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Int J Mol Sci. 2019 Feb 7;20(3). pii: E712. doi: 10.3390/ijms20030712.

Clinical Importance of Placental Testing among Suspected Cases of Congenital Zika Syndrome.

Author information

1
Departments of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX 77030, USA. maxim.seferovic@bcm.edu.
2
Departments of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX 77030, USA. michelle.turley@bcm.edu.
3
Departments of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX 77030, USA. gvalenti@bcm.edu.
4
Pediatrics, Section of Neonatology, Baylor College of Medicine, Houston, TX 77030, USA. gvalenti@bcm.edu.
5
Departments of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX 77030, USA. martha.rac@bcm.edu.
6
Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA. ecastro@bcm.edu.
7
Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA. amajor@bcm.edu.
8
Departments of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX 77030, USA. brianna.sanchez@bcm.edu.
9
Departments of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX 77030, USA. catherine.eppes@bcm.edu.
10
Departments of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX 77030, USA. magdalena.sanzcortes@bcm.edu.
11
Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA. jjdunn@texaschildrens.org.
12
Departments of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX 77030, USA. tiffany.kautz@bcm.edu.
13
Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA. jamesv@bcm.edu.
14
Microbiology and Molecular Virology, Baylor College of Medicine, Houston, TX 77030, USA. jamesv@bcm.edu.
15
Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA. kenneth.muldrew@bcm.edu.
16
Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA. tim.stout@bcm.edu.
17
Departments of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX 77030, USA. belfort@bcm.edu.
18
Pediatrics, Section of Infectious Diseases at Baylor College of Medicine and Texas Children's Hospital, Houston, TX 77030, USA. gdemmler@bcm.edu.
19
Departments of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX 77030, USA. aagaardt@bcm.edu.
20
Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. aagaardt@bcm.edu.

Abstract

Contemporaneous Zika virus (ZIKV) strains can cause congenital Zika syndrome (CZS). Current ZIKV clinical laboratory testing strategies are limited and include IgM serology (which may wane 12 weeks after initial exposure) and nucleic acid testing (NAT) of maternal serum, urine, and placenta for (+) strand ZIKV RNA (which is often transient). The objectives of this study were to determine if use of additional molecular tools, such as quantitative PCR and microscopy, would add to the diagnostic value of current standard placental ZIKV testing in cases with maternal endemic exposure and indeterminate testing. ZIKV RNA was quantified from dissected sections of placental villi, chorioamnion sections, and full cross-sections of umbilical cord in all cases examined. Quantitation with high-resolution automated electrophoresis determined relative amounts of precisely verified ZIKV (74-nt amplicons). In order to localize and visualize stable and actively replicating placental ZIKV in situ, labeling of flaviviridae glycoprotein, RNA ISH against both (+) and (⁻) ZIKV-specific ssRNA strands, and independent histologic examination for significant pathologic changes were employed. We demonstrate that the use of these molecular tools added to the diagnostic value of placental ZIKV testing among suspected cases of congenital Zika syndrome with poorly ascribed maternal endemic exposure.

KEYWORDS:

Zika virus; arbovirus; congenital Zika syndrome; congenital brain malformations; microcephaly; molecular virology; placental Zika infection; placental testing; viral pathogenicity

PMID:
30736425
PMCID:
PMC6387308
DOI:
10.3390/ijms20030712
[Indexed for MEDLINE]
Free PMC Article

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