De pathogene rol van hemozoïne en endotheelactivatie in malaria geassocieerde acute respiratory distress syndrome

Malaria is a severe disease and affects 200 million people with close to 600 000 deaths each year. Malarial symptoms range from non-lethal uncomplicated disease (e.g. fever, headache and nausea) to life-threatening complications, including cerebral malaria (CM) and malaria-associated
acute respiratory distress syndrome (MA-ARDS). Despite efficient antimalarial treatment,
complicated malaria has still a high mortality, and therefore a better understanding of the pathogenesis is crucial to improve therapies. In this project, we want to elucidate the roles and interrelations of hemozoin (malaria pigment crystals) and sequestration on the microvascular endothelium in malarial complications. Sequestration is the cytoadhesion of parasite-infected red blood cells to the vascular endothelium. Based on preliminary data, we will define the crucial interrelation between hemozoin production, local release by sequestering parasites, pathological endothelial activation and inflammation. To achieve this goal, we will use a set of unique transgenic parasites infecting mice, in vitro models with human cells and parasites, and an exceptional cohort of post mortem patient samples.