Use of Viremia to Evaluate the Baseline Case Fatality Ratio of Ebola Virus Disease and Inform Treatment Studies: A Retrospective Cohort Study.

<h4>Background</h4>The case fatality ratio (CFR) of Ebola virus disease (EVD) can vary over time and space for reasons that are not fully understood. This makes it difficult to define the baseline CFRs needed to evaluate treatments in the absence of randomized controls. Here, we investig...

Full description

Saved in:
Bibliographic Details
Main Authors: Oumar Faye, Alessio Andronico, Ousmane Faye, Henrik Salje, Pierre-Yves Boëlle, N'Faly Magassouba, Elhadj Ibrahima Bah, Lamine Koivogui, Boubacar Diallo, Alpha Amadou Diallo, Sakoba Keita, Mandy Kader Konde, Robert Fowler, Gamou Fall, Simon Cauchemez, Amadou Alpha Sall
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-12-01
Series:PLoS Medicine
Online Access:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1001908&type=printable
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850163012314333184
author Oumar Faye
Alessio Andronico
Ousmane Faye
Henrik Salje
Pierre-Yves Boëlle
N'Faly Magassouba
Elhadj Ibrahima Bah
Lamine Koivogui
Boubacar Diallo
Alpha Amadou Diallo
Sakoba Keita
Mandy Kader Konde
Robert Fowler
Gamou Fall
Simon Cauchemez
Amadou Alpha Sall
author_facet Oumar Faye
Alessio Andronico
Ousmane Faye
Henrik Salje
Pierre-Yves Boëlle
N'Faly Magassouba
Elhadj Ibrahima Bah
Lamine Koivogui
Boubacar Diallo
Alpha Amadou Diallo
Sakoba Keita
Mandy Kader Konde
Robert Fowler
Gamou Fall
Simon Cauchemez
Amadou Alpha Sall
author_sort Oumar Faye
collection DOAJ
description <h4>Background</h4>The case fatality ratio (CFR) of Ebola virus disease (EVD) can vary over time and space for reasons that are not fully understood. This makes it difficult to define the baseline CFRs needed to evaluate treatments in the absence of randomized controls. Here, we investigate whether viremia in EVD patients may be used to evaluate baseline EVD CFRs.<h4>Methods and findings</h4>We analyzed the laboratory and epidemiological records of patients with EVD confirmed by reverse transcription PCR hospitalized in the Conakry area, Guinea, between 1 March 2014 and 28 February 2015. We used viremia and other variables to model the CFR. Data for 699 EVD patients were analyzed. In the week following symptom onset, mean viremia remained stable, and the CFR increased with viremia, V, from 21% (95% CI 16%-27%) for low viremia (V < 104.4 copies/ml) to 53% (95% CI 44%-61%) for intermediate viremia (104.4 ≤ V < 105.2 copies/ml) and 81% (95% CI 75%-87%) for high viremia (V ≥ 105.2 copies/ml). Compared to adults (15-44 y old [y.o.]), the CFR was larger in young children (0-4 y.o.) (odds ratio [OR]: 2.44; 95% CI 1.02-5.86) and older adults (≥ 45 y.o.) (OR: 2.84; 95% CI 1.81-4.46) but lower in children (5-14 y.o.) (OR: 0.46; 95% CI 0.24-0.86). An order of magnitude increase in mean viremia in cases after July 2014 compared to those before coincided with a 14% increase in the CFR. Our findings come from a large hospital-based study in Conakry and may not be generalizable to settings with different case profiles, such as with individuals who never sought care.<h4>Conclusions</h4>Viremia in EVD patients was a strong predictor of death that partly explained variations in CFR in the study population. This study provides baseline CFRs by viremia group, which allow appropriate adjustment when estimating efficacy in treatment studies. In randomized controlled trials, stratifying analysis on viremia groups could reduce sample size requirements by 25%. We hypothesize that monitoring the viremia of hospitalized patients may inform the ability of surveillance systems to detect EVD patients from the different severity strata.
format Article
id doaj-art-43056f71dc8944a79ae210d2e2c75d7c
institution OA Journals
issn 1549-1277
1549-1676
language English
publishDate 2015-12-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Medicine
spelling doaj-art-43056f71dc8944a79ae210d2e2c75d7c2025-08-20T02:22:25ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762015-12-011212e100190810.1371/journal.pmed.1001908Use of Viremia to Evaluate the Baseline Case Fatality Ratio of Ebola Virus Disease and Inform Treatment Studies: A Retrospective Cohort Study.Oumar FayeAlessio AndronicoOusmane FayeHenrik SaljePierre-Yves BoëlleN'Faly MagassoubaElhadj Ibrahima BahLamine KoivoguiBoubacar DialloAlpha Amadou DialloSakoba KeitaMandy Kader KondeRobert FowlerGamou FallSimon CauchemezAmadou Alpha Sall<h4>Background</h4>The case fatality ratio (CFR) of Ebola virus disease (EVD) can vary over time and space for reasons that are not fully understood. This makes it difficult to define the baseline CFRs needed to evaluate treatments in the absence of randomized controls. Here, we investigate whether viremia in EVD patients may be used to evaluate baseline EVD CFRs.<h4>Methods and findings</h4>We analyzed the laboratory and epidemiological records of patients with EVD confirmed by reverse transcription PCR hospitalized in the Conakry area, Guinea, between 1 March 2014 and 28 February 2015. We used viremia and other variables to model the CFR. Data for 699 EVD patients were analyzed. In the week following symptom onset, mean viremia remained stable, and the CFR increased with viremia, V, from 21% (95% CI 16%-27%) for low viremia (V < 104.4 copies/ml) to 53% (95% CI 44%-61%) for intermediate viremia (104.4 ≤ V < 105.2 copies/ml) and 81% (95% CI 75%-87%) for high viremia (V ≥ 105.2 copies/ml). Compared to adults (15-44 y old [y.o.]), the CFR was larger in young children (0-4 y.o.) (odds ratio [OR]: 2.44; 95% CI 1.02-5.86) and older adults (≥ 45 y.o.) (OR: 2.84; 95% CI 1.81-4.46) but lower in children (5-14 y.o.) (OR: 0.46; 95% CI 0.24-0.86). An order of magnitude increase in mean viremia in cases after July 2014 compared to those before coincided with a 14% increase in the CFR. Our findings come from a large hospital-based study in Conakry and may not be generalizable to settings with different case profiles, such as with individuals who never sought care.<h4>Conclusions</h4>Viremia in EVD patients was a strong predictor of death that partly explained variations in CFR in the study population. This study provides baseline CFRs by viremia group, which allow appropriate adjustment when estimating efficacy in treatment studies. In randomized controlled trials, stratifying analysis on viremia groups could reduce sample size requirements by 25%. We hypothesize that monitoring the viremia of hospitalized patients may inform the ability of surveillance systems to detect EVD patients from the different severity strata.https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1001908&type=printable
spellingShingle Oumar Faye
Alessio Andronico
Ousmane Faye
Henrik Salje
Pierre-Yves Boëlle
N'Faly Magassouba
Elhadj Ibrahima Bah
Lamine Koivogui
Boubacar Diallo
Alpha Amadou Diallo
Sakoba Keita
Mandy Kader Konde
Robert Fowler
Gamou Fall
Simon Cauchemez
Amadou Alpha Sall
Use of Viremia to Evaluate the Baseline Case Fatality Ratio of Ebola Virus Disease and Inform Treatment Studies: A Retrospective Cohort Study.
PLoS Medicine
title Use of Viremia to Evaluate the Baseline Case Fatality Ratio of Ebola Virus Disease and Inform Treatment Studies: A Retrospective Cohort Study.
title_full Use of Viremia to Evaluate the Baseline Case Fatality Ratio of Ebola Virus Disease and Inform Treatment Studies: A Retrospective Cohort Study.
title_fullStr Use of Viremia to Evaluate the Baseline Case Fatality Ratio of Ebola Virus Disease and Inform Treatment Studies: A Retrospective Cohort Study.
title_full_unstemmed Use of Viremia to Evaluate the Baseline Case Fatality Ratio of Ebola Virus Disease and Inform Treatment Studies: A Retrospective Cohort Study.
title_short Use of Viremia to Evaluate the Baseline Case Fatality Ratio of Ebola Virus Disease and Inform Treatment Studies: A Retrospective Cohort Study.
title_sort use of viremia to evaluate the baseline case fatality ratio of ebola virus disease and inform treatment studies a retrospective cohort study
url https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1001908&type=printable
work_keys_str_mv AT oumarfaye useofviremiatoevaluatethebaselinecasefatalityratioofebolavirusdiseaseandinformtreatmentstudiesaretrospectivecohortstudy
AT alessioandronico useofviremiatoevaluatethebaselinecasefatalityratioofebolavirusdiseaseandinformtreatmentstudiesaretrospectivecohortstudy
AT ousmanefaye useofviremiatoevaluatethebaselinecasefatalityratioofebolavirusdiseaseandinformtreatmentstudiesaretrospectivecohortstudy
AT henriksalje useofviremiatoevaluatethebaselinecasefatalityratioofebolavirusdiseaseandinformtreatmentstudiesaretrospectivecohortstudy
AT pierreyvesboelle useofviremiatoevaluatethebaselinecasefatalityratioofebolavirusdiseaseandinformtreatmentstudiesaretrospectivecohortstudy
AT nfalymagassouba useofviremiatoevaluatethebaselinecasefatalityratioofebolavirusdiseaseandinformtreatmentstudiesaretrospectivecohortstudy
AT elhadjibrahimabah useofviremiatoevaluatethebaselinecasefatalityratioofebolavirusdiseaseandinformtreatmentstudiesaretrospectivecohortstudy
AT laminekoivogui useofviremiatoevaluatethebaselinecasefatalityratioofebolavirusdiseaseandinformtreatmentstudiesaretrospectivecohortstudy
AT boubacardiallo useofviremiatoevaluatethebaselinecasefatalityratioofebolavirusdiseaseandinformtreatmentstudiesaretrospectivecohortstudy
AT alphaamadoudiallo useofviremiatoevaluatethebaselinecasefatalityratioofebolavirusdiseaseandinformtreatmentstudiesaretrospectivecohortstudy
AT sakobakeita useofviremiatoevaluatethebaselinecasefatalityratioofebolavirusdiseaseandinformtreatmentstudiesaretrospectivecohortstudy
AT mandykaderkonde useofviremiatoevaluatethebaselinecasefatalityratioofebolavirusdiseaseandinformtreatmentstudiesaretrospectivecohortstudy
AT robertfowler useofviremiatoevaluatethebaselinecasefatalityratioofebolavirusdiseaseandinformtreatmentstudiesaretrospectivecohortstudy
AT gamoufall useofviremiatoevaluatethebaselinecasefatalityratioofebolavirusdiseaseandinformtreatmentstudiesaretrospectivecohortstudy
AT simoncauchemez useofviremiatoevaluatethebaselinecasefatalityratioofebolavirusdiseaseandinformtreatmentstudiesaretrospectivecohortstudy
AT amadoualphasall useofviremiatoevaluatethebaselinecasefatalityratioofebolavirusdiseaseandinformtreatmentstudiesaretrospectivecohortstudy