A commercial line probe assay for the rapid detection of rifampicin resistance in Mycobacterium tuberculosis: a systematic review and meta-analysis

Abstract

Background: Mycobacterium tuberculosis is a leading cause of death worldwide. In multi-drug resistant tuberculosis (MDR-TB) infectiousness is frequently prolonged, jeopardizing efforts to control TB. The conventional tuberculosis drug susceptibility tests are sensitive and specific, but they are not rapid. The INNO-LiPA Rif. TB (LiPA) is a commercial line probe assay designed to rapidly detect rifampicin resistance, a marker of MDR-TB. Although LiPA has shown promising results, its overall accuracy has not been systematically evaluated.

Methods: We did a systematic review and meta-analysis to evaluate the accuracy of LiPA for the detection of rifampicin-resistant tuberculosis among culture isolates and clinical specimens. We searched Medline, Embase, Web of Science, BIOSIS, and Google Scholar, and contacted authors, experts and the manufacturer. Fifteen studies met our inclusion criteria. Of these, 11 studies used culture isolates, one used clinical specimens, and three used both. We used a summary receiver operating characteristic (SROC) curve and Q* index to perform meta-analysis and summarize diagnostic accuracy.

Results: Twelve of 14 studies that applied LiPA to isolates had sensitivity greater than 95%, and 12 of 14 had specificity of 100%. The four studies that applied LiPA directly to clinical specimens had 100% specificity, and sensitivity that ranged between 80% and 100%. The SROC curve had an area of 0.99 and Q* of 0.97.

Conclusion: LiPA is a highly sensitive and specific test for the detection of rifampicin resistance in culture isolates. The test appears to have relatively lower sensitivity when used directly on clinical specimens. More evidence is needed before LiPA can be used to detect MDR-TB among populations at risk in clinical practice.

Figure 1

Study selection process and reasons for exclusion of studies.

Figure 2

Forrest plots of sensitivity and specificity. The point estimates of sensitivity and specificity from each study are shown as solid circles (culture isolates) and open rectangles (clinical specimens). Error bars are 95% confidence intervals (CI).

Figure 3

Summary Receiver Operator Curve (SROC) plot for line probe assay. Each solid circle (culture isolate) and open rectangle (clinical specimen) represents each study in the meta-analysis. The curve is the regression line that summarizes the overall diagnostic accuracy. SROC: summary receiver operating characteristic; AUC: area under the curve; SE(AUC): standard error of AUC; Q*: an index defined by the point on the SROC curve where the sensitivity and specificity are equal, which is the point closest to the top-left corner of the ROC space; SE(Q*): standard error of Q* index.