Cerebral Malaria Pathogenesis

Revisiting Parasite and Host Contributions

Georges Emile Raymond Grau; Alister Gordon Craig


Future Microbiol. 2012;7(2):291-302. 

In This Article

What is Cerebral Malaria?

Cerebral malaria (CM) forms part of the spectrum of severe malaria, with a case fatality rate ranging from 15% in adults in southeast Asia[1] to 8.5% in children in Africa.[2] Clinical signs of acidosis carry a higher risk of death but nevertheless CM accounts for a significant proportion of malaria mortality, as well as the potential for neurological deficits in survivors. The standard clinical definition of CM centers on a state of unarousable coma partnered with the presence of malaria infected red blood cells in the peripheral circulation and a lack of other potential causes of coma such as other infections or hypoglycemia (for a full definition see [3–5]). More recently, ophthalmic observations of retinopathy have been added to this definition in both adults and children to increase the specificity of the clinical diagnosis.[6,7] Most observations of the pathophysiology of disease come from postmortem observations of Plasmodium falciparum (Pf) infections, which are thought to account for the vast majority of CM cases, and show a common feature of vascular sequestration of infected erythrocytes (IE) in the brain.[8] There are also some differences, particularly between CM in adults and children, broadly separable into a 'pure' sequestration pattern and IE sequestration with variable (and moderate) vascular pathology. The latter varies from the accumulation of proinflammatory cells such as leukocytes and platelets to localized vascular damage (e.g., vessels partially denuded of endothelium).[9] With the hallmark of IE sequestration for CM (albeit based on postmortem studies), investigations into the pathology of disease have looked at the adhesive interactions between IE and host cells, including endothelium, but have also ranged from host genetic studies to clinical measurements of a wide range of systemic and local effectors. So, while we do not fully understand the pathology of CM and suspect that it may have multiple etiologies, we do know that it has some differences to, and some overlaps with, other brain inflammatory diseases and we have information about some of the potential contributions from the parasite and the host that could lead to CM.


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