#Zika Virus and #Pregnancy: Association between Acute #Infection and #Microcephaly in #Newborns in the State of #Rio de Janeiro, #Brazil (Geburtshilfe Frauenheilkd, abstract)

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

Geburtshilfe Frauenheilkd. 2020 Jan;80(1):60-65. doi: 10.1055/a-0972-2052. Epub 2020 Jan 13.

Zika Virus and Pregnancy: Association between Acute Infection and Microcephaly in Newborns in the State of Rio de Janeiro, Brazil.

Pereira AM1, Araujo Júnior E2,3, Werner H4, Monteiro DLM1.

Author information: 1 Perinatal Unit, State University of Rio de Janeiro (UERJ), Rio de Janeiro-RJ, Brazil. 2 Department of Obstetrics, Paulista School of Medicine – Federal University of São Paulo (EPM-UNIFESP), São Paulo-SP, Brazil. 3 Medical course, Municipal University of São Caetano do Sul (USCS), São Paulo-SP, Brazil. 4 Department of Radiology, Clínica de Diagnóstico por Imagem (CPDI), Rio de Janeiro-RJ, Brazil.

 

Abstract in English, German

Introduction Aim of the study was to evaluate the association between microcephaly and acute infection with Zika virus (ZIKV) in pregnant women in the state of Rio de Janeiro, Brazil. Infection was confirmed by laboratory testing. Materials and Methods A cross-sectional retrospective study of pregnant women with symptoms occurring between 2015 and 2016 suggestive of acute ZIKV infection was carried out, with confirmation of infection done by blood or urine RT-PCR. The relative proportions of categorical variables were calculated for two distinct groups: pregnant women whose newborns had microcephaly and pregnant women who gave birth to infants without microcephaly. Confidence intervals with a 95% level of agreement were estimated for the relative ratios. Results A total of 1609 pregnant women with a mean age of 26.4 ± 6.5 years were evaluated. As regards the time of acute infection, 19.6% (316) of cases occurred in the first trimester of pregnancy. Nineteen (76%) of the 25 cases with microcephaly (1.5%) were associated with an infection contracted in the first trimester of pregnancy (p < 0.001, OR = 13.7, 95% CI: 5.6 - 37.7). 48% (12/25) of the newborns with microcephaly had a birth weight of < 2500 grams, while only 7% (116/1597) of the group of newborns without microcephaly had a similarly low birth weight (p < 0.001, OR = 11.7, 95% CI: 5.2 - 26.2). Logistic regression showed that a birth weight of < 2500 g (OR = 12.54) and ZIKV infection in the first trimester of pregnancy (OR = 14.05) were associated with microcephaly (area under ROC curve = 0.86). Conclusion Acute ZIKV infection in the first trimester of pregnancy and low birth weight are associated with microcephaly.

KEYWORDS: Zika virus; congenital infection; first trimester of pregnancy; low birth weight; microcephaly

PMID: 31949320 PMCID: PMC6957353 DOI: 10.1055/a-0972-2052

Keywords: Zika Virus; Zika Congenital Infection; Microcephaly; Brazil; Pregnancy.

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#Congenital #Zika #syndrome in #Argentina: case series study (Arch Argent Pediatr., abstract)

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

Arch Argent Pediatr. 2019 Dec 1;117(6):e635-e639. doi: 10.5546/aap.2019.e635.

[Congenital Zika syndrome in Argentina: case series study].

[Article in Spanish]

Pastrana A1, Albarracín M2, Hoffmann M3, Delturco G3, López R3, Gil R3, Guzmán A3, Del Barco M2, Espeche A3.

Author information: 1 Servicio de Neurología, Hospital Público Materno Infantil de Salta, Argentina. analia.pastrana@gmail.com. 2 Servicio de Neonatología, Hospital Público Materno Infantil de Salta, Argentina. 3 Servicio de Neurología, Hospital Público Materno Infantil de Salta, Argentina.

 

Abstract

In 2015, there was an increase in the incidence of congenital microcephaly in newborns in Brazil. Months later, the causal relationship between Zika virus and these findings was discovered. In Argentina, during the first outbreak there were 5 cases of congenital Zika syndrome reported. In 2017, there was a new outbreak which involved Salta province. We describe 2 patients with autochthonous congenital Zika syndrome: one of the babies with severe congenital microcephaly with lissencephaly, calcifications and ventriculomegaly; and another baby with postnatal microcephaly with asymmetric polymicrogyria, calcifications and delayed myelination. The real impact of this disease is still uncertain, so it is necessary an adequate multidisciplinary monitoring of patients exposed to Zika virus to better understand the infection and its natural history.

Sociedad Argentina de Pediatría.

KEYWORDS: Zika virus; congenital Zika syndrome; microcephaly

PMID: 31758900 DOI: 10.5546/aap.2019.e635

Keywords: Zika Virus; Zika Congenital Syndrome; Microcephaly; Pediatrics; Argentina.

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#Zika virus #infection: A correlation between #prenatal ultrasonographic and #postmortem #neuropathologic changes (Neuropathology, abstract)

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

Neuropathology. 2019 Nov 11. doi: 10.1111/neup.12603. [Epub ahead of print]

Zika virus infection: A correlation between prenatal ultrasonographic and postmortem neuropathologic changes.

Gutiérrez Sánchez LA1,2, Sandoval Martínez DK1,3, Díaz-Martínez LA1, Becerra Mojica CH1,2.

Author information: 1 School of Medicine, Health Faculty, Universidad Industrial de Santander, Bucaramanga, Colombia. 2 Department of Gynecology and Obstetrics, Hospital Universitario de Santander, Bucaramanga, Colombia. 3 Department of Pathology, Hospital Universitario de Santander, Bucaramanga, Colombia.

 

Abstract

This study presents a correlation between prenatal ultrasonographic images and neuropathologic findings of postmortem tissue samples from five confirmed cases of perinatal Zika virus (ZIKV) infection belonging to the cohort of the ZEN Initiative in Bucaramanga, Colombia. Deaths occurred between June 2016 and March 2017. Mothers consulted with ZIKV infection clinical manifestations or fetal central nervous system (CNS) abnormalities or both. A detailed ultrasound scan and neurosonographic protocol was performed by maternal fetal specialists. Perinatal autopsies were performed following the Colombian National Health Institute’s ZIKV protocol. The autopsies were from two fetal deaths, and three early neonatal deaths. Gestational age was between 262/7 and 382/7 weeks. Two cases were classified as mild microcephaly. Few findings by ultrasound and pathology were found in case 1 because it was a late infection; the other cases presented findings corresponding to congenital Zika syndrome: craniofacial malformations, cerebellar hypoplasia, anomalies of the corpus callosum and ventriculomegaly, all confirmed in autopsy specimens. By ultrasonography, hyperechogenicities were seen in several brain structures, which correspond to cortical and periventricular calcifications, subependymal glial reactivity and perivascular rings. The ultrasound and pathological findings show a wide spectrum of CNS anomalies that confirm the neurotropic effect of the ZIKV, recognizing the neuroimaging findings of this disease (unilateral ventriculomegaly, alterations in the corpus callosum and cerebellum, and calcifications) are highly suggestive of ZIKV infection.

© 2019 Japanese Society of Neuropathology.

KEYWORDS: Zika virus infection; arthrogryposis; corpus callosum dysgenesis; lissencephaly; microcephaly

PMID: 31710135 DOI: 10.1111/neup.12603

Keywords: Zika Virus; Neuroimaging; Neuroinvasion; Pediatrics; Radiology.

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#Congenital #Zika Syndrome in a #Brazil – #Paraguay – #Bolivia #border region: #Clinical features of cases diagnosed between 2015 and 2018 (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Congenital Zika Syndrome in a Brazil-Paraguay-Bolivia border region: Clinical features of cases diagnosed between 2015 and 2018

Fabio Antonio Venancio  , Maria Eulina Quilião Bernal , Maria da Conceição de Barros Vieira Ramos, Neuma Rocha Chaves, Marcos Vinicius Hendges, Mattheus Marques Rodrigues de Souza, Márcio José de Medeiros , Cláudia Du Bocage Santos Pinto , Everton Falcão de Oliveira

Published: October 4, 2019 / DOI: https://doi.org/10.1371/journal.pone.0223408

 

Abstract

Congenital Zika Syndrome (CZS) is a unique pattern of congenital abnormalities found in fetuses and neonates infected with the Zika virus (ZIKV). Here, we clinically identify and characterize infants with CZS between 2015 and 2018 in Mato Grosso do Sul, Brazil—a border area with Paraguay and Bolivia. This cross-sectional study, based on primary and secondary data, tracks the cases registered in the Brazilian Public Health Reporting System through the following stages: (1) preliminary data analysis, (2) identification of the congenital syndrome cases, (3) etiologic classification of the cases, (4) active search, and (5) clinical assessment. Of the 72 investigated cases, 16 were probable cases of CZS. Of these, it was only possible to clinically assess 11 infants. Considering the 16 probable cases of CZS, nine were classified as confirmed cases, and five as potential cases of the syndrome. Regarding clinical features, brain palsy was identified in all analyzed infants. Moreover, microcephaly and pseudobulbar syndrome were found in eight infants, and hydrocephalus was found in three individuals. In addition to these conditions, seven children were malnourished. Our study may provide significant insights for other researches that aim to elucidate CZS and its clinical and populational consequences.

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Citation: Venancio FA, Bernal MEQ, Ramos MdCdBV, Chaves NR, Hendges MV, Souza MMRd, et al. (2019) Congenital Zika Syndrome in a Brazil-Paraguay-Bolivia border region: Clinical features of cases diagnosed between 2015 and 2018. PLoS ONE 14(10): e0223408. https://doi.org/10.1371/journal.pone.0223408

Editor: Angela Lupattelli, University of Oslo, NORWAY

Received: July 16, 2019; Accepted: September 21, 2019; Published: October 4, 2019

Copyright: © 2019 Venancio 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.

Data Availability: All relevant data are within the paper.

Funding: The authors received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Zika Virus; Zika Congenital Syndrome; Microcephaly; Brazil; Paraguay; Bolivia; Neurology; Pediatrics.

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Emergence of the #Asian #lineage of #Zika virus in #Angola: an #outbreak #investigation (Lancet Infect Dis., abstract)

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

Lancet Infect Dis. 2019 Oct;19(10):1138-1147. doi: 10.1016/S1473-3099(19)30293-2.

Emergence of the Asian lineage of Zika virus in Angola: an outbreak investigation.

Hill SC1, Vasconcelos J2, Neto Z2, Jandondo D2, Zé-Zé L3, Aguiar RS4, Xavier J5, Thézé J1, Mirandela M2, Micolo Cândido AL2, Vaz F2, Sebastião CDS6, Wu CH7, Kraemer MUG8, Melo A9, Schamber-Reis BLF10, de Azevedo GS9, Tanuri A11, Higa LM11, Clemente C12, da Silva SP12, da Silva Candido D1, Claro IM13, Quibuco D14, Domingos C15, Pocongo B15, Watts AG16, Khan K17, Alcantara LCJ18, Sabino EC13, Lackritz E19, Pybus OG1, Alves MJ20, Afonso J21, Faria NR22.

Author information: 1 Department of Zoology, University of Oxford, Oxford, UK. 2 Instituto Nacional de Investigação em Saúde, Ministry of Health, Luanda, Angola. 3 Instituto Nacional de Saúde Doutor Ricardo Jorge, Águas de Moura, Portugal; University of Lisboa, Faculty of Sciences, BioISI-Biosystems & Integrative Sciences Institute, Lisbon, Portugal. 4 Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.  5 Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. 6 Instituto Nacional de Investigação em Saúde, Ministry of Health, Luanda, Angola; Instituto Superior de Ciências da Saúde, Universidade Agostinho Neto, Luanda, Angola. 7 Department of Statistics, University of Oxford, Oxford, UK. 8 Department of Zoology, University of Oxford, Oxford, UK; Computational Epidemiology Lab, Boston Children’s Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. 9 Instituto de Pesquisa Professor Joaquim Amorim Neto, Campina Grande, Brazil. 10 Department of Human Genetics, Centro Universitário Unifacisa, Campina Grande, Brazil. 11 Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. 12 Cligest Clinic, Luanda, Angola. 13 Instituto de Medicina Tropical e Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. 14 Hospital Pediátrico David Bernardino, Luanda, Angola. 15 Instituto Nacional de Luta Contra SIDA, Luanda, Angola. 16 Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, ON, Canada; BlueDot, Toronto, ON, Canada. 17 Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, ON, Canada; BlueDot, Toronto, ON, Canada; Department of Medicine, University of Toronto, Canada. 18 Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Laboratório de Flavivirus, IOC-Fundação Oswaldo Cruz/MS, Rio de Janeiro, Brazil. 19 WHO, Switzerland, Geneva. 20 Instituto Nacional de Saúde Doutor Ricardo Jorge, Águas de Moura, Portugal. 21 Instituto Nacional de Investigação em Saúde, Ministry of Health, Luanda, Angola. Electronic address: jfm.morais9@gmail.com. 22 Department of Zoology, University of Oxford, Oxford, UK. Electronic address: nuno.faria@zoo.ox.ac.uk.

 

Abstract

BACKGROUND:

Zika virus infections and suspected microcephaly cases have been reported in Angola since late 2016, but no data are available about the origins, epidemiology, and diversity of the virus. We aimed to investigate the emergence and circulation of Zika virus in Angola.

METHODS:

Diagnostic samples collected by the Angolan Ministry of Health as part of routine arboviral surveillance were tested by real-time reverse transcription PCR by the Instituto Nacional de Investigação em Saúde (Ministry of Health, Luanda, Angola). To identify further samples positive for Zika virus and appropriate for genomic sequencing, we also tested samples from a 2017 study of people with HIV in Luanda. Portable sequencing was used to generate Angolan Zika virus genome sequences from three people positive for Zika virus infection by real-time reverse transcription PCR, including one neonate with microcephaly. Genetic and mobility data were analysed to investigate the date of introduction and geographical origin of Zika virus in Angola. Brain CT and MRI, and serological assays were done on a child with microcephaly to confirm microcephaly and assess previous Zika virus infection.

FINDINGS:

Serum samples from 54 people with suspected acute Zika virus infection, 76 infants with suspected microcephaly, 24 mothers of infants with suspected microcephaly, 336 patients with suspected dengue virus or chikungunya virus infection, and 349 samples from the HIV study were tested by real-time reverse transcription PCR. Four cases identified between December, 2016, and June, 2017, tested positive for Zika virus. Analyses of viral genomic and human mobility data suggest that Zika virus was probably introduced to Angola from Brazil between July, 2015, and June, 2016. This introduction probably initiated local circulation of Zika virus in Angola that continued until at least June, 2017. The infant with microcephaly in whom CT and MRI were done had brain abnormalities consistent with congenital Zika syndrome and serological evidence for Zika virus infection.

INTERPRETATION:

Our analyses show that autochthonous transmission of the Asian lineage of Zika virus has taken place in Africa. Zika virus surveillance and surveillance of associated cases of microcephaly throughout the continent is crucial.

FUNDING:

Royal Society, Wellcome Trust, Global Challenges Research Fund (UK Research and Innovation), Africa Oxford, John Fell Fund, Oxford Martin School, European Research Council, Departamento de Ciência e Tecnologia/Ministério da Saúde/National Council for Scientific and Technological Development, and Ministério da Educação/Coordenação de Aperfeicoamento de Pessoal de Nível Superior.

Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

PMID: 31559967 DOI: 10.1016/S1473-3099(19)30293-2

Keywords: Zika Virus; Microcephaly; Serology; Angola.

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#Inflammation #markers in the #saliva of #infants born from #Zika-infected #mothers: exploring potential mechanisms of #microcephaly during #fetal development (Sci Rep., abstract)

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

Sci Rep. 2019 Sep 20;9(1):13606. doi: 10.1038/s41598-019-49796-5.

Inflammation markers in the saliva of infants born from Zika-infected mothers: exploring potential mechanisms of microcephaly during fetal development.

de Oliveira DN1, Lima EO1, Melo CFOR1, Delafiori J1, Guerreiro TM1, Rodrigues RGM1, Morishita KN1, Silveira C2, Muraro SP3, de Souza GF3, Vieira A3, Silva A4, Batista RF4, Doriqui MJR4, Sousa PS4, Milanez GP3, Proença-Módena JL3, Cavalcanti DP2, Catharino RR5.

Author information: 1 Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, Brazil. 2 Medical Genetics Department, School of Medical Sciences, University of Campinas, Campinas, Brazil. 3 Emerging Viruses Study Laboratory, Department of Genetics, Evolution, Microbiology and Immunology, Biology Institute, University of Campinas, Campinas, Brazil. 4 Public Health Department, Universidade Federal do Maranhão, São Luís, Brazil. 5 Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, Brazil. rrc@g.unicamp.br.

 

Abstract

Zika virus (ZIKV) has emerged as one of the most medically relevant viral infections of the past decades; the devastating effects of this virus over the developing brain are a major matter of concern during pregnancy. Although the connection with congenital malformations are well documented, the mechanisms by which ZIKV reach the central nervous system (CNS) and the causes of impaired cortical growth in affected fetuses need to be better addressed. We performed a non-invasive, metabolomics-based screening of saliva from infants with congenital Zika syndrome (CZS), born from mothers that were infected with ZIKV during pregnancy. We were able to identify three biomarkers that suggest that this population suffered from an important inflammatory process; with the detection of mediators associated with glial activation, we propose that microcephaly is a product of immune response to the virus, as well as excitotoxicity mechanisms, which remain ongoing even after birth.

PMID: 31541139 DOI: 10.1038/s41598-019-49796-5

Keywords: Zika Virus; Immunopathology; Pregnancy; Microcephaly.

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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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