Dataset Information

Systematic review of the performance of rapid rifampicin resistance testing for drug-resistant tuberculosis.

ABSTRACT:

Introduction

Rapid tests for rifampicin resistance may be useful for identifying isolates at high risk of drug resistance, including multidrug-resistant TB (MDR-TB). However, choice of diagnostic test and prevalence of rifampicin resistance may both impact a diagnostic strategy for identifying drug resistant-TB. We performed a systematic review to evaluate the performance of WHO-endorsed rapid tests for rifampicin resistance detection.

Methods

We searched MEDLINE, Embase and the Cochrane Library through January 1, 2012. For each rapid test, we determined pooled sensitivity and specificity estimates using a hierarchical random effects model. Predictive values of the tests were determined at different prevalence rates of rifampicin resistance and MDR-TB.

Results

We identified 60 publications involving six different tests (INNO-LiPA Rif. TB assay, Genotype MTBDR assay, Genotype MTBDRplus assay, Colorimetric Redox Indicator (CRI) assay, Nitrate Reductase Assay (NRA) and MODS tests): for all tests, negative predictive values were high when rifampicin resistance prevalence was ? 30%. However, positive predictive values were considerably reduced for the INNO-LiPA Rif. TB assay, the MTBDRplus assay and MODS when rifampicin resistance prevalence was < 5%.

Limitations

In many studies, it was unclear whether patient selection or index test performance could have introduced bias. In addition, we were unable to evaluate critical concentration thresholds for the colorimetric tests.

Discussion

Rapid tests for rifampicin resistance alone cannot accurately predict rifampicin resistance or MDR-TB in areas with a low prevalence of rifampicin resistance. However, in areas with a high prevalence of rifampicin resistance and MDR-TB, these tests may be a valuable component of an MDR-TB management strategy.

SUBMITTER: Arentz M

PROVIDER: S-EPMC3789679 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Systematic review of the performance of rapid rifampicin resistance testing for drug-resistant tuberculosis.

Arentz Matthew M Sorensen Bess B Horne David J DJ Walson Judd L JL

PloS one 20131003 10

<h4>Introduction</h4>Rapid tests for rifampicin resistance may be useful for identifying isolates at high risk of drug resistance, including multidrug-resistant TB (MDR-TB). However, choice of diagnostic test and prevalence of rifampicin resistance may both impact a diagnostic strategy for identifying drug resistant-TB. We performed a systematic review to evaluate the performance of WHO-endorsed rapid tests for rifampicin resistance detection.<h4>Methods</h4>We searched MEDLINE, Embase and the C ...[more]

PMID: 24098523

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Project description:Background & objectivesThere is a need for an affordable, easy, high-sensitivity test usable at the peripheral health facility for diagnosis of drug-resistant (DR) tuberculosis (TB) to interrupt disease transmission. Nucleic acid amplification tests (NAATs) for early detection of DR-TB are ideal to bring testing near to the patient. TruenatTM MTB (Mycobacterium tuberculosis) and TruenatTM MTB-RIF (rifampicin) is an indigenous chip-based real-time polymerase chain reaction (PCR) based test for detection of multidrug-resistant (MDR) TB. The test involves extraction of DNA using automated, battery operated Trueprep instrument and real-time PCR performed on the Truelab analyzer. We report here multicentric validation of Truenat MTB-RIF for detection of DR-TB in suspected DR-TB patients.MethodsConsecutive patients aged 18-65 yr, with symptoms suggestive of TB and with a history of previous treatment, reporting to the National TB Elimination Programme (NTEP) clinics under four national institutes, namely AIIMS (All India Institute of Medical Sciences, New Delhi), NITRD (National Institute of Tuberculosis and Respiratory Diseases, New Delhi), NIRT (National Institute for Research in Tuberculosis, Chennai) and ICMR-National JALMA Institute for Leprosy and other Mycobacterial Diseases, Agra, were included in the study. Two sputum samples (one spot and one morning) were collected from each patient, after obtaining informed written consent. The samples were subjected to smear, GeneXpert and MGIT 960 culture (and drug susceptibility testing to RIF) (surrogate for MDR-TB) to serve as reference tests. The samples were coded to ensure blinding and subjected to Truenat MTB-RIF. Truenat MTB-RIF Version 1.5 was used for testing 1084 samples for RIF resistance, while Version 2.0 was used to test another 1201 samples.ResultsTruenat MTB-RIF Version 1.5 in comparison with comprehensive laboratory reference standards yielded sensitivity and specificity of 76.2 and 94.7 per cent, respectively for the detection of RIF resistance in 1084 samples, collected across four sites. Based on the analysis of discordant samples, Version 2.0 of Truenat was developed by the manufacturer and this was further tested on additional 1201 samples, yielding a sensitivity of 87.5 per cent and specificity of 99.5 per cent.Interpretation & conclusionsMulticentric trial of TruenatTM MTB-RIF demonstrated a great potential of this point of care NAAT for detection of MDR-TB. The test would be useful in limited resource settings and inaccessible areas without need for any additional infrastructure.

Project description:Resistance to anti-tuberculosis drugs is a serious public health problem. Multi-drug resistant tuberculosis (MDR-TB), defined as resistance to at least rifampicin and isoniazid, has been reported in all regions of the world. Current phenotypic methods of assessing drug susceptibility of M. tuberculosis are slow. Rapid molecular methods to detect resistance to rifampicin have been developed but they are not affordable in some high prevalence countries such as those in sub Saharan Africa. A simple multi-well plate assay using mycobacteriophage D29 has been developed to test M. tuberculosis isolates for resistance to rifampicin. The purpose of this study was to investigate the performance of this technology in Kampala, Uganda.In a blinded study 149 M. tuberculosis isolates were tested for resistance to rifampicin by the phage assay and results compared to those from routine phenotypic testing in BACTEC 460. Three concentrations of drug were used 2, 4 and 10 microg/ml. Isolates found resistant by either assay were subjected to sequence analysis of a 81 bp fragment of the rpoB gene to identify mutations predictive of resistance. Four isolates with discrepant phage and BACTEC results were tested in a second phenotypic assay to determine minimal inhibitory concentrations.Initial analysis suggested a sensitivity and specificity of 100% and 96.5% respectively for the phage assay used at 4 and 10 microg/ml when compared to the BACTEC 460. However, further analysis revealed 4 false negative results from the BACTEC 460 and the phage assay proved the more sensitive and specific of the two tests. Of the 39 isolates found resistant by the phage assay 38 (97.4%) were found to have mutations predictive of resistance in the 81 bp region of the rpoB gene. When used at 2 mug/ml false resistant results were observed from the phage assay. The cost of reagents for testing each isolate was estimated to be 1.3 US dollars when testing a batch of 20 isolates on a single 96 well plate. Results were obtained in 48 hours.The phage assay can be used for screening of isolates for resistance to rifampicin, with high sensitivity and specificity in Uganda. The test may be useful in poorly resourced laboratories as a rapid screen to differentiate between rifampicin susceptible and potential MDR-TB cases.

Project description:Tuberculosis (TB), caused by the Mycobacterium tuberculosis infection, continues to be a leading cause of morbidity and mortality in developing countries. Resistance to the first-line anti-TB drugs, isoniazid (INH) and rifampicin (RIF), is a major drawback to effective TB treatment. Genetic mutations in the β-subunit of the DNA-directed RNA polymerase (rpoB) are reported to be a major reason of RIF resistance. However, the structural basis and mechanisms of these resistant mutations are insufficiently understood. In the present study, thirty drug-resistant mutants of rpoB were initially modeled and screened against RIF via a comparative molecular docking analysis with the wild-type (WT) model. These analyses prioritized six mutants (Asp441Val, Ser456Trp, Ser456Gln, Arg454Gln, His451Gly, and His451Pro) that showed adverse binding affinities, molecular interactions, and RIF binding hinderance properties, with respect to the WT. These mutant models were subsequently analyzed by molecular dynamics (MD) simulations. One-hundred nanosecond all-atom MD simulations, binding free energy calculations, and a dynamic residue network analysis (DRN) were employed to exhaustively assess the impact of mutations on RIF binding dynamics. Considering the global structural motions and protein-ligand binding affinities, the Asp441Val, Ser456Gln, and His454Pro mutations generally yielded detrimental effects on RIF binding. Locally, we found that the electrostatic contributions to binding, particularly by Arg454 and Glu487, might be adjusted to counteract resistance. The DRN analysis revealed that all mutations mostly distorted the communication values of the critical hubs and may, therefore, confer conformational changes in rpoB to perturb RIF binding. In principle, the approach combined fundamental molecular modeling tools for robust "global" and "local" level analyses of structural dynamics, making it well suited for investigating other similar drug resistance cases.

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.

Dataset Information

Systematic review of the performance of rapid rifampicin resistance testing for drug-resistant tuberculosis.

Introduction

Methods

Results

Limitations

Discussion

Publications

Systematic review of the performance of rapid rifampicin resistance testing for drug-resistant tuberculosis.

Similar Datasets

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