Microscopic-observation drug susceptibility and thin layer agar assays for the detection of drug resistant tuberculosis: a systematic review and meta-analysis

Background Simple, rapid, and affordable tests are needed to detect drug resistance in Mycobacterium tuberculosis. We did a systematic review and meta-analysis to investigate the accuracy of microscopic-observation drug susceptibility (MODS) and thin layer agar (TLA) assays for rapid screening of patients at risk of drug-resistant tuberculosis. Methods In accordance with protocols and methods recommended by the Cochrane Diagnostic Test Accuracy Working Group, we systematically searched PubMed, Embase, and Biosis for reports published between January, 1990, and February, 2009. We included studies investigating detection of drug resistance in M tuberculosis with the MODS or TLA assay, and in which an accepted reference standard was used. Data extracted from the studies were combined by use of bivariate random-effects regression models and hierarchical summary receiver operating characteristic curves to estimate sensitivity and specificity for detection of resistance to specific drugs. Findings We identified 12 studies, of which nine investigated the MODS assay and three investigated the TLA assay. For the MODS assay of rifampicin resistance, pooled estimates were 98.0% (95% CI 94.5-99.3) for sensitivity and 99.4% (95.7-99.9) for specificity. For the MODS assay of isoniazid resistance with a 0.1 mu g/mL cutoff, pooled sensitivity was 97.7% (94.4-99.1) and pooled specificity was 95.8% (88.1-98.6), but with a 0.4 mu g/mL cutoff, sensitivity decreased to 90.0% (84-5-93-7) and specificity increased to 98.6% (96.9-99.4). All assessments of rifampicin and isoniazid resistance with the TLA assay yielded 100% accuracy. Mean turnaround time was 9.9 days (95% CI 4.1-15.8) for the MODS assay and 11.1 days (10.1-12.0) for the TLA assay. Interpretation MODS and TLA assays are inexpensive, rapid alternatives to conventional methods for drug susceptibility testing of M tuberculosis. Our data and expert opinion informed WHO's recommendation for use of selected non-commercial drug susceptibility tests, including MODS, as an interim solution until capacity for genotypic or automated liquid culture drug susceptibility testing is developed.