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      Zika Virus Infection and Stillbirths: A Case of Hydrops Fetalis, Hydranencephaly and Fetal Demise

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          Abstract

          Background

          The rapid spread of Zika virus in the Americas and current outbreak of microcephaly in Brazil has raised attention to the possible deleterious effects that the virus may have on fetuses.

          Methodology/Principal Findings

          We report a case of a 20-year-old pregnant woman who was referred to our service after a large Zika virus outbreak in the city of Salvador, Brazil with an ultrasound examination that showed intrauterine growth retardation of the fetus at the 18 th gestational week. Ultrasound examinations in the 2 nd and 3 rd trimesters demonstrated severe microcephaly, hydranencephaly, intracranial calcifications and destructive lesions of posterior fossa, in addition to hydrothorax, ascites and subcutaneous edema. An induced labor was performed at the 32 nd gestational week due to fetal demise and delivered a female fetus. ZIKV-specific real-time polymerase chain reaction amplification products were obtained from extracts of cerebral cortex, medulla oblongata and cerebrospinal and amniotic fluid, while extracts of heart, lung, liver, vitreous body of the eye and placenta did not yield detectable products.

          Conclusions/Significance

          This case report provides evidence that in addition to microcephaly, there may be a link between Zika virus infection and hydrops fetalis and fetal demise. Given the recent spread of the virus, systematic investigation of spontaneous abortions and stillbirths may be warranted to evaluate the risk that ZIKV infection imparts on these outcomes.

          Author Summary

          The rapid spread of Zika virus in the Americas and outbreak of microcephaly in Brazil has raised attention to the possible deleterious effects that the virus may have on fetuses. We report a case of a 20-year-old pregnant woman from Salvador, Brazil whose fetus had developed hydrops fetalis, a condition where there is abnormal accumulation of fluid in the fetus, as well as severe central nervous system defects such as microcephaly and hydranencephaly. After fetal demise, ZIKV RNA was detected in central nervous system tissues and amniotic fluid. The case report provides evidence that in addition to microcephaly, there may be a link between Zika virus infection and hydrops fetalis and fetal demise. Given the recent spread of the virus, systematic investigation of spontaneous abortions and stillbirths may be warranted to evaluate the risk that ZIKV infection imparts on these outcomes.

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          Most cited references3

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          First report of autochthonous transmission of Zika virus in Brazil

          In the early 2015, several cases of patients presenting symptoms of mild fever, rash, conjunctivitis and arthralgia were reported in the northeastern Brazil. Although all patients lived in a dengue endemic area, molecular and serological diagnosis for dengue resulted negative. Chikungunya virus infection was also discarded. Subsequently, Zika virus (ZIKV) was detected by reverse transcription-polymerase chain reaction from the sera of eight patients and the result was confirmed by DNA sequencing. Phylogenetic analysis suggests that the ZIKV identified belongs to the Asian clade. This is the first report of ZIKV infection in Brazil.
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            Zika virus genome from the Americas.

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              A diagnostic polymerase chain reaction assay for Zika virus.

              Zika virus (ZIKV) is a mosquito-borne flavivirus. Infection results in a dengue-like illness with fever, headache, malaise, and a maculopapular rash. Nearly all cases are mild and self-limiting but in 2007, a large outbreak of ZIKV was reported from the island of Yap (in Micronesia, northwest of Indonesia). Singapore is already endemic for dengue, and its impact on public health and economic burden is significant. Other dengue-like infections (e.g., Chikungunya virus) are present. Yet only 10% of reported dengue cases have laboratory confirmation. The identification and control of other dengue-like, mosquito-transmitted infections is thus important for the health of Singapore's population, as well as its economy. Given that ZIKV shares the same Aedes mosquito vector with both dengue and Chikungunya, it is possible that this virus is present in Singapore and causing some of the mild dengue-like illness. A specific and sensitive one-step, reverse transcription polymerase chain reaction (RT-PCR) with an internal control (IC) was designed and tested on 88 archived samples of dengue-negative, Chikungunya-negative sera from patients presenting to our hospital with a dengue-like illness, to determine the presence of ZIKV in Singapore. The assay was specific for detection of ZIKV and displayed a lower limit of detection (LoD) of 140 copies viral RNA/reaction when tested on synthetic RNA standards prepared using pooled negative patient plasma. Of the 88 samples tested, none were positive for ZIKV RNA, however, the vast majority of these were from patients admitted to hospital and further study may be warranted in community-based environments. Copyright © 2012 Wiley Periodicals, Inc.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                25 February 2016
                February 2016
                : 10
                : 2
                : e0004517
                Affiliations
                [1 ]Hospital Geral Roberto Santos, Secretaria Estadual da Saúde da Bahia, Salvador, Bahia, Brazil
                [2 ]Faculdade de Medicina da Bahia and Instituto da Saúde Coletiva, Universidade Federal da Bahia, Salvador, Bahia, Brazil
                [3 ]Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Ministério da Sáude, Salvador, Bahia, Brazil
                [4 ]Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America
                [5 ]Department of Pathology and Center of Biodefense and Emerging Infectious Diseases, Institute for Human Infections and Immunity, The University of Texas Medical Branch, Galveston, Texas, United States of America
                Baylor College of Medicine, Texas Children's Hospital, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MS MSdR ARPdA. Performed the experiments: MS MSdR ARPdA GA. Analyzed the data: MS MSdR ARPdA GAS RK FC LAS AIK NN. Contributed reagents/materials/analysis tools: MS ARPdA FC LAS AIK NV. Wrote the paper: MS FC LAS AIK ARPdA.

                Article
                PNTD-D-16-00248
                10.1371/journal.pntd.0004517
                4767410
                26914330
                895a8f19-b754-40ef-87a1-39fc8db11172
                © 2016 Sarno et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 16 February 2016
                : 16 February 2016
                Page count
                Figures: 1, Tables: 0, Pages: 5
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Ultrasound Imaging
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Ultrasound Imaging
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Ultrasound Imaging
                Biology and Life Sciences
                Developmental Biology
                Embryology
                Fetuses
                Biology and Life Sciences
                Anatomy
                Nervous System
                Central Nervous System
                Medicine and Health Sciences
                Anatomy
                Nervous System
                Central Nervous System
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Amniotic Fluid
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Amniotic Fluid
                Biology and Life Sciences
                Physiology
                Body Fluids
                Amniotic Fluid
                Medicine and Health Sciences
                Physiology
                Body Fluids
                Amniotic Fluid
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Stillbirths
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Edema
                Biology and Life Sciences
                Developmental Biology
                Embryology
                Placenta
                Biology and Life Sciences
                Anatomy
                Reproductive System
                Placenta
                Medicine and Health Sciences
                Anatomy
                Reproductive System
                Placenta
                Medicine and Health Sciences
                Women's Health
                Maternal Health
                Pregnancy
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Pregnancy
                Custom metadata
                All data will be available in the manuscript.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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