Pathology

Initial filovirus infection is followed by an incubation period lasting 4-10 days, before symptoms develop. Initial symptoms include fever, chills, myalgia, and malaise. As infection progresses, symptoms escalate to nausea, vomiting, abdominal pain, chest pain, coughing, shortness of breath, edema, diarrhea, headache, and coma. The bleeding that characterizes hemorrhagic fevers is particularly severe in filovirus infection. Mucosal hemorrhage, oozing from venipuncture sites and a macropapular rash are common by day 5 of infection and often useful diagnostic indicators. Worsening symptoms or signs of recovery are usually observed around day 7, coincident with the antibody response, with the majority of patients succumbing to death induced by metabolic disturbances and shock.

The pathogenesis of infection is similar for all observed species of filoviruses. Dendritic cells, monocytes and macrophages are implicated as sites of early infection, impairing the immune response from the beginning. These infected cells not only become ineffective in combating the virus, but may also serve as vehicles to transport virus to other locations throughout the body, such as the lymph nodes, liver, lungs, and spleen. It has also been shown that infection of cells with Ebola virus inhibits the activation and expression of immunomodulatory and antiviral genes, such as MHC Class I, IRF1, and PKR, allowing infected cells to escape immune surveillance. (Click image for larger version)

While infection of macrophages and dendritic cells disrupts their normal immunologic functions, it may also cause aberrant production of extremely high levels of cytokines such as TNF-a, IL-2, IL-10, and IFN-?. These cytokines may contribute directly to the pathology of the disease. Monocytes have also been implicated as a possible source of the overproduction of tissue factor (TF), a cell-surface glycoprotein that plays a key role in the initiation of coagulation protease cascades. These cascades result in the accumulation and deposition of thrombin and fibrin causing microthrombi to form in capillaries and microvasculature, block blood supply to vital organs. This disseminated intravascular coagulation provides another mechanism for the widespread organ failure associated with filovirus infection.

Characteristic pathology is seen in all filovirus infections. Extensive necrosis of the liver, spleen, kidneys, and gonads commonly noted, with the liver showing both the most severe necrotic damage and the highest viral titers. Infection also results in damage to endothelial cells, and particularly capillary endothelium. This increases capillary permeability and is responsible for the uncontrolled bleeding associated with infection. The extent to which the spleen and lymph nodes are damaged may be a direct contributor to the outcome of the disease, with survivors escaping irreparable damage to these organs.

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This page last updated: 14 April 2004.