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Molecular epidemiological analysis of hepatitis E as a zoonosis and investigation toward its prevention

人畜共患病戊型肝炎的分子流行病学分析及预防研究

基本信息

批准号：
16390137
负责人：
OKAMOTO Hiroaki
金额：
$ 9.28万
依托单位：
JICHI MEDICAL SCHOOL
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390137/
关键词：
Hepatitis E Hepatitis E virus Zoonosis ELISA IgA class anti-HEV Infectious source Food-borne transmission Genotype 感染経路劇症肝炎核酸診断法 IgAクラスHEV抗体輸血感染

项目摘要

Our previous studies revealed that domestically acquired hepatitis E as a zoonosis is occurring, much more frequently than previously thought in Japan. In the present study, we aimed to clarify the molecular epidemiology of HEV infection in humans and animals and the molecular basis for pathogenesis of hepatitis E and to present possible measures for preventing HEV infection in humans based on the epidemiological surveys. We developed an enzyme-linked immunosorbent assay (ELISA) system to detect IgM and IgA classes of anti-HEV using purified recombinant ORF2 proteins expressed in the pupae of silkworm as an antigen probe and evaluated the specificity and sensitivity of these two assays. Anti-HEV IgA was found to be useful for serological diagnosis of hepatitis E with increased sensitivity and specificity. The present study revealed that the zoonotic food-borne mode of transmission of HEV from domestic pigs and wild boars to humans may play an important role in the occurrence of domestic HEV infection, and provided evidence of transfusion-transmitted HEV infection in 1979 in Japan. We investigated the clinical and virological characteristics of hepatitis E in 32 patients who contracted the mild (n=23) or severe form (n=9) of domestically acquired hepatitis E in Hokkaido, where hepatitis E is most prevalent in Japan. When compared with the 7 patients with HEV genotype 3, the 25 patients with HEV genotype 4 had a significantly higher peak ALT level (P=0.0338) and a significantly lower level of lowest prothrombin activity (P=0.0340). The severe form of hepatitis E was associated with the presence of an underlying disease. Our study suggested that the HEV genotype and the presence of an underlying disease influence the severity of hepatitis E.

我们以前的研究表明，国内获得性戊型肝炎作为一种人畜共患病正在发生，比以前认为的在日本更频繁。本研究的目的是阐明戊型肝炎病毒（HEV）在人和动物中感染的分子流行病学和发病的分子基础，并在流行病学调查的基础上提出预防人类HEV感染的可能措施。以家蚕蛹中表达的重组ORF 2蛋白为抗原探针，建立了检测IgM和伊加类抗-HEV的酶联免疫吸附试验（ELISA）体系，并对这两种方法的特异性和敏感性进行了评价。抗-伊加可提高戊型肝炎血清学诊断的敏感性和特异性。本研究揭示了人畜共患的食源性戊型肝炎病毒从家猪和野猪传播给人类的模式可能在家庭戊型肝炎病毒感染的发生中起重要作用，并提供了1979年日本输血传播戊型肝炎病毒感染的证据。我们调查了32例戊型肝炎患者的临床和病毒学特征，这些患者在北海道感染了轻度（n=23）或重度（n=9）的国内获得性戊型肝炎，那里的戊型肝炎在日本最流行。25例基因型4型患者ALT峰值显著高于7例基因型3型患者（P=0.0338），最低凝血酶原活动度显著低于7例基因型3型患者（P=0.0340）。重度戊型肝炎与基础疾病的存在相关。我们的研究表明，戊型肝炎病毒基因型和基础疾病的存在影响戊型肝炎的严重程度。