The Course of Ebola Virus Disease

When a glycoprotein in the Ebola virus envelope binds to a receptor on an antigen-presenting cell, the activated cell goes right to a lymph node and “presents” the antigen (the virus) to cells in the immune system. Thus, like the AIDS virus, Ebola begins by attacking the body’s defenders. Then as it spreads through the body, it also attacks endothelial cells (the lining of blood vessels), liver cells, and many other cells.

Cells that are most seriously affected by Ebola virus disease include the trachea, the cornea, and the conjunctivae. The affected cells not only release viral progeny, but small proteins that are involved in the inflammatory response. Overreactivity of the response – called a “cytokine storm” – can be extremely damaging in itself.

Capillary beds throughout the body leak, causing low blood pressure that may become progressively unresponsive to intravenous fluid therapy or vasopressors (drugs that increase the blood pressure). This can lead to the formation of tiny blood clots, which block the tiny blood vessels in the system and can also consume the body’s clotting factors so that the blood becomes unable to clot, causing paradoxical bleeding. This is called disseminated intravascular coagulation, or DIC.

Damage to the vascular system contributes to the multiple organ dysfunction syndrome. Kidneys, liver, and heart may ultimately be involved. When blood supply to the bowel is compromised, bloody diarrhea may result. It is difficult to reverse established organ damage.

The chance of survival diminishes as the number of involved organs increases, and the mortality rate of the multiple organ dysfunction syndrome has changed little since it was first recognized in the 1980s. Classically, symptoms begin between two and twenty-one days after contracting the disease, eight to ten days being the most common time. It is suggested that the incubation period should be extended to twenty-five days, which would be two standard deviations from the mean.

The World Health Organization reports that some infections begin as long as forty-two days after exposure. Symptoms generally begin with fever. However, as many as 15 percent of cases may not have fever, so absence of fever does not absolutely rule out the disease. Other early symptoms and signs include a heart rate greater than ninety beats per minute, headache, muscle pain, nausea, and loss of appetite. In Sierra Leone, the most common symptoms reported between symptom onset and case detection included fever (87.1 percent), fatigue (76.4 percent), loss of appetite (64.5 percent), vomiting (67.6 percent), diarrhea (65.6 percent), headache (53.4 percent), and abdominal pain (44.3 percent). Hemorrhagic symptoms were rarely reported, but unexplained bleeding occurred in 18 percent of cases.

Of course, these symptoms also occur in many other illnesses. A flat spotty skin rash may develop on the face and chest on day two or three in about half of the cases, likely coinciding with an initial burst of virus in the blood and the onset of the systemic inflammatory response. Internal and external bleeding generally begins to appear within five to seven days after the first onset of symptoms. This may occur in the conjunctivae, giving the dreaded appearance of “bleeding eyes.”

Specialized rapid diagnostic tests exist, but are not generally available in your standard hospital or commercial laboratory, and specimens require very special handling. Severe vomiting and diarrhea can cause death from dehydration, with patients possibly needing up to ten liters of fluid replacement in a day. The mortality rate in West Africa is running at 70 percent.

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