GenoType MTBDR assays for the diagnosis of multidrug-resistant tuberculosis: a meta-analysis

Abstract

The global extensively drug-resistant tuberculosis (TB) response plan calls for implementation of rapid tests to screen patients at risk of drug-resistant TB. Currently, two line probe assays exist, the INNO-LiPA1Rif.TB assay (Innogenetics, Ghent, Belgium) and the GenoType1 MTBDR assay (Hain LifeScience GmbH, Nehren, Germany). While LiPA studies have been reviewed, the accuracy of GenoType assays has not been systematically reviewed.The present authors carried out a systematic review and used meta-analysis methods appropriate for diagnostic accuracy. After the literature searches, 14 comparisons for rifampicin and 15 comparisons for isoniazid were identified in 10 articles that used GenoType MTBDR assays. Accuracy results were summarised in forest plots and pooled using bivariate randomeffects regression.The pooled sensitivity (98.1%, 95% confidence interval (CI) 95.9-99.1) and specificity (98.7%, 95% CI 97.3-99.4) estimates for rifampicin resistance were very high and consistent across all subgroups, assay versions and specimen types. The accuracy for isoniazid was variable, with lower sensitivity (84.3%, 95% CI 76.6-89.8) and more inconsistent than specificity (99.5%, .GenoType MDTBR assays demonstrate excellent accuracy for rifampicin resistance, even when used on clinical specimens. While specificity is excellent for isoniazid, sensitivity estimates were modest and variable. Together with data from demonstration projects, the meta-analysis provides evidence for policy making and clinical practice.

Performance Assessment of the GenoType®MTBDRplus Assay for Rapid Detection of Multidrug-Resistant Tuberculosis among Clinical Isolates in Low Tuberculosis Burden Setting

“…Results from several studies conducted elsewhere in the world to evaluate the performance of GenoType ® MTBDRplus assay, have reported similar results to our findings. A meta-analysis to validate GenoType ® MTBDRplus assays for the diagnosis of MultidrugResistant Tuberculosis showed 98%, 89% of sensitivity and specificity respectively [8]. Others studies presented similar results with a slight high specificity (100%) for RIF resistance in South Africa.…”

“…The GenoType ® MTBDRplus assay has been used as a tool for early TB and MDR-TB diagnosis to support the Programmatic Management of Drug Resistant Tuberculosis in the country to institute early treatment. It has been shown that GenoType ® MTBDRplus assay is the ideal technique to diagnose TB and MDR-TB and it accelerates the laboratory results for MDR-TB treatment and control [7,8]. Although the GenoType ® MTBDRplus assay has been validated in different settings with high burden of tuberculosis like in Thailand, Asia and in Africa like in South Africa [7,9], there is a need to evaluate its performance to ensure the acceptable performance in other settings with low TB burden like Rwanda.…”

Mycobacterium tuberculosis Population Structure Determines the Outcome of Genetics-Based Second-Line Drug Resistance Testing

“…In 2008, the WHO approved the Hain GenoTypeMTBDRplus test for the rapid identification of M. tuberculosis complex strains in clinical isolates and the diagnosis of isoniazid and rifampin resistance by the detection of mutations in the inhA promoter and katG gene and in the rpoB gene, respectively (43). A recent meta-analysis demonstrated that the application of this test can reduce diagnostic delay (21), with a high sensitivity and specificity for identifying rifampin resistance, which is an important marker of MDR-and XDR-TB. Similarly, the XpertMTB/RIF test enables the genetic detection of rifampin resistance, with the added advantage that the result can be obtained in approximately 2 h for most smear-positive sputum samples and a significant number of smear-negative sputum samples (4,35).…”

Rapid Diagnosis of Mycobacterium tuberculosis Infection and Drug Susceptibility Testing

“…[32][33][34][35][36][37][38][39][40][41][42] Conceptually similar to the INNO-Lipa Rif.tb assay, the MTBDRplus assay has been reported to have a diagnostic sensitivity of approximately 94% for detecting M tuberculosis DNA in smear-positive respiratory specimens. 33 It is of interest that most clinical evaluations of this device have focused on its use for susceptibility testing, not detection of M tuberculosis, so the performance characteristics for the latter use are less well defined.…”