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BackgroundIndonesia reports the second highest dengue disease burden in the world; these data are from passive surveillance reports and are likely to be significant underestimates. Age-stratified seroprevalence data are relatively unbiased indicators of past exposure and allow understanding of transmission dynamics.Methodology/Principal FindingsTo better understand dengue infection history and associated risk factors in Indonesia, a representative population-based cross-sectional dengue seroprevalence study was conducted in 1–18-year-old urban children. From October to November 2014, 3,210 children were enrolled from 30 geographically dispersed clusters. Serum samples were tested for anti-dengue IgG antibodies by indirect ELISA. A questionnaire investigated associations between dengue serologic status and household socio-demographic and behavioural factors. Overall, 3,194 samples were tested, giving an adjusted national seroprevalence in this urban population of 69.4% [95% CI: 64.4–74.3] (33.8% [95% CI: 26.4–41.2] in the 1–4-year-olds, 65.4% [95% CI: 69.1–71.7] in the 5–9-year-olds, 83.1% [95% CI: 77.1–89.0] in the 10–14-year-olds, and 89.0% [95% CI: 83.9–94.1] in the 15–18-year–olds). The median age of seroconversion estimated through a linear model was 4.8 years. Using a catalytic model and considering a constant force of infection we estimated 13.1% of children experience a primary infection per year. Through a hierarchical logistic multivariate model, the subject’s age group (1–4 vs 5–9 OR = 4.25; 1–4 vs. 10–14 OR = 12.60; and 1–4 vs 15–18 OR = 21.87; p<0.0001) and the number of cases diagnosed in the household since the subject was born (p = 0.0004) remained associated with dengue serological status.Conclusions/SignificanceThis is the first dengue seroprevalence study in Indonesia that is targeting a representative sample of the urban paediatric population. This study revealed that more than 80% of children aged 10 years or over have experienced dengue infection at least once. Prospective incidence studies would likely reveal dengue burdens far in excess of reported incidence rates.

Dengue incidence has increased globally, but empirical burden estimates are scarce. Prospective methods are best-able to capture all severities of disease. CYD14 was an observer-blinded dengue vaccine study conducted in children 2–14 years of age in Indonesia, Malaysia, Thailand, the Philippines, and Vietnam. The control group received no vaccine and resembled a prospective, observational study. We calculated the rates of dengue according to different laboratory or clinical criteria to make inferences about dengue burden, and compared with rates reported in the passive surveillance systems to calculate expansion factors which describe under-reporting. Over 6,933 person-years of observation in the control group there were 319 virologically confirmed dengue cases, a crude attack rate of 4.6%/year. Of these, 92 cases (28.8%) were clinically diagnosed as dengue fever or dengue hemorrhagic fever by investigators and 227 were not, indicating that most symptomatic disease fails to satisfy existing case definitions. When examining different case definitions, there was an inverse relationship between clinical severity and observed incidence rates. CYD14’s active surveillance system captured a greater proportion of symptomatic dengue than national passive surveillance systems, giving rise to expansion factors ranging from 0.5 to 31.7. This analysis showed substantial, unpredictable and variable under-reporting of symptomatic dengue, even within a controlled clinical trial environment, and emphasizes that burden estimates are highly sensitive to case definitions. These data will assist in generating disease burden estimates and have important policy implications when considering the introduction and health economics of dengue prevention and control interventions.

Dengue is a public health concern across the globe, and an escalating problem in the Americas. As part of a wider programme (covering Latin America and South East Asia) to characterize the epidemiology of dengue in dengue endemic areas, we undertook a systematic literature review to assess epidemiological trends (incidence, timing and duration of outbreaks/epidemics, age and sex distribution, serotype distribution, seroprevalence and disease severity) for dengue across the French Territories of the Americas (FTA), in French Guiana, Guadeloupe, Martinique, Saint Martin and Saint Barthélemy between 2000 and 2012 (CRD42012002341: http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42012002341). Of 413 relevant data sources identified, 45 were eligible for inclusion. A large proportion of the available data were from national surveillance reports, and 12 publications were from peer-reviewed journals. During the review period, 3–5 epidemics were identified in each of the island territories and French Guiana, and epidemics were often associated with a shift in the predominant circulating dengue virus serotype. Substantial gaps in epidemiological knowledge were identified. In particular, information regarding dengue virus genotype distribution, seroprevalence and age distribution of dengue were lacking. Additionally, much of the available data were from epidemic years; data from inter-epidemic periods were sparse. Nevertheless, the available epidemiological data showed that dengue is endemic across the FTA and suggest an evolution towards hyperendemicity, highlighting the need to continue the efforts with the existing surveillance programmes to assist in planning an effective vaccination programme once a dengue vaccine is deployed.Protocol registrationPROSPERO CRD42012002341