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1.
J Gynecol Obstet Hum Reprod ; 50(7): 102041, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33310133

RESUMO

BACKGROUND: The prevalence of COVID-19 infection during pregnancy is not known. COVIPREG is a prospective French multicenter study to assess the seroprevalence at the time of delivery and the maternal and neonatal impact of COVID-19 infection during pregnancy. In order to study factors associated with poor outcomes after COVID-19 Infection during pregnancy and adapt the sample size of the study, a preliminary assessment of the prevalence of SARS-CoV-2 IgG was planned after 500 inclusions in a one perinatal center of Paris area. OBJECTIVES: To assess the prevalence of SARS-CoV-2 IgG antibody response in pregnant women at the time of delivery during the COVID-19 pandemia. STUDY DESIGN: A prospective observational study at Cochin hospital (Level III maternity). Patients admitted for delivery were offered to participate to the study. Each patient participating to the study was tested for anti-SARS-CoV-2-IgG antibodies using a commercially available ELISA. RESULTS: Among the 529 patients included in the COVIPREG study between April 29 and June 26, 529 were assessed for SARS-CoV-2 IgG antibody response and 25 had a positive test, ie 4.7 % with a confidence interval at 95 % [3.0 %-6.9 %]). CONCLUSIONS: Four months after the beginning of the infection in Paris, the seroprevalence of SARS-CoV-2 IgG in pregnant women at the time of delivery is low. Studies evaluating the impact of COVID-19 infection during pregnancy should take this information in account in order to adapt the sample size.

2.
Am J Transplant ; 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33346946

RESUMO

Graft artery stenosis can have a significant short- and long-term negative impact on renal graft function. From the beginning of the COVID-19 pandemic, we noticed an unusual number of graft arterial anomalies following kidney transplant (KTx) in children. Nine children received a KTx at our center between February and July 2020, eight boys and one girl, of median age 10 years. Seven presented Doppler features suggesting arterial stenosis, with an unusual extensive pattern. For comparison, over the previous five-year period, persistent spectral Doppler arterial anomalies (focal anastomotic stenoses) following KTx were seen in 5% of children at our center. We retrospectively evidenced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in 5/7 children with arterial stenosis. The remaining two patients had received a graft from a deceased adolescent donor with a positive serology at D0. These data led us to suspect immune post-viral graft vasculitis, triggered by SARS-CoV-2. Because the diagnosis of COVID-19 is challenging in children, we recommend pre-transplant monitoring of graft recipients and their parents by monthly RT-PCR and serology. We suggest balancing the risk of post-viral graft vasculitis against the risk of prolonged dialysis when considering transplantation in a child during the pandemic.

3.
Am J Transplant ; 2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33283406

RESUMO

Belatacept may increase cytomegalovirus (CMV) disease risk after conversion from CNI-based therapy. We analyzed CMV disease characteristics after belatacept conversion. Propensity score matching was used to compare CMV disease incidence in belatacept- and CNI-treated kidney transplant recipients (KTRs). CMV disease characteristics and risk factors under belatacept were analyzed. In total, 223 KTRs (median age [IQR] 59.2 years [45.4-68.5]) were converted to belatacept (median of 11.5 months [2.5-37.0] post-transplantation); 40/223 (17.9%) developed CMV disease. Independent risk factors included increased age (p = .0164), D+/R- CMV serostatus (p = .0220), and low eGFR at conversion (p = .0355). Among 181 belatacept-treated patients matched to 181 controls, 32/181 (17.7%) experienced CMV disease (vs. 5/181 controls [2.8%]). CMV disease cumulative incidences were 6.33 and 0.91/100 person-years (p-y) in belatacept and control groups, respectively. CMV disease risk was particularly high in elderly patients (converted >70 years) and those with eGFR <30 ml/min; cumulative incidences were 18.4 and 5.2/100 p-y, respectively. CMV diseases under belatacept were atypical, with late-onset disease (24/40 patients [60%]), high CMV seropositivity (27/40, 67%), increased severe and tissue-invasive disease rates (gastrointestinal involvement in 32/40 [80%]) and life-threatening diseases (4/40 [10%]). These findings should stimulate further research to secure the use of belatacept as a valuable rescue therapy in KTRs.

4.
Euro Surveill ; 25(48)2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33272357

RESUMO

We assessed the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and Kawasaki disease (KD)-like multisystem inflammatory syndrome in a retrospective case-control study in France. RT-PCR and serological tests revealed SARS-CoV-2 infection in 17/23 cases vs 11/102 controls (matched odds ratio: 26.4; 95% confidence interval: 6.0-116.9), indicating strong association between SARS-CoV-2 infection and KD-like illness. Clinicians should keep a high level of suspicion for KD-like illness during the COVID-19 pandemic.


Assuntos
Infecções por Coronavirus/diagnóstico , Coronavirus/genética , Síndrome de Linfonodos Mucocutâneos/virologia , Pneumonia Viral/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica , Estudos de Casos e Controles , Criança , Pré-Escolar , Coronavirus/isolamento & purificação , França/epidemiologia , Humanos , Síndrome de Linfonodos Mucocutâneos/complicações , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
5.
Virologie (Montrouge) ; 24(5): 315-324, 2020 10 01.
Artigo em Francês | MEDLINE | ID: mdl-33111705

RESUMO

The incidence of herpes simplex virus (HSV) neonatal infection is estimated to be 8.9 per 100,000 live births in Europe. Early treatment with intravenous acyclovir has transformed the prognosis but this infection remains severe since, despite the treatment, mortality is frequent in disseminated diseases and neurological sequelae are frequent when central nervous system is involved. The major risk factor for transmission is the type of maternal infection. In women shedding the virus in their genital tract during childbirth, neonatal infection rates are 44 %, 25 % and 1.3 % in primary, non-primary and recurrent infections, respectively. The goals for the management of this infection during pregnancy encompass 1) the prevention of any contact between the newborn and the maternal virus by suppressing viral replication in the genital tract in late pregnancy and recommending a cesarean section in cases of genital lesions at delivery, and 2) the development of strategies allowing rapid identification and treatment of infected newborns.

7.
Clin Infect Dis ; 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32663849

RESUMO

BACKGROUND: Health-care workers (HCW) have paid a heavy toll to the coronavirus disease-19 (COVID-19) outbreak. Routes of transmission remain to be fully understood. METHODS: This prospective study compared a 1,500-bed adult and a 600-bed pediatric setting of a tertiary-care university hospital located in central Paris. From February 24th until April 10th, 2020, all symptomatic HCW were screened for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on a nasopharyngeal swab. HCW screened positive were questioned on their profession, symptoms, occupational and non-occupational exposures to SARS-CoV-2. RESULTS: Among 1344 HCW tested, 373 were positive (28%) and 336 (90%) corresponding questionnaires were completed. Three hospitalizations and no death were reported. Most HCW (70%) had patient-facing occupational activities (22% in COVID-19 dedicated units). The total number of HCW cases peaked on March 23rd, then decreased slowly, concomitantly with a continuous increase of compliance to preventive measures (including universal medical masking and personal protective equipment (PPE) for direct care to COVID-19 patients). Attack rates were of 3.2% and 2.3% in the adult and pediatric setting, respectively (p=0.0022). In the adult setting, HCW more frequently reported exposure to COVID-19 patients without PPE (25% versus 15%, p=0.046). Report of contacts with children attending out-of-home care facilities dramatically decreased over the study period. CONCLUSION: Universal masking, reinforcement of hand hygiene, and PPE with medical masks for patients' care allowed protection of HCW and containment of the outbreak. Residual transmissions were related to persistent exposures with undiagnosed patients or colleagues and not to contacts with children attending out-of-home care facilities.

8.
Am J Obstet Gynecol ; 223(1): 91.e1-91.e4, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: covidwho-165418

RESUMO

COVID-19 can severely affect pregnant women Furthermore, issues regarding vertical transmission of severe acute respiratory syndrome coronavirus 2 are emerging. In patients and neonates who are showing symptoms of coronavirus disease 2019, real-time polymerase chain reaction of nasal and throat swabs, sputum, and feces is performed to detect the presence of severe acute respiratory syndrome coronavirus 2. In addition, real-time polymerase chain reaction of vaginal swabs, amniotic fluid, placenta, cord blood, neonatal blood, or breast milk for the detection of severe acute respiratory syndrome coronavirus 2 did not show substantial results. Viremia was present in 1% of adult patients who were showing symptoms of coronavirus disease 2019. Here, we reviewed 12 articles published between Feb. 10, 2020, and April 4, 2020, that reported on 68 deliveries and 71 neonates with maternal infection in the third trimester of pregnancy. To determine whether infection occurred congenitally or perinatally, perinatal exposure, mode of delivery, and time interval from delivery to the diagnosis of neonatal infection were considered. Neonates with severe acute respiratory syndrome coronavirus 2 infection are usually asymptomatic. In 4 cases, a diagnostic test for severe acute respiratory syndrome coronavirus 2 infection was performed within 48 hours of life. Furthermore, detection rates of real-time polymerase chain reaction and the interpretation of immunoglobulin M and immunoglobulin G antibodies levels in cord and neonatal blood were discussed in relation with the immaturity of the fetal and neonatal immune system.

9.
Am J Obstet Gynecol ; 223(1): 91.e1-91.e4, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32376317

RESUMO

COVID-19 can severely affect pregnant women Furthermore, issues regarding vertical transmission of severe acute respiratory syndrome coronavirus 2 are emerging. In patients and neonates who are showing symptoms of coronavirus disease 2019, real-time polymerase chain reaction of nasal and throat swabs, sputum, and feces is performed to detect the presence of severe acute respiratory syndrome coronavirus 2. In addition, real-time polymerase chain reaction of vaginal swabs, amniotic fluid, placenta, cord blood, neonatal blood, or breast milk for the detection of severe acute respiratory syndrome coronavirus 2 did not show substantial results. Viremia was present in 1% of adult patients who were showing symptoms of coronavirus disease 2019. Here, we reviewed 12 articles published between Feb. 10, 2020, and April 4, 2020, that reported on 68 deliveries and 71 neonates with maternal infection in the third trimester of pregnancy. To determine whether infection occurred congenitally or perinatally, perinatal exposure, mode of delivery, and time interval from delivery to the diagnosis of neonatal infection were considered. Neonates with severe acute respiratory syndrome coronavirus 2 infection are usually asymptomatic. In 4 cases, a diagnostic test for severe acute respiratory syndrome coronavirus 2 infection was performed within 48 hours of life. Furthermore, detection rates of real-time polymerase chain reaction and the interpretation of immunoglobulin M and immunoglobulin G antibodies levels in cord and neonatal blood were discussed in relation with the immaturity of the fetal and neonatal immune system.


Assuntos
Infecções por Coronavirus/transmissão , Transmissão Vertical de Doença Infecciosa , Pneumonia Viral/transmissão , Complicações Infecciosas na Gravidez/virologia , Líquido Amniótico/virologia , Betacoronavirus , Cesárea , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Recém-Nascido , Pandemias , Placenta/virologia , Pneumonia Viral/diagnóstico , Gravidez
10.
PLoS One ; 15(4): e0232140, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32353010

RESUMO

BACKGROUND: Congenital cytomegalovirus infection can lead to severe sequelae. When fetal infection is confirmed, we hypothesize that fetal treatment could improve the outcome. Maternal oral administration of an effective drug crossing the placenta could allow fetal treatment. Letermovir (LMV) and Maribavir (MBV) are new CMV antivirals, and potential candidates for fetal treatment. METHODS: The objective was to investigate the placental transfer of LMV and MBV in the ex vivo method of the human perfused cotyledon. Term placentas were perfused, in an open-circuit model, with LMV or MBV at concentrations in the range of clinical peak plasma concentrations. Concentrations were measured using ultraperformance liquid chromatography coupled with tandem mass spectrometry. Mean fetal transfer rate (FTR) (fetal (FC) /maternal concentration), clearance index (CLI), accumulation index (AI) (retention of each drug in the cotyledon tissue) were measured. Mean FC were compared with half maximal effective concentrations of the drugs (EC50(LMV) and EC50(MBV)). RESULTS: For LMV, the mean FC was (± standard deviation) 1.1 ± 0.2 mg/L, 1,000-fold above the EC50(LMV). Mean FTR, CLI and AI were 9 ± 1%, 35 ± 6% and 4 ± 2% respectively. For MBV, the mean FC was 1.4 ± 0.2 mg/L, 28-fold above the EC50(MBV). Mean FTR, CLI and AI were 10 ± 1%, 50 ± 7% and 2 ± 1% respectively. CONCLUSIONS: Drugs' concentrations in the fetal side should be in the range for in utero treatment of fetuses infected with CMV as the mean FC was superior to the EC50 for both molecules.


Assuntos
Infecções por Citomegalovirus/tratamento farmacológico , Troca Materno-Fetal/efeitos dos fármacos , Placenta/efeitos dos fármacos , Acetatos/farmacologia , Adulto , Antivirais/farmacologia , Benzimidazóis/farmacologia , Cromatografia Líquida/métodos , Feminino , Humanos , Cinética , Modelos Biológicos , Perfusão , Gravidez , Quinazolinas/farmacologia , Ribonucleosídeos/farmacologia , Espectrometria de Massas em Tandem/métodos
11.
Prenat Diagn ; 40(13): 1671-1680, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32459019

RESUMO

Congenital CMV infection (cCMV) is the most prevalent congenital infection, main non-genetic cause of sensorineural hearing loss (SNHL) and major cause of neurological disability. Despite the burden of cCMV, no Public Health body recommends universal serology screening in pregnancy. This was explained by gaps in knowledge of epidemiology, diagnosis, prognosis and the absence of any validated treatment. Over 10 years, progress has been made in our understanding of cCMV following primary maternal infection. Risk factors have been identified and quantified, notably it is now well recognized that among maternal primary infections only those occurring in the first trimester may lead to long-term sequelae. Algorithms combining IgG, IgM, and IgG avidity detection with serological assays adapted on high throughput platforms have demonstrated high sensitivity and specificity to diagnose maternal primary infection. The prognostic value of prenatal imaging combining ultrasound and MRI has been validated by many studies. Finally, recent data from a randomized controlled study demonstrated the efficacy of early antiviral therapy to prevent vertical transmission. Whether CMV serology screening in the first trimester of pregnancy meets the WHO's criteria for a screening program will therefore be reviewed.

12.
Am J Obstet Gynecol ; 223(3): 330-349, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32105678

RESUMO

Cytomegalovirus is the most common congenital infection, affecting 0.5-2% of all live births and the main nongenetic cause of congenital sensorineural hearing loss and neurological damage. Congenital cytomegalovirus can follow maternal primary infection or nonprimary infection. Sensorineurological morbidity is confined to the first trimester with up to 40-50% of infected neonates developing sequelae after first-trimester primary infection. Serological testing before 14 weeks is critical to identify primary infection within 3 months around conception but is not informative in women already immune before pregnancy. In Europe and the United States, primary infection in the first trimester are mainly seen in young parous women with a previous child younger than 3 years. Congenital cytomegalovirus should be evoked on prenatal ultrasound when the fetus is small for gestation and shows echogenic bowel, effusions, or any cerebral anomaly. Although the sensitivity of routine ultrasound in predicting neonatal symptoms is around 25%, serial targeted ultrasound and magnetic resonance imaging of known infected fetuses show greater than 95% sensitivity for brain anomalies. Fetal diagnosis is done by amniocentesis from 17 weeks. Prevention consists of both parents avoiding contact with body fluids from infected individuals, especially toddlers, from before conception until 14 weeks. Candidate vaccines failed to provide more than 75% protection for >2 years in preventing cytomegalovirus infection. Medical therapies such as cytomegalovirus hyperimmune globulins aim to reduce the risk of vertical transmission but 2 randomized controlled trials have not found any benefit. Valaciclovir given from the diagnosis of primary infection up to amniocentesis decreased vertical transmission rates from 29.8% to 11.1% in the treatment group in a randomized controlled trial of 90 pregnant women. In a phase II open-label trial, oral valaciclovir (8 g/d) given to pregnant women with a mildly symptomatic fetus was associated with a higher chance of delivering an asymptomatic neonate (82%), compared with an untreated historical cohort (43%). Valganciclovir given to symptomatic neonates is likely to improve hearing and neurological symptoms, the extent of which and the duration of treatment are still debated. In conclusion, congenital cytomegalovirus infection is a public health challenge. In view of recent knowledge on diagnosis and pre- and postnatal management, health care providers should reevaluate screening programs in early pregnancy and at birth.


Assuntos
Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/transmissão , Complicações Infecciosas na Gravidez/virologia , Infecções por Citomegalovirus/complicações , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/epidemiologia , Doenças Fetais/virologia , Perda Auditiva Neurossensorial/virologia , Humanos , Recém-Nascido , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Transmissão Vertical de Doença Infecciosa/estatística & dados numéricos , Imagem por Ressonância Magnética , Doenças do Sistema Nervoso/virologia , Cuidado Pré-Concepcional , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Primeiro Trimestre da Gravidez , Diagnóstico Pré-Natal , Testes Sorológicos , Ultrassonografia Pré-Natal , Valaciclovir/administração & dosagem
13.
Clin Res Hepatol Gastroenterol ; 44(2): 174-180, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31266724

RESUMO

INTRODUCTION: Hepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide, usually asymptomatic in children. However, a growing number of publications over the last decade have documented cases of chronic hepatitis related to HEV-genotype 3 infection, and progressing to cirrhosis in immuno-compromised patients, particularly in adult kidney transplant recipients. The aim of our study was to evaluate the prevalence and severity of HEV infection among pediatric liver transplant (PLT) recipients managed in our center. MATERIAL AND METHODS: Between November 1st 2014 and January 1st 2016, PLT recipients (less than 18 years-old) were screened for HEV infection [determined by HEV serology, HEV- immunoglobulin M (IgM) and immunoglobulin G (IgG), and HEV-ribonucleic acid (RNA) by reverse transcriptase polymerase chain reaction] at their annual follow-up visit. RESULTS: Eighty children were tested for HEV infection a mean of 5.4±5.3 years after liver transplantation (LT). The main indication for LT was biliary atresia (n=47, 59%). The prevalence of HEV-IgG was 8% (n=6; age range 1.3 to 14.2 years-old at the time of HEV testing). Prevalence increased to 30% when considering only the 20 children with a past history of an unexplained episode of elevated transaminases since LT. None had HEV IgM, serum HEV-RNA, or increased transaminases at the time of HEV testing. Among the six IgG seropositive children, two had received intravenous immunoglobulins prior to screening and four children had a negative control (seroreversion) 3 to 42 months after the first testing. CONCLUSION: The prevalence of HEV infection in our cohort is low and similar to other pediatric reports. We saw no cases of chronic hepatitis or fibrosis attributable to HEV. The lower immunosuppressive regimen used in PLT children compared to other solid organ transplant recipients may account for this good outcome.

16.
Clin Infect Dis ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31665306

RESUMO

BACKGROUND: In women seronegative before pregnancy, cCMV related sequelae are exclusively seen in those infected in the first trimester of pregnancy. Up to 30% of infected neonates following maternal primary infection in the first trimester suffer long-term sequelae. Maternal parity is an established risk factor of cCMV in previously seronegative women. OBJECTIVE: to quantify the risk of cCMV and related sequelae following primary infection in the first trimester in subsequent pregnancies in a population of women seronegative at their first pregnancy. METHODS: 739 women seronegative at their first pregnancy had at least one of 971 subsequent pregnancies and deliveries managed at our institution. All women had CMV IgG and IgM testing at 11-14 weeks' of each pregnancy. RESULTS: 15.6% (115/739) of women seroconverted between 2 consecutive pregnancies. 29% (33/115) of seroconversions occurred in the periconceptional period or in the first trimester. The risks for cCMV and related sequelae (neurologic and/or hearing loss) following maternal infection in the first trimester were respectively 24 and 6-fold higher (RR [95%CI] =24 [10.8-62.3] and 6 [1.5-24]) than the general pregnant population. 88% (29/33) and 92% (11/12) of, respectively, all primary maternal infections and fetal infections in the 1st trimester occurred when the inter-pregnancy interval was ≤2 years. CONCLUSION: Women seronegative at their first pregnancy with a subsequent pregnancy within 2 years have the highest risk of delivering a child with cCMV-related sequelae. These women should be made aware of the risk and given the opportunity of serology screening in the first trimester.

19.
Clin Infect Dis ; 69(9): 1526-1532, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30596974

RESUMO

BACKGROUND: The known relationship between the gestational age at maternal primary infection an the outcome of congenital CMV is based on small, retrospective studies conducted between 1980 and 2011. They reported that 32% and 15% of cases had sequelae following a maternal primary infection in the first and second or the third trimester, respectively. We aimed to revisit this relationship prospectively between 2011 and 2017, using accurate virological tools. METHODS: We collected data on women with a primary infection and an infected child aged at least 1 year at the time of analysis. An accurate determination of the timing of the primary infection was based upon serial measurements of immunoglobulin (Ig) M and IgG and on IgG avidity in sera collected at each trimester. The case outcome was assessed according to a structured follow-up between birth and 48 months. RESULTS: We included 255 women and their 260 fetuses/neonates. The dating of the maternal infection was prospective in 86% of cases and retrospective in 14%. At a median follow-up of 24 months, the proportion of sensorineural hearing loss and/or neurologic sequelae were 32.4% (95% confidence interval [CI] 23.72-42.09) after a maternal primary infection in the first trimester, 0 (95% CI 0-6.49) after an infection in the second trimester, and 0 (95% CI 0-11.95) after an infection in the third trimester (P < .0001). CONCLUSIONS: These results suggest that a cytomegalovirus infection can be severe only when the virus hits the fetus in the embryonic or early fetal period. Recent guidelines recommend auditory follow-ups for at least 5 years for all infected children. This raises parental anxiety and generates significant costs. We suggest that auditory and specialized neurologic follow-ups may be recommended only in cases of a maternal infection in the first trimester.

20.
Brain Pathol ; 29(1): 114-125, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30020561

RESUMO

BACKGROUND: The recent outbreak of Zika virus (ZIKV) infection and the associated increased prevalence of microcephaly in Brazil underline the impact of viral infections on embryo fetal development. The aim of the present study is to provide a detailed clinical and histopathological study of the fetal disruption caused by the ZIKV, with a special focus on the associated neuropathological findings. METHODS: A detailed feto-placental examination, as well as neuropathological and neurobiological studies were performed on three fetuses collected after pregnancy termination between 22 and 25 weeks of gestation (WG), because brain malformations associated with a maternal and fetal ZIKV infection was diagnosed. RESULTS: In all three cases, the maternal infection occurred during the first trimester of pregnancy. A small head was observed on the ultrasound examination of the second trimester of pregnancy and led to the diagnosis of ZIKV fetopathy and pregnancy termination. The fetal histopathological examination was unremarkable on the viscera but showed on the testis an interstitial lymphocytic infiltrate. The placenta contained a Hofbauer cells hyperplasia with signs of inflammation. Neuropathological findings included a meningoencephalitis and an ex vacuo hydrocephalus. Immunohistochemical studies showed the presence of T lymphocytic and histiocytic meningitis associated with an abundant cerebral astroglial and macrophagic reaction. In situ hybridization demonstrated, abundant ZIKV particles within the cerebral parenchyma mainly in the ventricular/subventricular zone and in the cortical plate. In addition massive cells death and endoplasmic reticulum damage were present. CONCLUSION: The present study reports on the clinical and histopathological findings observed in three fetuses infected by the ZIKV. It emphasizes the severity of brain damages and the minimal visceral and placental changes observed upon ZIKV infection. This confirms the selective neurotropism of ZIKV. Finally, it allows us to describe the cascade of multifactorial developmental defects leading to microcephaly.


Assuntos
Feto Abortado/fisiopatologia , Infecção por Zika virus/patologia , Encéfalo/patologia , Encéfalo/virologia , Brasil , Feminino , Feto , Humanos , Hidrocefalia/patologia , Microcefalia , Gravidez , Zika virus/patogenicidade
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