RATIONALE: 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. OBJECTIVES: 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. MEASUREMENTS AND MAIN 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.
RATIONALE: 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. OBJECTIVES: 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. MEASUREMENTS AND MAIN 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: Matthew C Mulvey; Margaret Lemmon; Stephanie Rotter; Jonathan Lees; Leo Einck; Carol A Nacy Journal: Antimicrob Agents Chemother Date: 2014-11-03 Impact factor: 5.191
Authors: V R Bollela; E I Namburete; C S Feliciano; D Macheque; L H Harrison; J A Caminero Journal: Int J Tuberc Lung Dis Date: 2016-08 Impact factor: 2.373
Authors: Nontuthuko E Maningi; Luke T Daum; John D Rodriguez; Halima M Said; Remco P H Peters; John Osei Sekyere; Gerald W Fischer; James P Chambers; P Bernard Fourie Journal: J Clin Microbiol Date: 2018-04-25 Impact factor: 5.948
Authors: David W Dowdy; Richard E Chaisson; Gary Maartens; Elizabeth L Corbett; Susan E Dorman Journal: Proc Natl Acad Sci U S A Date: 2008-08-11 Impact factor: 11.205
Authors: Karen R Jacobson; Danie Theron; Emily A Kendall; Molly F Franke; Marinus Barnard; Paul D van Helden; Tommie C Victor; Elizabeth M Streicher; Megan B Murray; Robin M Warren Journal: Clin Infect Dis Date: 2012-10-22 Impact factor: 9.079
Authors: Anne F Luetkemeyer; Michelle A Kendall; Xingye Wu; Maria Cristina Lourenço; Ute Jentsch; Susan Swindells; Sarojini S Qasba; Jorge Sanchez; Diane V Havlir; Beatriz Grinsztejn; Ian M Sanne; Cynthia Firnhaber Journal: J Clin Microbiol Date: 2014-01-15 Impact factor: 5.948