Hello, this is a short seminar for the FutureLearn module on vaccination for the prevention of infectious diseases and AMR. This seminar is on ring vaccination against Ebola, both the disease control tactic and the vaccine efficacy trial. So a brie recap on what Ebola is. It’s previously been known as a viral hemorrhagic fever, now, known as Ebola virus disease caused by a filovirus that might variously be described as an emerging infectious disease and neglected tropical disease. What was certainly the case is that in a– it’s caused public health emergencies sort of of note over the past decade, particularly, and a large outbreak in West Africa in 2013 and 2014.
And this is part of the epidemic kind of from Guinea, one of the three most affected countries. And this shows the [? invacuation ?] and the public health emergency in August of 2014 and the weekly numbers of cases arising during this time. I’ll put in the date as well for one of the WHO research and development meetings, which started to bring it because the process that led to [INAUDIBLE] the ring vaccination trial that was put in place in Guinea. So some of the factors that might affect trial planning and trial feasibility would be to be looking at the likely course of the epidemic. Is there still going to be transmission at the time that the trials even started?
How would the trial integrate with other public health response. So the trial itself has to be acceptable in the place that it’s going to be done. The trial should be meeting international standards for study conduct and to be an approach and interventions that are aligned with what and the affected activities would want them to be.
Then there are some trial-specific features, the endpoints that you choose, whether it’s infection, disease, and death will affect some of the feasibility of the study both in terms of the event rate with study size and study power, the data collection systems that you’ll need to place, whether you’ll need to be doing blood sampling of people, whether you can use routine data that’s being collected perhaps under surveillance as part of that, whether you’re looking at the high-risk groups or otherwise as part of your study design. Then you’re also looking at both how you choose your vaccine for the intervention arm and also what control arm looks like.
That might be placebo in the classical sense, a saltwater or saline injection or, more likely, you would use a– another vaccine so that people still have some kind of vaccine action, and don’t become aware that they’ve not had it and it’s [INAUDIBLE]. We did something quite different in the ring vax control arm. I’ll come up and explain why we did that.
Though I’ve mentioned it, the epidemic course can change during the time of study planning. And so these are the epidemic curves for the three worst-affected countries in the West African outbreak. And these, and the bar charts showed the registrations on clinicaltrials.gov of vaccine trials, clinical trials, and observational studies. By and large, registration’s happening after study peak, so with the public health response and communities themselves changing behaviours, thankfully, the epidemic was not continuing to accelerate exponentially as had been observed. But others had been thinking, well, what size of studies, or what size of vaccine response do we need? And there was the offer of up to 12 million vaccine courses being purchased. But, actually, that wasn’t an option at the time.
We weren’t sourcing like [INAUDIBLE] with a dose. [INAUDIBLE] So the alternative was to maybe look at those most likely to get or transmit infection, health workers, areas that are worse affected, people associated with known cases. That’s the ring vaccination approach. And also, they’d been looking at risk stratification, at those most likely to get severe disease if infected. For the ring vaccination, itself, we very much were inspired by the smallpox eradication campaigns and one of the kind of proven concepts of smallpox eradication being done in West Africa. And there was enough epidemiological similarities between the two diseases to be thinking that this was potentially a feasible approach. So neither of these diseases are– have significant transmission before symptom onset.
They’re relatively slow serial intervals, rather than long serial intervals from one case onset to the onset in the next case, which gives time for the surveillance teams to respond. In terms of their actual transmissibility, Ebola is less infectious than smallpox, a respiration virus, versus a contact disease. And so if it worked for smallpox, it had these [INAUDIBLE] for working for Ebola. In smallpox, they used essentially geographical ring.
But with greater mobility in West Africa in the present time, sort of the times that the [INAUDIBLE] the trial was ongoing, it was more appropriate to have a socio-epidemiological ring, so this may include not just the village, but other places that the person stayed, and other people who’d been involved in the care or transport of a case. Slightly more complex, well, this is the vaccine chosen for the study by a WHO committee. It was the VSV recombinant vaccine.
And the Ebola glycoprotein substituted in. More challenging, perhaps was the choice of the control arm. So many people, ourselves included, were very uncomfortable with the idea of placebo control. And so what we often did was to use a control arm with as little delay as we possibly can so if the vaccine was effective, we’d be minimising the number of cases arising during the study. But the [INAUDIBLE] that with a [INAUDIBLE] animation. This would be from typical notification and what might be expected to occur in close contact in that case, in terms of secondary and third generation and beyond cases, aligned for typical notification lines and onset of vaccine into similar.
So we see that the second generation cases aren’t protected, but ring vaccination potentially does protect later generational cases. [MACHINE HUMMING] [? Furnish ?] [INAUDIBLE] delay. Delay comes in, it seems that whilst the second generation cases are missed, the third generation cases potentially also more protection. That gives some window of opportunity to detect if there’s a vaccine effect. Whilst it seems that the vaccine is efficacious, it’s protecting fourth generational cases and beyond.
That’s not to say that third generation cases or others in the trial would go and [INAUDIBLE] to everybody that is in a vaccination ring, in one of these clusters, is given the kind of typical public health information, public health interventions on how they can reduce their risk of getting infected.
So if the equivalency of sending [INAUDIBLE] through the best available care. And additionally, for those that go on and do develop Ebola, they developed Ebola during the course of the trial, they had access to the best care in the Ebola treatment units. [INAUDIBLE] [MACHINE HUMMING] See, the problem was [INAUDIBLE] hard to trial [INAUDIBLE].. Well, this was the most conservative estimate for how well the vaccine worked. So they met on being the generational cases in the delayed vaccination on the blue line, the [INAUDIBLE] cases in the immediate vaccination arm. And the first 10 days were [INAUDIBLE] analysis, pre- [INAUDIBLE] analysis to allow time for people already infected to show symptoms, and for vaccine immunity to take root [INAUDIBLE] vaccinated [INAUDIBLE].
This dose meant effectively we were seeing close to about a 100% vaccine efficacy shown, and this [INAUDIBLE] towards a vaccination that we would feel comfortable using this as a [INAUDIBLE].. After the trial, the vaccine was used in West Africa for control of a number of flare ups from their transmission of Ebola, and subsequently used in the Democratic Republic of Congo, Eastern DRC, [INAUDIBLE] with many of the [INAUDIBLE] from [? Guinea ?] working with Congolese colleagues to bring the epidemic under control. This is the interim analysis done in April 2019, I believe, showing vaccine efficacy in high 90 percents, with [INAUDIBLE] from the scale here.
If you just wind it about vaccine [INAUDIBLE] is used under effectively [INAUDIBLE] standout conditions on the most reduced conditions, but now at the point where the vaccine has been approved for licensure in Europe and in North America, and that’s opened the way for WHO to say that they are ready to prequalify the vaccine. That’s if they recommend it for use in [INAUDIBLE] let them have such strong vaccine or medicines licencing regimes as Europe and North America. And so, fantastic step. I’m very pleased that the vaccine should now be much more widely available than it has been.