Treating Ebola patients with convalescent plasma from Ebola survivors is feasible, safe and acceptable to donors, patients and health workers, say findings from the Ebola-Tx trial, carried out during the recent crisis and published in the New England Journal of Medicine.
Until the 2014 outbreak, blood products from Ebola survivors had only been used experimentally for treatment in a small number of Ebola patients.
The Ebola-Tx trial was carried out at the Donka Ebola Treatment Center in Conakry, Guinea, run by Médecins Sans Frontières (MSF).
The trial was led by the Antwerp Institute of Tropical Medicine (ITM) and funded by the European Union (EU), and it is the largest ever trial of convalescent plasma (CP) for the treatment of Ebola.
It was the high fatality rate of Ebola that led to the need to identify treatments that directly targeted the virus, such as CP. The World Health Organization (WHO) had prioritized CP due to its success in treating other viral diseases like measles, yellow fever and influenza.
Experimental treatment in a crisis
Researchers did not know what impact, if any, CP might have against Ebola, what might be an effective dose, or whether patients and the community would accept transfusions with a blood product.
The Guinean national blood transfusion centre (CNTS) collected blood plasma for the trial, in close collaboration with the French public transfusion services, the Guinean Ebola survivors association from Conakry and a group of anthropologists.
Blood constituents were separated, and any parts not required were returned into the donor's circulation. This provided over 200 plasma units.
A total of 102 patients were enrolled, 84 of whom were then treated with CP. Patients were of any age, including pregnant women. They received two units of 200-250 ml from different convalescent donors within 48 hours of a laboratory-confirmed diagnosis of Ebola.
At the time, the levels of Ebola virus-neutralizing antibodies in the CP were unknown, as tests were not available on site to measure them.
Trial safe despite insignificant impact on survival rates
The 84 CP patients were compared with 418 patients who had been attending the same treatment center in the 5 months before the trial. The primary outcome was survival 14 days after transfusion, adjusted for age, and the level of Ebola virus in the blood at diagnosis.
Patients who died within 2 days of diagnosis were excluded. A 20% lower mortality in the CP group was considered significant.
Mortality from day 3-16 was 31% in the CP group and 37.8% in the comparator group; but the difference was reduced to only 2.6% after adjusting for age and viral load. The treatment as given in the trial did not significantly improve the survival rate, but no severe adverse reactions to CP were observed.
Coordinating investigator Prof. Johan van Griensven, of Antwerp ITM, believes that while a single administration of 2 units of CP does not save lives, a more targeted and concentrated use of plasma, with a different level of antibodies, could improve outcomes.
- In the 2014-15 Ebola crisis, there were 28,637 cases
- 11,315 people died
- The three countries most badly affected were Liberia, Guinea and Sierra Leone.
Despite the study not providing the answer that was hoped for, he says, scientists have gained important information about the role of CP in treating Ebola and the feasibility of organizing this kind of intervention in a crisis situation.
CP samples have been shipped to France for analysis; it is hoped that additional findings will indicate whether plasma with different levels of antibodies could be more effective. Researchers envisage a potential role for CP in a different dose and/or in combination with other treatments currently under investigation, such as Favipiravir.
CNTS director Dr. Nyankoye Haba says the Ebola survivors made the study possible by offering their plasma and encouraging their peers to do likewise. Long-term benefits of the study, he says, include the opportunity for the CNTS to use cutting-edge technology, as well as building the capacity of staff.
Dr. Ruxandra Draghia-Akli, director of the European Commission's Health Directorate, commends the achievement of performing a clinical trial under such challenging conditions, adding that it was the people of Guinea, the donors and local community support who made the trial possible.
Marie-Paule Kieny, of the WHO, says:
"This trial has been helpful in establishing the safety of convalescent plasma, and it tells us that the procedure was accepted by the community. While only a first step, it tells us that plasma may be worth exploring as a treatment in the future, potentially by using donations with high-antibody levels."
Medical News Today recently reported that the WHO declared that Ebola transmission had ended in Guinea.