Zika Virus Infection in Pregnancy: Advanced Diagnostic Approaches in Dengue-Naive and Dengue-Experienced Pregnant Women and Possible Implication for Cross-Reactivity and Cross-Protection.

Maurizio Zavattoni,Francesca Rovida,Alessia Arossa,Antonella Sarasini,Lina Bollani,Elena Percivalle,Giuseppina Lombardi,Simona Orcesi,Beatrice Tassis,Irene Cassaniti,Fausto Baldanti

doi:10.3390/microorganisms8010056

Maurizio Zavattoni, Francesca Rovida + Show 9 more

Open Access

https://doi.org/10.3390/microorganisms8010056

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Abstract

Zika virus (ZIKV) infection has been linked to congenital defects in fetuses and infants, as exemplified by the microcephaly epidemic in Brazil. Given the overlapping presence of Dengue virus (DENV) in the majority of ZIKV epidemic regions, advanced diagnostic approaches need to be evaluated to establish the role of pre-existing DENV immunity in ZIKV infection. From 2015 to 2017, five pregnant women with suspected ZIKV infection were investigated in Pavia, Italy. Among the five pregnant women, three were DENV–ZIKV immunologically cross-reactive, and two were DENV-naïve. Advanced diagnosis included the following: (i) NS1 blockade-of-binding (BOB) ELISA assay for ZIKV specific antibodies and (ii) ELISpot assay for the quantification of effector memory T cells for DENV and ZIKV. These novel assays allowed to distinguish between related flavivirus infections. The three DENV-experienced mothers did not transmit ZIKV to the fetus, while the two DENV-naive mothers transmitted ZIKV to the fetus. Pre-existing immunity in DENV experienced mothers might play a role in cross-protection.

Highlights

In 2015, the mosquito-borne Zika virus (ZIKV) began spreading throughout the Americas and clinicians reported unexpected increases in the numbers of babies born with microcephaly and of adults with Guillain-Barrè syndrome (GBS)
Transmission of ZIKV has declined in the Americas, outbreaks and infection clusters continue to occur in some regions, such as India and South-east Asia, where there are large populations of women of childbearing age who are susceptible to the virus [3]
Modeling of data from French Polynesia suggests about a 1% risk of microcephaly associated with maternal Zika virus infection in the first-trimester pregnancy, while a model based on data from a Zika outbreak in Bahia, Brazil, suggests a risk between 1% and 13% [4,5]

Summary

Introduction

In 2015, the mosquito-borne Zika virus (ZIKV) began spreading throughout the Americas and clinicians reported unexpected increases in the numbers of babies born with microcephaly and of adults with Guillain-Barrè syndrome (GBS). The population at risk in the United States, large, has significantly less exposure to the closely-related Dengue virus (DENV) than the Brazilian population affected by the Zika virus. This may have implications for the risk of fetal infection and disease [10,11]. Prospective studies in humans showed that prior dengue infection and pre-existing anti-DENV antibodies reduced, rather than enhanced, the risk of ZIKV infection and disease [14,15]. We discuss the possible mechanisms of protection from vertical transmission and associated congenital abnormalities

Patients and Methods

Patient 1

Patient 2