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​Inside a Cerebral Malaria Children’s Ward, Pt 1

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 will discuss his research and experiences working in Malawi.

Dr. Terrie Taylor can be certainly considered a celebrity in the malaria research field, known for her research on brain swelling in cerebral malaria. Having spent nearly 30 years in Malawi, she claims that her medical and research career began with serendipitous events: after a ”big picture” conversation with the Dean of the College of Osteopathic Medicine at MSU, she provided clinical support for an NIH-funded MSU-led tropical disease research project in the Sudan where she got “hooked” on tropical medicine early in her career. Her training at the Liverpool School of Tropical Medicine led her to Blantyre, Malawi, when there was virtually no research going on in the country. She teamed up with Malcolm Molyneux, her supervisor at that time, and a local pediatrician to establish a cerebral malaria research capacity in Blantyre’s Queen Elizabeth Central Hospital. Nowadays, the malaria ward in Blantyre could be considered one of the best malaria treatment centers in Africa.

Maria Bernabeu: What are the scientific accomplishments that stick out to you?

Terrie Taylor: At the time I landed in Blantyre, cerebral malaria in children was described in adjectives. They were “drowsy,” they were “stuporous,” they were “difficult to arouse,” but it wasn´t a very well characterized clinical syndrome. We were laying the groundwork for a clinical trial, but the disease was very fuzzy. So we started working out a way to measure the depth of coma, which gave rise to the Blantyre Coma Score [the criteria that the World Health Organization now uses to diagnose cerebral malaria], and we started basic clinical characterization of the disease.

Then, what put us on the map was extremely simple: Any unconscious person rolling through the door of an emergency department in the U.S. has their blood sugar checked. It was mind boggling, but by the late eighties, the level of blood sugar had not been studied in malaria. By measuring it, we were able to immediately identify that the contributor to coma in some kids was metabolic. However, many kids remained unconscious after we corrected their blood sugar and those who were hypoglycemic with their cerebral malaria had worse outcomes.

It stuck out to us from the first year that the mode of death of about two thirds of the patients involved irregular gasping respirations and a cessation of breathing. But, if we could be there with a mask and a bag and breathe for them, their heart beat would continue. For Malcolm and me that looked like this neurological process called herniation [in which the brain is squeezed out through the base of the skull due to high pressure inside the skull]. We had that idea, but we couldn´t prove it yet.

So by the early nineties, we still didn´t know why they were dying. Because we could only go so far by standing at bedside, we started an autopsy study to work out the cause of death. We were conducting studies like this in the hope of saving lives. We spent 10 years on the study that was fascinating, but grueling and emotionally challenging. It is so sad when a child dies and you have to have this conversation with the bereaved family. It was really hard and challenging, and the Malawians did counseling with the families. But it was illuminating; it showed that even our improved clinical case definition was not good enough --- about a third of the patients that met the clinical case definition for cerebral malaria lacked the histological hallmark (sequestered red cells in the small vessels of the brain) and were shown on autopsy to have non-malarial causes of death. Ultimately, we were able to link the autopsy study results to improved diagnostics by looking for parasite signs in the children’s retinas.

MB: Then what happened?

TT: We had a better idea of who actually had cerebral malaria, but we still didn´t know why they were dying. So then, we moved on to imaging. The head of radiology at MSU understood the importance of neuroimaging and persuaded General Electric to donate an MRI [to our malaria ward], and then that broke it open. We were able to capture the event of herniation in the MRI and realized then that the physical process of the autopsy…erased the signs of herniation. But now the question is, why are the brains swollen, and how can we intervene?

MB: So how can these findings help in the future treatment of cerebral malaria?

TT: The [brain] swelling reduces spontaneously as part of the natural history of the disease over a day or two, even without any special treatment directed at brain swelling, just antimalarial drugs and good clinical care. We just need to ensure they can keep breathing even when that brain function is interrupted. One of the interventions that we will try is ventilatory support. We will put kids under ventilators to sustain them for a day or two [to buy time as the child´s brain naturally reduces swelling]. Another is hyperosmolar therapy, adding salt to the blood and letting it draw water out of the brain. Now, we have the clinical trial funded. That provides the infrastructure and support to continue to admit patients to the research ward and to learn more about causes of brain swelling

MB: What are the main cultural differences between Malawi and the United States, and what do you enjoy about working there?

TT: Malawians are warm, much warmer, much friendlier and much more interactive. So, I always notice when I get back to the States, I will be checking out at the grocery store and I will strike up a conversation with the cashier, and I get these odd glances. In Malawi it is so much fun, running errands is fun, grocery shopping is fun, going to the market is fun, you just venture and joke with everybody all the time. It is a much more interactive life style. The activities of daily living are a lot of fun.

MB: What is your normal day in Malawi?

There is no normal day. That is what I love. You never know what is gonna happen. The two fixed points of the day are the ward rounds. At 8 in the morning and 4 in the afternoon we go around and see the patients. So that is every day, but what happens in between, you never know. After the ward round in the morning we generally, unless there some kind of a crisis, try to sit down and have a cup of coffee, and one of the cleaners makes samosas we pay her for. I can always gauge Karl´s [Seydel] mood by how many sugars he wants in his coffee. One sugar, great day; four sugars…. Oh! Hahaha… So if it is a four-sugar day we are really nice to him.

This interview has been edited for length and clarity. I would like to thank Terrie Taylor for her time chatting with me at a busy conference. If you would like to meet Dr. Karl Seydel and learn more about cerebral malaria, check here to see the second part of this interview.

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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