We should have safe and effective Ebola vaccines deployed in Africa in quantity, most likely starting in the Spring of 2015. We might have had them before the current outbreak were it not for Republican funding cuts, but that is now medical waste under the bridge.
The World Health Organization (WHO) had a meeting a week ago, on Oct. 23, on “access and financing” of Ebola vaccines. They discussed current progress and what is needed to make the vaccines happen. Public health organizations, countries, and health non-profits like Doctors Without Borders and the Vaccine Alliance were represented.
There are two candidate vaccines that have passed safety trials and are about to be tested for efficacy. There are also several possible treatments being researched.
Many questions have to be answered ASAP or researched further if we don't have the answers yet: medical questions about the disease and about vaccines and treatments; ethical questions about how to conduct trials during an epidemic, and at some point about mass vaccinations and treatments before production is ramped all the way up; and practical questions about funding, facilities, and organization.
We can examine answers to some of those questions below the Great Orange Virion, and discuss options for the others.
Leaked documents reveal behind-the-scenes Ebola vaccine issues
The documents put hard numbers on what until now have been somewhat fuzzy academic discussions. And they make clear to the attendees—who include representatives from governments, industry, philanthropies, and nongovernmental organizations—that although testing and production are moving forward at record speed, knotty issues remain.
The WHO conference is a big deal, because there are real possibilities for ending this Ebola epidemic. But at the same time, WHO does not want to distract from current efforts to isolate and treat patients without a vaccine and without antivirals known to be effective.
One of the largest components of isolation is not allowing traditional funerals where everybody for miles around comes and lays a hand on the body. Whole villages get wiped out that way, with every single person infected by only one corpse. The governments of the three countries most affected have ordered that bodies must either be cremated or buried in biocontainment bags. If families do not agree to leave the bags unopened, they may not get the body back at all.
The next problem is getting victims into hospitals. All beds are full, and people are turned away no matter how bad their symptoms. The US and UK are providing several thousand more beds in field hospitals now under construction. That is nowhere near enough even for current cases, much less projected growth of the epidemic.
Right now treatment primarily means intravenous fluids to prevent death from dehydration long enough for the patient's immune system to get ahead of the virus. It also means measures to cope with organ damage.
One of the vaccines started human safety trials in September, and a second in October. Both have been tested successfully for both safety and efficacy in primates.
[GlaxoSmithKline/GSK] expects to have preliminary data in November from phase I studies that analyze safety and immune response in small numbers of people not at risk of contracting Ebola. If those data are positive, efficacy trials could start as early as January in Guinea, Sierra Leone, and Liberia, the three West African countries hard hit by the epidemic.
The next step is to get perhaps 24,000 doses into the field to be given mainly to health care workers treating Ebola patients in Africa. GSK is planning trials in Liberia (double-blind, with some vaccinated and some getting a placebo) and Sierra Leone (stepped-wedge design, where different groups get vaccinated at different times). Protecting health care workers is of course a priority, and they make good test subjects when you want to take blood samples for analysis for months afterward to check on production of antibodies. However, there are also
first-line responders like those who do burials or track contacts of known infected people. WHO estimates that there are about 12,000 health care workers in the three affected countries and another 17,500 “community” responders.
NIH is interested in managing the trial in Liberia, and CDC is talking about managing the one in Sierra Leone. There is interest in getting trials started as early as December, but they may take until January to start. The biggest question is the stability of the countries. Is it going to be possible to do a proper trial with proper management and controls, and get meaningful results?
Another lesser-known company, NewLink Genetics, also has a vaccine in safety trials, and is interested in providing a third leg for the proposed Liberia efficacy trial, trying two vaccines against each other and placebos at the same time.
The Ebola vaccine underdog
Other possible vaccines from Johnson & Johnson and from Russia are not that far along.
One of the big unanswered questions so far is what dose of vaccine will be needed, which bears on how many doses can be made. The answer is not known within a factor of 100.
There are Ebola treatments also being tried. Giving blood plasma from survivors seems to have some merit. Organizing to collect (safely), type, manage, and administer plasma for tens of thousands of victims from thousands of survivors is going to be difficult, but probably doable.
Zmapp seems to work, but we don't know how to make it in quantity yet with appropriate quality control. Various antivirals are being tried, but we don't have reliable information on how well any of them work.
There is a real problem about trying to get ahead of the existing epidemic without a vaccine, unless one or more of the proposed treatments work. Getting ahead of the disease means getting transmission down to less than one new infection per patient from the present R0 = 1.5 or even higher in places. Once the number of cases is diminishing, we can organize to get them all into existing isolation and treatment facilities, and break off transmission almost completely fairly soon after that.
The extent to which we should vaccinate populations against Ebola when there is no outbreak will have to be discussed in light of other health care priorities, budget limitations, lack of staff and facilities, and so on. We might want to begin with everybody in the regions where there are fruit bats in the wild or in the markets. Certainly there will be no reason to vaccinate the public in the US.
Then there are the ethics questions. Can we withhold the vaccine from some health care workers? Can we get meaningful data if we give it to everybody? There is precedent for canceling double-blind studies during an epidemic. What about families of victims? Well, at this stage we don't have enough vaccine for everybody, because we can't ramp up production that fast. And it is generally unethical to give untested vaccines to large populations.
There are also legal questions of regulation and possible liability for side effects of vaccines that have an ethical dimension, but shade off into the next category, which includes practical questions about funding, facilities, organization, and so on. The well-established protocols that wiped out smallpox in the 1980s and have come close to wiping out polio except in war zones would require more than ten million doses of any vaccine to cover everybody for a considerable distance around any Ebola patient. But those protocols also provide for ramping up the areas of complete vaccination as supplies increase and the number of cases decreases.
A highly detailed, 28-page document by the Norwegian Institute of Public Health offered “crude cost estimates” for scaling up mass production of Ebola vaccines. By these calculations, 27 million doses of vaccine would cost up to $73 million, and the cost of the vaccination campaigns themselves will add another $78 million to the bill.
That's about the right scale. Cheap if it works.
Here is another account of the two vaccines, with particular attention to the problem of dose size.
Ebola vaccines racing forward faster than predicted, but high hurdles remain
The following paper is rather technical, but it is possible to ignore the complex language and get the idea about where the virus can be attacked, and how effective that might be.
What are some possible ways to cure Ebola in the future?
If you are familiar with the South Park episode Starvin' Marvin in Space, you may remember the alien language in which every noun was "marklar", but you could tell what they were talking about. Here is Kyle explaining the plight of the Ethiopian refugees being pursued by the evil Christian missionaries.
KYLE
Wait. Wait. I think I can explain this
whole thing. Marklar, these marklars
want to change your marklar. They don't
want Marklar or any of these marklars
to live here because it's bad for their
marklar. They use Marklar to try and
force marklars to believe they're marklar.
If you let them stay here, they will
build marklars and marklars. They will
take all your marklars and replace them
with Marklar. These marklar have no
good marklar to live on Marklar, so
they must come here to Marklar. Please,
let these marklars stay where they can
grow and prosper without any marklars,
marklars, eh or marklars.
MARKLAR
Young marklar, your marklars are wise
and true.
Scientific marklar works exactly the same way, as long as you don't need to get too deep into the marklar.