Emerging Neuroviruses and Neurological Inflammatory Diseases

新兴神经病毒和神经炎症性疾病

基本信息

批准号：
9976612
负责人：
CARLOS A PARDO-VILLAMIZAR
金额：
$ 32.47万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-15 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9976612
关键词：
Acute Address Adult Affect Americas Antibodies Antigens Arbovirus Infections Arboviruses Area Biological Biological Assay Blood Caribbean region Chikungunya virus Clinical Clinical Research Cohort Studies Collection Colombia Colombian Communicable Diseases Communities Competence Complex Country Data Dengue Development Devices Diagnosis Diagnostic Disease Disease Outbreaks Educational workshop Encephalitis Ensure Enterovirus Epidemic Epidemiology Fellowship Frequencies Genomics Genotype Goals Guillain-Barré Syndrome Immune Immune response Immunologic Techniques Immunological Diagnosis Immunologics Immunology procedure Incidence Infection Inflammatory Influenza Laboratories Latin American Liquid substance Measures Mediating Meningitis Metagenomics Methodology Methods Modeling Molecular Myelitis Neurologic Pathogenesis Pathogenicity Patient Recruitments Peptides Pilot Projects Population Public Health Research Research Personnel Resources Risk Factors Role Sampling Severities Severity of illness Site Study models Techniques Technology Training Training Programs Translational Research University Hospitals Urine Variant Viral Virus Virus Diseases ZIKA ZIKV infection Zika Virus base chikungunya chikungunya infection clinical research site data acquisition epidemiology study experience improved medical schools microbial nervous system disorder neuroinflammation next generation next generation sequencing novel pathogen pathogenic microbe pathogenic virus portability programs relating to nervous system response study population vaccine development virology webinar

项目摘要

PROJECT SUMMARY The recent outbreaks of arboviral infections such as Zika and Chikungunya in Latin American and Caribbean countries have uncovered the role of emergent viral infections in the increased incidence of neuroinflammatory disorders such as encephalitis, myelitis and Guillain-Barré syndrome (GBS). Here, we propose a multi-center model of university-hospital sites in Colombia to facilitate clinical, epidemiological, and virological surveillance and research of neurological disorders associated with emerging infections. The model already established as the Neurovirus Emerging in the Americas Study (NEAS), will serve as an observatory of neurological disorders associated with emerging viral infections and will facilitate the long-term goals of building and strengthening sustainable research capacity in Colombia to address the emerging threat of viral illnesses and their neurological complications. Based on our preliminary studies that helped to characterize clinical, immunological and virological features of Zika-associated GBS in Colombia (Parra et al., NEJM 2016), we hypothesize that acute neurological problems in the adult population of areas affected by emergent viral infections result from complex host-viral interactions driven by previously established circulating arboviruses (e.g., dengue, enteroviruses) as well as emergent pathogens (e.g., Zika and Chikungunya); and that variations in viral genotype as well as host immunological responses to previous viral infections drive pathogenicity and severity of neurological disease. To address this hypothesis, the specific aims of this proposal are: 1) To utilize the NEAS model to establish a sustainable approach for assessment of acute neuroinflammatory disorders such as GBS and encephalitis-myelitis and determine the role of emergent infections in the development of such complications, 2) To implement state of the art technologies to improve the diagnosis of emerging pathogens in the onset of acute neuroinflammatory disorders; and 3) To establish a training program to enhance the competence of Colombian researchers in the use of next generation molecular and immunological techniques, and computational biological approaches in metagenomics and pathogen discovery studies. We will take advantage of the past and present experience with patient recruitment and biosample collection in the NEAS cohort study population, the use of state-of-the-art immunological assays, next generation sequencing, and massive multiplexed viral peptides assay (VirScan) to achieve such aims. We believe the findings of this project will have a major public health impact and will address important questions related to viral diversity and impact on disease severity, information needed for understanding disease pathogenesis, management and vaccine development. This project will also contribute to building up capacity in Colombia by investing in clinical and translational research to better characterize neurological complications of emerging viral diseases.

项目摘要最近在拉丁美洲和加勒比海中爆发的灰烬病毒感染爆发各国发现了新兴病毒感染在增加神经炎症事件中的作用诸如脑炎，脊髓炎和Guillain-Barré综合征（GBS）等疾病。在这里，我们提出了一个多中心哥伦比亚大学医院地点的模型，以促进临床，流行病学和病毒学监测以及与紧急感染相关的神经系统疾病的研究。该模型已经建立为美洲研究（NEAS）中出现的神经病毒将作为神经系统疾病的观察与新兴的病毒感染相关，并将促进建立和加强的长期目标哥伦比亚可持续研究能力，以应对病毒疾病的新兴威胁及其神经系统并发症。基于我们有助于临床表征的初步研究 Zika相关GB的免疫学和病毒学特征在哥伦比亚（Parra等，NEJM，2016），，假设在新兴病毒影响的地区成年地区的急性神经问题感染是由复杂的宿主病毒相互作用引起的。（例如登革热，肠病毒）以及新兴的病原体（例如Zika和Chikungunya）；以及这一变化在病毒基因型以及对先前病毒感染的宿主免疫反应促进了致病性和神经疾病的严重程度。为了解决这一假设，该提议的具体目的是：1） NEAS模型建立一种可持续的方法来评估急性神经炎症性疾病例如GBS和脑炎脑炎，并确定新兴感染在发育中的作用这种并发症，2）实施艺术技术的状态以改善新兴的诊断急性神经炎症性疾病发作中的病原体； 3）建立一个培训计划增强哥伦比亚研究人员在使用下一代分子和免疫学方面的能力宏基因组学和病原体发现研究中的技术和计算生物学方法。我们将利用过去和现在的经验，并在患者招募和生物样品中收集 NEAS队列研究人群，最先进的免疫学测定，下一代测序，和大量的多重病毒肽测定法（VirScan）以实现此类目的。我们相信这一点的发现项目将对公共卫生产生重大影响，并将解决与病毒多样性有关的重要问题对疾病严重程度的影响，了解疾病发病机理所需的信息，管理和疫苗开发。该项目还将通过投资哥伦比亚建立能力临床和翻译研究以更好地表征新兴病毒疾病的神经系统并发症。