Publisher Correction: Experimental Zika Virus Infection in the Pregnant Common Marmoset Induces Spontaneous Fetal Loss and Neurodevelopmental Abnormalities

During its most recent outbreak across the Americas, Zika virus (ZIKV) was surprisingly shown to cause fetal loss and congenital malformations in acutely and chronically infected pregnant women. However, understanding the underlying pathogenesis of ZIKV congenital disease has been hampered by a lack of relevant in vivo experimental models. Here we present a candidate New World monkey model of ZIKV infection in pregnant marmosets that faithfully recapitulates human disease. ZIKV inoculation at the human-equivalent of early gestation caused an asymptomatic seroconversion, induction of type I/II interferon-associated genes and proinflammatory cytokines, and persistent viremia and viruria. Spontaneous pregnancy loss was observed 16-18 days post-infection, with extensive active placental viral replication and fetal neurocellular disorganization similar to that seen in humans. These findings underscore the key role of the placenta as a conduit for fetal infection, and demonstrate the utility of marmosets as a highly relevant model for studying congenital ZIKV disease and pregnancy loss.

Download Full-text

Vital Signs:Zika-Associated Birth Defects and Neurodevelopmental Abnormalities Possibly Associated with Congenital Zika Virus Infection — U.S. Territories and Freely Associated States, 2018

MMWR Morbidity and Mortality Weekly Report ◽

10.15585/mmwr.mm6731e1 ◽

2018 ◽

Vol 67 (31) ◽

Cited By ~ 76

Author(s):

Marion E. Rice ◽

Romeo R. Galang ◽

Nicole M. Roth ◽

Sascha R. Ellington ◽

Cynthia A. Moore ◽

...

Keyword(s):

Virus Infection ◽

Birth Defects ◽

Zika Virus ◽

Zika Virus Infection ◽

Neurodevelopmental Abnormalities

Download Full-text

Neurodevelopmental Abnormalities Associated With In Utero Zika Virus Infection in Infants and Children—The Unfolding Story

JAMA Pediatrics ◽

10.1001/jamapediatrics.2019.5257 ◽

2020 ◽

Vol 174 (3) ◽

pp. 237 ◽

Cited By ~ 1

Author(s):

Margaret A. Honein ◽

Kate R. Woodworth ◽

Christopher J. Gregory

Keyword(s):

Virus Infection ◽

Zika Virus ◽

In Utero ◽

Infants And Children ◽

Zika Virus Infection ◽

Neurodevelopmental Abnormalities ◽

In Infants And Children

Download Full-text

Maternal-fetal transmission and adverse perinatal outcomes in pregnant women infected with Zika virus: prospective cohort study in French Guiana

BMJ ◽

10.1136/bmj.k4431 ◽

2018 ◽

pp. k4431 ◽

Cited By ~ 48

Author(s):

Léo Pomar ◽

Manon Vouga ◽

Véronique Lambert ◽

Céline Pomar ◽

Najeh Hcini ◽

...

Keyword(s):

Cohort Study ◽

Relative Risk ◽

Virus Infection ◽

Zika Virus ◽

French Guiana ◽

Fetal Loss ◽

Adverse Outcomes ◽

Neonatal Outcomes ◽

Zika Virus Infection ◽

Maternal Fetal Transmission

AbstractObjectivesTo estimate the rates of maternal-fetal transmission of Zika virus, adverse fetal/neonatal outcomes, and subsequent rates of asymptomatic/symptomatic congenital Zika virus infections up to the first week of life.DesignCohort study with prospective data collection and subsequent review of fetal/neonatal outcomes.SettingsReferral centre for prenatal diagnosis of the French Guiana Western Hospital.ParticipantsPregnant women at any stage of pregnancy with a laboratory confirmed symptomatic or asymptomatic Zika virus infection during the epidemic period in western French Guiana. The cohort enrolled 300 participants and prospectively followed their 305 fetuses/newborns.Main outcome measuresRate of maternal-fetal transmission of Zika virus (amniotic fluid, fetal and neonatal blood, urine, cerebrospinal fluid, and placentas); clinical, biological, and radiological outcomes (blindly reviewed); and adverse outcomes defined as moderate signs potentially related to congenital Zika syndrome (CZS), severe complications compatible with CZS, or fetal loss. Associations between a laboratory confirmed congenital Zika virus infection and adverse fetal/neonatal outcomes were evaluated.ResultsMaternal-fetal transmission was documented in 26% (76/291) of fetuses/newborns with complete data. Among the Zika virus positive fetuses/newborns, 45% (34/76) presented with no signs/complications at birth, 20% (15/76) with moderate signs potentially related to CZS, 21% (16/76) with severe complications compatible with CZS, and 14% (11/76) with fetal loss. Compared with the Zika virus positive fetuses/neonates, those that were identified as negative for Zika virus (215/291) were less likely to present with severe complications (5%; 10/215) or fetal loss (0.5%; 1/215; relative risk 6.9, 95% confidence interval 3.6 to 13.3). Association between a positive Zika virus test and any adverse fetal/neonatal outcome was also significant (relative risk 4.4, 2.9 to 6.6). The population attributable fraction estimates that a confirmed congenital Zika virus infection contributes to 47% of adverse outcomes and 61% of severe adverse outcomes observed.ConclusionIn cases of a known maternal Zika virus infection, approximately a quarter of fetuses will become congenitally infected, of which a third will have severe complications at birth or fetal loss. The burden of CZS might be lower than initially described in South America and may not differ from other congenital infections.

Download Full-text

Fetal, neonatal, and infant outcomes associated with maternal Zika virus infection during pregnancy: A systematic review and meta-analysis

PLoS ONE ◽

10.1371/journal.pone.0246643 ◽

2021 ◽

Vol 16 (2) ◽

pp. e0246643

Author(s):

Marlos Melo Martins ◽

Antonio José Ledo Alves da Cunha ◽

Jaqueline Rodrigues Robaina ◽

Carlos Eduardo Raymundo ◽

Arnaldo Prata Barbosa ◽

...

Keyword(s):

Systematic Review ◽

Virus Infection ◽

Cohort Studies ◽

Pregnant Women ◽

Zika Virus ◽

Meta Analysis ◽

Fetal Loss ◽

Prevalence Ratio ◽

Zika Virus Infection ◽

The Impact

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.

Download Full-text

Congenital Zika Virus Infection Paradigm: What is in the Wardrobe? A Narrative Review

East Africa Science ◽

10.24248/easci.v1i1.4 ◽

2019 ◽

Vol 1 (1) ◽

pp. 49-56

Author(s):

Mariam M. Mirambo ◽

Lucas Matemba ◽

Mtebe Majigo ◽

Stephen E. Mshana

Keyword(s):

Virus Infection ◽

Neural Tube ◽

Zika Virus ◽

English Language ◽

Case Reports ◽

Case Series ◽

Epidemiological Studies ◽

Ocular Manifestations ◽

Zika Virus Infection ◽

N 93

Background: Zika virus infection during pregnancy has been recently associated with congenital microcephaly and other severe neural tube defects. However, the magnitude of confirmed cases and the scope of these anomalies have not been extensively documented. This review focuses on the magnitude of laboratory-confirmed congenital Zika virus cases among probable cases and describing the patterns of congenital anomalies allegedly caused by the Zika virus, information which will inform further research in this area. Methods: We conducted a literature search for English-language articles about congenital Zika virus infection using online electronic databases (PubMed/MEDLINE, POPLINE, Embase, Google Scholar, and Web of Knowledge). The search terms used were, “zika”, “pregnancy”, [year], “microcephaly”, “infants”, “children”, “neonates”, “foetuses”, “neural tube defect”, and “CNS manifestations” in different combinations. All articles reporting cases or case series between January 2015 and December 2016 were included. Data were entered into a Microsoft Excel database and analysed to obtain proportions of the confirmed cases and patterns of anomalies. Results: A total of 24 articles (11 case series, 9 case reports, and 4 others) were found to be eligible and included in this review. These articles reported 919 cases, with or without microcephaly, presumed to have congenital Zika virus infection. Of these cases, 884 (96.2%) had microcephaly. Of the 884 cases of microcephaly, 783 (88.6%) were tested for Zika virus infection, and 216 (27.6%; 95% confidence interval, 24.5% to 30.8%) were confirmed to be Zika virus-positive. In addition to microcephaly, other common abnormalities reported – out of 442 cases investigated – were calcifications of brain tissue (n=240, 54.3%), ventriculomegaly (n=93, 20.8%), cerebellar hypoplasia (n=52, 11.7%), and ocular manifestations (n=46, 10.4%). Conclusion: Based on the available literature, Zika virus infection during pregnancy might lead to a wide array of outcomes other than microcephaly. There is a need for more epidemiological studies in Zika-endemic areas, particularly in Africa, to ascertain the role of Zika virus in causing congenital neurological defects.

Download Full-text

Congenital Zika Virus Infection Paradigm: What is in the Wardrobe? A Narrative Review

East Africa Science ◽

10.24248/easci.v1.iss1.4 ◽

2019 ◽

Vol 1 (1) ◽

pp. 49-56

Author(s):

Mariam M. Mirambo ◽

Lucas Matemba ◽

Mtebe Majigo ◽

Stephen E. Mshana

Keyword(s):

Virus Infection ◽

Neural Tube ◽

Zika Virus ◽

English Language ◽

Case Reports ◽

Case Series ◽

Epidemiological Studies ◽

Ocular Manifestations ◽

Zika Virus Infection ◽

N 93

Background: Zika virus infection during pregnancy has been recently associated with congenital microcephaly and other severe neural tube defects. However, the magnitude of confirmed cases and the scope of these anomalies have not been extensively documented. This review focuses on the magnitude of laboratory-confirmed congenital Zika virus cases among probable cases and describing the patterns of congenital anomalies allegedly caused by the Zika virus, information which will inform further research in this area. Methods: We conducted a literature search for English-language articles about congenital Zika virus infection using online electronic databases (PubMed/MEDLINE, POPLINE, Embase, Google Scholar, and Web of Knowledge). The search terms used were, “zika”, “pregnancy”, [year], “microcephaly”, “infants”, “children”, “neonates”, “foetuses”, “neural tube defect”, and “CNS manifestations” in different combinations. All articles reporting cases or case series between January 2015 and December 2016 were included. Data were entered into a Microsoft Excel database and analysed to obtain proportions of the confirmed cases and patterns of anomalies. Results: A total of 24 articles (11 case series, 9 case reports, and 4 others) were found to be eligible and included in this review. These articles reported 919 cases, with or without microcephaly, presumed to have congenital Zika virus infection. Of these cases, 884 (96.2%) had microcephaly. Of the 884 cases of microcephaly, 783 (88.6%) were tested for Zika virus infection, and 216 (27.6%; 95% confidence interval, 24.5% to 30.8%) were confirmed to be Zika virus-positive. In addition to microcephaly, other common abnormalities reported – out of 442 cases investigated – were calcifications of brain tissue (n=240, 54.3%), ventriculomegaly (n=93, 20.8%), cerebellar hypoplasia (n=52, 11.7%), and ocular manifestations (n=46, 10.4%). Conclusion: Based on the available literature, Zika virus infection during pregnancy might lead to a wide array of outcomes other than microcephaly. There is a need for more epidemiological studies in Zika-endemic areas, particularly in Africa, to ascertain the role of Zika virus in causing congenital neurological defects.

Download Full-text