scholarly journals Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 325
Author(s):  
Julia A. Gomes ◽  
Eduarda Sgarioni ◽  
Juliano A. Boquett ◽  
Ana Cláudia P. Terças-Trettel ◽  
Juliana H. da Silva ◽  
...  
Keyword(s):  
Risk Factors ◽  
Zika Virus ◽  
Genetic Variants ◽  
Educational Level ◽  
Congenital Anomalies ◽  
Family Income ◽  
First Trimester ◽  
In Utero ◽  
Zikv Infection ◽  
Congenital Zika Syndrome

Zika virus (ZIKV) causes Congenital Zika Syndrome (CZS) in individuals exposed prenatally. Here, we investigated polymorphisms in VEGFA, PTGS2, NOS3, TNF, and NOS2 genes as risk factors to CZS. Forty children with CZS and forty-eight children who were in utero exposed to ZIKV infection, but born without congenital anomalies, were evaluated. Children with CZS were predominantly infected by ZIKV in the first trimester (p < 0.001) and had mothers with lower educational level (p < 0.001) and family income (p < 0.001). We found higher risk of CZS due the allele rs2297518[A] of NOS2 (OR = 2.28, CI 95% 1.17–4.50, p = 0.015). T allele and TT/CT genotypes of the TNF rs1799724 and haplotypes associated with higher expression of TNF were more prevalent in children with CZS and severe microcephaly (p = 0.029, p = 0.041 and p = 0.030, respectively). Our findings showed higher risk of CZS due ZIKV infection in the first trimester and suggested that polymorphisms in NOS2 and TNF genes affect the risk of CZS and severe microcephaly.

scholarly journals Zika Virus Pathogenesis: From Early Case Reports to Epidemics

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 886 ◽  
Author(s):  
Ryan D. Pardy ◽  
Martin J. Richer
Keyword(s):  
Risk Factors ◽  
Zika Virus ◽  
Case Reports ◽  
Viral Persistence ◽  
The Body ◽  
Therapeutic Approaches ◽  
Zikv Infection ◽  
Congenital Zika Syndrome ◽  
Early Case ◽  
The Impact

For the first 60 years following its isolation, Zika virus (ZIKV) remained a relatively poorly described member of the Flaviviridae family. However, since 2007, it has caused a series of increasingly severe outbreaks and is now associated with neurological symptoms such as Guillain-Barré syndrome and congenital Zika syndrome (CZS). A number of reports have improved our understanding of rare complications that may be associated with ZIKV infection in adults, the areas of the body to which it spreads, and viral persistence in various tissues. Likewise, studies on the effect of ZIKV infection during pregnancy have identified risk factors for CZS and the impact this syndrome has on early childhood. Understanding these outcomes and the factors that drive ZIKV pathogenesis are key to developing vaccination and therapeutic approaches to avoid these severe and potentially debilitating symptoms.

scholarly journals Zika virus infection during development impairs the formation of corpus callosum by disturbing axon guidance and growth of callosal neurons.

2021 ◽  
Author(s):  
Raissa Rilo Christoff ◽  
Jefferson H. Quintanilha ◽  
Raiane O Ferreira ◽  
Jessica C. C. G. Ferreira ◽  
Daniel Menezes Guimaraes ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Axon Guidance ◽  
Birth Defects ◽  
Zika Virus ◽  
In Utero ◽  
Mouse Embryos ◽  
Rna Seq ◽  
Zikv Infection ◽  
Density Reduction ◽  
Congenital Zika Syndrome

Congenital Zika Syndrome (CZS) is a set of birth defects caused by Zika virus (ZIKV) infection during pregnancy. Microcephaly is its main feature, but other brain abnormalities are found in CZS patients, such as ventriculomegaly, brain calcifications, and dysgenesis of the corpus callosum. Many studies have focused on microcephaly, but it remains unknown how ZIKV infection leads to callosal malformation. To tackle this issue, we infected mouse embryos in utero with Brazilian ZIKV and found that they are born with a reduction in callosal area and density of callosal neurons. ZIKV infection also causes a density reduction of PH3+ cells, intermediate progenitor cells and SATB2+ neurons. Moreover, axonal tracing revealed that callosal axons are reduced and misrouted. Also, ZIKV infected cultures show a reduction of callosal axon length. GFAP labelling showed that in utero infection compromises glial cells responsible for midline axon guidance. The RNA-Seq data from infected brains identified downregulation of axon guidance and axonogenesis related genes. In sum, we showed that ZIKV infection impairs critical steps of corpus callosum formation by disrupting not only neurogenesis but also axon guidance and growth across the midline.

scholarly journals Another piece on the Zika puzzle: assessing the associated factors to microcephaly in a systematic review and meta-analysis.

2019 ◽  
Author(s):  
Luciana Guerra Gallo ◽  
Jorge L Martinez-Cajas ◽  
Henry Maia Peixoto ◽  
Ana Carolina Esteves da Silva Pereira ◽  
Jillian E Carter ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Zika Virus ◽  
Meta Analysis ◽  
First Trimester ◽  
Primary Data ◽  
Zikv Infection ◽  
Factors Associated ◽  
Ovid Medline ◽  
Definition Of

Abstract Background: Although it is known that Zika virus (ZIKV) infection during pregnancy may lead to microcephaly in the foetus, the risk factors associated to this tragic disorder remain unclear. We conducted a systematic review and meta-analysis toto assess risk 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 authors of the studies included in this review to calculate summary estimates and conduct meta-analysis of the most prevalent factors. Results: We screened 4,106 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 6,154 children/foetuses were enrolled; of those, 1,120 (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 foetuses/ children. Half of the studies provided primary data. Two out of eleven factors of interest were associated with microcephaly: infant’s sex – males presented a higher risk of microcephaly compared to females (RR 1.30, 95% CI 1.14, 1.49); and the stage of pregnancy when infection occurred - infection in the first trimester of pregnancy had a higher risk of microcephaly (RR 1.41, 95% CI 1.09 to 1.82), compared to infection at other stages of pregnancy. Conclusion: Our findings support the female-biased resistance hypothesis and reinforce the risk associated with the stage of pregnancy when Zika virus infection occurs. Continued surveillance of ZIKV during pregnancy is needed to identify additional factors that could contribute to developing microcephaly in affected foetuses.

scholarly journals Another piece on the Zika puzzle: assessing the associated factors to microcephaly in a systematic review and meta-analysis.

2020 ◽  
Author(s):  
Luciana Guerra Gallo(Former Corresponding Author) ◽  
Jorge L Martinez-Cajas ◽  
Henry Maia Peixoto ◽  
Ana Carolina Esteves da Silva Pereira ◽  
Jillian E Carter ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Zika Virus ◽  
Meta Analysis ◽  
First Trimester ◽  
Primary Data ◽  
Zikv Infection ◽  
Factors Associated ◽  
Ovid Medline ◽  
Definition Of

Abstract Background: Although it is known that Zika virus (ZIKV) infection during pregnancy may lead to microcephaly in the foetus, the risk factors associated to this tragic disorder remain unclear. We conducted a systematic review and meta-analysis toto assess risk 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 authors of the studies included in this review to calculate summary estimates and conduct meta-analysis of the most prevalent factors. Results: We screened 4,106 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 6,154 children/foetuses were enrolled; of those, 1,120 (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 foetuses/ children. Half of the studies provided primary data. Two out of eleven factors of interest were associated with microcephaly: infant’s sex – males presented a higher risk of microcephaly compared to females (RR 1.30, 95% CI 1.14, 1.49); and the stage of pregnancy when infection occurred - infection in the first trimester of pregnancy had a higher risk of microcephaly (RR 1.41, 95% CI 1.09 to 1.82), compared to infection at other stages of pregnancy. Conclusion: Our findings support the female-biased resistance hypothesis and reinforce the risk associated with the stage of pregnancy when Zika virus infection occurs. Continued surveillance of ZIKV during pregnancy is needed to identify additional factors that could contribute to developing microcephaly in affected foetuses.

scholarly journals 84. Clarifying the Congenital Zika Syndrome Phenotype and Expanding to Congenital Zika Spectrum in the Absence of Laboratory Evidence

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S173-S173
Author(s):  
Laura D Zambrano ◽  
Augustina Delaney ◽  
Charles E Rose ◽  
Suzanne Gilboa ◽  
Van Tong ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Optic Nerve ◽  
Virus Infection ◽  
Zika Virus ◽  
Congenital Anomalies ◽  
Zikv Infection ◽  
Distinct Phenotype ◽  
Laboratory Evidence ◽  
Zika Virus Infection ◽  
Congenital Zika Syndrome

Abstract Background Congenital Zika syndrome (CZS) is a term used to describe the pattern of anomalies in infants due to congenital Zika virus (ZIKV) infection. To date, published reports of infants with these anomalies have been primarily small case series of the most severely affected infants and attempts to determine the CZS phenotype have been based on those reports. Lack of a standard definition has led to inconsistencies in the term’s use in the literature and uncertainty about the full spectrum of anomalies, limiting the application for diagnostic and surveillance purposes. Cluster analysis of brain and eye anomalies associated with congenital Zika infection. Clustering occurred independent of laboratory evidence of Zika virus infection, yielding a clinically distinct phenotype associated with congenital infection. Methods We sought to understand which defects co-occur with possible congenital ZIKV infection using data from 415 mother-infant dyads with laboratory evidence of confirmed or presumptive Zika virus infection from the U.S. Zika Pregnancy and Infant Registry, and a comparison group of 4534 mother-infant dyads with no documented or plausible ZIKV infection from the Zika Birth Defects Surveillance System. We use k-means cluster analysis, discriminant analysis, and regression approaches to identify combinations of defects consistent with possible congenital ZIKV infection. Results A clinically distinct phenotype emerged as a single cluster in infants for whom both brain and eye defects were recorded that corresponded to evidence of confirmed or probable ZIKV infection. A combination of six defects (sub-cortical calcifications, chorioretinal atrophy/pigmentary anomalies, arthrogryposis or clubfoot, cerebral atrophy or ventriculomegaly, abnormal cortical gyration, and optic nerve atrophy/pallor/other optic nerve abnormalities) predicted the presence of laboratory evidence (area under the receiver operating characteristics curve: 0.95, 95% confidence interval: 0.90–0.99). Conclusion Further analyses are underway to develop a scoring rubric to weigh evidence of specific congenital anomalies, separately and in combination, that are consistent with laboratory evidence of congenital ZIKV infection. A quantitatively determined spectrum of Zika-associated anomalies, based on the presence of specific combinations of congenital anomalies, will inform a clinical decision tool to improve patient counseling and public health surveillance practices. Disclosures All Authors: No reported disclosures

scholarly journals Zika viruses of both African and Asian lineages cause fetal harm in a vertical transmission model

2018 ◽  
Author(s):  
Anna S. Jaeger ◽  
Reyes A. Murreita ◽  
Lea R. Goren ◽  
Chelsea M. Crooks ◽  
Ryan V. Moriarty ◽  
...  
Keyword(s):  
Mouse Model ◽  
Vertical Transmission ◽  
Birth Defects ◽  
Asian American ◽  
Zika Virus ◽  
French Polynesia ◽  
Transmission Model ◽  
Foreseeable Future ◽  
Zikv Infection ◽  
Congenital Zika Syndrome

AbstractCongenital Zika virus (ZIKV) infection was first linked to birth defects during the American outbreak 1–3. It has been proposed that mutations unique to the Asian/American-genotype explain, at least in part, the ability of Asian/American ZIKV to cause congenital Zika syndrome (CZS) 4,5. Recent studies identified mutations in ZIKV infecting humans that arose coincident with the outbreak in French Polynesia and were stably maintained during subsequent spread to the Americas 5. Here we show that African ZIKV can infect and harm fetuses and that the S139N mutation that has been associated with the American outbreak is not essential for fetal harm. Our findings, in a vertical transmission mouse model, suggest that ZIKV will remain a threat to pregnant women for the foreseeable future, including in Africa, southeast Asia, and the Americas. Additional research is needed to better understand the risks associated with ZIKV infection during pregnancy, both in areas where the virus is newly endemic and where it has been circulating for decades.

Clinical and Epidemiological Features of Acute Zika Virus Infections in León, Nicaragua

2021 ◽  
Author(s):  
Natalie M. Bowman ◽  
Filemón Bucardo ◽  
Matthew H. Collins ◽  
Yaoska Reyes ◽  
Edwing Centeno Cuadra ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sore Throat ◽  
Zika Virus ◽  
Clinical Symptoms ◽  
Laboratory Data ◽  
Maculopapular Rash ◽  
Laboratory Diagnosis ◽  
Zikv Infection ◽  
Serological Tests ◽  
Laboratory Findings

The American Zika virus (ZIKV) epidemic has highlighted the need to gain a better understanding of this emerging virus. The goal of this study was to describe the clinical symptoms, laboratory findings, and risk factors for symptomatic ZIKV infection in an area with ongoing transmission of other arboviral infections. We recruited patients at least 2 years of age seeking care at public health centers in León, Nicaragua, between January 2016 and August 2017, for fever, maculopapular rash, and/or nonsuppurative conjunctivitis with a duration of less than 1 week. A laboratory diagnosis of ZIKV was established using a combination of molecular and serological tests. Clinical and laboratory findings and potential risk factors were compared between participants with and without acute ZIKV infection. Fifty-eight (26%) of the 225 participants included in the analysis were found to have acute ZIKV infection. Pregnancy and reports of previous arboviral infection were associated with a higher risk of ZIKV infection. Rash, conjunctivitis, sore throat, and lower absolute neutrophil counts were associated with acute ZIKV infection. The clinical characteristics and risk factors identified were consistent with those identified by previous studies; however, we found sore throat to be a feature of ZIKV infection. We also found that neutrophil counts were lower in ZIKV-infected subjects. These clinical symptoms and laboratory data may help clinicians suspect ZIKV infection during future outbreaks.

scholarly journals Zika Virus-Derived E-DIII Protein Displayed on Immunologically Optimized VLPs Induces Neutralizing Antibodies without Causing Enhancement of Dengue Virus Infection

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 72 ◽  
Author(s):  
Gustavo Cabral-Miranda ◽  
Stephanie M. Lim ◽  
Mona O. Mohsen ◽  
Ilya V. Pobelov ◽  
Elisa S. Roesti ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Clinical Manifestations ◽  
First Trimester ◽  
Neurological Complications ◽  
Zikv Infection ◽  
First Trimester Of Pregnancy ◽  
Specific Igg

Zika virus (ZIKV) is a flavivirus similar to Dengue virus (DENV) in terms of transmission and clinical manifestations, and usually both viruses are found to co-circulate. ZIKV is usually transmitted by mosquitoes bites, but may also be transmitted by blood transfusion, via the maternal–foetal route, and sexually. After 2015, when the most extensive outbreak of ZIKV had occurred in Brazil and subsequently spread throughout the rest of South America, it became evident that ZIKV infection during the first trimester of pregnancy was associated with microcephaly and other neurological complications in newborns. As a result, the development of a vaccine against ZIKV became an urgent goal. A major issue with DENV vaccines, and therefore likely also with ZIKV vaccines, is the induction of antibodies that fail to neutralize the virus properly and cause antibody-dependent enhancement (ADE) of the infection instead. It has previously been shown that antibodies against the third domain of the envelope protein (EDIII) induces optimally neutralizing antibodies with no evidence for ADE for other viral strains. Therefore, we generated a ZIKV vaccine based on the EDIII domain displayed on the immunologically optimized Cucumber mosaic virus (CuMVtt) derived virus-like particles (VLPs) formulated in dioleoyl phosphatidylserine (DOPS) as adjuvant. The vaccine induced high levels of specific IgG after a single injection. The antibodies were able to neutralise ZIKV without enhancing infection by DENV in vitro. Thus, the here described vaccine based on EDIII displayed on VLPs was able to stimulate production of antibodies specifically neutralizing ZIKV without potentially enhancing disease caused by DENV.

scholarly journals Clinical Outcomes of a Zika Virus Mother–Child Pair Cohort in Spain

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 352 ◽  
Author(s):  
Antoni Soriano-Arandes ◽  
Marie Antoinette Frick ◽  
Milagros García López-Hortelano ◽  
Elena Sulleiro ◽  
Carlota Rodó ◽  
...  
Keyword(s):  
Zika Virus ◽  
Adverse Outcomes ◽  
Zikv Infection ◽  
Child Pair ◽  
Referral Hospitals ◽  
Congenital Zika Syndrome ◽  
Endemic Areas ◽  
Neurodevelopmental Abnormalities ◽  
Congenital Microcephaly

Background: Zika virus (ZIKV) infection has been associated with congenital microcephaly and other neurodevelopmental abnormalities. There is little published research on the effect of maternal ZIKV infection in a non-endemic European region. We aimed to describe the outcomes of pregnant travelers diagnosed as ZIKV-infected in Spain, and their exposed children. Methods: This prospective observational cohort study of nine referral hospitals enrolled pregnant women (PW) who travelled to endemic areas during their pregnancy or the two previous months, or those whose sexual partners visited endemic areas in the previous 6 months. Infants of ZIKV-infected mothers were followed for about two years. Results: ZIKV infection was diagnosed in 163 PW; 112 (70%) were asymptomatic and 24 (14.7%) were confirmed cases. Among 143 infants, 14 (9.8%) had adverse outcomes during follow-up; three had a congenital Zika syndrome (CZS), and 11 other potential Zika-related outcomes. The overall incidence of CZS was 2.1% (95%CI: 0.4–6.0%), but among infants born to ZIKV-confirmed mothers, this increased to 15.8% (95%CI: 3.4–39.6%). Conclusions: A nearly 10% overall risk of neurologic and hearing adverse outcomes was found in ZIKV-exposed children born to a ZIKV-infected traveler PW. Longer-term follow-up of these children is needed to assess whether there are any later-onset manifestations.

scholarly journals Factors related to non-adherence to mammography in a city of the Brazilian Amazonian area: A population-based study

2017 ◽  
Vol 63 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Camila Iasmim de Andrade Souza ◽  
◽  
Daniela Souza Araújo ◽  
Daniele Aparecida de Freitas Teles ◽  
Stéphanie Gomes Lins de Carvalho ◽  
...  
Keyword(s):  
Risk Factors ◽  
Educational Level ◽  
Family Income ◽  
Univariate Analysis ◽  
Cancer Control ◽  
Household Survey ◽  
Target Population ◽  
Cluster Sampling ◽  
Government Assistance ◽  
Cross Sectional

Summary Objective: To assess the prevalence of mammography use and factors related to non-adherence in Boa Vista, capital of Roraima, Brazil. Method: A cross sectional study, quantitative analysis, based on household survey was performed between June and August 2013, using a face-to-face interview with a pre-tested form. Target population was women between 40 and 69 years. The sample size target was 240 participants, and the sampling method was random cluster sampling. The study was approved by the Institutional Review Board of Federal University of Roraima. Results: 241 women were included without refusals. The prevalence of non-use of mammography in the past two years was 55.6% (95CI 49.1-61.9). In univariate analysis, the risk factors for non-adherence to mammography were having low educational level, family income below three minimum wages, receiving government assistance, not having consulted with a doctor and no health insurance. In multivariate analysis, only low educational level and receiving government assistance remained as risk factors. Medical consultation or health worker visiting were protective factors. Conclusion: Adherence to mammography is unsatisfactory in Boa Vista, Roraima, and has a predominantly opportunistic character. Low educational level is confirmed as an independent risk factor, but belonging to a family that receives government assistance can be interpreted as a social marker of families and/or areas lacking of government intervention to increase access to breast cancer control programs.

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