Abstract
Cerebral malaria is the deadliest complication of malaria, a febrile infectious disease caused by Plasmodium parasite. Any of the five human Plasmodium species can cause disease, but, for unknown reasons, in approximately 2 million cases each year P. falciparum progresses to severe disease, ultimately resulting in half a million deaths. The majority of these deaths are in children under the age of five. Currently, there is no way to predict which child will progress to severe disease and there are no adjunctive therapies to halt the symptoms after onset. Herein, we discuss what is known about the disease mechanism of one form of severe malaria, cerebral malaria, and how we might exploit this understanding to rescue children in the throes of cerebral disease.
Highlights
Malaria is an infectious disease caused by mosquito-borne parasites of the Plasmodium species, the deadliest of which, Plasmodium falciparum (Pf), takes the lives of nearly 500,000 children each year in Africa alone[1,2]
Therapies based on disruption of infected red blood cell (iRBC) surface Pf Plasmodium falciparum erythrocyte membrane protein 1 (EMP1) and their brain endothelial receptors are of particular interest, as are treatments that can modulate or reverse endothelial activation and damage, coagulation, and hemorrhaging
Work demonstrated the efficacy of treatment of Plasmodium berghei ANKA (PbA)-infected CBA/Ca mice with lymphocyte function-associated antigen 1 (LFA-1)–specific antibodies[59,60]. Building on this previous work, we provided evidence that treatment of C57BL/6 mice with a combination of monoclonal antibodies specific for LFA-1 and VLA-4, which disrupted the integrin-dependent association of T cells with the brain endothelium, was effective at rescuing 100% of mice from experimental CM (ECM) when administered on d5.5 p.i. and again on d6.5 p.i
Summary
Malaria is an infectious disease caused by mosquito-borne parasites of the Plasmodium species, the deadliest of which, Plasmodium falciparum (Pf), takes the lives of nearly 500,000 children each year in Africa alone[1,2]. These receptors are not selectively expressed in the brain, this is an exciting finding that suggests the possibility of targeting the binding of Pf EMP1s to these receptors for adjunctive therapy in CM.
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