Dissecting Age-Stratified Immunity to Different Dengue Virus Serotypes and Zika Viruses Among Children in a Highly Endemic Region in Sri Lanka.

Abstract

Determining serotype-specific, age-stratified dengue virus (DENV) and Zika virus (ZIKV) seroprevalence rates is crucial for implementing vaccines and vector control strategies. Therefore, we sought to assess the age-stratified seroprevalence of monotypic or multitypic exposure in a community cohort in Sri Lanka. DENV-specific serostatus was assessed in 4161 children aged 4 to 16 years, using an in-house DENV-specific IgG enzyme-linked immunosorbent assay (ELISA), and results were compared with those of a widely used commercial assay (Panbio Dengue IgG Indirect ELISA). We also used a multiplexed, microsphere-based serological assay to characterize monotypic vs multitypic responses and to differentiate exposure rates to different DENV serotypes and ZIKV in a subcohort of children (n = 604). By IgG ELISA, DENV seropositivity was 72.34% (3010/4161), and the seropositivity rate significantly increased with age (Spearman <i>r</i> = 1.0, <i>P</i> = .003). The estimated force of infection was 0.16 (95% credible interval, 0.14-0.17). Of the 604 individuals tested by Luminex, 258 (42.7%) had a monotypic dengue response, whereas 209 (34.9%) had a multitypic response. Moreover, 100 (16.5%) had evidence of a past infection to Zika, while 20 (3.33%) children had antibodies only to ZIKV. Of the 258 individuals with evidence of a monotypic response to DENV, DENV2 (56.83%) and DENV1 (30.57%) accounted for the most infections. There was an inverse correlation between exposure to ZIKV and age (Spearman <i>r</i> = -0.72, <i>P</i> = .007). An overall 72.3% of children were seropositive for dengue, with 42.7% having been infected with only 1 DENV in the past. The data suggest that prior immunity to DENV may reduce the risk of ZIKV infection, which should be further assessed.