Severe malaria: what's new on the pathogenesis front?
Plasmodium falciparum causes the most severe and fatal form of malaria in humans with over half a million deaths each year. Cerebral malaria, a complex neurological syndrome of severe falciparum malaria, is often fatal and represents a major public health burden. Despite vigorous efforts, the pathophysiology of cerebral malaria remains to be elucidated, thereby hindering the development of adjunctive therapies. In recent years, multidisciplinary and collaborative approaches have led to groundbreaking progress both in the laboratory and in the field. Here we review the latest breakthroughs in severe malaria pathogenesis, with a specific focus on new pathogenetic mechanisms leading to cerebral malaria. The most recent findings point towards specific parasite phenotypes targeting brain microvasculature, endothelial dysfunction and subsequent oedema-induced brain swelling.
Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom; Vascular Immunology Unit, Department of Pathology, School of Medical Sciences & Marie Bashir Institute, The University of Sydney, Camperdown, Australia. Electronic address: sam.wassmer@lshtm.ac.uk.
Samuel Crocodile
SC
Wassmer
Vascular Immunology Unit, Department of Pathology, School of Medical Sciences & Marie Bashir Institute, The University of Sydney, Camperdown, Australia.
Georges Emile Raymond
GE
Grau
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use; D035843:Biomedical Research; D001929:Brain Edema / Q000469:parasitology; D004730:Endothelium, Vascular / Q000503:physiopathology; D006790:Host-Parasite Interactions; D006801:Humans; D016779:Malaria, Cerebral / Q000188:drug therapy / Q000469:parasitology* / Q000503:physiopathology; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology* / Q000503:physiopathology; D055806:Microvessels / Q000503:physiopathology; D010963:Plasmodium falciparum / Q000472:pathogenicity
D000962:Antimalarials
Cerebral malaria; Endothelial dysfunction; Malaria in pregnancy; Pathophysiology; Plasmodium spp.; Sequestration
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