Understanding malaria

MORU undertakes a range of studies on the pathogenesis of falciparum and vivax malaria. In the laboratory we try to identify parasite virulence factors which can be responsible for the development of severe disease. We identified that P. falciparum parasites that cause severe disease have the potency to multiply faster because they are less selective in the red cell populations that they can invade. In addition to P. falciparum infected red cells, which stick to the vessel wall using a wide range of endothelial receptors, we have shown that P. vivax can also stick, but to a limited arsenal of receptors, including chondroitin sulphate (CSA), a receptor abundant in the placenta. This can contribute to the negative effects on birth weight if women get vivax malaria during pregnancy. We have also visualized the smallest blood vessels (the microcirculation) in living patients with severe malaria using a microscopic camera. In this way we can show that indeed the smallest blood vessels get blocked, and more so with increasing severity of the disease. These parasites that are stuck (sequestered) in the microcirculation and are a major cause of organ dysfunction are not detectable in a blood sample taken from a vein in for instance the arm. We developed a model to estimate the number of the sequestered parasites through the measurement of a protein (PfHRP2) that is released by these parasites. MORU also performs studies on the vasculature in the back of the eye in patients with severe malaria. These vessels strongly resemble the vessels in the brain, and can reveal a lot about the events likely to occur in the brain. Blood flow in the smallest blood vessels in severe malaria is further compromised by rigidity of the infected and uninfected red blood cells and identification of the factors responsible for this rigidification is a continuing research subject in MORU. Obstruction of flow causes the blood to get acidotic; the nature of this acidosis is another subject for detailed study at MORU.