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Link to original content: https://pubmed.ncbi.nlm.nih.gov/26625118/
Use of Viremia to Evaluate the Baseline Case Fatality Ratio of Ebola Virus Disease and Inform Treatment Studies: A Retrospective Cohort Study - PubMed Skip to main page content
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. 2015 Dec 1;12(12):e1001908.
doi: 10.1371/journal.pmed.1001908. eCollection 2015 Dec.

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

Oumar Faye  1 , Alessio Andronico  2 , Ousmane Faye  1 , Henrik Salje  2   3 , Pierre-Yves Boëlle  4   5 , N'Faly Magassouba  6 , Elhadj Ibrahima Bah  7 , Lamine Koivogui  8 , Boubacar Diallo  9 , Alpha Amadou Diallo  10 , Sakoba Keita  10 , Mandy Kader Konde  11 , Robert Fowler  12 , Gamou Fall  1 , Simon Cauchemez  2 , Amadou Alpha Sall  1
Affiliations

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

Oumar Faye et al. PLoS Med. .

Abstract

Background: 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.

Methods and findings: 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.

Conclusions: 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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. The Ebola virus disease epidemic in the Conakry area, Guinea, March 2014 to February 2015.
(A) Map of the study area, which consists of Conakry and the surrounding prefectures of Boffa, Coyah, Dubreka, Forecariah, Fria, Kindia, and Telimele (for which diagnoses were mostly performed by the IPD-LFHP laboratory) (the administrative boundaries were taken from the GADM database; http://www.gadm.org/). (B) Number of cases by month of symptom onset. The total number of probable and confirmed cases in the study area that were hospitalized is indicated in grey. The number of those that were diagnosed by reverse transcription PCR (RT-PCR) by the IPD-LFHP laboratory is in blue.
Fig 2
Fig 2. STROBE figure of patients included in this study.
Fig 3
Fig 3. Viremia and the probability of death.
(A) Mean viremia as a function of the time from symptom onset to sample collection. (B) Mean viremia by gender. (C) Mean viremia by age group. (D) Probability of death as a function of viremia, when viremia was measured in the week following symptom onset. Three viremia groups are defined: low (V < 104.4 copies/ml), intermediate (104.4 ≤ V < 105.2 copies/ml), and high (V ≥ 105.2 copies/ml) viremia. The probability of death according to viremia group is represented as dotted line. The grey line corresponds to the predictions of the univariable logistic regression model. (E) Probability of death (dot: observed mean; thick line: 95% CI) as a function of the time from symptom onset to sample collection and the viremia group. Mean predicted values obtained with the multivariable logistic regression (triangle) and the bootstrap prediction intervals (thin lines) are also provided.
Fig 4
Fig 4. Variation of CFR and viremia over time.
(A) Observed CFR by month (black) and predictions obtained from multivariable logistic regression (orange) and from the simple univariable logistic regression model that relies only on viremia (violet). Lines provide 95% CI. The shaded area indicates the bootstrap prediction interval. (B) Mean viremia by month. (C) Proportion of patients in the low (red; V < 104.4 copies/ml), intermediate (green; 104.4 ≤ V < 105.2 copies/ml), and high (blue; V ≥ 105.2 copies/ml) viremia groups by month.
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