Immunopathogenesis of Dengue Hemorrhagic Fever
The dengue virus (DENV) with its four unique serotypes is transmitted by the Aedes mosquito vector in tropical countries worldwide. All serotypes can cause illness ranging from asymptomatic, self-limiting flu, Dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). DHF and DSS are characterized by a sudden increase in vascular permeability due to a unique set of cytokines released by DENV-infected monocytes. The method by which DHF/DSS arises is largely accepted to be due to Antibody Dependent Enhancement (ADE) whereby upon secondary infection with a different serotype, the immune system generates non-neutralizing antibody-antigen complexes that permit a greater number of viruses to enter monocytes via Fc-receptors than DENV alone. These DENV-infected monocytes release cytokines resulting in DHF/DSS, the severe and life-threatening forms of the disease. Although the number of people that develop potentially fatal DHF/DSS is relatively small, the effect of all symptomatic DENV infections on Dengue endemic areas is impetus for the large-scale prevention of viral transmission. Given the serotype specific immunity to DENV infections and the possibility of ADE-induced DHF/DSS, prevention of DF is critical. There is currently no Dengue vaccine for the estimated 2.5 billion people at risk of infection; however vaccines under development are being designed to provide protective immunity against all four DENV serotypes to minimize the devastating consequences of ADE-induced DHF/DSS.