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Scenes of wildlife from around Malawi's Blantyre Malaria Project, which collaborates with CIDR to study cerebral malaria. Photo courtesy of Terrie Taylor.

Inside a Cerebral Malaria Children's Ward, Pt 2

Maria Bernabeu, PhD

Posted on Apr 25th, 2018

It is estimated that malaria kills a person every minute. Of these, the great majority, around 70%, are children under 5 years suffering from cerebral malaria. We have shared before the breakthroughs in cerebral malaria research that we are achieving at CID Research.

To study the disease where it is endemic, CID Research frequently partners with organizations working on the front lines of the fight against malaria. The Blantyre Malaria Project is a research affiliate of the University of Malawi College of Medicine led by Dr. Terrie Taylor, Professor at Michigan State University (MSU) and Dr. Karl Seydel, Assistant Research Professor at MSU. In part one of this two-part interview series, CIDR scientist Dr. Maria Bernabeu talks to Dr. Taylor about her work with Blantyre Malaria Project. In part two, Dr. Seydel discusses his research and experiences working in Malawi.

Dr. Karl Seydel is an assistant professor at Michigan State University. Soon after he finished his MD-PhD, Karl knew he wanted to work on infectious diseases. Early in his career, he spent time in Pakistan working with TB and in Malawi learning about malaria. In Malawi he found a strong infrastructure dedicated to cerebral malaria research at the Queen Elizabeth Central Hospital in Blantyre. He fell in love with the country and for 14 years has spent more than half of each year in Malawi.

He splits his time between research and clinical practice for children with cerebral malaria. Dr. Seydel has been a leading force behind some of the most significant advances in understanding cerebral malaria, including recent collaborations with CIDR.

Maria Bernabeu: How would you describe a typical cerebral malaria case?

Karl Seydel: It is a frightening disease. Especially cerebral malaria, it is the worst of the worst. What we hear from mum in a typical cerebral malaria case is, “He was fine yesterday, he was playing soccer in the field and then he came in, ate dinner, and went to bed. We heard something in the other room at 2 am, and he was convulsing on the floor.” The children are in coma when they come to us. Many times, within the first 24 hours, they die. That is what is so frightening about cerebral malaria. It goes from a completely normal kid, out there playing soccer, to dead in 36 hours. 18% of our kids still die, despite our ward probably being the best in Africa. I´m not patting ourselves on the back too hard, it is not about the clinicians, it is a matter of resources. We have an MRI machine, we can do EEG tests [electroencephalography] and we have excellent nurses. We have nurses who have worked on that ward for 15 years and they are extremely dedicated. They are what leads to our excellent clinical care.

MB: What is your role when you’re working in Malawi?

KS: In Malawi I have dual roles. I´m an MD-PhD and in my career, I found I need both aspects of biomedical research. I did all clinical for a while and I hated it. I also did pure research as a postdoc at the NIH, and after a while I found I was getting too far away from the disease. I need some immediate gratification, and that is what you get from the clinical work. It is great to be there, taking care of the kids, seeing them get better. The other half of the time I direct the molecular and genomics core facility, which is a lab that is set up within the College of Medicine at the University of Malawi. We started it about eight years ago with the funds that came from the International Centers of Excellence for Malaria Research (ICEMR) program from the NIH. Now we have lots of equipment, and we have really good techs who are very motivated. We don´t really feel inhibited in science by a lack of technology, lack of equipment or lack of human capability.

MB: What are your biggest scientific accomplishments?

KS: By the outside world’s standards, a few years ago Terrie [Taylor] (pictured below) and I led an article that was published in the New England Journal of Medicine, in which we describe for the first time the neurological mechanisms associated with the death of kids with cerebral malaria.

But at the same time this was happening, there was another study that I was personally more excited about and that I continue to be more excited about. Only one out of 200 kids with malaria get cerebral complications; the other 199 are going to be fine if you give them oral meds and you send them home. But this is such a problem in the rural health setting because we can’t predict which kids will progress to cerebral malaria.

By measuring a single parasite protein in the blood of the patients, we are developing a nice little algorithm that will determine which kids are going to get extremely sick from cerebral malaria. This is going to have a big impact on malaria treatment, eventually. It will help the kids in a rural setting get to medical care quickly before they have a swollen brain.

MB: Do you work with other diseases?

KS: We are starting to do a little work on non-malarial fevers. There is a huge need for RDTs [Rapid Diagnostic Tests] to diagnose diseases other than malaria. In Blantyre, we test a kid for malaria but sometimes it comes up negative, but they’re sick, so, what do you tell mum? Mum has taken a bicycle or maybe a few buses. Maybe it has taken three hours to get to the hospital and you walk in and say, “Sorry, they don´t have malaria, here is some paracetamol, go home.” Doing nothing is, sometimes, the correct treatment, but it is hard to tell mum. And it is even harder to tell a mum who has invested so much time and money to get her kid to the hospital.

It would be really nice if we can figure out what are the top three non-malarial causes of fever, and make an RDT for them. I think that is the way some funding agencies are going now: multi-pathogen RDTs, which will be great. That is really the only non-malaria stuff that I do.

MB: What are the main challenges about working in Malawi?

KS: Clinically, the challenges are just dealing with such ill kids. One can go through pediatric training in the States and see only a handful of kids that die. You don´t see a lot of kids dying in the US because we have excellent healthcare. Over there, mostly because of infectious diseases, the infant mortality rate is 10 times higher than here. The first day that I worked in Malawi, three kids died in our ward. That is difficult emotionally, so you have to figure out how you are going to deal with kids dying from preventable and treatable diseases.

MB: And what are the main challenges in the lab?

KS: On the research side, the biggest issue for me continues to be procurement. In the States, you have a freezer system, and if I run out of an enzyme, I can run across campus and I pick it up, or you can put in a rush order and it comes the next day. In Malawi, it is more like three weeks… and it just kills me. Companies will not ship to Malawi. So you have to have something ordered to Michigan or to somewhere else, wait until somebody is travelling and put into the luggage with ice blocks. That is what is a huge challenge. We have great people, we have great equipment, but oftentimes we don´t have the reagents.

MB: What do you value about doing collaborations with groups like the Smith lab at CID Research?

KS: This is absolutely important. There is no way any group can do it all by themselves. What we can do is admit kids in Blantyre, and characterize them as well as we can. But then we need expertise in other fields – immunology, high tech diagnostics, parasite-host interactions. We are thrilled to be able to supply our end of the collaboration, so people like you at CID Research can do this high-tech analysis.

This interview has been edited for length and clarity. I would like to thank Karl Seydel for his time talking with me at a busy conference. If you would like to learn more, read Dr. Terrie Taylor’s interview and Dr. Selasi Dankwa’s explanation of applying next generation sequencing to study cerebral malaria.

About the Author

Maria Bernabeu is a Postdoctoral Scientist in the Smith lab. Maria received her PhD in biology from University of Barcelona in 2013. Her research focused on the functional analysis of VIR proteins of Plasmodium vivax and their role in host-pathogen interactions. In Barcelona, she generated transgenic lines of P. falciparum that expressed VIR proteins from different subfamilies and performed adhesion assays to the spleen. While working with both organisms, she became fascinated by the biology of Plasmodium parasites. Maria joined the Smith lab in 2014 as a postdoctoral scientist. She is trying to understand the mechanisms that cause severe malaria in adults and working on a 3D-microvascular platform for the study of P. falciparum-endothelial interactions. Maria loves to travel, and her research has taken her to work in Australia, India, UK and Brazil. When not in the lab, she enjoys dancing, hiking and she is a devoted supporter of Football Club Barcelona.

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