#Fibroblast growth factor 2 enhances #Zika virus #infection in human #fetal #brain (J Infect Dis., abstract)

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

Fibroblast growth factor 2 enhances Zika virus infection in human fetal brain

Daniel Limonta, Juan Jovel, Anil Kumar, Julia Lu, Shangmei Hou, Adriana M Airo, Joaquin Lopez-Orozco, Cheung Pang Wong, Leina Saito, William Branton, Gane Ka-Shu Wong, Andrew Mason, Christopher Power, Tom C Hobman

The Journal of Infectious Diseases, jiz073, https://doi.org/10.1093/infdis/jiz073

Published: 13 February 2019

 

Abstract

Zika virus (ZIKV) is an emerging pathogen that can cause microcephaly and other neurological defects in developing fetuses. The cellular response to ZIKV in the fetal brain is not well understood. Here, we show that ZIKV infection of human fetal astrocytes (HFAs), the most abundant cell type in the brain, results in elevated expression and secretion of fibroblast growth factor 2 (FGF2). This cytokine was shown to enhance replication and spread of ZIKV in HFAs and human fetal brain explants. The pro-viral effect of FGF2 is likely mediated in part by suppression of the interferon response, which would represent a novel mechanism by which viruses antagonize host antiviral defenses. We posit that FGF2-enhanced virus replication in the fetal brain contributes to the neurodevelopmental disorders associated with in utero ZIKV infection. As such, targeting FGF2-dependent signaling should be explored further as a strategy to limit replication of ZIKV.

Zika virus, fibroblast growth factor 2, astrocytes, fetal brain, explant, interferon, congenital, MAP kinase

Issue Section: Major Article

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Keywords: Zika Virus; Zika Congenital Infection.

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#Clinical, #Neuroimaging, and #Neurophysiological Findings in #Children with #Microcephaly Related to #Congenital #Zika Virus Infection (Int J Environ Res Public Health, abstract)

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

Int J Environ Res Public Health. 2019 Jan 23;16(3). pii: E309. doi: 10.3390/ijerph16030309.

Clinical, Neuroimaging, and Neurophysiological Findings in Children with Microcephaly Related to Congenital Zika Virus Infection.

C Lage ML1, Carvalho AL2, Ventura PA3, Taguchi TB4, Fernandes AS5, Pinho SF6, Santos-Junior OT7, Ramos CL8, Nascimento-Carvalho CM9,10.

Author information: 1 Post-graduate Programme in Health Sciences, Federal University of Bahia School of Medicine, Praça XV de Novembro-Largo do Terreiro de Jesus, 40025-010 Bahia, Brazil. marylulage@hotmail.com. 2 Pediatric Rehabilitation Centre, Salvador Hospital, SARAH Network of Rehabilitation Hospitals, Avenida Tancredo Neves, Caminho das Árvores, Salvador, 41820-900 Bahia, Brazil. 13110@sarah.br. 3 Pediatric Rehabilitation Centre, Salvador Hospital, SARAH Network of Rehabilitation Hospitals, Avenida Tancredo Neves, Caminho das Árvores, Salvador, 41820-900 Bahia, Brazil. 701064@sarah.br. 4 Pediatric Rehabilitation Centre, Salvador Hospital, SARAH Network of Rehabilitation Hospitals, Avenida Tancredo Neves, Caminho das Árvores, Salvador, 41820-900 Bahia, Brazil. 11786@sarah.br. 5 Pediatric Rehabilitation Centre, Salvador Hospital, SARAH Network of Rehabilitation Hospitals, Avenida Tancredo Neves, Caminho das Árvores, Salvador, 41820-900 Bahia, Brazil. 400868@sarah.br. 6 Pediatric Rehabilitation Centre, Salvador Hospital, SARAH Network of Rehabilitation Hospitals, Avenida Tancredo Neves, Caminho das Árvores, Salvador, 41820-900 Bahia, Brazil. 701053@sarah.br. 7 Diagnostic Imaging Department, Salvador Hospital, SARAH Network of Rehabilitation Hospital, Avenida Tancredo Neves, Caminho das ÁrvoresSalvador, 41820-900 Bahia, Brazil. 700991@sarah.br. 8 Bahiana School of Medicine, Bahiana Foundation for Science Development, Dom João VI, Salvador, 40290-000 Bahia, Brazil. ccclr1@gmail.com. 9 Post-graduate Programme in Health Sciences, Federal University of Bahia School of Medicine, Praça XV de Novembro-Largo do Terreiro de Jesus, 40025-010 Bahia, Brazil. nascimentocarvalho@hotmail.com. 10 Departament of Paediatrics, Federal University of Bahia School of Medicine, Praça XV de Novembro-Largo do Terreiro de Jesus, 40025-010 Bahia, Brazil. nascimentocarvalho@hotmail.com.

 

Abstract

Zika virus (ZIKV) infection appeared in Brazil in 2015, causing an epidemic outbreak with increased rates of microcephaly and other serious birth disorders. We reviewed 102 cases of children who were diagnosed with microcephaly at birth and who had gestational exposure to ZIKV during the outbreak. We describe the clinical, neuroimaging, and neurophysiological findings. Most mothers (81%) reported symptoms of ZIKV infection, especially cutaneous rash, during the first trimester of pregnancy. The microcephaly was severe in 54.9% of the cases. All infants presented with brain malformations. The most frequent neuroimaging findings were cerebral atrophy (92.1%), ventriculomegaly (92.1%), malformation of cortical development (85.1%), and cortical⁻subcortical calcifications (80.2%). Abnormalities in neurological exams were found in 97.0% of the cases, epileptogenic activity in 56.3%, and arthrogryposis in 10.8% of the infants. The sensorineural screening suggested hearing loss in 17.3% and visual impairment in 14.1% of the infants. This group of infants who presented with microcephaly and whose mothers were exposed to ZIKV early during pregnancy showed clinical and radiological criteria for congenital ZIKV infection. A high frequency of brain abnormalities and signs of early neurological disorders were found, and epileptogenic activity and signs of sensorineural alterations were common. This suggests that microcephaly can be associated with a worst spectrum of neurological manifestations.

KEYWORDS: Zika virus; microcephaly; neuroimaging; neurologic examination

PMID: 30678125 DOI: 10.3390/ijerph16030309 Free full text

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

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Association of #Infants Exposed to Prenatal #Zika Virus #Infection With Their Clinical, #Neurologic, and Developmental Status Evaluated via the #GMA #Tool (JAMA Netw Open., abstract)

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

JAMA Netw Open. 2019 Jan 4;2(1):e187235. doi: 10.1001/jamanetworkopen.2018.7235.

Association of Infants Exposed to Prenatal Zika Virus Infection With Their Clinical, Neurologic, and Developmental Status Evaluated via the General Movement Assessment Tool.

Einspieler C1, Utsch F2, Brasil P3, Panvequio Aizawa CY4, Peyton C5,6, Hydee Hasue R4, Françoso Genovesi F4, Damasceno L3, Moreira ME7, Adachi K8, Marschik PB1,9,10, Nielsen-Saines K8; GM Zika Working Group.

Author information: 1 Interdisciplinary Developmental Neuroscience-iDN, Medical University of Graz, Graz, Austria. 2 Rede SARAH de Hospitais de Reabilitação, Reabilitação Infantil, Belo Horizonte, Brazil. 3 Laboratorio de Doenças Febris Agudas, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil. 4 Department of Physical Therapy, Communication Sciences & Disorders, and Occupational Therapy, Faculty of Medicine, University of São Paulo, São Paulo, Brazil. 5 Department of Physical Therapy and Human Movement Science, Northwestern University, Chicago, Illinois. 6 Department of Pediatrics, University of Chicago, Chicago, Illinois. 7 Department of Pediatrics, Instituto Fernandes Figueira, Fiocruz, Rio de Janeiro, Brazil. 8 Division of Pediatric Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles. 9 Interdisciplinary Developmental Neuroscience-iDN, Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany. 10 Center of Neurodevelopmental Disorders (KIND), Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.

 

Abstract

IMPORTANCE:

There is an urgent need to assess neurodevelopment in Zika virus (ZIKV)-exposed infants.

OBJECTIVES:

To perform general movement assessment (GMA) at 9 to 20 weeks’ postterm age and to evaluate whether the findings are associated with neurodevelopmental outcomes at age 12 months in infants prenatally exposed to acute maternal illness with rash in Brazil during the ZIKV outbreak and in age-matched controls.

DESIGN, SETTING, AND PARTICIPANTS:

In this cohort study, infants prenatally exposed to acute maternal illness with rash were recruited at medical institutions in Rio de Janeiro and Belo Horizonte, Brazil, from February 1, 2016, to April 30, 2017, while infants without any exposure to maternal illness originated from the Graz University Audiovisual Research Database for the Interdisciplinary Analysis of Neurodevelopment. Participants were 444 infants, including 76 infants without congenital microcephaly, 35 infants with microcephaly, and 333 neurotypical children matched for sex, gestational age at birth, and age at GMA.

MAIN OUTCOMES AND MEASURES:

General movement assessment performed at 9 to 20 weeks’ postterm age, with negative predictive value, positive predictive value, sensitivity, and specificity generated, as well as clinical, neurologic, and developmental status (Bayley Scales of Infant and Toddler Development, Third Edition [Bayley-III] scores) at age 12 months. Motor Optimality Scores were generated based on the overall quality of the motor repertoire. Adverse outcomes were defined as a Bayley-III score less than 2 SD in at least 1 domain, a score less than 1 SD in at least 2 domains, and/or atypical neurologic findings.

RESULTS:

A total of 444 infants were enrolled, including 111 children prenatally exposed to a maternal illness with rash and 333 children without any prenatal exposure to maternal illness (57.7% male and mean [SD] age, 14 [2] weeks for both groups); 82.1% (46 of 56) of ZIKV-exposed infants without congenital microcephaly were healthy at age 12 months. Forty-four of 46 infants were correctly identified by GMA at 3 months, with a negative predictive value of 94% (95% CI, 85%-97%). Seven of 10 ZIKV-exposed children without microcephaly with adverse neurodevelopmental outcomes were identified by GMA. The GMA positive predictive value was 78% (95% CI, 46%-94%), sensitivity was 70% (95% CI, 35%-93%), specificity was 96% (95% CI, 85%-99%), and accuracy was 91% (95% CI, 80%-97%). Children with microcephaly had bilateral spastic cerebral palsy; none had normal movements. The Motor Optimality Score differentiated outcomes: the median Motor Optimality Score was 23 (interquartile range [IQR], 21-26) in children with normal development, 12 (IQR, 8-19) in children with adverse outcomes, and 5 (IQR, 5-6) in children with microcephaly, a significant difference (P = .001).

CONCLUSIONS AND RELEVANCE:

This study suggests that although a large proportion of ZIKV-exposed infants without microcephaly develop normally, many do not. The GMA should be incorporated into routine infant assessments to enable early entry into targeted treatment programs.

PMID: 30657537 DOI: 10.1001/jamanetworkopen.2018.7235

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

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#Zika virus #infection at mid- #gestation results in #fetal #cerebral cortical injury and fetal death in the olive baboon (PLoS Pathogens, abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

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

Sunam Gurung, Nicole Reuter, Alisha Preno, Jamie Dubaut, Hugh Nadeau, Kimberly Hyatt, Krista Singleton, Ashley Martin, W. Tony Parks, James F. Papin, Dean A. Myers

Published: January 18, 2019 / DOI: https://doi.org/10.1371/journal.ppat.1007507 / This is an uncorrected proof.

 

Abstract

Zika 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 as Congenital Zika Syndrome (CZS). Animal models for ZIKV infection in pregnancy have been developed including mice and non-human primates (NHPs). In macaques, fetal CZS outcomes from maternal ZIKV infection range from none to significant. In the present study we develop the olive baboon (Papio anubis), as a model for vertical transfer of ZIKV during pregnancy. Four mid-gestation, timed-pregnant baboons were inoculated with the French Polynesian ZIKV isolate (104 ffu). This study specifically focused on the acute phase of vertical transfer. Dams were terminated at 7 days post infection (dpi; n = 1), 14 dpi (n = 2) and 21 dpi (n = 1). All dams exhibited mild to moderate rash and conjunctivitis. Viremia peaked at 5–7 dpi with only one of three dams remaining mildly viremic at 14 dpi. An anti-ZIKV IgM response was observed by 14 dpi in all three dams studied to this stage, and two dams developed a neutralizing IgG response by either 14 dpi or 21 dpi, the latter included transfer of the IgG to the fetus (cord blood). A systemic inflammatory response (increased IL2, IL6, IL7, IL15, IL16) was observed in three of four dams. Vertical transfer of ZIKV to the placenta was observed in three pregnancies (n = 2 at 14 dpi and n = 1 at 21 dpi) and ZIKV was detected in fetal tissues in two pregnancies: one associated with fetal death at ~14 dpi, and the other in a viable fetus at 21 dpi. ZIKV RNA was detected in the fetal cerebral cortex and other tissues of both of these fetuses. In the fetus studied at 21 dpi with vertical transfer of virus to the CNS, the frontal cerebral cortex exhibited notable defects in radial glia, radial glial fibers, disorganized migration of immature neurons to the cortical layers, and signs of pathology in immature oligodendrocytes. In addition, indices of pronounced neuroinflammation were observed including astrogliosis, increased microglia and IL6 expression. Of interest, in one fetus examined at 14 dpi without detection of ZIKV RNA in brain and other fetal tissues, increased neuroinflammation (IL6 and microglia) was observed in the cortex. Although the placenta of the 14 dpi dam with fetal death showed considerable pathology, only minor pathology was noted in the other three placentas. ZIKV was detected immunohistochemically in two placentas (14 dpi) and one placenta at 21 dpi but not at 7 dpi. This is the first study to examine the early events of vertical transfer of ZIKV in a NHP infected at mid-gestation. The baboon thus represents an additional NHP as a model for ZIKV induced brain pathologies to contrast and compare to humans as well as other NHPs.

 

Author summary

Zika 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 of transfer of ZIKV across the placenta, 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 at a critical period of neurodevelopment in primates. 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 other non-human primates.

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Citation: Gurung S, Reuter N, Preno A, Dubaut J, Nadeau H, Hyatt K, et al. (2019) Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon. PLoS Pathog 15(1): e1007507. https://doi.org/10.1371/journal.ppat.1007507

Editor: Carolyn B. Coyne, University of Pittsburgh, UNITED STATES

Received: October 10, 2018; Accepted: December 5, 2018; Published: January 18, 2019

Copyright: © 2019 Gurung 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 manuscript and its Supporting Information files.

Funding: These studies were supported in part by the National Institutes of Health, NS103772 (DAM) and OD01988 (JFP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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

Keywords: Zika Virus; Zika Congenital Infection; Zika Congenital Syndrome; Pregnancy; Animal models.

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#Zika Virus #Epidemic in #Pregnant Women, #Dominican Republic, 2016–2017 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 2—February 2019 / CME ACTIVITY – Synopsis

Zika Virus Epidemic in Pregnant Women, Dominican Republic, 2016–2017

Farah Peña, Raquel Pimentel, Shaveta Khosla, Supriya D. Mehta, and Maximo O. Brito

Author affiliations: Ministry of Health, Santo Domingo, Dominican Republic (F. Peña, R. Pimentel); University of Illinois at Chicago, Chicago, Illinois, USA (S. Khosla, S.D. Mehta, M.O. Brito)

 

Abstract

Zika virus infection during pregnancy may result in birth defects and pregnancy complications. We describe the Zika virus outbreak in pregnant women in the Dominican Republic during 2016–2017. We conducted multinomial logistic regression to identify factors associated with fetal losses and preterm birth. The Ministry of Health identified 1,282 pregnant women with suspected Zika virus infection, a substantial proportion during their first trimester. Fetal loss was reported for ≈10% of the reported pregnancies, and 3 cases of fetal microcephaly were reported. Women infected during the first trimester were more likely to have early fetal loss (adjusted odds ratio 5.9, 95% CI 3.5–10.0). Experiencing fever during infection was associated with increased odds of premature birth (adjusted odds ratio 1.65, 95% CI 1.03–2.65). There was widespread morbidity during the epidemic. Our findings strengthen the evidence for a broad range of adverse pregnancy outcomes resulting from Zika virus infection.

Keywords: Zika Virus; Pregnancy; Zika Congenital Infection; Dominical Republic.

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Association of #Prenatal #Ultrasonographic Findings With Adverse #Neonatal Outcomes Among #Pregnant Women With Zika Virus Infection in #Brazil (JAMA Netw Open., abstract)

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

JAMA Netw Open. 2018 Dec 7;1(8):e186529. doi: 10.1001/jamanetworkopen.2018.6529.

Association of Prenatal Ultrasonographic Findings With Adverse Neonatal Outcomes Among Pregnant Women With Zika Virus Infection in Brazil.

Pereira JP Jr1, Nielsen-Saines K2, Sperling J3, Maykin MM3, Damasceno L4, Cardozo RF1, Valle HA1, Dutra BRT1, Gama HD1, Adachi K2, Zin AA1, Tsui I5, Vasconcelos Z1, Brasil P4, Moreira ME1, Gaw SL3.

Author information: 1 Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira-Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. 2 Division of Pediatric Infectious Diseases, Department of Pediatrics, University of California, Los Angeles. 3 Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco. 4 Laboratorio de Doenças Febris Agudas, Instituto de Infectologia Evandro Chagas-Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. 5 Jules Stein Eye Institute, Retina Division, UCLA (University of California, Los Angeles).

 

Abstract

IMPORTANCE:

Congenital Zika virus infection causes a spectrum of adverse birth outcomes, including severe birth defects of the central nervous system. The association of prenatal ultrasonographic findings with adverse neonatal outcomes, beyond structural anomalies such as microcephaly, has not been described to date.

OBJECTIVE:

To determine whether prenatal ultrasonographic examination results are associated with abnormal neonatal outcomes in Zika virus-affected pregnancies.

DESIGN, SETTING, AND PARTICIPANTS:

A prospective cohort study conducted at a single regional referral center in Rio de Janeiro, Brazil, from September 1, 2015, to May 31, 2016, among 92 pregnant women diagnosed during pregnancy with Zika virus infection by reverse-transcription polymerase chain reaction, who underwent subsequent prenatal ultrasonographic and neonatal evaluation.

EXPOSURES:

Prenatal ultrasonography.

MAIN OUTCOMES AND MEASURES:

The primary outcome measure was composite adverse neonatal outcome (perinatal death, abnormal finding on neonatal examination, or abnormal finding on postnatal neuroimaging). Secondary outcomes include association of specific findings with neonatal outcomes.

RESULTS:

Of 92 mother-neonate dyads (mean [SD] maternal age, 29.4 [6.3] years), 55 (60%) had normal results and 37 (40%) had abnormal results on prenatal ultrasonographic examinations. The median gestational age at delivery was 38.6 weeks (interquartile range, 37.9-39.3). Of the 45 neonates with composite adverse outcome, 23 (51%) had normal results on prenatal ultrasonography. Eleven pregnant women (12%) had a Zika virus-associated finding that was associated with an abnormal result on neonatal examination (adjusted odds ratio [aOR], 11.6; 95% CI, 1.8-72.8), abnormal result on postnatal neuroimaging (aOR, 6.7; 95% CI, 1.1-38.9), and composite adverse neonatal outcome (aOR, 27.2; 95% CI, 2.5-296.6). Abnormal results on middle cerebral artery Doppler ultrasonography were associated with neonatal examination abnormalities (aOR, 12.8; 95% CI, 2.6-63.2), postnatal neuroimaging abnormalities (aOR, 8.8; 95% CI, 1.7-45.9), and composite adverse neonatal outcome (aOR, 20.5; 95% CI, 3.2-132.6). There were 2 perinatal deaths. Abnormal findings on prenatal ultrasonography had a sensitivity of 48.9% (95% CI, 33.7%-64.2%) and a specificity of 68.1% (95% CI, 52.9%-80.1%) for association with composite adverse neonatal outcomes. For a Zika virus-associated abnormal result on prenatal ultrasonography, the sensitivity was lower (22.2%; 95% CI, 11.2%-37.1%) but the specificity was higher (97.9%; 95% CI, 88.7%-99.9%).

CONCLUSIONS AND RELEVANCE:

Abnormal results on prenatal ultrasonography were associated with adverse outcomes in congenital Zika infection. The absence of abnormal findings on prenatal ultrasonography was not associated with a normal neonatal outcome. Comprehensive evaluation is recommended for all neonates with prenatal Zika virus exposure.

PMID: 30646333 DOI: 10.1001/jamanetworkopen.2018.6529

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

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#Zika virus #infection as a cause of #congenital #brain abnormalities and #GBS: From systematic review to living systematic review (F1000Res., abstract)

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

F1000Res. 2018 Feb 15;7:196. doi: 10.12688/f1000research.13704.1. eCollection 2018.

Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: From systematic review to living systematic review.

Counotte MJ1, Egli-Gany D1, Riesen M1, Abraha M1, Porgo TV2, Wang J1, Low N1.

Author information: 1 Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. 2 Department of Social and Preventative Medicine, Université Laval, Québec, Canada.

 

Abstract

Background.

The Zika virus (ZIKV) outbreak in the Americas has caused international concern due to neurological sequelae linked to the infection, such as microcephaly and Guillain-Barré syndrome (GBS). The World Health Organization stated that there is “sufficient evidence to conclude that Zika virus is a cause of congenital abnormalities and is a trigger of GBS”. This conclusion was based on a systematic review of the evidence published until 30.05.2016. Since then, the body of evidence has grown substantially, leading to this update of that systematic review with new evidence published from 30.05.2016 – 18.01.2017, update 1.

Methods.

We review evidence on the causal link between ZIKV infection and adverse congenital outcomes and the causal link between ZIKV infection and GBS or immune-mediated thrombocytopaenia purpura. We also describe the transition of the review into a living systematic review, a review that is continually updated.

Results.

Between 30.05.2016 and 18.01.2017, we identified 2413 publications, of which 101 publications were included. The evidence added in this update confirms the conclusion of a causal association between ZIKV and adverse congenital outcomes. New findings expand the evidence base in the dimensions of biological plausibility, strength of association, animal experiments and specificity. For GBS, the body of evidence has grown during the search period for update 1, but only for dimensions that were already populated in the previous version. There is still a limited understanding of the biological pathways that potentially cause the occurrence of autoimmune disease following ZIKV infection.

Conclusions.

This systematic review confirms previous conclusions that ZIKV is a cause of congenital abnormalities, including microcephaly, and is a trigger of GBS. The transition to living systematic review techniques and methodology provides a proof of concept for the use of these methods to synthesise evidence about an emerging pathogen such as ZIKV.

KEYWORDS: Guillain-barre syndrome; Zika virus; causality; congenital abnormalities; living systematic review; microcephlay

PMID: 30631437 PMCID: PMC6290976 DOI: 10.12688/f1000research.13704.1

Keywords: Zika Virus; Zika Congenital Infection; GBS.

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