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Infection and Immunity, December 1998, p. 5972-5979, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Evidence for Multiple Pathologic and Protective Mechanisms of Murine Cerebral Malaria

Veronica M. Jennings,1,* Altaf A. Lal,2 and Robert L. Hunter3

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia 303221; Immunology Branch, Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services, Atlanta, Georgia 300332; and Health Science Center, The University of Texas, Houston, Medical School, Houston, Texas 770303

Received 5 June 1998/Returned for modification 27 July 1998/Accepted 16 September 1998

Murine cerebral malaria (CM) induced by Plasmodium berghei ANKA kills susceptible mice within 24 to 48 h of onset of symptoms and is characterized by the production of inflammatory cytokines in the brain. C57BL/6J mice are sensitive to lethal CM, while A/J mice are resistant. These strains of mice were immunized with an adjuvant vaccine of killed whole-blood-stage parasites. The immunization protected C57BL/6 mice from lethal CM following virulent challenge. The same immunization increased the incidence of lethal CM in A/J mice challenged similarly. Histopathologic examination of the brains of mice from these studies revealed two distinct types of lesions. Type I CM is acute in onset; usually lethal; and characterized by widespread microglial activation, endothelial cell damage, and microvascular disruption in the brain. Type II CM is characterized by intense, but focal, mononuclear cell inflammation without endothelial cell damage or microvascular destruction. Animals with type II lesions were clinically normal and protected from type I lesions. Available clinical, epidemiological, and biochemical evidence suggests that type I and type II lesions might exist in human CM as well.


* Corresponding author. Mailing address: Centers for Disease Control and Prevention, 4770 Buford Highway, Building 15, Mail Stop F-33, Chamblee, GA 30341. Phone: (770) 488-4357. Fax: (770) 488-4986. E-mail: vaj7{at}cdc.gov.


Infection and Immunity, December 1998, p. 5972-5979, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



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