Zika Virus: A Neurotropic Warrior against High-Grade Gliomas-Unveiling Its Potential for Oncolytic Virotherapy.

Gliomas account for approximately 75-80% of all malignant primary tumors in the central nervous system (CNS), with glioblastoma multiforme (GBM) considered the deadliest. Despite aggressive treatment involving a combination of chemotherapy, radiotherapy, and surgical intervention, patients with GBM have limited survival rates of 2 to 5 years, accompanied by a significant decline in their quality of life. In recent years, novel management strategies have emerged, such as immunotherapy, which includes the development of vaccines or T cells with chimeric antigen receptors, and oncolytic virotherapy (OVT), wherein wild type (WT) or genetically modified viruses are utilized to selectively lyse tumor cells. In vitro and in vivo studies have shown that the Zika virus (ZIKV) can infect glioma cells and induce a robust oncolytic activity. Consequently, interest in exploring this virus as a potential oncolytic virus (OV) for high-grade gliomas has surged. Given that ZIKV actively circulates in Colombia, evaluating its neurotropic and oncolytic capabilities holds considerable national and international importance, as it may emerge as an alternative for treating highly complex gliomas. Therefore, this literature review outlines the generalities of GBM, the factors determining ZIKV's specific tropism for nervous tissue, and its oncolytic capacity. Additionally, we briefly present the progress in preclinical studies supporting the use of ZIKV as an OVT for gliomas.

Genetically modified ZIKA virus as a microRNA-sensitive oncolytic virus against central nervous system tumors.

Here we introduce a first-in-class microRNA-sensitive oncolytic Zika virus (ZIKV) for virotherapy application against central nervous system (CNS) tumors. The described methodology produced two synthetic modified ZIKV strains that are safe in normal cells, including neural stem cells, while preserving brain tropism and oncolytic effects in tumor cells. The microRNA-sensitive ZIKV introduces genetic modifications in two different virus sites: first, in the established 3'UTR region, and secondly, in the ZIKV protein coding sequence, demonstrating for the first time that the miRNA inhibition systems can be functional outside the UTR RNA sites. The total tumor remission in mice bearing human CNS tumors, including metastatic tumor growth, after intraventricular and systemic modified ZIKV administration, confirms the promise of this virotherapy as a novel agent against brain tumors-highly deadly diseases in urgent need of effective advanced therapies.

Rehabilitation Practices Delivered by Physical and Occupational Therapists to Brazilian Children With Congenital Zika Syndrome: A Cross-Sectional Study.

INTRODUCTION: Congenital Zika syndrome (CZS) is a health condition that has affected the development of thousands of children in Brazil. Because it is a new condition, its understanding is an ongoing process. Therefore, it is important to know the rehabilitation interventions being delivered to improve the functioning of these children. We aimed to describe the practices of physical therapists (PTs) and occupational therapists (OTs) who provide follow-up care for children with CZS in Brazil. METHODS: This cross-sectional study included PTs and OTs who assist children with CZS in Brazil. An online questionnaire was used to verify the participants' personal characteristics and professional work environment, as well as the rehabilitation programs they implemented in Brazil for children with CZS. Data were analyzed using descriptive statistics. RESULTS: A total of 116 professionals (79 PT and 37 OT) who work mainly in public health services (81.9%) participated in the study. Of these, 24.1% plan interventions based on reading scientific articles, 66.4% did not report using the biopsychosocial model, 52.6% do not perform any assessments before starting an intervention, 31.9% use neurodevelopmental treatment, and 22.4% use sensorimotor stimulation interventions. The majority of the interventions are delivered 1 to 2 times a week, lasting up to 1 hour. CONCLUSIONS: Professional training and knowledge translation strategies are needed to implement evidence-based practices and improve the quality of rehabilitation programs for Brazilian children with CZS.

Health care network for children with zika virus from the perspective of professionals.

OBJECTIVE: To know the perspective of health professionals working in specialized care regarding the assistance offered to children with Congenital Zika Virus Syndrome in the Health Care Network. METHOD: Qualitative study carried out in Campo Grande-MS through semi-structured interviews, between September and October 2020, with 12 professionals working in a reference service for people with physical and intellectual disabilities. Minayo's thematic analysis and the theoretical subsidies of the care model for chronic conditions were used for interpretation. RESULTS: Assistance in the network is weakened by aspects related to access, monitoring and integration between different professionals/services. The potential involves the implementation of the referral and counter-referral system, the communication/integration between these services and the training of professionals. FINAL CONSIDERATIONS: The participants perceive that assistance is influenced by the availability of trained professionals to work in a network and the optimization of access and follow-up at different points of care.

The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies.

IMPORTANCE: The wide endemic range of mosquito-vectored flaviviruses-such as Zika virus and dengue virus serotypes 1-4-places hundreds of millions of people at risk of infection every year. Despite this, there are no widely available vaccines, and treatment of severe cases is limited to supportive care. An avenue toward development of more widely applicable vaccines and targeted therapies is the characterization of monoclonal antibodies that broadly neutralize all these viruses. Here, we measure how single amino acid mutations in viral envelope protein affect neutralizing antibodies with both broad and narrow specificities. We find that broadly neutralizing antibodies with potential as vaccine prototypes or biological therapeutics are quantifiably more difficult to escape than narrow, virus-specific neutralizing antibodies.

Oncolytic Zika Virus: New Option for Glioblastoma Treatment.

Glioblastoma (GBM) is one of the most aggressive brain tumors and has a high recurrence rate, and effective treatment is urgently needed. GBM stem cells (GSCs) contribute to GBM recurrence as well as therapeutic resistance to radiation and chemotherapy. Several oncolytic viruses (OVs) have been developed and validated in clinical trials with favorable safety profiles and efficacy against GBM. Recently, Zika virus (ZIKV), a mosquito-borne flavivirus, was shown to preferentially target and kill GSCs and showed promising therapeutic effects in treating GBM in preclinical models. In this review, we summarize the known OVs for the treatment of GBM and highlight the major advantages and existing challenges for the clinical development of oncolytic ZIKV.

Advancement in the Development of Therapeutics Against Zika Virus Infection.

Zika virus (ZIKV), a re-emerging arbovirus, causes teratogenic effects on the fetus and normal nerve functions, resulting in harmful autoimmune responses, which call for the development of therapeutics against ZIKV infection. In this review, we introduce the pathogenesis of ZIKV infection and summarize the advancement in the development of therapeutics against ZIKV infection. It provides guidance for the development of effective therapeutics against ZIKV infection.

Efficient Gene Transfer to Kidney Using a Lentiviral Vector Pseudotyped with Zika Virus Envelope Glycoprotein.

Gene therapy's entrance into clinical settings has made it an ever more attractive field of study for various diseases. However, relatively little progress has been made in targeting kidney diseases due to poor gene delivery efficiency in renal cells. The development of novel gene therapy vectors for medical intervention to treat kidney diseases is needed. In this study, we designed and produced a pseudotyped lentiviral vector with envelope glycoproteins of Zika virus (ZIKV), and evaluated its potential use in viral vector entry, neutralization assay, and gene delivery especially in the renal context. The lentiviral vector, simplified as ZIKV-E, is pseudotyped with Env/G-TC representing the transmembrane (TM) and cytoplasmic (CY) domains of Env replaced with the TM and CY domains of the glycoprotein (G) of the vesicular stomatitis virus. In vivo results show that ZIKV-E induced efficient transduction in tubular epithelial cells in mouse kidneys, demonstrating >100-fold higher expression of exogenous green fluorescent protein gene compared with that achieved by vesicular stomatitis virus G (VSV-G) protein pseudotyped lentiviral vector. The results also showed that the vector ZIKV-E transduced cells in a pH-independent manner and the transduction was inhibited by anti-ZIKV Env domain III antibodies. Results also show that ZIKV-E can be used as a surrogate for studies of ZIKV entry mechanisms and neutralization antibody assay. In all, this study successfully demonstrated a novel pseudotyped lentiviral vector ZIKV-E for inducing high transduction efficiency in renal tubular epithelial cells that could serve as a foundation for gene therapy for the treatment of inherited renal diseases in humans.

Effect of neurodevelopmental treatment in children with congenital Zika syndrome: A pilot study.

AIM: To evaluate the effects of neurodevelopmental treatment (NDT) in children with congenital Zika syndrome (CZS). METHODS: This prospective, interventional cohort study involved children with CZS undergoing follow-up at a specialist centre in northeastern Brazil. The duration of the proposed NDT protocol was 1 year, with 45-min sessions delivered one to five times weekly. Motor function, weight, height, head circumference and the incidence of comorbidities were evaluated in children before protocol initiation and then at 3, 6 and 12 months of treatment. RESULTS: Thirty children were evaluated (age mean 30.1 ± 3 months). Motor function improved from baseline to 6 months (P = 0.001). No difference in weight and head circumference z-score (P = 0.51 and P = 0.29, respectively), but an increase in height z-score (P < 0.001) was observed over the evaluation period. There was a reduction in the incidence of upper respiratory tract infections, pneumonia and urinary tract infections over the follow-up period. CONCLUSIONS: NDT proved to be a viable treatment approach that can improve motor function and reduce the incidence of comorbidities in children with CZS, while having no harmful effects on their growth.

[Primary care in the context of the Zika epidemic and congenital Zika syndrome in the state of Pernambuco, Brazil: context, bond and care]. / Atenção primária no contexto da epidemia zika e da síndrome congênita da zika em Pernambuco, Brasil: contexto, vínculo e cuidado.

The Zika epidemic brought to the fore the birth of children with unknown and unexpected needs that demand longitudinal follow-up, strengthening the bond, comprehensiveness and coordination of care in health, which are essential attributes of primary health care (PHC). This article aims to evaluate the orientation of PHC care, using the PCATool-Brasil. The data were collected between 2016 and 2019, by means of interviews with parents of children who were born in a public maternity hospital in Recife (state of Pernambuco) between October 2015 and February 2016, a critical period of the microcephaly outbreak, especially in the Northeast of Brazil. The parents of 109 children participated in the survey, 15.6% of which had a confirmed microcephaly diagnosis. The degree of affiliation and access was sufficient, but the aspects of coordination of care, longitudinality, comprehensiveness, family and community orientation were insufficient. In the context of congenital Zika syndrome, these attributes are essential for the care of children and families. The fostering of health from these domains depends on the orientation of the models of care and their management with state and federal investments. The defense of life depends on the ability to place life above all other rationalities.

A epidemia zika trouxe ao cenário o nascimento de crianças com necessidades desconhecidas e inesperadas que exigem acompanhamento longitudinal, fortalecimento do vínculo, integralidade e coordenação do cuidado, atributos essenciais da atenção primária em saúde (APS). Este artigo tem o objetivo de avaliar a orientação da APS utilizando o instrumento PCATool-Brasil. Os dados foram coletados entre 2016 e 2019 por meio de entrevistas com responsáveis de crianças que nasceram em uma maternidade pública do Recife-PE no período crítico do surto de microcefalia, sobretudo no Nordeste do Brasil. Participaram do inquérito 109 responsáveis, dos quais 15,6% tiveram diagnóstico confirmado de microcefalia para suas crianças. Evidenciou-se a suficiência do grau de afiliação e acesso, mas a insuficiência da coordenação de cuidado, longitudinalidade, integralidade, orientação familiar e comunitária. No contexto da síndrome congênita da zika, esses atributos são imprescindíveis para o cuidado integral de crianças e famílias. A produção de saúde a partir desses domínios depende da orientação dos modelos de atenção e gestão com fortes investimentos estaduais e federal. A defesa da vida depende da capacidade de colocar a vida acima de todas as outras racionalidades.

Specialized care services for children with congenital zika virus syndrome in Rio de Janeiro, Brazil: a social network analysis. / Serviços da atenção especializada para crianças com síndrome congênita pelo vírus zika no Rio de Janeiro, Brasil, a partir da análise de rede social.

In 2015 the correlation between increasing numbers of cases of microcephaly and a zika virus outbreak led to recognition of an epidemic of congenital zika virus syndrome (CZVS), highlighting well-known weaknesses in health care measures. This article examines the network of virtual information available on health service provision for children suffering from CZVS in Rio de Janeiro. Using social media analysis, data on information about services and care institutions were collected from virtual sources using the Google search engine, so as to assess relations among these actors in 2018. The results revealed a fragmented network centred on virtual sources and secondary and tertiary public care services, with striking proximity of press sources to public services. Also salient was the isolation of private services and the lack of dialogue between philanthropic and public services. Moreover, the information offered was found to be insufficient and superficial, despite the gaps in the formal rehabilitation network. The evidence thus suggested the importance of a well-established health care service network and the necessity of fostering communication through virtual media.

A correlação do aumento na incidência de casos de microcefalia em 2015, simultaneamente ao surto do zika vírus, levou ao reconhecimento de uma epidemia pela síndrome congênita pelo vírus zika (SCVZ), que ressaltou as já conhecidas fragilidades nas ações do cuidado em saúde. O objetivo do artigo é analisar a rede virtual de informações sobre a oferta de serviços de saúde para crianças com SCVZ no Rio de Janeiro. A partir da análise de redes sociais, foram coletados dados de fontes virtuais sobre informações de serviços e instituições de atendimento, utilizando o buscador Google, a fim de avaliar as relações entre esses atores em 2018. Os resultados apresentaram uma rede fragmentada, com centralização em fontes virtuais e serviços públicos da atenção secundária e terciária, destacando-se a proximidade das fontes de imprensa com os serviços públicos. Destacou-se também o isolamento dos serviços privados e a não interlocução entre os serviços filantrópicos e os serviços públicos. Além disso, as informações oferecidas mostraram-se insuficientes e superficiais, apesar da lacuna da rede formal de reabilitação. Consequentemente, as evidências apontam para a importância de uma rede bem estabelecida de serviços, bem como a necessidade de fomentar a comunicação por meio de mídias virtuais.

Atenção primária no contexto da epidemia zika e da síndrome congênita da zika em Pernambuco, Brasil: contexto, vínculo e cuidado / Primary care in the context of the Zika epidemic and congenital Zika syndrome in the state of Pernambuco, Brazil: context, bond and care

Resumo A epidemia zika trouxe ao cenário o nascimento de crianças com necessidades desconhecidas e inesperadas que exigem acompanhamento longitudinal, fortalecimento do vínculo, integralidade e coordenação do cuidado, atributos essenciais da atenção primária em saúde (APS). Este artigo tem o objetivo de avaliar a orientação da APS utilizando o instrumento PCATool-Brasil. Os dados foram coletados entre 2016 e 2019 por meio de entrevistas com responsáveis de crianças que nasceram em uma maternidade pública do Recife-PE no período crítico do surto de microcefalia, sobretudo no Nordeste do Brasil. Participaram do inquérito 109 responsáveis, dos quais 15,6% tiveram diagnóstico confirmado de microcefalia para suas crianças. Evidenciou-se a suficiência do grau de afiliação e acesso, mas a insuficiência da coordenação de cuidado, longitudinalidade, integralidade, orientação familiar e comunitária. No contexto da síndrome congênita da zika, esses atributos são imprescindíveis para o cuidado integral de crianças e famílias. A produção de saúde a partir desses domínios depende da orientação dos modelos de atenção e gestão com fortes investimentos estaduais e federal. A defesa da vida depende da capacidade de colocar a vida acima de todas as outras racionalidades.

Abstract The Zika epidemic brought to the fore the birth of children with unknown and unexpected needs that demand longitudinal follow-up, strengthening the bond, comprehensiveness and coordination of care in health, which are essential attributes of primary health care (PHC). This article aims to evaluate the orientation of PHC care, using the PCATool-Brasil. The data were collected between 2016 and 2019, by means of interviews with parents of children who were born in a public maternity hospital in Recife (state of Pernambuco) between October 2015 and February 2016, a critical period of the microcephaly outbreak, especially in the Northeast of Brazil. The parents of 109 children participated in the survey, 15.6% of which had a confirmed microcephaly diagnosis. The degree of affiliation and access was sufficient, but the aspects of coordination of care, longitudinality, comprehensiveness, family and community orientation were insufficient. In the context of congenital Zika syndrome, these attributes are essential for the care of children and families. The fostering of health from these domains depends on the orientation of the models of care and their management with state and federal investments. The defense of life depends on the ability to place life above all other rationalities.

Serviços da atenção especializada para crianças com síndrome congênita pelo vírus zika no Rio de Janeiro, Brasil, a partir da análise de rede social / Specialized care services for children with congenital zika virus syndrome in Rio de Janeiro, Brazil: a social network analysis

Resumo A correlação do aumento na incidência de casos de microcefalia em 2015, simultaneamente ao surto do zika vírus, levou ao reconhecimento de uma epidemia pela síndrome congênita pelo vírus zika (SCVZ), que ressaltou as já conhecidas fragilidades nas ações do cuidado em saúde. O objetivo do artigo é analisar a rede virtual de informações sobre a oferta de serviços de saúde para crianças com SCVZ no Rio de Janeiro. A partir da análise de redes sociais, foram coletados dados de fontes virtuais sobre informações de serviços e instituições de atendimento, utilizando o buscador Google, a fim de avaliar as relações entre esses atores em 2018. Os resultados apresentaram uma rede fragmentada, com centralização em fontes virtuais e serviços públicos da atenção secundária e terciária, destacando-se a proximidade das fontes de imprensa com os serviços públicos. Destacou-se também o isolamento dos serviços privados e a não interlocução entre os serviços filantrópicos e os serviços públicos. Além disso, as informações oferecidas mostraram-se insuficientes e superficiais, apesar da lacuna da rede formal de reabilitação. Consequentemente, as evidências apontam para a importância de uma rede bem estabelecida de serviços, bem como a necessidade de fomentar a comunicação por meio de mídias virtuais.

Abstract In 2015 the correlation between increasing numbers of cases of microcephaly and a zika virus outbreak led to recognition of an epidemic of congenital zika virus syndrome (CZVS), highlighting well-known weaknesses in health care measures. This article examines the network of virtual information available on health service provision for children suffering from CZVS in Rio de Janeiro. Using social media analysis, data on information about services and care institutions were collected from virtual sources using the Google search engine, so as to assess relations among these actors in 2018. The results revealed a fragmented network centred on virtual sources and secondary and tertiary public care services, with striking proximity of press sources to public services. Also salient was the isolation of private services and the lack of dialogue between philanthropic and public services. Moreover, the information offered was found to be insufficient and superficial, despite the gaps in the formal rehabilitation network. The evidence thus suggested the importance of a well-established health care service network and the necessity of fostering communication through virtual media.

Itinerários Terapêuticos de familiares de crianças com Síndrome Congênita pelo Zika Vírus de uma cidade da região metropolitana de Salvador/Bahia / Therapeutic Journeys of family members of children with Congenital Zika Syndrome in the metropolitan region of Salvador/Bahia / Rutas terapéuticas de familiares de niños con síndrome congénito por el virus Zika en una ciudad de la zona metropolitana de Salvador/Bahia

Introdução: As condições de vida e saúde de crianças com Síndrome Congênita pelo Zika vírus (SCZV) constituem importante questão de Saúde Pública. As alterações no neurodesenvolvimento impactam na vida familiar e implicam cuidados multi e interdisciplinares. São necessários estudos de itinerários terapêuticos dos familiares em busca de assistência à saúde e educação. Objetivo: Conhecer os itinerários terapêuticos de familiares de crianças com SCZV de uma cidade da região metropolitana de Salvador/Bahia. Método: Estudo descritivo e transversal de abordagem qualitativa. Foram gravados, transcritos e analisados vídeos de entrevistas com oito familiares. Estabeleceram-se eixos temáticos: conhecimento e impacto do diagnóstico, busca e suporte no cuidado em saúde e inclusão educacional. Resultados: O conhecimento do diagnóstico da SCZV ocorreu depois do parto, para maioria dos familiares. Todos receberam orientação e encaminhamentos, principalmente, de profissionais da rede pública de saúde. As crianças foram encaminhadas para diferentes especialidades. Receberam prioridade em atendimento emergencial. Algumas participantes referiram angústia ao receber o diagnóstico, mudanças na dinâmica e vida familiar, longa espera para cadeira de rodas, dificuldades de acesso às instituições especializadas pela distância e falta de transporte e problemas na inclusão educacional por falta de auxiliares de sala. A maioria apontou o apoio de parentes e amigos. Conclusão: Os achados evidenciam os impactos dos itinerários terapêuticos na vida dessas famílias e as dificuldades enfrentadas pelas repercussões no neurodesenvolvimento das crianças na busca pela assistência. Os resultados contribuem para formulações de políticas públicas consonantes às necessidades dessas crianças.

Introduction: The living and health conditions of children with Congenital Zika Syndrome (CZS) are an important public health issue. Neurodevelopment changes impact family life and imply multi and interdisciplinary care.  Therefore, studies on the therapeutic journeys of family members in search for health care and education are needed. Objective: To investigate the therapeutic journeys of family members of children with SCZV in the metropolitan region of Salvador/Bahia. Methods: Descriptive and cross-sectional study with a qualitative approach, including recording, transcribing and analyzing videos of interviews with eight family members. The following thematic axes were defined: knowledge and impact of diagnosis, search and support in healthcare and educational inclusion. Results: Most family members became aware of the diagnosis of CZS only after the birth. All received guidance and referrals, mainly from public health professionals. The children were referred to different specializations and received priority assistance. Some participants reported anguish receiving the diagnosis, changes in dynamics and family life, long waiting for a wheelchair, difficulties to access specialized institutions due to distance and lack of transportation, and problems in educational inclusion due to the lack of classroom assistants. Most family members reported having support from relatives and friends. Conclusion: The findings show the impacts of therapeutic journeys on the lives of these families and the difficulties faced due to the effects on the neurodevelopment of children in search for assistance. The results suggest the need to formulate public policies in line with the needs of these children.

Introducción: Las condiciones de vida y de salud de los niños con síndrome congénito por el virus Zika congénito (SCZV) son un importante problema de salud pública. Los cambios del neurodesarrollo impactan la vida familiar y implican cuidados multidisciplinarios y interdisciplinarios. Son necesarios estudios sobre rutas terapéuticas de los familiares en busca de atención sanitaria y educación. Objetivo: Conocer las rutas terapéuticas de familiares de niños con SCZV en una ciudad de la zona metropolitana de Salvador/Bahia. Métodos: Estudio descriptivo y transversal con abordaje cualitativo. Las entrevistas de ocho familiares fueron videograbadas, transcritas y analizadas. Se establecieron ejes temáticos: conocimiento y impacto del diagnóstico, búsqueda y apoyo en salud y educación inclusiva. Resultados: El conocimiento del diagnóstico de SCZV ocurrió después del parto para la mayoría de los familiares. Todos recibieron orientación y derivaciones, principalmente de profesionales de salud pública. Los niños referidos a diferentes especialidades. Recibieron prioridad en la atención. Algunos participantes refirieron angustia al recibir el diagnóstico, cambios en la dinámica y la vida familiar, larga espera por silla de ruedas, dificultades para acceder a instituciones especializadas por la distancia y falta de transporte y educación inclusiva por falta del maestro asistente. La mayoría señaló el apoyo de familiares y amigos. Conclusión: Hallazgos muestran lo impacto en las rutas terapéuticas en la vida de estas familias y las dificultades frente las repercusiones del neurodesarrollo infantil en la búsqueda de cuidados. Los resultados contribuyen a la formulación de políticas públicas para atender las necesidades de estos niños.

Current Understanding of the Role of T Cells in Chikungunya, Dengue and Zika Infections.

Arboviral infections such as Chikungunya (CHIKV), Dengue (DENV) and Zika (ZIKV) are a major disease burden in tropical and sub-tropical countries, and there are no effective vaccinations or therapeutic drugs available at this time. Understanding the role of the T cell response is very important when designing effective vaccines. Currently, comprehensive identification of T cell epitopes during a DENV infection shows that CD8 and CD4 T cells and their specific phenotypes play protective and pathogenic roles. The protective role of CD8 T cells in DENV is carried out through the killing of infected cells and the production of proinflammatory cytokines, as CD4 T cells enhance B cell and CD8 T cell activities. A limited number of studies attempted to identify the involvement of T cells in CHIKV and ZIKV infection. The identification of human immunodominant ZIKV viral epitopes responsive to specific T cells is scarce, and none have been identified for CHIKV. In CHIKV infection, CD8 T cells are activated during the acute phase in the lymph nodes/blood, and CD4 T cells are activated during the chronic phase in the joints/muscles. Studies on the role of T cells in ZIKV-neuropathogenesis are limited and need to be explored. Many studies have shown the modulating actions of T cells due to cross-reactivity between DENV-ZIKV co-infections and have repeated heterologous/homologous DENV infection, which is an important factor to consider when developing an effective vaccine.

A review of severe thrombocytopenia in Zika patients - Pathophysiology, treatment and outcome.

BACKGROUND: During the 2015 Zika virus infection (ZVI) epidemic swiping through the Americas, few cases of ZVI with severe, potentially life-threatening thrombocytopenia were reported. Platelet transfusion, corticosteroids and intravenous immunoglobulins (IVIG) were in most cases applied as therapeutic options, predominantly with success. We present a comprehensive overview concerning the pathophysiology, treatment strategies and outcomes of patients with ZVI and severe thrombocytopenia (platelet count <50 × 109/L). METHOD: A literature search was performed. RESULTS: Eleven case reports and case series with a total of 28 patients met the inclusion criteria; including five cases with lethal outcome. Therapeutic strategies, including platelet transfusion, administration of steroids and/or IVIG were described in 24 cases. CONCLUSIONS: Severe thrombocytopenia is a rare, but potentially life-threatening complication of ZVI. The principal pathophysiological mechanism appears to immune-induced thrombocytopenia. Due to a paucity of cases, the optimal treatment strategy remains to be elucidated.

Fatores que interferem na evolução urológica de pacientes com disfunção neurogênica do trato urinário inferior causada pela Síndrome Congênita do Zika Vírus / Factors that interfere with the urological evolution of patients with neurogenic lower urinary tract dysfunction caused by Zika Virus Congenital Syndrome

Introdução: A disfunção neurogênica do trato urinário inferior (DNTUI) é uma sequela urológica da Síndrome Congênita do Zika vírus6 (SCZV). Apesar de os pacientes com SCZV e DNTUI receberem o mesmo tratamento, tem-se observado evolução diferente. Objetivo: Avaliar a existência de fatores de interferência para a resposta ao tratamento urológico nas crianças portadoras de SCZV, especificamente: (1) Identificar seu perfil sociodemográfico, clínico, neurológico e urológico; (2) Avaliar o efeito do tratamento nas variáveis de risco urológico e (3) Avaliar o efeito dos fatores sociodemográficos, clínicos e neurológicos na resposta ao tratamento urológico destes pacientes. Metodologia: Estudo transversal incluindo crianças assistidas na coorte institucional do IFF com SCZV e DNTUI, tratadas nos ambulatórios de Urodinâmica e Neurologia entre 2015 e 2021 e com duas avaliações urodinâmicas realizadas. Variáveis sociodemográficas, clínicas, neurológicas e urológicas foram coletadas através de ficha própria. O primeiro e o segundo exame de urodinâmica foram comparados para avaliar a evolução, após a intervenção terapêutica. Com a finalidade de avaliar fatores de interferência para a resposta ao tratamento urológico, as crianças foram separadas em dois grupos - as que apresentaram alguma melhora urodinâmica e as que não, correlacionando as variáveis com a resposta ao tratamento. Analisou-se as variáveis categóricas pela frequência de ocorrência e as numéricas pela média e desvio padrão, comparando os grupos pelo chi-square test. Resultados: Foram incluídas 50 crianças, 50% do sexo feminino e 54% acima de 12 meses de idade; 70% tiveram exposição vertical ao vírus no primeiro trimestre da gestação, 62% com microcefalia grave e a maioria com dilatação ventricular, síndrome cortical e epiléptica, todas com DNTUI, 74% com perfil urológico. Resultados: Foram incluídas 50 crianças, 50% do sexo feminino e 54% acima de 12 meses de idade; 70% tiveram exposição vertical ao vírus no primeiro trimestre da gestação, 62% com microcefalia grave e a maioria com dilatação ventricular, síndrome cortical e epiléptica, todas com DNTUI, 74% com perfil urológico de risco para trato urinário superior. No parto, 86% das mães tinham entre 18 e 36 anos de idade e menos de oito anos de estudo. Entre as 50 crianças, 41 apresentaram alguma melhora urodinâmica pós-tratamento, com redução significativa da pressão vesical máxima (p= 0.001) e aumento significativo da capacidade vesical máxima (p=0.001) e da complacência vesical (p=0.000). Não se observou significância estatística que confirmasse a interferência dos fatores analisados no tratamento urológico. Conclusão: O estudo confirmou a significativa melhora dos padrões urodinâmicos observada nos exames de controle, reafirmando a importância de investigar a sequela urológica nestas crianças.

Introduction: Neurogenic Lower Urinary Tract Dysfunction (NLUTD) is a urological sequel of Congenital Zika Syndrome6 (CZS). Although these patients received the same treatment, they did not respond in the same way. Objective: To evaluate the presence of interference factors in the response to the urological treatment in children with CZS, specifically: (1) To identify their sociodemographic, clinical, neurological and urological profile; (2) To evaluate the effect of treatment on the urological risk variables and (3) To evaluate the effect of sociodemographic, clinical and neurological factors on the response to their urological treatment. Methodology: Cross-sectional study including children assisted in the institutional cohort of IFF with CZS and NLUTD, treated in the Urodynamic and in the Neurology outpatient clinics between 2015 and 2021, who have performed two urodynamic evaluations. Sociodemographic, clinical, neurological, and urological variables were collected through a specific research form. The first and second urodynamics exams were compared to evaluate urological response after the therapeutic intervention. To evaluate the presence of interference factors on urological treatment, the children were separated into two groups - those that presented any urodynamic improvement and those that did not, correlating the variables with the response to treatment. Categorical variables were analyzed by frequency of occurrence and numerical variables by mean and standard deviation, comparing the groups by chi-square test. Results: Fifty children were included, 50% female and 54% older than 12 months of age; 70% were vertically exposed to the virus during in the first trimester of pregnancy, 62% developed severe microcephaly and the majority also presented ventricular dilation, and cortical and epileptic syndrome. All presented DNTUI, 74% with an urological risk profile to the upper urinary tract. At birth, 86% of the mothers were between 18 and 36 years of age and had completed less than eight years of schooling. Among the 50 children, 41 presented some post-treatment urodynamic improvements, including a significant reduction in the maximum bladder pressure (p= 0.001) and a significant increase in the maximum bladder capacity (p=0.001) and bladder compliance (p=0.000). There was no statistical significance that confirmed the interference of the factors in the urological treatment. Conclusion: The study confirmed the significant improvement in urodynamic patterns, when compared the first with the control exams, reaffirming the importance of investigating urological sequelae in these children.

Congenital Infections of the Nervous System.

PURPOSE OF REVIEW: This article provides an overview of congenital infections affecting the central nervous system (CNS), discussing the epidemiology, clinical features, diagnostic tools, and preventive and treatment measures for a variety of pathogens with the potential to infect the developing fetal brain. RECENT FINDINGS: Contrary to popular belief, many congenital CNS infections are preventable and treatable. Treatment options exist for congenital cytomegalovirus, human immunodeficiency virus (HIV), herpes simplex virus, toxoplasmosis, and syphilis, although the efficacy of these treatments and the populations that may benefit from treatment are variable. Zika virus has recently emerged as a pathogen affecting the fetal brain, and new data suggest that the pathogenesis of Zika virus involves direct infection of neuronal progenitor cells leading to destruction of CNS tissue. The incidence of congenital syphilis has been increasing in the United States over the past decade as a direct result of new syphilis cases among adults and poor access to adequate maternal health care. SUMMARY: Congenital CNS infections often result in significant neurologic morbidity in pediatric patients. Therefore, early identification of maternal illness and implementation of preventive measures are important in improving developmental outcomes and quality of life.

[Evidence based guidelines. Diagnosis and management of Guillain-Barré syndrome in ten steps]. / Guía basada en la evidencia. Diagnóstico y manejo del síndrome de Guillain-Barré en diez pasos.

Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and in 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae.

El síndrome de Guillain-Barré (SGB) es una enfermedad inmunológica del nervio periférico y las raíces nerviosas, poco frecuente, potencialmente mortal y que suele desencadenarse por infecciones. La incidencia del SGB puede aumentar durante el brote de enfermedades infecciosas, tal como se observó en las epidemias del virus Zika en la Polinesia Francesa en 2013 y en América Latina en 2015. El diagnóstico y el manejo clínico del SGB pueden ser complicados ya que su presentación y el curso de la enfermedad son heterogéneos, y actualmente no se cuenta con guías clínicas internacionales. Para respaldar a los médicos, especialmente en el contexto de un brote de una enfermedad infecciosa, hemos desarrollado una guía clínica aplicable en todo el mundo para el diagnóstico y el tratamiento del SGB. La guía se basa en literatura actualizada y el consenso de expertos, y tiene una estructura de diez pasos para facilitar su uso en la práctica clínica. Inicialmente, brindamos una introducción a los criterios de diagnóstico, variantes clínicas y diagnósticos diferenciales del SGB. Los diez pasos luego abordan el reconocimiento y el diagnóstico temprano del SGB, la admisión a la unidad de cuidados intensivos, indicación y selección de tratamiento, seguimiento y tratamiento de la progresión de la enfermedad, predicción del curso clínico, resultados y tratamiento de complicaciones y secuelas.