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Towards Understanding the Morbidity of HEV Infection

了解 HEV 感染的发病率

基本信息

批准号：
7282686
负责人：
Mohamed Tarek Shata
金额：
$ 20.78万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-15 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7282686
关键词：
Accounting Acute Address Animals Antibodies Area Award Biological Assay Blood donor Cells Chronic Hepatitis Clinical Collaborations Communities Data Developed Countries Developing Countries Development Disasters Disease Disease Outbreaks Doctor of Philosophy Domestic Animals Down-Regulation Egypt Emerging Communicable Diseases Epidemiology Epitopes Exposure to Feces Future General Population Genotype Geographic Distribution Hepatitis Hepatitis E Hepatitis E virus High Prevalence Human Hurricane Immune Immune response Immunity Immunoglobulin G Immunoglobulin M In Vitro Infection Iraq Kinetics Lead Life Measures Mediating Military Personnel Morbidity - disease rate National Institute of Allergy and Infectious Disease Oral Outcome Pan Genus Pan troglodytes Pathogenesis Patients Pattern Peripheral Blood Mononuclear Cell Play Population Pregnant Women Prevalence Prevention Protocols documentation Purpose RNA Viruses Range Rate Recovery Refugees Relative (related person)Reporting Research Personnel Risk Role Rural Rural Community Sampling Serological Serum Sorting - Cell Movement Species Specificity Sudan Surrogate Markers Techniques Testing Viral hepatitis Viremia Virulence Virulent Virus Virus Diseases Visit Water cell mediated immune response cohort cross reactivity design immunopathology innovation man mortality programs transmission process viral RNA

项目摘要

DESCRIPTION (provided by applicant): Hepatitis E (HEV) is enterically transmitted RNA virus that causes acute viral hepatitis (AVH) in many lesser developed countries (LDC), with frequent reports of fulminant hepatitis in pregnant women. Although HEV- caused AVH is not endemic in the US, the prevalence of antibodies to HEV (anti-HEV) is as high as 20% among blood donors in certain areas of the US. HEV is a zoonotic disease with several animal species being reservoir hosts. The four genotypes of HEV are cross-reactive serologically but have different geographical distributions, species specificity, and virulence. However, cross-species infections have been reported. In the Indian subcontinent, and recently in outbreaks in Baghdad and in refugees in Darfur Sudan, the virulent genotype-1 strain of HEV was isolated from AVH cases. We reported HEV is endemic in rural villages in Egypt. In spite of community-wide anti-HEV prevalence of 70-85%, HEV-caused AVH was rare and fulminant HEV-hepatitis was not detected among pregnant women. However, HEV genotype-1 has been isolated from the stool of two hospitalized AVH patients in Cairo; and HEV has accounted for 10-to-30% of AVH in hospitalized Egyptians. We have recently isolated avirulent genotype-3 HEV (the same strain found in the US) from domestic animals in Egypt. Our exploratory development award's purpose is to prepare, and obtain preliminary data, to test hypotheses that may explain why HEV-caused AVH may be rare in some areas, like Egypt and the US, despite the presence of high anti-HEV prevalence. Among these are: (1) Prior early exposures to avirulent strains of HEV lead to asymptomatic or mild infections, prime immunity, and suppress viremia and clinical manifestations during subsequent infections with more virulent strains. (2) Two HEV genotypes are transmitted in Egypt: (a) genotype 3 is endemic and zoonotically transmitted among animal reservoirs causing avirulent infections in humans; and (b) the virulent genotype-1 HEV sporadically causes AVH. Cell-mediated immune (CMI) testing is necessary to test our hypotheses; and HEV-specific CMI responses may be a long-lasting reliable marker of prior exposure and/or protection to subsequent infection/morbidity. There are no reported HEV CMI studies, and the serological cross-reactivity among HEV strains, limits utilization of anti-HEV as surrogate markers for prior exposure to avirulent strains of HEV. Therefore, we plan to develop, standardize and use reliable tests to measure CMI responses against unique epitopes for HEV strains. This will provide the means to sort-out the different roles the virus and the host's immune response have on transmission and morbidity of HEV in Egypt, and the results would be applicable to other areas, including the US. Consequently, this application will provide the means and preliminary data to design a protocol to understand the factors involved in the pathogenesis of HEV, as one of the important emerging infectious diseases that appears to have spread from animals to man.

描述(申请人提供)：戊型肝炎(HEV)是一种肠道传播的RNA病毒，在许多欠发达国家(LDC)会导致急性病毒性肝炎(AVH)，经常有孕妇暴发性肝炎的报告。尽管HEV引起的AVH在美国并不流行，但在美国某些地区的献血者中，HEV(抗-HEV)抗体的流行率高达20%。HEV是一种人畜共患病，有几种动物是宿主。HEV的四种基因型在血清学上是交叉反应的，但具有不同的地理分布、物种特异性和毒力。然而，已经有跨物种感染的报告。在印度次大陆，以及最近在巴格达爆发的疫情和在苏丹达尔富尔的难民中，从AVH病例中分离出HEV毒力基因1型毒株。我们报道了HEV在埃及农村流行。尽管整个社区的抗-HEV流行率为70%-85%，但HEV引起的AVH是罕见的，在孕妇中也没有检测到暴发性HEV肝炎。然而，已从开罗两名住院的AVH患者的粪便中分离出HEV基因1型；在埃及住院的AVH患者中，HEV占AVH的10%至30%。我们最近从埃及的家畜中分离出了无毒的3型HEV(与美国发现的毒株相同)。我们的探索性发展奖的目的是准备和获得初步数据，测试可能解释为什么HEV引起的AVH在某些地区可能很少见的假设，例如埃及和美国，尽管存在较高的抗HEV流行率。其中包括：(1)早期接触HEV强毒株可导致无症状或轻度感染，增强免疫力，抑制病毒血症和临床表现。(2)在埃及传播两种HEV基因类型：(A)基因3是地方性的，在动物宿主中通过人畜传播，导致人类无毒感染；以及(B)强毒基因-1 HEV零星导致AVH。细胞免疫(CMI)测试对于检验我们的假设是必要的；HEV特异的CMI反应可能是先前暴露和/或对后续感染/发病的保护的长期可靠的标志。目前还没有关于HEV CMI研究的报道，HEV毒株之间的血清学交叉反应限制了抗-HEV作为先前暴露于HEV强毒株的替代标志物的利用。因此，我们计划开发、标准化和使用可靠的测试来测量针对HEV毒株独特表位的CMI反应。这将提供方法来区分病毒和宿主的免疫反应对埃及HEV传播和发病率的不同作用，结果将适用于其他地区，包括美国。因此，这项应用将提供手段和初步数据来设计一项协议，以了解HEV作为一种似乎已从动物传播到人类的重要新兴传染病之一的致病因素。