Towards Understanding the Morbidity of HEV Infection

了解 HEV 感染的发病率

• 批准号: 7148968
• 负责人: Mohamed Tarek Shata
• 金额: $ 19.21万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7148968
• 关键词: clinical research; genotype; hepatitis; infection

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.

戊型肝炎（HEV）是一种肠内传播的RNA病毒，在许多欠发达国家（LDC）引起急性病毒性肝炎（AVH），在孕妇中经常报道暴发性肝炎。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抗体（抗HEV）的流行率高达20%。戊型肝炎是一种人畜共患疾病，有数种动物为宿主。四种HEV基因型在血清学上具有交叉反应性，但具有不同的地理分布、种特异性和毒力。然而，也有跨物种感染的报道。在印度次大陆以及最近在巴格达和苏丹达尔富尔难民中暴发的疫情中，从AVH病例中分离出了致命的基因型1型HEV毒株。我们报告了戊型肝炎在埃及农村流行。尽管社区范围内的抗hev患病率为70-85%，但hev引起的AVH很少见，在孕妇中未检出暴发性hev肝炎。然而，已从开罗两名住院AVH患者的粪便中分离出HEV基因型1；在住院的埃及人中，戊型肝炎占AVH的10%至30%。我们最近从埃及的家畜中分离出了无毒的基因3型戊型病毒（与在美国发现的毒株相同）。我们探索性发展奖的目的是准备和获得初步数据，以检验可能解释为什么在一些地区，如埃及和美国，尽管存在很高的抗hev患病率，但hev引起的AVH可能很少见的假设。其中包括：(1)先前早期暴露于HEV无毒性毒株可导致无症状或轻度感染，产生初级免疫，并在随后感染更强毒性毒株时抑制病毒血症和临床表现。(2)两种HEV基因型在埃及传播：(a)基因型3在动物宿主中地方性和人畜共患传播，在人类中引起无毒感染；(b)毒性基因型为1的HEV偶尔引起AVH。细胞介导免疫（CMI）测试是检验我们假设的必要条件；和hev特异性CMI反应可能是先前暴露和/或保护后续感染/发病率的长期可靠标志。目前还没有HEV CMI研究的报道，而且HEV毒株之间的血清学交叉反应性限制了使用抗HEV作为先前暴露于HEV无毒毒株的替代标记物。因此，我们计划开发、标准化和使用可靠的测试来测量CMI对HEV菌株独特表位的反应。这将为梳理该病毒和宿主免疫反应对埃及HEV传播和发病的不同作用提供手段，其结果将适用于包括美国在内的其他地区。因此，该申请将为设计方案提供手段和初步数据，以了解HEV的发病机制所涉及的因素，HEV是一种重要的新兴传染病，似乎已经从动物传播到人。