Performance of GenoType® MTBDRplus assay in the diagnosis of drug-resistant tuberculosis in Tangier, Morocco

Karimi, Hind; En-Nanai, Latifa; Oudghiri, Amal; Chaoui, Imane; Laglaoui, Amin; Bourkadi, Jamal Eddine; Mzibri, Mohammed El; Abid, Mohammed

doi:10.1016/j.jgar.2017.09.002

Cited by 19 publications

(24 citation statements)

References 26 publications

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“…A total of 1589 clinical isolates were collected from TB confirmed pulmonary patients [ 24 , 26 , 28 , 29 ], and 203 isolates were collected from suspected TB patients [ 25 , 27 ]. 25.55% (458/1792) of TB patients were new cases, 30.25% (542/1792) were previously treated, and 1.84% (33/1792) of patients were under treatment.…”

Section: Resultsmentioning

confidence: 99%

“…Conventional drug susceptibility testing (DST) was performed on a Lowenstein–Jensen (L-J) medium [ 24 – 26 , 29 ] or using the proportion method [ 27 , 28 ]. Results showed various phenotypic resistance profiles ( Table 2 ); out of total 1792 MTB specimens, 874 (48.77%) were susceptible for all first-line drugs, 248 (13.84%) were isoniazid resistant (INH R ), 436 (24.33%) were RIF resistant, and 234 (13.05%) were MDR.…”

Section: Resultsmentioning

confidence: 99%

“…Results showed various phenotypic resistance profiles ( Table 2 ); out of total 1792 MTB specimens, 874 (48.77%) were susceptible for all first-line drugs, 248 (13.84%) were isoniazid resistant (INH R ), 436 (24.33%) were RIF resistant, and 234 (13.05%) were MDR. Among 918 MTB strains phenotypically resistant to rifampicin and/or isoniazid (248 INH R , 436 RIF R , and 234 MDR), 495 (238 RIF R , 234 MDR, and 23 INH R ) were subjected to rpoB mutation analysis by various genotyping resistance tests: PCR and DNA sequencing [ 25 , 26 ], qPCR-HRM [ 29 ], and rifoligotyping [ 24 ], where the genotypic tests were done after culture and the DNA was immediately used or stored at −20°C until use; however, for GenoType® MTBDR plus V2.0 [ 27 , 28 ], the assay was applied directly in the sputum specimens or after solid culture ( Table 2 ). In comparison to phenotypic data, 49 (10.38%) (8 MDR and 41 RIF R ) MTB strains phenotypically resistant to RIF did not exhibit any mutation in the rpoB gene ( Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

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Mutations Associated with Rifampicin Resistance in Mycobacterium tuberculosis Isolates from Moroccan Patients: Systematic Review

Eddabra

Neffa²

2020

Interdisciplinary Perspectives on Infectious Diseases

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Background. In recent years, the treatment of tuberculosis has been threatened by the increasing number of patients with drug resistance, especially rifampicin resistance, which is the most effective first-line antibiotic against Mycobacterium tuberculosis. Methods. We performed a systematic review of the literature by searching the PubMed database for studies of rifampicin-resistant Mycobacterium tuberculosis (MTB) isolates from Moroccan patients, published between 2010 and 2020. The aim of this review was to quantify the frequency of the most common mutations associated with rifampicin resistance, to describe the frequency at which these mutations co-occur. Identified studies were critically appraised according to the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Results. 6 studies met our inclusion criteria. Results show that 99.36% of MTB isolates had a single-point mutation, and the most commonly mutated codon of rpoB gene is 531 with 70.33% of phenotypically resistant strains. However, 10.38% of MTB strains phenotypically resistant to RIF did not exhibit any mutation in the rpoB gene. Conclusion. Identification of a resistance-associated mutation to rifampicin can be a good marker of drug-resistant TB, but lack of a mutation in the target sequence must be interpreted with caution.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Mutations Associated with Rifampicin Resistance in Mycobacterium tuberculosis Isolates from Moroccan Patients: Systematic Review

Eddabra

Neffa²

2020

Interdisciplinary Perspectives on Infectious Diseases

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“…As in other TB endemic settings, Tanzania has deployed rapid molecular methods for dual detection of MTBC and susceptibility to either RIF alone or along with INH and second-line injectable and fluoroquinolones. For example, while the Xpert®MTB/Rif assay (Cepheid, USA) detects MTBC and provides information about susceptibility to RIF only [16], the genotype MTBDRplus and MTBDRsl assays (Hain Life sciences, Germany) detect mutations that are strongly associated with multiple types of MDR-TB and also XDR-TB respectively [17,18]. These assays have potential to guide implementation of the new WHO shorter regimen for treating MDR-TB [15,19].…”

Section: Introductionmentioning

confidence: 99%

Whole genome sequencing of Mycobacterium tuberculosis isolates and clinical outcomes of patients treated for multidrug-resistant tuberculosis in Tanzania

Katale

Mbelele

Lema³

et al. 2020

BMC Genomics

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Background: Tuberculosis (TB), particularly multi-and or extensive drug resistant TB, is still a global medical emergency. Whole genome sequencing (WGS) is a current alternative to the WHO-approved probe-based methods for TB diagnosis and detection of drug resistance, genetic diversity and transmission dynamics of Mycobacterium tuberculosis complex (MTBC). This study compared WGS and clinical data in participants with TB.Results: This cohort study performed WGS on 87 from MTBC DNA isolates, 57 (66%) and 30 (34%) patients with drug resistant and susceptible TB, respectively. Drug resistance was determined by Xpert® MTB/RIF assay and phenotypic culture-based drug-susceptibility-testing (DST). WGS and bioinformatics data that predict phenotypic resistance to anti-TB drugs were compared with participant's clinical outcomes. They were 47 female participants (54%) and the median age was 35 years (IQR): 29-44). Twenty (23%) and 26 (30%) of participants had TB/HIV coinfection BMI < 18 kg/m 2 respectively. MDR-TB participants had MTBC with multiple mutant genes, compared to those with mono or polyresistant TB, and the majority belonged to lineage 3 Central Asian Strain (CAS). Also, MDR-TB was associated with delayed culture-conversion (median: IQR (83: 60-180 vs. 51:30-66) days). WGS had high concordance with both culture-based DST and Xpert® MTB/RIF assay in detecting drug resistance (kappa = 1.00). Conclusion: This study offers comparison of mutations detected by Xpert and WGS with phenotypic DST of M. tuberculosis isolates in Tanzania. The high concordance between the different methods and further insights provided by WGS such as PZA-DST, which is not routinely performed in most resource-limited-settings, provides an avenue for inclusion of WGS into diagnostic matrix of TB including drug-resistant TB.

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“…Peru is one of the 30 countries in the world with the highest burden of multidrug-resistant tuberculosis (MDR-TB). e public health system provides free diagnosis and drugsusceptibility testing with phenotypic (proportions in 7H10) [1] and molecular methods (Genotype, Hain Lifesciences (Genotype ™ )) [2] for first-and second-line drugs. Molecular diagnosis of drug resistance has been shown to significantly reduce the time to diagnosis, most of all to isoniazid and rifampicin, the pillars of antituberculosis regimens, and thus contribute to improve the clinical outcomes [3] However, the reference standard continue to be phenotypic methods, such as MGIT 960 and proportions in agar plaque, both currently used at the National Reference Laboratory of Mycobacteria of Peru.…”

Section: Introductionmentioning

confidence: 99%

Mutations inMycobacterium tuberculosisIsolates with Discordant Results for Drug-Susceptibility Testing in Peru

Solari

Santos-Lázaro

Puyén

2020

International Journal of Microbiology

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Evaluation of resistance to antituberculosis drugs is routinely performed with genotypic or phenotypic methods; however, discordance can be seen between these different methodologies. Our objective was to identify mutations that could explain discordant results in the evaluation of susceptibility to rifampicin and isoniazid between molecular and phenotypic methods, using whole genome sequencing (WGS). Peruvian strains showing sensitive results in the GenoType MTBDRplus v2.0 test and resistant results in the proportions in the agar-plaque test for isoniazid or rifampin were selected. Discordance was confirmed by repeating both tests, and WGS was performed, using the Next Generation Sequencing methodology. Obtained sequences were aligned “through reference” (genomic mapping) using the program BWA with the algorithm “mem”, using as a reference the genome of the M. tuberculosis H37Rv strain. Discordance was confirmed in 14 strains for rifampicin and 21 for isoniazid, with 1 strain in common for both antibiotics, for a total of 34 unique strains. The most frequent mutation in the rpoB gene in the discordant strains for rifampicin was V170F. The most frequent mutations in the discordant strains for isoniazid were katG R463L, kasA G269S, and Rv1592c I322V. Several other mutations are reported. This is the first study in Latin America addressing mutations present in strains with discordant results between genotypic and phenotypic methods to rifampicin and isoniazid. These mutations could be considered as future potential targets for genotypic tests for evaluation of susceptibility to these drugs.

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Performance of GenoType® MTBDRplus assay in the diagnosis of drug-resistant tuberculosis in Tangier, Morocco

Cited by 19 publications

References 26 publications

Mutations Associated with Rifampicin Resistance in Mycobacterium tuberculosis Isolates from Moroccan Patients: Systematic Review

Mutations Associated with Rifampicin Resistance in Mycobacterium tuberculosis Isolates from Moroccan Patients: Systematic Review

Whole genome sequencing of Mycobacterium tuberculosis isolates and clinical outcomes of patients treated for multidrug-resistant tuberculosis in Tanzania

Mutations inMycobacterium tuberculosisIsolates with Discordant Results for Drug-Susceptibility Testing in Peru

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