Baseline Characterization of Dengue Epidemiology in Yogyakarta City, Indonesia, before a Randomized Controlled Trial of Wolbachia for Arboviral Disease Control

Abstract

Dengue is endemic in Indonesia. Here, we describe the epidemiology of dengue in the city of Yogyakarta, Central Java, as a prelude to implementation of a cluster-randomized trial of Wolbachia for the biocontrol of arboviral transmission. Surveillance records from 2006 to 2016 demonstrate seasonal oscillations of dengue incidence with varying magnitude. Two lines of evidence demonstrate a high force of infection; the hospitalized case burden of patients diagnosed with dengue hemorrhagic fever or dengue shock syndrome over the last decade consisted predominantly of children/adolescents, and a serosurvey of 314 healthy children aged 1-10 years found 68% possessed dengue virus-neutralizing antibodies. Finally, a mobility survey indicated children aged 1-10 years, and particularly 1-5 year-olds, spent most of their daytime hours at home. These findings inform the design of clinical trials to measure the impact of novel vector control methods such as Wolbachia introgression into Aedes aegypti mosquitoes, by providing baseline data on disease incidence and identifying subpopulations for recruitment into prospective studies of dengue virus infection and disease. The mobility survey findings indicate that in cluster trials of interventions applied at the community level, young children can reasonably be expected to spend most of their exposure time, in epidemiological terms, within the treatment arm to which they were randomized.

Figure 1.

Geographical location of Yogyakarta city in Indonesia (A) and in Special Region of Yogyakarta (B), with details of administrative boundaries (C). This figure appears in color at www.ajtmh.org.

Figure 2.

(A) Time series of notified dengue cases (bars) and incidence per 100,000 population (line) per month in Yogyakarta city between 2006 and 2016. Data include all hospitalized dengue hemorrhagic fever and dengue shock syndrome cases reported to the passive surveillance system coordinated by the Yogyakarta District Health office. (B) Median age (with 5–95 percentiles) of notified dengue cases in Yogyakarta city, 2006–2014.

Figure 3.

(A) Map of 45 administrative areas (kelurahans) in Yogyakarta city, shaded by annual dengue incidence (per 100,000 population) for each year, 2006–2016. (B) Nonparametric correlation function shows pairwise correlation (solid line) between 45 kelurahans in Yogyakarta city in their annual dengue incidence (square root transformed and standardized to zero mean and standard deviation of one), as a function of the distance between the centroids of kelurahans. Dashed lines represent 95% confidence intervals, and the horizontal line is the overall correlation in kelurahan-level annual dengue incidence across Yogyakarta city. The Mantel test coefficient reports average spatial dependence in annual dengue incidence over all pairwise inter-kelurahan distances.

Figure 4.

Age-specific dengue seroprevalence among children aged 1–10 years resident in Yogyakarta city, sampled cross-sectionally in May–June 2015. (A) Proportion of samples (N = 314 total) positive in Panbio dengue IgG indirect ELISA, by 2-year age group, with 95% binomial confidence interval. (B) Monotypic and multitypic DENV-neutralizing antibody profiles, determined via PRNT₅₀ assay, in a random subset of 98 plasma samples that had previously tested positive in the Panbio IgG indirect ELISA. Three samples positive in IgG indirect ELISA but with PRNT₅₀ titers < 40 to all DENV serotypes are not shown.

Figure 5.

Mobility of children aged 1–10 years in Yogyakarta city, determined by a self-reported travel diary for 7 days (5 am–9 pm) of children’s activity, including weekdays and weekend. The graph shows the median and interquartile range cumulative distribution of the proportion of time (5 am–9 pm aggregated over seven consecutive days) that respondents spent at home and within increasing distances from home, by age group: children aged 1–5 years (preschool) and children aged 6–10 years (school aged).