Validity of Modelling Cerebral Malaria in Mice: Argument and Counter Argument

The clinical manifestations of Plasmodium falciparum infection of humans that are collectively recognised as cerebral malaria produce profound changes in mental status and induce coma. The histopathological hallmark of this encephalopathy is the sequestration of cerebral capillaries and venules with both infected and uninfected erythrocytes. The underlying cause of cerebral malaria is the subject of vigorous debate. A major reason for this is that human brain tissue is only available post mortem. In order to dissect the pathology of this acute disease, therefore, a number of models using murine malarias have been developed. While these have undoubtedly proved useful in helping to identify immunological mechanisms involved, recognition of the differences between the pathological processes during cerebral malaria in mice and man has led to some researchers questioning the validity of extrapolating findings from mouse models to the human condition with a view to informing therapeutic interventions. In turn, this has provoked lively debate within the malaria research community. This commentary sets out our current understanding of cerebral disease in humans and evaluates what meaningful contribution the study of mouse models has made to this knowledge.