Dengue fever and dengue haemorrhagic fever: challenges of controlling an enemy still at large.

Dengue virus infections are a serious cause of morbidity and mortality in most tropical and subtropical areas of the world: mainly Southeast and South Asia, Central and South America, and the Caribbean. Understanding the pathogenesis of dengue haemorrhagic fever (DHF), the severe form of dengue illness, is a very important and challenging research subject. Viral virulence and immune responses have been considered as two major factors responsible for the pathogenesis. Virological studies are attempting to define the molecular basis of viral virulence. The immunopathological mechanisms appear to include a complex series of immune responses. A rapid increase in the levels of cytokines and chemical mediators apparently plays a key role in inducing plasma leakage, shock and haemorrhagic manifestations. It is likely that the entire process is initiated by infection with a so-called virulent dengue virus, often with the help of enhancing antibodies in secondary infection, and then triggered by rapidly elevated cytokines and chemical mediators produced by intense immune activation. However, understanding of the DHF pathogenesis is not complete. We still have a long way to go.