RESUMEN
Oropouche virus could be linked to brain malformation and stillbirths, Brazilian health officials say.
Asunto(s)
Encéfalo , Infecciones por Bunyaviridae , Transmisión Vertical de Enfermedad Infecciosa , Microcefalia , Orthobunyavirus , Mortinato , Femenino , Humanos , Embarazo , Encéfalo/anomalías , Encéfalo/virología , Brasil/epidemiología , Feto/virología , Mortinato/epidemiología , Infecciones por Bunyaviridae/epidemiología , Microcefalia/virologíaRESUMEN
Bovine Papillomaviruses (BPVs) constitute a diverse group within the Papillomaviridae family, playing a crucial role in bovine health and economic considerations. This study investigates the dynamics of vertical transmission of BPV in cattle, focusing on five cows and their reproductive tissues, as well as three gravid cows and their fetuses. DNA and RNA samples were extracted from the warts, fetal skin, placenta, uterus, ovary, and blood of cows, as well as the skin and blood of fetuses. Polymerase Chain Reaction (PCR) targeted BPV types 1-6 and 8-14, was assessed in both cows and fetuses. Additionally, Reverse Transcription PCR (RT-PCR) examined BPV-2 E5 oncogene expression in the skin and reproductive sites of mother cows and fetuses. Our findings unveil a rich diversity of BPV types, including BPV-2, 3, 9, 10, 12, and 14, present in both maternal and fetal tissues. Intriguingly, certain types, namely BPV-4, 6, 8, and 11, were exclusively identified in maternal tissues A higher diversity of BPVs was observed in cow warts, followed by cow blood, fetal blood, and fetal skin. Strikingly similar BPV types in gravid cow blood and fetuses suggest primary dissemination through the bloodstream and transmission via the placenta, though detected in lower numbers in cow uterus and ovary. Histopathological analysis revealed no abnormalities in the reproductive tissues despite the presence of BPV. However, in one bladder sample from a cow that did not consume bracken fern, urothelial neoplasia in situ was observed. The study extends beyond detection, exploring the expression of the BPV-2 E5 oncogene in fetal tissues, providing insights into potential cell implications. Comparative analyses with previous studies highlight the uniqueness of our investigation, encompassing a broader array of BPV types in the gravid cows and their fetuses. The findings not only establish a foundation for further investigations into the mechanisms of vertical transmission but also highlight the need for targeted interventions and surveillance strategies to mitigate potential health risks associated with specific BPV types.
Asunto(s)
Enfermedades de los Bovinos , Feto , Transmisión Vertical de Enfermedad Infecciosa , Infecciones por Papillomavirus , Animales , Bovinos , Femenino , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/transmisión , Infecciones por Papillomavirus/veterinaria , Transmisión Vertical de Enfermedad Infecciosa/veterinaria , Enfermedades de los Bovinos/virología , Enfermedades de los Bovinos/transmisión , Embarazo , Feto/virología , Placenta/virología , Papillomavirus Bovino 1/genética , Papillomavirus Bovino 1/aislamiento & purificación , Piel/virologíaRESUMEN
Ovine gammaherpesvirus 2 (OvGHV2) produces sheep-associated malignant catarrhal fever (SA-MCF), a frequently lethal, lymphoproliferative disease that is characterized by widespread vascular lesions. Most studies that evaluated the viral load in tissues of animals with SA-MCF were done in the Northern Hemisphere, with scant information from the Southern part of the globe. This study investigated the viral load of OvGHV2 in the tissues of cattle and an underdeveloped fetus with SA-MCF from three distinct biomes of Brazil. All animals had clinical and histopathological manifestations consistent with SA-MCF. Molecular testing identified the OvGHV2 tegument protein and glycoprotein B genes in the tissues of all animals and the fetus. Viral quantification based on the DNA polymerase gene detected elevated loads of OvGHV2 in tissues with histopathological evidence of SA-MCF and organs with unknown histological data, except for the tissues of the fetus, where the viral load was comparatively reduced. The viral loads detected in multiple organs of cattle from this study with SA-MCF are consistent with those identified in different animal species from the USA and Europe. The detection of a low viral load of OvGHV2 in fetal tissue confirmed transplacental dissemination since elevated viral loads were detected in multiple tissues of the cow with SA-MCF. Furthermore, the elevated viral loads detected in the pulmonary tissues of cattle with interstitial pneumonia indicate that OvGHV2 is an inductor of pulmonary disease in cattle.
Asunto(s)
Gammaherpesvirinae , Fiebre Catarral Maligna , Carga Viral , Animales , Fiebre Catarral Maligna/virología , Fiebre Catarral Maligna/patología , Gammaherpesvirinae/aislamiento & purificación , Gammaherpesvirinae/genética , Bovinos , Brasil , Ovinos , Femenino , Enfermedades de las Ovejas/virología , Enfermedades de las Ovejas/patología , ADN Viral/genética , Enfermedades de los Bovinos/virología , Infecciones por Herpesviridae/veterinaria , Infecciones por Herpesviridae/virología , Feto/virologíaRESUMEN
Zika virus (ZIKV) is a mosquito-borne pathogen that recently caused a major epidemic in the Americas. Although the majority of ZIKV infections are asymptomatic, the virus has been associated with birth defects in fetuses and newborns of infected mothers as well as neurological complications in adults. We performed a descriptive analysis on approximately 106,000 suspected and laboratory-confirmed cases of Zika virus disease (ZVD) that were reported during the 2015-2017 epidemic in Colombia. We also analyzed a dataset containing patients with neurological complications and recent febrile illness compatible with ZVD. Females had higher cumulative incidence of ZVD than males. Compared to the general population, cases were more likely to be reported in young adults (20 to 39 years of age). We estimated the cumulative incidence of ZVD in pregnant females at 3,120 reported cases per 100,000 population (95% CI: 3,077-3,164), which was considerably higher than the incidence in both males and non-pregnant females. ZVD cases were reported in all 32 departments. Four-hundred and eighteen patients suffered from ZIKV-associated neurological complications, of which 85% were diagnosed with Guillain-Barré syndrome. The median age of ZIKV cases with neurological complications was 12 years older than that of ZVD cases. ZIKV-associated neurological complications increased with age, and the highest incidence was reported among individuals aged 75 and older. Even though neurological complications and deaths due to ZIKV were rare in this epidemic, better risk communication is needed for people living in or traveling to ZIKV-affected areas.
Asunto(s)
Enfermedades del Sistema Nervioso/epidemiología , Infección por el Virus Zika/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Américas/epidemiología , Niño , Preescolar , Colombia/epidemiología , Brotes de Enfermedades , Femenino , Feto/virología , Síndrome de Guillain-Barré/epidemiología , Síndrome de Guillain-Barré/virología , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/virología , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/virología , Adulto Joven , Virus Zika/patogenicidad , Infección por el Virus Zika/virologíaRESUMEN
BACKGROUND: PCV3 is a member of the Circovirus family, associated with disease and mortality in pigs. It is not clear whether PCV3 putatively causes clinical symptoms and disease. In the present case, we reported a gilt infected with PCV3 associated with reproductive failures, vertical transmission, tissue lesions, viral replication by in situ hybridization, and the hypothesis that some strains of PCV3 clade one are associated with reproductive failures at the field level. CASE PRESENTATION: In May 2019, a pig farm in Colombia reported increased reproductive failures, and the presence of PCV3 in gilts and sows was established in a single form or coinfections, mainly with PCV2 and PPV7. Ten sows with a single infection with PCV3 were found, and one gilt with a pre-farrowing serum viral load above 103 was studied. This gilt was followed up during the pre-farrowing, farrowing period and on her litter for 6 weeks. During dystocic farrowing, a mummy and ten piglets were released, including two weak-born piglets. The highest viral loads for PCV3 were found in the mummy and the placenta. In the weak-born piglets, there were viral loads both in serum and in tissues, mainly in the mesenteric ganglia and lung. Replication of PCV3 in these tissues was demonstrated by in situ hybridizations. PCV3 was also found in the precolostrum sera of piglets and colostrum, showing vertical transmission. The viral load in piglets decreased gradually until week six of life. The viral genome's complete sequencing was made from the mummy, and its analysis classified it as PCV3 clade one. CONCLUSIONS: This report confirms that PCV3 can cause disease at the field level, and putatively, in this case, we find the generation of reproductive failures. The ability of PCV3 to cause disease as a putative pathogen may be associated with the viral load present in the pig and the strain that is affecting the farm. For this case, we found that viral loads above 103 (4.93 log genomic copies / mL) in the gilt were associated with clinical manifestation and that some PCV3 strains belonging to clade one are more associated with the reproductive presentation.
Asunto(s)
Infecciones por Circoviridae/veterinaria , Circovirus/clasificación , Transmisión Vertical de Enfermedad Infecciosa/veterinaria , Complicaciones Infecciosas del Embarazo/veterinaria , Enfermedades de los Porcinos/virología , Aborto Veterinario/virología , Animales , Infecciones por Circoviridae/patología , Infecciones por Circoviridae/virología , Circovirus/genética , Femenino , Feto/virología , Filogenia , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Mortinato/veterinaria , Porcinos , Enfermedades de los Porcinos/patologíaRESUMEN
To date, mother-to-fetus transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19) pandemic, remains controversial. Although placental COVID-19 infection has been documented in some cases during the second- and third-trimesters, no reports are available for the first trimester of pregnancy, and no SARS-CoV-2 protein has been found in fetal tissues. We studied the placenta and fetal organs from an early pregnancy miscarriage in a COVID-19 maternal infection by immunohistochemical, reverse transcription quantitative real-time polymerase chain reaction, immunofluorescence, and electron microscopy methods. SARS-CoV-2 nucleocapsid protein, viral RNA, and particles consistent with coronavirus were found in the placenta and fetal tissues, accompanied by RNA replication revealed by double-stranded RNA (dsRNA) positive immunostain. Prominent damage of the placenta and fetal organs were associated with a hyperinflammatory process identified by histological examination and immunohistochemistry. The findings provided in this study document that congenital SARS-CoV-2 infection is possible during the first trimester of pregnancy and that fetal organs, such as lung and kidney, are targets for coronavirus. The infection and multi-organic fetal inflammation produced by SARS-CoV-2 during early pregnancy should alert clinicians in the assessment and management of pregnant women for possible fetal consequences and adverse perinatal outcomes.
Asunto(s)
COVID-19/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Placenta/virología , Complicaciones Infecciosas del Embarazo/virología , SARS-CoV-2/metabolismo , Aborto Espontáneo/virología , Adulto , COVID-19/patología , Femenino , Feto/patología , Feto/virología , Humanos , Placenta/patología , Embarazo , Resultado del Embarazo , Primer Trimestre del Embarazo , Mujeres Embarazadas , ARN Viral/análisisRESUMEN
The occurrence of fetal and neonatal disorders in pregnant women with Zika virus infection in the literature is not consistent. This study aims to estimate the prevalence rate of these disorders in fetuses/neonates of pregnant women with confirmed or probable infection by Zika virus. A systematic review with meta-analysis was conducted in November 2020. Cohort studies that contained primary data on the prevalence of unfavorable outcomes in fetuses or neonates of women with confirmed or probable Zika virus infection during pregnancy were included. A total of 21 cohort studies were included, with a total of 35,568 pregnant women. The meta-analysis showed that central nervous system abnormalities had the highest prevalence ratio of 0.06 (95% CI 0.03-0.09). Intracranial calcifications had a prevalence ratio of 0.01 (95% CI 0.01-0.02), and ventriculomegaly 0.01 (95% CI 0.01-0.02). The prevalence ratio of microcephaly was 0.03 (95% CI 0.02-0.05), fetal loss (miscarriage and stillbirth) was 0.04 (95% CI 0.02-0.06), Small for Gestational Age was 0.04 (95% CI 0.00-0,09), Low Birth Weight was 0.05 (95% CI 0.03-0.08) and Prematurity was 0.07 (95% CI 0.04-0.10). The positivity in RT-PCR for ZIKV performed in neonates born to infected mothers during pregnancy was 0.25 (95% CI 0.06-0.44). We also performed the meta-analysis of meta-analysis for microcephaly with the prevalence ratios from other two previously systematic reviews: 0.03 (95% CI 0.00-0.25). Our results contribute to measuring the impact of Zika virus infection during pregnancy on children's health. The continuous knowledge of this magnitude is essential for the implementation development of health initiatives and programs, in addition to promoting disease prevention, especially in the development of a vaccine for Zika virus. PROSPERO protocol registration: http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42019125543.
Asunto(s)
Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/virología , Infección por el Virus Zika/epidemiología , Aborto Espontáneo/virología , Estudios de Cohortes , Femenino , Enfermedades Fetales/epidemiología , Enfermedades Fetales/virología , Feto/virología , Humanos , Hidrocefalia/virología , Lactante , Recién Nacido de Bajo Peso , Recién Nacido , Masculino , Microcefalia/epidemiología , Malformaciones del Sistema Nervioso/virología , Embarazo , Complicaciones Infecciosas del Embarazo/mortalidad , Resultado del Embarazo , Atención Prenatal , Prevalencia , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/mortalidadRESUMEN
BACKGROUND: Although it is known that Zika virus (ZIKV) infection during pregnancy may lead to microcephaly in the fetus, the prognostic factors associated with this tragic disorder remain unclear. We conducted a systematic review and meta-analysis to assess the prognostic factors associated with the incidence of microcephaly in congenital ZIKV infection. METHODS: We conducted a comprehensive search in Ovid MEDLINE, Ovid MEDLINE (R) Epub ahead of print, Embase, Embase Classic, Web of Science, CINAHL, Cochrane CENTRAL, LILACS, and various thesis databases to identify human studies reporting microcephaly associated with congenital ZIKV infection. We requested primary data from the authors of the included studies to calculate summary estimates and conduct the meta-analysis of the most prevalent factors. RESULTS: We screened 4106 titles and abstracts, and identified 12 studies for inclusion in the systematic review. The assessment of ZIKV infection and the definition of microcephaly varied among studies. A total of 6154 newborns/fetuses were enrolled; of those, 1120 (18.20%) had a diagnostic of ZIKV infection, of which 509 (45.45%) were diagnosed with microcephaly. Nine studies addressed the link between congenital ZIKV infection and neurological findings in newborns/fetuses. Half of the studies provided primary data. Three out of 11 factors of interest seem to be prognostic factors of microcephaly: infant's sex - males compared to females: Relative Risk (RR) 1.30, 95% Confidence Interval (95% CI) 1.14 to 1.49; the stage of pregnancy when infection occurred - infection in the first trimester of pregnancy compared to infection at other stages of pregnancy: RR 1.41, 95% CI 1.09 to 1.82; and asymptomatic infection compared to symptomatic infection during pregnancy: RR 0.68; 95% CI 0.60 to 0.77. CONCLUSION: Our findings support the female-biased resistance hypothesis and reinforce the risk associated with the stage of pregnancy when ZIKV infection occurs. Continued surveillance of ZIKV infection during pregnancy is needed to identify additional factors that could contribute to developing microcephaly in affected fetuses. PROTOCOL REGISTRATION: This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration no. CRD 42018088075.
Asunto(s)
Feto/virología , Microcefalia/fisiopatología , Complicaciones Infecciosas del Embarazo/fisiopatología , Infección por el Virus Zika/fisiopatología , Virus Zika/patogenicidad , Adulto , Edad de Inicio , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Microcefalia/epidemiología , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/virología , Trimestres del Embarazo , Prevalencia , Factores Sexuales , Infección por el Virus Zika/epidemiologíaRESUMEN
During pregnancy, the organization of complex tolerance mechanisms occurs to assure non-rejection of the semiallogeneic fetus. Pregnancy is a period of vulnerability to some viral infections, mainly during the first and second trimesters, that may cause congenital damage to the fetus. Recently, Zika virus (ZIKV) infection has gained great notoriety due to the occurrence of congenital ZIKV syndrome, characterized by fetal microcephaly, which results from the ability of ZIKV to infect placental cells and neural precursors in the fetus. Importantly, in addition to the congenital effects, studies have shown that perinatal ZIKV infection causes a number of disorders, including maculopapular rash, conjunctivitis, and arthralgia. In this paper, we contextualize the immunological aspects involved in the maternal-fetal interface and vulnerability to ZIKV infection, especially the alterations resulting in perinatal outcomes. This highlights the need to develop protective maternal vaccine strategies or interventions that are capable of preventing fetal or even neonatal infection.
Asunto(s)
Intercambio Materno-Fetal/inmunología , Complicaciones Infecciosas del Embarazo/inmunología , Infección por el Virus Zika/inmunología , Virus Zika/inmunología , Femenino , Feto/inmunología , Feto/virología , Humanos , Microcefalia/inmunología , Microcefalia/virología , Placenta/inmunología , Placenta/virología , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Virus Zika/fisiología , Infección por el Virus Zika/virologíaRESUMEN
The clinical implications of recently discovered porcine circovirus 3 (PCV3) infections are still unknown. The potential role of this emerging virus in reproductive loss in swine has been described. Herein, we report a high prevalence of PCV3 in mummified fetuses from sows maintained in modern farms in Rio Grande do Sul, Santa Catarina, Paraná, Goiás, and Mato Grosso do Sul states, Brazil. For this analysis, 276 mummified fetuses from 11 commercial swine farms were included. The presence of PCV3 DNA was confirmed using PCR, and the complete sequence of five different viral strains was obtained. Sequences of PCV3 genomes available on GenBank were then used for phylogenetic tree construction. Of the 276 mummified fetuses examined, 270 (nearly 97%) were positive for PCV3. In 93.1% of the fetuses, co-infections with at least one of the following agents were identified: porcine parvovirus (PPV), porcine circovirus 2 (PCV2) and Leptospira spp. Twelve fetuses were positive for PCV3 alone. The amino acid sequence of the capsid gene for the five viral strains shared 98-100% homology among them. Analysis of the DNA sequence indicates that the viruses identified in this study belong to the PCV3a1 subgroup. In summary, PCV3 DNA was detected in mummified fetuses at a surprisingly high rate. The role of PCV3 in porcine circovirus-associated disease (PCVAD) is still uncertain. However, considering that PCV3 has been detected in a variety of conditions, even in healthy animals, the present results confirm the need to investigate PCV3 as a causative agent of fetal mummification in swine.
Asunto(s)
Circovirus/genética , Feto/virología , Genoma Viral , Animales , Brasil/epidemiología , Proteínas de la Cápside/genética , Infecciones por Circoviridae/epidemiología , Infecciones por Circoviridae/veterinaria , Circovirus/clasificación , Circovirus/patogenicidad , Coinfección/epidemiología , Coinfección/veterinaria , Granjas , Leptospira/aislamiento & purificación , Leptospirosis/veterinaria , Infecciones por Parvoviridae/veterinaria , Parvovirus Porcino/aislamiento & purificación , Filogenia , Prevalencia , Porcinos , Enfermedades de los Porcinos/virologíaRESUMEN
Dengue virus (DENV) is an emerging virus involved in outbreaks in Brazil. The association between the virus and vertical transmission, with disorders in the placenta, has raised a worldwide concern. On the 29th gestational week, a pregnant woman presented severe complications due to a DENV infection leading to maternal and fetus death. Postmortem analysis of fetal organs demonstrated the presence of DENV using reverse transcriptase polymerase chain reaction (RT-PCR) in the fetal brain and DENV non-structural protein 3 (NS3) staining in placenta and several peripheral fetal tissues, such as the brain, liver, lungs, and spleen. Histological analysis of the placenta and fetal organs revealed different types of tissue abnormalities, which included inflammation, hemorrhage, edema, and necrosis in placenta and tissue disorganization in the fetus, such as spongiform parenchyma, microglial inflammation, steatosis, hyalinose arteriolar, inflammatory cells in the alveolar septa, and disorganization of the lymphoid follicle. Increased cellularity (macrophage, Hofbauer cells and TCD8+ lymphocytes) and up-regulation of inflammatory mediators such as IFN-γ, TNF-α, RANTES/CCL5, MCP1/CCL2, and VEGF/R2 were detected in the liver, lung, spleen, brain, and placenta, supporting placental and fetus peripheral tissues inflammation. Maternal infection leading to the production of those vascular mediators may alter the vascular permeability, facilitating the virus entry and tissue and barrier dysfunction.
Asunto(s)
Dengue/patología , Dengue/virología , Mediadores de Inflamación/metabolismo , Complicaciones Infecciosas del Embarazo/patología , Complicaciones Infecciosas del Embarazo/virología , Adulto , Brasil , Dengue/fisiopatología , Virus del Dengue/aislamiento & purificación , Virus del Dengue/fisiología , Femenino , Feto/metabolismo , Feto/patología , Feto/virología , Edad Gestacional , Humanos , Transmisión Vertical de Enfermedad Infecciosa , Muerte Materna , Placenta/metabolismo , Placenta/patología , Placenta/virología , Embarazo , Complicaciones Infecciosas del Embarazo/fisiopatología , MortinatoRESUMEN
Bovine parainfluenza virus-3 (BPIV-3) is a recognized respiratory pathogen of cattle, and it has also been identified in aborted fetuses. However, little is known of this agent as a reproductive pathogen and detailed descriptions of fetal pathology on natural cases are lacking in the scientific literature. This article describes and illustrates lesions in a fetus spontaneously aborted by a first-calving Holstein heifer, naturally infected with BPIV-3 genotype A, broadening the current knowledge on fetal pathology by this virus. Fetal autopsy revealed diffusely reddened, rubbery and unexpanded lungs. Histologically, there was necrotizing bronchiolitis/alveolitis with intraluminal fibrin exudate and syncytial cells in the bronchiolar/alveolar spaces, and non-suppurative peribronchiolitis and perivascular interstitial pneumonia. In the small intestine there was multifocal necrotizing cryptitis and occasional necrotic syncytial enterocytes. Intralesional and extralesional BPIV-3 antigen was detected by immunohistochemistry in the lung and small intestine, and BPIV-3a was identified in fetal tissues by RT-PCR and sequencing.
Asunto(s)
Aborto Veterinario/patología , Enfermedades de los Bovinos/patología , Enfermedades Fetales/veterinaria , Virus de la Parainfluenza 3 Bovina , Infecciones por Respirovirus/veterinaria , Aborto Veterinario/etiología , Aborto Veterinario/virología , Animales , Bovinos , Enfermedades de los Bovinos/virología , Femenino , Enfermedades Fetales/patología , Enfermedades Fetales/virología , Feto/patología , Feto/virología , Virus de la Parainfluenza 3 Bovina/genética , Filogenia , Embarazo , Infecciones por Respirovirus/complicaciones , Infecciones por Respirovirus/patología , Infecciones por Respirovirus/virologíaRESUMEN
BACKGROUND: An intricate fetal-maternal immune crosstalk during pregnancy is essential for a healthy birth. Hence, the infection-induced alterations of maternal immunity often lead to adverse outcomes for mother and/or child. The emergence of Zika virus (ZIKV) infection in pregnant women has been associated with more than 3,000 cases of microcephaly and nervous system malformations. METHODS: To explore the potential correlation of ZIKV-induced alteration of maternal immunity with fetal abnormalities, we performed extensive sera immunoprofiling of 74 pregnant women: 30 symptomatic ZIKV+ pregnant patients and 30 healthy pregnant controls in ZIKV-endemic Rio de Janeiro, along with 14 healthy pregnant controls in non-endemic Los Angeles. RESULTS: Extensive multiplexing analysis of 69 cytokines revealed that CXCL10, CCL2, and CCL8 chemokines were specifically associated with symptomatic ZIKV+ infection during pregnancy, and distinct immunoprofiles were detected at different trimesters in ZIKV-infected pregnant women. Intriguingly, the high CCL2 level and its inverse correlation with CD163, TNFRSF1A, and CCL22 levels was apparently associated with ZIKV-induced abnormal birth. CONCLUSION: Our findings provide insights into the alteration of ZIKV-elicited maternal immunity, serving as a potential clinical biomarker platform. FUNDING: NIH (CA200422, CA180779, DE023926, AI073099, AI116585, AI129496, AI140705, AI069120, AI056154, AI078389, AI28697, AI40718 and AI129534-01), Hastings Foundation, Fletcher Jones Foundation, Departamento de Ciência e Tecnologia (DECIT/25000.072811/2016-17) do Ministério da Saúde do Brasil, and Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior CAPES/88887.116627/2016-01.
Asunto(s)
Biomarcadores/metabolismo , Feto/anomalías , Microcefalia/etiología , Infección por el Virus Zika/metabolismo , Virus Zika/inmunología , Adolescente , Adulto , Biomarcadores/sangre , Brasil/epidemiología , Citocinas/sangre , Citocinas/metabolismo , Femenino , Feto/metabolismo , Feto/virología , Voluntarios Sanos , Humanos , Inmunidad Materno-Adquirida/fisiología , Microcefalia/epidemiología , Embarazo , Resultado del Embarazo/epidemiología , Trimestres del Embarazo , Estados Unidos/epidemiología , Adulto Joven , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/epidemiologíaRESUMEN
The recent emergence of Zika virus (ZIKV) in Brazil was associated with an increased number of fetal brain infections that resulted in a spectrum of congenital neurological complications known as congenital Zika syndrome (CZS). Herein, we generated de novo from sequence data an early Asian lineage ZIKV isolate (ZIKV-MY; Malaysia, 1966) not associated with microcephaly and compared the in vitro replication kinetics and fetal brain infection in interferon α/ß receptor 1 knockout (IFNAR1-/-) dams of this isolate and of a Brazilian isolate (ZIKV-Natal; Natal, 2015) unequivocally associated with microcephaly. The replication efficiencies of ZIKV-MY and ZIKV-Natal in A549 and Vero cells were similar, while ZIKV-MY replicated more efficiently in wild-type (WT) and IFNAR-/- mouse embryonic fibroblasts. Viremias in IFNAR1-/- dams were similar after infection with ZIKV-MY or ZIKV-Natal, and importantly, infection of fetal brains was also not significantly different. Thus, fetal brain infection does not appear to be a unique feature of Brazilian ZIKV isolates.
Asunto(s)
Encéfalo/virología , Feto/virología , Complicaciones Infecciosas del Embarazo/virología , Infección por el Virus Zika/patología , Infección por el Virus Zika/virología , Animales , Chlorocebus aethiops , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Placenta/virología , Embarazo , Receptor de Interferón alfa y beta/deficiencia , Receptor de Interferón alfa y beta/genética , Células Vero , Viremia , Replicación Viral , Virus Zika/fisiologíaRESUMEN
Zika virus (ZIKV) has caused substantial concern worldwide owing to its association with severe birth defects, such as microcephaly and other congenital malformations. Inflammasomes, i.e., multi-protein complexes that induce inflammation and pyroptosis, are predicted to contribute to the immune response to this flavivirus. Accordingly, in this study, the in situ inflammasome response was evaluated in fatal cases of ZIKV-linked microcephaly. Brain tissue samples were collected from eight babies, including four ZIKV-positive microcephalic neonates who died after birth and four flavivirus-negative neonatal controls who died of other causes and whose central nervous system (CNS) architecture was preserved. In the ZIKV-positive newborn/stillbirth babies, the major histopathological alterations included atrophy of the cortical layer, a predominance of mononuclear cell infiltration in the Virchow-Robin space, neuronal necrosis, vacuolization and neuronal degeneration, neuronophagy, and gliosis. An immunohistochemical analysis of tissues in the neural parenchyma showed significantly higher expression of the receptors NLRP1, NLRP3, and AIM2, cytokines IL-1ß, IL-18, and IL-33, and enzymes caspase 1, iNOS, and arginase 1 in ZIKV-positive microcephaly cases than in flavivirus-negative controls. These results suggest that inflammasome activation can aggravate the neuroinflammatory response and consequently increase CNS damage in neonates with fetal neural ZIKV infection and microcephaly.
Asunto(s)
Sistema Nervioso Central/patología , Sistema Nervioso Central/virología , Inflamasomas/fisiología , Microcefalia/patología , Microcefalia/virología , Infección por el Virus Zika/patología , Virus Zika/patogenicidad , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/virología , Sistema Nervioso Central/metabolismo , Citocinas/metabolismo , Femenino , Feto/metabolismo , Feto/virología , Humanos , Recién Nacido , Inflamasomas/metabolismo , Masculino , Microcefalia/metabolismo , Embarazo , Complicaciones Infecciosas del Embarazo/metabolismo , Complicaciones Infecciosas del Embarazo/patología , Complicaciones Infecciosas del Embarazo/virología , Infección por el Virus Zika/metabolismo , Infección por el Virus Zika/virologíaRESUMEN
Early miscarriage is still a concern, and viral infections are recognised as one of the causes of this adverse outcome. The causal relationship between HPV and miscarriage remains controversial. The aim of the study was to evaluate whether HPV infection indeed may occur in both the maternal and placental tissue in cases of miscarriage. Decidual and chorionic villi fragments (n = 118) were dissected from 81 miscarriage cases, 68 spontaneous and 13 intentional. HPV DNA was detected using the consensus primers MY09/11; in eight cases (9.9%, 8/81), seven of which (10.3%) were from spontaneous miscarriages and one (7.7%), was from an intentional miscarriage. The deciduas (4/8) and chorionic villi (5/8) were both infected with HPV. A reverse line blot was used to genotype HPV positive samples and revealed HPV6, 11, 58, 66 and 82. Although the results obtained cannot infer an association between HPV and pregnancy loss, it cannot be ruled out. Impact Statement What is already known on this subject? Miscarriages are considered to be the most common complication in pregnancy. Several possible causes of miscarriage have been considered, and the role of infections as one of those is confirmed, especially during the second trimester of pregnancy. The prevalence of HPV in conception products is still questionable. However, an HPV infection should not be ignored and its association with miscarriage must be considered. What the results of this study add? The present study reveals the presence of HPV in the foetal and maternal tissues of conception. What the implications are of these findings for clinical practice and/or further research? This issue deserves further investigation aiming to clarify the role of HPV in miscarriage cases; which are mainly related to the specific type and grade of tissues' abnormalities found co-topographically with a virus presence.
Asunto(s)
Aborto Espontáneo/virología , Infecciones por Papillomavirus/complicaciones , Adolescente , Adulto , Estudios Transversales , Femenino , Feto/virología , Humanos , Papillomaviridae/genética , Placenta/virología , Embarazo , Adulto JovenAsunto(s)
Anomalías Congénitas/virología , Feto/anomalías , Leche Humana/virología , Enfermedades del Sistema Nervioso/virología , Virus Zika/aislamiento & purificación , Adulto , Líquidos Corporales/virología , Brasil , Anomalías Congénitas/diagnóstico por imagen , Femenino , Feto/diagnóstico por imagen , Feto/virología , Genotipo , Humanos , Recién Nacido , Madres , Enfermedades del Sistema Nervioso/diagnóstico por imagen , Filogenia , Embarazo , ARN Viral/análisis , ARN Viral/orina , Ultrasonografía , Virus Zika/genéticaRESUMEN
Congenital tremor in pigs involves several etiologies, including pestivirus, which may cause neurological injuries in different animal species. To evaluate whether bovine viral diarrhea virus (BVDV), an important pestivirus, is one of the etiological agents of congenital tremor in swine, gilts and the fetuses were challenged at 45 days of gestation with BVDV-2. Four pregnant gilts were inoculated oronasally, four gilts underwent fetal intrauterine inoculation, and two gilts constituted the control group. Antibody titers were determined by virus neutralization (VN), and viral RNA was detected by RT-PCR. Blood samples were collected from all gilts and piglets born to obtain whole blood and serum for analysis. One third of the neonates were euthanized at three days old, and samples of the encephalon, brain stem and spinal cord were collected for anatomopathological evaluation and viral RNA detection. The piglets that remained alive were clinically evaluated every day, and blood sampling was performed regularly for 35 days. The piglets from gilts in both inoculation treatment groups showed no clinical neurological signs and were born with no viral RNA in their blood and organs. Piglets born from oronasally inoculated gilts did not present antibodies against BVDV-2 at birth, although they were acquired by passive maternal transfer. In contrast, intrauterine-inoculated piglets were born with high antibody titers (80 to 640) against the agent, which remained high until the end of the experimental period. Microscopically, no noticeable changes were observed. Macroscopically, 29.5% of the total piglets euthanized, from both inoculation groups, were born with a low cerebellar:brain ratio. Nevertheless, some piglets had a high cerebellar:brain ratio, indicating the need for standardizing this value. Thus, it was concluded that BVDV is not an etiological agent for congenital swine tremor.
Asunto(s)
Diarrea Mucosa Bovina Viral/virología , Cerebelo/anomalías , Malformaciones del Sistema Nervioso/veterinaria , Enfermedades de los Porcinos/congénito , Temblor/congénito , Temblor/etiología , Animales , Animales Lactantes , Anticuerpos Antivirales/sangre , Encéfalo/virología , Bovinos , Cerebelo/virología , Discapacidades del Desarrollo/virología , Virus de la Diarrea Viral Bovina Tipo 2/genética , Virus de la Diarrea Viral Bovina Tipo 2/aislamiento & purificación , Femenino , Feto/virología , Malformaciones del Sistema Nervioso/virología , Placenta/virología , Embarazo , Complicaciones Infecciosas del Embarazo/virología , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Porcinos , Enfermedades de los Porcinos/virología , Temblor/virologíaRESUMEN
BACKGROUND: Antenatal exposure to Zika virus (ZIKV) is related to severe neurological manifestations. A previous study in Brazil reported an increased incidence of non-severe congenital heart defects in infants with diagnosis of congenital Zika syndrome but without laboratory confirmation of ZIKV infection in the mother or infant. The objective of this study is to report echocardiographic (ECHO) findings in infants with laboratory confirmed antenatal exposure to ZIKV. METHODOLOGY: Cross sectional study of cardiologic assessments of infants born between November 2015 and January 2017 with confirmed vertical exposure to ZIKV in Rio de Janeiro, Brazil. RESULTS: The study enrolled 120 children with a median age of 97 days (1 to 376 days). In utero exposure to ZIKV was confirmed in 97 children (80,8%) through positive maternal polymerase chain reaction (PCR) results during pregnancy or a positive PCR result at birth; 23 additional children (19.2%) had maternal positive PCR results during pregnancy and postnatally. Forty- eight infants (40%) had cardiac defects noted on ECHO. Thirteen infants (10.8%) had major cardiac defects (atrial septal defect, ventricular septal defect, patent ductus arteriosus). None of the defects were severe. The frequency of major defects was higher in infants whose mothers had a rash in the 2nd trimester of pregnancy, or who had altered Central Nervous System (CNS) imaging postnatally or were preterm. CONCLUSIONS: Infants with in utero ZIKV exposure have a higher prevalence of major cardiac defects, however none were severe enough to require immediate intervention. For this reason, guidelines for performance of postnatal ECHO in this population should follow general newborn screening guidelines, which significantly reduces the burden of performing emergent fetal or neonatal ECHOs in a setting where resources are not available, such as most Brazilian municipalities.
Asunto(s)
Cardiopatías Congénitas/diagnóstico por imagen , Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika/congénito , Líquido Amniótico/virología , Brasil/epidemiología , Sistema Nervioso Central/diagnóstico por imagen , Sistema Nervioso Central/virología , Estudios Transversales , Ecocardiografía , Femenino , Feto/virología , Humanos , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Masculino , Madres , Reacción en Cadena de la Polimerasa , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/virología , Virus Zika/genética , Virus Zika/patogenicidad , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/transmisión , Infección por el Virus Zika/virologíaRESUMEN
OBJECTIVE: To evaluate the fetal brain in pregnant women infected with Zika virus in a limited-resource setting. METHODS: In an observational study in Trinidad and Tobago, 100 pregnant women infected with Zika virus who were referred for fetal medicine services provided by a single clinician were enrolled from March 31 to September 2, 2016. Two-dimensional ultrasonography was undertaken. RESULTS: The women were aged 17-41 years (mean 27.5 ± 5.7). Six cases of fetal brain abnormalities consistent with Zika infection were detected before 26 gestational weeks. The gestational period at infection and time of presentation ranged, respectively, from 7+3 to 16+0 weeks and from 23+2 to 25+5 weeks. In all cases, centiles of the biparietal diameter and head circumference decreased progressively over time to below the third centile. The skull contour appeared irregular, owing to collapse or overlap of the fetal skull bones. In four cases, brain anomalies were not obvious on the transabdominal scan but were diagnosed on the transvaginal scan. In a further two cases, brain abnormalities presented after 26 weeks of gestation. CONCLUSION: Overall, 8.0% of women infected with Zika virus had fetuses with brain abnormalities suggestive of Zika congenital syndrome. Six cases were detected before 26 weeks and two cases after 26 weeks.