The pathogenesis of EVD is not well understood and most data are derived from laboratory studies. This is due, in part, to the inaccessibility of areas where Ebola arises and the lack of adequate medical facilities to treat cases.9 Once the Ebola virus enters the body, it has deleterious effects on multiple cell types. Macrophages are the first targeted cells and are major players in the proinflammatory cascade.16 Filoviruses have the ability to replicate rapidly, causing a large release of viral particles into the bloodstream. Subsequent spread to multiple tissues and organs causes extensive tissue damage and a systemic inflammatory response.10 Large amounts of chemokines, cytokines, and other proinflammatory mediators are released from cells.19 This systemic response, along with tissue damage, leads to diffuse vascular leakage and multiorgan failure.
The hemorrhagic effects of Ebola virus are due to the host inflammatory response, which induces the extrinsic coagulation pathway, by the presence of tissue factor synthesis and release.15,27 However, frank hemorrhage is seen in a minority of patients; unexplained bleeding was reported in 18% of cases during the 2014 outbreak.28 Progression of the disease to include hepatic injury and necrosis further disrupts the coagulation pathway.10,14 Viral effects on the gastrointestinal tract lead to vomiting and diarrhea, resulting in massive volume depletion and shock.18 Vascular leakage from the gastrointestinal tract can also lead to translocation of bacteria and development of bacterial septic shock.25,29 The multiorgan dysfunction associated with EVD leads to high levels of morbidity and mortality; 2014 data from the WHO Ebola Response Team indicated a case fatality rate of over 70% in Guinea, Liberia, and Sierra Leone, 21 though this may be an underestimate due to underreporting.
Though our understanding of EVD continues to improve, predicting who is at increased risk of death remains a challenge. A 2014 paper by Peacock et al that evaluated biomarkers of survival found that children aged < 5 years had an increased rate of death; however, the specific reasons for this have not been fully elucidated.4 Significant elevations of certain markers such as IL-10 or increased endothelial responsiveness, especially early in the disease, were associated with increased mortality in children and adolescents. It is therefore possible that, despite being infected with the same virus, the unique physiology of children results in different pathophysiological mechanisms of disease.5,30
Marlie Dulaurier, MD;Katherine Moyer, DO;Rebecca Wallihan, MD
July 2, 2016
August 2, 2019
4 AMA PRA Category 1 Credits™, 4 ACEP Category I Credits, 4 AAFP Prescribed Credits, 4 AOA Category 2-A or 2-B Credits. Specialty CME Credits: Included as part of the 4 credits, this CME activity is eligible for 0.5 Pharmacology CME credits