Age-Specificity of Clinical Dengue during Primary and Secondary Infections.

Background: This study aims to estimate the age-specific risks of clinical dengue attack (i.e., the risk of symptomatic dengue among the total number of dengue virus (DENV) infections) during primary and secondary infections. Methods: We analyzed two pieces of epidemiological information in Binh Thuan province, southern Vietnam, i.e., age-specific seroprevalence and a community-wide longitudinal study of clinical dengue attack. The latter data set stratified febrile patients with DENV infection by age as well as infection parity. A simple modeling approach was employed to estimate the age-specific risks of clinical dengue attack during primary and secondary infections. Results: Using the seroprevalence data, the force of infection was estimated to be 11.7% (95% confidence intervals (CI): 10.8–12.7) per year. Median age (and the 25–75 percentiles) of dengue fever patients during primary and secondary infections were 12 (9–20) and 20 (14–31) years, respectively. The estimated age-specific risk of clinical dengue increases as a function of age for both primary and secondary infections; the estimated proportion of symptomatic patients among the total number of infected individuals was estimated to be <7% for those aged <10 years for both primary and secondary infections, but increased as patients become older, reaching to 8–11% by the age of 20 years. Conclusions/Significance: For both primary and secondary infections, higher age at DENV infection was shown to result in higher risk of clinical attack. Age as an important modulator of clinical dengue explains recent increase in dengue notifications in ageing countries in Southeast Asia, and moreover, poses a paradoxical problem of an increase in adult patients resulting from a decline in the force of infection, which may be caused by various factors including time-dependent variations in epidemiological, ecological and demographic dynamics. Author Summary: Although age at dengue virus (DENV) infection is recognized as playing a key role in characterizing the risks of clinical attack and disease severity, the contributions of age to disease development have yet to be quantified in detail. We estimated the age-specific risk of clinical attack (i.e., the risk of symptomatic dengue among the total number of DENV infections) during primary and secondary DENV infections in Vietnam, by employing a simple epidemiological modeling approach in which two pieces of epidemiological data sets were used, i.e., (i) age-specific seroprevalence and (ii) age-specific frequency of clinical attack of dengue during primary and secondary infections. We showed that those at higher age are more likely to develop symptomatic dengue than younger individuals for both primary and secondary infections; the estimated proportion of symptomatic patients among the total number of infected individuals was below 7% for those aged younger than 10 years of age for both primary and secondary infections, but was shown to be elevated as the patients become older, reaching to 8–11% by the age of 20 years. Age as an important modulator of clinical dengue attack explains recent increase in dengue notifications in ageing countries in Southeast Asia, and moreover, poses a paradoxical problem of an increase in adult patients resulting from a decline in the force of infection, which may be caused by various factors including time-dependent variations in epidemiological, ecological and demographic dynamics. [ABSTRACT FROM AUTHOR]