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

PLoS One. 2013 Oct 3;8(10):e76533. doi: 10.1371/journal.pone.0076533. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antitubercular Agents / therapeutic use*
  • Bias
  • Drug Resistance, Multiple, Bacterial*
  • Humans
  • Microbial Sensitivity Tests / statistics & numerical data*
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / pathogenicity
  • Mycobacterium tuberculosis / physiology
  • Predictive Value of Tests
  • Reagent Kits, Diagnostic
  • Rifampin / therapeutic use*
  • Tuberculosis, Multidrug-Resistant / drug therapy
  • Tuberculosis, Multidrug-Resistant / microbiology
  • Tuberculosis, Pulmonary / drug therapy
  • Tuberculosis, Pulmonary / microbiology

Substances

  • Antitubercular Agents
  • Reagent Kits, Diagnostic
  • Rifampin

Grants and funding

This work was supported through funding from the National Institutes of Health and the World Health Organization. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.