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1
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Santos-Silva S, Santos N, López-López P, Nascimento MSJ, Gonçalves HMR, Van der Poel WHM, Rivero-Juarez A, Mesquita JR. Hepatitis E virus in wild and domestic rabbits from Portugal: a combined molecular and longitudinal serological study. Vet Res Commun 2024; 48:3283-3289. [PMID: 38935173 PMCID: PMC11457708 DOI: 10.1007/s11259-024-10452-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 06/24/2024] [Indexed: 06/28/2024]
Abstract
Hepatitis E virus (HEV), species Paslahepevirus balayani, poses a global public health threat, especially in developing countries, by causing acute enterically transmitted hepatitis. HEV infects various mammalian hosts and belongs to the genus Paslahepevirus in the family Hepeviridae. While swine are recognized as the main hosts of HEV, rabbits, which can also be affected by swine HEV-3 related strains, serve as the primary reservoir for the distinct emerging and zoonotic HEV-3ra subtype. In Portugal, where the European wild rabbit is abundant, their role in HEV epidemiology remains unclear. The primary aim of the present research was to evaluate the circulation and the potential for HEV infection within these species. This study employed a molecular and longitudinal serological approach to investigate HEV in Portuguese rabbits. Among the 205 wild rabbits tested, a seroprevalence of 2.44% (95% CI: 0.80-5.60) was found, with no significant associations with age, sex, localization, or sampling dates. Seropositive animals were found in the south and center regions of the country. HEV RNA was not detected in 120 fecal samples, suggesting a natural, low level, and widespread viral circulation. The study underscores the need for further research to comprehend HEV dynamics in these species, which is crucial for assessing potential transmission risks to humans.
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Affiliation(s)
- Sérgio Santos-Silva
- School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal
| | - Nuno Santos
- CIBIO/InBio, Research Center in Biodiversity and Genetic Resources, Campus of Vairão, University of Porto, Vila do Conde, Portugal
| | - Pedro López-López
- Unit of Infectious Diseases, Hospital Universitario Reina Sofia, Clinical Virology and Zoonoses, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Cordoba, Spain
- Center for Biomedical Research Network (CIBER) in Infectious Diseases, Health Institute Carlos III, Madrid, Spain
| | | | - Helena M R Gonçalves
- LAQV, REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal
| | - Wim H M Van der Poel
- Quantitative Veterinary Epidemiology, Wageningen University, Wageningen, The Netherlands
- Department Virology & Molecular Biology, Wageningen Bioveterinary Research, Lelystad, the Netherlands
| | - António Rivero-Juarez
- Unit of Infectious Diseases, Hospital Universitario Reina Sofia, Clinical Virology and Zoonoses, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Cordoba, Spain
- Center for Biomedical Research Network (CIBER) in Infectious Diseases, Health Institute Carlos III, Madrid, Spain
| | - João R Mesquita
- School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal.
- Epidemiology Research Unit (EPIUnit), Public Health Institute of the University of Porto, Porto, Portugal.
- Laboratory for Integrative and Translational Research in Population Health (ITR), Porto, Portugal.
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2
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Letafati A, Taghiabadi Z, Roushanzamir M, Memarpour B, Seyedi S, Farahani AV, Norouzi M, Karamian S, Zebardast A, Mehrabinia M, Ardekani OS, Fallah T, Khazry F, Daneshvar SF, Norouzi M. From discovery to treatment: tracing the path of hepatitis E virus. Virol J 2024; 21:194. [PMID: 39180020 PMCID: PMC11342613 DOI: 10.1186/s12985-024-02470-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Accepted: 08/14/2024] [Indexed: 08/26/2024] Open
Abstract
The hepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide. HEV is classified into eight genotypes, labeled HEV-1 through HEV-8. Genotypes 1 and 2 exclusively infect humans, while genotypes 3, 4, and 7 can infect both humans and animals. In contrast, genotypes 5, 6, and 8 are restricted to infecting animals. While most individuals with a strong immune system experience a self-limiting infection, those who are immunosuppressed may develop chronic hepatitis. Pregnant women are particularly vulnerable to severe illness and mortality due to HEV infection. In addition to liver-related complications, HEV can also cause extrahepatic manifestations, including neurological disorders. The immune response is vital in determining the outcome of HEV infection. Deficiencies in T cells, NK cells, and antibody responses are linked to poor prognosis. Interestingly, HEV itself contains microRNAs that regulate its replication and modify the host's antiviral response. Diagnosis of HEV infection involves the detection of HEV RNA and anti-HEV IgM/IgG antibodies. Supportive care is the mainstay of treatment for acute infection, while chronic HEV infection may be cleared with the use of ribavirin and pegylated interferon. Prevention remains the best approach against HEV, focusing on sanitation infrastructure improvements and vaccination, with one vaccine already licensed in China. This comprehensive review provides insights into the spread, genotypes, prevalence, and clinical effects of HEV. Furthermore, it emphasizes the need for further research and attention to HEV, particularly in cases of acute hepatitis, especially among solid-organ transplant recipients.
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Affiliation(s)
- Arash Letafati
- Department of Virology, Faculty of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran.
| | - Zahra Taghiabadi
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Mahshid Roushanzamir
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
- Department of Pharmacological and Biomolecular Science, University of Milan, Milan, Italy
| | - Bahar Memarpour
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
- Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Saba Seyedi
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | | | - Masoomeh Norouzi
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Saeideh Karamian
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Arghavan Zebardast
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Marzieh Mehrabinia
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Omid Salahi Ardekani
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Tina Fallah
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Fatemeh Khazry
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Samin Fathi Daneshvar
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Mehdi Norouzi
- Department of Virology, Faculty of Public Health, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
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3
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Veneri C, Brandtner D, Mancini P, Bonanno Ferraro G, Iaconelli M, Del Giudice C, Ciccaglione AR, Bruni R, Equestre M, Marcantonio C, Suffredini E, La Rosa G. Detection and full genomic sequencing of rare hepatitis E virus genotype 4d in Italian wastewater, undetected by clinical surveillance. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 913:169698. [PMID: 38160838 DOI: 10.1016/j.scitotenv.2023.169698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 12/22/2023] [Accepted: 12/24/2023] [Indexed: 01/03/2024]
Abstract
Hepatitis E is a liver disease caused by the hepatitis E virus (HEV), primarily transmitted through contaminated water or food. There are four different HEV genotypes in humans, with genotypes 1 and 2 being the most widespread. Genotypes 3 and 4 are found in animals and can also infect humans. Genotype 4 is prevalent in Asia, mainly in China. In Italy, only one outbreak of HEV-4 has been documented, which occurred in 2011, involving five patients. In 2013, HEV G4 was also detected in a pig farm. Since then, no further evidence of HEV genotype 4 has been found in the country. This study describes the first detection of HEV genotype 4, subtype d, in wastewater in central Italy, despite a lack of any clinical case reported in the area. By using a multiplex PCR protocol and two sequencing strategies, Illumina and ONT, the virus's complete genome was sequenced and characterized as subtype 4d. These findings shed light on the potential of environmental surveillance for infectious agents to improve our understanding of epidemiology and support public health efforts.
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Affiliation(s)
- C Veneri
- National Center for Water Safety (CeNSiA), Istituto Superiore di Sanità, Rome, Italy
| | - D Brandtner
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - P Mancini
- National Center for Water Safety (CeNSiA), Istituto Superiore di Sanità, Rome, Italy
| | - G Bonanno Ferraro
- National Center for Water Safety (CeNSiA), Istituto Superiore di Sanità, Rome, Italy
| | - M Iaconelli
- National Center for Water Safety (CeNSiA), Istituto Superiore di Sanità, Rome, Italy
| | - C Del Giudice
- National Center for Water Safety (CeNSiA), Istituto Superiore di Sanità, Rome, Italy
| | - A R Ciccaglione
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - R Bruni
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - M Equestre
- Department of Neurosciences, Istituto Superiore di Sanità, 00161 Rome, Italy
| | - C Marcantonio
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - E Suffredini
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Rome, Italy
| | - G La Rosa
- National Center for Water Safety (CeNSiA), Istituto Superiore di Sanità, Rome, Italy.
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Songtanin B, Molehin AJ, Brittan K, Manatsathit W, Nugent K. Hepatitis E Virus Infections: Epidemiology, Genetic Diversity, and Clinical Considerations. Viruses 2023; 15:1389. [PMID: 37376687 DOI: 10.3390/v15061389] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 06/13/2023] [Accepted: 06/15/2023] [Indexed: 06/29/2023] Open
Abstract
According to the World Health Organization, approximately 20 million people worldwide are infected annually with the hepatitis E virus (HEV). There are four main genotypes of HEV. Genotype 1 and genotype 2 are common in developing countries and are transmitted by contaminated water from a fecal-oral route. Genotype 3 and genotype 4 are common in developed countries and can lead to occasional transmission to humans via undercooked meat. Hepatitis E virus 1 and HEV3 can lead to fulminant hepatitis, and HEV3 can lead to chronic hepatitis and cirrhosis in immunocompromised patients. The majority of patients with HEV infection are asymptomatic and usually have spontaneous viral clearance without treatment. However, infection in immunocompromised individuals can lead to chronic HEV infection. Both acute and chronic HEV infections can have extrahepatic manifestations. No specific treatment is required for acute HEV infection, no treatment has been approved in chronic infection, and no HEV vaccine has been approved by the (United States) Food and Drug Administration. This review focuses on the molecular virology (HEV life cycle, genotypes, model systems, zoonosis), pathogenesis, clinical manifestation, and treatment of chronic HEV infection, especially in immunocompromised patients, to provide clinicians a better understanding of the global distribution of these infections and the significant effect they can have on immunocompromised patients.
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Affiliation(s)
- Busara Songtanin
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Adebayo J Molehin
- Department of Microbiology & Immunology, College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USA
| | - Kevin Brittan
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Wuttiporn Manatsathit
- Department of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Kenneth Nugent
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
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5
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Elkhawaga AA, El-Mokhtar MA, Mahmoud AA, Ali WE, Mohamed DS, Kamel AM, Mesalam AA, Mousa NHS, Ashmawy AM, Abdel Aziz EM, Sayed IM, Ramadan HKA, Elkholy YS. First Report on Abnormal Renal Function in Acute Hepatitis E Genotype 1 Infection. Pathogens 2023; 12:pathogens12050687. [PMID: 37242358 DOI: 10.3390/pathogens12050687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Revised: 04/28/2023] [Accepted: 04/29/2023] [Indexed: 05/28/2023] Open
Abstract
Impaired renal functions have been reported with Hepatitis E virus (HEV) infections, especially with genotypes 3 and 4. These complications were reported during the acute and chronic phases of infection. HEV genotype 1 causes acute infection, and the effect of HEV-1 infections on renal functions is not known. We examined the kidney function parameters in the serum of HEV-1 patients (AHE, n = 31) during the acute phase of infection. All of the included patients developed an acute self-limiting course of infection, without progression to fulminant hepatic failure. We compared the demographic, laboratory, and clinical data between AHE patients with normal kidney function parameters and those with abnormal renal parameters. Out of 31 AHE patients, 5 (16%) had abnormal kidney function tests (KFTs) during the acute phase of infection. Three patients had abnormal serum urea and creatinine, and two patients had either abnormal urea or creatinine. Four out of five patients had an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2. AHE patients with abnormal KFTs were older and had a lower level of albumin, but a slightly elevated alanine transaminase (ALT) compared to AHE patients with normal KFTs. There were no significant differences between the two groups in terms of age, sex, liver transaminase levels, and the viral load. Similarly, the clinical presentations were comparable in both groups. Interestingly, these KFTs in patients with abnormal renal parameters returned to normal levels at the recovery. The serum creatinine level was not correlated with patients' age or liver transaminase levels, but it was significantly negatively correlated with albumin level. In conclusion, this study is the first report that evaluated KFTs in patients during the acute phase of HEV-1 infections. Impaired KFTs in some AHE patients resolved at convalescence. KFTs and renal complications should be monitored during HEV-1 infections.
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Affiliation(s)
- Amal A Elkhawaga
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Mohamed A El-Mokhtar
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Amal A Mahmoud
- Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Wael Esmat Ali
- Department of Clinical Pathology, Faculty of Medicine, Al-Azhar University Assuit Branch, Assiut 71524, Egypt
| | - Doaa Safwat Mohamed
- Department of Microbiology & Immunology, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt
| | - Ayat M Kamel
- Microbiology and Immunology Department, Faculty of Pharmacy, Assiut University, Assiut 71515, Egypt
| | - Ahmed Atef Mesalam
- Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Centre (NRC), Dokki, Cairo 12622, Egypt
| | - Nermien H S Mousa
- Botany & Microbiology Department, Faculty of Science, Assiut University, Assiut 71515, Egypt
| | - Ahmed M Ashmawy
- Department of Internal Medicine, Gastroenterology and Hepatology Unit, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Essam M Abdel Aziz
- Department of Internal Medicine, Nephrology Division, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Ibrahim M Sayed
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Haidi Karam-Allah Ramadan
- Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Yasmine Samy Elkholy
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Cairo University, Cairo 12613, Egypt
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Castro-Scholten S, Caballero-Gómez J, Rivero-Juarez A, Cano-Terriza D, Gómez-Guillamón F, Jiménez-Martín D, Rivero A, García-Bocanegra I. Monitoring of Hepatitis E Virus in Wild Lagomorphs in Spanish Mediterranean Ecosystems. Transbound Emerg Dis 2023; 2023:7947220. [PMID: 40303740 PMCID: PMC12017187 DOI: 10.1155/2023/7947220] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 04/05/2023] [Accepted: 04/08/2023] [Indexed: 05/02/2025]
Abstract
Hepatitis E virus (HEV) is an emerging zoonotic pathogen in Europe. Even though swine species are considered the main host of the zoonotic HEV-3 genotype, rabbits are recognized as the main reservoir of the divergent HEV-3ra subtype. However, the role of wild lagomorphs in the epidemiology of this virus in Mediterranean ecosystems is under debate. The aims of this study were to assess exposure of HEV in wild rabbit (Oryctolagus cuniculus) and Iberian hare (Lepus granatensis) populations in southern Spain and to determine potential risk factors associated with HEV exposure in these species. Between 2018 and 2021, blood and fecal samples from 370 wild rabbits and 60 Iberian hares were collected. A total of 29 (6.7%; 95%CI: 4.4-9.1) out of 430 sampled animals showed anti-HEV antibodies. By species, the seroprevalences in wild rabbit and Iberian hare were 6.8% (29/370; 95%CI: 4.2-9.3) and 6.7% (4/60; 95%CI: 0.4-13.0), respectively. Seropositive animals were detected on 17 (26.2%; 95%CI: 15.4-36.8) of the 65 sampled hunting estates. The generalized estimating equations model showed that geographical area was a risk factor potentially associated with HEV exposure in wild lagomorphs in the study region. HEV RNA was not detected in any of the 242 (0.0%; 95%CI: 0.0-1.5) fecal samples tested. This is the first large-scale serosurvey performed in wild rabbits in the Iberian Peninsula and in Iberian hares worldwide. Our results provide evidence of low, widespread, and heterogeneous distribution of HEV among wild rabbit and Iberian hare populations in Spanish Mediterranean ecosystems, which indicates a limited role of wild lagomorphs in the maintenance of the virus and a low risk of transmission of HEV to other species, including humans.
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Affiliation(s)
- Sabrina Castro-Scholten
- Departamento de Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, 14004 Córdoba, Spain
| | - Javier Caballero-Gómez
- Departamento de Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, 14004 Córdoba, Spain
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba 14014, Spain
- CIBERINFEC, ISCIII CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Antonio Rivero-Juarez
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba 14014, Spain
- CIBERINFEC, ISCIII CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid 28029, Spain
| | - David Cano-Terriza
- Departamento de Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, 14004 Córdoba, Spain
- CIBERINFEC, ISCIII CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Félix Gómez-Guillamón
- Programa de Vigilancia Epidemiológica de la Fauna Silvestre (PVE), Consejería de Sostenibilidad, Medio Ambiente y Economía Azul, Junta de Andalucía, Málaga 29002, Spain
| | - Débora Jiménez-Martín
- Departamento de Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, 14004 Córdoba, Spain
| | - Antonio Rivero
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba 14014, Spain
- CIBERINFEC, ISCIII CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Ignacio García-Bocanegra
- Departamento de Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, 14004 Córdoba, Spain
- CIBERINFEC, ISCIII CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid 28029, Spain
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Ianiro G, Pavoni E, Aprea G, Romantini R, Alborali GL, D'Angelantonio D, Garofolo G, Scattolini S, De Sabato L, Magistrali CF, Burow E, Ostanello F, Smith RP, Di Bartolo I. Cross-sectional study of hepatitis E virus (HEV) circulation in Italian pig farms. Front Vet Sci 2023; 10:1136225. [PMID: 37143498 PMCID: PMC10151646 DOI: 10.3389/fvets.2023.1136225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Accepted: 03/29/2023] [Indexed: 05/06/2023] Open
Abstract
Foodborne transmission is considered the main way of spreading zoonotic hepatitis E virus (HEV) infection in Europe. In recent years, the human cases of hepatitis E in subjects without history of travel in endemic areas have raised, suggesting that domestic HEV transmission is increasing. Pork products with or without liver, are often indicated as the source of many human foodborne HEV cases as well as small outbreaks. Pigs are recognized as the main reservoir of the zoonotic HEV-3 genotype, the most frequently detected in human cases in the EU. In the absence of a harmonized surveillance of HEV circulation, data on prevalence are heterogeneous but confirm a widespread circulation of HEV-3 in pig herds across EU. HEV-3 can pass through the food chain from farm to fork when infected animals are slaughtered. In Italy, several studies reported the circulation of HEV-3 in pig farms, but results are heterogeneous due to different methodologies applied. In the present study, we performed a survey over 51 pig herds belonging to three main types of farms: breeding, fattening and farrow-to-finish. HEV-RNA was analyzed by broad range Real-time RT-PCR on 20 samples for each farm, obtained by pooling together feces from 10 individuals. Overall, HEV RNA was confirmed on 150 fecal pooled samples out of 1,032 (14.5%). At least one positive pooled sample was detected from 18 farms out of 51 tested (35.3%). By lowering the number of infected pigs at primary production, the risk of HEV-3 entering into the food chain can be reduced. Hence, information on HEV circulation in herds is highly relevant for choosing preventive measures and deserves development of a monitoring program and further investigations.
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Affiliation(s)
- Giovanni Ianiro
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Rome, Italy
| | - Enrico Pavoni
- Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia-Romagna “Bruno Ubertini”, Brescia, Italy
- *Correspondence: Enrico Pavoni
| | - Giuseppe Aprea
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise “Giuseppe Caporale”, Teramo, Italy
| | - Romina Romantini
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise “Giuseppe Caporale”, Teramo, Italy
| | - Giovanni Loris Alborali
- Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia-Romagna “Bruno Ubertini”, Brescia, Italy
| | - Daniela D'Angelantonio
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise “Giuseppe Caporale”, Teramo, Italy
| | - Giuliano Garofolo
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise “Giuseppe Caporale”, Teramo, Italy
| | - Silvia Scattolini
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise “Giuseppe Caporale”, Teramo, Italy
| | - Luca De Sabato
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Rome, Italy
| | | | - Elke Burow
- Department of Biological Safety, German Federal Institute for Risk Assessment, Berlin, Germany
| | - Fabio Ostanello
- Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell'Emilia, Italy
| | - Richard Piers Smith
- Department of Epidemiological Sciences, Animal and Plant Health Agency, Weybridge, United Kingdom
| | - Ilaria Di Bartolo
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Rome, Italy
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8
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Geng Y, Shi T, Wang Y. Epidemiology of Hepatitis E. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:33-48. [PMID: 37223857 DOI: 10.1007/978-981-99-1304-6_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Hepatitis E virus (HEV) is globally prevalent with relatively high percentages of anti-HEV immunoglobulin G-positive individuals in the populations of developing and developed countries. There are two distinct epidemiological patterns of hepatitis E. In areas with high disease endemicity, primarily developing countries in Asia and Africa, this disease is caused mainly by genotypes HEV-1 or HEV-2; both genotypes transmit predominantly through contaminated water and occur as either outbreaks or sporadic cases of acute hepatitis. The acute hepatitis has the highest attack rate in young adults and is particularly severe among pregnant women. In developed countries, sporadic cases of locally acquired HEV-3 or HEV-4 infection are observed. The reservoir of HEV-3 and HEV-4 is believed to be animals, such as pigs, with zoonotic transmission to humans. The affected persons are often elderly, and persistent infection has been well documented among immunosuppressed persons. A subunit vaccine has been shown to be effective in preventing clinical disease and has been licensed in China.
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Affiliation(s)
- Yansheng Geng
- Key Laboratory of Public Health Safety of Hebei Province, School of Public Health, Hebei University, Baoding, China
| | - Tengfei Shi
- Key Laboratory of Public Health Safety of Hebei Province, School of Public Health, Hebei University, Baoding, China
| | - Youchun Wang
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, China.
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Priemer G, Cierniak F, Wolf C, Ulrich RG, Groschup MH, Eiden M. Co-Circulation of Different Hepatitis E Virus Genotype 3 Subtypes in Pigs and Wild Boar in North-East Germany, 2019. Pathogens 2022; 11:pathogens11070773. [PMID: 35890018 PMCID: PMC9317891 DOI: 10.3390/pathogens11070773] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 06/27/2022] [Accepted: 07/01/2022] [Indexed: 12/25/2022] Open
Abstract
Hepatitis E is a major cause of acute liver disease in humans worldwide. The infection is caused by hepatitis E virus (HEV) which is transmitted in Europe to humans primarily through zoonotic foodborne transmission from domestic pigs, wild boar, rabbits, and deer. HEV belongs to the family Hepeviridae, and possesses a positive-sense, single stranded RNA genome. This agent usually causes an acute self-limited infection in humans, but in people with low immunity, e.g., immunosuppressive therapy or underlying liver diseases, the infection can evolve to chronicity and is able to induce a variety of extrahepatic manifestations. Pig and wild boar have been identified as the primary animal reservoir in Europe, and consumption of raw and undercooked pork is known to pose a potential risk of foodborne HEV infection. In this study, we analysed pig and wild boar liver, faeces, and muscle samples collected in 2019 in Mecklenburg-Western Pomerania, north-east Germany. A total of 393 animals of both species were investigated using quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR), conventional nested RT-PCR and sequence analysis of amplification products. In 33 animals, HEV RNA was detected in liver and/or faeces. In one individual, viral RNA was detected in muscle tissue. Sequence analysis of a partial open reading frame 1 region demonstrated a broad variety of genotype 3 (HEV-3) subtypes. In conclusion, the study demonstrates a high, but varying prevalence of HEV RNA in swine populations in Mecklenburg-Western Pomerania. The associated risk of foodborne HEV infection needs the establishment of sustainable surveillance and treatment strategies at the interface between humans, animals, and the environment within a One Health framework.
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Affiliation(s)
- Grit Priemer
- Department 2—Animal Disease Diagnostics, State Office for Agriculture, Food Safety and Fisheries Mecklenburg—Western Pomerania, 18059 Rostock, Germany; (G.P.); (C.W.)
| | - Filip Cierniak
- Institute of Novel and Emerging Infectious Diseases at the Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany; (F.C.); (R.G.U.); (M.H.G.)
| | - Carola Wolf
- Department 2—Animal Disease Diagnostics, State Office for Agriculture, Food Safety and Fisheries Mecklenburg—Western Pomerania, 18059 Rostock, Germany; (G.P.); (C.W.)
| | - Rainer G. Ulrich
- Institute of Novel and Emerging Infectious Diseases at the Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany; (F.C.); (R.G.U.); (M.H.G.)
- Partner Site Hamburg-Lübeck-Borstel-Riems, German Centre for Infection Research (DZIF), 17493 Greifswald-Insel Riems, Germany
| | - Martin H. Groschup
- Institute of Novel and Emerging Infectious Diseases at the Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany; (F.C.); (R.G.U.); (M.H.G.)
- Partner Site Hamburg-Lübeck-Borstel-Riems, German Centre for Infection Research (DZIF), 17493 Greifswald-Insel Riems, Germany
| | - Martin Eiden
- Institute of Novel and Emerging Infectious Diseases at the Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany; (F.C.); (R.G.U.); (M.H.G.)
- Correspondence:
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10
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Potential zoonotic swine enteric viruses: The risk ignored for public health. Virus Res 2022; 315:198767. [PMID: 35421434 DOI: 10.1016/j.virusres.2022.198767] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 03/30/2022] [Accepted: 04/03/2022] [Indexed: 12/28/2022]
Abstract
Swine could serve as a natural reservoir for a large variety of viruses, including potential zoonotic enteric viruses. The presence of viruses with high genetic similarity between porcine and human strains may result in the emergence of zoonotic or xenozoonotic infections. Furthermore, the globalization and intensification of swine industries exacerbate the transmission and evolution of zoonotic viruses among swine herds and individuals working in swine-related occupations. To effectively prevent the public health risks posed by zoonotic swine enteric viruses, designing, and implementing a comprehensive measure for early diagnosis, prevention, and mitigation, requires interdisciplinary a collaborative ''One Health" approach from veterinarians, environmental and public health professionals, and the swine industry. In this paper, we reviewed the current knowledge of selected potential zoonotic swine enteric viruses and explored swine intensive production and its associated public health risks.
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11
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Fang L, Zhang J, Chen H, Lv F, Yu Y, Du X. Epidemiological Characteristics and Clinical Manifestations of Hepatitis E in a Tertiary Hospital in China: A Retrospective Study. Front Microbiol 2022; 12:831968. [PMID: 35310389 PMCID: PMC8928388 DOI: 10.3389/fmicb.2021.831968] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 12/31/2021] [Indexed: 01/12/2023] Open
Abstract
Background Hepatitis E virus (HEV) infection is the most common cause of acute viral hepatitis worldwide and one of the main causes of death in the last decade, causing chronic hepatitis and liver failure in some populations. The aging population and obesity are two major factors threatening human health. Therefore, we want to understand the relationship between these two groups and HEV infection. Objectives The study aimed to analyze the epidemiological, clinical, and laboratory features of HEV infection and evaluate probable high-risk factors for disease progression and the current diagnostic strategies of hepatitis E infection. Study Design Patients diagnosed with acute hepatitis E with symptoms and liver dysfunction were enrolled. For statistical analysis, clinical features and laboratory findings were collected between the elderly and non-elderly and HEV+ fatty liver disease (FLD) groups. Statistical analysis was performed using Excel and the platform VassarStats, and statistical significance was taken as P < 0.05. Results Jaundice and the bilirubin peak were significantly deeper, the duration of hospitalization was significantly longer, and the proportion of ascites and liver failure was significantly higher in the elderly group. The aging population is one of the risk factors of severe hepatitis E. Hepatitis E becomes more serious in the HEV + FLD group, although the results did not reach statistical significance. Conclusion The aging and FLD were suggested to aggravate HEV infection. However, the diagnosis of HEV infection remains a challenge. A prospective study with sufficient sample size is needed to confirm this conclusion.
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Affiliation(s)
- Li Fang
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Junli Zhang
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Huiying Chen
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Fangfang Lv
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yunsong Yu
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiaoxing Du
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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12
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Sintusek P, Thanapirom K, Komolmit P, Poovorawan Y. Eliminating viral hepatitis in children after liver transplants: How to reach the goal by 2030. World J Gastroenterol 2022; 28:290-309. [PMID: 35110951 PMCID: PMC8771616 DOI: 10.3748/wjg.v28.i3.290] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 08/12/2021] [Accepted: 01/06/2022] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis infections are a great burden in children who have received liver transplant. Hepatotropic viruses can cause liver inflammation that can develop into liver graft fibrosis and cirrhosis over the long term. Immunological reactions due to viral hepatitis infections are associated with or can mimic graft rejection, rendering the condition difficult to manage. Prevention strategies using vaccinations are agreeable to patients, safe, cost-effective and practical. Hence, strategies to eliminate viral hepatitis A and B focus mainly on immunization programmes for children who have received a liver transplant. Although a vaccine has been developed to prevent hepatitis C and E viruses, its use is not licensed worldwide. Consequently, eliminating hepatitis C and E viruses mainly involves early detection in children with suspected cases and effective treatment with antiviral therapy. Good hygiene and sanitation are also important to prevent hepatitis A and E infections. Donor blood products and liver grafts should be screened for hepatitis B, C and E in children who are undergoing liver transplantation. Future research on early detection of viral hepatitis infections should include molecular techniques for detecting hepatitis B and E. Moreover, novel antiviral drugs for eradicating viral hepatitis that are highly effective and safe are needed for children who have undergone liver transplantation.
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Affiliation(s)
- Palittiya Sintusek
- The Thai Pediatric Gastroenterology, Hepatology and Immunology (TPGHAI) Research Unit, Chulalongkorn University, Bangkok 10330, Thailand
- Division of Gastroenterology, Department of Pediatrics, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Kessarin Thanapirom
- Division of Gastroenterology, Department of Medicine, Liver Fibrosis and Cirrhosis Research Unit, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Piyawat Komolmit
- Division of Gastroenterology, Department of Medicine, Liver Fibrosis and Cirrhosis Research Unit, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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13
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Fanelli A, Tizzani P, Buonavoglia D. A systematic review and meta-analysis of hepatitis E virus (HEV) in wild boars. Res Vet Sci 2021; 142:54-69. [PMID: 34864434 DOI: 10.1016/j.rvsc.2021.11.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 05/02/2021] [Accepted: 11/26/2021] [Indexed: 12/19/2022]
Abstract
This systematic review and meta-analysis summarize the available information on Hepatitis E virus (HEV) -specific antibody seroprevalence and HEV RNA prevalence in wild boar, one of the most abundant game species worldwide. A literature search (CAB Abstracts, Web of Science, Embase and Scopus) was performed to find relevant peer-reviewed works published during the period 1990-2020. A random-effect model was carried out to calculate the pooled HEV-specific antibody seroprevalence and HEV RNA prevalence estimates with 95% confidence intervals, and I2 statistic was used to assess the heterogeneity of the data. Values by subgroups were compared according to the geographical area, age class (≤ 12 months old and > 12 months old), and sample type (bile, faeces, liver, meat/muscle, serum). Sixty-nine publications were selected, with the majority of the studies from Southern Europe (n = 27). The pooled HEV-specific antibody seroprevalence in wild boar was 28% (CI95% 23-34) and the HEV RNA prevalence 8% (CI95% 6-10). The analysis highlighted a significant heterogeneity among the estimates from the included studies (I2 = 98% and I2 = 95% for HEV-specific antibody seroprevalence and viral prevalence respectively). The moderator analysis indicated a statistically significant difference (p-value = 0.03) for the HEV RNA prevalence according to the sample type, with the highest value in bile (17%, CI95% 9-27), followed by liver (10%, CI95% 7-14), serum (7%, CI95% 4-10), faeces (5%, CI95% 2-9), and meat/muscle (3%, CI95% 0.04-10). Finally, the HEV RNA prevalence in Europe (8.7, CI95% 6.7-11) was significantly (p-value = 0.04) higher than in Asia (4, CI95% 0.6-8). The analysis highlights the important role of wild boar in the epidemiology of HEV.
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Affiliation(s)
- Angela Fanelli
- Department of Veterinary Medicine, University of Bari, Valenzano, Bari, Italy.
| | - Paolo Tizzani
- Department of Veterinary Sciences, University of Turin, Grugliasco, Turin, Italy
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14
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Sakata H, Matsubayashi K, Iida J, Nakauchi K, Kishimoto S, Sato S, Ikuta K, Satake M, Kino S. Trends in hepatitis E virus infection: Analyses of the long-term screening of blood donors in Hokkaido, Japan, 2005-2019. Transfusion 2021; 61:3390-3401. [PMID: 34632593 DOI: 10.1111/trf.16700] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 08/30/2021] [Accepted: 09/23/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND After experiencing several cases of transfusion-transmitted hepatitis E (TT-HE) in Hokkaido, Northern Japan, hepatitis E virus (HEV) screening in blood donors, using a nucleic acid amplification test (NAT), was introduced in 2005. STUDY DESIGN AND METHODS The frequency of HEV RNA-positive donations (2005-2019) was investigated, and the HEV RNA-positive specimens were phylogenetically analyzed. In August 2014, the 20-pooled NAT (20P-NAT) was replaced with an individual-NAT (ID-NAT) system. RESULTS Until 2019, the frequency of HEV RNA-positive donors was 0.011% (289/2,638,685) with 20P-NAT and 0.043% (597/1,379,750) with ID-NAT, and no TT-HE cases were observed in Hokkaido. The prevalence among male, but not female donors, increased significantly between 2015 and 2019. Eighty-nine percent of HEV isolates from donors were genotype 3 and the remainder were genotype 4, and many clusters existed in each genotype. ALT levels at the time of donation were significantly higher in donors with genotype 4. Four subgenotypes, namely 3a (37%), 3b (41%), 3e (6%), and 4c (10%), comprised 94% of the total. During this period, the most identified subgenotype, 3a, transitioned to 3b. Majority of the HEV strains within the same clusters were detected in the same geographical region around the same period. Many of the human HEV isolates were shown to coexist closely with animal HEV isolates phylogenetically. CONCLUSION In Hokkaido, multiple divergent HEV strains have been circulating, and small outbreaks of hepatitis E have occurred in the last 15 years. The results suggested that HEV NAT can contribute significantly in ensuring safety during blood transfusions.
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Affiliation(s)
| | - Keiji Matsubayashi
- Central Blood Institute, Blood Service Headquarters, Japanese Red Cross Society, Tokyo, Japan
| | - Juri Iida
- Japanese Red Cross Hokkaido Block Blood Center, Sapporo, Japan
| | - Kenta Nakauchi
- Japanese Red Cross Hokkaido Block Blood Center, Sapporo, Japan
| | | | - Shinichiro Sato
- Japanese Red Cross Hokkaido Block Blood Center, Sapporo, Japan
| | - Katsuya Ikuta
- Japanese Red Cross Hokkaido Blood Center, Sapporo, Japan
| | - Masahiro Satake
- Central Blood Institute, Blood Service Headquarters, Japanese Red Cross Society, Tokyo, Japan
| | - Shuichi Kino
- Japanese Red Cross Hokkaido Block Blood Center, Sapporo, Japan
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15
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Micas F, Suin V, Péron JM, Scholtes C, Tuaillon E, Vanwolleghem T, Bocket L, Lhomme S, Dimeglio C, Izopet J, Abravanel F. Analyses of Clinical and Biological Data for French and Belgian Immunocompetent Patients Infected With Hepatitis E Virus Genotypes 4 and 3. Front Microbiol 2021; 12:645020. [PMID: 33936003 PMCID: PMC8079808 DOI: 10.3389/fmicb.2021.645020] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 03/22/2021] [Indexed: 12/01/2022] Open
Abstract
Hepatitis E virus (HEV) genotypes 3 and 4 are the major causes of acute hepatitis in industrialized countries. Genotype 3 is mainly found in Europe and America, while genotype 4 is predominant in Asia. Several Japanese studies have suggested that genotype 4 is more virulent than genotype 3. We investigated this aspect by analyzing the clinical and biological data for 27 French and Belgian immunocompetent patients infected with HEV genotype 4. Their infections were probably acquired locally, since none of these patients reported traveling outside France or Belgium during the 2–8 weeks before symptoms onset. Each patient was matched for age (±5 years) and gender with two patients infected with HEV genotype 3. Bivariate analysis indicated that the HEV genotype 4-infected patients had significantly higher alanine aminotransferase (ALT) (2067 IU/L) and aspartate aminotransferase (AST) (1581 IU/L) activities and total bilirubin concentrations (92.4 μmol/L) than did those infected with HEV genotype 3 (1566 IU/L, p = 0.016; 657 IU/L, p = 0.003 and 47 μmol/L, p = 0.046) at diagnosis. In contrast, more patients infected with HEV genotype 3 reported dark urine (71% vs. 39%, p = 0.02) and experienced asthenia (89% vs. 58%, p < 0.01) than did those infected with HEV genotype 4. Two HEV genotype 4-infected patients died of multi-organ failure, while none of the genotype 3-infected patients died (p = 0.035). Finally, stepwise regression analysis retained only a greater increase in ALT (odds-ratio: 1.0005, 95% confidence interval: 1.00012–1.00084) and less frequent fever (odds-ratio = 0.1244; 95% confidence interval: 0.01887–0.82020) for patients infected with HEV genotype 4. We conclude that HEV-4 infections are likely to be associated with higher ALT activity than HEV-3 infections. Additional immunological and virological studies are required to confirm these findings and better understand the influence, if any, of genotype on HEV pathophysiology.
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Affiliation(s)
- Florence Micas
- Virology Laboratory, National Reference Centre of Hepatitis E Viruses, Federal Institute of Biology, University Hospital Center, Toulouse, France
| | - Vanessa Suin
- National Reference Centre of Hepatitis Viruses, Sciensano, Brussels, Belgium
| | - Jean-Marie Péron
- Department of Gastroenterology, Rangueil University Hospital, Toulouse, France
| | - Caroline Scholtes
- INSERM U1052-Cancer Research Center of Lyon (CRCL), Lyon, France.,University of Lyon, University Claude Bernard Lyon 1 (UCBL1), Lyon, France.,Department of Virology, Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France
| | - Edouard Tuaillon
- Pathogenesis and Control of Chronic Infections, INSERM, University of Montpellier, Etablissement Français du Sang, CHU Montpellier, Montpellier, France
| | - Thomas Vanwolleghem
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium.,Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Antwerp, Belgium
| | - Laurence Bocket
- Virology Laboratory EA3610, Faculty of Medicine, University Hospital Center, Lille, France
| | - Sébastien Lhomme
- Virology Laboratory, National Reference Centre of Hepatitis E Viruses, Federal Institute of Biology, University Hospital Center, Toulouse, France.,UMR Inserm U1043, UMR CNRS, U5282, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France
| | - Chloé Dimeglio
- Virology Laboratory, National Reference Centre of Hepatitis E Viruses, Federal Institute of Biology, University Hospital Center, Toulouse, France.,UMR Inserm U1043, UMR CNRS, U5282, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France
| | - Jacques Izopet
- Virology Laboratory, National Reference Centre of Hepatitis E Viruses, Federal Institute of Biology, University Hospital Center, Toulouse, France.,UMR Inserm U1043, UMR CNRS, U5282, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France
| | - Florence Abravanel
- Virology Laboratory, National Reference Centre of Hepatitis E Viruses, Federal Institute of Biology, University Hospital Center, Toulouse, France.,UMR Inserm U1043, UMR CNRS, U5282, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France
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16
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Anti-HEV IgG Avidity Testing: Utility for Diagnosing Acute and Resolved Genotype 3 Infections. Viruses 2021; 13:v13020236. [PMID: 33546482 PMCID: PMC7913725 DOI: 10.3390/v13020236] [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] [Received: 01/12/2021] [Revised: 01/27/2021] [Accepted: 01/29/2021] [Indexed: 11/24/2022] Open
Abstract
European Association of the Study of the Liver (EASL) guidelines specify HEV RNA, as well as anti-HEV IgG and IgM as positive markers for acute HEV infection. HEV RNA assay sensitivity limitations may lead to false negative test results in patients with low levels of viremia. Moreover, anti-HEV IgM positivity is not a reliable indicator for distinguishing between acute and resolved infections given the ability of this antibody to persist several months after a resolved infection. Our study aims were to assess HEV IgG avidity for diagnosing acute and resolved infections, regardless of the anti-HEV IgM serostatus, and examine assay reliability when evaluating different genotype 3 (GT3) HEV subtypes. Patient serum samples (n = 104) were tested for HEV IgG avidity by utilizing the DIA.PRO kit on a DSX automated instrument. Among patients identified with acute HEV infections, 32 were infected with GT3: GT3c (n = 5), GT3e (n = 8), 3f (n = 17) and GT3-unsubtyped (n = 2). Avidity sensitivity was 91.2% and specificity was 100%. For patients with long-lasting anti-HEV IgM persistence, an Avidity Index >70% was observed. Thus, the DIA.PRO avidity assay may be utilized to distinguish between recently acquired and resolved HEV GT3 infections. However, for equivocal results (Avidity Index > 40–70%), HEV RNA molecular testing will be required to confirm a recent infection.
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17
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Clinical Characteristics of Acute Hepatitis E and Their Correlation with HEV Genotype 3 Subtypes in Italy. Pathogens 2020; 9:pathogens9100832. [PMID: 33050666 PMCID: PMC7650787 DOI: 10.3390/pathogens9100832] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 10/04/2020] [Accepted: 10/09/2020] [Indexed: 02/08/2023] Open
Abstract
Genotype 3 (GT3) is responsible for most European autochthonous hepatitis E virus (HEV) infections. This study analyzed circulating genotypes and GT3 subtypes in the Lazio region, Italy, between 2011 and 2019, as well as their pathogenic characteristics. Of the 64 evaluable HEV GT3 patient-derived sequences, identified subtypes included GT3f (n = 36), GT3e (n = 15), GT3c (n = 9), GT3a (n = 1) and three unsubtyped GT3 sequences. GT3c strains were similar to Dutch sequences (96.8–98.1% identity), GT3e strains showed high similarity (96.8%) with a United Kingdom sequence, while the most related sequences to GT3f Italian strains were isolated in France, Belgium and Japan. One sequence was closely related to another Italian strain isolated in raw sewage in 2016. The liver functioning test median values for 56 evaluable GT3 patients were: alanine aminotransferase (ALT), 461 (range 52–4835 U/L); aspartate aminotransferase (AST), 659 (range 64–6588 U/L); and total bilirubin, 3.49 (range 0.4–33 mg/dL). The median HEV RNA viral load for 26 evaluable GT3 patients was 42,240 IU/mL (range 5680–895,490 IU/mL). Of the 37 GT3 patients with available clinical information, no correlation was observed between HEV clinical manifestations and GT3 subtype. HEV symptoms were comparable among GT3c/e/f patients across most analyzed categories except for epigastric pain, which occurred more frequently in patients with HEV GT3e (75%) than in patients with GT3c (50%) or GT3f (19%) (p = 0.01). Additionally, patients with HEV GT3c exhibited significantly higher median international normalized ratio (INR) than patients with GT3e and GT3f (p = 0.033). The severity of GT3 acute hepatitis E was not linked to HEV RNA viral load or to the GT3 subtype.
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18
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Santos-Ferreira N, Mesquita JR, Rivadulla E, Inácio ÂS, Martins da Costa P, Romalde JL, Nascimento MSJ. Hepatitis E virus genotype 3 in echinoderms: First report of sea urchin (Paracentrotus lividus) contamination. Food Microbiol 2020; 89:103415. [PMID: 32138985 DOI: 10.1016/j.fm.2020.103415] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 01/07/2020] [Accepted: 01/08/2020] [Indexed: 11/28/2022]
Abstract
Hepatitis E virus (HEV) deriving from manure application runoffs and faecal waste spill over of swine and human origin bypass wastewater treatment plants and contaminate coastal waters. Shellfish bioaccumulate enteric viruses such as HEV from fecally contaminated coastal waters and under current European Regulations, shellfish sanitary status surveillance is mandatory but only by means of bacterial faecal indicators. The sea urchins are under the same regulations and their vulnerability to fecal contamination has been pointed out. Since they are consumed raw and with no steps to control/reduce hazards, sea urchin contamination with enteric viruses can represent a food safety risk. Hence, the aim of the present study was to screen sea urchin gonads destined for human consumption for the presence of HEV. HEV was detected and quantified in gonads of sea urchins collected in north Portugal by a reverse transcription-quantitative PCR (RT-qPCR) assay targeting the ORF3 region, followed by genotyping by a nested RT-PCR targeting the ORF2 region. Sequencing and phylogenetic analysis clustered the HEV sequence within genotype 3, subgenotype e. This the first study reporting HEV contamination of sea urchins. We hypothesize that like shellfish, sea urchins can also be a food vehicle for HEV transmission to humans.
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Affiliation(s)
- Nânci Santos-Ferreira
- Interdisciplinary Centre of Marine and Environmental Research, University of Porto (CIIMAR/CIMAR), Matosinhos, Portugal.
| | - João Rodrigo Mesquita
- Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade Do Porto, Porto, Portugal; Epidemiology Research Unit (EPIUnit), Instituto de Saúde Pública, Universidade Do Porto, Portugal.
| | - Enrique Rivadulla
- Departamento de Microbiología y Parasitología, CIBUS-Facultad de Biología, Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain.
| | - Ângela S Inácio
- Interdisciplinary Centre of Marine and Environmental Research, University of Porto (CIIMAR/CIMAR), Matosinhos, Portugal.
| | - Paulo Martins da Costa
- Interdisciplinary Centre of Marine and Environmental Research, University of Porto (CIIMAR/CIMAR), Matosinhos, Portugal; Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade Do Porto, Porto, Portugal.
| | - Jesus L Romalde
- Departamento de Microbiología y Parasitología, CIBUS-Facultad de Biología, Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain.
| | - Maria São José Nascimento
- Epidemiology Research Unit (EPIUnit), Instituto de Saúde Pública, Universidade Do Porto, Portugal; Faculdade de Farmácia, Universidade Do Porto (FFUP), Porto, Portugal.
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Kitaura S, Wakabayashi Y, Okazaki A, Okada Y, Okamoto K, Ikeda M, Okugawa S, Moriya K. The First Case Report of Acute Symptomatic HEV Genotype 4 Infection in an HIV-positive Patient in Japan. Intern Med 2020; 59:1655-1658. [PMID: 32269193 PMCID: PMC7402963 DOI: 10.2169/internalmedicine.4505-20] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Hepatitis E virus (HEV) is a common cause of acute hepatitis. Four major genotypes of HEV have been studied, with genotype 4 being the predominant genotype across Asia. We herein describe the case of a 50-year-old man with a history of human immunodeficiency virus (HIV) infection who was admitted with acute transaminitis. Serum anti-HEV-IgA and HEV-RNA were detected at the time of presentation and further testing revealed HEV genotype 4. To the best of our knowledge, this represents the first clinical case report of acute symptomatic HEV genotype 4 infection in an HIV-positive patient in Japan.
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Affiliation(s)
- Satoshi Kitaura
- Department of Infectious Diseases, The University of Tokyo Hospital, Japan
| | - Yoshitaka Wakabayashi
- Department of Infectious Diseases, The University of Tokyo Hospital, Japan
- Department of Internal Medicine, Teikyo University, Japan
| | - Aiko Okazaki
- Department of Infectious Diseases, The University of Tokyo Hospital, Japan
| | - Yuta Okada
- Department of Infectious Diseases, The University of Tokyo Hospital, Japan
| | - Koh Okamoto
- Department of Infectious Diseases, The University of Tokyo Hospital, Japan
| | - Mahoko Ikeda
- Department of Infection Control and Prevention, The University of Tokyo, Japan
| | - Shu Okugawa
- Department of Infectious Diseases, The University of Tokyo Hospital, Japan
| | - Kyoji Moriya
- Department of Infectious Diseases, The University of Tokyo Hospital, Japan
- Department of Infection Control and Prevention, The University of Tokyo, Japan
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20
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Janahi EM, Parkar SFD, Mustafa S, Eisa ZM. Implications of Hepatitis E Virus in Blood Transfusions, Hemodialysis, and Solid Organ Transplants. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:E206. [PMID: 32344807 PMCID: PMC7279256 DOI: 10.3390/medicina56050206] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 04/19/2020] [Accepted: 04/21/2020] [Indexed: 01/05/2023]
Abstract
Hepatitis E Virus (HEV) is emerging as the primary cause of acute viral hepatitis in humans. The virus is commonly transmitted by the fecal-oral route via contaminated water in endemic regions or through the consumption of inadequately cooked swine products or game meats in industrialized regions. HEV genotypes 1 and 2 are predominantly associated with waterborne transmission in developing countries, whereas HEV3 and HEV4 are mainly zoonotically transmitted in industrialized countries. Seroprevalence in populations determined by detecting anti-HEV antibodies and serum HEV RNA is commonly used to analyze the presence of HEV. Although HEV RNA-based detection is now standardized, there is a lack of agreement between the assaying methods used for gathering seroprevalence data. Since 2004, HEV has been considered as a transmissible infectious agent through blood transfusion. Recent seroprevalence studies in European countries indicate an underestimated risk for blood transfusion and hence warrant testing the blood supply. HEV infection is usually self-limiting and spontaneously cleared. However, in about 60% of recipients of solid organ transplants, HEV progresses to chronic hepatitis. Immunosuppressive drugs such as tacrolimus are a major cause of chronic hepatitis and reducing its dosage results in viral clearance in about 30% of patients. In hemodialysis patients, the parenteral route is implicated as an important mechanism of transmission. In this review, we explore the clinical and epidemiological characteristics of various HEV genotypes in blood donors, hemodialysis patients, and transplant recipients.
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Affiliation(s)
- Essam M. Janahi
- Department of Biology, College of Science, University of Bahrain, Sakhir 32038, Bahrain; (S.F.D.P.); (S.M.)
| | - Saba F. D. Parkar
- Department of Biology, College of Science, University of Bahrain, Sakhir 32038, Bahrain; (S.F.D.P.); (S.M.)
| | - Sakina Mustafa
- Department of Biology, College of Science, University of Bahrain, Sakhir 32038, Bahrain; (S.F.D.P.); (S.M.)
| | - Zaki M. Eisa
- The National Center for Disease Prevention and Control, Jazan 82722-2476, Saudi Arabia;
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21
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Quantification and genetic diversity of Hepatitis E virus in wild boar (Sus scrofa) hunted for domestic consumption in Central Italy. Food Microbiol 2019; 82:194-201. [PMID: 31027773 DOI: 10.1016/j.fm.2019.02.005] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Revised: 02/07/2019] [Accepted: 02/11/2019] [Indexed: 12/19/2022]
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22
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Primadharsini PP, Nagashima S, Okamoto H. Genetic Variability and Evolution of Hepatitis E Virus. Viruses 2019; 11:E456. [PMID: 31109076 PMCID: PMC6563261 DOI: 10.3390/v11050456] [Citation(s) in RCA: 80] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 05/15/2019] [Accepted: 05/16/2019] [Indexed: 12/16/2022] Open
Abstract
Hepatitis E virus (HEV) is a single-stranded positive-sense RNA virus. HEV can cause both acute and chronic hepatitis, with the latter usually occurring in immunocompromised patients. Modes of transmission range from the classic fecal-oral route or zoonotic route, to relatively recently recognized but increasingly common routes, such as via the transfusion of blood products or organ transplantation. Extrahepatic manifestations, such as neurological, kidney and hematological abnormalities, have been documented in some limited cases, typically in patients with immune suppression. HEV has demonstrated extensive genomic diversity and a variety of HEV strains have been identified worldwide from human populations as well as growing numbers of animal species. The genetic variability and constant evolution of HEV contribute to its physiopathogenesis and adaptation to new hosts. This review describes the recent classification of the Hepeviridae family, global genotype distribution, clinical significance of HEV genotype and genomic variability and evolution of HEV.
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Affiliation(s)
- Putu Prathiwi Primadharsini
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi 329-0498, Japan.
| | - Shigeo Nagashima
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi 329-0498, Japan.
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi 329-0498, Japan.
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23
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Wang H, Karlsson M, Lindberg M, Nyström K, Norder H. Hepatitis E virus strains infecting Swedish domestic pigs are unique for each pig farm and remain in the farm for at least 2 years. Transbound Emerg Dis 2019; 66:1314-1323. [PMID: 30784199 PMCID: PMC6850098 DOI: 10.1111/tbed.13153] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 02/10/2019] [Accepted: 02/12/2019] [Indexed: 12/15/2022]
Abstract
Hepatitis E virus (HEV) genotype 3 (HEV3) is distributed globally and infects both humans and animals, mainly domestic pigs and wild boars, which are the major reservoirs. In this study, the prevalence of HEV among Swedish pigs was investigated by HEV RNA analysis in 363 faecal samples from 3-month-old piglets sampled twice (2013 and 2014) in 30 Swedish pig farms. Four different types of farms were investigated; organic, conventional closed (keeping the sow), satellites in a sow pool (conventional farms sharing sows) and conventional non-closed farms (purchasing gilts). More than two-thirds (77%) of the farms had HEV-infected pigs. HEV RNA was found in faeces from 79 pigs (22%). Partial ORF1 could be sequenced in 46 strains. Phylogenetic analysis revealed a unique HEV3 strain for each farm. Strains sampled more than a year apart from the same farm were closely related, indicating that the same HEV strain is present for several years on the farm. Despite that only 4% of the Swedish pig farms were investigated, two farms had strains similar to those from humans, another had strains similar to wild boar HEV. The uniqueness of strains from each farm indicates a possibility to identify a source of infection down to farm level. This knowledge may be used by the farms to investigate the effectiveness of good hygiene routines to reduce the amount of HEV and thus the infection risk in the farm, and for Swedish public health authorities to identify cases of HEV transmissions from consumption of uncooked pork.
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Affiliation(s)
- Hao Wang
- Department of Infectious DiseasesInstitute of BiomedicineSahlgrenska AcademyGothenburg UniversityGothenburgSweden
| | - Marie Karlsson
- Department of Infectious DiseasesInstitute of BiomedicineSahlgrenska AcademyGothenburg UniversityGothenburgSweden
| | | | - Kristina Nyström
- Department of Infectious DiseasesInstitute of BiomedicineSahlgrenska AcademyGothenburg UniversityGothenburgSweden
| | - Heléne Norder
- Department of Infectious DiseasesInstitute of BiomedicineSahlgrenska AcademyGothenburg UniversityGothenburgSweden
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24
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Yue N, Wang Q, Zheng M, Wang D, Duan C, Yu X, Zhang X, Bao C, Jin H. Prevalence of hepatitis E virus infection among people and swine in mainland China: A systematic review and meta-analysis. Zoonoses Public Health 2019; 66:265-275. [PMID: 30884147 DOI: 10.1111/zph.12555] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2018] [Revised: 11/19/2018] [Accepted: 11/24/2018] [Indexed: 12/17/2022]
Abstract
Hepatitis E virus (HEV) infection remains an important public health problem, and it is endemic primarily in developing countries. This study aimed to evaluate the seroprevalence of HEV among the general population, occupational population and swine in mainland China and its risk factors based on a systematic review and meta-analysis. Systematic search from EMBASE, PubMed, Web of Science, Cochrane Library and several Chinese databases, such as Wanfang (WF) Data, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP) and SINOMED, was searched from inception up to 25 April 2018. The overall seroprevalence of HEV and its corresponding 95% confidence interval (CI) as well as the correlation coefficients between different groups were estimated using stata 12.0 and r-3.4.1 software. Potential sources of heterogeneity were explored using subgroup and sensitivity analyses. Twenty-eight studies with 57,274 participants (including human and swine) were included. The seroprevalence of anti-HEV immunoglobulin G (IgG) among the general population, occupational population and swine was 27.3% (95% CI: 22.4-32.2), 47.4% (95% CI: 40.1-54.8) and 66.4% (95% CI: 61.7-71.1), respectively. The overall prevalence of IgM among the general population was 1.8% (95% CI: 0.7-2.9). The odds ratio for the occupational population, as compared to the general population, was 2.63. The highest anti-HEV IgG prevalence (59%) was observed in East China, whereas the lowest (34.8%) was noted in Northeast and North China. In the occupational population, the highest prevalence (77.0%) was observed among swine vendors. Seven studies included 30,392 participants (humans and swine); the correlation coefficient for the prevalence of anti-HEV IgG between the professional population and adult pigs was 0.88. Sensitivity analyses showed that the stability of results was not considered significant. This research found that HEV is common in China, and contact with pork or other pig products may be an important mode of HEV transmission.
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Affiliation(s)
- Na Yue
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China.,Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
| | - Qiang Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China.,Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
| | - Mengyun Zheng
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China.,Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
| | - Donglei Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China.,Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
| | - Chunxiao Duan
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China.,Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
| | - Xiaoge Yu
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China.,Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
| | - Xuefeng Zhang
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China
| | - Changjun Bao
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China
| | - Hui Jin
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China.,Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
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25
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Denner J. Hepatitis E virus (HEV)-The Future. Viruses 2019; 11:E251. [PMID: 30871152 PMCID: PMC6466233 DOI: 10.3390/v11030251] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 03/05/2019] [Accepted: 03/09/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatitis (HEV) is widely distributed in pigs and is transmitted with increasing numbers to humans by contact with pigs, contaminated food and blood transfusion. The virus is mostly apathogenic in pigs but may enhance the pathogenicity of other pig viruses. In humans, infection can lead to acute and chronic hepatitis and extrahepatic manifestations. In order to stop the emerging infection, effective counter-measures are required. First of all, transmission by blood products can be prevented by screening all blood donations. Meat and sausages should be appropriately cooked. Elimination of the virus from the entire pork production can be achieved by sensitive testing and elimination programs including early weaning, colostrum deprivation, Caesarean delivery, embryo transfer, treatment with antivirals, protection from de novo infection, and possibly vaccination. In addition, contaminated water, shellfish, vegetables, and fruits by HEV-contaminated manure should be avoided. A special situation is given in xenotransplantation using pig cells, tissues or organs in order to alleviate the lack of human transplants. The elimination of HEV from pigs, other animals and humans is consistent with the One Health concept, preventing subclinical infections in the animals as well as preventing transmission to humans and disease.
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26
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Cella E, Golkocheva-Markova E, Sagnelli C, Scolamacchia V, Bruni R, Villano U, Ciccaglione AR, Equestre M, Sagnelli E, Angeletti S, Ciccozzi M. Human hepatitis E virus circulation in Bulgaria: Deep Bayesian phylogenetic analysis for viral spread control in the country. J Med Virol 2019; 91:132-138. [PMID: 30168583 DOI: 10.1002/jmv.25296] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Accepted: 07/07/2018] [Indexed: 12/23/2022]
Abstract
Hepatitis E virus (HEV) infection in Bulgaria is endemic, as demonstrated by the seroprevalence of antibody against the virus in the general population and by the high prevalence of clinical cases registered. In this study, a deep Bayesian phylogenetic analysis has been performed to provide information on the genetic diversity and the spread of HEV genotypes in Bulgaria. Three different data sets of HEV virus was built for genotyping by the maximum likelihood method, for evolutionary rate estimated by Bayesian Markov Chain Monte Carlo approach, for demographic history investigation and for selective pressure analysis. The evolutionary rate for genotype 3e, was 351 × 10-3 substitution/site/year (95% highest posterior density [95% HPD]: 145 × 10 -3 -575 × 10 -3 ). The root of the time to the most recent common ancestor of the Bayesian maximum clade credibility tree of HEV 3e genotype corresponded to 1965 (HPD 95% 1949-1994). The Bulgarian sequences mainly clustered in the main clade (clade A). The monophyletic clade included all Bulgarian genotype 3e sequences. The demographic history showed a slight growth from 1995 to 2000, followed by a sort of bottleneck in 2010s, a peak in 2011 and a new growth to 2015. Selection pressure analysis did not show sites under positive pressure but 64 statistically significant sites under negative selection. Molecular epidemiological surveillance by Bayesian phylogeny of HEV virus can contribute to trace the way of human infection after contact with swine source directly or heating meat improving public health control.
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Affiliation(s)
- Eleonora Cella
- Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, Rome, Italy
| | - Elitsa Golkocheva-Markova
- NRL of Viral Hepatitis, Virology Department, National Center of Infectious and Parasitic Diseases (NCIPD), Sofia, Bulgaria
| | - Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Vittoria Scolamacchia
- Unit of Clinical Laboratory Science, University Campus Bio-Medico of Rome, Rome, Italy
| | - Roberto Bruni
- Viral Hepatitis and Oncovirus and Retrovirus Diseases Unit, Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Umbertina Villano
- Viral Hepatitis and Oncovirus and Retrovirus Diseases Unit, Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Anna Rita Ciccaglione
- Viral Hepatitis and Oncovirus and Retrovirus Diseases Unit, Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Michele Equestre
- Department of Neurosciences, Istituto Superiore di Sanità, Rome, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Silvia Angeletti
- Unit of Clinical Laboratory Science, University Campus Bio-Medico of Rome, Rome, Italy
| | - Massimo Ciccozzi
- Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, Rome, Italy
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27
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Su Q, Zhang Y, Li Y, Cui Z, Chang S, Zhao P. Epidemiological investigation of the novel genotype avian hepatitis E virus and co-infected immunosuppressive viruses in farms with hepatic rupture haemorrhage syndrome, recently emerged in China. Transbound Emerg Dis 2018; 66:776-784. [PMID: 30484967 DOI: 10.1111/tbed.13082] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Revised: 10/24/2018] [Accepted: 11/20/2018] [Indexed: 01/25/2023]
Abstract
Since 2016, hepatic rupture haemorrhage syndrome (HRHS) appeared in chickens of China and caused huge economic loss. To assess the infection status of the avian hepatitis E virus (HEV) and co-infected viruses, including avian leukosis virus (ALV), reticuloendotheliosis virus (REV), fowl adenovirus (FAdV), and chicken infectious anaemia virus (CIAV), in farms with HRHS, 180 liver samples were collected from 24 farms in different provinces and detected by strict molecular virology methods. Results showed that the positive rates of HEV, ALV, REV, FAdV, and CIAV were 74.44%, 20.00%, 27.78%, 31.11%, and 12.22%, respectively, whereas there are also 112 samples with co-infection, for a rate of 58%. Meanwhile, the positive rate of HEV decreased gradually with age; the lowest positive rate of ALV (5.76%) and REV (19.23%) appeared in 25-35 weeks age, during which the positive rate of CIAV was the highest (19.23%); the positive rate of HEV in layers (64.00%) was lower than that of broilers (83.33%), but the positive rates of ALV (38.46%) and CIAV (15.38%) in layers were higher than that of broilers (5.88%, 9.80%); the positive rates of HEV (75.88%) and CIAV (15.60%) in parental generation (PG) were higher than that of commodity generation (CG, 64.10%, 0.00%), whereas the positive rate of ALV showed inverse relationship (PG: 14.89%; CG: 38.46%). Additionally, phylogenetic analysis showed that all the avian HEV identified this study belong to a novel genotype, and found the close relationship between the wild strains (REV and CIAV) and corresponding isolates from contaminated vaccine. The data presented in this report will enhance the current understanding of the epidemiology characteristics in farms with HRHS in China.
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Affiliation(s)
- Qi Su
- College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, Shandong, China.,Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, Shandong, China
| | - Yawen Zhang
- College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, Shandong, China.,Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, Shandong, China
| | - Yang Li
- China Animal Health and Epidemiology Center, Qingdao, Shandong, China
| | - Zhizhong Cui
- College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, Shandong, China.,Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, Shandong, China
| | - Shuang Chang
- College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, Shandong, China.,Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, Shandong, China
| | - Peng Zhao
- College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, Shandong, China.,Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, Shandong, China
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28
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Dalton HR, Izopet J. Transmission and Epidemiology of Hepatitis E Virus Genotype 3 and 4 Infections. Cold Spring Harb Perspect Med 2018. [PMID: 29530946 DOI: 10.1101/cshperspect.a032144] [Citation(s) in RCA: 72] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Following the introduction of robust serological and molecular tools, our understanding of the epidemiology of zoonotic hepatitis E virus (HEV) has improved considerably in recent years. Current thinking suggests that consumption of pork meat products is the key route of infection in humans, but it is certainly not the only one. Other routes of infection include environmental spread, contaminated water, and via the human blood supply. The epidemiology of HEV genotype (gt)3 and gt4 is complex, as there are several sources and routes of infection, and it is likely that these vary between and within countries and over time.
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Affiliation(s)
- Harry R Dalton
- Royal Cornwall Hospital, Truro TR1 3LJ, United Kingdom.,European Centre for Environment and Human Health, University of Exeter, Truro TR1 3LJ, United Kingdom
| | - Jacques Izopet
- Department of Virology, Hepatitis E Virus National Reference Centre, Toulouse University Hospital, 31059 Toulouse, France.,Toulouse-Purpan Centre for Pathophysiology, INSERM UMR1043/CNRS UMR 5282, CPTP, Toulouse University Paul Sabatier, 31024 Toulouse, France
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29
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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: 24] [Impact Index Per Article: 3.4] [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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30
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Su Q, Li Y, Zhang Y, Zhang Z, Meng F, Cui Z, Chang S, Zhao P. Characterization of the novel genotype avian hepatitis E viruses from outbreaks of hepatic rupture haemorrhage syndrome in different geographical regions of China. Transbound Emerg Dis 2018; 65:2017-2026. [PMID: 30086212 DOI: 10.1111/tbed.12987] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Revised: 08/01/2018] [Accepted: 08/02/2018] [Indexed: 12/21/2022]
Abstract
Since 2016, hepatic rupture haemorrhage syndrome (HRHS) has emerged in layer and broiler breeder hens in several provinces of China, and novel genotype avian hepatitis E viruses were detected from these chickens. To gain a better understanding of the genetic properties of the novel avian HEV strain, the capsid gene of four isolates from birds at four farms experiencing HRHS in different geographical regions were determined and compared with those of reported pathogenic and nonpathogenic avian HEV isolates as well as mammalian HEVs. Results showed that all those isolates share 80.1%-88.2% nucleotide sequence identity and 89.3%-91.9% amino acid sequence identity with other published avian HEV strains, while phylogenetic analysis further demonstrate that a novel genotype avian HEV was epidemic in China. Meanwhile, sequence analysis revealed that those novel isolates contain various amino acid mutations and even a hypervariable region in their major antigenic domains, which might be the critical factors for the pathogenicity elevation and even change their antigenicity. The data presented in this report will enhance the current understanding of the epidemiology and genetic diversity of the novel genotype avian HEV in China and provide additional insight into the critical factors that determine the pathogenicity of it.
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Affiliation(s)
- Qi Su
- College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, Shandong, China.,Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, Shandong, China
| | - Yang Li
- China Animal Health and Epidemiology Center, Qingdao, Shandong, China
| | - Yawen Zhang
- College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, Shandong, China.,Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, Shandong, China
| | - Zhihui Zhang
- College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, Shandong, China.,Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, Shandong, China
| | - Fanfeng Meng
- College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, Shandong, China.,Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, Shandong, China
| | - Zhizhong Cui
- College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, Shandong, China.,Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, Shandong, China
| | - Shuang Chang
- College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, Shandong, China.,Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, Shandong, China
| | - Peng Zhao
- College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, Shandong, China.,Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, Shandong, China
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Su Q, Li Y, Meng F, Cui Z, Chang S, Zhao P. Hepatic rupture hemorrhage syndrome in chickens caused by a novel genotype avian hepatitis E virus. Vet Microbiol 2018; 222:91-97. [PMID: 30080679 DOI: 10.1016/j.vetmic.2018.06.019] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Revised: 06/25/2018] [Accepted: 06/25/2018] [Indexed: 01/01/2023]
Abstract
Since 2016, severe outbreaks of hepatic rupture hemorrhage syndrome (HRHS) have emerged in chickens in several Chinese provinces and caused huge economic losses to the poultry industry, but the etiological characteristics and pathogenic potential of it has remained unclear. This study sequenced the partial helicase and capsid gene of the potentially novel avian hepatitis E virus (HEV) isolated from chickens with HRHS and tested the pathogenicity of it on SPF chicks, while the appearance of clinical signs, histopathological changes, viral distribution, viremia and viral shedding were monitored for 14 days post-infection (dpi). Analysis revealed that the HRHS related avian HEV belongs to a novel genotype, and infected chicks developed the typical symptoms of HRHS. Thus, this study successfully developed an experimental infection model for studying the pathogenicity and role of the novel avian HEV in HRHS. Meanwhile, the novel avian HEV mainly existed in the liver and spleen, inducing a rapid viremia and chronic viral shedding in infected chicks, and could cause 40% mortality before 14 dpi. In conclusion, this study found the novel genotype avian HEV and confirmed its role in HRHS.
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Affiliation(s)
- Qi Su
- College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Tai'an City, Shandong Province, 271018, China; Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, 61 Daizong Street, Tai'an City, Shandong Province, 271018, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, 61 Daizong Street, Tai'an City, Shandong Province, 271018, China
| | - Yang Li
- China Animal Health and Epidemiology Center, 369 Nanjing Street, Qingdao, Shandong, 266000, China
| | - Fanfeng Meng
- College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Tai'an City, Shandong Province, 271018, China; Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, 61 Daizong Street, Tai'an City, Shandong Province, 271018, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, 61 Daizong Street, Tai'an City, Shandong Province, 271018, China
| | - Zhizhong Cui
- College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Tai'an City, Shandong Province, 271018, China; Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, 61 Daizong Street, Tai'an City, Shandong Province, 271018, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, 61 Daizong Street, Tai'an City, Shandong Province, 271018, China
| | - Shuang Chang
- College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Tai'an City, Shandong Province, 271018, China; Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, 61 Daizong Street, Tai'an City, Shandong Province, 271018, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, 61 Daizong Street, Tai'an City, Shandong Province, 271018, China
| | - Peng Zhao
- College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Tai'an City, Shandong Province, 271018, China; Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, 61 Daizong Street, Tai'an City, Shandong Province, 271018, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, 61 Daizong Street, Tai'an City, Shandong Province, 271018, China.
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Dalton HR, Kamar N, Baylis SA, Moradpour D, Wedemeyer H, Negro F. EASL Clinical Practice Guidelines on hepatitis E virus infection. J Hepatol 2018; 68:1256-1271. [PMID: 29609832 DOI: 10.1016/j.jhep.2018.03.005] [Citation(s) in RCA: 434] [Impact Index Per Article: 62.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Accepted: 03/09/2018] [Indexed: 02/08/2023]
Abstract
Infection with hepatitis E virus (HEV) is a significant cause of morbidity and mortality, representing an important global health problem. Our understanding of HEV has changed completely over the past decade. Previously, HEV was thought to be limited to certain developing countries. We now know that HEV is endemic in most high-income countries and is largely a zoonotic infection. Given the paradigm shift in our understanding of zoonotic HEV and that locally acquired HEV is now the commonest cause of acute viral hepatitis in many European countries, the focus of these Clinical Practice Guidelines will be on HEV genotype 3 (and 4).
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Absence of zoonotic hepatitis E virus infection in Flemish dairy cows. Int J Food Microbiol 2018; 281:54-59. [PMID: 29852395 DOI: 10.1016/j.ijfoodmicro.2018.05.009] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Revised: 03/28/2018] [Accepted: 05/08/2018] [Indexed: 02/08/2023]
Abstract
Recently, infectious HEV particles were discovered in milk and fecal samples of dairy cows in China. Given the recent increase of autochthonous HEV infections in Europe, we wanted to assess whether cows constitute an HEV reservoir in this region and hence may be responsible for the advance of HEV through consumption of cow produce. To verify the zoonotic risk cows potentially pose towards European consumers, we screened >10% of dairy milk farms in Flanders, Belgium for the presence of HEV. A quarter of these housed both cows and pigs, the latter a well-known reservoir for HEV. Milk and fecal samples were analyzed for the presence of HEV RNA and HEV-specific antibodies. Despite the fact that HEV is circulating amongst pig farms in Flanders and proof of active HEV infection in the pigs of at least one of the mixed farms included in our study, we could not detect any sign of active or past HEV infection in cows. The HEV prevalence in our study was 0%, with a 99.99% confidence interval (CI) for HEV RNA and anti-HEV antibody of [0%-2.30%] and [0%-4.23%] respectively. Our results suggest that, at least in Flanders, cows are not an HEV reservoir and hence do not pose a major health risk towards humans.
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Melgaço JG, Gardinali NR, de Mello VDM, Leal M, Lewis-Ximenez LL, Pinto MA. Hepatitis E: Update on Prevention and Control. BIOMED RESEARCH INTERNATIONAL 2018; 2018:5769201. [PMID: 29546064 PMCID: PMC5818934 DOI: 10.1155/2018/5769201] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Revised: 11/28/2017] [Accepted: 12/13/2017] [Indexed: 12/20/2022]
Abstract
Hepatitis E virus (HEV) is a common etiology of acute viral hepatitis worldwide. Recombinant HEV vaccines have been developed, but only one is commercially available and licensed in China since 2011. Epidemiological studies have identified genotype 3 as the major cause of chronic infection in immunocompromised individuals. Ribavirin has been shown to be effective as a monotherapy to induce HEV clearance in chronic patients who have undergone solid organ transplant (SOT) under immunosuppressive therapy. Efforts and improvements in prevention and control have been made to reduce the instances of acute and chronic hepatitis E in endemic and nonendemic countries. However, this review shows that further studies are required to demonstrate the importance of preventive vaccination and treatment worldwide, with emphasis on hepatitis E infection in the public health system.
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Affiliation(s)
- Juliana Gil Melgaço
- Ambulatório/Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Noemi Rovaris Gardinali
- Laboratório de Desenvolvimento Tecnológico em Virologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Vinicius da Motta de Mello
- Ambulatório/Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Mariana Leal
- Ambulatório/Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Lia Laura Lewis-Ximenez
- Ambulatório/Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Marcelo Alves Pinto
- Laboratório de Desenvolvimento Tecnológico em Virologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
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Detection and Characterization of Hepatitis E Virus in Goats at Slaughterhouse in Tai'an Region, China. BIOMED RESEARCH INTERNATIONAL 2017; 2017:3723650. [PMID: 29379797 PMCID: PMC5742876 DOI: 10.1155/2017/3723650] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Accepted: 11/26/2017] [Indexed: 12/11/2022]
Abstract
Background Hepatitis E virus (HEV) is a significant pathogen of viral hepatitis and can be transmitted through fecal-oral route. Epidemiological data concerning HEV in goats, however, are relatively sparse to date. Here, the prevalence and characteristics of HEV isolated from goats at slaughterhouse were investigated in Tai'an region, China. Methods Anti-HEV immunoglobulin G (IgG) in blood samples and HEV RNA in the liver samples were determined by using an enzyme-linked immunosorbent assay (ELISA) and a nested reverse transcription polymerase chain reaction (RT-PCR), respectively. In addition, partial nucleotide sequences of open reading frame 2 (ORF-2) of HEV isolates were analyzed. Results Fifty goat blood samples (46.7%, 50/120) were masculine for anti-HEV IgG. HEV RNA was detected in 2 liver samples (4.0%, 2/50) and belonged to genotype 4 subtype 4 h, with high identity (91.2-93%) with cow HEV strains detected in the same province, China. Conclusions These findings demonstrated that goats may be an important reservoir for HEV and can become a major source of HEV infection in humans via food chain.
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Abstract
Hepatitis E virus (HEV) is globally prevalent with relatively high percentages of anti-HEV immunoglobulin G-positive individuals in the populations of developing and developed countries. There are two distinct epidemiologic patterns of hepatitis E. In areas with high disease endemicity, primarily developing countries in Asia and Africa, this disease is caused mainly by genotype 1 or 2 HEV, both of which transmit predominantly through contaminated water and occur as either outbreaks or as sporadic cases of acute hepatitis. The acute hepatitis caused by either of these two genotypes has the highest attack rate in young adults, and the disease is particularly severe among pregnant women. In developed countries, sporadic cases of locally acquired genotype 3 or 4 HEV infection are observed. The reservoir of genotype 3 and 4 HEV is believed to be animals, such as pigs, with zoonotic transmission to humans. The affected persons are often elderly, and persistent infection has been well documented among immunosuppressed persons. A subunit vaccine has been shown to be effective in preventing clinical disease and has been licensed in China.
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Affiliation(s)
- Yansheng Geng
- School of Public Health, Hebei University, No. 342 Yuhuadonglu, Baoding, 071000, China.
| | - Youchun Wang
- Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, No. 2 Tiantanxili, Dongcheng District, Beijing, 100050, China
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Mauceri C, Grazia Clemente M, Castiglia P, Antonucci R, Schwarz KB. Hepatitis E in Italy: A silent presence. J Infect Public Health 2017; 11:1-8. [PMID: 28864359 DOI: 10.1016/j.jiph.2017.08.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Revised: 07/03/2017] [Accepted: 08/04/2017] [Indexed: 01/18/2023] Open
Abstract
Hepatitis E virus (HEV) was discovered in the 1980s and has been considered as being confined to developing countries. The purpose of this critical review was to determine the reported HEV seroprevalence rates in Italy, to identify predisposing factors and individuals at risk and to assess possible importation of HEV by immigrants. A critical review of 159 articles published in PubMed from 1994 to date was done. Only 27 original reports of 50 or more subjects, written in the English or Italian language, were included. Over three decades, the HEV seroprevalence varied from 0.12% to 49%, with the highest rates being reported from the central region of Italy. Risk factors included ingestion of raw pork or potentially contaminated food. The seroprevalence among immigrants ranged from 15.3% to 19.7% in Apulia. Italy has a population of 60656000; the total number of individuals surveyed was only 21.882 (0.036%). A national epidemiological survey program is needed to capture more comprehensive seroprevalence data.
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Affiliation(s)
- Carlo Mauceri
- Pediatric Clinic, Department of Surgical, Microsurgical and Medical Sciences, University of Sassari Medical School, 07100 Sassari, Italy.
| | - Maria Grazia Clemente
- Pediatric Clinic, Department of Surgical, Microsurgical and Medical Sciences, University of Sassari Medical School, 07100 Sassari, Italy.
| | - Paolo Castiglia
- Department of Biomedical Sciences-Hygiene and Preventive Medicine Unit, University-AOU of Sassari, 07100 Sassari, Italy.
| | - Roberto Antonucci
- Pediatric Clinic, Department of Surgical, Microsurgical and Medical Sciences, University of Sassari Medical School, 07100 Sassari, Italy.
| | - Kathleen B Schwarz
- Pediatric Liver Center, Johns Hopkins University School of Medicine, Baltimore 21287, MD, USA.
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Mykytczuk O, Harlow J, Bidawid S, Corneau N, Nasheri N. Prevalence and Molecular Characterization of the Hepatitis E Virus in Retail Pork Products Marketed in Canada. FOOD AND ENVIRONMENTAL VIROLOGY 2017; 9:208-218. [PMID: 28197972 PMCID: PMC5429394 DOI: 10.1007/s12560-017-9281-9] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Accepted: 01/31/2017] [Indexed: 05/21/2023]
Abstract
Infection with the hepatitis E virus (HEV) is very common worldwide. HEV causes acute viral hepatitis with approximately 20 million cases per year. While HEV genotypes 1 and 2 cause large waterborne and foodborne outbreaks with a significant mortality in developing countries, genotypes 3 and 4 are more prevalent in developed countries with transmission being mostly zoonotic. In North America and Europe, HEV has been increasingly detected in swine, and exposure to pigs and pork products is considered to be the primary source of infection. Therefore we set out to investigate the prevalence of HEV in retail pork products available in Canada, by screening meal-size portions of pork pâtés, raw pork sausages, and raw pork livers. The presence of the HEV genomes was determined by RT-PCR and viral RNA was quantified by digital droplet PCR. Overall, HEV was detected in 47% of the sampled pork pâtés and 10.5% of the sampled raw pork livers, but not in the sampled pork sausages, and sequencing confirmed that all HEV strains belonged to genotype 3. Further phylogenetic analysis revealed that except for one isolate that clusters with subtype 3d, all isolates belong to subtype 3a. Amino acid variations between the isolates were also observed in the sequenced capsid region. In conclusion, the prevalence of HEV in pâtés and raw pork livers observed in this study is in agreement with the current HEV distribution in pork products reported in other developed countries.
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Affiliation(s)
- Oksana Mykytczuk
- National Food Virology Reference Centre, Bureau of Microbial Hazards, Food Directorate, Health Canada, 251 Sir Frederick Banting Driveway, Ottawa, ON, K1A 0K9, Canada
| | - Jennifer Harlow
- National Food Virology Reference Centre, Bureau of Microbial Hazards, Food Directorate, Health Canada, 251 Sir Frederick Banting Driveway, Ottawa, ON, K1A 0K9, Canada
| | - Sabah Bidawid
- National Food Virology Reference Centre, Bureau of Microbial Hazards, Food Directorate, Health Canada, 251 Sir Frederick Banting Driveway, Ottawa, ON, K1A 0K9, Canada
| | - Nathalie Corneau
- National Food Virology Reference Centre, Bureau of Microbial Hazards, Food Directorate, Health Canada, 251 Sir Frederick Banting Driveway, Ottawa, ON, K1A 0K9, Canada
| | - Neda Nasheri
- National Food Virology Reference Centre, Bureau of Microbial Hazards, Food Directorate, Health Canada, 251 Sir Frederick Banting Driveway, Ottawa, ON, K1A 0K9, Canada.
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Jeong SH, Park BJ, Kim YH, Choi YS, Ahn HS, Han SH, Choi IS. Isolation of hepatitis E virus genotype 4 from patients with acute cryptogenic hepatitis in Korea. J Clin Virol 2017; 89:10-13. [PMID: 28189935 DOI: 10.1016/j.jcv.2017.02.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Revised: 01/23/2017] [Accepted: 02/05/2017] [Indexed: 01/24/2023]
Abstract
BACKGROUND Autochthonous hepatitis E occurs sporadically in developed countries. The consumption of undercooked pork containing hepatitis E virus genotype 3 (HEV-3) or 4 (HEV-4) is the major risk factor for infection. The serological diagnostic kits currently used in hospitals sometimes produce false-negative or -positive results. Therefore, detection of both HEV RNA and antibodies to the virus is required for confirmative diagnosis of hepatitis E. OBJECTIVES We aimed to detect HEV in serum samples from patients with cryptogenic hepatitis and to determine the origin of HEV. STUDY DESIGN A nested polymerase chain reaction (PCR) method was developed for detection of HEV-3 and HEV-4 in patients with hepatitis. A total of 23 serum samples, deposited in 2006-2012, from patients with acute cryptogenic hepatitis who were serologically negative for hepatitis A, B, C, and E were examined using this method. The amplified PCR products were genetically analyzed. RESULTS Four HEV-4 isolates were detected from the 23 serum samples. Phylogenetic analysis indicated that three of the four isolates were closely related to HEV-4 isolates found in pigs in Korea and in patients with hepatitis E in Japan. CONCLUSIONS The newly developed nested PCR method was useful for detection of HEV in patients with cryptogenic hepatitis. The close relationship between the human HEV-4 isolates identified in this study and swine isolates implied that zoonotic transmission of HEV might be a source of infection in patients with hepatitis.
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Affiliation(s)
- Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, College of Medicine, Seoul National University, Seongnam, Gyeonggi 13620, Republic of Korea
| | - Byung-Joo Park
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Yong-Hyun Kim
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Yun Suk Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, College of Medicine, Seoul National University, Seongnam, Gyeonggi 13620, Republic of Korea
| | - Hee-Seop Ahn
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Sang-Hoon Han
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - In-Soo Choi
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea.
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40
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Baechlein C, Becher P. No evidence for zoonotic hepatitis E virus infection through dairy milk in Germany. Hepatology 2017; 65:394-395. [PMID: 27718279 DOI: 10.1002/hep.28863] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Revised: 08/24/2016] [Accepted: 08/24/2016] [Indexed: 02/02/2023]
Affiliation(s)
- Christine Baechlein
- Institute of Virology, Department of Infectious Diseases, University of Veterinary Medicine Hannover, Germany, Hannover, Germany.,German Center for Infection Research, Partner Site Hannover-Braunschweig, Hannover, Germany
| | - Paul Becher
- Institute of Virology, Department of Infectious Diseases, University of Veterinary Medicine Hannover, Germany, Hannover, Germany.,German Center for Infection Research, Partner Site Hannover-Braunschweig, Hannover, Germany
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Roth A, Lin J, Magnius L, Karlsson M, Belák S, Widén F, Norder H. Markers for Ongoing or Previous Hepatitis E Virus Infection Are as Common in Wild Ungulates as in Humans in Sweden. Viruses 2016; 8:E259. [PMID: 27657108 PMCID: PMC5035973 DOI: 10.3390/v8090259] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Revised: 08/30/2016] [Accepted: 09/13/2016] [Indexed: 12/18/2022] Open
Abstract
Hepatitis E virus (HEV) is a human pathogen with zoonotic spread, infecting both domestic and wild animals. About 17% of the Swedish population is immune to HEV, but few cases are reported annually, indicating that most infections are subclinical. However, clinical hepatitis E may also be overlooked. For identified cases, the source of infection is mostly unknown. In order to identify whether HEV may be spread from wild game, the prevalence of markers for past and/or ongoing infection was investigated in sera and stool samples collected from 260 hunted Swedish wild ungulates. HEV markers were found in 43 (17%) of the animals. The most commonly infected animal was moose (Alces alces) with 19 out of 69 animals (28%) showing HEV markers, followed by wild boar (Sus scrofa) with 21 out of 139 animals (15%), roe deer (Capreolus capreolus) with 2 out of 30 animals, red deer (Cervus elaphus) with 1 out of 15 animals, and fallow deer (Dama dama) 0 out of 7 animals. Partial open reading frame 1 (ORF1) of the viral genomes from the animals were sequenced and compared with those from 14 endemic human cases. Phylogenetic analysis revealed that three humans were infected with HEV strains similar to those from wild boar. These results indicate that wild animals may be a source of transmission to humans and could be an unrecognized public health concern.
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Affiliation(s)
- Anette Roth
- Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, 413 46 Gothenburg, Sweden.
| | - Jay Lin
- Department of Virology, Microbiology, National Veterinary Institute, 756 51 Uppsala, Sweden.
- Department of Biomedical Science and Veterinary Public Health, Swedish University of Agricultural Sciences (SLU), 756 51 Uppsala, Sweden.
- The OIE (World Organisation for Animal Health) Collaborating Centre for the Biotechnology-Based Diagnosis of Infectious Diseases in Veterinary Medicine, 756 51 Uppsala, Sweden.
| | - Lars Magnius
- Ulf Lundahl Foundation, 116 21 Stockholm, Sweden.
| | - Marie Karlsson
- Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, 413 46 Gothenburg, Sweden.
| | - Sándór Belák
- Department of Biomedical Science and Veterinary Public Health, Swedish University of Agricultural Sciences (SLU), 756 51 Uppsala, Sweden.
- The OIE (World Organisation for Animal Health) Collaborating Centre for the Biotechnology-Based Diagnosis of Infectious Diseases in Veterinary Medicine, 756 51 Uppsala, Sweden.
| | - Frederik Widén
- Department of Virology, Microbiology, National Veterinary Institute, 756 51 Uppsala, Sweden.
- Department of Biomedical Science and Veterinary Public Health, Swedish University of Agricultural Sciences (SLU), 756 51 Uppsala, Sweden.
- The OIE (World Organisation for Animal Health) Collaborating Centre for the Biotechnology-Based Diagnosis of Infectious Diseases in Veterinary Medicine, 756 51 Uppsala, Sweden.
| | - Heléne Norder
- Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, 413 46 Gothenburg, Sweden.
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Huang F, Li Y, Yu W, Jing S, Wang J, Long F, He Z, Yang C, Bi Y, Cao W, Liu C, Hua X, Pan Q. Excretion of infectious hepatitis E virus into milk in cows imposes high risks of zoonosis. Hepatology 2016; 64:350-9. [PMID: 27286751 DOI: 10.1002/hep.28668] [Citation(s) in RCA: 161] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Revised: 06/02/2016] [Accepted: 06/02/2016] [Indexed: 12/23/2022]
Abstract
UNLABELLED Hepatitis E virus (HEV) represents the main cause of acute hepatitis worldwide. HEV infection in immunocompromised patients involves a high risk for the development of chronic hepatitis. Because HEV is recognized as a zoonotic pathogen, it is currently believed that swine is the primary reservoir. However, this is not sufficient to justify the strikingly high seroprevalence of HEV in both developing and Western countries. Thus, this study aimed to identify new zoonotic sources that bear a high risk of transmission to humans. We collected fecal, blood, and milk samples of cows in a typical rural region of Yunnan Province in southwest China, where mixed farming of domestic animals is a common practice. HEV RNA was quantified by quantitative real-time polymerase chain reaction, and the whole genome was sequenced. HEV infectivity was assessed in rhesus macaques. We found a high prevalence of active HEV infection in cows as determined by viral RNA positivity in fecal samples. Surprisingly, we discovered that HEV is excreted into milk that is produced by infected cows. Phylogenetic analysis revealed that all HEV isolates from cow/milk belong to genotype 4 and subtype 4h. Gavage with HEV-contaminated raw and even pasteurized milk resulted in active infection in rhesus macaques. Importantly, a short period of boiling, but not pasteurization, could completely inactivate HEV. CONCLUSION Infectious HEV-contaminated cow milk is recognized as a new zoonotic source that bears a high risk of transmission to humans; these results call attention to understanding and establishing proper measurement and control of HEV zoonotic transmission, particularly in the setting of mixed farming of domestic animals. (Hepatology 2016;64:350-359).
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Affiliation(s)
- Fen Huang
- Medical Faculty, Kunming University of Science and Technology, Kunming, PR China
| | - Yunlong Li
- Medical Faculty, Kunming University of Science and Technology, Kunming, PR China
| | - Wenhai Yu
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, PR China
| | - Shenrong Jing
- Medical Faculty, Kunming University of Science and Technology, Kunming, PR China
| | - Jue Wang
- Medical Faculty, Kunming University of Science and Technology, Kunming, PR China
| | - Feiyan Long
- Medical Faculty, Kunming University of Science and Technology, Kunming, PR China
| | - Zhanlong He
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, PR China
| | - Chenchen Yang
- Medical Faculty, Kunming University of Science and Technology, Kunming, PR China
| | - Yanhong Bi
- Medical Faculty, Kunming University of Science and Technology, Kunming, PR China
| | - Wentao Cao
- Medical Faculty, Kunming University of Science and Technology, Kunming, PR China
| | - Chengbo Liu
- Medical Faculty, Kunming University of Science and Technology, Kunming, PR China
| | - Xiuguo Hua
- Agriculture and Biotechnology, Shanghai Jiaotong University, Shanghai, PR, China
| | - Qiuwei Pan
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
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43
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Hépatite E aiguë sévère autochtone à virus de génotype 4. Presse Med 2016; 45:705-6. [DOI: 10.1016/j.lpm.2016.04.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2015] [Revised: 04/13/2016] [Accepted: 04/18/2016] [Indexed: 11/23/2022] Open
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Affiliation(s)
- Philippe Colson
- Méditerranée Infection, Aix-Marseille Univ., URMITE UM 63 CNRS 7278 IRD 198 INSERM U1905, Marseille, France.,IHU Méditerranée Infection, Assistance Publique-Hôpitaux de Marseille, Centre Hospitalo-Universitaire Timone, Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Fédération de Bactériologie-Hygiène-Virologie, Marseille, France
| | - Philippe Brunet
- Assistance Publique-Hôpitaux de Marseille, Centre Hospitalo-Universitaire Conception, Centre de Néphrologie et Transplantation Rénale, Marseille, France
| | - Guillaume Lano
- Assistance Publique-Hôpitaux de Marseille, Centre Hospitalo-Universitaire Conception, Centre de Néphrologie et Transplantation Rénale, Marseille, France
| | - Valérie Moal
- Méditerranée Infection, Aix-Marseille Univ., URMITE UM 63 CNRS 7278 IRD 198 INSERM U1905, Marseille, France.,Assistance Publique-Hôpitaux de Marseille, Centre Hospitalo-Universitaire Conception, Centre de Néphrologie et Transplantation Rénale, Marseille, France
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45
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Di Bartolo I, Angeloni G, Monini M, Maione E, Marrone R, Ostanello F, Ruggeri FM. Complete genome sequencing of a genotype 3 hepatitis E virus strain identified in a swine farm in Italy. Virus Res 2016; 211:89-95. [DOI: 10.1016/j.virusres.2015.09.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Revised: 09/22/2015] [Accepted: 09/23/2015] [Indexed: 01/19/2023]
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Petrik J, Lozano M, Seed CR, Faddy HM, Keller AJ, Prado Scuracchio PS, Wendel S, Andonov A, Fearon M, Delage G, Zhang J, Shih JWK, Gallian P, Djoudi R, Tiberghien P, Izopet J, Dreier J, Vollmer T, Knabbe C, Aggarwal R, Goel A, Ciccaglione AR, Matsubayashi K, Satake M, Tadokoro K, Jeong SH, Zaaijer HL, Zhiburt E, Chay J, Teo D, Chua SS, Piron M, Sauleda S, Echevarría JM, Dalton H, Stramer SL. Hepatitis E. Vox Sang 2016; 110:93-130. [PMID: 26198159 DOI: 10.1111/vox.12285] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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47
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Costanzo N, Sarno E, Peretti V, Ciambrone L, Casalinuovo F, Santoro A. Serological and Molecular Investigation of Swine Hepatitis E Virus in Pigs Raised in Southern Italy. J Food Prot 2015; 78:2099-102. [PMID: 26555536 DOI: 10.4315/0362-028x.jfp-15-159] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Hepatitis E virus (HEV) infection is a common acute hepatitis transmitted by the fecal-oral route. In developed countries, the virus has a zoonotic potential, and domestic pigs and wild boars are considered main reservoirs. To assess the prevalence of HEV-positive animals in the Calabria region (southern Italy) on a serological and molecular level, a total of 216 autochthonous healthy pigs (Apulo-Calabrese breed) were sampled. Both sera and feces were collected. Pigs were grouped based on age: 117 pigs <6 months and 99 pigs >6 months. By using a commercial enzyme-linked immunosorbent assay system, a total of 173 (80%) of the 216 pigs tested seropositive. In all sampled farms (n = 8), pigs with antibodies (immunoglobulin G) against HEV were detected at a level higher than 60%, with a significant difference among age groups (P < 0.0001). Moreover, 16 fattening pigs were found to be nested reverse transcription PCR positive and thus to shed viral genomes in their feces. These positive findings resulted in a prevalence of 48.4% on the farm level (16 of 35 pigs) and an overall prevalence of 7.4% at the animal level (16 of 216 pigs). Based on the present study, HEV seems to circulate among the autochthonous domestic pig population of southern Italy with a low sharing rate. Further studies exploring the origin of infection are needed to minimize the risk of human exposure and to reduce consequences for public health.
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Affiliation(s)
- Nicola Costanzo
- Dipartimento di Scienze della Salute, Università Magna Graecia di Catanzaro, Viale Europa-Germaneto, 88100 Catanzaro, Italy.
| | - Eleonora Sarno
- Institute for Food Safety and Hygiene, Univerity of Zurich, Winterthurerstrasse 272, 8057 Zurich, Switzerland
| | - Vincenzo Peretti
- Dipartimento di Medicina Veterinaria e Produzioni Animali, Università Federico II di Napoli, Via Delpino 1, 80137 Napoli, Italy
| | - Lucia Ciambrone
- Istituto Zooprofilattico Sperimentale del Mezzogiorno-Sezione di Catanzaro, viale Crotone, 88100 Catanzaro, Italy
| | - Francesco Casalinuovo
- Istituto Zooprofilattico Sperimentale del Mezzogiorno-Sezione di Catanzaro, viale Crotone, 88100 Catanzaro, Italy
| | - Adriano Santoro
- Dipartimento di Medicina Veterinaria e Produzioni Animali, Università Federico II di Napoli, Via Delpino 1, 80137 Napoli, Italy
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48
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[Hepatitis E virus: opinions of the Working Group of the Federal Ministry of Health Blood]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2015; 58:198-218. [PMID: 25608627 DOI: 10.1007/s00103-014-2103-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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49
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Murali AR, Kotwal V, Chawla S. Chronic hepatitis E: A brief review. World J Hepatol 2015; 7:2194-2201. [PMID: 26380044 PMCID: PMC4561773 DOI: 10.4254/wjh.v7.i19.2194] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 07/28/2015] [Accepted: 08/20/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E viral infection has traditionally been considered an acute, self-limited, water borne disease similar to hepatitis A, endemic to developing countries. However, over the past decade, zoonotic transmission and progression to chronicity in human patients has been identified, resulting in persistently elevated transaminase levels, progressive liver injury and cirrhosis. In addition to liver injury, neurological, renal and rheumatological manifestations have also been reported. Chronic hepatitis E occurs mainly in immunosuppressed individuals such as transplant recipients, human immunodeficiency virus patients with low CD4 counts and in patients with hematological malignancies receiving chemotherapy. Diagnosis is established by persistent elevation of hepatitis E virus RNA in the stool or serum. This population often requires treatment with antiviral agents, particularly ribavirin, as spontaneous clearance with reduction in immunosuppression occurs only in about a third of the patients. The purpose of this review, is to further discuss the clinical presentation, and recent advances in diagnosis, treatment and prophylaxis of chronic hepatitis E.
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Affiliation(s)
- Arvind R Murali
- Arvind R Murali, Department of Gastroenterology and Hepatology, University of Iowa Hospitals and Clinics, Iowa City, IA 52246, United States
| | - Vikram Kotwal
- Arvind R Murali, Department of Gastroenterology and Hepatology, University of Iowa Hospitals and Clinics, Iowa City, IA 52246, United States
| | - Saurabh Chawla
- Arvind R Murali, Department of Gastroenterology and Hepatology, University of Iowa Hospitals and Clinics, Iowa City, IA 52246, United States
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50
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Blasco-Perrin H, Madden RG, Stanley A, Crossan C, Hunter JG, Vine L, Lane K, Devooght-Johnson N, Mclaughlin C, Petrik J, Stableforth B, Hussaini H, Phillips M, Mansuy JM, Forrest E, Izopet J, Blatchford O, Scobie L, Peron JM, Dalton HR. Hepatitis E virus in patients with decompensated chronic liver disease: a prospective UK/French study. Aliment Pharmacol Ther 2015; 42:574-581. [PMID: 26174470 DOI: 10.1111/apt.13309] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Revised: 06/05/2015] [Accepted: 06/16/2015] [Indexed: 12/24/2022]
Abstract
BACKGROUND In developed countries, hepatitis E is a porcine zoonosis caused by hepatitis E virus (HEV) genotype 3. In developing countries, hepatitis E is mainly caused by genotype 1, and causes increased mortality in patients with pre-existing chronic liver disease (CLD). AIM To determine the role of HEV in patients with decompensated CLD. METHODS Prospective HEV testing of 343 patients with decompensated CLD at three UK centres and Toulouse France, with follow-up for 6 months or death. IgG seroprevalence was compared with 911 controls. RESULTS 11/343 patients (3.2%) had acute hepatitis E infection, and three died. There were no differences in mortality (27% vs. 26%, OR 1.1, 95% CI 0.28-4.1), age (P = 0.9), bilirubin (P = 0.5), alanine aminotransferase (P = 0.06) albumin (P = 0.5) or international normalised ratio (P = 0.6) in patients with and without hepatitis E infection. Five cases were polymerase chain reaction (PCR) positive (genotype 3). Hepatitis E was more common in Toulouse (7.9%) compared to the UK cohort (1.2%, P = 0.003). HEV IgG seroprevalence was higher in Toulouse (OR 17, 95% CI 9.2-30) and Truro (OR 2.5, 95% CI 1.4-4.6) than in Glasgow, but lower in cases, compared to controls (OR 0.59, 95% CI 0.41-0.86). CONCLUSIONS Hepatitis E occurs in a minority of patients with decompensated chronic liver disease. The mortality is no different to the mortality in patients without hepatitis E infection. The diagnosis can only be established by a combination of serology and PCR, the yield and utility of which vary by geographical location.
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Affiliation(s)
- H Blasco-Perrin
- Service d'Hépato-Gastro-Entérologie, Hôpital Purpan, Université Paul Sabatier III, Toulouse, France
| | - R G Madden
- Royal Cornwall Hospital Trust, Truro, UK
| | - A Stanley
- Glasgow Royal Infirmary, Glasgow, UK
| | - C Crossan
- Glasgow Caledonian University, Glasgow, UK
| | - J G Hunter
- Royal Cornwall Hospital Trust, Truro, UK
| | - L Vine
- Royal Cornwall Hospital Trust, Truro, UK
| | - K Lane
- Royal Cornwall Hospital Trust, Truro, UK
| | | | | | - J Petrik
- Scottish National Blood Transfusion Service, Edinburgh, UK
| | | | - H Hussaini
- Royal Cornwall Hospital Trust, Truro, UK
| | - M Phillips
- Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
| | - J M Mansuy
- Laboratoire de virologie, Hôpital Purpan, CHU de Toulouse, Toulouse, France
| | - E Forrest
- Glasgow Royal Infirmary, Glasgow, UK
| | - J Izopet
- Laboratoire de virologie, Hôpital Purpan, CHU de Toulouse, Toulouse, France
- INSERM, U1043, Toulouse, France
- Université Toulouse III Paul Sabatier, Toulouse, France
| | | | - L Scobie
- Glasgow Caledonian University, Glasgow, UK
| | - J M Peron
- Service d'Hépato-Gastro-Entérologie, Hôpital Purpan, Université Paul Sabatier III, Toulouse, France
| | - H R Dalton
- Royal Cornwall Hospital Trust, Truro, UK
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