270: Commensal microbes confer protection against Zika virus infection in a murine gnotobiotic model of congenital Zika syndrome

Abstract To investigate to what extent asymptomatic vs symptomatic prenatal Zika virus infections contribute to birth defects, we identified 3 prospective and 8 retrospective studies. The ratio varied greatly in the retrospective studies, most likely due to recruitment and recall bias. The prospective studies revealed a ratio of 1:1 for asymptomatic vs symptomatic maternal Zika infections resulting in adverse fetal outcomes.

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Zika virus infection from a newborn point of view. TORCH or TORZiCH?

Interdisciplinary Toxicology ◽

10.2478/intox-2018-0023 ◽

2018 ◽

Vol 11 (4) ◽

pp. 241-246 ◽

Cited By ~ 2

Author(s):

Adriana Tahotná ◽

Jana Brucknerová ◽

Ingrid Brucknerová

Keyword(s):

Virus Infection ◽

Zika Virus ◽

Clinical Symptoms ◽

Global Climate ◽

Point Of View ◽

Zikv Infection ◽

Global Climate Changes ◽

Zika Virus Infection ◽

Congenital Zika Syndrome ◽

The Media

Abstract Zika virus (ZIKV) belongs to the group of viruses called arboviruses. Congenital Zika syndrome is a new disease with infectious teratogenic aetiology. The clinical symptoms are divided into morphological and functional. Most severe complication is the foetal brain disruption sequence that includes severe microcephaly, anomalies of the eyes and congenital contractions of joints. The aim of this paper was to review available facts about Zika virus infection from a newborn point of view in a form of the summary of all important information. Zika virus infection is a problem of past, present and future. Epidemics may occur because of global climate changes, also in countries where natural conditions for life of mosquitos are not present. This clearly indicates the need to continue developing of vaccines and specific antiviral drugs. Until this happens, we must adhere individual preventive measures. Zika virus has proven to us how it can affect the health of adults and neonates but also thinking of healthy people. Newborns with microcephaly on the front pages of the media caused in 2015 panic and fear around the world – for this reason education of people is necessary. Due to serious congenital disorders associated with ZIKV infection and global impact of virus we suggest modifying old acronym TORCH for new TORZiCH to accent the position of Zika virus.

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Congenital Zika syndrome: A systematic review

PLoS ONE ◽

10.1371/journal.pone.0242367 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0242367

Author(s):

Danielle A. Freitas ◽

Reinaldo Souza-Santos ◽

Liege M. A. Carvalho ◽

Wagner B. Barros ◽

Luiza M. Neves ◽

...

Keyword(s):

Systematic Review ◽

Virus Infection ◽

Zika Virus ◽

Low Birthweight ◽

Signs And Symptoms ◽

Neurological Complications ◽

Zika Virus Infection ◽

Peripheral Nerve Involvement ◽

Congenital Zika Syndrome ◽

Meta Analyses

Background The signs and symptoms of Zika virus infection are usually mild and self-limited. However, the disease has been linked to neurological complications such as Guillain-Barré syndrome and peripheral nerve involvement, and also to abortion and fetal deaths due to vertical transmission, resulting in various congenital malformations in newborns, including microcephaly. This review aimed to describe the o signs and symptoms that characterize the congenital Zika syndrome. Methods and findings A systematic review was performed with a protocol and described according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The search strategy yielded 2,048 studies. After the exclusion of duplicates and application of inclusion criteria, 46 studies were included. The main signs and symptoms associated with the congenital Zika syndrome were microcephaly, parenchymal or cerebellar calcifications, ventriculomegaly, central nervous system hypoplasia or atrophy, arthrogryposis, ocular findings in the posterior and anterior segments, abnormal visual function and low birthweight for gestational age. Conclusions Zika virus infection during pregnancy can cause a series of changes in the growth and development of children, while impacting the healthcare system due to the severity of cases. Our findings outline the disease profile in newborns and infants and may contribute to the development and updating of more specific clinical protocols.

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The Role of Amniocentesis in the Diagnosis of Congenital Zika Syndrome

Clinical Infectious Diseases ◽

10.1093/cid/ciz013 ◽

2019 ◽

Vol 69 (4) ◽

pp. 713-716 ◽

Cited By ~ 7

Author(s):

Jose Paulo Pereira ◽

Melanie M Maykin ◽

Zilton Vasconcelos ◽

Elyzabeth Avvad-Portari ◽

Andrea A Zin ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Virus Infection ◽

Diagnostic Tool ◽

Zika Virus ◽

Prospective Cohort ◽

Endemic Area ◽

Limited Data ◽

Zika Virus Infection ◽

Congenital Zika Syndrome

Abstract There are limited data on amniocentesis as a diagnostic tool for congenital Zika syndrome. Here we report on a prospective cohort of 16 women with suspected Zika virus infection in a highly endemic area, and discuss the role of amniocentesis in the prenatal diagnosis of fetal Zika infection.

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Zika Virus Infection and Implications for Reproduction

Fertility & Reproduction ◽

10.1142/s2661318219300010 ◽

2019 ◽

Vol 01 (01) ◽

pp. 7-10

Author(s):

Michelle L. Giles ◽

Stephen Cole

Keyword(s):

Virus Infection ◽

Potential Risk ◽

Zika Virus ◽

Zika Virus Infection ◽

Congenital Zika Syndrome

Zika virus infection during pregnancy can have devastating effects on the foetus leading to congenital Zika syndrome. It is relevant therefore for couples living in countries with endemic Zika virus to understand the strategies they can utilise to reduce the chance of infection. In addition, couples planning pregnancy, or who are already pregnant, travelling to countries with Zika virus need to be informed of the potential risk and implications for future reproductive planning.

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Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon

10.1101/331108 ◽

2018 ◽

Author(s):

Sunam Gurung ◽

Nicole Reuter ◽

Alisha Preno ◽

Jamie Dubaut ◽

Hugh Nadeau ◽

...

Keyword(s):

Virus Infection ◽

Zika Virus ◽

Fetal Death ◽

Fetal Brain ◽

Zikv Infection ◽

Vertical Transfer ◽

Zika Virus Infection ◽

Congenital Zika Syndrome ◽

Human Primate ◽

In Pregnancy

ABSTRACTZika virus (ZIKV) infection during pregnancy in humans is associated with an increased incidence of congenital anomalies including microcephaly as well as fetal death and miscarriage and collectively has been referred to a Congenital Zika Syndrome (CZS). Animal models for ZIKV infection in pregnancy have been developed including mice and macaques. While microcephaly has been achieved in mice via direct injection of ZIKV into the fetal brain or via interference with interferon signaling, in macaques the primary fetal CZS outcome are ocular defects. In the present study we develope the olive baboon (Papio anubis), as a model for the vertical transfer of ZIKV during pregnancy. We infected four mid-gestation, timed-pregnant baboons with the French Polynesian ZIKV isolate (104ffu) and examined the acute phase of vertical transfer by stopping the study of one dam at 7 days post infection (dpi), two at 14 dpi and one at 21 dpi. All dams exhibited mild to moderate rash and conjunctivitis; three of four dams exhibited viremia at 7 dpi. Of the three dams studied to 14 to 21 days, only one still exhibited viremia on day 14. Vertical transfer of ZIKV to the fetus was found in two pregnancies; in one, vertical transfer was associated with fetal death at ∼14 dpi. In the other, vertical transfer was observed at 21 dpi. Both fetuses had ZIKV RNA in the fetal cerebral cortex as well as other tissues. The 21 dpi fetal cerebral cortex exhibited notable defects in radial glia, radial glial fibers, loss and or damage of immature oligodendrocytes and a loss in neuroprogenitor cells (NPCs). In addition, indices of pronounced neuroinflammation were observed including astrogliosis, increased microglia and IL-6 expression. The dams studied to 14 dpi (n=2) and 21 dpi (n=1) exhibited a anti-ZIKV IgM response and IgG response (21 dpi) that included transfer of the IgG to the fetal compartment (cord blood). The severity of systemic inflammatory response (cytokines and chemokines) reflected the vertical transfer of ZIKV in the two pregnancies. As such, these events likely represent the early mechanisms that lead to microcephaly and/or other CNS pathologies in a primate infected with ZIKV and are the first to be described in a non-human primate during the acute phase of ZIKV infection with a contemporaneous ZIKV strain. The baboon thus represents a major NHP for advancing as a model for ZIKV induced brain pathologies to contrast and compare to humans as well as other NHPs such as macaques.AUTHOR SUMMARYZika virus is endemic in the Americas, primarily spread through mosquitos and sexual contact. Zika virus infection during pregnancy in women is associated with a variety of fetal pathologies now referred to as Congenital Zika Syndrome (CZS), with the most severe pathology being fetal microcephaly. Developing model organisms that faithfully recreate Zika infection in humans is critical for future development of treatments and preventions. In our present study, we infected Olive baboons at mid-gestation with Zika virus and studied the acute period of viremia and transfer of Zika virus to the fetus during the first three weeks after infection to better understand the timing and mechanisms leading to CZS. We observed Zika virus transfer to fetuses resulting in fetal death in one pregnancy and in a second pregnancy, significant damage to the frontal cortex of the fetal brain consistent with development of microcephaly, closely resembling infection in pregnant women. Our baboon model differs from macaque non-human primate models where the primary fetal outcome during pregnancy following infection with contemporary strains of Zika virus is ocular pathology. Thus, the baboon provides a promising new non-human primate model to further compare and contrast the consequences of Zika virus infection in pregnancy to humans and macaques to better understand the disease.

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84. Clarifying the Congenital Zika Syndrome Phenotype and Expanding to Congenital Zika Spectrum in the Absence of Laboratory Evidence

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.394 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S173-S173

Author(s):

Laura D Zambrano ◽

Augustina Delaney ◽

Charles E Rose ◽

Suzanne Gilboa ◽

Van Tong ◽

...

Keyword(s):

Cluster Analysis ◽

Optic Nerve ◽

Virus Infection ◽

Zika Virus ◽

Congenital Anomalies ◽

Zikv Infection ◽

Distinct Phenotype ◽

Laboratory Evidence ◽

Zika Virus Infection ◽

Congenital Zika Syndrome

Abstract Background Congenital Zika syndrome (CZS) is a term used to describe the pattern of anomalies in infants due to congenital Zika virus (ZIKV) infection. To date, published reports of infants with these anomalies have been primarily small case series of the most severely affected infants and attempts to determine the CZS phenotype have been based on those reports. Lack of a standard definition has led to inconsistencies in the term’s use in the literature and uncertainty about the full spectrum of anomalies, limiting the application for diagnostic and surveillance purposes. Cluster analysis of brain and eye anomalies associated with congenital Zika infection. Clustering occurred independent of laboratory evidence of Zika virus infection, yielding a clinically distinct phenotype associated with congenital infection. Methods We sought to understand which defects co-occur with possible congenital ZIKV infection using data from 415 mother-infant dyads with laboratory evidence of confirmed or presumptive Zika virus infection from the U.S. Zika Pregnancy and Infant Registry, and a comparison group of 4534 mother-infant dyads with no documented or plausible ZIKV infection from the Zika Birth Defects Surveillance System. We use k-means cluster analysis, discriminant analysis, and regression approaches to identify combinations of defects consistent with possible congenital ZIKV infection. Results A clinically distinct phenotype emerged as a single cluster in infants for whom both brain and eye defects were recorded that corresponded to evidence of confirmed or probable ZIKV infection. A combination of six defects (sub-cortical calcifications, chorioretinal atrophy/pigmentary anomalies, arthrogryposis or clubfoot, cerebral atrophy or ventriculomegaly, abnormal cortical gyration, and optic nerve atrophy/pallor/other optic nerve abnormalities) predicted the presence of laboratory evidence (area under the receiver operating characteristics curve: 0.95, 95% confidence interval: 0.90–0.99). Conclusion Further analyses are underway to develop a scoring rubric to weigh evidence of specific congenital anomalies, separately and in combination, that are consistent with laboratory evidence of congenital ZIKV infection. A quantitatively determined spectrum of Zika-associated anomalies, based on the presence of specific combinations of congenital anomalies, will inform a clinical decision tool to improve patient counseling and public health surveillance practices. Disclosures All Authors: No reported disclosures

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Congenital Zika Virus Infection Paradigm: What is in the Wardrobe? A Narrative Review

East Africa Science ◽

10.24248/easci.v1i1.4 ◽

2019 ◽

Vol 1 (1) ◽

pp. 49-56

Author(s):

Mariam M. Mirambo ◽

Lucas Matemba ◽

Mtebe Majigo ◽

Stephen E. Mshana

Keyword(s):

Virus Infection ◽

Neural Tube ◽

Zika Virus ◽

English Language ◽

Case Reports ◽

Case Series ◽

Epidemiological Studies ◽

Ocular Manifestations ◽

Zika Virus Infection ◽

N 93

Background: Zika virus infection during pregnancy has been recently associated with congenital microcephaly and other severe neural tube defects. However, the magnitude of confirmed cases and the scope of these anomalies have not been extensively documented. This review focuses on the magnitude of laboratory-confirmed congenital Zika virus cases among probable cases and describing the patterns of congenital anomalies allegedly caused by the Zika virus, information which will inform further research in this area. Methods: We conducted a literature search for English-language articles about congenital Zika virus infection using online electronic databases (PubMed/MEDLINE, POPLINE, Embase, Google Scholar, and Web of Knowledge). The search terms used were, “zika”, “pregnancy”, [year], “microcephaly”, “infants”, “children”, “neonates”, “foetuses”, “neural tube defect”, and “CNS manifestations” in different combinations. All articles reporting cases or case series between January 2015 and December 2016 were included. Data were entered into a Microsoft Excel database and analysed to obtain proportions of the confirmed cases and patterns of anomalies. Results: A total of 24 articles (11 case series, 9 case reports, and 4 others) were found to be eligible and included in this review. These articles reported 919 cases, with or without microcephaly, presumed to have congenital Zika virus infection. Of these cases, 884 (96.2%) had microcephaly. Of the 884 cases of microcephaly, 783 (88.6%) were tested for Zika virus infection, and 216 (27.6%; 95% confidence interval, 24.5% to 30.8%) were confirmed to be Zika virus-positive. In addition to microcephaly, other common abnormalities reported – out of 442 cases investigated – were calcifications of brain tissue (n=240, 54.3%), ventriculomegaly (n=93, 20.8%), cerebellar hypoplasia (n=52, 11.7%), and ocular manifestations (n=46, 10.4%). Conclusion: Based on the available literature, Zika virus infection during pregnancy might lead to a wide array of outcomes other than microcephaly. There is a need for more epidemiological studies in Zika-endemic areas, particularly in Africa, to ascertain the role of Zika virus in causing congenital neurological defects.

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Congenital Zika Virus Infection Paradigm: What is in the Wardrobe? A Narrative Review

East Africa Science ◽

10.24248/easci.v1.iss1.4 ◽

2019 ◽

Vol 1 (1) ◽

pp. 49-56

Author(s):

Mariam M. Mirambo ◽

Lucas Matemba ◽

Mtebe Majigo ◽

Stephen E. Mshana

Keyword(s):

Virus Infection ◽

Neural Tube ◽

Zika Virus ◽

English Language ◽

Case Reports ◽

Case Series ◽

Epidemiological Studies ◽

Ocular Manifestations ◽

Zika Virus Infection ◽

N 93

Background: Zika virus infection during pregnancy has been recently associated with congenital microcephaly and other severe neural tube defects. However, the magnitude of confirmed cases and the scope of these anomalies have not been extensively documented. This review focuses on the magnitude of laboratory-confirmed congenital Zika virus cases among probable cases and describing the patterns of congenital anomalies allegedly caused by the Zika virus, information which will inform further research in this area. Methods: We conducted a literature search for English-language articles about congenital Zika virus infection using online electronic databases (PubMed/MEDLINE, POPLINE, Embase, Google Scholar, and Web of Knowledge). The search terms used were, “zika”, “pregnancy”, [year], “microcephaly”, “infants”, “children”, “neonates”, “foetuses”, “neural tube defect”, and “CNS manifestations” in different combinations. All articles reporting cases or case series between January 2015 and December 2016 were included. Data were entered into a Microsoft Excel database and analysed to obtain proportions of the confirmed cases and patterns of anomalies. Results: A total of 24 articles (11 case series, 9 case reports, and 4 others) were found to be eligible and included in this review. These articles reported 919 cases, with or without microcephaly, presumed to have congenital Zika virus infection. Of these cases, 884 (96.2%) had microcephaly. Of the 884 cases of microcephaly, 783 (88.6%) were tested for Zika virus infection, and 216 (27.6%; 95% confidence interval, 24.5% to 30.8%) were confirmed to be Zika virus-positive. In addition to microcephaly, other common abnormalities reported – out of 442 cases investigated – were calcifications of brain tissue (n=240, 54.3%), ventriculomegaly (n=93, 20.8%), cerebellar hypoplasia (n=52, 11.7%), and ocular manifestations (n=46, 10.4%). Conclusion: Based on the available literature, Zika virus infection during pregnancy might lead to a wide array of outcomes other than microcephaly. There is a need for more epidemiological studies in Zika-endemic areas, particularly in Africa, to ascertain the role of Zika virus in causing congenital neurological defects.

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