Characterization of placental infection by zika virus in humans: A review of the literature / Caracterização da infecção placentária pelo vírus zika em humanos: Uma revisão da literatura

Abstract Objective The aim of the current review is to present a systematic evaluation of reported human placental findings in cases of zika virus (ZIKV) infection. Data sources We reviewed the EMBASE, PUBMED, and SCIELO databases until June 2019, without language restrictions. Selection of studies The search terms placenta AND zika virus were used. The inclusion criteria of the studies were studies that reported placental findings in humans. Experimental studies, reviews, notes or editorials were excluded. A total of 436 studies were retrieved; after duplicate exclusion, 243 articles had their titles screened, and 128 had their abstract read; of those, 32 were included in the final analysis (18 case reports, 10 case series, and 4 cohorts) Data collection We collected data concerning the author, year of publication, study design, number of participants, number of placental samples, onset of symptoms, perinatal outcomes, and main findings on histological analysis. Data synthesis The placental pathologic findings were described as mild and nonspecific, similar to those of other placental infections, including chronic placentitis, chronic villitis, increased Hofbauer cells, irregular fibrin deposits, increased mononuclear cells in the villus stroma, villous immaturity, edema, hypervascularization, stromal fibrosis, calcification, and focal necrosis of syncytiotrophoblasts. Conclusion Zika infection presents unspecific placental findings, similar to other infections in the toxoplasmosis, other agents, rubella, cytomegalovirus, and herpes (TORCH)group. Characterizing and standardizing placental findings after zika virus infection is key to understanding the mechanisms of congenital diseases.

Resumo Objetivo O objetivo desta revisão é apresentar uma avaliação sistemática dos achados relacionados à infecção por zika vírus (ZIKV) na placenta humana. Fontes de dados As bases de dados EMBASE, PUBMED, e SCIELO foram pesquisadas, até junho de 2019, sem qualquer restrição de língua. Seleção dos estudos Os termos placenta E zika virus foram utilizados na busca. Foram incluídos estudos que reportassem achados placentários de infecção em seres humanos, enquanto estudos experimentais, revisões, notas e editoriais foram excluídos. Um total de 436 estudos foram identificados, e 243 tiveram seus títulos lidos após a exclusão de duplicatas. Cento e vinte e oito artigos tiveram seus resumos avaliados, dos quais 32 foram incluídos na análise final (18 relatos de caso, 10 séries de casos, e 4 estudos de coorte). Dados obtidos Foram pesquisados dados relativos ao autor, ano da publicação, desenho do estudo, número de participantes, número de amostras de placenta, início dos sintomas, desfechos perinatais, e principais achados histológicos. Síntese dos dados Os principais achados placentários descritos foram leves e inespecíficos, similares a outras infecções placentárias, incluindo infecção placentária crônica, vilosite crônica, aumento das células de Hofbauer, depósitos irregulares de fibrina, aumento das células mononucleares no estroma viloso, imaturidade vilosa, edema, hipervascularização, fibrose estromal, calcificação, e necrose focal dos sincicitrofoblastos. Conclusão Infecções por ZIKV têm achados placentários inespecíficos, similares aos de outras infecções do grupo toxoplasmose, rubéola, citomegalovírus e herpes (TORCH). Caracterizar e padronizar os achados placentários após infecção por ZIKV é fundamental para entender o mecanismo das infecções congênitas.

Zika Virus Infection at Different Pregnancy Stages: Anatomopathological Findings, Target Cells and Viral Persistence in Placental Tissues.

Zika virus (ZIKV) infection in humans has been associated with congenital malformations and other neurological disorders, such as Guillain-Barré syndrome. The mechanism(s) of ZIKV intrauterine transmission, the cell types involved, the most vulnerable period of pregnancy for severe outcomes from infection and other physiopathological aspects are not completely elucidated. In this study, we analyzed placental samples obtained at the time of delivery from a group of 24 women diagnosed with ZIKV infection during the first, second or third trimesters of pregnancy. Villous immaturity was the main histological finding in the placental tissues, although placentas without alterations were also frequently observed. Significant enhancement of the number of syncytial sprouts was observed in the placentas of women infected during the third trimester, indicating the development of placental abnormalities after ZIKV infection. Hyperplasia of Hofbauer cells (HCs) was also observed in these third-trimester placental tissues, and remarkably, HCs were the only ZIKV-positive fetal cells found in the placentas studied that persisted until birth, as revealed by immunohistochemical (IHC) analysis. Thirty-three percent of women infected during pregnancy delivered infants with congenital abnormalities, although no pattern correlating the gestational stage at infection, the IHC positivity of HCs in placental tissues and the presence of congenital malformations at birth was observed. Placental tissue analysis enabled us to confirm maternal ZIKV infection in cases where serum from the acute infection phase was not available, which reinforces the importance of this technique in identifying possible causal factors of birth defects. The results we observed in the samples from naturally infected pregnant women may contribute to the understanding of some aspects of the pathophysiology of ZIKV.

Maternal-fetal transmission of the zika virus: An intriguing interplay.

In this review, we give an overview of aspects related to the congenital transmission of the Zika virus (ZIKV). Although we acknowledge that important advances in research on ZIKV pathogenesis have come from studies using animal models, particularly non-human primates, this review emphasizes studies using ex-vivo human cells and tissues as well as natural infections in pregnant women. The possible routes used by ZIKV to cross or breach the placental barrier and infect the fetal central nervous system are presented. Understanding the viral infection biology and ZIKV pathogenesis during pregnancy may guide the design of affordable antiviral strategies to benefit pregnant women in areas at risk.

Zika virus damages the human placental barrier and presents marked fetal neurotropism

An unusually high incidence of microcephaly in newborns has recently been observed in Brazil. There is a temporal association between the increase in cases of microcephaly and the Zika virus (ZIKV) epidemic. Viral RNA has been detected in amniotic fluid samples, placental tissues and newborn and fetal brain tissues. However, much remains to be determined concerning the association between ZIKV infection and fetal malformations. In this study, we provide evidence of the transplacental transmission of ZIKV through the detection of viral proteins and viral RNA in placental tissue samples from expectant mothers infected at different stages of gestation. We observed chronic placentitis (TORCH type) with viral protein detection by immunohistochemistry in Hofbauer cells and some histiocytes in the intervillous spaces. We also demonstrated the neurotropism of the virus via the detection of viral proteins in glial cells and in some endothelial cells and the observation of scattered foci of microcalcifications in the brain tissues. Lesions were mainly located in the white matter. ZIKV RNA was also detected in these tissues by real-time-polymerase chain reaction. We believe that these findings will contribute to the body of knowledge of the mechanisms of ZIKV transmission, interactions between the virus and host cells and viral tropism.

Hofbauer cells morphology and density in placentas from normal and pathological gestations / Morfologia e densidade das células de Hofbauer em placentas de gestações normais e patológicas

PURPOSE: In placentas from uncomplicated pregnancies, Hofbauer cells either disappear or become scanty after the fourth to fifth month of gestation. Immunohistochemistry though, reveals that a high percentage of stromal cells belong to Hofbauer cells. The aim of this study was to investigate the changes in morphology and density of Hofbauer cells in placentas from normal and pathological pregnancies. METHODS: Seventy placentas were examined: 16 specimens from normal term pregnancies, 10 from first trimester's miscarriages, 26 from cases diagnosed with chromosomal abnormality of the fetus, and placental tissue specimens complicated with intrauterine growth restriction (eight) or gestational diabetes mellitus (10). A histological study of hematoxylin-eosin (HE) sections was performed and immunohistochemical study was performed using the markers: CD 68, Lysozyme, A1 Antichymotrypsine, CK-7, vimentin, and Ki-67. RESULTS: In normal term pregnancies, HE study revealed Hofbauer cells in 37.5% of cases while immunohistochemistry revealed in 87.5% of cases. In first trimester's miscarriages and in cases with prenatal diagnosis of fetal chromosomal abnormalities, both basic and immunohistochemical study were positive for Hofbauer cells. In pregnancies complicated with intrauterine growth restriction or gestational diabetes mellitus, a positive immunoreaction was observed in 100 and 70% of cases, respectively. CONCLUSIONS: Hofbauer cells are present in placental villi during pregnancy, but with progressively reducing density. The most specific marker for their detection seems to be A1 Antichymotrypsine. It is remarkable that no mitotic activity of Hofbauer cells was noticed in our study, as the marker of cellular multiplication Ki-67 was negative in all examined specimens.

OBJETIVO: Em placentas de gestações sem complicações, as células de Hofbauer desaparecem ou se tornam raras após o quarto ou quinto mês de gestação. Entretanto, a imunohistoquímica revela que uma alta porcentagem de células estromais pertencem às células de Hofbauer. O objetivo do presente estudo foi investigar as alterações da morfologia e densidade das células de Hofbauer em placentas de gestações normais e patológicas. MÉTODOS: Foram examinadas 70 placentas: 16 provenientes de gestações normais a termo, 10 de abortos espontâneos no primeiro trimestre, 26 de casos diagnosticados como anormalidade cromossômica do feto, e amostras de tecido placentário com complicações causadas pela restrição de crescimento intrauterino (8) ou pelo diabetes mellitus gestacional (10). Cortes corados com hematoxilina-eosina (HE) foram submetidos a estudo histológico e imunohistoquímico utilizando-se os seguintes marcadores: CD 68, lisozima, antiquimotripsina A1, CK-7, vimentina, e Ki-67. RESULTADOS: Em gestações normais a termo, o estudo HE revelou células de Hofbauer em 37,5% dos casos, enquanto a imunohistoquímica as revelou em 87,5% dos casos. Em abortos do primeiro trimestre e em casos de diagnóstico prenatal de anormalidades cromossômicas fetais, tanto o estudo básico como o estudo imunohistoquímico foram positivos para células de Hofbauer. Em gestações complicadas pela restrição de crescimento intrauterino ou pelo diabetes mellitus gestacional, imunoreação positiva foi observada respectivamente em 100 e 70% dos casos. CONCLUSÕES: As células de Hofbauer estão presentes nos vilos placentários durante a gestação, embora com densidade progressivamente reduzida. O marcador mais específico para sua detecção parece ser a antiquimotripsina A1. Vale salientar que atividade mitótica de células de Hofbauer não foi detectada em nosso estudo, uma vez que o marcador de multiplicação celular Ki-67 foi negativo em todas as amostras examinadas.

Histomorphometry of preterm and term human placentas / Histomorfometría de placentas de pretérmino y término

The intra-uterine existence of foetus is dependent on placenta, a major organ of nutrition and homeostasis.The present study was carried out to compare morphometric and histological changes in preterm and term human placentas. Eighty placentas collected from Department of Obstetrics and Gynecology, JNMCH, AMU, Aligarh, were divided into group first of preterm placentas up to 36 weeks (n =30) and second group of full term placentas i.e. 37 to 40 weeks ( n = 50) respectively. The samples were fixed in 10 percent formol-saline solution. The gross morphological variables of placentas were studied. There was a significant increase in the placental weight, decidual area and umbilical cord diameter of term placenta as compared to that of the preterm ones. From each placenta whole thickness tissue blocks were taken and processed for paraffin sectioning. Five µ-thick sections were stained with Haematoxylin-eosin and Van Gieson stains and processed for light microscopy. A total of 200 villi were studied in each sample under high power field and occurrence of different features was expressed as percentages for each parameter. The appearance of microvilli and syncytial bud on the syncytium were almost absent in the villi of term placentas. It was concluded that with increasing gestational age there was a gradual increase in the number of capillaries in villi from preterm to term placenta.There was a significant increase in syncytial knot count, fibrinoid necrosis, vasculosyncytial membrane and decrease in the percentage of villi showing cytotrophoblastic cells and number of Hofbauer cells in term group as compared to preterm group.

La existencia intrauterina del feto depende de la placenta, el mayor órgano de nutrición y homeostasis. El estudio se llevó a cabo para comparar los cambios morfométricos e histológicos de la placenta humana de término y pretérmino. Ochenta placentas fueron obtenidas del Departamento de Obstetricia y Ginecología, JNMCH, AMU, Aligarh y se dividieron en grupos, el primer grupo de placentas de pretérmino hasta 36 semanas (n = 30) y el segundo grupo de placentas de término, de 37 a 40 semanas (n = 50 ). Las muestras fueron fijadas en solución de formol-salina al 10 por ciento. Se estudiaron las variables morfológicas macroscópicas de las placentas. Hubo un aumento significativo en el peso de la placenta, el área de decidua y el diámetro del cordón umbilical de la placenta a término en comparación con la de los prematuros. De cada placenta se tomaron y se procesaron bloques de tejido para incluirlos en parafina. Cortes de 5 µm fueron teñidos con HE y Van Gieson para microscopía óptica. De cada muestra fueron estudiadas 200 vellosidades, bajo campo de alta resolución y la aparición de diferentes características se expresó como porcentajes para cada parámetro. La aparición de las microvellosidades y brote sincitial en el sincitio estaban casi ausente en las vellosidades de las placentas de término. Se puede concluir que al aumentar la edad gestacional hubo un aumento gradual en el número de capilares en las vellosidades de la placenta de término. Existe un aumento significativo en el recuento de nudo sincitial, necrosis fibrinoide, membrana vasculosincisial y disminución en el porcentaje de las vellosidades que muestran células citotrofoblástica y número de células de Hofbauer en las placentas del término de grupo en comparación con el grupo de pretérmino.