June 2019 – Dr. Maria Bernabeu shares insights from a recent publication in mBio with contributing authors from the Smith and Aitchison labs at the Center for Global Infectious Disease Research (CGIDR).

Meta-analysis of Plasmodium falciparum var Signatures Contributing to Severe Malaria in African Children and Indian Adults

Fergal Duffy, Maria Bernabeu, Prasad H. Babar, Anne Kessler, Christian W. Wang, Marina Vaz, Laura Chery, Wilson L. Mandala, Stephen J. Rogerson, Terrie E. Taylor, Karl B. Seydel, Thomas Lavstsen, Edwin Gomes, Kami Kim, John Lusingu, Pradipsinh K. Rathod, John D. Aitchison, Joseph D. Smith

Published in mBio: April 30, 2019

Read the publication on mBio.

What were the key findings?

Severe malaria patients experience different complications depending on the age of the patient, but we currently don´t understand why this is the case. Severe anemia (extremely low red blood cell counts in blood) is more frequent in children, while liver and kidney damage are common in adults. This study wanted to address if different types of parasites are associated with these different disease complications. We have done a large, multi-site study that compares children with severe malaria in Africa (Malawi and Tanzania) and adults with severe malaria in India. Our study used advanced new computational approaches, called machine learning, to discover hidden patterns in the data. We first found that an increased number of parasites in the blood is highly predictive of severe disease in both children and adults. From previous work, we know that malaria-infected red blood cells bind to a different array of human proteins present in the blood vessel walls, but it is challenging to understand which of these interactions are most important for progression to severe disease. In this study we found evidence that an expansion of parasites that bind to EPCR is present in both children and adults. As this protein is essential to maintain healthy blood vessels, we hypothesize that blocking the normal protein’s function leads to severe symptomatology.

What does this research tell us that we didn’t know before?

Collectively, these findings represent the most comprehensive picture so for of the relationship between parasite load, parasite binding types, and the presence of different disease manifestation. Earlier studies have focused either in children or adults or in a single geographic region. This study is the first to directly compare them in three different countries highly affected by malaria. This is important, as the higher patient number and direct comparison gives us more confidence in our findings and allowed us to do a more sophisticated analysis than previous studies. Our study provides evidence that the same dangerous type of parasite causes disease in both children and adults, but this results in different organ complications in the younger and older patients.

What are the broad implications of this research?

Understanding how malaria causes the severe complications of the disease could guide in the design of better treatments to severe disease. This study showed that the same parasite factors are contributing to severe disease in different age groups, revealing that future severe malaria treatment that specifically targets these dangerous parasite types might be effective in both children and adults.

Why do we need to develop better ways to treat, prevent and diagnose malaria?

Malaria causes every year around half a million deaths. 70% if these deaths occur in children younger than 5 years. Current malaria control strategies are not sufficient to prevent these deaths, so new treatment strategies are needed.

Seattle Children’s CGIDR contributing authors: