The Contribution of Ebola Viral Load at Admission and Other Patient Characteristics to Mortality in a Médecins Sans Frontières Ebola Case Management Centre, Kailahun, Sierra Leone, June–October 2014

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Abstract

This paper describes patient characteristics, including Ebola viral load, associated with mortality in a Médecins Sans Frontières Ebola case management centre (CMC).

Out of 780 admissions between June and October 2014, 525 (67%) were positive for Ebola with a known outcome. The crude mortality rate was 51% (270/525). Ebola viral load (whole-blood sample) data were available on 76% (397/525) of patients. Univariate analysis indicated viral load at admission, age, symptom duration prior to admission, and distance traveled to the CMC were associated with mortality ( P < .05). The multivariable model predicted mortality in those with a viral load at admission greater than 10 million copies per milliliter ( P < .05, odds ratio >10), aged ≥50 years ( P = .08, odds ratio = 2) and symptom duration prior to admission less than 5 days ( P = .14). The presence of confusion, diarrhea, and conjunctivitis were significantly higher ( P < .05) in Ebola patients who died.

These findings highlight the importance viral load at admission has on mortality outcomes and could be used to cohort cases with viral loads greater than 10 million copies into dedicated wards with more intensive medical support to further reduce mortality.

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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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Analysis of human peripheral blood samples from fatal and nonfatal cases of Ebola (Sudan) hemorrhagic fever: cellular responses, virus load, and nitric oxide levels.

Anthony Sanchez, Matthew Lukwiya, Daniel Bausch … (2004)

Peripheral blood samples obtained from patients during an outbreak of Ebola virus (Sudan species) disease in Uganda in 2000 were used to phenotype peripheral blood mononuclear cells (PBMC), quantitate gene expression, measure antigenemia, and determine nitric oxide levels. It was determined that as the severity of disease increased in infected patients, there was a corresponding increase in antigenemia and leukopenia. Blood smears revealed thrombocytopenia, a left shift in neutrophils (in some cases degenerating), and atypical lymphocytes. Infected patients who died had reduced numbers of T cells, CD8(+) T cells, and activated (HLA-DR(+)) CD8(+) T cells, while the opposite was noted for patients who survived the disease. Expression levels of cytokines, Fas antigen, and Fas ligand (TaqMan quantitation) in PBMC from infected patients were not significantly different from those in uninfected patients (treated in the same isolation wards), nor was there a significant increase in expression compared to healthy volunteers (United States). This unresponsive state of PBMC from infected patients despite high levels of circulating antigen and virus replication suggests that some form of immunosuppression had developed. Ebola virus RNA levels (virus load) in PBMC specimens were found to be much higher in infected patients who died than patients who survived the disease. Similarly, blood levels of nitric oxide were much higher in fatal cases (increasing with disease severity), and extremely elevated levels (>/=150 microM) would have negatively affected vascular tone and contributed to virus-induced shock.

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Use of bacteriophage MS2 as an internal control in viral reverse transcription-PCR assays.

Jens Dreier, Melanie Störmer, Knut Kleesiek (2005)

Diagnostic systems based on reverse transcription (RT)-PCR are widely used for the detection of viral genomes in different human specimens. The application of internal controls (IC) to monitor each step of nucleic acid amplification is necessary to prevent false-negative results due to inhibition or human error. In this study, we designed various real-time RT-PCRs utilizing the coliphage MS2 replicase gene, which differ in detection format, amplicon size, and efficiency of amplification. These noncompetitive IC assays, using TaqMan, hybridization probe, or duplex scorpion probe techniques, were tested on the LightCycler and Rotorgene systems. In our approach, clinical specimens were spiked with the control virus to monitor the efficiency of extraction, reverse transcription, and amplification steps. The MS2 RT-PCR assays were applied for internal control when using a second target hepatitis C virus RNA in duplex PCR in blood donor screening. The 95% detection limit was calculated by probit analysis to 44.9 copies per PCR (range, 38.4 to 73.4). As demonstrated routinely, application of MS2 IC assays exhibits low variability and can be applied in various RT-PCR assays. MS2 phage lysates were obtained under standard laboratory conditions. The quantification of phage and template RNA was performed by plating assays to determine PFU or via real-time RT-PCR. High stability of the MS2 phage preparations stored at -20 degrees C, 4 degrees C, and room temperature was demonstrated.

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Author and article information

Journal

Journal ID (nlm-ta): J Infect Dis

Journal ID (iso-abbrev): J. Infect. Dis

Journal ID (publisher-id): jid

Journal ID (hwp): jinfdis

Title: The Journal of Infectious Diseases

Publisher: Oxford University Press

ISSN (Print): 0022-1899

ISSN (Electronic): 1537-6613

Publication date (Print): 01 December 2015

Publication date (Electronic): 22 May 2015

Publication date PMC-release: 22 May 2015

Volume: 212

Issue: 11

Pages: 1752-1758

Affiliations

[1 ]Médecins Sans Frontières , Dublin, Ireland

[2 ]Médecins Sans Frontières, Operational Research Department , Brussels, Belgium

[3 ]Primary Health Care Unit Kailahun, Ministry of Health and Sanitation , Sierra Leone

[4 ]Médecins Sans Frontières, Operational Research Department , Luxembourg

[5 ]School of Mathematical Sciences, Dublin City University , Ireland

[6 ]Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba

Author notes

Correspondence: Gabriel Fitzpatrick, MD, Operational Research, 46, Rue de l'Arbre Bénit 1050 Brussels, Belgium ( gabriel.fitzpatrick@ 123456gmail.com ).

Article

Publisher ID: jiv304

DOI: 10.1093/infdis/jiv304

PMC ID: 4633764

PubMed ID: 26002981

SO-VID: dc2a0fd9-c787-4046-8867-0277ad021d0c

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@ 123456oup.com .

History

Date received : 8 February 2015

Date accepted : 14 May 2015

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The Contribution of Ebola Viral Load at Admission and Other Patient Characteristics to Mortality in a Médecins Sans Frontières Ebola Case Management Centre, Kailahun, Sierra Leone, June–October 2014

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Abstract

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Coronaviruses, COVID-19 and SARS-CoV-2

Most cited references 10

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.

Analysis of human peripheral blood samples from fatal and nonfatal cases of Ebola (Sudan) hemorrhagic fever: cellular responses, virus load, and nitric oxide levels.

Use of bacteriophage MS2 as an internal control in viral reverse transcription-PCR assays.

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Cited by 47

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