Sahu, Praveen K; Duffy, Fergal J; Dankwa, Selasi; Vishnyakova, Maria; Majhi, Megharay; Pirpamer, Lukas; Vigdorovich, Vladimir; Bage, Jabamani; Maharana, Sameer; Mandala, Wilson; Rogerson, Stephen J; Seydel, Karl B; Taylor, Terrie E; Kim, Kami; Sather, D Noah; Mohanty, Akshaya; Mohanty, Rashmi R; Mohanty, Anita; Pattnaik, Rajyabardhan; Aitchison, John D; ... (2021). Determinants of brain swelling in pediatric and adult cerebral malaria. JCI insight, 6(18) JCI Insight 10.1172/jci.insight.145823
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145823.2-20220118114756-covered-e0fd13ba177f913fd3156f593ead4cfd.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (6MB) | Preview |
Cerebral malaria (CM) affects children and adults, but brain swelling is more severe in children. To investigate features associated with brain swelling in malaria, we performed blood profiling and brain MRI in a cohort of pediatric and adult patients with CM in Rourkela, India, and compared them with an African pediatric CM cohort in Malawi. We determined that higher plasma Plasmodium falciparum histidine rich protein 2 (PfHRP2) levels and elevated var transcripts that encode for binding to endothelial protein C receptor (EPCR) were linked to CM at both sites. Machine learning models trained on the African pediatric cohort could classify brain swelling in Indian children CM cases but had weaker performance for adult classification, due to overall lower parasite var transcript levels in this age group and more severe thrombocytopenia in Rourkela adults. Subgrouping of patients with CM revealed higher parasite biomass linked to severe thrombocytopenia and higher Group A-EPCR var transcripts in mild thrombocytopenia. Overall, these findings provide evidence that higher parasite biomass and a subset of Group A-EPCR binding variants are common features in children and adult CM cases, despite age differences in brain swelling.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic and Interventional Neuroradiology |
UniBE Contributor: |
Hoffmann, Angelika |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2379-3708 |
Publisher: |
JCI Insight |
Language: |
English |
Submitter: |
Martin Zbinden |
Date Deposited: |
14 Apr 2022 16:15 |
Last Modified: |
05 Dec 2022 16:18 |
Publisher DOI: |
10.1172/jci.insight.145823 |
PubMed ID: |
34549725 |
Uncontrolled Keywords: |
Infectious disease Malaria Microbiology Parasitology Platelets |
BORIS DOI: |
10.48350/169242 |
URI: |
https://boris.unibe.ch/id/eprint/169242 |
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