Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Determinants of brain swelling in pediatric and adult cerebral malaria
Praveen K. Sahu, … , Maria Bernabeu, Samuel C. Wassmer
Praveen K. Sahu, … , Maria Bernabeu, Samuel C. Wassmer
Published September 22, 2021
Citation Information: JCI Insight. 2021;6(18):e145823. https://doi.org/10.1172/jci.insight.145823.
View: Text | PDF
Research Article Infectious disease Microbiology

Determinants of brain swelling in pediatric and adult cerebral malaria

  • Text
  • PDF
Abstract

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.

Authors

Praveen K. Sahu, Fergal J. Duffy, Selasi Dankwa, Maria Vishnyakova, Megharay Majhi, Lukas Pirpamer, Vladimir Vigdorovich, Jabamani Bage, Sameer Maharana, Wilson Mandala, Stephen J. Rogerson, Karl B. Seydel, Terrie E. Taylor, Kami Kim, D. Noah Sather, Akshaya Mohanty, Rashmi R. Mohanty, Anita Mohanty, Rajyabardhan Pattnaik, John D. Aitchison, Angelika Hoffmann, Sanjib Mohanty, Joseph D. Smith, Maria Bernabeu, Samuel C. Wassmer

×

Figure 5

Machine learning analysis of CM and brain swelling in the combined India and Malawi cohorts.

Options: View larger image (or click on image) Download as PowerPoint
Machine learning analysis of CM and brain swelling in the combined India...
(A) Random forest models were trained on different patient subsets: CM versus UM (left) and brain swelling versus UM (right) that combine patients from Rourkela and Blantyre. Each individual bar represents the predictive performance of the feature in the model ordered by predictive importance (measured by MDCA). Features include: circulating platelet levels (platelets), plasma PfHRP2 concentration (PfHRP2), and var domain transcriptional units. Positive MDCA scores indicate higher presence of a feature in CM or patients with brain swelling, and vice versa. Asterisks indicate that these features showed significant difference between groups measured by mProbes algorithm (family-wise error rate [FWER] ≤ 0.2). (B) Receiver operating characteristic (ROC) curves of CM model (CM versus UM), CM with brain swelling model (CMBS+ versus UM), brain swelling within patients with CM (CMBS2–4 versus CMBS1), and severe brain swelling within patients with CM (CMBS4 versus CMBS1). Area under the ROC curve (ROC AUC) and accompanying 95% CI in parentheses are indicated in the ROC plot legend for each model.

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts