Zika-related adverse outcomes in a cohort of pregnant women with rash in Pernambuco, Brazil.

BACKGROUND: While Zika virus (ZIKV) is now widely recognized as a teratogen, the frequency and full spectrum of adverse outcomes of congenital ZIKV infection remains incompletely understood. METHODS: Participants in the MERG cohort of pregnant women with rash, recruited from the surveillance system from December/2015-June/2017. Exposure definition was based on a combination of longitudinal data from molecular, serologic (IgM and IgG3) and plaque reduction neutralization tests for ZIKV. Children were evaluated by a team of clinical specialists and by transfontanelle ultrasound and were classified as having microcephaly and/or other signs/symptoms consistent with congenital Zika syndrome (CZS). Risks of adverse outcomes were quantified according to the relative evidence of a ZIKV infection in pregnancy. FINDINGS: 376 women had confirmed and suspected exposure to ZIKV. Among evaluable children born to these mothers, 20% presented with an adverse outcome compatible with exposure to ZIKV during pregnancy. The absolute risk of microcephaly was 2.9% (11/376), of calcifications and/or ventriculomegaly was 7.2% (13/180), of additional neurologic alterations was 5.3% (13/245), of ophthalmologic abnormalities was 7% (15/214), and of dysphagia was 1.8% (4/226). Less than 1% of the children experienced abnormalities across all of the domains simultaneously. Interpretation: Although approximately one-fifth of children with confirmed and suspected exposure to ZIKV in pregnancy presented with at least one abnormality compatible with CZS, the manifestations presented more frequently in isolation than in combination. Due to the rare nature of some outcomes and the possibility of later manifestations, large scale individual participant data meta-analysis and the long-term evaluation of children are imperative to identify the full spectrum of this syndrome and to plan actions to reduce damages.

Comparison of Oropharyngeal Dysphagia in Brazilian Children with Prenatal Exposure to Zika Virus, With and Without Microcephaly.

Severe brain damage associated with Zika-related microcephaly (ZRM) have been reported to result in oropharyngeal dysphagia (OPD); however, it is unknown if OPD presents in children with prenatal Zika virus (ZIKV) exposure but only mild or undetectable abnormalities. The aims of this study were: to compare the frequency and characteristics of OPD in children with ZRM and in children without microcephaly born to mothers who tested polymerase chain reaction positive (PCR+) for ZIKV during pregnancy; and to investigate the concordance of caregiver reports of OPD with the diagnosis from the clinical swallowing assessment (CSA). Between Mar/2017 and May/2018, we evaluated 116 children (n = 58 with microcephaly, n = 58 children without microcephaly born to ZIKV PCR + mothers) participating in the Microcephaly Epidemic Research Group (MERG) cohort of children born during the 2015-2016 ZIKV epidemic in Pernambuco, Brazil. To assess OPD we used: a CSA; a clinical assessment of the stomatognathic system; and a questionnaire administered to caregivers. The frequency of OPD was markedly higher in children with ZRM (79.3%) than in the exposed but normocephalic group (8.6%). The children with microcephaly also presented more frequently with anatomic and functional abnormalities in the stomatognathic system. There was a high degree of agreement between the caregiver reports of OPD and the CSA (κ = 0.92). In conclusion, our findings confirm that OPD is a feature of Congenital Zika Syndrome that primarily occurs in children with microcephaly and provide support for policies in which children are referred for rehabilitation with an OPD diagnosis based on caregiver report.

Dental development in children born to Zikv-infected mothers: a case-based study.

BACKGROUND: In Brazil, in October 2015, an outbreak of Zika virus (ZIKV) infection and an increase in newborns with microcephaly suggested a relationship between maternal infection and microcephaly in children. OBJECTIVE: First, to assess the presence of dental bud sin 13 infants with a confirmed diagnosis of congenital ZIKV syndrome, born to mothers infected with the virus during pregnancy; second, to evaluate the dental development of these children at a 36-month follow-up. DESIGN: Case-based longitudinal study. RESULTS: Dental radiographs in the first semester showed that all children had dental buds. Along with the study, the individuals presented with various dental disturbances. At the end of the evaluation period, some children still had incomplete deciduous dentition. CONCLUSION: The abnormal chronology of dental eruption and dental development disturbances in children with microcephaly infected with ZIKV born to infected mothers indicate a possible role of the virus in odontogenesis.

Sleep EEG patterns in infants with congenital Zika virus syndrome.

OBJECTIVES: To describe sleep EEG patterns of neonates, and infants with microcephaly due to congenital Zika virus (ZikV) syndrome. METHODS: A descriptive case series of EEGs performed in a cohort of neonates with microcephaly monitored from October 2015 to February 2016 at a University Hospital in Northeast Brazil. Infants were investigated following an established protocol that includes EEG, neuroimaging studies, PCR and specific antibodies for ZikV detection. RESULTS: EEGs (n=37) from 37 infants were reviewed. Age at investigation varied from 1 to 5months (mean=2.6). Diffuse low voltage (n=7), background asymmetry (n=6) and modified hypsarrhythmia with or without burst-suppression (n=11), were the main background abnormalities identified. Interictal EEG abnormalities were identified in 23 recordings (62%) and localized as focal frontal (n=8) or occipital (n=2) spikes/sharp, multifocal spikes/sharp waves (n=13). Electrographic seizures without clinical manifestation were identified in 4 recordings and characterized as focal pseudo rhythmic pattern. Further findings were focal high amplitude slow waves that were registered in the frontal (n=3) or occipital (n=1) regions. CONCLUSIONS: Different types of EEG abnormalities were encountered with a predominance of interictal epileptogenic activity and hypsarrhythmia. SIGNIFICANCE: Sleep EEGs in congenital Zika virus syndrome are consistently abnormal even in infants who have not yet developed epilepsy.

Congenital Zika syndrome with arthrogryposis: retrospective case series study.

OBJECTIVE: To describe the clinical, radiological, and electromyographic features in a series of children with joint contractures (arthrogryposis) associated with congenital infection presumably caused by Zika virus. DESIGN: Retrospective case series study. SETTING: Association for Assistance of Disabled Children, Pernambuco state, Brazil. PARTICIPANTS: Seven children with arthrogryposis and a diagnosis of congenital infection presumably caused by Zika virus during the Brazilian microcephaly epidemic. MAIN OUTCOME MEASURES: Main clinical, radiological, and electromyographic findings, and likely correlation between clinical and primary neurological abnormalities. RESULTS: The brain images of all seven children were characteristic of congenital infection and arthrogryposis. Two children tested positive for IgM to Zika virus in the cerebrospinal fluid. Arthrogryposis was present in the arms and legs of six children (86%) and the legs of one child (14%). Hip radiographs showed bilateral dislocation in seven children, subluxation of the knee associated with genu valgus in three children (43%), which was bilateral in two (29%). All the children underwent high definition ultrasonography of the joints, and there was no evidence of abnormalities. Moderate signs of remodeling of the motor units and a reduced recruitment pattern were found on needle electromyography (monopolar). Five of the children underwent brain computed tomography (CT) and magnetic resonance imaging (MRI) and the remaining two CT only. All presented malformations of cortical development, calcifications predominantly in the cortex and subcortical white matter (especially in the junction between the cortex and white matter), reduction in brain volume, ventriculomegaly, and hypoplasia of the brainstem and cerebellum. MRI of the spine in four children showed apparent thinning of the cord and reduced ventral roots. CONCLUSIONS: Congenital Zika syndrome should be added to the differential diagnosis of congenital infections and arthrogryposis. The arthrogryposis was unrelated to the abnormalities of the joints themselves, but was possibly of neurogenic origin, with chronic involvement of central and peripheral motor neurones leading to deformities as a result of fixed postures in utero. Based on the neurophysiological observations, we suggest two possible mechanisms: tropism of neurones, with involvement of peripheral and central motor neurones, or a relation with vascular disorders.

Initial Description of the Presumed Congenital Zika Syndrome.

OBJECTIVES: To provide an initial description of the congenital syndrome presumably associated with infection by Zika virus compared with other syndromes including congenital infections of established etiologies. METHODS: We provide an overview of a published case series of 35 cases, a clinical series of 104 cases, and published and unpublished reports of clinical and laboratory findings describing cases diagnosed since the beginning of the epidemic of microcephaly in Brazil. RESULTS: About 60% to 70% of mothers report rash during pregnancy; mainly in the first trimester. Principal features are microcephaly, facial disproportionality, cutis girata, hypertonia/spasticity, hyperreflexia, and irritability; abnormal neuroimages include calcifications, ventriculomegaly, and lissencephaly. Hearing and visual abnormalities may be present. CONCLUSIONS: Preliminary data suggest that severe congenital abnormalities are linked to Zika virus infection. Cases have severe abnormalities, and although sharing many characteristics with congenital abnormalities associated with other viral infections, abnormalities presumably linked to the Zika virus may have distinguishing characteristics. These severe neurologic abnormalities may result in marked mental retardation and motor disabilities for many surviving offspring. POLICY IMPLICATIONS: Affected nations need to prepare to provide complex and costly multidisciplinary care that children diagnosed with this new congenital syndrome will require.

O uso da DL-Carnitina como proteçäo miocárdica na difteria / Use of DL-Carnitina as miocardic protection in diphteria

Visando avaliar o valor da DL-Carnitina (DLC) como protetor contra a açäo da toxina diftérica sobre o miocárdio, foram estudados prospectivamente 186 pacientes diftéricos internados no Isolamento Infantil do Hospital Oswaldo Cruz, no período de janeiro a dezembro de 85. Os pacientes foram submetidos ao tratamento tradicional (antibióticos e SAD) e divididos aleatoriamente em 2 grupos DLC-90 pacientes que usaram a droga, e grupo controle-96 pacientes que näo a usaram. Os 2 grupos similares quanto a idade, sexo, v acina prévia e tempo início sintomas - ínicio tratamento. No grupo DLC surgiram 9 casos de miocardite, sendo um discutível, motivo pelo qual foi excluído (paciente foi a óbito por provável sepsis e insuficiência repiratória). Dos 8 casos considerados (8,8%) 7 foram de miocardite leve e um de miocardite grave, todos com recuperaçäo total sem seqüelas. No grupo controle surgiram 16 casos de miocardite, dois dos quais discutíveis e que foram excluídos. Dos 14 considerados (14,6%) 6 foram de miocardite leve (todos recuperados sem seqüelas) e 8 de miocardite grave dos quais 7 foram a óbito e um sobreviveu, porém com seqüela importante (fibrose miocárdica com insuficiência cardíaca grau funcional II com medicaçäo). A diferença na incidência de miocrdite nos dois grupos näo foi significante. Entretanto, se considerarmos o número de casos graves e de óbitos, a diferença teve significância estatística (p < 0,05). Os autores concluem que embora reconheçam a necessidade de mais estudos, o uso da DLC na difteria parece conferir proteçäo miocárdica contra a açäo da toxina ciftérica