Anti-alpha synuclein and anti-tau immunotherapies: Can a cocktail approach work?

The hypothesis that neurodegenerative diseases are proteinopathies due to toxic effect of different underlying proteins, such as amyloid-beta and 3+4R-tau in Alzheimer's disease (AD) and alpha-synuclein in Parkinson's disease (PD), while still controversial is supported by several studies in the literature. This has led to conduct clinical trials attempting to reduce the load of these allegedly toxic proteins by immunotherapy, mostly but not solely based on antibodies against these proteins. Already completed clinical trials have ranged from initially negative results to recently partial positive outcomes, specifically for anti-amyloid antibodies in AD but also albeit to lesser degree for anti-synuclein antibodies in PD. Currently, there are several ongoing clinical trials in degenerative parkinsonisms with anti-synuclein approaches in PD and multiple system atrophy (MSA), as well as with anti-tau antibodies in 4R-tauopathies such as progressive supranuclear palsy (PSP). While it can be argued that expectations that part of these clinical trials will be positive can be hope or hype, it is reasonable to consider the future possibility of "cocktail" combination of different antibodies after the available experimental evidence of cross-talk between these proteins and neuropathological evidence of coexistence of these proteinopathies more frequently than expected by chance. Moreover, such "cocktail" approaches are widespread and accepted common practice in other fields such as oncology, and the complexity of neurodegenerative parkinsonisms makes reasonable the option for testing and eventually applying such combined approaches, should these prove useful separately, in the setting of patients with evidence of underlying concomitant proteinopathies, for example through biomarkers.

Fluid and tissue biomarkers in Parkinson's disease: Immunodetection or seed amplification? Central or peripheral?

Over the last two decades there have been meaningful developments on biomarkers of neurodegenerative diseases, extensively (but not solely) focusing on their proteinopathic nature. Accordingly, in Alzheimer's disease determination of levels of total and phosphorylated tau (τ and p-τ, usually p-τ181) along with amyloid-beta1-42 (Aß1-42) by immunodetection in cerebrospinal fluid (CSF) and currently even in peripheral blood, have been widely accepted and introduced to routine diagnosis. In the case of Parkinson's disease, α-synuclein as a potential biomarker (both for diagnosis and progression tracking) has proved more elusive under the immunodetection approach. In recent years, the emergence of the so-called seed amplification assays is proving to be a game-changer, with mounting evidence under different technical approaches and using a variety of biofluids or tissues, yielding promising diagnostic accuracies. Currently the least invasive but at once more reliable source of biosamples and techniques are being sought. Here we overview these advances.

Spatial analysis of hospital-related mortality due to COVID-19 among children and adolescents in Brazil.

The objective was to perform a spatial analysis of the hospital mortality rate (HMR) due to severe acute respiratory syndrome (SARS) attributed to COVID-19 among children and adolescents in Brazil from 2020 to 2021. A cluster method was used to group federal units (FUs) based on HMR. In 2020, clusters with high HMRs were formed by north/northeast FUs. In 2021, there was a reduction in HMR. Clusters with higher rates remained in the N/NE region. Regional differences were observed in the HMR. The findings may reflect social inequalities and access to hospital care, especially in the under 1-year-old age group due to the severity of the disease in this group.

Image-guided programming deep brain stimulation improves clinical outcomes in patients with Parkinson's disease.

Deep brain stimulation (DBS) is an effective treatment for patients with Parkinson's disease (PD). However, some patients may not respond optimally to clinical programming adjustments. Advances in DBS technology have led to more complex and time-consuming programming. Image-guided programming (IGP) could optimize and improve programming leading to better clinical outcomes in patients for whom DBS programming is not ideal due to sub-optimal response. We conducted a prospective single-center study including 31 PD patients with subthalamic nucleus (STN) DBS and suboptimal responses refractory to clinical programming. Programming settings were adjusted according to the volumetric reconstruction of the stimulation field using commercial postoperative imaging software. Clinical outcomes were assessed at baseline and at 3-month follow-up after IGP, using motor and quality of life (QoL) scales. Additionally, between these two assessment points, follow-up visits for fine-tuning amplitude intensity and medication were conducted at weeks 2, 4, 6, and 9. After IGP, twenty-six patients (83.9%) experienced motor and QoL improvements, with 25.8% feeling much better and 38.7% feeling moderately better according to the patient global impression scale. Five patients (16.1%) had no clinical or QoL changes after IGP. The MDS-UPDRS III motor scale showed a 21.9% improvement and the DBS-IS global score improved by 41.5%. IGP optimizes STN-DBS therapy for PD patients who are experiencing suboptimal clinical outcomes. These findings support using IGP as a standard tool in clinical practice, which could save programming time and improve patients' QoL.

Spatial analysis of hospital-related mortality due to COVID-19 among children and adolescents in Brazil / Análise espacial da mortalidade hospitalar por COVID-19 em crianças e adolescentes no Brasil

Abstract The objective was to perform a spatial analysis of the hospital mortality rate (HMR) due to severe acute respiratory syndrome (SARS) attributed to COVID-19 among children and adolescents in Brazil from 2020 to 2021. A cluster method was used to group federal units (FUs) based on HMR. In 2020, clusters with high HMRs were formed by north/northeast FUs. In 2021, there was a reduction in HMR. Clusters with higher rates remained in the N/NE region. Regional differences were observed in the HMR. The findings may reflect social inequalities and access to hospital care, especially in the under 1-year-old age group due to the severity of the disease in this group.

Resumo Objetivou-se realizar uma análise espacial da taxa de mortalidade hospitalar (TMH) por síndrome respiratória aguda grave (SRAG) atribuída à COVID-19 em crianças e adolescentes no Brasil no período de 2020 a 2021. Utilizou-se o método de cluster para agrupar as unidades federativas (UFs) com base na TMH. Em 2020, clusters com altas TMHs foram formados por UFs Norte/Nordeste. Em 2021, houve redução na TMH. Os clusters com maiores taxas permaneceram na região N/NE. Diferenças regionais foram observadas nas TMHs. Os achados podem refletir as desigualdades sociais e o acesso à atenção hospitalar, principalmente na faixa etária de menores de 1 ano pela gravidade da doença neste grupo.

Implementation of Exome Sequencing in Clinical Practice for Neurological Disorders.

Neurological disorders (ND) are diseases that affect the brain and the central and autonomic nervous systems, such as neurodevelopmental disorders, cerebellar ataxias, Parkinson's disease, or epilepsies. Nowadays, recommendations of the American College of Medical Genetics and Genomics strongly recommend applying next generation sequencing (NGS) as a first-line test in patients with these disorders. Whole exome sequencing (WES) is widely regarded as the current technology of choice for diagnosing monogenic ND. The introduction of NGS allows for rapid and inexpensive large-scale genomic analysis and has led to enormous progress in deciphering monogenic forms of various genetic diseases. The simultaneous analysis of several potentially mutated genes improves the diagnostic process, making it faster and more efficient. The main aim of this report is to discuss the impact and advantages of the implementation of WES into the clinical diagnosis and management of ND. Therefore, we have performed a retrospective evaluation of WES application in 209 cases referred to the Department of Biochemistry and Molecular Genetics of the Hospital Clinic of Barcelona for WES sequencing derived from neurologists or clinical geneticists. In addition, we have further discussed some important facts regarding classification criteria for pathogenicity of rare variants, variants of unknown significance, deleterious variants, different clinical phenotypes, or frequency of actionable secondary findings. Different studies have shown that WES implementation establish diagnostic rate around 32% in ND and the continuous molecular diagnosis is essential to solve the remaining cases.

PKD phosphorylation and COP9/Signalosome modulate intracellular Spry2 protein stability.

Spry2 is a molecular modulator of tyrosine kinase receptor signaling pathways that has cancer-type-specific effects. Mammalian Spry2 protein undergoes tyrosine and serine phosphorylation in response to growth factor stimulation. Spry2 expression is distinctly altered in various cancer types. Inhibition of the proteasome functionality results in reduced intracellular Spry2 degradation. Using in vitro and in vivo assays, we show that protein kinase D (PKD) phosphorylates Spry2 at serine 112 and interacts in vivo with the C-terminal half of this protein. Importantly, missense mutation of Ser112 decreases the rate of Spry2 intracellular protein degradation. Either knocking down the expression of all three mammalian PKD isoforms or blocking their kinase activity with a specific inhibitor contributes to the stabilization of Spry2 wild-type protein. Downregulation of CSN3, a component of the COP9/Signalosome that binds PKD, significantly increases the half-life of Spry2 wild-type protein but does not affect the stability of a Spry2 after mutating Ser112 to the non-phosphorylatable residue alanine. Our data demonstrate that both PKD and the COP9/Signalosome play a significant role in control of Spry2 intracellular stability and support the consideration of the PKD/COP9 complex as a potential therapeutic target in tumors where Spry2 expression is reduced.

Evaluating different levels of papain as texture modifying agent in bovine meat loaf containing transglutaminase.

In this study, bovine meat loaves were produced with different levels of papain (0.00125%, 0.0025%, 0.00375%, and 0.005%) combined with transglutaminase (1%). The effect of this reformulation on pH, instrumental color, water activity, proximate composition, texture, yield, and scanning electron microscopy (SEM) of meat loaves was investigated. In addition, the enzymatic activity of papain was also analyzed. The papain addition increased the pH and the yield of the samples. The hardness was progressively reduced with the increase of papain level. Such changes could be seen through the images recorded by SEM, where an extremely fragmented structure was observed in treatments with higher papain concentration. Papain showed an optimum temperature of 80 °C. This study allowed to observe an intense proteolytic effect in all treatments, despite the papain concentration. Therefore, lower levels should be applied so that the product does not alter its sensory characteristics, such as soft and crumbly texture.

Análise espacial de casos prováveis de dengue no município de São Luís, Maranhão, Brasil / Spatial analysis of probable dengue cases in the municipality of São Luís, Maranhão, Brazil / Análisis espacial de los casos probables de dengue en el municipio de São Luís, Maranhão, Brasil

INTRODUÇÃO: A dengue é considerada uma das principais arboviroses mundiais, caracterizada no Brasil pelo aumento de casos graves e óbitos. OBJETIVO: realizar análise espacial dos casos prováveis de dengue em São Luís - MA. MÉTODOS: Estudo ecológico de base populacional dos casos prováveis de dengue, notificados no Sistema de Informação de Agravos de Notificação (SINAN) em 2015 e 2016, ocorridos no município de São Luís ­ MA. Foram georreferenciados 4.681 casos prováveis de dengue por setores censitários, calculadas as taxas de incidência e ajustadas através do estimador bayesiano empírico local. Foi utilizado o estimador de densidade de Kernel e Moran Global e Local para a análise espacial. RESULTADOS: Evidenciou-se através do estimador de densidade de Kernel, áreas quentes (alta-densidade) nos setores censitários da região noroeste do município. As taxas de incidência foram ajustadas pela aplicação do método bayesiano empírico local, identificando-se maior quantidade de setores com média e alta incidência. A partir do índice de Moran global foi evidenciada autocorrelação espacial positiva estatisticamente significativa para as taxas de incidência de dengue (I=0,69; p<0,001) e para as taxas de incidência ajustadas pelo método bayesiano (I=0,80; p<0,001). De acordo com o índice de Moran local, identificou-se clusters de setores de alta incidência de dengue em áreas com alta densidade populacional na região nordeste e noroeste do município. CONCLUSÃO: A pesquisa demonstrou que os estimadores bayesianos ajudaram a minimizar os problemas de subnotificação e da influência do tamanho populacional nos setores censitários.

INTRODUCTION: Dengue is considered one of the main arboviruses in the world, characterized in Brazil by the increase in severe cases and deaths. OBJECTIVE: to perform spatial analysis of probable dengue cases in São Luís - MA. METHODS: Population-based ecological study of probable dengue cases, reported in the Notifiable Diseases Information System (SINAN) in 2015 and 2016, which took place in the city of São Luís - MA. 4,681 probable dengue cases were georeferenced by census sectors, incidence rates were calculated and adjusted using the local empirical Bayesian estimator. The Kernel and Moran Global and Local density estimator was used for spatial analysis. RESULTS: Hot areas (high-density) in the census sectors of the northwest region of the municipality were evidenced through the Kernel density estimator. Incidence rates were adjusted by applying the local empirical Bayesian method, identifying a greater number of sectors with medium and high incidence. From the global Moran index, statistically significant positive spatial autocorrelation was evidenced for the dengue incidence rates (I = 0.69; p <0.001) and for the incidence rates adjusted by the Bayesian method (I = 0.80; p <0.001). According to the local Moran index, clusters of sectors with a high incidence of dengue were identified in areas with high population density in the northeast and northwest regions of the municipality. CONCLUSION: The research demonstrated that Bayesian estimators helped to minimize the problems of underreporting and the influence of population size on census tracts.

INTRODUCCIÓN: El dengue es considerado una de las principales arbovirosis a nivel mundial, caracterizada en Brasil por el aumento de casos graves y muertes. OBJETIVO: Realizar un análisis espacial de los casos probables de dengue en São Luís - MA. MÉTODOS: Estudio ecológico de base poblacional de los casos probables de dengue, notificados en el Sistema de Informação de Agravos de Notificação (SINAN) en 2015 y 2016, ocurridos en el municipio de São Luís - MA. Se georreferenciaron 4.681 casos probables de dengue por sectores censales, se calcularon las tasas de incidencia y se ajustaron mediante el estimador empírico bayesiano local. Para el análisis espacial se utilizó el estimador de densidad Kernel y Moran global y local. RESULTADOS: Se evidenció a través del estimador de densidad Kernel, áreas calientes (de alta densidad) en los sectores censales de la región noroeste del municipio. Las tasas de incidencia se ajustaron mediante la aplicación del método bayesiano empírico local, identificándose una mayor cantidad de setores con incidencia media y alta. A partir del índice global de Moran se evidenció una autocorrelación espacial positiva estadísticamente significativa para las tasas de incidencia de dengue (I=0,69; p<0,001) y para las tasas de incidencia ajustadas por el método bayesiano (I=0,80; p<0,001). Según el índice local de Moran, se identificaron clusters de sectores de alta incidencia de dengue en áreas con alta densidad de población en las regiones noreste y noroeste del municipio. CONCLUSIÓN: La investigación demostró que los estimadores bayesianos ayudaron a minimizar los problemas de infradeclaración y la influencia del tamaño de la población en los sectores censales.

Cognitive Behavioral Therapy Plus a Serious Game as a Complementary Tool for a Patient With Parkinson Disease and Impulse Control Disorder: Case Report.

BACKGROUND: Impulse control disorders (ICDs) are commonly developed among patients who take dopamine agonist drugs as a treatment for Parkinson disease (PD). Gambling disorder and hypersexuality are more frequent in male patients with PD, with a prevalence over 4% in dopamine agonists users. Although impulsive-compulsive behaviors are related to antiparkinsonian medication, and even though ICD symptomatology, such as hypersexuality, often subsides when the dopaminergic dose is reduced, sometimes ICD persists in spite of drug adjustment. Consequently, a multidisciplinary approach should be considered to address these comorbidities and to explore new forms of complementary interventions, such as serious games or therapies adapted to PD. OBJECTIVE: The aim of this study is to present the case of a patient with ICD (ie, hypersexuality) triggered by dopaminergic medication for PD. A combined intervention was carried out using cognitive behavioral therapy (CBT) for ICD adapted to PD, plus an intervention using a serious game-e-Estesia-whose objective is to improve emotion regulation and impulsivity. The aim of the combination of these interventions was to reduce the harm of the disease. METHODS: After 20 CBT sessions, the patient received the e-Estesia intervention over 15 sessions. Repeated measures, before and after the combined intervention, were administered to assess emotion regulation, general psychopathology, and emotional distress and impulsivity. RESULTS: After the intervention with CBT techniques and e-Estesia, the patient presented fewer difficulties to regulate emotion, less emotional distress, and lower levels of impulsivity in comparison to before the treatment. Moreover, the frequency and severity of the relapses also decreased. CONCLUSIONS: The combined intervention-CBT and a serious game-showed positive results in terms of treatment outcomes.

Increased Phospho-AKT in Blood Cells from LRRK2 G2019S Mutation Carriers.

The purpose of this study was to investigate whether  differential phosphorylation states of blood markers can identify patients with LRRK2 Parkinson's disease (PD). We assessed phospho(P)-Ser-935-LRRK2 and P-Ser-473-AKT levels in peripheral blood cells from patients with G2019S LRRK2-associated PD (L2PD, n = 31), G2019S LRRK2 non-manifesting carriers (L2NMC, n = 26), idiopathic PD (iPD, n = 25), and controls (n = 40, total n = 122). We found no differences at P-Ser-935-LRRK2 between groups but detected a specific increase of P-Ser-473-AKT levels in all G2019S carriers, either L2PD or L2NMC, absent in iPD. Although insensitive to LRRK2 inhibition, our study identifies P-Ser-473-AKT as an endogenous candidate biomarker for peripheral inflammation in G2019S carriers using accessible blood cells. ANN NEUROL 2022;92:888-894.

Acalculous cholecystitis associated with levodopa-carbidopa intestinal infusion therapy: A case report.

Continuous intra jejunal infusion of levodopa-carbidopa intestinal gel (LCIG) is one of the primary therapies for improving advanced Parkinson's disease symptoms. Placement of the jejunal catheter through the abdominal wall for drug administration requires a percutaneous interventional procedure called percutaneous endoscopic gastrostomy (PEG). PEG is considered a safe and straightforward procedure, and it is performed very commonly in clinical practice. In the context of LCIG treatment, severe adverse events have been identified, such as intestinal bleeding and acute abdomen [1], but acute acalculous cholecystitis (AAC) has never been reported.

Utility of Postoperative Imaging Software for Deep Brain Stimulation Targeting in Patients with Movement Disorders.

OBJECTIVE: The objective of this study was to evaluate the accuracy of the SureTune3 postoperative imaging software in determining the location of a deep brain stimulation (DBS) electrode based on clinical outcomes and the adverse effects (AEs) observed. METHODS: Twenty-six consecutive patients with Parkinson disease (n = 17), essential tremor (n = 8), and dystonia (n = 1) who underwent bilateral DBS surgery (52 electrodes) were included in this study. Presurgical assessments were performed in all patients prior to surgery and at 3 and 6 months after surgery, using quality-of-life and clinical scales in each case. The SureTune3 software was used to evaluate the anatomical positioning of the DBS electrodes. RESULTS: Following DBS surgery, motor and quality-of-life improvement was observed in all patients. Different AEs were detected in 12 patients, in 10 of whom (83.3%) SureTune3 related the symptoms to the positioning of an electrode. A clinical association was observed with SureTune3 for 48 of 52 (92.3%) electrodes, whereas no association was found between the AEs or clinical outcomes and the SureTune3 reconstructions for 4 of 52 electrodes (7.7%) from 4 different patients. In 2 patients, the contact chosen was modified based on the SureTune3 data, and in 2 cases, the software helped determine that second electrode replacement surgery was necessary. CONCLUSIONS: The anatomical position of electrodes analyzed with SureTune3 software was strongly correlated with both the AEs and clinical outcomes. Thus, SureTune3 may be useful in clinical practice, and it could help improve stimulation parameters and influence decisions to undertake electrode replacement surgery.

Spatial Analysis of Notified Zika Virus Congenital Syndrome, Maranhão, 2015 to 2018. / Análise espacial da taxa de detecção de casos suspeitos de síndrome congênita pelo vírus Zika, Maranhão, 2015 a 2018.

OBJECTIVE: To identify spatial patterns in cases of changes in growth and development related to Zika virus infection and other infectious etiologies (denominated Zika virus congenital syndrome in this study) reported in Maranhão from 2015 to 2018 and their relation with socioeconomic and demographic variables. METHODS: Ecological study of notified Zika virus congenital syndrome cases in the 217 cities of Maranhão, Brasil. Spatial autocorrelation was calculated using GeoDa 1.14 software and the local and global (I) Moran's index in univariate and bivariate analyses on Zika virus congenital syndrome incidence rate with Municipal Human Development Index (MHDI), population density, Gini coefficient and the cities' time of administrative political emancipation. Local Moran's Index was calculated to identify clusters with significant spatial autocorrelation. RESULTS: Spatial autocorrelation was checked in univariate analysis of the incidence rate of Zika virus congenital syndrome (I=0,494; p=0,001) and positive correlation in bivariate analysis of the incidence rate with Municipal Human Development Index (I=0,252; p=0,001), population density (I=0,338; p=0,001) and the cities' time of administrative political emancipation (I=0,134; p=0,001). The correlation between incidence rate with Gini coefficient was not significant (I= -0,033; p=0,131). Five high-incidence clusters were found in distinct areas of the state. CONCLUSIONS: Cities with higher MHDI, higher population density and more years of administrative political emancipation had more cases of Zika virus congenital syndrome notified.

OBJETIVO: Identificar padrões espaciais em casos de lactentes com alterações de crescimento e desenvolvimento relacionadas à infecção pelo vírus Zika e outras etiologias infecciosas (neste trabalho denominado de síndrome congênita pelo vírus Zika), notificados no Maranhão de 2015 a 2018 e sua relação com variáveis socioeconômicas e demográficas. MÉTODOS: Estudo ecológico de casos suspeitos notificados de síndrome congênita pelo vírus Zika nos 217 municípios do Maranhão, Brasil. Calculou-se a autocorrelação espacial pelos índices de Moran local e global (I) univariado e bivariado da taxa de detecção de casos suspeitos de síndrome congênita pelo vírus Zika com índice de desenvolvimento humano municipal, densidade demográfica, índice de Gini e tempo de emancipação político-administrativa dos municípios. O índice de Moran local foi calculado para localizar clusters com autocorrelação espacial significativa. RESULTADOS: Houve autocorrelação espacial na análise univariada da taxa municipal de detecção de casos suspeitos de síndrome congênita pelo vírus Zika (I=0,494; p=0,001) e, na análise bivariada, correlação positiva da taxa de detecção de casos suspeitos com índice de desenvolvimento humano municipal (I=0,252; p=0,001), densidade demográfica (I=0,338; p=0,001) e tempo de emancipação dos municípios (I=0,134; p=0,001). Não houve correlação significativa da taxa de detecção de casos suspeitos com o índice de Gini (I= -0,033; p=0,131). Cinco clusters de alta detecção de casos suspeitos foram encontrados em áreas distintas do estado. CONCLUSÕES: Os municípios com maior índice de desenvolvimento humano municipal, maior densidade demográfica e mais tempo de emancipação político-administrativa tiveram mais casos suspeitos notificados de síndrome congênita pelo vírus Zika.

Non-motor symptoms in spasmodic dysphonia: A case control-study.

OBJECTIVE: Non-motor symptoms (NMS) have been identified in some focal adult-onset dystonia. In the present study we aimed to evaluate the presence of NMS in patients with spasmodic dysphonia (SD), a focal action-induced dystonia that affects intrinsic laryngeal muscle control. METHODS: Seventeen SD patients and 17 control subjects not significantly different in age and sex were evaluated for the presence of NMS. Additionally, voice handicap index (VHI-10), reflux symptom index, neuropsychiatric symptoms and QoL were assessed by validated scales and questionnaires. RESULTS: Patients' group significantly differed from control group in mild depressive symptoms (4.35 ± 3.9 vs. 1.47 ± 2; p=0.01), insomnia (35.3% vs. 14.7%; p=0.016), smell and taste loss (11.8% vs. 0%; p=0.033), swallowing difficulties (17.6% vs. 0%; p=0.007) and throat pain (17.6% vs. 0%; p=0.007). In the group of SD, there was no correlation between voice perception evaluated by VHI-10, number of NMS or QoL. CONCLUSION: Patients with SD have a greater burden of depressive, smell, taste, and sleep NMS than control subjects.

Inulin gelled emulsion as a fat replacer and fiber carrier in healthier Bologna sausage.

The effects of gelled emulsions (GE) used as animal fat replacers in terms of the nutritional, technological, and sensory properties of Bologna sausages during 60 days of chilled storage have been studied. Samples with GE added exhibited a fat reduction of 31%. Sausages with GE had higher values of L* and lower values of a* compared to the control. Harder sausages were obtained by the addition of GE. Higher lipid oxidation rates were found with increasing amounts of GE in the reformulated products. In addition, the relaxation time was not affected by the reformulation. All samples were deemed acceptable by consumer tests. However, CATA (Check-all-that-apply) tests showed that Bolognas formulated with partial or total pork fat replaced with GE were described as rubbery, not very spicy and firm, appeared to be dry and opaque, and had an aftertaste. Chilled storage significantly affected the Thiobarbituric Acid Reactive Substances (TBARS) values and slightly affected the pH values, texture, color, and NMR data. An important result is that the panelists did not detect the oxidation results in relation to the TBARS values, and the addition of a GE with inulin as dietary fiber may be a good strategy to make Bologna sausage healthier.

Análise espacial da taxa de detecção de casos suspeitos de síndrome congênita pelo vírus Zika, Maranhão, 2015 a 2018 / Spatial Analysis of Notified Zika Virus Congenital Syndrome, Maranhão, 2015 to 2018

RESUMO: Objetivo: Identificar padrões espaciais em casos de lactentes com alterações de crescimento e desenvolvimento relacionadas à infecção pelo vírus Zika e outras etiologias infecciosas (neste trabalho denominado de síndrome congênita pelo vírus Zika), notificados no Maranhão de 2015 a 2018 e sua relação com variáveis socioeconômicas e demográficas. Métodos: Estudo ecológico de casos suspeitos notificados de síndrome congênita pelo vírus Zika nos 217 municípios do Maranhão, Brasil. Calculou-se a autocorrelação espacial pelos índices de Moran local e global (I) univariado e bivariado da taxa de detecção de casos suspeitos de síndrome congênita pelo vírus Zika com índice de desenvolvimento humano municipal, densidade demográfica, índice de Gini e tempo de emancipação político-administrativa dos municípios. O índice de Moran local foi calculado para localizar clusters com autocorrelação espacial significativa. Resultados: Houve autocorrelação espacial na análise univariada da taxa municipal de detecção de casos suspeitos de síndrome congênita pelo vírus Zika (I=0,494; p=0,001) e, na análise bivariada, correlação positiva da taxa de detecção de casos suspeitos com índice de desenvolvimento humano municipal (I=0,252; p=0,001), densidade demográfica (I=0,338; p=0,001) e tempo de emancipação dos municípios (I=0,134; p=0,001). Não houve correlação significativa da taxa de detecção de casos suspeitos com o índice de Gini (I= -0,033; p=0,131). Cinco clusters de alta detecção de casos suspeitos foram encontrados em áreas distintas do estado. Conclusões: Os municípios com maior índice de desenvolvimento humano municipal, maior densidade demográfica e mais tempo de emancipação político-administrativa tiveram mais casos suspeitos notificados de síndrome congênita pelo vírus Zika.

ABSTRACT: Objective: To identify spatial patterns in cases of changes in growth and development related to Zika virus infection and other infectious etiologies (denominated Zika virus congenital syndrome in this study) reported in Maranhão from 2015 to 2018 and their relation with socioeconomic and demographic variables. Methods: Ecological study of notified Zika virus congenital syndrome cases in the 217 cities of Maranhão, Brasil. Spatial autocorrelation was calculated using GeoDa 1.14 software and the local and global (I) Moran's index in univariate and bivariate analyses on Zika virus congenital syndrome incidence rate with Municipal Human Development Index (MHDI), population density, Gini coefficient and the cities' time of administrative political emancipation. Local Moran's Index was calculated to identify clusters with significant spatial autocorrelation. Results: Spatial autocorrelation was checked in univariate analysis of the incidence rate of Zika virus congenital syndrome (I=0,494; p=0,001) and positive correlation in bivariate analysis of the incidence rate with Municipal Human Development Index (I=0,252; p=0,001), population density (I=0,338; p=0,001) and the cities' time of administrative political emancipation (I=0,134; p=0,001). The correlation between incidence rate with Gini coefficient was not significant (I= -0,033; p=0,131). Five high-incidence clusters were found in distinct areas of the state. Conclusions: Cities with higher MHDI, higher population density and more years of administrative political emancipation had more cases of Zika virus congenital syndrome notified.