Field Validation of the ReEBOV Antigen Rapid Test for Point-of-Care Diagnosis of Ebola Virus Infection

Matthew L. Boisen, Robert Cross, Jessica N. Hartnett, Augustine Goba, Mambu Momoh, Mohamed Fullah, Michael Gbakie, Sidiki Safa, Mbalu Fonnie, Francis Baimba, Veronica J. Koroma, Joan B. Geisbert, Stephanie McCormick, DIana K S Nelson, Molly M. Millett, Darin Oottamasathien, Abby B. Jones, Ha Pham, Bethany L. Brown, Jeffrey G. ShafferJohn S. Schieffelin, Brima Kargbo, Momoh Gbetuwa, Sahr M. Gevao, Russell B. Wilson, Kelly R. Pitts, Thomas Geisbert, Luis M. Branco, Sheik H. Khan, Donald S. Grant, Robert F. Garry

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background. The 2013-2016 West African Ebola virus disease (EVD) epidemic is the largest recorded. Triage on the basis of clinical signs had limited success, and the time to diagnosis by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) could exceed 5 days. Here we describe the development and field validation of the ReEBOV Antigen Rapid Test (ReEBOV RDT) to aid triage of individuals with suspected EVD. Methods. Samples from patients with suspected EVD were submitted to Kenema Government Hospital, Sierra Leone, for Lassa fever and EVD screening throughout 2014. Banked residual clinical samples were tested in November 2014 and January 2015 in a blinded field trial to estimate the clinical effectiveness of the ReEBOV RDT, compared with EBOV-specific qRT-PCR. Results. Preliminary ReEBOV RDT performance demonstrated a positive percentage agreement (PPA) of 91.1% (195 of 214 results; 95% confidence interval [CI], 86.5%-94.6%) and a negative percentage agreement (NPA) of 90.2% (175 of 194; 95% CI, 85.1%-94.0%). The final estimates used by the Food and Drug Administration to determine whether to grant emergency use authorization for the test, which excluded a qRT-PCR reference method threshold cutoff, were a PPA of 62.1% (72 of 116 results; 95% CI, 52.6%-70.9%) and a NPA of 96.7% (58 of 60; 95% CI, 88.5%-99.6%), with a diagnostic likelihood of 18.6. A subsequent, independent evaluation by the World Health Organization generated results consistent with the preliminary performance estimates. Conclusions. The ReEBOV RDT demonstrated the potential to provide clinically effective rapid and accurate point-of-care test results and, thus, to be a powerful tool for increasing triage efficiency.

Original languageEnglish (US)
Pages (from-to)S203-S209
JournalJournal of Infectious Diseases
Volume214
DOIs
StatePublished - Oct 15 2016

Fingerprint

Ebola Hemorrhagic Fever
Point-of-Care Systems
Triage
Confidence Intervals
Reverse Transcription
Antigens
Polymerase Chain Reaction
Lassa Fever
Lassa virus
Sierra Leone
United States Food and Drug Administration
Emergencies

Keywords

  • Clinical
  • Ebola
  • Lateral flow immunoassay
  • Point of care
  • Validation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Field Validation of the ReEBOV Antigen Rapid Test for Point-of-Care Diagnosis of Ebola Virus Infection. / Boisen, Matthew L.; Cross, Robert; Hartnett, Jessica N.; Goba, Augustine; Momoh, Mambu; Fullah, Mohamed; Gbakie, Michael; Safa, Sidiki; Fonnie, Mbalu; Baimba, Francis; Koroma, Veronica J.; Geisbert, Joan B.; McCormick, Stephanie; Nelson, DIana K S; Millett, Molly M.; Oottamasathien, Darin; Jones, Abby B.; Pham, Ha; Brown, Bethany L.; Shaffer, Jeffrey G.; Schieffelin, John S.; Kargbo, Brima; Gbetuwa, Momoh; Gevao, Sahr M.; Wilson, Russell B.; Pitts, Kelly R.; Geisbert, Thomas; Branco, Luis M.; Khan, Sheik H.; Grant, Donald S.; Garry, Robert F.

In: Journal of Infectious Diseases, Vol. 214, 15.10.2016, p. S203-S209.

Research output: Contribution to journalArticle

Boisen, ML, Cross, R, Hartnett, JN, Goba, A, Momoh, M, Fullah, M, Gbakie, M, Safa, S, Fonnie, M, Baimba, F, Koroma, VJ, Geisbert, JB, McCormick, S, Nelson, DIKS, Millett, MM, Oottamasathien, D, Jones, AB, Pham, H, Brown, BL, Shaffer, JG, Schieffelin, JS, Kargbo, B, Gbetuwa, M, Gevao, SM, Wilson, RB, Pitts, KR, Geisbert, T, Branco, LM, Khan, SH, Grant, DS & Garry, RF 2016, 'Field Validation of the ReEBOV Antigen Rapid Test for Point-of-Care Diagnosis of Ebola Virus Infection', Journal of Infectious Diseases, vol. 214, pp. S203-S209. https://doi.org/10.1093/infdis/jiw261
Boisen, Matthew L. ; Cross, Robert ; Hartnett, Jessica N. ; Goba, Augustine ; Momoh, Mambu ; Fullah, Mohamed ; Gbakie, Michael ; Safa, Sidiki ; Fonnie, Mbalu ; Baimba, Francis ; Koroma, Veronica J. ; Geisbert, Joan B. ; McCormick, Stephanie ; Nelson, DIana K S ; Millett, Molly M. ; Oottamasathien, Darin ; Jones, Abby B. ; Pham, Ha ; Brown, Bethany L. ; Shaffer, Jeffrey G. ; Schieffelin, John S. ; Kargbo, Brima ; Gbetuwa, Momoh ; Gevao, Sahr M. ; Wilson, Russell B. ; Pitts, Kelly R. ; Geisbert, Thomas ; Branco, Luis M. ; Khan, Sheik H. ; Grant, Donald S. ; Garry, Robert F. / Field Validation of the ReEBOV Antigen Rapid Test for Point-of-Care Diagnosis of Ebola Virus Infection. In: Journal of Infectious Diseases. 2016 ; Vol. 214. pp. S203-S209.
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T1 - Field Validation of the ReEBOV Antigen Rapid Test for Point-of-Care Diagnosis of Ebola Virus Infection

AU - Boisen, Matthew L.

AU - Cross, Robert

AU - Hartnett, Jessica N.

AU - Goba, Augustine

AU - Momoh, Mambu

AU - Fullah, Mohamed

AU - Gbakie, Michael

AU - Safa, Sidiki

AU - Fonnie, Mbalu

AU - Baimba, Francis

AU - Koroma, Veronica J.

AU - Geisbert, Joan B.

AU - McCormick, Stephanie

AU - Nelson, DIana K S

AU - Millett, Molly M.

AU - Oottamasathien, Darin

AU - Jones, Abby B.

AU - Pham, Ha

AU - Brown, Bethany L.

AU - Shaffer, Jeffrey G.

AU - Schieffelin, John S.

AU - Kargbo, Brima

AU - Gbetuwa, Momoh

AU - Gevao, Sahr M.

AU - Wilson, Russell B.

AU - Pitts, Kelly R.

AU - Geisbert, Thomas

AU - Branco, Luis M.

AU - Khan, Sheik H.

AU - Grant, Donald S.

AU - Garry, Robert F.

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N2 - Background. The 2013-2016 West African Ebola virus disease (EVD) epidemic is the largest recorded. Triage on the basis of clinical signs had limited success, and the time to diagnosis by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) could exceed 5 days. Here we describe the development and field validation of the ReEBOV Antigen Rapid Test (ReEBOV RDT) to aid triage of individuals with suspected EVD. Methods. Samples from patients with suspected EVD were submitted to Kenema Government Hospital, Sierra Leone, for Lassa fever and EVD screening throughout 2014. Banked residual clinical samples were tested in November 2014 and January 2015 in a blinded field trial to estimate the clinical effectiveness of the ReEBOV RDT, compared with EBOV-specific qRT-PCR. Results. Preliminary ReEBOV RDT performance demonstrated a positive percentage agreement (PPA) of 91.1% (195 of 214 results; 95% confidence interval [CI], 86.5%-94.6%) and a negative percentage agreement (NPA) of 90.2% (175 of 194; 95% CI, 85.1%-94.0%). The final estimates used by the Food and Drug Administration to determine whether to grant emergency use authorization for the test, which excluded a qRT-PCR reference method threshold cutoff, were a PPA of 62.1% (72 of 116 results; 95% CI, 52.6%-70.9%) and a NPA of 96.7% (58 of 60; 95% CI, 88.5%-99.6%), with a diagnostic likelihood of 18.6. A subsequent, independent evaluation by the World Health Organization generated results consistent with the preliminary performance estimates. Conclusions. The ReEBOV RDT demonstrated the potential to provide clinically effective rapid and accurate point-of-care test results and, thus, to be a powerful tool for increasing triage efficiency.

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KW - Ebola

KW - Lateral flow immunoassay

KW - Point of care

KW - Validation

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