Magnetic Resonance Imaging of Cerebral Malaria Patients Reveals Distinct Pathogenetic Processes in Different Parts of the Brain

Author:

Mohanty Sanjib1,Benjamin Laura A.2,Majhi Megharay3,Panda Premanand3,Kampondeni Sam4,Sahu Praveen K.1,Mohanty Akshaya5,Mahanta Kishore C.6,Pattnaik Rajyabardhan6,Mohanty Rashmi R.7,Joshi Sonia7,Mohanty Anita6,Turnbull Ian W.8,Dondorp Arjen M.910,Taylor Terrie E.1112,Wassmer Samuel C.13ORCID

Affiliation:

1. Center for the Study of Complex Malaria in India, Ispat General Hospital, Rourkela, Odisha, India

2. Brain Infections Group, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom

3. Department of Radiology, Ispat General Hospital, Rourkela, Odisha, India

4. Department of Radiology, Queen Elizabeth Central Hospital, Blantyre, Malawi

5. Infectious Diseases Biology Unit, Institute of Life Sciences, Bhubaneswar, Odisha, India

6. Department of Intensive Care, Ispat General Hospital, Rourkela, Odisha, India

7. Department of Ophthalmology, Ispat General Hospital, Rourkela, Odisha, India

8. North Manchester General Hospital, Manchester, United Kingdom

9. Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

10. Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford, United Kingdom

11. Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan, USA

12. Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi

13. Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, United Kingdom

Abstract

The pathophysiology and molecular mechanisms underlying cerebral malaria (CM) are still poorly understood. Recent neuroimaging studies demonstrated that brain swelling is a common feature in CM and a major contributor to death in pediatric patients. Consequently, determining the precise mechanisms responsible for this swelling could open new adjunct therapeutic avenues in CM patients. Using an MRI scanner with a higher resolution than the ones used in previous reports, we identified two distinct origins of brain swelling in both adult and pediatric patients from India, occurring in distinct parts of the brain. Our results support the hypothesis that both endothelial dysfunction and microvascular obstruction by Plasmodium falciparum -infected erythrocytes make independent contributions to the pathogenesis of CM, providing opportunities for novel therapeutic interventions.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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