The Transcriptional and Protein Profile From #Human Infected #Neuroprogenitor Cells Is Strongly Correlated to #Zika Virus #Microcephaly #Cytokines Phenotype Evidencing a Persistent Inflammation in the #CNS (Front Immunol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Front Immunol. 2019 Aug 16;10:1928. doi: 10.3389/fimmu.2019.01928. eCollection 2019.

The Transcriptional and Protein Profile From Human Infected Neuroprogenitor Cells Is Strongly Correlated to Zika Virus Microcephaly Cytokines Phenotype Evidencing a Persistent Inflammation in the CNS.

Lima MC1, de Mendonça LR1, Rezende AM1, Carrera RM2, Aníbal-Silva CE1, Demers M3, D’Aiuto L3, Wood J3, Chowdari KV3, Griffiths M2, Lucena-Araujo AR4, Barral-Netto M5, Azevedo EAN1, Alves RW1, Farias PCS1, Marques ETA1,6, Castanha PMS6, Donald CL7, Kohl A7, Nimgaonkar VL3,8, Franca RFO1.

Author information: 1 Oswaldo Cruz Foundation/Fiocruz, Institute Aggeu Magalhães, Recife, Brazil. 2 Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom. 3 Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States. 4 Federal University of Pernambuco/UFPE, Recife, Brazil. 5 Oswaldo Cruz Foundation/Fiocruz, Institute Gonçalo Moniz, Salvador, Brazil. 6 Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, United States. 7 MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom. 8 Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States.

 

Abstract

Zika virus (ZIKV) infection during pregnancy is associated with microcephaly, a congenital malformation resulting from neuroinflammation and direct effects of virus replication on the developing central nervous system (CNS). However, the exact changes in the affected CNS remain unknown. Here, we show by transcriptome analysis (at 48 h post-infection) and multiplex immune profiling that human induced-neuroprogenitor stem cells (hiNPCs) respond to ZIKV infection with a strong induction of type-I interferons (IFNs) and several type-I IFNs stimulated genes (ISGs), notably cytokines and the pro-apoptotic chemokines CXCL9 and CXCL10. By comparing the inflammatory profile induced by a ZIKV Brazilian strain with an ancestral strain isolated from Cambodia in 2010, we observed that the response magnitude differs among them. Compared to ZIKV/Cambodia, the experimental infection of hiNPCs with ZIKV/Brazil resulted in a diminished induction of ISGs and lower induction of several cytokines (IFN-α, IL-1α/β, IL-6, IL-8, and IL-15), consequently favoring virus replication. From ZIKV-confirmed infant microcephaly cases, we detected a similar profile characterized by the presence of IFN-α, CXCL10, and CXCL9 in cerebrospinal fluid (CSF) samples collected after birth, evidencing a sustained CNS inflammation. Altogether, our data suggest that the CNS may be directly affected due to an unbalanced and chronic local inflammatory response, elicited by ZIKV infection, which contributes to damage to the fetal brain.

KEYWORDS: Zika congenital syndrome and cytokines; Zika virus; central nervous system; inflammation; interferonopathy; microcephaly; type-I interferon

PMID: 31474994 PMCID: PMC6707094 DOI: 10.3389/fimmu.2019.01928

Keywords: Zika Virus; Microcephaly; Zika Congenital Syndrome.

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#Zika Virus #Infection and #Microcephaly: A Case-Control Study in #Brazil (Ann Glob Health, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Ann Glob Health. 2019 Aug 28;85(1). pii: 116. doi: 10.5334/aogh.2394.

Zika Virus Infection and Microcephaly: A Case-Control Study in Brazil.

Rocha SGMO1, Correia LL1, Da Cunha AJLA2, Rocha HAL1,3, Leite ÁJM1, Campos JS3, Bandeira TJPG3, Do Nascimento LS1, E Silva AC3.

Author information: 1 Federal University of Ceará, Community Health Department, Fortaleza, Ceará, BR. 2 Federal University of Rio de Janeiro, Rio de Janeiro, BR. 3 Christus University Center (Unichristus), Fortaleza, Ceará, BR.

 

Abstract

BACKGROUND:

Brazil presented an alarming number of newborns with microcephaly in the years 2015 and 2016. The investigation of the cases raised the suspicion of the association of these cases with maternal infections by the zika virus. Also, in 2015, there was an epidemic of zika virus infection in Brazil, reinforcing this hypothesis.

OBJECTIVE:

The objective of this study was to identify factors associated with the diagnosis of microcephaly in newborns, including zika virus infection.

METHODS:

We conducted a case-control study. The cases were defined as children who received clinical and imaging diagnosis of microcephaly, born after October 2015 in Ceará, Brazil, which recorded the highest number of microcephaly cases in Brazil during the outbreak. The cases were identified in medical records of public and private maternity hospitals and in child development stimulation clinics tracked until June 2017. Epidemiological, clinical, and socioeconomic variables were collected, visiting their homes and confirming data from their medical records. Controls were children without microcephaly identified in the vicinity of the residence of each case. Logistic regression models were used to control confounding.

FINDINGS:

We evaluated 58 cases and 116 controls. The odds of having a baby with microcephaly was 14 times higher among mothers who had zika virus infection (p < 0.001), after multivariate analysis. Arboviruses infections symptoms, as fever (p = 0.220), skin change (p < 0.001), and joint pain (p = 0.002) also demonstrated an association with microcephaly.

CONCLUSIONS:

Maternal infection zika virus was associated with a diagnosis of microcephaly. Our study contributes to the investigation of the epidemiological factors associated with the diagnosis of microcephaly.

© 2019 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0/.

PMID: 31468955 DOI: 10.5334/aogh.2394

Keywords: Zika Virus; Zika Congenital Syndrome; Microcephaly; Brazil.

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Early Gross #Motor #Development Among Brazilian #Children with #Microcephaly Born Right After #Zika Virus #Infection #Outbreak (J Dev Behav Pediatr., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Dev Behav Pediatr. 2019 Aug 22. doi: 10.1097/DBP.0000000000000722. [Epub ahead of print]

Early Gross Motor Development Among Brazilian Children with Microcephaly Born Right After Zika Virus Infection Outbreak.

A Ventura P1,2, C Lage ML1, L de Carvalho A2, S Fernandes A2, B Taguchi T2, Nascimento-Carvalho CM1,3.

Author information: 1 Post-graduation Program in Health Sciences, Federal University of Bahia School of Medicine, Salvador, Brazil. 2 SARAH Network of Rehabilitation Hospital, Salvador, Brazil. 3 Department of Paediatrics, Federal University of Bahia School of Medicine, Salvador, Brazil.

 

Abstract

OBJECTIVE:

To assess the gross motor development of children with presumed congenital Zika virus (ZIKV) infection over the first 2 years of their lives.

METHODS:

Seventy-seven children were assessed at the median ages of 11, 18, and 24 months, using the evaluative instrument Gross Motor Function Measure (GMFM-66). At the third assessment, the children with diagnoses of cerebral palsy (CP) were classified by severity through the Gross Motor Function Classification System (GMFCS) and stratified by topography indicating the predominantly affected limbs. With these instruments in combination and using the motor development curves as reference, the rate of development and functional ability were estimated.

RESULTS:

At 2 years of age, all children had the diagnosis of CP. Seventy-four (96.1%) presented gross motor skills similar to those of children aged 4 months or younger, according to the World Health Organization’s standard. The GMFM-66 median score among the 73 (94.8%) children with quadriplegia and GMFCS level V showed significant change between 11 and 18 months (p < 0.001) and between 11 and 24 months (p < 0.001). No significant difference (p = 0.076) was found between 18 and 24 months.

CONCLUSION:

Despite showing some gross motor progress during the initial 18 months of life, these children with presumed congenital ZIKV infection and CP experienced severe motor impairment by 2 years of age. According to the motor development curves, these children with quadriplegia have probably already reached about 90% of their motor development potential.

PMID: 31453893 DOI: 10.1097/DBP.0000000000000722

Keywords: Zika Virus; Zika Congenital Syndrome; Neurology; Pediatrics; Brazil.

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#Host and viral #mechanisms of #congenital #Zika #syndrome (Virulence, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Virulence. 2019 Dec;10(1):768-775. doi: 10.1080/21505594.2019.1656503.

Host and viral mechanisms of congenital Zika syndrome.

Liang B1, Guida JP2, Costa Do Nascimento ML2, Mysorekar IU1,3,4.

Author information: 1 Department of Obstetrics and Gynecology, Washington University School of Medicine , St. Louis , MO , USA. 2 Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas , Campinas , Brazil. 3 Department of Pathology and Immunology, Washington University School of Medicine , St. Louis , MO , USA. 4 Center for Reproductive Health Sciences, Washington University School of Medicine , St. Louis , MO , USA.

 

Abstract

In 2015-2016, in the Americas, and especially in northeast Brazil, a significant number of cases of microcephaly and other congenital brain abnormalities were linked with an outbreak of Zika virus (ZIKV) infection in pregnant women. While maternal symptoms of ZIKV are generally mild and self-limiting, clinical presentation in fetuses and newborns infected is extensive and includes microcephaly, decreased cortical development, atrophy and hypoplasia of the cerebellum and cerebellar vermis, arthrogryposis, and polyhydramnios. The term congenital ZIKV syndrome (CZS) was introduced to describe the range of findings associated with maternal-fetal ZIKV transmission. ZIKV is primarily transmitted by Aedes aegypti mosquitoes, however non-vector-dependent routes are also possible. Mechanisms of maternal-fetal transmission remain unknown, and the trans-placental route has been extensively studied in animal models and in human samples. The aim of this review was to summarize recent studies that helped to elucidate the mechanism of CZS in animal models and observational studies. There are still challenges in the diagnosis and prevention of CZS in humans, due to the large gap that remains in translating ZIKV research to clinical practice. Translational research linking governments, local health workers, scientists and industry is fundamental to improve care for mothers and children.

KEYWORDS: Placenta; autophagy; hydroxychloroquine; interferon lambda; trophoblast; type I interferon

PMID: 31451049 DOI: 10.1080/21505594.2019.1656503

Keywords: Zika Virus; Zika Congenital Syndrome; Pregnancy.

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Association Between #Neonatal #Neuroimaging and #Clinical Outcomes in #Zika-Exposed #Infants From #Rio de Janeiro, #Brazil (JAMA Netw Open., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

JAMA Netw Open. 2019 Jul 3;2(7):e198124. doi: 10.1001/jamanetworkopen.2019.8124.

Association Between Neonatal Neuroimaging and Clinical Outcomes in Zika-Exposed Infants From Rio de Janeiro, Brazil.

Pool KL1, Adachi K1, Karnezis S1, Salamon N1, Romero T1, Nielsen-Saines K1, Pone S2, Boechat M2, Aibe M2, Gomes da Silva T2, Ribeiro CTM2, Boechat MI1, Brasil P2, Zin A2, Tsui I1, Gaw SL3, Daltro P4, Ribeiro BG4, Fazecas T4, Hygino da Cruz LC4, Nogueira R4, Vasconcelos Z2, Pereira JP Jr2, Saad Salles T2, Barbosa CN2, Chen W5, Foo SS5, Jung J5, Moreira ME2, Pone M2.

Author information: 1 David Geffen School of Medicine, University of California, Los Angeles. 2 Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. 3 University of California San Francisco School of Medicine. 4 Clinica de Diagnostico por Imagem CDPI, Rio de Janeiro, Brazil. 5 University of Southern California School of Medicine, Los Angeles.

 

Abstract

IMPORTANCE:

Congenital Zika virus (ZIKV) infection may present with a spectrum of clinical and neuroradiographic findings.

OBJECTIVE:

To determine whether neuroimaging findings for infants with a history of ZIKV exposure are associated with infant clinical outcomes and gestational age at antenatal ZIKV infection.

DESIGN, SETTING, AND PARTICIPANTS:

This cohort study retrospectively reviewed neuroimaging results (computed tomography and/or magnetic resonance imaging scans) of 110 ZIKV-exposed infants from a maternity and children’s hospital in Rio de Janeiro, Brazil, following the 2015 to 2016 ZIKV epidemic. Neuroimaging from March 1, 2016, to June 30, 2017, was evaluated to determine whether findings were associated with clinical outcomes and the timing of maternal ZIKV infection. Data were analyzed from July 1, 2017, to August 30, 2018.

EXPOSURES:

Neuroimaging (computed tomography and/or magnetic resonance imaging) was performed on ZIKV-exposed infants after birth. Blood and/or urine specimens from mothers and infants were tested for ZIKV by polymerase chain reaction assay.

MAIN OUTCOMES AND MEASURES:

Neuroimaging studies were evaluated for structural abnormalities and other forms of brain injury.

RESULTS:

A total of 110 infants with a mean (SD) gestational age of 38.4 (2.1) weeks had neuroimaging and clinical outcome data reviewed. Of these, 71 (65%) had abnormal neuroimaging findings, with the majority (96%) classified as having severe ZIKV infection at birth. The most common neuroimaging abnormalities were structural abnormalities including brain calcifications, especially at the cortico-subcortical white matter junction, cortex malformations, ventriculomegaly, and reduced brain volumes, followed by brainstem hypoplasia, cerebellar hypoplasia, and corpus callosum abnormalities. Frequency of abnormal imaging was higher in infants with specific clinical findings as opposed to those without them; these findings included fetal brain disruption sequence (100% vs 35%), microcephaly (100% vs 30%), congenital contractures (100% vs 58%), ophthalmologic abnormalities (95% vs 44%), hearing abnormalities (100% vs 58%), and neurologic symptoms (94% vs 10%). Four of 39 infants (10%) without initial evidence of severe ZIKV infection and normal findings on neurologic evaluation at birth had abnormal neuroimaging findings. Neuroimaging abnormalities differed by trimester of maternal ZIKV infection, with 63% of infants born to mothers infected in the first trimester, 13% of infants born to mothers infected in the second trimester, and 1% of infants born to mothers infected in the third trimester exhibiting neuroimaging abnormalities. The odds of abnormal neuroimaging were 7.9 times greater for infants with first trimester ZIKV exposure compared with other trimesters combined (odds ratio, 7.9; 95% CI, 3.0-20.4; P < .001).

CONCLUSIONS AND RELEVANCE:

Neuroimaging abnormalities of computed tomography and/or magnetic resonance imaging scans were common in ZIKV-exposed infants. While neuroimaging abnormalities were seen in 10% of infants without clinically severe ZIKV, most occurred almost exclusively among those with clinically severe ZIKV, especially among those with a history of ZIKV exposure in the first trimester.

PMID: 31365112 DOI: 10.1001/jamanetworkopen.2019.8124

Keywords: Zika Virus; Zika Congenital Infection; Zika Congenital Syndrome; Neurology; Neuroimaging.

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#Association between #Zika virus #microcephaly in the #newborn with the rs3775291 variant in Toll-Like receptor 3 and rs1799964 variant at TNFα gene (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Association between Zika virus microcephaly in the newborn with the rs3775291 variant in Toll-Like receptor 3 and rs1799964 variant at TNFα gene

Camilla N O Santos, Danielle R Ribeiro, Juliana A Cardoso, Rodrigo A Cazzaniga, Lucas S Magalhães, Mércia S F de Souza, Adriana B L Fonseca, Ana J B Bispo,Roseane L S Porto, Cliomar Alves dos Santos, Ângela M da Silva, Mauro M Teixeira, Roque P de Almeida, Amélia R de Jesus

The Journal of Infectious Diseases, jiz392, https://doi.org/10.1093/infdis/jiz392

Published: 28 July 2019

 

Abstract

Congenital Zika syndrome (CZS) is a cluster of malformation and the mechanisms that lead it are still unclear. Using hypothesis-driven candidate genes and their function in viral infections, Single Nucleotide Polymorphisms (SNP) were genotyped by qPCR in a sample population from Sergipe State, Brazil. This study shows that rs3775291 SNP at TLR3, that trigger to type I interferons antiviral responses, in mothers infected by Zika during pregnancy is associated with CZS occurrence (OR2.19, 95% CI1.158 – 4.148). Moreover, the rs1799964 SNP at TNFα gene in the CZS babies is associated with severe microcephaly (OR2.63, 95% CI 1.13 – 6.21).

Congenital Zika Syndrome, Microcephaly, Polymorphism, TLR3, TNFα

This content is only available as a PDF.

 

Author notes

These authors contributed equally to this article.

Scientists sponsored by CNPq.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Zika Virus; Zika Congenital Syndrome; Pregnancy; Microcephaly; Genetics.

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Descriptive study of suspected #congenital #Zika #syndrome cases during the 2015-2016 #epidemic in #Brazil (Rev Soc Bras Med Trop., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Rev Soc Bras Med Trop. 2019 Jul 18;52:e20190105. doi: 10.1590/0037-8682-0105-2019.

Descriptive study of suspected congenital Zika syndrome cases during the 2015-2016 epidemic in Brazil.

Roma JHF1,2, Alves RC1, Silva VSD1, Ferreira MJ1, Araújo C1, Pavoni JHC1.

Author information: 1 Curso de Graduação em Medicina, Instituto de Ciências Exatas e Naturais, Universidade Federal de Mato Grosso, Rondonópolis, MT, Brasil. 2 Programa de Pós-graduação em Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.

 

Abstract

INTRODUCTION:

Clinical and epidemiological data on suspected congenital Zika syndrome (CZS) cases from southern Mato Grosso (MT) in Brazil during the Zika virus (ZIKV) outbreak in 2015-2016 were evaluated.

METHODS:

This is a descriptive case series study of newborns whose mothers were suspected cases of ZIKV infections during their pregnancies. The medical records of all the suspected CZS cases (mothers and newborns) treated by the specialized ambulatory service from June 2015 to August 2016 were analyzed.

RESULTS:

Twenty suspected CZS cases were included in these analyses. They were categorized into four groups based on the clinical and laboratory findings: confirmed cases (n=1), highly probable cases (n=13), moderately probable cases (n=5), and somewhat probable cases (n=1). The mothers tested negative for STORCH (syphilis, toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex) and other important congenital infections; however, specific ZIKV tests were not performed during the study period. Microcephaly was observed in the majority of these newborns, and all the patients showed altered cranial computed tomography image findings. Extracranial abnormalities such as arthrogryposis, and otological and ophthalmological manifestations were also observed.

CONCLUSIONS:

Although ZIKV was not confirmed to cause the congenital malformations, this study demonstrated that the clinical and epidemiological findings associated with a STORCH exclusion strengthened the CZS diagnosis. The suspected cases in MT occurred simultaneously with the first CZS cases reported in Brazil, suggesting ZIKV circulation in the study region during the same period.

PMID: 31340371 DOI: 10.1590/0037-8682-0105-2019

Keywords: Zika Virus; Zika Congenital Syndrome; Microcephaly; Brazil.

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