Cerebral malaria: of mice and men

Abstract

Background: Cerebral malaria is a major cause of death in endemic areas. An animal model of cerebral malaria has been studied widely in which C57BL/6 mice are infected with the Plasmodium berghei ANKA strain. The histopathology and the response to interventions of human cerebral malaria and the murine model are very different. In 2012, a consensus guideline was published recommending that in order to represent better the clinical setting, interventions in the murine model should be tested together with antimalarial drug treatment and after development of the cerebral syndrome. Methods: A systematic review of publications on human and murine cerebral malaria since 2010 was conducted. Results: Clinical research on human cerebral malaria has declined and still no adjuvant intervention has proved effective. Meanwhile, since 2010, 149 interventions (118 adjuvants) have been evaluated in the mouse model, of which 142 (95%) were reportedly successful. Only 26% of interventions were evaluated after the development of the murine cerebral syndrome and 65% of the adjuvants were tested without a concomitant antimalarial. Conclusion: The predictive value of the murine model in identifying adjuvant therapeutic interventions in human cerebral malaria is very poor.