Studies on the Pathogenesis of Dengue Infection in Monkeys. I. Clinical Laboratory Responses to Primary Infection

Abstract

Virologic, serologic, and clinical responses to infection were studied in 122 Macaca mulatto monkeys and 17 monkeys of three other species that were inoculated with dengue 1–4 viruses passaged in tissue culture. Susceptible rhesus monkeys, inoculated with either high (10^3.7–10^5.7pfu) or low (8–50 pfu) doses of virus always developed antibody. Frequently with dengue 2 infection, but less frequently with dengue 1 infection, lymphadenomegaly, depression of leukocyte count, and lymphocytosis were noted. In approximately 90% of infected animals viremia began two to six days after inoculation; 90% of dengue 2 and 4 viremias lasted six days or less; the average duration of dengue 1 viremia was somewhat longer, and of dengue 3 viremia shorter than this. HAI titers to the homologous antigen in convalescent sera were usually twofold higher than titers to heterologous dengue viruses; antibody response to dengue 4 infection was relatively specific. No abnormalities were observed in serial hematocrit, prothrombin time, and determinations of total protein. Levels of complement in serum rose several days after the start of serial bleedings in both infected and control animals. The courses of infection due to dengue viruses are similar in humans and monkeys.