scholarly journals Maternal immunity and antibodies to dengue promote Zika virus-induced microcephaly in fetuses

2018 ◽  
Author(s):  
Abhay P. S. Rathore ◽  
Wilfried A. A. Saron ◽  
Ting Lim ◽  
Nusrat Jahan ◽  
Ashley L. St John
Keyword(s):  
Vertical Transmission ◽  
Zika Virus ◽  
First Trimester ◽  
Maternal Antibodies ◽  
Zikv Infection ◽  
Specific Antibodies ◽  
Target Populations ◽  
Immune Mediated ◽  
Fetal Infection ◽  
First Trimester Of Pregnancy

AbstractZika virus (ZIKV), a recently emerged flaviviral pathogen, has been linked to microcephaly in neonates1. Yet, it is not understood why some fetuses develop severe microcephaly due to maternal ZIKV infection while others do not. The risk for ZIKV-induced microcephaly is greatest during the first trimester of pregnancy in humans2,3, yet this alone cannot account for the varied presentation of microcephaly observed. Given the antigenic similarity between ZIKV and closely related dengue virus (DENV)4, combined with the substantial immunity to DENV in ZIKV target populations in recent outbreaks, we hypothesized that maternal antibodies against DENV could promote ZIKV-induced microcephaly. Here, using immune-competent mice, we show that maternal to fetal transmission of ZIKV occurs, leading to fetal infection and disproportionate microcephaly. DENV-specific antibodies in pregnant female mice enhance vertical transmission of infection and result in a severe microcephaly like-syndrome during ZIKV infection. Furthermore, fetal infection was promoted by the neonatal Fc receptor (FcRN). Our results identify a novel immune-mediated mechanism of vertical transmission of viral infection and raise caution since ZIKV epidemic regions are also endemic to DENV.

scholarly journals Maternal immunity and antibodies to dengue virus promote infection and Zika virus–induced microcephaly in fetuses

2019 ◽  
Vol 5 (2) ◽  
pp. eaav3208 ◽  
Author(s):  
Abhay P. S. Rathore ◽  
Wilfried A. A. Saron ◽  
Ting Lim ◽  
Nusrat Jahan ◽  
Ashley L. St. John
Keyword(s):  
Dengue Virus ◽  
Zika Virus ◽  
First Trimester ◽  
Target Populations ◽  
Immune Mediated ◽  
Fetal Infection ◽  
Pregnant Mice ◽  
First Trimester Of Pregnancy ◽  
Special Concern ◽  
Immunocompetent Mice

Zika virus (ZIKV), an emergent flaviviral pathogen, has been linked to microcephaly in neonates. Although the risk is greatest during the first trimester of pregnancy in humans, timing alone cannot explain why maternal ZIKV infection leads to severe microcephaly in some fetuses, but not others. The antigenic similarities between ZIKV and dengue virus (DENV), combined with high levels of DENV immunity among ZIKV target populations in recent outbreaks, suggest that anti-DENV maternal antibodies could promote ZIKV-induced microcephaly. We demonstrated maternal-to-fetal ZIKV transmission, fetal infection, and disproportionate microcephaly in immunocompetent mice. We show that DENV-specific antibodies in ZIKV-infected pregnant mice enhance vertical ZIKV transmission and result in a severe microcephaly-like syndrome, which was dependent on the neonatal Fc receptor, FcRN. This novel immune-mediated mechanism of vertical transmission of viral infection is of special concern because ZIKV epidemic regions are also endemic to DENV.

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 Risk estimates for microcephaly related to Zika virus infection - from French Polynesia to Bahia, Brazil

2016 ◽  
Author(s):  
Michael A Johansson ◽  
Luis Mier-y-Teran-Romero ◽  
Jennita Reefhuis ◽  
Suzanne M Gilboa ◽  
Susan L Hills
Keyword(s):  
Virus Infection ◽  
Confidence Interval ◽  
Infection Rate ◽  
Birth Defects ◽  
Zika Virus ◽  
First Trimester ◽  
French Polynesia ◽  
Zikv Infection ◽  
Risk Estimates ◽  
First Trimester Of Pregnancy

Zika virus (ZIKV) infection during pregnancy has been linked to birth defects,1 yet the magnitude of risk remains uncertain. A study of the Zika outbreak in French Polynesia estimated that the risk of microcephaly due to ZIKV infection in the first trimester of pregnancy was 0.95% (95% confidence interval: 0.34-1.91%), based on eight microcephaly cases identified retrospectively in a population of approximately 270,000 people with an estimated 66% ZIKV infection rate.2

scholarly journals Clinical, Neuroimaging, and Neurophysiological Findings in Children with Microcephaly Related to Congenital Zika Virus Infection

2019 ◽  
Vol 16 (3) ◽  
pp. 309 ◽  
Author(s):  
Maria-Lucia C. Lage ◽  
Alessandra Carvalho ◽  
Paloma Ventura ◽  
Tania Taguchi ◽  
Adriana Fernandes ◽  
...  
Keyword(s):  
Zika Virus ◽  
Cerebral Atrophy ◽  
First Trimester ◽  
Zikv Infection ◽  
Radiological Criteria ◽  
Gestational Exposure ◽  
Malformation Of Cortical Development ◽  
Brain Malformations ◽  
Cutaneous Rash ◽  
First Trimester Of Pregnancy

Zika virus (ZIKV) infection appeared in Brazil in 2015, causing an epidemic outbreak with increased rates of microcephaly and other serious birth disorders. We reviewed 102 cases of children who were diagnosed with microcephaly at birth and who had gestational exposure to ZIKV during the outbreak. We describe the clinical, neuroimaging, and neurophysiological findings. Most mothers (81%) reported symptoms of ZIKV infection, especially cutaneous rash, during the first trimester of pregnancy. The microcephaly was severe in 54.9% of the cases. All infants presented with brain malformations. The most frequent neuroimaging findings were cerebral atrophy (92.1%), ventriculomegaly (92.1%), malformation of cortical development (85.1%), and cortical–subcortical calcifications (80.2%). Abnormalities in neurological exams were found in 97.0% of the cases, epileptogenic activity in 56.3%, and arthrogryposis in 10.8% of the infants. The sensorineural screening suggested hearing loss in 17.3% and visual impairment in 14.1% of the infants. This group of infants who presented with microcephaly and whose mothers were exposed to ZIKV early during pregnancy showed clinical and radiological criteria for congenital ZIKV infection. A high frequency of brain abnormalities and signs of early neurological disorders were found, and epileptogenic activity and signs of sensorineural alterations were common. This suggests that microcephaly can be associated with a worst spectrum of neurological manifestations.

scholarly journals Zika Virus and Pregnancy: Association between Acute Infection and Microcephaly in Newborns in the State of Rio de Janeiro, Brazil

2020 ◽  
Vol 80 (01) ◽  
pp. 60-65 ◽  
Author(s):  
Alessandra Mendelski Pereira ◽  
Edward Araujo Júnior ◽  
Heron Werner ◽  
Denise Leite Maia Monteiro
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Pregnant Women ◽  
Zika Virus ◽  
Rio De Janeiro ◽  
Acute Infection ◽  
First Trimester ◽  
The State ◽  
Zikv Infection ◽  
First Trimester Of Pregnancy

Abstract Introduction Aim of the study was to evaluate the association between microcephaly and acute infection with Zika virus (ZIKV) in pregnant women in the state of Rio de Janeiro, Brazil. Infection was confirmed by laboratory testing. Materials and Methods A cross-sectional retrospective study of pregnant women with symptoms occurring between 2015 and 2016 suggestive of acute ZIKV infection was carried out, with confirmation of infection done by blood or urine RT-PCR. The relative proportions of categorical variables were calculated for two distinct groups: pregnant women whose newborns had microcephaly and pregnant women who gave birth to infants without microcephaly. Confidence intervals with a 95% level of agreement were estimated for the relative ratios. Results A total of 1609 pregnant women with a mean age of 26.4 ± 6.5 years were evaluated. As regards the time of acute infection, 19.6% (316) of cases occurred in the first trimester of pregnancy. Nineteen (76%) of the 25 cases with microcephaly (1.5%) were associated with an infection contracted in the first trimester of pregnancy (p < 0.001, OR = 13.7, 95% CI: 5.6 – 37.7). 48% (12/25) of the newborns with microcephaly had a birth weight of < 2500 grams, while only 7% (116/1597) of the group of newborns without microcephaly had a similarly low birth weight (p < 0.001, OR = 11.7, 95% CI: 5.2 – 26.2). Logistic regression showed that a birth weight of < 2500 g (OR = 12.54) and ZIKV infection in the first trimester of pregnancy (OR = 14.05) were associated with microcephaly (area under ROC curve = 0.86). Conclusion Acute ZIKV infection in the first trimester of pregnancy and low birth weight are associated with microcephaly.

Increase in Reported Prevalence of Microcephaly in Infants Born to Women Living in Areas with Confirmed Zika Virus Transmission During the First Trimester of Pregnancy — Brazil, 2015

2016 ◽  
Vol 65 (9) ◽  
Author(s):  
Wanderson Kleber de Oliveira ◽  
Juan Cortez-Escalante ◽  
Wanessa Tenório Gonçalves Holanda De Oliveira ◽  
Greice Madeleine Ikeda do Carmo ◽  
Cláudio Maierovitch Pessanha Henriques ◽  
...  
Keyword(s):  
Zika Virus ◽  
Virus Transmission ◽  
First Trimester ◽  
First Trimester Of Pregnancy

Increase in Reported Prevalence of Microcephaly in Infants Born to Women Living in Areas with Confirmed Zika Virus Transmission During the First Trimester of Pregnancy — Brazil, 2015

2016 ◽  
Vol 65 (9) ◽  
pp. 242-247 ◽  
Author(s):  
Wanderson Kleber de Oliveira ◽  
Juan Cortez-Escalante ◽  
Wanessa Tenório Gonçalves Holanda De Oliveira ◽  
Greice Madeleine Ikeda do Carmo ◽  
Cláudio Maierovitch Pessanha Henriques ◽  
...  
Keyword(s):  
Zika Virus ◽  
Virus Transmission ◽  
First Trimester ◽  
First Trimester Of Pregnancy

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 Fetal infection resulting from maternal rubella after the first trimester of pregnancy

1980 ◽  
Vol 85 (3) ◽  
pp. 381-391 ◽  
Author(s):  
J. E. Cradock-Watson ◽  
Margaret K. S. Ridehalgh ◽  
Mary J. Anderson ◽  
J. R. Pattison ◽  
H. O. Kangro
Keyword(s):  
First Trimester ◽  
Menstrual Period ◽  
Last Menstrual Period ◽  
Igg Antibody ◽  
True Rate ◽  
Igm Antibody ◽  
Prenatal Infection ◽  
Fetal Infection ◽  
First Trimester Of Pregnancy ◽  
Specific Igg

SUMMARYWe have tried to measure the incidence of prenatal infection in 304 infants whose mothers had had rubella at various times after the first 12 weeks of pregnancy. Two methods of assessment were used: first, serum obtained soon after birth was tested for specific IgM antibody; secondly, serum obtained after the age of eight months was tested for specific IgG. When maternal rubella occurred 12–16 weeks after the last menstrual period specific IgM antibody was detected in 28 out of 50 infants (56%). The proportion fell progressively to 12% after maternal rubella at 24–28 weeks, rose to 19% after rubella at 28–36 weeks and then to 58% when the illness occurred during the last month of pregnancy. In all, IgM antibody was detected in 77 out of 260 infants (29%). The fetus can thus be infected at any time during the second and third trimesters of pregnancy, but the risk varies at different stages.The figures for the prevalence of IgG antibody were greater throughout, because some infants had IgG who had previously lacked specific IgM. After maternal rubella at 12–16 weeks IgG antibody persisted in 22 out of 31 infants (71%). The proportion fell to 28% after rubella at 24–28 weeks and then increased progressively to 94% after rubella during the last month. In all, IgG antibody persisted in 94 out of 190 infants (49%). The true rate of fetal infection probably lies between the rates estimated from the presence of IgM antibody and the subsequent prevalence of IgG.Infants whose mothers had rubella at any time during pregnancy should be examined regularly for possible evidence of damage.

scholarly journals Management of Acute Severe Ulcerative Colitis in a Pregnant Woman With COVID-19 Infection: A Case Report and Review of the Literature

2020 ◽  
Vol 26 (7) ◽  
pp. 971-973 ◽  
Author(s):  
Melissa H Rosen ◽  
Jordan Axelrad ◽  
David Hudesman ◽  
David T Rubin ◽  
Shannon Chang
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
First Trimester ◽  
Review Of The Literature ◽  
Severe Ulcerative Colitis ◽  
Immune Mediated ◽  
First Trimester Of Pregnancy ◽  
Inflammatory Bowel ◽  
High Level

Abstract First detected in Wuhan, China, the novel 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA beta-coronavirus responsible for an unprecedented, worldwide pandemic caused by COVID-19. Optimal management of immunosuppression in inflammatory bowel disease (IBD) patients with COVID-19 infection currently is based on expert opinion, given the novelty of the infection and the corresponding lack of high-level evidence in patients with immune-mediated conditions. There are limited data regarding IBD patients with COVID-19 and no data regarding early pregnancy in the era of COVID-19. This article describes a patient with acute severe ulcerative colitis (UC) during her first trimester of pregnancy who also has COVID-19. The case presentation is followed by a review of the literature to date on COVID-19 in regard to inflammatory bowel disease and pregnancy, respectively.

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