As the Ebola outbreaks rages on in West Africa, the World Health Organization (WHO), desperate for a way to help infected people, is reconsidering a potential Ebola treatment tried as far back as 1976, after the first documented outbreak of the deadly viral disease: using the blood of people who have recovered from an infection to treat those still fighting the virus. “Convalescent serum is high on our list of potential therapies and has been used in other outbreaks (eg in China during SARS),” WHO said in a written statement to ScienceInsider. “There is a long history of its use, so lots of experience of what needs to be done, what norms and standards need to be met.”
There are not yet official plans to administer convalescent serum to ill people, but WHO said it will assess if the treatment approach was “safe and feasible” and was already working with officials in Ebola-affected areas to strengthen the blood-banking systems there. These moves come as researchers debate the mixed results of past uses of convalescent serum. “The jury is still out” on the approach, says Daniel Bausch, an Ebola expert at Tulane University in New Orleans, Louisiana. Nonetheless, he and others believe the therapy should be explored. “I feel we have a moral imperative to push forward with all the scientifically plausible modalities,” Bausch says.
The Ebola virus has sickened at least 2127 people and killed 1145 of them in Sierra Leone, Guinea, Liberia, and Nigeria. Those numbers may “vastly underestimate the magnitude of the outbreak,” WHO warned on Thursday. It is already the largest Ebola outbreak ever recorded, and the unprecedented number of deaths has led to calls to try out experimental therapies that are in the early stages of development. On Tuesday, an ethics committee at WHO declared it was ethical under the special circumstance to use unapproved Ebola treatments such as ZMapp, a mix of antibodies that has been tested in animals and was given to two U.S. health care workers who fell sick in Liberia. Other experts are advocating the use of drugs that are approved to treat other diseases but may help Ebola patients, too. And Nigeria is reportedly exploring a controversial treatment called Nano Silver.
As for using convalescent serum to treat patients, it is an attractive option for a number of reasons, Bausch says. Getting blood transfusions has become commonplace; no approval from agencies such as the U.S. Food or Drug Administration or European Medicines Agency is needed, and in the affected countries in West Africa many people have survived Ebola, meaning there can be a ready supply of the serum. In fact, the therapy has already been tried in the current outbreak. One of the two U.S. health care workers who was treated with ZMapp, Kent Brantly, earlier received a blood transfusion from a 14-year-old boy he had cared for and who had survived Ebola.
But like the other treatments under discussion, it is far from proven that convalescent serum will help Ebola patients. The idea is simple: Because survivors have usually developed antibodies to fight the virus, transferring their blood could help patients. In the past, the strategy was used to treat people with SARS and Lassa fever, a viral hemorrhagic fever, like Ebola. David Heymann, an epidemiologist at the London School of Hygiene & Tropical Medicine and a former executive director of communicable diseases at WHO, says that the therapy’s use in 1976 was encouraging. Heymann, who was part of a team investigating the outbreak in Zaire, stayed behind for 2.5 months collecting a unit of blood every week from survivors, he says. The outbreak ended before the serum could be used in Africa, but some of it was given later that same year to a researcher in the United Kingdom who accidentally pricked infected himself while transferring blood from a guinea pig infected with Ebola. He survived. “The blood was stored in South Africa and at the CDC in Atlanta, but I don’t know what happened to it,” Heymann says.
Convalescent serum was tried again in 1995 in an Ebola outbreak in Kikwit in the Democratic Republic of the Congo. Doctors at the Kikwit General Hospital treated eight Ebola patients with blood donated by five people who had survived their infections. Seven of those receiving the serum also survived. A later reanalysis, however, concluded that the patients had survived their infection long enough before receiving the serum that they likely would have recovered without it. And a study in rhesus macaques, published in 2007, found no benefit from transferring blood of convalescent monkeys. “There are many variables and the quality of the immune blood or serum may vary widely from person to person,” says Thomas Geisbert, a researcher at the University of Texas Medical Branch in Galveston and one of the authors of that study.
The WHO filovirus clinical working group, convened in response to the current outbreak, discussed the evidence on convalescents’ serum at a meeting in Geneva, Switzerland, at the end of July, says Bausch, who is part of the group. A plan was proposed to fly blood of Ebola survivors to the United States and have Geisbert or Heinz Feldmann, a researcher at the National Institute of Allergy and Infectious Diseases , try the therapy in nonhuman primates, Bausch says. But Geisbert, in an e-mail, notes that there are “no current plans to test this in nonhuman primates” and there has been “no official request from any agency” though he and Heinz “are both willing and ready to do whatever is needed to support the outbreak response.” Tom Solomon, director of the United Kingdom's Health Protection Research Unit in Emerging Infections based at the University of Liverpool, says he is also considering a trial of the therapy in humans. “We are in discussions with WHO and an international group of partners to develop a trial and are looking at both convalescent plasma and novel therapeutics,” he says. If serum is tested on humans, it should be checked in advance that it can neutralize the virus, says Stephan Günther, a virologist at the Bernhard Nocht Institute for Tropical Medicine, who is now in Nigeria. “Otherwise, you don’t need to give the serum.” Neutralization could be measured in cell culture with real virus or a recombinant vaccine virus expressing the Ebola virus surface protein, Günther says.
Even if the therapy works, there are challenges. One is the risk of infecting patients with other pathogens such as HIV or hepatitis C. Getting blood from recovered patients in the first place may also be a problem, Bausch says. “Blood is an entity that people pay a lot of attention to in West Africa. When people feel like they are losing blood that is an important and bad thing,” he says. Still, trying the therapy in nonhuman primates and then implementing it in the affected countries in West Africa makes sense, Bausch says. “It’s gonna be messy, it’s gonna be difficult to do, but at some point we’ll just have to try to plunge in and move forward.” Robert Colebunders, an infectious disease clinician at the University of Antwerp in Belgium, who was involved in treating Ebola patients in the 1995 outbreak, says if there are survivors willing to donate blood, doctors should try the therapy. “And then they need to follow it up scientifically, so we learn something from it.”
Still, WHO warned today in a statement, the focus on untested therapies is “creating some unrealistic expectations. … The public needs to understand that these medical products are under investigation. They have not yet been tested in humans and are not approved by regulatory authorities, beyond use for compassionate care.”
Focus on the therapies is also distracting from what really needs to be done, says Steven Riley, an infectious disease epidemiologist at Imperial College London. “We don’t need to export drugs. We need to export gold-standard public health processes,” he says. Infectious disease experts agree that tracing those who have been in contact with an infected person and isolating them is the key to containing the deadly virus.
*The Ebola Files: Given the current Ebola outbreak, unprecedented in terms of number of people killed and rapid geographic spread, Science and Science Translational Medicine have made a collection of research and news articles on the viral disease freely available to researchers and the general public.