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1
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Animal reservoirs for hepatitis E virus within the Paslahepevirus genus. Vet Microbiol 2023; 278:109618. [PMID: 36640568 DOI: 10.1016/j.vetmic.2022.109618] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 11/23/2022] [Accepted: 12/03/2022] [Indexed: 12/14/2022]
Abstract
Hepatitis E virus (HEV) is responsible for acute hepatitis in humans. It is a single-stranded, positive-sense RNA virus that belongs to the Hepeviridae family. The majority of concerning HEV genotypes belong to the Paslahepevirus genus and are subsequently divided into eight genotypes. HEV genotypes 1 and 2 exclusively infect humans and primates while genotypes 3 and 4 infect both humans and other mammals. Whereas HEV genotypes 5 and 6 are isolated from wild boars and genotypes 7 and 8 were identified from camels in the United Arab Emirates and China, respectively. HEV mainly spreads from humans to humans via the fecal-oral route. However, some genotypes with the capability of zoonotic transmissions, such as 3 and 4 transmit from animals to humans through feces, direct contact, and ingestion of contaminated meat products. As we further continue to uncover novel HEV strains in various animal species, it is becoming clear that HEV has a broad host range. Therefore, understanding the potential animal reservoirs for this virus will allow for better risk management and risk mitigation of infection with HEV. In this review, we mainly focused on animal reservoirs for the members of the species Paslahepevirus balayani and provided a comprehensive list of the host animals identified to date.
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2
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Current Knowledge of Hepatitis E Virus (HEV) Epidemiology in Ruminants. Pathogens 2022; 11:pathogens11101124. [PMID: 36297181 PMCID: PMC9609093 DOI: 10.3390/pathogens11101124] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 09/26/2022] [Accepted: 09/27/2022] [Indexed: 12/20/2022] Open
Abstract
Hepatitis E virus (HEV) infection represents an emerging public health concern worldwide. In industrialized countries, increasing numbers of autochthonous cases of human HEV infection are caused by zoonotic transmission of genotypes 3 and 4, mainly through the consumption of contaminated raw or undercooked meat of infected pigs and wild boars, which are considered the main reservoirs of HEV. However, in the last few years, accumulating evidence seems to indicate that several other animals, including different ruminant species, may harbor HEV. Understanding the impact of HEV infection in ruminants and identifying the risk factors affecting transmission among animals and to humans is critical in order to determine their role in the epidemiological cycle of HEV. In this review, we provide a summary of current knowledge on HEV ecology in ruminants. A growing body of evidence has revealed that these animal species may be potential important hosts of HEV, raising concerns about the possible implications for public health.
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3
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Yamasaki E, Fukumoto S. Prevalence of Shiga toxin-producing Escherichia coli in Yezo sika deer (Cervus nippon yesoensis) in the Tokachi sub-prefecture of Hokkaido, Japan. J Vet Med Sci 2022; 84:770-776. [PMID: 35387920 PMCID: PMC9246679 DOI: 10.1292/jvms.21-0591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
In food hygiene, the surveillance of foodborne pathogens in wild animals is indispensable because we cannot control hygienic status of them. Yezo sika deer (Cervus nippon yesoensis), which are found only on the island of Hokkaido, Japan, are the most common game animal in the country. In this study, we analyzed the incidence of Shiga toxin-producing Escherichia coli (STEC) in Yezo sika deer hunted in the Tokachi sub-prefecture, which is one of the densest zones for the sub-species. Real-time polymerase chain reaction testing detected STEC in 18.3% of fecal samples (59/323) collected from deer hunted between 2016 and 2017, whereas no Shigella and Salmonella markers were detected. No correlation was found between STEC detection from fecal samples and characteristics of carcasses, such as hunting area, age, and fascioliasis. From 59 STEC-positive fecal samples, we isolated 37 STEC strains, including 34 O- and H-genotyped strains, in which 16 different serogroups were detected. Genetic analysis revealed that our isolates included various stx gene types (stx1+/stx2-, stx1+/stx2+, and stx1-/stx2+) and carried eae. This study demonstrated that STEC strains with various features colonized the Yezo sika deer, similar to other subspecies of sika deer. We conclude that continuous surveillance activity is important to monitor the suitability of game animals as a food source and to assess the validity of the food safety management system for game meat production.
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Affiliation(s)
- Eiki Yamasaki
- Division of Food Hygiene, Department of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine
| | - Shinya Fukumoto
- National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine
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4
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Identification of hepatitis E virus in wild sika deer in Japan. Virus Res 2022; 308:198645. [PMID: 34822952 DOI: 10.1016/j.virusres.2021.198645] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 11/17/2021] [Accepted: 11/18/2021] [Indexed: 12/12/2022]
Abstract
Hepatitis E virus (HEV) is a zoonotic agent mainly transmitted through the consumption of uncooked or undercooked meat products derived from infected animals. In Japan, domestic pigs and wild boars are the major animal reservoirs, and whether or not deer are an HEV reservoir remains controversial. We analyzed 395 serum and 199 liver samples from 405 sika deer (Cervus nippon) caught in the wild between 1997 and 2020 in 11 prefectures of Japan for markers of HEV infection. Overall, 17 deer had anti-HEV IgG (4.3%), while 1 (0.2%) had HEV RNA (genotype 3b), indicating the occurrence of ongoing HEV infection in wild deer in Japan. An analysis of the complete HEV genome (deJOI_14) recovered from a viremic deer in Oita Prefecture revealed only 88.8% identity with the first HEV strain in sika deer (JDEER-Hyo03L) in Japan, being closest (96.3%) to the HEV obtained from a hepatitis patient living in the same prefecture. Of note, the deJOI_14 strain was 8.7-9.0% different from the wild boar HEV strains obtained in the same habitat and the same year, suggesting that difference in infected HEV strains between boar and deer may be explained by the limited possibility of close contact with each other, although boars are a known source of HEV infection. Increased numbers of hepatitis E cases after consumption of raw or undercooked meat products of wild deer have been reported in Japan. These results suggest a low but nonnegligible zoonotic risk of HEV infection in wild deer in this country.
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Treagus S, Wright C, Baker-Austin C, Longdon B, Lowther J. The Foodborne Transmission of Hepatitis E Virus to Humans. FOOD AND ENVIRONMENTAL VIROLOGY 2021; 13:127-145. [PMID: 33738770 PMCID: PMC8116281 DOI: 10.1007/s12560-021-09461-5] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 01/16/2021] [Indexed: 05/04/2023]
Abstract
Globally, Hepatitis E virus (HEV) causes over 20 million cases worldwide. HEV is an emerging and endemic pathogen within economically developed countries, chiefly resulting from infections with genotype 3 (G3) HEV. G3 HEV is known to be a zoonotic pathogen, with a broad host range. The primary source of HEV within more economically developed countries is considered to be pigs, and consumption of pork products is a significant risk factor and known transmission route for the virus to humans. However, other foods have also been implicated in the transmission of HEV to humans. This review consolidates the information available regarding transmission of HEV and looks to identify gaps where further research is required to better understand how HEV is transmitted to humans through food.
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Affiliation(s)
- Samantha Treagus
- Biosciences, College of Life and Environmental Sciences, University of Exeter, Penryn Campus, Penryn, Cornwall, UK.
- Centre for Environment Fisheries and Aquaculture Science, Barrack Road, Weymouth, Dorset, DT4 8UB, UK.
| | | | - Craig Baker-Austin
- Centre for Environment Fisheries and Aquaculture Science, Barrack Road, Weymouth, Dorset, DT4 8UB, UK
| | - Ben Longdon
- Biosciences, College of Life and Environmental Sciences, University of Exeter, Penryn Campus, Penryn, Cornwall, UK
| | - James Lowther
- Centre for Environment Fisheries and Aquaculture Science, Barrack Road, Weymouth, Dorset, DT4 8UB, UK
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6
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The Current Host Range of Hepatitis E Viruses. Viruses 2019; 11:v11050452. [PMID: 31108942 PMCID: PMC6563279 DOI: 10.3390/v11050452] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 05/08/2019] [Accepted: 05/14/2019] [Indexed: 01/01/2023] Open
Abstract
Hepatitis E virus (HEV) is an emerging zoonotic pathogen transmitting both human to human via the fecal oral route and from animals to humans through feces, direct contact, and consumption of contaminated meat products. Understanding the host range of the virus is critical for determining where potential threats to human health may be emerging from and where potential reservoirs for viral persistence in the environment may be hiding. Initially thought to be a human specific disease endemic to developing countries, the identification of swine as a primary host for genotypes 3 and 4 HEV in industrialized countries has begun a long journey of discovering novel strains of HEV and their animal hosts. As we continue identifying new strains of HEV in disparate animal species, it is becoming abundantly clear that HEV has a broad host range and many of these HEV strains can cross between differing animal species. These cross-species transmitting strains pose many unique challenges to human health as they are often unrecognized as sources of viral transmission.
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7
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Meister TL, Bruening J, Todt D, Steinmann E. Cell culture systems for the study of hepatitis E virus. Antiviral Res 2019; 163:34-49. [PMID: 30653997 DOI: 10.1016/j.antiviral.2019.01.007] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Revised: 01/08/2019] [Accepted: 01/13/2019] [Indexed: 12/26/2022]
Abstract
Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and is the leading cause of enterically-transmitted viral hepatitis worldwide. Increasing numbers of HEV infections, together with no available specific anti-HEV treatment, contributes to the pathogen's major health burden. A robust cell culture system is required for virologic studies and the development of new antiviral drugs. Unfortunately, like other hepatitis viruses, HEV is difficult to propagate in conventional cell lines. Many different cell culture systems have been tested using various HEV strains, but viral replication usually progresses very slowly, and infection with low virion counts results in non-productive HEV replication. However, recent progress involving generation of cDNA clones and passaging primary patient isolates in distinct cell lines has improved in vitro HEV propagation. This review describes various approaches to cultivate HEV in cellular and animal models and how these systems are used to study HEV infections and evaluate anti-HEV drug candidates.
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Affiliation(s)
- Toni L Meister
- Ruhr-University Bochum, Faculty of Medicine, Department of Molecular and Medical Virology, Bochum, Germany
| | - Janina Bruening
- Ruhr-University Bochum, Faculty of Medicine, Department of Molecular and Medical Virology, Bochum, Germany
| | - Daniel Todt
- Ruhr-University Bochum, Faculty of Medicine, Department of Molecular and Medical Virology, Bochum, Germany.
| | - Eike Steinmann
- Ruhr-University Bochum, Faculty of Medicine, Department of Molecular and Medical Virology, Bochum, Germany.
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Torii S, Matsuno K, Qiu Y, Mori-Kajihara A, Kajihara M, Nakao R, Nao N, Okazaki K, Sashika M, Hiono T, Okamatsu M, Sakoda Y, Ebihara H, Takada A, Sawa H. Infection of newly identified phleboviruses in ticks and wild animals in Hokkaido, Japan indicating tick-borne life cycles. Ticks Tick Borne Dis 2018; 10:328-335. [PMID: 30478009 DOI: 10.1016/j.ttbdis.2018.11.012] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Revised: 10/31/2018] [Accepted: 11/12/2018] [Indexed: 11/25/2022]
Abstract
Recent discoveries of tick-borne pathogens have raised public health concerns on tick-borne infectious diseases and emphasize the need to assess potential risks of unrecognized tick-borne pathogens. First, to determine the existence of tick-borne phleboviruses (TBPVs), genetic surveillance of phleboviruses in ticks was conducted mainly in Hokkaido, the northernmost island in Japan from 2013 to 2015. Genes of two TBPVs, previously reported as Mukawa virus (MKWV) and a newly identified relative of MKWV, Kuriyama virus (KURV), were detected and the viruses were isolated from Ixodes persulcatus collected in Hokkaido, but not in I. persulcatus collected from other areas of Japan. These viruses were phylogenetically and antigenically similar to each other. Next, to investigate the infection of MKWV in mammals, serum samples from wildlife captured in Hokkaido from 2007 to 2011 were used for serological screening. Neutralizing antibodies against MKWV were detected in both Yezo-deer (Cervus nippon yesoensis) (2/50) and raccoons (Procyon lotor) (16/64). However, no infectious MKWV was recovered from laboratory mice in experimental infections, though viral RNAs were detected in their tissues. Thus, MKWV and KURV may maintain tick-mammalian life cycles in Hokkaido, suggesting their potential as causative agents of tick-borne diseases in mammals.
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Affiliation(s)
- Shiho Torii
- Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan; Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan
| | - Keita Matsuno
- Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan; Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan.
| | - Yongjin Qiu
- Division of Collaboration and Education, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan
| | - Akina Mori-Kajihara
- Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan
| | - Masahiro Kajihara
- Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan
| | - Ryo Nakao
- Laboratory of Parasitology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan
| | - Naganori Nao
- Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan
| | - Katsunori Okazaki
- Laboratory of Microbiology and Immunology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Tobetsu, Japan
| | - Mariko Sashika
- Laboratory of Wildlife Biology and Medicine, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan
| | - Takahiro Hiono
- Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan
| | - Masatoshi Okamatsu
- Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan
| | - Yoshihiro Sakoda
- Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan; Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan
| | - Hideki Ebihara
- Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA
| | - Ayato Takada
- Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan; Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan; Department of Disease Control, School of Veterinary Medicine, University of Zambia, Lusaka, Zambia
| | - Hirofumi Sawa
- Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan; Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan; Department of Disease Control, School of Veterinary Medicine, University of Zambia, Lusaka, Zambia; Global Virus Network, Baltimore, USA
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9
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King NJ, Hewitt J, Perchec-Merien AM. Hiding in Plain Sight? It's Time to Investigate Other Possible Transmission Routes for Hepatitis E Virus (HEV) in Developed Countries. FOOD AND ENVIRONMENTAL VIROLOGY 2018; 10:225-252. [PMID: 29623595 DOI: 10.1007/s12560-018-9342-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/17/2017] [Accepted: 03/29/2018] [Indexed: 06/08/2023]
Abstract
Historically in developed countries, reported hepatitis E cases were typically travellers returning from countries where hepatitis E virus (HEV) is endemic, but now there are increasing numbers of non-travel-related ("autochthonous") cases being reported. Data for HEV in New Zealand remain limited and the transmission routes unproven. We critically reviewed the scientific evidence supporting HEV transmission routes in other developed countries to inform how people in New Zealand may be exposed to this virus. A substantial body of indirect evidence shows domesticated pigs are a source of zoonotic human HEV infection, but there is an information bias towards this established reservoir. The increasing range of animals in which HEV has been detected makes it important to consider other possible animal reservoirs of HEV genotypes that can or could infect humans. Foodborne transmission of HEV from swine and deer products has been proven, and a large body of indirect evidence (e.g. food surveys, epidemiological studies and phylogenetic analyses) support pig products as vehicles of HEV infection. Scarce data from other foods suggest we are neglecting other potential sources of foodborne HEV infection. Moreover, other transmission routes are scarcely investigated in developed countries; the role of infected food handlers, person-to-person transmission via the faecal-oral route, and waterborne transmission from recreational contact or drinking untreated or inadequately treated water. People have become symptomatic after receiving transfusions of HEV-contaminated blood, but it is unclear how important this is in the overall hepatitis E disease burden. There is need for broader research efforts to support establishing risk-based controls.
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Affiliation(s)
- Nicola J King
- Institute of Environmental Science and Research, 34 Kenepuru Drive, Kenepuru, Porirua, 5022, New Zealand
| | - Joanne Hewitt
- Institute of Environmental Science and Research, 34 Kenepuru Drive, Kenepuru, Porirua, 5022, New Zealand.
| | - Anne-Marie Perchec-Merien
- New Zealand Ministry for Primary Industries, Pastoral House, 25 The Terrace, Wellington, New Zealand
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10
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Navas-Suárez PE, Díaz-Delgado J, Matushima ER, Fávero CM, Sánchez Sarmiento AM, Sacristán C, Ewbank AC, Marques Joppert A, Barbanti Duarte JM, dos Santos-Cirqueira C, Cogliati B, Mesquita L, Maiorka PC, Catão-Dias JL. A retrospective pathology study of two Neotropical deer species (1995-2015), Brazil: Marsh deer (Blastocerus dichotomus) and brown brocket deer (Mazama gouazoubira). PLoS One 2018; 13:e0198670. [PMID: 29879222 PMCID: PMC5991706 DOI: 10.1371/journal.pone.0198670] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Accepted: 05/23/2018] [Indexed: 11/18/2022] Open
Abstract
This retrospective study describes the biological and epidemiological aspects, gross and microscopical findings, and most likely causes of death (CD) in two species of Neotropical deer in Brazil. The animals were collected between 1995 and 2015 and represented 75 marsh deer (MD) and 136 brown brocket deer (BBD). Summarized, pneumonia was diagnosed microscopically in 48 MD and 52 BBD; 76 deer suffered trauma, involving dog attack (14 BBD) and vehicle-collision (14 BBD). Pulmonary edema (50 MD; 55 BBD) and congestion (57 MD; 78 BBD) were the most common findings for both species. Additionally, we diagnosed ruminal and myocardial mycosis in MD and BBD, respectively; ovarian dysgerminoma and pancreatic trematodiasis in BBD; and lesions suggestive of malignant catarrhal fever and orbiviral hemorrhagic disease in both species. The main CD in MD was: respiratory (41/75), alimentary, nutritional, trauma and euthanasia (3/75 each). Correspondingly, in BBD were: trauma (34/131), respiratory (30/131) and euthanasia (9/131). Respiratory disease was often defined by pulmonary edema and pneumonia. We provide evidence that respiratory disease, mainly pneumonia, is a critical pathological process in these Neotropical deer species. Although no etiological agents were identified, there is evidence of bacterial and viral involvement. Our results show trauma, mainly anthropogenic, as a common ailment in BBD. We propose to prioritize respiratory disease in future research focused on South American deer health aspects. We believe anthropogenic trauma may be a primary threat for populations of BBD.
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Affiliation(s)
- Pedro Enrique Navas-Suárez
- Laboratory of Wildlife Comparative Pathology - LAPCOM, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, Brazil
| | - Josué Díaz-Delgado
- Laboratory of Wildlife Comparative Pathology - LAPCOM, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, Brazil
| | - Eliana Reiko Matushima
- Laboratory of Wildlife Comparative Pathology - LAPCOM, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, Brazil
| | - Cintia Maria Fávero
- Laboratory of Wildlife Comparative Pathology - LAPCOM, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, Brazil
| | - Angélica Maria Sánchez Sarmiento
- Laboratory of Wildlife Comparative Pathology - LAPCOM, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, Brazil
| | - Carlos Sacristán
- Laboratory of Wildlife Comparative Pathology - LAPCOM, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, Brazil
| | - Ana Carolina Ewbank
- Laboratory of Wildlife Comparative Pathology - LAPCOM, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, Brazil
| | - Adriana Marques Joppert
- Divisão Técnica de Medicina Veterinária e Manejo da Fauna Silvestre (DEPAVE-3), São Paulo, Brazil
| | - Jose Mauricio Barbanti Duarte
- Deer Research and Conservation Center (NUPECCE), Department of Animal Science, São Paulo State University, Jaboticabal, São Paulo, Brazil
| | | | - Bruno Cogliati
- Laboratory of Morphological and Molecular Pathology, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, Brazil
| | - Leonardo Mesquita
- Laboratory of Animal Models, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, Brazil
| | - Paulo César Maiorka
- Laboratory of Animal Models, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, Brazil
| | - José Luiz Catão-Dias
- Laboratory of Wildlife Comparative Pathology - LAPCOM, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, Brazil
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11
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Spahr C, Knauf-Witzens T, Vahlenkamp T, Ulrich RG, Johne R. Hepatitis E virus and related viruses in wild, domestic and zoo animals: A review. Zoonoses Public Health 2017; 65:11-29. [PMID: 28944602 DOI: 10.1111/zph.12405] [Citation(s) in RCA: 84] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Indexed: 01/15/2023]
Abstract
Hepatitis E is a human disease mainly characterized by acute liver illness, which is caused by infection with the hepatitis E virus (HEV). Large hepatitis E outbreaks have been described in developing countries; however, the disease is also increasingly recognized in industrialized countries. Mortality rates up to 25% have been described for pregnant women during outbreaks in developing countries. In addition, chronic disease courses could be observed in immunocompromised transplant patients. Whereas the HEV genotypes 1 and 2 are mainly confined to humans, genotypes 3 and 4 are also found in animals and can be zoonotically transmitted to humans. Domestic pig and wild boar represent the most important reservoirs for these genotypes. A distinct subtype of genotype 3 has been repeatedly detected in rabbits and a few human patients. Recently, HEV genotype 7 has been identified in dromedary camels and in an immunocompromised transplant patient. The reservoir animals get infected with HEV without showing any clinical symptoms. Besides these well-known animal reservoirs, HEV-specific antibodies and/or the genome of HEV or HEV-related viruses have also been detected in many other animal species, including primates, other mammals and birds. In particular, genotypes 3 and 4 infections are documented in many domestic, wildlife and zoo animal species. In most cases, the presence of HEV in these animals can be explained by spillover infections, but a risk of virus transmission through contact with humans cannot be excluded. This review gives a general overview on the transmission pathways of HEV to humans. It particularly focuses on reported serological and molecular evidence of infections in wild, domestic and zoo animals with HEV or HEV-related viruses. The role of these animals for transmission of HEV to humans and other animals is discussed.
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Affiliation(s)
- C Spahr
- Wilhelma Zoological-Botanical Gardens, Stuttgart, Germany.,Faculty of Veterinary Medicine, Institute of Virology, University of Leipzig, Leipzig, Germany
| | | | - T Vahlenkamp
- Faculty of Veterinary Medicine, Institute of Virology, University of Leipzig, Leipzig, Germany
| | - R G Ulrich
- Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Novel and Emerging Infectious Diseases, Greifswald-Insel Riems, Germany.,German Center for Infection Research (DZIF), partner site Hamburg-Luebeck-Borstel-Insel Riems, Braunschweig, Germany
| | - R Johne
- Department Biological Safety, German Federal Institute for Risk Assessment, Berlin, Germany
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12
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Al-Sadeq DW, Majdalawieh AF, Nasrallah GK. Seroprevalence and incidence of hepatitis E virus among blood donors: A review. Rev Med Virol 2017; 27:e1937. [PMID: 28876496 DOI: 10.1002/rmv.1937] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 07/16/2017] [Accepted: 07/18/2017] [Indexed: 12/19/2022]
Abstract
Hepatitis E virus (HEV) is an RNA virus with 4 main genotypes. HEV-1 and HEV-2 infect solely humans, while HEV-3 and HEV-4 infect humans and various animals such as pigs, deer, and rabbits. HEV-5 and HEV-6 infect mainly wild boar. Recently, new genotypes, known as HEV-7 and HEV-8, were found to infect camels and humans. HEV is globally distributed into different epidemiological patterns based on socioeconomic factors and ecology. Although HEV is mainly transmitted through the fecal-oral route, it was also recognized as a transfusion-transmitted virus. Transmission through blood donation was documented worldwide with rising annual observations, accounting for more than 2.5% of all transmissions. HEV infection is usually asymptomatic or subclinical in immunocompetent individuals, so it remains questionable whether there is an urgent need to screen for HEV prior to blood transfusion. Moreover, recent studies conducted in the Middle East and North Africa (MENA) region indicate that HEV is highly endemic. Here, we provide a review on HEV epidemiology, transmission, and laboratory diagnosis, giving special emphasis to the newly discovered genotypes, HEV-7 and HEV-8. Furthermore, we underscore the findings of recent HEV seroprevalence and viremia studies among blood donors worldwide. We also shed light on similar studies performed among blood donors in the MENA region.
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Affiliation(s)
- Duaa W Al-Sadeq
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Amin F Majdalawieh
- Department of Biology, Chemistry, and Environmental Sciences, College of Arts and Sciences, American University of Sharjah, Sharjah, United Arab Emirates
| | - Gheyath K Nasrallah
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
- Biomedical Research Center, Qatar University, Doha, Qatar
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13
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Khuroo MS, Khuroo MS, Khuroo NS. Hepatitis E: Discovery, global impact, control and cure. World J Gastroenterol 2016; 22:7030-7045. [PMID: 27610014 PMCID: PMC4988308 DOI: 10.3748/wjg.v22.i31.7030] [Citation(s) in RCA: 112] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2016] [Revised: 06/10/2016] [Accepted: 07/06/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E was identified as an epidemic of non-A, non-B hepatitis from Kashmir, India in 1978. Hepatitis E virus (HEV), the etiological agent is the sole member of family Hepeviridae. The virus has marked heterogeneity and infects many animals like bats, camel, chicken, deer, boar, mongoose, pigs, rats, rabbit and cutthroat trout. Hepatitis E is a disease with a major global impact and has two distinct epidemiological patterns. Hepatitis E is an imperative health issue in developing nations, transmitted through sullied water and happens most every now in young adults. The disease is particularly severe during pregnancy and in people with underlying liver cirrhosis. Autochthonous hepatitis E is increasingly recognized in developed countries. The virus infects domestic pigs, wild boar and Sika deer in these countries. HEV infections in humans occur by eating the undercooked game flesh, raw liver from supermarkets and Figatelli sausages. Blood transfusion-associated HEV infections occur in many countries and screening of donors for HEV RNA is under consideration. Hepatitis E causes a number of extrahepatic diseases, including a wide spectrum of neurological syndromes. HEV genotype 3 causes prolonged viremia, chronic hepatitis, liver fibrosis and cirrhosis in organ transplant patients. The virus is amenable to ribavirin monotherapy and most patients clear the virus in a few weeks. Hepatitis E vaccine -239, marketed in China, has shown high efficacy with sustained protection for over four years.
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Weger S, Elkin B, Lindsay R, Bollinger T, Crichton V, Andonov A. Hepatitis E Virus Seroprevalence in Free-Ranging Deer in Canada. Transbound Emerg Dis 2016; 64:1008-1011. [PMID: 26752436 DOI: 10.1111/tbed.12462] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Indexed: 12/15/2022]
Abstract
Hepatitis E virus infection (HEV) is an important public health concern not only in traditional endemic areas, but also in some industrialized countries where both domesticated and wild animals have been recognized as potential zoonotic reservoirs implicated in HEV transmission. While the prevalence of infection in the deer population in Europe and Asia has been thoroughly investigated, it remains largely undetermined in North America. We assessed the presence of HEV in three different species of free-range deer in Canada. The seroprevalence of HEV among deer in Canada was 8.8% in white-tailed deer, 4.5% in mule deer and 3.2% in caribou. Hepatitis E virus RNA was not detected. Overall, data indicate that HEV infection occurs in deer in Canada. The absence of viraemia and the low seroprevalence especially in barren-ground caribou which is an important part of the diet in many northern communities suggests that the risk of zoonotic transmission may be less pronounced compared to other countries.
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Affiliation(s)
- S Weger
- University of Manitoba, Winnipeg, MB, Canada
| | - B Elkin
- Wildlife Division, Wildlife Veterinarian, Government of NorthWest Territories Environment & Natural Resources, Yellowknife, NT, Canada
| | - R Lindsay
- Public Health Agency of Canada, Winnipeg, MB, Canada
| | - T Bollinger
- Department of Veterinary Pathology, Canadian Wildlife Health Cooperative (CWHC), Saskatoon, SK, Canada
| | - V Crichton
- Wildlife and Ecosystem Protection Branch, Manitoba Conservation, Winnipeg, MB, Canada
| | - A Andonov
- Public Health Agency of Canada, Winnipeg, MB, Canada
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Liu L, Wang L, Xia J, Zhang Y, Zeng H, Liu P, Zou Q, Wang L, Zhuang H. Mix-breeding with HEV-infected swine induced inapparent HEV infection in SPF rabbits. J Med Virol 2015; 88:681-5. [PMID: 26334930 DOI: 10.1002/jmv.24374] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/01/2015] [Indexed: 01/25/2023]
Abstract
Studies have shown that swine HEV (sHEV) and rabbit HEV (rHEV) can experimentally infect rabbits and swine, respectively. However, no published data have documented isolating sHEV strains from rabbits in natural environment so far. To clarify the possibility of natural cross-species transmission of sHEV to rabbits, the pigs with HEV infection were farmed along with SPF rabbits in the same enclosed space. Five of 10 rabbits had seroconversion for anti-HEV antibody from the third week after mix-breeding. However, HEV RNA remained undetectable in feces, serum, liver and bile of the ten rabbits; and no obvious elevation of ALT was observed. The results possibly suggested that sHEV might lead to an inapparent infection of SPF rabbits by fecal-oral route.
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Affiliation(s)
- Lin Liu
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Lin Wang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Junke Xia
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Yulin Zhang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Hang Zeng
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Peng Liu
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Qinghua Zou
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Ling Wang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Hui Zhuang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
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16
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17
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First report of hepatitis E virus infection in sika deer in China. BIOMED RESEARCH INTERNATIONAL 2015; 2015:502846. [PMID: 25949999 PMCID: PMC4407398 DOI: 10.1155/2015/502846] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Revised: 03/25/2015] [Accepted: 03/25/2015] [Indexed: 01/31/2023]
Abstract
Hepatitis E virus (HEV), a single stranded RNA, nonenveloped virus, belongs to the genus Hepevirus, in the family of Hepeviridae. In this study, 46 (5.43%) out of the 847 serum samples from sika deer (Cervus nippon) were detected as seropositive with hepatitis E virus (HEV) by enzyme linked immunosorbent assay (ELISA). These samples were collected from Inner Mongolia and Jilin and Heilongjiang provinces in China, between October 2012 and October 2013. Seroprevalence of HEV infection in male and female deer was 4.82% and 6.52%, respectively. HEV seroprevalence in sika deer from different geographical locations varied from 3.13% to 6.73%. There was no significant difference in HEV seroprevalence between sika deer collected in autumn (5.65%) and winter (4.85%). This is the first report of HEV seroprevalence in sika deer in China, which will provide foundation information for estimating the effectiveness of future measures to control HEV infection in sika deer in China and assessing the potential risk of humans infected with HEV after consumption of undercooked or raw meat from infected sika deer.
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Behrendt P, Steinmann E, Manns MP, Wedemeyer H. The impact of hepatitis E in the liver transplant setting. J Hepatol 2014; 61:1418-29. [PMID: 25195557 DOI: 10.1016/j.jhep.2014.08.047] [Citation(s) in RCA: 98] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2014] [Revised: 08/25/2014] [Accepted: 08/29/2014] [Indexed: 12/27/2022]
Abstract
Hepatitis E virus (HEV) infection has been identified as a cause of graft hepatitis in liver transplant recipients. The true frequency and clinical importance of HEV infections after liver transplantations is a matter of debate. It is proposed that consumption of HEV-contaminated undercooked meat is a main source for HEV infections in developed countries--which might also account for some hepatitis E cases after organ transplantation. However, HEV is also transmitted by transfusion of blood products, likely representing a previously underestimated risk particularly for patients in the transplant setting. HEV infection can take chronic courses in immunocompromised individuals, associated in some cases with rapid progression to cirrhosis within 1-2 years of infection. Diagnosis in transplanted patients is based on HEV RNA testing as antibody assays are not sensitive enough. Selection of immunosuppressive drugs is important as different compounds may influence viral replication and the course of liver disease. Ribavirin has antiviral activity against HEV and should be administered for at least three months in chronically infected individuals; however, treatment failure may occur. HEV infections have also been linked to a variety of extrahepatic manifestations both during and after resolution of infection. In this review we summarize the emerging data on hepatitis E with a particular focus on the importance of HEV infections for liver transplant recipients.
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Affiliation(s)
- Patrick Behrendt
- Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; German Center for Infection Research, Hannover, Germany; Twincore, Centre for Experimental and Clinical Infection Research, A Joint Venture Between Medical School Hannover and Helmholtz Centre for Infection Research, Hannover, Germany
| | - Eike Steinmann
- Twincore, Centre for Experimental and Clinical Infection Research, A Joint Venture Between Medical School Hannover and Helmholtz Centre for Infection Research, Hannover, Germany
| | - Michael P Manns
- Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; German Center for Infection Research, Hannover, Germany
| | - Heiner Wedemeyer
- Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; German Center for Infection Research, Hannover, Germany.
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Han J, Zeng H, Wang L, Liu P, Liu L, Xia J, Zhang Y, Wang L, Zhuang H. Hepatitis E virus infection in farmed rabbits and swine in the Eastern Chinese city Lianyungang: Showing no potential interspecies transmission. J Med Virol 2014; 86:1898-904. [DOI: 10.1002/jmv.24003] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/30/2014] [Indexed: 12/16/2022]
Affiliation(s)
- Jian Han
- Department of Microbiology; School of Basic Medical Sciences; Peking University Health Science Center; Beijing China
| | - Hang Zeng
- Department of Microbiology; School of Basic Medical Sciences; Peking University Health Science Center; Beijing China
| | - Ling Wang
- Department of Microbiology; School of Basic Medical Sciences; Peking University Health Science Center; Beijing China
| | - Peng Liu
- Department of Microbiology; School of Basic Medical Sciences; Peking University Health Science Center; Beijing China
| | - Lin Liu
- Department of Microbiology; School of Basic Medical Sciences; Peking University Health Science Center; Beijing China
| | - Junke Xia
- Department of Microbiology; School of Basic Medical Sciences; Peking University Health Science Center; Beijing China
| | - Yulin Zhang
- Department of Microbiology; School of Basic Medical Sciences; Peking University Health Science Center; Beijing China
| | - Lin Wang
- Department of Microbiology; School of Basic Medical Sciences; Peking University Health Science Center; Beijing China
| | - Hui Zhuang
- Department of Microbiology; School of Basic Medical Sciences; Peking University Health Science Center; Beijing China
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SPF rabbits infected with rabbit hepatitis E virus isolate experimentally showing the chronicity of hepatitis. PLoS One 2014; 9:e99861. [PMID: 24937350 PMCID: PMC4061063 DOI: 10.1371/journal.pone.0099861] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2014] [Accepted: 05/13/2014] [Indexed: 12/19/2022] Open
Abstract
This study focused on investigating the pathogenesis seen in specific-pathogen-free (SPF) rabbits following infection with a homologous rabbit HEV isolate (CHN-BJ-rb14) and comparing it to that seen following infection with a heterologous swine genotype 4 HEV isolate (CHN-XJ-SW13). Three of the four animals inoculated with the homologous rabbit HEV became infected, exhibiting an intermittent viremia, obvious fluctuations of liver function biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and persistent fecal virus shedding throughout the nine month study. In addition, liver histopathology showed both chronic inflammation and some degree of fibrosis. Both positive and negative-stranded HEV RNA and HEV antigen expression were detected in liver, brain, stomach, duodenum and kidney from the necropsied rabbits. Inflammation of extrahepatic tissue (duodenum and kidney) was also observed. Three of the four rabbits inoculated with the heterologous genotype 4 swine HEV also became infected, showing similar levels of anti-HEV antibody to that generated following infection with the homologous virus isolate. The duration of both viremia and fecal shedding of virus was however shorter following infection with the heterologous virus and there was no significant elevation of liver function biomarkers. These results suggest that rabbit HEV infection may cause more severe hepatitis and prolong the course of the disease, with a possible chronic trend of hepatitis in SPF rabbits.
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Abstract
A novel virus was detected in a sample collected from a Swedish moose (Alces alces). The virus was suggested as a member of the Hepeviridae family, although it was found to be highly divergent from the known four genotypes (gt1–4) of hepatitis E virus (HEV). Moose are regularly hunted for consumption in the whole of Scandinavia. Thus, the finding of this virus may be important from several aspects: (a) as a new diverged HEV in a new animal species, and (b) potential unexplored HEV transmission pathways for human infections. Considering these aspects, we have started the molecular characterization of this virus. A 5.1 kb amplicon was sequenced, and corresponded to the partial ORF1, followed by complete ORF2, ORF3 and poly(A) sequence. In comparison with existing HEVs, the moose HEV genome showed a general nucleotide sequence similarity of 37–63 % and an extensively divergent putative ORF3 sequence. The junction region between the ORFs was also highly divergent; however, two putative secondary stem–loop structures were retained when compared to gt1–4, but with altered structural appearance. In the phylogenetic analysis, the moose HEV deviated and formed its own branch between the gt1–4 and other divergent animal HEVs. The characterization of this highly divergent genome provides important information regarding the diversity of HEV infecting various mammalian species. However, further studies are needed to investigate its prevalence in the moose populations and possibly in other host species, including the risk for human infection.
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Affiliation(s)
- Jay Lin
- Department of Virology, Immunobiology and Parasitology (VIP), National Veterinary Institute (SVA), Uppsala, Sweden
| | - Heléne Norder
- Department of Infectious Diseases/Section of Clinical Virology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
| | - Henrik Uhlhorn
- Department of Pathology and Wildlife Diseases, National Veterinary Institute (SVA), Uppsala, Sweden
| | - Sándor Belák
- Department of Virology, Immunobiology and Parasitology (VIP), National Veterinary Institute (SVA), Uppsala, Sweden
| | - Frederik Widén
- Department of Virology, Immunobiology and Parasitology (VIP), National Veterinary Institute (SVA), Uppsala, Sweden
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Ijaz S, Said B, Boxall E, Smit E, Morgan D, Tedder RS. Indigenous hepatitis E in England and wales from 2003 to 2012: evidence of an emerging novel phylotype of viruses. J Infect Dis 2013; 209:1212-8. [PMID: 24273173 DOI: 10.1093/infdis/jit652] [Citation(s) in RCA: 95] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Enhanced surveillance and molecular characterisation studies of hepatitis E virus (HEV) in England and Wales have been undertaken since 2003. The dynamics of hepatitis E have changed recently with an increase in the number of indigenous cases and an observed viral shift. METHODS HEV antibody and RNA data were analysed to ascertain the annual number of acute infections, the HEV genotype disposition and viral phylogeny. These data were investigated in the context of collected travel history and demographic data. RESULTS In total, 2713 acute hepatitis E cases were diagnosed, of which 1376 were indigenous infections. Travel associated cases remained steady and mainly associated with Genotype 1 infections. In contrast, major fluctuations were noted in indigenously-acquired cases with a dramatic year on year increase during 2010-2012. Molecular characterisation demonstrated indigenous infections to cluster into two distinct phylogenetic groups with the emergence of a novel group of Genotype 3 viruses coinciding with the recent increase in cases. CONCLUSIONS HEV infection rates are dynamic in England and Wales, influenced by changing trends in indigenously-acquired cases. The recent increase in indigenous cases and the emergence of indigenous viruses not commonly circulating prior to 2010 suggest that the risk of acquiring HEV has changed.
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Affiliation(s)
- Samreen Ijaz
- Blood Borne Virus Unit, MS-Colindale, Public Health England, London NW9 5EQ, United Kingdom
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Hepatitis E virus: foodborne, waterborne and zoonotic transmission. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2013; 10:4507-33. [PMID: 24071919 PMCID: PMC3823334 DOI: 10.3390/ijerph10104507] [Citation(s) in RCA: 168] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/02/2013] [Revised: 08/20/2013] [Accepted: 09/03/2013] [Indexed: 02/07/2023]
Abstract
Hepatitis E virus (HEV) is responsible for epidemics and endemics of acute hepatitis in humans, mainly through waterborne, foodborne, and zoonotic transmission routes. HEV is a single-stranded, positive-sense RNA virus classified in the family Hepeviridae and encompasses four known Genotypes (1–4), at least two new putative genotypes of mammalian HEV, and one floating genus of avian HEV. Genotypes 1 and 2 HEVs only affect humans, while Genotypes 3 and 4 are zoonotic and responsible for sporadic and autochthonous infections in both humans and several other animal species worldwide. HEV has an ever-expanding host range and has been identified in numerous animal species. Swine serve as a reservoir species for HEV transmission to humans; however, it is likely that other animal species may also act as reservoirs. HEV poses an important public health concern with cases of the disease definitively linked to handling of infected pigs, consumption of raw and undercooked animal meats, and animal manure contamination of drinking or irrigation water. Infectious HEV has been identified in numerous sources of concern including animal feces, sewage water, inadequately-treated water, contaminated shellfish and produce, as well as animal meats. Many aspects of HEV pathogenesis, replication, and immunological responses remain unknown, as HEV is an extremely understudied but important human pathogen. This article reviews the current understanding of HEV transmission routes with emphasis on food and environmental sources and the prevalence of HEV in animal species with zoonotic potential in humans.
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Rabbit and human hepatitis E virus strains belong to a single serotype. Virus Res 2013; 176:101-6. [PMID: 23742853 DOI: 10.1016/j.virusres.2013.05.013] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2013] [Revised: 05/25/2013] [Accepted: 05/28/2013] [Indexed: 01/14/2023]
Abstract
Hepatitis E virus (HEV) is a zoonotic pathogen and all four established genotypes of HEV belong to a single serotype. The recently identified rabbit HEV is antigenically and genetically related to human HEV. It is unclear whether rabbit HEV belongs to the same serotype as human HEV. The purpose of this study was to determine the serotypic relationship between rabbit and human HEVs. HEV ORF2 recombinant capsid protein p166 (amino acids 452-617) of four known HEV genotypes and rabbit HEV were used to induce immune serum, which were evaluated for their ability to neutralize human HEV genotype 1, 4, and rabbit HEV strains by an in vitro PCR-based HEV neutralization assay. Immune sera of five kinds of p166 proteins were all found to neutralize or cross-neutralize the three different HEV strains, suggesting a common neutralization epitope(s) existing between human and rabbit HEV. Rabbit models of a second-passage rabbit HEV strain, JS204-2, and a genotype 4 human HEV strain, NJ703, were established as evidenced by fecal virus shedding, viremia and anti-HEV IgG seroconversion. Six rabbits, recovered from JS204 infection, were challenged with NJ703, and another six recovered from NJ703 infection were challenged with JS204-2. After challenge, viremia was not detected, shorter fecal virus shedding durations and obvious early stage declines in anti-HEV IgG values were observed. The results from this study indicate that rabbit HEV belongs to the same serotype as human HEV.
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Wedemeyer H, Pischke S, Manns MP. Pathogenesis and treatment of hepatitis e virus infection. Gastroenterology 2012; 142:1388-1397.e1. [PMID: 22537448 DOI: 10.1053/j.gastro.2012.02.014] [Citation(s) in RCA: 208] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2012] [Revised: 02/14/2012] [Accepted: 02/14/2012] [Indexed: 12/14/2022]
Abstract
Hepatitis E has been considered to be a travel-associated, acute, self-limiting liver disease that causes fulminant hepatic failure in specific high-risk groups only. However, hepatitis E virus (HEV) infection can also be acquired in industrialized countries-HEV genotype 3 infection is a zoonosis, with pigs and rodents serving as animal reservoirs. In recent years, cases of chronic HEV infection that were associated with progressive liver disease have been described in several cohorts of immunocompromised individuals, including recipients of organ transplants. The topic of hepatitis E is therefore re-emerging and has raised the following important questions: what is the risk for HEV infection in Western countries (eg, from eating uncooked meat)? How frequently does chronic hepatitis E develop among human immunodeficiency virus-infected patients and recipients of organ transplants? What are the treatment options? What is the current status of vaccine development? What do we know about the pathogenesis of HEV infection, and why does it have a more severe course in pregnant women? This review summarizes the current knowledge on the pathogenesis and treatment of HEV infection.
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Affiliation(s)
- Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
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26
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Meng XJ. From barnyard to food table: the omnipresence of hepatitis E virus and risk for zoonotic infection and food safety. Virus Res 2011; 161:23-30. [PMID: 21316404 DOI: 10.1016/j.virusres.2011.01.016] [Citation(s) in RCA: 216] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2010] [Revised: 01/27/2011] [Accepted: 01/30/2011] [Indexed: 12/12/2022]
Abstract
Hepatitis E virus (HEV) is an important but extremely understudied pathogen. The mechanisms of HEV replication and pathogenesis are poorly understood, and a vaccine against HEV is not yet available. HEV is classified in the family Hepeviridae consisting of at least four recognized major genotypes. Genotypes 1 and 2 HEV are restricted to humans and associated with epidemics in developing countries, whereas genotypes 3 and 4 HEV are zoonotic and responsible for sporadic cases worldwide. The identification and characterization of a number of animal strains of HEV from pigs, chickens, rabbits, rats, mongoose, deer, and possibly cattle and sheep have significantly broadened the host range and diversity of HEV. The demonstrated ability of cross-species infection by some animal strains of HEV raises public health concerns for zoonotic HEV infection. Pigs are a recognized reservoir for HEV, and pig handlers are at increased risk of zoonotic HEV infection. Sporadic cases of hepatitis E have been definitively linked to the consumption of raw or undercooked animal meats such as pig livers, sausages, and deer meats. In addition, since large amounts of viruses excreted in feces, animal manure land application and runoffs can contaminate irrigation and drinking water with concomitant contamination of produce or shellfish. HEV RNA of swine origin has been detected in swine manure, sewage water and oysters, and consumption of contaminated shellfish has also been implicated in sporadic cases of hepatitis E. Therefore, the animal strains of HEV pose not only a zoonotic risk but also food and environmental safety concerns.
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Affiliation(s)
- Xiang-Jin Meng
- Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0913, USA.
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Pavio N, Meng XJ, Renou C. Zoonotic hepatitis E: animal reservoirs and emerging risks. Vet Res 2010; 41:46. [PMID: 20359452 PMCID: PMC2865210 DOI: 10.1051/vetres/2010018] [Citation(s) in RCA: 259] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2009] [Accepted: 04/01/2010] [Indexed: 12/23/2022] Open
Abstract
Hepatitis E virus (HEV) is responsible for enterically-transmitted acute hepatitis in humans with two distinct epidemiological patterns. In endemic regions, large waterborne epidemics with thousands of people affected have been observed, and, in contrast, in non-endemic regions, sporadic cases have been described. Although contaminated water has been well documented as the source of infection in endemic regions, the modes of transmission in non-endemic regions are much less known. HEV is a single-strand, positive-sense RNA virus which is classified in the Hepeviridae family with at least four known main genotypes (1–4) of mammalian HEV and one avian HEV. HEV is unique among the known hepatitis viruses, in which it has an animal reservoir. In contrast to humans, swine and other mammalian animal species infected by HEV generally remain asymptomatic, whereas chickens infected by avian HEV may develop a disease known as Hepatitis-Splenomegaly syndrome. HEV genotypes 1 and 2 are found exclusively in humans while genotypes 3 and 4 are found both in humans and other mammals. Several lines of evidence indicate that, in some cases involving HEV genotypes 3 and 4, animal to human transmissions occur. Furthermore, individuals with direct contact with animals are at higher risk of HEV infection. Cross-species infections with HEV genotypes 3 and 4 have been demonstrated experimentally. However, not all sources of human infections have been identified thus far and in many cases, the origin of HEV infection in humans remains unknown.
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Affiliation(s)
- Nicole Pavio
- Ecole Nationale Vétérinaire d'Alfort, 94704 Maisons-Alfort, France.
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28
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Teo CG. Much meat, much malady: changing perceptions of the epidemiology of hepatitis E. Clin Microbiol Infect 2010; 16:24-32. [PMID: 20002688 DOI: 10.1111/j.1469-0691.2009.03111.x] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Hepatitis E, which is caused by hepatitis E virus (HEV), may now be considered a zoonosis as well as an anthroponosis. Pigs, boars and deer have been identified as reservoirs, and their flesh and entrails--as meat and offal--as vehicles of HEV transmission. Shellfish also act as vehicles. Dietary, gastronomic and culinary preferences influence how extensively HEV conveyed by these vehicles can be inactivated before their ingestion by the host. Another route of infection is paved by HEV that is enterically shed by humans and by live animals into the environment. Although anthroponotic transmission of HEV is primarily environmental, zoonotic transmission may proceed along both foodborne and environmental routes.
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Affiliation(s)
- C G Teo
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA.
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