In regions where dengue is endemic, understanding exactly when children acquire immunity — and to which viral strains — has direct consequences for vaccine timing, dosing strategy, and outbreak prediction. This large serological survey from Sri Lanka offers rare granularity on how flavivirus exposure accumulates across childhood, with implications extending well beyond South Asia to any tropical population facing dengue vaccination decisions.
Among 4,161 children aged 4 to 16 years in a Sri Lankan community cohort, 72.3% tested seropositive for dengue IgG antibodies, with seropositivity rising steeply and significantly with age (Spearman r = 1.0). The estimated annual force of infection — a measure of transmission intensity — was 0.16, meaning roughly 16% of susceptible children acquired a new infection each year. In a subset of 604 children analyzed with a multiplexed microsphere-based Luminex assay, 42.7% showed a monotypic response (single serotype exposure) while 34.9% displayed multitypic responses indicating sequential infections. Among monotypic cases, DENV2 dominated at 56.8%, followed by DENV1 at 30.6%. Notably, 16.5% of children showed serological evidence of past Zika virus infection, and 3.3% had antibodies exclusively to Zika — a finding that complicates dengue serology interpretation.
These data carry important nuance for dengue vaccine programs. The licensed vaccine Dengvaxia, for instance, is contraindicated in seronegative individuals due to enhanced disease risk upon subsequent natural infection; this study's age-stratified force-of-infection data could help calibrate pre-vaccination screening thresholds. The cross-reactive nature of flavivirus antibodies — particularly between dengue and Zika — also raises questions about serological misclassification in surveillance systems relying on standard ELISA platforms, as the Panbio commercial assay comparison in this study highlights. This is a well-powered observational cohort with meaningful subcohort serotyping, though it captures a single geographic and temporal snapshot. Replication across multiple endemic seasons and regions would strengthen generalizability.