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

Research output: Contribution to journal › Article › peer-review

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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Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials
Phillips, P. P. J., Mendel, C. M., Burger, D. A., Crook, A., Nunn, A. J., Dawson, R., Diacon, A. H. & Gillespie, S. H., 4 Feb 2016, In: BMC Medicine. 14, 11 p., 19.
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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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Research output

Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials

Cite this