02 Jul New Rapid Test For Ebola May Be Useful In High-Risk Populations
MedicalResearch.com Interview with:
Jana Broadhurst, MD, PhD
Nira R Pollock MD PhD
Boston Children’s Hospital, Boston, MA
Medical Research: What is the background for this study? What are the main findings?
Response: At present, diagnosis of Ebola virus disease (EVD) in west Africa requires transport of venipuncture blood to field laboratories for testing by real-time RT-PCR, resulting in delays that complicate patient care and infection control efforts. Therefore, an urgent need exists for a point-of-care rapid diagnostic test (RDT) for this disease. In this study, we performed a field validation of the Corgenix ReEBOV Antigen Rapid Test kit, the only Ebola RDT authorized for emergency use by the WHO and FDA. This test is a dipstick lateral flow immunoassay designed to detect the Ebola virus VP40 protein in whole blood (collected by either fingerstick or whole blood) or plasma.
We performed the rapid diagnostic test at the point-of-care on fingerstick blood samples from 106 individuals with suspected EVD presenting at two Ebola clinical centers in Sierra Leone. Separately, we performed the RDT on 284 venous whole blood samples submitted to the Public Health England field reference laboratory for clinical testing. Two readers independently scored each RDT as positive, negative, or invalid, with any disagreements resolved by a third. RDT results were compared with clinical real-time RT-PCR results obtained with the RealStar Filovirus RT-PCR kit 1.0 (altona Diagnostics GmBH).
In point-of-care testing of fingerstick blood, the RDT had 100% sensitivity (95% CI 87.7-100) and 92% specificity (95% CI 83.8-97.1). Similarly, in venipuncture blood tested in the reference laboratory the rapid diagnostic test had 100% sensitivity (95% CI 92.1-100) and 92% specificity (95% CI 88.0-95.3). The two independent readers agreed for 95.2% of point-of-care and 98.6% of reference laboratory RDT results. The maximum cycle threshold (Ct) value was 26.3 in PCR-positive samples tested from both point-of-care (mean Ct 22.6) and reference laboratory (mean Ct 21.5) cohorts. Six of 16 banked plasma samples from RDT-positive and altona-negative patients were positive by an alternative real-time RT-PCR assay (the Trombley assay); 3 of 18 samples from individuals who were negative by both the RDT and altona test were also positive by Trombley.
Medical Research: What should clinicians and patients take away from your report?
Response: In our study cohort (maximum Ct of 26.3) the ReEBOV RDT detected all patients who were positive for Ebola virus by the altona real-time RT-PCR. However, our study also revealed that the altona RT-PCR test, as deployed in the field for clinical testing, had imperfect sensitivity. The RDT was feasible to perform in restricted patient care areas (the red zone) by operators wearing full personal protective equipment, and showed high inter-operator agreement when performed in both point-of-care and reference laboratory settings. Thus, we can conclude that the ReEBOV RDT could be very useful as a rapid test for Ebola virus disease in high-risk populations. Earlier test results would allow much improved triage of patients, enabling clinical staff to focus their attention and resources on those most likely to have the disease and reducing the opportunity for infection of patients who do not have EVD. However, the performance of the RDT in patients with low viral loads (e.g. those presenting very early in their disease course) remains to be ascertained.
Medical Research: What recommendations do you have for future research as a result of this study?
Response: Further studies are needed to evaluate the performance of the RDT in different patient populations and patient-care settings. In particular, better characterization of RDT performance in patients with low viral loads (such as those very early in their disease course) would be valuable.
Broadhurst, Mara Jana et al.
Mara Jana Broadhurst, MD,John Daniel Kelly, MD,Ann Miller, PhD,Amanda Semper, DPhil,Daniel Bailey, PhD,Elisabetta Groppelli, PhD,Andrew Simpson, FRCPath,Tim Brooks, FRCPath,Susan Hula, MSc,Wilfred Nyoni, MSc,Alhaji B Sankoh, DLT,Santigi Kanu, DLT,Alhaji Jalloh,Quy Ton, MD
Jana Broadhurst, MD, PhD, University of California, San Francisco, Nira R Pollock MD PhD, & Boston Children’s Hospital, Boston, MA (2015). New Rapid Test For Ebola May Be Useful In High-Risk Populations