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Yellow fever in Brazil: new insights on an old disease

巴西黄热病：对一种古老疾病的新见解

基本信息

批准号：
10583529
负责人：
OLINDO ASSIS MARTINS FILHO
金额：
$ 15.24万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-18 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10583529
关键词：
Acute Admission activity Adult Africa Americas Angola Antibody Response Area Bilirubin Biological Biology Brazil Caring Cause of Death Cellular Immunity Cessation of life Clinical Clinical Data Communicable Diseases Convalescence Data Data Analyses Data Set Databases Democratic Republic of the Congo Development Disease Disease Outbreaks Disease Outcome Epidemic Epidemiology Fever Flaviviridae Flavivirus Functional disorder Future Hepatic Hepatitis Hospitalization Hospitals Human IL8 gene Immune response Immunologic Markers Immunologics Immunology In Vitro Infection Inflammation Mediators Inflammatory Interleukin-10 Investigation Knowledge Label Laboratories Life Longterm Follow-up MEKs Measures Mediator Medical Morbidity - disease rate Names Outcome Oxidative Stress Pathogenesis Patient-Focused Outcomes Patients Pattern Peripheral Blood Mononuclear Cell Persons Phase Predictive Factor Preventative vaccination Prevention Preventive vaccine Prognosis Protocols documentation Public Health RANTES Reporting Research Risk Factors Sampling South Africa South America Syndrome TNF gene Testing Therapeutic Transaminases Viral Yellow Fever Yellow Fever Virus Infection Yellow fever virus biobank clinical care clinically significant cohort comorbidity data repository emerging pathogen epidemiologic data experience follow-up holistic approach in vivo inhibitor insight interdisciplinary approach longitudinal database molecular marker mortality mouse model neutralizing antibody novel off-label use pathogen pharmacologic predictive marker preservation prevent social transmission process virology

项目摘要

ABSTRACT Yellow fever virus (YFV) is widely distributed in the tropics of South America and Africa, being responsible for massive yellow fever outbreaks causing deaths of thousands of people in recent years. YF usually occurs in remote areas of Africa and the Americas where patients have little or no access to advanced medical care and laboratory tests; therefore, much of what we know about YF in humans is very limited including poorly understood epidemiology, pathogenesis, therapeutic approaches, and host/virological determinants of disease during different phases of infection. In December 2016, a massive sylvatic YF outbreak (2,155 human cases) took place in Southeast Brazil, with 46% of total cases (n=1,002) and 37% of deaths (n=340) occuring in Minas Gerais state. From 2016 to 2018, a total of 299 confirmed YF cases were admitted at Eduardo de Menezes Hospital, in Belo Horizonte, Minas Gerais. Our group has maintained a database containing epidemiological and clinical data with long-term follow up from those patients, as well a biological bank of clinical samples that can be probed to redefine the clinical course and pathogenesis of this important pathogen. Our unique well-characterized cohorts include: (i) patients who evolved to death; (ii) patients who recovered; (iii) patients who recovered and developed a novel clinical syndrome named late hepatitis-like syndrome after yellow fever (LHep-YF); and (iv) patients who received off-label treatment with sofosbuvir. Here we propose to (i) redefine the clinical course of YF and determine the social, demographic, and co-morbid risk factors for severe presentations of disease, including development of LHep-YF, (ii) investigate the viral and immunologic pathogenesis of YF throughout the continuum of disease and (iii) predict YF prognosis by identifying virological and immunological biomarkers associated with severe disease and assessing the effects of potential treatments. Our experienced research team will take an interdisciplinary approach that integrates basic and applied virology, immunology, epidemiology, and clinical infectious disease to fill important gaps on epidemiology, clinical disease, pathophysiology, and biology of YFV. The recent YFV outbreaks in Southeast Brazil create an unprecedented opportunity to analyze our unique bank of data and well-preserved samples from hundreds of hospitalized YF patients. This information will be crucial for the establishment of protocols and more applied studies to prevent morbidity and mortality from this important pathogen.

摘要黄热病病毒（YFV）广泛分布于南美洲和非洲的热带地区，近年来，黄热病大规模爆发，造成数千人死亡。YF 通常发生在非洲和美洲的偏远地区，患者很少或根本无法获得先进的医疗保健和实验室测试;因此，我们对人类YF的了解非常多，有限的，包括对流行病学、发病机理、治疗方法和在感染的不同阶段，宿主/病毒学决定因素的疾病。2016年12月，巴西东南部发生森林型YF暴发（2，155例人间病例），占病例总数的46%（n= 1，002）米纳斯吉拉斯州340例死亡病例中有37%发生在该州。从2016年到2018年，共有299名确诊的YF 病例在米纳斯吉拉斯贝洛奥里藏特的Eduardo de Menezes医院住院。我们集团维持一个数据库，其中载有流行病学和临床数据，并对这些数据进行长期跟踪。患者，以及临床样本的生物库，可以探测以重新定义临床过程，这一重要病原体的发病机制。我们独特的特征明确的队列包括：（i）发展至死亡;（ii）恢复的患者;（iii）恢复并发展新的临床综合征命名为黄热病后晚期肝炎样综合征（LHep-YF）;和（iv）接受索非布韦标签外治疗。在这里，我们建议（i）重新定义YF的临床过程，并确定严重疾病表现的社会、人口统计学和共病风险因素，包括 LHep-YF的发展，（ii）研究整个过程中YF的病毒和免疫发病机制。疾病的连续性和（iii）通过鉴定病毒学和免疫学生物标志物预测YF预后与严重疾病相关，并评估潜在治疗的效果。我们经验丰富研究小组将采取跨学科的方法，整合基础和应用病毒学，免疫学、流行病学和临床传染病，以填补流行病学、临床 YFV的疾病、病理生理学和生物学。最近在巴西东南部爆发的YFV造成了这是一个前所未有的机会，可以分析我们独特的数据库和数百个保存完好的样本，住院的YF患者。这些信息对于制定协议等至关重要应用研究，以防止发病率和死亡率从这个重要的病原体。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Yellow Fever Molecular Diagnosis Using Urine Specimens during Acute and Convalescent Phases of the Disease.

DOI：
10.1128/jcm.00254-22
发表时间：
2022-08-17
期刊：
JOURNAL OF CLINICAL MICROBIOLOGY
影响因子：
9.4
作者：
de Rezende, Izabela Mauricio;Garcia Oliveira, Gabriela Fernanda;Costa, Thais Alkifeles;Khan, Aslam;Pereira, Leonardo Soares;Santos, Tayrine Araujo;Alves, Pedro Augusto;Calzavara-Silva, Carlos Eduardo;Martins-Filho, Olindo Assis;Teixeira-Carvalho, Andrea;LaBeaud, Angelle Desiree;Drumond, Betania Paiva
通讯作者：
Drumond, Betania Paiva

Characterization and Investigation of Risk Factors for Late-Relapsing Hepatitis After Yellow Fever.