Studies on the Pathogenesis of Dengue Infection in Monkeys. II. Clinical Laboratory Responses to Heterologous Infection

Laboratory responses to a second inoculation of a dengue virus were studied in 118 rhesus monkeys challenged at intervals of two, six, 12, and 26 weeks. Nine animals received the same virus twice; the others received a heterologous type. A single animal manifested leukocytosis, thrombocytopenia, elevation of prothrombin time, and decrease in complement during an infection due to dengue 2 virus that followed a pimary dengue 4 infection at an interval of three months. A mild thrombocytopenia was significantly correlated with secondary dengue 2 infections. A sharp decrease in total complement was observed early after secondary infection with dengue 2 in six of eight monkeys. In secondary dengue 1 and 4 infections, titers of viremia were depressed, while viremia was not detected after secondary challenge with dengue 3. Peak titers of secondary dengue 2 viremia were 13-fold higher than peak titers in primary dengue 2 infections. The greater production of virus in certain secondary infections due to dengue viruses could be a controlling mechanism in the postulated immunologic injury in dengue shock syndrome in man.