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1.
Texto & contexto enferm ; 29: e20180517, Jan.-Dec. 2020.
Artículo en Inglés | LILACS-Express | ID: biblio-1094554

RESUMEN

ABSTRACT Objective: to know how mothers affected by the Zika virus during pregnancy became aware on the diagnosis of Congenital Zika Virus Syndrome in their child and to understand the way in which the communication of the diagnosis was transmitted. Method: a qualitative approach study, with interpretative research, based on the Resilience, Stress, Adjustment and Family Adaptation Model. The research was conducted in a Specialized Rehabilitation Center in a city of Paraíba (Brazil), from June to November 2017, with 40 mothers of children with congenital Zika virus syndrome. The empirical material was produced from a semi-structured script developed by the researcher, related to the different phases and components of the adaptation and resilience process. The findings were submitted to content analysis. Results: two thematic categories were unveiled: The discovery of Congenital Zika Virus Syndrome: period of diagnosis and maternal expectations, and How to communicate the diagnosis: implications for the discovery of Congenital Zika Virus Syndrome. Conclusion: Communication of the diagnosis and professional conduct at the time of information play important roles in re-signifying the meaning of congenital malformation. The interaction established by the health professional and their posture are directly related to the satisfaction about the information received.


RESUMEN Objetivos: conocer de qué manera las madres afectadas por el virus del Zika se enteraron del diagnóstico del Síndrome Congénito del Virus del Zika en sus hijos, y determinar cómo se comunicó el diagnóstico. Método: estudio de enfoque cualitativo, con investigación interpretativa, fundamentado en el Modelo de Resiliencia, Estrés, Ajustes y Adaptación Familiar. La investigación se realizó en un Centro Especializado en Rehabilitación de un municipio da Paraíba (Brasil) entre junio y noviembre de 2017 con 40 madres de niños con el Síndrome Congénito del Virus del Zika. El material empírico se produjo a partir de un guión con carácter semiestructurado desarrollado por la investigadora, relacionado con las diferentes fases y componentes del proceso de adaptación y resiliencia. Los hallazgos se sometieron a análisis de contenido. Resultados: surgieron dos categorías temáticas: La detección del Síndrome Congénito del Virus del Zika: período del diagnóstico y expectativas maternas, y Cómo comunicar el diagnóstico: implicancias al momento de detectar el Síndrome Congénito del Virus del Zika. Conclusión: comunicar el diagnóstico y la conducta profesional al momento de dar la noticia tienen un peso importante en la resignificación del sentido de la malformación congénita. La interacción que establece el profesional de la salud y su postura están directamente relacionadas con el nivel de satisfacción con respecto a la información recibida.


RESUMO Objetivo: conhecer como as mães acometidas pelo Zika vírus na gestação souberam do diagnóstico da Síndrome Congênita do Zika vírus em seu(sua) filho(a) e apreender a forma com que a comunicação do diagnóstico foi transmitida. Método: estudo de abordagem qualitativa, com investigação interpretativa, fundamentado no Modelo de Resiliência, Estresse, Ajustamento e Adaptação Familiar. A pesquisa foi realizada em um Centro Especializado em Reabilitação de um município da Paraíba (Brasil), no período de junho a novembro de 2017, com 40 mães de crianças com a Síndrome Congênita do Zika vírus. O material empírico foi produzido a partir de um roteiro com caráter semiestruturado desenvolvido pela pesquisadora, relacionado com as diferentes fases e componentes do processo de adaptação e resiliência. Os achados foram submetidos à analise de conteúdo. Resultados: foram desveladas duas categorias temáticas: A descoberta da Síndrome Congênita do Zika vírus: período do diagnóstico e expectativas maternas, e A forma da comunicação do diagnóstico: implicações diante da descoberta da Síndrome Congênita do Zika vírus. Conclusão: a comunicação do diagnóstico e a conduta profissional no momento da informação possuem papéis importantes na ressignificação do sentido da malformação congênita. A interação estabelecida pelo profissional de saúde e sua postura estão diretamente relacionadas com a satisfação sobre a informação recebida.

2.
J Gen Virol ; 2020 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-32375993

RESUMEN

Zika virus (ZIKV) has recently emerged as an important human pathogen due to the strong evidence that it causes disease of the central nervous system, particularly microcephaly and Guillain-Barré syndrome. The pathogenesis of disease, including mechanisms of neuroinvasion, may include both invasion via the blood-brain barrier and via peripheral (including cranial) nerves. Cellular responses to infection are also poorly understood. This study characterizes the in vitro infection of laboratory-adapted ZIKV African MR766 and two Asian strains of (1) brain endothelial cells (hCMEC/D3 cell line) and (2) olfactory ensheathing cells (OECs) (the neuroglia populating cranial nerve I and the olfactory bulb; both human and mouse OEC lines) in comparison to kidney epithelial cells (Vero cells, in which ZIKV infection is well characterized). Readouts included infection kinetics, intracellular virus localization, viral persistence and cytokine responses. Although not as high as in Vero cells, viral titres exceeded 104 plaque-forming units (p.f.u.) ml-1 in the endothelial/neuroglial cell types, except hOECs. Despite these substantial titres, a relatively small proportion of neuroglial cells were primarily infected. Immunolabelling of infected cells revealed localization of the ZIKV envelope and NS3 proteins in the cytoplasm; NS3 staining overlapped with that of dsRNA replication intermediate and the endoplasmic reticulum (ER). Infected OECs and endothelial cells produced high levels of pro-inflammatory chemokines. Nevertheless, ZIKV was also able to establish persistent infection in hOEC and hCMEC/D3 cells. Taken together, these results provide basic insights into ZIKV infection of endothelial and neuroglial cells and will form the basis for further study of ZIKV disease mechanisms.

3.
Methods Mol Biol ; 2142: 1-8, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32367354

RESUMEN

From its discovery in Uganda in 1947, Zika virus (ZIKV) was considered a relatively innocuous viral pathogen with sporadic and infrequent occurrence of human infection. It was during an outbreak in French Polynesia in 2014 when cases of Guillain-Barré syndrome were identified as a serious complication of ZIKV infection in adults. However, in 2015, ZIKV emerged into and swept through South and Central America infecting millions of people. As part of the latter ZIKV outbreak, in Brazil, cases of microcephaly and other serious congenital complications affecting a large fraction of infants born to mothers infected during pregnancy were first identified and linked to ZIKV. This chapter reviews the history and clinical manifestations of ZIKV infection and mechanisms of immunoprotection. It is notable that, while limited, historical monographs identified most, if not all, of the precepts that are considered as newly discovered.

4.
Methods Mol Biol ; 2142: 9-22, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32367355

RESUMEN

Zika virus (ZIKV) is an important pathogen transmitted to humans by the mosquito vector Aedes aegypti. ZIKV is able to infect several tissues and organs and, importantly, has been associated with microcephaly and central nervous system abnormalities in fetuses and newborn babies of mothers exposed to ZIKV during pregnancy, as well as neurological diseases such as Guillain-Barré syndrome in adults. There is currently no vaccine or drug licensed to prevent or treat ZIKV infections. The use of ZIKV isolation in disease diagnosis has been largely replaced by new techniques. However, virus isolation is still considered as a gold standard for the detection of ZIKV and is usually performed in research and reference laboratories for characterization, sequencing, and a variety of research experiments including pathogenesis, drug susceptibility, and vaccine efficacy. The experimental procedures presented here describe the most common techniques used for ZIKV isolation, propagation, purification, and quantification.

5.
Methods Mol Biol ; 2142: 103-112, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32367362

RESUMEN

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus, which has recently caused global epidemics with its association with congenital Zika syndrome such as severe microcephaly. The recombinant ZIKV envelope (Env) glycoprotein is useful for immunological applications such as serodiagnosis of ZIKV infection and for monitoring immune responses in preclinical and clinical ZIKV vaccine developments. In this chapter, we describe the optimization of production of Zika virus envelope glycoprotein in Human Embryonic Kidney (HEK 293T) cells by small-scale expression followed by large-scale protein production. Small-scale expression of HEK 293T cells allows screening of a large number of vectors simultaneously to select the vectors with best secretory profiles for scale-up in Expi293 mammalian system to maximize the protein yield followed by purification for research and clinical applications.

6.
Methods Mol Biol ; 2142: 113-122, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32367363

RESUMEN

Maternal Zika virus (ZIKV) infection during pregnancy can have profound teratogenic effects including microcephaly and intracranial calcification. In adults, infection may cause acute inflammatory polyneuropathy. These complications appear after resolution of viremia. Thus, molecular assays of blood are typically insufficient to make the link between ZIKV infection and disease. An alternative approach to testing for ZIKV exposure is serology. However, specific serological implication of ZIKV can be confounded by cross-reactivity with closely related flaviviruses. We used high-density peptide arrays that tile the proteomes of a selection of arboviruses to search for ZIKV-specific linear epitopes that would enable the development of accurate serological tests. We identified a 20-amino-acid-long diagnostic peptide sequence in the NS2B protein of ZIKV that was immunoreactive with sera from patients with a confirmed history of infection with ZIKV but not other flaviviruses. We then established a ZIKV peptide ELISA (ZIKV-NS2B-concat ELISA) that enables sensitive and specific diagnosis of exposure to ZIKV.

7.
Methods Mol Biol ; 2142: 251-259, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32367372

RESUMEN

Zika virus (ZIKV) infection during pregnancy can result in congenital Zika syndrome which is characterized by microcephaly and other neurodevelopmental disorders. In this chapter, we describe methods to model ex vivo ZIKV infection in astrocytes and tissue explants from human fetal brain. These cell- and tissue-based platforms have been useful to elucidate mechanisms of ZIKV persistence and might lead to important clues about virus-induced neuropathogenesis. In addition, these ex vivo model systems allow researchers to conduct drug discovery and development experiments in more representative settings of the developing human brain.

8.
Microbes Infect ; 2020 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-32353601

RESUMEN

Zika Virus (ZIKV), an arbovirus that belongs to the Flaviviridae family, has become a global concern since its outbreak in the Americas in 2015. With symptoms similar to other Flavivirus as Dengue and Yellow Fever viruses, infections by ZIKV have also been related to several neurological complications such as microcephaly in newborns and Guillain-Barre syndrome. Considering the high prevalence of ZIKV infection in certain areas, the risks that the virus poses to fetal brain development, and the fact that there is no vaccine or specific prophylaxis available, an effective treatment capable of preventing the infection is of potential interest. Therefore, in the present investigation, the antiviral activity on ZIKV of a group of xanthenodiones and intermediate ketones involved in their synthesis was evaluated for the first time. It was found that the compound 2-(2,6-dichlorobenzylidene)cyclohexane-1,3-dione 27 was able to completely inhibit the viral infection of Vero cells as well as to significantly reduce viral load in the brains of newborn Swiss mice. These effects are related to a direct interaction of the compound with the viral particle, blocking the viral adsorption.

9.
Infect Genet Evol ; : 104364, 2020 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-32422351

RESUMEN

Despite worldwide research efforts since 2015, Zika virus infection and its consequences are not fully understood yet. Nowadays, it is known that microcephaly is only one of the possible outcomes of being infected by ZIKV during the early stages of life. Musashi 1 (MSI1) is an RNA-binding protein that is involved in neurodevelopmental processes. Also, ZIKV genome (a single-stranded positive-sense RNA) uses MSI1 for its replication. Here we perform an evolutionary analysis of MSI1 coding sequence and their orthologs in vertebrate species. We added original sequencing data from selected regions of interest (RNA-binding domains-RBDs of MSI1) of sixteen Platyrrhini (or New World monkeys), known to have high evolutionary rates. The Musashi family (MF) includes MSI2, TARDBP, DAZAP1, HNRNPD, HNRNPDL, and HNRNPAB, which do not interact with the virus but are critical RNA-binding proteins that act on many regulatory processes ubiquitously. We found that all sixteen primate species have the RBD1 of MSI1 conserved. While the general code sequences of MF genes are under purifying selection, the evolution of regulatory mechanisms, especially alternative splicing, seems to be a frequent phenomenon in these genes. Different isoforms differ in the N-terminal region and it affects protein size. Existing MSI1 isoforms probably diverge in their binding affinity, the kinetics of interaction, and other aspects when in MSI1-ZIKV complex. It is a signal that some RBD-containing MSI1 isoforms can be incompatible to ZIKV binding and replication. Consequently, the chance of ZIKV successfully infect and replicate into the host cell could also be associated with alternative splicing and expression of ZIKV-compatible MSI1 isoforms in both inter and intraspecific levels.

10.
Chromosoma ; 2020 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-32424716

RESUMEN

The International University of Andalucía (UNIA) Current Trends in Biomedicine Workshop on Molecular Causes of Primary Microcephaly and Related Diseases took place in Baeza, Spain, November 18-20, 2019. This meeting brought together scientists from Europe, the USA and China to discuss recent advances in our molecular and genetic understanding of a group of rare neurodevelopmental diseases characterised by primary microcephaly, a condition in which head circumference is smaller than normal at birth. Microcephaly can be caused by inherited mutations that affect key cellular processes, or environmental exposure to radiation or other toxins. It can also result from viral infection, as exemplified by the recent Zika virus outbreak in South America. Here we summarise a number of the scientific advances presented and topics discussed at the meeting.

11.
PLoS Pathog ; 16(5): e1008204, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32357162

RESUMEN

Zika virus (ZIKV) can infect and cause microcephaly and Zika-associated neurological complications in the developing fetal and adult brains. In terms of pathogenesis, a critical question is how ZIKV overcomes the barriers separating the brain from the circulation and gains access to the central nervous system (CNS). Despite the importance of ZIKV pathogenesis, the route ZIKV utilizes to cross CNS barriers remains unclear. Here we show that in mouse models, ZIKV-infected cells initially appeared in the periventricular regions of the brain, including the choroid plexus and the meninges, prior to infection of the cortex. The appearance of ZIKV in cerebrospinal fluid (CSF) preceded infection of the brain parenchyma. Further the brain infection was significantly attenuated by neutralization of the virus in the CSF, indicating that ZIKV in the CSF at the early stage of infection might be responsible for establishing a lethal infection of the brain. We show that cells infected by ZIKV in the choroid plexus were pericytes. Using in vitro systems, we highlight the possibility that ZIKV crosses the blood-CSF barrier by disrupting the choroid plexus epithelial layer. Taken together, our results suggest that ZIKV might exploit the blood-CSF barrier rather than the blood-brain barrier to invade the CNS.

12.
PLoS One ; 15(5): e0233023, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32401826

RESUMEN

Zika virus (ZIKV) is a mosquito-transmitted flavivirus, recently linked to microcephaly and central nervous system anomalies following infection in pregnancy. Striking findings of disproportionate growth with a smaller than expected head relative to body length have been observed more commonly among fetuses with exposure to ZIKV in utero compared to pregnancies without ZIKV infection regardless of other signs of congenital infection including microcephaly. This study's objective was to determine the diagnostic accuracy of femur-sparing profile of intrauterine growth restriction for the identification of ZIKV-associated congenital injuries on postnatal testing. A retrospective cohort study of pregnant women with possible or confirmed ZIKV infection between January 1, 2016 and December 31, 2017 were included. Subjects were excluded if no prenatal ultrasound was available. A femur-sparing profile of growth restriction determined using INTERGROWTH-21st sonographic standard for head circumference to femur length (HC: FL). Congenital injuries were determined postnatally by imaging, comprehensive eye exam and standard newborn hearing screen. A total of 111 pregnant women diagnosed with ZIKV infection underwent fetal ultrasound and 95 neonates had complete postnatal evaluation. Prenatal microcephaly was detected in 5% of fetuses (6/111). Postnatal testing detected ZIKV-associated congenital injuries in 25% of neonates (24/95). A HC: FL Z-score ≤ -1.3 had a 52% specificity (95% CI 41-63%), 82% negative predictive value (NPV, 95% CI 73-88%) for the detection of ZIKV-associated congenital injuries in the neonatal period. A more stringent threshold with a Z-score ≤ -2 was associated with a 90% specificity (95% CI 81-95%), 81% NPV (95% CI 77-85%). Excluding cases of fetal microcephaly, HC: FL (Z-score ≤ -2) demonstrated a similar specificity (89%, 95% CI 81-95%) with superior NPV (87%, 95% CI 84-90%). The sonographic recognition of a normally proportioned fetus may be useful prenatally to exclude a wider spectrum of ZIKV-associated congenital injuries detected postnatally.

13.
BMC Infect Dis ; 20(1): 332, 2020 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-32393198

RESUMEN

BACKGROUND: Between 2016 and 2019, 265 cases of Zika virus (ZIKV) infection were reported in Vietnam, predominantly in southern Vietnam. In 2016, a case of ZIKV-associated microcephaly was confirmed in the Central Highlands, and several members of the infant's family were confirmed to be infected with ZIKV. The study aims to determine the level of immunity to ZIKV in the general population of the ZIKV epidemic region. METHODS: A total of 879 serum samples were collected from 801 participants between January 2017 and July 2018, during and after the ZIKV epidemic in Vietnam. The samples were tested for anti-ZIKV immunoglobulin M (IgM) and immunoglobulin G (IgG), and anti-dengue virus (DENV) IgG antibodies using enzyme-linked immunosorbent assays (ELISA). Plaque-reduction neutralization test (PRNT) for ZIKV was performed on all samples, and for DENV on the samples that ZIKV neutralizing antibody positive. RESULTS: A total of 83 (10.3%) participants had anti-ZIKV IgM. Of the 83, 6 were confirmed to be ZIKV antibodies positive using PRNT and anti-ZIKV IgG ELISA. Of the 718 participants who were anti-ZIKV IgM negative, a further 3 cases were confirmed as positive for antibodies against ZIKV. Of the 9 participants with ZIKV infection, 5 lived in the same village as the infant with ZIKV-associated microcephaly and the other 4 lived in 2 neighboring communes. Repeat samples were collected from the 83 ZIKV IgM positive participants 1.5 years after the first collection. No new cases of ZIKV infection were detected. In addition, 2 of 3 participants with anti-ZIKV NS1 IgG demonstrated a 4- to 8-fold increase in ZIKV neutralizing antibody titer. CONCLUSIONS: ZIKV was present in the area around Krong Buk, with the rate of ZIKV-specific antibodies was 1.1% in the community since at least 2016. While the low levels of circulation together with low seroprevalence suggests a limited outbreak in the region, the results also reflect on low levels of protective immunity to Zika within the population. These results provide a better understanding of the current ZIKV epidemic status in the region and demonstrate a need for implementation of more effective ZIKV infection control measures.

14.
Demography ; 2020 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-32399856

RESUMEN

In late 2015, the Brazilian Ministry of Health and the Pan American Health Organization classified the increase in congenital malformations associated with the Zika virus (ZIKV) as a public health emergency. The risk of ZIKV-related congenital syndrome poses a threat to reproductive outcomes that could result in declining numbers of live births and potentially fertility. Using monthly microdata on live births from the Brazilian Information System on Live Births (SINASC), this study examines live births and fertility trends amid the ZIKV epidemic in Brazil. Findings suggest a decline in live births that is stratified across educational and geographic lines, beginning approximately nine months after the link between ZIKV and microcephaly was publicly announced. Although declines in total fertility rates were small, fertility trends estimated by age and maternal education suggest important differences in how Zika might have impacted Brazil's fertility structure. Further findings confirm the significant declines in live births in mid-2016 even when characteristics of the municipality are controlled for; these results highlight important nuances in the timing and magnitude of the decline. Combined, our findings illustrate the value of understanding how the risk of a health threat directed at fetuses has led to declines in live births and fertility.

15.
Viruses ; 12(5)2020 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-32429277

RESUMEN

Mathematical models of in vitro viral kinetics help us understand and quantify the main determinants underlying the virus-host cell interactions. We aimed to provide a numerical characterization of the Zika virus (ZIKV) in vitro infection kinetics, an arthropod-borne emerging virus that has gained public recognition due to its association with microcephaly in newborns. The mathematical model of in vitro viral infection typically assumes that degradation of extracellular infectious virus proceeds in an exponential manner, that is, each viral particle has the same probability of losing infectivity at any given time. We incubated ZIKV stock in the cell culture media and sampled with high frequency for quantification over the course of 96 h. The data showed a delay in the virus degradation in the first 24 h followed by a decline, which could not be captured by the model with exponentially distributed decay time of infectious virus. Thus, we proposed a model, in which inactivation of infectious ZIKV is gamma distributed and fit the model to the temporal measurements of infectious virus remaining in the media. The model was able to reproduce the data well and yielded the decay time of infectious ZIKV to be 40 h. We studied the in vitro ZIKV infection kinetics by conducting cell infection at two distinct multiplicity of infection and measuring viral loads over time. We fit the mathematical model of in vitro viral infection with gamma distributed degradation time of infectious virus to the viral growth data and identified the timespans and rates involved within the ZIKV-host cell interplay. Our mathematical analysis combined with the data provides a well-described example of non-exponential viral decay dynamics and presents numerical characterization of in vitro infection with ZIKV.

16.
Emerg Infect Dis ; 26(6): 1084-1090, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32441631

RESUMEN

During 2015-2016, Cape Verde, an island nation off the coast of West Africa, experienced a Zika virus (ZIKV) outbreak involving 7,580 suspected Zika cases and 18 microcephaly cases. Analysis of the complete genomes of 3 ZIKV isolates from the outbreak indicated the strain was of the Asian (not African) lineage. The Cape Verde ZIKV sequences formed a distinct monophylogenetic group and possessed 1-2 (T659A, I756V) unique amino acid changes in the envelope protein. Phylogeographic and serologic evidence support earlier introduction of this lineage into Cape Verde, possibly from northeast Brazil, between June 2014 and August 2015, suggesting cryptic circulation of the virus before the initial wave of cases were detected in October 2015. These findings underscore the utility of genomic-scale epidemiology for outbreak investigations.

17.
Viruses ; 12(5)2020 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-32397176

RESUMEN

Mosquito-borne Zika virus (ZIKV) can cause congenital microcephaly and Guillain-Barré syndrome, among other symptoms. Specific treatments and vaccines for ZIKV are not currently available. To further understand the host factors that support ZIKV replication, we used mass spectrometry to characterize mammalian proteins that associate with the ZIKV NS1 protein and identified the TRiC/CCT complex as an interacting partner. Furthermore, the suppression of CCT2, one of the critical components of the TRiC/CCT complex, inhibited ZIKV replication in both mammalian cells and mosquitoes. These results highlight an important role for the TRiC/CCT complex in ZIKV infection, suggesting that the TRiC/CCT complex may be a promising therapeutic target.

18.
J Pediatr ; 2020 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-32417080

RESUMEN

OBJECTIVE: To estimate the prevalence of microcephaly and central nervous system (CNS) defects during the Zika virus (ZIKV) epidemic in Colombia and proportion attributable to congenital ZIKV infection. STUDY DESIGN: Clinical and laboratory data for cases of microcephaly and/or CNS defects reported to national surveillance between 2015 and 2017 were reviewed and classified by a panel of clinical subject matter experts. Maternal and fetal/infant biologic specimens were tested for congenital infection and chromosomal abnormalities. Infants/fetuses with microcephaly and/or CNS defects (cases) were classified into broad etiologic categories (teratogenic, genetic, multifactorial, and unknown). Cases classified as potentially attributable to congenital ZIKV infection were stratified by strength of evidence for ZIKV etiology (strong, moderate, or limited) using a novel strategy considering birth defects unique or specific to ZIKV or other infections and laboratory evidence. RESULTS: Among 858 reported cases with sufficient information supporting a diagnosis of microcephaly or CNS defects, 503 were classified as potentially attributable to congenital ZIKV infection. Of these, the strength of evidence was considered strong in 124 (24.7%) cases; moderate in 232 (46.1%) cases; and limited in 147 (29.2%). Of the remaining, 355 (41.4%) were attributed to etiologies other than ZIKV infection (syphilis, toxoplasmosis, rubella, cytomegalovirus, herpes 1 and herpes 2 viruses only, n = 32 [3.7%]; genetic, n = 16 [1.9%]; multifactorial, n = 42 [4.9%]; unknown, n = 265 [30.9%]). CONCLUSIONS: Fifty-eight percent of cases of microcephaly and/or CNS defects were potentially attributable to congenital ZIKV infection; however, the strength of evidence varied considerably. This surveillance protocol might serve as a model approach for investigation and etiologic classification of complex congenital conditions.

19.
PLoS Pathog ; 16(5): e1008521, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32392268

RESUMEN

Zika virus (ZIKV) infection may lead to congenital microcephaly and pregnancy loss in pregnant women. In the context of pregnancy, folic acid (FA) supplementation may reduce the risk of abnormal pregnancy outcomes. Intriguingly, FA may have a beneficial effect on the adverse pregnancy outcomes associated with ZIKV infection. Here, we show that FA inhibits ZIKV replication in human umbilical vein endothelial cells (HUVECs) and a cell culture model of blood-placental barrier (BPB). The inhibitory effect of FA against ZIKV infection is associated with FRα-AMPK signaling. Furthermore, treatment with FA reduces pathological features in the placenta, number of fetal resorptions, and stillbirths in two mouse models of in utero ZIKV transmission. Mice with FA treatment showed lower viral burden and better prognostic profiles in the placenta including reduced inflammatory response, and enhanced integrity of BPB. Overall, our findings suggest the preventive role of FA supplementation in ZIKV-associated abnormal pregnancy and warrant nutritional surveillance to evaluate maternal FA status in areas with active ZIKV transmission.

20.
Indian J Pediatr ; 2020 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-32281058

RESUMEN

Congenital infections affecting newborn infants can have potentially devastating clinical outcomes. They are usually caused by viruses that infect mothers during pregnancy and are transmitted to the fetus or newborn during the prenatal, perinatal or postnatal periods. Congenital cytomegalovirus (cCMV) is the most common congenital infection affecting up to 2.5% of all live births. Even though most infected infants are asymptomatic at birth, cCMV is an important cause of neurodevelopmental impairment and represents the main cause of non-hereditary sensorineural hearing loss. Also, congenital Zika infection has emerged in recent years as a cause of microcephaly and neurodevelopmental delays. Currently, universal screening is not recommended for either infection in pregnant women or newborn infants. Therefore, screening for both conditions is based on multiple factors such as maternal immune status, exposure, and clinical manifestations of the infant. Use of antiviral medications on symptomatic cCMV has shown improvement in outcomes, in contrast with congenital Zika for which there are no therapeutic options available. Even though both viruses can be present in breast milk, there are no recommendations against breastfeeding in full-term infants. Close follow-up for affected infants is necessary to monitor for developmental delays and sensory impairments to implement interventional therapies at the earliest time possible.

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