Discordant clinical outcomes of congenital Zika virus infection in twin pregnancies

Linden, Vanessa van der; Linden, Hélio van der; Leal, Mariana de Carvalho; Filho, Epitácio Leite Rolim; Linden, Ana van der; Aragão, Máría de Fátima Viana Vasco; Brainer-Lima, Alessandra Mertens; Cruz, Danielle Di Cavalcanti Sousa; Ventura, Liana; Florêncio, Telma Lúcia Tabosa; Cordeiro, Marli Tenório; Neto, Silvio da Silva Caudas; Ramos, Regina Coeli Ferreira

doi:10.1590/0004-282x20170066

Cited by 33 publications

(31 citation statements)

References 22 publications

(22 reference statements)

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“…In agreement with the literature 43 , the involvement of the twins described here is in different degrees. Even in the absence of microcephaly, the first twin presented neurological alterations compatible with congenital Zika spectrum 36,44 ventriculomegaly, cerebral calcifications and epilepsy, but with an atypical phenotype of lower expression.…”

Section: Discussionsupporting

confidence: 93%

Description of atypical pattern in twins with presumed congenital Zika and without microcephaly - Case Report

Fontes¹,

Bezerra²,

Abreu³

2018

J. Hum. Growth Dev.

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Introduction: Zika virus (ZIKV) infection was a public health emergency of Brazilian national interest until May 2017, due to the sudden increase in newborns with microcephaly and other neurological alterations during the epidemic started in Brazil in November 2015. The manifestations of Intrauterine infections by ZIKV are more severe when they occur in the first and second trimesters of gestation, especially in the first trimester. In this situation, early diagnosis of visual problems is essential for patients to progress in the neurological and motor fields, and there are complications such as refractive errors (myopia, astigmatism and hyperopia), strabismus and hypoactomy. The absence of microcephaly in infants exposed to the zika virus is not indicative of changes in ophthalmology, and it is essential that the ophthalmologist perform the investigations that are relevant to the clinical case. Any and all eye lesions and their consequences are serious. The earlier the diagnosis, the sooner the child can undergo an intervention to enable vision. Objective: To analyze atypical pattern in twins with presumed congenital zika and without microcephaly. Methods: This is a case report, developed in the city of Serra Talhada, in the state of Pernambuco, Northeast Brazil. Report: Case of twins whose mother was exposed to zika virus in the second trimester of gestation (eleventh week). The children were born prematurely and without microcephaly. One of the twins had hydrocephalus requiring surgery. The same child was taken for ophthalmologic examination because of convergent strabismus; and hypocortical optic nerve and chorioretinal scar were found in the macular region in both eyes similar to the lesions described by zika virus. A similar scenario, but with less visual impairment was identified in the second twin. Skull tomography demonstrated bilateral calcification foci in the cerebral hemispheres. Conclusion: There was presence of convergent deviation and nystagmus to lateroversions. In the funduscopy, the optic nerve was pale and with cicatricial chorioretinal lesion with well delimited edges in the macular area of both eyes.

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Section: Discussionsupporting

confidence: 93%

Description of atypical pattern in twins with presumed congenital Zika and without microcephaly - Case Report

Fontes¹,

Bezerra²,

Abreu³

2018

J. Hum. Growth Dev.

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“…Another important aspect of ocular pathologies in congenital ZIKV infection will be the discordant clinical outcomes in twin pregnancies. 105 Indeed, studying ocular abnormalities in twins with congenital ZIKV infection should help elucidate the mechanism of ZIKV eye infection. The identification of early molecular alterations can improve our understanding of these effects and help in predicting clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Cellular Imprinting Proteomics Assay: A Novel Method for Detection of Neural and Ocular Disorders Applied to Congenital Zika Virus Syndrome

et al. 2020

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Congenital Zika syndrome was first described due to increased incidence of congenital abnormalities associated with Zika virus (ZIKV) infection. Since the eye develops as part of the embryo central nervous system (CNS) structure, it becomes a specialized compartment able to display symptoms of neurodegenerative diseases and has been proposed as a noninvasive approach to the early diagnosis of neurological diseases. Ocular lesions result from defects that occurred during embryogenesis and can become apparent in newborns exposed to ZIKV. Furthermore, the absence of microcephaly cannot exclude the occurrence of ocular lesions and other CNS manifestations. Considering the need for surveillance of newborns and infants with possible congenital exposure, we developed a method termed cellular imprinting proteomic assay (CImPA) to evaluate the ocular surface proteome specific to infants exposed to ZIKV during gestation compared to nonexposure. CImPA combines surface cells and fluid capture using membrane disks and a large-scale quantitative proteomics approach, which allowed the first-time report of molecular alterations such as neutrophil degranulation, cell death signaling, ocular and neurological pathways, which are associated with ZIKV infection with and without the development of congenital Zika syndrome, CZS. Particularly, infants exposed to ZIKV during gestation and without early clinical symptoms could be detected using the CImPA method. Lastly, this methodology has broad applicability as it could be translated in the study of several neurological diseases to identify novel diagnostic biomarkers. Data are available via ProteomeXchange with identifier PXD014038.

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“…Due to that, these parameters should be considered to get a deeper understanding of this disease. Another important aspect of ocular pathologies in congenital ZIKV infection will be the discordant clinical outcomes in twin pregnancies (163). Indeed, studying ocular abnormalities in twins with congenital ZIKV infection should help elucidate the mechanism of ZIKV eye infection.…”

Section: Discussionmentioning

confidence: 99%

CImP: Cellular Imprinting Proteomics applied to ocular disorders elicited by Congenital Zika virus Syndrome

Rosa-Fernandes

Mlb

et al. 2019

Preprint

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IMPORTANCE:Ocular complications in infants with Congenital Zika Syndrome (CZS) have been reported. However, the molecular mechanisms underlying of eye dysfunctions are presently unknown. OBJECTIVE:A method (termed Cellular Imprinting Proteomics, CImP) for the identification and quantification of the ocular surface proteome using a minimally invasive membrane filter device is described. Moreover, The CImP method was applied to profile the molecular alterations in the eyes of infants exposed to Zika virus (ZIKV) infection during gestation. DESIGN, SETTINGS AND PARTICIMPANTS:The CImP method was applied to a cohort divided into three conditions: 1) Ctrl (infants with no infectious diseases, n=5). 2) Zikv (infants exposed to ZIKV gestation, with no microcephaly, n=5). 3) Zikv CZS (infants exposed to ZIKV, with microcephaly, n=3). All conditions were age and sex-matched. An improved impression cytology method was used to capture the outermost ocular surface cells. The number of impression cytology membrane collected was: Ctrl (12), Zikv (14) and Zikv CZS (8). Proteins were extracted and analysed using mass spectrometry-based proteomics technology followed by statistical analysis. Parallel reaction monitoring was performed to validate the expression of specific protein markers. RESULTS:Using the CImP method, 2209 proteins were identified on the membrane-captured conjunctiva epithelial cells. Modulation of neutrophil degranulation, cell death, ocular and neurodevelopment pathways are reported in infants with CZS compared to matched controls.Moreover, the molecular pattern of ocular surface cells retrieved from infants infected during the gestation but with no CZS was different from matched controls. CONCLUSIONS AND PERSPECTIVES: Molecular alterations in the ocular cell surface associatedto ZIKV infection with and without CZS complications are reported for the first time. We predict that this method will be introduced successfully in the study of several neurological diseases with the aim to identify novel diagnostic and therapeutic biomarkers. Introduction:Zika virus (ZIKV) is a positive-strand RNA virus belonging to the Flaviviridae family that is transmitted to humans predominantly by the female Aedes aegypti and Aedes albopictus mosquitos (1). Moreover, sexual contact, blood transfusions, laboratory and healthcare settings Subjects, materials and methods Patient cohortThis study comprises 13 infants with and without CZS referred to the Pediatric Service of the Antonio Pedro University Hospital, Fluminense Federal University, Niteroi, Brazil. This study was approved by Institutional review board and ethics committee of Fluminense Federal University, protocol CAAE number 79890517.6.0000.5243, and followed the guidelines of the Declaration of Helsinki. All samples were collected upon informed and written consent from the parents/legal guardians of each participant. Clinical examination was performed by a multidisciplinary team and all infants included in this study are part of a clinical follow up program currently in pr...

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Discordant clinical outcomes of congenital Zika virus infection in twin pregnancies

Cited by 33 publications

References 22 publications

Description of atypical pattern in twins with presumed congenital Zika and without microcephaly - Case Report

Description of atypical pattern in twins with presumed congenital Zika and without microcephaly - Case Report

Cellular Imprinting Proteomics Assay: A Novel Method for Detection of Neural and Ocular Disorders Applied to Congenital Zika Virus Syndrome

CImP: Cellular Imprinting Proteomics applied to ocular disorders elicited by Congenital Zika virus Syndrome

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