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. 2008 Jun 28;7(1):569–582. doi: 10.1111/j.1750-3639.1997.tb01075.x

Cerebral Malaria

Gareth Turner 1,✉
PMCID: PMC8098241  PMID: 9034566

Abstract

Malaria infection of the Central Nervous System (CNS) can cause a severe neurological syndrome termed Cerebral Malaria (CM). The central neuropathological feature of CM is the preferential sequestration of parasitised red blood cells (PRBC) in the cerebral microvasculature. The level of sequestration is related to the incidence of cerebral symptoms in severe malaria. Other neuropathological features of CM include petechial hemorrhages in the brain parenchyma, ring hemorrhages and Diirck's granuloma's. Immunohisto‐chemical and electron microscopy studies have shown widespread cerebral endothelial cell activation and morphological changes occur in CM, as well as focal endothelial cell damage and necrosis. The immune cell response to intravascular sequestration appears to be limited, although activation of pigment‐phagocytosing monocytes is a late feature. The mechanisms by which PRBC cause coma in malaria remain unclear. In vitro parasitised erythrocytes bind to endothelial cells by specific, receptor mediated interactions with host adhesion molecules such as ICAM‐1, whose expression on cerebral endothelial cells is increased during CM as part of a systemic endothelial activation. Induction of local neuro‐active mediators such as nitric oxide and systemic cytokines like TNFα may be responsible for the rapidly reversible symptoms of the coma of CM. The recent cloning of the parasite ligand PfEMP‐1, thought to mediate binding to host sequestration receptors, promises further insight into the relationship between patterns of sequestration and the incidence and pathogenesis of coma in cerebral malaria.

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