Journal article
Linking EPCR-Binding PfEMP1 to Brain Swelling in Pediatric Cerebral Malaria
A Kessler, S Dankwa, M Bernabeu, V Harawa, SA Danziger, F Duffy, SD Kampondeni, MJ Potchen, N Dambrauskas, V Vigdorovich, BG Oliver, SE Hochman, WB Mowrey, IJC MacCormick, WL Mandala, SJ Rogerson, DN Sather, JD Aitchison, TE Taylor, KB Seydel Show all
Cell Host and Microbe | CELL PRESS | Published : 2017
Abstract
Brain swelling is a major predictor of mortality in pediatric cerebral malaria (CM). However, the mechanisms leading to swelling remain poorly defined. Here, we combined neuroimaging, parasite transcript profiling, and laboratory blood profiles to develop machine-learning models of malarial retinopathy and brain swelling. We found that parasite var transcripts encoding endothelial protein C receptor (EPCR)-binding domains, in combination with high parasite biomass and low platelet levels, are strong indicators of CM cases with malarial retinopathy. Swelling cases presented low platelet levels and increased transcript abundance of parasite PfEMP1 DC8 and group A EPCR-binding domains. Remarkab..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank the patients and their families who made this study possible. We thank Patricia Phula and the Blantyre Malaria Project (BMP) laboratory staff for help with sample collection and processing, Alice Liomba (BMP) for organizing data, Jack Gormley for the 2016 ophthalmoscopy, Matt Levy for sharing equipment, and Adriana Lippy for illustration. The study was made possible by NIH grants K08MH089848 and T32 AI 070117 (S.E.H.), R01AI34969 (T.E.T.), R01AI114766 and R01HL130488 (J.D.S.), and P41GM109824 (J.D.A.); NIH National Center for Advancing Translational Science (NCATS) Einstein-Montefiore CTSA TL1TR001072 (A.K.); the Burroughs Wellcome Fund (A.K.); grant 1061993 from the National Health and Medical Research Council of Australia (S.J.R.); and support from the Michigan State University College of Osteopathic Medicine (T.E.T.). Data in this paper are from a thesis submitted in partial fulfillment of the requirements for the Degree of Doctor of Philosophy in the Graduate Division of Medical Sciences at Albert Einstein College of Medicine Yeshiva University.