Association between confirmed congenital Zika infection at birth and outcomes up to 3 years of life.
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ABSTRACT:
SUBMITTER: Hcini N
PROVIDER: S-EPMC8169933 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In 2015-2016, a large Zika virus (ZIKV) outbreak occurred in the Americas. Although the exact ZIKV antibody kinetics after infection are unknown, recent evidence indicates the rapid waning of ZIKV antibodies in humans. Therefore, we aimed to determine the levels of ZIKV antibodies more than three years after a ZIKV infection. We performed ZIKV virus neutralization tests (VNT) and a commercial ZIKV non-structural protein 1 (NS1) IgG ELISA in a cohort of 49 participants from Suriname who had a polymerase-chain-reaction-confirmed ZIKV infection more than three years ago. Furthermore, we determined the presence of antibodies against multiple dengue virus (DENV) antigens. The ZIKV seroprevalence in this cohort, assessed with ZIKV VNT and ZIKV NS1 IgG ELISA, was 59.2% and 63.3%, respectively. There was, however, no correlation between these two tests. Furthermore, we did not find evidence of a potential negative influence of DENV immunity on ZIKV antibody titers. ZIKV seroprevalence, assessed with two commonly used serological tests, was lower than expected in this cohort of participants who had a confirmed previous ZIKV infection. This can have implications for future ZIKV seroprevalence studies and possibly for the duration of immunological protection after a ZIKV infection.
| S-EPMC8310224 | biostudies-literature
Project description:Human infants with congenital Zika virus (ZIKV) infection exhibit a range of symptoms including microcephaly, intracranial calcifications, macular atrophy and arthrogryposis. More importantly, prognosis data have lagged far behind the recent outbreak of ZIKV in 2015. In this work, we allow congenitally ZIKV-infected mice to grow into puberty. These mice exhibited motor incoordination and visual dysfunctions, which can be accounted by anatomical defects in the retina and cerebellar cortex. In contrary, anxiety level of the ZIKV-infected mice is normal. The spectrum of anatomical and behavioral deficits is consistent across different mice. Our data provided evidence that may help predict the public health burden in terms of prognosis of ZIKV-related congenital brain malformations in an animal model. Our study provided behavioral evaluation for the prognosis of congenital ZIKV infection and provides a platform for screening and evaluation of drugs candidates and treatment aiming at improving regeneration of infected neurons to prevent sequelae caused by ZIKV infection of fetus.
| S-EPMC5478201 | biostudies-literature
Project description:Following the large outbreak of Zika virus in the Western Hemisphere, many infants have been born with congenital Zika virus infection. It is important to describe the functional outcomes seen with congenital infections to allow for their recognition and appropriate interventions. We evaluated 120 children conceived during the 2015-2016 Zika virus outbreak in Paraíba, Brazil, who were approximately 24 months old, to assess functional outcomes. All children met either anthropometric criteria or laboratory criteria suggestive of possible congenital Zika virus infection. We collected results of previous medical evaluations, interviewed parents, and performed physical examinations and functional assessments, for example, the Hammersmith Infant Neurological Examination (HINE). We compared patterns of neurologic outcomes and developmental delay at age 24 months by whether children met anthropometric or laboratory criteria, or both. Among children meeting both criteria, 60% (26/43) were multiply affected (had severe motor impairment, severe developmental delay, and suboptimal HINE scores), compared with 5% (3/57) meeting only laboratory criteria and none (0/20) meeting only anthropometric criteria. Of the remaining 91 children, 49% (45) had developmental delay, with more severe delay seen in children meeting both criteria. Although children meeting physical and laboratory criteria for potential congenital Zika virus infection were more severely affected, we did identify several children with notable adverse neurologic outcomes and developmental delay with no physical findings but potential laboratory evidence of Zika virus infection. Given this, all children who were potentially exposed in utero to Zika virus should be monitored in early childhood for deficits to allow for early intervention.
| S-EPMC7204564 | biostudies-literature
Project description:Zika virus (ZIKV) infection during pregnancy causes a wide spectrum of congenital abnormalities and postnatal developmental sequelae such as fetal loss, intrauterine growth restriction (IUGR), microcephaly, or motor and neurodevelopmental disorders. Here, we investigated whether a mouse pregnancy model recapitulated a wide range of symptoms after congenital ZIKV infection, and whether the embryonic age of congenital infection changed the fetal or postnatal outcomes. Infection with ZIKV strain PRVABC59 from embryonic day 6.5 (E6.5) to E8.5, corresponding to the mid-first trimester in humans, caused fetal death, fetal resorption, or severe IUGR, whereas infection from E9.5 to E14.5, corresponding to the late-first to second trimester in humans, caused stillbirth, neonatal death, microcephaly, and postnatal growth deficiency. Furthermore, 4-week-old offspring born to dams infected at E12.5 showed abnormalities in neuropsychiatric state, motor behavior, autonomic function, or reflex and sensory function. Thus, our model recapitulated the multiple symptoms seen in human cases, and the embryonic age of congenital infection was one of the determinant factors of offspring outcomes in mice. Furthermore, maternal neutralizing antibodies protected the offspring from neonatal death after congenital infection at E9.5, suggesting that neonatal death in our model could serve as criteria for screening of vaccine candidates.
| S-EPMC8473443 | biostudies-literature
Project description:Zika virus (ZIKV) infection during pregnancy in humans results in intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we found that fetus-derived type I interferon (IFN-I) signaling can enhance anti-ZIKV responses and provide clinical benefits to the fetus. Because IFN-λ shares signaling cascades and antiviral functions with IFN-I, we investigated the in vivo effects of IFN-λ in ZIKV-infected pregnant mice. IFN-λ administration during mid-pregnancy reduced ZIKV burden in maternal and fetal organs and alleviated placental injuries and fetal demise. In addition, prophylactic and therapeutic treatment of IFN-λ1 in a human trophoblast line, as well as in primary human amniotic epithelial cells, greatly reduced the ZIKV burden. Our data highlight IFN-λ1 as a potential therapeutic useful for women at risk for congenital Zika disease.
| S-EPMC5726784 | biostudies-literature
Project description: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 a Brazilian ZIKV isolate and found that they were born with a reduction in callosal area and density of callosal neurons. ZIKV infection also causes a density reduction in 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 in callosal axon length. GFAP labeling showed that an in utero infection compromises glial cells responsible for midline axon guidance. 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.
| S-EPMC10748342 | biostudies-literature
Project description:ImportanceHydrocephalus is a treatable but potentially fatal complication that has not been previously described in congenital Zika syndrome (CZS).ObjectiveTo describe the clinical features and imaging findings in 24 patients with congenital Zika syndrome (CZS) who developed hydrocephalus.Design, setting, and participantsThis case series included patients with hydrocephalus who were born in October and November 2015 and followed up until mid-2017 in the 2 largest national referral centers for CZS in Brazil. The participants included consecutively enrolled children with a clinical and laboratorial diagnosis of CZS who developed clinical and/or image findings suggestive of hydrocephalus and who were confirmed to experience increased intracranial hypertension during ventriculoperitoneal shunt procedures.Main outcomes and measuresTo retrospectively describe clinical and image findings in these 24 patients.ResultsThis multicenter cohort included 308 patients with CZS; 24 consecutive children were enrolled in this study. These children were aged between 3 to 18 months, and 13 of 24 (54%) were female. All patients presented with at least 1 positive test result for anti-Zika antibodies in cerebrospinal fluid or serum and had classic signs of CZS. At the time of hydrocephalus diagnosis, only 14 of 24 patients (58%) had symptoms and signs suggestive of hydrocephalus (mainly worsening seizures, vomiting, irritability, and/or sudden increase of head circumference percentile). Two of 24 patients (8%) had no symptoms suggestive of hydrocephalus but were found to have reduced brain volume on repeated imaging. Cerebellar or brainstem hypoplasia on baseline imaging were found in 18 of 23 patients (78%). At the second computed tomographic scan, all patients showed a marked increase of ventricular volume, compatible with communicating hydrocephalus, and reduction of brain tissue that was visibly worse than on baseline imaging for the 23 patients with repeated scans.Conclusions and relevanceWe present evidence that hydrocephalus is a complication of CZS in at least a proportion of patients. The clinical spectrum of this condition continues to evolve, but given that presenting signs and symptoms of hydrocephalus can be challenging to recognize in CZS, we provisionally recommend that high suspicion and appropriate monitoring for hydrocephalus should be part of the standard care of patients with CZS.
| S-EPMC6439957 | biostudies-literature
Project description:Zika virus: Zika virus chimeric vaccineZika virus (ZIKV) infection generally results in mild symptoms but can cause serious developmental abnormalities in infants born to ZIKV infected mothers. Kai Dallmeier and colleagues at the KU Leuven in Belgium, engineered a chimeric live-attenuated vaccine (YF-ZIKprM/E) by swapping the glycoprotein from the Yellow Fever vaccine YFV-17D with that of a pre-epidemic ZIKV strain. YF-ZIKprM/E is very well tolerated with no adverse effects even following high dose intracranial infection. Mice highly susceptible to ZIKV infection—including AG129 and type I interferon receptor deficient strains—vaccinated with a single dose of YF-ZIKprM/E are fully protected from lethal ZIKV challenge. Protection can be achieved within 7 days and by low doses of YF-ZIKprM/E, is durable and generally results in sterilizing immunity. YF-ZIKprM/E elicits both neutralizing antibodies and robust cellular immunity. Finally, YF-ZIKprM/E can also prevent vertical transmission of ZIKV and achieve efficient protection of pups from neurological defects following intraplacental challenge.
| S-EPMC6292895 | biostudies-other
Project description:ObjectiveTo analyze adverse fetal and neonatal outcomes of Zika virus infection by the timing of infection during pregnancy. Method: Cohort study of 190 pregnancies with 193 offspring with a positive RT-PCR test for Zika virus (March/2016 to April/2017).ResultsDeath or defects related to congenital Zika virus infection were identified in 37.3% of fetuses and newborns, and microcephaly in 21.4% of the newborns. The proportion of small for gestational age newborns was 21.9%. Maternal symptoms in the first trimester were significantly associated with the birth of newborns with microcephaly/cerebral atrophy, small for gestational age and with the deaths (one abortion, one stillbirth and the two neonatal deaths). Maternal infection during the second trimester was further associated with asymptomatic newborns at birth. The study showed that 58.5% of the offspring with microcephaly and / or cortical atrophy were small for gestational age, with an evident decrease in symptomatic offspring without microcephaly, 24.1%, and with only 9.1% in the asymptomatic group.ConclusionThis study showed that the earlier the symptoms appear during gestation, the more severe the endpoints. We found a higher percentage of small for gestational age newborns exposed to Zika virus early in gestation. We also found a group of apparently asymptomatic newborns with proven Zika infection, which highlights the importance of follow up studies in this population.
| S-EPMC7781387 | biostudies-literature
Project description:Zika virus (ZIKV), an emerging virus belonging to the Flaviviridae family, causes severe neurological clinical complications and has been associated with Guillain-Barré syndrome, fetal abnormalities known collectively as congenital Zika syndrome, and microcephaly. Studies have shown that ZIKV infection can alter cellular metabolism, directly affecting neural development. Brain growth requires controlled cellular metabolism, which is essential for cell proliferation and maturation. However, little is known regarding the metabolic profile of ZIKV-infected newborns and possible associations related to microcephaly. Furthering the understanding surrounding underlying mechanisms is essential to developing personalized treatments for affected individuals. Thus, metabolomics, the study of the metabolites produced by or modified in an organism, constitutes a valuable approach in the study of complex diseases. Here, 26 serum samples from ZIKV-positive newborns with or without microcephaly, as well as controls, were analyzed using an untargeted metabolomics approach involving gas chromatography-mass spectrometry (GC-MS). Significant alterations in essential and non-essential amino acids, as well as carbohydrates (including aldohexoses, such as glucose or mannose) and their derivatives (urea and pyruvic acid), were observed in the metabolic profiles analyzed. Our results provide insight into relevant metabolic processes in patients with ZIKV and microcephaly.
| S-EPMC8070065 | biostudies-literature