Incidence of Dengue Virus Infection in Adults and Children in a Prospective Longitudinal Cohort in the Philippines

Background: The mean age of dengue has been increasing in some but not all countries. We sought to determine the incidence of dengue virus (DENV) infection in adults and children in a prospective cohort study in the Philippines where dengue is hyperendemic. Methodology/Principal Findings: A prospective cohort of subjects ≥6 months old in Cebu City, Philippines, underwent active community-based surveillance for acute febrile illnesses by weekly contact. Fever history within the prior seven days was evaluated with an acute illness visit followed by 2, 5, and 8-day, and 3-week convalescent visits. Blood was collected at the acute and 3-week visits. Scheduled visits took place at enrolment and 12 months that included blood collections. Acute samples were tested by DENV PCR and acute/convalescent samples by DENV IgM/IgG ELISA to identify symptomatic infections. Enrolment and 12-month samples were tested by DENV hemagglutination inhibition (HAI) assay to identify subclinical infections. Of 1,008 enrolled subjects, 854 completed all study activities at 12 months per-protocol undergoing 868 person-years of surveillance. The incidence of symptomatic and subclinical infections was 1.62 and 7.03 per 100 person-years, respectively. However, in subjects >15 years old, only one symptomatic infection occurred whereas 27 subclinical infections were identified. DENV HAI seroprevalence increased sharply with age with baseline multitypic HAIs associated with fewer symptomatic infections. Using a catalytic model, the historical infection rate among dengue naïve individuals was estimated to be high at 11–22%/year. Conclusions/Significance: In this hyperendemic area with high seroprevalence of multitypic DENV HAIs in adults, symptomatic dengue rarely occurred in individuals older than 15 years. Our findings demonstrate that dengue is primarily a pediatric disease in areas with high force of infection. However, the average age of dengue could increase if force of infection decreases over time, as is occurring in some hyperendemic countries such as Thailand. Author Summary: The average age of dengue has been increasing in some but not all dengue endemic countries. To investigate the age pattern of dengue in people of all ages ≥6 months old, a prospective community-based cohort study was undertaken in Cebu City, Philippines where dengue virus has been circulating for many decades. Active surveillance for acute fevers was performed, and acute/convalescent blood samples were tested for evidence of symptomatic dengue. Blood was also collected at enrolment and one year later, and tested serologically to identify subclinical infections. Overall, 1.62 symptomatic and 7.03 subclinical infections per 100 person-years of surveillance were detected. Among people older than 15 years, only one symptomatic dengue case occurred while 27 subclinical infections were identified. By analyzing age-specific dengue serology data, the historical infection rate among people with no prior dengue virus infection was found to be high at around 11–22% per year. Our results show that dengue is primarily a childhood disease in endemic settings where the historical infection rate has been high. However, the average age of dengue could increase if the infection rate decreases over time as is happening in some endemic countries like Thailand.