Observations related to pathogenesis of dengue hemorrhagic fever. I. Experience with classification of dengue viruses.

Two distinct syndromes associated with dengue virus infection are prevalent in tropical Asia; dengue fever, a benign disease characterized by fever, myalgia, leucopenia and a maculo-papular rash and dengue hemorrhagic fever (DHF), accompanied by fever, shock, hemorrhagic diathesis and a significant mortality.1 The dengue viruses, a group of antigenically related members of the Group B arthropod-borne virus family, are transmitted from man to man by the mosquito, Aedes aegypti. Multiple members of the group are known to be simultaneously transmitted in large urban areas of tropical Asia. Dengue disease syndromes of both types may occur concurrently, DHF usually is restricted to the indigenous population, while dengue fever may occur in both indigenous and non-indigenous residents of an area." When dengue hemorrhagic fever was first described in the Philippines, two new dengue viruses, types 3 and 4 were recovered from patients.' Shortly thereafter, dengue strains recovered from DHF patients in Thailand were tentatively designated types 5 and 6.5 As one explanation of the malignant type of dengue fever, it was suggested that dengue viruses had acquired virulence properties.6 A corollary to this hypothesis was that virulence and surface antigen were genetically linked and thus, the "newer" types of dengue viruses were the cause of the severe dengue syndrome. The hypothesis that DHF is due to a self-destructive host response has been proposed by Halstead and associates.7 They suggested that some persons are sensitized by their first dengue infection. In such a host the course