cape Town, South Africa. Results were compared with conventional liquid culture and drug susceptibility testing on solid medium.
  
  
  RESULTS
  Overall, 97% of smear-positive specimens gave interpretable results within 1-2 days using the molecular assay. Sensitivity, specificity, and positive and negative predictive values were 98.9, 99.4, 97.9, and 99.7%, respectively, for detection of rifampicin resistance; 94.2, 99.7, 99.1, and 97.9%, respectively, for detection of isoniazid resistance; and 98.8, 100, 100, and 99.7%, respectively, for detection of multidrug resistance compared with conventional results. The assay also performed well on specimens that were contaminated on conventional culture and on smear-negative, culture-positive specimens.
  
  
  CONCLUSIONS
  This molecular assay is a highly accurate screening tool for MDR TB, which achieves a substantial reduction in diagnostic delay. With overall performance characteristics that are superior to conventional culture and drug susceptibility testing and the possibility for high throughput with substantial cost savings, molecular testing has the potential to revolutionize MDR TB diagnosis.
authors.affiliation: Foundation for Innovative New Diagnostics, 71 av Louis-Casai, 1216 Cointrin, Switzerland.
authors.forename: Marinus
authors.initials: M
authors.lastname: Barnard
authors.forename: Heidi
authors.initials: H
authors.lastname: Albert
authors.forename: Gerrit
authors.initials: G
authors.lastname: Coetzee
authors.forename: Richard
authors.initials: R
authors.lastname: O'Brien
authors.forename: Marlein E
authors.initials: ME
authors.lastname: Bosman
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015336:Molecular Probe Techniques; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D011933:Reagent Kits, Diagnostic; D012293:Rifampin / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013019:South Africa; D013183:Sputum / Q000382:microbiology; D013997:Time Factors; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis*
chemical_list: D000995:Antitubercular Agents; D011933:Reagent Kits, Diagnostic; D007538:Isoniazid; D012293:Rifampin