Interpretation of Negative Molecular Test Results in Patients With Suspected or Confirmed Ebola Virus Disease: Report of Two Cases

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Abstract

Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) is the most sensitive quantitative diagnostic assay for detection of Ebola virus in multiple body fluids. Despite the strengths of this assay, we present 2 cases of Ebola virus disease (EVD) and highlight the potential for false-negative results during the early and late stages of EVD. The first case emphasizes the low negative-predictive value of qRT-PCR during incubation and the early febrile stage of EVD, and the second case emphasizes the potential for false-negative results during recovery and late neurologic complications of EVD. Careful interpretation of test results are needed to guide difficult admission and discharge decisions in suspected or confirmed EVD.

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Ebola virus disease in West Africa--clinical manifestations and management.

Daniel Chertow, Christian Kleine, Jeffrey K. Edwards … (2014)

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Rapid diagnosis of Ebola hemorrhagic fever by reverse transcription-PCR in an outbreak setting and assessment of patient viral load as a predictor of outcome.

Jonathan S. Towner, Pierre Rollin, Daniel Bausch … (2004)

The largest outbreak on record of Ebola hemorrhagic fever (EHF) occurred in Uganda from August 2000 to January 2001. The outbreak was centered in the Gulu district of northern Uganda, with secondary transmission to other districts. After the initial diagnosis of Sudan ebolavirus by the National Institute for Virology in Johannesburg, South Africa, a temporary diagnostic laboratory was established within the Gulu district at St. Mary's Lacor Hospital. The laboratory used antigen capture and reverse transcription-PCR (RT-PCR) to diagnose Sudan ebolavirus infection in suspect patients. The RT-PCR and antigen-capture diagnostic assays proved very effective for detecting ebolavirus in patient serum, plasma, and whole blood. In samples collected very early in the course of infection, the RT-PCR assay could detect ebolavirus 24 to 48 h prior to detection by antigen capture. More than 1,000 blood samples were collected, with multiple samples obtained from many patients throughout the course of infection. Real-time quantitative RT-PCR was used to determine the viral load in multiple samples from patients with fatal and nonfatal cases, and these data were correlated with the disease outcome. RNA copy levels in patients who died averaged 2 log(10) higher than those in patients who survived. Using clinical material from multiple EHF patients, we sequenced the variable region of the glycoprotein. This Sudan ebolavirus strain was not derived from either the earlier Boniface (1976) or Maleo (1979) strain, but it shares a common ancestor with both. Furthermore, both sequence and epidemiologic data are consistent with the outbreak having originated from a single introduction into the human population.

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Ebola: translational science considerations

Francesco Chiappelli, Andre Bakhordarian, April D Thames … (2015)

We are currently in the midst of the most aggressive and fulminating outbreak of Ebola-related disease, commonly referred to as “Ebola”, ever recorded. In less than a year, the Ebola virus (EBOV, Zaire ebolavirus species) has infected over 10,000 people, indiscriminately of gender or age, with a fatality rate of about 50%. Whereas at its onset this Ebola outbreak was limited to three countries in West Africa (Guinea, where it was first reported in late March 2014, Liberia, where it has been most rampant in its capital city, Monrovia and other metropolitan cities, and Sierra Leone), cases were later reported in Nigeria, Mali and Senegal, as well as in Western Europe (i.e., Madrid, Spain) and the US (i.e., Dallas, Texas; New York City) by late October 2014. World and US health agencies declared that the current Ebola virus disease (EVD) outbreak has a strong likelihood of growing exponentially across the world before an effective vaccine, treatment or cure can be developed, tested, validated and distributed widely. In the meantime, the spread of the disease may rapidly evolve from an epidemics to a full-blown pandemic. The scientific and healthcare communities actively research and define an emerging kaleidoscope of knowledge about critical translational research parameters, including the virology of EBOV, the molecular biomarkers of the pathological manifestations of EVD, putative central nervous system involvement in EVD, and the cellular immune surveillance to EBOV, patient-centered anthropological and societal parameters of EVD, as well as translational effectiveness about novel putative patient-targeted vaccine and pharmaceutical interventions, which hold strong promise, if not hope, to curb this and future Ebola outbreaks. This work reviews and discusses the principal known facts about EBOV and EVD, and certain among the most interesting ongoing or future avenues of research in the field, including vaccination programs for the wild animal vectors of the virus and the disease from global translational science perspective.

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Author and article information

Journal

Journal ID (nlm-ta): Open Forum Infect Dis

Journal ID (iso-abbrev): Open Forum Infect Dis

Journal ID (publisher-id): ofid

Journal ID (hwp): ofids

Title: Open Forum Infectious Diseases

Publisher: Oxford University Press

ISSN (Electronic): 2328-8957

Publication date Collection: December 2015

Publication date (Electronic): 19 September 2015

Volume: 2

Issue: 4

Electronic Location Identifier: ofv137

Affiliations

[1 ]Médecins Sans Frontières, Operational Center of Brussels , Belgium

[2 ]Department of International Health, School of Public Health, Johns Hopkins University , Baltimore, Maryland

[3 ]Department of Infectious Diseases and Tropical Medicine, J.W. Goethe-University Hospital , Frankfurt, Germany

[4 ]Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Rocky Mountain Laboratories , Hamilton, Montana

[5 ]Clinton Health Initiative , Monrovia, Liberia

[6 ]Department of Critical Care Medicine, Clinical Center, National Institutes of Health , Bethesda, Maryland

Author notes

[a]

J. K. E. and C. K. are co-first authors.

Correspondence: Jeffrey K. Edwards, MD, MPH, Medical Department, Médecins Sans Frontières, Rue de l′Arbre Bénit 46, Brussels 1050, Belgium ( jeffrey.edwards@ 123456brussels.msf.org ).

Article

Publisher ID: ofv137

DOI: 10.1093/ofid/ofv137

PMC ID: 4621457

PubMed ID: 26512358

SO-VID: 86e406c0-79b3-45de-be64-0b2e9a73256f

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.

History

Date received : 13 August 2015

Date accepted : 10 September 2015

Page count

Pages: 4

Funding

Funded by: National Institutes of Health http://dx.doi.org/10.13039/100000002

Funded by: Intramural Research Program

Funded by: National Institute of Allergy and Infectious Diseases http://dx.doi.org/10.13039/100000060

Funded by: National Institutes of Health (NIH)

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cover-date Fall 2015

Keywords: ebola,hemorrhagic fever,liberia,pcr,west africa

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Keywords: ebola, hemorrhagic fever, liberia, pcr, west africa

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Most cited references 6

Ebola virus disease in West Africa--clinical manifestations and management.

Rapid diagnosis of Ebola hemorrhagic fever by reverse transcription-PCR in an outbreak setting and assessment of patient viral load as a predictor of outcome.

Ebola: translational science considerations

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