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. 2019 Jan 22;16(1):e1002726.
doi: 10.1371/journal.pmed.1002726. eCollection 2019 Jan.

Prior dengue virus infection and risk of Zika: A pediatric cohort in Nicaragua

Affiliations

Prior dengue virus infection and risk of Zika: A pediatric cohort in Nicaragua

Aubree Gordon et al. PLoS Med. .

Abstract

Background: Zika virus (ZIKV) emerged in northeast Brazil in 2015 and spread rapidly across the Americas, in populations that have been largely exposed to dengue virus (DENV). The impact of prior DENV infection on ZIKV infection outcome remains unclear. To study this potential impact, we analyzed the large 2016 Zika epidemic in Managua, Nicaragua, in a pediatric cohort with well-characterized DENV infection histories.

Methods and findings: Symptomatic ZIKV infections (Zika cases) were identified by real-time reverse transcription PCR and serology in a community-based cohort study that follows approximately 3,700 children aged 2-14 years old. Annual blood samples were used to identify clinically inapparent ZIKV infections using a novel, well-characterized serological assay. Multivariable Poisson regression was used to examine the relation between prior DENV infection and incidence of symptomatic and inapparent ZIKV infection. The generalized-growth method was used to estimate the effective reproduction number. From January 1, 2016, to February 28, 2017, 560 symptomatic ZIKV infections and 1,356 total ZIKV infections (symptomatic and inapparent) were identified, for an overall incidence of 14.0 symptomatic infections (95% CI: 12.9, 15.2) and 36.5 total infections (95% CI: 34.7, 38.6) per 100 person-years. Effective reproduction number estimates ranged from 3.3 to 3.4, depending on the ascending wave period. Incidence of symptomatic and total ZIKV infections was higher in females and older children. Analysis of the effect of prior DENV infection was performed on 3,027 participants with documented DENV infection histories, of which 743 (24.5%) had experienced at least 1 prior DENV infection during cohort follow-up. Prior DENV infection was inversely associated with risk of symptomatic ZIKV infection in the total cohort population (incidence rate ratio [IRR]: 0.63; 95% CI: 0.48, 0.81; p < 0.005) and with risk of symptomatic presentation given ZIKV infection (IRR: 0.62; 95% CI: 0.44, 0.86) when adjusted for age, sex, and recent DENV infection (1-2 years before ZIKV infection). Recent DENV infection was significantly associated with decreased risk of symptomatic ZIKV infection when adjusted for age and sex, but not when adjusted for prior DENV infection. Prior or recent DENV infection did not affect the rate of total ZIKV infections. Our findings are limited to a pediatric population and constrained by the epidemiology of the site.

Conclusions: These findings support that prior DENV infection may protect individuals from symptomatic Zika. More research is needed to address the possible immunological mechanism(s) of cross-protection between ZIKV and DENV and whether DENV immunity also modulates other ZIKV infection outcomes such as neurological or congenital syndromes.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Classification tree showing the algorithm for distinguishing symptomatic Zika cases, dengue cases, and non-cases (negative cases) based on serological data.
Results from 5 serological assays (ZIKV and DENV MAC-ELISAs on acute and convalescent samples, ZIKV and DENV iELISAs on acute and convalescent samples, and ZIKV NS1 BOB ELISA on the post-infection annual sample) were used to classify the cases. The numbers of rRT-PCR-confirmed Zika, dengue, and negative cases according to their assay results are shown in blue, orange, and grey, respectively. BOB, blockade-of-binding; conv., convalescent; DENV, dengue virus; iELISA, inhibition ELISA; MAC-ELISA, IgM antibody capture ELISA; rRT-PCR, real-time reverse transcription PCR; ZIKV, Zika virus.
Fig 2
Fig 2. Weekly incidence of Zika in the Pediatric Dengue Cohort Study, January 2016–February 2017.
Incidence of symptomatic ZIKV infection (all cases detected by rRT-PCR and/or the serological algorithm) and incidence of rRT-PCR-positive cases. rRT-PCR, real-time reverse transcription PCR; ZIKV, Zika virus.

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