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

Date Published: January 22, 2019

Publisher: Public Library of Science

Author(s): Aubree Gordon, Lionel Gresh, Sergio Ojeda, Leah C. Katzelnick, Nery Sanchez, Juan Carlos Mercado, Gerardo Chowell, Brenda Lopez, Douglas Elizondo, Josefina Coloma, Raquel Burger-Calderon, Guillermina Kuan, Angel Balmaseda, Eva Harris, Lorenz von Seidlein

Abstract: BackgroundZika 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 findingsSymptomatic 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.ConclusionsThese 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.

Partial Text: Zika virus (ZIKV) belongs to the Flavivirus genus in the Flaviviridae family. It was initially isolated in Uganda in 1947 [1], and the first evidence of human ZIKV infection came from serological studies conducted in Uganda in 1952 [2]. While the first human case was described in 1964 [3], few cases were detected until 2007, though serological evidence existed of circulation in Africa and southeast Asia [4]. In 2007, the first major outbreak of Zika occurred on Yap Island [5,6], and larger outbreaks were documented in Oceania in 2013–2014, in particular in French Polynesia [7]. ZIKV caused a major epidemic in Brazil starting in 2015, which rapidly spread to South, Central, and North America and the Caribbean. In Nicaragua, the first Zika case was identified in January 2016.



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