Malaria is responsible for more than 2 million deaths amongst children every year. As the mortality rate of 20-30% for severe falciparum malaria under even the best clinical conditions testifies, access to anti-malarial drugs is not sufficient to prevent an appreciable mortality from this disease. Understanding the cause of death at a cellular level is essential if additional rational treatments are to be developed. Most vaccine efforts are aimed at immunity against infection (antiparasitic) by targeting p arasite proteins. However, it has long been suggested that understanding the factors associated with resistance to severe clinical manifestations (anti-disease immunity) would lead to alternative approaches for malaria control. In these regard, parasite gl ycosylphosphatidylinositols (GPIs) appear to offer new opportunities. GPIs are a distinct class of glycolipids found ubiquitously in eukaryotic cells and implicated in several biological responses. GPIs are particularly abundant in parasites where they are found as free lipids and attached to proteins. In intraerythrocytic P. falciparum, GPIs represent the major glycoconjugates. P. falciparum GPIs have been identified as malaria pathogenicity factors based on their ability to induce inflammatory cytokines i n macrophages and cause symptoms reminiscentent of acute malaria infectionin experimental animals. We propose to determine the effect that Plasmodium GPIs have on this host mammalian cells and the importance of the GPIs role on the course of a malaria infe ction. We strongly believe this project will highly increases our possibilities of finding targets for pharmacological treatments of the disease.
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