The Case for the Use of PPARγ Agonists as an Adjunctive Therapy for Cerebral Malaria.

Lena Serghides

doi:10.1155/2012/513865

Abstract

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 PPARγ agonists as an adjunctive therapy for the treatment of cerebral malaria. The current knowledge of PPARγ agonist use in malaria is summarized. Findings from experimental CNS injury and disease models that demonstrate the potential for PPARγ agonists as an adjunctive therapy for cerebral malaria are also discussed.

Highlights

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]
The majority of morbidity and mortality is caused by P. falciparum infection, with the highest burden born by children and pregnant women

Summary

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]. 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 [4,5,6]. Several adjunctive therapeutic strategies have been tested in P. falciparum cerebral and severe malaria so far, with-out much success (see [11] for a recent review). This review will focus on the utility of PPARγ agonists as an adjunctive therapy for the treatment of cerebral malaria. PPAR Research mechanisms of action attributed to PPARγ agonists that may be of benefit in cerebral malaria

The Pathogenesis of Cerebral Malaria

PPARγ and Its Agonists

Generation of Endogenous PPARγ Ligands in Malaria Infection

Findings

The Use of PPARγ Agonists in Malaria