Use of a Molecular Diagnostic Test in AFB Smear Positive Tuberculosis Suspects Greatly Reduces Time to Detection of Multidrug Resistant Tuberculosis

• Type of Material: Article
• Authors: N Tukvadze, Natl Ctr TB & Lung Dis; Russell Ryan Kempker, Emory University; I Kalandadze, Natl Ctr TB & Lung Dis; Ekaterina Kurbatova, Emory University; MK Leonard, Emory University; R Apsindzelashvili, Natl Ctr TB & Lung Dis; N Bablishvili, Natl Ctr TB & Lung Dis; M Kipiani, Natl Ctr TB & Lung Dis; Henry Michael Blumberg, Emory University
• Language: English
• Date: 2012-02-09
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Tukvadze et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0031563
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 7
• Issue: 2
• Start Page: e31563
• End Page: e31563
• Grant/Funding Information: This work was supported in part by the NIH Fogarty International Center [D43TW007124 and D43TW007124-06S1], the Atlanta Clinical and Translational Science Institute [NIH/NCRR UL1RR025008], the U.S. Civilian and Research Development Foundation (CRDF GEB2-2935-TB-08), and the Emory Global Health Institute.
• Keywords: Multidisciplinary Sciences; SOUTH-AFRICA; METAANALYSIS; CHEMOTHERAPY; Science & Technology - Other Topics; MTBDRPLUS ASSAY; COUNTRIES; MYCOBACTERIUM-TUBERCULOSIS; DRUG-RESISTANCE; Science & Technology; CLINICAL SPECIMENS; HIGH PREVALENCE; MULTIDISCIPLINARY SCIENCES; TREATMENT OUTCOMES
• Research Categories: Health Sciences, General; Health Sciences, Medicine and Surgery

Abstract

Background: The WHO has recommended the implementation of rapid diagnostic tests to detect and help combat M/XDR tuberculosis (TB). There are limited data on the performance and impact of these tests in field settings. Methods: The performance of the commercially available Genotype MTBDRplus molecular assay was compared to conventional methods including AFB smear, culture and drug susceptibility testing (DST) using both an absolute concentration method on Löwenstein-Jensen media and broth-based method using the MGIT 960 system. Sputum specimens were obtained from TB suspects in the country of Georgia who received care through the National TB Program. Results: Among 500 AFB smear-positive sputum specimens, 458 (91.6%) had both a positive sputum culture for Mycobacterium tuberculosis and a valid MTBDRplus assay result. The MTBDRplus assay detected isoniazid (INH) resistance directly from the sputum specimen in 159 (89.8%) of 177 specimens and MDR-TB in 109 (95.6%) of 114 specimens compared to conventional methods. There was high agreement between the MTBDRplus assay and conventional DST results in detecting MDR-TB (kappa = 0.95, p < 0.01). The most prevalent INH resistance mutation was S315T (78%) in the katG codon and the most common rifampicin resistance mutation was S531L (68%) in the rpoB codon. Among 13 specimens from TB suspects with negative sputum cultures, 7 had a positive MTBDRplus assay (3 with MDR-TB). The time to detection of MDR-TB was significantly less using the MTBDRplus assay (4.2 days) compared to the use of standard phenotypic tests (67.3 days with solid media and 21.6 days with broth-based media). Conclusions: Compared to conventional methods, the MTBDRplus assay had high accuracy and significantly reduced time to detection of MDR-TB in an area with high MDR-TB prevalence. The use of rapid molecular diagnostic tests for TB and drug resistance should increase the proportion of patients promptly placed on appropriate therapy.