Involvement of Th1Th17 Cell Subpopulations in the Immune Responses of Mothers Who Gave Birth to Children with Congenital Zika Syndrome (CZS).
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ABSTRACT:
SUBMITTER: Paiva IA
PROVIDER: S-EPMC8879837 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
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Involvement of Th1Th17 Cell Subpopulations in the Immune Responses of Mothers Who Gave Birth to Children with Congenital Zika Syndrome (CZS).
Paiva Iury Amancio IA Familiar-Macedo Débora D Badolato-Corrêa Jéssica J Carvalho Fabiana Rabe FR Dias Helver Gonçalves HG Pauvolid-Corrêa Alex A Santos Caroline Fernandes Dos CFD Silva Andréa Alice AA Azeredo Elzinandes Leal de EL Vianna Renata Artimos de Oliveira RAO Cardoso Claudete Aparecida Araújo CAA Grifoni Alba A Sette Alessandro A Weiskopf Daniela D de-Oliveira-Pinto Luzia Maria LM
Viruses 20220126 2
High levels of T helper 17 cell (Th17)-related cytokines have been shown in acute Zika virus (ZIKV) infection. We hypothesized that the high levels of Th17-related cytokines, associated with a regulatory environment during pregnancy, create a favorable milieu for the differentiation of CD4+Th17 cells. We present data from a cross-sectional study on mothers who confirmed ZIKV infection by qRT-PCR and their children. We also recruited non-pregnant women infected with ZIKV in the same period. ZIKV ...[more]
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Project description:BACKGROUND:A Zika virus (ZIKV) infection outbreak occurred in Brazil in 2015, accompanied by a marked increase in the number of newborns presenting with microcephaly and other neurological disorders. This characteristic set of birth defects was later termed congenital Zika syndrome (CZS). The therapeutic itinerary of mothers and children infected by ZIKV can be determined by several factors, including the relationship established with existing healthcare services. Here, we aimed to describe and analyze the extent to which children with CZS, born from 2015 to 2018 in the state of Mato Grosso do Sul, Brazil, and their mothers were treated according to the guidelines established by the Brazilian Ministry of Health. METHODS:This was a descriptive cross-sectional study that considered all children (and respective mothers) with confirmed or suspected CZS born in Mato Grosso do Sul. Children and their mothers were identified based on all suspected or confirmed cases of congenital anomalies in Mato Grosso do Sul that were reported to the Registry of Public Health Events. We analyzed data on the epidemiological profile of mother-child pairs and the care received by them. Data were summarized using statistical descriptive analysis. RESULTS:We showed that most mothers were white women (57%) with low income. Among pregnant women, 73% had a diagnosis of fever caused by ZIKV infection at a primary health care institution (PHCI), but only 36% received the necessary information regarding the risk of CZS. Over a third (36%) of the mothers did not receive guidance about childcare follow-up and 73% did not receive guidance regarding the availability of social support after childbirth. Gaps in medical care were observed mainly in pregnant women treated at a PHCI. Specialized assistance for children was adequate in most cases. Psychosocial support was not made available to women throughout their therapeutic itineraries. CONCLUSIONS:Here, we identified gaps in the care of families and children with disabilities, which can have an important impact on their quality of life. Beyond protocols, practical interventions must cover all the needs that arise throughout the therapeutic itineraries not only of children but also of pregnant women and mothers.
| S-EPMC7245942 | biostudies-literature
Project description:BackgroundChildren with in utero Zika virus (ZIKV) exposure without congenital Zika syndrome (CZS) are at risk for abnormal neurodevelopment. Preschool-age outcomes for children with antenatal ZIKV exposure have not yet been established.MethodsChildren with in utero ZIKV exposure and non-exposed controls had neurodevelopmental evaluations at age 3-5 years in Sabanalarga, Colombia. Cases did not have CZS and were previously evaluated prenatally through age 18 months. Controls were born before ZIKV arrival to Colombia. Neurodevelopmental assessments included Pediatric Evaluation of Disability Inventory (PEDI-CAT), Behavior Rating Inventory of Executive Function (BRIEF-P), Bracken School Readiness Assessment (BSRA), and Movement Assessment Battery for Children (MABC). Family demographics and child medical history were recorded.ResultsFifty-five ZIKV-exposed children were evaluated at mean age 3.6 years and 70 controls were evaluated at 5.2 years. Family demographics were similar between groups. BRIEF-P t-scores were higher for cases than controls in shift and flexibility domains. Cases had lower PEDI-CAT mobility t-scores compared to controls. There was no difference in MABC between groups. In 11% of cases and 1% of controls, parents reported child mood problems.ConclusionsChildren with in utero ZIKV exposure without CZS may demonstrate emerging differences in executive function, mood, and adaptive mobility that require continued evaluation.ImpactPreschool neurodevelopmental outcome in children with in utero Zika virus exposure is not yet known, since the Zika virus epidemic occurred in 2015-2017 and these children are only now entering school age. This study finds that Colombian children with in utero Zika virus exposure without congenital Zika syndrome are overall developing well but may have emerging differences in executive function, behavior and mood, and adaptive mobility compared to children without in utero Zika virus exposure. Children with in utero Zika virus exposure require continued multi-domain longitudinal neurodevelopmental evaluation through school age.
| S-EPMC10227180 | biostudies-literature
Project description:Background: There is an urgent need to understand the complex relationship between cross-reactive anti-viral immunity, disease susceptibility, and severity in the face of differential exposure to related, circulating Flaviviruses. Co-exposure to Dengue virus and Zika virus in Brazil is a case in point. A devastating aspect of the 2015-2016 South American Zika outbreak was the dramatic increase in numbers of infants born with microcephaly to mothers exposed to Zika virus during pregnancy. It has been proposed that this is more likely to ensue from Zika infection in women lacking cross-protective Dengue immunity. In this case series we measure the prevalence of Dengue immunity in a cohort of mothers exposed to Zika virus during pregnancy in the 2015-2016 Zika outbreak that gave birth to an infant affected by microcephaly and explore their adaptive immunity to Zika virus. Results: Fifty women from Sergipe, Brazil who gave birth to infants with microcephaly following Zika virus exposure during the 2015-16 outbreak were tested for serological evidence of Dengue exposure and IFN? ELISpot spot forming cell (SFC) response to Zika virus. The majority (46/50) demonstrated Dengue immunity. IFN? ELISpot responses to Zika virus antigens showed the following hierarchy: Env>NS1>NS3>C protein. Twenty T cell epitopes from Zika virus Env were identified. Responses to Zika virus antigens Env and NS1 were polyfunctional with cells making IFN?, TNF?, IL-4, IL-13, and IL-10. In contrast, responses to NS5 only produced the immune regulatory TGF?1 cytokine. There were SFC responses against Zika virus Env (1-20) and variant peptide sequences from West Nile virus, Dengue virus 1-4 and Yellow Fever virus. Conclusion: Almost all the women in our study showed serological evidence of Dengue immunity, suggesting that microcephaly can occur in DENV immune mothers. T cell immunity to Zika virus showed a multifunctional response to the antigens Env and NS1 and immune regulatory responses to NS5 and C protein. Our data support an argument that different viral products may skew the antiviral response to a more pro or anti-inflammatory outcome, with an associated impact on immunopathogenesis.
| S-EPMC7040481 | biostudies-literature
Project description:Congenital Zika Syndrome (CZS) is a condition that has emerged only recently, bringing together multiple changes, including significant changes in the stomatognathic system, which may compromise sucking behavior and consequently the breastfeeding practice. The aim of this study was to investigate the breastfeeding behaviors in children with CZS. A longitudinal study was carried out in two reference centers in Northeastern Brazil. The nonprobabilistic sample consisted of 79 children diagnosed with physical, neurological, and behavioral alterations compatible with CZS. Information regarding the child, nutritive, and nonnutritive sucking behavior and changes related to the sucking reflex was collected. Data were presented through descriptive and inferential statistics. In the bivariate analyses, the chi-squared test was used and 5% significance level was adopted. The majority of children had severe microcephaly (59.7%). Breastfeeding was performed at birth in most of CZS children (89.9%) but only 36.6% of them presented exclusive breastfeeding in the six months of life. Bottle feeding and pacifier were used in 89.9% and 55.7%, respectively. Sucking and swallowing difficulties and occurrence of gastroesophageal reflux were observed in 27.8%, 48.0%, and 29.2% of children, respectively. Early weaning was associated with bottle feeding (p=0.005) and pacifier sucking (p=0.003). Although breastfeeding practice at birth constitutes a behavior adopted by most of mothers, adherence to this exclusive habit until the first six months of life was low since the children presenting a large number of comorbidities with direct interference in the suction reflex, sucking, and swallowing difficulty.
| S-EPMC7102404 | biostudies-literature
Project description:ObjectiveTo describe the neurological and neurodevelopmental outcomes of children with Congenital Zika Syndrome (CZS) associated microcephaly beyond 2 years of age.MethodWe followed children with CZS-associated microcephaly in an outpatient clinic in Salvador, Brazil. Neurological and neurodevelopmental assessments were performed using the Hammersmith Infant Neurological Examination (HINE) and Bayley Scales of Infant and Toddler Neurodevelopment (Bayley-III) respectively.ResultsOf the 42 children included, 19 were male (45.2%); median (interquartile range) age at neurological evaluation was 28 (25-32) months, and 36 (85.7%) had severe microcephaly. HINE and Bayley-III results were completed for 35/42 (83.3%) and 33/42 (78.5%) children respectively. Bayley-III identified a severe developmental delay in 32/33 (97.0%) children while 1/33 (3.0%) had only a mild delay. In the multivariable analysis, we found that Bayley-III and HINE scores were correlated. Better HINE scores were associated with higher Bayley-III cognitive raw scores (β = 0.29; CI 95% = 0.02-0.57) and motor raw scores (β = 0.43; CI 95% = 0.04-0.82) after adjusting for head circumference, prematurity, and age at neurodevelopmental evaluation. Furthermore, we found that greater head circumference at follow up was associated with higher cognitive (β = 1.27; CI 95% = 0.01-2.53) and motor raw scores (β = 2.03; CI 95% = 0.25-3.81).ConclusionChildren with CZS-associated microcephaly demonstrate severe neurodevelopmental delays and slower growth rates than their peers over time. Still, they have remarkably heterogeneous neurodevelopmental profiles according to neurological exam scores which correlate with their long-term outcomes. We found that HINE scores effectively captured the heterogeneity of neurological capabilities among these children and could be predictive of cognitive and motor development progress.
| S-EPMC8443077 | biostudies-literature
Project description:Importance:Although birth defects in children with congenital Zika syndrome (CZS) are expected to result in significant intellectual disabilities, the extent of delay and profiles of development have yet to be fully described. Objectives:To describe the neurodevelopmental profiles of children with CZS and to test whether prenatal and postpartum characteristics were associated with the severity of developmental delays. Design, Setting, and Participants:This is a case series of the trajectories of developmental, behavioral, and medical needs of 121 young children with CZS who were assessed at a specialized rehabilitation center in Recife, Brazil, beginning in January 2018 as part of 5-year longitudinal study. Children were included if they had serologic confirmation of Zika virus and met clinical criteria accompanied by parental report of suspected exposure to Zika virus during pregnancy. Exposures:Prenatal Zika virus exposure. Main Outcomes and Measures:The Brazilian version of the Bayley Scales of Infant and Toddler Development, Third Edition, was administered by trained assessors as part of an initial comprehensive assessment battery. Caregiver interviews and medical record reviews were conducted to gather basic demographic information and medical comorbidities. Linear regression was used to identify potential factors for development. Results:The sample included 121 young children (mean [SD] age, 31.2 [1.9] months; 61 [50.4%] girls). At age approximately 2.5 years, nearly all children in this sample demonstrated profound developmental delays across all domains of functioning, with a mean (SD) developmental age equivalent to approximately 2 to 4 months (eg, cognitive domain, 2.24 [3.09] months; fine motor subscale, 2.15 [2.93] months; expressive language subscale, 2.30 [2.52] months). A relative strength was found in receptive language, with scores on this scale significantly higher than most other domains (eg, cognition: t?=?3.73; P?<?.001; fine motor: t?=?6.99; P?<?.001). Head circumference at birth was the single strongest factor associated with outcomes across all developmental domains (eg, cognitive: ??=?1.41; SE, 0.67; P?=?.04; fine motor: ??=?1.36; SE, 0.49; P?=?.007). Conclusions and Relevance:The findings of this study provide important information regarding the severity of disability that these children and their families will experience. The findings also establish an initial point from which to monitor developmental trajectories, medical comorbidities (eg, seizures), effectiveness of interventions, and cumulative consequences on families.
| S-EPMC7201309 | biostudies-literature
Project description:BackgroundThe Zika virus outbreak in Brazil (2015-2016) affected thousands of children who were born with Congenital Zika Syndrome (CZS). Families play an important role in their care of children with complex needs, yet their knowledge, experience and skills are rarely harnessed in existing interventions to best support these families.ObjectiveThis study explores the use of mothers as facilitators for a community-based group intervention for children with CZS and their caregivers in Brazil.MethodsFour facilitators were trained to deliver the 10-week intervention called "Juntos". Two were mothers of a child with CZS ("expert mothers") and two were therapists (speech therapist and physiotherapist). The intervention was delivered to three groups, generally including 8-10 caregivers. Two researchers, who were psychologists, observed the groups and held focus group discussions at the end of each session. They undertook semi-structured interviews post intervention with a purposive sample of caregivers, and with the facilitators. Observation notes were collated and summarised. Transcripts were transcribed and thematically analysed using five elements to assess feasibility: acceptability, demand, implementation, practicality and adaptation.ResultsThe use of expert mothers as facilitators was considered to be acceptable and there was demand for their role. Their experiential knowledge was viewed as important for sharing and learning, and supporting and encouraging the group. The intervention was delivered with fidelity by the expert mothers. The practicality of the intervention was facilitated by holding the group sessions in the community, providing transport costs to facilitators and participants, paying expert mothers and therapist facilitators equally and supporting the expert mothers through a mentorship programme. Equal payment with the therapist enabled the expert mothers to better facilitate the groups, through increased confidence in the value of their role. Adaptation of the intervention included development of video resources and mentoring guidelines.ConclusionThe use of expert mothers as facilitators of caregiver groups provides a unique approach to harness the knowledge, experience, and skills of families to provide care, and is likely to be feasible in similar contexts.
| S-EPMC7482954 | biostudies-literature
Project description:The link between Zika virus infection during pregnancy and microcephaly and other neurodevelopmental defects in infants, referred to as congenital Zika syndrome (CZS), was recently discovered. One key question that remains is whether such neurodevelopmental abnormalities are limited to the recently evolved Asiatic ZIKV strains or if they can also be induced by endemic African strains. Thus, we examined birth registries from one particular hospital from a country in West Africa, where ZIKV is endemic. Results showed a seasonal pattern of birth defects that is consistent with potential CZS, which corresponds to a range of presumed maternal infection that encompasses both the peak of the warm, rainy season as well as the months immediately following it, when mosquito activity is likely high. While we refrain from definitively linking ZIKV infection and birth defects in West Africa at this time, in part due to scant data available from the region, we hope that this report will initiate broader surveillance efforts that may help shed light onto mechanisms underlying CZS.
| S-EPMC6058464 | biostudies-literature
Project description:Brazil is one of the countries that experienced an epidemic of microcephaly and other congenital manifestations related to maternal Zika virus infection which can result in Congenital Zika Syndrome (CZS). Since the Zika virus can modulate the immune system, studying mothers' and children's immune profiles become essential to better understanding CZS development. Therefore, we investigated the lymphocyte population profile of children who developed CZS and their mothers' immune response in this study. The study groups were formed from the Plaque Reduction Neutralization Test (PRNT) (CZS+ group) result. To evaluate the lymphocyte population profile, we performed phenotyping of peripheral lymphocytes and quantification of serum cytokine levels. The immunophenotyping and cytokine profile was correlated between CSZ+ children and their mothers. Both groups exhibited increased interleukin-17 levels and a reduction in the subpopulation of CD4+ T lymphocytes. In contrast, the maternal group showed a reduction in the population of B lymphocytes. Thus, the development of CZS is related to the presence of an inflammatory immune profile in children and their mothers characterized by Th17 activation.
| S-EPMC10301288 | biostudies-literature
Project description:In this study, we analyzed by a shotgun proteomic approach the amniotic fluid of pregnant women infected with Zika carrying microcephalic (ZIKV+M+) or healthy fetuses (ZIKV+M-) compared to Zika negative controls (ZIKV-M-) to identify and understand the biological process and pathways affected by CZS development. Up-abundant proteins in the ZIKV+M- group showed enrichment mainly in the extracellular matrix (ECM) structure and organization. The innate immune system (i.e. neutrophil degranulation) and fibrin clot formation processes were dysregulated in the ZIKV+M+ group, with an increase in the abundance of proteins associated with these biological processes. In both groups, a decrease in the abundance of proteins associated with neutrophil degranulation was observed. ZIKV+M+ group presented a decrease of abundance in the dysregulated extracellular matrix proteins compared to ZIKV+M-. These results could suggest that the development of microcephalic or healthy phenotypes is more associated with the ECM and immune system protein abundances than the dysregulated processes in each group.
2024-07-02 | PXD023776 | Pride