A serendipitous finding suggests a malaria drug may be useful as a treatment against Ebola, scientists reported Wednesday in the New England Journal of Medicine. That encouraging news was tempered, though, by a report that suggests a treatment many had hoped would help Ebola patients survive didn’t work in another study.
The second study, published in the same journal, found that giving Ebola patients two transfusions of plasma — a blood product — from survivors of the disease did not improve their chances. It was thought antibodies in survivors’ blood might intensify the immune response in Ebola patients.
Researchers and the World Health Organization were quick to point out the disappointing findings shouldn’t be read to mean survivors’ blood has no place in Ebola treatment. They said transfusions containing high concentrations — known as titers — of antibodies might still work.
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Combined, the two studies show both the importance of testing would-be therapies and of sheer luck in research.
In August 2014, when the West African Ebola outbreak was at its peak, there wasn’t much talk of good luck. And it didn’t seem fortuitous when a Doctors Without Borders treatment facility in Foya, Liberia, ran out of its standard malaria drug.
The group, known by its French acronym MSF, routinely gives patients suspected of having Ebola anti-malarial drugs because if they are infected with malaria, the drugs will help, and if they are not, the drugs will protect them from malaria for a time.
But when the drug, artemether-lumefantrine, ran out, the team in Foya turned to a different anti-malarial, artesunate-amodiaquine. Twelve days later, when the first drug became available again, they switched back.
Health professionals working at the treatment unit didn’t notice a difference at the time. But months later, when the crush of patients had subsided and there was time to look at treatment data, researchers noticed something unexpected.
The survival rate of patients who took artesunate-amodiaquine was higher than that of patients who received artemether-lumefantrine. Patients who got the replacement drug actually had a 31 percent lower risk of dying than those who received the anti-malarial typically used.
“Essentially what you’ve got here is MSF changed the treatment because they were forced to. … And in doing so, this was serendipity. They made an observation. And that observation was statistically valid,” said Martin Friede, who leads the WHO’s efforts to promote development of therapeutic products for Ebola. Friede was not involved in the research, but helped the scientists write up the study.
The researchers admitted they don’t know how to interpret the finding. Artesunate-amodiaquine had been previously shown to have some effect against Ebola viruses in test tubes. So was the drug actually fighting Ebola? Or was artemether-lumefantrine, which has some known side effects, actually lowering survival chances?
MSF didn’t wait for those answers. Dr. Iza Ciglenecki, the group’s research coordinator and senior author of the new study, told STAT that when the organization saw the data, it changed its policy. From then on, suspected Ebola patients received artesunate-amodiaquine.
But the WHO and others would like to know the answer. If artesunate-amodiaquine actually helps Ebola patients survive, it should be given to them — even if the Ebola cases crop up in places where malaria doesn’t spread, Friede said. He noted scientists at the US National Institutes of Health are testing artesunate-amodiaquine in animals to see if it helps improve Ebola survival.
The convalescent plasma study, which was conducted in Guinea, will also lead to more research.
At the time it was conducted, there was no way to test on the spot donated blood from survivors to check the levels of antibodies it contained. But a little bit of each donation was saved to be tested later.
David Wood, a WHO scientist who was not involved in the study, said those samples will be analyzed to determine antibody concentrations. That information could show there is an optimal time to collect blood or plasma from survivors — say a couple of months after their infection. If that’s the case, using plasma drawn from more recent survivors might not help.
The additional research may also show that two transfusions were too few and more plasma would be needed to fight the infection, said lead author Dr. Johan van Griensven, of the Institute of Tropical Medicine in Antwerp, Belgium. He suggested additional work in animals might help to answer these questions.
That said, some longtime Ebola researchers had been doubtful about the value of trying to treat patients with blood from survivors.
Tom Geisbert of the University of Texas Medical Branch in Galveston published a study in 2007 showing whole blood drawn from non-human primates that had survived Ebola did not save primates that were experimentally infected with the virus.
Last year his group reported that they had repeated the effort, using plasma instead of whole blood. But it still didn’t save infected primates. “So the [human] results … are not too surprising to me,” Geisbert said in an email.
It’s unlikely that researchers will throw in the towel on convalescent plasma for Ebola just yet. In the absence of drugs that are proven to be effective against Ebola, it’s a response that can be tried in even relatively low-resource settings.
“It comes into people’s minds immediately. This is something that can be done,” Wood said. “And I think that therefore it is imperative that we learn more about how to do it and how to do it effectively.”