While Ebola case numbers are rising exponentially in western Africa, and a handful of cases have appeared in the U.S., doctors are scrambling to understand how the virus affects humans and how best to treat those infected. Until last summer, when the NEJM began publishing reviews and perspectives on the current outbreak, few physicians were knowledgeable of Ebola Virus Disease (EVD).
Yesterday I spoke with Dr. Louis Katz, an infectious disease expert and Chief Medical Officer of America’s Blood Centers. This week he and that agency, with help from the Community Blood Center of Greater Kansas City, orchestrated donation of plasma – the fluid part of blood – from a recovering Ebola patient to be given to another person receiving treatment.
Doctors first referred to Ebola as a hemorrhagic fever when it was initially described in 1976. Many of the feverish patients seeking care had noticeable blood in what they vomited and in diarrhea. A smaller group experienced oozing in other body parts such as in the mouth or inside the eyes. Today, the Centers for Disease Control lists Ebola on its page of viral hemorrhagic fevers.
It turns out that most patients don’t bleed so much. “Ebola has that reputation,” Katz said. “But it’s really just a small minority of people infected who bleed significantly.” Ebola patients often develop low platelet counts, he confirmed. With Ebola, the platelets – clotting cells – typically dip to the range of 50-100 thousand platelets per microliter of blood (a normal range, in most labs, falls between 150 and 400 thousand). “That drop may not be sufficient to cause bleeding,” he said.
What happens in some severe cases is that the liver fails, leading to reduced synthesis of coagulation (clotting) proteins. Ebola can infect and destroy endothelial cells – the cells lining the inside of blood vessels – which adds to problems with the circulation and clotting. Some patients develop a condition called disseminated intravascular coagulation (DIC), a condition in which clotting proteins and platelets are inappropriately consumed inside of blood vessels, rendering them unavailable to stabilize nicks where bleeding begins.
“The virus infects lots of different cells, the lining of blood vessels. It can make the platelets go low, and can produce a shock state that can result in loss of clotting factors,” Katz said. “It’s multifactorial, not a simple thing. So how much the low platelets contribute to bleeding is unknown,” he said.
Recently Dr. Anthony Fauci summarized one of the largest published series of Ebola cases, a 1999 review of 103 patients treated in the Democratic Republic of the Congo. There and then, most patients suffered fever and extreme fatigue with nausea, vomiting, abdominal pain and diarrhea. As reported, under half of those patients experienced bleeding.
Controlled clinical observations are lacking. Prior to this year’s outbreak, most published Ebola reports date to the 1980s and 1990s and include limited if any laboratory information about the patients. “There were no trials. Reports are incomplete," Katz said. “Every bit of information we have on Ebola treatment is provisional.”
When someone has an Ebola infection, their immune system is compromised because the virus infects white blood cells including macrophages. The virus causes death of lymphocytes, jeopardizing patients’ capacity to manufacture antibodies or mount other components of a virus-fighting response.
Convalescent plasma – removed from someone who’s recovered from an infection – contains antibodies that may neutralize the virus. This sort of treatment, a passive immune therapy, goes at least as far back to the late 19th Century. A German immunologist, Emil von Behring, received a 1901 Nobel Prize in medicine for developing serum with anti-toxins to counter diphtheria. “It was used in some patients who recovered from the 1918 flu,” Katz said. Other examples include its use in patients with Argentine hemorrhagic fever. “For that viral disease, convalescent plasma is considered a key intervention,” he added.
Proof is lacking, he acknowledges. That’s mainly because all Ebola patients who’ve received convalescent plasma have also received other supportive care, like intravenous fluids.
“But those antibodies in the plasma may be life-saving,” Katz said. “We don’t know for sure. It could be that healthy plasma, without the antibodies, could help too.” he considered. “We need to do a trial for that.”
Before whole blood or plasma from a may be given to another Ebola patient, it is checked by very sensitive methods including PCR to assure the Ebola is gone according to WHO criteria, Katz explained.
“Very little convalescent or whole blood is being used in West Africa,” he noted. Collecting and processing blood may be more difficult there. “Screening the blood is hard, and the infrastructure is limited. So convalescent plasma hasn’t been used much, despite the fact that the WHO has supported its use in Ebola patients,” he said.
Overall, Katz is optimistic about the prognosis for Ebola patients in the United States. “The mortality statistics will be much lower here,” he said. You can’t compare what happens here with the circumstances in western Africa. “Without basic laboratory monitoring, or even providing basic fluids, it’s much harder to take care of people.”
“Here we can take care of people with goal-directed, supportive care,” he concluded. “And we can carefully study how these treatments may work.”
