#Epidemiological and #clinical suspicion of #congenital #Zika virus #infection: #serological findings in #mothers and #children from #Brazil (J Med Virol., abstract)

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

J Med Virol. 2019 May 15. doi: 10.1002/jmv.25504. [Epub ahead of print]

Epidemiological and clinical suspicion of congenital Zika virus infection: serological findings in mothers and children from Brazil.

Venturi G1, Fortuna C1, Alves RM2, Passos do Prado Paschoal AG2, da Silva Júnior PJ3, Remoli ME1, Benedetti E1, Amendola A1, da Silva Batista E3, Gama DVN2, Barros DH3, Fiorentini C1, Rezza G1, Leite Primo Chagas JR2,3.

Author information: 1 Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy. 2 Pediatric Neurology Service, S. Antonio das Obras Sociais Irmã Dulce Hospital(HSA/OSID), Salvador, Bahia, Brazil. 3 Neurologia Pediátrica, Universidade Salvador (UNIFACS), Salvador, Bahia, Brazil.

 

Abstract

The emergence of Zika virus in the Americas has caused an increase of babies born with microcephaly or other neurological malformations. The differential diagnosis of Zika infection, particularly serological diagnosis, is an important but complex issue. In this study, we describe clinical manifestations of 94 suspected cases of congenital Zika from Bahia state, Brazil, and the results of serological tests performed on children and/or their mothers at an average of 71 days after birth. Anti-Zika IgM antibodies were detected in 44.4% and in 7.1% of samples from mothers and children, respectively. Nearly all the IgM, and 92% of IgG positive results were confirmed by neutralization test. Zika specific neutralizing antibodies were detected in as much as 90.4 % of the cases. Moreover, dengue specific neutralizing antibodies were detected in 79.0% of Zika seropositive mothers. In conclusion, Zika IgM negative results should be considered with caution, due to a possible rapid loss of sensitivity after birth, while the NS1-based Zika IgM ELISA test we have used has demonstrated to be highly specific. In a high percentage of cases, Zika specific neutralizing antibodies were detected, which are indicative of a past Zika infection, probably occurred during pregnancy in this population.

This article is protected by copyright. All rights reserved.

KEYWORDS: Congenital infection; Flavivirus; diagnosis; microcephaly; neutralization test; serological tests

PMID: 31090222 DOI: 10.1002/jmv.25504

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

——

Advertisements

#Children Born to #Mothers with #Rash During #Zika Virus #Epidemic in #Brazil: First 18 Months of Life (J Trop Pediatr., abstract)

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

J Trop Pediatr. 2019 Apr 21. pii: fmz019. doi: 10.1093/tropej/fmz019. [Epub ahead of print]

Children Born to Mothers with Rash During Zika Virus Epidemic in Brazil: First 18 Months of Life.

Vianna RAO1, Lovero KL2, Oliveira SA1, Fernandes AR1, Santos TCSD1, Lima LCSS1, Carvalho FR1, Quintans MDS1, Bueno AC1, Torbey AFM1, Souza ALAAG1, Farias AOP1, Camacho LAB3, Riley LW4, Cardoso CAA1.

Author information: 1 Faculdade de Medicina, Universidade Federal Fluminense, RJ 24.033-900, Brazil. 2 Department of Psychiatry, University of Columbia, New York 10032, USA. 3 Departamento de Epidemiologia e Métodos Quantitativos em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, RJ 21.041-210, Brazil. 4 Division of Infectious Diseases and Vaccinology, University of California, Berkeley 94720, USA.

 

Abstract

OBJECTIVE:

To better understand the clinical spectrum and course of congenital Zika syndrome (CZS) during the first 18 months of life of children whose mothers had rash during pregnancy.

METHODS:

This longitudinal observational study evaluated the clinical progress from birth until 18 months of life of children of mothers who developed rash during or up to 3 months before gestation. Maternal rash occurred from November 2015 to May 2017. The study subjects were divided into three groups: children whose mothers tested positive by RT-qPCR for Zika virus (ZIKV) (Group 1), children whose mothers tested negative by RT-qPCR for ZIKV (Group 2), and children whose mothers did not undergo any testing for ZIKV (Group 3) but tested negative for other congenital infections.

RESULTS:

Between April 2016 and July 2018, we studied 108 children: 43 in Group 1, 26 in Group 2 and 39 in Group 3. The majority of children were admitted into the study within 6 months of life. CZS was diagnosed in 26 children, equally distributed in Groups 1 and 3. Of 18 children with microcephaly, 6 were in Group 1 (1 postnatal) and 12 were in Group 3 (5 postnatal). Maternal rash frequency was 10 times higher during the first trimester than in the other trimesters (OR: 10.35; CI 95%: 3.52-30.41). CZS was diagnosed during the follow-up period in 14 (54%) cases. Developmental delays and motor abnormalities occurred in all children and persisted up to 18 months. Epilepsy occurred in 18 (69%) of the cases.

CONCLUSIONS:

Infants born of mothers exposed to ZIKV during pregnancy showed progression of developmental, motor and neurologic abnormalities even if they were born asymptomatic. Continued postnatal monitoring of such newborns is necessary to preclude disability-associated complications.

© The Author(s) [2019]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

KEYWORDS: Congenital Zika syndrome; RT-PCR; Zika virus; microcephaly

PMID: 31006031 DOI: 10.1093/tropej/fmz019

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

——-

#Zika viruses of #African and #Asian lineages cause #fetal #harm in a mouse model of vertical #transmission (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Zika viruses of African and Asian lineages cause fetal harm in a mouse model of vertical transmission

Anna S. Jaeger, Reyes A. Murrieta, Lea R. Goren, Chelsea M. Crooks, Ryan V. Moriarty, Andrea M. Weiler, Sierra Rybarczyk, Matthew R. Semler, Christopher Huffman, Andres Mejia, Heather A. Simmons, Michael Fritsch, Jorge E. Osorio,  [ … ], Matthew T. Aliota

Published: April 17, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007343 / This is an uncorrected proof.

 

Abstract

Congenital Zika virus (ZIKV) infection was first linked to birth defects during the American outbreak in 2015/2016. It has been proposed that mutations unique to the Asian/American-genotype explain, at least in part, the ability of Asian/American ZIKV to cause congenital Zika syndrome (CZS). Recent studies identified mutations in ZIKV infecting humans that arose coincident with the outbreak in French Polynesia and were stably maintained during subsequent spread to the Americas. Here we show that African ZIKV can infect and harm fetuses and that the S139N substitution that has been associated with the American outbreak is not essential for fetal harm. Our findings, in a vertical transmission mouse model, suggest that ZIKV will remain a threat to pregnant women for the foreseeable future, including in Africa, Southeast Asia, and the Americas. Additional research is needed to better understand the risks associated with ZIKV infection during pregnancy, both in areas where the virus is newly endemic and where it has been circulating for decades.

 

Author summary

Zika virus (ZIKV) was first discovered in Uganda in 1947, and is thought to have spread from Africa through equatorial Asia in the middle of the 20th century. Along the way the virus diversified, so that now two genetic lineages, African and Asian/American, are recognized. Congenital Zika syndrome (CZS), the set of fetal and neonatal complications associated with ZIKV infection in pregnancy, was noted during the recent outbreak in the Americas. But the origins of CZS remain a mystery. In particular, it is unclear whether ZIKV recently acquired the ability to cause CZS, perhaps as Asian-lineage viruses spread to the Americas, or whether African-lineage viruses can also cause CZS. To address this question, we used a mouse model of vertical ZIKV transmission to assess pathogenic potential to the fetus of African and Asian/American ZIKV. Our data show that ZIKV of both African and Asian/American lineages can cause fetal harm in the mouse pregnancy model, and that this capacity does not require asparagine at amino acid residue 139, which recently emerged in Asian-lineage viruses and has been suggested to increase ZIKV’s pathogenic potential for fetuses. Our results, therefore imply that ZIKV infection during pregnancy poses a risk for fetal harm in all regions where the virus is endemic.

___

Citation: Jaeger AS, Murrieta RA, Goren LR, Crooks CM, Moriarty RV, Weiler AM, et al. (2019) Zika viruses of African and Asian lineages cause fetal harm in a mouse model of vertical transmission. PLoS Negl Trop Dis 13(4): e0007343. https://doi.org/10.1371/journal.pntd.0007343

Editor: Anita K. McElroy, CDC, UNITED STATES

Received: December 6, 2018; Accepted: March 27, 2019; Published: April 17, 2019

Copyright: © 2019 Jaeger 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: Zika virus sequence data have been deposited in the Sequence Read Archive (SRA) with accession code SRP150883 and SRP156459. The authors declare that all other data supporting the findings of this study are available within the article.

Funding: Funding for this project came from National Institutes of Health grants R21AI131454, R01AI132563, R56AI132563, and start-up funds from the University of Minnesota Department of Veterinary and Biomedical Sciences to MTA; and National Institutes of Health grants R01AI067380 and R21AI125996 to GDE. RAM is supported in part by NSF training grant DGE-1450032 and by a Kirschstein National Research Service Award Individual Fellowship F31AI134108. The publication’s contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCRR or NIH. 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 Syndrome; Zika Congenital Infection; Animal models.

——

#Outcomes of #Congenital #Zika Virus Infection During an #Outbreak in Valle del Cauca, #Colombia (Pediatr Infect Dis J., abstract)

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

Pediatr Infect Dis J. 2019 Apr 10. doi: 10.1097/INF.0000000000002307. [Epub ahead of print]

Outcomes of Congenital Zika Virus Infection During an Outbreak in Valle del Cauca, Colombia.

Calle-Giraldo JP1, Rojas CA2, Hurtado IC2,3,4, Barco C2, Libreros D5,6, Sánchez PJ7, López P2,8, Arias A6, Dávalos DM9, Lesmes MC4, Pinzón E4, Ortiz VA4, López-Medina E2,6,8.

Author information: 1 From the Department of Pediatrics, Universidad del Quindío, Armenia, Colombia. 2 Department of Pediatrics, Universidad del Valle, Cali, Colombia. 3 Hospital Universitario del Valle, Cali, Colombia. 4 Department of Health, Valle del Cauca. Cali, Colombia. 5 Department of Ophthalmology, Universidad del Valle, Cali, Colombia. 6 Centro Médico Imbanaco. Cali, Colombia. 7 Department of Pediatrics, Nationwide Children´s Hospital, The Ohio State University College of Medicine, Columbus, Ohio. 8 Centro de Estudios en Infectología Pediátrica. Cali, Colombia. 9 Department of Public Health, Universidad Icesi, Cali, Colombia.

 

Abstract

BACKGROUND:

Despite increasing information in the literature regarding congenital Zika infection, gaps remain in our knowledge of its clinical manifestations.

METHODS:

We did a prospective observational study of exposed fetuses and infants whose mothers developed symptomatic and confirmed Zika infection during pregnancy in Valle del Cauca, Colombia. We performed neurological, ophthalmological and audiological evaluations, and classified outcomes as possibly or uncertainly related to Zika. Frequencies of outcomes were compared according to the trimester of pregnancy when infection occurred.

RESULTS:

We evaluated 171 products of gestation including 17 pregnancy losses and 154 patients evaluated postnatally. Ninety (52.6%) pregnancies presented an adverse outcome, 36% possibly related with Zika and the remaining 64% of uncertain relation. Infection in the first trimester had the highest frequencies of adverse outcomes possibly related with Zika compared with the second and third trimesters (39% vs. 12.5% vs. 12%) with risk ratios of adverse outcomes possibly related to Zika in pregnancies infected in the first versus second or third trimester of 3.1 (95% CI: 2.4-4.1) and 3.3 (95% CI: 2.5-4.2), respectively. The frequencies of pregnancy loss and microcephaly were 9.4% and 4.5%, respectively. Auditory and ophthalmic abnormalities possibly related with Zika were present in 3% and 6% of the patients evaluated, respectively.

CONCLUSIONS:

We observed a high frequency of gestational and neonatal complications in pregnant women who acquired Zika infection, especially in early pregnancy, resulting in a broad spectrum of clinical manifestations. Preventive measures are urgently needed to reduce the clinical burden during future Zika outbreaks.

PMID: 30985517 DOI: 10.1097/INF.0000000000002307

Keywords: Zika Virus; Pregancy; Zika Congenital Infection; Zika Congenital Syndrome; Microcephaly; Colombia.

—–

#Zika virus during #pregnancy: From #maternal exposure to #congenital Zika virus #syndrome (Prenat Diagn., abstract)

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

Prenat Diagn. 2019 Mar 13. doi: 10.1002/pd.5446. [Epub ahead of print]

Zika virus during pregnancy: From maternal exposure to congenital Zika virus syndrome.

Pomar L1, Musso D2, Malinger G3, Vouga M1, Panchaud A4, Baud D1.

Author information: 1 Materno-Fetal and Obstetrics Research Unit, Department “Woman-Mother-Child”, Lausanne University Hospital, Lausanne, Switzerland. 2 IRD, AP-HM, SSA, VITROME, IHU-Méditerranée infection, Aix Marseille University, Marseille, France. 3 Division of Ultrasound in Obstetrics & Gynecology, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center & Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 4 School of Pharmaceutical Sciences, Geneva University and Service of Pharmacy, Lausanne University Hospital, Lausanne, Switzerland.

 

Abstract

The risk of Zika virus (ZIKV) infection during pregnancy depends on the incidence of the disease, which is highly variable in different affected geographic areas (<1% to 75%). Among infected pregnant women, the risk of any adverse fetal/neonatal outcome was estimated at 5-42%, with 1-4% of fetal loss and 4-9% of suspected CZS. The estimated rate of maternal-fetal transmission ranges between 7% and 26%, depending on the methodology of the study. Findings associated with CZS are microcephaly (33-64%), ventriculomegaly (63-92%), calcifications (71-92%), malformations of cortical development (79-82%), anomalies of the corpus callosum (71-100%) and of the posterior fossa (21-82%), arthrogryposis (10-25%), eye abnormalities (25%), and extra-neurologic signs such as intra uterine growth restriction (14%), placentomegaly, transient hepatitis, mild anemia. Infants who present with CZS at birth suffer from motor abnormalities (77-100%), epilepsy (9-54%), hearing loss and neurologic impairments. Prenatal ultrasound with advanced neurosonography and appropriate virological follow-up represent the state-of-the art approach to adequately monitor at-risk pregnancies, in order to diagnose early signs of CZS and to inform parents about the neonatal prognosis.

This article is protected by copyright. All rights reserved.

PMID: 30866073 DOI: 10.1002/pd.5446

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

——

Case Report: #Histopathologic Changes in #Placental Tissue Associated With Vertical #Transmission of #Zika Virus (Int J Gynaecol Pathol., abstract)

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

Int J Gynecol Pathol. 2019 Feb 14. doi: 10.1097/PGP.0000000000000586. [Epub ahead of print]

Case Report: Histopathologic Changes in Placental Tissue Associated With Vertical Transmission of Zika Virus.

Santos GR1, Pinto CAL, Prudente RCS, Bevilacqua EMAF, Witkin SS, Passos SD; Zika Virus Cohort Study Group.

Author information: 1 Departments of Morphology and Pathology (G.R.S., C.A.L.P., R.C.S.P.) Pediatrics (S.D.P.), Jundiaí Medical School (FMJ), Jundiaí University Teaching Hospital, Jundiaí Medical School (S.D.P.) Pathology Department, AC Camargo Cancer Center (C.A.L.P.) Biomedical Science Institute, University of São Paulo (E.M.A.F.B.) Institute of Tropical Medicine, University of Sao Paulo (S.S.W.), São Paulo, SP, Brazil Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, New York (S.S.W.).

 

Abstract

Zika virus (ZIKV) is highly neurotropic after crossing the placenta, inducing teratogenic effects that result in delayed development and microcephaly in infants. The available evidence for vertical transmission of this infection is based on placental studies showing alterations in trophoblastic tissue. However, complete characterization of ZIKV-infected placenta and involved pathways has yet to be fully clarified. This case report of placental ZIKV infection describes morphologic and molecular changes in the placenta. Hyperplasia of placental Hofbauer cells in chorionic villi and numerous histiocyte-like cells in the decidua were observed. The decidua, fibroblasts, and chorion, as well as circulating cells in the intravascular compartment stained positive for ZIKV envelop protein. Deciduitis was present on the maternal surface of the placenta, with a prevalence of lymphocytes associated with vasculitis. A high level of uncommitted CD3 T lymphocytes were present, in addition to CD4 and CD8 cells. Elevated expression of the apoptosis inhibitor, Bcl-2, was observed in syncytiotrophoblasts. These parameters may promote the persistence of ZIKV in placental tissue and transmission to the fetus.

PMID: 30789499 DOI: 10.1097/PGP.0000000000000586

Keywords: Zika Virus; Zika Congenital Infection; Pregnancy.

—–

#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

This content is only available as a PDF.

© 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 Infection.

——