Assessment of the sensitivity and specificity of Xpert MTB/RIF assay as an early sputum biomarker of response to tuberculosis treatment
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Background An accurate biomarker for monitoring response to treatment of pulmonary tuberculosis is urgently needed. The Xpert® MTB/RIF assay is a commercially available real-time PCR that detects Mycobacterium tuberculosis-specific DNA sequences in sputum samples. Methods Sputum samples from 221 patients with smear-positive tuberculosis enrolled in a multi-centre randomized clinical trial of anti-tuberculosis treatment were analysed weekly (weeks 0 to 8), then at weeks 12, 17, 22, 26 after treatment initiation. The Xpert® MTB/RIF results over time were compared with the results of standard smear and culture methods. Findings Xpert® MTB/RIF positivity rates declined slower than those of standard methods. At week 8, smear, solid culture, liquid culture, and the Xpert® MTB/RIF were positive in 29·2%, 26·3%, 42·1% and 84·1%, respectively, and at 26 weeks in 5·0%, 2·5%, 4·1%, and 26·5%, respectively. The decline of quantitative M. tuberculosis DNA detection via the Xpert® MTB/RIF correlated with smear grades (rho=-0·74; P<0·01), solid culture grades (rho=-0·73; P<0·01), and liquid culture time to positivity (rho=0·73; P<0·01). Compared to combined binary smear and culture results as reference standard, the Xpert® MTB/RIF assay had high sensitivity (97·0%) but poor specificity (48·6%). Interpretation Quantitative Xpert® MTB/RIF readouts correlate well with M tuberculosis smear and culture results during anti-tuberculosis treatment. The poor specificity precludes the use of Xpert® MTB/RIF assay as a biomarker for tuberculosis treatment monitoring.
Friedrich , S O , Rachow , A , Saathoff , E , Singh , K , Mangu , C D , Dawson , R , Phillips , P , Venter , A , Bateson , A , Boehme , C C , Heinrich , N , Hunt , R , Boeree , M J , Zumla , A , McHugh , T D , Gillespie , S H , Diacon , A & Hoelscher , M 2013 , ' Assessment of the sensitivity and specificity of Xpert MTB/RIF assay as an early sputum biomarker of response to tuberculosis treatment ' The Lancet Respiratory Medicine , vol 1 , no. 6 , pp. 462-470 . DOI: 10.1016/S2213-2600(13)70119-X
The Lancet Respiratory Medicine
Copyright © 2013 Elsevier Ltd. All rights reserved. Published open access.
Funding: PanACEA is funded by the European and Developing Countries Clinical Trials Partnership (grants numbers CT.2004.32011.001, IP.2007.32011.011, IP.2007.32011.012, IP.2007.32011.013), Global Alliance for TB Drug Development, Bill & Melinda Gates Foundation, UK Medical Research Council, and German Ministry of Science and Technology (grant number 01KA0901).
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