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Background: Ebola Virus Disease (EVD) causes high case fatality rates (CFRs) in young children, yet there are limited data focusing on predicting mortality in pediatric patients. Here we present machine learning-derived prognostic models to predict clinical outcomes in children infected with Ebola virus. Methods: Using retrospective data from the Ebola Data Platform, we investigated children with EVD from the West African EVD outbreak in 2014–2016. Elastic net regularization was used to create a prognostic model for EVD mortality. In addition to external validation with data from the 2018–2020 EVD epidemic in the Democratic Republic of the Congo (DRC), we updated the model using selected serum biomarkers. Findings: Pediatric EVD mortality was significantly associated with younger age, lower PCR cycle threshold (Ct) values, unexplained bleeding, respiratory distress, bone/muscle pain, anorexia, dysphagia, and diarrhea. These variables were combined to develop the newly described EVD Prognosis in Children (EPiC) predictive model. The area under the receiver operating characteristic curve (AUC) for EPiC was 0.77 (95% CI: 0.74–0.81) in the West Africa derivation dataset and 0.76 (95% CI: 0.64–0.88) in the DRC validation dataset. Updating the model with peak aspartate aminotransferase (AST) or creatinine kinase (CK) measured within the first 48 hours after admission increased the AUC to 0.90 (0.77–1.00) and 0.87 (0.74–1.00), respectively. Conclusion: The novel EPiC prognostic model that incorporates clinical information and commonly used biochemical tests, such as AST and CK, can be used to predict mortality in children with EVD. Author summary: Although case fatality rates remain high, there are limited data on predicting mortality in children with Ebola Virus Disease (EVD). Furthermore, challenges in predicting EVD outcomes using clinical and laboratory data highlight the need for the development and validation of pediatric predictive models. The novel EVD Prognosis in Children (EPiC) model uses clinical and biochemical information, such as AST and CK, to predict mortality in infected children. While few prognostic models or scoring systems have been developed to predict clinical outcomes of EVD, the majority of them were limited in geographical and temporal scope having been derived using data from one location. As such, the EPiC model is the first externally validated model for the prognosis of pediatric EVD using diverse datasets from geographically and temporally separate outbreaks. This model can be easily applied by bedside clinicians to assess pediatric patients at risk for death and help to allocate resources accordingly. [ABSTRACT FROM AUTHOR]

Background: Empiric antimalarial treatment is a component of protocol-based management of Ebola virus disease (EVD), yet this approach has limited clinical evidence for patient-centered benefits.Methods: This retrospective cohort study evaluated the association between antimalarial treatment and mortality among patients with confirmed EVD. The data was collected from five International Medical Corps operated Ebola Treatment Units (ETUs) in Sierra Leone and Liberia from 2014 through 2015. The standardized protocol used for patient care included empiric oral treatment with combination artemether and lumefantrine, twice daily for three days; however, only a subset of patients received treatment due to resource variability. The outcome of interest was mortality, comparing patients treated with oral antimalarials within 48-h of admission to those not treated. Analysis was conducted with logistic regression to generate adjusted odds ratios (aORs). Multivariable analyses controlled for ETU country, malaria rapid diagnostic test result, age, EVD cycle threshold value, symptoms of bleeding, diarrhea, dysphagia and dyspnea, and additional standard clinical treatments.Results: Among the 424 cases analyzed, 376 (88.7%) received early oral antimalarials. Across all cases, mortality occurred in 57.5% (244). In comparing unadjusted mortality prevalence, early antimalarial treated cases yielded 55.1% mortality versus 77.1% mortality for those untreated (p = 0.005). Multivariable analysis demonstrated evidence of reduced aOR for mortality with early oral antimalarial treatment versus non-treatment (aOR = 0.34, 95% Confidence Interval: 0.12, 0.92, p = 0.039).Conclusion: Early oral antimalarial treatment in an EVD outbreak was associated with reduced mortality. Further study is warranted to investigate this association between early oral antimalarial treatment and mortality in EVD patients. [ABSTRACT FROM AUTHOR]

Background Intravenous fluid (IVF) is a frequently recommended intervention in Ebola virus disease (EVD), yet its impact on patient outcomes remains unclear. Methods This retrospective cohort study evaluated patients with EVD admitted to 5 Ebola treatment units (ETUs) in West Africa. The primary outcome was the difference in 28-day survival between cases treated and not treated with IVF. To control for demographic and clinical factors related to both IVF exposure and survival, cases were compared using propensity score matching. To control for time-varying patient and treatment factors over the course of ETU care, a marginal structural proportional hazards model (MSPHM) with inverse probability weighting was used to assess for 28-day survival differences. Results Among 424 EVD-positive cases with data for analysis, 354 (83.5%) were treated with IVF at some point during their ETU admission. Overall, 146 (41.3%) cases treated with IVF survived, whereas 31 (44.9%) cases not treated with any IVF survived (P =.583). Matched propensity score analysis found no significant difference in 28-day survival between cases treated and not treated with IVF during their first 24 and 48 hours of care. Adjusted MSPHM survival analyses also found no significant difference in 28-day survival for cases treated with IVF (27.3%) compared to those not treated with IVF (26.9%) during their entire ETU admission (P =.893). Conclusions After adjustment for patient- and treatment-specific time-varying factors, there was no significant difference in survival among patients with EVD treated with IVF as compared to those not treated with IVF. [ABSTRACT FROM AUTHOR]

Background: Micronutrient supplementation is recommended in Ebola virus disease (EVD); however, there are limited data on therapeutic impacts of specific micronutrients.Objective: To evaluate the association between vitamin A supplementation and mortality in EVD.Methods: This retrospective cohort included patients with EVD admitted to 5 International Medical Corps Ebola Treatment Units (ETUs) in 2 countries during 2014-2015. Protocolized treatments with micronutrients were used at all ETUs: however, because of resource constraints, only a subset of patients received vitamin A. Standardized data on demographics, clinical characteristics, malaria status, and Ebola viral loads (cycle threshold values) were collected. The outcome of interest was mortality between cases treated with 200,000 IU of vitamin A on care days 1 and/or 2, and those not. Propensity scores based on the first 48 h of care were derived using covariates of age, ETU duration, malaria status, cycle threshold values, and clinical symptoms. Patients were matched 1:1 using nearest neighbors with replacement. Mortality between cases treated and not treated with vitamin A was compared using generalized estimating equations to calculate RR with associated 95% CI.Results: There were 424 cases analyzed, of which 330 (77.8%) were treated with vitamin A. The mean age was 30.5 y and 40.3% were men. The most common symptoms were diarrhea (85.6%), anorexia (80.7%), and abdominal pain (76.9%). Mortality proportions among cases treated and not treated with vitamin A were 55.0% and 71.9%, respectively. In the propensity-matched analysis, mortality was significantly lower among cases receiving vitamin A (RR = 0.77, 95% CI: 0.59, 0.99; P = 0.041). In a subgroup analysis of patients treated with multivitamins already containing vitamin A, additional vitamin A supplementation did not impact mortality.Conclusion: Early vitamin A supplementation was associated with reduced mortality in patients with EVD, and should be further studied and considered for use in future epidemics. [ABSTRACT FROM AUTHOR]

Background Experiments in vitro have shown that the drug amodiaquine may inhibit Ebola virus activity. During the Ebola virus disease (EVD) epidemic in West Africa in 2014–2016, 2 mass drug administrations (MDAs) of artesunate-amodiaquine (ASAQ) were implemented to decrease the burden of malaria. The objective of this study was to assess the effect of the ASAQ MDAs on the mortality of patients with EVD. Methods A retrospective cohort design was used to analyze mortality data for patients with EVD admitted to 5 Ebola treatment units in Liberia and Sierra Leone. Patients admitted to the ETUs during the time period of ASAQ's therapeutic effect from areas where the MDA was implemented were matched to controls not exposed to ASAQ, using a range of covariates, including malaria co-infection status, and a logistic regression analysis was performed. The primary outcome was Ebola treatment unit mortality. Results A total of 424 patients with EVD had sufficient data for analysis. Overall, the mortality of EVD patients was 57.5%. A total of 22 EVD patients were exposed to ASAQ during the MDAs and were found to have decreased risk of death compared with those not exposed in a matched analysis, but this did not reach statistical significance (relative risk, 0.63; 95% confidence interval, 0.37–1.07; P =.086). Conclusions There was a non–statistically significantly decreased risk of mortality in EVD patients exposed to ASAQ during the 2 MDAs as compared with EVD patients not exposed to ASAQ. Further prospective trials are needed to determine the direct effect of ASAQ on EVD mortality. [ABSTRACT FROM AUTHOR]