Assessment of the sensitivity and specificity of Xpert MTB/RIF assay as an early sputum biomarker of response to tuberculosis treatment

Sven Olaf Friedrich; Andrea Rachow; Elmar Saathoff; Kasha Singh; Chacha D Mangu; Rodney Dawson; Patrick Phillips; Amour Venter; Anna Bateson; Catharina C  Boehme; Norbert Heinrich; Robert Hunt; Martin J Boeree; Alimudden Zumla; Timothy D  McHugh; Stephen Henry Gillespie; Andreas Diacon; Michael Hoelscher

doi:10.1016/S2213-2600(13)70119-X

Assessment of the sensitivity and specificity of Xpert MTB/RIF assay as an early sputum biomarker of response to tuberculosis treatment

Sven Olaf Friedrich, Andrea Rachow, Elmar Saathoff, Kasha Singh, Chacha D Mangu, Rodney Dawson, Patrick Phillips, Amour Venter, Anna Bateson, Catharina C Boehme, Norbert Heinrich, Robert Hunt, Martin J Boeree, Alimudden Zumla, Timothy D McHugh, Stephen Henry Gillespie, Andreas Diacon, Michael Hoelscher

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Abstract

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.

Original language	English
Pages (from-to)	462-470
Number of pages	9
Journal	The Lancet Respiratory Medicine
Volume	1
Issue number	6
Early online date	1 Jul 2013
DOIs	https://doi.org/10.1016/S2213-2600(13)70119-X
Publication status	Published - 2013

Keywords

Tuberculosis
Biomarker
Mycobacterium tuberculosis
Sputum
Xpert® MTB/RIF assay
Clinical trials
Tuberculosis drugs
Smear microscopy
Culture

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S2213-2600(13)70119-X

friedrich2013lancetrespmed462
Copyright © 2013 Elsevier Ltd. All rights reserved. Published open access.
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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, 1(6), 462-470. https://doi.org/10.1016/S2213-2600(13)70119-X

@article{131074b9bac14176b97e1e29ee4a920c,

title = "Assessment of the sensitivity and specificity of Xpert MTB/RIF assay as an early sputum biomarker of response to tuberculosis treatment",

abstract = "BackgroundAn accurate biomarker for monitoring response to treatment of pulmonary tuberculosis is urgently needed. The Xpert{\textregistered} MTB/RIF assay is a commercially available real-time PCR that detects Mycobacterium tuberculosis-specific DNA sequences in sputum samples.MethodsSputum 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{\textregistered} MTB/RIF results over time were compared with the results of standard smear and culture methods.FindingsXpert{\textregistered} MTB/RIF positivity rates declined slower than those of standard methods. At week 8, smear, solid culture, liquid culture, and the Xpert{\textregistered} 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{\textregistered} 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{\textregistered} MTB/RIF assay had high sensitivity (97·0%) but poor specificity (48·6%).InterpretationQuantitative Xpert{\textregistered} MTB/RIF readouts correlate well with M tuberculosis smear and culture results during anti-tuberculosis treatment. The poor specificity precludes the use of Xpert{\textregistered} MTB/RIF assay as a biomarker for tuberculosis treatment monitoring.",

keywords = "Tuberculosis, Biomarker, Mycobacterium tuberculosis, Sputum, Xpert{\textregistered} MTB/RIF assay, Clinical trials, Tuberculosis drugs, Smear microscopy, Culture",

author = "Friedrich, {Sven Olaf} and Andrea Rachow and Elmar Saathoff and Kasha Singh and Mangu, {Chacha D} and Rodney Dawson and Patrick Phillips and Amour Venter and Anna Bateson and Boehme, {Catharina C} and Norbert Heinrich and Robert Hunt and Boeree, {Martin J} and Alimudden Zumla and McHugh, {Timothy D} and Gillespie, {Stephen Henry} and Andreas Diacon and Michael Hoelscher",

note = "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). ",

year = "2013",

doi = "10.1016/S2213-2600(13)70119-X",

language = "English",

volume = "1",

pages = "462--470",

journal = "The Lancet Respiratory Medicine",

issn = "2213-2600",

publisher = "Elsevier",

number = "6",

}

Friedrich, SO, Rachow, A, Saathoff, E, Singh, K, Mangu, CD, Dawson, R, Phillips, P, Venter, A, Bateson, A, Boehme, CC, Heinrich, N, Hunt, R, Boeree, MJ, Zumla, A, McHugh, TD, Gillespie, SH, 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. https://doi.org/10.1016/S2213-2600(13)70119-X

TY - JOUR

T1 - Assessment of the sensitivity and specificity of Xpert MTB/RIF assay as an early sputum biomarker of response to tuberculosis treatment

AU - Friedrich, Sven Olaf

AU - Rachow, Andrea

AU - Saathoff, Elmar

AU - Singh, Kasha

AU - Mangu, Chacha D

AU - Dawson, Rodney

AU - Phillips, Patrick

AU - Venter, Amour

AU - Bateson, Anna

AU - Boehme, Catharina C

AU - Heinrich, Norbert

AU - Hunt, Robert

AU - Boeree, Martin J

AU - Zumla, Alimudden

AU - McHugh, Timothy D

AU - Gillespie, Stephen Henry

AU - Diacon, Andreas

AU - Hoelscher, Michael

N1 - 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).

PY - 2013

Y1 - 2013

N2 - BackgroundAn 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.MethodsSputum 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.FindingsXpert® 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%).InterpretationQuantitative 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.

AB - BackgroundAn 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.MethodsSputum 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.FindingsXpert® 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%).InterpretationQuantitative 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.

KW - Tuberculosis

KW - Biomarker

KW - Mycobacterium tuberculosis

KW - Sputum

KW - Xpert® MTB/RIF assay

KW - Clinical trials

KW - Tuberculosis drugs

KW - Smear microscopy

KW - Culture

U2 - 10.1016/S2213-2600(13)70119-X

DO - 10.1016/S2213-2600(13)70119-X

M3 - Article

SN - 2213-2600

VL - 1

SP - 462

EP - 470

JO - The Lancet Respiratory Medicine

JF - The Lancet Respiratory Medicine

IS - 6

ER -

Assessment of the sensitivity and specificity of Xpert MTB/RIF assay as an early sputum biomarker of response to tuberculosis treatment

Abstract

Keywords

UN SDGs

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