%0 Journal Article
%T The Case for the Use of PPAR¦Ã Agonists as an Adjunctive Therapy for Cerebral Malaria
%A Lena Serghides
%J PPAR Research
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/513865
%X Cerebral malaria is a severe complication of Plasmodium falciparum infection associated with high mortality even when highly effective antiparasitic therapy is used. Adjunctive therapies that modify the pathophysiological processes caused by malaria are a possible way to improve outcome. This review focuses on the utility of PPAR¦Ã agonists as an adjunctive therapy for the treatment of cerebral malaria. The current knowledge of PPAR¦Ã agonist use in malaria is summarized. Findings from experimental CNS injury and disease models that demonstrate the potential for PPAR¦Ã agonists as an adjunctive therapy for cerebral malaria are also discussed. 1. Introduction Few diseases have the global health and economic impact of malaria [1]. In 2009, an estimated 225 million people were infected with malaria and close to a million people succumbed to their infection [2]. Malaria is caused by apicomplexan parasites belonging to the genus Plasmodium. Five species infect humans, Plasmodium falciparum, P. vivax, P. ovale, P. malariae, and most recently, P. knowlesi [3]. The majority of morbidity and mortality is caused by P. falciparum infection, with the highest burden born by children and pregnant women. In the absence of prompt and effective treatment, P. falciparum infection can progress quickly, rapidly becoming severe and fatal. The rise in drug-resistant parasites complicates the administration of effective treatment. Severe malaria has multiple manifestations that can occur singly or in combination. They include hyperparasitemia, high fever, haemoglobinuria, acute renal failure, acute pulmonary edema, metabolic acidosis and respiratory distress, hypoglycemia, anemia, and cerebral malaria, which is characterized by coma and convulsions. Cerebral malaria has the highest mortality rate of all the severe complications and is associated with long-term cognitive and neurological deficits in surviving children [4¨C6]. Intravenous artesunate is now the standard of care for severe malaria in both adults and children following the landmark SEAQUAMAT and AQUAMAT trials that demonstrated the superiority of artesunate over quinine in adults and in children [7, 8]. However, even with the improved efficacy of artesunate, fatality rates remained high, 15% in adults and 10.9% in children. Adjunctive therapies, defined as therapies administered in combination with antiparasitic drugs that modify pathophysiological processes caused by malaria, have been pursued as a way to improve the outcome of severe malaria. Adjunctive therapies may also help extend the efficacy of antiparasitic
%U http://www.hindawi.com/journals/ppar/2012/513865/