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Serricchio M, Gowland P, Widmer N, Stolz M, Niederhauser C. HEV in Blood Donors in Switzerland: The Route to Safe Blood Products. Pathogens 2024; 13:911. [PMID: 39452782 PMCID: PMC11510004 DOI: 10.3390/pathogens13100911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 10/08/2024] [Accepted: 10/16/2024] [Indexed: 10/26/2024] Open
Abstract
The hepatitis E virus (HEV) is an emerging infectious disease with zoonotic potential, causing acute hepatitis in humans. Infections in healthy individuals are often acute, self-limiting and asymptomatic, thus leading to the underdiagnosis of HEV infections. Asymptomatic HEV infections pose a problem for blood transfusion safety by increasing the risk for transfusion-transmitted HEV infections. Here, we describe the journey from determining the HEV seroprevalence among blood donors to the implementation of routine HEV RNA testing of all blood products in Switzerland in 2018 and summarise the HEV cases detected since. In total, 290 HEV-positive blood donations were detected by mini-pool nucleic acid testing (NAT) in Switzerland in the period of October 2018-December 2023, equal to an incidence of 20.7 per 100,000 donations. Thanks to the implemented scheme, no transfusion-transmitted infections occurred in this period. Furthermore, blood donation monitoring has proven to be an effective means of detecting HEV outbreaks in the general population. HEV cases in Swiss blood donors are caused by two major genotypes, the Swiss-endemic subtypes 3h3 and 3c. Interestingly, 11 HEV cases (5%) were of genotype 3ra, a variant found in wild and farmed rabbits. Our results indicate that mini-pool NAT is an efficient method to reduce the risk of transfusion-transmitted HEV infections.
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Affiliation(s)
- Mauro Serricchio
- Interregional Blood Transfusion SRC, 3008 Bern, Switzerland; (M.S.); (P.G.); (M.S.)
| | - Peter Gowland
- Interregional Blood Transfusion SRC, 3008 Bern, Switzerland; (M.S.); (P.G.); (M.S.)
| | - Nadja Widmer
- Interregional Blood Transfusion SRC, 3008 Bern, Switzerland; (M.S.); (P.G.); (M.S.)
| | - Martin Stolz
- Interregional Blood Transfusion SRC, 3008 Bern, Switzerland; (M.S.); (P.G.); (M.S.)
| | - Christoph Niederhauser
- Interregional Blood Transfusion SRC, 3008 Bern, Switzerland; (M.S.); (P.G.); (M.S.)
- Institute for Infectious Diseases, University of Bern, 3012 Bern, Switzerland
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Mah JK, Keck M, Chu DY, Sooryanarain H, Sahoo MK, Lau P, Huang C, Weber J, Belanger GA, Keck Z, Shan H, Meng XJ, Foung SKH, Pinsky BA, Pham TD. Hepatitis E virus seropositivity in an ethnically diverse community blood donor population. Vox Sang 2023; 118:674-680. [PMID: 37366233 DOI: 10.1111/vox.13487] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 06/05/2023] [Accepted: 06/07/2023] [Indexed: 06/28/2023]
Abstract
BACKGROUND AND OBJECTIVES Hepatitis E virus (HEV) is an underrecognized and emerging infectious disease that may threaten the safety of donor blood supply in many parts of the world. We sought to elucidate whether our local community blood supply is at increased susceptibility for transmission of transfusion-associated HEV infections. MATERIALS AND METHODS We screened 10,002 randomly selected donations over an 8-month period between 2017 and 2018 at the Stanford Blood Center for markers of HEV infection using commercial IgM/IgG serological tests and reverse transcriptase quantitative polymerase chain reaction assays (RT-qPCR). Donor demographic information, including gender, age, self-identified ethnicity, location of residence and recent travel, were obtained from the donor database and used to generate multivariate binary logistic regressions for risk factors of IgG seropositivity. RESULTS A total of 10,002 blood donations from 7507 unique donors were screened, and there was no detectable HEV RNA by RT-qPCR. The overall seropositivity rate was 12.1% for IgG and 0.56% for IgM. Multivariate analysis of unique donors revealed a significantly higher risk of IgG seropositivity with increasing age, White/Asian ethnicities and residence in certain local counties. CONCLUSION Although HEV IgG seroprevalence in the San Francisco Bay Area is consistent with ongoing infection, the screening of a large donor population did not identify any viraemic blood donors. While HEV is an underrecognized and emerging infection in other regions, there is no evidence to support routine blood screening for HEV in our local blood supply currently; however, periodic monitoring may still be required to assess the ongoing risk.
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Affiliation(s)
- Jordan K Mah
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
| | - MeiLe Keck
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
- Stanford Blood Center, Stanford Health Care, Palo Alto, California, USA
| | - Daniel Y Chu
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
- Stanford Blood Center, Stanford Health Care, Palo Alto, California, USA
| | - Harini Sooryanarain
- Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Malaya K Sahoo
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
| | - Patrick Lau
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
| | - ChunHong Huang
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
| | - Jenna Weber
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
| | | | - Zhenyong Keck
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
| | - Hua Shan
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
| | - Xiang-Jin Meng
- Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Steven K H Foung
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
| | - Benjamin A Pinsky
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
- Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California, USA
| | - Tho D Pham
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
- Stanford Blood Center, Stanford Health Care, Palo Alto, California, USA
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Lopez-Lopez P, Frias M, Perez-Jimenez AB, Freyre-Carrillo C, Pineda JA, Fuentes A, Alados JC, Ramirez-Arellano E, Viciana I, Corona-Mata D, Caballero-Gomez J, Garcia-Bocanegra I, Risalde MA, Rivero-Juarez A, Rivero A. Temporal changes in the genotypes of Paslahepevirus balayani in southern Spain and their possible link with changes in pig trade imports. One Health 2023; 16:100539. [PMID: 37363253 PMCID: PMC10288091 DOI: 10.1016/j.onehlt.2023.100539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 04/11/2023] [Accepted: 04/11/2023] [Indexed: 06/28/2023] Open
Abstract
Introduction Paslahepevirus balayani (HEV) is an endemic zoonotic disease ranked as a major cause of acute hepatitis in Europe. Most infections occurring in Europe are due to the endemic several subtypes of genotype 3, through the consumption of raw or undercooked pork, observing a genotype geographical distribution pattern among countries Because of global changes in the pig and pork trading markets, subtype distribution might vary. We aimed to evaluate the temporal distribution of HEV genotypes in patients from southern Spain with acute hepatitis to determine whether these changes were related to the pig import trade during the study period between 2018 and 2022. Methods Prospective longitudinal study including patients with acute hepatitis from southern Spain between 2018 and 2022. HEV RNA and antibodies was tested in all patients. In patients with detectable HEV RNA, genotype was obtained. To determine the number of imported pigs and their origins, we checked the official data from the Spanish statistics on international trade of Spanish Minister of Industry during by country of origin during the same study period. Results A total of 659 patients with acute hepatitis were included in the study. Among them, 162 (24.5%) had at least one marker (IgM or RNA) of acute HEV infection. Among the 71 patients with detectable viral RNA, genotypes could be obtained for 58 (81.6%). The most prevalent HEV genotype was 3f (n = 48; 78.6%), showing a decreasing prevalence of over time, from 100% in 2018 to 70.6% in 2022. Since 2021, the emergence of other genotypes has been determined. A significant increase in the number of animals imported was observed since the beginning of the study. Denmark experienced a significant rise, from 0.03% in 2018 of total imports to 10.4% in 2022. Conclusions HEV molecular diversity is changing in Spain, could be linked to changes in fattening pig import origin.
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Affiliation(s)
- Pedro Lopez-Lopez
- Service of Infectious Diseases, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Cordoba, Spain
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Mario Frias
- Service of Infectious Diseases, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Cordoba, Spain
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Ana Belén Perez-Jimenez
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Clinical Microbiology Unit, Hospital Universitario Reina Sofía, Córdoba, Spain
- Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
| | | | - Juan A. Pineda
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Seville, Spain
| | - Ana Fuentes
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Clinical Microbiology Unit, Hospital Universitario Clínico San Cecilio, Granada, Spain
- Instituto de Investigacion Biosanitaria Ibs. Granada, Granada, Spain
| | - Juan Carlos Alados
- Clinical Microbiology Unit, Hospital Universitario de Jerez, Cádiz, Spain
- Insituto de investigación e innovación biomédica de Cadiz (INIBICA), Spain
| | - Encarnación Ramirez-Arellano
- Infectious Diseases, Microbiology and Preventive Medicine Unit, Virgen Macarena Univ. Hospital, and Department of Medicine, University of Sevilla/Biomedicine Institute of Sevilla, Sevilla, Spain
| | - Isabel Viciana
- Infectious Diseases, Microbiology and Preventive Medicine Unit, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Diana Corona-Mata
- Service of Infectious Diseases, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Cordoba, Spain
| | - Javier Caballero-Gomez
- Service of Infectious Diseases, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Cordoba, Spain
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Departamento Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, 14014 Córdoba, Spain
| | - Ignacio Garcia-Bocanegra
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Departamento Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, 14014 Córdoba, Spain
| | - María A. Risalde
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Departamento Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, 14014 Córdoba, Spain
| | - Antonio Rivero-Juarez
- Service of Infectious Diseases, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Cordoba, Spain
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Antonio Rivero
- Service of Infectious Diseases, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Cordoba, Spain
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain
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Mättö J, Putkuri N, Rimhanen-Finne R, Laurila P, Clancy J, Ihalainen J, Ekblom-Kullberg S. Hepatitis E Virus in Finland: Epidemiology and Risk in Blood Donors and in the General Population. Pathogens 2023; 12:pathogens12030484. [PMID: 36986406 PMCID: PMC10054892 DOI: 10.3390/pathogens12030484] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/14/2023] [Accepted: 03/15/2023] [Indexed: 03/30/2023] Open
Abstract
Autochthonous hepatitis E (HEV) cases have been increasingly recognized and reported in Europe, caused predominantly by the zoonotic HEV genotype 3. The clinical picture is highly variable, from asymptomatic to acute severe or prolonged hepatitis in immunocompromised patients. The main route of transmission to humans in Europe is the ingestion of undercooked pork meat. Transfusion-transmitted HEV infections have also been reported. The aim of the study was to determine the HEV epidemiology and risk in the Finnish blood donor population. A total of 23,137 samples from Finnish blood donors were screened for HEV RNA from individual samples and 1012 samples for HEV antibodies. Additionally, laboratory-confirmed hepatitis E cases in 2016-2022 were extracted from national surveillance data. The HEV RNA prevalence data was used to estimate the risk of transfusion transmission of HEV in the Finnish blood transfusion setting. Four HEV RNA-positive were found, resulting in 1:5784 (0.02%) RNA prevalence. All HEV RNA-positive samples were IgM-negative, and genotyped samples represented genotype HEV 3c. HEV IgG seroprevalence was 7.4%. From the HEV RNA rate found in this study and data on blood component usage in Finland in 2020, the risk estimate for a severe transfusion-transmitted HEV infection is 1:1,377,000 components or one in every 6-7 years. In conclusion, the results indicate that the risk of transfusion-transmitted HEV (HEV TTI) in Finland is low. However, continuous follow-up of the HEV epidemiology in relation to the transfusion risk landscape in Finland is necessary, as well as promoting awareness in the medical community of the small risk for HEV TTI, especially for immunocompromised patients.
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Affiliation(s)
- Jaana Mättö
- Finnish Red Cross Blood Service, 01730 Vantaa, Finland
| | - Niina Putkuri
- Finnish Red Cross Blood Service, 01730 Vantaa, Finland
| | | | - Päivi Laurila
- Finnish Institute for Health and Welfare, 00100 Helsinki, Finland
| | - Jonna Clancy
- Finnish Red Cross Blood Service Biobank, 01730 Vantaa, Finland
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Higher Risk of HEV Transmission and Exposure among Blood Donors in Europe and Asia in Comparison to North America: A Meta-Analysis. Pathogens 2023; 12:pathogens12030425. [PMID: 36986347 PMCID: PMC10059948 DOI: 10.3390/pathogens12030425] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/01/2023] [Accepted: 03/05/2023] [Indexed: 03/10/2023] Open
Abstract
Background and aims: The increasing number of diagnosed hepatitis E virus (HEV) infections in Europe has led to the implementation of the testing of blood products in various countries. Many nations have not yet implemented such screening. To assess the need for HEV screening in blood products worldwide, we conducted a systematic review and meta-analysis assessing HEV RNA positivity and anti-HEV seroprevalence in blood donors. Methods: Studies reporting anti-HEV IgG/IgM or HEV RNA positivity rates among blood donors worldwide were identified via predefined search terms in PubMed and Scopus. Estimates were calculated by pooling study data with multivariable linear mixed-effects metaregression analysis. Results: A total of 157 (14%) of 1144 studies were included in the final analysis. The estimated HEV PCR positivity rate ranged from 0.01 to 0.14% worldwide, with strikingly higher rates in Asia (0.14%) and Europe (0.10%) in comparison to North America (0.01%). In line with this, anti-HEV IgG seroprevalence in North America (13%) was lower than that in Europe (19%). Conclusions: Our data demonstrate large regional differences regarding the risk of HEV exposure and blood-borne HEV transmission. Considering the cost–benefit ratio, this supports blood product screening in high endemic areas, such as Europe and Asia, in contrast to low endemic regions, such as the U.S.
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Zhou YH, Zhao H. Immunobiology and Host Response to HEV. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:93-118. [PMID: 37223861 DOI: 10.1007/978-981-99-1304-6_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Hepatitis E virus (HEV) usually causes acute self-limiting hepatitis but sometimes leads to chronic infection in immunocompromised persons. HEV is not directly cytopathic. Immunologically mediated events after HEV infection are believed to play important roles in the pathogenesis and clearance of infection. The anti-HEV antibody responses have been largely clarified since the determination of major antigenic determinant of HEV, which is located in the C-terminal portion of ORF2. This major antigenic determinant also forms the conformational neutralization epitopes. Robust anti-HEV immunoglobulin M (IgM) and IgG responses usually develop 3-4 weeks after infection in experimentally infected nonhuman primates. In humans, potent specific IgM and IgG responses occur in the very early phase of the disease and are critical in eliminating the virus, in concert with the innate and adaptive T-cell immune responses. Testing anti-HEV IgM is valuable in the diagnosis of acute hepatitis E. The long-term persistence and protection of anti-HEV IgG provide the basis for estimating the prevalence of HEV infection and for the development of a hepatitis E vaccine. Although human HEV has four genotypes, all the viral strains are considered to belong to a single serotype. It is becoming increasingly clear that the innate and adaptive T-cell immune responses play critical roles in the clearance of the virus. Potent and multispecific CD4+ and CD8+ T cell responses to the ORF2 protein occur in patients with acute hepatitis E, and weaker HEV-specific CD4+ and CD8+ T cell responses appear to be associated with chronic hepatitis E in immunocompromised individuals.
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Affiliation(s)
- Yi-Hua Zhou
- Departments of Experimental Medicine and Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Hong Zhao
- Department of Infectious Diseases, Second Hospital of Nanjing, Southeast University School of Medicine, Nanjing, China
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Aziz AB, Øverbø J, Dudman S, Julin CH, Kwon YJG, Jahan Y, Ali M, Dembinski JL. Hepatitis E Virus (HEV) Synopsis: General Aspects and Focus on Bangladesh. Viruses 2022; 15:63. [PMID: 36680103 PMCID: PMC9866510 DOI: 10.3390/v15010063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 12/15/2022] [Accepted: 12/21/2022] [Indexed: 12/28/2022] Open
Abstract
HEV is the most common cause of acute hepatitis globally. This review summarizes the latest knowledge on the epidemiology, clinical characteristics, testing, and treatment of HEV infection. We also focused on Bangladesh to highlight the distinct challenges and the possible remedies. In low-income settings, the virus is mainly transmitted between people by fecal contamination of drinking water causing large outbreaks, and sporadic cases. The disease is usually mild and self-limiting acute hepatitis. Still, pregnant women and their offspring in low-income countries are at particular risk for severe disease, with up to 20% maternal mortality. Despite the high burden of the disease, HEV remains a relatively neglected virus, with detection hampered by costly tests and a lack of suitable treatments. Molecular PCR diagnostics, together with ELISA antibody tests, remain the preferred methods for diagnosis of HEV; however, rapid bedside diagnostics are available and could offer a practical alternative, especially in low-income countries. One vaccine (HEV 239) is only available in China and Pakistan, as efficacy against the other genotypes remains uncertain. The effectiveness trial conducted in Bangladesh might lead the way in gathering more efficacy data and could, together with improved surveillance and raised awareness, dramatically reduce the global burden of HEV.
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Affiliation(s)
- Asma Binte Aziz
- Institute of Clinical Medicine, University of Oslo, 0315 Oslo, Norway
- International Vaccine Institute (IVI), Seoul 08800, Republic of Korea
| | - Joakim Øverbø
- Institute of Clinical Medicine, University of Oslo, 0315 Oslo, Norway
- Norwegian Institute of Public Health (NIPH), Division of Infection Control and Environmental Health, 0213 Oslo, Norway
| | - Susanne Dudman
- Institute of Clinical Medicine, University of Oslo, 0315 Oslo, Norway
| | - Cathinka Halle Julin
- Norwegian Institute of Public Health (NIPH), Division of Infection Control and Environmental Health, 0213 Oslo, Norway
| | | | - Yasmin Jahan
- Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-0046, Japan
| | - Mohammad Ali
- Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, MD 21205, USA
| | - Jennifer L. Dembinski
- Norwegian Institute of Public Health (NIPH), Division of Infection Control and Environmental Health, 0213 Oslo, Norway
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Fontana RJ, Engle RE, Hayashi PH, Gu J, Kleiner DE, Nguyen H, Barnhart H, Hoofnagle JH, Farci P. Incidence of Hepatitis E Infection in American Patients With Suspected Drug-Induced Liver Injury Is Low and Declining: The DILIN Prospective Study. Am J Gastroenterol 2022; 117:1462-1470. [PMID: 35973149 PMCID: PMC9437122 DOI: 10.14309/ajg.0000000000001869] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 06/07/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Hepatitis E virus (HEV) infection rarely causes icteric hepatitis, yet 10%-40% of adult Americans have serological evidence of previous infection. The aim of this study was to investigate the incidence, presentation, and outcome of acute and previous HEV infection in a large cohort of patients with suspected drug-induced liver injury (DILI). METHODS Serum samples from 2012 patients enrolled in the DILI Network were tested for anti-HEV immunoglobulin G (IgG). Those with detectable anti-HEV IgG underwent testing for anti-HEV IgM; those with detectable anti-HEV immunoglobulin m (IgM) were tested for HEV RNA. RESULTS Anti-HEV IgG was detected in 407 (20%) patients and associated with increasing subject age and earlier year of enrollment. The median age of seropositive subjects was more than a decade higher than seronegative subjects (59.8 vs 48.7 years). The overall prevalence of anti-HEV declined from 22% (2004-2011) to 18% (2012-2019), suggestive of a cohort effect. The frequency of acute hepatitis E (median ALT = 1231 IU/L) also decreased from 3% (2004-2008) to 1.2% (2009-2013) to 0.6% (2014-2019). These results suggest that acute HEV infection is usually subclinical and was much more frequent in this cohort before 2004. DISCUSSION Acute HEV infection accounts for less than 1% of suspected American DILI cases and is more frequent in older men. Previous HEV infection is also most commonly seen in older individuals. Clinicians should consider testing for unsuspected acute HEV infection in older adult patients with acute hepatocellular DILI and jaundice.
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Affiliation(s)
- Robert John Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Ronald E Engle
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| | - Paul H Hayashi
- Food and Drug Administration, Silver Spring, Maryland, USA
| | - Jiezhun Gu
- Duke Clinical Research Institute, Durham, North Carolina, USA
| | - David E Kleiner
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Hahn Nguyen
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| | - Huiman Barnhart
- Duke Clinical Research Institute, Durham, North Carolina, USA
| | - Jay H Hoofnagle
- Department of Medicine, Ohio State University, Columbus, Ohio, USA
- National Institute of Diabetes and Digestive and Kidney-Diseases, Bethesda, Maryland, USA
| | - Patrizia Farci
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
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Spada E, Simeoni M, Martina A, Pati I, Villano U, Adriani D, D'Angiò A, Tritarelli E, Taffon S, Bellino S, Boros S, Urciuoli R, Masiello F, Marano G, Bruni R, Pezzotti P, Ciccaglione AR, Pupella S, De Angelis V, Pisani G. Prevalence and risk factors for hepatitis E virus infection in blood donors: a nationwide survey in Italy, 2017 to 2019. EURO SURVEILLANCE : BULLETIN EUROPEEN SUR LES MALADIES TRANSMISSIBLES = EUROPEAN COMMUNICABLE DISEASE BULLETIN 2022; 27. [PMID: 35656832 PMCID: PMC9164674 DOI: 10.2807/1560-7917.es.2022.27.22.2100516] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Background In high-income countries, hepatitis E virus (HEV) infection is mainly a zoonosis. However, it is also transfusion-transmissible and some countries, but not Italy, have introduced HEV screening for blood donations. Aim We assessed HEV infection prevalence and risk factors in a nationwide sample of Italian blood donors. Methods We selected 107 blood establishments (BE) distributed in the 20 Italian regions by a stratified two-stage design and invited them to participate in the study. Donors were tested for anti-HEV IgG and IgM and HEV RNA. Sociodemographic data and risk factors were collected through a questionnaire. Results Overall, 60 BE from 60 provinces in 19 Italian regions joined the study. We assessed HEV markers in 7,172 blood donors, of whom 6,235 completed the questionnaire. Overall crude and adjusted anti-HEV IgG prevalences were 8.3% and 5.5%, respectively. Overall anti-HEV IgM prevalence was 0.5%, while no blood donor was HEV RNA-positive. Anti-HEV IgG prevalence varied widely among regions (range: 1.3%–27.20%) and hyperendemic prevalences (> 40%) were detected in some provinces in two regions. Older age (AOR = 1.81; 95% CI: 1.36–2.41), foreign nationality (AOR = 2.77; 95% CI: 1.06–7.24), eating raw pork liver sausages (AOR = 2.23; 95% CI: 1.55–3.20) and raw homemade sausages (AOR = 3.63; 95% CI: 2.50–5.24) were independent infection predictors. Conclusion Italian blood donors showed a low to moderate HEV seroprevalence. High levels in some regions and/or provinces were mainly attributable to eating habits. Prevention should include avoiding consumption of raw or undercooked meat and safe production of commercial pork products.
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Affiliation(s)
- Enea Spada
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Matteo Simeoni
- National Centre for the Control and Evaluation of Medicines, Istituto Superiore di Sanità, Rome, Italy
| | - Antonio Martina
- National Centre for the Control and Evaluation of Medicines, Istituto Superiore di Sanità, Rome, Italy
| | - Ilaria Pati
- Italian National Blood Centre, Istituto Superiore di Sanità, Rome, Italy
| | - Umbertina Villano
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Daniela Adriani
- National Centre for the Control and Evaluation of Medicines, Istituto Superiore di Sanità, Rome, Italy
| | - Agnese D'Angiò
- National Centre for the Control and Evaluation of Medicines, Istituto Superiore di Sanità, Rome, Italy
| | - Elena Tritarelli
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Stefania Taffon
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Stefania Bellino
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Stefano Boros
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Roberta Urciuoli
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Francesca Masiello
- Italian National Blood Centre, Istituto Superiore di Sanità, Rome, Italy
| | - Giuseppe Marano
- Italian National Blood Centre, Istituto Superiore di Sanità, Rome, Italy
| | - Roberto Bruni
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Patrizio Pezzotti
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | | | - Simonetta Pupella
- Italian National Blood Centre, Istituto Superiore di Sanità, Rome, Italy
| | | | - Giulio Pisani
- National Centre for the Control and Evaluation of Medicines, Istituto Superiore di Sanità, Rome, Italy
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Cheung CKM, Wong SH, Law AWH, Law MF. Transfusion-transmitted hepatitis E: What we know so far? World J Gastroenterol 2022; 28:47-75. [PMID: 35125819 PMCID: PMC8793017 DOI: 10.3748/wjg.v28.i1.47] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 07/16/2021] [Accepted: 12/22/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) is a major cause of viral hepatitis globally. There is growing concern about transfusion-transmitted HEV (TT-HEV) as an emerging global health problem. HEV can potentially result in chronic infection in immunocompromised patients, leading to a higher risk of liver cirrhosis and even death. Between 0.0013% and 0.281% of asymptomatic blood donors around the world have HEV viremia, and 0.27% to 60.5% have anti-HEV immunoglobulin G. HEV is infectious even at very low blood concentrations of the virus. Immunosuppressed patients who develop persistent hepatitis E infection should have their immunosuppressant regimen reduced; ribavirin may be considered as treatment. Pegylated interferon can be considered in those who are refractory or intolerant to ribavirin. Sofosbuvir, a nucleotide analog, showed modest antiviral activity in some clinical studies but sustained viral response was not achieved. Therefore, rescue treatment remains an unmet need. The need for HEV screening of all blood donations remains controversial. Universal screening has been adopted in some countries after consideration of risk and resource availability. Various pathogen reduction methods have also been proposed to reduce the risk of TT-HEV. Future studies are needed to define the incidence of transmission through transfusion, their clinical features, outcomes and prognosis.
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Affiliation(s)
| | - Sunny Hei Wong
- Institute of Digestive Disease and Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong 852, China
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 639798, Singapore
| | | | - Man Fai Law
- Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
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11
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Lienhard J, Vonlanthen-Specker I, Sidler X, Bachofen C. Screening of Swiss Pig Herds for Hepatitis E Virus: A Pilot Study. Animals (Basel) 2021; 11:3050. [PMID: 34827782 PMCID: PMC8614339 DOI: 10.3390/ani11113050] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 10/20/2021] [Accepted: 10/21/2021] [Indexed: 12/14/2022] Open
Abstract
Hepatitis E virus (HEV) is an important cause of acute hepatitis in humans worldwide. In industrialised countries, most infections are caused by the zoonotic genotype 3. The main reservoir was found in pigs, with fattening pigs as the main shedders. The aim of this study was to establish a screening tool to detect HEV in pig farms. HEV-positive samples were sequenced using Sanger sequencing. First, different sample materials, including floor swabs, slurry, dust swabs and faeces were tested for HEV. Floor swabs turned out to give the best results and, in the form of sock swabs, were used for the screening of Swiss pig herds. A total of 138 pig farms were tested, with a focus on fattening pigs. Overall, 81 farms (58.8%) were HEV positive. Most sequences belonged to subtype 3h, in which they formed a specific cluster (Swiss cluster). In addition, subtype 3l and two unassigned sequences were detected. As a conclusion, sock swabs were found to be a helpful tool to screen pig herds for HEV and establish a sequence collection that may enable molecular epidemiology and support outbreak investigation and prevention.
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Affiliation(s)
- Julia Lienhard
- Institute of Virology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland; (J.L.); (I.V.-S.)
| | | | - Xaver Sidler
- Division of Swine Medicine, Department of Farm Animals, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland;
| | - Claudia Bachofen
- Institute of Virology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland; (J.L.); (I.V.-S.)
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12
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Gynthersen RMM, Rønn CP, Brandt CT, Mens H. Severe acute hepatitis E infection presenting with acute abdomen and meningoencephalitis. BMJ Case Rep 2020; 13:13/12/e236922. [PMID: 33318241 PMCID: PMC7737054 DOI: 10.1136/bcr-2020-236922] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
We present a case of a 50-year-old man admitted due to acute abdomen, icterus and fever. The patient had a history of sufficiently treated type 2 diabetes and a high daily alcohol consumption, no recent travel history and had a strictly heterosexual and monogamous way of living. A full blood count displayed severe elevated liver enzymes. A CT of the abdomen was performed and revealed steatosis but no acute abdominal pathology. During admission, the patient developed signs of meningoencephalitis. A lumbar puncture was performed, and the cerebrospinal fluid revealed lymphocytic pleocytosis consistent with mild inflammation. Furthermore, hepatitis E was found in the blood and the definitive diagnosis was established. The patient gradually recovered and was discharged within 8 days of admission. To the best of our knowledge, we present the second case describing concomitant hepatitis and meningoencephalitis, resolving spontaneously and not giving rise to sequelae.
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Affiliation(s)
| | | | - Christian Thomas Brandt
- Infectious Diseases, University Hospital Zealand, University of Copenhagen, Roskilde, Denmark
| | - Helene Mens
- Infectious Diseases, Rigshospitalet, Copenhagen, Denmark
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13
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Fontana RJ, Engle RE, Gottfried M, Hammed B, Hanje J, Durkalski V, Kleiner DE, Nguyen H, Nishimura N, Lee WM, Farci P. Role of Hepatitis E Virus Infection in North American Patients With Severe Acute Liver Injury. Clin Transl Gastroenterol 2020; 11:e00273. [PMID: 33259165 PMCID: PMC7665257 DOI: 10.14309/ctg.0000000000000273] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 10/07/2020] [Indexed: 12/17/2022] Open
Abstract
INTRODUCTION The aim of this study was to determine the role of hepatitis E virus (HEV) infection in a large cohort of prospectively enrolled patients with severe acute liver injury (ALI). METHODS Serum samples from 594 consecutive adults enrolled between 2008 and 2018 in the US Acute Liver Failure Study Group ALI registry were tested for anti-HEV IgM and anti-HEV IgG levels. Those with detectable anti-HEV IgM underwent further testing for HEV RNA using real-time polymerase chain reaction. RESULTS The median age of patients was 38 years; 41% were men and 72% Caucasian. Etiologies of ALI included acetaminophen hepatotoxicity (50%), autoimmune hepatitis (8.9%), hepatitis B virus (8.9%), and idiosyncratic drug-induced liver injury (7.9%). Overall, 62 patients (10.4%) were negative for anti-HEV IgM but positive for IgG, whereas only 3 men (0.5%) were positive for both anti-HEV IgM and IgG. These 3 cases were initially diagnosed as having indeterminate, HEV, and hepatitis B virus-related ALI. One of these patients had detectable HEV RNA genotype 3, and another anti-HEV IgM+ patient had detectable HEV antigens by immunohistochemistry on liver biopsy. On multivariate modeling, older (odds ratio: 1.99) and non-Caucasian subjects (odds ratio: 2.92) were significantly more likely to have detectable anti-HEV IgG (P < 0.0001). DISCUSSION Acute HEV infection is an infrequent cause of ALI in hospitalized North American adults. The anti-HEV IgG+ patients were significantly older and more likely to be non-Caucasian. These data are consistent with other population-based studies that indicate exposure to HEV in the general US population is declining over time and might reflect a cohort effect.
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Affiliation(s)
- Robert J. Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Ronald E. Engle
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| | - Michelle Gottfried
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Bilal Hammed
- Department of Medicine, UCSF, San Francisco, California, USA
| | - James Hanje
- Department of Medicine, Ohio State University, Columbus, Ohio, USA
| | - Valerie Durkalski
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - David E. Kleiner
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Hanh Nguyen
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| | - Norihisa Nishimura
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| | - William M. Lee
- Department of Medicine, University of Texas Southwestern, Dallas, Texas, USA
| | - Patrizia Farci
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
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14
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Abstract
While the majority of worldwide hepatitis E viral (HEV) infections that occur in people are from contaminated water or food sources, there has also been a steadily rising number of reported cases of transfusion-transmitted HEV (TT-HEV) in blood donation recipients. For most, HEV infection is acute, self-limiting and asymptomatic. However, patients that are immunocompromised, especially transplant patients, are at much higher risk for developing chronic infections, which can progress to cirrhosis and liver failure, along with overall increased mortality. Because of the rising trend of HEV serological prevalence among the global population, and the fact that TT-HEV infection can cause serious clinical consequences among those patients most at need for blood donation, the need for screening for TT-HEV has been gaining in prominence as an important public health concern for both developing and developed countries. In the review, we summarise evidence for and notable cases of TT-HEV infections, the various aspects of HEV screening protocols and recent trends in the implementation of TT-HEV broad-based blood screening programmes.
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15
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Paraličová Z, Halánová M, Schréter I, Kalinová Z, Novotný M, Sekula J, Paralič J, Kristian P. Seroprevalence of hepatitis E among hospitalized patients in Slovakia: first report. Cent Eur J Public Health 2020; 28:70-73. [PMID: 32228821 DOI: 10.21101/cejph.a5346] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Accepted: 12/16/2019] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Hepatitis E infection is one of the most frequent acute hepatitis in the world. Currently five human genotypes with different geographical distributions and distinct epidemiologic patterns are identified. In Slovakia, only rare cases of hepatitis E have been reported in recent years. Therefore, the aim of the study was to evaluate the prevalence of anti-HEV total antibodies and the main risk factors for HEV in the general population in Eastern Slovakia. METHODS Detection of anti-HEV total antibodies samples was done by a commercial enzyme-linked immunosorbent assay (ELISA) kit. RESULTS Of 175 hospitalized patients included in the study, 76 (43.5%) showed positivity for anti-HEV total antibodies. No statistically significant differences were found in anti-HEV positivity between men and women or in the groups of different living areas (town/village - urban/rural). CONCLUSION Prevalence of anti-HEV total antibodies of hospitalised patients was high. The risk factor significantly associated with antibody positivity was eating raw meat. Other factors, such as sex, age, living area and contact with animals were not associated with antibody positivity.
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16
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Li Y, Huang X, Zhang Z, Li S, Zhang J, Xia N, Zhao Q. Prophylactic Hepatitis E Vaccines: Antigenic Analysis and Serological Evaluation. Viruses 2020; 12:v12010109. [PMID: 31963175 PMCID: PMC7020013 DOI: 10.3390/v12010109] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 01/10/2020] [Accepted: 01/13/2020] [Indexed: 12/13/2022] Open
Abstract
Hepatitis E virus (HEV) infection causes sporadic outbreaks of acute hepatitis worldwide. HEV was previously considered to be restricted to resource-limited countries with poor sanitary conditions, but increasing evidence implies that HEV is also a public health problem in developed countries and regions. Fortunately, several vaccine candidates based on virus-like particles (VLPs) have progressed into the clinical development stage, and one of them has been approved in China. This review provides an overview of the current HEV vaccine pipeline and future development with the emphasis on defining the critical quality attributes for the well-characterized vaccines. The presence of clinically relevant epitopes on the VLP surface is critical for eliciting functional antibodies against HEV infection, which is the key to the mechanism of action of the prophylactic vaccines against viral infections. Therefore, the epitope-specific immunochemical assays based on monoclonal antibodies (mAbs) for HEV vaccine antigen are critical methods in the toolbox for epitope characterization and for in vitro potency assessment. Moreover, serological evaluation methods after immunization are also discussed as biomarkers for clinical performance. The vaccine efficacy surrogate assays are critical in the preclinical and clinical stages of VLP-based vaccine development.
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Affiliation(s)
- Yike Li
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China; (Y.L.); (X.H.); (Z.Z.); (S.L.); (J.Z.); (N.X.)
| | - Xiaofen Huang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China; (Y.L.); (X.H.); (Z.Z.); (S.L.); (J.Z.); (N.X.)
| | - Zhigang Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China; (Y.L.); (X.H.); (Z.Z.); (S.L.); (J.Z.); (N.X.)
| | - Shaowei Li
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China; (Y.L.); (X.H.); (Z.Z.); (S.L.); (J.Z.); (N.X.)
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, China
| | - Jun Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China; (Y.L.); (X.H.); (Z.Z.); (S.L.); (J.Z.); (N.X.)
| | - Ningshao Xia
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China; (Y.L.); (X.H.); (Z.Z.); (S.L.); (J.Z.); (N.X.)
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, China
| | - Qinjian Zhao
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China; (Y.L.); (X.H.); (Z.Z.); (S.L.); (J.Z.); (N.X.)
- Correspondence: ; Tel.: +86-59-2218-0936
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17
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Harritshøj LH, Hother CE, Sengeløv H, Daugaard G, Sørensen SS, Jacobsen S, Perch M, Holm DK, Sækmose SG, Aagaard B, Erikstrup C, Hogema BM, Lundgren JD, Ullum H. Epidemiology of hepatitis E virus infection in a cohort of 4023 immunocompromised patients. Int J Infect Dis 2019; 91:188-195. [PMID: 31756566 DOI: 10.1016/j.ijid.2019.11.014] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Revised: 11/11/2019] [Accepted: 11/12/2019] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVES The prevalence of active, chronic, and former hepatitis E virus (HEV) infections was investigated in a cohort of immunocompromised patients. The association with transfusion transmitted HEV was evaluated, and the HEV seroprevalence was compared with that in healthy blood donors. STUDY DESIGN AND METHODS Serum samples from 4023 immunocompromised patients at Rigshospitalet, Denmark were retrospectively tested for HEV RNA and anti-HEV IgG. HEV RNA-positive patients were followed up by HEV testing, clinical symptoms, and transfusion history. Factors associated with anti-HEV were explored by multivariable logistic regression analysis. Samples from 1226 blood donors were retrospectively tested for anti-HEV IgG. RESULTS HEV RNA was detected in six patients (0.15%) with no indications of chronic HEV infection. HEV RNA prevalence rates among recipients of allogeneic haematopoietic stem cell transplantation (allo-HSCT) and solid organ transplantation (SOT) were 0.58% and 0.21%, respectively. Transfusion transmitted infections were refuted, and transfusion history was not associated with anti-HEV positivity. The difference in HEV seroprevalence between patients (22.0%) and blood donors (10.9%) decreased when adjusting for age and sex (odds ratio 1.20, 95% confidence interval 0.97-1.48). CONCLUSIONS HEV viremia among allo-HSCT and SOT recipients suggests that clinicians should be aware of this diagnosis. The lack of association of blood transfusion with anti-HEV positivity supports food-borne transmission as the main transmission route of HEV common to both patients and blood donors.
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Affiliation(s)
- Lene H Harritshøj
- Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
| | - Christoffer E Hother
- Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Henrik Sengeløv
- Department of Haematology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark
| | - Gedske Daugaard
- Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark; Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Søren S Sørensen
- Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark; Department of Nephrology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Søren Jacobsen
- Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark; Copenhagen Lupus and Vasculitis Clinic, Centre for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark
| | - Michael Perch
- Department of Cardiology, Section for Lung Transplantation, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Dorte K Holm
- Department of Clinical Immunology, Odense University Hospital, Odense, Denmark
| | - Susanne G Sækmose
- Department of Clinical Immunology, Næstved Hospital, Næstved, Denmark
| | - Bitten Aagaard
- Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark
| | - Christian Erikstrup
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
| | - Boris M Hogema
- Sanquin Research and Diagnostic Services, Departments of Blood-borne Infections and Virology, Amsterdam, The Netherlands
| | - Jens D Lundgren
- Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark; Centre for Health, Immunity and Infectious Diseases (CHIP), Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Henrik Ullum
- Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark
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18
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Niederhauser C, Widmer N, Hotz M, Tinguely C, Fontana S, Allemann G, Borri M, Infanti L, Sarraj A, Sigle J, Stalder M, Thierbach J, Waldvogel S, Wiengand T, Züger M, Gowland P. Current hepatitis E virus seroprevalence in Swiss blood donors and apparent decline from 1997 to 2016. ACTA ACUST UNITED AC 2019; 23. [PMID: 30180927 PMCID: PMC6124188 DOI: 10.2807/1560-7917.es.2018.23.35.1700616] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Hepatitis E virus (HEV) is a virus of emerging importance to transfusion medicine. Studies from several European countries, including Switzerland, have reported high seroprevalence of hepatitis E as a consequence of endemic infections. Published HEV seroprevalence estimates within developed countries vary considerably; primarily due to improved diagnostic assays. The purpose of this study was to investigate the seroprevalence of anti-HEV IgG in Swiss blood donations. Methods: We used the highly sensitive Wantai HEV IgG EIA and assessed regional distribution patterns. We analysed age- and sex-matched archive plasma dating back 20 years from canton Bern to investigate recent changes in HEV seroprevalence levels. Results: On average, 20.4% (95% confidence intervals: 19.1–21.8) of the 3,609 blood samples collected in 2014–16 were anti-HEV IgG positive; however, distinct differences between geographical regions were observed (range: 12.8–33.6%). Seroprevalence increased with age with 30.7% of males and 34.3% of women being positive donors over > 60 years old. Differences between sexes may be attributed to dissimilarities in the average age of this group. Within the specified region of the Bern canton, overall prevalence has declined over two decades from 30.3% in 1997/98 to 27.0% in 2006 and 22.3% in 2015/6. Conclusions: HEV seroprevalence in Switzerland is high, but has declined over the last decades. The result shows that primarily endemic HEV infections occur and that current blood products may pose a risk to vulnerable transfusion recipients. Nucleic acid screening of all blood products for HEV will begin in November 2018.
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Affiliation(s)
| | - Nadja Widmer
- Interregional Blood Transfusion SRC, Berne Switzerland
| | | | | | - Stefano Fontana
- Servizio Trasfusionale CRS della Svizzera Italiana, Lugano, Switzerland.,Interregional Blood Transfusion SRC, Berne Switzerland
| | | | - Mauro Borri
- Servizio Trasfusionale CRS della Svizzera Italiana, Lugano, Switzerland
| | - Laura Infanti
- Blood Transfusion Service Beider Basel, Basel, Switzerland
| | - Amira Sarraj
- Blood Transfusion Service SRC Neuchâtel/Jura, Neuchâtel, Switzerland
| | - Jörg Sigle
- Blood Transfusion Service SRC, Aargau/Solothurn, Switzerland
| | | | - Jutta Thierbach
- Blood Transfusion Service SRC Nordostschweiz, St. Gallen, Switzerland
| | | | - Tina Wiengand
- Blood Transfusion Service SRC Zentralschweiz, Luzern, Switzerland
| | - Max Züger
- Blood Transfusion Service SRC Thurgau, Münsterlingen, Switzerland
| | - Peter Gowland
- Interregional Blood Transfusion SRC, Berne Switzerland
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19
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Estimation of the hepatitis E assay-dependent seroprevalence among Croatian blood donors. Transfus Clin Biol 2019; 26:229-233. [PMID: 31277986 DOI: 10.1016/j.tracli.2019.06.234] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Accepted: 06/12/2019] [Indexed: 01/18/2023]
Abstract
BACKGROUND Seroprevalence of hepatitis E virus (HEV) in blood donors presenting to the Croatian Institute of Transfusion Medicine was assessed with 4 available tests (3 ELISA tests and 1 immunoblot (IB) test). MATERIALS AND METHODS In October and November 2014, a total of 1,036 serum samples of blood donors were collected for the study. Samples were primarily tested for total HEV antibodies by Dia.Pro HEV Ab test (a). All reactive samples were tested by ELISA tests: Dia.Pro HEV IgG (b) and IgM (c), Mikrogen recomWell HEV IgG_old (d) and IgM_old (e), recomWell HEV IgG_new (f) and IgM_new (g), and IB Mikrogen recomLine HEV IgG (h) and IgM (i). HEV IgM reactive samples also positive by the IB were further tested for HEV RNA. RESULTS There were 21.5% of samples reactive for total HEV antibodies (a). Seroprevalence of HEV IgG according to the b, d, f and h tests was 20.2%, 9.6%, 18.1% and 17.8%, respectively. Seroprevalence of HEV IgM according to the c, e, g and i tests was 4.4%, 1.5%, 2.0% and 1.7%, respectively. Out of 46 HEV IgM (Dia.Pro HEV IgM) positive samples, 18 (39.1%) were also positive by IB. HEV RNA was not detected in any of those samples. There was a significant association between age and HEV seroprevalence (P<0.001). CONCLUSION Different HEV antibody detection assays showed a high HEV IgG seroprevalence in Croatian blood donors. Among HEV IgG and HEV IgM positive samples HEV RNA was not detected.
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20
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Wilhelm B, Waddell L, Greig J, Young I. Systematic review and meta-analysis of the seroprevalence of hepatitis E virus in the general population across non-endemic countries. PLoS One 2019; 14:e0216826. [PMID: 31173594 PMCID: PMC6555507 DOI: 10.1371/journal.pone.0216826] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Accepted: 04/29/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) has commonly been associated with large waterborne outbreaks of human jaundice in endemic areas but it has been increasingly recognised as a cause of sporadic human cases of jaundice in non-endemic areas, in individuals with no history of travel. Zoonotic exposure is widely hypothesized to be an important potential transmission route in these sporadic human cases. Serosurveys conducted to determine the frequency of HEV human exposure report wide ranges in prevalence across studies and locations. Our study objective was to compute meta-analysis summary estimates of human seroprevalence of HEV IgG within countries considered HEV non-endemic, where possible, and to determine whether this varied significantly across these countries, as well as investigating the role of potential HEV seroprevalence predictors such as population age structure. MATERIALS AND METHODS A broad literature search was conducted in six electronic databases. Citations were appraised, and relevant data extracted using forms designed and pre-tested a priori. Meta-analysis and meta-regression were conducted in R, with HEV IgG seroprevalence in blood donors or the general population being the outcome of interest, and country, assay, population age and sex structure, and chronological time investigated as predictors of the outcome. RESULTS From 4163 unique citations initially captured, data were extracted from 135 studies investigating HEV serology in blood donors or the general population, of 31 countries among those categorised as 'very high human development' by the United Nations. Country of sampling and assay employed were consistently significant predictors of HEV IgG seroprevalence with chronological time being a non-significant predictor in the dataset of captured studies. CONCLUSIONS While country of sampling and assay employed were significant predictors of HEV seroprevalence, comparison of HEV seroprevalence across non-endemic countries is hampered by the lack of a gold standard assay and uncertainty regarding residual bias across studies, as well as regional differences within some countries.
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Affiliation(s)
| | - Lisa Waddell
- National Microbiology Laboratory at Guelph, Public Health Agency of Canada, Guelph, Ontario, Canada
| | - Judy Greig
- National Microbiology Laboratory at Guelph, Public Health Agency of Canada, Guelph, Ontario, Canada
| | - Ian Young
- School of Occupational and Public Health, Ryerson University, Toronto, Ontario, Canada
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21
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Harritshøj LH, Kirkegaard-Klitbo DM, Mejer N, Panum I, Midgley SE, Ullum H, Benfield T. Prevalence of anti-hepatitis E virus immunoglobulin G in HIV-infected individuals over three decades. Int J Infect Dis 2019; 84:67-72. [PMID: 31063824 DOI: 10.1016/j.ijid.2019.04.029] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 04/25/2019] [Accepted: 04/26/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) genotype 3 is endemic in Europe, and the infection is mostly subclinical or acute and self-limiting. However, persistent infection is described among HIV-infected individuals. The prevalence of antibodies against HEV (anti-HEV) among HIV-infected persons varies geographically and is unknown in Denmark. Rates of co-infection with HEV among HIV-infected individuals in Denmark over three decades, from the early 1980s to 2013, were investigated. METHODS A total of 2506 HIV-infected persons were investigated from two cohorts followed at Hvidovre Hospital, Denmark. Blood samples were tested retrospectively for anti-HEV, including samples from 2216 persons who were enrolled in a prospective clinical cohort and followed between 1995 and 2013, as well as samples from 290 persons from a historical cohort followed between 1980 and 1994. For anti-HEV seroconverting individuals, serial samples were tested for HEV RNA. Factors associated with anti-HEV status were explored using multivariable logistic regression analysis. RESULTS The overall HEV seroprevalence rates were stable during the 1980s, 1990s, and 2000-2013 (23.1%, 22.9%, and 23.7%, respectively). In all decades, rates of anti-HEV increased with older age, and anti-HEV seropositivity was associated with older generations, HIV risk group, and geographic origin. Persistent HEV infection was not detected in any of 57 individuals with anti-HEV seroconversion. CONCLUSIONS HEV seroprevalence rates were stable in HIV-infected individuals from the early 1980s to 2013. Rates increased with age. No evidence of persistent HEV infection was detected. Infection with HEV is frequent, but persistent HEV infection is rare among HIV-infected individuals.
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Affiliation(s)
| | - Ditte Marie Kirkegaard-Klitbo
- Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Niels Mejer
- Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
| | - Inge Panum
- Department of Clinical Microbiology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
| | | | - Henrik Ullum
- Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Thomas Benfield
- Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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22
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Meta-Analysis of Human IgG anti-HEV Seroprevalence in Industrialized Countries and a Review of Literature. Viruses 2019; 11:v11010084. [PMID: 30669517 PMCID: PMC6357031 DOI: 10.3390/v11010084] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 01/16/2019] [Accepted: 01/18/2019] [Indexed: 12/11/2022] Open
Abstract
Although Hepatitis E is increasingly described as a major cause of liver disease in industrialized countries, the epidemiology is far from being fully elucidated. We provide here a comprehensive review of documented clusters of cases, and of serological studies conducted in populations with distinct types of exposure. Seroprevalence rates range from <5% to >50% depending on the countries and the groups of population. Such discrepancies can be attributed to the type of serological assay used, but this solves only a part of the problem. We performed a meta-analysis of studies performed with the broadly used Wantai HEV-IgG ELISA and found striking differences that remain difficult to understand with the current knowledge of transmission pathways.
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23
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Kyuregyan KK, Polyakov AD, Potemkin IA, Karlsen AA, Isaeva OV, Lopatukhina MA, Mullin EV, Slukinova OS, Malinnikova EY, Shibrik EV, Oglezneva EE, Mikhailov MI. [Belgorod region - the territory endemic for hepatitis E.]. Vopr Virusol 2019; 64:274-280. [PMID: 32168441 DOI: 10.36233/0507-4088-2019-64-6-274-280] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2019] [Accepted: 12/24/2019] [Indexed: 12/27/2022]
Abstract
INTRODUCTION Belgorod region is the territory with the highest incidence of hepatitis E in the Russian Federation. OBJECTIVES The aim of the study was to comprehensively characterize the circulation of hepatitis E virus (HEV) in the Belgorod region, including the study of population immunity to the virus, determining the prevalence of infection among the pig population and analysis of the genetic diversity of HEV from patients and animals. MATERIAL AND METHODS Serum samples of a conditionally healthy population (n = 2027) of all age groups were tested for anti-HEV IgG and IgM by ELISA with commercial assays. HEV RNA was determined in fecal samples from pigs aged 2-4 months (n = 526), in sewage samples from pig farms (n = 10), as well as in stool samples from patients with hepatitis E (n = 6) using reverse transcription polymerase chain reaction (RT-PCR). Phylogenetic analysis was performed for an amplified 300 nt fragment corresponding to HEV open reading frame 2. RESULTS AND DISCUSSION The prevalence of anti-HEV IgG in general population averaged 16.4% (95% CI: 14.8-18.1; 332/2027). The proportion of individuals who had both anti-HEV IgM and IgG averaged 2.8% (95% CI: 2.2-3.6; 57/2027). The incidence rate of anti-HEV IgG increased with age, from 2.8% (95% CI: 1.3-5.8) in children aged 1-14 years to 40.1% (95% CI: 34.9-45.6) in people 70 years or older. The detection rate of HEV RNA in pigs was 20% (95% CI: 16.8-23.6; 105/526). HEV RNA was detected in 2 out of 10 sewage samples. The HEV sequences isolated from patients with hepatitis E, pigs, and sewage samples in Belgorod region belonged to the HEV genotype 3, had a 95-100% homology, and formed common clusters on a phylogenetic tree. CONCLUSIONS The high prevalence of HEV in pigs population has led to the formation of an endemic territory in the Belgorod region, which is the center of pig breeding. Measures aimed at reducing the circulation of HEV among pig population and decontamination of sewage from pig farms are necessary to control HEV infection.
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Affiliation(s)
- K K Kyuregyan
- Mechnikov Research Institute for Vaccines and Sera, Moscow, 105064, Russia.,Russian Medical Academy of Continuous Professional Education, Moscow, 125993, Russia
| | - A D Polyakov
- Skolkovo Territorial Division of the Office of Rospotrebnadzor for the City of Moscow Russia, Moscow, 143026, Russia.,Belgorod State National Research University, Belgorod, 308015, Russia
| | - I A Potemkin
- Mechnikov Research Institute for Vaccines and Sera, Moscow, 105064, Russia.,Russian Medical Academy of Continuous Professional Education, Moscow, 125993, Russia
| | - A A Karlsen
- Mechnikov Research Institute for Vaccines and Sera, Moscow, 105064, Russia.,Russian Medical Academy of Continuous Professional Education, Moscow, 125993, Russia
| | - O V Isaeva
- Mechnikov Research Institute for Vaccines and Sera, Moscow, 105064, Russia.,Russian Medical Academy of Continuous Professional Education, Moscow, 125993, Russia
| | - M A Lopatukhina
- Mechnikov Research Institute for Vaccines and Sera, Moscow, 105064, Russia
| | - E V Mullin
- Mechnikov Research Institute for Vaccines and Sera, Moscow, 105064, Russia
| | - O S Slukinova
- Mechnikov Research Institute for Vaccines and Sera, Moscow, 105064, Russia
| | - E Y Malinnikova
- Mechnikov Research Institute for Vaccines and Sera, Moscow, 105064, Russia.,Russian Medical Academy of Continuous Professional Education, Moscow, 125993, Russia
| | - E V Shibrik
- Department of Health and Social Protection of the Population of Belgorod Region, Belgorod, 308005, Russia
| | - E E Oglezneva
- Belgorod State National Research University, Belgorod, 308015, Russia.,Belgorod Regional Department of Rospotrebnadzor, Belgorod, 308023, Russia
| | - M I Mikhailov
- Mechnikov Research Institute for Vaccines and Sera, Moscow, 105064, Russia.,Russian Medical Academy of Continuous Professional Education, Moscow, 125993, Russia
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24
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Webb GW, Dalton HR. Hepatitis E: an underestimated emerging threat. Ther Adv Infect Dis 2019; 6:2049936119837162. [PMID: 30984394 PMCID: PMC6448100 DOI: 10.1177/2049936119837162] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 02/08/2019] [Indexed: 12/22/2022] Open
Abstract
Hepatitis E virus (HEV) is the most common cause of viral hepatitis in the world. It is estimated that millions of people are infected every year, resulting in tens of thousands of deaths. However, these estimates do not include industrialized regions and are based on studies which employ assays now known to have inferior sensitivity. As such, this is likely to represent a massive underestimate of the true global burden of disease. In the developing world, HEV causes large outbreaks and presents a significant public-health problem. Until recently HEV was thought to be uncommon in industrialized countries, and of little relevance to clinicians in these settings. We now know that this is incorrect, and that HEV is actually very common in developed regions. HEV has proved difficult to study in vitro, with reliable models only recently becoming available. Our understanding of the lifecycle of HEV is therefore incomplete. Routes of transmission vary by genotype and location: endemic regions experience large waterborne epidemics, while sporadic cases in industrialized regions are zoonotic infections likely spread via the food chain. Both acute and chronic infection has been observed, and a wide range of extrahepatic manifestations have been reported. This includes neurological, haematological and renal conditions. As the complete clinical phenotype of HEV infection is yet to be characterized, a large proportion of cases go unrecognized or misdiagnosed. In many cases HEV infection does not feature in the differential diagnosis due to a lack of knowledge and awareness of the disease amongst clinicians. In combination, these factors have contributed to an underestimation of the threat posed by HEV. Improvements are required in terms of recognition and diagnosis of HEV infection if we are to understand the natural history of the disease, improve management and reduce the burden of disease around the world.
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Affiliation(s)
- Glynn W. Webb
- University of Manchester NHS Foundation Trust, 7 Radnor Rd London NW6 6TT Manchester, UK
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25
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Horn J, Hoodgarzadeh M, Klett-Tammen CJ, Mikolajczyk RT, Krause G, Ott JJ. Epidemiologic estimates of hepatitis E virus infection in European countries. J Infect 2018; 77:544-552. [DOI: 10.1016/j.jinf.2018.09.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Accepted: 09/20/2018] [Indexed: 12/16/2022]
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26
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Intharasongkroh D, Thongmee T, Sa-Nguanmoo P, Klinfueng S, Duang-In A, Wasitthankasem R, Theamboonlers A, Charoonruangrit U, Oota S, Payungporn S, Vongpunsawad S, Chirathaworn C, Poovorawan Y. Hepatitis E virus infection in Thai blood donors. Transfusion 2018; 59:1035-1043. [PMID: 30443992 DOI: 10.1111/trf.15041] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Revised: 09/10/2018] [Accepted: 09/20/2018] [Indexed: 12/19/2022]
Abstract
BACKGROUND Hepatitis E virus (HEV) infection in several industrialized and developing countries is associated with the consumption of pork and other meat products, an exposure risk among the majority of blood donors. We aimed to evaluate the prevalence of HEV in plasma from healthy blood donors in Thailand. STUDY DESIGN AND METHODS We screened blood samples collected between October and December 2015, from 30,115 individual blood donors in 5020 pools of six, for HEV RNA using in-house real-time reverse-transcription polymerase chain reaction (RT-PCR). Thrice-reactive samples were subjected to a commercial real-time RT-PCR (cobas HEV test) and evaluated for anti-HEV immunoglobulin M and immunoglobulin G antibodies. Genotyping using nested RT-PCR, nucleotide sequencing, and phylogenetic analysis was performed. RESULTS Twenty-six donors were positive for HEV RNA by the in-house assay, nine of whom were also positive by cobas test. None of the latter were reactive for anti-HEV immunoglobulin M or immunoglobulin G antibodies. Six samples were successfully genotyped and found to be HEV genotype 3. Thus, the frequency of HEV infection among healthy Thai blood donors is 1 in 1158. CONCLUSION The presence of HEV RNA in the Thai blood supply was comparable to the rates reported in western European countries, but higher than in North America and Australia.
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Affiliation(s)
- Duangnapa Intharasongkroh
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Thanunrat Thongmee
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Pattaratida Sa-Nguanmoo
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sirapa Klinfueng
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Ausanee Duang-In
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Rujipat Wasitthankasem
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Apiradee Theamboonlers
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | | | | | - Sunchai Payungporn
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sompong Vongpunsawad
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Chintana Chirathaworn
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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27
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Dalton HR, Izopet J. Transmission and Epidemiology of Hepatitis E Virus Genotype 3 and 4 Infections. Cold Spring Harb Perspect Med 2018. [PMID: 29530946 DOI: 10.1101/cshperspect.a032144] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Following the introduction of robust serological and molecular tools, our understanding of the epidemiology of zoonotic hepatitis E virus (HEV) has improved considerably in recent years. Current thinking suggests that consumption of pork meat products is the key route of infection in humans, but it is certainly not the only one. Other routes of infection include environmental spread, contaminated water, and via the human blood supply. The epidemiology of HEV genotype (gt)3 and gt4 is complex, as there are several sources and routes of infection, and it is likely that these vary between and within countries and over time.
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Affiliation(s)
- Harry R Dalton
- Royal Cornwall Hospital, Truro TR1 3LJ, United Kingdom.,European Centre for Environment and Human Health, University of Exeter, Truro TR1 3LJ, United Kingdom
| | - Jacques Izopet
- Department of Virology, Hepatitis E Virus National Reference Centre, Toulouse University Hospital, 31059 Toulouse, France.,Toulouse-Purpan Centre for Pathophysiology, INSERM UMR1043/CNRS UMR 5282, CPTP, Toulouse University Paul Sabatier, 31024 Toulouse, France
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28
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Mahrt H, Schemmerer M, Behrens G, Leitzmann M, Jilg W, Wenzel JJ. Continuous decline of hepatitis E virus seroprevalence in southern Germany despite increasing notifications, 2003-2015. Emerg Microbes Infect 2018; 7:133. [PMID: 30042475 PMCID: PMC6057927 DOI: 10.1038/s41426-018-0136-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 07/03/2018] [Accepted: 07/03/2018] [Indexed: 12/28/2022]
Abstract
Hepatitis E virus (HEV) is viewed as an emerging pathogen. Many European countries, including Germany, have observed a steep increase of notified autochthonous hepatitis E cases in recent years. Our study investigated time trends in HEV seroprevalence in southern Germany between 2003 and 2015. A total of 3000 study sera were evenly distributed over sampling years 2003, 2006, 2009, 2012, and 2015, two age groups (20-29 and 30-39 years) and genders and were tested for anti-HEV IgG. Positive samples were quantified. The seroprevalence declined from 32.8% in 2003 over 22.5% in 2006 (p < 0.001) and 22.3% in 2009 to 17.7% and 17.8% in 2012 and 2015. A higher prevalence was found for males (p = 0.018) and the older age group (p < 0.001). Anti-HEV IgG concentrations ranged from 0.22 to 1783.19 WU mL-1. A higher median concentration (2.41 vs. 1.89 WU mL-1, p < 0.001) was found in the younger age group. The anti-HEV IgG seroprevalence decreased since 2003 and remains constant at ~18% since 2012. A rather low anti-HEV prevalence in young adults is indicative of a susceptible population and denotes a higher risk of HEV infections in this age group in the future. Therefore, reduction of HEV infection sources, close monitoring, and vigilance for proper control measures are warranted.
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Affiliation(s)
- Hannah Mahrt
- Institute of Clinical Microbiology and Hygiene, University Medical Center Regensburg, 93053, Regensburg, Germany
| | - Mathias Schemmerer
- Institute of Clinical Microbiology and Hygiene, University Medical Center Regensburg, 93053, Regensburg, Germany
| | - Gundula Behrens
- Department of Epidemiology and Preventive Medicine, University of Regensburg, 93053, Regensburg, Germany
| | - Michael Leitzmann
- Department of Epidemiology and Preventive Medicine, University of Regensburg, 93053, Regensburg, Germany
| | - Wolfgang Jilg
- Institute of Clinical Microbiology and Hygiene, University Medical Center Regensburg, 93053, Regensburg, Germany
| | - Jürgen J Wenzel
- Institute of Clinical Microbiology and Hygiene, University Medical Center Regensburg, 93053, Regensburg, Germany.
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29
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Seroprevalence of hepatitis E virus among blood donors in northern Italy (Sondrio, Lombardy) determined by three different assays. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2018; 15:502-505. [PMID: 29059041 DOI: 10.2450/2017.0089-17] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Accepted: 06/20/2017] [Indexed: 02/08/2023]
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30
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Faber M, Willrich N, Schemmerer M, Rauh C, Kuhnert R, Stark K, Wenzel JJ. Hepatitis E virus seroprevalence, seroincidence and seroreversion in the German adult population. J Viral Hepat 2018; 25:752-758. [PMID: 29377436 DOI: 10.1111/jvh.12868] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Accepted: 12/18/2017] [Indexed: 01/26/2023]
Abstract
A steep rise in Hepatitis E diagnoses is currently being observed in Germany and other European countries. The objective of this study was (i) to assess whether this trend mirrors an increase in infection pressure or is caused by increased attention and testing and (ii) estimate individual and population-based Hepatitis E Virus (HEV) seroconversion and seroreversion rates for Germany. We measured anti-HEV IgG prevalence in 10 407 adults participating in two linked, population-representative serosurveys (total n = 12 971) conducted in 1998 and 2010. In this period, we found a moderate but statistically significant decline of overall anti-HEV IgG prevalence from 18.6% to 15.3%. At both time points, seroprevalence increased with age and peaked in persons born between 1935 and 1959 suggesting a past period of increased infection pressure. Paired samples of individuals participating in 1998 and 2010 (n = 2564) revealed respective seroconversion and seroreversion rates of 6.2% and 22.6% among seronegative and seropositive individuals during 12 years, or 5.2 and 2.9 per 1000 inhabitants per year. This corresponds to a total of 417 242 [95%CI: 344 363-495 971] new seroconversions per year in the German population. While anti-HEV seroprevalence has decreased in the last decade, infection pressure and seroincidence remains high in Germany. Continuously rising numbers of Hepatitis E diagnoses in Europe are likely due to an increased awareness of clinicians and indicate that still there is a gap between incident and diagnosed cases. Studies on the true burden of the disease, specific risk factors and sources of autochthonous infections as well as targeted prevention measures are urgently needed.
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Affiliation(s)
- M Faber
- Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
| | - N Willrich
- Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
| | - M Schemmerer
- Institute of Clinical Microbiology and Hygiene, University Medical Center Regensburg, Regensburg, Germany
| | - C Rauh
- Institute of Clinical Microbiology and Hygiene, University Medical Center Regensburg, Regensburg, Germany
| | - R Kuhnert
- Department of Epidemiology and Health Reporting, Robert Koch Institute, Berlin, Germany
| | - K Stark
- Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
| | - J J Wenzel
- Institute of Clinical Microbiology and Hygiene, University Medical Center Regensburg, Regensburg, Germany
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31
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Dalton HR, Kamar N, Baylis SA, Moradpour D, Wedemeyer H, Negro F. EASL Clinical Practice Guidelines on hepatitis E virus infection. J Hepatol 2018; 68:1256-1271. [PMID: 29609832 DOI: 10.1016/j.jhep.2018.03.005] [Citation(s) in RCA: 415] [Impact Index Per Article: 59.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Accepted: 03/09/2018] [Indexed: 02/08/2023]
Abstract
Infection with hepatitis E virus (HEV) is a significant cause of morbidity and mortality, representing an important global health problem. Our understanding of HEV has changed completely over the past decade. Previously, HEV was thought to be limited to certain developing countries. We now know that HEV is endemic in most high-income countries and is largely a zoonotic infection. Given the paradigm shift in our understanding of zoonotic HEV and that locally acquired HEV is now the commonest cause of acute viral hepatitis in many European countries, the focus of these Clinical Practice Guidelines will be on HEV genotype 3 (and 4).
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32
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A nationwide retrospective study on prevalence of hepatitis E virus infection in Italian blood donors. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2018; 16:413-421. [PMID: 29757135 DOI: 10.2450/2018.0033-18] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 04/10/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND In Europe, hepatitis E virus (HEV) infection is mainly a food-borne zoonosis, but it can also be transmitted by blood transfusion. It is usually a mild and self-limited infection. However, immunocompromised persons, who are also those more likely to undergo blood transfusions, may develop chronic hepatitis and often cirrhosis. Since this is a potential threat to blood safety, we aimed to investigate HEV prevalence in Italian blood donors. MATERIALS AND METHODS We used plasma donations collected during 2015-2016 by blood services (BS) scattered throughout the Italian regions and intended for the production of plasma-derived medicines. Plasma samples were tested for IgG and IgM anti-HEV and for HEV RNA using validated assays. Data concerning donor's age and sex, and the location of the BS were collected. RESULTS A total of 10,011 plasma samples were tested. Overall IgG and IgM prevalence rates were 8.7 and 0.4%, respectively. No sample was HEV RNA-positive. IgG prevalence was significantly higher in males and in donors aged 44 years and over. IgG prevalence differed greatly according to region. Overall regional rates over 15% were found in Abruzzo and in Sardinia, and rates of 10-15% were found in Lazio, Umbria and the Marche. Considering IgG prevalence according to the province where the BS was located, rates over 30% were found in Sardinia and Abruzzo. Age, sex and donor's region of residence were independently associated with IgG positivity. BS location produced significant heterogeneity on prevalence rates within the regions. DISCUSSION The detected IgG rate of 8.7% in this study represents one of the lowest seroprevalence rates reported among blood donors in Europe. Particularly high prevalence rates in some regions and provinces may be explained by local eating habits and/or intensive environmental HEV contamination. Before considering the introduction of HEV RNA screening for blood donations in Italy, further important issues should be addressed and prospective incidence and reliable cost-benefit studies are needed.
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33
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Grabarczyk P, Sulkowska E, Gdowska J, Kopacz A, Liszewski G, Kubicka-Russel D, Baylis SA, Corman VM, Noceń E, Piotrowski D, Antoniewicz-Papis J, Łętowska M. Molecular and serological infection marker screening in blood donors indicates high endemicity of hepatitis E virus in Poland. Transfusion 2018; 58:1245-1253. [PMID: 29492976 DOI: 10.1111/trf.14531] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 12/11/2017] [Accepted: 01/04/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND Until now, markers of hepatitis E virus (HEV) infection have not been studied in blood donors throughout Poland, and no acute case of HEV infection has been closely documented or confirmed by HEV RNA detection. The prevalence of HEV infection markers, including HEV RNA in Polish blood donors and virus genotypes was investigated. STUDY DESIGN AND METHODS In total, 12,664 individual donations from 22 Polish blood transfusion centers were tested for HEV RNA by transcription-mediated amplification. In addition, 3079 first-time donors sampled throughout Poland also were screened for antibodies to HEV. HEV RNA and immunoglobulin M-positive donations were confirmed using real-time reverse transcription-polymerase chain reaction and Western blotting, respectively. RESULTS Ten donors were identified as RNA initial reactive (one of 1266 donors), and six (one of 2109) were identified as repeat reactive and confirmed by real-time reverse transcription-polymerase chain reaction or seroconversion. Sequence analysis identified HEV Genotype 3c in one donor and Genotype 3i in two others. On average, 43.5% of donors were immunoglobulin G-positive. Immunoglobulin G seroprevalence ranged from 22.7% to 60.8% in group ages 18 to 27 years and 48 to 57 years, respectively and differed between administrative regions from 28.9% in Podlasie to 61.3% in Wielkopolska. Thirty-nine of the donors were immunoglobulin M-positive, and seven donors were IgM positive only (0.2%). Of 37 immunoglobulin M-reactive samples tested by Western blot, 24 (64.9%) were confirmed. CONCLUSIONS The current results indicate a high level of HEV endemicity throughout Poland compared with other countries. There is an urgent need to consider the protection of recipients of blood components against transfusion-transmitted HEV infection.
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Affiliation(s)
| | | | | | - Aneta Kopacz
- Institute of Haematology and Transfusion Medicine
| | | | | | - Sally A Baylis
- Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich-Institut, Langen, Germany
| | - Victor M Corman
- Institute of Virology, Charité-Universitätsmedizin Berlin.,German Centre for Infection Research (DZIF), Berlin, Germany
| | - Ewa Noceń
- Institute of Haematology and Transfusion Medicine
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O'Gorman J, Burke Á, O'Flaherty N. Hepatitis E virus - key points for the clinical haematologist. Br J Haematol 2018; 181:579-589. [PMID: 29468650 DOI: 10.1111/bjh.15133] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2017] [Accepted: 01/06/2018] [Indexed: 12/13/2022]
Abstract
In recent years there has been a paradigm shift in our understanding of the epidemiology and clinical features of hepatitis E virus (HEV) infection. Once classically described as an acute hepatitis associated with waterborne outbreaks in areas of poor sanitation, HEV is now recognised to be endemic in Europe and is probably zoonotic in origin. Evidence for transfusion-transmitted HEV has prompted the introduction of blood donor screening in a number of countries, but the risk to the haematology patient from food sources remains. The aim of this review therefore, is to equip the clinical haematologist with the knowledge required to diagnose HEV infection and to aid decision-making in patient management. The article also provides information on addressing patient concerns about their risk of acquiring hepatitis E and how this risk can be mitigated.
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Affiliation(s)
- Joanne O'Gorman
- Consultant Clinical Microbiologist, National Virus Reference Laboratory, University College Dublin, Dublin, Ireland
| | - Áine Burke
- Consultant Haematologist, Sligo University Hospital, Sligo, Ireland
| | - Niamh O'Flaherty
- Consultant Clinical Microbiologist, National Virus Reference Laboratory, University College Dublin, Dublin, Ireland.,Consultant Clinical Microbiologist, Irish Blood Transfusion Service, Dublin 8, Ireland
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35
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Immunobiology and Host Response to HEV. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 948:113-141. [PMID: 27738982 DOI: 10.1007/978-94-024-0942-0_7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hepatitis E virus (HEV) causes acute self-limiting hepatitis in most cases and chronic infection in rare circumstances. It is believed to be noncytopathic, so immunologically mediated events should play important roles in its pathogenesis and infection outcomes. The anti-HEV antibody response was clarified when the major antigenic determinants on the ORF2 polypeptide were determined, which are located in its C-terminal portion. This subregion also forms the conformational neutralization epitopes. Robust anti-HEV immunoglobulin M (IgM) and IgG responses usually develop 3-4 weeks after infection in experimentally infected nonhuman primates. In humans, potent specific IgM and IgG responses occur in the very early phase of the disease and are critical in eliminating the virus, in concert with the innate and adaptive T-cell immune responses. They are also very valuable in the diagnosis of acute hepatitis E, when patients are tested for both anti-HEV IgM and IgG. The long-term persistence and protection of anti-HEV IgG provide the basis for estimating the prevalence of HEV infection and for the development of a hepatitis E vaccine. Although HEV has four genotypes, all the viral strains are considered to belong to a single serotype. It is becoming increasingly clear that the innate and adaptive T-cell immune responses play critical roles in the clearance of the virus. Potent and multispecific CD4+ and CD8+ T-cell responses to the ORF2 protein occur in patients with acute hepatitis E, and weaker HEV-specific CD4+ and CD8+ T-cell responses appear to be associated with chronic hepatitis E in immunocompromised individuals.
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36
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Al-Sadeq DW, Majdalawieh AF, Nasrallah GK. Seroprevalence and incidence of hepatitis E virus among blood donors: A review. Rev Med Virol 2017; 27:e1937. [PMID: 28876496 DOI: 10.1002/rmv.1937] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 07/16/2017] [Accepted: 07/18/2017] [Indexed: 12/19/2022]
Abstract
Hepatitis E virus (HEV) is an RNA virus with 4 main genotypes. HEV-1 and HEV-2 infect solely humans, while HEV-3 and HEV-4 infect humans and various animals such as pigs, deer, and rabbits. HEV-5 and HEV-6 infect mainly wild boar. Recently, new genotypes, known as HEV-7 and HEV-8, were found to infect camels and humans. HEV is globally distributed into different epidemiological patterns based on socioeconomic factors and ecology. Although HEV is mainly transmitted through the fecal-oral route, it was also recognized as a transfusion-transmitted virus. Transmission through blood donation was documented worldwide with rising annual observations, accounting for more than 2.5% of all transmissions. HEV infection is usually asymptomatic or subclinical in immunocompetent individuals, so it remains questionable whether there is an urgent need to screen for HEV prior to blood transfusion. Moreover, recent studies conducted in the Middle East and North Africa (MENA) region indicate that HEV is highly endemic. Here, we provide a review on HEV epidemiology, transmission, and laboratory diagnosis, giving special emphasis to the newly discovered genotypes, HEV-7 and HEV-8. Furthermore, we underscore the findings of recent HEV seroprevalence and viremia studies among blood donors worldwide. We also shed light on similar studies performed among blood donors in the MENA region.
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Affiliation(s)
- Duaa W Al-Sadeq
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Amin F Majdalawieh
- Department of Biology, Chemistry, and Environmental Sciences, College of Arts and Sciences, American University of Sharjah, Sharjah, United Arab Emirates
| | - Gheyath K Nasrallah
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
- Biomedical Research Center, Qatar University, Doha, Qatar
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Aspinall EJ, Couturier E, Faber M, Said B, Ijaz S, Tavoschi L, Takkinen J, Adlhoch C. Hepatitis E virus infection in Europe: surveillance and descriptive epidemiology of confirmed cases, 2005 to 2015. ACTA ACUST UNITED AC 2017; 22. [PMID: 28681720 PMCID: PMC6518348 DOI: 10.2807/1560-7917.es.2017.22.26.30561] [Citation(s) in RCA: 114] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Accepted: 03/28/2017] [Indexed: 12/31/2022]
Abstract
Hepatitis E virus (HEV) is an under-recognised cause of acute hepatitis in high-income countries. The purpose of this study was to provide an overview of testing, diagnosis, surveillance activities, and data on confirmed cases in the European Union/European Economic Area (EU/EEA). A semi-structured survey was developed and sent to 31 EU/EEA countries in February 2016, 30 responded. Twenty of these countries reported that they have specific surveillance systems for HEV infection. Applied specific case definition for HEV infection varied widely across countries. The number of reported cases has increased from 514 cases per year in 2005 to 5,617 in 2015, with most infections being locally acquired. This increase could not be explained by additional countries implementing surveillance for HEV infections over time. Hospitalisations increased from less than 100 in 2005 to more than 1,100 in 2015 and 28 fatal cases were reported over the study period. EU/EEA countries are at different stages in their surveillance, testing schemes and policy response to the emergence of HEV infection in humans. The available data demonstrated a Europe-wide increase in cases. Standardised case definitions and testing policies would allow a better understanding of the epidemiology of HEV as an emerging cause of liver-related morbidity.
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Affiliation(s)
- Esther J Aspinall
- NHS National Services Scotland, Glasgow, United Kingdom.,Glasgow Caledonian University, Glasgow, United Kingdom
| | | | | | - Bengü Said
- National Infection Service, Public Health England, London, United Kingdom
| | - Samreen Ijaz
- National Infection Service, Public Health England, London, United Kingdom
| | - Lara Tavoschi
- European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden
| | - Johanna Takkinen
- European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden
| | - Cornelia Adlhoch
- European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden
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- Country experts are listed at the end of the article
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38
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Roth NJ, Schäfer W, Alexander R, Elliott K, Elliott-Browne W, Knowles J, Wenzel JJ, Simon TL. Low hepatitis E virus RNA prevalence in a large-scale survey of United States source plasma donors. Transfusion 2017; 57:2958-2964. [PMID: 28833188 DOI: 10.1111/trf.14285] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Revised: 06/12/2017] [Accepted: 07/05/2017] [Indexed: 01/18/2023]
Abstract
BACKGROUND Hepatitis E virus (HEV) is a small, nonenveloped, single-stranded, RNA virus of emerging concern in industrialized countries. HEV transmission through transfusion of blood components has been reported, but not via plasma-derived medicinal products (PDMPs) manufactured with virus inactivation and/or removal steps. This study aimed to determine the prevalence of HEV among US source plasma donors. STUDY DESIGN AND METHODS Samples were collected from US source plasma donors at centers across the United States and were initially screened for HEV RNA in 96-sample minipools using the Roche cobas HEV test on the cobas 8800 system. Assuming a sensitivity of 18.6 IU/mL, the minipool screening strategy allowed for reliable detection of individual donations with HEV RNA titers of more than 2 × 103 IU/mL. Reactive minipools were resolved to individual donations, which were further analyzed to quantify viral RNA concentration, determine HEV genotype, and immunoglobulin (Ig)G and IgM HEV antibody status. RESULTS A total of 128,020 samples were collected from 96 CSL Plasma centers in the United States, representing 27 states. The prevalence of HEV RNA-positive samples was 0.002% with three unique HEV-positive donors identified, all HEV Subgenotype 3a. Virus titers of HEV-positive samples were relatively low (103 -104 IU HEV RNA/mL). One positive donation was HEV IgG seropositive. CONCLUSION Routine screening of US source plasma donations for HEV would not substantially improve the safety of most PDMPs. The low prevalence and potential viral load of HEV, together with effective virus reduction steps in manufacturing processes, results in a low residual risk and acceptable safety margins for PDMPs derived from US plasma donors.
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Affiliation(s)
| | | | | | | | | | | | - Jürgen J Wenzel
- Institute of Clinical Microbiology and Hygiene, University Medical Center Regensburg, Regensburg, Germany
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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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40
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Domanović D, Tedder R, Blümel J, Zaaijer H, Gallian P, Niederhauser C, Sauleda Oliveras S, O'Riordan J, Boland F, Harritshøj L, Nascimento MSJ, Ciccaglione AR, Politis C, Adlhoch C, Flan B, Oualikene-Gonin W, Rautmann G, Strengers P, Hewitt P. Hepatitis E and blood donation safety in selected European countries: a shift to screening? ACTA ACUST UNITED AC 2017; 22:30514. [PMID: 28449730 PMCID: PMC5404480 DOI: 10.2807/1560-7917.es.2017.22.16.30514] [Citation(s) in RCA: 123] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Accepted: 02/09/2017] [Indexed: 12/15/2022]
Abstract
The public health implications of hepatitis E virus (HEV) in Europe have changed due to increasing numbers of hepatitis E cases and recent reports of chronic, persistent HEV infections associated with progression to cirrhosis in immunosuppressed patients. The main infectious risk for such immunosuppressed patients is exposure to undercooked infected pork products and blood transfusion. We summarised the epidemiology of HEV infections among blood donors and also outlined any strategies to prevent transfusion-transmitted HEV, in 11 European countries. In response to the threat posed by HEV and related public and political concerns, most of the observed countries determined seroprevalence of HEV in donors and presence of HEV RNA in blood donations. France, Germany, Spain and the United Kingdom (UK) reported cases of transfusion-transmitted HEV. Ireland and the UK have already implemented HEV RNA screening of blood donations; the Netherlands will start in 2017. Germany and France perform screening for HEV RNA in several blood establishments or plasma donations intended for use in high-risk patients respectively and, with Switzerland, are considering implementing selective or universal screening nationwide. In Greece, Portugal, Italy and Spain, the blood authorities are evaluating the situation. Denmark decided not to implement the HEV screening of blood donations.
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Affiliation(s)
- Dragoslav Domanović
- European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden
| | - Richard Tedder
- Hepatitis E Study Group, Joint PHE/NHSBT Blood Borne Virus Unit, PHE, Colindale, London, United Kingdom
| | - Johannes Blümel
- Paul-Ehrlich-Institute, Federal Institute for Vaccines and Biomedicines, Virus Safety Section, Langen, Germany
| | - Hans Zaaijer
- Sanquin, Blood-borne Infections & AMC, Clinical Virology, Amsterdam, the Netherlands
| | | | | | | | | | - Fiona Boland
- Irish Blood Transfusion Service, Dublin, Ireland
| | - Lene Harritshøj
- Rigshospitalet, Department of Clinical Immunology, Copenhagen, Denmark
| | | | - Anna Rita Ciccaglione
- National Health Institute, Viral Hepatitis Division, Department of Infectious Diseases, Rome, Italy
| | | | - Cornelia Adlhoch
- European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden
| | - Benoit Flan
- LFB Biomedicaments, Biological Safety Surveillance, Courtaboeuf Cedex, France
| | - Wahiba Oualikene-Gonin
- Agence nationale de sécurité du médicament et des produits de santé, Saint-Denis Cedex, France
| | - Guy Rautmann
- European Directorate for the Quality of Medicines and HealthCare, Strasbourg, France
| | - Paul Strengers
- International Plasma Fractionation Association, Amsterdam, Netherlands
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Fearon MA, O'Brien SF, Delage G, Scalia V, Bernier F, Bigham M, Weger S, Prabhu S, Andonov A. Hepatitis E in Canadian blood donors. Transfusion 2017; 57:1420-1425. [PMID: 28394029 DOI: 10.1111/trf.14089] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Revised: 01/19/2017] [Accepted: 01/19/2017] [Indexed: 12/25/2022]
Abstract
BACKGROUND Hepatitis E virus (HEV) is a virus of emerging importance to transfusion medicine as studies on blood donors and other populations demonstrate that the prevalence of endemic cases is higher than previously recognized and the risk to vulnerable transfusion recipients is not insignificant. STUDY DESIGN AND METHODS We carried out an HEV prevalence study on 13,993 Canadian blood donors with polymerase chain reaction (PCR) testing on all donors and antibody testing on a subset of 4102 donors. HEV antibody-positive and age- and sex-matched antibody-negative donors were invited to participate in a scripted telephone interview about risk factors. RESULTS There were no PCR-positive samples found (95% confidence interval [CI], 0%-0.026%). The seroprevalence of HEV in our tested population was 5.9% (95% CI, 5.16%-6.59%). HEV antibody positivity was associated with male sex and increasing age. In case-control analysis history of living outside Canada (odds ratio [OR], 2.9; 95% CI, 1.56-5.32) and contact with farm animals (OR, 1.5; 95% CI, 1.01-2.28) were associated with HEV seropositivity. CONCLUSION This is the largest data set to date on HEV infection in Canada. Results suggest low lifetime exposure to HEV and that infectious donations are rare.
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Affiliation(s)
- Margaret A Fearon
- Canadian Blood Services, Toronto, Ontario, Canada.,Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | - Sheila F O'Brien
- Canadian Blood Services, Ottawa, Ontario, Canada.,University of Ottawa, School of Epidemiology, Public Health and Preventative Medicine, Ottawa, Ontario, Canada
| | - Gilles Delage
- Microbiology, Héma-Québec, Saint-Laurent, Québec, Canada
| | - Vito Scalia
- Canadian Blood Services, Ottawa, Ontario, Canada
| | - France Bernier
- Microbiology, Héma-Québec, Saint-Laurent, Québec, Canada
| | - Mark Bigham
- Medical Department, Canadian Blood Services, BC and Yukon, Vancouver, British Columbia, Canada
| | - Steven Weger
- University of Manitoba, Winnipeg, Manitoba, Canada
| | - Sneha Prabhu
- Institute for Health Promotion Research, University of Texas Medical School at San Antonio, San Antonio, Texas
| | - Anton Andonov
- Molecular and Immunodiagnostics, Bloodborne Pathogens and Hepatitis, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
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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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43
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Fontana RJ, Engle RE, Scaglione S, Araya V, Shaikh O, Tillman H, Attar N, Purcell RH, Lee WM. The role of hepatitis E virus infection in adult Americans with acute liver failure. Hepatology 2016; 64:1870-1880. [PMID: 27215797 PMCID: PMC5115940 DOI: 10.1002/hep.28649] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Revised: 04/04/2016] [Accepted: 05/17/2016] [Indexed: 12/11/2022]
Abstract
UNLABELLED Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries, yet rarely identified in Western countries. Given that antibody testing for HEV infection is not routinely obtained, we hypothesized that HEV-related ALF might be present and unrecognized in North American ALF patients. Serum samples of 681 adults enrolled in the U.S. Acute Liver Failure Study Group were tested for anti-HEV immunoglobulin (Ig) M and anti-HEV IgG levels. Subjects with a detectable anti-HEV IgM also underwent testing for HEV RNA. Mean patient age was 41.8 years, 32.9% were male, and ALF etiologies included acetaminophen (APAP) hepatotoxicity (29%), indeterminate ALF (23%), idiosyncratic drug-induced liver injury DILI (22%), acute hepatitis B virus infection (12%), autoimmune hepatitis (12%), and pregnancy-related ALF (2%). Three men ages 36, 39, and 70 demonstrated repeatedly detectable anti-HEV IgM, but all were HEV-RNA negative and had other putative diagnoses. The latter 2 subjects died within 3 and 11 days of enrollment whereas the 36-year-old underwent emergency liver transplantation on study day 2. At admission, 294 (43.4%) of the ALF patients were anti-HEV IgG positive with the seroprevalence being highest in those from the Midwest (50%) and lowest in those from the Southeast (28%). Anti-HEV IgG+ subjects were significantly older, less likely to have APAP overdose, and had a lower overall 3-week survival compared to anti-HEV IgG- subjects (63% vs. 70%; P = 0.018). CONCLUSION Acute HEV infection is very rare in adult Americans with ALF (i.e., 0.4%) and could not be implicated in any indeterminate, autoimmune, or pregnancy-related ALF cases. Past exposure to HEV with detectable anti-HEV IgG was significantly more common in the ALF patients compared to the general U.S. POPULATION (Hepatology 2016;64:1870-1880).
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Affiliation(s)
| | - Ronald E. Engle
- National Institute of Allergy and Infectious Diseases, Bethesda, MD
| | | | | | | | | | - Nahid Attar
- University of Texas Southwestern, Dallas, TX
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44
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Geng Y, Wang Y. Transmission of Hepatitis E Virus. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2016; 948:89-112. [PMID: 27738981 DOI: 10.1007/978-94-024-0942-0_6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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45
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Transmission of Hepatitis E Virus in Developing Countries. Viruses 2016; 8:v8090253. [PMID: 27657112 PMCID: PMC5035967 DOI: 10.3390/v8090253] [Citation(s) in RCA: 106] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Revised: 09/08/2016] [Accepted: 09/08/2016] [Indexed: 12/11/2022] Open
Abstract
Hepatitis E virus (HEV), an RNA virus of the Hepeviridae family, has marked heterogeneity. While all five HEV genotypes can cause human infections, genotypes HEV-1 and -2 infect humans alone, genotypes HEV-3 and -4 primarily infect pigs, boars and deer, and genotype HEV-7 primarily infects dromedaries. The global distribution of HEV has distinct epidemiological patterns based on ecology and socioeconomic factors. In resource-poor countries, disease presents as large-scale waterborne epidemics, and few epidemics have spread through person-to-person contact; however, endemic diseases within these countries can potentially spread through person-to-person contact or fecally contaminated water and foods. Vertical transmission of HEV from infected mother to fetus causes high fetal and perinatal mortality. Other means of transmission, such as zoonotic transmission, can fluctuate depending upon the region and strain of the virus. For instance, zoonotic transmission can sometimes play an insignificant role in human infections, such as in India, where human and pig HEV infections are unrelated. However, recently China and Southeast Asia have experienced a zoonotic spread of HEV-4 from pigs to humans and this has become the dominant mode of transmission of hepatitis E in eastern China. Zoonotic HEV infections in humans occur by eating undercooked pig flesh, raw liver, and sausages; through vocational contact; or via pig slurry, which leads to environmental contamination of agricultural products and seafood. Lastly, blood transfusion-associated HEV infections occur in many countries and screening of donors for HEV RNA is currently under serious consideration. To summarize, HEV genotypes 1 and 2 cause epidemic and endemic diseases in resource poor countries, primarily spreading through contaminated drinking water. HEV genotypes 3 and 4 on the other hand, cause autochthonous infections in developed, and many developing countries, by means of a unique zoonotic food-borne transmission.
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46
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Khuroo MS, Khuroo MS, Khuroo NS. Hepatitis E: Discovery, global impact, control and cure. World J Gastroenterol 2016; 22:7030-7045. [PMID: 27610014 PMCID: PMC4988308 DOI: 10.3748/wjg.v22.i31.7030] [Citation(s) in RCA: 112] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2016] [Revised: 06/10/2016] [Accepted: 07/06/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E was identified as an epidemic of non-A, non-B hepatitis from Kashmir, India in 1978. Hepatitis E virus (HEV), the etiological agent is the sole member of family Hepeviridae. The virus has marked heterogeneity and infects many animals like bats, camel, chicken, deer, boar, mongoose, pigs, rats, rabbit and cutthroat trout. Hepatitis E is a disease with a major global impact and has two distinct epidemiological patterns. Hepatitis E is an imperative health issue in developing nations, transmitted through sullied water and happens most every now in young adults. The disease is particularly severe during pregnancy and in people with underlying liver cirrhosis. Autochthonous hepatitis E is increasingly recognized in developed countries. The virus infects domestic pigs, wild boar and Sika deer in these countries. HEV infections in humans occur by eating the undercooked game flesh, raw liver from supermarkets and Figatelli sausages. Blood transfusion-associated HEV infections occur in many countries and screening of donors for HEV RNA is under consideration. Hepatitis E causes a number of extrahepatic diseases, including a wide spectrum of neurological syndromes. HEV genotype 3 causes prolonged viremia, chronic hepatitis, liver fibrosis and cirrhosis in organ transplant patients. The virus is amenable to ribavirin monotherapy and most patients clear the virus in a few weeks. Hepatitis E vaccine -239, marketed in China, has shown high efficacy with sustained protection for over four years.
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O'Riordan J, Boland F, Williams P, Donnellan J, Hogema BM, Ijaz S, Murphy WG. Hepatitis E virus infection in the Irish blood donor population. Transfusion 2016; 56:2868-2876. [DOI: 10.1111/trf.13757] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Revised: 06/23/2016] [Accepted: 06/23/2016] [Indexed: 12/17/2022]
Affiliation(s)
- Joan O'Riordan
- Irish Blood Transfusion Service, National Blood Centre; Dublin Ireland
| | - Fiona Boland
- Irish Blood Transfusion Service, National Blood Centre; Dublin Ireland
| | - Padraig Williams
- Irish Blood Transfusion Service, National Blood Centre; Dublin Ireland
| | - Joe Donnellan
- Irish Blood Transfusion Service, National Blood Centre; Dublin Ireland
| | - Boris M. Hogema
- Departments of Blood-borne Infections and Virology; Sanquin Research and Diagnostic Services; Amsterdam the Netherlands
| | - Samreen Ijaz
- Blood Borne Virus Unit, Virus Reference Department; National Infection Service, Public Health England; London UK
| | - William G. Murphy
- Irish Blood Transfusion Service, National Blood Centre; Dublin Ireland
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Hartl J, Otto B, Madden RG, Webb G, Woolson KL, Kriston L, Vettorazzi E, Lohse AW, Dalton HR, Pischke S. Hepatitis E Seroprevalence in Europe: A Meta-Analysis. Viruses 2016; 8:v8080211. [PMID: 27509518 PMCID: PMC4997573 DOI: 10.3390/v8080211] [Citation(s) in RCA: 168] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Revised: 07/12/2016] [Accepted: 07/25/2016] [Indexed: 02/06/2023] Open
Abstract
UNLABELLED There have been large numbers of studies on anti-HEV IgG seroprevalence in Europe, however, the results of these studies have produced high variability of seroprevalence rates, making interpretation increasingly problematic. Therefore, the aim of this study was to develop a clearer understanding of anti-HEV IgG seroprevalence in Europe and identify risk groups for HEV exposure by a meta-analysis of published studies. METHODS All European HEV-seroprevalence studies from 2003 to 2015 were reviewed. Data were stratified by assay, geographical location, and patient cohort (general population, patients with HIV, solid-organ transplant recipients, chronic liver disease patients, and individuals in contact with swine/wild animals). Data were pooled using a mixed-effects model. RESULTS Four hundred thirty-two studies were initially identified, of which 73 studies were included in the analysis. Seroprevalence estimates ranged from 0.6% to 52.5%, increased with age, but were unrelated to gender. General population seroprevalence varied depending on assays: Wantai (WT): 17%, Mikrogen (MG): 10%, MP-diagnostics (MP): 7%, DiaPro: 4%, Abbott 2%. The WT assay reported significantly higher seroprevalence rates across all cohorts (p < 0.001). Individuals in contact with swine/wild animals had significantly higher seroprevalence rates than the general population, irrespective of assay (p < 0.0001). There was no difference between any other cohorts. The highest seroprevalence was observed in France (WT: 32%, MP: 16%) the lowest in Italy (WT: 7.5%, MP 0.9%). Seroprevalence varied between and within countries. The observed heterogeneity was attributed to geographical region (23%), assay employed (23%) and study cohort (7%). CONCLUSION Seroprevalcence rates primarily depend on the seroassy that is used, followed by the geographical region and study cohort. Seroprevalence is higher in individuals exposed to swine and/or wild animals, and increases with age.
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Affiliation(s)
- Johannes Hartl
- First Medical Department, University Medical Center Hamburg-Eppendorf, University Hospital Hamburg Eppendorf (UKE), 20246, Hamburg, Germany.
| | - Benjamin Otto
- First Medical Department, University Medical Center Hamburg-Eppendorf, University Hospital Hamburg Eppendorf (UKE), 20246, Hamburg, Germany.
| | - Richie Guy Madden
- Royal Cornwall Hospital Trust and European Centre for Environment and Human Health, University of Exeter, Truro TR1 3HD, UK.
| | - Glynn Webb
- Royal Cornwall Hospital Trust and European Centre for Environment and Human Health, University of Exeter, Truro TR1 3HD, UK.
| | - Kathy Louise Woolson
- Royal Cornwall Hospital Trust and European Centre for Environment and Human Health, University of Exeter, Truro TR1 3HD, UK.
| | - Levente Kriston
- Department of Medical Psychology, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
| | - Eik Vettorazzi
- Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
| | - Ansgar W Lohse
- First Medical Department, University Medical Center Hamburg-Eppendorf, University Hospital Hamburg Eppendorf (UKE), 20246, Hamburg, Germany.
| | - Harry Richard Dalton
- Royal Cornwall Hospital Trust and European Centre for Environment and Human Health, University of Exeter, Truro TR1 3HD, UK.
| | - Sven Pischke
- First Medical Department, University Medical Center Hamburg-Eppendorf, University Hospital Hamburg Eppendorf (UKE), 20246, Hamburg, Germany.
- Royal Cornwall Hospital Trust and European Centre for Environment and Human Health, University of Exeter, Truro TR1 3HD, UK.
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Lucarelli C, Spada E, Taliani G, Chionne P, Madonna E, Marcantonio C, Pezzotti P, Bruni R, La Rosa G, Pisani G, Dell'Orso L, Ragone K, Tomei C, Ciccaglione AR. High prevalence of anti-hepatitis E virus antibodies among blood donors in central Italy, February to March 2014. Euro Surveill 2016; 21:30299. [DOI: 10.2807/1560-7917.es.2016.21.30.30299] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2015] [Accepted: 02/25/2016] [Indexed: 12/23/2022] Open
Abstract
Prevalence of anti-hepatitis E virus (HEV) antibodies is highly variable in developed countries, which seems partly due to differences in assay sensitivity. Using validated sensitive assays, we tested 313 blood donors attending a hospital transfusion unit in central Italy in January and February 2014 for anti-HEV IgG and IgM and HEV RNA. Data on HEV exposure were collected from all donors. Overall anti-HEV IgG prevalence was 49% (153/313). Eating raw dried pig-liver sausage was the only independent predictor of HEV infection (adjusted prevalence rate ratio = 2.14; 95% confidence interval: 1.23–3.74). Three donors were positive for either anti-HEV IgM (n = 2; 0.6%) or HEV RNA (n = 2; 0.6%); they were completely asymptomatic, without alanine aminotransferase (ALT) abnormalities. Of the two HEV RNA-positive donors (both harbouring genotype 3), one was anti-HEV IgG- and IgM-positive, the other was anti-HEV IgG- and IgM-negative. The third donor was positive for anti-HEV IgG and IgM but HEV RNA-negative. HEV infection is therefore hyperendemic among blood donors (80% men 18–64 years-old) from central Italy and associated with local dietary habits. Nearly 1% of donors have acute or recent infection, implying potential transmission to blood recipients. Neither ALT nor anti-HEV IgM testing seems useful to prevent transfusion-transmitted HEV infection.
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Affiliation(s)
- Claudia Lucarelli
- European Program for Public Health Microbiology Training, European Centre for Disease Prevention and Control, Stockholm, Sweden
- These authors contributed equally to this work
- Department of Infectious Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Enea Spada
- These authors contributed equally to this work
- Department of Infectious Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Gloria Taliani
- Department of Infectious and Tropical Diseases, University of Rome La Sapienza, Rome, Italy
| | - Paola Chionne
- Department of Infectious Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Elisabetta Madonna
- Department of Infectious Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Cinzia Marcantonio
- Department of Infectious Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Patrizio Pezzotti
- Department of Infectious Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Roberto Bruni
- Department of Infectious Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Giuseppina La Rosa
- Environment and Primary Prevention Department, Istituto Superiore di Sanità, Rome, Italy
| | - Giulio Pisani
- National Centre for Immunobiologicals Research and Evaluation, Istituto Superiore di Sanità, Rome, Italy
| | - Luigi Dell'Orso
- Immunohematology and Blood Transfusion Unit, San Salvatore Hospital, L'Aquila, Italy
| | - Katia Ragone
- National Centre for Immunobiologicals Research and Evaluation, Istituto Superiore di Sanità, Rome, Italy
| | - Carla Tomei
- Blood Collection Centre, Regional Committee of the Italian Red Cross of Abruzzo, L’Aquila, Italy
| | - Anna Rita Ciccaglione
- Department of Infectious Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy
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Huang H, Xu C, Zhou X, Liu L, Dai Y, Xu B, Yang J, Chen T, Hu Y, Zhou YH. Incidence and seroprevalence of hepatitis E virus infection in pregnant women infected with hepatitis B virus and antibody placental transfer in infants. J Clin Virol 2016; 82:84-88. [PMID: 27467017 DOI: 10.1016/j.jcv.2016.07.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Revised: 07/15/2016] [Accepted: 07/20/2016] [Indexed: 01/15/2023]
Abstract
BACKGROUND Hepatitis E has poor outcomes in pregnant women. Superinfection of hepatitis E virus (HEV) in patients infected with hepatitis B virus (HBV) may worsen liver disease. OBJECTIVES To estimate the incidence and seroprevalence of HEV infection among HBV-infected pregnant women, to investigate the transplacental transfer of maternal anti-HEV IgG, and to compare the maternal and neonatal outcomes in anti-HEV positive and negative pregnant women. STUDY DESIGN Totally 391 HBV-infected pregnant women were recruited from April 2012 to October 2014. Paired mothers and infants were followed up at an average 9.8 months postpartum. Anti-HEV IgG and IgM were tested by ELISA. RESULTS Of the pregnant women, none was anti-HEV IgM positive and 42 (10.7%) were IgG positive. At the follow-up, 3 seronegative women converted to anti-HEV IgG positive, with an estimated incidence of 17 per 1000 person-years. No significant differences of gestational age, preterm birth rate, Apgar score and birthweight were observed between newborns of anti-HEV IgG positive and negative mothers. Of the 42 neonates born to anti-HEV IgG positive mothers, 38 (90.5%) had anti-HEV IgG in their cord blood. The neonatal and maternal anti-HEV IgG levels were positively correlated (r=0.827, p<0.05). All infants were negative for both anti-HEV IgM and IgG at the follow-up. CONCLUSIONS HBV-infected pregnant women rarely have novel HEV infection during late pregnancy in Jiangsu, China. Maternal anti-HEV IgG efficiently transfers into the fetuses, and disappears in infants before 10 months old.
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Affiliation(s)
- Hongyu Huang
- Department of Experimental Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China; Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing 210008, China.
| | - Chenyu Xu
- Department of Obstetrics and Gynecology, Zhenjiang Fourth People's Hospital, Zhenjiang 212000, China.
| | - Xuan Zhou
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
| | - Lanhua Liu
- Department of Obstetrics and Gynecology, Taixing People's Hospital, Taizhou 225400, China.
| | - Yimin Dai
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
| | - Biao Xu
- Department of Obstetrics and Gynecology, Taixing People's Hospital, Taizhou 225400, China.
| | - Jishi Yang
- Department of Obstetrics and Gynecology, Taixing People's Hospital, Taizhou 225400, China.
| | - Tingmei Chen
- Department of Obstetrics and Gynecology, Zhenjiang Fourth People's Hospital, Zhenjiang 212000, China.
| | - Yali Hu
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
| | - Yi-Hua Zhou
- Department of Experimental Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China; Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing 210008, China; Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
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