The Ebola virus
There have been 24 outbreaks of Ebola virus disease (also known as Ebola hemorrhagic fever) in Africa since 1976. It spreads through contact with infected body fluids. Case fatality rates have ranged from 25-90%, and the only treatment has been supportive care. The largest outbreak killed 11,323 people out of 28,646 infected, a 40% death rate. The current Ebola outbreak is the second-worst ever. 2,800 people have been infected and 1,900 have died (a 68% death rate). The World Health Organization has declared it a public health emergency of international concern.
Experimental treatments
A news release from the National Institutes of Health has just announced the early termination of an Ebola therapeutics trial in the Democratic Republic of the Congo because of favorable results with two of the four investigational agents being tested. These two drugs produced a 90% survival rate when given early in the course of the disease:
One of the drugs, REGN-EB3, is a cocktail of three monoclonal antibodies against Ebola made by Regeneron Pharmaceuticals of Tarrytown, New York. The second, mAB114, is derived from a single antibody recovered from the blood of a person who survived Ebola in the DRC in 1995, and was developed by the US National Institute of Allergy and Infectious Diseases (NIAID).
These two drugs outperformed the two other candidates. 53%of patients who got the anti-viral drug remdesivir died, as did 49% of those who got ZMapp, an antibody treatment that was used in an earlier Ebola outbreak.
Experimental vaccines
At least eight vaccines are in development. There is a handy list on Wikipedia . Most are in Phase I or animal studies, but two have reached the stage of Phase 3 trials. Clinical trials have been expedited due to the emergency. The two vaccines that have been tested in clinical trials have both been shown to be safe and effective: rVSV-ZEBOV and ChAd3-ZEBOV.
rVSV-ZEBOV (recombinant vesicular stomatitis virus – Zaire Ebola virus) is a live, attenuated, recombinant, replication-competent vaccine in which the vesicular stomatitis virus has been genetically engineered to express an Ebola protein, thereby provoking an immune response. It was developed by the Public Health Agency of Canada and is now licensed to Merck. It has been used in outbreaks in Africa. Interim results of an open-label study were published in The Lancet in 2015 and final results were published in 2017. They used a ring vaccination cluster-randomized strategy to vaccinate contacts and contacts of contacts of Ebola cases and compared immediate to delayed (21 days later) vaccination. One dose of vaccine was given by intramuscular injection. Immediate vaccination was 100% effective in preventing the development of the disease from 10 days after vaccination; protection appears not to kick in during the first 9 days. Serious adverse events were rare; only three were judged related to the vaccine and all three recovered with no sequelae. Part way through the trial, preliminary results were so impressive that randomization was stopped and immediate vaccination was offered to all participants. It was thought that the vaccine program had even benefitted non-participants by helping to shorten the outbreak.
In a more recent study in the Democratic Republic of Congo, preliminary results have been reported by the World Health Organization (WHO) on the efficacy of rVSV-ZEBOV-GP (Apparently GP stands for glycoprotein nanoparticle). 93,965 at-risk individuals were vaccinated using a ring vaccination strategy. “The estimated Ebola attack rate for vaccinated individuals was about 0.017%, compared with an estimated 0.656% in unvaccinated individuals. This yields an estimated vaccine efficacy of 97.5%, 95% CI [95.8 – 98.5%].” And no deaths occurred in anyone who developed symptoms 10 or more days after vaccination, for an estimated efficacy in preventing death of 100%. Even those already infected at the time of vaccination had improved survival.
The replication-defective chimpanzee adenovirus 3 (CAd3-ZEBOV) is an experimental vaccine for two Ebola viruses, Ebola virus and Sudan virus. It was genetically engineered by scientists at GlaxoSmithKline from a chimpanzee adenovirus to express Ebola protein. It appeared to be safe and effective in early trials and is currently being tested in Liberia in a three-arm double blind study comparing it to VSV-ZEBOV and placebo. Because of the declining incidence of the disease in Liberia, they have had to expand the trial to other countries. Results are not yet available.
Good news
Ebola is a horrible disease with a high fatality rate. A vaccine that is 100% effective in preventing disease and two medications that produce a 90% survival rate in patients who are already infected? It seems almost too good to be true, but the evidence is convincing. There is a phenomenon known as the decline effect, where studies with initially impressive results tend to be followed by larger, better studies with less impressive results. Because this is a public health emergency, short-cuts have been taken in the usual drug- and vaccine-development procedures, and the treatments have been rushed into use under compassionate use guidelines. It appears that the vaccines have already had an impact in shortening outbreaks, and the treatments have saved lives.
Science works!
This is a great demonstration of science in action. Science-based medicine works! Complementary and alternative medicine can’t offer anything even remotely comparable. The CDC has even had to issue this warning:
Since the outbreak of the Ebola virus in West Africa, the U.S. Food and Drug Administration (FDA) has seen and received consumer complaints about a variety of products claiming to either prevent the Ebola virus or treat the infection. The FDA is advising consumers to be aware of products sold online claiming to prevent or treat the Ebola virus. There are currently no FDA-approved vaccines or drugs to prevent or treat Ebola, and there are no known herbal treatments or other “natural” or “alternative” therapies that prevent or cure this disease.