Menzies School of Health Research
Bridget Barber is an NHMRC Early Career Fellow, Senior Research Fellow at Menzies School of Health Research, and Head of Clinical Research in the Clinical Tropical Medicine Group at QIMR Berghofer. She has been involved in clinical malaria studies in Sabah, Malaysia, for the past 8 years. The focus of her research to-date has been the epidemiology, clinical features and treatment of knowlesi malaria, in addition to the microvascular pathophysiology of severe malaria from any species.
The free haemoglobin, endothelial activation, acute kidney injury, pathway in knowlesi malaria
Intravascular haemolysis and nitric oxide-dependent endothelial dysfunction are important features of severe falciparum malaria but have not been evaluated in knowlesi malaria. In Malaysian adults with knowlesi malaria, cell-free haemoglobin (CFHb) is increased in proportion to disease severity, and is independently associated with parasitaemia, and the Weibel-Palade body (WPB) constituents angiopoietin-2 and osteoprotegerin (OPG). As previously shown with angiopoietin-2, OPG is increased in proportion to disease severity, and is independently associated with creatinine, lactate, interleukin-6, endothelial cell adhesion molecules ICAM-1 and E-selectin, and impaired microvascular reactivity. OPG is also independently associated with nitric oxide-dependent endothelial dysfunction. Angiopoietin-2 and OPG are both independent risk factors for acute kidney injury. These findings suggest that haemolysis-mediated endothelial activation and release of WPB constituents is likely a key contributor to end-organ dysfunction, including AKI, in severe knowlesi malaria.