Ebola, Ça suffit! (Ebola, that’s enough!): Progress has been made on Ebola and other diseases

Part 2 of 2


Ebola virus periodically leaps out of a reservoir in Africa and causes high mortality in humans and great apes. We do not know for sure where the virus hides in the interim, but speculation centers on fruit bats. 

Usually the epidemics are small and are contained by quarantine and isolation, but the large outbreak in Sierra Leone, Liberia and Guinea in 2014 and 2015 caught the World Health Organization and other agencies unprepared. 

You may recall a heroic but disorganized response with many deaths and desperately sick doctors and nurses being evacuated. Yet, the scientific and medical community did assemble a clinical trial of a vaccine that was based on a virus called rVSV-ZEBOV. That trial, in French speaking Guinea, was called Ebola, Ça suffit!  

The epidemic was waning early in 2015, but it presented an opportunity because infections became patchy — a single person would come down with Ebola disease and infect those nearby, perhaps caregivers. The infection would spread outward with a ripple effect, and there were many such clusters of infection, all isolated one from the other.

From April 1, 2015, through July 20, 2015, the Ebola Ça suffit clinical trial team found 90 clusters of disease. The idea, borrowed from the successful smallpox elimination campaign, was to vaccinate all people who were in contact with the initial patient in each cluster and then ask if the clusters stopped adding new patients.

There was a catch — that ethical dilemma of any clinical trial: who was going to be the control? Without a control population, researchers do not know if the vaccine worked. Clinical trials are expensive, and if they fail, which happens, people tend to lose confidence in vaccines.

The trial team immediately treated 4,123 exposed people in 48 clusters with live recombinant virus. They treated 3,528 in 42 clusters with a placebo and then with the rVSV-ZEBOV Ebola vaccine after 21 days. Nobody knew at the time which of the 90 clusters got the real vaccine. If the rVSV-ZEBOV were effective, clusters that got placebo injections should have more new cases of Ebola, while those that got the real vaccine should have fewer or no cases.

In the immediate vaccination group, among the 4,123 people vaccinated, there were no new cases of Ebola 10 days after vaccination. Among the delayed vaccination group of 3,528 people, there were 16 cases. These results are encouraging.

Yet, of the 42 clusters given a placebo virus, 35 had no cases of disease. Still, the results are not conclusive. What is the possibility that the groups vaccinated with the real vaccine were just lucky? 

The statistical analysis that went into these results was serious and concluded that the rVSV-ZEBOV vaccine is probably effective. After all, it works in macaques and induces Ebola specific immune responses in humans. 

Importantly, there were few serious adverse reactions among the 7,361 people who eventually got the vaccine. Nevertheless, the vaccine remains, according to World Health Organization (WHO) standards, an experimental vaccine, which means that use in the next large Ebola outbreak will require control populations. These results were reported in the British journal The Lancet on July 31, 2015.

There is another trial going on in Sierra Leone, called STRIVE, which stands for the Sierra Leone Trial to Introduce a Vaccine against Ebola. It is a combined Phase 2 and Phase 3 clinical trial of the same rVSV-ZEBOV Ebola vaccine. 

There is no outbreak at the moment. STRIVE is directed at doctors and nurses, maintenance and cleaning staff, surveillance teams and burial teams. So far, 8,650 frontline workers have been enlisted in districts that suffered heavily from the previous outbreak. Part of their justification was the seeming success of the Ebola Ça suffit study and its absence of serious side effects. 

STRIVE is not a blind study, and everyone is vaccinated, although half of the participants will be vaccinated after six months.  If there is a large outbreak, the trial may provide information. Otherwise it provides peace of mind for frontline workers.

There was a small outbreak of Ebola in a remote area of the Democratic Republic of Congo in May of 2017. It was contained after several deaths, although the vaccine was not used. The virus was identified in Kinshasa, which apparently now has that capacity, and WHO was notified. Resources were mobilized and on the way in 24 to 48 hours. That is encouraging. 

I have used Ebola as a surrogate. Responses to other diseases will vary, but it all comes down to determination and preparation. That includes contributions from many fields, including virology, statistics, logistics and ethics. 

Containing epidemics also depends on groups that provide funding and infrastructure, including WHO and The Coalition for Epidemic Preparedness Innovations (CEPI).  As someone once said, “It takes a village.”

Richard Kessin is Professor Emeritus of Pathology and Cell Biology at Columbia University. He lives in Norfolk, CT. Contact Richard.kessin@gmail.com for original papers or other matters.