RETROSPECTIVE STUDY ON DENGUE FATAL CASES

Immunohistochemical procedure (avidin biotin peroxidase complex) was a pplied in formalin-fixed and paraffin-embedded tissues obtained from 5 fatal cases of dengue infection associated with encephalopathy. Dengu e virus antigen was demonstrated in the cytoplasm of phagocytic mononu clear cells from liver, spleen, and lung. Moreover, dengue viral antig ens were here, to our knowledge, first demonstrated in the central ner vous system (CNS) and numerous immunolabelled cells were found in brai n sections from 3 cases. Extended immunohistochemical studies carried out in 1 case showed virus-positive cells mostly located within Vircho w Robin space of medium size and small veins, infiltrating the white a nd grey matter, and often situated close to neurons displaying apparen t cytopathic features. Furthermore, immunostaining for CD68 antigens d emonstrated that most CD68+ macrophages and dengue antigen-positive ce lls share similar morphology and localization, suggesting a unique ide ntity for at least part of these cells. Since in dengue fever, virus r eplicates mostly in cells of macrophage lineage, our results seem to i ndicate that infiltration of virus-infected macrophages could be one o f the pathways by which viruses enter the brain in dengue encephalitis . Whether bone marrow-derived infected macrophages and viral-free part icles induce CSN lesions through immune, metabolic, and/or direct vira l-induced mechanisms will be essential to better understand the pathog enesis and provide new therapeutic strategies for dengue-associated en cephalitis. As the evidence of tissue damage was nonspecific, the dete ction of virus antigen by immunoperoxidase technique appeared to be hi ghly reliable for dengue diagnosis.