The best chance for an immediate treatment for Ebola patients in the worst outbreak ever may be readily available, in the blood of survivors.
With experimental drugs in short supply or not ready to be used, global health officials are exploring whether the natural immunity survivors gain after they shed the virus can be shared with others. The idea would be to use their plasma, the part of blood that contains immune system warriors called antibodies, to help fight off the infection.
Some early research suggests using blood from survivors could work. In 1995, during an outbreak in Kikwit in the Democratic Republic of Congo, seven of eight infected people given the therapy survived during an outbreak with an 80 percent fatality rate. While lab studies since then have shown conflicting results, the strategy is worth trying again as the current death toll rises, said David Wood, who leads a World Health Organization team evaluating the approach.
It is “a feasible option,” Wood said in a telephone interview. “We’re consulting with the blood operators who have capability to assist, so that we can get some realistic sense of when this could be available as an option. We’ll have that information pretty soon.”
The WHO reported that 1,145 people have died as of Aug. 13 from Ebola in Guinea, Sierra Leone, Liberia and Nigeria since the outbreak began. The virus carries a terrible toll, causing bleeding from the eyes, ears and nose with most patients dying from multiple organ failure.
About 40 percent of people infected in the current outbreak have beaten the disease, according to the WHO. It’s that minority that researchers are targeting for a treatment that may not require drugmakers to be involved at all. Once the researchers get the blood, they’ll test it for other diseases, including HIV and hepatitis, and then separate out the plasma.
Antibodies in plasma are produced by white blood cells in response to foreign invaders in the body. They bind to the microbes, either neutralizing them or flagging them for other parts of the immune system to attack.
Mary Kate Hart, an immunology researcher who did early studies of Ebola antibodies for the U.S. Army, said that transfusions from survivors may carry a benefit, especially if given early in the course of the disease, and are likely to be relatively safe.
“It is not a crazy idea to try,” said Hart, who is now chief scientific officer for DynPort Vaccine Co. and no longer involved in the antibody research.
Kent Brantly, the American aid worker infected with Ebola in Liberia last month, was given such a treatment.
Brantly received a blood transfusion from a 14-year-old survivor, according to Samaritan’s Purse, a North Carolina-based aid group. He also received an experimental antibody-based therapy from Mapp Biopharmaceutical Inc.
While Brantly has been improving, it’s not known if either the blood transfusion or the treatment called ZMapp aided his recovery, or whether his own immune system fought off the virus.
Last week, the WHO said that unproven drugs and vaccines could ethically be used during the current outbreak given there are no approved treatments. The supply of Mapp’s drug has already been exhausted, however, and preventive vaccines may not be available for at least a month.
“While many efforts are under way to accelerate production, supplies will not be augmented for several months to come,” the WHO said in an Aug. 15 statement. “Even then, supplies will be too small to have a significant impact.”
The blood serum has also been used in outbreaks of SARS and severe influenza, and was associated with a 75 percent reduction in the risk of death, according to a review study published last month.
“This would be something that countries could try themselves, and it would be much more feasible and much more immediate,” said David Heymann, a professor of infectious diseases at the London School of Hygiene and Tropical Medicine. “But it shouldn’t take precedence over outbreak containment.”
In addition to the eight patients in Congo, serum was also used to treat a researcher infected in a laboratory accident in the U.K. in 1976. The researcher recovered, but it’s not clear whether the serum helped, according to Heymann, who collected blood from survivors of the first outbreak in 1976.
Doctors treating a researcher in the U.S. infected in a similar accident in 2004 decided against using serum because there was no safe readily available source and little evidence existed to support its use.
The evidence remains piecemeal and conflicting. A 2007 study using blood from survivor animals to treat monkeys infected with Ebola virus found no effect.
“The whole idea of convalescent serum is controversial,” said Thomas Geisbert, the virologist at the University of Texas Medical Branch who was a senior author on that study. The patients who received the serum in Congo may have gotten better anyway, according to Geisbert.
“I’m very nervous about anything that hasn’t been shown to be efficacious in a non-human primate,” he said.
In 1995, the transfusions were done by Congolese medical officials, and some international doctors were skeptical and not supportive at the time, said Robert Colebunders, a professor of infectious diseases at the University of Antwerp, Belgium, who co-authored a study describing the experiment.
‘Lot of Skepticism’
“There was a lot of skepticism about this result; the explanation is not clear,” said Colebunders, who was in Congo for part of the outbreak but left before the transfusions were given. “It is still a very interesting result.”
There are several reasons that may explain the high survival rate in the transfused patients apart from gaining the antibodies of Ebola survivors.
The transfusions occurred at the end of the outbreak, when care for Ebola patients might have been better. Giving blood that contains coagulation factors to severely sick people who are hemorrhaging may be helpful, Colebunders said.
“Whether it was the antibodies that did the job, that is more questionable,” he said.
Still, San Diego-based Mapp said last week that the supply of its experimental medicine has already been exhausted. And the WHO said about 1,000 doses of an experimental vaccine donated by the Canadian government probably won’t be ready for at least a month as the agency tries to confirm its safety.
“Since the crisis is severe and growing there is an urgent need to evaluate potentially useful therapies such as convalescent plasma,” said Jonathan Nguyen-Van-Tam, a professor of health protection at the University of Nottingham School of Medicine.