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2.
PLoS One ; 15(10): e0235877, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33091010

RESUMO

Congenital Zika virus (ZIKV) exposure results in a spectrum of disease ranging from severe birth defects to delayed onset neurodevelopmental deficits. ZIKV-related neuropathogenesis, predictors of birth defects, and neurodevelopmental deficits are not well defined in people. Here we assess the methodological and statistical feasibility of a congenital ZIKV exposure macaque model for identifying infant neurobehavior and brain abnormalities that may underlie neurodevelopmental deficits. We inoculated five pregnant macaques with ZIKV and mock-inoculated one macaque in the first trimester. Following birth, growth, ocular structure/function, brain structure, hearing, histopathology, and neurobehavior were quantitatively assessed during the first week of life. We identified the typical pregnancy outcomes of congenital ZIKV infection, with fetal demise and placental abnormalities. We estimated sample sizes needed to define differences between groups and demonstrated that future studies quantifying brain region volumes, retinal structure, hearing, and visual pathway function require a sample size of 14 animals per group (14 ZIKV, 14 control) to detect statistically significant differences in at least half of the infant exam parameters. Establishing the parameters for future studies of neurodevelopmental outcomes following congenital ZIKV exposure in macaques is essential for robust and rigorous experimental design.


Assuntos
Transtornos da Audição/patologia , Malformações do Sistema Nervoso/patologia , Complicações Infecciosas na Gravidez/patologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Transtornos da Visão/patologia , Infecção por Zika virus/complicações , Zika virus/fisiologia , Animais , Animais Recém-Nascidos , Feminino , Transtornos da Audição/etiologia , Macaca mulatta , Malformações do Sistema Nervoso/etiologia , Gravidez , Complicações Infecciosas na Gravidez/etiologia , Resultado da Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Transtornos da Visão/etiologia , Infecção por Zika virus/virologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-33027393

RESUMO

The Northeast of Brazil has experienced a triple epidemic, with the simultaneous circulation of dengue virus (DENV), chikungunya virus (CHIKV) and Zika virus (ZIKV), which may have contributed to the observed increase across this region of atypical forms of disease and deaths. In view of this fact, non-congenital neurological disorders related to arboviruses were compared with other etiologies, mortality and survival rates of patients admitted to referral neurology hospitals in Pernambuco State, Northeast Brazil, from 2015 to 2018. Blood and cerebrospinal fluid samples were collected and tested using molecular and serological assays. The arbovirus-exposed groups were compared with respect to epidemiological, clinical and neurologic characteristics by using the Pearson's chi-square test. For the survival analysis, the Kaplan-Meier and Hazard Ratio (HR) tests were used, with a 95% confidence interval (CI). Encephalitis and encephalomyelitis were more frequent in arboviruses, while myelitis predominated in the neurological disorders of other etiologies. Guillain-Barré Syndrome (GBS) was similarly distributed amongst the groups. Exposure to one of the arboviruses caused a six-fold increase in the risk of death (HR: 6.37; CI: 2.91 - 13.9). Amongst the arbovirus-exposed groups, infection (DENV/CHIKV) increased nine times the risk of death (HR: 9.07; CI: 3.67 - 22.4). The survival curve indicates that have been exposed to some arbovirus decreased the likelihood of survival compared to those with other etiologies (Log-Rank: p<0.001). Within this scenario, neurologic manifestations of DENV, CHIKV and ZIKV have the potential to increase mortality and decrease survival, and concomitant infection (DENV/CHIKV) is an aggravating factor in reducing the likelihood of survival when compared to monoinfections.


Assuntos
Febre de Chikungunya/diagnóstico , Vírus da Dengue/isolamento & purificação , Dengue/diagnóstico , Encefalite Viral/epidemiologia , Encefalomielite/virologia , Doenças do Sistema Nervoso/virologia , Infecção por Zika virus/diagnóstico , Zika virus/isolamento & purificação , Adulto , Brasil , Febre de Chikungunya/complicações , Dengue/complicações , Encefalomielite/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Doenças do Sistema Nervoso/diagnóstico , Análise de Sobrevida , Infecção por Zika virus/complicações
4.
PLoS Negl Trop Dis ; 14(10): e0008612, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33006989

RESUMO

BACKGROUND: Recent Zika virus (ZIKV) outbreaks in the Pacific and the Americas have highlighted clinically significant congenital neurological abnormalities resulting from ZIKV infection in pregnancy. However, little is known about ZIKV infections in children and adolescents, a group that is potentially vulnerable to ZIKV neurovirulence. METHODS: We conducted a systematic review on the clinical presentation and complications of children and adolescents aged 0 to 18 years with a robust diagnosis of ZIKV infection. We searched PubMed, Web of Science, LILACs, and EMBASE until 13 February 2020 and screened reference lists of eligible articles. We assessed the studies' risk of bias using pre-specified criteria. FINDINGS: Our review collated the evidence from 2543 pediatric ZIKV cases representing 17 countries and territories, identified in 1 cohort study, 9 case series and 22 case reports. The most commonly observed signs and symptoms of ZIKV infection in children and adolescents were mild and included fever, rash, conjunctivitis and arthralgia. The frequency of neurological complications was reported only in the largest case series (identified in 1.0% of cases) and in an additional 14 children identified from hospital-based surveillance studies and case reports. ZIKV-related mortality was primarily accompanied by co-morbidity and was reported in one case series (<0.5% of cases) and three case reports. One death was attributed to complications of Guillain-Barré Syndrome secondary to ZIKV infection. CONCLUSIONS AND RELEVANCE: Based on the current evidence, the clinical presentation of ZIKV infection in children and adolescents appears to be primarily mild and similar to the presentation in adults, with rare instances of severe complications and/or mortality. However, reliable estimation of the risks of ZIKV complications in these age groups is limited by the scarcity and quality of published data. Additional prospective studies are needed to improve understanding of the relative frequency of the signs, symptoms, and complications associated with pediatric ZIKV infections and to investigate any potential effects of early life ZIKV exposure on neurodevelopment.


Assuntos
Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia , Adolescente , Criança , Pré-Escolar , Comorbidade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/virologia , Zika virus , Infecção por Zika virus/complicações , Infecção por Zika virus/mortalidade
5.
Artigo em Inglês | MEDLINE | ID: mdl-32967070

RESUMO

Children with congenital Zika syndrome (CZS) present severe motor disability and can benefit from early powered mobility. The Go Zika Go project uses modified ride-on toy cars, which may advance the body functions, activities, and participation of children. This paper describes the study protocol aiming to assess the feasibility of a modified ride-on car intervention for children with CZS in Brazil. A mixed-methods design with a multiple 1-week baseline, 3-month intervention, and 1-month follow-up will be implemented. Modified ride-on car training sessions will be conducted three times a week at the participants' home or in the clinic. The primary outcome will be a narrative description of study feasibility (photovoice method, focus groups, parent feasibility questionnaire and assessment of learning powered mobility). Secondary outcomes will be switch activation, driving sessions journal, social-cognitive interactions, mobility (pediatric evaluation of disability inventory computer adaptive test), goal attainment scaling (GAS), and participation (young children's participation and environment measure). Go Zika Go is expected to be viable and to improve function, activity, and participation of children with CZS, providing a low-cost, evidence-based rehabilitation option that will be relevant to early child development in a global perspective.


Assuntos
Transtornos Motores , Infecção por Zika virus , Automóveis , Brasil , Criança , Pré-Escolar , Estudos de Viabilidade , Humanos , Transtornos Motores/reabilitação , Transtornos Motores/virologia , Equipamentos de Autoajuda , Infecção por Zika virus/complicações
6.
Value Health ; 23(7): 969-976, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32762999

RESUMO

OBJECTIVES: In this systematic review, we synthesize the current evidence on health-related quality of life (HRQoL) for the two of the most relevant outcomes of Zika virus infection in humans, microcephaly and Guillain-Barré Syndrome (GBS). METHODS: We searched the following databases: MEDLINE, Embase, CINAHL, LILACS, WHO's ICTRP clinical trials registries database and PROSPERO. Search terms included quality of life, microcephaly, and Guillain-Barré Syndrome. We included primary studies where HRQoL was quantitatively assessed for microcephaly and GBS using validated instruments. We used the Joanna Briggs Institute Critical Appraisal Tools to assess the risk of bias of individual studies. RESULTS: From a total of 1,657 abstracts screened and 66 full texts reviewed, 21 studies met the eligibility criteria; one study for microcephaly and 20 for GBS. Adjusted disutilities for microcephaly compared to a normative childhood utility ranged from -0.745 to -0.820. For GBS, time traded-off the expected lifetime ranged from 16 days to 3 years. HRQoL follows the clinical course of GBS, with lower scores in the first months, recovery within the first year post onset, and stabilization after one year. CONCLUSIONS: Included studies reported a wide range of HRQoL for GBS, due in part to a high level of heterogeneity in methods, inclusion criteria, follow-up and reporting of results. Opportunities exist for primary studies assessing the longitudinal HRQoL over the entire course of the diseases to inform clinical practice, economic evaluations and health policy.


Assuntos
Qualidade de Vida , Infecção por Zika virus/complicações , Criança , Síndrome de Guillain-Barré/epidemiologia , Síndrome de Guillain-Barré/virologia , Humanos , Microcefalia/epidemiologia , Microcefalia/virologia , Fatores de Tempo , Infecção por Zika virus/epidemiologia
7.
N Engl J Med ; 383(6): 537-545, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32757522

RESUMO

BACKGROUND: In 2015 and 2016, Colombia had a widespread outbreak of Zika virus. Data from two national population-based surveillance systems for symptomatic Zika virus disease (ZVD) and birth defects provided complementary information on the effect of the Zika virus outbreak on pregnancies and infant outcomes. METHODS: We collected national surveillance data regarding cases of pregnant women with ZVD that were reported during the period from June 2015 through July 2016. The presence of Zika virus RNA was identified in a subgroup of these women on real-time reverse-transcriptase-polymerase-chain-reaction (rRT-PCR) assay. Brain or eye defects in infants and fetuses and other adverse pregnancy outcomes were identified among the women who had laboratory-confirmed ZVD and for whom data were available regarding pregnancy outcomes. We compared the nationwide prevalence of brain and eye defects during the outbreak with the prevalence both before and after the outbreak period. RESULTS: Of 18,117 pregnant women with ZVD, the presence of Zika virus was confirmed in 5926 (33%) on rRT-PCR. Of the 5673 pregnancies with laboratory-confirmed ZVD for which outcomes had been reported, 93 infants or fetuses (2%) had brain or eye defects. The incidence of brain or eye defects was higher among pregnancies in which the mother had an onset of ZVD symptoms in the first trimester than in those with an onset during the second or third trimester (3% vs. 1%). A total of 172 of 5673 pregnancies (3%) resulted in pregnancy loss; after the exclusion of pregnancies affected by birth defects, 409 of 5426 (8%) resulted in preterm birth and 333 of 5426 (6%) in low birth weight. The prevalence of brain or eye defects during the outbreak was 13 per 10,000 live births, as compared with a prevalence of 8 per 10,000 live births before the outbreak and 11 per 10,000 live births after the outbreak. CONCLUSIONS: In pregnant women with laboratory-confirmed ZVD, brain or eye defects in infants or fetuses were more common during the Zika virus outbreak than during the periods immediately before and after the outbreak. The frequency of such defects was increased among women with a symptom onset early in pregnancy. (Funded by the Colombian Instituto Nacional de Salud and the Centers for Disease Control and Prevention.).


Assuntos
Encéfalo/anormalidades , Surtos de Doenças , Anormalidades do Olho/epidemiologia , Complicações Infecciosas na Gravidez , Infecção por Zika virus/complicações , Zika virus/isolamento & purificação , Adolescente , Adulto , Colômbia/epidemiologia , Feminino , Doenças Fetais/epidemiologia , Feto/anormalidades , Geografia Médica , Humanos , Incidência , Recém-Nascido , Masculino , Microcefalia/epidemiologia , Distribuição de Poisson , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez , Prevalência , RNA Viral/sangue , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem , Zika virus/genética , Infecção por Zika virus/epidemiologia
8.
JAMA Netw Open ; 3(7): e209303, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32633763

RESUMO

Importance: Zika virus (ZIKV) is a mosquito-borne flavivirus recognized as teratogenic since the 2015 to 2016 epidemic. Antenatal ZIKV exposure causes brain anomalies, yet the full spectrum has not been delineated. Objective: To characterize the clinical features of ZIKV infection at a pediatric referral center in Rio de Janeiro, Brazil, among children with antenatal ZIKV exposure. Design, Setting, and Participants: Retrospective cohort study conducted from May to July 2019 of a prospective cohort of 296 infants with antenatal ZIKV exposure followed up since December 2015 at a tertiary maternity-pediatric hospital. Exposures: Zika virus infection during pregnancy. Main Outcomes and Measures: Characterization of clinical features with anthropometric, neurologic, cardiologic, ophthalmologic, audiometric, and neuroimaging evaluations in infancy and neurodevelopmental assessments (Bayley Scales of Infant and Toddler Development, Third Edition) from 6 to 42 months of age, stratified by head circumference at birth (head circumference within the reference range, or normocephaly [NC] vs microcephaly [MC]). Results: Antenatal exposure to ZIKV was confirmed for 219 of 296 children (74.0%) referred to Instituto Fernandes Figueira with suspected ZIKV infection through positive maternal or neonatal polymerase chain reaction analysis or IgM serology results. Of these children, 110 (50.2%) were boys, ages ranged from 0 to 4 years, and 53 (24.2%) had congenital microcephaly. The anomalies observed in ZIKV-exposed children with MC or NC were failure to thrive (MC: 38 of 53 [71.7%]; NC: 73 of 143 [51.0%]), cardiac malformations (MC: 19 of 46 [41.3%]; NC: 20 of 100 [20.0%]), excess nuchal skin (MC: 16 of 22 [72.7%]; NC: 35 of 93 [37.6%]), auditory abnormalities (MC: 13 of 50 [26.0%]; NC: 14 of 141 [9.9%]), and eye abnormalities (MC: 42 of 53 [79.2%]; NC: 28 of 158 [17.7%]). Although they experienced fewer neurologic abnormalities than children born with MC, those with NC also had frequent neurologic abnormalities (109 of 160 [68.1%]), including hyperreflexia (36 of 136 [26.5%]), abnormal tone (53 of 137 [38.7%]), congenital neuromotor signs (39 of 93 [41.9%]), feeding difficulties (15 of 143 [10.5%]), and abnormal brain imaging results (44 of 150 [29.3%]). Among 112 children with NC with Bayley-III evaluations, 72 (64.3%) had average or above-average scores; 30 (26.8%) scored 1 SD below average in at least 1 domain; and 10 (8.9%) scored 2 SD below average in at least 1 domain. Among 112 children with NC, a smaller head circumference at birth was significantly associated with subsequent below-average cognitive scores (U = 499.5; z = -2.833; P = .004) and language scores (U = 235.5; z = -2.491; P = .01). Conclusions and Relevance: Children without MC who were exposed to ZIKV in utero had a high frequency of anatomical and neurodevelopmental abnormalities. The head circumference at birth for children with NC was associated with neurocognitive development. Recognition of the wide spectrum of clinical phenotypes is critical to ensure early referral to rehabilitative interventions.


Assuntos
Microcefalia , Transtornos do Neurodesenvolvimento , Complicações Infecciosas na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Infecção por Zika virus , Encéfalo/diagnóstico por imagem , Brasil/epidemiologia , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Microcefalia/diagnóstico , Microcefalia/epidemiologia , Microcefalia/etiologia , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/etiologia , Neuroimagem/métodos , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/virologia , Estudos Retrospectivos , Infecção por Zika virus/complicações , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia
9.
Arq Neuropsiquiatr ; 78(7): 403-411, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32627805

RESUMO

BACKGROUND: The congenital Zika syndrome involves structural brain changes, including ventriculomegaly, thin cerebral cortices, abnormal gyral pattern, cortical malformations, hypoplasia of the corpus callosum, myelination delay, subcortical diffuse calcifications, brainstem hypoplasia, and microcephaly in newborns. OBJECTIVE: This study aimed to describe the clinical characteristics of children with congenital Zika syndrome; to compare the outcomes of infants infected in the first (1T, n=20) and second trimesters of pregnancy (2T, n=11); to investigate correlations between birth weight, birth and follow-up head circumference, birth gestational age, and gross motor scores. METHODS: Participants were evaluated with Alberta Infant Motor Scale (AIMS) and part A of the Gross Motor Function Measure (GMFM-A). ANOVA compared head circumference, birth gestational age, birth weight, and gross motor performance of 1T and 2T. RESULTS: The correlations were investigated by Pearson correlation coefficients. ANOVA showed differences in birth and follow-up head circumferences. Head circumference was smaller in 1T, compared to 2T. Motor performance was classified as below the fifth percentile in AIMS in all children and 1T showed lower scores in prone, sitting, and total AIMS score, compared to 2T. Children ranged from 8 to 78% on GMFM-A and there was a poorer motor performance of 1T. Nineteen children showed hypertonia, six showed normal tone and six showed hypotonia. Birth head circumference was correlated with AIMS prone postural control. Follow-up head circumference was correlated to prone, supine and total AIMS scores. Smaller head circumference at birth and follow-up denoted poorer postural control. DISCUSSION: Children with congenital Zika syndrome showed microcephaly at birth and follow-up. Smaller head circumferences and poorer motor outcomes were observed in 1T. Infants showed poor visual and motor outcomes. Moderate positive correlations between birth and follow-up head circumference and gross motor function were found.


Assuntos
Microcefalia/virologia , Infecção por Zika virus/diagnóstico , Zika virus/isolamento & purificação , Encéfalo , Cefalometria , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Imagem por Ressonância Magnética , Microcefalia/diagnóstico , Destreza Motora , Gravidez , Complicações Infecciosas na Gravidez , Infecção por Zika virus/complicações , Infecção por Zika virus/congênito
10.
Artigo em Inglês | MEDLINE | ID: mdl-32667392

RESUMO

Severe neurological problems and other special manifestations such as high prevalence of structural cardiac changes has been described in infants vertically exposed to the Zika virus (ZIKV) and has been called congenital Zika virus syndrome (CZS). Previous studies have shown that the 24-hour Holter heart rate variability (HRV) analysis allows the prediction of worse outcomes in infants with neurological impairment and higher risk of sudden infant death syndrome (SIDS), hypertension, diabetes mellitus and other cardiovascular diseases. This study describes the 24-hour Holter findings of infants with confirmed vertical exposure to the ZIKV by positive polymerase chain reaction (PCR) assays in the mother's blood during pregnancy and/or in the urine or cerebrospinal fluid of the newborn. Data analysis was descriptive and included two subgroups according to the presence of fetal distress, positive PCR to ZIKV in the newborn, CZS and severe microcephaly. Heart rate, pauses, arrhythmias, ST segment and QT interval analyses and HRV evaluation through R-R, SDNN, pNN50 and rMMSD were described. The Mann-Whitney test was performed to assess differences between the two subgroups. The sample consisted of 15 infants with a mean age of 16 months, nine of whom were male. No arrhythmias or QT interval changes were observed. The comparison of HRV through the Mann-Whitney test showed a significant difference between patients with and without CZS, with and without severe microcephaly, with lower HRV in the groups with severe microcephaly and CZS. The study suggests that there is an increased risk of SIDS and cardiovascular diseases in this group of patients.


Assuntos
Transmissão Vertical de Doença Infecciosa , Malformações do Sistema Nervoso/etiologia , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/complicações , Zika virus/isolamento & purificação , Doenças Cardiovasculares/etiologia , Feminino , Frequência Cardíaca , Humanos , Lactente , Recém-Nascido , Masculino , Microcefalia/etiologia , Reação em Cadeia da Polimerase , Gravidez , Morte Súbita do Lactente , Zika virus/genética , Infecção por Zika virus/congênito
11.
Rev Fac Cien Med Univ Nac Cordoba ; 77(2): 100-105, 2020 04 07.
Artigo em Espanhol | MEDLINE | ID: mdl-32558512

RESUMO

Introduction: Microcephaly and brain abnormalities may be due to multiple etiologies, one of them is the congenital infection by Zika virus (ZIKV). From 2016 to the present, there has been a series of ZIKV outbreaks in Argentina. Methods: National Network of Congenital Anomalies (RENAC) and the National Institute of Viral Diseases (INEVH), under the National Administration of Laboratories and Health Institutes "Carlos Malbrán" (ANLIS), carry out the intensified surveillance of newborns with microcephaly and brain abnormalities. This article presents the clinical characteristics and laboratory testof patients detected with congenital infection by ZIKV between April 2016 to March 2018, Results: 10 cases with embryopathy were detected, six autochthonous and four imported; in two cases, the mothers were asymptomatic during pregnancy; all the cases presented microcephaly and cranial facial disproportion, ventriculomegaly in seven cases and in six cerebral calcifications. The diagnosis of congenital infection by Zika in the newborn was made by antigen-specific Immunoglobulin M (MAC-ELISA) and plaque-reduction neutralization test (PRNT90 ). PCR was negative in all cases. Conclusion: the patients presented clinical features that were consistent with those reported in other countries. The need for serological studies that allow confirmation is emphasized, ruling out cross-reactivity with other Flaviviruses.


Assuntos
Microcefalia/virologia , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/complicações , Argentina/epidemiologia , Feminino , Humanos , Recém-Nascido , Masculino , Microcefalia/diagnóstico , Microcefalia/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Infecção por Zika virus/epidemiologia
12.
BMC Public Health ; 20(1): 947, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546159

RESUMO

INTRODUCTION: Chikungunya and Zika Virus are vector-borne diseases responsible for a substantial disease burden in the Americas. Between 2013 and 2016, no cases of Chikungunya or Zika Virus were reported by the Venezuelan Ministry of Health. However, peaks of undiagnosed fever cases have been observed during the same period. In the context of scarce data, alternative surveillance methods are needed. Assuming that unusual peaks of acute fever cases correspond to the incidences of both diseases, this study aims to evaluate the use of Google Trends as an indicator of the epidemic behavior of Chikungunya and Zika. METHODS: Time-series cross-correlations of acute fever cases reported by the Venezuelan Ministry of Health and data on Google search queries related to Chikungunya and Zika were calculated. RESULTS: A temporal distinction has been made so that acute febrile cases occurring between 25th of June 2014 and 23rd of April 2015 were attributed to the Chikungunya virus, while cases occurring between 30th of April 2015 and 29th of April 2016 were ascribed to the Zika virus. The highest cross-correlations for each disease were shown at a lag of 0 (r = 0.784) for Chikungunya and at + 1 (r = 0.754) for Zika. CONCLUSION: The strong positive correlation between Google search queries and official data on acute febrile cases suggests that this resource can be used as an indicator of endemic urban arboviruses activity. In the Venezuelan context, Internet search queries might help to overcome some of the gaps that exist in the national surveillance system.


Assuntos
Arbovirus , Febre de Chikungunya/epidemiologia , Febre/etiologia , Comportamento de Busca de Informação , Internet , Vigilância da População/métodos , Infecção por Zika virus/epidemiologia , Febre de Chikungunya/complicações , Febre de Chikungunya/virologia , Vírus Chikungunya , Dengue/epidemiologia , Dengue/virologia , Vírus da Dengue , Epidemias , Febre/virologia , Órgãos Governamentais , Humanos , Incidência , Ferramenta de Busca/tendências , População Urbana , Venezuela/epidemiologia , Zika virus , Infecção por Zika virus/complicações , Infecção por Zika virus/virologia
13.
PLoS One ; 15(5): e0233023, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401826

RESUMO

Zika virus (ZIKV) is a mosquito-transmitted flavivirus, recently linked to microcephaly and central nervous system anomalies following infection in pregnancy. Striking findings of disproportionate growth with a smaller than expected head relative to body length have been observed more commonly among fetuses with exposure to ZIKV in utero compared to pregnancies without ZIKV infection regardless of other signs of congenital infection including microcephaly. This study's objective was to determine the diagnostic accuracy of femur-sparing profile of intrauterine growth restriction for the identification of ZIKV-associated congenital injuries on postnatal testing. A retrospective cohort study of pregnant women with possible or confirmed ZIKV infection between January 1, 2016 and December 31, 2017 were included. Subjects were excluded if no prenatal ultrasound was available. A femur-sparing profile of growth restriction determined using INTERGROWTH-21st sonographic standard for head circumference to femur length (HC: FL). Congenital injuries were determined postnatally by imaging, comprehensive eye exam and standard newborn hearing screen. A total of 111 pregnant women diagnosed with ZIKV infection underwent fetal ultrasound and 95 neonates had complete postnatal evaluation. Prenatal microcephaly was detected in 5% of fetuses (6/111). Postnatal testing detected ZIKV-associated congenital injuries in 25% of neonates (24/95). A HC: FL Z-score ≤ -1.3 had a 52% specificity (95% CI 41-63%), 82% negative predictive value (NPV, 95% CI 73-88%) for the detection of ZIKV-associated congenital injuries in the neonatal period. A more stringent threshold with a Z-score ≤ -2 was associated with a 90% specificity (95% CI 81-95%), 81% NPV (95% CI 77-85%). Excluding cases of fetal microcephaly, HC: FL (Z-score ≤ -2) demonstrated a similar specificity (89%, 95% CI 81-95%) with superior NPV (87%, 95% CI 84-90%). The sonographic recognition of a normally proportioned fetus may be useful prenatally to exclude a wider spectrum of ZIKV-associated congenital injuries detected postnatally.


Assuntos
Fêmur/embriologia , Retardo do Crescimento Fetal/diagnóstico por imagem , Microcefalia/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Infecção por Zika virus/complicações , Feminino , Fêmur/diagnóstico por imagem , Desenvolvimento Fetal , Humanos , Microcefalia/epidemiologia , Cuidado Pós-Natal , Gravidez , Estudos Retrospectivos , Sensibilidade e Especificidade , Infecção por Zika virus/congênito
14.
JAMA Netw Open ; 3(5): e204096, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32369180

RESUMO

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: ß = 1.41; SE, 0.67; P = .04; fine motor: ß = 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.


Assuntos
Deficiências do Desenvolvimento/epidemiologia , Microcefalia/complicações , Infecção por Zika virus/complicações , Brasil/epidemiologia , Pré-Escolar , Deficiências do Desenvolvimento/complicações , Feminino , Humanos , Estudos Longitudinais , Masculino , Gravidez , Infecção por Zika virus/congênito
16.
Sci Rep ; 10(1): 6763, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32317689

RESUMO

Modulation of brain activity is one of the main mechanisms capable of demonstrating the synchronization dynamics of neural oscillations. In epilepsy, modulation is a key concept since seizures essentially result from neural hypersynchronization and hyperexcitability. In this study, we have introduced a time-dependent index based on the Kullback-Leibler divergence to quantify the effects of phase and frequency modulations of neural oscillations in neonatal mice exhibiting epileptiform activity induced by Zika virus (ZIKV) infection. Through this index, we demonstrate that fast oscillations (gamma and beta 2) are the more susceptible modulated rhythms in terms of phase, during seizures, whereas slow waves (delta and theta) mainly undergo changes in frequency. The index also allowed detection of specific patterns associated with the interdependent modulation of phase and frequency in neural activity. Furthermore, by comparing ZIKV modulations with the general computational model Epileptors, we verify different signatures related to the brain rhythms modulation in phase and frequency. These findings instigate new studies on the effects of ZIKV infection on neuronal networks from electrophysiological activities, and how different mechanisms can trigger epilepsy.


Assuntos
Ondas Encefálicas/fisiologia , Epilepsia/fisiopatologia , Neurônios/fisiologia , Infecção por Zika virus/virologia , Animais , Ritmo beta/fisiologia , Encéfalo/patologia , Encéfalo/virologia , Modelos Animais de Doenças , Epilepsia/complicações , Epilepsia/virologia , Ritmo Gama/fisiologia , Humanos , Camundongos , Neurônios/virologia , Zika virus/patogenicidade , Infecção por Zika virus/complicações , Infecção por Zika virus/fisiopatologia
17.
PLoS Negl Trop Dis ; 14(4): e0007502, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32348302

RESUMO

BACKGROUND: Between January 2015 and August 2016, two epidemic waves of Zika virus (ZIKV) disease swept the Northeastern (NE) region of Brazil. As a result, two waves of Guillain-Barré Syndrome (GBS) were observed concurrently. The mandatory reporting of ZIKV disease began region-wide in February 2016, and it is believed that ZIKV cases were significantly under-reported before that. The changing reporting rate has made it difficult to estimate the ZIKV infection attack rate, and studies in the literature vary widely from 17% to > 50%. The same applies to other key epidemiological parameters. In contrast, the diagnosis and reporting of GBS cases were reasonably reliable given the severity and easy recognition of the disease symptoms. In this paper, we aim to estimate the real number of ZIKV cases (i.e., the infection attack rate) and their dynamics in time, by scaling up from GBS surveillance data in NE Brazil. METHODOLOGY: A mathematical compartmental model is constructed that makes it possible to infer the true epidemic dynamics of ZIKV cases based on surveillance data of excess GBS cases. The model includes the possibility that asymptomatic ZIKV cases are infectious. The model is fitted to the GBS surveillance data and the key epidemiological parameters are inferred by using a plug-and-play likelihood-based estimation. We make use of regional weather data to determine possible climate-driven impacts on the reproductive number [Formula: see text], and to infer the true ZIKV epidemic dynamics. FINDINGS AND CONCLUSIONS: The GBS surveillance data can be used to study ZIKV epidemics and may be appropriate when ZIKV reporting rates are not well understood. The overall infection attack rate (IAR) of ZIKV is estimated to be 24.1% (95% confidence interval: 17.1%-29.3%) of the population. By examining various asymptomatic scenarios, the IAR is likely to be lower than 33% over the two ZIKV waves. The risk rate from symptomatic ZIKV infection to develop GBS was estimated as ρ = 0.0061% (95% CI: 0.0050%-0.0086%) which is significantly less than current estimates. We found a positive association between local temperature and the basic reproduction number, [Formula: see text]. Our analysis revealed that asymptomatic infections affect the estimation of ZIKV epidemics and need to also be carefully considered in related modelling studies. According to the estimated effective reproduction number and population wide susceptibility, we comment that a ZIKV outbreak would be unlikely in NE Brazil in the near future.


Assuntos
Epidemias , Monitoramento Epidemiológico , Síndrome de Guillain-Barré/epidemiologia , Síndrome de Guillain-Barré/etiologia , Infecção por Zika virus/complicações , Infecção por Zika virus/epidemiologia , Número Básico de Reprodução , Brasil/epidemiologia , Humanos , Incidência , Modelos Teóricos , Tempo (Meteorologia)
18.
PLoS Negl Trop Dis ; 14(4): e0008264, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32339199

RESUMO

BACKGROUND: The Zika virus (ZIKV) has been associated with Guillain-Barré syndrome (GBS) in epidemiological studies. Whether ZIKV-associated GBS is related to a specific clinical or electrophysiological phenotype has not been established. To this end, we performed a systematic review and meta-analysis of all published studies on ZIKV-related GBS. METHODS: We searched Pubmed, EMBASE and LILACS, and included all papers, reports or bulletins with full text in English, Spanish or Portuguese, reporting original data of patients with GBS and a suspected, probable or confirmed recent ZIKV infection. Data were extracted according to a predefined protocol, and pooled proportions were calculated. RESULTS: Thirty-five studies were included (13 single case reports and 22 case series, case-control or cohort studies), reporting on a total of 601 GBS patients with a suspected, probable or confirmed ZIKV infection. Data from 21 studies and 587 cases were available to be summarized. ZIKV infection was confirmed in 21%, probable in 22% and suspected in 57% of cases. ZIKV PCR was positive in 30% (95%CI 15-47) of tested patients. The most common clinical features were: limb weakness 97% (95%CI 93-99), diminished/absent reflexes 96% (95%CI 88-100), sensory symptoms 82% (95%CI 76-88), and facial palsy 51% (95%CI 44-58). Median time between infectious and neurological symptoms was 5-12 days. Most cases had a demyelinating electrophysiological subtype and half of cases were admitted to the Intensive Care Unit (ICU). Heterogeneity between studies was moderate to substantial for most variables. CONCLUSIONS: The clinical phenotype of GBS associated with ZIKV infection reported in literature is generally a sensorimotor demyelinating GBS with frequent facial palsy and a severe disease course often necessitating ICU admittance. Time between infectious and neurological symptoms and negative PCR in most cases suggests a post-infectious disease mechanism. Heterogeneity between studies was considerable and results may be subject to reporting bias. This study was registered on the international Prospective Register of Systematic Reviews (CRD42018081959).


Assuntos
Doenças Desmielinizantes/patologia , Fenômenos Eletrofisiológicos , Síndrome de Guillain-Barré/patologia , Infecção por Zika virus/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Am J Trop Med Hyg ; 102(5): 955-963, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32228785

RESUMO

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.


Assuntos
Desenvolvimento Infantil , Infecção por Zika virus/congênito , Adolescente , Adulto , Fatores Etários , Brasil/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/virologia , Surtos de Doenças , Feminino , Seguimentos , Audição , Humanos , Lactente , Recém-Nascido , Masculino , Microcefalia/etiologia , Microcefalia/virologia , Desempenho Psicomotor , Visão Ocular , Adulto Jovem , Infecção por Zika virus/complicações , Infecção por Zika virus/epidemiologia
20.
PLoS Negl Trop Dis ; 14(3): e0008060, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32163415

RESUMO

The northeast (NE) region of Brazil commonly goes through drought periods, which favor cyanobacterial blooms, capable of producing neurotoxins with implications for human and animal health. The most severe dry spell in the history of Brazil occurred between 2012 and 2016. Coincidently, the highest incidence of microcephaly associated with the Zika virus (ZIKV) outbreak took place in the NE region of Brazil during the same years. In this work, we tested the hypothesis that saxitoxin (STX), a neurotoxin produced in South America by the freshwater cyanobacteria Raphidiopsis raciborskii, could have contributed to the most severe Congenital Zika Syndrome (CZS) profile described worldwide. Quality surveillance showed higher cyanobacteria amounts and STX occurrence in human drinking water supplies of NE compared to other regions of Brazil. Experimentally, we described that STX doubled the quantity of ZIKV-induced neural cell death in progenitor areas of human brain organoids, while the chronic ingestion of water contaminated with STX before and during gestation caused brain abnormalities in offspring of ZIKV-infected immunocompetent C57BL/6J mice. Our data indicate that saxitoxin-producing cyanobacteria is overspread in water reservoirs of the NE and might have acted as a co-insult to ZIKV infection in Brazil. These results raise a public health concern regarding the consequences of arbovirus outbreaks happening in areas with droughts and/or frequent freshwater cyanobacterial blooms.


Assuntos
Morte Celular/efeitos dos fármacos , Microcefalia/patologia , Envenenamento/complicações , Envenenamento/patologia , Saxitoxina/toxicidade , Infecção por Zika virus/complicações , Infecção por Zika virus/patologia , Animais , Toxinas Bacterianas/análise , Toxinas Bacterianas/toxicidade , Encéfalo/patologia , Brasil/epidemiologia , Células Cultivadas , Modelos Animais de Doenças , Surtos de Doenças , Feminino , Humanos , Incidência , Toxinas Marinhas/análise , Toxinas Marinhas/toxicidade , Camundongos Endogâmicos C57BL , Microcistinas/análise , Microcistinas/toxicidade , Modelos Teóricos , Neurotoxinas/análise , Neurotoxinas/toxicidade , Saxitoxina/análise , Água/química
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