Presence of Flavivirus Antibodies Does Not Lead to a Greater Number of Symptoms in a Small Cohort of Canadian Travelers Infected with Zika Virus.

Robert A Kozak,Christine Frantz,Olivia Varsaneux,Jonathan B Gubbay,Lee W Goneau,Cedric Delima,Romy Olsha,David Safronetz,Stephen Perusini,Alireza Eshaghi,Erik Kristjanson

doi:10.3390/v12020140

Abstract

Zika virus (ZIKV) is a mosquito-borne flavivirus associated with a febrile illness as well as severe complications, including microcephaly and Guillain-Barré Syndrome. Antibody cross-reactivity between flaviviruses has been documented, and in regions where ZIKV is circulating, dengue virus (DENV) is also endemic, leaving the potential that previous exposure to DENV could alter clinical features of ZIKV infection. To investigate this, we performed a retrospective case-control study in which we compared Canadian travellers who had been infected with ZIKV and had serological findings indicating previous DENV or other flavivirus exposure (n = 16) to those without any previous exposure (n = 44). Patient samples were collected between February 2016 and September 2017 and submitted to Public Health Ontario for testing. ZIKV infection was determined using real-time RT-PCR and antibodies against DENV were identified by the plaque-reduction neutralization test. The mean time from symptom onset to sample collection was 5 days for both groups; the magnitude of viremia was not statistically different (Ct values: 35.6 vs. 34.9, p-value = 0.2). Clinical scores were also similar. Our findings indicate that previous DENV or other flavivirus exposure did not result in greater viremia or a higher illness score.

Highlights

Zika virus (ZIKV) is a mosquito-borne flavivirus spread primarily by the Aedes spp., and is a significant public health concern [1]
This study investigated the relative viral load as well as the number, and severity of reported symptoms in ZIKV-positive patients with serological evidence of previous dengue virus (DENV) or other flavivirus exposure compared to ZIKV-positive patients with no serological evidence of previous exposure
All 60 patients included in this study were travelers to countries in the Caribbean and South America where ZIKV was circulating during the Zika virus epidemic, and ZIKV infection was confirmed by RT-PCR

Summary

Introduction

Zika virus (ZIKV) is a mosquito-borne flavivirus spread primarily by the Aedes spp., and is a significant public health concern [1]. According to data from WHO, as of March 2018 there were 71 countries that reported introduction, re-introduction or ongoing transmission of the virus (www.who.int). In regions where ZIKV has been reported there are other vector-borne flaviviruses that are endemic, most notably dengue virus (DENV), likely due to these. A potential mechanism could be the presence of cross-reactive antibodies against DENV that may result in antibody-dependent enhancement (ADE). In heterotypic DENV infections, this process results in more severe disease due to high concentrations of antibodies that bind, but do not neutralize the virus [5]. It has been hypothesized that ADE causes increased ZIKV replication and possibly more severe disease [4,6,7]. It has been shown that ZIKV induces activation of cross-reactive B-cells in individuals who were previously exposed to DENV [8]

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Results

Conclusion