Analytical and clinical evaluation of the epistem genedrive assay for detection of mycobacterium tuberculosis

Shubhada Shenai, Derek T. Armstrong, Eloise Valli, David L. Dolinger, Lydia Nakiyingi, Reynaldo Dietze, Margareth Pretti Dalcolmo, Mark P. Nicol, Widaad Zemanay, Yuka Manabe, David Jamil Hadad, Patricia Marques-Rodrigues, Moises Palaci, Renata L. Peres, Mary Gaeddert, Sandra Armakovitch, Bareng A.S. Nonyane, Claudia M. Denkinger, Padmapriya Banada, Moses L. Joloba & 4 others Jerrold Ellner, Catharina Boehme, David Alland, Susan E. Dorman

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The Epistem Genedrive assay rapidly detects the Mycobacterium tuberculosis complex from sputum and is currently available for clinical use. However, the analytical and clinical performance of this test has not been fully evaluated. The analytical limit of detection (LOD) of the Genedrive PCR amplification was tested with genomic DNA; the performance of the complete (sample processing plus amplification) system was tested by spiking M. tuberculosis mc26030 cells into distilled water and M. tuberculosis- negative sputum. Specificity was tested using common respiratory pathogens and nontuberculosis mycobacteria. A clinical evaluation enrolled adults with suspected pulmonary tuberculosis, obtained three sputum samples from each participant, and compared the accuracy of the Genedrive to that of the Xpert MTB/RIF assay using M. tuberculosis cultures as the reference standard. The Genedrive assay had an LOD of 1 pg/-l (100 genomic DNA copies/reaction). The LODs of the system were 2.5-104 CFU/ml and 2.5-105 CFU/ml for cells spiked into water and sputum, respectively. False-positive rpoB probe signals were observed in 3/32 (9.4%) of the negative controls and also in few samples containing Mycobacterium abscessus, Mycobacterium gordonae, or Mycobacterium thermoresistibile. In the clinical study, among 336 analyzed participants, the overall sensitivities for the tuberculosis case detection of Genedrive, Xpert, and smear microscopy were 45.4% (95% confidence interval [CI], 35.2% to 55.8%), 91.8% (95% CI, 84.4% to 96.4%), and 77.3% (95% CI, 67.7% to 85.2%), respectively. The sensitivities of Genedrive and Xpert for the detection of smear-microscopy-negative tuberculosis were 0% (95% CI, 0% to 15.4%) and 68.2% (95% CI, 45.1% to 86.1%), respectively. The Genedrive assay did not meet performance standards recommended by the World Health Organization for a smear microscopy replacement tuberculosis test. Epistem is working on modifications to improve the assay.

Original languageEnglish (US)
Pages (from-to)1051-1057
Number of pages7
JournalJournal of clinical microbiology
Volume54
Issue number4
DOIs
StatePublished - Apr 1 2016

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Mycobacterium tuberculosis
Sputum
Confidence Intervals
Mycobacterium
Microscopy
Tuberculosis
Limit of Detection
Nontuberculous Mycobacteria
Water
DNA
Pulmonary Tuberculosis
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)

Cite this

Shenai, S., Armstrong, D. T., Valli, E., Dolinger, D. L., Nakiyingi, L., Dietze, R., ... Dorman, S. E. (2016). Analytical and clinical evaluation of the epistem genedrive assay for detection of mycobacterium tuberculosis. Journal of clinical microbiology, 54(4), 1051-1057. https://doi.org/10.1128/JCM.02847-15
Shenai, Shubhada ; Armstrong, Derek T. ; Valli, Eloise ; Dolinger, David L. ; Nakiyingi, Lydia ; Dietze, Reynaldo ; Dalcolmo, Margareth Pretti ; Nicol, Mark P. ; Zemanay, Widaad ; Manabe, Yuka ; Hadad, David Jamil ; Marques-Rodrigues, Patricia ; Palaci, Moises ; Peres, Renata L. ; Gaeddert, Mary ; Armakovitch, Sandra ; Nonyane, Bareng A.S. ; Denkinger, Claudia M. ; Banada, Padmapriya ; Joloba, Moses L. ; Ellner, Jerrold ; Boehme, Catharina ; Alland, David ; Dorman, Susan E. / Analytical and clinical evaluation of the epistem genedrive assay for detection of mycobacterium tuberculosis. In: Journal of clinical microbiology. 2016 ; Vol. 54, No. 4. pp. 1051-1057.
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abstract = "The Epistem Genedrive assay rapidly detects the Mycobacterium tuberculosis complex from sputum and is currently available for clinical use. However, the analytical and clinical performance of this test has not been fully evaluated. The analytical limit of detection (LOD) of the Genedrive PCR amplification was tested with genomic DNA; the performance of the complete (sample processing plus amplification) system was tested by spiking M. tuberculosis mc26030 cells into distilled water and M. tuberculosis- negative sputum. Specificity was tested using common respiratory pathogens and nontuberculosis mycobacteria. A clinical evaluation enrolled adults with suspected pulmonary tuberculosis, obtained three sputum samples from each participant, and compared the accuracy of the Genedrive to that of the Xpert MTB/RIF assay using M. tuberculosis cultures as the reference standard. The Genedrive assay had an LOD of 1 pg/-l (100 genomic DNA copies/reaction). The LODs of the system were 2.5-104 CFU/ml and 2.5-105 CFU/ml for cells spiked into water and sputum, respectively. False-positive rpoB probe signals were observed in 3/32 (9.4{\%}) of the negative controls and also in few samples containing Mycobacterium abscessus, Mycobacterium gordonae, or Mycobacterium thermoresistibile. In the clinical study, among 336 analyzed participants, the overall sensitivities for the tuberculosis case detection of Genedrive, Xpert, and smear microscopy were 45.4{\%} (95{\%} confidence interval [CI], 35.2{\%} to 55.8{\%}), 91.8{\%} (95{\%} CI, 84.4{\%} to 96.4{\%}), and 77.3{\%} (95{\%} CI, 67.7{\%} to 85.2{\%}), respectively. The sensitivities of Genedrive and Xpert for the detection of smear-microscopy-negative tuberculosis were 0{\%} (95{\%} CI, 0{\%} to 15.4{\%}) and 68.2{\%} (95{\%} CI, 45.1{\%} to 86.1{\%}), respectively. The Genedrive assay did not meet performance standards recommended by the World Health Organization for a smear microscopy replacement tuberculosis test. Epistem is working on modifications to improve the assay.",
author = "Shubhada Shenai and Armstrong, {Derek T.} and Eloise Valli and Dolinger, {David L.} and Lydia Nakiyingi and Reynaldo Dietze and Dalcolmo, {Margareth Pretti} and Nicol, {Mark P.} and Widaad Zemanay and Yuka Manabe and Hadad, {David Jamil} and Patricia Marques-Rodrigues and Moises Palaci and Peres, {Renata L.} and Mary Gaeddert and Sandra Armakovitch and Nonyane, {Bareng A.S.} and Denkinger, {Claudia M.} and Padmapriya Banada and Joloba, {Moses L.} and Jerrold Ellner and Catharina Boehme and David Alland and Dorman, {Susan E.}",
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Shenai, S, Armstrong, DT, Valli, E, Dolinger, DL, Nakiyingi, L, Dietze, R, Dalcolmo, MP, Nicol, MP, Zemanay, W, Manabe, Y, Hadad, DJ, Marques-Rodrigues, P, Palaci, M, Peres, RL, Gaeddert, M, Armakovitch, S, Nonyane, BAS, Denkinger, CM, Banada, P, Joloba, ML, Ellner, J, Boehme, C, Alland, D & Dorman, SE 2016, 'Analytical and clinical evaluation of the epistem genedrive assay for detection of mycobacterium tuberculosis', Journal of clinical microbiology, vol. 54, no. 4, pp. 1051-1057. https://doi.org/10.1128/JCM.02847-15

Analytical and clinical evaluation of the epistem genedrive assay for detection of mycobacterium tuberculosis. / Shenai, Shubhada; Armstrong, Derek T.; Valli, Eloise; Dolinger, David L.; Nakiyingi, Lydia; Dietze, Reynaldo; Dalcolmo, Margareth Pretti; Nicol, Mark P.; Zemanay, Widaad; Manabe, Yuka; Hadad, David Jamil; Marques-Rodrigues, Patricia; Palaci, Moises; Peres, Renata L.; Gaeddert, Mary; Armakovitch, Sandra; Nonyane, Bareng A.S.; Denkinger, Claudia M.; Banada, Padmapriya; Joloba, Moses L.; Ellner, Jerrold; Boehme, Catharina; Alland, David; Dorman, Susan E.

In: Journal of clinical microbiology, Vol. 54, No. 4, 01.04.2016, p. 1051-1057.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Analytical and clinical evaluation of the epistem genedrive assay for detection of mycobacterium tuberculosis

AU - Shenai, Shubhada

AU - Armstrong, Derek T.

AU - Valli, Eloise

AU - Dolinger, David L.

AU - Nakiyingi, Lydia

AU - Dietze, Reynaldo

AU - Dalcolmo, Margareth Pretti

AU - Nicol, Mark P.

AU - Zemanay, Widaad

AU - Manabe, Yuka

AU - Hadad, David Jamil

AU - Marques-Rodrigues, Patricia

AU - Palaci, Moises

AU - Peres, Renata L.

AU - Gaeddert, Mary

AU - Armakovitch, Sandra

AU - Nonyane, Bareng A.S.

AU - Denkinger, Claudia M.

AU - Banada, Padmapriya

AU - Joloba, Moses L.

AU - Ellner, Jerrold

AU - Boehme, Catharina

AU - Alland, David

AU - Dorman, Susan E.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - The Epistem Genedrive assay rapidly detects the Mycobacterium tuberculosis complex from sputum and is currently available for clinical use. However, the analytical and clinical performance of this test has not been fully evaluated. The analytical limit of detection (LOD) of the Genedrive PCR amplification was tested with genomic DNA; the performance of the complete (sample processing plus amplification) system was tested by spiking M. tuberculosis mc26030 cells into distilled water and M. tuberculosis- negative sputum. Specificity was tested using common respiratory pathogens and nontuberculosis mycobacteria. A clinical evaluation enrolled adults with suspected pulmonary tuberculosis, obtained three sputum samples from each participant, and compared the accuracy of the Genedrive to that of the Xpert MTB/RIF assay using M. tuberculosis cultures as the reference standard. The Genedrive assay had an LOD of 1 pg/-l (100 genomic DNA copies/reaction). The LODs of the system were 2.5-104 CFU/ml and 2.5-105 CFU/ml for cells spiked into water and sputum, respectively. False-positive rpoB probe signals were observed in 3/32 (9.4%) of the negative controls and also in few samples containing Mycobacterium abscessus, Mycobacterium gordonae, or Mycobacterium thermoresistibile. In the clinical study, among 336 analyzed participants, the overall sensitivities for the tuberculosis case detection of Genedrive, Xpert, and smear microscopy were 45.4% (95% confidence interval [CI], 35.2% to 55.8%), 91.8% (95% CI, 84.4% to 96.4%), and 77.3% (95% CI, 67.7% to 85.2%), respectively. The sensitivities of Genedrive and Xpert for the detection of smear-microscopy-negative tuberculosis were 0% (95% CI, 0% to 15.4%) and 68.2% (95% CI, 45.1% to 86.1%), respectively. The Genedrive assay did not meet performance standards recommended by the World Health Organization for a smear microscopy replacement tuberculosis test. Epistem is working on modifications to improve the assay.

AB - The Epistem Genedrive assay rapidly detects the Mycobacterium tuberculosis complex from sputum and is currently available for clinical use. However, the analytical and clinical performance of this test has not been fully evaluated. The analytical limit of detection (LOD) of the Genedrive PCR amplification was tested with genomic DNA; the performance of the complete (sample processing plus amplification) system was tested by spiking M. tuberculosis mc26030 cells into distilled water and M. tuberculosis- negative sputum. Specificity was tested using common respiratory pathogens and nontuberculosis mycobacteria. A clinical evaluation enrolled adults with suspected pulmonary tuberculosis, obtained three sputum samples from each participant, and compared the accuracy of the Genedrive to that of the Xpert MTB/RIF assay using M. tuberculosis cultures as the reference standard. The Genedrive assay had an LOD of 1 pg/-l (100 genomic DNA copies/reaction). The LODs of the system were 2.5-104 CFU/ml and 2.5-105 CFU/ml for cells spiked into water and sputum, respectively. False-positive rpoB probe signals were observed in 3/32 (9.4%) of the negative controls and also in few samples containing Mycobacterium abscessus, Mycobacterium gordonae, or Mycobacterium thermoresistibile. In the clinical study, among 336 analyzed participants, the overall sensitivities for the tuberculosis case detection of Genedrive, Xpert, and smear microscopy were 45.4% (95% confidence interval [CI], 35.2% to 55.8%), 91.8% (95% CI, 84.4% to 96.4%), and 77.3% (95% CI, 67.7% to 85.2%), respectively. The sensitivities of Genedrive and Xpert for the detection of smear-microscopy-negative tuberculosis were 0% (95% CI, 0% to 15.4%) and 68.2% (95% CI, 45.1% to 86.1%), respectively. The Genedrive assay did not meet performance standards recommended by the World Health Organization for a smear microscopy replacement tuberculosis test. Epistem is working on modifications to improve the assay.

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