The Hip of Children with Congenital Zika Syndrome: A Prospective Observational Study.

OBJECTIVE: To assess the clinical and radiographic characteristics of hip joint deformities in children with congenital Zika syndrome (CZS), and the evolution of hip joint deformities in affected infants for the first 3 years of life. STUDY DESIGN: This prospective observational study evaluated orthopedic clinical examinations performed every 3 months to assess hip flexion and extension, lateral and medial rotation, and abduction and adduction, as well as lower limb muscle length and tone. The biannual radiograph comprised anteroposterior panoramic pelvic radiographs with the lower limbs in extension. Percentage of migration was used as a radiographic study tool to measure and evaluate linear hip displacement. RESULTS: From November 2018 to March 2020, we followed 30 children with CZS, of whom 15 (50%) had normal pelvic radiographs on admission; 5 (33.3%) developed hip displacement by the second radiograph examination. During follow-up radiographic examinations, 20 of the 30 children (66.7%) were diagnosed with hip displacement and/or dislocation of at least 1 side, and 10 of the 30 (33.3%) remained normal. Among 30 affected patients, 13 (43.3%) had hip displacement on the right side and 9 (30%) on the left side. Logistic regression analysis revealed that spasticity (P = .0033; OR, 15.9) and ophthalmologic abnormalities (P = .0163; OR, 16.9) were associated with hip dislocation during follow-up. CONCLUSIONS: Pelvic radiographic follow-up for all children with CZS will complement physical examination, diagnosis, and monitoring for hip joint deformities.

Two-year follow-up of children with congenital Zika syndrome: the evolution of clinical patterns.

The aim of the study was to describe neurological manifestations in children with congenital Zika syndrome (CZS) in the first 2 years of age. In this prospective observational study, children with CZS treated at a university hospital received a neurological assessment and were evaluated using two neurodevelopmental scales (the Denver II test and the assessment of gross motor development of the World Health Organization) by a pediatric neurologist on admission to the study and at 4, 8, 12, 18, and 24 months of age. The data collected were stored in Microsoft Excel version 14.6.3. Thirty-eight children (27 males and 11 females; a median age of 4.3 months (interquartile range (IQR): 1.6-11.4)) with CZS were evaluated. Irritability was present in 50% and 27% of the children at 8 months and 24 months, respectively. Axial hypertonia was highly prevalent at 4 months (77%), with a decrease to 50% at 24 months. At all ages, spastic tetraparesis was the most common motor abnormality (> 80%). Twenty-seven (71%) participants were diagnosed with epilepsy, and the median age at seizure onset was 6 months (IQR: 3.5-8). The most frequent types of seizures were focal seizures and spasms, with spasms being the most frequent in the first year of life (52%) and focal crises being the most frequent in the second year of life (50%).Conclusion: This study allowed observation of neurological abnormalities over time, the evolution of epileptic manifestations, and recognition of new patterns of clinical neurological abnormalities, helping clinicians to recognize CZS earlier, minimizing the impact of new outbreaks. What is Known: • Clinical patterns of SZC patients at pre-established ages or date of data collection • More frequent studies with data collection of clinical-radiological features of patient's over his first year of life What is New: • Comprehensive clinical neurological progression data regarding CZS in the first 2 years of life, recognizing patterns • Hypothesis including a new CZS spectrum with milder clinical-radiological features.

Differential Longevity of Memory CD4 and CD8 T Cells in a Cohort of the Mothers With a History of ZIKV Infection and Their Children.

Background: Zika virus (ZIKV) infection causes for mild and self-limiting disease in healthy adults. In newborns, it can occasionally lead to a spectrum of malformations, the congenital Zika syndrome (CZS). Thus, little is known if mothers and babies with a history of ZIKV infection were able to develop long-lasting T-cell immunity. To these issues, we measure the prevalence of ZIKV T-cell immunity in a cohort of mothers infected to the ZIKV during pregnancy in the 2016-2017 Zika outbreak, who gave birth to infants affected by neurological complications or asymptomatic ones. Results: Twenty-one mothers and 18 children were tested for IFN-γ ELISpot and T-cell responses for flow cytometry assays in response to CD4 ZIKV and CD8 ZIKV megapools (CD4 ZIKV MP and CD8 ZIKV MP). IFN-γ ELISpot responses to ZIKV MPs showed an increased CD4 and CD8 T-cell responses in mothers compared to children. The degranulation activity and IFN-γ-producing CD4 T cells were detected in most mothers, and children, while in CD8 T-cells, low responses were detected in these study groups. The total Temra T cell subset is enriched for IFN-γ+ CD4 T cells after stimulation of CD4 ZIKV MP. Conclusion: Donors with a history of ZIKV infection demonstrated long-term CD4 T cell immunity to ZIKV CD4 MP. However, the same was not observed in CD8 T cells with the ZIKV CD8 MP. One possibility is that the cytotoxic and pro-inflammatory activities of CD8 T cells are markedly demonstrated in the early stages of infection, but less detected in the disease resolution phase, when the virus has already been eliminated. The responses of mothers' T cells to ZIKV MPs do not appear to be related to their children's clinical outcome. There was also no marked difference in the T cell responses to ZIKV MP between children affected or not with CZS. These data still need to be investigated, including the evaluation of the response of CD8 T cells to other ZIKV peptides.

Serum Proteomics Reveals Alterations in Protease Activity, Axon Guidance, and Visual Phototransduction Pathways in Infants With In Utero Exposure to Zika Virus Without Congenital Zika Syndrome.

In 2015, ZIKV infection attracted international attention during an epidemic in the Americas, when neurological disorders were reported in infants who had their mothers exposed to ZIKV during pregnancy. World Health Organization (WHO) epidemiological data show that 5 to 15% of neonates exposed to ZIKV in the uterus have complications included in abnormalities related to Congenital Zika Syndrome (CZS). The risk of complications after birth is not well documented, however, clinical evidence shows that 6% of infants exposed to ZIKV during pregnancy have complications present at birth, and this rate rises to 14% when medical monitoring is performed in all exposed infants, regardless of birth condition. Thus, the evaluation and monitoring of all exposed infants are of foremost importance as the development of late complications has been increasingly supported by clinical evidence. The identification of changes in protein profile of infants exposed to ZIKV without CZS could provide valuable findings to better understand molecular changes in this cohort. Here, we use a shotgun-proteomics approach to investigate alterations in the serum of infants without CZS symptoms but exposed to intrauterine ZIKV (ZIKV) compared to unexposed controls (CTRL). A complex pattern of differentially expressed proteins was identified, highlighting the dysregulation of proteins involved in axon orientation, visual phototransduction, and global protease activity in children exposed to ZIKV without CZS. These data support the importance of monitoring children exposed to ZIKV during gestation and without early CZS symptoms. Our study is the first to assess molecular evidence of possible late disorders in children victims of the ZIKV outbreak in the Americas. We emphasize the importance of medical monitoring of symptomatic and asymptomatic children, as apparently unexplained late neurological and eye disorders may be due to intrauterine ZIKV exposure.

The accuracy of anti-human herpesvirus 6 IgM detection in children with recent primary infection.

Human herpesvirus 6 (HHV-6) has been shown to infect almost all children by 4 years of age. Even with a typical clinical presentation, HHV-6 infection is misdiagnosed frequently as measles or rubella. The aim of this study was to assess the accuracy of the IgM test for detection of recent primary HHV-6 infection. The study was conducted between January, 1998 and December, 2006 at primary health care units in Niterói, Rio de Janeiro, Brazil. Sera from 185 children, in whom measles, rubella, dengue fever and parvovirus B19 infections were excluded, were studied for anti-HHV-6 IgG and IgM antibodies using an indirect immunofluorescence test. Seventy-one (38.4%) of the children had evidence of primary HHV-6 infection. Taking the IgG avidity test as the "gold standard", the following results for IgM were obtained-sensitivity: 76.1%; specificity: 87.5%; accuracy: 82.4%. This study confirmed the low accuracy of IgM detection for the diagnosis of primary HHV-6 infection.