help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on January 17, 2008, doi:10.1164/rccm.200709-1436OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
200709-1436OCv1
177/7/787    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Related articles in AJRCCM
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Barnard, M.
Right arrow Articles by Bosman, M. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Barnard, M.
Right arrow Articles by Bosman, M. E.
American Journal of Respiratory and Critical Care Medicine Vol 177. pp. 787-792, (2008)
© 2008 American Thoracic Society
doi: 10.1164/rccm.200709-1436OC

Original Article

Rapid Molecular Screening for Multidrug-Resistant Tuberculosis in a High-Volume Public Health Laboratory in South Africa

Marinus Barnard1, Heidi Albert2, Gerrit Coetzee3, Richard O'Brien2 and Marlein E. Bosman1

1 National Health Laboratory Services (NHLS), Greenpoint, Cape Town, South Africa; 2 Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland; and 3 National TB Reference Laboratory, NHLS, Sandringham, Johannesburg, South Africa

Correspondence and requests for reprints should be addressed to Richard O'Brien, M.D., Foundation for Innovative New Diagnostics, 71 av Louis-Casai, 1216 Cointrin, Switzerland. E-mail: rick.obrien{at}finddiagnostics.org

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.

Key Words: tuberculosis • MDR TB • molecular diagnosis


AT A GLANCE COMMENTARY

Scientific Knowledge on the Subject
Molecular assays for diagnosis of drug-resistant tuberculosis (TB) are available but not widely used. There is no information on their performance in multidrug-resistant (MDR) TB screening in high-burden settings.

What This Study Adds to the Field
Molecular assays for MDR TB diagnosis from sputum specimens can be implemented in high-burden settings. The high accuracy, large reduction in reporting time, and high-volume capacity suggest the assay may revolutionize MDR TB diagnosis.

 

Related articles in AJRCCM:

Coming Out of the Darkness
Max Salfinger and David Ashkin
AJRCCM 2008 177: 676-677. [Full Text]  



This article has been cited by other articles:


Home page
 ChestHome page
J.-H. Choi, K. W. Lee, H.-R. Kang, Y. I. Hwang, S. Jang, D.-G. Kim, C.-H. Kim, I.-G. Hyun, T.-R. Shin, S.-M. Park, et al.
Clinical Efficacy of Direct DNA Sequencing Analysis on Sputum Specimens for Early Detection of Drug-Resistant Mycobacterium tuberculosis in a Clinical Setting
Chest, February 1, 2010; 137(2): 393 - 400.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
D. Helb, M. Jones, E. Story, C. Boehme, E. Wallace, K. Ho, J. Kop, M. R. Owens, R. Rodgers, P. Banada, et al.
Rapid Detection of Mycobacterium tuberculosis and Rifampin Resistance by Use of On-Demand, Near-Patient Technology
J. Clin. Microbiol., January 1, 2010; 48(1): 229 - 237.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
N. R. Gandhi, N. S. Shah, J. R. Andrews, V. Vella, A. P. Moll, M. Scott, D. Weissman, C. Marra, U. G. Lalloo, G. H. Friedland, et al.
HIV Coinfection in Multidrug- and Extensively Drug-Resistant Tuberculosis Results in High Early Mortality
Am. J. Respir. Crit. Care Med., January 1, 2010; 181(1): 80 - 86.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
D. C. Perlman, C. C. Leung, and W. W. Yew
Diagnosing Tuberculosis in Patients with HIV: Do We Know Enough?
Am. J. Respir. Crit. Care Med., November 1, 2009; 180(9): 800 - 801.
[Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
S.-Y. G. Lin, E. Desmond, D. Bonato, W. Gross, and S. Siddiqi
Multicenter Evaluation of Bactec MGIT 960 System for Second-Line Drug Susceptibility Testing of Mycobacterium tuberculosis Complex
J. Clin. Microbiol., November 1, 2009; 47(11): 3630 - 3634.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
A. Van Deun, L. Barrera, I. Bastian, L. Fattorini, H. Hoffmann, K. M. Kam, L. Rigouts, S. Rusch-Gerdes, and A. Wright
Mycobacterium tuberculosis Strains with Highly Discordant Rifampin Susceptibility Test Results
J. Clin. Microbiol., November 1, 2009; 47(11): 3501 - 3506.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
N. W. Schluger
Drug-Resistant Tuberculosis: What Is To Be Done?
Chest, August 1, 2009; 136(2): 333 - 335.
[Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
W.-L. Huang, H.-Y. Chen, Y.-M. Kuo, and R. Jou
Performance Assessment of the GenoType MTBDRplus Test and DNA Sequencing in Detection of Multidrug-Resistant Mycobacterium tuberculosis
J. Clin. Microbiol., August 1, 2009; 47(8): 2520 - 2524.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
D. Wilson, R. M. Hurtado, and S. Digumarthy
Case 18-2009 -- A 24-Year-Old Woman with AIDS and Tuberculosis with Progressive Cough, Dyspnea, and Wasting
N. Engl. J. Med., June 4, 2009; 360(23): 2456 - 2464.
[Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
P. W. Uys, R. Warren, P. D. van Helden, M. Murray, and T. C. Victor
Potential of Rapid Diagnosis for Controlling Drug-Susceptible and Drug-Resistant Tuberculosis in Communities Where Mycobacterium tuberculosis Infections Are Highly Prevalent
J. Clin. Microbiol., May 1, 2009; 47(5): 1484 - 1490.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
W. W. Yew and C. C. Leung
Update in Tuberculosis 2008
Am. J. Respir. Crit. Care Med., March 1, 2009; 179(5): 337 - 343.
[Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
J. Evans, M. C. Stead, M. P. Nicol, and H. Segal
Rapid genotypic assays to identify drug-resistant Mycobacterium tuberculosis in South Africa
J. Antimicrob. Chemother., January 1, 2009; 63(1): 11 - 16.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
T. Cohen, C. Colijn, A. Wright, M. Zignol, A. Pym, and M. Murray
Does Current Drug Resistance Surveillance Provide Useful Information in Tuberculosis?
Am. J. Respir. Crit. Care Med., January 1, 2009; 179(1): 82 - 83.
[Full Text] [PDF]

Home page
 NEJMHome page
K. Dheda, K. Shean, M. Badri, M. Cheruvu, S. Bhadriraju, C. D. Mitnick, J. Bayona, and M. C. Becerra
Extensively Drug-Resistant Tuberculosis
N. Engl. J. Med., November 27, 2008; 359(22): 2390 - 2391.
[Full Text] [PDF]

Home page
 Eur Respir JHome page
D. I. Ling, A. A. Zwerling, and M. Pai
GenoType MTBDR assays for the diagnosis of multidrug-resistant tuberculosis: a meta-analysis
Eur. Respir. J., November 1, 2008; 32(5): 1165 - 1174.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. W. Dowdy, R. E. Chaisson, G. Maartens, E. L. Corbett, and S. E. Dorman
Impact of enhanced tuberculosis diagnosis in South Africa: A mathematical model of expanded culture and drug susceptibility testing
PNAS, August 12, 2008; 105(32): 11293 - 11298.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
D. V. Havlir, H. Getahun, I. Sanne, and P. Nunn
Opportunities and Challenges for HIV Care in Overlapping HIV and TB Epidemics
JAMA, July 23, 2008; 300(4): 423 - 430.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
K. DeRiemer and B. C. de Jong
Catch Them While You Can!
Am. J. Respir. Crit. Care Med., July 1, 2008; 178(1): 5 - 6.
[Full Text] [PDF]

Home page
 JWatch Infect. DiseasesHome page
Rapid Screening for MDR-TB
Journal Watch Infectious Diseases, April 23, 2008; 2008(423): 1 - 1.
[Full Text]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. Salfinger and D. Ashkin
Coming Out of the Darkness
Am. J. Respir. Crit. Care Med., April 1, 2008; 177(7): 676 - 677.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2008 American Thoracic Society 		  Subscribe to PATS