Laboratory Findings, Compassionate Use of Favipiravir, and Outcome in Patients With Ebola Virus Disease, Guinea, 2015-A Retrospective Observational Study

Abstract

Background: In 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. The cycle threshold (Ct) of an Ebola virus-specific reverse transcription-polymerase chain reaction assay and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to patients with EVD on a compassionate-use basis.

Methods: To reduce biases in the raw field data, we carefully selected 163 of 286 patients with EVD for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry findings, favipiravir treatment, and outcome.

Results: The case-fatality rate in favipiravir-treated patients was lower than in untreated patients (42.5% [31 of 73] vs 57.8% [52 of 90]; P = .053 by univariate analysis). In multivariate regression analysis, a higher Ct and a younger age were associated with survival (P < .001), while favipiravir treatment showed no statistically significant effect (P = .11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (P = .015). The study also showed characteristic changes in blood chemistry findings in patients who died, compared with survivors.

Conclusions: Consistent with the JIKI trial, this retrospective study revealed a trend toward improved survival in favipiravir- treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time.

Keywords: Ebola virus disease; Favipiravir; Filovirus; Guinea; epidemic; mobile laboratory.

Figure 1.

Epidemic curve of Ebola virus disease (EVD) cases diagnosed at the European Mobile Laboratory unit during the study period. A, Ebola virus (EBOV)–specific reverse transcription–polymerase chain reaction (RT-PCR) results for 813 patients with suspected EVD who attended an Ebola treatment center, and case-fatality rates (CFRs) among hospitalized patients with EVD over time. B, EBOV RT-PCR results for 3823 individuals who died in the community.

Figure 2.

Multivariate logistic regression model for the association between the cycle threshold (Ct), age, favipiravir treatment status, and probability of a fatal outcome. The association between the Ct and the probability of death, depending on favipiravir treatment status, is displayed by regression curves. The curves were calculated for a mean age of 31.5 years among patients in the analysis. The estimated improvement in the chance of survival due to favipiravir treatment (absolute reduction in the probability of dying is defined as the difference between the “No treatment” curve and the “Favipiravir” curve) is shown. The curves were calculated from the parameters of the multivariate logistic regression analysis of data from the 163 patients with Ebola virus disease (EVD) included in the retrospective study (Table 3). For the age dependency of the curves, see Supplementary Figure 8.

Figure 3.

Kaplan-Meier analysis of survival time among patients in the retrospective study. The analysis was performed under the assumption that survivors were lost to follow-up on discharge. Therefore, survivors were censored at discharge (small vertical ticks on the curves). Numbers of patients at risk are indicated for the nontreatment (A) and treatment (B) groups. For Kaplan-Meier analysis without censoring at the time of discharge, see Supplementary Figure 9.