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Pathogenesis of Cerebral Malaria: New Tools, Recent Discoveries and Innovative Therapeutic Approaches

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Plasmodium falciparum malaria is a major cause of morbidity and mortality worldwide, leading to over a million deaths annually. Cerebral malaria (CM), the most severe complication of falciparum infection leads to a mortality rate of approximately 15%-25% even when appropriate treatment and intensive care are ...

Plasmodium falciparum malaria is a major cause of morbidity and mortality worldwide, leading to over a million deaths annually. Cerebral malaria (CM), the most severe complication of falciparum infection leads to a mortality rate of approximately 15%-25% even when appropriate treatment and intensive care are provided. The fundamental pathogenesis of fatal CM is still not well understood and treatments are currently precariously limited to antimalarial drugs and emergency supportive care.

Over the past decade, cutting edge research on both Plasmodium falciparum and its human host has promoted a tremendous advance in our comprehension of the pathophysiology of CM and has opened new paths for therapeutic avenues.

Murine models have made important contributions to our understanding of CM pathogenesis and enabled revolutionary functional genomic and systems biology approaches not possible in human subjects. However, sequestration of infected erythrocytes - a critical component of pathogenesis in human disease - does not occur to a significant extent in experimental murine models. This has necessitated the development of innovative cell culture and ex vivo approaches using human tissue to study sequestration-induced pathology. In parallel, autopsy-based studies and more recently brain imaging analyses in malaria-endemic countries have provided invaluable insight into the neuropathology of the disease. Finally, while new antiparasitic strategies are being evaluated, the need for innovative adjunctive therapeutic approaches in CM has become evident. Indeed, its pathogenesis is believed to be due, in part, to an aberrant immune response of the patient, leading to deleterious consequences that could be targeted to reduce CM-associated mortality.

This Research Topic is dedicated to provide a snapshot of the current state of research on CM by bringing together leading experts in the field. Clinical, pathological, theoretical, modeling and cross-disciplinary reviews are encouraged to contribute to a comprehensive picture and promote new ideas and pathways of future research on CM.


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