Contagion&reg Connect Episode 5: Ebola: Past, Present, Future

Contagion® Connect Podcast Episode 5: Ebola: Past, Present, Future

Interview transcript (modified slightly for readability):

Contagion: Welcome to Contagion® Connect, a podcast dedicated to bringing you expert insights on trending infectious disease topics. In this episode, we take a dual look at the past, present and future of Ebola.

First, we'll speak to John Johnson, project lead for Ebola vaccination with Médecins Sans Frontières (MSF), France. We’ll discuss how the ongoing effort in the Democratic Republic of the Congo compares with the response to the West African epidemic, the role of vaccination in the outbreak control strategy, and the unique challenges the ongoing epidemic has presented.

Then, we'll speak to microbiologist Jason Kindrachuk, PhD, about his experiences on the ground in Liberia during the West African epidemic. Kindrachuk is also an expert on current research pertaining to lasting effects in Ebola survivors, so we'll also speak to him for a clinical perspective on what the future holds for those who survive the disease.

Johnson: My name is John Johnson. I'm project lead for Ebola vaccination with MSF, France. I've been working with them for the last 8 years in different places around the world. Over the last year, I've spent most of my time working in North Kivu on the outbreak of Ebola. Since the outbreak started, I've been here basically in 3 different positions. I started out early on as a project coordinator for infection prevention and control activity. At the time, we were working in Beni, which is a city in North Kivu. That was, at the moment, the epicenter of the outbreak.

I came back a few months later as emergency coordinator and that was more of a role that was based in Goma, the capital of North Kivu, and I was working more on sort of the Ebola response in general for MSF. At the time, we were running several different projects, and our role was anywhere from general non-Ebola support in health centers to managing Ebola treatment facilities.

Since September I've been working on a project to put in place a study for one of the Ebola vaccines, the Ad26.ZEBOV regimen that's produced by Johnson and Johnson. They've been working very closely with MSF, the Ebola response, as well as partners in a consortium to put the study in place.

Contagion: Thank you for that background. You mentioned the role you have in vaccination efforts and the availability of vaccines is one of the many differences between the outbreak of Ebola few years ago in West Africa and the outbreak we're seeing today in the Democratic Republic of the Congo. Overall, how do you compare these different outbreaks?

Johnson: Nothing compares to the West African outbreak in terms of scope. You know, it was it was an extremely large outbreak that was in several countries at the same time.

This outbreak in North Kivu and Ituri has unfortunately become the world's second largest outbreak after West Africa. But it's still one-tenth of the number of cases that we saw in West Africa.

But if West Africa taught us anything, it's that we weren't prepared for a large Ebola outbreak. We didn't have effective treatment. We didn't have effective prevention.

What we really were forced to rely on, back at that time, were public health interventions of isolation, surveillance, and trying to improve case detection to remove [patients] from the population so that they didn’t infect more people.

And then once they were in the treatment centers, we didn't have many options. We didn't have effective Ebola treatments at the time, all we had was supportive care. [The way] Ebola attacks a person, it basically resembles a viral sepsis. You can treat a patient like you would in an intensive care unit with rehydration, other supportive measures like making sure they're well rested and fed, but you don't have much else to treat them with. Since that time, we've been able to develop more experimental therapies.

We've been able to have the preliminary results of a randomized clinical trial published in the New England Journal of Medicine showing that we have 2 pretty promising candidates for treatment. Those are mAb114 and regeneron, which have given early results showing a reduction in mortality. But the thing that that clinical trial really showed us, among other things, was that the longer a patient waits before coming into receive treatment, the higher the risk for mortality. What we saw in that study was for every day a patient waited before coming to receive treatment there was an 11% increase in mortality. So still, the best option is to come in for treatment early.

The other one of the other big differences between 2014-15 West Africa and this outbreak is that we now have vaccine options, and the one that's been deployed most widely in this outbreak is the rVSV vaccine that was trialed back in Guinea at the end of the 2015 outbreak and was used earlier in 2018, in equatorial Congo during that outbreak.

Contagion: What role has vaccination had in this in this response? And why was the additional Johnson and Johnson vaccine brought in? Has it been helpful to have that additional tool in the arsenal, those sorts of things?

Johnson: The rVSV vaccine is really a game changer. We see that it's an effective vaccine. After the West African outbreak this was the vaccine that was the most advanced and the most studied. There was a global stockpile created of about 300,000 doses.

When we started using the Merck vaccine it was 300,000 doses, that's a lot for an Ebola outbreak. Most Ebola outbreaks are less than 100 patients. You wouldn't need a large stockpile. And nobody really expected another large Ebola outbreak anytime soon.

When we started vaccinating right away in August of 2018, things were going fine until we started really worrying about if we would run out of Merck vaccines. It was at this point that people started looking for plan B.

But just to give you a bit of background on the role that vaccines played, the strategy that was used for the deployment of Merck was what they call a ring strategy. The ring strategy is nothing new. It's what was used to eradicate smallpox. To very briefly explain the ring strategy, what you do is you take your index case, you vaccinate their contacts—so anyone that they've come in contact with the past few days—and then you go to those contacts, and you make a list of the people they've been in contact with over the past few days, and you vaccinate their contacts. So it's called the ring strategy because it's a ring around the patient, and then a second ring around the contacts.

The people that have already been exposed to Ebola, may or may not have already

developed the virus in their body and we may be vaccinating someone who already has Ebola but hasn't exhibited symptoms. The protection really starts at the second ring, the second line of contacts of contacts. But what we saw with a Merck vaccine was that there was also some protection offered to people even if they'd already been exposed to Ebola. It did reduce the risk of mortality.

We were using the ring strategy with [the Merck vaccine]. But the problem with the ring strategy, well, there's no problem with a ring strategy. Theoretically, it's quite sound. The problem was always with the implementation of it. In the context of North Kivu where there's a mobile population, and people that are already somewhat resistant to the Ebola response, we never were able to vaccinate enough people because we were never able to identify and follow all of the contacts.

The interest in having a second vaccine, for example, the J&J [Johnson and Johnson] vaccine has a global stockpile of 1.5 million doses. And with that vaccine, we could do a complimentary strategy, where contacts and contacts and contacts get the Merck vaccine, which is now proven to be very effective, and the J&J Vaccine could be used for a larger percentage of the population living in those areas that are affected but have not come into direct contact. That would therefore be a preventive strategy for these populations at risk.

Contagion: You mentioned some of the community resistance to the response, right? The outbreak response area has several armed groups operating within it, there's a conflict which ultimately dates back to the 1990s, and that rightly gets attention. But outside these groups in everyday Congolese society, it seems there's a degree of skepticism when it comes to the national and international response as well.

Johnson: Congolese people are just like people everywhere. They want to go see their family doctor. They want to be treated by people that speak their language and that understand them and that they know. Instead of being treated by their family doctor, they were sent through a sort of grinder of the Ebola response.

A lot of the things that we heard were that you guys aren't here because we're sick. You're here because we're contagious. We've been sick for years, we've had cholera, we've had malaria, we've had malnutrition, we've had armed groups attacking us, and nobody came. And all of a sudden, there's a disease that scares you. And you come with a massive response with lots of money. And I think they've got a good point, we really pay so much attention to

threats of global pandemics. And we've not really supported them in the last 20 years when there's been the Kivu conflict, when there's been outbreaks of different other diseases. I think there's something to be said for that line of reasoning.

A simple example is right now in the country you have the world's largest measles outbreak, ever. And it attracts far less attention than the Ebola outbreak and measles has killed 6000 people already, where the Ebola outbreak over the last 18 months has killed 2000. And that's not to diminish what Ebola is or the fear that Ebola causes. But to say that when you're when you're living through it and see children dying of measles, and nobody's really interested, it is hard for them maybe to understand why.

Contagion: That's a thoughtful response. I appreciate that.

Is there anything else infectious disease clinicians around the world should know about Ebola as a virus, about the Ebola outbreak response, to better understand what's going on in this international effort?

Johnson: We really don't know much. Still, we really don't have a lot of information about this disease. We really are trying to understand it and trying to learn. I think it's important to be able to do research and to study and to pay attention when we do have these Ebola outbreaks so that we can better respond next time and try to gain as much experience as we can

during these very unfortunate events.

And I think I think things like the randomized clinical trial that was carried out, the study with the Merck vaccine and the study that's going on with the J&J vaccine, really will help us in the next outbreak. We need to be prepared for the next outbreak to study something new that can help us prepare for the next one. Ebola is always going to be one step ahead of us and we need to prepare for that.

Contagion: Now we're speaking with Jason Kindrachuk, PhD, Assistant Professor of viral pathogenesis in the Department of Medical Microbiology at the University of Manitoba. Let's start with your involvement in the West Africa Ebola epidemic.

Kindrachuk: Where I got involved in outbreak response was really when we saw Ebola hit West Africa. We saw that the case numbers initially were fairly low. But there was this long steady increase over time. And I think most of us that are within the filovirus field of research were getting the feeling that this was different.

We were starting to see cases that were spreading across Guinea, Sierra Leone and Liberia. And we were starting to see cases that were going into the heavy populated regions. Once cases got announced in in West Point, which is one of the main slum areas of Monrovia, Liberia, we got nervous, we knew something was going awry with this.

Around the same time, Nancy Writebol, and Kent Brantly, who were both physicians with

Samaritan's Purse got infected while serving in West Africa, and they were brought back to Emory in Atlanta. There was suddenly a surge in the media representation of healthcare workers getting infected in West Africa, media coverage increased, and there was suddenly a pressure to get an international response effort together.

The NIH and the US Centers for Disease Control looked for volunteers that had high containment experience, research experience within the biosafety level 4 laboratory and had a comfortability with the idea of going out and working in the field.

The initial call came mid to late July 2014. I volunteered the first week of August, and was on a plane by the first week of September. I landed in Monrovia not long after one of the protest groups was actually digging up bodies and putting them onto the highways because they didn't feel that the virus was real, or that the outbreak was real.

I went over as a scientific lead for one of the diagnostic laboratories that was serving all of Liberia. Our laboratory, which was at the Liberian Institute for Biomedical Research, we were getting samples from across all Liberia, so not only hospitals or Ebola treatment centers in Monrovia, but across the entire country.

On average, we were getting you're probably around 70 samples a day. I think we ultimately processed 1600 samples over four weeks.

There were three of us that came from the US, including myself, and we had 4 or 5 Liberian researchers that were volunteering their time with us who'd worked in malaria diagnostics.

We had a makeshift containment lab, which is it was not a BSL-4 [Biosafety Level 4] lab, but we were in respirators and protective suits, with no air conditioning, and we processed blood in whatever samples we received all day and all night for , seven days a week.

Contagion: Did you get much interaction with any patients, or was it mostly in the lab there?

Kindrachuk: Most of it was in the lab, I had a little bit of interaction with patients. I was fortunate enough that one of my closest friends Dr. Daniel Chertow, a physician and principal investigator at the National Institutes of Health, had volunteered with MSF/Doctors Without Borders to provide medical assistance. He was the first NIH physician to go over.

We were actually staying at the same hotel, and we were able to interact and talk about the case.

We also were just down the street from Elwa-3, which was the largest Ebola treatment center in Liberia. We would drive by every day to see the increasing number of people that were, it sounds horrible but dying essentially, outside of the gates because there weren't enough beds or supplies to be able to take in extra patients.

But there were still open markets where we interacted with the public. To some degree, though, everybody was pretty cautious. I was involved in some of the studies that we did at NIH with patients that were met have backed out of West Africa as well.

Contagion: Ebola has a fairly high case fatality rate, but when we're successful in treating a patient, that's not the end of the story for that person. What are some of the long-term health complications for Ebola survivors from physical to psychological?

Kindrachuk: We're just starting to really understand what the long-term ramifications of disease survival are.

Historically if you look back at reviews and different papers that have talked about Ebola virus pathogenesis and survival, there would always be a table talking about the long-term physical impairments that patients would face. It was often people would have eye pain, they might have some neurological abnormalities. But they were always fairly obtuse. We didn't have the number of patients to establish how frequent these things occurred. West Africa obviously changed that.

What we have an appreciation for now is both in those that were medevac’d back to either Europe or North America as well as local patients within West Africa. What we're seeing now is a high presence of posttraumatic stress disorder in patients that have survived.

One of our key areas of interest right now with my own program in Sierra Leone is we're looking at trying to get in touch with the different Ebola virus disease survivor networks to identify what long term health complications those survivors are facing, beyond just the normal kind of physical abnormalities that they may be feeling but we also want to be appreciative of those.

And that is mostly in the sense to try and guide long term response efforts within these regions.

Once international health response efforts do leave an outbreak zone, do we have the type of infrastructure in place to be able to provide long term mental health care networks for patients? And can we start identify what the major impediments are?

We also are starting to get a sense that there's been somewhat of an underrepresentation in terms of the long-term implications in female health, in female survivors, in particular

with the ability to conceive children, and there's actually quite a striking number of miscarriages that were identified in female survivors.

One of the areas that we saw with West Africa we're now seeing with the outbreak in the Democratic Republic of Congo is this idea of Ebola persistence.

We know that Ebola can get into the central nervous system. This was made fairly famous with the case of Pauline Cafferkey, the Scottish nurse who relapsed with Ebola virus disease, because she had virus that that had been essentially sitting latent for months in her central nervous system.

But we actually are seeing that in male patients that survive there's a high percentage of those patients that will carry virus in their semen for long periods of time. Some of the recent cohort studies have suggested that up to 50% of patients that survive out to 4 months post-recovery will still have virus in their semen, but they have no physiological symptoms of disease and they

test negative.

What are the long-term ramifications of that on fertility or reproductive health? Those are avenues that I don't think we have really any data to suggest what the consequences will be.

We are still, I think, at a learning phase with Ebola. The vaccine has been fantastic. We have a new weapon in our arsenal to combat Ebola, but the story is not over. We will continue to see outbreaks, the magnitude of those will hopefully be less than then what they would have been without the vaccine, but we still need to be vigilant and the main area of focus for that is community engagement in the regions that are most affected by the virus.

Contagion: Thanks for tuning into this contagion Connect podcast. Be sure to like, share and subscribe. And for the latest infectious disease news, be sure to check out Contagionlive.com.