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Haase JA, Schlienkamp S, Ring JJ, Steinmann E. Transmission patterns of hepatitis E virus. Curr Opin Virol 2025; 70:101451. [PMID: 39892085 DOI: 10.1016/j.coviro.2025.101451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 01/10/2025] [Accepted: 01/13/2025] [Indexed: 02/03/2025]
Abstract
Hepatitis E virus (HEV) causes sporadic cases in industrialized countries and endemic outbreaks in areas with lower sanitation standards. The wide host reservoir of HEV makes it a potential source of new zoonotic transmission and dissemination in humans. Thus, the perception of HEV as a confined ailment has shifted to one of global concern. Considering HEV's environmental stability and heterogeneity in the host range of HEV's genotypes, various transmission pathways and sources for HEV infections are plausible. Here, we provide an overview on HEV's transmission routes and discuss the role of HEV as a foodborne zoonosis, as well as preventive measures and open research questions.
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Affiliation(s)
- Jil A Haase
- Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany
| | - Sarah Schlienkamp
- Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany
| | - Julian J Ring
- Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany
| | - Eike Steinmann
- Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany; German Centre for Infection Research (DZIF), External Partner Site, Bochum, Germany.
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2
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Loikkanen E, Mikkelä A, Joutsen S, Tuominen P, Maunula L. Effectiveness of Cold Smoking on Inactivating Murine Norovirus in Salami-Like Pork Sausages (Mettwurst), and Hepatitis E Virus and Murine Norovirus in Solution. FOOD AND ENVIRONMENTAL VIROLOGY 2025; 17:17. [PMID: 39794680 PMCID: PMC11723849 DOI: 10.1007/s12560-024-09631-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 12/24/2024] [Indexed: 01/13/2025]
Abstract
Hepatitis E virus (HEV) is a zoonotic virus that infects humans when virus-containing pork products are consumed. This study aimed to explore MNV (murine norovirus) and HEV inactivation during cold smoking and ripening/fermentation treatments used for salami-like sausages (mettwurst). MNV inactivation was monitored in culture medium solution and in sausage while being subjected to a salami-like sausage manufacturing process. The inactivation of MNV in the solution was also monitored at room temperature (RT) for four weeks. HEV inactivation was monitored in solution during the cold smoking process and at RT. A TCID50 assay was used to calculate the infectious MNV and HEV titres. MNV survival was modelled using Bayesian inference. MNV load in solution decreased by as much as 4.7 (SD 0.9) log10 TCID50/ml when it was subjected to the cold smoking process. Modelling revealed that 99.999% MNV might be inactivated during the treatment when observed at a level of 95% CI (Bayesian Confidence Interval). On the contrary, MNV load decreased by only 1.8 (0.2) log10 when stored at RT. The low-titre HEV in solution was inactivated (> 1.1 (0.2) log10) when treated, and at RT. However, MNV was resistant in the sausage matrix during the cold smoking process (log10 reduction of 1.9 (0.5) TCID50/ml). Based on modelling, a substantial amount of virus would remain in the product, even when the uncertainty was considered. Hence, viruses, here exemplified by MNV, may not be inactivated from salami-like pork sausages during manufacturing, which poses a risk for consumers in real-life situations.
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Affiliation(s)
- Emil Loikkanen
- Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Antti Mikkelä
- Risk Assessment Unit, Laboratory and Research Department, Finnish Food Authority, Helsinki, Finland
| | - Suvi Joutsen
- Risk Assessment Unit, Laboratory and Research Department, Finnish Food Authority, Helsinki, Finland
| | - Pirkko Tuominen
- Risk Assessment Unit, Laboratory and Research Department, Finnish Food Authority, Helsinki, Finland
| | - Leena Maunula
- Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
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Monini M, Ianiro G, De Sabato L, Bivona M, Ostanello F, Di Bartolo I. Persistence of hepatitis E virus (HEV) subtypes 3c and 3e: Long-term cold storage and heat treatments. Food Microbiol 2024; 121:104529. [PMID: 38637065 DOI: 10.1016/j.fm.2024.104529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 03/06/2024] [Accepted: 03/29/2024] [Indexed: 04/20/2024]
Abstract
Hepatitis E virus (HEV) is the causative agent of foodborne infections occurring in high income countries mainly by consumption of undercooked and raw pork products. The virus is zoonotic with pigs and wild boars as the main reservoirs. Several studies proved the presence of HEV-RNA in pork liver sausages, pâté and other pork by-products. However, the detection of HEV nucleic acids does not necessary correspond to infectious virus and information on the persistence of the virus in the food is still limited. To which extent and how long the virus can survive after conventional industrial and home-made conservation and cooking procedures is largely unknown. In the present study, we investigated the persistence of two subtypes of HEV-3, by measuring the viral RNA on cell supernatant of infected A549 cells, after long-term storage at +4 °C and -20 °C and after heating for short or long-time span. Results confirmed that either low temperature storage (+4 °C) or freezing (-20 °C) do not influence the survival of the virus, and only a moderate reduction of presence of its RNA after 12 weeks at +4 °C was observed. To the other side, heating at 56 °C for long time (1 h) or at higher temperatures (>65 °C) for shorter time inactivated the virus successfully.
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Affiliation(s)
- Marina Monini
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy
| | - Giovanni Ianiro
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.
| | - Luca De Sabato
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy
| | - Marta Bivona
- Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra, 50, 40064, Ozzano Dell'Emilia, BO, Italy
| | - Fabio Ostanello
- Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra, 50, 40064, Ozzano Dell'Emilia, BO, Italy
| | - Ilaria Di Bartolo
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy
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Liu D, Liu B, He Z, Qiao C, Luo Q, Chen X, Wang X, Xiang H, Chen J, Zhang P, Huang Y, Wang G, Tan C, Cai R. Seroprevalence survey of Hepatitis E Virus in Domestic Pigs in Guangdong, China. Animals (Basel) 2024; 14:1861. [PMID: 38997973 PMCID: PMC11240697 DOI: 10.3390/ani14131861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 06/20/2024] [Accepted: 06/20/2024] [Indexed: 07/14/2024] Open
Abstract
The Hepatitis E virus (HEV) causes acute and chronic Hepatitis E and is a global public health concern. HEV genotypes 3 (HEV-3) and 4 (HEV-4) are common to humans and animals, and domestic pigs and wild boars have been identified as the main reservoirs. However, limited information is available on the status of HEV infection in pigs, particularly in the Guangdong Province, China. This study aimed to investigate the seroprevalence of HEV in pig farms within the Guangdong Province. A total of 1568 serum samples were collected from 25 farms and tested for anti-HEV IgG antibodies. Enzyme-linked immunosorbent assay (ELISA) results revealed that 57.53% (902/1568) of serum samples from 24 farms (24/25, 96%) were positive for anti-HEV IgG antibodies. Year, season, region, and age were all linked risk factors for HEV in Guangdong, with season and region showing more significant impacts. The results showing a high seroprevalence of HEV confirmed its circulation among domestic pigs in the Guangdong Province, China. The presence of this antibody indicates that HEV infection was or is present on farms, posing a risk of zoonotic transmission of HEV from pigs to exposed workers and from pork or organs to consumption.
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Affiliation(s)
- Dingyu Liu
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
| | - Baoling Liu
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Zhenwen He
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
- College of Animal Science and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou 510225, China
| | - Changhong Qiao
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Qin Luo
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Xiangyu Chen
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Xiaohu Wang
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Hua Xiang
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Jing Chen
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Pian Zhang
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Yuan Huang
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Gang Wang
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Chen Tan
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
| | - Rujian Cai
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
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La Bella G, Basanisi MG, Nobili G, D’Antuono AM, Suffredini E, La Salandra G. Duplex Droplet Digital PCR Assay for Quantification of Hepatitis E Virus in Food. Viruses 2024; 16:413. [PMID: 38543778 PMCID: PMC10975721 DOI: 10.3390/v16030413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 02/29/2024] [Accepted: 03/05/2024] [Indexed: 05/23/2024] Open
Abstract
Hepatitis E virus (HEV) represents an emerging risk in industrialized countries where the consumption of contaminated food plays a pivotal role. Quantitative real-time RT-PCR (RT-qPCR) is one of the most suitable methods for the detection and quantification of viruses in food. Nevertheless, quantification using RT-qPCR has limitations. Droplet digital PCR (ddPCR) provides the precise quantification of nucleic acids without the need for a standard curve and a reduction in the effect on virus quantification due to the presence of inhibitors. The objectives of the present work were (i) to develop a method for the absolute quantification of HEV in swine tissues based on ddPCR technology and provide internal process control for recovery assessment and (ii) to evaluate the performance of the method by analyzing a selection of naturally contaminated wild boar muscle samples previously tested using RT-qPCR. The method was optimized using a set of in vitro synthesized HEV RNA and quantified dsDNA. The limit of detection of the developed ddPCR assay was 0.34 genome copies/µL. The analysis of the wild boar samples confirmed the validity of the ddPCR assay. The duplex ddPCR method showed no reduction in efficiency compared to individual assays. The method developed in the present study could represent a sensitive assay for the detection and absolute quantification of HEV RNA in food samples with the advantage of presenting the co-amplification of internal process control.
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Affiliation(s)
- Gianfranco La Bella
- Istituto Zooprofilattico Sperimentale della Puglia e della Basilicata, Via Manfredonia 20, 71121 Foggia, Italy (G.N.); (A.M.D.); (G.L.S.)
| | - Maria Grazia Basanisi
- Istituto Zooprofilattico Sperimentale della Puglia e della Basilicata, Via Manfredonia 20, 71121 Foggia, Italy (G.N.); (A.M.D.); (G.L.S.)
| | - Gaia Nobili
- Istituto Zooprofilattico Sperimentale della Puglia e della Basilicata, Via Manfredonia 20, 71121 Foggia, Italy (G.N.); (A.M.D.); (G.L.S.)
| | - Anna Mattea D’Antuono
- Istituto Zooprofilattico Sperimentale della Puglia e della Basilicata, Via Manfredonia 20, 71121 Foggia, Italy (G.N.); (A.M.D.); (G.L.S.)
| | - Elisabetta Suffredini
- Department of Food Safety Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, 00161 Rome, Italy;
| | - Giovanna La Salandra
- Istituto Zooprofilattico Sperimentale della Puglia e della Basilicata, Via Manfredonia 20, 71121 Foggia, Italy (G.N.); (A.M.D.); (G.L.S.)
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6
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Johne R, Scholz J, Falkenhagen A. Heat stability of foodborne viruses - Findings, methodological challenges and current developments. Int J Food Microbiol 2024; 413:110582. [PMID: 38290272 DOI: 10.1016/j.ijfoodmicro.2024.110582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 01/12/2024] [Accepted: 01/14/2024] [Indexed: 02/01/2024]
Abstract
Heat treatment of food represents an important measure to prevent pathogen transmission. Thus far, evaluation of heat treatment processes is mainly based on data from bacteria. However, foodborne viruses have gained increasing attention during the last decades. Here, the published literature on heat stability and inactivation of human norovirus (NoV), hepatitis A virus (HAV) and hepatitis E virus (HEV) was reviewed. Data for surrogate viruses were not included. As stability assessment for foodborne viruses is often hampered by missing infectivity assays, an overview of applied methods is also presented. For NoV, molecular capsid integrity assays were mainly applied, but data from initial studies utilizing novel intestinal enteroid or zebrafish larvae assays are available now. However, these methods are still limited in applicability and sensitivity. For HAV, sufficient cell culture-based inactivation data are available, but almost exclusively for one single strain, thus limiting interpretation of the data for the wide range of field strains. For HEV, data are now available from studies using pig inoculation or cell culture. The results of the reviewed studies generally indicate that NoV, HAV and HEV possess a high heat stability. Heating at 70-72 °C for 2 min significantly reduces infectious titers, but often does not result in a >4 log10 decrease. However, heat stability greatly varied dependent on virus strain, matrix and heating regime. In addition, the applied method largely influenced the result, e.g. capsid integrity assays tend to result in higher measured stabilities than cell culture approaches. It can be concluded that the investigated foodborne viruses show a high heat stability, but can be inactivated by application of appropriate heating protocols. For HAV, suggestions for safe time/temperature combinations for specific foods can be derived from the published studies, with the limitation that they are mostly based on one strain only. Although significant improvement of infectivity assays for NoV and HEV have been made during the last years, further method development regarding sensitivity, robustness and broader applicability is important to generate more reliable heat inactivation data for these foodborne viruses in future.
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Affiliation(s)
- Reimar Johne
- German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany.
| | - Johannes Scholz
- German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany
| | - Alexander Falkenhagen
- German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany
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7
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Viral agents (2nd section). Transfusion 2024; 64 Suppl 1:S19-S207. [PMID: 38394038 DOI: 10.1111/trf.17630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Accepted: 12/02/2023] [Indexed: 02/25/2024]
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Das A, Rivera-Serrano EE, Yin X, Walker CM, Feng Z, Lemon SM. Cell entry and release of quasi-enveloped human hepatitis viruses. Nat Rev Microbiol 2023; 21:573-589. [PMID: 37185947 PMCID: PMC10127183 DOI: 10.1038/s41579-023-00889-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/22/2023] [Indexed: 05/17/2023]
Abstract
Infectious hepatitis type A and type E are caused by phylogenetically distinct single-stranded, positive-sense RNA viruses that were once considered to be non-enveloped. However, studies show that both are released nonlytically from hepatocytes as 'quasi-enveloped' virions cloaked in host membranes. These virion types predominate in the blood of infected individuals and mediate virus spread within the liver. They lack virally encoded proteins on their surface and are resistant to neutralizing anti-capsid antibodies induced by infection, yet they efficiently enter cells and initiate new rounds of virus replication. In this Review, we discuss the mechanisms by which specific peptide sequences in the capsids of these quasi-enveloped virions mediate their endosomal sorting complexes required for transport (ESCRT)-dependent release from hepatocytes through multivesicular endosomes, what is known about how they enter cells, and the impact of capsid quasi-envelopment on host immunity and pathogenesis.
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Affiliation(s)
- Anshuman Das
- Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Lentigen Technology, Inc., Gaithersburg, MD, USA
| | - Efraín E Rivera-Serrano
- Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Department of Biology, Elon University, Elon, NC, USA
| | - Xin Yin
- Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China
| | - Christopher M Walker
- Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA
- Department of Paediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Zongdi Feng
- Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
- Department of Paediatrics, The Ohio State University College of Medicine, Columbus, OH, USA.
| | - Stanley M Lemon
- Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- Department of Microbiology & Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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Geng Y, Shi T, Wang Y. Transmission of Hepatitis E Virus. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:73-92. [PMID: 37223860 DOI: 10.1007/978-981-99-1304-6_6] [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
Transmission of hepatitis E virus (HEV) occurs predominantly by the fecal-oral route. Large epidemics of hepatitis E in the developing countries of Asia and Africa are waterborne and spread through contaminated drinking water. The reservoir of HEV in developed countries is believed to be in animals with zoonotic transmission to humans, possibly through direct contact or the consumption of undercooked contaminated meat. And HEV transmission through blood transfusion, organ transplantation, and vertical transmission has been reported.
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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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Zhang F, Wang Y. HEV Cell Culture. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:119-131. [PMID: 37223862 DOI: 10.1007/978-981-99-1304-6_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Cell culture is an important research method in virology. Although many attempts have been conducted to culture HEV in cells, only a few cell culture systems were considered to be efficient enough for usage. Concentration of virus stocks, host cells, and medium components affects the culture efficiency and the genetic mutations during HEV passage were found to be associated with the increased virulence in cell culture. As an alternative method for traditional cell culture, the infectious cDNA clones were constructed. The viral thermal stability, factors that impact the host range, post-translation of viral proteins, and function of different viral proteins were studied using the infectious cDNA clones. HEV cell culture studies on progeny virus showed that the viruses secreted from host cells have an envelope and its formation was associated with pORF3. This result explained the phenomenon that virus could infect host cells in the presence of anti-HEV antibodies.
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Affiliation(s)
- Feng Zhang
- Division of Therapeutical Monoclonal Antibodies, National Institutes for Food and Drug Control, Beijing, China
| | - Youchun Wang
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, Yunnan Province, China.
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11
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Shata MTM, Hetta HF, Sharma Y, Sherman KE. Viral hepatitis in pregnancy. J Viral Hepat 2022; 29:844-861. [PMID: 35748741 PMCID: PMC9541692 DOI: 10.1111/jvh.13725] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 12/17/2021] [Accepted: 06/13/2022] [Indexed: 12/09/2022]
Abstract
Viral hepatitis is caused by a heterogenous group of viral agents representing a wide range of phylogenetic groups. Many viruses can involve the liver and cause liver injury but only a subset are delineated as 'hepatitis viruses' based upon their primary site of replication and tropism for hepatocytes which make up the bulk of the liver cell population. Since their discovery, beginning with the agent that caused serum hepatitis in the 1960s, the alphabetic designations have been utilized. To date, we have five hepatitis viruses, A through E, though it is postulated that others may exist. This chapter will focus on those viruses. Note that hepatitis D is included as a subset of hepatitis B, as it cannot exist without concurrent hepatitis B infection. Pregnancy has the potential to affect all aspects of these viral agents due to the unique immunologic and physiologic changes that occur during and after the gestational period. In this review, we will discuss the most common viral hepatitis and their effects during pregnancy.
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Affiliation(s)
- Mohamed Tarek M. Shata
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA
| | - Helal F. Hetta
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA,Department of Medical Microbiology and Immunology, Faculty of MedicineAssiut UniversityAssiutEgypt
| | - Yeshika Sharma
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA
| | - Kenneth E. Sherman
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA
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Villalba R, Mirabet V. Risk assessment of hepatitis E transmission through tissue allografts. World J Gastrointest Pathophysiol 2022; 13:50-58. [PMID: 35433096 PMCID: PMC8976234 DOI: 10.4291/wjgp.v13.i2.50] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/06/2021] [Accepted: 01/25/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) is a small non-enveloped single stranded RNA virus whose genotypes 3 and 4 have been associated with zoonotic transmission in industrialized countries. HEV infection is considered the main cause of acute hepatitis worldwide. In some cases, transfusion of blood components or organ transplantation have been reported as the source of infection. We have conducted a literature review on the risk of transmission through cell and tissue allografts. Although no case was found, measures to control this risk should be taken when donor profile (based upon geographical and behavioural data) recommended it. Issues to be considered in donor screening and tissue processing to assess and to reduce the risk of HEV transmission are approached.
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Affiliation(s)
- Rafael Villalba
- Center for Blood Transfusion, Tissues and Cells, Córdoba 14004, Spain
| | - Vicente Mirabet
- Cell and Tissue Bank, Centro de Transfusión de Valencia, Valencia 46014, Spain
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13
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Jian Z, Li Y, Xu Z, Zhao J, Li F, Deng H, Sun X, Zhu L. Research on a rat model of genotype IV swine hepatitis E virus. Vet Med Sci 2022; 8:886-898. [PMID: 34981892 PMCID: PMC8959259 DOI: 10.1002/vms3.707] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) is an important zoonotic pathogen, Genotypes 3 and 4 are the main zoonotic genotype. Due to the lack of mature and effective culture cell lines, researches on genotype IV swine HEV (SHEV-4) infection and pathogenic mechanism have been carried out in pigs, gerbils and non-human primate models. OBJECTIVES The aim of this study was to establish a rat infection model by intra-peritoneal infection with SHEV-4, which provided a new research idea and scientific basis for further revealing the mechanism of HEV infection and preventing HEV infection. METHODS SHEV-4 virus was administered intra-peritoneally to 6- to 8-week-old mice to observe the serological changes and virus release. RESULTS According to the results of the rat serum HEV IgG, ALT and AST levels, swine HEV, minus-strand HEV RNA can infect Sprague-Dawley rats across species, and there are no obvious clinical symptoms after infection. HEV RNA was detected in most tissues and organs after infection, but the viral load was low. The liver had pathological changes of chronic hepatitis. CONCLUSIONS We found that the rat model of porcine HEV infection is a small animal model suitable for the study of HEV infection.
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Affiliation(s)
- Zhijie Jian
- College of Veterinary MedicineSichuan Agricultural UniversityChengduP. R. China
| | - Youyou Li
- Sichuan Water Conservancy College, College of Veterinary MedicineChengduP. R. China
| | - Zhiwen Xu
- Key Laboratory of Animal Diseases and Human Health of Sichuan Province, College of Veterinary MedicineSichuan Agricultural UniversityChengduP. R. China
| | - Jun Zhao
- College of Veterinary MedicineSichuan Agricultural UniversityChengduP. R. China
| | - Fengqin Li
- College of Veterinary MedicineSichuan Agricultural UniversityChengduP. R. China
- College of Animal ScienceXichang UniversityXichangSichuanP. R. China
| | - Huidan Deng
- College of Veterinary MedicineSichuan Agricultural UniversityChengduP. R. China
| | - Xiangang Sun
- College of Veterinary MedicineSichuan Agricultural UniversityChengduP. R. China
| | - Ling Zhu
- Key Laboratory of Animal Diseases and Human Health of Sichuan Province, College of Veterinary MedicineSichuan Agricultural UniversityChengduP. R. China
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14
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Treagus S, Wright C, Baker-Austin C, Longdon B, Lowther J. The Foodborne Transmission of Hepatitis E Virus to Humans. FOOD AND ENVIRONMENTAL VIROLOGY 2021; 13:127-145. [PMID: 33738770 PMCID: PMC8116281 DOI: 10.1007/s12560-021-09461-5] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 01/16/2021] [Indexed: 05/04/2023]
Abstract
Globally, Hepatitis E virus (HEV) causes over 20 million cases worldwide. HEV is an emerging and endemic pathogen within economically developed countries, chiefly resulting from infections with genotype 3 (G3) HEV. G3 HEV is known to be a zoonotic pathogen, with a broad host range. The primary source of HEV within more economically developed countries is considered to be pigs, and consumption of pork products is a significant risk factor and known transmission route for the virus to humans. However, other foods have also been implicated in the transmission of HEV to humans. This review consolidates the information available regarding transmission of HEV and looks to identify gaps where further research is required to better understand how HEV is transmitted to humans through food.
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Affiliation(s)
- Samantha Treagus
- Biosciences, College of Life and Environmental Sciences, University of Exeter, Penryn Campus, Penryn, Cornwall, UK.
- Centre for Environment Fisheries and Aquaculture Science, Barrack Road, Weymouth, Dorset, DT4 8UB, UK.
| | | | - Craig Baker-Austin
- Centre for Environment Fisheries and Aquaculture Science, Barrack Road, Weymouth, Dorset, DT4 8UB, UK
| | - Ben Longdon
- Biosciences, College of Life and Environmental Sciences, University of Exeter, Penryn Campus, Penryn, Cornwall, UK
| | - James Lowther
- Centre for Environment Fisheries and Aquaculture Science, Barrack Road, Weymouth, Dorset, DT4 8UB, UK
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15
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Dähnert L, Schlosser J, Fast C, Fröhlich A, Gröner A, Lange E, Roth NJ, Schäfer W, Schröder C, Eiden M, Groschup MH. Hepatitis E virus: Efficacy of pasteurization of plasma-derived VWF/FVIII concentrate determined by pig bioassay. Transfusion 2021; 61:1266-1277. [PMID: 33605455 DOI: 10.1111/trf.16298] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 12/17/2020] [Accepted: 12/18/2020] [Indexed: 11/30/2022]
Abstract
BACKGROUND Hepatitis E virus (HEV) is the leading cause of acute hepatitis throughout the world. Increasing blood component transfusion-associated HEV infections highlight the need for reliable virus inactivation procedures for plasma derivatives from pooled plasma donations. STUDY DESIGN AND METHODS An animal infection study was conducted to evaluate the efficiency of HEV inactivation by pasteurization during the manufacturing process of the von Willebrand Factor/Factor VIII (VWF/FVIII) concentrate Haemate P/Humate-P (CSL Behring, Marburg, Germany). For this purpose, groups of pigs were inoculated with stabilized VWF/FVIII intermediate spiked with HEV-positive liver homogenate and exposed to increasing incubation times of 0, 3, 6, and 10 h at 60°C. Animals were evaluated for virus replication over 27 days and in a subsequent trial over 92 days. RESULTS Virus replication was detected in animals up to the 6-h pasteurization group. In contrast, pasteurization for 10 h did not reveal virus detection when the observation period was 27 days. In an additional experiment using the 10-h pasteurized material, two individuals started virus excretion and seroconverted when the observation period was extended to 92 days. Based on the total infection rate (2 of 12) of the animals inoculated with the sample pasteurized for 10 h, a virus reduction factor of at least 4.7 log10 is calculated. CONCLUSION This study demonstrates that pasteurization at 60°C for 10 h of an HEV-positive plasma derivative leads to the effective reduction of infectivity, resulting in a VWF/FVIII product with an appropriate margin of safety for HEV.
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Affiliation(s)
- Lisa Dähnert
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald, Germany
| | - Josephine Schlosser
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald, Germany.,Department of Veterinary Medicine, Freie Universität Berlin, Institute of Immunology, Berlin, Germany
| | - Christine Fast
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald, Germany
| | - Andreas Fröhlich
- Institute of Epidemiology, Friedrich-Loeffler-Institut, Greifswald, Germany
| | | | - Elke Lange
- Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald, Germany
| | - Nathan J Roth
- Global Pathogen Safety, CSL Behring AG, Bern, Switzerland
| | | | - Charlotte Schröder
- Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald, Germany
| | - Martin Eiden
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald, Germany
| | - Martin H Groschup
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald, Germany
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16
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Di Cola G, Fantilli AC, Pisano MB, Ré VE. Foodborne transmission of hepatitis A and hepatitis E viruses: A literature review. Int J Food Microbiol 2021; 338:108986. [PMID: 33257099 DOI: 10.1016/j.ijfoodmicro.2020.108986] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 11/04/2020] [Accepted: 11/05/2020] [Indexed: 12/19/2022]
Abstract
Foodborne viruses have been recognized as a growing concern to the food industry and a serious public health problem. Hepatitis A virus (HAV) is responsible for the majority of viral outbreaks of food origin worldwide, while hepatitis E virus (HEV) has also been gaining prominence as a foodborne viral agent in the last years, due to its zoonotic transmission through the consumption of uncooked or undercooked infected meat or derivatives. However, there is a lack of scientific reports that gather all the updated information about HAV and HEV as foodborne viruses. A search of all scientific articles about HAV and HEV in food until March 2020 was carried out, using the keywords "HAV", "HEV", "foodborne", "outbreak" and "detection in food". Foodborne outbreaks due to HAV have been reported since 1956, mainly in the USA, and in Europe in recent years, where the number of outbreaks has been increasing throughout time, and nowadays it has become the continent with the highest foodborne HAV outbreak report. Investigation and detection of HAV in food is more recent, and the first detections were performed in the 1990s decade, most of them carried out on seafood, first, and frozen food, later. On the other hand, HEV has been mainly looked for and detected in food derived from reservoir animals, such as meat, sausages and pate of pigs and wild boars. For this virus, only isolated cases and small outbreaks of foodborne transmission have been recorded, most of them in industrialized countries, due to HEV genotype 3 or 4. Virus detection in food matrices requires special processing of the food matrix, followed by RNA detection by molecular techniques. For HAV, a real-time PCR has been agreed as the standard method for virus detection in food; in the case of HEV, a consensus assay for its detection in food has not been reached yet. Our investigation shows that there is still little data about HAV and HEV prevalence and frequency of contamination in food, prevalent viral strains, and sources of contamination, mainly in developing countries, where there is no research and legislation in this regard. Studies on these issues are needed to get a better understanding of foodborne viruses, their maintenance and their potential to cause diseases.
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Affiliation(s)
- Guadalupe Di Cola
- Instituto de Virología "Dr. J. M. Vanella", Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gomez s/n, CP: 5016 Córdoba, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.
| | - Anabella C Fantilli
- Instituto de Virología "Dr. J. M. Vanella", Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gomez s/n, CP: 5016 Córdoba, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
| | - María Belén Pisano
- Instituto de Virología "Dr. J. M. Vanella", Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gomez s/n, CP: 5016 Córdoba, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
| | - Viviana E Ré
- Instituto de Virología "Dr. J. M. Vanella", Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gomez s/n, CP: 5016 Córdoba, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
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17
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Wright BW, Ruan J, Molloy MP, Jaschke PR. Genome Modularization Reveals Overlapped Gene Topology Is Necessary for Efficient Viral Reproduction. ACS Synth Biol 2020; 9:3079-3090. [PMID: 33044064 DOI: 10.1021/acssynbio.0c00323] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Sequence overlap between two genes is common across all genomes, with viruses having high proportions of these gene overlaps. Genome modularization and refactoring is the process of disrupting natural gene overlaps to separate coding sequences to enable their individual manipulation. The biological function and fitness effects of gene overlaps are not fully understood, and their effects on gene cluster and genome-level refactoring are unknown. The bacteriophage φX174 genome has ∼26% of nucleotides involved in encoding more than one gene. In this study we use an engineered φX174 phage containing a genome with all gene overlaps removed to show that gene overlap is critical to maintaining optimal viral fecundity. Through detailed phenotypic measurements we reveal that genome modularization in φX174 causes virion replication, stability, and attachment deficiencies. Quantitation of the complete phage proteome across an infection cycle reveals 30% of proteins display abnormal expression patterns. Taken together, we have for the first time comprehensively demonstrated that gene modularization severely perturbs the coordinated functioning of a bacteriophage replication cycle. This work highlights the biological importance of gene overlap in natural genomes and that reducing gene overlap disruption should be an integral part of future genome engineering projects.
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Affiliation(s)
- Bradley W. Wright
- Department of Molecular Sciences, Macquarie University, Sydney, NSW 2109, Australia
| | - Juanfang Ruan
- Electron Microscope Unit, Mark Wainwright Analytical Centre, The University of New South Wales, Sydney, NSW 2052, Australia
- School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia
| | - Mark P. Molloy
- Kolling Institute, Northern Clinical School, The University of Sydney, Sydney, NSW 2006, Australia
| | - Paul R. Jaschke
- Department of Molecular Sciences, Macquarie University, Sydney, NSW 2109, Australia
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18
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Pitino MA, O'Connor DL, McGeer AJ, Unger S. The impact of thermal pasteurization on viral load and detectable live viruses in human milk and other matrices: a rapid review. Appl Physiol Nutr Metab 2020; 46:10-26. [PMID: 32650645 DOI: 10.1139/apnm-2020-0388] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Holder pasteurization (62.5 °C, 30 min) of human milk is thought to reduce the risk of transmitting viruses to an infant. Some viruses may be secreted into milk - others may be contaminants. The effect of thermal pasteurization on viruses in human milk has yet to be rigorously reviewed. The objective of this study is to characterize the effect of common pasteurization techniques on viruses in human milk and non-human milk matrices. Databases (MEDLINE, Embase, Web of Science) were searched from inception to April 20th, 2020, for primary research articles assessing the impact of pasteurization on viral load or detection of live virus. Reviews were excluded, as were studies lacking quantitative measurements or those assessing pasteurization as a component of a larger process. Overall, of 65 131 reports identified, 109 studies were included. Pasteurization of human milk at a minimum temperature of 56-60 °C is effective at reducing detectable live virus. In cell culture media or plasma, coronaviruses (e.g., SARS-CoV, SARS-CoV-2, MERS-CoV) are highly susceptible to heating at ≥56 °C. Although pasteurization parameters and matrices reported vary, all viruses studied, except parvoviruses, were susceptible to thermal killing. Future research important for the study of novel viruses should standardize pasteurization protocols and should test inactivation in human milk. Novelty In all matrices, including human milk, pasteurization at 62.5 °C was generally sufficient to reduce surviving viral load by several logs or to below the limit of detection. Holder pasteurization (62.5 °C, 30 min) of human milk should be sufficient to inactivate nonheat resistant viruses, including coronaviruses, if present.
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Affiliation(s)
- Michael A Pitino
- Department of Nutritional Sciences, University of Toronto, Toronto, ON M5S 1A8, Canada.,Translational Medicine Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
| | - Deborah L O'Connor
- Department of Nutritional Sciences, University of Toronto, Toronto, ON M5S 1A8, Canada.,Translational Medicine Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
| | - Allison J McGeer
- Department of Microbiology, Sinai Health, Toronto, ON M5G 1X5, Canada.,Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A1, Canada.,Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada
| | - Sharon Unger
- Department of Nutritional Sciences, University of Toronto, Toronto, ON M5S 1A8, Canada.,Division of Neonatology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.,Department of Pediatrics, Sinai Health, Toronto, ON M5G 1X5, Canada.,Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada
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19
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Goel A, Aggarwal R. Hepatitis E: Epidemiology, Clinical Course, Prevention, and Treatment. Gastroenterol Clin North Am 2020; 49:315-330. [PMID: 32389365 DOI: 10.1016/j.gtc.2020.01.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/19/2023]
Abstract
Hepatitis E virus is a common cause of acute hepatitis and acute liver failure in resource-constrained parts of the world. The disease is particularly severe when the infection occurs during pregnancy. In developed countries, human infections occur primarily through zoonotic transmission from animal reservoirs; however, clinical disease is less frequent than in the developing world. The virus strains prevalent in these areas also cause chronic infection in immunocompromised persons, which, if untreated, can progress to cirrhosis; such infection responds well to oral ribavirin. A safe and highly effective recombinant vaccine is available in China, but is not available elsewhere.
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Affiliation(s)
- Amit Goel
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Rakesh Aggarwal
- Department of Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
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20
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Su Q, Chen Y, Wang B, Huang C, Han S, Yuan G, Zhang Q, He H. Epidemiology and genetic diversity of zoonotic pathogens in urban rats (Rattus spp.) from a subtropical city, Guangzhou, southern China. Zoonoses Public Health 2020; 67:534-545. [PMID: 32452163 DOI: 10.1111/zph.12717] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 04/13/2020] [Accepted: 04/13/2020] [Indexed: 12/13/2022]
Abstract
Commensal rats (Rattus spp.), which are globally distributed, harbour many pathogens responsible for significant human diseases. Despite this, we have a poor understanding of the epidemiology and genetic diversity of some recently neglected zoonotic pathogens, such as Leptospira spp., Bartonella spp. and hepatitis E virus (HEV), which constitute a major public health threat. Thus, we surveyed the occurrences, co-infection and genetic diversity of these pathogens in 129 urban rats from China. For Rattus tanezumi, the prevalences of Leptospira spp., Bartonella spp. and HEV infection were 6.67%, 0% and 46.67%, respectively. The prevalences of Leptospira spp., Bartonella spp. and HEV infection were 57.89%, 9.65% and 57.89% for Rattus norvegicus respectively. Leptospira spp. and HEV infections were more likely to occur in mature R. norvegicus. Phylogenetic analyses showed that pathogenic Leptospira interrogans and Leptospira borgpetersenii might exist. We also found that Bartonella spp. showed high similarity to Bartonella elizabethae, Bartonella rochalimae and Bartonella tribocorum, which are implicated in human disease. Dual and triple infections were both detected. Moreover, dual infections with Leptospira spp. and HEV represented the most frequent co-infection, and there was a significantly positive association between them. High genetic diversity was observed in genes segments from Leptospira, Bartonella and HEV. Our results first discover the occurrence of multiple co-infections and genetic diversity of Leptospira, Bartonella and HEV in commensal rats from China. Altogether, the present study provides an insight into evaluating the risk of rat-borne zoonoses in urban China.
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Affiliation(s)
- Qianqian Su
- National Research Center for Wildlife-Borne Diseases, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Yi Chen
- University of Chinese Academy of Sciences, Beijing, China.,State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
| | - Bo Wang
- National Research Center for Wildlife-Borne Diseases, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Chengmei Huang
- National Research Center for Wildlife-Borne Diseases, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Shuyi Han
- National Research Center for Wildlife-Borne Diseases, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
| | - Guohui Yuan
- National Research Center for Wildlife-Borne Diseases, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
| | - Qingxun Zhang
- National Research Center for Wildlife-Borne Diseases, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
| | - Hongxuan He
- National Research Center for Wildlife-Borne Diseases, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
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21
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Grigas J, Simkute E, Simanavicius M, Pautienius A, Streimikyte-Mockeliune Z, Razukevicius D, Stankevicius A. Hepatitis E genotype 3 virus isolate from wild boar is capable of replication in non-human primate and swine kidney cells and mouse neuroblastoma cells. BMC Vet Res 2020; 16:95. [PMID: 32199460 PMCID: PMC7085153 DOI: 10.1186/s12917-020-02315-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 03/12/2020] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Wild boar-derived hepatitis E (HEV) genotype 3 virus has been successfully isolated in cell lines of human origin only. Considering the zoonotic potential and possible extrahepatic localisation of genotype 3 strain, it is important to investigate the viability of cell lines of different animal and tissue origins. Therefore, the objective of the present study was to determine the permissiveness of non-human primate (MARC-145 and Vero) and swine (PK-15) cell lines of kidney origin, and a mouse neuroblastoma (Neuro-2a) cell line for isolation of wild boar-derived HEV genotype 3. RESULTS This study showed that MARC-145, PK-15, Neuro-2a and Vero cell lines were permissive to wild boar-derived HEV genotype 3 subtype 3i harbouring viral genome equivalents of 1.12 × 107 copies/ml, 2.38 × 105 copies/ml, 2.97 × 107 copies/ml and 4.01 × 107 copies/ml after five serial passages respectively. In all permissive cell lines, HEV was continuously recovered from growth medium between five and at least 28 days post-infection. Peak loads of HEV genome equivalents were observed on days 7, 12, 19 and 30 in MARC-145 (2.88 × 107 copies/ml), Vero (4.23 × 106 copies/ml), Neuro-2a (3.15 × 106 copies/ml) and PK-15 (2.24 × 107 copies/ml) cell lines respectively. In addition, successful virus isolation was confirmed by immunofluorescence assay targeting HEV capsid protein and sequencing of HEV isolate retrieved from cell cultures. CONCLUSIONS This study showed that wild boar-derived HEV genotype 3 subtype 3i strain was capable of infecting cell lines of animal origin, including primate and porcine kidney cells (MARC-145, PK-15 and Vero), and mouse neuroblastoma cells (Neuro-2a), supporting the notion of the capacity of HEV genotype 3 to cross the species barrier and extra-hepatic localisation of the virus. These findings warrant further studies of tested cell lines to investigate their capacity as an efficient system for HEV propagation. HEV isolates from other wild animal hosts should be isolated on tested cell lines in order to generate more data on HEV transmission between wild animal populations and their role as sources of human infections.
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Affiliation(s)
- Juozas Grigas
- Faculty of Veterinary Medicine, Laboratory of Immunology, Department of Anatomy and Physiology, Lithuanian University of Health Sciences, Tilzes str. 18, Kaunas, Lithuania.
| | - Evelina Simkute
- Faculty of Veterinary Medicine, Laboratory of Immunology, Department of Anatomy and Physiology, Lithuanian University of Health Sciences, Tilzes str. 18, Kaunas, Lithuania
| | - Martynas Simanavicius
- Vilnius University Life Sciences Centre, Institute of Biotechnology, Sauletekio al. 7, Vilnius, Lithuania
| | - Arnoldas Pautienius
- Faculty of Veterinary Medicine, Laboratory of Immunology, Department of Anatomy and Physiology, Lithuanian University of Health Sciences, Tilzes str. 18, Kaunas, Lithuania.,Faculty of Veterinary Medicine, Institute of Microbiology and Virology, Lithuanian University of Health Sciences, Tilzes str. 18, Kaunas, Lithuania
| | - Zaneta Streimikyte-Mockeliune
- Faculty of Veterinary Medicine, Institute of Microbiology and Virology, Lithuanian University of Health Sciences, Tilzes str. 18, Kaunas, Lithuania
| | - Dainius Razukevicius
- Faculty of Medicine, Lithuanian University of Health Sciences, A. Mickeviciaus str. 9, Kaunas, Lithuania
| | - Arunas Stankevicius
- Faculty of Veterinary Medicine, Laboratory of Immunology, Department of Anatomy and Physiology, Lithuanian University of Health Sciences, Tilzes str. 18, Kaunas, Lithuania
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22
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Capelli N, Dubois M, Pucelle M, Da Silva I, Lhomme S, Abravanel F, Chapuy-Regaud S, Izopet J. Optimized Hepatitis E Virus (HEV) Culture and its Application to Measurements of HEV Infectivity. Viruses 2020; 12:v12020139. [PMID: 31991673 PMCID: PMC7077187 DOI: 10.3390/v12020139] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 01/08/2020] [Accepted: 01/21/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatitis E virus (HEV) is a major concern in public health worldwide. Infections with HEV genotypes 3, 4, or 7 can lead to chronic hepatitis while genotype 1 infections can trigger severe hepatitis in pregnant women. Infections with all genotypes can worsen chronic liver diseases. As virions are lipid-associated in blood and naked in feces, efficient methods of propagating HEV clinical strains in vitro and evaluating the infectivity of both HEV forms are needed. We evaluated the spread of clinical strains of HEV genotypes 1 (HEV1) and 3 (HEV3) by quantifying viral RNA in culture supernatants and cell lysates. Infectivity was determined by endpoint dilution and calculation of the tissue culture infectious dose 50 (TCID50). An enhanced HEV production could be obtained varying the composition of the medium, including fetal bovine serum (FBS) and dimethylsulfoxide (DMSO) content. This increased TCID50 from 10 to 100-fold and allowed us to quantify HEV1 infectivity. These optimized methods for propagating and measuring HEV infectivity could be applied to health safety processes and will be useful for testing new antiviral drugs.
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Affiliation(s)
- Nicolas Capelli
- Department of Virology, National Reference Center for HEV, CHU Purpan, 31059 Toulouse, France
- Centre de Physiopathologie de Toulouse Purpan (CPTP), Institut National de la Santé et de la Recherche Médicale, Inserm UMR1043, Centre National de la Recherche Scientifique, CNRS UMR5282, Université de Toulouse, 31024 Toulouse, France
| | - Martine Dubois
- Department of Virology, National Reference Center for HEV, CHU Purpan, 31059 Toulouse, France
- Centre de Physiopathologie de Toulouse Purpan (CPTP), Institut National de la Santé et de la Recherche Médicale, Inserm UMR1043, Centre National de la Recherche Scientifique, CNRS UMR5282, Université de Toulouse, 31024 Toulouse, France
| | - Mélanie Pucelle
- Department of Virology, National Reference Center for HEV, CHU Purpan, 31059 Toulouse, France
| | - Isabelle Da Silva
- Department of Virology, National Reference Center for HEV, CHU Purpan, 31059 Toulouse, France
| | - Sébastien Lhomme
- Department of Virology, National Reference Center for HEV, CHU Purpan, 31059 Toulouse, France
- Centre de Physiopathologie de Toulouse Purpan (CPTP), Institut National de la Santé et de la Recherche Médicale, Inserm UMR1043, Centre National de la Recherche Scientifique, CNRS UMR5282, Université de Toulouse, 31024 Toulouse, France
| | - Florence Abravanel
- Department of Virology, National Reference Center for HEV, CHU Purpan, 31059 Toulouse, France
- Centre de Physiopathologie de Toulouse Purpan (CPTP), Institut National de la Santé et de la Recherche Médicale, Inserm UMR1043, Centre National de la Recherche Scientifique, CNRS UMR5282, Université de Toulouse, 31024 Toulouse, France
| | - Sabine Chapuy-Regaud
- Department of Virology, National Reference Center for HEV, CHU Purpan, 31059 Toulouse, France
- Centre de Physiopathologie de Toulouse Purpan (CPTP), Institut National de la Santé et de la Recherche Médicale, Inserm UMR1043, Centre National de la Recherche Scientifique, CNRS UMR5282, Université de Toulouse, 31024 Toulouse, France
- Correspondence: ; Tel.: +33-567-690-431
| | - Jacques Izopet
- Department of Virology, National Reference Center for HEV, CHU Purpan, 31059 Toulouse, France
- Centre de Physiopathologie de Toulouse Purpan (CPTP), Institut National de la Santé et de la Recherche Médicale, Inserm UMR1043, Centre National de la Recherche Scientifique, CNRS UMR5282, Université de Toulouse, 31024 Toulouse, France
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Saraswat S, Chaudhary M, Sehgal D. Hepatitis E Virus Cysteine Protease Has Papain Like Properties Validated by in silico Modeling and Cell-Free Inhibition Assays. Front Cell Infect Microbiol 2020; 9:478. [PMID: 32039053 PMCID: PMC6989534 DOI: 10.3389/fcimb.2019.00478] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 12/27/2019] [Indexed: 12/11/2022] Open
Abstract
Hepatitis E virus (HEV) has emerged as a global health concern during the last decade. In spite of a high mortality rate in pregnant women with fulminant hepatitis, no antiviral drugs or licensed vaccine is available in India. HEV-protease is a pivotal enzyme responsible for ORF1 polyprotein processing leading to cleavage of the non-structural enzymes involved in virus replication. HEV-protease region encoding 432–592 amino acids of Genotype-1 was amplified, expressed in Sf21 cells and purified in its native form. The recombinant enzyme was biochemically characterized using SDS-PAGE, Western blotting and Immunofluorescence. The enzyme activity and the inhibition studies were conducted using Zymography, FTC-casein based protease assay and ORF1 polyprotein digestion. To conduct ORF1 digestion assay, the polyprotein, natural substrate of HEV-protease, was expressed in E. coli and purified. Cleavage of 186 kDa ORF1 polyprotein by the recombinant HEV-protease lead to appearance of non-structural proteins viz. Methyltransferase, Protease, Helicase and RNA dependent RNA polymerase which were confirmed through immunoblotting using antibodies generated against specific epitopes of the enzymes. FTC-casein substrate was used for kinetic studies to determine Km and Vmax of the enzyme and also the effect of different metal ions and other protease inhibitors. A 95% inhibition was observed with E-64 which was validated through in silico analysis. The correlation coefficient between inhibition and docking score of Inhibitors was found to have a significant value of r2 = 0.75. The predicted 3D model showed two domain architecture structures similar to Papain like cysteine protease though they differed in arrangements of alpha helices and beta sheets. Hence, we propose that HEV-protease has characteristics of “Papain-like cysteine protease,” as determined through structural homology, active site residues and class-specific inhibition. However, conclusive nature of the enzyme remains to be established.
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Affiliation(s)
- Shweta Saraswat
- Virology Lab, Department of Life Sciences, Shiv Nadar University, Greater Noida, India
| | - Meenakshi Chaudhary
- Virology Lab, Department of Life Sciences, Shiv Nadar University, Greater Noida, India
| | - Deepak Sehgal
- Virology Lab, Department of Life Sciences, Shiv Nadar University, Greater Noida, India
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Seroprevalence Study of Anti-HEV IgG among Different Adult Populations in Corsica, France, 2019. Microorganisms 2019; 7:microorganisms7100460. [PMID: 31623185 PMCID: PMC6843757 DOI: 10.3390/microorganisms7100460] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 09/19/2019] [Accepted: 10/15/2019] [Indexed: 02/07/2023] Open
Abstract
Hepatitis E virus (HEV) is a major cause of acute hepatitis worldwide. In France, hyperendemic areas including Corsica have an anti-HEV Immunoglobulin G (IgG) prevalence higher than 50%. The aim of this study was to determine the seroprevalence of anti-HEV IgG in three adult populations in Corsica and the risk factors associated with antibody detection. Between 2017 and 2019, a total of 930 individuals, including 467 blood donors, 393 students or university staff members and 70 patients from general practice, were tested for the presence of anti-HEV IgG using the Wantai HEV IgG enzyme immunoassay kit and filled a questionnaire. The association between seropositivity and potential risk factors was tested with univariate and multivariate analyses. Out of the 930 samples, 52.3% (486/930) were seropositive—54.4% (254/467) among blood donors, 47.6% (187/393) among university students and 64.3% (45/70) among patients of general practice. Three main risk factors were identified: (i) skinning and butchering (Adjusted Odds Ratio aOR = 2.76, 95% confidence interval [95% CI] [1.51–5.37]; p-value < 10−3), (ii) consumption of a local pork live raw sausage (fittonu) (aOR = 1.95 95% CI [1.45–2.64]; p-value = 10−5), and (iii) increasing age (p-value = 0.003). Seropositivity rates between the different populations were homogeneous after age stratification. This cross-sectional study indicates a high anti-HEV IgG seroprevalence in the Corsican adult population, not significantly different between women and men and increasing with age. This serosurvey also showed homogeneity regarding the exposure to HEV among three different types of populations. Finally, we confirmed the endemicity of Corsica with respect to HEV and identified a strong association between consumption of figatellu/fittonu and the practice of skinning and butchering with the detection of anti-HEV IgG.
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25
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Capai L, Maestrini O, Casabianca F, Villechenaud N, Masse S, Bosseur F, Lamballerie X, Charrel RN, Falchi A. Drastic decline of hepatitis E virus detection in domestic pigs after the age of 6 months, Corsica, France. Transbound Emerg Dis 2019; 66:2462-2473. [DOI: 10.1111/tbed.13304] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 06/08/2019] [Accepted: 07/15/2019] [Indexed: 12/15/2022]
Affiliation(s)
- Lisandru Capai
- EA 7310, Laboratoire de Virologie Université de Corse Corte France
| | - Oscar Maestrini
- Laboratoire de Recherche sur le Développement de l’Elevage (LRDE) Institut National de la Recherche Agronomique (INRA) Corte France
| | - François Casabianca
- Laboratoire de Recherche sur le Développement de l’Elevage (LRDE) Institut National de la Recherche Agronomique (INRA) Corte France
| | | | - Shirley Masse
- EA 7310, Laboratoire de Virologie Université de Corse Corte France
| | - Frédéric Bosseur
- Sciences Pour l’Environnement – UMR CNRS 6134 niversité de Corse Corte France
| | - Xavier Lamballerie
- IRD 190, INSERM 1207 IHU Méditerranée Infection, Unité des Virus Émergents (UVE): Aix Marseille Univ Marseille France
| | - Rémi N. Charrel
- IRD 190, INSERM 1207 IHU Méditerranée Infection, Unité des Virus Émergents (UVE): Aix Marseille Univ Marseille France
- Emerging Pathogens Institute University of Florida Gainesville Florida
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26
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Fenaux H, Chassaing M, Berger S, Gantzer C, Bertrand I, Schvoerer E. Transmission of hepatitis E virus by water: An issue still pending in industrialized countries. WATER RESEARCH 2019; 151:144-157. [PMID: 30594083 DOI: 10.1016/j.watres.2018.12.014] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 12/05/2018] [Accepted: 12/07/2018] [Indexed: 06/09/2023]
Abstract
Hepatitis E virus (HEV) is an enteric virus divided into eight genotypes. Genotype 1 (G1) and G2 are specific to humans; G3, G4 and G7 are zoonotic genotypes infecting humans and animals. Transmission to humans through water has been demonstrated for G1 and G2, mainly in developing countries, but is only suspected for the zoonotic genotypes. Thus, the water-related HEV hazard may be due to human and animal faeces. The high HEV genetic variability allows considering the presence in wastewater of not only different genotypes, but also quasispecies adding even greater diversity. Moreover, recent studies have demonstrated that HEV particles may be either quasi-enveloped or non-enveloped, potentially implying differential viral behaviours in the environment. The presence of HEV has been demonstrated at the different stages of the water cycle all over the world, especially for HEV G3 in Europe and the USA. Concerning HEV survival in water, the virus does not have higher resistance to inactivating factors (heat, UV, chlorine, physical removal), compared to viral indicators (MS2 phage) or other highly resistant enteric viruses (Hepatitis A virus). But the studies did not take into account genetic (genogroups, quasispecies) or structural (quasi- or non-enveloped forms) HEV variability. Viral variability could indeed modify HEV persistence in water by influencing its interaction with the environment, its infectivity and its pathogenicity, and subsequently its transmission by water. The cell culture methods used to study HEV survival still have drawbacks (challenging virus cultivation, time consuming, lack of sensitivity). As explained in the present review, the issue of HEV transmission to humans through water is similar to that of other enteric viruses because of their similar or lower survival. HEV transmission to animals through water and how the virus variability affects its survival and transmission remain to be investigated.
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Affiliation(s)
- H Fenaux
- Laboratoire de Virologie, CHRU de Nancy Brabois, F-54511 Vandoeuvre lès Nancy, France; Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement, LCPME UMR 7564 CNRS-UL, F-54600 Villers lès Nancy, France
| | - M Chassaing
- Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement, LCPME UMR 7564 CNRS-UL, F-54600 Villers lès Nancy, France
| | - S Berger
- Laboratoire de Virologie, CHRU de Nancy Brabois, F-54511 Vandoeuvre lès Nancy, France
| | - C Gantzer
- Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement, LCPME UMR 7564 CNRS-UL, F-54600 Villers lès Nancy, France
| | - I Bertrand
- Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement, LCPME UMR 7564 CNRS-UL, F-54600 Villers lès Nancy, France
| | - E Schvoerer
- Laboratoire de Virologie, CHRU de Nancy Brabois, F-54511 Vandoeuvre lès Nancy, France; Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement, LCPME UMR 7564 CNRS-UL, F-54600 Villers lès Nancy, France.
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27
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Schlabe S, van Bremen K, Goldmann G, Oldenburg J, Eis-Hübinger AM, Zeitler H, Spengler U. Acute Hepatitis E Virus infection in a hemophilic patient with acquired inhibitor during immune tolerance therapy according to modified Bonn-Malmö protocol. Haemophilia 2019; 25:e117-e120. [PMID: 30694010 DOI: 10.1111/hae.13688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2018] [Revised: 12/16/2018] [Accepted: 01/08/2019] [Indexed: 06/09/2023]
Affiliation(s)
- Stefan Schlabe
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany
- German Center for Infectious Diseases, Partner site Cologne-Bonn, Cologne, Germany
| | - Kathrin van Bremen
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany
- German Center for Infectious Diseases, Partner site Cologne-Bonn, Cologne, Germany
| | - Georg Goldmann
- German Center for Infectious Diseases, Partner site Cologne-Bonn, Cologne, Germany
- Institute for Experimental Hematology and Blood Transfusion, University Hospital of Bonn, Bonn, Germany
| | - Johannes Oldenburg
- German Center for Infectious Diseases, Partner site Cologne-Bonn, Cologne, Germany
- Institute for Experimental Hematology and Blood Transfusion, University Hospital of Bonn, Bonn, Germany
| | - Anna-Maria Eis-Hübinger
- German Center for Infectious Diseases, Partner site Cologne-Bonn, Cologne, Germany
- Institute of Virology, University of Bonn Medical Centre, Bonn, Germany
| | - Heike Zeitler
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany
- German Center for Infectious Diseases, Partner site Cologne-Bonn, Cologne, Germany
| | - Ulrich Spengler
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany
- German Center for Infectious Diseases, Partner site Cologne-Bonn, Cologne, Germany
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28
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Meister TL, Bruening J, Todt D, Steinmann E. Cell culture systems for the study of hepatitis E virus. Antiviral Res 2019; 163:34-49. [PMID: 30653997 DOI: 10.1016/j.antiviral.2019.01.007] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Revised: 01/08/2019] [Accepted: 01/13/2019] [Indexed: 12/26/2022]
Abstract
Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and is the leading cause of enterically-transmitted viral hepatitis worldwide. Increasing numbers of HEV infections, together with no available specific anti-HEV treatment, contributes to the pathogen's major health burden. A robust cell culture system is required for virologic studies and the development of new antiviral drugs. Unfortunately, like other hepatitis viruses, HEV is difficult to propagate in conventional cell lines. Many different cell culture systems have been tested using various HEV strains, but viral replication usually progresses very slowly, and infection with low virion counts results in non-productive HEV replication. However, recent progress involving generation of cDNA clones and passaging primary patient isolates in distinct cell lines has improved in vitro HEV propagation. This review describes various approaches to cultivate HEV in cellular and animal models and how these systems are used to study HEV infections and evaluate anti-HEV drug candidates.
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Affiliation(s)
- Toni L Meister
- Ruhr-University Bochum, Faculty of Medicine, Department of Molecular and Medical Virology, Bochum, Germany
| | - Janina Bruening
- Ruhr-University Bochum, Faculty of Medicine, Department of Molecular and Medical Virology, Bochum, Germany
| | - Daniel Todt
- Ruhr-University Bochum, Faculty of Medicine, Department of Molecular and Medical Virology, Bochum, Germany.
| | - Eike Steinmann
- Ruhr-University Bochum, Faculty of Medicine, Department of Molecular and Medical Virology, Bochum, Germany.
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29
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Hepatitis E virus: reasons for emergence in humans. Curr Opin Virol 2018; 34:10-17. [PMID: 30497051 DOI: 10.1016/j.coviro.2018.11.006] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 11/08/2018] [Accepted: 11/13/2018] [Indexed: 12/11/2022]
Abstract
Hepatitis E virus (HEV) infects both humans and other animal species. Recently, we have seen a steady increase in autochthonous cases of human HEV infection in certain areas especially in Europe, and large outbreaks in several African countries among the displaced population. This mini-review critically analyzes potential host, environmental, and viral factors that may be associated with the emergence of hepatitis E in humans. The existence of numerous HEV reservoir animals such as pig, deer and rabbit results in human exposure to infected animals via direct contact or through animal meat consumption. Contamination of drinking, irrigation and coastal water by animal and human wastes lead to emergence of endemic cases in industrialized countries and outbreaks in displaced communities especially in war-torn countries.
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30
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King NJ, Hewitt J, Perchec-Merien AM. Hiding in Plain Sight? It's Time to Investigate Other Possible Transmission Routes for Hepatitis E Virus (HEV) in Developed Countries. FOOD AND ENVIRONMENTAL VIROLOGY 2018; 10:225-252. [PMID: 29623595 DOI: 10.1007/s12560-018-9342-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/17/2017] [Accepted: 03/29/2018] [Indexed: 06/08/2023]
Abstract
Historically in developed countries, reported hepatitis E cases were typically travellers returning from countries where hepatitis E virus (HEV) is endemic, but now there are increasing numbers of non-travel-related ("autochthonous") cases being reported. Data for HEV in New Zealand remain limited and the transmission routes unproven. We critically reviewed the scientific evidence supporting HEV transmission routes in other developed countries to inform how people in New Zealand may be exposed to this virus. A substantial body of indirect evidence shows domesticated pigs are a source of zoonotic human HEV infection, but there is an information bias towards this established reservoir. The increasing range of animals in which HEV has been detected makes it important to consider other possible animal reservoirs of HEV genotypes that can or could infect humans. Foodborne transmission of HEV from swine and deer products has been proven, and a large body of indirect evidence (e.g. food surveys, epidemiological studies and phylogenetic analyses) support pig products as vehicles of HEV infection. Scarce data from other foods suggest we are neglecting other potential sources of foodborne HEV infection. Moreover, other transmission routes are scarcely investigated in developed countries; the role of infected food handlers, person-to-person transmission via the faecal-oral route, and waterborne transmission from recreational contact or drinking untreated or inadequately treated water. People have become symptomatic after receiving transfusions of HEV-contaminated blood, but it is unclear how important this is in the overall hepatitis E disease burden. There is need for broader research efforts to support establishing risk-based controls.
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Affiliation(s)
- Nicola J King
- Institute of Environmental Science and Research, 34 Kenepuru Drive, Kenepuru, Porirua, 5022, New Zealand
| | - Joanne Hewitt
- Institute of Environmental Science and Research, 34 Kenepuru Drive, Kenepuru, Porirua, 5022, New Zealand.
| | - Anne-Marie Perchec-Merien
- New Zealand Ministry for Primary Industries, Pastoral House, 25 The Terrace, Wellington, New Zealand
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31
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Kantala T, Maunula L. Hepatitis E virus: zoonotic and foodborne transmission in developed countries. Future Virol 2018. [DOI: 10.2217/fvl-2018-0062] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Hepatitis E virus (HEV), together with hepatitis A virus, transmits via the fecal–oral route. The number of domestic hepatitis E cases among Europeans has grown alarmingly during the past 5 years. Surveillance studies suggest that the number of foodborne HEV infections is increasing most rapidly. Zoonotic HEV genotype HEV-3 is prevalent among pigs and wild boars in Europe and many developed countries, whereas zoonotic genotype HEV-4 is more common in pigs in some Asian countries. This review presents the most recent data about possible foodborne transmission of HEV via pigs and other production animals and about the presence of HEV in high-risk foods, such as ready-to-eat meat products. Possible solutions about how to tackle this problem are discussed here.
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Affiliation(s)
- Tuija Kantala
- Department of Food Hygiene & Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014, Helsinki, Finland
- Finnish Food Safety Authority Evira, Mustialankatu 3, FI-00790 Helsinki, Finland
| | - Leena Maunula
- Department of Food Hygiene & Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014, Helsinki, Finland
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32
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Randazzo W, Vasquez-García A, Aznar R, Sánchez G. Viability RT-qPCR to Distinguish Between HEV and HAV With Intact and Altered Capsids. Front Microbiol 2018; 9:1973. [PMID: 30210465 PMCID: PMC6119771 DOI: 10.3389/fmicb.2018.01973] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Accepted: 08/06/2018] [Indexed: 01/08/2023] Open
Abstract
The hepatitis E virus (HEV) is an emerging pathogen showing a considerable increase in the number of reported cases in Europe mainly related to the ingestion of contaminated food. As with other relevant viral foodborne pathogens, real-time reverse transcriptase polymerase chain reaction (RT-qPCR) is the gold standard for HEV detection in clinical, food, and environmental samples, but these procedures cannot discriminate between inactivated and potentially infectious viruses. Thus, the aim of this study was to develop a viability PCR method to discriminate between native, heat-, and high-pressure processing (HPP)-treated HEV using the hepatitis A virus (HAV) as a cultivable surrogate. To this end, different concentrations of viability markers (PMAxx and platinum chloride, PtCl4) were screened firstly on purified viral RNA using different RT-qPCR assays. Reductions of HEV RNA signals of >17.5, >15.0, and >15.5 quantification cycles (Cq) were reported for PtCl4 and 1.6, 2.9, and 8.4 Cq for PMAxx, clearly indicating a better performance of PtCl4 than PMAxx irrespective of the RT-qPCR assay used. The most efficient viability pretreatment (500 μM PtCl4 incubated at 5°C for 30 min) was then assessed on native, heat-, and HPP-treated HEV suspension. The optimized viability RT-qPCR discriminated successfully between native, heat-, and HPP-treated HEV, to different extents depending on the experimental conditions. In particular, approximately 2-log10 reduction was reported by PtCl4-RT-qPCR at both 72 and 95°C compared to the control. Additionally, both viability pretreatments were tested for HPP-treated HAV without success, while PtCl4-RT-qPCR completely eliminated (>5.6-log10 reduction) the RT-qPCR signals of HPP-treated HEV. Although this viability procedure may still overestimate infectivity, the PtCl4 pretreatment represents progress to better interpreting the quantification of intact HEV, and it could be included in molecular procedures used to quantify enteric viruses in food and environmental samples.
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Affiliation(s)
- Walter Randazzo
- Department of Microbiology and Ecology, University of Valencia, Valencia, Spain
- Department of Preservation and Food Safety Technologies, Instituto de Agroquímica y Tecnología de Alimentos – Consejo Superior de Investigaciones Científicas, Valencia, Spain
| | - Andrea Vasquez-García
- Faculty of Animal Science and Food Engineering, University of São Paulo, São Paulo, Brazil
| | - Rosa Aznar
- Department of Microbiology and Ecology, University of Valencia, Valencia, Spain
- Department of Preservation and Food Safety Technologies, Instituto de Agroquímica y Tecnología de Alimentos – Consejo Superior de Investigaciones Científicas, Valencia, Spain
| | - Gloria Sánchez
- Department of Preservation and Food Safety Technologies, Instituto de Agroquímica y Tecnología de Alimentos – Consejo Superior de Investigaciones Científicas, Valencia, Spain
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Imagawa T, Sugiyama R, Shiota T, Li TC, Yoshizaki S, Wakita T, Ishii K. Evaluation of Heating Conditions for Inactivation of Hepatitis E Virus Genotypes 3 and 4. J Food Prot 2018; 81:947-952. [PMID: 29745758 DOI: 10.4315/0362-028x.jfp-17-290] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Hepatitis E virus (HEV) is a causative agent of acute hepatitis throughout the world. HEV genotypes 1 through 4 infect humans, whereas genotypes 3 and 4 (Gt3 and Gt4) also infect other animals. In developed countries, the main HEV infection route is by foodborne transmission, resulting from the consumption of undercooked meat. It is important to know the criteria for HEV control in daily cooking. In this study, we assessed the heat conditions required to inactivate HEV Gt3 and Gt4 in culture supernatants and spiked minced pork meat. HEV inactivation was determined by measuring viral RNA amplification in PLC/PRF/5 cell culture. In our cell culture assay, an inoculum containing HEV titer that is equivalent to >105 genome RNA copies can be determined as infectious. The internal temperature of pork during heating was measured to represent that achieved during cooking. Both HEV Gt3 and Gt4 were inactivated in culture supernatants heated at >65°C for 5 min and at >80°C for 1 min and in minced meat at 70°C for 5 min. Inoculated culture supernatant contained 108 HEV genome RNA copies (103 infectious units [IU]); therefore, it was indicated that HEV titer decreased >3 log IU after heating. In a comparison of Gt3 and Gt4, Gt4 showed slightly greater heat stability than Gt3. Boiling showed superior heating efficacy compared with roasting, and pork liver was slightly easier to heat than pork loin. Heating for 5 min by both boiling and roasting increased the internal temperature of pork products to more than 70°C. Although our data revealed that HEV Gt4 was slightly more heat stable than Gt3, both genotypes were inactivated by the appropriate heating conditions. Therefore, the risk of HEV foodborne infection could be mitigated by the appropriate cooking of pork meat. It is also important that both the supplier and the consumer are cognizant of the risk of HEV foodborne infection from livestock products.
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Affiliation(s)
- Toshifumi Imagawa
- 1 Department of Virology and Parasitology, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi, Hamamatsu, Shizuoka 431-3192, Japan.,2 Department of Virology II, National Institute of Infectious Disease, 4-7-1, Gakuen, Musashimurayama, Tokyo 208-0011, Japan
| | - Ryuichi Sugiyama
- 2 Department of Virology II, National Institute of Infectious Disease, 4-7-1, Gakuen, Musashimurayama, Tokyo 208-0011, Japan
| | - Tomoyuki Shiota
- 2 Department of Virology II, National Institute of Infectious Disease, 4-7-1, Gakuen, Musashimurayama, Tokyo 208-0011, Japan
| | - Tian-Cheng Li
- 2 Department of Virology II, National Institute of Infectious Disease, 4-7-1, Gakuen, Musashimurayama, Tokyo 208-0011, Japan
| | - Sayaka Yoshizaki
- 2 Department of Virology II, National Institute of Infectious Disease, 4-7-1, Gakuen, Musashimurayama, Tokyo 208-0011, Japan
| | - Takaji Wakita
- 3 Department of Virology II, National Institute of Infectious Disease, 1-23-1, Toyama, Shinjuku, Tokyo 162-8640, Japan
| | - Koji Ishii
- 2 Department of Virology II, National Institute of Infectious Disease, 4-7-1, Gakuen, Musashimurayama, Tokyo 208-0011, Japan
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Hepatitis E in High-Income Countries: What Do We Know? And What Are the Knowledge Gaps? Viruses 2018; 10:v10060285. [PMID: 29799485 PMCID: PMC6024799 DOI: 10.3390/v10060285] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Revised: 05/16/2018] [Accepted: 05/23/2018] [Indexed: 12/11/2022] Open
Abstract
Hepatitis E virus (HEV) is a positive-strand RNA virus transmitted by the fecal–oral route. HEV genotypes 1 and 2 infect only humans and cause mainly waterborne outbreaks. HEV genotypes 3 and 4 are widely represented in the animal kingdom, and are mainly transmitted as a zoonosis. For the past 20 years, HEV infection has been considered an imported disease in developed countries, but now there is evidence that HEV is an underrecognized pathogen in high-income countries, and that the incidence of confirmed cases has been steadily increasing over the last decade. In this review, we describe current knowledge about the molecular biology of HEV, its clinical features, its main routes of transmission, and possible therapeutic strategies in developed countries.
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35
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Rodríguez-Lázaro D, Hernandez M, Cook N. Hepatitis E Virus: A New Foodborne Zoonotic Concern. ADVANCES IN FOOD AND NUTRITION RESEARCH 2018; 86:55-70. [PMID: 30077224 DOI: 10.1016/bs.afnr.2018.04.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Hepatitis E virus (HEV) is an enteric nonenveloped single-stranded RNA virus. Among the mammalian lineages, four genotypes are associated to human infection: genogroups 1 and 2 infect only humans and are mainly found in developing countries, while genogroups 3 and 4 are zoonotic, being found in a variety of animal species including pigs, and are autochthonous in developed countries. HEV infection can result in liver damage and with genotypes 1 and 2 symptoms can be particularly severe in pregnant women, with a high lethality ratio. Several cases of foodborne transmission of hepatitis E have been reported, often involving consumption of meat, especially raw or undercooked. Information is lacking on the exact extent of foodborne transmission of HEV.
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Affiliation(s)
- David Rodríguez-Lázaro
- Microbiology Division, Department of Biotechnology and Food Science, University of Burgos, Burgos, Spain.
| | - Marta Hernandez
- Microbiology Division, Department of Biotechnology and Food Science, University of Burgos, Burgos, Spain; Laboratory of Molecular Biology and Microbiology, ITACyL, Valladolid, Spain
| | - Nigel Cook
- Jorvik Food and Environmental Virology, York, United Kingdom
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Abstract
Background Hepatitis E (HE) caused by Hepatitis E virus (HEV) is an emerging global public health threat. It has been identified as potentially zoonotic and swine act as main reservoirs. Objectives The objective of this study was to determine the seroprevalence and risk factors associated with HEV in swine abattoir workers. Methods This was a cross-sectional study where 45 workers were sampled (N=50), serum collected and tested for presence of anti HEV IgM using ELISA. Results A seroprevalence of 13.3% was obtained with the highest 50% among slaughterers and the lowest amongst sanitary cleaner, cloth cleaners and inspector. Those in direct contact with live pigs, their carcasses and tissues were at a higher risk compared to those in indirect contact. Seroprevalence was seen to increase with age, with the highest rate among those above 24 years. Conclusion There is silent HE virus infection in abattoir workers at Wambizi as reflected by presence anti HEV IgM in 13% of the tested serum. However, no single case of HE has ever been reported in swine abattoir workers or general population in Kampala city. This silent maintenance of HEV infection amongst swine abattoir workers is an occupational risk that could challenge public health systems.
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Abstract
Hepatitis E virus (HEV) infection can lead to acute and chronic hepatitis as well as to extrahepatic manifestations such as neurological and renal disease; it is the most common cause of acute viral hepatitis worldwide. Four genotypes are responsible for most infection in humans, of which HEV genotypes 1 and 2 are obligate human pathogens and HEV genotypes 3 and 4 are mostly zoonotic. Until quite recently, HEV was considered to be mainly responsible for epidemics of acute hepatitis in developing regions owing to contamination of drinking water supplies with human faeces. However, HEV is increasingly being recognized as endemic in some developed regions. In this setting, infections occur through zoonotic transmission or contaminated blood products and can cause chronic hepatitis in immunocompromised individuals. HEV infections can be diagnosed by measuring anti-HEV antibodies, HEV RNA or viral capsid antigen in blood or stool. Although an effective HEV vaccine exists, it is only licensed for use in China. Acute hepatitis E is usually self-limiting and does not require specific treatment. Management of immunocompromised individuals involves lowering the dose of immunosuppressive drugs and/or treatment with the antiviral agent ribavirin.
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Abstract
PURPOSE OF REVIEW Infection with the hepatitis E virus (HEV) is very common worldwide. The epidemiology, viral genotypes, and transmission routes differ between low-resource countries and economically developed countries. These differences have resulted in the design of diverse prevention and treatment strategies to combat HEV. RECENT FINDINGS The population seroprevalence of HEV immunoglobulin G varies between 5 and 50%. However, the diagnosis of acute hepatitis from HEV has not been common in the United States or Western Europe. Chronic progressive HEV infections have been reported among patients who are immunocompromised. Successful treatment of patients with chronic hepatitis from HEV infection with antiviral agents, such as ribavirin or interferon-α, has been reported. Extrahepatic manifestations of HEV infection are common. Large epidemics of hundreds or thousands of cases continue to be reported among populations in Asia and Africa. A subunit peptide HEV vaccine has been found to be highly efficacious in a large clinical trial. However, the vaccine has not been evaluated in populations of pregnant women or other risk groups and is only available in China. SUMMARY Although HEV infections are increasingly recognized as a global public health problem, there are few methods for prevention and treatment that are widely available.
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Cook N, D'Agostino M, Johne R. Potential Approaches to Assess the Infectivity of Hepatitis E Virus in Pork Products: A Review. FOOD AND ENVIRONMENTAL VIROLOGY 2017; 9:243-255. [PMID: 28470455 DOI: 10.1007/s12560-017-9303-7] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Accepted: 04/26/2017] [Indexed: 05/04/2023]
Abstract
The zoonotic transmission of hepatitis E, caused by the hepatitis E virus (HEV), is an emerging issue. HEV appears common in pigs (although infected pigs do not show clinical signs), and evidence suggests that a number of hepatitis E cases have been associated with the consumption of undercooked pork meat and products. Little information is available on whether cooking can eliminate HEV, since there is currently no robust method for measuring its infectivity. HEV infectivity can be clearly demonstrated by monitoring for signs of infection (e.g., shedding of virus) in an animal model. However, this approach has several disadvantages, such as lack of reproducibility and unsuitability for performing large numbers of tests, high costs, and not least ethical considerations. Growth in cell culture can unambiguously show that a virus is infectious and has the potential for replication, without the disadvantages of using animals. Large numbers of tests can also be performed, which can make the results more amenable to statistical interpretation. However, no HEV cell culture system has been shown to be applicable to all HEV strains, none has been standardized, and few studies have demonstrated their use for measurement of HEV infectivity in food samples. Nonetheless, cell culture remains the most promising approach, and the main recommendation of this review is that there should be an extensive research effort to develop and validate a cell culture-based method for assessing HEV infectivity in pork products. Systems comprising promising cell lines and HEV strains which can grow well in cell culture should be tested to select an assay for effective and reliable measurement of HEV infectivity over a wide range of virus concentrations. The assay should then be harnessed to a procedure which can extract HEV from pork products, to produce a method suitable for further use. The method can then be used to determine the effect of heat or other elimination processes on HEV in pork meat and products, or to assess whether HEV detected in any surveyed foodstuffs is infectious and therefore poses a risk to public health.
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Affiliation(s)
- Nigel Cook
- Fera Science Ltd., Sand Hutton, York, YO41 1LZ, UK.
- Jorvik Food and Environmental Virology Ltd., York, UK.
| | - Martin D'Agostino
- Fera Science Ltd., Sand Hutton, York, YO41 1LZ, UK
- Campden BRI, Chipping Campden, UK
| | - Reimar Johne
- German Federal Institute for Risk Assessment, Berlin, Germany
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Zhang L, Li K, Huang S, Liu D, Rehman MU, Lan Y, Zhang H, Wang L, Hao Y, Iqbal MK, Mehmood K, Chamba Y, Li J. Seroprevalence and risk factors associated with hepatitis E virus infections among people and pigs in Tibet, China. Acta Trop 2017; 172:102-106. [PMID: 28472617 DOI: 10.1016/j.actatropica.2017.04.033] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Revised: 04/24/2017] [Accepted: 04/29/2017] [Indexed: 12/17/2022]
Abstract
Hepatitis E virus (HEV), the causative agent of hepatitis E, is an important public health problem throughout the world. There is little information available on the autochthonous HEV infection in highland inhabitants (Tibet, average elevation >3000m) of China. Therefore, we conducted a cross-sectional survey to determine the sero-prevalence of Hepatitis E and association of different risk factors in local people and pigs in Tibet, China. For this purpose, serum samples were collected from 600 local volunteers and 453 Tibetan pigs from July 2014 to August 2015. All the samples were examined for the presence of anti-HEV IgG antibodies by using enzyme-linked immunosorbent assay (ELISA). While socio-demographic and behavioral characteristics were also obtained through questionnaire. The present survey found a close relationship among the HEV of Tibetan people and pigs. The prevalence of anti-HEV IgG was detected 39.33% (236/600) and 42.38% (192/453) in local people and pigs, respectively. There was a significance association of different age groups, ethnic groups, people having contact with pigs or consuming uncooked meat, and gender of Tibetan pigs. Our findings confirmed the presence of autochthonous HEV among people and pigs in Tibet, China. Therefore, effective measures should be taken to prevent and control HEV infection in Tibet, China.
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Affiliation(s)
- Lihong Zhang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China
| | - Kun Li
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China
| | - Shucheng Huang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China
| | - Dongyu Liu
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China
| | - Mujeeb Ur Rehman
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China
| | - Yanfang Lan
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China
| | - Hui Zhang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China
| | - Lei Wang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China
| | - Yanan Hao
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China
| | - Muhammad Kashif Iqbal
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China
| | - Khalid Mehmood
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China; University College of Veterinary & Animal Sciences, Islamia University of Bahawalpur, Pakistan
| | - Yangczom Chamba
- Laboratory of Detection and Monitoring of Highland Animal Disease, Tibet Agriculture and Animal Husbandry College, Linzhi, 860000, Tibet, People's Republic of China
| | - Jiakui Li
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China; Laboratory of Detection and Monitoring of Highland Animal Disease, Tibet Agriculture and Animal Husbandry College, Linzhi, 860000, Tibet, People's Republic of China.
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Ricci A, Allende A, Bolton D, Chemaly M, Davies R, Fernandez Escamez PS, Herman L, Koutsoumanis K, Lindqvist R, Nørrung B, Robertson L, Ru G, Sanaa M, Simmons M, Skandamis P, Snary E, Speybroeck N, Ter Kuile B, Threlfall J, Wahlström H, Di Bartolo I, Johne R, Pavio N, Rutjes S, van der Poel W, Vasickova P, Hempen M, Messens W, Rizzi V, Latronico F, Girones R. Public health risks associated with hepatitis E virus (HEV) as a food-borne pathogen. EFSA J 2017; 15:e04886. [PMID: 32625551 PMCID: PMC7010180 DOI: 10.2903/j.efsa.2017.4886] [Citation(s) in RCA: 82] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Hepatitis E virus (HEV) is an important infection in humans in EU/EEA countries, and over the last 10 years more than 21,000 acute clinical cases with 28 fatalities have been notified with an overall 10-fold increase in reported HEV cases; the majority (80%) of cases were reported from France, Germany and the UK. However, as infection in humans is not notifiable in all Member States, and surveillance differs between countries, the number of reported cases is not comparable and the true number of cases would probably be higher. Food-borne transmission of HEV appears to be a major route in Europe; pigs and wild boars are the main source of HEV. Outbreaks and sporadic cases have been identified in immune-competent persons as well as in recognised risk groups such as those with pre-existing liver damage, immunosuppressive illness or receiving immunosuppressive treatments. The opinion reviews current methods for the detection, identification, characterisation and tracing of HEV in food-producing animals and foods, reviews literature on HEV reservoirs and food-borne pathways, examines information on the epidemiology of HEV and its occurrence and persistence in foods, and investigates possible control measures along the food chain. Presently, the only efficient control option for HEV infection from consumption of meat, liver and products derived from animal reservoirs is sufficient heat treatment. The development of validated quantitative and qualitative detection methods, including infectivity assays and consensus molecular typing protocols, is required for the development of quantitative microbial risk assessments and efficient control measures. More research on the epidemiology and control of HEV in pig herds is required in order to minimise the proportion of pigs that remain viraemic or carry high levels of virus in intestinal contents at the time of slaughter. Consumption of raw pig, wild boar and deer meat products should be avoided.
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Salines M, Andraud M, Rose N. From the epidemiology of hepatitis E virus (HEV) within the swine reservoir to public health risk mitigation strategies: a comprehensive review. Vet Res 2017; 48:31. [PMID: 28545558 PMCID: PMC5445439 DOI: 10.1186/s13567-017-0436-3] [Citation(s) in RCA: 112] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Accepted: 04/19/2017] [Indexed: 02/07/2023] Open
Abstract
Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans, an emerging zoonosis mainly transmitted via food in developed countries and for which domestic pigs are recognised as the main reservoir. It therefore appears important to understand the features and drivers of HEV infection dynamics on pig farms in order to implement HEV surveillance programmes and to assess and manage public health risks. The authors have reviewed the international scientific literature on the epidemiological characteristics of HEV in swine populations. Although prevalence estimates differed greatly from one study to another, all consistently reported high variability between farms, suggesting the existence of multifactorial conditions related to infection and within-farm transmission of the virus. Longitudinal studies and experimental trials have provided estimates of epidemiological parameters governing the transmission process (e.g. age at infection, transmission parameters, shedding period duration or lag time before the onset of an immune response). Farming practices, passive immunity and co-infection with immunosuppressive agents were identified as the main factors influencing HEV infection dynamics, but further investigations are needed to clarify the different HEV infection patterns observed in pig herds as well as HEV transmission between farms. Relevant surveillance programmes and control measures from farm to fork also have to be fostered to reduce the prevalence of contaminated pork products entering the food chain.
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Affiliation(s)
- Morgane Salines
- ANSES-Ploufragan-Plouzané Laboratory, BP 53, 22440, Ploufragan, France. .,Université Bretagne Loire, Rennes, France.
| | - Mathieu Andraud
- ANSES-Ploufragan-Plouzané Laboratory, BP 53, 22440, Ploufragan, France.,Université Bretagne Loire, Rennes, France
| | - Nicolas Rose
- ANSES-Ploufragan-Plouzané Laboratory, BP 53, 22440, Ploufragan, France.,Université Bretagne Loire, Rennes, France
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Pavio N, Bagdassarian E, Pellerin M, Doceul V. Réservoirs animaux du Virus de l’Hépatite E et transmissions zoonotiques. BULLETIN DE L'ACADÉMIE NATIONALE DE MÉDECINE 2017; 201:657-670. [DOI: 10.1016/s0001-4079(19)30448-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Emmoth E, Rovira J, Rajkovic A, Corcuera E, Wilches Pérez D, Dergel I, Ottoson JR, Widén F. Inactivation of Viruses and Bacteriophages as Models for Swine Hepatitis E Virus in Food Matrices. FOOD AND ENVIRONMENTAL VIROLOGY 2017; 9:20-34. [PMID: 27783334 DOI: 10.1007/s12560-016-9268-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Accepted: 10/19/2016] [Indexed: 06/06/2023]
Abstract
Hepatitis E virus has been recognised as a food-borne virus hazard in pork products, due to its zoonotic properties. This risk can be reduced by adequate treatment of the food to inactivate food-borne viruses. We used a spectrum of viruses and bacteriophages to evaluate the effect of three food treatments: high pressure processing (HPP), lactic acid (LA) and intense light pulse (ILP) treatments. On swine liver at 400 MPa for 10 min, HPP gave log10 reductions of ≥4.2, ≥5.0 and 3.4 for feline calicivirus (FCV) 2280, FCV wildtype (wt) and murine norovirus 1 (MNV 1), respectively. Escherichia coli coliphage ϕX174 displayed a lower reduction of 1.1, while Escherichia coli coliphage MS2 was unaffected. For ham at 600 MPa, the corresponding reductions were 4.1, 4.4, 2.9, 1.7 and 1.3 log10. LA treatment at 2.2 M gave log10 reductions in the viral spectrum of 0.29-2.1 for swine liver and 0.87-3.1 for ham, with ϕX174 and MNV 1, respectively, as the most stable microorganisms. The ILP treatment gave log10 reductions of 1.6-2.8 for swine liver, 0.97-2.2 for ham and 1.3-2.3 for sausage, at 15-60 J cm-2, with MS2 as the most stable microorganism. The HPP treatment gave significantly (p < 0.05) greater virus reduction on swine liver than ham for the viruses at equivalent pressure/time combinations. For ILP treatment, reductions on swine liver were significantly (p < 0.05) greater than on ham for all microorganisms. The results presented here could be used in assessments of different strategies to protect consumers against virus contamination and in advice to food producers. Conservative model indicators for the pathogenic viruses could be suggested.
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Affiliation(s)
- Eva Emmoth
- Department of Microbiology, National Veterinary Institute (SVA), 751 89, Uppsala, Sweden.
- Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
| | - Jordi Rovira
- Department of Biotechnology and Food Science, Faculty of Sciences, University of Burgos, Pza. Misael Bañuelos s/n, 09001, Burgos, Spain
| | - Andreja Rajkovic
- Laboratory of Food Microbiology and Food Preservation, Department of Food Safety and Food Quality, Faculty of Bioscience Engineering, Ghent University, Food2Know, Coupure Links 653, 9000, Ghent, Belgium
- Department of Food Safety and Quality Management, Faculty of Agriculture, Belgrade University, Nemanjina 6, Zemun-Belgrade, 11080, Serbia
| | - Elena Corcuera
- Department of Biotechnology and Food Science, Faculty of Sciences, University of Burgos, Pza. Misael Bañuelos s/n, 09001, Burgos, Spain
| | - Diego Wilches Pérez
- Hiperbaric España Polígono Industrial Villalonquéjar, C/Condado de Treviño, 6, 09001, Burgos, Spain
| | - Irene Dergel
- Department of Microbiology, National Veterinary Institute (SVA), 751 89, Uppsala, Sweden
| | - Jakob R Ottoson
- Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden
- Department of Risk-Benefit Analysis, National Food Agency, Uppsala, Sweden
| | - Frederik Widén
- Department of Microbiology, National Veterinary Institute (SVA), 751 89, Uppsala, Sweden
- Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden
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Pathogens of Food Animals: Sources, Characteristics, Human Risk, and Methods of Detection. ADVANCES IN FOOD AND NUTRITION RESEARCH 2017; 82:277-365. [PMID: 28427535 DOI: 10.1016/bs.afnr.2016.12.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Pathogens associated with food production (livestock) animals come in many forms causing a multitude of disease for humans. For the purpose of this review, these infectious agents can be divided into three broad categories: those that are associated with bacterial disease, those that are associated with viruses, and those that are parasitic in nature. The goal of this chapter is to provide the reader with an overview of the most common pathogens that cause disease in humans through exposure via the food chain and the consequence of this exposure as well as risk and detection methods. We have also included a collection of unusual pathogens that although rare have still caused disease, and their recognition is warranted in light of emerging and reemerging diseases. These provide the reader an understanding of where the next big outbreak could occur. The influence of the global economy, the movement of people, and food makes understanding production animal-associated disease paramount to being able to address new diseases as they arise.
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Pelosi E, Clarke I. Hepatitis E: a complex and global disease. EMERGING HEALTH THREATS JOURNAL 2017. [DOI: 10.3402/ehtj.v1i0.7069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- E Pelosi
- Department of Microbiology and Virology, Health Protection Agency, Southeast Regional Laboratory, Southampton General Hospital, Southampton, UK; and
| | - I Clarke
- Department of Molecular Microbiology, Southampton Medical School, Southampton General Hospital, Southampton, UK
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Hepatitis E Virus in Industrialized Countries: The Silent Threat. BIOMED RESEARCH INTERNATIONAL 2016; 2016:9838041. [PMID: 28070522 PMCID: PMC5192302 DOI: 10.1155/2016/9838041] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 11/07/2016] [Accepted: 11/15/2016] [Indexed: 12/11/2022]
Abstract
Hepatitis E virus (HEV) is the main cause of acute viral hepatitis worldwide. Its presence in developing countries has been documented for decades. Developed countries were supposed to be virus-free and initially only imported cases were detected in those areas. However, sporadic and autochthonous cases of HEV infection have been identified and studies reveal that the virus is worldwide spread. Chronic hepatitis and multiple extrahepatic manifestations have also been associated with HEV. We review the data from European countries, where human, animal, and environmental data have been collected since the 90s. In Europe, autochthonous HEV strains were first detected in the late 90s and early 2000s. Since then, serological data have shown that the virus infects quite frequently the European population and that some species, such as pigs, wild boars, and deer, are reservoirs. HEV strains can be isolated from environmental samples and reach the food chain, as shown by the detection of the virus in mussels and in contaminated pork products as sausages or meat. All these data highlight the need of studies directed to control the sources of HEV to protect immunocompromised individuals that seem the weakest link of the HEV epidemiology in industrialized regions.
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CHEN YJ, CAO NX, XIE RH, DING CX, CHEN EF, ZHU HP, SUN JM, SHANG XP, WANG XX, MIAO ZP. Epidemiological investigation of a tap water-mediated hepatitis E virus genotype 4 outbreak in Zhejiang Province, China. Epidemiol Infect 2016; 144:3387-3399. [PMID: 27546066 PMCID: PMC9150197 DOI: 10.1017/s0950268816001898] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Revised: 07/30/2016] [Accepted: 07/31/2016] [Indexed: 12/19/2022] Open
Abstract
An outbreak of acute hepatitis recently occurred in a nursing home in Zhejiang Province, China. The objectives of this study were to confirm the outbreak and identify the aetiology, source and transmission patterns. All residents and staff in or near the nursing home during the period from 1 October 2014 to 21 May 2015 were investigated regarding hygiene and for epidemiological information including water and food (eating meat especially pork products). Serum and stool specimens were collected for detection of hepatitis E virus (HEV) antibodies using ELISA and RNA using RT-PCR. Samples that were RNA positive were genotyped. Of 185 senior residents and 24 staff in the nursing home, there were 37 laboratory-confirmed cases during the outbreak. Of these cases, 12 patients (three deaths) were symptomatic with jaundice, a common clinical symptom for hepatitis E infection. HEV strains were isolated from three cases and they formed a single cluster within genotype 4d. A case-control study was conducted to investigate potential risk factors for the outbreak and the results revealed that cases more often washed their dishes and rinsed their mouths using tap water than the controls (P < 0·05). Based on hygiene investigation and meteorological information, it is likely that HEV-infected sewage and faeces contaminated the water network on rainy days. Collectively, these results suggest that the outbreak of HEV genotype 4 infection was most likely caused by contaminated tap water rather than food.
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Affiliation(s)
- Y. J. CHEN
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
| | - N. X. CAO
- Jiashan County Centre for Disease Control and Prevention, Jiaxing, China
| | - R. H. XIE
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
| | - C. X. DING
- Jiashan County Centre for Disease Control and Prevention, Jiaxing, China
| | - E. F. CHEN
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
| | - H. P. ZHU
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
| | - J. M. SUN
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
| | - X. P. SHANG
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
| | - X. X. WANG
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
| | - Z. P. MIAO
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
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Pisano MB, Balderramo D, Wassaf MM, Lotto M, Carlino Y, Ré VE, Debes JD. Hepatitis E virus infection in patients on dialysis and in solid organ transplant recipients in Argentina: exploring associated risk factors. Arch Virol 2016; 162:787-792. [DOI: 10.1007/s00705-016-3171-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Accepted: 10/27/2016] [Indexed: 12/21/2022]
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