[00:00:08] Dr. Emma Carter: Very excited today to have Dr. Edwin Trevathan join us for our topic for the podcast.
We're going to specifically be talking about Dr. Trevathan's research, what he's most recently been doing in Nigeria and the project called Bridging the Childhood Epilepsy Treatment Gap in Africa, also known as the BRIDGE Project. We may also dive into another NIH-funded study that he's been doing in Nigeria as well as we chat today.
But without further ado, I was going to let Dr. Trevathan introduce himself and tell us a little bit about his background in pediatric neurology and global health.
[00:00:49] Dr. Edwin Trevathan: It's a pleasure to be here. And I know maybe speaking to people at all levels in their career and maybe in different parts of the world.
It's a pleasure to be here with you. I don't know that my career is that interesting to talk about in terms of a lot of details, but like some of you out there, I'm a pediatric neurologist. I came to pediatric neurology after I was already an epidemiologist. So I sort of trained in public health epidemiology and then went into pediatric neurology. And so sometimes the way I approach problems is more like a neurologist, and sometimes the way I approach problems is more like an epidemiologist, public health, global health professional.
But that combined background has sort of led me to some of the projects that we're doing in Africa, specifically in northern Nigeria, because I think that the combination of public health approaches, epidemiology, and then solid neurological principles are really important.
[00:02:01] Dr. Emma Carter: You can dive in and talk a little bit more about all the work you've been doing in northern Nigeria over the last couple of years. We can just start maybe by sharing just a little bit about what led you to create the BRIDGE project. Are there some experiences or motivations that you had that led you to think about this project?
[00:02:22] Dr. Edwin Trevathan: Well, I would say just in general, this is just my experience. My approach is I think the most important part of doing research is to find a problem that's really important and then ask the right questions about how do you solve the problem, and then getting good people to help you. The problem that really struck me as being critically important is really the fact that, at least looking at old data, that about 80 percent of children with epilepsy in the world live in low- and middle-income countries, many of them in sub Saharan Africa, India, Southeast Asia, and that the rough estimate was well, about half these people are untreated.
And that's the epilepsy treatment gap. And so what can we do to close that gap? And I think what led me to seriously get more interested in it was when it became clear, and this is maybe ahead of what's in the literature now, that that's an underestimate. The estimate of half the people in the world with epilepsy are untreated was based upon prevalence data, epidemiologic studies that didn't even include people with non-convulsive epilepsy.
So it turns out that the prevalence of epilepsy is much higher than we used to think. It's more like instead of being, you know, 9, 10, 15 per 1,000, higher than it is in the U. S., which is about 7 per 1,000, it turns out that it's about 38 per 1,000 or even 70 per 1,000. So it's tenfold higher prevalence perhaps even than it is in some rich countries like the United States. And the treatment gap is much higher than 50 percent there. It’s more like 70 to 90 percent and in northern Nigeria, it's over 95 percent.
What that means is that more than half of the children in the world with epilepsy are not treated. And so this is to me just a moral imperative. We have got to do something about it.
And if you start doing the math, we figured out in northern Nigeria where there's 210 million people, half of them are children. And you start doing the math of how many people have epilepsy that's untreated. It's in the hundreds of thousands of people. You realize that the system we have for taking care of epilepsy that we use, developed in the West with physicians doing it, just doesn't work.
If you ask the question, “How many physicians do you need to train to take care of a few extra hundred thousand people with epilepsy?” I mean, if I was going to ask you to do that in your clinics, you would think I was kidding. That's what we're asking in northern Nigeria, where there are literally hundreds of thousands of children in the northern part of Nigeria, probably, that need treatment that don't have it. You can't train your way out of that with physicians.
So you have to develop a new system. And so coming to that realization, we looked at where we could do some studies of some innovative care systems. And we chose Northern Nigeria because it's one of the poorest places on the planet, and yet they have good physicians and specialists. They just don't have enough of them.
And there weren't too many other people working in this area, or almost nobody. And so we basically chose that area to develop relationships and to start these studies. And that was about six years ago, and so we've developed a system that was actually an idea we didn't come up with. We just sort of implemented it, which was task shifting care, moving the task of epilepsy care primarily from physicians to community health workers. There are enough of them to actually see all these people, but then they don't have the training. So we developed a system for training these community health workers in epilepsy care.
And then we developed a system for them, a training screening system for them to be able to go out and go door to door and screen people for epilepsy because they weren't in the health care system. We then developed a clinical trial to and got funding from NIH to do a clinical trial comparing a system of care where physicians take care of people with epilepsy previously undiagnosed to this system and where the community health workers take care of the people with epilepsy that were previously undiagnosed, with physicians sort of supervising them, remotely leveraging the physician expertise as much as possible.
So we just completed collecting all the data on that clinical trial pretty recently, last fall, mid to late fall. We're working on these submissions and getting the papers accepted and so forth.
The general things we've learned is that there are a lot more people with untreated epilepsy in that part of the world than we thought. We thought that it would take us two years to enroll enough people for our clinical trial, and the enrollment was so fast, we had to stop it early.
We thought that people that were undiagnosed and untreated with epilepsy in the community wouldn't be as severely affected as people who were already in the system, with the idea that if you had really severe epilepsy, you'd end up in the hospital, right? And we were wrong about that. The severity of undiagnosed epilepsy at least equals what was already in the system.
And we also underestimated the comorbid conditions that these children would have like cerebral palsy, which occurs in about a third of them, a quarter of them. Malnutrition, which occurs in about half of the children.
So, you know, when we go and we address these problems now, we have to think about how we are going to treat malnutrition in people with epilepsy. How are we going to manage their neurodevelopmental problems? It is a big problem, but I think the community, broadly speaking in neurology, and now I think in public health, global public health, hopefully we'll be developing tools to address this big problem during the lifetime of our careers.
[00:09:28] Dr. Emma Carter: I'm backtracking a little bit just talking about, this is a hard question to ask with six years, the studies been going on, but just to ask you a little bit about implementing all of the tools that you guys have used and talking about maybe lack of resources in that area to start with. I was just curious, you know, for other people that are hoping to maybe implement some of the tools that you guys have used in other regions in Africa or other countries.
[00:09:59] Dr. Edwin Trevathan: We've developed tools for educating people about epilepsy who are not physicians, for radio broadcast in local tribal languages, to educate the general public tools for screening and explaining epilepsy to people that have never heard of it.
Part of our commitment to NIH [U.S. National Institutes of Health], which is what we're going to be doing over the next several months to a year, is taking the ones that look like they work really well and developing what we're calling tool kits, which we will then make available for free to people that want to adapt them to use in other places.
We've made some progress in northern Nigeria. But the culture and the environment and the genomics and everything is very different in northern Nigeria than it is say in Democratic Republic of Congo or in South Africa or Tanzania. The local languages are different. So there's one of the real challenges with this problem of bridging the epilepsy treatment gap is that all of these tools will then have to be adapted to the local reality, which takes work.
So I think one of the challenges we have now is understanding how we can scale up and get adapted to different environments. Some of the systems that have been developed and seem to be working pretty well in in at least the environment where we're working, but I think it would be a mistake to assume if it works, you just cut and paste and it's going to work everywhere in the world because you know, these cultures are all different and unique. You sort of have to have local people really guide the process.
[00:12:01] Dr. Emma Carter: And talking about that, obviously being an obstacle long term and just talking about some obstacles in general that you guys have come across. If you're able to talk about any of those. Things that you weren't planning on or that came up in the process.
[00:12:17] Dr. Edwin Trevathan: When you talk about the epilepsy treatment gap, you're describing people that are out there that you don't know about. The question is, what are all those people like out in the community that you've never seen before?
I mean, you sort of don't know the answer to that question until you go out and you find them. I'll say two things. One is that the children were much sicker and had more comorbid conditions and were much more complicated than we thought. Their epilepsy is complicated. Their comorbid conditions are complex. And the idea that sicker people make their way to the hospital turns out to be wrong. People that have money make their way to the hospital, it seems like. That's one of the I think that's one of the things we learned.
And I think the other general concept is there is a sense in which in Africa, we're starting to think of epilepsy as a disease or disorder of poverty. I mean, we think about that with some infectious diseases. But there's a sense in which, and we don't understand the etiology, etiologic risk factors and so forth like we should. And that's a big area of needed research. But these the prevalence rates seem to be higher in these poor communities and their ability to get access to care is…there's so many barriers, transportation, literacy issues, the fact that someone has to bring a disabled child a long distance to get care of, if they have to travel a long distance and then who's going to take care of all the other children, you know, all the things that we all understand as parents or grandparents and providers, but it's just sort of multiplied because of the great distances and the poverty there.
Solving this problem is going to require not just neurological expertise, but people that have real expertise in logistics and delivering systems of care are going to be really important.
[00:14:36] Dr. Emma Carter: I wanted to see if you wanted to tell us a little bit about your second NIH study unless there were some more things that you wanted to share about the BRIDGE project.
[00:14:46] Dr. Edwin Trevathan: There's a sense in which we're just getting started with the BRIDGE project.
You know, this was really the first big study of task shifting epilepsy care to community health workers. So I think there's going to be a lot more to come. The SEED project, I can just briefly say, is one that there was another big problem that was nagging me a bit, and others.
We see all these people who have first-time seizures and children who have status epilepticus as a first seizure and some of those children develop epilepsy. And some of them don't.
And if you follow these children for a long time, like I and many of you have, sometimes our clinical impressions and predictions aren't very accurate about what's going to happen to an individual. Knowledge of the predictors of outcome in childhood status epilepticus is limited in part because some of our studies have been sort of small, the sample size has been too small.
Another thing that really got my attention, the more I've spent time in sub–Saharan Africa is that there's more genomic diversity in sub-Saharan Africa than in the rest of the world combined, and it's actually not even close. So when we do these studies in epilepsy or anything and we use European and North American populations, even when we can have adequate participation by people who are African American and other minorities here in the U. S., it in no way gives us insight into the vast amount of genomic diversity in the African continent.
So, I felt like we need to do more genomics of epilepsy, seizures and epilepsy, in sub–Saharan Africa. And we really need a big cohort study of childhood status epilepticus so we can look at predictors of some of these important outcomes.
The SEED project, which is childhood Status Epilepticus and Epilepsy Determinants of outcome, is a large cohort study, and we just finished enrollment, so we don't have data on long term, but we just finished enrollment December 31st of 2023, so we've enrolled 1,551 children that have status epilepticus, and all of these children have detailed EEG and clinical data. We developed EEG services that they didn't have just for this study. And then all of these children are being followed prospectively for two years. And we're looking at clinical and genomic predictors of outcome. Genomic predictors of development of epilepsy among children that have status epilepticus as their first seizure is one of our goals. Clinical predictors of that outcome.
And we're also looking at clinical predictors of mortality and genomic predictors of mortality. Mortality there in status epilepticus is much higher than it is here, and we don't really know all the reasons why. Some is because they don't have ready access to emergency treatment and so forth, but there may be other reasons too, but the mortality, short-term mortality is between 15% and 25%. So it's much higher than in the U.S. So we're in the process now of following this large cohort of children to do genome-wide association studies and clinical outcome studies in that population.
We're finishing getting all the blood. And getting the DNA extracted and you know, all that stuff. And, you know, the logistics, if you're doing all of this in one of the poorest parts of the world is you have to, we had to set up the lab to do the DNA extraction and, working with people there, in places where it's 110 degrees—how do you draw the blood, maintain the cold chain to the lab where you can then get the blood processed and prepared for DNA extraction? Those processes are a lot of what we've taken time to develop.
[00:19:22] Dr. Emma Carter: I was curious moving forward, if there are thoughts about future projects already, or just continuing with these. Do you have any branching studies or other colleagues or collaborators that you're working with to have offshoots of these studies, potentially.
[00:19:41] Dr. Edwin Trevathan: One of the things that we're hoping to do with this, which I hope we're doing with this broadcast, is to encourage people to collaborate with colleagues in low- and middle-income countries.
And you know, it takes more time and it's harder to get things done sometimes in places where you don't live. I don't know the culture yet, but it's just rewarding, I think, in so many ways. Those of you who are have an interest in doing it, I encourage you to seek out some people like me, and there are many others of us that have some experience and we're happy to help you provide you some advice and encouragement.
We have a training grant from Fogarty International Center that we're very happy about, and we're training junior investigators there in Nigeria. So, for example, one of them is doing research on the pharmacokinetics of anti-seizure medicines among children who have malnutrition, especially those with stunting, because stunting adversely affects the intestinal villi and there's some evidence that may negatively impact absorption or change absorption of anti-seizure medicines.
There are things like that that have never been done. Just basic pharmacokinetics of drugs that are available. That's important. But there really isn't an area of neurology that I can tell that we know about here in the U. S., or in North America. Europe, Asia, wherever you are, there isn't a neurological disorder that isn't also a problem in some of these low- and middle-income countries.
And more often than not, when you search for it, you find out the problem's bigger there. So if your skill set is not in epilepsy, I know this is ILAE, but anything in any area of neurology, there's probably a big need. And so I just happen to be working in epilepsy because that’s my love, but there's plenty of opportunities in other areas.
We have some stroke projects in northern Nigeria as well that are directed by Michael DeBaun and Lori Jordan and some others at Vanderbilt. But think that there's much work to do.
[00:22:12] Dr. Emma Carter: You've given us already some great insights, takeaways from your experiences, and some good plugs to just get more people involved. I wanted to see if you have other takeaways, things you wanted to share that I might not have asked you before we wrap up today.
[00:22:28] Dr. Edwin Trevathan: I would just like to thank the ILAE, International League Against Epilepsy. The International League Against Epilepsy has been tirelessly championing the needs of people with epilepsy in poor countries in the world for decades. And I really hope that now we're starting to get some real traction on that.
There are a number of groups around the world that I think are doing some very important, good work. And one thing that all of them have in common, our group included, is that we're largely doing the work because we have been inspired and encouraged to do so by people of directly representing ILAE or who have been influenced by the International League Against Epilepsy. So I think that the ILAE is responsible, really, for any progress that we're seeing. And it's taken 30, 40 years to get there, but I want to thank them for persisting.