Review Article

Cerebral malaria: why experimental murine models are required to understand the pathogenesis of disease

J. BRIAN de SOUZA^a1a2, JULIUS C. R. HAFALLA^a1, ELEANOR M. RILEY^a1 and KEVIN N. COUPER^a1 c1

^a1 Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK

^a2 Department of Immunology and Molecular Pathology, University College London Medical School, 46 Cleveland Street, London W1T 4JF, UK

SUMMARY

Cerebral malaria is a life-threatening complication of malaria infection. The pathogenesis of cerebral malaria is poorly defined and progress in understanding the condition is severely hampered by the inability to study in detail, ante-mortem, the parasitological and immunological events within the brain that lead to the onset of clinical symptoms. Experimental murine models have been used to investigate the sequence of events that lead to cerebral malaria, but there is significant debate on the merits of these models and whether their study is relevant to human disease. Here we review the current understanding of the parasitological and immunological events leading to human and experimental cerebral malaria, and explain why we believe that studies with experimental models of CM are crucial to define the pathogenesis of the condition.

(Received September 14 2009)

(Revised October 20 2009)

(Accepted October 26 2009)

(Online publication December 23 2009)

Key Words:

• cerebral malaria;
• murine model;
• pathogenesis

Correspondence:

^c1 Corresponding author: Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. Tel: +44 207 927 2690. Fax: +44 207 927 2807. E-mail: kevin.couper@lshtm.ac.uk