|
1
|
da Silva-Sampaio JP, Sinimbu RB, Marques JT, Neto AFDO, Villar LM. Seroprevalence of hepatitis E virus infection in blood donors from Piauí State, Northeast Brazil. Braz J Infect Dis 2025; 29:104466. [PMID: 39602852 PMCID: PMC11626794 DOI: 10.1016/j.bjid.2024.104466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 09/27/2024] [Accepted: 10/30/2024] [Indexed: 11/29/2024] Open
Abstract
A retrospective and cross-sectional study was carried out on blood donors from Piauí State located at Northeastern Brazil to evaluate the prevalence of Hepatitis E Virus (HEV) infection. Serum samples were tested for anti-HEV IgG and IgM using electrochemiluminescence and HEV RNA was tested using real time PCR. A total of 890 individuals were included with median age of 33.4 years and most of them were male and lived at Mid-Northern region of the State. Prevalences of anti-HEV IgG and IgM were 1.35 % and 0.11 %, respectively. None HEV-RNA was detected. This study demonstrated low prevalence of HEV infection in blood donors in this region.
Collapse
Affiliation(s)
- João Paulo da Silva-Sampaio
- Fiocruz Piauí, Teresina, PI, Brazil; Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Hepatites Virais, Rio de Janeiro, RJ, Brazil
| | - Raniela Borges Sinimbu
- Fiocruz Piauí, Teresina, PI, Brazil; Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Hepatites Virais, Rio de Janeiro, RJ, Brazil
| | - Julia Trece Marques
- Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Hepatites Virais, Rio de Janeiro, RJ, Brazil
| | | | - Livia Melo Villar
- Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Hepatites Virais, Rio de Janeiro, RJ, Brazil.
| |
Collapse
|
|
2
|
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.
Collapse
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
| |
Collapse
|
|
3
|
Singson S, Shastry S, Sudheesh N, Chawla K, Madiyal M, Kandasamy D, Mukhopadhyay C. Assessment of Hepatitis E virus transmission risks: a comprehensive review of cases among blood transfusion recipients and blood donors. Infect Ecol Epidemiol 2024; 14:2406834. [PMID: 39421644 PMCID: PMC11486055 DOI: 10.1080/20008686.2024.2406834] [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: 02/18/2024] [Accepted: 09/17/2024] [Indexed: 10/19/2024] Open
Abstract
Background Hepatitis E Virus is a major cause of acute and fulminant hepatitis, particularly in developing countries. While the virus is commonly spread through the fecal-oral route, numerous cases of transfusion transmitted Hepatitis E Virus (TT-HEV) have been reported, raising concerns about its transmission via blood transfusions, especially in industrialized countries. The high prevalence of antibodies and viremia among asymptomatic blood donors further heightens the risk of transfusion-related transmission. However, there is still debate about the best strategy to minimize TT-HEV. Objective The review was conducted to Summarize the literature on TT-HEV infection cases and the prevalence of HEV among blood donors. Methods The databases PubMed, Scopus, Web of Science, Embase, and CINAHL were searched for relevant studies from 2000 to 2022.Serological and molecular screening data of HEV in blood donors were used to gather prevalence and incidence rates.TT-HEV cases were reviewed by examining evidence of HEV infection before and after transfusion. Results A total of 121 manuscripts reports the prevalence and incidence of HEV among blood donors and cases of TT-HEV. Twenty-six articles reported confirmed cases of TT-HEV and 101 articles reported on HEV prevalence or incidence among blood donors. Conclusion TT-HEV transmission through blood products is a real concern, especially for immunocompromised patients.The risk and severity of infection could vary between immunocompetent and immunosuppressed patients.To increase transfusion safety, the evaluation recommends HEV screening protocols, especially in endemic region.
Collapse
Affiliation(s)
- Sangthang Singson
- Department of Immunohematology and Blood Transfusion, Kasturba Medical College, Manipal. Manipal Academy of Higher Education, Manipal, Karnatka, India
| | - Shamee Shastry
- Department of Immunohematology and Blood Transfusion, Kasturba Medical College, Manipal. Manipal Academy of Higher Education, Manipal, Karnatka, India
| | - N. Sudheesh
- Department of Microbiology, Kasturba Medical College, Manipal. Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Kiran Chawla
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, India
| | - Mridula Madiyal
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, India
| | - Dhivya Kandasamy
- Department of Immunohematology and Blood Transfusion, Kasturba Medical College, Manipal. Manipal Academy of Higher Education, Manipal, Karnatka, India
| | - Chiranjay Mukhopadhyay
- Department of Microbiology, Kasturba Medical College, Manipal. Manipal Academy of Higher Education, Manipal, Karnataka, India
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, India
| |
Collapse
|
|
4
|
Bienz M, Renaud C, Liu JR, Wong P, Pelletier P. Hepatitis E Virus in the United States and Canada: Is It Time to Consider Blood Donation Screening? Transfus Med Rev 2024; 38:150835. [PMID: 39059853 DOI: 10.1016/j.tmrv.2024.150835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 04/14/2024] [Accepted: 04/17/2024] [Indexed: 07/28/2024]
Abstract
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the world and can lead to severe complications in immunocompromised individuals. HEV is primarily transmitted through eating pork, which has led to an increased in anti-HEV IgG seropositivity in the general population of Europe in particular. However, it can also be transmitted intravenously, such as through transfusions. The growing evidence of HEV contamination of blood products and documented cases of transmission have given rise to practice changes and blood product screening of HEV in many European countries. This review covers the abundant European literature and focuses on the most recent data pertaining to the prevalence of HEV RNA positivity and IgG seropositivity in the North American general population and in blood products from Canada and the United States. Currently, Health Canada and the Food and Drug Administration do not require testing of HEV in blood products. For this reason, awareness among blood product prescribers about the possibility of HEV transmission through blood products is crucial. However, we also demonstrate that the province of Quebec has a prevalence of anti-HEV and HEV RNA positivity similar to some European countries. In light of this, we believe that HEV RNA blood donation screening be reevaluated with the availability of more cost-effective assays.
Collapse
Affiliation(s)
- Marc Bienz
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Division of Hematology, Department of Medicine, McGill University, Montreal, Quebec, Canada.
| | - Christian Renaud
- Department of Microbiology, Infectious diseases, and Immunology, Université de Montréal, Montreal, Quebec, Canada; Medical Affairs and Innovation, Héma-Québec, Montreal, Quebec, Canada
| | - Jia Ru Liu
- Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada
| | - Philip Wong
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Patricia Pelletier
- Division of Hematology, Department of Medicine, McGill University, Montreal, Quebec, Canada
| |
Collapse
|
|
5
|
Niederhauser C, Gowland P, Widmer N, Amar EL Dusouqui S, Mattle-Greminger M, Gottschalk J, Frey BM. Prevalence of Acute Hepatitis E Virus Infections in Swiss Blood Donors 2018-2020. Viruses 2024; 16:744. [PMID: 38793625 PMCID: PMC11125967 DOI: 10.3390/v16050744] [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: 03/14/2024] [Revised: 04/26/2024] [Accepted: 05/06/2024] [Indexed: 05/26/2024] Open
Abstract
INTRODUCTION Hepatitis E virus (HEV) genotype 3 is the major cause of acute viral hepatitis in several European countries. It is acquired mainly by ingesting contaminated pork, but has also been reported to be transmitted through blood transfusion. Although most HEV infections, including those via blood products, are usually self-limiting, they may become chronic in immunocompromised persons. It is thus essential to identify HEV-infected blood donations to prevent transmission to vulnerable recipients. AIMS Prior to the decision whether to introduce HEV RNA screening for all Swiss blood donations, a 2-year nationwide prevalence study was conducted. METHODS All blood donations were screened in pools of 12-24 samples at five regional blood donation services, and HEV RNA-positive pools were subsequently resolved to the individual donation index donation (X). The viral load, HEV IgG and IgM serology, and HEV genotype were determined. Follow-up investigations were conducted on future control donations (X + 1) and previous archived donations of the donor (X - 1) where available. RESULTS Between October 2018 and September 2020, 541,349 blood donations were screened and 125 confirmed positive donations were identified (prevalence 1:4331 donations). At the time of blood donation, the HEV RNA-positive individuals were symptom-free. The median viral load was 554 IU/mL (range: 2.01-2,500,000 IU/mL). Men (88; 70%) were more frequently infected than women (37; 30%), as compared with the sex distribution in the Swiss donor population (57% male/43% female, p < 0.01). Of the 106 genotyped cases (85%), all belonged to genotype 3. Two HEV sub-genotypes predominated; 3h3 (formerly 3s) and 3c. The remaining sub-genotypes are all known to circulate in Europe. Five 3ra genotypes were identified, this being a variant associated with rabbits. In total, 85 (68%) X donations were negative for HEV IgM and IgG. The remaining 40 (32%) were positive for HEV IgG and/or IgM, and consistent with an active infection. We found no markers of previous HEV in 87 of the 89 available and analyzed archive samples (X - 1). Two donors were HEV IgG-positive in the X - 1 donation suggesting insufficient immunity to prevent HEV reinfection. Time of collection of the 90 (72%) analyzed X + 1 donations varied between 2.9 and 101.9 weeks (median of 35 weeks) after X donation. As expected, none of those tested were positive for HEV RNA. Most donors (89; 99%) were positive for anti-HEV lgG/lgM (i.e., seroconversion). HEV lgM-positivity (23; 26%) indicates an often-long persistence of lgM antibodies post-HEV infection. CONCLUSION The data collected during the first year of the study provided the basis for the decision to establish mandatory HEV RNA universal screening of all Swiss blood donations in minipools, a vital step in providing safer blood for all recipients, especially those who are immunosuppressed.
Collapse
Affiliation(s)
- Christoph Niederhauser
- Interregional Blood Transfusion SRC, 3008 Berne, Switzerland; (P.G.)
- Institute of Infectious Disease, University of Berne, 3008 Berne, Switzerland
| | - Peter Gowland
- Interregional Blood Transfusion SRC, 3008 Berne, Switzerland; (P.G.)
| | - Nadja Widmer
- Interregional Blood Transfusion SRC, 3008 Berne, Switzerland; (P.G.)
| | | | - Maja Mattle-Greminger
- Regional Blood Transfusion SRC, 8952 Schlieren, Switzerland; (M.M.-G.); (J.G.); (B.M.F.)
| | - Jochen Gottschalk
- Regional Blood Transfusion SRC, 8952 Schlieren, Switzerland; (M.M.-G.); (J.G.); (B.M.F.)
| | - Beat M. Frey
- Regional Blood Transfusion SRC, 8952 Schlieren, Switzerland; (M.M.-G.); (J.G.); (B.M.F.)
| |
Collapse
|
|
6
|
Luo Q, Chen J, Zhang Y, Xu W, Liu Y, Xie C, Peng L. Viral hepatitis E: Clinical manifestations, treatment, and prevention. LIVER RESEARCH 2024; 8:11-21. [PMID: 39959034 PMCID: PMC11771268 DOI: 10.1016/j.livres.2024.01.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 11/17/2023] [Accepted: 01/03/2024] [Indexed: 02/18/2025]
Abstract
Hepatitis E is a globally distributed infection that varies in seroprevalence between developed and developing regions. In the less developed regions of Asia and Africa, a high seropositivity rate has been reported for hepatitis E virus (HEV) antibodies. Although acute hepatitis E is often self-limited and has a favorable prognosis, some populations experience severe manifestations, which may progress to liver failure. Moreover, some immunocompromised patients are at risk of developing chronic HEV infection and cirrhosis. Proactive screening, reducing misdiagnosis, improving patient management, timely antiviral therapy for severe and chronic cases, and vaccination of high-risk groups are important measures to reduce the morbidity of hepatitis E. This review focused on the clinical presentation, management, and prevention of hepatitis E.
Collapse
Affiliation(s)
- Qiumin Luo
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Jia Chen
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yeqiong Zhang
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Wenxiong Xu
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Ying Liu
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Chan Xie
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Liang Peng
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| |
Collapse
|
|
7
|
Cardoso M, Ragan I, Hartson L, Goodrich RP. Emerging Pathogen Threats in Transfusion Medicine: Improving Safety and Confidence with Pathogen Reduction Technologies. Pathogens 2023; 12:911. [PMID: 37513758 PMCID: PMC10383627 DOI: 10.3390/pathogens12070911] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 06/30/2023] [Accepted: 07/02/2023] [Indexed: 07/30/2023] Open
Abstract
Emerging infectious disease threats are becoming more frequent due to various social, political, and geographical pressures, including increased human-animal contact, global trade, transportation, and changing climate conditions. Since blood products for transfusion are derived from donated blood from the general population, emerging agents spread by blood contact or the transfusion of blood products are also a potential risk. Blood transfusions are essential in treating patients with anemia, blood loss, and other medical conditions. However, these lifesaving procedures can contribute to infectious disease transmission, particularly to vulnerable populations. New methods have been implemented on a global basis for the prevention of transfusion transmissions via plasma, platelets, and whole blood products. Implementing proactive pathogen reduction methods may reduce the likelihood of disease transmission via blood transfusions, even for newly emerging agents whose transmissibility and susceptibility are still being evaluated as they emerge. In this review, we consider the Mirasol PRT system for blood safety, which is based on a photochemical method involving riboflavin and UV light. We provide examples of how emerging threats, such as Ebola, SARS-CoV-2, hepatitis E, mpox and other agents, have been evaluated in real time regarding effectiveness of this method in reducing the likelihood of disease transmission via transfusions.
Collapse
Affiliation(s)
- Marcia Cardoso
- Terumo BCT, Inc., TERUMO Böood and Cell Technologies, Zaventem, 41 1930 Brussels, Belgium
| | - Izabela Ragan
- Infectious Disease Research Center, Department of Biomedical Science, Colorado State University, Fort Collins, CO 80521, USA
| | - Lindsay Hartson
- Infectious Disease Research Center, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80521, USA
| | - Raymond P Goodrich
- Infectious Disease Research Center, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80521, USA
| |
Collapse
|
|
8
|
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.
Collapse
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
| | | | | |
Collapse
|
|
9
|
Laperche S, Maugard C, Lhomme S, Lecam S, Ricard C, Dupont I, Richard P, Tiberghien P, Abravanel F, Morel P, Izopet J, Gallian P. Seven years (2015-2021) of blood donor screening for HEV-RNA in France: lessons and perspectives. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2023; 21:110-118. [PMID: 35969132 PMCID: PMC10072995 DOI: 10.2450/2022.0052-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 07/05/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND The French health authorities are considering expanding the current selective hepatitis E virus (HEV)-RNA testing procedure to include all donations in order to further reduce transfusion-transmitted HEV infection. Data obtained from blood donors (BDs) tested for HEV-RNA between 2015 and 2021 were used to assess the most efficient nucleic acid testing (NAT) strategy. MATERIALS AND METHODS Viral loads (VLs) and the plasma volume of blood components, as well as an HEV-RNA dose of 3.85 log IU as the infectious threshold and an assay with a 95% limit of detection (LOD) at 17 IU/mL, were used to assess the proportion of: (i) HEV-RNA-positive BDs that would remain undetected; and (ii) blood components associated with these undetected BDs with an HEV-RNA dose >3.85 log IU, considering 4 NAT options (Individual testing [ID], MP-6, MP-12, and MP-24). RESULTS Of the 510,118 BDs collected during the study period, 510 (0.10%) were HEV-RNA-positive. Based on measurable VLs available in 388 cases, 1%, 15.2%, 21.8%, and 32.6% of BDs would theoretically pass undetected due to a VL below the LOD of ID, MP-6, MP-12, and MP-24 testing, respectively. All BDs associated with a potentially infectious blood component would be detected with ID-NAT while 13% of them would be undetected with MP-6, 19.6% with MP-12, and 30.4% with MP-24 depending on the plasma volume. No red blood cell (RBC) components with an HEV-RNA dose >3.85 log IU would enter the blood supply, regardless of the NAT strategy used. DISCUSSION A highly sensitive ID-NAT would ensure maximum safety. However, an MP-based strategy can be considered given that: (i) the risk of transmission is closely related to the plasma volume of blood components; (ii) RBC are the most commonly transfused components and have a low plasma content; and (iii) HEV-RNA doses transmitting infection exceed 4 log IU. To minimise the potential risk associated with apheresis platelet components and fresh frozen plasma, less than 12 donations should be pooled using an NAT assay with a LOD of approximately 20 IU/mL.
Collapse
Affiliation(s)
- Syria Laperche
- Etablissement Français du Sang, La Plaine St-Denis, France
- Unité des Virus Émergents (UVE) Aix-Marseille-IRD 190-Inserm 1207-Marseille, France
| | - Claude Maugard
- Etablissement Français du Sang Occitanie, Montpellier, France
| | - Sébastien Lhomme
- Infinity, Université Toulouse III, CNRS, INSERM, Toulouse, France
- Laboratoire de Virologie, Hôpital Purpan, CHU, Toulouse, France
| | - Sophie Lecam
- Etablissement Français du Sang, La Plaine St-Denis, France
- Etablissement Français du Sang, Centre Pays de la Loire, Angers, France
| | - Céline Ricard
- Etablissement Français du Sang Hauts de France Normandie, Loos, France
| | | | | | - Pierre Tiberghien
- Etablissement Français du Sang, La Plaine St-Denis, France
- UMR 1098 RIGHT INSERM Université de Franche-Comté Etablissement Français du Sang, Besançon, France
| | - Florence Abravanel
- Infinity, Université Toulouse III, CNRS, INSERM, Toulouse, France
- Laboratoire de Virologie, Hôpital Purpan, CHU, Toulouse, France
| | - Pascal Morel
- Etablissement Français du Sang, La Plaine St-Denis, France
- UMR 1098 RIGHT INSERM Université de Franche-Comté Etablissement Français du Sang, Besançon, France
| | - Jacques Izopet
- Infinity, Université Toulouse III, CNRS, INSERM, Toulouse, France
- Laboratoire de Virologie, Hôpital Purpan, CHU, Toulouse, France
| | - Pierre Gallian
- Etablissement Français du Sang, La Plaine St-Denis, France
- Unité des Virus Émergents (UVE) Aix-Marseille-IRD 190-Inserm 1207-Marseille, France
| |
Collapse
|
|
10
|
Pitman JP, Payrat JM, Park MS, Liu K, Corash L, Benjamin RJ. Longitudinal analysis of annual national hemovigilance data to assess pathogen reduced platelet transfusion trends during conversion to routine universal clinical use and 7-day storage. Transfusion 2023; 63:711-723. [PMID: 36802055 DOI: 10.1111/trf.17285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 01/27/2023] [Accepted: 01/28/2023] [Indexed: 02/20/2023]
Abstract
BACKGROUND France converted to universal pathogen reduced (PR; amotosalen/UVA) platelets in 2017 and extended platelet component (PC) shelf-life from 5- to 7-days in 2018 and 2019. Annual national hemovigilance (HV) reports characterized longitudinal PC utilization and safety over 11 years, including several years prior to PR adoption as the national standard of care. METHODS Data were extracted from published annual HV reports. Apheresis and pooled buffy coat [BC] PC use was compared. Transfusion reactions (TRs) were stratified by type, severity, and causality. Trends were assessed for three periods: Baseline (2010-14; ~7% PR), Period 1 ([P1] 2015-17; 8%-21% PR), and Period 2 ([P2] 2018-20; 100% PR). RESULTS PC use increased by 19.1% between 2010 and 2020. Pooled BC PC production increased from 38.8% to 68.2% of total PCs. Annual changes in PCs issued averaged 2.4% per year at baseline, -0.02% (P1) and 2.8% (P2). The increase in P2 coincided with a reduction in the target platelet dose and extension to 7-day storage. Allergic reactions, alloimmunization, febrile non-hemolytic TRs, immunologic incompatibility, and ineffective transfusions accounted for >90% of TRs. Overall, TR incidence per 100,000 PCs issued declined from 527.9 (2010) to 345.7 (2020). Severe TR rates declined 34.8% between P1-P2. Forty-six transfusion-transmitted bacterial infections (TTBI) were associated with conventional PCs during baseline and P1. No TTBI were associated with amotosalen/UVA PCs. Infections with Hepatitis E (HEV) a non-enveloped virus resistant to PR, were reported in all periods. DISCUSSION Longitudinal HV analysis demonstrated stable PC utilization trends with reduced patient risk during conversion to universal 7-day amotosalen/UVA PCs.
Collapse
Affiliation(s)
- John P Pitman
- Scientific and Medical Affairs, Cerus Corporation, Concord, California, USA
| | | | - Min-Sun Park
- Biostatistics and Data Management, Cerus Corporation, Concord, California, USA
| | - Kathy Liu
- Biostatistics and Data Management, Cerus Corporation, Concord, California, USA
| | - Laurence Corash
- Scientific and Medical Affairs, Cerus Corporation, Concord, California, USA
| | - Richard J Benjamin
- Scientific and Medical Affairs, Cerus Corporation, Concord, California, USA
| |
Collapse
|
|
11
|
Zhang J, Zheng Z, Xia N. Prophylactic Hepatitis E Vaccine. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:227-245. [PMID: 37223870 DOI: 10.1007/978-981-99-1304-6_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
The hepatitis E has been increasingly recognized as an underestimated global disease burden in recent years. Subpopulations with more serious infection associated damage or death include pregnant women, patients with basic liver diseases, and elderly persons. Vaccine would be the most effective means for prevention of HEV infection. The lack of an efficient cell culture system for HEV makes the development of classic inactive or attenuated vaccine infeasible. Hence, the recombinant vaccine approaches are explored deeply. The neutralizing sites are located almost exclusively in the capsid protein, pORF2, of the virion. Based on pORF2, many vaccine candidates showed potential of protecting primate animals, two of them were tested in human and evidenced to be well-tolerated in adults and highly efficacious in preventing hepatitis E. The world's first hepatitis E vaccine, Hecolin® (HEV 239 vaccine), was licensed in China and launched in 2012.
Collapse
Affiliation(s)
- 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, China.
| | - Zizheng Zheng
- 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, China
| | - 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, China
| |
Collapse
|
|
12
|
Liu X, Qi S, Yin X. Morphogenesis of Hepatitis E Virus. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:159-169. [PMID: 37223865 DOI: 10.1007/978-981-99-1304-6_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Hepatitis E virus, a leading cause of acute hepatitis worldwide, has been recognized as non-enveloped virus since its discovery in the 1980s. However, the recent identification of lipid membrane-associated form termed as "quasi-enveloped" HEV has changed this long-held notion. Both naked HEV and quasi-enveloped HEV play important roles in the pathogenesis of hepatitis E. However, the biogenesis and the mechanisms underlying the composition, biogenesis regulation, and functions of the novel quasi-enveloped virions remain enigmatic. In this chapter, we highlight the most recent discoveries on the dual life cycle of these two different types of virions, and further discuss the implication of the quasi-envelopment in our understanding of the molecular biology of HEV.
Collapse
Affiliation(s)
- Xing Liu
- State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
| | - Shuhui Qi
- State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
| | - Xin Yin
- State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
| |
Collapse
|
|
13
|
Accelerating the Laboratory Testing Capacity through Saliva Pooling Prior to Direct RT-qPCR for SARS-CoV-2 Detection. Diagnostics (Basel) 2022; 12:diagnostics12123160. [PMID: 36553167 PMCID: PMC9777453 DOI: 10.3390/diagnostics12123160] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 12/04/2022] [Accepted: 12/09/2022] [Indexed: 12/23/2022] Open
Abstract
The testing capacity of the laboratory is paramount for better control of the pandemic caused by SARS-CoV-2. The pooling method is promising to increase testing capacity, and the use of direct NAAT-based detection of SARS-CoV-2 on a non-invasive specimen such as saliva will ultimately accelerate the testing capacity. This study aims to validate the pooling-of-four method to quadruple the testing capacity using RNA-extraction-free saliva specimens. In addition, we intend to investigate the preferable stage of pooling, including pre- or post-heating. The compatibility of this approach was also tested on five commercial kits. Saliva specimens stored at -80 °C for several months were proven viable and were used for various tests in this study. Our findings revealed that pooling-of-four specimens had an overall agreement rate of 98.18% with their individual testing. Moreover, we proved that the pooling procedure could be conducted either pre- or post-heating, with no discordance and no significant difference in Ct values generated. When compared to other commercial detection kits, it demonstrated an overall agreement greater than 85%, which exhibits broad compatibility and ensures easy adaptability in clinical settings. This method has been proven reliable and increases the testing capacity up to fourfold.
Collapse
|
|
14
|
Pillonel J, Maugard C, Sommen C, Figoni J, Pierre C, LeCam S, Richard P, Morel P, Gallian P, Laperche S. Risk of a blood donation contaminated with hepatitis E virus entering the blood supply before the implementation of universal RNA screening in France. Vox Sang 2022; 117:1411-1414. [PMID: 36394899 DOI: 10.1111/vox.13375] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 10/13/2022] [Accepted: 10/13/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND AND OBJECTIVES The risk of a blood donation contaminated with hepatitis E virus (HEV) entering the blood supply before introducing universal HEV-RNA screening in France was estimated to assess the benefit of such a measure. MATERIALS AND METHODS The results of selective HEV nucleic acid testing (HEV-NAT) performed in mini pool of six plasma donations between 2018 and 2020 were extrapolated to the whole blood donor (BD) population after adjustment on three variables: regional establishment, sex and age group. RESULTS Among the 246,285 plasma donations collected from 172,635 BDs tested for HEV-RNA, 248 (10.1/10,000) were positive. The extrapolation to all BDs led to an estimated rate of 5.9/10,000 donations (95% confidence interval [CI]: 4.5-7.4) which would be positive to HEV-RNA and a prevalence of 9.9/10,000 BDs (95% CI: 7.5-12.3). This prevalence was 4.4 times higher in males than females (16.8/10,000 vs. 3.8/10,000, p < 10-4 ). The highest prevalence was observed in males in the 30-39 age group (20.5/10,000) and the lowest in females in the 50-70 age group (2.8/10,000). CONCLUSION The risk of an HEV-RNA-positive donation entering the blood supply was estimated at 1 in 1682 donations. This risk does not translate directly to the risk of HEV transfusion transmission, which mainly depends on the total number of viral particles in the transfused blood component and the sensitivity of NAT.
Collapse
Affiliation(s)
| | - Claude Maugard
- Etablissement Français du Sang Occitanie, Montpellier, France
| | | | | | - Chloé Pierre
- Etablissement Français du Sang, La Plaine St-Denis, France
| | - Sophie LeCam
- Etablissement Français du Sang, La Plaine St-Denis, France
| | | | - Pascal Morel
- Etablissement Français du Sang, La Plaine St-Denis, France.,UMR 1098 RIGHT INSERM, Université de Franche-Comté Etablissement Français du Sang, Besançon, France
| | - Pierre Gallian
- Etablissement Français du Sang, La Plaine St-Denis, France.,Unité des Virus Émergents (UVE), Aix-Marseille, IRD 190, Inserm 1207, Marseille, France
| | - Syria Laperche
- Etablissement Français du Sang, La Plaine St-Denis, France.,Unité des Virus Émergents (UVE), Aix-Marseille, IRD 190, Inserm 1207, Marseille, France
| |
Collapse
|
|
15
|
Harvala H, Reynolds C, Brailsford S, Davison K. Fulminant Transfusion-Associated Hepatitis E Virus Infection Despite Screening, England, 2016-2020. Emerg Infect Dis 2022; 28:1805-1813. [PMID: 35997399 PMCID: PMC9423923 DOI: 10.3201/eid2809.220487] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
In England, all blood donations are screened in pools of 24 by nucleic acid test (NAT) for hepatitis E virus (HEV) RNA. During 2016-2020, this screening successfully identified and intercepted 1,727 RNA-positive donations. However, review of previous donations from infected platelet donors identified 9 donations in which HEV RNA detection was missed, of which 2 resulted in confirmed transmission: 1 infection resolved with ribavirin treatment, and 1 proceeded to fatal multiorgan failure within a month from infection. Residual risk calculations predict that over the 5-year study period, HEV RNA detection was missed by minipool NAT in 12-23 platelet and 177-354 whole-blood donations, but transmission risk remains undetermined. Although screening has been able to largely eliminate infectious HEV from the blood supply in England, missed detection of low levels of HEV RNA in donated blood can lead to a severe, even fulminant, infection in recipients and could be prevented by more sensitive screening.
Collapse
|
|
16
|
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.
Collapse
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
| |
Collapse
|
|
17
|
Al Dossary RA, Alnafie AN, Aljaroodi SA, Rahman JU, Hunasemarada BC, Alkharsah KR. Prevalence of Hepatitis E Virus Infection Among Blood Donors in the Eastern Province of Saudi Arabia. J Multidiscip Healthc 2021; 14:2381-2390. [PMID: 34475765 PMCID: PMC8407670 DOI: 10.2147/jmdh.s328029] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 08/16/2021] [Indexed: 12/15/2022] Open
Abstract
PURPOSE Hepatitis E virus (HEV) causes acute hepatitis in humans and constitutes a major problem for immunocompromised patients, patients with hematological diseases, and pregnant women. It is transmitted mainly through fecal oral route; however, transmission through blood and blood products is reported globally and becoming a health concern. We sought to determine the prevalence of HEV among blood donors in the Eastern Province of Saudi Arabia using molecular as well as serological assays to assess the safety of blood transfusion and the need for HEV screening among blood donors. PATIENTS AND METHODS A total of 806 whole blood samples were collected from blood donors between May and November 2020 and tested for anti-HEV IgG and IgM antibodies by ELISA and for HEV RNA by RT-PCR. RESULTS The overall seroprevalence of HEV IgG antibodies was 3.2% with no statistically significant difference between the non-Saudis (3.28%) and Saudis (3.17%) (p value 0.929) or between males (3.14%) and females (4.88%) (p value 0.527). None of the IgG positive individuals had IgM antibodies. HEV RNA was not detected in any of the blood donors. CONCLUSION HEV seroprevalence is low among blood donors in the Eastern Province of Saudi Arabia and may constitute minimal risk for transfusion associated infections.
Collapse
Affiliation(s)
- Reem A Al Dossary
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| | - Awatif N Alnafie
- Department of Pathology, College of Medicine, King Fahad Hospital of the University, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Salma Ali Aljaroodi
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| | - Jawad Ur Rahman
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| | - Basavaraj C Hunasemarada
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| | - Khaled R Alkharsah
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| |
Collapse
|
|
18
|
Fu P, Lin B, Wu B, Ke L, Yang T, Du Y, Cheng L, Li Z, Li T, Liu Y. Hepatitis E virus prevalence among blood donors in Dali, China. Virol J 2021; 18:141. [PMID: 34233712 PMCID: PMC8261953 DOI: 10.1186/s12985-021-01607-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 06/23/2021] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) is a nonenveloped RNA virus causing hepatitis E worldwide. The increase in transfusion-transmitted cases of HEV infections from asymptomatic blood donors causing serious illnesses among immunosuppressed recipients has been reported in the past few years. China is one of the most prevalent regions of HEV; as a result, it is important to evaluate the risk of transfusion-transmitted HEV. METHODS A total of 1864 serum samples (including demographic characteristics) from blood donors were randomly collected from February to March 2018 in Dali city. Anti-HEV IgG, IgM and IgA antibodies and HEV antigen were examined by enzyme-linked immunosorbent assay (ELISA). HEV RNA was detected by real-time PCR. Multivariable logistic regression modelling was used to examine the risk factors associated with HEV prevalence. RESULTS Overall, the positive rates of anti-HEV IgG, IgM, and IgA antibodies were 13.36% (249/1864), 1.13% (21/1864), and 1.82% (34/1864), respectively. However, none of the 1864 serum samples were HEV antigen positive or HEV RNA positive. Females (16.69%) had a significantly higher HEV seroprevalence than males (13.04%) (odds ratio [OR] 1.34 [95% CI, 1.02-1.75]). Bai (18.85%) donors had a significantly higher HEV seroprevalence than Han (12.21%) blood donors (odds ratio [OR], 1.65 [95% CI, 1.24-2.19] for Bai). CONCLUSIONS HEV showed a seroprevalence among blood donors in Yunnan Province, some of which were even recent infections, indicating a threat to the safety of blood transfusions. Whether to formulate a strategy for HEV screening in blood centres needs further research.
Collapse
Affiliation(s)
- Ping Fu
- Transfusion Medicine Research Center, The Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, 610052, China
| | - Baochai Lin
- Transfusion Medicine Research Center, The Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, 610052, China
| | - Bingting Wu
- Transfusion Medicine Research Center, The Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, 610052, China
| | - Ling Ke
- Transfusion Medicine Research Center, The Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, 610052, China
| | | | - Yue'e Du
- Dali Blood Center, Dali, Yunnan, China
| | - Lishan Cheng
- Transfusion Medicine Research Center, The Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, 610052, China
| | - Zhou Li
- Transfusion Medicine Research Center, The Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, 610052, China
| | - Tiancheng Li
- Department of Virology II, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashi-murayama, Tokyo, 208-0011, Japan.
| | - Yu Liu
- Transfusion Medicine Research Center, The Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, 610052, China.
| |
Collapse
|
|
19
|
Alhatlani BY, Aljabr WA, Almarzouqi MS, Alhatlani SM, Alzunaydi RN, Alsaykhan AS, Almaiman SH, Aleid AA, Alsughayir AH, Bishawri YE, Almusallam AA. Seroprevalence of the hepatitis E virus antibodies among blood donors in the Qassim region, Saudi Arabia. Future Virol 2021. [DOI: 10.2217/fvl-2021-0013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Aim: Hepatitis E virus (HEV) transmission through blood transfusion is a major public health issue worldwide. We aimed to determine the seroprevalence of HEV in blood donors in the Qassim region of Saudi Arabia. Materials & methods: Serum samples (n = 1078) were collected from volunteer blood donors and tested for the presence of anti-HEV IgG and IgM by indirect ELISA. Results: The seroprevalence of anti-HEV IgG among the blood donors was 5.7% overall. Anti-HEV IgG and IgM seropositivity were significantly higher in non-Saudi donors than in Saudi donors (22.1 vs 3 and 7.8 vs 0.2% for anti-HEV IgG and IgM, respectively). Conclusion: The seroprevalence of HEV among blood donors in the Qassim region was lower than previous estimates for other regions of the country and neighboring countries.
Collapse
Affiliation(s)
- Bader Y Alhatlani
- Department of Applied Medical Sciences, Unayzah Community College, Qassim University, Unayzah, Saudi Arabia
| | - Waleed A Aljabr
- Research Center, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Mohammed S Almarzouqi
- Department of Applied Medical Sciences, Unayzah Community College, Qassim University, Unayzah, Saudi Arabia
| | - Sami M Alhatlani
- Department of Medical Laboratory, Blood Donor Unit, King Saud Hospital, Unayzah, Saudi Arabia
| | - Rayan N Alzunaydi
- Department of Medical Laboratory, Blood Donor Unit, King Saud Hospital, Unayzah, Saudi Arabia
| | - Abeer S Alsaykhan
- Department of Medical Laboratory, Blood Donor Unit, King Saud Hospital, Unayzah, Saudi Arabia
| | - Sulaiman H Almaiman
- Department of Medical Laboratory, Blood Donor Unit, King Saud Hospital, Unayzah, Saudi Arabia
| | - Ahmed A Aleid
- Gastroenterology & Department of Hepatology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Ammar H Alsughayir
- Transfusion Medicine & Department of Hematopathology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Yara E Bishawri
- Research Center, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Abdulrahman A Almusallam
- Department of Applied Medical Sciences, Unayzah Community College, Qassim University, Unayzah, Saudi Arabia
| |
Collapse
|
|
20
|
Gallian P, Lhomme S, Morel P, Gross S, Mantovani C, Hauser L, Tinard X, Pouchol E, Djoudi R, Assal A, Abravanel F, Izopet J, Tiberghien P. Risk for Hepatitis E Virus Transmission by Solvent/Detergent-Treated Plasma. Emerg Infect Dis 2021; 26:2881-2886. [PMID: 33219652 PMCID: PMC7706953 DOI: 10.3201/eid2612.191482] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Hepatitis E has emerged as a major transfusion-transmitted infectious risk. Two recipients of plasma from 2 lots (A and B) of pooled solvent/detergent-treated plasma were found to be infected by hepatitis E virus (HEV) that was determined to have been transmitted by the solvent/detergent-treated plasma. HEV RNA viral loads were 433 IU in lot A and 55 IU in lot B. Retrospective studies found that 100% (13/13) of evaluable lot A recipients versus 18% (3/17) of evaluable lot B recipients had been infected by HEV (p<0.001), albeit not necessarily at time of transfusion. Among evaluable recipients, 86% with a transfused HEV RNA load >50,000 IU were infected, most likely by the HEV-containing solvent/detergent-treated plasma, versus only 7% with a transfused HEV RNA load <50,000 IU (p<0.001). Overall, solvent/detergent-treated plasma might harbor HEV. Such an occurrence might result in a dose-dependent risk for transfusion-transmitted hepatitis E.
Collapse
|
|
21
|
Bagulo H, Majekodunmi AO, Welburn SC. Hepatitis E in Sub Saharan Africa - A significant emerging disease. One Health 2020; 11:100186. [PMID: 33204807 PMCID: PMC7653283 DOI: 10.1016/j.onehlt.2020.100186] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 10/09/2020] [Accepted: 10/17/2020] [Indexed: 12/17/2022] Open
Abstract
Hepatitis E is an emerging endemic disease found across the African continent, but there are clear differences in epidemiology between North Africa and countries south of the Sahara. In this systematic review, Google scholar and PubMed databases were searched for peer-reviewed articles on HEV epidemiology. Publications meeting our inclusion criteria were critically reviewed to extract consistent findings and identify knowledge gaps. Hepatitis E has been reported in 25 of the 49 countries in Sub Saharan Africa. Mortality rates of 1–2% in the general population and ~ 20% in pregnant women. Outbreaks were closely linked to refugees and Internally Displaced Persons in camps which accounted for 50% of reported outbreaks. There was very little research and concrete evidence for sources of contamination and transmission routes. There are indications of zoonotic transmission of Hepatitis E Virus infection but further research in these fields is required.
No data from 50% of African countries Outbreaks closely linked to refugee and IDP camps Little data on sources of HEV contamination Indications but little evidence of zoonotic transmission Low awareness amongst health professionals and general public
Collapse
Affiliation(s)
- Husein Bagulo
- Zhejiang University - University of Edinburgh Institute, Zhejiang University International Campus, 718 East Haizhou Rd, Haining, Zhejiang Province, 314400, China.,Livestock and Poultry Research Centre, College of Basic and Applied Sciences, University of Ghana, P. O Box LG 25, Legon, Accra, Ghana
| | - Ayodele O Majekodunmi
- Zhejiang University - University of Edinburgh Institute, Zhejiang University International Campus, 718 East Haizhou Rd, Haining, Zhejiang Province, 314400, China.,Livestock and Poultry Research Centre, College of Basic and Applied Sciences, University of Ghana, P. O Box LG 25, Legon, Accra, Ghana.,School of Biomedical Sciences, Edinburgh Medical School, College of Medicine & Veterinary Medicine, The University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, United Kingdom
| | - Susan C Welburn
- Zhejiang University - University of Edinburgh Institute, Zhejiang University International Campus, 718 East Haizhou Rd, Haining, Zhejiang Province, 314400, China.,School of Biomedical Sciences, Edinburgh Medical School, College of Medicine & Veterinary Medicine, The University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, United Kingdom
| |
Collapse
|
|
22
|
Abstract
PURPOSE OF REVIEW Hepatitis E virus (HEV) has gained increased global recognition in recent years, particularly in developed countries. We summarized here a selection of the literature published since the 1st of June, 2017. RECENT FINDINGS Longitudinal studies are increasingly conducted in Europe, to determine trends in HEV prevalence. The spectrum of mammals infected with HEV and potentially capable to transmit it to humans has widened. New virological data on HEV repCon and pathogenicity have been reported and clinical features of HEV infections have been precised or newly described. Finally, there are some new data on the therapeutic management of HEV infections in various clinical settings. SUMMARY HEV emergence in developed countries appears to be based on improved diagnosis tools and increased awareness of clinicians that HEV transmission is essentially autochthonous and is a possible cause of life-threatening acute hepatitis, chronic hepatitis, cirrhosis, and extra-hepatic symptoms. In addition, the distribution of HEV strains evolves. Ribavirin remains to date the only specific treatment recommended for HEV infection, being efficient in the majority but not in all cases.
Collapse
|
|
23
|
Maponga TG, Lopes T, Cable R, Pistorius C, Preiser W, Andersson MI. Prevalence and risks of hepatitis E virus infection in blood donors from the Western Cape, South Africa. Vox Sang 2020; 115:695-702. [PMID: 32597542 DOI: 10.1111/vox.12966] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 06/03/2020] [Accepted: 06/03/2020] [Indexed: 01/18/2023]
Abstract
BACKGROUND Transfusion-transmitted hepatitis E virus (HEV) infection is a potential risk to recipients of blood transfusions. Infection with HEV poses a high risk to immunocompromised recipients with an increased likelihood of developing chronic infection. The aims of this study were to determine the prevalence of past and active HEV infections in donors from the Western Cape and to identify the risk factors associated with infection. MATERIALS AND METHODS We prospectively tested 10 250 blood donors for HEV infection. A risk factor sub-study investigated 250 donors who completed a questionnaire, and plasma samples were tested for HEV IgG antibodies and pooled for HEV RNA detection. The demographic and risk factors associated with HEV infection were assessed. The molecular study tested 10 000 individual donations using a commercial assay to detect viraemia. HEV viral load and genotype were also determined. RESULTS The overall anti-HEV IgG seroprevalence was 42·8% (107/250) among donors participating in the risk factor sub-study. The likelihood of past HEV infection was higher with an increase in age. Of the 10 000 donor samples individually tested for HEV RNA, one sample was positive with a viral load of 7·9 x 104 IU/ml and belonged to HEV genotype 3. CONCLUSION We found a high seroprevalence of anti-HEV IgG but a low HEV RNA prevalence among donors in the Western Cape, South Africa. The study provides evidence for a potential risk of HEV contamination in the blood supply in South Africa. A cost-benefit analysis is needed before considering the introduction of routine donor screening in our setting.
Collapse
Affiliation(s)
- Tongai G Maponga
- Division of Medical Virology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, South Africa
| | - Tatum Lopes
- Division of Medical Virology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, South Africa
| | | | | | - Wolfgang Preiser
- Division of Medical Virology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, South Africa.,Tygerberg Business Unit, National Health Laboratory Service, Cape Town, South Africa
| | - Monique I Andersson
- Division of Medical Virology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, South Africa.,Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| |
Collapse
|
|
24
|
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.
Collapse
|
|
25
|
Goel A, Vijay HJ, Katiyar H, Aggarwal R. Prevalence of hepatitis E viraemia among blood donors: a systematic review. Vox Sang 2020; 115:120-132. [PMID: 32030767 DOI: 10.1111/vox.12887] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 12/18/2019] [Accepted: 12/19/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Hepatitis E virus (HEV) is usually transmitted by faecal-oral route. Recent reports have documented HEV viraemia in donated blood units and HEV transmission through blood transfusion. This systematic review summarizes the available data on prevalence of HEV viraemia in blood donors. METHODS Electronic databases were searched on 17 December 2018 to identify full-text English papers reporting original data on prevalence of HEV RNA in donated blood units. Two authors independently extracted the relevant data, which were pooled using simple aggregation as well as a random-effects meta-analysis; heterogeneity was assessed using the I2 method. RESULTS In all, 59 data sets from 28 countries were identified. The available data showed marked heterogeneity. Of a total of 2 127 832 units studied, 561 (263·6 [95% confidence intervals = 242·7-286·4] per million units) tested positive for HEV RNA. On random-effects meta-analysis, the pooled prevalence was 60·9 [6·7-155·4] per million units. In the viraemic units, HEV RNA titre varied by nearly one million-fold, and most had genotype 3 HEV. The prevalence was higher in blood units with anti-HEV antibodies or elevated alanine aminotransferase. Only nearly one-fourth of viraemic units had anti-HEV antibodies. CONCLUSIONS The prevalence of HEV viraemia among healthy blood donors is low, though the available data had limited geographical representation and marked heterogeneity. There is a need for further data on HEV viraemia in blood donors from areas with non-3 HEV genotype preponderance.
Collapse
Affiliation(s)
- Amit Goel
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | | | - Harshita Katiyar
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| |
Collapse
|
|
26
|
Seroprevalence of hepatitis E virus in dromedary camels, Bedouins, Muslim Arabs and Jews in Israel, 2009-2017. Epidemiol Infect 2020; 147:e92. [PMID: 30869027 PMCID: PMC6518832 DOI: 10.1017/s0950268819000062] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Hepatitis E virus (HEV) is an emerging cause of viral hepatitis worldwide. Recently, HEV-7 has been shown to infect camels and humans. We studied HEV seroprevalence in dromedary camels and among Bedouins, Arabs (Muslims, none-Bedouins) and Jews and assessed factors associated with anti-HEV seropositivity. Serum samples from dromedary camels (n = 86) were used to determine camel anti-HEV IgG and HEV RNA positivity. Human samples collected between 2009 and 2016 from >20 years old Bedouins (n = 305), non-Bedouin Arabs (n = 320) and Jews (n = 195), were randomly selected using an age-stratified sampling design. Human HEV IgG levels were determined using Wantai IgG ELISA assay. Of the samples obtained from camels, 68.6% were anti-HEV positive. Among the human populations, Bedouins and non-Bedouin Arabs had a significantly higher prevalence of HEV antibodies (21.6% and 15.0%, respectively) compared with the Jewish population (3.1%). Seropositivity increased significantly with age in all human populations, reaching 47.6% and 34.8% among ⩾40 years old, in Bedouins and non-Bedouin Arabs, respectively. The high seropositivity in camels and in ⩾40 years old Bedouins and non-Bedouin Arabs suggests that HEV is endemic in Israel. The low HEV seroprevalence in Jews could be attributed to higher socio-economic status.
Collapse
|
|
27
|
Capelli N, Dubois M, Pucelle M, Da Silva I, Lhomme S, Abravanel F, Chapuy-Regaud S, Izopet J. Optimized Hepatitis E Virus (HEV) Culture and its Application to Measurements of HEV Infectivity. Viruses 2020; 12:v12020139. [PMID: 31991673 PMCID: PMC7077187 DOI: 10.3390/v12020139] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 01/08/2020] [Accepted: 01/21/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatitis E virus (HEV) is a major concern in public health worldwide. Infections with HEV genotypes 3, 4, or 7 can lead to chronic hepatitis while genotype 1 infections can trigger severe hepatitis in pregnant women. Infections with all genotypes can worsen chronic liver diseases. As virions are lipid-associated in blood and naked in feces, efficient methods of propagating HEV clinical strains in vitro and evaluating the infectivity of both HEV forms are needed. We evaluated the spread of clinical strains of HEV genotypes 1 (HEV1) and 3 (HEV3) by quantifying viral RNA in culture supernatants and cell lysates. Infectivity was determined by endpoint dilution and calculation of the tissue culture infectious dose 50 (TCID50). An enhanced HEV production could be obtained varying the composition of the medium, including fetal bovine serum (FBS) and dimethylsulfoxide (DMSO) content. This increased TCID50 from 10 to 100-fold and allowed us to quantify HEV1 infectivity. These optimized methods for propagating and measuring HEV infectivity could be applied to health safety processes and will be useful for testing new antiviral drugs.
Collapse
Affiliation(s)
- Nicolas Capelli
- Department of Virology, National Reference Center for HEV, CHU Purpan, 31059 Toulouse, France
- Centre de Physiopathologie de Toulouse Purpan (CPTP), Institut National de la Santé et de la Recherche Médicale, Inserm UMR1043, Centre National de la Recherche Scientifique, CNRS UMR5282, Université de Toulouse, 31024 Toulouse, France
| | - Martine Dubois
- Department of Virology, National Reference Center for HEV, CHU Purpan, 31059 Toulouse, France
- Centre de Physiopathologie de Toulouse Purpan (CPTP), Institut National de la Santé et de la Recherche Médicale, Inserm UMR1043, Centre National de la Recherche Scientifique, CNRS UMR5282, Université de Toulouse, 31024 Toulouse, France
| | - Mélanie Pucelle
- Department of Virology, National Reference Center for HEV, CHU Purpan, 31059 Toulouse, France
| | - Isabelle Da Silva
- Department of Virology, National Reference Center for HEV, CHU Purpan, 31059 Toulouse, France
| | - Sébastien Lhomme
- Department of Virology, National Reference Center for HEV, CHU Purpan, 31059 Toulouse, France
- Centre de Physiopathologie de Toulouse Purpan (CPTP), Institut National de la Santé et de la Recherche Médicale, Inserm UMR1043, Centre National de la Recherche Scientifique, CNRS UMR5282, Université de Toulouse, 31024 Toulouse, France
| | - Florence Abravanel
- Department of Virology, National Reference Center for HEV, CHU Purpan, 31059 Toulouse, France
- Centre de Physiopathologie de Toulouse Purpan (CPTP), Institut National de la Santé et de la Recherche Médicale, Inserm UMR1043, Centre National de la Recherche Scientifique, CNRS UMR5282, Université de Toulouse, 31024 Toulouse, France
| | - Sabine Chapuy-Regaud
- Department of Virology, National Reference Center for HEV, CHU Purpan, 31059 Toulouse, France
- Centre de Physiopathologie de Toulouse Purpan (CPTP), Institut National de la Santé et de la Recherche Médicale, Inserm UMR1043, Centre National de la Recherche Scientifique, CNRS UMR5282, Université de Toulouse, 31024 Toulouse, France
- Correspondence: ; Tel.: +33-567-690-431
| | - Jacques Izopet
- Department of Virology, National Reference Center for HEV, CHU Purpan, 31059 Toulouse, France
- Centre de Physiopathologie de Toulouse Purpan (CPTP), Institut National de la Santé et de la Recherche Médicale, Inserm UMR1043, Centre National de la Recherche Scientifique, CNRS UMR5282, Université de Toulouse, 31024 Toulouse, France
| |
Collapse
|
|
28
|
Hepatitis E virus infections in Europe. J Clin Virol 2019; 120:20-26. [PMID: 31536936 DOI: 10.1016/j.jcv.2019.09.004] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 09/06/2019] [Indexed: 12/11/2022]
|
|
29
|
Lhomme S, Gallian P, Dimeglio C, Assal A, Abravanel F, Tiberghien P, Izopet J. Viral load and clinical manifestations of hepatitis E virus genotype 3 infections. J Viral Hepat 2019; 26:1139-1142. [PMID: 31099059 DOI: 10.1111/jvh.13128] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Accepted: 05/01/2019] [Indexed: 12/27/2022]
Abstract
A fraction of plasma donations undergoes hepatitis E virus (HEV) RNA screening since late 2014 in France. The aim of this study was to determine the frequency of HEV RNA as well as the viral load and the evolution of genotype distribution over a 3-year period (2015-2017) in asymptomatic blood donors in comparison with symptomatic patients routinely diagnosed. The overall detection rate of HEV RNA in plasma donations was 0.10% during the 3-year period, with a median viral load of 717 IU/mL (range: <60-168 000 IU/mL) in the 189 samples found HEV RNA positive. One hundred and twenty samples (64.4%) were successfully HEV genotyped. Most strains were HEV3f (n = 54; 44.3%) and HEV3c (n = 46; 37.7%). The genotype distribution was not different throughout the 3-year period and we found no association between the genotype and where the blood donors lived (P = 0.96). The HEV genotype distributions in infected blood donors and symptomatic patients were similar. However, the symptomatic patients had a higher viral load (median 282 000 IU/mL; range: <60-136 000 000 IU/mL; P < 0.01) than the blood donors. Overall, asymptomatic blood donors and patients with symptomatic hepatitis E had similar genotype distributions but the blood donors had lower viral loads.
Collapse
Affiliation(s)
- Sebastien Lhomme
- Laboratoire de Virologie, CHU Purpan, Toulouse, France.,INSERM, UMR1043, Toulouse, France.,Université Paul Sabatier, Toulouse, France
| | - Pierre Gallian
- Etablissement Français du Sang (EFS), La Plaine St Denis, France.,Unité des Virus Emergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207, IHU Méditerranée Infection), Marseille, France
| | | | - Azzedine Assal
- Etablissement Français du Sang (EFS), Aquitaine Limousin, Bordeaux, France
| | - Florence Abravanel
- Laboratoire de Virologie, CHU Purpan, Toulouse, France.,INSERM, UMR1043, Toulouse, France.,Université Paul Sabatier, Toulouse, France
| | - Pierre Tiberghien
- Etablissement Français du Sang (EFS), La Plaine St Denis, France.,Inserm, Etablissement Français du Sang, UMR 1098, Université de Franche-Comté, Besançon, France
| | - Jacques Izopet
- Laboratoire de Virologie, CHU Purpan, Toulouse, France.,INSERM, UMR1043, Toulouse, France.,Université Paul Sabatier, Toulouse, France
| |
Collapse
|
|
30
|
Kamar N, Pischke S. Acute and Persistent Hepatitis E Virus Genotype 3 and 4 Infection: Clinical Features, Pathogenesis, and Treatment. Cold Spring Harb Perspect Med 2019; 9:cshperspect.a031872. [PMID: 29735575 DOI: 10.1101/cshperspect.a031872] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Hepatitis E virus (HEV) genotype (gt)3 and 4 infections are prevalent in industrialized and high-income countries. Although most HEV gt3 and gt4 infections are clinically silent, acute infection may be symptomatic in some patients. In persons with underlying liver disease and in elderly men, HEV infections may present as acute or acute-on-chronic liver failure. Chronic hepatitis may develop in immunosuppressed individuals, including transplant recipients, human immunodeficiency virus (HIV)-infected patients, and persons with hematologic malignancy undergoing chemotherapy, and may progress to life-threatening liver cirrhosis. Extrahepatic manifestations of infection may include neurological and renal disease. Although there is no approved specific therapy for the treatment of acute or chronic HEV gt3 or gt4 infection, off-label use of ribavirin appears to be capable of eliminating chronic HEV infection, and may reduce disease severity in patients suffering from acute liver failure.
Collapse
Affiliation(s)
- Nassim Kamar
- Department of Nephrology and Organ Transplantation, Université Paul Sabatier, Toulouse 31059, France
| | - Sven Pischke
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany
| |
Collapse
|
|
31
|
Transfusion-Transmitted Hepatitis E Virus Infection in France. Transfus Med Rev 2019; 33:146-153. [PMID: 31327668 DOI: 10.1016/j.tmrv.2019.06.001] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Revised: 05/27/2019] [Accepted: 06/04/2019] [Indexed: 12/14/2022]
|
|
32
|
Denner J, Pischke S, Steinmann E, Blümel J, Glebe D. Why all blood donations should be tested for hepatitis E virus (HEV). BMC Infect Dis 2019; 19:541. [PMID: 31221098 PMCID: PMC6585104 DOI: 10.1186/s12879-019-4190-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 06/13/2019] [Indexed: 02/06/2023] Open
Abstract
Background Hepatitis E is a liver disease caused by a small RNA virus known as hepatitis E virus (HEV). Four major genotypes infect humans, of which genotype 1 and 2 (HEV-1, HEV-2) are endemic mainly in Asia and responsible for waterborne epidemics. HEV-3 and HEV-4 are widely distributed in pigs and can be transmitted to humans mainly by undercooked meat, and contact with pigs. HEV-3 is the main genotype in industrialised countries with moderate climate conditions and object of this debate. Main text Whereas an HEV-3 infection in healthy humans is mostly asymptomatic, HEV-3 can induce chronic infection in immunocompromised individuals and acute-on-chronic liver failure (ACLF) in patients with underlying liver diseases. The number of reported cases of HEV-infections in industrialised nations increased significantly in the last years. Since HEV-3 has been transmitted by blood transfusion to other humans, testing of blood donors has been introduced or introduction is being discussed in some industrialised countries. In this article we summarise the arguments in favour of testing all blood donations for HEV-3. Conclusion The number of HEV infection in the population and the possibility of HEV transmission by blood transfusion are increasing. Transmission by blood transfusion can be dangerous for the recipients considering their immunosuppressive status, underlying disease or other circumstances requiring blood transfusion. This argues in favour of testing all blood donations for HEV-3 to prevent transmission.
Collapse
Affiliation(s)
- Joachim Denner
- Robert Koch Institute, Nordufer 20, 13353, Berlin, Germany.
| | - Sven Pischke
- 1. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany
| | - Eike Steinmann
- Ruhr-Universität Bochum, Universitätsstraße 150, 44801, Bochum, Germany
| | - Johannes Blümel
- Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Germany
| | - Dieter Glebe
- Institute of Medical Virology, National Reference Centre for Hepatitis B and D Viruses, German Center for Infection Research (DZIF), Schubertstr. 81, Justus-Liebig-Universität Giessen, 35392, Giessen, Germany
| |
Collapse
|
|
33
|
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.
Collapse
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
| |
Collapse
|
|
34
|
Lhomme S, Legrand-Abravanel F, Kamar N, Izopet J. Screening, diagnosis and risks associated with Hepatitis E virus infection. Expert Rev Anti Infect Ther 2019; 17:403-418. [DOI: 10.1080/14787210.2019.1613889] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Sébastien Lhomme
- Department of Virology, National reference center for Hepatitis E Virus, CHU Purpan, Toulouse, France
- Inserm UMR1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
- Université de Toulouse, Toulouse III, Toulouse, France
| | - Florence Legrand-Abravanel
- Department of Virology, National reference center for Hepatitis E Virus, CHU Purpan, Toulouse, France
- Inserm UMR1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
- Université de Toulouse, Toulouse III, Toulouse, France
| | - Nassim Kamar
- Inserm UMR1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
- Université de Toulouse, Toulouse III, Toulouse, France
- Department of Nephrology and Organs Transplantation, CHU Rangueil, Toulouse, France
| | - Jacques Izopet
- Department of Virology, National reference center for Hepatitis E Virus, CHU Purpan, Toulouse, France
- Inserm UMR1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
- Université de Toulouse, Toulouse III, Toulouse, France
| |
Collapse
|
|
35
|
Boland F, Martinez A, Pomeroy L, O'Flaherty N. Blood Donor Screening for Hepatitis E Virus in the European Union. Transfus Med Hemother 2019; 46:95-103. [PMID: 31191195 PMCID: PMC6514502 DOI: 10.1159/000499121] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 02/25/2019] [Indexed: 12/11/2022] Open
Abstract
This review article summarises hepatitis E virus (HEV) blood donation screening strategies in effect in the European Union (EU). Since 2012, eight EU countries have implemented HEV screening. Local rates of seroprevalence, RNA incidence, and molecular epidemiology are variable and not usually directly comparable. We report a range of HEV-RNA reactivity rates from 1 in 744 donations (France) to 1 in 8,636 donations (Wales) with an overall EU rate of 1 in 3,109 donations (3.2 million donations screened). HEV genotypes 3c, 3e, and 3f are the most frequently reported subtypes. In these 8 countries, both universal (n = 5) and selective (n = 3) screening policies have been introduced utilising either individual donation (ID; n = 1) or mini-pool (MP; n = 7; MP-6, -16, -24, and -96) testing. We also describe the Irish experience of HEV screening utilising an ID-NAT-based donor screening algorithm which intercepts donations even from those with low-level viraemia; 21 of 56 donors (37.5%) had a viral load (VL) < 100 IU/mL. We performed a MP-24 experiment which may prove useful to colleagues in relation to donor screening and associated blood component transmissibility. Irish results indicate that 59% of donors with a HEV-VL < 450 IU/mL may have screened negative in a MP-24.
Collapse
Affiliation(s)
- Fiona Boland
- Irish Blood Transfusion Service (IBTS), NAT Laboratory, Dublin, Ireland
| | | | - Louise Pomeroy
- Irish Blood Transfusion Service (IBTS), NAT Laboratory, Dublin, Ireland
| | - Niamh O'Flaherty
- Irish Blood Transfusion Service (IBTS), NAT Laboratory, Dublin, Ireland
- National Virus Reference Laboratory, University College Dublin (UCD), Dublin, Ireland
| |
Collapse
|
|
36
|
Denner J. Hepatitis E virus (HEV)-The Future. Viruses 2019; 11:E251. [PMID: 30871152 PMCID: PMC6466233 DOI: 10.3390/v11030251] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 03/05/2019] [Accepted: 03/09/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatitis (HEV) is widely distributed in pigs and is transmitted with increasing numbers to humans by contact with pigs, contaminated food and blood transfusion. The virus is mostly apathogenic in pigs but may enhance the pathogenicity of other pig viruses. In humans, infection can lead to acute and chronic hepatitis and extrahepatic manifestations. In order to stop the emerging infection, effective counter-measures are required. First of all, transmission by blood products can be prevented by screening all blood donations. Meat and sausages should be appropriately cooked. Elimination of the virus from the entire pork production can be achieved by sensitive testing and elimination programs including early weaning, colostrum deprivation, Caesarean delivery, embryo transfer, treatment with antivirals, protection from de novo infection, and possibly vaccination. In addition, contaminated water, shellfish, vegetables, and fruits by HEV-contaminated manure should be avoided. A special situation is given in xenotransplantation using pig cells, tissues or organs in order to alleviate the lack of human transplants. The elimination of HEV from pigs, other animals and humans is consistent with the One Health concept, preventing subclinical infections in the animals as well as preventing transmission to humans and disease.
Collapse
|
|
37
|
Vectorial Release of Hepatitis E Virus in Polarized Human Hepatocytes. J Virol 2019; 93:JVI.01207-18. [PMID: 30463960 DOI: 10.1128/jvi.01207-18] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Accepted: 11/07/2018] [Indexed: 12/26/2022] Open
Abstract
Hepatitis E virus (HEV) is a common cause of acute viral hepatitis worldwide. Most HEV infections are asymptomatic, but immunocompromised patients infected with HEV genotype 3 (HEV3), HEV4, or HEV7 may develop chronic infections. The HEV particles in stools are naked (nHEV), while those in the serum and culture supernatants (eHEV) are associated with lipids. Hepatocytes are polarized epithelial cells that have basolateral (oriented toward the blood) and apical (oriented toward the bile) exosomal pathways. We isolated a subclone, F2, from the human hepatocarcinoma cell line HepG2/C3A that grew as a polarized monolayer culture and had better HEV production than HepG2/C3A cells. F2 cells cultured on semipermeable collagen inserts and infected basolaterally with nHEV3 released 94.6% of virus particles apically, those infected with eHEV3 released 96.8% apically, and eHEV1-infected cells released 99.3% apically. Transcytosis was not involved. Density gradient centrifugation and NP-40 treatment showed that HEV particles released both apically and basolaterally were lipid associated. The apically released HEV3 and HEV1 particles were six and nine times more infectious than those released basolaterally, respectively. Confocal microscopy indicated that the open reading frame 2 (ORF2) capsid protein colocalized apically with ORF3 virus protein, the apical marker DPP4, and the recycling endosome GTPase Rab27a. The amounts of soluble glycosylated ORF2 secreted apically and basolaterally were similar. These polarized-hepatocyte data suggest that infectious HEV particles are mainly released into bile, while the small fraction released into blood could spread HEV throughout the host.IMPORTANCE Hepatitis E virus (HEV) in stools is naked, while that in culture supernatants and patients' blood is lipid associated. Its life cycle in hepatocytes, polarized cells with a basolateral side communicating with blood and an apical side connected with bile, is incompletely understood. We have developed a polarized hepatocyte model and used the cells to analyze the supernatants bathing the apical and basolateral sides and HEV subcellular distribution. HEV particles from both sides were lipid associated, and most infectious HEV particles left the cell via its apical side. Similar amounts of the open reading frame 2 (ORF2) soluble capsid protein were secreted from both sides of the hepatocytes. This model mimicking physiological conditions should help clarify the HEV cell cycle in polarized hepatocytes.
Collapse
|
|
38
|
Luciani L, Deharo P, Aherfi S, Chalvignac V, Borentain P, Colson P. Hepatitis E virus infection in heart transplant recipients, Southeastern France. Clin Res Hepatol Gastroenterol 2019; 43:108-111. [PMID: 30497845 DOI: 10.1016/j.clinre.2018.09.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Revised: 08/28/2018] [Accepted: 09/15/2018] [Indexed: 02/04/2023]
Affiliation(s)
- Léa Luciani
- Aix-Marseille université, institut de recherche pour le développement (IRD), Assistance publique - hôpitaux de Marseille (AP-HM), microbes, evolution, phylogeny and infection (MEΦI), institut hospitalo-universitaire (IHU) - Méditerranée Infection, 19-21, boulevard Jean-Moulin, 13005 Marseille, France
| | - Pierre Deharo
- Assistance publique - hôpitaux de Marseille (AP-HM), centre hospitalo-universitaire Timone, service de cardiologie, 264, rue Saint-Pierre, 13385 Marseille cedex 05, France
| | - Sarah Aherfi
- Aix-Marseille université, institut de recherche pour le développement (IRD), Assistance publique - hôpitaux de Marseille (AP-HM), microbes, evolution, phylogeny and infection (MEΦI), institut hospitalo-universitaire (IHU) - Méditerranée Infection, 19-21, boulevard Jean-Moulin, 13005 Marseille, France
| | - Virginie Chalvignac
- Assistance publique - hôpitaux de Marseille (AP-HM), centre hospitalo-universitaire Timone, service de chirurgie cardio-thoracique, 264, rue Saint-Pierre, 13385 Marseille cedex 05, France
| | - Patrick Borentain
- Assistance publique - hôpitaux de Marseille (AP-HM), centre hospitalo-universitaire Timone, service d'hépatologie-gastrologie-entérologie, 264, rue Saint-Pierre, 13385 Marseille cedex 05, France
| | - Philippe Colson
- Aix-Marseille université, institut de recherche pour le développement (IRD), Assistance publique - hôpitaux de Marseille (AP-HM), microbes, evolution, phylogeny and infection (MEΦI), institut hospitalo-universitaire (IHU) - Méditerranée Infection, 19-21, boulevard Jean-Moulin, 13005 Marseille, France.
| |
Collapse
|
|
39
|
Vollmer T, Diekmann J, Knabbe C, Dreier J. Hepatitis E virus blood donor NAT screening: as much as possible or as much as needed? Transfusion 2018; 59:612-622. [PMID: 30548866 DOI: 10.1111/trf.15058] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 09/16/2018] [Accepted: 10/18/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND The cost-benefit question of general screening of blood products for the hepatitis E virus (HEV) is currently being discussed. One central question is the need for individual nucleic acid amplification techniques (NAT) screening (ID-NAT) versus minipool NAT screening (MP-NAT) approaches to identify all relevant viremias in blood donors. Here, the findings of ID-NAT versus MP-NAT in pools of 96 samples were compared. STUDY DESIGN AND METHODS From November 2017 to January 2018, a total of 10,141 allogenic blood donations from 7650 individual German blood donors were screened for the presence of HEV RNA using MP-NAT (96 samples) (RealStar HEV RT-PCR Kit) compared to ID-NAT (cobas HEV assay) on the fully automated cobas 6800 platform. RESULTS Parallel screening of MP (n = 122, 96 samples/MP) using both methods detected seven reactive pools. After pool resolution, 8 HEV RNA-positive donations were identified by the in-house detection method, whereas 17 HEV RNA-positive donations were identified by ID-NAT with the cobas HEV assay. This resulted in an incidence of 1:1268 donations (0.079%) for MP-NAT screening and 1:597 donations (0.168%) for ID-NAT screening. CONCLUSIONS The detection frequency of HEV RNA was approximately 50% higher if ID-NAT was used compared to MP-NAT. However, viral loads of ID-NAT-only samples were below 25 IU/mL and will often not result in transfusion-transmitted HEV (TT-HEV) infection, taking into account the currently known infectious dose of 5.0E + 04 IU inevitably resulting in TT-HEV infection. The clinical relevance and need for identification of these low-level HEV-positive donors still require further investigation.
Collapse
Affiliation(s)
- T Vollmer
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein- Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| | - J Diekmann
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein- Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| | - C Knabbe
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein- Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| | - J Dreier
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein- Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| |
Collapse
|
|
40
|
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.
Collapse
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
| |
Collapse
|
|
41
|
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.
Collapse
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
| |
Collapse
|
|
42
|
Nouhin J, Madec Y, Prak S, Ork M, Kerleguer A, Froehlich Y, Pavio N, Rouet F. Declining hepatitis E virus antibody prevalence in Phnom Penh, Cambodia during 1996-2017. Epidemiol Infect 2018; 147:e26. [PMID: 30309396 PMCID: PMC6518538 DOI: 10.1017/s0950268818002790] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Revised: 09/06/2018] [Accepted: 09/18/2018] [Indexed: 12/27/2022] Open
Abstract
Hepatitis E virus (HEV) infection is endemic in Cambodia. However, little relevant data were available and there is no clue if HEV is an emerging or decreasing pathogen in that setting. The aim of our study was to describe temporal trends of anti-HEV IgG and IgM prevalences during the last two decades (1996-2017) in the context of population growth and urbanisation in Cambodia. A total of 2004 human plasma samples collected between 1996 and 2017 were tested for anti-HEV IgG and IgM using the commercial Wantai anti-HEV assays. Overall, the prevalences of anti-HEV IgG and IgM were 41.1% and 2.7%, respectively. Analysis by calendar period showed a decreasing trend of anti-HEV IgG prevalence over the last 21 years. After age- and gender-standardisation, the anti-HEV IgG prevalence rates decreased from 61.3% during the 1996-2000 period to 32.3% during the 2016-2017 period, but no trends were observed for anti-HEV IgM rates, which fluctuated around the overall one. In conclusion, our results suggest that HEV is not an emerging pathogen, but rather seems to circulate less in Cambodia, in particular, in Phnom Penh, since the prevalence of anti-HEV IgG has been significantly decreased during the past two decades.
Collapse
Affiliation(s)
- J. Nouhin
- Virology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia
| | - Y. Madec
- Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France
| | - S. Prak
- Virology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia
| | - M. Ork
- Virology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia
| | - A. Kerleguer
- Medical Laboratory, Institut Pasteur du Cambodge, Phnom Penh, Cambodia
| | - Y. Froehlich
- Epidemiology and Public Health Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia
| | - N. Pavio
- UMR 1161 Virologie, Anses Laboratoire de Santé Animale, Maisons-Alfort, France
| | - F. Rouet
- Virology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia
| |
Collapse
|
|
43
|
Hepatitis E in High-Income Countries: What Do We Know? And What Are the Knowledge Gaps? Viruses 2018; 10:v10060285. [PMID: 29799485 PMCID: PMC6024799 DOI: 10.3390/v10060285] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Revised: 05/16/2018] [Accepted: 05/23/2018] [Indexed: 12/11/2022] Open
Abstract
Hepatitis E virus (HEV) is a positive-strand RNA virus transmitted by the fecal–oral route. HEV genotypes 1 and 2 infect only humans and cause mainly waterborne outbreaks. HEV genotypes 3 and 4 are widely represented in the animal kingdom, and are mainly transmitted as a zoonosis. For the past 20 years, HEV infection has been considered an imported disease in developed countries, but now there is evidence that HEV is an underrecognized pathogen in high-income countries, and that the incidence of confirmed cases has been steadily increasing over the last decade. In this review, we describe current knowledge about the molecular biology of HEV, its clinical features, its main routes of transmission, and possible therapeutic strategies in developed countries.
Collapse
|
|
44
|
Shindo M, Takemae H, Kubo T, Soeno M, Ando T, Morishita Y. Acute hepatitis E in a renal transplantation recipient: a case report. Int Med Case Rep J 2018; 11:77-80. [PMID: 29670408 PMCID: PMC5896657 DOI: 10.2147/imcrj.s163865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Hepatitis E is caused by infection with the hepatitis E virus (HEV). HEV is transmitted orally via HEV-contaminated food or drink. Hepatitis E usually shows mild symptoms and is self-limiting in the general population; however, it may progress to chronic hepatitis in immunosuppressed patients such as recipients of organ transplantation. However, a few cases of acute hepatitis E have been reported in organ transplantation recipients. We herein report a case of acute hepatitis E in a 31-year-old male renal transplant recipient. The patient underwent renal transplantation 2 years ago, and his postoperative course was uneventful without rejection. After complaining of general fatigue and low-grade fever for 1 week, he was referred to and admitted to our hospital. Careful interview revealed that he ate undercooked pork 10 weeks prior. Blood analysis revealed liver dysfunction but was serologically negative for hepatitis A, B and C virus, cytomegalovirus infection and collagen diseases. Immunoglobulin A antibody against hepatitis E virus (HEV-IgA) was also negative at that point. After 2 weeks of admission, HEV-IgA and HEV-RNA were measured again as hepatitis E could not be ruled out due to history of ingestion of undercooked meat that may have been contaminated with HEV. At that time, HEV-IgA and HEV-RNA (genotype 3) were positive. Thus, an acute hepatitis E was diagnosed. His liver function gradually improved to within the normal range, and HEV-IgA and HEV-RNA were negative at 11 weeks after admission. In conclusion, we describe here a case of acute hepatitis E in a renal transplant recipient. Careful interview regarding the possibility of ingestion of HEV-contaminated food and repeated measurements of HEV-IgA were helpful in finalizing a diagnosis.
Collapse
Affiliation(s)
- Mitsutoshi Shindo
- Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Saitama, Japan
| | - Hiroaki Takemae
- Department of Dialysis and Transplant Surgery, Hidaka Hospital, Gunma, Japan
| | - Takafumi Kubo
- Department of Dialysis and Transplant Surgery, Hidaka Hospital, Gunma, Japan
| | - Masatsugu Soeno
- Department of Dialysis and Transplant Surgery, Hidaka Hospital, Gunma, Japan
| | - Tetsuo Ando
- Department of Dialysis and Transplant Surgery, Hidaka Hospital, Gunma, Japan
| | - Yoshiyuki Morishita
- Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Saitama, Japan
| |
Collapse
|
|
45
|
von Wulffen M, Westhölter D, Lütgehetmann M, Pischke S. Hepatitis E: Still Waters Run Deep. J Clin Transl Hepatol 2018; 6:40-47. [PMID: 29577031 PMCID: PMC5862998 DOI: 10.14218/jcth.2017.00030] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2017] [Accepted: 08/19/2017] [Indexed: 12/11/2022] Open
Abstract
Hepatitis E is an infectious inflammatory disease of the liver caused by the hepatitis E virus (HEV), a single-stranded RNA virus. Today, it is estimated that there are more than 20 million HEV infections every year, leading to 3.3 million symptomatic cases and more than 56,000 deaths. For a long time it was believed that HEV was a travel-associated disease, endemic in developing countries with poor hygienic standards and unsafe water supply. However, over the past years, publications have demonstrated that autochthonous HEV infections in industrialized countries are far more common than previously thought. Awareness for HEV amongst health care practitioners in industrialized countries is still limited. This relatively rare disease is of great importance, especially in immunocompromised patients where it can cause chronic liver disease. This article comprehensively reviews current literature to give an overview on clinically important topics. It will focus on epidemiological aspects, acute and chronic HEV infection as well as extra-hepatic manifestations, diagnostic approach and treatment options. Furthermore, the article is concluded with a brief outlook on perspectives and urgent problems to be addressed in the future.
Collapse
Affiliation(s)
- Moritz von Wulffen
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Dirk Westhölter
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marc Lütgehetmann
- Institute for Medical Microbiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sven Pischke
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| |
Collapse
|
|
46
|
Ripellino P, Norton B, van Eijk J, Dalton HR. Non-traumatic neurological injury and hepatitis E infection. Expert Rev Anti Infect Ther 2018; 16:255-257. [PMID: 29486136 DOI: 10.1080/14787210.2018.1446827] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Affiliation(s)
- Paolo Ripellino
- a Department of Neurology , Neurocenter of Southern Switzerland , Lugano , Switzerland
| | - Benjamin Norton
- b Department of Medicine , King's College Hospital , London , UK
| | - Jeroen van Eijk
- c Department of Neurology , Jeroen Bosch Hospital , 's-Hertogenbosch , Netherlands
| | - Harry R Dalton
- d Royal Cornwall Hospital and European Centre for the Environment and Human Health , University of Exeter , Truro , UK
| |
Collapse
|
|
47
|
Al-Sadeq DW, Majdalawieh AF, Mesleh AG, Abdalla OM, Nasrallah GK. Laboratory challenges in the diagnosis of hepatitis E virus. J Med Microbiol 2018; 67:466-480. [PMID: 29485390 DOI: 10.1099/jmm.0.000706] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Hepatitis E virus (HEV) is an RNA virus that is an important cause of both acute and chronic hepatitis worldwide. To date, there are eight HEV genotypes that can infect mammals. HEV-1 and HEV-2 infect exclusively humans, while HEV-3 and HEV-4 infect humans and various animals, mainly pigs and deer. Additionally, two new genotypes (HEV-5 and HEV-6) infect mainly wild boar. Recently, newly discovered genotypes HEV-7 and HEV-8 were found to infect camels and possibly humans. Nevertheless, the epidemiological distribution of HEV-7 is not well established. HEV-8 is another newly discovered genotype that was identified in 2016 in Chinese Bactrian camels. Although faecal-oral transmission is the most common route of HEV transmission, HEV can be vertically transmitted from infected mothers to their fetuses. HEV may also spread by zoonotic transmission from infected animals to humans and through person-to-person contact. Nowadays, since the number of reported cases linked to blood donations is increasing annually, HEV is recognized as a transfusion-transmitted virus. Laboratory diagnostic techniques vary in their specificity and sensitivity for HEV detection. Direct techniques allow for detection of the viral proteins, antigens and viral nucleic acid, while HEV-specific IgG and IgM antibodies can help establish a diagnosis in acute and chronic infections. In this review, we will discuss recent technologies in the laboratory diagnosis of HEV, including serological and molecular methods to assess the specificity and sensitivity of currently available HEV commercial assays.
Collapse
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, UAE
| | - Areej G Mesleh
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Omnya M Abdalla
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Gheyath K Nasrallah
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar.,Biomedical Research Center, Qatar University, Doha, Qatar
| |
Collapse
|
|
48
|
Lhomme S, Bardiaux L, Abravanel F, Gallian P, Kamar N, Izopet J. Hepatitis E Virus Infection in Solid Organ Transplant Recipients, France. Emerg Infect Dis 2018; 23:353-356. [PMID: 28098552 PMCID: PMC5324811 DOI: 10.3201/eid2302.161094] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
The rate of transfusion-transmitted hepatitis E virus (HEV) in transplant recipients is unknown. We identified 60 HEV-positive solid organ transplant patients and retrospectively assessed their blood transfusions for HEV. Seven of 60 patients received transfusions; 3 received HEV-positive blood products. Transfusion is not the major route of infection in this population.
Collapse
|
|
49
|
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.
Collapse
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
| |
Collapse
|
|
50
|
Izopet J. [HEV and transfusion-recipient risk]. ANNALES PHARMACEUTIQUES FRANÇAISES 2018; 76:89-96. [PMID: 29395014 DOI: 10.1016/j.pharma.2017.12.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 12/18/2017] [Indexed: 02/06/2023]
Abstract
HEV infections are mainly food- and water-borne but transfusion-transmission has occurred in both developing and developed countries. The infection is usually asymptomatic but it can lead to fulminant hepatitis in patients with underlying liver disease and pregnant women living in developing countries. It also causes chronic hepatitis E, with progressive fibrosis and cirrhosis, in approximately 60 % of immunocompromised patients infected with HEV genotype 3. Extra-hepatic manifestations such as neurological and renal manifestations have been reported. The risk of a transfusion-transmitted HEV infection is linked to the frequency of viremia in blood donors, the donor virus load and the volume of plasma in the final transfused blood component. Several developed countries have adopted measures to improve blood safety based on the epidemiology of HEV.
Collapse
Affiliation(s)
- J Izopet
- Laboratoire de virologie, centre national de référence virus des hépatites à transmission entérique (hépatites A et E), institut fédératif de biologie, CHU de Purpan, 330, avenue de Grande-Bretagne, TSA 40031, 31059 Toulouse, France; Inserm U1043/CNRS 5282, université Paul-Sabatier, centre de physiopathologie de Toulouse-Purpan, 31024 Toulouse cedex 03, France.
| |
Collapse
|