Abstract

Here we propose a strategy allowing implementing efficient and practicable large-scale seroepidemiological studies for Zika Virus (ZIKV). It combines screening by a commercial NS1 protein-based Zika IgG ELISA, and confirmation by a cytopathic effect-based virus neutralization test (CPE-based VNT). In post-epidemic samples from Martinique Island blood donors (a population with a dengue seroprevalence above 90%), this strategy allowed reaching specificity and sensitivity values over 98%. The CPE-based VNT consists of recording CPE directly under the optical microscope, which is easy to identify with ZIKV strain H/PF/2013 at day 5 pi. Overall, considered that CPE-based VNT is cost effective and widely automatable, the NS1 protein-based Zika IgG ELISA+CPE-based VNT combination strategy represents a convenient tool to expedite ZIKV seroprevalence studies.

Highlights

  • Zika virus (ZIKV) is an enveloped RNA virus [1] of African origin, first identified as the aetiological agent of mild arboviral fever [2] and mainly transmitted to human by the bite of infected Aedes mosquitoes [3]

  • Serum samples In order to compare virus neutralization test (VNT) and Plaque Reduction Neutralization Test (PRNT), we used a panel of sera from blood donors of different origins: 90 from Martinique Island and 10 from Guadeloupe Island; 7 from Cameroon; 35 from Metropolitan France

  • Validation of the virus neutralisation test (VNT) In order to estimate the analytical specificity and sensitivity of the VNT for ZIKV, VNT results of the panel were compared with the plaque reduction neutralization test (PRNT) which is considered to be the “gold standard technique”

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Summary

Introduction

Zika virus (ZIKV) is an enveloped RNA virus (family Flaviviridae, genus Flavivirus) [1] of African origin, first identified as the aetiological agent of mild arboviral fever [2] and mainly transmitted to human by the bite of infected Aedes mosquitoes [3]. Intra-uterine [5] and sexual routes of transmission have been identified [6] and severe neurological presentations have been reported in adults (myelitis, encephalitis, Guillain-Barré syndrome) [7] and in foetus (including microcephaly) [8]. Due to frequent asymptomatic infections (ranging between 29 to 82% in different populations) [9], the survey of ZIKV clinically suspected cases is poorly adapted to estimate the attack rate during ZIKV outbreaks. This information can be provided by seroprevalence studies [10]. Antigenic cross-reactivity between ZIKV and other flaviviruses ( dengue virus) makes seroprevalence studies challenging and requires wide use of seroneutralization assays [11]

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