Study in PLoS Pathogens finds that infection disrupts the lining, releasing an adhesive protein, and decreases cleaving enzyme.

An international group of researchers have identified a pathway that may contribute to the high mortality associated with severe malaria in sub-Saharan African children. They found that severe P. falciparum infection causes disruption of the endothelium, resulting in the release of large amounts of an adhesive protein, which traps infected erythrocytes. Moreover, this protein cannot be inactivated due to a concurrent decrease in plasma levels of its cleaving enzyme.

Past studies have shown that red blood cells infected with malaria parasites can adhere to the endothelium of small blood vessels. In the current study, which appears in the March 20 issue of PLoS Pathogens, the scientists set out to investigate the significance of this interaction.

Over a one-year period, the investigators studied children under six years with severe P. falciparum malaria at the Komfo Anokye hospital in Kumasi, Ghana. In blood samples from these children, the researchers found that plasma levels of the adhesive protein called von Willebrand factor (VWF) were markedly increased.

The VWF protein is synthesized within endothelial cells and plays a critical role in tethering circulating blood cells to the vascular wall at sites of injury. The researchers thus suggest that infections cause disruption of the endothelium, which leads to the accessive amounts of VWF in the blood stream and answers why erythrocytes adhere to the endothelium.

Normally, to prevent excessive blood clot formation, VWF activity in the blood is regulated by ADAMTS13. In the Ghanaian children, however, the plasma levels of this enzyme were also found to be significantly reduced.

Next the scientists will look to define the role played by the abnormal, highly adhesive VWF in mediating the critical small-vessel obstruction associated with severe malaria.

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