#Postnatal #Zika virus #infection of #NHP #infants born to mothers infected with homologous #Brazilian Zika virus (Sci Rep., abstract)

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

Sci Rep. 2019 Sep 5;9(1):12802. doi: 10.1038/s41598-019-49209-7.

Postnatal Zika virus infection of nonhuman primate infants born to mothers infected with homologous Brazilian Zika virus.

Maness NJ1,2, Schouest B3,4, Singapuri A5, Dennis M6, Gilbert MH3, Bohm RP3, Schiro F3, Aye PP3, Baker K3, Van Rompay KKA5,7, Lackner AA3, Bonaldo MC8, Blair RV3, Permar SR6,9, Coffey LL5, Panganiban AT10,3, Magnani D11.

Author information: 1 Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, USA. nmaness@tulane.edu. 2 Tulane National Primate Research Center, Tulane University, Covington, Louisiana, USA. nmaness@tulane.edu. 3 Tulane National Primate Research Center, Tulane University, Covington, Louisiana, USA. 4 Biomedical Sciences Training Program, Tulane University School of Medicine, New Orleans, Louisiana, USA. 5 Department of Pathology, Microbiology and Immunology, University of California, Davis, CA, USA. 6 Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA. 7 California National Primate Research Center, University of California, Davis, California, USA. 8 Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil. 9 Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA. 10 Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, USA. 11 MassBiologics of the University of Massachusetts Medical School, Boston, Massachusetts, USA.

 

Abstract

Recent data in a nonhuman primate model showed that infants postnatally infected with Zika virus (ZIKV) were acutely susceptible to high viremia and neurological damage, suggesting the window of vulnerability extends beyond gestation. In this pilot study, we addressed the susceptibility of two infant rhesus macaques born healthy to dams infected with Zika virus during pregnancy. Passively acquired neutralizing antibody titers dropped below detection limits between 2 and 3 months of age, while binding antibodies remained detectable until viral infection at 5 months. Acute serum viremia was comparatively lower than adults infected with the same Brazilian isolate of ZIKV (n = 11 pregnant females, 4 males, and 4 non-pregnant females). Virus was never detected in cerebrospinal fluid nor in neural tissues at necropsy two weeks after infection. However, viral RNA was detected in lymph nodes, confirming some tissue dissemination. Though protection was not absolute and our study lacks an important comparison with postnatally infected infants born to naïve dams, our data suggest infants born healthy to infected mothers may harbor a modest but important level of protection from postnatally acquired ZIKV for several months after birth, an encouraging result given the potentially severe infection outcomes of this population.

PMID: 31488856 DOI: 10.1038/s41598-019-49209-7

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

——

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#International prospective observational cohort #study of #Zika in #infants and #pregnancy (#ZIP study): study protocol (BMC Pregnancy Childbirth, abstract)

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

BMC Pregnancy Childbirth. 2019 Aug 7;19(1):282. doi: 10.1186/s12884-019-2430-4.

International prospective observational cohort study of Zika in infants and pregnancy (ZIP study): study protocol.

Lebov JF1, Arias JF2, Balmaseda A3, Britt W4, Cordero JF5, Galvão LA6, Garces AL7, Hambidge KM8, Harris E9, Ko A10,11, Krebs N8, Marques ETA12,13, Martinez AM14, McClure E15, Miranda-Filho DB16, Moreira MEL17, Mussi-Pinhata MM18, Ochoa TJ19, Osorio JE20, Scalabrin DMF10,11, Schultz-Cherry S2, Seage GR 3rd21, Stolka K15, Ugarte-Gil CA19, Vega CMV22, Welton M5, Ximenes R23, Zorrilla C24.

Author information: 1 Social, Statistical and Environmental Sciences, RTI International, Durham, NC, USA. jlebov@rti.org. 2 Department of Infectious Diseases, St Jude Children’s Research Hospital, Memphis, TN, 38105, USA. 3 Centro Nacional de Diagnostico y Referencia, Complejo Nacional de Salud, Managua, Nicaragua. 4 Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA. 5 Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, GA, USA. 6 Center for Global Health – CRIS, FIOCRUZ, Rio de Janeiro, Brazil. 7 Fundación para la Alimentación y Nutrición de Centro América y Panamá (INCAP), Guatemala City, Guatemala. 8 Section of Nutrition, Pediatrics, University of Colorado, Aurora, CO, USA. 9 Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA, USA. 10 Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA. 11 Instituto Gonçalo Moniz, Fundação Oswaldo Cruz/MS, Salvador, Brazil. 12 School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. 13 Instituto Aggeu Magalhães, Department of Virology and Experimental Therapeutics, FIOCRUZ, Pernambuco, Brazil. 14 Director of Research Institute at Imbanaco Medical Center, Cali, Colombia. 15 Social, Statistical and Environmental Sciences, RTI International, Durham, NC, USA. 16 Programa de Pós-Graduação em Ciências da Saúde (PPGCS) da Universidade de Pernambuco, Microcephaly Epidemic Research Group, Recife, Brazil. 17 Instituto Fernandes Figueira – FIOCRUZ, Rio de Janeiro, Brazil. 18 Ribeirão Preto Medical School, Ribeirão Preto, Brazil. 19 Instituto de Medicina Tropical Alexander von Humboldt and Facultad de Medicina, Universidad Peruana Cayetano Heredia, Lima, Peru. 20 Department of Pathobiological Sciences, University of Wisconsin, Madison, WI, USA. 21 Department of Epidemiology, Harvard Chan School of Public Health, Boston, MA, USA. 22 University of Puerto Rico, San Juan, Puerto Rico. 23 Departamento de Medicina Tropical da Universidade Federal de Pernambuco, Microcephaly Epidemic Research Group, Recife, Brazil. 24 Maternal-Infant Studies Center (CEMI), San Juan, Puerto Rico.

 

Abstract

BACKGROUND:

Until recently, Zika virus (ZIKV) infections were considered mild and self-limiting. Since 2015, they have been associated with an increase in microcephaly and other birth defects in newborns. While this association has been observed in case reports and epidemiological studies, the nature and extent of the relationship between ZIKV and adverse pregnancy and pediatric health outcomes is not well understood. With the unique opportunity to prospectively explore the full spectrum of issues related to ZIKV exposure during pregnancy, we undertook a multi-country, prospective cohort study to evaluate the association between ZIKV and pregnancy, neonatal, and infant outcomes.

METHODS:

At research sites in ZIKV endemic regions of Brazil (4 sites), Colombia, Guatemala, Nicaragua, Puerto Rico (2 sites), and Peru, up to 10,000 pregnant women will be recruited and consented in the first and early second trimesters of pregnancy and then followed through delivery up to 6 weeks post-partum; their infants will be followed until at least 1 year of age. Pregnant women with symptomatic ZIKV infection confirmed by presence of ZIKV RNA and/or IgM for ZIKV will also be enrolled, regardless of gestational age. Participants will be tested monthly for ZIKV infection; additional demographic, physical, laboratory and environmental data will be collected to assess the potential interaction of these variables with ZIKV infection. Delivery outcomes and detailed infant assessments, including physical and neurological outcomes, will be obtained.

DISCUSSION:

With the emergence of ZIKV in the Americas and its association with adverse pregnancy outcomes in this region, a much better understanding of the spectrum of clinical outcomes associated with exposure to ZIKV during pregnancy is needed. This cohort study will provide information about maternal, fetal, and infant outcomes related to ZIKV infection, including congenital ZIKV syndrome, and manifestations that are not detectable at birth but may appear during the first year of life. In addition, the flexibility of the study design has provided an opportunity to modify study parameters in real time to provide rigorous research data to answer the most critical questions about the impact of congenital ZIKV exposure.

TRIAL REGISTRATION: NCT02856984 . Registered August 5, 2016. Retrospectively registered.

KEYWORDS: Latin America; Microcephaly; Pregnancy; Zika virus

PMID: 31391005 DOI: 10.1186/s12884-019-2430-4

Keywords: Zika Virus; Pregnancy; Zika Congenital Infection.

——

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.

——

Alterations in #visual acuity and visual #development in #infants 1-24 months old either exposed to or infected by #Zika virus during #gestation, with and without #microcephaly (J AAPOS., abstract)

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

J AAPOS. 2019 Jun 20. pii: S1091-8531(19)30137-5. doi: 10.1016/j.jaapos.2019.03.005. [Epub ahead of print]

Alterations in visual acuity and visual development in infants 1-24 months old either exposed to or infected by Zika virus during gestation, with and without microcephaly.

Baran LCP1, da Costa MF2, Vidal KS2, Damico FM3, Barboni MTS4, da S Lima D2, de C R de M França V5, Martins CMG2, Tabares HS2, Dias SL5, Silva LA2, Decleva D2, Hamer RD6, Zatz M7, Bertozzi APAP8, Gazeta RE8, Passos SD8, Ventura DF2.

Author information: 1 Department of Experimental Psychology, University of São Paulo Institute of Psychology, São Paulo, SP, Brazil; Nucleus of Neurosciences and Behavior, University of São Paulo, São Paulo, SP, Brazil. Electronic address: baranejbio@gmail.com. 2 Department of Experimental Psychology, University of São Paulo Institute of Psychology, São Paulo, SP, Brazil; Nucleus of Neurosciences and Behavior, University of São Paulo, São Paulo, SP, Brazil. 3 Department of Ophthalmology, University of São Paulo College of Medicine, São Paulo, SP, Brazil. 4 Department of Experimental Psychology, University of São Paulo Institute of Psychology, São Paulo, SP, Brazil; Nucleus of Neurosciences and Behavior, University of São Paulo, São Paulo, SP, Brazil; Department of Ophthalmology, Semmelweis University, Budapest, Hungary. 5 Department of Experimental Psychology, University of São Paulo Institute of Psychology, São Paulo, SP, Brazil. 6 Department of Experimental Psychology, University of São Paulo Institute of Psychology, São Paulo, SP, Brazil; Nucleus of Neurosciences and Behavior, University of São Paulo, São Paulo, SP, Brazil; Department of Psychology, Florida Atlantic University, Boca Raton, Florida. 7 Human Genome and Stem Cells Center, Bioscience Institute, University of São Paulo. 8 University of Jundiai Medical School, Jundiai, São Paulo, SP, Brazil.

 

Abstract

PURPOSE:

To evaluate visual acuity and visual acuity development in children from the state of São Paulo, Brazil, who were exposed to the Zika virus (ZIKV) gestationally.

METHODS:

Children who had been exposed to ZIKV during gestation and age-matched control subjects received visual acuity and funduscopic examination. ZIKV exposure was confirmed by maternal quantitative polymerase chain reaction testing or serology assay. The ZIKV group was divided into two subgroups: Zika-exposed (ZE), with only the mother having confirmed ZIKV-infection, and Zika-infected (ZI), with confirmed infection. Visual acuity development was compared with prior norms and quantified by measuring visual acuity correlation with age.

RESULTS:

A total of 110 children were included: 47 who had been exposed to ZIKV (ZE, 23; ZI, 24) and 63 controls. Abnormal visual acuity was found in 5 of 24 ZI children. Of the 4 children with microcephaly, only 2 had visual acuity loss (only 1 also had abnormal funduscopic findings). There was significant correlation between age and visual acuity in both the control group (R2 = 0.8; P < 0.0000) and the ZE subgroup (R2 = 0.6; P < 0.0000). However, visual acuity did not correlate with age in the ZI subgroup (R2 = 0.04; P = 0.38). Furthermore, the increment in octaves/month was much lower in the ZI subgroup.

CONCLUSIONS:

Our data indicates that visual acuity losses only occur in infants who suffered gestational-infection, not simply exposure. Lack of correlation between age and visual acuity in the ZI subgroup suggests a slowing of visual development even in the absence of microcephaly. This result may have broad implications for the deleterious effects of ZIKV on the central nervous system.

Copyright © 2019 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

PMID: 31229606 DOI: 10.1016/j.jaapos.2019.03.005

Keywords: Zika Virus; Zika Congenital Infection; Zika Congenital Syndrome; Microcephaly; Pediatrics; Ophthalmology; Neurology.

——-

#Understanding the #relation between #Zika virus #infection during #pregnancy and adverse #fetal, #infant and #child #outcomes: a protocol … (BMJ Open., abstract)

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

BMJ Open. 2019 Jun 18;9(6):e026092. doi: 10.1136/bmjopen-2018-026092.

Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children.

Wilder-Smith A1, Wei Y2, Araújo TVB3, VanKerkhove M4, Turchi Martelli CM5, Turchi MD6, Teixeira M7, Tami A8, Souza J9, Sousa P10, Soriano-Arandes A11, Soria-Segarra C12, Sanchez Clemente N13, Rosenberger KD14, Reveiz L15, Prata-Barbosa A16, Pomar L17, Pelá Rosado LE18, Perez F19, Passos SD20, Nogueira M21, Noel TP22, Moura da Silva A23, Moreira ME24, Morales I14, Miranda Montoya MC25, Miranda-Filho DB26, Maxwell L27,28, Macpherson CNL22, Low N29, Lan Z30, LaBeaud AD31, Koopmans M32, Kim C33, João E34, Jaenisch T14, Hofer CB35, Gustafson P36, Gérardin P37,38, Ganz JS39, Dias ACF7, Elias V40, Duarte G41, Debray TPA42, Cafferata ML43, Buekens P44, Broutet N33, Brickley EB45, Brasil P46, Brant F7, Bethencourt S47, Benedetti A48, Avelino-Silva VL49, Ximenes RAA50, Alves da Cunha A51, Alger J52; Zika Virus Individual Participant Data Consortium.

Collaborators (33): Abreu de Carvalho LM, Batista R, Bertozzi AP, Carles G, Cotrim D, Damasceno L, Dimitrakis L, Duarte Rodrigues MM, Estofolete CF, Fragoso da Silveira Gouvêa MI, Fumadó-Pérez V, Gazeta RE, Kaydos-Daniels N, Gilboa S, Krystosik A, Lambert V, López-Hortelano MG, Mussi-Pinhata MM, Nelson C, Nielsen K, Oliani DM, Rabello R, Ribeiro M, Rockx B, Rodrigues LC, Salgado S, Silveira K, Sulleiro E, Tong V, Valencia D, De Souza WV, Villar Centeno LA, Zin A.

Author information: 1 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. 2 Centre for Mathematical Sciences, University of Plymouth, Plymouth, UK. 3 Department of Social Medicine, Universidade Federal de Pernambuco, Recife, Brazil. 4 Health Emergencies Programme, Organisation mondiale de la Sante, Geneve, Switzerland. 5 Department of Collective Health, Institute Aggeu Magalhães (CPqAM), Oswaldo Cruz Foundation, Recife, Brazil. 6 Institute of Tropical Pathology and Public Health, Federal University of Goias, Goiânia, Brazil. 7 Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. 8 Department of Medical Microbiology, University Medical Center Groningen, Groningen, The Netherlands. 9 Department of Social Medicine, University of São Paulo, São Paulo, Brazil. 10 Reference Center for Neurodevelopment, Assistance, and Rehabilitation of Children, State Department of Health of Maranhão, Sao Luís, Brazil. 11 Department of Pediatrics, University Hospital Vall d’Hebron, Barcelona, Spain. 12 SOSECALI C. Ltda, Guayaquil, Ecuador. 13 Department of Epidemiology, University of São Paulo, São Paulo, Brazil. 14 Department of Infectious Diseases, Section Clinical Tropical Medicine, UniversitatsKlinikum Heidelberg, Heidelberg, Germany. 15 Evidence and Intelligence for Action in Health, Pan American Health Organization, Washington, District of Columbia, USA. 16 Department of Pediatrics, D’Or Institute for Research & Education, Rio de Janeiro, Brazil. 17 Department of Obstetrics and Gynecology, Centre Hospitalier de l’Ouest Guyanais, Saint-Laurent du Maroni, French Guiana. 18 Hospital Materno Infantil de Goiânia, Goiânia State Health Secretary, Goiás, Brazil. 19 Communicable Diseases and Environmental Determinants of Health Department, Pan American Health Organization, Washington, District of Columbia, USA. 20 Department of Pediatrics, FMJ, São Paulo, Brazil. 21 Faculdade de Medicina de Sao Jose do Rio Preto, Department of Dermatologic Diseases, São José do Rio Preto, Brazil. 22 Windward Islands Research and Education Foundation, St. George’s University, True Blue Point, Grenada. 23 Department of Public Health, Universidade Federal do Maranhão – São Luís, São Luís, Brazil. 24 Department of Neonatology, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil. 25 Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia. 26 Faculty of Medical Sciences, University of Pernambuco, Recife, Brazil. 27 Reproductive Health and Research, World Health Organization, Geneva, Switzerland. 28 Hubert Department of Global Health, Emory University, Atlanta, Georgia, USA. 29 Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. 30 McGill University Health Centre, McGill University, Montréal, Canada. 31 Pediatric Infectious Diseases, Stanford Hospital, Palo Alto, California, USA. 32 Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands. 33 Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland. 34 Department of Infectious Diseases, Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil. 35 Instituto de Puericultura e Pediatria Martagão Gesteira, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. 36 Statistics, University of British Columbia, British Columbia, Vancouver, Canada. 37 INSERM CIC1410 Clinical Epidemiology, CHU La Réunion, Saint Pierre, Réunion. 38 UM 134 PIMIT (CNRS 9192, INSERM U1187, IRD 249, Université de la Réunion), Universite de la Reunion, Sainte Clotilde, Réunion. 39 Children’s Hospital Juvencio Matos, São Luís, Brazil. 40 Sustainable Development and Environmental Health, Pan American Health Organization, Washington, District of Columbia, USA. 41 Department of Gynecology and Obstetrics, University of São Paulo, São Paulo, Brazil. 42 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. 43 Mother and Children Health Research Department, Instituto de Efectividad Clinica y Sanitaria, Buenos Aires, Argentina. 44 School of Public Health and Tropical Medicine, Tulane University, New Orleans, USA. 45 Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. 46 Instituto de pesquisa Clínica Evandro Chagas, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil. 47 Facultad de Ciencias de la Salud, Universidad de Carabobo, Valencia, Carabobo, Bolivarian Republic of Venezuela. 48 Departments of Medicine and of Epidemiology, Biostatistics & Occupational Health, McGill University, Montreal, Quebec, Canada. 49 Department of Infectious and Parasitic Diseases, Faculdade de Medicina da Universidade de Sao Paulo, São Paulo, Brazil. 50 Department of Tropical Medicine, Federal University of Pernambuco, Recife, Brazil. 51 Department of Pediatrics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 52 Facultad de Ciencias Médicas, Universidad Nacional Autónoma de Honduras, Tegucigalpa, Honduras.

 

Abstract

INTRODUCTION:

Zika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes.

METHODS AND ANALYSIS:

We will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty.

ETHICS AND DISSEMINATION:

The IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals.

TRIAL REGISTRATION NUMBER:

PROSPERO International prospective register of systematic reviews (CRD42017068915).

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

KEYWORDS: Microcephaly; Zika Virus; congenital Zika syndrome; individual participant data meta-analysisis; prognosis; risk prediction model

PMID: 31217315 DOI: 10.1136/bmjopen-2018-026092

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

—–

#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.

——

#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.

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