Estimating Zika Virus Seroprevalence in a Dengue Virus-Endemic Population: The Use of Blood Donors and Multiplex Serology to Monitor Arbovirus Outbreaks in the Dutch Caribbean.

Abstract

The geographic range of flaviviruses is expanding, as evidenced by the increase in dengue virus (DENV) cases and the recent emergence of Zika virus (ZIKV) in the Americas. Studying seroprevalence of flaviviruses in (hyper)endemic regions is challenging due to extensive antibody cross-reactivity. Over the past decade, Aruba and Curaçao have experienced DENV and ZIKV outbreaks, of which the magnitude and impact remain unclear due to the challenges of disentangling DENV from ZIKV (past) infection. Here, we study the potential utility of blood donors for monitoring the extent of circulation, on 2 Caribbean islands. We report a longitudinal cross-sectional study using randomly selected blood donor sera (n = 715) during the ZIKV outbreaks on Aruba and Curaçao (January 2016-July 2017). Flavivirus seroprevalence was estimated using a validated multiplex protein microarray containing NS1 proteins for 11 flaviviruses, in combination with confirmation virus neutralization tests on a selection of sera. It was possible to disentangle ZIKV exposure from exposure to other flaviviruses. In Curaçao, the seroprevalence of ZIKV antibodies was 25% and significantly higher than the prevalence of antibodies attributable to ZIKV exposure in Aruba (8%). Flavivirus immunoglobulin G antibody (IgG) titers increased with age (P < .05). This methodology allows estimation of ZIKV seroprevalence during and after the ZIKV outbreaks. This study shows the importance of including age in the interpretation of serology data. Furthermore, it gives insights into the complex antibody (background) patterns of flaviviruses over time, and highlights the utility of an existing voluntary blood donor program to monitor and respond to (flavivirus) outbreaks.