Unraveling the role of hemozoin and sequestration on lethal malarial complications

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-associatedacute 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.