Analytical Performance Characteristics of the Cepheid GeneXpert Ebola Assay for the Detection of Ebola Virus

PLoS One. 2015 Nov 12;10(11):e0142216. doi: 10.1371/journal.pone.0142216. eCollection 2015.

Abstract

Background: The recently developed Xpert® Ebola Assay is a novel nucleic acid amplification test for simplified detection of Ebola virus (EBOV) in whole blood and buccal swab samples. The assay targets sequences in two EBOV genes, lowering the risk for new variants to escape detection in the test. The objective of this report is to present analytical characteristics of the Xpert® Ebola Assay on whole blood samples.

Methods and findings: This study evaluated the assay's analytical sensitivity, analytical specificity, inclusivity and exclusivity performance in whole blood specimens. EBOV RNA, inactivated EBOV, and infectious EBOV were used as targets. The dynamic range of the assay, the inactivation of virus, and specimen stability were also evaluated. The lower limit of detection (LoD) for the assay using inactivated virus was estimated to be 73 copies/mL (95% CI: 51-97 copies/mL). The LoD for infectious virus was estimated to be 1 plaque-forming unit/mL, and for RNA to be 232 copies/mL (95% CI 163-302 copies/mL). The assay correctly identified five different Ebola viruses, Yambuku-Mayinga, Makona-C07, Yambuku-Ecran, Gabon-Ilembe, and Kikwit-956210, and correctly excluded all non-EBOV isolates tested. The conditions used by Xpert® Ebola for inactivation of infectious virus reduced EBOV titer by ≥6 logs.

Conclusion: In summary, we found the Xpert® Ebola Assay to have high analytical sensitivity and specificity for the detection of EBOV in whole blood. It offers ease of use, fast turnaround time, and remote monitoring. The test has an efficient viral inactivation protocol, fulfills inclusivity and exclusivity criteria, and has specimen stability characteristics consistent with the need for decentralized testing. The simplicity of the assay should enable testing in a wide variety of laboratory settings, including remote laboratories that are not capable of performing highly complex nucleic acid amplification tests, and during outbreaks where time to detection is critical.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chlorocebus aethiops
  • Ebolavirus / genetics*
  • Ebolavirus / physiology
  • Genes, Viral / genetics
  • Hemorrhagic Fever, Ebola / blood
  • Hemorrhagic Fever, Ebola / diagnosis*
  • Hemorrhagic Fever, Ebola / virology
  • Host-Pathogen Interactions
  • Humans
  • Mass Screening / methods*
  • Nucleic Acid Amplification Techniques / methods*
  • RNA, Viral / blood
  • RNA, Viral / genetics
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Time Factors
  • Vero Cells
  • Virus Inactivation

Substances

  • RNA, Viral

Grants and funding

This work was supported by a grant from the Bill and Melinda Gates Foundation, and the Paul Allen Family Foundation administered by the National Philanthropic Trust. Portions of this work were performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.