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Interview transcript (modified slightly for readability):

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 

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.

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.

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?

 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 

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.

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?

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&mdash;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.

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.

 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.

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?

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

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.

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.

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.

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

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.

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?

 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

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.

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.

In this episode, our guests compare the West African Ebola outbreak to the ongoing outbreak in the Democratic Republic of the Congo.

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

Pandemic Bonds: An Investor's Dream, A Public Health Nightmare 

 Connect. This new podcast will bring you expert perspectives on trending infectious disease topics.

In this episode, we are joined by Dr. Alexandra Phelan from the Georgetown University Center for Global Health Science and Security. Dr. Phelan

works in the intersection between infectious diseases and international law and we'll be discussing an editorial published in 

 regarding the impact of pandemic bonds on the ongoing Ebola outbreak and the Democratic Republic of the Congo.

 Hi, my name is Dr. Alexandra Phelan. I am on the faculty of Medicine at Georgetown University at the Center for Global Health Science and Security and also an adjunct professor of law at Georgetown University Law Center.

Can you provide me with some background on what the World Bank's Pandemic Emergency Financing Facility and the International Development Association fund are?

Sure, I'll start with the latter first. The International Development Association is a part of the World Bank, and it aims to reduce poverty in the world's 76 poorest nations and the way it does that is by providing credits, which are zero, or very low, interest rate loans. They typically have a long-term repayment schedule, 30 to 38 years, and often a 5- to 10-year grace period before repayments begin. The IDA also provides grants for programs that aim to target inequalities or improve people's living conditions.

The Pandemic Emergency Financing Facilities is a little different. It aims to provide finance to countries eligible for IDA funding, as well as other UN agencies and aid organizations. And it does that through 2 financial mechanisms. The first is what's known as a cash window. And that's a small $50 to $100 million fund that's financed by World Bank donors, not the private sector. And it doesn't have the same specific payout criteria as the other mechanism, which I'll talk a little bit more detail in a moment. And the idea is that the cash window can be used more quickly, and it can fund single country outbreaks or novel pathogens, that haven't already been identified as particular epidemic risks.

The PEF has this in the second mechanism, which is the insurance window and that's one thing getting a little bit more attention. It's financed by the private sector, and it's intended to provide essentially insurance coverage up to $425 million. This coverage is purchased just like insurance and it has annual premiums at 8.5%, which is about $36.2 million, that it pays to the private sector.

There are very specific criteria for when money is to be released from this insurance window. The first is that it must be a specified disease, and that's from a list of diseases that the WHO says is most likely to cause major epidemics, which includes pandemic influenza, SARS, MERS, Ebola, and a number of other diseases.

The second criterion is that an outbreak must meet a certain size, so the number of cases must be triggered. There must also be a rate of growth, of the outbreak that triggers the release of the money, so a number of cases per month for example. And then, it has to satisfy a criterion of spread, that is that it has to spread to 2 or more countries. And there are so different levels, so if you've got more than, say 8 countries, that first step is it must also spread beyond a country has to go to 2 countries.

So, the IDA so far in the Ebola outbreak has released, I think there are 2 different tranches, so $80 million whose was first released, and then they have also done a $300 million supplementary package of grants and credits of Ebola outbreak in DRC. It's not quite clear yet, what breakdown between grants and credits that $300 million is. In terms of the PEF, the Pandemic Emergency Financing facility, the cash window has distributed $20 million and the issue that's started to garner a lot of tension is the fact that the insurance window hasn't been activated as yet.

From my understanding, there are contingencies in place to ensure that a payout from PEF is not given inappropriately. And in Olga Jonas's piece in 

, it says that PEF stipulates that a payout of $45 million for Ebola would be given if the death toll reaches 250 confirmed deaths, but only if at least 20 of the deaths occurred outside of the nation where the outbreak began. So, in the ongoing outbreak right now, we're clearly seeing way more than 250 deaths, but they're predominantly isolated inside the DRC. So, how are these stipulations, in turn, hurting the outbreak response?

Yeah, this goes to the real the tension between what the PEF insurance window aims to do and how it gets its financing. And what that is, is that there are very strict criteria for the release of that money. And that criteria are in place, because this is essentially an investment instrument. And the idea is that the private sector will only invest in the PEF if they can have certain criteria that they know is when the release is going to occur. And that fundamental attention, what investors want to see, is not necessarily consistent with what global health needs.

And so, you know, these criteria were set up with this cross border spread of more than 20 cases, which although we had reported cross border spread into Uganda, there were only 3 cases, and it has to be within a particular time period as well. So that certainty from investors, what they're after, which is very favorable turns, is completely at odds with what's needed for the outbreak response. What we need is financing to stop the outbreak at its source and to save lives. And it does seem absurd, or is absurd when you have the criteria when that's what that money would do on the ground in terms of public health capacity, surveillance, contact tracing. distribution of vaccines, what you need to control the response that requires that money.

That being said, the PEF insurance window is doing exactly what it was set up to do. I mean, these criteria were set up back in 2016 when it was established. So, this tension has existed before this outbreak. And this is the challenge of relying on innovative financing mechanisms that really are about marketplace mechanisms when what global health necessarily needs is not market-based, particularly if we've defined global health and outbreak prepared so, you know, global public good. So we have a conflict of philosophies in many ways.

The other thing to note is also that there are there is money coming from other from countries, from other aspects of the world bank financing, as spoke about before. But, the challenges for this outbreak, beyond financial challenges, are about having the technical capacity on the ground, but also the severe insecurity, conflict, and public health system.

Resource constraints are already existing on the ground in northeast DRC. And my concern, and I will say I think the criticisms are very valid, is I think these criteria were already set; this isn't necessarily a surprise, it's just this outbreak is demonstrating that the PEF as it operates now, is perhaps not sophisticated enough for what's required for financing outbreaks like we're seeing the DRC.

I think that's a perfect lead in to the last question that I have. In your opinion, how can these pandemic fund programs be altered in the future to be effective for outbreaks and health crises that are similar to what we're seeing right now in the DRC?

Yeah, so I think there have been calls to cancel the bonds and release the money immediately. The terms of the prospectus, the terms of the bonds in place, you know, is about 400 something pages, and I'm not familiar with whether there is any provision for cancellation of the bonds in particular circumstances. I would be very surprised if any of the circumstances right now, like the fact that the criteria aren't working, if that would be considered a reasonable cancellation.

There is a good argument that from a rule of law, and a legal certainty point of view that the World Bank would be very hesitant to do that would undermine its lending credibility, if so. That being said, there is clearly a need to revise, and either form a different pandemic facility or for future outbreaks some form of revision. And I think the first thing would be is getting more clarity over how much the bank and donors are actually paying to the private sector in premiums and interest.

And I think the figures are about $75.5 million in premiums, perhaps, that figure would have to be checked. When you compare the amount of money that has actually gone out of the PEF insurance window, you know, there hasn't been any money released to the DRC at this stage. So, I think clarity of the premiums and interest will be very important; reassessment of the requirement for border, or cross border. Under international law the World Health Organization's criteria for declaring a Public Health Emergency of International Concern, which this outbreak has been declared as such, is a risk of international spread, not waiting for international spread. So, given the leading piece of global health law in this field is not a 2-country requirement rather a risk, perhaps there should be consideration of the broad international legal system and if the criteria can be modified in that respect, it's also giving sufficient certainty to the private sector.

And I also note that critically the relying on the private sector to fund this also might be an interesting innovative financing mechanism could be a supplement. Really the responsibility comes down to donor countries to be financing directly to build health systems, not just in the DRC, but in the region in other countries around the world that have severe resource constraints. To build up capacities for diagnostics, vaccination surveillance, all these standard public health tools that we know to prevent, detect and respond to outbreaks at their source rather than relying on an interesting perhaps, convoluted perhaps, and perhaps unreliable or not useful, private sector funding mechanisms.

® Connect podcast. For the latest infectious disease news, be sure to check out ContagionLive.com

The first Contagion® Connect podcast features a conversation with Dr. Alexandra Phelan about the impact of pandemic bonds in the ongoing Ebola outbreak in the DRC.

Contagion® Connect Podcast Tackles Pandemic Bonds

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In Response to Ebola Outbreak, Vaccine Development for the Disease Saw Early Promise

This first-in-human, phase 1 vaccine trial produced a lasting immune response against Marburg virus.

Marburg Virus Investigational Vaccine Safe and Immunogenic in Humans

After their first Sudan ebolavirus outbreak in 10 years, resulting in 164 cases, Uganda today announced the Ebola outbreak is over.

Deadly Ebola Outbreak Is Over, Uganda Declares

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The World Health Organization (WHO) reported that the emerging Ebola outbreak in western Democratic Republic of Congo (DRC) has infected at least 100 people as of last week. Of these 100 people, at least 43 have passed.

The US Centers for Disease Control and Prevention recently issued a level 2 travel notice for Ebola in DRC based on the situation in Équateur province.

The last outbreak of Ebola, in Kivu, only just ended as the current one in Équateur began. The new Ebola outbreak is in a less volatile region in terms of armed conflict, however there are still substantial challenges ahead.

 by local health care workers in Mbandaka, who argue that they are putting their lives on the line despite low pay scales and delays with paychecks.

spoke with John Johnson, an emergency coordinator at Doctors Without Borders.

In the following clip, Johnson describes the vaccine "ring strategy" used historically in controlling several infectious disease threats, including the recent Ebola outbreak. 

WHO has already began using the ring strategy in Équateur, with health workers racing to reach remote rural areas and perform contact tracing.

John Johnson, lead for Ebola vaccination with MSF France, describes the "ring strategy" used in controlling several infectious disease threats.

 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?

 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.

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.

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