The Pathogenesis of Ebola Virus Disease

Abstract

For almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the African continent to cause epidemics of highly fatal hemorrhagic fever. The 2013-2015 West African epidemic, by far the most geographically extensive, most fatal, and longest lasting epidemic in Ebola's history, presented an enormous international public health challenge, but it also provided insights into Ebola's pathogenesis and natural history, clinical expression, treatment, prevention, and control. Growing understanding of ebolavirus pathogenetic mechanisms and important new clinical observations of the disease course provide fresh clues about prevention and treatment approaches. Although viral cytopathology and immune-mediated cell damage in ebolavirus disease often result in severe compromise of multiple organs, tissue repair and organ function recovery can be expected if patients receive supportive care with fluids and electrolytes; maintenance of oxygenation and tissue perfusion; and respiratory, renal, and cardiovascular support. Major challenges for managing future Ebola epidemics include establishment of early and aggressive epidemic control and earlier and better patient care and treatment in remote, resource-poor areas where Ebola typically reemerges. In addition, it will be important to further develop Ebola vaccines and to adopt policies for their use in epidemic and pre-epidemic situations.

Post-exposure treatments for Ebola and Marburg virus infections

“…Clinical and laboratory signs of disease caused by filovirus infection are nonspecific and usually associated with an incubation period of 2-21 days (mean 4-10 days) 8,17 . Illness begins with an abrupt onset of fever, asthenia, myalgia and arthralgia, and can include a number of other nonspecific indications 8,17 .…”

“…Illness begins with an abrupt onset of fever, asthenia, myalgia and arthralgia, and can include a number of other nonspecific indications 8,17 . Hypovolaemic shock and multiple organ failure are associated with severe and fatal cases.…”

“…Humans and NHPs are naturally exposed to filoviruses through mucosal surfaces or small abrasions and/or breaks in the skin 8,17 . Filoviruses have a broad cell tropism and productively replicate in numerous cell types.…”

Clinical Evaluation of Ebola Virus Disease Therapeutics

“…EBOV belongs to the genus Ebolavirus , which causes EBOV disease (EVD) – clinically manifested by a spectrum of symptoms including fever, fatigue, muscle pain, vomiting, diarrhea, anorexia, rash, bleeding and multi-organ failure [1, 2]. Disease fatality rate can be up to 90% (http://www.who.int/mediacentre/factsheets/fs103/en/).…”

“…Indeed, dysfunctional macrophages and dendritic cells likely cause deregulated innate immunity through the excessive production of proinflammatory cytokines and chemokines, as well as by suppression of adaptive immune responses against EBOV due to compromised presentation of antigen to lymphocytes and inadequate expression of co-stimulatory factors [12]. While there have been studies in mice [13] and humans [14] showing substantial involvement of adaptive immunity in advanced EVD, particularly the activation CD8 + T-cells, the systemic dissemination and robust viral replication stemming from an inability to control the infection at early disease stages eventually leads to multi-organ failure [1]. Therefore, strategies to develop targeted therapies against EVD are mostly focused on blocking viral entry and inhibiting viral replication [15].…”