Hepatitis E virus genotype 3 and sporadically also genotype 1 circulate in the population of Catalonia, Spain

Autochthonous hepatitis E virus (HEV) strains have been described infecting populations of industrialized countries, previously considered as non-endemic areas. The HEV strains circulating in one of those areas in south-western Europe (Barcelona, Spain) have been studied by analysing amplicons obtained from HEV genomes identified in wastewater, biosolids and sludge. Six sewage and two biosolid HEV positive samples from urban wastewater treatment plants and two positive HEV sludge samples with animal contamination were analysed by cloning and sequencing of 10–12 clones per sample. The results proved the presence of HEV strains belonging to genotype 3 and also sporadically to genotype 1 in urban sewage and biosolids, showing the simultaneous circulation of diverse HEV strains in the human population of the studied area. Only HEV genotype 3 was identified in slaughterhouse sludge samples. The circulation of genotype 1 in industrialized areas may have further health implications since this genotype has been associated with important epidemics in developing areas. Contamination of food and water through their contact with sewage not properly treated and biosolids presenting HEV may represent a significant risk for human populations in relation to HEV even in industrialized areas.     

Recombinant vaccine against hepatitis E: dose response and protection against heterologous challenge

Thirty-two rhesus monkeys were used to evaluate the dose response of a recombinant HEV vaccine, and the efficacy of the vaccine based on the ORF2 protein of the Pakistani strain for pre- and post-exposure vaccination against intravenous challenge with homologous or heterologous virus was examined. Post-exposure vaccination did not protect animals against hepatitis. Although primates vaccinated twice with 50-μg, 10-μg, 2-μg, or 0.4-μg doses of the recombinant 55 kDa ORF-2 protein were infected, they were protected from hepatitis when they were challenged with very high doses of the homologous strain of HEV. Primates vaccinated twice with a 50 μg dose of the recombinant protein were protected from hepatitis after heterologous challenge with the Mexican strain, the strain of HEV most genetically distant from the Pakistani strain.     

Wildlife Reservoir for Hepatitis E Virus,Southwestern France

Pigs are a reservoir for hepatitis E virus (HEV). To determine the relative contribution of game to the risk for human HEV infection in southwestern France, we tested wildlife samples. HEV RNA was in 3.3% of wildlife livers, indicating that in this region, eating game meat is as risky as eating pork.     

烟台市戊型肝炎流行特征及危险因素分析

目的 探讨烟台市戊型肝炎(HE)流行特征及发病危险因素.方法 根据法定传染病报告系统分析烟台市2005-2009年HE疫情资料;采用ELISA检测2028人HE抗体水平,用巢式RT-PCR检测患者粪便,阳性者开展戊肝病毒(HEV)基因测序;采取病例对照研究方法,对HE危险因素进行调查分析.结果 烟台市HE呈散在发病,年均发病率为5.70/10万,春季为流行季节,发病年龄以＞40岁中老年人为主,地区分布呈现沿海岸线分布特点,职业以农民较多;血清流行病学调查显示,人群感染率为25.10%;病毒序列分析表明患者的HEV基因型为4型,健康体检HEVIgM阳性者HEV基因为1型.单因素分析显示,食海产贝类、居住环境、不良生活习惯等均为HE发病的危险因素;多因素分析显示,食海产贝类、外出就餐、饮酒、喝生水仍为发病的独立危险因素.结论 烟台市HE发病率将维持在较高水平,但不会出现大范围暴发或流行,发病人群仍以农民为主.     

Hepatitis E Virus Seroprevalence among Adults, Germany

We assessed hepatitis E virus (HEV) antibody seroprevalence in a sample of the adult population in Germany. Overall HEV IgG prevalence was 16.8% (95% CI 15.6%–17.9%) and increased with age, leveling off at >60 years of age. HEV is endemic in Germany, and the lifetime risk for exposure is high.     

Hepatitis E virus in rabbits, Virginia, USA

We identified hepatitis E virus (HEV) in rabbits in Virginia, USA. HEV RNA was detected in 14 (16%) of 85 serum samples and 13 (15%) of 85 fecal samples. Antibodies against HEV were detected in 31 (36%) of 85 serum samples. Sequence analyses showed that HEV from rabbits is closely related to genotype 3.     

Neurologic Disorders in Immunocompetent Patients with Autochthonous Acute Hepatitis E

Neurologic disorders, mainly Guillain-Barré syndrome and Parsonage–Turner syndrome (PTS), have been described in patients with hepatitis E virus (HEV) infection in industrialized and developing countries. We report a wider range of neurologic disorders in nonimmunocompromised patients with acute HEV infection. Data from 15 French immunocompetent patients with acute HEV infection and neurologic disorders were retrospectively recorded from January 2006 through June 2013. The disorders could be divided into 4 main entities: mononeuritis multiplex, PTS, meningoradiculitis, and acute demyelinating neuropathy. HEV infection was treated with ribavirin in 3 patients (for PTS or mononeuritis multiplex). One patient was treated with corticosteroids (for mononeuropathy multiplex), and 5 others received intravenous immunoglobulin (for PTS, meningoradiculitis, Guillain-Barré syndrome, or Miller Fisher syndrome). We conclude that pleiotropic neurologic disorders are seen in HEV-infected immunocompetent patients. Patients with acute neurologic manifestations and aminotransferase abnormalities should be screened for HEV infection.     

北京铁路部分人群散发性急性非甲非乙非丙型肝炎病原学分析

对北京铁路地区部分人群５８例散发性急性非甲非乙非丙型肝炎进行了ＨＥＶ和ＨＧＶ血清学调查。结果如下,抗－ＨＥＶ阳性２２例（３７．９３％）,抗－ＨＧＶ和ＨＧＶＲＮＡ阳性共１２例（２０．６８％）,其中３例为戊型和庚型肝炎病毒混合感染。戊肝、庚肝病毒感染均以３１～４０岁发病最多,且男多于女;戊肝主要发生在冬春季,多有肠道暴露史;庚型肝炎病毒感染无明显季节性,有肠道外暴露史。ＨＧＶ可单独感染,提示它可能有一定的致病性。     

Hepatitis E Virus Genotype 4, Nanjing,China, 2001–2011

During 2001–2011, hepatitis E virus (HEV) was found in the blood of patients in Nanjing, China. All HEV-positive patients had virus genotype 4; subgenotype 4a was predominant. The effective population of HEV in Nanjing increased in ≈1980 and continued until ≈2003 when it plateaued.     

慢性病毒性乙型肝炎合并戊型肝炎病毒感染的临床及实验指标变化

目的 比较慢性病毒性乙型肝炎和其重叠戊型肝炎病毒(HEV)感染的临床特点，乙型肝炎病毒(HBV)复制指标，以及肝功能方面是否存在差异；了解HEV感染对HBV复制的影响。方法 应用酶联免疫吸附试验和聚合酶链反应分别检测HBV组和HBV HEV组中的乙型肝炎两对半，抗-HBc IgG，抗-HBc IgM，HBV DNA，抗-HEV IgM。结果 重叠HEV感染较单纯HBV感染病情重，肝功能损害明显；100例HBV重叠HEV感染者的HBV DNA和乙型肝炎e抗原(HBeAg)阳性率分别为36％和23％，100例单纯HBV感染者的HBV DNA和HBeAg阳性率分别为86％和60％。结论 重叠HEV感染可加重HBV感染者的病情，并能抑制HBV复制。     

Seroprevalence of Hepatitis A and E Viruses Based on the Third Korea National Health and Nutrition Survey in Korea

Objectives

The purpose of this study was to investigate the seroprevalence of hepatitis A virus (HAV) and hepatitis E virus (HEV) in Korea during 2005.

Methods

Study subjects were selected from across Korea using a stratified multistage probability sampling design, and HAV and HEV seroprevalence was compared on the basis of sex, age, and residency. A total of 497 rural and urban people aged 10–99 years of age (mean ± SD age = 28.87 ± 17.63 years) were selected by two-stage cluster sampling and tested serologically for anti-HAV and anti-HEV IgG using an enzyme-linked immunosorbent assay.

Results

Among this population, the overall seroprevalence of HAV was 63.80% (55.21% aged in their 20s and 95.92% in their 30s, p < 0.01) and that of HEV was 9.40% (5.21% aged in their 20s and 7.14% in their 30s, p < 0.01). Seroprevalence also varied according to area of residence. HEV prevalence in rural areas was higher than that of urban regions based on the anti-HEV antibody, odds ratio 3.22 (95% confidence interval: 1.46–7.10, p < 0.01). There were no significant differences between male and female against anti-HAV/HEV antibodies.

Conclusion

Our study suggested that the seropositive rates of HAV and HEV might be related to age and environmental conditions.     

3种戊型肝炎病毒抗原检测血清抗—HEV IgG的比例研究

目的：用3种抗原检测国家戊型肝炎参比血清和急性戊型肝炎病人血清抗－HEV IgG。方法：人工合成戊型肝炎病毒（HEV）ORF2和ORF3多肽抗原（BMU抗原）检测参比血清的灵敏度（90．0％），特异度（100．0％）和符合率（97．5％）均高于杆状病毒表达的HEV重组蛋白空粒子抗原（JP抗原）（分别为70．0％，93．3％和87．5％）及大肠杆菌表达的重组蛋白抗原（HKU抗原）（分别为70．0％，90．0％和85．0％），检测84例急性戊型肝炎病人血清抗－HEV IgG，用BMU抗在检测抗－HEV IgG的阳性率为1000％（84／84），高于JP抗原（83／84，98．8％）和HKU抗原（71．84，84．5％）。结果：不同HEV抗原检测国家参比血清和急性戊型肝炎病人血清抗－HEV IgG的灵敏度和特异性不同，其差异主要与编码该3种抗原的HEV基因片段不同有关，ORF3抗原在检测急性HE病人中具有重要意义。联合应用ORF2和ORF3抗原可提高抗－HEVIgG检出率，结论：抗－HEV IgG ELISA诊断试剂至少应包括ORF2和ORF3 2种抗原。     

Genotype analysis of hepatitis E virus from sporadic hepatitis E cases in northern China

Hepatitis E is an important public health problem in many countries. However, there is no definite conclusion about the zoonotic reservoir, transmission patterns and risk factors of hepatitis E in the human population. The aim of this study was to analyze the epidemiological and viral genotype characteristics of hepatitis E cases in northern China. Surveillance was conducted in two hospitals in Liaoning and Hebei province from July 2010 to June 2012. Out of a total of 116 diagnosed patients, 88 (75.9%) were male and 28 (24.1%) were female and most (73%) were in the age group 40–70 years. In both hospitals, cases were diagnosed more frequently in March than in other months. HEV RNA was amplified from 41 patients and characterized by nucleotide sequencing and phylogenetic analysis. Most of the isolates (37 strains, 90.3%) were genotype 4, including subgenotypes 4a, 4b, 4d, 4h, 4i and a new subgenotype. One subgenotype 3a strain was isolated from Baoding, Hebei province. Three genotype 1b strains were found from patients in Jinzhou, Liaoning province. Most of the genotype 4 strains and the genotype 3 strains were phylogenetically related to known swine isolates. In conclusion, the finding that HEV infects mostly middle-aged and elderly men and that the incidence spiked in March may reflect the zoonotic transmission characteristics of HEV infection. Pigs, but not rabbits, were the important reservoirs in this area, because genotype 4 HEV was found to be responsible for the majority hepatitis E cases. However, genotype 1 is still present in northern China. Also, the first isolation of genotype 3 HEV in this area indicates that alternative routes of HEV transmission might exist.     

Hepatitis E virus and neurologic disorders

Information about the spectrum of disease caused by hepatitis E virus (HEV) genotype 3 is emerging. During 2004-2009, at 2 hospitals in the United Kingdom and France, among 126 patients with locally acquired acute and chronic HEV genotype 3 infection, neurologic complications developed in 7 (5.5%): inflammatory polyradiculopathy (n = 3), Guillain-Barre syndrome (n = 1), bilateral brachial neuritis (n = 1), encephalitis (n = 1), and ataxia/proximal myopathy (n = 1). Three cases occurred in nonimmunocompromised patients with acute HEV infection, and 4 were in immunocompromised patients with chronic HEV infection. HEV RNA was detected in cerebrospinal fluid of all 4 patients with chronic HEV infection but not in that of 2 patients with acute HEV infection. Neurologic outcomes were complete resolution (n = 3), improvement with residual neurologic deficit (n = 3), and no improvement (n = 1). Neurologic disorders are an emerging extrahepatic manifestation of HEV infection.     

Hepatitis E Virus Variant in Farmed Mink,Denmark

Hepatitis E virus (HEV) is a zoonotic virus for which pigs are the primary animal reservoir. To investigate whether HEV occurs in mink in Denmark, we screened feces and tissues from domestic and wild mink. Our finding of a novel HEV variant supports previous findings of HEV variants in a variety of species.     

Case–Control Study of Risk Factors for Acquired Hepatitis E Virus Infections in Blood Donors,United Kingdom, 2018–2019

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in England. Substantial yearly increases of autochthonous infections were observed during 2003–2016 and again during 2017–2019. Previous studies associated acute HEV cases with consumption of processed pork products, we investigated risk factors for autochthonous HEV infections in the blood donor population in England. Study participants were 117 HEV RNA–positive blood donors and 564 HEV RNA–negative blood donors. No persons with positive results were vegetarian; 97.4% of persons with positive results reported eating pork products. Consuming bacon (OR 3.0, 95% CI 1.7–5.5; p<0.0001), cured pork meats (OR 3.5, 95% CI 2.2–5.4; p<0.0001), and pigs’ liver (OR 2.9, 95% CI 1.0–8.3; p = 0.04) were significantly associated with HEV infection. Our findings confirm previous links to pork products and suggest that appropriate animal husbandry is essential to reduce the risk for HEV infection.     

Virulent Strain of Hepatitis E Virus Genotype 3, Japan

Hepatitis E virus (HEV) genotype 3, which usually causes asymptomatic infection in Japan, induced severe hepatitis in 8 patients. To better understand genetic features of HEV associated with increased virulence, we determined the complete or near-complete nucleotide sequences of HEV from these 8 patients and from 5 swine infected with genotype 3 strain swJ19. Phylogenetic analysis showed that the isolates from the 8 patients and the 5 swine grouped separately from the other genotype 3 isolates to create a unique cluster, designated JIO. The human JIO-related viruses encoded 18 amino acids different from those of the other HEV genotype 3 strains. One substitution common to almost all human HEV strains in the JIO cluster was located in the helicase domain (V239A) and may be associated with increased virulence. A zoonotic origin of JIO-related viruses is suspected because the isolates from the 5 swine also possessed the signature V239A substitution in helicase.     

戊型肝炎病毒嵌合基因疫苗的初步研究

目的　构建含戊型肝炎病毒 (HEV)开放读码框架 (ORF2 )和ORF3嵌合基因的重组质粒 ,并探讨其作为DNA疫苗的可能性。方法　利用PCR方法获得约 0 8kb的戊型肝炎ORF2片段和ORF3的完整片段 ,同时将 2段片段克隆到同一真核表达载体 pcDNA3中 ,构建出含有ORF2和ORF3嵌合基因的质粒 pcHEV2 3;该重组质粒作为DNA疫苗免疫BALB/c小鼠 ,观察其在小鼠体内诱发的体液免疫应答和细胞免疫应答。结果　质粒DpcHEV2 3免疫组小鼠特异性抗体水平明显高于对照组。T细胞增殖反应显著强于空质粒对照组 (P <0 0 5 ) ,与生理盐水对照组比较有显著性差异 (P <0 0 1)。结论　重组质粒 pcHEV2 3可诱发小鼠产生特异性体液和细胞免疫应答 ,可为戊型肝炎DNA疫苗的研制提供依据。     

天津铁路疾病预防控制所辖区内戊型肝炎病毒感染状况的血清分析

目的了解北京铁路局天津铁路疾病预防控制所辖区内人群戊型肝炎病毒IgM(HEV-IgM)抗体的水平和分布状况及丙氨酸转氨酶(ALT)和总胆红素(TBil)2项生化指标的基本情况,为今后预防工作提供科学依据。方法采用血清流行病学调查方法,对辖区内9 297名参加预防性健康检查的观察对象,利用酶联免疫吸附试验(ELISA),对其血清中HEV-IgM抗体进行检测,同时利用生化分析仪检测其ALT和TBil水平,并进行统计分析。结果 9 297名观察者中,HEV-IgM抗体阳性率为0.25%。HEV-IgM抗体阳性者平均ALT及TBil水平无显著增高。对1例HEV-IgM抗体阳性者进行跟踪检测,其HEV-IgM抗体在8个月内未见下降,其ALT及TBil水平也无显著增高。结论该辖区内HEV呈隐性潜伏感染,健康人群内有传播HEV病毒的风险。     

广西地区猪、鼠、狗戊型肝炎病毒感染血清学分析

目的了解广西地区猪、鼠和狗血清中抗．戊型肝炎病毒（HEV）IgG抗体流行情况。方法应用HEV基因1型开放读码框（ORF）2和ORF3多肽包被酶标板，辣根过氧化物酶（HRP）标记的羊抗猪、羊抗鼠和羊抗狗建立的酶联免疫吸附试验（ELISA）法检测猪、鼠和狗血清中抗．HEV IgG。结果总抗．HEV IgG阳性率为31．84％（170／534），其中猪血清抗．HEV IgG阳性率为26．40％（66／250），鼠血清抗．HEV IgG阳性率为43．02％（77／179），狗血清抗．HEV IgG阳性率为25．71％（27／105）。结论猪、鼠和狗血清中存在HEV感染，鼠抗．HEV IgG阳性率最高。