Markers of dengue disease severity.

Infection with one of the four serotypes of dengue virus (DENV) causes a wide spectrum of clinical disease ranging from asymptomatic infection, undifferentiated fever, dengue fever (DF) to dengue hemorrhagic fever (DHF). DHF occurs in a minority of patients and is characterized by bleeding and plasma leakage which may lead to shock. There are currently no reliable clinical or laboratory indicators that accurately predict the development of DHF. Human studies have shown that high viral load and intense activation of the immune system are associated with DHF. Recently, endothelial cells and factors regulating vascular permeability have been demonstrated to play a role. In the absence of animal models that closely mimic DHF, human studies are essential in identifying predictors of severe illness. Well planned prospective studies with samples collected at different time points of the illness in well characterized patients are crucial for this effort. Ideally, clinical and laboratory predictive tools should be suitable for resource poor countries where dengue is endemic.