Global Health and Malaria with Dr. Chandy John


Welcome back to the Healthcare Trieste podcast this. PODCAST is sponsored by Indiana University School of Medicine, whose mission is to advance health in the state of Indiana beyond promoting innovation and excellence in education research patient. Care I, you school of Medicine. Leading Indiana University's first Grand Challenge, the precision health initiative with bold goals to cure multiple myeloma, triple, negative breast, cancer, childhood, Sarcoma, and prevent type, two diabetes and Alzheimer's Disease Today we. We have with US Dr Chandi John He is the Ryan White Professor of Pediatrics and the Director of the Division of Infectious Diseases in global health at Indiana University School of Medicine I should note that this episode was recorded before the pandemic started since then. Dr John's Infectious Disease Expertise helped lay the foundation for to covert related studies tactic, which is looking at how many. People in Indiana Wade. Actually be infected and discover which is looking at how immunity responses occur. After people are infected, we should also note that his research about sickle cell anemia, African children was recently published in the New England, Journal of Medicine and people might want to check that out as well Chandy. Welcome, thank you so you're the Ryan Way Professor Pediatrics. Who Is Ryan White? And what does he have to do? With Indiana Ryan White is in Indiana. Indiana heroes everyone in Indiana and the United States should know about him. Ryan White was really the first child in the United States, who was publicly known to have issued in make a secret and the reason he got into the news was because we lived. They didn't want him attending school with all the kids and he insisted on going to school. This is a very brave individual and kind of push this where a lot of. Of other people just kind of shrunk into themselves and bring it up because it's one of those things where it's like I remember I did live in Indiana at the time, but I remember it being in the news for people old enough. It was a huge huge deal I mean because up until that point. It felt like it was a pretty stigmatized disease were many people were blamed, but he seemed to be the face. If I'm remembering correctly. Correctly like the first quit I'm putting in quotes. Nobody else can see my equity. You're like innocent. Where we sort of public in this child at a big deal that everybody was so public about it. Yeah, it was a huge deal is very brave of him because he got a lot of discrimination and hate mail, and the rest of it, or you know hateful comments right to his face where he lived but he refused to sort. Back away from that and also I. Think very importantly. He also refused to be the quote unquote innocent face of it. He said that everybody who has HIV is say they should be respected. However, it was easier for the public to handle that than maybe to handle gay men who they thought of as other or or something he really did in the United States help to give face HIV that many people could relate to more And I'm the Ryan White Professor, of Pediatrics, and I always mentioned this because our whole division was supported. By an endowment for the Indiana University, Dance Marathon, and that endowment and the Indiana University dance, marathon itself were started by Ryan White's best friend from High Yeah To Stewart I believe her name was, and so she started at more than twenty five years ago and to start, it was started in honor of him, so he was supposed to start at you that fall and died before he could start the started, and she organized a dance marathons, and they've evolved this massive huge. Yeah, and if your local Indiana's a big deal with your kids and these guys are amazing, high school kids in college, kids and they raise funds for Hospital for children, but for the first many years they raised it just for our division, and so that was amazing. It's funny because I knew I knew there is money for Riley but I didn't know it was for that purpose and I. It's funny. One of those I knew Ryan White was, but when I moved here I was like. Why do they have the professorship year? Like didn't know He. INDIANA. No, it's it's amazing, and so now the funds from the Indiana. Brisy dance marathon go to the whole department of beating. US For the first twenty years it was to raise his endowment, and so when people ask me who this rich donor was, who gave the endowment that allowed us to create this amazing or build this amazing division It was It's the college kids, and and I should also very important dimension. The connection there is that writes. Doctor was Marty climate. Who is the? The founder of our division, so that was when they wanted a way to honor Ryan White and and support the things that were important to him. The sought out Dr Climate. He said supporting research in this areas is critical, and that's what they did. Well, that's great and not just completely veer directions, but you know the time what we wanted to talk about. About. Today is global health. So I like to always start by talking to you like. How did you decide? This is the area that what you wanted to be in in studying not just infectious diseases, but how they the impact, the world, not just even the United States. How'd you get here? Yeah, so there are many answers that question, but the beginning always starts with. With my parents so My parents are from India. They came here to do their residency I. always mention because this is a fact that. When they came here, they were paid to come here, so there was a doctor shortage. So when people are talking about all these terrible foreign medical grads and stuff boy. The US has relied on those foreign medical grads and. Show all the time. Yeah, it's it's a big deal and they've added a lot to the country. research wise clinical is an in every aspect of so. They came here for their residencies, and then they went back to India to work at a mission hospital and so we sort of went back and forth from the United States indie when I was a kid, but when they were there this mission hospital, its mission was to serve the poor, and so they would take us on rounds or to the hospital on a fairly regular basis because they really wanted us to be sure to see why. Why they were doing what they're doing. Their lives were very busy. They both doctors and so They were at the hospital a lot and you know kids could sort of feel like hey, why aren't you you know here with me? But we never felt that way because we saw what they were doing, and it was important, so that sense of those who have have a responsibility to serve those who have less because none of us earned what we have. It's all just you kind of like what we started with. was very strong in my parents, and they pass that onto us and so. The idea of doing something for underserved populations, and then when you think about places like India and Africa. Have you know the under served there are. An Order of magnitude, more underserved than those in most other places and so that led me into thinking. What could I do for that population? That medicine was kind of an obvious path, because my parents were doctors, and they loved what they did, and I could see its immediate impact Then you probably don't know about me, is that my big interest was in writing? It still is my first love was writing, and so I wanted to do something with writing, but I couldn't figure out a way to do that and serve that population now I? Know there are many ways you could do that, but back then I haven't. And so so when I was thinking about this, you know my mom was sort of giving me advice and she said. If you decide later that you want to be a doctor, it's going to be hard to do that where you can keep writing even if you decide to go into medicine. So that was what I did, and it was more of a pragmatic decision than a love of medicine to be totally honest, but like would. There you go. I could do something with. This wasn't sure that I really as kind of like I didn't like blood, and God's but then of course I got into it, and it's amazing like professional. Madison is just incredible and. Being part of people's lives and especially pediatrics than these kids get better and in our domain of infectious diseases. They almost always get better, and so that's very fulfilling. How did you decide to do infectious diseases? Though yeah, so it was the same thing I wanted to do something globally and historically, and to this day the biggest problems globally for sure infectious diseases and so. So why spent a couple of months at a mission hospital in Bangladesh when I was a fourth year medical student, and then in my residency added chance to do this. and I wonder if you where'd you go to Medical School University of Michigan was that was that common that people would go? No, no, it wasn't so. University Michigan was the most. Medical School I just loved it there and so was such a privileged to be there and in-state tuition was amazingly low, and it was just it was a marvelous place to be, but at the time I was there. They were not a big global health center. They are now have rectified that that problem, but back then they weren't so. It's a little unusual to do the rotation to sort of work things and then in residency. Residency I did I spent nine months. Nigeria as an absent international health, and that was really radical, because it was taking a break from residency to do this and was kind of like I. Don't know the recipe was totally happy with me for doing it, but they did support it so I give them serious credit for that. Because I'm residencies would have just said no, you're. We're not going to do that but they. They supported me and so I was doing a med peas, razzies in Nigeria the getting to the point of why did I do infectious disease? I saw all these kids with malaria was by far the number one reason for both inpatient admissions and outpatient visits at that time, if a kid had fever in pretty much any African malaria endemic region, you just treated them without a malaria. You didn't even do any other work and then. Then, if they didn't get better, you do the other workup unless there was some clinically obvious reason that was actually who standards was you gave an malaria for fever. That's how calm and it was. And at that time there were very few pediatricians doing research on malaria. In the United States, there were. There are a number of good malaria research program. Almost none in pediatrics just so hard to believe I mean. Malaria is a major. War. Back then it was like maybe number or three. There are more than a million kids every year. I mean and the statistics, and how like mosquitoes killed more people like anything else? On Evan, it's a it's an online and a lot of them are clearly children's. Why why I don't know why. It was one of those you know to be honest. I love our disappointed pediatrics, but I think we have lagged behind internal medicine and some other disciplines in terms of the global health aspect of things in some aspects. No, because if you think of vaccines, that's very much. And in pediatrics, pediatricians largely leading the way they're and they're probably the. Biggest medical in most successful medical intervention absolutely yes, so in some ways you know right there for global health for a lot of problems like this pediatricians weren't doing that and when I talk to people who like Oh is this career suicide? Nobody's out there doing this. It's kind of out there and these kinds of responses. I would get from some people. There are definitely people that are supportive. So I think that pediatrics took a little while to kind of grow into wanting to do more in the research space of global people were thinking more about volunteer things and stuff like that, which is important, but even when? When we talk about even I think clinically go. I see I see a fair number. Medical students even see a fair number residents who say they want to do it and spend a month or go, but it feels almost as if it's vacation destination. He Yeah, not now like dedicating lot. Which is why I'm always impressed by. You know people who are like I'm going. It's a hard road like you had make it. No one was saying we have a plan. That says he'll do a a month here and then nine months here. That's how you get to to do that so I mean especially I think. Years ago it probably took a fair amount of effort to carve out those kinds of careers yeah. I mean it was much less much more of the road. Less traveled within pediatrics I I'll happily say things are vastly different now and I feel like pediatrics is in many ways leading the way in education in terms of those very things you talked about that global health work should never be medical tourism that there should be a. Mutually beneficial partnership in every case, I think they're really outstanding pediatricians at every level education and research rent doing now, but back then kind of across the board. It was just it was hard to do so You had to be pretty. determined that this was what you wanted to, but that was the one thing that I will say is I was determined and and. I if I like if there is somebody listening to this, who's starting or whatever I think you know like I'm not the smartest person on block. I'm not the most you know like the have the brightest ideas but I work hard and I was willing to persevere, and I think those things matter more than anything, especially global health because you just have to. Just have to like there's a lot of things that go get a lot of things. Do not succeed. You Know Rachel Freeman, who is one of our? We've had a props. My my fellow when she declared that this is what she wanted to doing entered our fellowship in a completely different path, but this is where I want to. Make my life, I remember not trying to talk her out of it, but being like I have literally no idea what muscle to flex to make any of this work. You'll be entirely on your own and the story. She's telling me about what she had to do to get stuff done. In Kenya where I think most of her work is one of the things I focus on how hard it is to get people healthcare in the United States of America, which is a pretty wealthy research country, and it's so difficult I can't even fathom how hard it must be not only get healthy, but research done in some of these settings I mean the number of extra steps and things that you have to do it. It's impressive. Anyone engages with it. Let alone succeeds, and it's such testament I think to how people are willing to work. Yeah, I think. Rachel's like the poster child for dedication and perseverance in the face of obstacles because she knew what she's doing was in is important and and I think that's just it. Is that you if you're in that setting and you have a research type of mindset, you see the possibilities for the difference that research can make in those populations, and that along with really great partnerships with incredibly smart and engaged people in the country. who kind of provide mentorship in how to do this and. And what you can contribute I always say if everything is being contributed by your partners overseas, and there's really no room for you so you should have something to contribute as well, but she got an I got so much mentorship with the people outside are like. Hey, this is what you should focus on. This is what's important. Here's how to do it in this setting, but then you work with them, and you see the difference it can make an I will say you know like the people that are working there the people that she works at people that I work with could have jobs anyway. and they work in what can often be an extremely. Frustrating and difficult system day in and day out whereas we're going there, but we have the support of a US university, and so it's a real tribute to them that this work gets done. Because ultimately, that's what matters is that people on the ground have the know-how and expertise to work with you to get it done, and they're willing to just keep going I. Think I remember now when Rachel was on the program, we talked about empathic general, but but in university has a long standing relationship with. My correct entire hospital systems yeah, yeah, Kanye Ghia talk briefly about it. Just people that haven't heard about absolutely so amp hat stands for the APP academic model to provide access to healthcare, and I should say up front I came here from the University of Minnesota so I work together with path, but I'm not really You know one of the Path physicians or researchers or educators, but I decided to move to Indiana University in part, because path is here because it's such an extraordinary program and I think what set set apart from every other program. I believe every other academic program in the. The United States is two things. One is that the decision was made right at the beginning to focus on access to healthcare who it is not primarily a research group. Amazing research gets done with it at like Rachel's cameras and and many others, but that is not be that is a goal. The primary goal is providing access to healthcare, so that is unusual, and so it's a university using its knowledge in partnership with another university more university to work on access to healthcare, and then the other thing is Indiana University. When right when this started, it was an academic model, so it was not just Indiana University and No, you know universities are wonder places to work, but they're kind of territorial. People want to the glory to come to a you, so they started from the beginning. This is a model and any university that wants to be a partner if they meet these criteria for partnership, and so multiple other universities I won't. Remember them all, but Brown Mount Sinai do University of Toronto University Massachusetts. Many others are part of this consortium so together they're working to provide access to healthcare, and then within that they degrade research and education programs. It really is just amazing. One of those things that the more you hear about it, it's just it's stunning. I mean just what they've accomplished and. You know not that great appeared at time is just amazing. It's incredible. I mean the the this whole model to provide access to healthcare. They're now working with the government of Kenya which wants to provide universal healthcare to help model how that could happen, and how could work within the areas where they work? There's a huge amount of work in HIV, and they've revolutionized care of. Of HIV they're now working in chronic diseases cancer center. I mean it's really a a most extraordinary program and great things for me as I try to recruit people within our Pediatric Infectious Diseases Division. An Path is a huge draw because work in that setting is just you know it the opportunities to do great things or so I think didn't draw from at the medical school. Medical since all the time where this is. What drew them? Which is amazing? Yeah, it's fantastic. Let's shift course a little bit I WanNa talk about malaria, 'cause it's other things where again worldwide such a massive problem. It's not the United States. I'd be plenty of people. Don't even know what it what it is. So what is malaria so malaria as a parasitic infection that is spread by mosquitoes it. Can't be transmitted person to person in general I can get it from blood treasurers, but it's really ninety nine point, nine nine nine percent of it is spread by mosquitoes which take infected blood from one person and injected into another, and this parasite goes into your liver, and then escapes from your liver into your bloodstream, and when it gets into your bloodstream, it causes symptoms, so you can get a very high fevers from it, and if you get really sick from it, you can go into coma. Severe Anemia, you can get very bad respiratory distress, a bunch of things, and if you don't get treatment, you can die from it, and it is still one of the leading killers of death in children, which is just again just stunning I mean just the because it's. Can't we worry about all these things that are so dangerous and it's still one of the top five I'm sure. Yeah, I think it is although I like one very happy thing, and in the course of my career is seeing. The progress has been made in malaria, I wish I could say it was all do. Not But but you know bednets and better drugs and other things have reduced the death toll estimate when I started working two million deaths a year. Pretty rough estimates. It's now down to under five hundred thousand, so it's even if it was a million. It's a massive decrease in the number of so, why is it such a big problem in other countries, so many reasons if I talk about Africa specifically It turns out that the African malaria, mosquito, vector or vectors are much more efficient transmission than ones that occur elsewhere, so we have an awfully mosquitoes in the United States, and there was malaria here up till night the nineteen forties, so it was a problem here. interesting sidelights. CDC was started as the office of War Research to combat malaria don't. But it has its genesis in the word. Combat Malaria Yeah. So so CDC has a long history with malaria, but The African vectors are much more efficient transmission, so that's one big problem. and then access to health care is a huge issues of people are living in rural areas more often occurs in rural areas most of Africa's still rural so That's a problem, and then they can't get to the care they need to in time. and things that worked here, so we had malaria here and it's gone. wising gone in Africa will it's a long. Long story but a number of things that worked here are harder to implement across the sub continent of Africa than they were in the United States and a lot of it has to do with a public health system that's able to detect cases and then treat those cases in anyone near those cases kind of across the board so many different factors, but those are some of them, but I would see the biggest thing probably as the public health system in access to healthcare so when it's the public health. Health system is it. Is it prevention from getting bitten? Is it not getting rid of mosquitoes enough? Is it that we don't treat people fast enough? And therefore that allows a mosquito transmitted from, or is it all? It's all of those so in the US. When they were getting down to the end, anybody who had malaria got to the House of that preside malaria, the treat everyone there they might even do spraying of the areas. It's very intense campaign at the end to get you know. Get things down to zero. Zero, so that's difficult to do. Especially in rural areas in Africa, to that same extent and then if you're in a rural area, if the healthcare facilities are far and few between, then people may not come in anti. It's quite late in the meantime. Not only. Is it bad for them? Because it's caused severe disease, but they've had a chance to transmit it to more people, so many of these things together see, said bednets I mean. How much is it? Is it nighttime when a real problem? Yes. It's a female off mosquito that. and She Bites at night so What bednets themselves are not that effective, but insecticide-treated bednets very effective, and they're effective, because the mosquitoes land on them and die They don't get a chance to bite the child, so they going a transfer transmit, and they don't get a chance to transmit to others, either so it's not just the prevention of biting the child. It's also killing. The mosquito on contact is prevented medication I mean. Is there a way I? AM asking totally out of ignorance. Yes, so the next time you come to Kenya Uganda. Aaron inviting you now. Many times just trying to find the time and then. You will take malaria prophylaxis I guess if you want. Now even around elder at their mosquitoes. You Good Nairobi. There's just really there's I mean. There are mosquitos, but there's really no transmission of of malaria. The guidelines will save. You're going solely tonight, roby. You don't need take perplexes, but pretty much. If you're going to Uganda Kenya, you take prophylaxis to prevent malaria medications to malaria, and they're quite effective. They're not one hundred percent, but anywhere from eighty to ninety five percent effective every time I go to Uganda or Kenya I, take a medicine and There have been campaigns to have this in Africa. And there are there is actually so the difficulty is in many places. The whole populations expose e have kids going on this medicine for years and sometimes it's a you can get away with weekly medicine, but that's as long as you can do. Some of them are daily, and so it's tough to. It's tough to do that in a population, but there are W recommended regimens for places that. That have seasonal malaria that during the malaria season, the youngest children will take chemo-prevention in pregnancy. Women are more susceptible to malaria, and it's bad for them and for their fetus, and so there's also recommendations that all pregnant women Milan daycares. Get Chemo friendship, so there are these targeted populations again. Clearly, we radically for the most part in the united. States was that because we just treated so much just. killed it off while there are many different factors, one was as good housing and kind of drainage of swamped areas and things like that, so kind of good general public health measures and better health overall tend to decrease rates of malaria pretty substantially themselves that just by itself. Then there were campaign so a lot of things we wouldn't do now like spring with Paris Green and DDT. Who's your pretty toxic and they do it and sprayed everywhere, but it works. So if you get it down if you get it down to a certain level, then that can sort of take zero I mean many years in Africa. There are some more focused spraying efforts, but they're so much higher than we were that. You'RE NOT GONNA get it down to zero like it works for a while, and then the b-actor comes right back, so the spraying campaigns toxic have been had their effect, and then it was the public health component of if somebody comes with malaria. Go out to that house. Treat the people. So what are your research interests? Overlap in malaria, so three major areas one is to figure out why kids get severe malaria. WHY CERTAIN CHILDREN GET Severe Malaria? Because some kids get very bad Blair hospitals in some kids don't and why you know. Can we prevent severe malaria? another is that a major complication of severe malaria is Noor Developmental impairments of kids, not thinking as well functioning. Functioning as well as they could be, so, why does that happen? And what can we do to prevent that and that so those are sort of on the sick child with malaria side, and then and in Uganda, and then in Kenya, the work focuses on an area, very low transmission. That's gotten lower over the twenty years. We've been there and my original work. On trying to understand how immunity changes as your exposure to malaria goes down, we're still looking at that because we're interested in. If you wanted to vaccinate a population like that where there's not much malaria, how would a vaccine work versus where the areas where it's traditionally tried which have a lot of malaria, because it may be quite different, your immune system may respond differently to the vaccine but now we're in addition to working on that. We're working on while we've gotten malaria down so low. How can we actually get to know local transmission because it's really low, but then periodically they'll be outbreak, so it seems to me like we have to get to to to know malaria the area, but the complicated part of that is that the areas surrounding it have much higher transmission. Transmission so you have to do something. That's both effective and sustainable, and there's not an easy answer to that, but I feel personal commitment I in the one area of Kenya. I've been working there for nineteen years now. and we've just watched this trend with malaria and I felt like okay. The time has come for us to work with the Ministry of Health. Really get it down to zero. Zero. There's one other area that I work in a again back in Uganda which is infections, the kids with sickle cell disease, and the Genesis of this is actually that the reason we have sickle cell. Disease is because of malaria hemoglobin, A. S. or one copy of the sickle gene is highly protected against severe malaria. How is that? Yeah, it's amazing so well I get the genetic. Trait with exists, but how does it work? Yeah, so there are many different reasons why it's positive that it works which have a fair amount of evidence for them, so the having hemoglobin as sickles yourselves a little bit when the parasite goes in and so it makes the red cell less hospitable to the parasite may get cleared by the spleen. It seems to decrease oxygen concentration in the cell, and to that's less good for the parasite, and it helps decrease parasite burden and decrease parasite load, and there are a number of other factors like nitric oxide. It seemed to be altered by. Sal that has hemoglobin in it, and so they never were almost never get sick. Cling crises, but they do have alterations in their cells that make them less hospitable to the parasites, and so I mean is the reason we have sickle cell disease today because of malaria it is, there's no the it's incontrovertible evidence, because if you look at where malaria historically has been and where sickles, all diseases including outside of Africa it's a perfect overlap. That's just so may yes is sickle cell disease exists because Hemoglobin A.. A. S. or sickle cell trait was protective protected against malaria, and what we we've done. These studies of severe malaria that is telling you about, and we get group of control children from the same neighborhoods or households as the kids with severe malaria to look at what how they think, and how is that different from kids with severe malaria? That's how we get our our population norm and only looked at the prevalence of hemoglobin, A. Astor sickle cell trait in the control kids versus the kids with severe malaria. I think eighteen percent and the control kids and two percent and the kids with severe. We rediscovered protective effect that's I. Mean that's just so I mean it's just so amazing to see such a concrete example of how natural yeah, natural selection at work, so what happened though is of course that if you I mean and places where the most malaria, there's almost twenty percent prevalence globally ass. If you do the math that would mean roughly four percent, ish of kids would be would have been s s, and historically these kids get a diagnosis. And they died before the age of five from infection or complications, other complications of sickle cell disease, and so I was working in these malaria democ areas. Caisley kids with sickle cell and not know what to. To do with them and you know like they were pretty neglected population in Uganda. When I started working there there was a very foresighted doctor named Professor Christopher Undo Gua who, in nineteen, sixty nine started sickle cell clinic. I'm Malaga Hospitals? That's more than fifty years ago now and it was one of the first clinic of its kind, and so he identified that this population was a population in need and got them good clinical services, and so the kids who are attending that clink did better than kids in general, but still there were many things that were available here. That were not available in Uganda, because the research had been done or. Or whatever, and so, that was what drew me to looking about population was it was such a such neglected population, and there were simple things that could be done. That were not being done yet. How did you choose to work in Uganda boy? That is a long story that will shorten by saying that I was working in Kenya for many years before I started working in Uganda. and I had an opportunity to do a slightly longer version of the story when I was in Nigeria. I worked at a mission hospital there with a doctor named Cindy Howard is a pediatrician. One of my kind of life influences cindy after she had finished her work. Work in Nigeria started working in Uganda, so she had some connections there when I would meet her, she'd say should meet these people that are working Uganda, some of their amazing. There was one resident I work. He was incredible. I was at Case Western at the time. This resident incredible resident one research award. He decided to want to come out to case Western because Case Western was doing TB. Studies and Uganda said they were well known university there. I met him and he's a I was trying to highland hospitalized. Malaria study in Kenya wasn't working out for complicated reasons they said well. We have islands in Uganda. Why don't you come work there? So I did? we switched the study to Uganda and then an opportunity came up between residency and fellowship I decided that I've been on the fast track do long, and I wanted some time to write and travel and do some global health work and so I worked as a PDD docking to pick you up again for those that are listening like. It's always good to go out in the real world and be away from academics for little bit. Bit. I felt like they gave me some really good. Like critical thinking. I doc on the on site skills. I spent time in Laos helping setting pediatric residency in Laos and when I came back the person who sent me out their car and Olmos who is an amazing global health. Person said we should talk to Michael Boivin. He's going out there to look at cognition in these kids with malaria. You talked just to you know like. Let him know what your experience there was, and what he should be triggered, so he was in Michigan, I was in Michigan. We talk. And then he came to case Western instead like we should study cognitive impairment in these kids with severe malaria, and at that time was like now. He just needs to get rid of malaria. Let's not you know like I don't think we should do that, but he veered and convince me like his his line, which was absolutely true was, but you're still seeing these kids severe, so it's not gone yet. Yet! Are you going to do something for them? So I said yes. You're right and so together. We put in this grant and I decided to do it in Uganda. Because my hospital based connections were much stronger in Uganda. And that's how I ended up in. You KINDA. How do you go about setting up these things I mean they sound I can't even I don't know what muscle to flex. How do you do it yet? So it was learning experience for me. My Mentor Case Western. I went to Case Western for fellowship. Precede on! On their Jim Zara was real master at this, he worked in Papua New Guinea in and we worked together. In Kenya, and it's all about knowing the people locally and areas, they identify important the first study for example been working this highland area for a long time as I told you and it start because Kenyan colleague of Jim's while these highland areas, they keep getting outbreaks. Do you think that could have anything to do with them? Losing Immunity Jim said will you're starting as as a fallow and you know like you're interested in learning. Learning lab stuff. Why don't you think about how you can look at immunity? These populations you can work on this study with me and John Uma was our Kenyan colleagues name, so it starts with identifying what's important to your local collaborators? You know the situation far better than you do. Sometimes there are requests for applications. Nih and you have to see if it fits what they want. And then I think it's identifying good people. It's very important to me to always talk about The people I work with in Uganda and Kenya in. The? Baba? Poke is my main clinical EPI research collaborator Paul Bungee Rana is by primary neuropsychologist claburn. He actually got are his PhD with our project. And now he's a pin is own on several. That's granted Richard Rose. Collaborator and we have some up and coming collaborators ruth nause is our hematology collaborate so these are amazing people, and they all have different strengths, and so as a question of we like each other. We like the work that the others do. How can we work together to address an important problem? Israel local people yeah. They're all bracket Democrats in the United States. No, no, they're all based at mccarey university, and then in in Kenya my main collaborator is. Is Georgia Yodo who works with Kanye Medical Research Institute and with a university there Jaramogi Oginga Odinga, university and so he and I been working for many years in his strength was actually genetics, but now he's doing more epidemiology work, but in all cases we enjoy the work together, and we've always been able to figure out roles for each of us, and for the people like for me, junior faculty or post, docs or PhD students and For them the same thing on the Ugandan side. Like how can this work so it helps both groups, and it leads to the bigger goal so I I was like dimensioned them. Just because I think that people think like you go out there and you do these projects, but you don't know it's the people they're doing the project and you are doing your part of it. That can be useful to them in the project. What are you most excited by right now? Where do you what things are coming down the pike that you have the most optimism for a very excited about the reduction in cases and deaths of malaria, and I think it can go further there are vaccines in development. There's this possibility of genetic modified Mosquitos. or mosquitoes with other organisms in them that make them. Them less hospitable to to the parasite, there are campaigns of mass treatment that can reduce the population burn overall, even things we've used for a while like bednets spraying still have their place, and so there are many different ways in which we can very actively work to reduce malaria, so I think that we're going to keep seeing reductions and I'm I'm optimistic about that. That, the flip side of that is that we've stalled the last two or three years, and so I'm also worried like drug-resistance like malaria. They can big die from the fifties in seventies, drug-resistance came at the tail end of the sixties and Seventies. It just skyrocketed again and so I feel like I feel like the pressure is on for us to be aggressive about interventions. Interventions and research now because we have this opportunity to keep driving down, but if we get satisfied, it will come back in in blaze. Can you any more than once oh? Yes, okay, so then. How would a vaccine work? That's a great question because we don't have a great vaccine for malaria, so designing a vaccine for a parasite, which is much more complex or Bacteria or virus is very difficult. There's never been a successful human parasite vaccine. The vaccine is that we have for malaria have worked, but it's been like maybe thirty percent efficacy. There are some vaccines right now. That seemed to show in very small trials, maybe more efficacy, but you have to give him intravenously. That's obviously not a great thing for you know mass deployment. The trick with a vaccine is to end up. Generating response. It's better than the parasite itself generates, and it's been really hard to ensure its and yeah, and then things at work here and people that are completely malaria naive may not work as well in kids who are not totally malaria Ni- because they've been prime, maybe have immune tolerance, whatever, so it is quite tricky thing, but the goal with the vaccine is actually improve on. On the natural response, so the wouldn't get repeated episodes. So this is going to be totally naive again, but what about better? Just mosquito repellent? Yeah, well, that's being worked on. It's not naive at all. There's big studies looking at spatial repellents and other ways of using it has to be something. Probably, that's not something that people are going to be on themselves because they just won't. Is that I was going to that biggest issue. I'm speaking from experience like. People in the United States, spray them say yeah. Yeah. People don't want to do it and so something that would repel, but doesn't require the person to do it every day I. think that's the key. repellents are being used as well so there's a lot of things I mean it's really an exciting time to malaria because he's been a lot of success and is kind of promised success, but there's also the specter of like. You Take Your foot off the pedal a minute and suddenly are. Just I I mean I know upset, even multiple times in this conversation, but it's one of those things where I don't think people understand how big a deal it is. Yeah, it's a huge deal and what we've shown like, so you always wonder like what is your contribution like any of our work? Really Reduce Malaria because that wasn't what we were focusing on implementation. Implementation we researched, but what I can say is that some of the work in Uganda show that there's this big cost of child neurodevelopment from Severe Malaria, and we actually are doing a study right now we're. We're taking the three cohorts. We enrolled to study this and following them anywhere from five to twenty years after the had the episode, said now we can. Can See things like. Is there a health related quality of life caused? Is there an economic cost? Is there a cost academic achievement? Kids who had are they less likely to go to college, and we have a control group that's from the same households or neighborhoods, so they're pretty good control group for all these other factors might affect that so we're trying to. To define that for the very long term bet, even like as far as two years out. We shown a cost here and so there's a cost in terms of debts, but there's probably a societal cost that's as substantial when you look at all the survivors, and what happens to their brains. The other thing that I'm very excited about is sickle cell disease because. We, did this studied yeah of of using hydroxy Rio which is used for kids here in sickle cell with sickle cell disease and we've. There was no reason to believe it wouldn't be effective. It's very effectively reducing complications and probably prolonging life. There's enough data to show that yet, but it's likely because it produces end organ damage, but there was reason to believe that maybe it would be harmful in. In terms of making kids more at risk for severe malaria for severe infection, and so the long, the short of it is the study that we did it was first placebo controlled Rcti Roxie and kids in Africa and it showed that and it was done with our with Baba told you about in our collaborate Russell where his pediatric hematologist. That was another thing I wanted to study. Sickle cell disease, but couldn't study it without an expert in sickle cell disease research, we had the experts in clinical disease, and Uganda, but we needed the research expert, which was Russell, where and so Russell joined us, and we did. The study together showed hydroxy was not only effective, but safe and so that's actually one of the more satisfying. These ever been involved with my usual stuff is like what happens with immunity, or what happens renders not an immediate translational step, but the Ministry of Health has actually already proved hydroxyurea for using sickles these it was a cancer drug before to cancer drug and now it's expanding the guidelines and we're there trying to get subsidized Roxy Rea-, so kids who need it can get it so I feel like within five years. Most kids with cycles of these. Will be on hydroxy. It can have side effects, so you need. Do it right like if it's just given out like water, no one's falling. These things can be bad, but that's another thing that Bob and a colleague. Here at a you are studying together. How can you do this so that it's effective, but also safe follow up in resource, poor areas, but it's exciting to see it being used. Be Used at all when we started. And now it is so I, feel like and we're doing a study on zinc to see if it can prevent infection kids with sickle cell disease so. We, yes, so it turns out that people can't see like a mega face. The United States so this is so interesting to me. Because the few things I think one is that there were studies done in the United States that suggested that there was an effect. on preventing infection and a large effect, and then there was another study, but they were all done in adults or older children, and then there was another study that was dining India, that showed it had a large effect as well I'm talking like fifty to eighty percent reduction. I'm like I think really it's I would be thrilled. Don't get me wrong I. Want to see yeah, so so and the reason why? Why it may work, is that when kids with sickle cell disease bone crises is all stuff I learned from my colleague. Nutrition Syracuse. She sort of brought this up because I'm not a nutrition expert and I I like parenthetically. That's the joy of academics as you collaborate with super sharp people, and they give you new ideas that are like really inspiring. She found this data that I never knew about we were. Were writing a book chapter ever and it was like. Don't write book taxes terrible, but we writing books. I agree to, and like she found this data on zinc, being productive in sickle cell disease, more looking at it turns out in bone in these basically crises that they have when the cell cycle and they they clot off circulation to the bones, the bones released zinc, and it goes out into the bloodstream. Bloodstream and kids with sickle cell disease often have some renal impairment, and so it sort of escapes in the urine as well even without renal impairment it can be excreted in the urine, and so there are studies that show that kids with sickle cell disease, low zinc plasma levels, but there's reasons to believe that their actual whole bodies glowed is even lower than what you see in their plasma, so they are. Zinc deficient for a reason, and this is why zinc might okay, so that makes a lot of sense versus just the whole like. Just that someone. But but the great thing about it is if it works, we have Ecuador's. We don't sure there's a couple studies showing that it does. They were an older kids. Maybe the younger kids don't have as much zinc deficiency but if it worked, it's almost completely nontoxic. Yeah, and it's easy to take and it's cheap as dirt already got it for less than a sent a pill, so if it worked here be an intervention that you could give. It's like it. You wouldn't require any monitoring and if he also just take the pill, and it's like three bucks a year going on now. Yes, going on now. We want to have you back. Yeah, exactly. Hopefully it won't be to say like didn't work now. Sean we take negative results but. Healthcare Trash podcast, is sponsored by the School of Medicine whose mission is to advance health state of Indiana beyond by promoting innovation and excellence in education, research and patient care. They're also leading universities first grand challenge, the precision health initiative with bold goals to cure multiple myeloma, triple, negative breast, cancer, and Childhood Sarcoma and prevent type, two diabetes and Alzheimer's disease.

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