S-50. Dengue virus – its epidemiology and immuno-pathogenesis

Dengue is most rapidly spreading arboviral disease in the tropics and sub-tropics. The global burden of dengue has increased at least four fold over the last three decades and almost half the world's population is estimated to be at risk. The primary vectors Aedes aegypti and the probably less important Aedes albopicus have spread throughout the tropics. An estimated 50 million dengue infections now occur annually, particularly in South-East Asia, the Americas and the Western Pacific islands. About 500,000 severe dengue cases are reported annually and some 20.000 deaths occur. Dengue virus causes simple flu like symptoms dengue fever (DF) and severe disease dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). The majority of severe infections occur upon secondary encounters with heterologus dengue virus serotypes. Despite extensive studies, the pathogenesis of DHF is still not fully understood. Severe disease is linked to high levels of antibody- enhanced viral replication early in illness and is followed by a cascade of memory T-cell activation and a ‘storm ‘of inflammatory cytokines and other chemical mediators. We observed that a unique cytokine, cytotoxic factor (CF) is produced by CD4+ T-cells during dengue virus infection of mice (mCF) and man (hCF). Cytotoxic factor kills the lymphoid cells and also alters their functions. It induces macrophages to produce free radicals, nitrite, reactive oxygen and peroxynitrite. It damages the blood – brain barrier and increases vascular permeability, thus appears to be pathogenesis related protein. Further, highest levels of hCF auto-antibodies are seen in the sera of patients with mild fever (DF) and decline sharply with the development of DHF. This suggests that higher levels of hCF auto-antibodies protect the patient against the development of DHF and may be used as prognostic indicator.