The murine cerebral malaria phenomenon

Abstract

P.berghei ANKA infection in CBA or CB57BL/6 mice is used widely as a murine 'model' of human cerebral malaria (HCM), despite markedly different histopathological features. The pathology of the murine model is characterised by marked inflammation with little or no intracerebral sequestration of parasitised erythrocytes, whereas HCM is associated with intense intracerebral sequestration, often with little inflammatory response. There are now more than ten times as many studies each year of the murine model than on HCM. Of 48 adjunctive interventions evaluated in the murine model, 44 (92%) were successful, compared with only 1 (6%) of 17 evaluated in HCM during the same period. The value of the mouse model in identifying pathological processes or therapeutic interventions in human cerebral malaria is questionable.

Figure 1

Annual numbers of publications describing studies on human cerebral malaria (HCM) (blue) and murine models of cerebral malaria (orange) since 1980 listed on the National Library of Medicine (NLM) PubMed. The medical subject headings (MeSH) search terms were: human/cerebral malaria; subheadings, therapy, drug therapy, diet therapy/physiopathology, pathology; limits, concerning therapy: clinical trials. MeSH: mouse/cerebral malaria; subheadings, therapy, drug therapy, diet therapy/physiopathology, pathology; limits, none. After compilation, the lists were checked manually.

Figure 2

A comparison of the histopathological hallmarks of human cerebral malaria (HCM) and the Plasmodium berghei ANKA murine model. (a) Parasitised erythrocyte sequestration in small and large vessels from a patient who died during the acute phase of cerebral malaria. (b) A large vessel containing numerous mononuclear leukocytes but no sequestered parasitised erythrocytes from a mouse at the terminal stage of the disease. Sections are from cerebral cortex counterstained with haematoxylin. Scale bar, 50 μm.