Ann Lab Med.  2020 Mar;40(2):142-147. 10.3343/alm.2020.40.2.142.

Evaluation of the QuantaMatrix Multiplexed Assay Platform for Molecular Diagnosis of Multidrug- and Extensively Drug-Resistant Tuberculosis Using Clinical Strains Isolated in Myanmar

Affiliations
  • 1Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, Korea. Hyelee@yonsei.ac.kr
  • 2International Tuberculosis Research Center, Changwon, Korea.
  • 3Department of Laboratory Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea.

Abstract

BACKGROUND
Although the incidence of tuberculosis (TB) is decreasing, cases of multidrug-resistant (MDR) TB and extensively drug-resistant (XDR) TB continue to increase. As conventional phenotype drug susceptibility testing (pDST) takes six to eight weeks, molecular assays are widely used to determine drug resistance. we developed QuantaMatrix Multiplexed Assay Platform (QMAP) MDR/XDR assay (QuantaMatrix Inc., Seoul, Korea) that can simultaneously detect mutations related to both first- and second-line drug resistance (rifampin, isoniazid, ethambutol, fluoroquinolones, second-line injectable drugs, and streptomycin).
METHODS
We used 190 clinical Mycobacterium tuberculosis (MTB) strains isolated from Myanmar, compared QMAP and pDST results, and determined concordance rates. Additionally, we performed sequence analyses for discordant results.
RESULTS
QMAP results were 87.9% (167/190) concordant with pDST results. In the 23 isolates with discordant results, the QMAP and DNA sequencing results completely matched.
CONCLUSIONS
The QMAP MDR/XDR assay can detect all known DNA mutations associated with drug resistance for both MDR- and XDR-MTB strains. It can be used for molecular diagnosis of MDR- and XDR-TB to rapidly initiate appropriate anti-TB drug therapy.

Keyword

Mycobacterium tuberculosis; Multidrug-resistant tuberculosis; Extensively drug-resistant tuberculosis; QuantaMatrix Multiplexed Assay Platform

MeSH Terms

Diagnosis*
DNA
Drug Resistance
Drug Therapy
Ethambutol
Extensively Drug-Resistant Tuberculosis*
Fluoroquinolones
Incidence
Isoniazid
Myanmar*
Mycobacterium tuberculosis
Phenotype
Seoul
Sequence Analysis
Sequence Analysis, DNA
Tuberculosis
Tuberculosis, Multidrug-Resistant
DNA
Ethambutol
Fluoroquinolones
Isoniazid

Reference

1. WHO. Global tuberculosis report 2017. Updated on Aug 2019. https://www.who.int/tb/publications/global_report/gtbr2017_main_text.pdf.
2. WHO. Global tuberculosis report 2018. Updated on Aug 2019. http://apps.who.int/iris/bitstream/handle/10665/274453/9789241565646-eng.pdf.
3. WHO. Definitions and reporting framework for tuberculosis-2013 revision. Updated on Aug 2019. https://apps.who.int/iris/bitstream/handle/10665/79199/9789241505345_eng.pdf.
4. Choi J, Yoo J, Kim KJ, Kim EG, Park KO, Kim H, et al. Rapid drug susceptibility test of Mycobacterium tuberculosis using microscopic time-lapse imaging in an agarose matrix. Appl Microbiol Biotechnol. 2016; 100:2355–2365. PMID: 26754815.
5. Pang Y, Dong H, Tan Y, Deng Y, Cai X, Jing H, et al. Rapid diagnosis of MDR and XDR tuberculosis with the MeltPro TB assay in China. Sci Rep. 2016; 6:25330. PMID: 27149911.
6. Kim LN, Kim M, Jung K, Bae HJ, Jang J, Jung Y, et al. Shape-encoded silica microparticles for multiplexed bioassays. Chem Commun (Camb). 2015; 51:12130–12133. PMID: 26125980.
7. Wang HY, Uh Y, Kim S, Cho E, Lee JS, Lee H. Detection of rifampicin- and isoniazid-resistant Mycobacterium tuberculosis using the QuantaMatrix Multiplexed Assay Platform system. Ann Lab Med. 2018; 38:569–577. PMID: 30027701.
8. Han ET, Lee JS, Cheong JH, Chang CL, Nyunt MH, Aung WW, et al. Current status of standard diagnostics and treatment for malaria, tuberculosis, and hepatitis in Myanmar. Lab Med Online. 2017; 7:94–102.
9. Jensen MA, Webster JA, Straus N. Rapid identification of bacteria on the basis of polymerase chain reaction-amplified ribosomal DNA spacer polymorphisms. Appl Environ Microbiol. 1993; 59:945–952. PMID: 8476298.
10. Kim J, Park YJ, Lee NY, Chang CL, Lee M, Shin JH. Evaluation of the AdvanSure MDR-TB GenoBlot assay for detection of rifampin and isoniazid resistant Mycobacterium tuberculosis complex in respiratory specimens. Korean J Clin Microbiol. 2012; 15:117–124.
11. Maurya AK, Umrao J, Singh AK, Kant S, Kushwaha RA, Dhole TN. Evaluation of GenoType MTBDRplus assay for rapid detection of drug susceptibility testing of multi-drug resistance tuberculosis in Northern India. Indian J Pathol Microbiol. 2013; 56:139–143. PMID: 24056651.
12. Bedewi Omer Z, Mekonnen Y, Worku A, Zewde A, Medhin G, Mohammed T, et al. Evaluation of the GenoType MTBDRplus assay for detection of rifampicin- and isoniazid-resistant Mycobacterium tuberculosis isolates in central Ethiopia. Int J Mycobacteriol. 2016; 5:475–481. PMID: 27931690.
13. Tagliani E, Cabibbe AM, Miotto P, Borroni E, Toro JC, Mansjo M, et al. Diagnostic performance of the new version (v2.0) of GenoType MTBDRsl assay for detection of resistance to fluoroquinolones and second-line injectable drugs: a multicenter study. J Clin Microbiol. 2015; 53:2961–2969. PMID: 26179309.
14. WHO. The use of molecular line probe assays for the detection of resistance to second-line anti-tuberculosis drugs: policy guidance. WHO HTM/TB/2016.07. Updated on Aug 2019. http://www.who.int/iris/bitstream/10665/246131/1/9789241510561-eng.pdf.
15. Laurenzo D. Mechanisms of drug resistance in Mycobacterium tuberculosis and current status of rapid molecular diagnostic testing. Acta Trop. 2011; 119:5–10. PMID: 21515239.
16. Lee AS, Lim IH, Tang LL, Wong SY. High frequency of mutations in the rpoB gene in rifampin-resistant clinical isolates of Mycobacterium tuberculosis from Singapore. J Clin Microbiol. 2005; 43:2026–2027. PMID: 15815052.
17. Dookie N, Rambaran S, Padayatchi N, Mahomed S, Naidoo K. Evolution of drug resistance in Mycobacterium tuberculosis: a review on the molecular determinants of resistance and implications for personalized care. J Antimicrob Chemother. 2018; 73:1138–1151. PMID: 29360989.
18. Chien JY, Chiu WY, Chien ST, Chiang CJ, Yu CJ, Hsueh PR. Mutations in gyrA and gyrB among fluoroquinolone- and multidrug-resistant Mycobacterium tuberculosis isolates. Antimicrob Agents Chemother. 2016; 60:2090–2096. PMID: 26787695.
19. Hofmann-Thiel S, van Ingen J, Feldmann K, Turaev L, Uzakova GT, Murmusaeva G, et al. Mechanisms of heteroresistance to isoniazid and rifampin of Mycobacterium tuberculosis in Tashkent, Uzbekistan. Eur Respir J. 2009; 33:368–374. PMID: 18829680.
20. Chakravorty S, Aladegbami B, Thoms K, Lee JS, Lee EG, Rajan V, et al. Rapid detection of fluoroquinolone-resistant and heteroresistant Mycobacterium tuberculosis by use of sloppy molecular beacons and dual melting-temperature codes in a real-time PCR assay. J Clin Microbiol. 2011; 49:932–940. PMID: 21191047.
21. Shin SS, Modongo C, Baik Y, Allender C, Lemmer D, Colman RE, et al. Mixed Mycobacterium tuberculosis-strain infections are associated with poor treatment outcomes among patients with newly diagnosed tuberculosis, independent of pretreatment heteroresistance. J Infect Dis. 2018; 218:1974–1982. PMID: 30085153.
22. Mekonnen D, Admassu A, Mulu W, Amor A, Benito A, Gelaye W, et al. Multidrug-resistant and heteroresistant Mycobacterium tuberculosis and associated gene mutations in Ethiopia. Int J Infect Dis. 2015; 39:34–38. PMID: 26119857.
23. Liang B, Tan Y, Li Z, Tian X, Du C, Li H, et al. Highly sensitive detection of isoniazid heteroresistance in Mycobacterium tuberculosis by DeepMelt assay. J Clin Microbiol. 2018; 56:e01239–e01217. PMID: 29118176.
24. Ocheretina O, Escuyer VE, Mabou MM, Royal-Mardi G, Collins S, Vilbrun SC, et al. Correlation between genotypic and phenotypic testing for resistance to rifampin in Mycobacterium tuberculosis clinical isolates in Haiti: investigation of cases with discrepant susceptibility results. PLoS One. 2014; 9:e90569. PMID: 24599230.
25. WHO. The use of next-generation sequencing technologies for the detection of mutations associated with drug resistance in Mycobacterium tuberculosis complex: technical guide. WHO CDS/TB/2018.19. Updated on Aug 2019. https://apps.who.int/iris/bitstream/handle/10665/274443/WHO-CDS-TB-2018.19-eng.pdf.
26. Khosravi AD, Sirous M, Abdi M, Ahmadkhosravi N. Characterization of the most common embCAB gene mutations associated with ethambutol resistance in Mycobacterium tuberculosis isolates from Iran. Infect Drug Resist. 2019; 12:579–584. PMID: 30881063.
27. Sun Q, Xiao TY, Liu HC, Zhao XQ, Liu ZG, Li YN, et al. Mutations within embCAB are associated with variable level of ethambutol resistance in Mycobacterium tuberculosis isolates from China. Antimicrob Agents Chemother. 2017; 62:e01279–e01217. PMID: 29084750.
28. Gkaravela L, Papadimitriou-Olivgeris M, Foka A, Kolonitsiou F, Spiliopoulou A, Charokopos N, et al. Combination of commercially available molecular assays and culture based methods in diagnosis of tuberculosis and drug resistant tuberculosis. Braz J Microbiol. 2017; 48:785–790. PMID: 28689813.
Full Text Links
  • ALM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr