TORONTO - As West Africa's Ebola outbreak continues to rage, some experts are coming to the conclusion that it may take large amounts of vaccines and maybe even drugs — all still experimental and in short supply — to bring the outbreak under control.
Embedded in that notion is the reality that the catastrophic epidemic may remain unchecked for months, given that these products haven't yet been proven to be safe or effective in people, and won't be available in significant amounts any time soon. Experimental Ebola drugs in particular will remain in scarce supply for a considerable time.
"It is conceivable that this epidemic will not turn around even if we pour resources into it. It may just keep going and going and it might require a vaccine," Dr. Anthony Fauci, director of the U.S. National Institute for Allergy and Infectious Diseases, told The Canadian Press in an interview.
"As the epidemic gets more and more formidable and in some cases out of control it is quite conceivable, if not likely, that we may need to deploy the vaccine to the entire country to be able to shut the epidemic down. That is clearly a possibility."
Earlier in the outbreak many experts insisted experimental vaccines could not be tested and produced in large enough amounts in time to have an impact on the outcome. They stressed — publicly, some still do — that the "tried and true" measures used to contain Ebola outbreaks in the past would eventually control this one.
Those measures are aimed at breaking the chains of transmission. The sick are housed in isolation units, where the only people they have contact with are garbed head-to-toe in protective apparel. Those who don't survive are buried in thick body bags, without the cultural rituals that often spread the disease.
Contacts of the sick are monitored for 21 days and are whisked into isolation if they start to get ill. People with Ebola are believed to be contagious only when they have symptoms, which is when you need to ensure they don't come into contact with others.
But this epidemic is so large it has long since outstripped the capacity of responders to care for all the sick, let alone trace their contacts. People are dying at home, infecting their families in the process. Some are dying abandoned on streets, or outside the gates of over-full treatment centres.
On Sunday, Sierra Leone reported 121 deaths. That is more deaths in a single day than recorded in most Ebola outbreaks from start to finish. The World Health Organization says to date about 7,500 people are known to have been infected with the virus, and more than 3,400 have died.
The head of the Wellcome Trust says it's time to stop telling the public the traditional way of containing Ebola can quell this epidemic.
Dr. Jeremy Farrar, who runs the global charitable foundation, says that message is now counterproductive, getting in the way of spurring the pharmaceutical industry to put on the type of full-court press that the situation demands.
"Although we do know what to do in a smaller outbreak at the very start, the truth is ... when that now extends to thousands of individuals in multiple countries across borders and your health-care system is not functional, it is impossible to control it if that is your only intervention. That's my view," says Farrar. The British-based Wellcome Trust has offered to fund clinical trials of a number of the experimental drugs and vaccines.
"I think anybody who says that there's a single answer to this is wrong in the sense that 'more of the same' will sort the problem out.... I think we've gone beyond that now."
Two experimental Ebola vaccines have been shown to protect primates; several others are further back in the pipeline. But human clinical trials have only just begun on one — designed by scientists in Fauci's institute and being brought to market by pharma giant GlaxoSmithKline or GSK.
It is hoped that clinical trials will start soon on a second, created at Canada National Microbiology Laboratory in Winnipeg. That vaccine is licensed to a small U.S.-based biotech company, NewLink Genetics, which does not have the experience or the deep pockets that GSK has. The U.S. government, through its Biomedical Advanced Research and Development Authority, is helping NewLink to structure and run the needed clinical trials as well as find partners to help it ramp up production of supplies.
"We have found them to be co-operative in what we want to do and we're working very collegially together," says BARDA Director Dr. Robin Robinson. "They have a very big challenge ahead of them and we are going to assist them to do that."
These initial small trials are needed to show that the vaccines are safe to use in people and to see how much vaccine is required for what is thought to be a protective dose. But larger studies will be needed, experts who recently met at the World Health Organization to plan this work decided.
That meeting determined the vaccines will need to be tested in traditional studies known as randomized controlled trials, where volunteers are randomly assigned to get the Ebola vaccine or another injection — likely something like a hepatitis B shot. Ideally neither the researchers nor the volunteers know who got what.
The groups would then be followed for a specified amount of time to see if Ebola infections were less frequent among those given a vaccine.
A number of experts are not comfortable with the idea of withholding the vaccine from some trial participants, saying other trial designs could answer the question in a less ethically challenging approach. One suggestion, says German researcher Stephan Becker, would be to vaccinate inhabitants in a village in an infected country, and compare infection rates there to those in similar villages where vaccine has not yet been made available.
"For me this sounds a bit ... not practical," Becker, who is at the University of Marburg, in Germany, says of a traditional randomized controlled trial. Becker is negotiating with NewLink to conduct a small clinical trial of the Canadian vaccine in Germany.
Becker is not the only scientist to question the agreed-to approach. But a source who asked not to be named says the U.S. government — which has footed the bill for much of the research behind the vaccines and drugs, and which will likely take a lead role in paying for production and dissemination of Ebola vaccines — wants to know the vaccines work before it spends hundreds of millions of dollars on them.
Fauci points to a clinical trial of an HIV vaccine that was stopped a couple of years ago as an example of why it's critical to know whether the vaccine is actually effective before it is broadly used.
The HIV vaccine looked good in animal studies and seemed safe in the small initial human trials in healthy volunteers. But when it was given in the field, people who got the vaccine actually contracted HIV at a higher rate than people in the placebo arm of the trial.
"So those are the kinds of things that you have to take into consideration, particularly if there's even a possibility that you're going to widely deploy a vaccine," Fauci says.
Farrar prefers the trial design Becker suggested, but says the important thing is not to let differences about which approach is better delay the work.
"We mustn't be in a situation where we're having the same conversation six months from now as the epidemic is still raging and we're still only discussing how we might move things through into Phase 1 and Phase 2 testing," Farrar insists.
He also says work must be done concurrently to answer the questions on how vaccine would be rolled out when it becomes available. Who gets it first? How will delivery be organized? How will it be delivered to remote parts of the affected countries?
"Can you throw it out of a helicopter? Do you need a cold chain?" Farrar asks, a term that means a product must be kept refrigerated or frozen or else it becomes unusable. "We can't be scratching our heads when we got a vaccine."
Farrar also insists work must be done to test and make the experimental Ebola drugs. Having a treatment to offer people who are sick will inspire more to turn themselves in for care when they become infected, he says.