Multiplex allele specific PCR for rapid detection of extensively drug resistant tuberculosis

Vadwai, Viral; Shetty, Anjali; Rodrigues, Camilla

doi:10.1016/j.tube.2012.01.004

Cited by 17 publications

(13 citation statements)

References 19 publications

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“…NIHR Journals Library www.journalslibrary.nihr.ac.uk studies (n = 18), 34,[62][63][64][65][66][67][68][69][70][71][72][73][74][75][98][99][100] MTBDRsl studies (n = 6) 37,76-80 and other rapid diagnostic studies (n = 17); [81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97] the last category comprised any report with insufficient information about the type and manufacture of the assay tested, or assays that had been designed in-house.…”

Section: Systematic Reviewmentioning

confidence: 99%

“…In addition to the studies that reported diagnostic data from the widely used commercial tests, 17 studies [81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97] reporting data on other genetic rapid diagnostic tests were identified using the inclusion criteria. These tests were broadly broken into those studies that utilised a variety of TB biochip assays (n = 7, 41.2%) and those that used in-house PCR assays (n = 10, 59.8%).…”

Section: Other Studiesmentioning

confidence: 99%

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Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis

Drobniewski

Cooke

Jordan

et al. 2015

Health Technology Assessment

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BackgroundDrug-resistant tuberculosis (TB), especially multidrug-resistant (MDR, resistance to rifampicin and isoniazid) disease, is associated with a worse patient outcome. Drug resistance diagnosed using microbiological culture takes days to weeks, as TB bacteria grow slowly. Rapid molecular tests for drug resistance detection (1 day) are commercially available and may promote faster initiation of appropriate treatment.ObjectivesTo (1) conduct a systematic review of evidence regarding diagnostic accuracy of molecular genetic tests for drug resistance, (2) conduct a health-economic evaluation of screening and diagnostic strategies, including comparison of alternative models of service provision and assessment of the value of targeting rapid testing at high-risk subgroups, and (3) construct a transmission-dynamic mathematical model that translates the estimates of diagnostic accuracy into estimates of clinical impact.Review methods and data sourcesA standardised search strategy identified relevant studies from EMBASE, PubMed, MEDLINE, Bioscience Information Service (BIOSIS), System for Information on Grey Literature in Europe Social Policy & Practice (SIGLE) and Web of Science, published between 1 January 2000 and 15 August 2013. Additional ‘grey’ sources were included. Quality was assessed using quality assessment of diagnostic accuracy studies version 2 (QUADAS-2). For each diagnostic strategy and population subgroup, a care pathway was constructed to specify which medical treatments and health services that individuals would receive from presentation to the point where they either did or did not complete TB treatment successfully. A total cost was estimated from a health service perspective for each care pathway, and the health impact was estimated in terms of the mean discounted quality-adjusted life-years (QALYs) lost as a result of disease and treatment. Costs and QALYs were both discounted at 3.5% per year. An integrated transmission-dynamic and economic model was used to evaluate the cost-effectiveness of introducing rapid molecular testing (in addition to culture and drug sensitivity testing). Probabilistic sensitivity analysis was performed to evaluate the impact on cost-effectiveness of diagnostic and treatment time delays, diagnosis and treatment costs, and associated QALYs.ResultsA total of 8922 titles and abstracts were identified, with 557 papers being potentially eligible. Of these, 56 studies contained sufficient test information for analysis. All three commercial tests performed well when detecting drug resistance in clinical samples, although with evidence of heterogeneity between studies. Pooled sensitivity for GenoType®MTBDRplus (Hain Lifescience, Nehren, Germany) (isoniazid and rifampicin resistance), INNO-LiPA Rif.TB®(Fujirebio Europe, Ghent, Belgium) (rifampicin resistance) and Xpert®MTB/RIF (Cepheid Inc., Sunnyvale, CA, USA) (rifampicin resistance) was 83.4%, 94.6%, 95.4% and 96.8%, respectively; equivalent pooled specificity was 99.6%, 98.2%, 99.7% and 98.4%, respectively. Results of the transmission model suggest that all of the rapid assays considered here, if added to the current diagnostic pathway, would be cost-saving and achieve a reduction in expected QALY loss compared with current practice. GenoType MTBDRplus appeared to be the most cost-effective of the rapid tests in the South Asian population, although results were similar for GeneXpert. In all other scenarios GeneXpert appeared to be the most cost-effective strategy.ConclusionsRapid molecular tests for rifampicin and isoniazid resistance were sensitive and specific. They may also be cost-effective when added to culture drug susceptibility testing in the UK. There is global interest in point-of-care testing and further work is needed to review the performance of emerging tests and the wider health-economic impact of decentralised testing in clinics and primary care, as well as non-health-care settings, such as shelters and prisons.Study registrationThis study is registered as PROSPERO CRD42011001537.FundingThe National Institute for Health Research Health Technology Assessment programme.

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Section: Systematic Reviewmentioning

confidence: 99%

Section: Other Studiesmentioning

confidence: 99%

Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis

Drobniewski

Cooke

Jordan

et al. 2015

Health Technology Assessment

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“…Several other molecular techniques which detect resistance to the injectable drugs have been described recently. These include in-house reverse line blot hybridization assays, multiplex allele-specific PCR, mass spectrometry of PCR products using iPLEX Gold assay (MassArray System; Sequenom, Inc., San Diego, CA, USA), oligonucleotide microarray, and melting curves using dually labeled probes (19)(20)(21)(22)(23)(24). However, most of these techniques require open handling of PCR amplicons or have not been systematically validated in clinical settings.…”

mentioning

confidence: 99%

Genotypic Susceptibility Testing of Mycobacterium tuberculosis Isolates for Amikacin and Kanamycin Resistance by Use of a Rapid Sloppy Molecular Beacon-Based Assay Identifies More Cases of Low-Level Drug Resistance than Phenotypic Lowenstein-Jensen Testing

et al. 2015

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eResistance to amikacin (AMK) and kanamycin (KAN) in clinical Mycobacterium tuberculosis strains is largely determined by specific mutations in the rrs gene and eis gene promoter. We developed a rapid, multiplexed sloppy molecular beacon (SMB) assay to identify these mutations and then evaluated assay performance on 603 clinical M. tuberculosis DNA samples collected in South Korea. Assay performance was compared to gold-standard phenotypic drug susceptibility tests, including LowensteinJensen (LJ) absolute concentration, mycobacterial growth indicator tubes (MGIT), and TREK Sensititre MycoTB MIC plate (MycoTB) methods. Target amplicons were also tested for mutations by Sanger sequencing. The SMB assay correctly detected 115/116 mutant and mixed sequences and 487/487 wild-type sequences (sensitivity and specificity of 99.1 and 100%, respectively). Using the LJ method as the reference, sensitivity and specificity for AMK resistance were 92.2% and 100%, respectively, and sensitivity and specificity for KAN resistance were 87.7% and 95.6%, respectively. Mutations in the rrs gene were unequivocally associated with high-level cross-resistance to AMK and KAN in all three conventional drug susceptibility testing methods. However, eis promoter mutations were associated with KAN resistance using the MGIT or MycoTB methods but not the LJ method. No testing method associated eis promoter mutations with AMK resistance. Among the discordant samples with AMK and/or KAN resistance but wild-type sequence at the target genes, we discovered four new mutations in the whiB7 5= untranslated region (UTR) in 6/22 samples. All six samples were resistant only to KAN, suggesting the possible role of these whiB7 5= UTR mutations in KAN resistance.T uberculosis (TB) was declared a global public emergency nearly 20 years ago (1). Although the rate of new cases of TB has been decreasing worldwide, the millennium developmental goal target of a 50% disease reduction by 2015 is unlikely to be achieved (1). An increase in the incidence of multidrug-resistant (MDR) and extensively drug resistant (XDR) TB is a serious threat to these reduction goals (1). Patients with drug-resistant TB are best identified as rapidly as possible so that appropriate infection control and treatments can be quickly initiated (2).Conventional phenotypic methods can take weeks to months to fully define the drug resistance pattern of Mycobacterium tuberculosis isolates due to the very slow growth of this bacterium (3-5). Molecular tests offer the promise of more rapid drug resistance detection. A number of tests are available to detect resistance to many of the first-line anti-TB drugs (6-8). However, there are fewer rapid tests available to test for resistance to the injectable second-line drugs amikacin (AMK), kanamycin (KAN), and capreomycin (CAP). DNA sequencing studies suggest that most cases of resistance to injectable drugs can be identified by detecting mutations in positions 1401, 1402, and 1484 in the M. tuberculosis 16S rRNA (rrs) gene and between nucleotides Ϫ...

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“…The target hybridization provides more than 150 fold stronger signal intensity than the non-specific hybridization, which serves as a key to the accurate detection and discrimination of multiple mutations by using MTB-DR-RIF 9G test. The diagnostic accuracy in terms of sensitivity and specificity of MTB-DR-RIF 9G test were high as compared to the reported methods [30,31]. It is important to notice that sequencing analysis and MTB-DR-RIF 9G test showed 100% agreement in the results for the detection and discrimination of the wild MTB and MTB-DR-RIF infections.…”

Section: Discussionmentioning

confidence: 75%

MTB-DR-RIF 9G test: Detection and discrimination of tuberculosis and multi-drug resistant tuberculosis strains

Song¹,

Nimse

Cho

et al. 2015

Tuberculosis

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Multiplex allele specific PCR for rapid detection of extensively drug resistant tuberculosis

Cited by 17 publications

References 19 publications

Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis

Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis

Genotypic Susceptibility Testing of Mycobacterium tuberculosis Isolates for Amikacin and Kanamycin Resistance by Use of a Rapid Sloppy Molecular Beacon-Based Assay Identifies More Cases of Low-Level Drug Resistance than Phenotypic Lowenstein-Jensen Testing

MTB-DR-RIF 9G test: Detection and discrimination of tuberculosis and multi-drug resistant tuberculosis strains

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