Equivalence of the GeneXpert System and GeneXpert Omni System for tuberculosis and rifampicin resistance detection.
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ABSTRACT:
SUBMITTER: Georghiou SB
PROVIDER: S-EPMC8682871 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe dual challenge of low diagnostic sensitivity of microscopy test and technical challenge of performing a TB culture test poses a problem for case detection and initiation of Tuberculosis (TB) second-line treatment. There is thus need for a rapid, reliable and easily accessible assay. This comparative analysis was performed to assess diagnostic performance characteristics of GeneXpert MTB/RIF and Line Probe Assay (LPA).MethodsThree hundred twenty nine sputum samples of patients across the 47 counties in Kenya suspected to have drug resistant TB were picked and subjected to GeneXpert, LPA and Culture MGIT at the National TB Reference Laboratory. Sensitivity, specificity and predictive values were then determined to assess the performance characteristics of the various assays.ResultsAgainst culture MGIT as the gold standard for TB diagnosis, GeneXpert had a sensitivity, specificity, positive predictive value, and negative predictive value of 78.5, 64.9, 59.4 and 82.2% respectively while LPA had 98.4, 66.0, 65.4 and 98.4%. For diagnosis of rifampicin mono-resistance GeneXpert had a moderate agreement (Kappa 0.59, P < 0.01) (sensitivity 62.50%, specificity 96.50%) while LPA that had almost perfect agreement (Kappa = 0.89, p < 0.01) with a (sensitivity 90.0% and specificity 99.1%).ConclusionLPA has a better performance characteristic to GeneXpert and an alternative to culture with regards to detection of RIF's mono-resistance.
| S-EPMC6794895 | biostudies-literature
Project description:Despite a Mycobacterium tuberculosis control programme and anti-tuberculosis drugs, drug-resistant tuberculosis (DR-TB) is one of the most serious public health issues worldwide. Rapid laboratory diagnosis of M. tuberculosis is needed for the diagnosis of multidrug-resistant (MDR) TB and to find the optimal treatment protocol. The purpose of this study was to detect resistance to rifampicin in new cases of TB using the GeneXpert MTB/RIF (M. tuberculosis/rifampicin) assay and the standard proportional method in west and northwest Iran. In this descriptive cross-sectional study, sputum samples were enrolled and screened for M. tuberculosis using Ziehl-Neelsen stain and mycobacterial culture. Samples from individuals with smear-positive TB were cultured on Lowenstein-Jensen medium; afterwards, the presence of resistance to rifampicin was examined by the GeneXpert MTB/RIF and standard proportional methods. A total of 400 new cases of suspected TB were collected, 162 (40.5%) of which were smear- and culture-positive for M. tuberculosis. The frequencies of rifampicin resistance in new smear-positive TB cases were 3.1% and 4.3% for GeneXpert and standard proportional method, respectively. Sensitivity and specificity of GeneXpert were 71% and 100%, respectively, compared with the proportional method. GeneXpert can be a quick and helpful method for the diagnosis of rifampicin-resistant TB in regions with high rates of DR-TB or MDR-TB. GeneXpert MTB-RIF assay must be used as an early diagnostic method whose results must be confirmed by the standard proportional method. The GeneXpert and proportional methods complement but do not replace each other.
| S-EPMC5547232 | biostudies-other
Project description:BackgroundDrug-resistant tuberculosis continues to be a global public health threat. Ethiopia is one of the high-burden countries for tuberculosis and multi-drug resistant tuberculosis. The estimated annual incidents of tuberculosis were 119 per 100,000 populations in 2021 and the prevalence of multi-drug resistance tuberculosis is about 0.7% among newly diagnosed cases in Ethiopia. On time detection of rifampicin resistance is essential for the management of the disease and earlier treatment initiation. Among the different diagnostic tests; Xpert is widely used for the rapid detection of Mycobacterium tuberculosis and rifampicin resistant in the country. The prevalence of rifampicin resistance-pulmonary tuberculosis varied from locality to locality and the estimated national prevalence of rifampicin resistance pulmonary tuberculosis is not available in the country. Therefore, the aim of this meta-analysis was to summarize the results of available studies and generate pooled prevalence estimate of rifampicin resistance pulmonary tuberculosis in Ethiopia.MethodsLiterature search was carried out using PubMed and Scopus public databases. Original articles conducted in Ethiopia and those containing a prevalence report of rifampicin resistance pulmonary tuberculosis diagnosed by Xpert Mycobacterium tuberculosis/rifampicin resistance assay were included in the meta-analysis. All retrospective and prospective studies published until May 2022 were screened in the study. The methodological qualities of included article were assessed using Joanna Briggs Institute quality assessment tool for cross-sectional studies. Random effect model was used to determine the pooled prevalence of rifampicin resistance pulmonary tuberculosis. Subgroup analysis and regression were carried out across regional states and study designs. Heterogeneity across studies was assessed using I2 test. The data were analyzed using STATA version 14.ResultA total of 1570 titles were identified and 34 studies met the inclusion criteria. Of the total 17,292 pulmonary tuberculosis patients who were identified from the included articles, 1669 were rifampicin resistance pulmonary tuberculosis. The pooled prevalence of rifampicin resistant among pulmonary tuberculosis patients diagnosed with Xpert Mycobacterium tuberculosis/rifampicin resistance assay was 9.67% (95% CI: 8.11-11.24). The highest pooled prevalence was from Oromia11.84% (95% CI: 4.49-19.2%) and the lowest rifampicin resistance was identified in Amhara Regional State, 8.51% (95% CI: 5.96-11.06%). The pooled prevalence rates of rifampicin resistant among pulmonary tuberculosis patients were 10.18% (95% CI: 6.85-13.51) and 9.57% (95% CI: 7.68-11.47) in prospective and retrospective types of cross-sectional studies.ConclusionOur study showed that the pooled prevalence of rifampicin resistance among pulmonary tuberculosis patients was 9.67%. This showed that the occurrence of rifampicin resistance pulmonary tuberculosis among Mycobacterium tuberculosis patients remains high in Ethiopia. Regional state wise, rifampicin resistance variation was small. Further meta-analysis of factors associated with rifampicin resistance among pulmonary tuberculosis patients as well as among extrapulmonary Mycobacterium tuberculosis cases should be carried out.
| S-EPMC10558782 | biostudies-literature
Project description:BACKGROUND:The increasing prevalence of drug-resistant tuberculosis (TB) infection represents a global public health emergency. We evaluated the usefulness of a newly developed multiplexed, bead-based bioassay (Quantamatrix Multiplexed Assay Platform [QMAP], QuantaMatrix, Seoul, Korea) to rapidly identify the Mycobacterium tuberculosis complex (MTBC) and detect rifampicin (RIF) and isoniazid (INH) resistance-associated mutations. METHODS:A total of 200 clinical isolates from respiratory samples were used. Phenotypic anti-TB drug susceptibility testing (DST) results were compared with those of the QMAP system, reverse blot hybridization (REBA) MTB-MDR assay, and gene sequencing analysis. RESULTS:Compared with the phenotypic DST results, the sensitivity and specificity of the QMAP system were 96.4% (106/110; 95% confidence interval [CI] 0.9072-0.9888) and 80.0% (72/90; 95% CI 0.7052-0.8705), respectively, for RIF resistance and 75.0% (108/144; 95% CI 0.6731-0.8139) and 96.4% (54/56; 95% CI 0.8718-0.9972), respectively, for INH resistance. The agreement rates between the QMAP system and REBA MTB-MDR assay for RIF and INH resistance detection were 97.6% (121/124; 95% CI 0.9282-0.9949) and 99.1% (109/110; 95% CI 0.9453-1.0000), respectively. Comparison between the QMAP system and gene sequencing analysis showed an overall agreement of 100% for RIF resistance (110/110; 95% CI 0.9711-1.0000) and INH resistance (124/124; 95% CI 0.9743-1.0000). CONCLUSIONS:The QMAP system may serve as a useful screening method for identifying and accurately discriminating MTBC from non-tuberculous mycobacteria, as well as determining RIF- and INH-resistant MTB strains.
| S-EPMC6056394 | biostudies-literature
Project description:Control of the global epidemic tuberculosis is severely hampered by the emergence of drug-resistant Mycobacterium tuberculosis strains. Molecular methods offer a more rapid means of characterizing resistant strains than phenotypic drug susceptibility testing. We have developed a molecular method for detection of rifampicin-resistant M. tuberculosis based on padlock probes and magnetic nanobeads. Padlock probes were designed to target the most common mutations associated with rifampicin resistance in M. tuberculosis, i.e. at codons 516, 526 and 531 in the gene rpoB. For detection of the wild type sequence at all three codons simultaneously, a padlock probe and two gap-fill oligonucleotides were used in a novel assay configuration, requiring three ligation events for circularization. The assay also includes a probe for identification of the M. tuberculosis complex. Circularized probes were amplified by rolling circle amplification. Amplification products were coupled to oligonucleotide-conjugated magnetic nanobeads and detected by measuring the frequency-dependent magnetic response of the beads using a portable AC susceptometer.
| S-EPMC3632517 | biostudies-literature
Project description:The disease tuberculosis, caused by Mycobacterium tuberculosis (MTB), remains a major cause of morbidity and mortality in developing countries. The evolution of drug-resistant tuberculosis causes a foremost threat to global health. Most drug-resistant MTB clinical strains are showing resistance to isoniazid and rifampicin (RIF), the frontline anti-tuberculosis drugs. Mutation in rpoB, the beta subunit of DNA-directed RNA polymerase of MTB, is reported to be a major cause of RIF resistance. Amongst mutations in the well-defined 81-base-pair central region of the rpoB gene, mutation at codon 450 (S450L) and 445 (H445Y) is mainly associated with RIF resistance. In this study, we modeled two resistant mutants of rpoB (S450L and H445Y) using Modeller9v10 and performed a docking analysis with RIF using AutoDock4.2 and compared the docking results of these mutants with the wild-type rpoB. The docking results revealed that RIF more effectively inhibited the wild-type rpoB with low binding energy than rpoB mutants. The rpoB mutants interacted with RIF with positive binding energy, revealing the incapableness of RIF inhibition and thus showing resistance. Subsequently, this was verified by molecular dynamics simulations. This in silico evidence may help us understand RIF resistance in rpoB mutant strains.
| S-EPMC4330266 | biostudies-literature
Project description:BackgroundActive tuberculosis (TB) case finding is important as it helps detect pulmonary TB cases missed by the other active screening methods. It requires periodic mass screening in risk population groups such as prisoners and refugees. Unfortunately, in these risk population groups periodic mass screening can be challenging due to lengthy turnaround time (TAT), cost and implementation constraints. The aim of this study was to evaluate a diagnostic algorithm that can reduce the TAT and cost for TB and Rifampicin resistance (RR) detection. The algorithm involves testing with TB-LAMP followed by Xpert MTB/RIF for positive TB-LAMP cases to diagnose TB during mass campaigns in prisons and refugee camps.MethodsThe National Tuberculosis Control Program (NTCP) organized routine TB mass-screening campaigns in 34 prisons and 3 villages with refugees camps in Cameroon in 2019. TB LAMP was used for initial TB diagnosis and all TB-LAMP positive cases tested with the Xpert MTB/RIF assay to determine RR. TAT and cost benefits analysis of the combined use of TB-LAMP and Xpert MTB/RIF assays was determined and compared to the Xpert MTB/RIF assay when used only.ResultsA total of 4075 sputum samples were collected from TB presumptive, 3672 cases in 34 prisons and 403 samples in 3 villages. Of the 4,075 samples screened with TB-LAMP, 135 were TB positive (3.31%) and run on the Xpert MTB/RIF. Of the 135 positives cases, Xpert MTB/RIF revealed 3 were RR (2.22%). The use of TB-LAMP followed by testing with Xpert MTB/RIF for TB and RR detection reduced the TAT by 73.23% in prisons and 74.92% in villages. In addition to a reduced TAT, the two molecular tests used in synergy is cost benefit from year 2 onwards.ConclusionThis study demonstrates the advantages of a diagnostic algorithm based on an initial testing with TB-LAMP followed by testing with Xpert MTB/RIF for TB diagnosis. This approach improved early and rapid TB detection with an added advantage of providing RR status. The proposed algorithm is effective and less costly from the second year of implementation and should be used by TB control programs.
| S-EPMC8895851 | biostudies-literature
Project description:ObjectivesDrug-resistant TB remains a public health challenge. Rifamycins are among the most potent anti-TB drugs. They are known to target the RpoB subunit of RNA polymerase; however, our understanding of how rifamycin resistance is genetically encoded remains incomplete. Here we investigated rpoB genetic diversity and cross-resistance between the two rifamycin drugs rifampicin and rifabutin.MethodsWe performed WGS of 1003 Mycobacterium tuberculosis clinical isolates and determined MICs of both rifamycin agents on 7H10 agar using the indirect proportion method. We generated rpoB mutants in a laboratory strain and measured their antibiotic susceptibility using the alamarBlue reduction assay.ResultsOf the 1003 isolates, 766 were rifampicin resistant and 210 (27%) of these were rifabutin susceptible; 102/210 isolates had the rpoB mutation D435V (Escherichia coli D516V). Isolates with discordant resistance were 17.2 times more likely to harbour a D435V mutation than those resistant to both agents (OR 17.2, 95% CI 10.5-27.9, P value <10-40). Compared with WT, the D435V in vitro mutant had an increased IC50 of both rifamycins; however, in both cases to a lesser degree than the S450L (E. coli S531L) mutation.ConclusionsThe observation that the rpoB D435V mutation produces an increase in the IC50 of both drugs contrasts with findings from previous smaller studies that suggested that isolates with the D435V mutation remain rifabutin susceptible despite being rifampicin resistant. Our finding thus suggests that the recommended critical testing concentration for rifabutin should be revised.
| S-EPMC6524487 | biostudies-literature
Project description:Rationale:Previously treated persons with bacteriologically confirmed pulmonary tuberculosis (BC-PTB) have increased risk of developing multi-drug resistant or rifampicin resistant tuberculosis (MDR/RR-TB). Surveillance for resistance is critical to identify and treat MDR/RR-TB to ensure cure and prevent transmission. There are limited studies conducted on this subject. Objectives:We examined the frequency and factors associated with MDR/RR-TB surveillance among previously treated persons with BC-PTB, and described their treatment outcomes in rural eastern Uganda. Methods:We reviewed treatment records for BC-PTB between January 2015 and June 2018 at 10 clinics in eastern Uganda. We collected data on demographics, surveillance for MDR/RR, use of GeneXpert and treatment outcomes. We performed bivariate and multivariate analyses. For multivariate analysis, we used the modified Poisson regression analysis with robust standard errors and stated the results as adjusted risk ratio (aRR) with 95% confidence intervals (CI). All analyses were conducted in R version 3.5.2. Measurements and main results:We obtained records for 135 previously treated persons with BC-PTB and of these, 41 (30.4%) had undergone surveillance for MDR/RR-TB. Treatment failures were less likely to have surveillance compared to relapses (aRR, 0.28; 95% CI, 0.08-0.95), and there was an increasing trend in the likelihood for surveillance between 2015 and 2018 (aRR, 1.77; 95% CI, 1.39-2.25). There was no difference in MDR/RR-TB surveillance rate between health facilities with and without GeneXpert on-site (aRR, 1.52; 95% CI, 0.81-2.86) and between male and female patients (aRR, 0.54; 95% CI, 0.21-1.37). Overall, 92 (68.1%) previously treated persons with BC-PTB were successfully treated for tuberculosis. Conclusions:MDR/RR-TB surveillance and treatment success rates among previously treated persons with BC-PTB in rural eastern Uganda are low. Tuberculosis programs should strengthen MDR/RR-TB surveillance and especially target those with treatment failure.
| S-EPMC7038458 | biostudies-literature
Project description:BackgroundTuberculosis accounted for 8.7 million new cases in 2011 and continues to be one of the leading human infectious diseases. Burdensome is the increasing rate of multi-drug resistant tuberculosis (MDRTB) and the difficulties created for treatment and public health control programs, especially in developing countries. Resistance to rifampicin (RIF), a first line antibiotic, is commonly associated with point mutations within the rpoB gene of Mycobacterium tuberculosis (Mtb) whose detection is considered the best early molecular predictor for MDRTB. Gold nanoparticles functionalized with thiol-modified oligonucleotides (Au-nanoprobes) have shown the potential to provide a rapid and sensitive detection method for Mtb and single base alterations associated with antibiotic resistance, namely in rpoB gene associated to RIF resistance.ResultsWe developed a strategy based on the isothermal amplification of sample DNA (LAMP) coupled to specific Au-nanoprobes capable of identifying members of the Mtb complex (MTBC) and discriminating specific mutations within the rpoB gene. Integration of LAMP and Au-nanoprobe assay allowed to detect MTBC member and identify mutations linked to RIF resistance. A total of 12 biological samples were tested and a 100% specificity and sensitivity was attained.ConclusionsThere is an increasing demand for simple, fast and cheap methods for the molecular identification of Mtb and for the detection of molecular tags associated to drug resistance suitable for use at point-of-need. Here we describe such a method, that as the potential to get molecular diagnostic of tuberculosis to remote environments.
| S-EPMC4222569 | biostudies-literature