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BACKGROUND: ZIKV has neuroinvasive properties, and in utero exposure can cause birth defects, but little is known about the neurological and neurocognitive impacts of acquired ZIKV infection, particularly in children. METHODS: We assessed neurological symptoms frequency among ZIKV-infected children within one year after ZIKV infection. Three to 5 years post-infection, these children and a matched group of uninfected children were assessed via questionnaires, neurological exams, and neuropsychological testing to evaluate the association between prior ZIKV infection and subsequent neurological symptoms, and cognitive-behavioral function. RESULTS: Among 194 ZIKV-infected children, 3 reported asthenia, 4 reported neck pain, and 10 reported back pain within one year post-infection. At follow-up, clinician-observed cranial nerve abnormalities were significantly more common among ZIKV-infected vs. uninfected children (16 vs. 3; p < 0.01), with vestibulocochlear nerve abnormalities observed most frequently. While ZIKV-infected children scored better than uninfected on cognitive measures, this difference was not clinically meaningful. CONCLUSIONS: Neurological signs, including paresthesia and cranial nerve abnormalities, were observed among ZIKV-infected participants in our study. However, we did not observe a meaningful link between acquired ZIKV infection and subsequent neurological, cognitive, or behavioral outcomes in a representative sample. An exception may be hearing impairment and loss, which should be explored further in future studies. IMPACT: Neurological symptoms, though rare, were observed and reported more frequently among ZIKV-infected vs. uninfected children. These included: asthenia, neck pain, back pain, paresthesia, and cranial nerve abnormalities. Neurocognitive and behavioral test scores were similar among ZIKV-infected and uninfected children. Our study suggests that ZIKV-infected children should be monitored for neurological symptoms and cranial neuropathy to better understand the full burden of acquired ZIKV infection among children.
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Objectives: To describe the presence and persistence of neurological and neuropsychological sequelae among children with acquired Zika virus infection and assess whether those sequelae were more common in children infected with Zika virus compared to uninfected children. Methods: We conducted a prospective cohort study of children with and without Zika virus infection in León, Nicaragua, using a standard clinical assessment tool and questionnaire to collect data on symptoms at three visits, about 6 months apart, and a battery of standardized instruments to evaluate neurocognitive function, behavior, depression, and anxiety at the last two visits. Results: Sixty-two children were enrolled, with no significant differences in demographics by infection group. Children infected with Zika virus had a range of neurological symptoms, some of which persisted for 6 to 12 months; however, no consistent pattern of symptoms was observed. At baseline a small percentage of children infected with Zika virus had an abnormal finger-to-nose test (13%), cold touch response (13%), and vibration response (15%) versus 0% in the uninfected group. Neurocognitive deficits and behavioral problems were common in both groups, with no significant differences between the groups. Children infected with Zika virus had lower cognitive efficiency scores at the 6-month visit. Anxiety and depression were infrequent in both groups. Conclusions: Larger studies are needed to definitively investigate the relationship between Zika virus infection and neurological symptoms and neurocognitive problems, with adjustment for factors affecting cognition and behavior, including mood and sleep disorders, home learning environment, history of neuroinvasive infections, and detailed family history of neuropsychological problems.
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[ABSTRACT]. Objectives. To describe the presence and persistence of neurological and neuropsychological sequelae among children with acquired Zika virus infection and assess whether those sequelae were more common in children infected with Zika virus compared to uninfected children. Methods. We conducted a prospective cohort study of children with and without Zika virus infection in León, Nicaragua, using a standard clinical assessment tool and questionnaire to collect data on symptoms at three visits, about 6 months apart, and a battery of standardized instruments to evaluate neurocognitive function, behavior, depression, and anxiety at the last two visits. Results. Sixty-two children were enrolled, with no significant differences in demographics by infection group. Children infected with Zika virus had a range of neurological symptoms, some of which persisted for 6 to 12 months; however, no consistent pattern of symptoms was observed. At baseline a small percentage of children infected with Zika virus had an abnormal finger-to-nose test (13%), cold touch response (13%), and vibration response (15%) versus 0% in the uninfected group. Neurocognitive deficits and behavioral problems were common in both groups, with no significant differences between the groups. Children infected with Zika virus had lower cognitive efficiency scores at the 6-month visit. Anxiety and depression were infrequent in both groups. Conclusions. Larger studies are needed to definitively investigate the relationship between Zika virus infec- tion and neurological symptoms and neurocognitive problems, with adjustment for factors affecting cognition and behavior, including mood and sleep disorders, home learning environment, history of neuroinvasive infec- tions, and detailed family history of neuropsychological problems.
[RESUMEN]. Objetivos. Describir la presencia y persistencia de secuelas neurológicas y neuropsicológicas en pacientes pediátricos que contrajeron la infección por el virus del Zika y evaluar si dichas secuelas fueron más comunes en los infectados con el virus del Zika en comparación con los no infectados. Métodos. Se realizó un estudio de cohorte prospectivo en pacientes pediátricos con y sin infección por el virus del Zika en León (Nicaragua), con una herramienta de evaluación clínica estándar y un cuestionario para recopilar datos sobre los síntomas en tres visitas, con aproximadamente seis meses de diferencia, y un con- junto de instrumentos estandarizados para evaluar la función neurocognitiva, el comportamiento, la depresión y la ansiedad en las últimas dos visitas. Resultados. Participaron 62 niños y niñas sin diferencias significativas en la demografía por grupo de infección. Los participantes infectados con el virus del Zika mostraron una variedad de síntomas neurológi- cos, algunos de los cuales persistieron entre 6 y 12 meses; no obstante, no se observó un patrón sistemático en los síntomas. Al inicio del estudio, un pequeño porcentaje de participantes infectados con el virus del Zika mostró resultados anormales a las pruebas dedo-nariz (13%), respuesta al tacto (frío) (13%) y respuesta a la vibración (15%), frente a un 0% en el grupo no infectado. Los déficits neurocognitivos y los problemas de comportamiento fueron comunes en ambos grupos, sin diferencias significativas entre los grupos. Los partic- ipantes infectados con el virus del Zika mostraron puntuaciones de eficiencia cognitiva más bajas en la visita a los 6 meses. La ansiedad y la depresión fueron poco frecuentes en ambos grupos. Conclusiones. Son necesarios estudios más amplios para investigar definitivamente la relación entre la infec- ción por el virus del Zika y los síntomas neurológicos y los problemas neurocognitivos, haciendo ajustes para los factores relacionados con la cognición y el comportamiento, incluidos los trastornos del estado de ánimo y el sueño, el entorno de aprendizaje en el hogar, los antecedentes de infecciones neuroinvasivas y los antecedentes familiares detallados de problemas neuropsicológicos.
[RESUMO]. Objetivos. Descrever a presença e a persistência de sequelas neurológicas e neuropsicológicas em crianças com infecção pelo vírus zika e avaliar se essas sequelas foram mais comuns em crianças infectadas pelo vírus zika em comparação com crianças não infectadas. Métodos. Realizamos um estudo de coorte prospectivo em crianças com e sem infecção pelo vírus zika em León, Nicarágua, usando uma ferramenta de avaliação clínica padrão e um questionário para coletar dados de sintomas em três consultas, com cerca de 6 meses de intervalo, além de um conjunto de ferramentas padronizadas para avaliar função neurocognitiva, comportamento, depressão e ansiedade nas duas últimas consultas. Resultados. Foram incluídas 62 crianças, sem diferenças significativas nas características demográficas por grupo de infecção. As crianças infectadas pelo vírus zika tinham uma gama de sintomas neurológicos, alguns dos quais persistiram por 6 a 12 meses. Entretanto, não se observou nenhum padrão consistente de sintomas. No início do estudo, uma pequena porcentagem de crianças infectadas com o vírus zika apresen- tou resultado anormal na prova índex-nariz (13%), resposta ao toque frio (13%) e sensibilidade vibratória (15%), em comparação a 0% no grupo não infectado. Déficits neurocognitivos e problemas comportamentais foram frequentes em ambos os grupos, mas sem diferenças significativas entre eles. As crianças infectadas com o vírus zika tiveram resultados mais baixos de eficiência cognitiva na consulta de 6 meses. Ansiedade e depressão não foram observadas com frequência em ambos os grupos. Conclusões. São necessários estudos mais amplos para investigar a relação exata entre a infecção pelo vírus zika e sintomas neurológicos e problemas neurocognitivos, com ajuste para fatores que afetam a cog- nição e o comportamento, incluindo distúrbios do humor e do sono, ambiente de aprendizagem em casa, história de infecções neuroinvasivas e história familiar detalhada de problemas neuropsicológicos.
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Infecção por Zika virus , Criança , Doenças do Sistema Nervoso , Testes Neuropsicológicos , Nicarágua , Infecção por Zika virus , Criança , Doenças do Sistema Nervoso , Testes Neuropsicológicos , Infecção por Zika virus , Criança , Doenças do Sistema Nervoso , Testes Neuropsicológicos , NicaráguaRESUMO
ABSTRACT Objectives. To describe the presence and persistence of neurological and neuropsychological sequelae among children with acquired Zika virus infection and assess whether those sequelae were more common in children infected with Zika virus compared to uninfected children. Methods. We conducted a prospective cohort study of children with and without Zika virus infection in León, Nicaragua, using a standard clinical assessment tool and questionnaire to collect data on symptoms at three visits, about 6 months apart, and a battery of standardized instruments to evaluate neurocognitive function, behavior, depression, and anxiety at the last two visits. Results. Sixty-two children were enrolled, with no significant differences in demographics by infection group. Children infected with Zika virus had a range of neurological symptoms, some of which persisted for 6 to 12 months; however, no consistent pattern of symptoms was observed. At baseline a small percentage of children infected with Zika virus had an abnormal finger-to-nose test (13%), cold touch response (13%), and vibration response (15%) versus 0% in the uninfected group. Neurocognitive deficits and behavioral problems were common in both groups, with no significant differences between the groups. Children infected with Zika virus had lower cognitive efficiency scores at the 6-month visit. Anxiety and depression were infrequent in both groups. Conclusions. Larger studies are needed to definitively investigate the relationship between Zika virus infection and neurological symptoms and neurocognitive problems, with adjustment for factors affecting cognition and behavior, including mood and sleep disorders, home learning environment, history of neuroinvasive infections, and detailed family history of neuropsychological problems.
RESUMEN Objetivos. Describir la presencia y persistencia de secuelas neurológicas y neuropsicológicas en pacientes pediátricos que contrajeron la infección por el virus del Zika y evaluar si dichas secuelas fueron más comunes en los infectados con el virus del Zika en comparación con los no infectados. Métodos. Se realizó un estudio de cohorte prospectivo en pacientes pediátricos con y sin infección por el virus del Zika en León (Nicaragua), con una herramienta de evaluación clínica estándar y un cuestionario para recopilar datos sobre los síntomas en tres visitas, con aproximadamente seis meses de diferencia, y un conjunto de instrumentos estandarizados para evaluar la función neurocognitiva, el comportamiento, la depresión y la ansiedad en las últimas dos visitas. Resultados. Participaron 62 niños y niñas sin diferencias significativas en la demografía por grupo de infección. Los participantes infectados con el virus del Zika mostraron una variedad de síntomas neurológicos, algunos de los cuales persistieron entre 6 y 12 meses; no obstante, no se observó un patrón sistemático en los síntomas. Al inicio del estudio, un pequeño porcentaje de participantes infectados con el virus del Zika mostró resultados anormales a las pruebas dedo-nariz (13%), respuesta al tacto (frío) (13%) y respuesta a la vibración (15%), frente a un 0% en el grupo no infectado. Los déficits neurocognitivos y los problemas de comportamiento fueron comunes en ambos grupos, sin diferencias significativas entre los grupos. Los participantes infectados con el virus del Zika mostraron puntuaciones de eficiencia cognitiva más bajas en la visita a los 6 meses. La ansiedad y la depresión fueron poco frecuentes en ambos grupos. Conclusiones. Son necesarios estudios más amplios para investigar definitivamente la relación entre la infección por el virus del Zika y los síntomas neurológicos y los problemas neurocognitivos, haciendo ajustes para los factores relacionados con la cognición y el comportamiento, incluidos los trastornos del estado de ánimo y el sueño, el entorno de aprendizaje en el hogar, los antecedentes de infecciones neuroinvasivas y los antecedentes familiares detallados de problemas neuropsicológicos.
RESUMO Objetivos. Descrever a presença e a persistência de sequelas neurológicas e neuropsicológicas em crianças com infecção pelo vírus zika e avaliar se essas sequelas foram mais comuns em crianças infectadas pelo vírus zika em comparação com crianças não infectadas. Métodos. Realizamos um estudo de coorte prospectivo em crianças com e sem infecção pelo vírus zika em León, Nicarágua, usando uma ferramenta de avaliação clínica padrão e um questionário para coletar dados de sintomas em três consultas, com cerca de 6 meses de intervalo, além de um conjunto de ferramentas padronizadas para avaliar função neurocognitiva, comportamento, depressão e ansiedade nas duas últimas consultas. Resultados. Foram incluídas 62 crianças, sem diferenças significativas nas características demográficas por grupo de infecção. As crianças infectadas pelo vírus zika tinham uma gama de sintomas neurológicos, alguns dos quais persistiram por 6 a 12 meses. Entretanto, não se observou nenhum padrão consistente de sintomas. No início do estudo, uma pequena porcentagem de crianças infectadas com o vírus zika apresentou resultado anormal na prova índex-nariz (13%), resposta ao toque frio (13%) e sensibilidade vibratória (15%), em comparação a 0% no grupo não infectado. Déficits neurocognitivos e problemas comportamentais foram frequentes em ambos os grupos, mas sem diferenças significativas entre eles. As crianças infectadas com o vírus zika tiveram resultados mais baixos de eficiência cognitiva na consulta de 6 meses. Ansiedade e depressão não foram observadas com frequência em ambos os grupos. Conclusões. São necessários estudos mais amplos para investigar a relação exata entre a infecção pelo vírus zika e sintomas neurológicos e problemas neurocognitivos, com ajuste para fatores que afetam a cognição e o comportamento, incluindo distúrbios do humor e do sono, ambiente de aprendizagem em casa, história de infecções neuroinvasivas e história familiar detalhada de problemas neuropsicológicos.
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BACKGROUND: Until recently, Zika virus (ZIKV) infections were considered mild and self-limiting. Since 2015, they have been associated with an increase in microcephaly and other birth defects in newborns. While this association has been observed in case reports and epidemiological studies, the nature and extent of the relationship between ZIKV and adverse pregnancy and pediatric health outcomes is not well understood. With the unique opportunity to prospectively explore the full spectrum of issues related to ZIKV exposure during pregnancy, we undertook a multi-country, prospective cohort study to evaluate the association between ZIKV and pregnancy, neonatal, and infant outcomes. METHODS: At research sites in ZIKV endemic regions of Brazil (4 sites), Colombia, Guatemala, Nicaragua, Puerto Rico (2 sites), and Peru, up to 10,000 pregnant women will be recruited and consented in the first and early second trimesters of pregnancy and then followed through delivery up to 6 weeks post-partum; their infants will be followed until at least 1 year of age. Pregnant women with symptomatic ZIKV infection confirmed by presence of ZIKV RNA and/or IgM for ZIKV will also be enrolled, regardless of gestational age. Participants will be tested monthly for ZIKV infection; additional demographic, physical, laboratory and environmental data will be collected to assess the potential interaction of these variables with ZIKV infection. Delivery outcomes and detailed infant assessments, including physical and neurological outcomes, will be obtained. DISCUSSION: With the emergence of ZIKV in the Americas and its association with adverse pregnancy outcomes in this region, a much better understanding of the spectrum of clinical outcomes associated with exposure to ZIKV during pregnancy is needed. This cohort study will provide information about maternal, fetal, and infant outcomes related to ZIKV infection, including congenital ZIKV syndrome, and manifestations that are not detectable at birth but may appear during the first year of life. In addition, the flexibility of the study design has provided an opportunity to modify study parameters in real time to provide rigorous research data to answer the most critical questions about the impact of congenital ZIKV exposure. TRIAL REGISTRATION: NCT02856984 . Registered August 5, 2016. Retrospectively registered.
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Anormalidades Congênitas/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Infecção por Zika virus/epidemiologia , Adolescente , Adulto , Anticorpos Antivirais/sangue , Brasil/epidemiologia , Estudos de Coortes , Colômbia/epidemiologia , Feminino , Retardo do Crescimento Fetal/epidemiologia , Guatemala/epidemiologia , Humanos , Imunoglobulina M , Lactente , Recém-Nascido , Masculino , Nicarágua/epidemiologia , Peru/epidemiologia , Pré-Eclâmpsia/epidemiologia , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Porto Rico/epidemiologia , RNA Viral/sangue , Adulto Jovem , Zika virusRESUMO
BACKGROUND: Recent studies have shown an excess of chronic kidney disease (CKD) among younger adult males in the Pacific coastal region of Nicaragua and suggest a non-conventional CKD etiology in this region. These studies have been conducted in small, non-representative populations. OBJECTIVES: We conducted a large population-based cross-sectional study to estimate CKD prevalence in León, Nicaragua, and to evaluate the association between previously investigated risk factors and CKD. METHODS: Estimated glomerular filtration rate, derived using the MDRD equation, was assessed to determine CKD status of 2275 León residents. Multivariable logistic regression was used to estimate adjusted prevalence odds ratios. León CKD prevalence was also standardized to the demographic distributions of the León Health and Demographic Surveillance System and the León 2005 Census. RESULTS: CKD prevalence was 9.1%; twice as high for males (13.8%) than females (5.8%). In addition to gender, older age, rural zone, lower education level, and self-reported high blood pressure, more years of agricultural work, lija (unregulated alcohol) consumption, and higher levels of daily water consumption were significantly associated with CKD. Notably, self-reported diabetes was associated with CKD in adjusted models for females but not males. CONCLUSIONS: Our findings are comparable to those found in regional studies and further support the hypothesis of a Mesoamerican Nephropathy.
CONTEXTE: Selon de récentes études, il existerait une prévalence d'insuffisance rénale chronique (IRC) excessive chez les jeunes adultes de sexe masculin de la côte du Pacifique du Nicaragua. Ces études, qui ont été conduites sur des échantillons non représentatifs de la population, suggèrent une étiologie non classique de l'IRC dans cette région. OBJECTIFS DE L'ÉTUDE: Nous avons effectué une étude transversale portant sur un vaste échantillon de population, afin de pouvoir estimer la prévalence d'IRC dans la ville nicaraguéenne de León, d'une part, et évaluer la présence de liens entre l'IRC et certains facteurs de risque ayant été étudiés, d'autre part. MÉTHODE: Pour déterminer le statut d'IRC de 2275 résidents de la ville de León, nous avons utilisé le débit de filtration glomérulaire estimé, selon l'équation du MDRD. Une régression logistique multivariée a été utilisée pour estimer les ratios de probabilité corrigés de prévalence. La prévalence d'IRC de León a également été normalisée sur la base de la distribution démographique du Health and Demographic Surveillance System de León et avec son recensement de 2005. RÉSULTATS: La prévalence d'IRC était de 9,1%; elle était deux fois plus élevée chez les hommes (13,8%) que chez les femmes (5,8%). D'autres facteurs ont été liés de façon significative à l'IRC: la vieillesse, la vie rurale, un niveau d'éducation faible, une hypertension autodéclarée, plusieurs années de travail en agriculture, et la consommation de lija (alcool non contrôlé) et de grandes quantités d'eau. Le diabète autodéclaré était également lié à l'IRC dans les modèles ajustés chez les femmes, mais non chez les homm es. CONCLUSIONS: Nos résultats sont comparables à ceux des études locales et supportent l'hypothèse de l'existence d'une néphropathie méso-américaine.