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In Vivo Tracking of Edema Development and Microvascular Pathology in a Model of Experimental Cerebral Malaria Using Magnetic Resonance Imaging
Published on: June 8, 2017
Determinants of brain swelling in pediatric and adult cerebral malaria
Praveen K Sahu1, Fergal J Duffy2, Selasi Dankwa2
1Center for the Study of Complex Malaria in India, Ispat General Hospital (IGH), Rourkela, Odisha, India.
Insights
Cerebral malaria (CM) involves higher Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and specific var transcripts. These markers help predict brain swelling in children but are less effective in adults with CM.
Area of Science:
- Infectious Diseases
- Neurology
- Genetics
Background:
- Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection.
- Brain swelling is a hallmark of CM, but its severity differs between pediatric and adult patients.
- Understanding the molecular and parasitic factors associated with brain swelling is crucial for improving diagnosis and treatment.
Purpose of the Study:
- To investigate the association between parasite markers and brain swelling in pediatric and adult CM patients.
- To compare CM features between Indian and African cohorts.
- To evaluate the utility of machine learning models in predicting brain swelling based on parasite profiles.
Main Methods:
- Blood profiling and brain MRI were conducted on CM patients in India and Malawi.
- Plasma Plasmodium falciparum histidine-rich protein 2 (PfHRP2) levels and var transcript expression were analyzed.
- Machine learning models were developed and tested using data from the African pediatric cohort.
Main Results:
- Elevated plasma PfHRP2 and specific EPCR-binding var transcripts were linked to CM in both Indian and African cohorts.
- Machine learning models successfully classified brain swelling in Indian children but showed weaker performance in adults.
- Differences in parasite var transcript levels and thrombocytopenia severity contributed to the age-related performance gap in machine learning models.
- Higher parasite biomass correlated with severe thrombocytopenia, while higher Group A-EPCR var transcripts were associated with mild thrombocytopenia.
Conclusions:
- Higher parasite biomass and specific EPCR-binding variants are common features in both pediatric and adult CM.
- Parasite factors influencing brain swelling severity may differ between age groups.
- Further research is needed to refine diagnostic and prognostic tools for CM across different populations and age groups.
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.
