Observations related to pathogenesis of dengue hemorrhagic fever. V. Examination of agspecific sequential infection rates using a mathematical model.

Experimental studies of dengue infections in humans suggest that immunity to homologous virus challenge is probably of lifelong duration.' Individuals infected with one type of dengue virus and then exposed to a second serotype within 3-6 months may develop modified disease or no disease at all.' Studies of dengue infection in Bangkok have suggested that infection with one type of dengue virus sensitizes an individual so that subsequent infection with another type elicits a hypersensitivity reaction producing the dengue hemorrhagic fever (DHF) syndrome.2 Since at least four types of dengue viruses are simultaneously endemic in Bangkok, it is theoretically possible that hypersensitivity reactions could occur during the second, third or fourth heterologous infection. The limits of the interval between sensitizing and eliciting infections are unknown, but the evidence of short duration heterologous protection cited above plus the seasonal periodicity of dengue transmission in the tropics suggests that most DHF may result from heterologous infections occurring at an interval of one year or more.8" It is the purpose of this paper to utilize the above observations in a study of mathematical models which permit prediction of age specific secondary or tertiary infection rates in populations exposed to three or four different dengue viruses. Results from models have been compared with available epidemiologic data, particularly age specific hemorrhagic fever hospitalization rates, to evaluate hypotheses concerning the number of infections and the interval between infections required to produce DHF.