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Oh J, Choi GH, Chang Y, Kim J, Park K, Yeom H, Seo S, Gwack J, Jeong SH. A Silent Outbreak of Hepatitis E Virus (HEV) Infection or False-Positive Reaction of Anti-HEV IgM after COVID-19 Vaccination? Epidemiological Investigation of an Outbreak in a Korean Factory Complex in 2022. Gut Liver 2024; 18:531-538. [PMID: 37800317 PMCID: PMC11096911 DOI: 10.5009/gnl230098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 05/24/2023] [Accepted: 05/29/2023] [Indexed: 10/07/2023] Open
Abstract
Background/Aims To investigate a reported outbreak of presumed hepatitis E virus (HEV) infection in a Korean food manufacturing facility and to explore the association between anti-HEV immunoglobulin M (IgM) positivity and coronavirus disease 2019 (COVID-19) infection or vaccination. Methods Twenty-four cases of anti-HEV IgM positivity were reported among 646 workers at the facility in 2022. An epidemiological investigation was conducted, comprising HEV-RNA testing of blood and environmental samples, analysis of group meal records, and an association between anti-HEV IgM positivity and confirmed COVID-19 infection or vaccination. Results All 24 patients were asymptomatic, with cases spread sporadically across the facility. HEV RNA was not detected in the serum or environmental samples. Four out of 340 meals (1.2%) showed a significantly higher proportion of anti-HEV positivity in each meal intake group than in the non-intake group on certain days. Although the cumulative rate of COVID-19 infection showed no difference, the anti-HEV IgM positive group showed significantly higher proportions of >2 doses of COVID-19 vaccination (83.3% vs 48.7%, p=0.021), vaccination within 90 days (45.8% vs 19.7%, p=0.008), and having the Moderna vaccine administered as the last vaccine (75.0% vs 14.5%, p<0.001) than those of the anti-HEV negative group. In four multivariable models, three or more COVID-19 vaccinations and the Moderna vaccine as the last vaccine were consistently associated with anti-HEV IgM positivity, while the specific day group meal intake was also a significant factor. Conclusions This epidemiological investigation showed that anti-HEV IgM positivity may occur as a false-positive result related to COVID-vaccination over three times and use of the Moderna vaccine, although a portion of true HEV infection may not be excluded.
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Affiliation(s)
- Jeonghyeon Oh
- Gyeonggi Infectious Disease Control Center, Health Bureau, Gyeonggi Provincial Government, Suwon, Korea
| | - Gwang Hyeon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Yeonhwa Chang
- Gyeonggi Infectious Disease Control Center, Health Bureau, Gyeonggi Provincial Government, Suwon, Korea
| | - Jina Kim
- Gyeonggi Infectious Disease Control Center, Health Bureau, Gyeonggi Provincial Government, Suwon, Korea
| | - Kunhee Park
- Gyeonggi Infectious Disease Control Center, Health Bureau, Gyeonggi Provincial Government, Suwon, Korea
| | - Hansol Yeom
- Division of Infectious Disease Control, Korea Disease Control and Prevention Agency, Osong Health Technology Administration Complex, Cheongju, Korea
| | - Soonryu Seo
- Division of Infectious Disease Control, Korea Disease Control and Prevention Agency, Osong Health Technology Administration Complex, Cheongju, Korea
| | - Jin Gwack
- Division of Infectious Disease Control, Korea Disease Control and Prevention Agency, Osong Health Technology Administration Complex, Cheongju, Korea
| | - Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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Jeong CY, Choi GH, Jang ES, Kim YS, Lee YJ, Kim IH, Cho SB, Yoon JH, Kim KA, Choi DH, Chung WJ, Cho HC, Na SK, Kim YT, Lee BS, Jeong SH. Etiology and clinical characteristics of acute viral hepatitis in South Korea during 2020-2021: a prospective multicenter study. Sci Rep 2023; 13:14271. [PMID: 37652984 PMCID: PMC10471758 DOI: 10.1038/s41598-023-40775-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 08/16/2023] [Indexed: 09/02/2023] Open
Abstract
This prospective, 12-center study investigated the etiology and clinical characteristics of acute viral hepatitis (AVH) during 2020-2021 in South Korea, and the performance of different diagnostic methods for hepatitis E virus (HEV). We enrolled 428 patients with acute hepatitis, of whom 160 (37.4%) were diagnosed with AVH according to predefined serologic criteria. The clinical data and risk factors for AVH were analyzed. For hepatitis E patients, anti-HEV IgM and IgG were tested with two commercial ELISA kits (Abia and Wantai) with HEV-RNA real-time RT-PCR. HAV, HEV, HBV, HCV, Epstein-Barr virus (EBV), cytomegalovirus, and herpes simplex virus accounted for AVH in 78.8% (n = 126), 7.5% (n = 12), 3.1% (n = 5), 1.9% (n = 3), 6.9% (n = 11), 1.2% (n = 2), and 0.6% (n = 1) of 160 patients (median age, 43 years; men, 52.5%; median ALT, 2144 IU/L), respectively. Hospitalization, hemodialysis, and intensive care unit admission were required in 137 (86.7%), 5 (3.2%), and 1 (0.6%) patient, respectively. Two patients developed acute liver failure (1.3%), albeit without mortality or liver transplantation. Ingestion of uncooked clams/oysters and wild boars' blood/bile was reported in 40.5% and 16.7% of patients with HAV and HEV, respectively. The concordance rate between the anti-HEV-IgM results of both ELISA kits was 50%. HEV RNA was detected in only 17% of patients with HEV. The diagnosis of HEV needs clinical consideration due to incomplete HEV diagnostics.
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Affiliation(s)
- Chan Young Jeong
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam, 13620, Republic of Korea
| | - Gwang Hyeon Choi
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam, 13620, Republic of Korea
| | - Eun Sun Jang
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam, 13620, Republic of Korea
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea
| | - Youn-Jae Lee
- Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea
| | - In Hee Kim
- Department of Internal Medicine, Jeonbuk National University Hospital, Jeonju, Republic of Korea
| | - Sung Bum Cho
- Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea
| | - Jae Hyun Yoon
- Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - Kyung-Ah Kim
- Departments of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Republic of Korea
| | - Dae Hee Choi
- Departments of Internal Medicine, Kangwon National University Hospital, Chunchon, Republic of Korea
| | - Woo Jin Chung
- Departments of Internal Medicine, Keimyung University Dongsan Hospital, Daegu, Republic of Korea
| | - Hyun Chin Cho
- Departments of Internal Medicine, Gyeongsang National University Hospital, Jinju, Republic of Korea
| | - Seong Kyun Na
- Departments of Internal Medicine, Jeju National University Hospital, Jeju, Republic of Korea
| | - Yun-Tae Kim
- Seoul Clinical Laboratories, Yongin, Republic of Korea
| | - Byung Seok Lee
- Departments of Internal Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, Republic of Korea.
| | - Sook-Hyang Jeong
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam, 13620, Republic of Korea.
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Kogias D, Skeva A, Smyrlis A, Mourvati E, Kantartzi K, Romanidou G, Kalientzidou M, Rekari V, Konstantinidou E, Kiorteve P, Paroglou I, Papadopoulos V, Konstantinidis T, Panopoulou M, Mimidis K. Hepatitis E Virus (HEV) Infection in Hemodialysis Patients: A Multicenter Epidemiological Cohort Study in North-Eastern Greece. Pathogens 2023; 12:667. [PMID: 37242337 PMCID: PMC10222133 DOI: 10.3390/pathogens12050667] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 04/24/2023] [Accepted: 04/27/2023] [Indexed: 05/28/2023] Open
Abstract
Hepatitis E virus (HEV), a common cause of viral hepatitis in developing countries, is mainly transmitted via the fecal-oral route, but also may be a prevalent hospital-transmitted agent among patients on regular hemodialysis due to parenteral transmission. Previous epidemiological studies among hemodialysis patients in Greece, using different diagnostic techniques, gave conflicting results. Τhe present study aimed to measure the exposure rate of hemodialysis patients of north-eastern Greece to HEV by estimating the overall seroprevalence, and to identify potential risk factors. Serum samples from all patients attending the hemodialysis centers of north-eastern Greece (n = 6) were tested for the presence of anti-HEV IgG antibodies using a modern and sensitive ELISA (Enzyme-linked Immunosorbent Assay) technique (Wantai). In total, 42 out of 405 hemodialysis patients were positive for anti-HEV IgG (10.4%), while all samples were negative for HEV RNA when tested using nested RT-PCR. HEV seropositivity among hemodialysis patients was significantly associated with area of residence and contact with specific animals (pork, deer). No association was found with religion, gender distribution and hemodialysis duration. This study showed an increased seroprevalence of HEV among hemodialysis patients in Greece. Agricultural or livestock occupation and place of residence seem to be independent factors that increase the risk of HEV infection. In conclusion, HEV infection calls for the regular screening of hemodialysis patients regardless of the hemodialysis duration or clinical symptoms.
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Affiliation(s)
- Dionysios Kogias
- First Department of Internal Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece;
| | - Aikaterini Skeva
- Laboratory of Microbiology, Department of Medicine, Faculty of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (M.P.)
| | - Andreas Smyrlis
- Department of Nephrology, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (E.M.); (K.K.)
| | - Efthymia Mourvati
- Department of Nephrology, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (E.M.); (K.K.)
| | - Konstantinia Kantartzi
- Department of Nephrology, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (E.M.); (K.K.)
| | - Gioulia Romanidou
- Nephrology Department, General Hospital “Sismanogleio”, 69100 Komotini, Greece;
| | - Maria Kalientzidou
- Department of Nephrology, General Hospital of Kavala, 65500 Kavala, Greece;
| | - Vasiliki Rekari
- Blood Transfusion Center, General Hospital of Xanthi, 67100 Xanthi, Greece;
| | | | - Parthena Kiorteve
- Nephrology Department, General Hospital of Drama, 66100 Drama, Greece;
| | - Ioannis Paroglou
- Nephrology Department, General Hospital of Didymoteicho, 68300 Didymoteicho, Greece;
| | | | - Theocharis Konstantinidis
- Blood Transfusion Center, University General Hospital of Alexandroupolis and Laboratory of Microbiology, Democritus University of Thrace, 68100 Alexandroupolis, Greece;
| | - Maria Panopoulou
- Laboratory of Microbiology, Department of Medicine, Faculty of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (M.P.)
| | - Konstantinos Mimidis
- First Department of Internal Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece;
- Laboratory for the Study of Gastrointestinal System and Liver, Democritus University of Thrace, 68100 Alexandroupolis, Greece
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Yeom H, Seo S, Yoon Y, Lee J, Han MG, Lee DY, Park SW, Park SA, Jeong SH, Gwack J. The first reported hepatitis E outbreak in a food manufacturing factory: Korea, 2022. Osong Public Health Res Perspect 2023; 14:15-22. [PMID: 36944341 DOI: 10.24171/j.phrp.2022.0305] [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: 12/02/2022] [Accepted: 01/30/2023] [Indexed: 02/24/2023] Open
Abstract
OBJECTIVES On February 16, 2022, 12 cases of hepatitis E virus (HEV) infection were reported in a food manufacturing factory in Korea. The aim of this study was to identify additional cases and to determine the source of this HEV outbreak. METHODS This study was an in-depth investigation of 12 HEV immunoglobulin M (IgM)-positive cases and their demographic, clinical, and epidemiological characteristics. On-site specimens were collected from the environment and from humans, and a follow-up investigation was conducted 2 to 3 months after the outbreak. RESULTS Among 80 production workers in the factory, 12 (15.0%) had acute HEV infection, all of whom were asymptomatic. The follow-up investigation showed that 3 cases were HEV IgMpositive, while 6 were HEV IgG-positive. HEV genes were not detected in the HEV IgM-positive specimens. HEV genes were not detected in the food products or environmental specimens collected on-site. HEV was presumed to be the causative pathogen. However, it could not be confirmed that the source of infection was common consumption inside the factory. CONCLUSIONS This was the first domestic case of an HEV infection outbreak in a food manufacturing factory in Korea. Our results provide information for the future control of outbreaks and for the preparation of measures to prevent domestic outbreaks of HEV infection.
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Affiliation(s)
- Hansol Yeom
- Division of Infectious Disease Response, Capital Regional Center for Disease Control and Prevention, Seoul, Korea
| | - Soonryu Seo
- Division of Infectious Disease Control, Bureau of Infectious Disease Policy, Korea Disease Control and Prevention Agency, Cheongju, Korea
| | - Youngsil Yoon
- Division of Infectious Disease Control, Bureau of Infectious Disease Policy, Korea Disease Control and Prevention Agency, Cheongju, Korea
| | - Jaeeun Lee
- Division of Immunization, Bureau of Healthcare Safety and Immunization, Korea Disease Control and Prevention Agency, Cheongju, Korea
| | - Myung-Guk Han
- Division of Viral Disease, Bureau of Infectious Disease Diagnosis Control, Korea Disease Control and Prevention Agency, Cheongju, Korea
| | - Deog-Yong Lee
- Division of Viral Disease, Bureau of Infectious Disease Diagnosis Control, Korea Disease Control and Prevention Agency, Cheongju, Korea
| | - Sun-Whan Park
- Division of Viral Disease, Bureau of Infectious Disease Diagnosis Control, Korea Disease Control and Prevention Agency, Cheongju, Korea
| | - Song A Park
- Division of Viral Disease, Bureau of Infectious Disease Diagnosis Control, Korea Disease Control and Prevention Agency, Cheongju, Korea
| | - Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Jin Gwack
- Division of Infectious Disease Control, Bureau of Infectious Disease Policy, Korea Disease Control and Prevention Agency, Cheongju, Korea
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Wong LP, Tay ST, Chua KH, Goh XT, Alias H, Zheng Z, Zhao Q, Wu T, Xia N, Hu Z, Lin Y. Serological Evidence of Hepatitis E Virus (HEV) Infection Among Ruminant Farmworkers: A Retrospective Study from Malaysia. Infect Drug Resist 2022; 15:5533-5541. [PMID: 36164335 PMCID: PMC9508706 DOI: 10.2147/idr.s367394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 05/27/2022] [Indexed: 11/23/2022] Open
Abstract
Background As scant data are available about Hepatitis E virus (HEV) infection in Malaysia, this study aimed to determine the seroprevalence of HEV amongst ruminant farmworkers in Malaysia. Methods A total of 87 farmworkers provided serum samples, which were collected from eight farms. All serum samples were tested for anti-HEV IgG and anti-HEV IgM by an enzyme-linked immunosorbent assay (ELISA) using the Wantai HEV-IgG and HEV-IgM ELISA kits from Beijing Wantai Biological Pharmacy Enterprise Co., Ltd, Beijing, China. Results Farmworkers from six cattle farms, one sheep farm and one goat farm were investigated in this study. Only one farm practices zero-grazing, with the rest using rotational grazing. Of the 87 farmworkers, males comprised 83.9%, and almost half (47.1%) were aged 20-35 years old. By ethnic group, the vast majority were Malay. Most of the farmworkers have good hygiene practices; washing or changing their clothes and showering after dealing with farm animals were common. None of the farmworker serum samples had anti-HEV IgM and IgG detected (95% confidence interval (CI): 0, 0.0415). Conclusion The finding suggests that the farmworkers had no previous exposure to Hepatitis E, and were not at risk of occupational exposure to HEV infection. Our findings suggest that a zero seroprevalence of HEV infection among ruminant farmworkers in the Muslim majority country. Good farm management, hygiene practices and the absence of contact with swine-related contamination might have contributed to the no or minimal zoonotic risks of HEV amongst farmworkers surveyed in this study.
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Affiliation(s)
- Li Ping Wong
- Centre for Epidemiology and Evidence-Based Practice, Department of Social and Preventive Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia.,Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, Fujian, 350122, People's Republic of China
| | - Sun Tee Tay
- Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia
| | - Kek Heng Chua
- Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia
| | - Xiang Ting Goh
- Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia
| | - Haridah Alias
- Centre for Epidemiology and Evidence-Based Practice, Department of Social and Preventive Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia
| | - 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, 361102, People's Republic of China
| | - Qinjian Zhao
- College of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China
| | - Ting Wu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, 361102, People's Republic of 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, 361102, People's Republic of China.,The Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, 361102, People's Republic of China
| | - Zhijian Hu
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, Fujian, 350122, People's Republic of China
| | - Yulan Lin
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, Fujian, 350122, People's Republic of China
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Choi JW, Son HJ, Lee SS, Jeon H, Cho JK, Kim HJ, Cha RR, Lee JM, Kim HJ, Jung WT, Lee OJ. Acute hepatitis E virus superinfection increases mortality in patients with cirrhosis. BMC Infect Dis 2022; 22:62. [PMID: 35042464 PMCID: PMC8767750 DOI: 10.1186/s12879-022-07050-w] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 01/12/2022] [Indexed: 12/20/2022] Open
Abstract
Background Although acute hepatitis E is not fatal in healthy individuals, it is unclear whether hepatitis E superinfection increases the mortality in patients with pre-existing liver disease. Thus, we investigated the prognosis of patients with acute hepatitis E according to their cirrhosis diagnosis, and the prognosis according to the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis and chronic liver disease (CLD).
Methods This study included 74 consecutive patients who were diagnosed with acute viral hepatitis E between January 2007 and December 2019. Of them, 39 patients without CLD, 13 patients with non-cirrhotic CLD, and 22 patients with cirrhotic CLD were analyzed.
Results Among the 74 patients with HEV infection, 7 (9.5%) died within 180 days: 5 with underlying cirrhosis (71.4%) and 2 without cirrhosis (28.6%). The 180-day mortality was significant higher for patients with cirrhosis than for patients without cirrhosis (22.7% vs. 3.8%, P = 0.013). The age- and sex-adjusted proportional-hazard model revealed an approximately eightfold increase in the 180-day mortality risk in patients with cirrhosis compared to patients without cirrhosis. In addition, development of hepatitis E virus-related ACLF due to acute liver function deterioration in patients with pre-existing CLD or cirrhosis worsened the 180-day mortality rate. Conclusions Our findings suggest that the acute hepatitis E mortality rate was low in healthy individuals but higher in patients with cirrhosis, and especially high in those with ACLF. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-022-07050-w.
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Cheung CKM, Wong SH, Law AWH, Law MF. Transfusion-transmitted hepatitis E: What we know so far? World J Gastroenterol 2022; 28:47-75. [PMID: 35125819 PMCID: PMC8793017 DOI: 10.3748/wjg.v28.i1.47] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 07/16/2021] [Accepted: 12/22/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) is a major cause of viral hepatitis globally. There is growing concern about transfusion-transmitted HEV (TT-HEV) as an emerging global health problem. HEV can potentially result in chronic infection in immunocompromised patients, leading to a higher risk of liver cirrhosis and even death. Between 0.0013% and 0.281% of asymptomatic blood donors around the world have HEV viremia, and 0.27% to 60.5% have anti-HEV immunoglobulin G. HEV is infectious even at very low blood concentrations of the virus. Immunosuppressed patients who develop persistent hepatitis E infection should have their immunosuppressant regimen reduced; ribavirin may be considered as treatment. Pegylated interferon can be considered in those who are refractory or intolerant to ribavirin. Sofosbuvir, a nucleotide analog, showed modest antiviral activity in some clinical studies but sustained viral response was not achieved. Therefore, rescue treatment remains an unmet need. The need for HEV screening of all blood donations remains controversial. Universal screening has been adopted in some countries after consideration of risk and resource availability. Various pathogen reduction methods have also been proposed to reduce the risk of TT-HEV. Future studies are needed to define the incidence of transmission through transfusion, their clinical features, outcomes and prognosis.
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Affiliation(s)
| | - Sunny Hei Wong
- Institute of Digestive Disease and Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong 852, China
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 639798, Singapore
| | | | - Man Fai Law
- Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
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Dichtl K, Zimmermann J, Koeppel MB, Böhm S, Osterman A. Evaluation of a Novel CLIA Monotest Assay for the Detection of Anti-Hepatitis E Virus-IgG and IgM: A Retrospective Comparison with a Line Blot and an ELISA. Pathogens 2021; 10:pathogens10060689. [PMID: 34206114 PMCID: PMC8228023 DOI: 10.3390/pathogens10060689] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 05/25/2021] [Accepted: 05/28/2021] [Indexed: 12/27/2022] Open
Abstract
Despite the increasing relevance of Hepatitis E, an emerging disease endemic in developing and with increasing numbers of sporadic cases in industrialized countries, commercial tests are mainly based on batch oriented serological assays. In this retrospective study, we compared a line immunoassay (LIA; recomLine HEV, Mikrogen) and an ELISA (EIA; Anti-Hepatitis E Virus ELISA, Euroimmun) with a novel chemoluminescence immunoassay in a monotest format (CLIA; Hepatitis E VirClia, Vircell). Twenty sera of PCR proven cases of hepatitis E and 68 blood samples serologically pre-characterized were included. Applying the WHO reference standard, the CLIA demonstrated the highest analytical sensitivity for IgG and IgM. The combinations of CLIA/EIA (IgG and IgM) and CLIA/LIA (IgG) measurements showed substantial correlation. Compared to overall antibody detection (seropositivity in ≥2 assays), CLIA correlation was excellent, outperforming LIA (IgM) and EIA (IgG and IgM). Minor IgM cross reactivity in samples of patients with acute EBV infection was observed in all three assays. The CLIA showed good performance in diagnostic samples compared to established LIA and EIA assays. Due to its ready-to-use monotest format, the CLIA allows simple, time- and cost-effective handling of single samples. These qualities make the assay suitable for diagnostics, especially in the emergency setting and for low-throughput laboratories.
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Affiliation(s)
- Karl Dichtl
- Chair of Medical Microbiology and Hospital Epidemiology, Faculty of Medicine, Max von Pettenkofer-Institute, LMU Munich, D-80336 München, Germany; (K.D.); (J.Z.)
| | - Julia Zimmermann
- Chair of Medical Microbiology and Hospital Epidemiology, Faculty of Medicine, Max von Pettenkofer-Institute, LMU Munich, D-80336 München, Germany; (K.D.); (J.Z.)
- Chair of Virology, National Reference Center for Retroviruses, Faculty of Medicine, Max von Pettenkofer Institut, LMU München, D-80336 München, Germany;
- German Center for Infection Research (DZIF), Partner Site Munich, D-80539 Munich, Germany
| | | | - Stephan Böhm
- Chair of Virology, National Reference Center for Retroviruses, Faculty of Medicine, Max von Pettenkofer Institut, LMU München, D-80336 München, Germany;
- German Center for Infection Research (DZIF), Partner Site Munich, D-80539 Munich, Germany
| | - Andreas Osterman
- Chair of Virology, National Reference Center for Retroviruses, Faculty of Medicine, Max von Pettenkofer Institut, LMU München, D-80336 München, Germany;
- German Center for Infection Research (DZIF), Partner Site Munich, D-80539 Munich, Germany
- Correspondence:
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9
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Capai L, Hozé N, Chiaroni J, Gross S, Djoudi R, Charrel R, Izopet J, Bosseur F, Priet S, Cauchemez S, de Lamballerie X, Falchi A, Gallian P. Seroprevalence of hepatitis E virus among blood donors on Corsica, France, 2017. ACTA ACUST UNITED AC 2020; 25. [PMID: 32046820 PMCID: PMC7014670 DOI: 10.2807/1560-7917.es.2020.25.5.1900336] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Background Hepatitis E virus (HEV) is an emerging zoonotic pathogen and an important cause of acute viral hepatitis in European countries. Corsica Island has been previously identified as a hyperendemic area for HEV. Aim Our aim was to characterise the prevalence and titres of IgG antibodies to HEV among blood donors on Corsica and establish a model of the annual force of infection. Methods Between September 2017 and January 2018, 2,705 blood donations were tested for anti-HEV IgG using the Wantai HEV IgG enzyme immunoassay. Results The overall seroprevalence was 56.1%. In multivariate analysis, seroprevalence was higher in men than in women (60.0% vs 52.2%; p < 0.01), increased with age and was significantly higher among donors born on Corsica (60.6% vs 53.2%; p < 0.01). No significant difference was observed between the five districts of the island. IgG anti-HEV titres were mostly low (70% of positive donors had titres < 3 IU/mL). In Corsican natives, increasing seroprevalence by age could be explained by models capturing a loss of immunity (annual probability of infection: 4.5%; duration of immunity: 55 years) or by age-specific probabilities of infection (3.8% for children, 1.3% for adults). Conclusion We confirmed the high HEV seroprevalence on Corsica and identified three aspects that should be further explored: (i) the epidemiology in those younger than 18 years, (ii) common sources of contamination, in particular drinking water, that may explain the wide exposure of the population, and (iii) the actual protection afforded by the low IgG titres observed and the potential susceptibility to secondary HEV infection.
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Affiliation(s)
- Lisandru Capai
- EA 7310, Laboratoire de Virologie, Université de Corse, Corte, France
| | - Nathanaël Hozé
- Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, UMR2000, CNRS, Paris, France
| | - Jacques Chiaroni
- Etablissement Français du Sang Provence alpes Côte d'Azur et Corse, Marseille, France
| | - Sylvie Gross
- Etablissement Français du Sang, 93210, La Plaine-Saint-Denis, France
| | - Rachid Djoudi
- Etablissement Français du Sang, 93210, La Plaine-Saint-Denis, France
| | - Rémi Charrel
- Unité des Virus Émergents (UVE): Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France
| | - Jacques Izopet
- Institut National de la Santé et de la Recherche Médicale Unité 1043, Université Toulouse III, Toulouse, France.,Laboratoire de Virologie, Institut Fédératif de Biologie, Centre Hospitalier et Universitaire, Toulouse, France
| | - Frédéric Bosseur
- Sciences Pour l'Environnement - UMR CNRS 6134 Université de Corse, Corte, France
| | - Stéphane Priet
- Unité des Virus Émergents (UVE): Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France
| | - Simon Cauchemez
- Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, UMR2000, CNRS, Paris, France
| | - Xavier de Lamballerie
- Unité des Virus Émergents (UVE): Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France
| | - Alessandra Falchi
- EA 7310, Laboratoire de Virologie, Université de Corse, Corte, France
| | - Pierre Gallian
- Unité des Virus Émergents (UVE): Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France.,Etablissement Français du Sang, 93210, La Plaine-Saint-Denis, France.,Etablissement Français du Sang Provence alpes Côte d'Azur et Corse, Marseille, France
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10
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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: 30] [Impact Index Per Article: 6.0] [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
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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
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11
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Thodou V, Bremer B, Anastasiou OE, Cornberg M, Maasoumy B, Wedemeyer H. Performance of Roche qualitative HEV assay on the cobas 6800 platform for quantitative measurement of HEV RNA. J Clin Virol 2020; 129:104525. [PMID: 32623349 DOI: 10.1016/j.jcv.2020.104525] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Revised: 06/17/2020] [Accepted: 06/22/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatitis E virus (HEV) infection is an increasingly recognized cause of acute and chronic hepatitis in high-income countries and is the most frequent cause of acute viral hepatitis in many European countries. Appropriate tools to detect and quantify HEV RNA are needed. This study aimed to evaluate the performance of the Roche cobas® HEV assay and compare it with the Fast Track Diagnostics (FTD) Hepatitis E RNA assay. METHODS HEV viral load determination and lower limit of detection (LOD, defined as the lowest amount of viral copies that could be detected in 95 % of repeats) were assessed using a WHO standard dilution panel, testing 240 samples of various concentrations. Reproducibility was tested at three different concentration levels, for different genotypes, and with different sample types (serum, plasma) in 30 samples. Sample stability was analyzed after three freeze/thaw cycles in 25 samples. RESULTS Cobas HEV assay showed a strong linear relationship between log of HEV WHO dilution series and Ct values over the reportable range from 200-5000 IU/mL HEV RNA copies. The amplification efficiency was higher than 92 %. LOD was 22 IU/mL (95 % CI: 17.4-31.8) and reproducibility tests showed a 100 % nucleic acid test (NAT) reactivity of cobas HEV for WHO dilution series (range 200-5000 IU/mL, n = 90). Cobas HEV assay detected all different HEV genotypes from biobank samples irrespective of the sample type. NAT reactivity of cobas HEV was not affected by three freeze/thaw cycles. CONCLUSIONS Roche cobas HEV assay is a powerful NAT tool in terms of robustness, reproducibility and linearity. It is a feasible alternative for high-volume testing.
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Affiliation(s)
- Viktoria Thodou
- Dept. of Gastroenterology and Hepatology, Essen University Hospital, German Center for Infection Research, Germany.
| | - Birgit Bremer
- Dept. of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany
| | - Olympia E Anastasiou
- Dept. of Gastroenterology and Hepatology & Institute of Virology, Essen University Hospital, Germany
| | - Markus Cornberg
- Dept. of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Center for Individualized Infection Medicine, Helmholotz Institute for Infection Research, Braunschweig, Hannover, Germany
| | - Benjamin Maasoumy
- Dept. of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany
| | - Heiner Wedemeyer
- Dept. of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Dept. of Gastroenterology and Hepatology, Essen University Hospital, German Center for Infection Research, Germany
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12
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Zhang Q, Zong X, Li D, Lin J, Li L. Performance Evaluation of Different Commercial Serological Kits for Diagnosis of Acute Hepatitis E Viral Infection. Pol J Microbiol 2020; 69:217-222. [PMID: 32548990 PMCID: PMC7324857 DOI: 10.33073/pjm-2020-025] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Revised: 05/04/2020] [Accepted: 05/09/2020] [Indexed: 12/24/2022] Open
Abstract
Clinical diagnosis of hepatitis E viral (HEV) infection mainly relies on serological assays, and the current status of misdiagnoses regarding HEV infection is uncertain. In this study, patients with acute HEV infection were tested for anti-HEV IgM and IgG, a HEV antigen (Ag), and viral loads (HEV RNA). Serology was performed using four commercial HEV ELISA kits: Wantai, Kehua, Lizhu, and Genelabs IgM and IgG. The HEV RNA was detected using RT-PCR assays. The sensitivities of different kits for anti-HEV IgM ranged from 82.6% to 86%. Each kit for anti-HEV IgM was highly specific (97.8–100%). The sensitivities of all kits to detect anti-HEV IgG with (87.2–91.9%) had a substantial agreement, but the Kehua and Genelabs tests were more specific than the Wantai and Lizhu tests. The Wantai tests for the HEV Ag and HEV RNA were also important for acute HEV infections (Kappa = 0.787). Furthermore, a total of 6.98% of HEV infections were positive for HEV RNA but negative for both the HEV Ag and anti-HEV antibodies of IgM and IgG classes. Our findings demonstrate that the diagnosis of hepatitis E may be missed if only serological assays are used. Thus, a combination of serological and nucleic acid testing provides the optimal sensitivity and specificity to the diagnostic process.
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Affiliation(s)
- Qiang Zhang
- Department of Clinical Laboratory , Branch of Tianjin Third Central Hospital , Tianjin , China
| | - Xiaolong Zong
- Department of Clinical Laboratory , The Second Hospital of Tianjin Medical University , Tianjin , China
| | - Dongming Li
- Department of Clinical Laboratory , Tianjin Third Central Hospital , Tianjin , China
| | - Jing Lin
- Department of Clinical Laboratory , Branch of Tianjin Third Central Hospital , Tianjin , China
| | - Lihua Li
- Department of Clinical Laboratory , Branch of Tianjin Third Central Hospital , Tianjin , China
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13
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Janahi EM, Parkar SFD, Mustafa S, Eisa ZM. Implications of Hepatitis E Virus in Blood Transfusions, Hemodialysis, and Solid Organ Transplants. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:E206. [PMID: 32344807 PMCID: PMC7279256 DOI: 10.3390/medicina56050206] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 04/19/2020] [Accepted: 04/21/2020] [Indexed: 01/05/2023]
Abstract
Hepatitis E Virus (HEV) is emerging as the primary cause of acute viral hepatitis in humans. The virus is commonly transmitted by the fecal-oral route via contaminated water in endemic regions or through the consumption of inadequately cooked swine products or game meats in industrialized regions. HEV genotypes 1 and 2 are predominantly associated with waterborne transmission in developing countries, whereas HEV3 and HEV4 are mainly zoonotically transmitted in industrialized countries. Seroprevalence in populations determined by detecting anti-HEV antibodies and serum HEV RNA is commonly used to analyze the presence of HEV. Although HEV RNA-based detection is now standardized, there is a lack of agreement between the assaying methods used for gathering seroprevalence data. Since 2004, HEV has been considered as a transmissible infectious agent through blood transfusion. Recent seroprevalence studies in European countries indicate an underestimated risk for blood transfusion and hence warrant testing the blood supply. HEV infection is usually self-limiting and spontaneously cleared. However, in about 60% of recipients of solid organ transplants, HEV progresses to chronic hepatitis. Immunosuppressive drugs such as tacrolimus are a major cause of chronic hepatitis and reducing its dosage results in viral clearance in about 30% of patients. In hemodialysis patients, the parenteral route is implicated as an important mechanism of transmission. In this review, we explore the clinical and epidemiological characteristics of various HEV genotypes in blood donors, hemodialysis patients, and transplant recipients.
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Affiliation(s)
- Essam M. Janahi
- Department of Biology, College of Science, University of Bahrain, Sakhir 32038, Bahrain; (S.F.D.P.); (S.M.)
| | - Saba F. D. Parkar
- Department of Biology, College of Science, University of Bahrain, Sakhir 32038, Bahrain; (S.F.D.P.); (S.M.)
| | - Sakina Mustafa
- Department of Biology, College of Science, University of Bahrain, Sakhir 32038, Bahrain; (S.F.D.P.); (S.M.)
| | - Zaki M. Eisa
- The National Center for Disease Prevention and Control, Jazan 82722-2476, Saudi Arabia;
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14
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Arce LP, Müller MF, Martinez A, Baiker A, Marranzino G, Agote F, Vizoso-Pinto MG. A Novel In-House Enzyme-Linked Immunosorbent Assay for Genotype 3 Hepatitis E Virus Reveals High Seroprevalence in Blood Donors in Northern Argentina. Front Microbiol 2019; 10:2481. [PMID: 31736916 PMCID: PMC6838658 DOI: 10.3389/fmicb.2019.02481] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Accepted: 10/15/2019] [Indexed: 12/19/2022] Open
Abstract
The Hepatitis E virus (HEV) is an emergent virus that causes acute hepatitis in immunocompetent hosts and chronic hepatitis in immunocompromised hosts. In Latin America, the main circulating genotype HEV-3 is usually of zoonotic origin. Diagnosis and seroprevalence studies mainly rely on the detection of specific antibodies. There are scarce data on the seroprevalence of HEV infection in Latin America mainly due to the lack of awareness of HEV circulation. Furthermore, in some countries, like Argentina, HEV testing is not included in routine assays. In order to provide tools to deepen the knowledge on HEV epidemiology in South America, we designed a new in-house ELISA based on the native recombinant protein ORF2 aa112–608 and demonstrated its potential for detecting anti-HEV immunoglobulin G (IgG) in human serum samples. The following conditions were determined: an optimal antigen concentration of 0.25 μg/ml, a serum dilution of 1:80, gelatin as a blocking agent, and a secondary antibody dilution of 1:2000. A relative sensitivity of 93.33% (95% CI: 77.9–99.2%) and a relative specificity of 99.4% (95% CI: 96.7–100%) were determined using a panel of previously characterized sera and a gold standard (HEV IgG ELISA, DIA.PRO, Italy). Further, we obtained a very good agreement (κ index = 0.94, 95% CI: 0.87–1.00) with the gold standard. We screened 813 blood donor samples with this newly developed ELISA and found a seroprevalence of 9.23% (95% confidence interval, 7.33–11.43%). We show for the first time evidence of past HEV infection in Tucuman, the most populated city in northern Argentina. We expect that this study will raise the interest of health decision makers who should intercede to include indirect testing of HEV in regular diagnostic protocols. In conclusion, the in-house ELISA developed in this work shows a very good agreement with an already licensed commercial HEV IgG ELISA (DIA.PRO, ITALY), which can be used as an epidemiologic tool for HEV surveillance.
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Affiliation(s)
- Lorena Paola Arce
- Infection Biology Laboratory, Instituto de Investigaciones en Medicina Molecular y Celular Aplicada (IMMCA), SIPROSA, CONICET, UNT, San Miguel de Tucumán, Argentina.,Laboratorio de Ciencias Básicas and Or. Genética, Facultad de Medicina de la Universidad Nacional de Tucumán, Tucumán, Argentina
| | - Melisa Florencia Müller
- Infection Biology Laboratory, Instituto de Investigaciones en Medicina Molecular y Celular Aplicada (IMMCA), SIPROSA, CONICET, UNT, San Miguel de Tucumán, Argentina.,Laboratorio de Ciencias Básicas and Or. Genética, Facultad de Medicina de la Universidad Nacional de Tucumán, Tucumán, Argentina
| | - Alfredo Martinez
- Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina
| | - Armin Baiker
- Bavarian Health and Food Safety Authority (LGL), Oberschleissheim, Germany
| | - Gabriela Marranzino
- Banco Central de Sangre de Tucumán "Dr. César Guerra," PRIS-Si.PRO.SA, San Miguel de Tucumán, Argentina
| | - Felicitas Agote
- Banco Central de Sangre de Tucumán "Dr. César Guerra," PRIS-Si.PRO.SA, San Miguel de Tucumán, Argentina
| | - Maria Guadalupe Vizoso-Pinto
- Infection Biology Laboratory, Instituto de Investigaciones en Medicina Molecular y Celular Aplicada (IMMCA), SIPROSA, CONICET, UNT, San Miguel de Tucumán, Argentina.,Laboratorio de Ciencias Básicas and Or. Genética, Facultad de Medicina de la Universidad Nacional de Tucumán, Tucumán, Argentina
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15
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Yaşar O, Karatayli E, Cengiz G, Kızılpınar M, Yurdcu E, Albayrak R, Güven A, Arslan Ö, Karahan C, Otlu B, Güdücüoğlu H, Gökahmetoğlu S, Berk E, Kirişci Ö, Sertöz R, Yurdaydin C, Bozdayi AM, Karatayli SC. HEV seroprevalence in blood donors in Turkey by two commercial total anti-HEV Ab ELISA kits. J Med Virol 2019; 91:2174-2181. [PMID: 31403185 DOI: 10.1002/jmv.25567] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 08/07/2019] [Indexed: 12/24/2022]
Abstract
Previous hepatitis E virus (HEV) seroprevalence studies in Turkey have shown high variabilities, leading to conflicting results. We aimed to re-evaluate HEV seroprevalence among blood donors in Turkey using the Wantai (Beijing, China) and the Dia.Pro (Milan, Italy) total anti-HEV antibody (Ab) enzyme-linked immunosorbent assay (ELISA) kits and compare their performances and to investigate the presence of HEV RNA in blood donors. Serum total anti-HEV antibodies were determined in a total of 2011 volunteer blood donor samples collected from different regions of Turkey (807 from Ankara, 243 from Kayseri, 284 from İzmir, 200 from Malatya, 200 from Kahramanmaraş, and 277 from Van). HEV RNA was evaluated by a real-time polymerase chain reaction in a total of 272 anti-HEV seropositive samples. The country-wide HEV seroprevalence was calculated as 11.5% (Dia.Pro) and 12.2% (Wantai) with seropositivity rates of 12.0%-12.5% in Ankara, 7.4%-8.2% in Kayseri, 14.5%-15.5% in Malatya, 8.1%-8.8% in İzmir, 15.0%-16.0% in Kahramanmaraş, and 12.6%-13.4% in Van by Dia.Pro and Wantai kits, respectively. The lowest detectable Ab concentrations were 0.16 and 0.14 units/mL WHO, for the Dia.Pro and the Wantai assays, respectively, showing no significant difference between assays. HEV RNA was not detected in any of the anti-HEV seropositive samples. Compared with previous studies, HEV was shown to have a higher overall seroprevalence in Turkey. Despite its limitation, the current study represents the most comprehensive HEV seroprevalence study in Turkey performed with two different commercial ELISA assays with high sensitivities so far. Further investigation is required to determine HEV genotypes in Turkey.
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Affiliation(s)
- Osman Yaşar
- Institute of Hepatology, Ankara University, Ankara, Turkey
| | | | - Güniz Cengiz
- Institute of Hepatology, Ankara University, Ankara, Turkey
| | | | - Esra Yurdcu
- Institute of Hepatology, Ankara University, Ankara, Turkey
| | - Rabia Albayrak
- Department of Biometry and Genetics, Faculty of Agriculture, Ankara University, Ankara, Turkey
| | - Aysel Güven
- Vocational School of Health, Başkent University, Ankara, Turkey
| | - Önder Arslan
- Department of Hematology, School of Medicine, Ankara University, Ankara, Turkey
| | - Ceren Karahan
- Department of Microbiology and Clinical Microbiology, School of Medicine, Ankara University, Ankara, Turkey
| | - Barış Otlu
- Department of Medical Microbiology, School of Medicine, Inönü University, Malatya, Turkey
| | - Hüseyin Güdücüoğlu
- Department of Medical Microbiology, Faculty of Medicine, Van Yüzüncü Yıl University, Van, Turkey
| | - Selma Gökahmetoğlu
- Department of Medical Microbiology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Elife Berk
- Department of Medical Microbiology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Özlem Kirişci
- Laboratory of Medical Microbiology, Necip Fazıl City Hospital, Kahramanmaraş, Turkey
| | - Rüçhan Sertöz
- Department of Medical Microbiology, Faculty of Medicine, Ege University, İzmir, Turkey
| | - Cihan Yurdaydin
- Institute of Hepatology, Ankara University, Ankara, Turkey.,Department of Gastroenterology and Hepatology, Koc University Medical School, Istanbul, Turkey
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16
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Wilhelm B, Waddell L, Greig J, Young I. Systematic review and meta-analysis of the seroprevalence of hepatitis E virus in the general population across non-endemic countries. PLoS One 2019; 14:e0216826. [PMID: 31173594 PMCID: PMC6555507 DOI: 10.1371/journal.pone.0216826] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Accepted: 04/29/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) has commonly been associated with large waterborne outbreaks of human jaundice in endemic areas but it has been increasingly recognised as a cause of sporadic human cases of jaundice in non-endemic areas, in individuals with no history of travel. Zoonotic exposure is widely hypothesized to be an important potential transmission route in these sporadic human cases. Serosurveys conducted to determine the frequency of HEV human exposure report wide ranges in prevalence across studies and locations. Our study objective was to compute meta-analysis summary estimates of human seroprevalence of HEV IgG within countries considered HEV non-endemic, where possible, and to determine whether this varied significantly across these countries, as well as investigating the role of potential HEV seroprevalence predictors such as population age structure. MATERIALS AND METHODS A broad literature search was conducted in six electronic databases. Citations were appraised, and relevant data extracted using forms designed and pre-tested a priori. Meta-analysis and meta-regression were conducted in R, with HEV IgG seroprevalence in blood donors or the general population being the outcome of interest, and country, assay, population age and sex structure, and chronological time investigated as predictors of the outcome. RESULTS From 4163 unique citations initially captured, data were extracted from 135 studies investigating HEV serology in blood donors or the general population, of 31 countries among those categorised as 'very high human development' by the United Nations. Country of sampling and assay employed were consistently significant predictors of HEV IgG seroprevalence with chronological time being a non-significant predictor in the dataset of captured studies. CONCLUSIONS While country of sampling and assay employed were significant predictors of HEV seroprevalence, comparison of HEV seroprevalence across non-endemic countries is hampered by the lack of a gold standard assay and uncertainty regarding residual bias across studies, as well as regional differences within some countries.
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Affiliation(s)
| | - Lisa Waddell
- National Microbiology Laboratory at Guelph, Public Health Agency of Canada, Guelph, Ontario, Canada
| | - Judy Greig
- National Microbiology Laboratory at Guelph, Public Health Agency of Canada, Guelph, Ontario, Canada
| | - Ian Young
- School of Occupational and Public Health, Ryerson University, Toronto, Ontario, Canada
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17
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Seroprevalence of hepatitis E virus (HEV) in a general adult population in Northern Norway: the Tromsø study. Med Microbiol Immunol 2019; 208:715-725. [PMID: 30903372 DOI: 10.1007/s00430-019-00599-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Accepted: 03/13/2019] [Indexed: 02/07/2023]
Abstract
Hepatitis E virus (HEV) is a major cause of acute viral hepatitis in many parts of the world but only a few cases have been diagnosed in Norway. To investigate the HEV exposure rate in a presumed low-risk area, we have conducted a population-based study of anti-HEV IgG seroprevalence in Northern Norway. A total of 1800 serum samples from 900 women and 900 men, age 40-79 years, were randomly selected from the 21,083 participants in the 7th Tromsø Study, representing the 32,591 inhabitants of the Tromsø municipality that were ≥ 40 years. All samples were analyzed by ELISA-1 (recomWell HEV IgG). Samples testing positive or borderline, as well as a 1.5-fold excess of negative samples, were retested by ELISA-2 (DiaPro HEV IgG). If still borderline or a result discordant from ELISA-1, the sample was retested by ELISA-3 (Wantai HEV IgG) and strip-immunoassay (recomLine HEV IgG). Anti-HEV IgG was detected in 205 individuals (11.4%), yielding an estimated seroprevalence of 10.4% in the age-matched population of Tromsø. Using logistic regression analysis followed by multivariable backward elimination analysis, increasing age (OR 1.036 per year; p < 0.001) and higher education (OR 2.167; p < 0.001) were found as potential risk factors, whereas travel abroad or eating of red meat were not. Our results indicate that HEV-infection is common in Northern Norway and suggest that HEV testing should be included in the evaluation of elevated liver enzymes.
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18
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Meta-Analysis of Human IgG anti-HEV Seroprevalence in Industrialized Countries and a Review of Literature. Viruses 2019; 11:v11010084. [PMID: 30669517 PMCID: PMC6357031 DOI: 10.3390/v11010084] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 01/16/2019] [Accepted: 01/18/2019] [Indexed: 12/11/2022] Open
Abstract
Although Hepatitis E is increasingly described as a major cause of liver disease in industrialized countries, the epidemiology is far from being fully elucidated. We provide here a comprehensive review of documented clusters of cases, and of serological studies conducted in populations with distinct types of exposure. Seroprevalence rates range from <5% to >50% depending on the countries and the groups of population. Such discrepancies can be attributed to the type of serological assay used, but this solves only a part of the problem. We performed a meta-analysis of studies performed with the broadly used Wantai HEV-IgG ELISA and found striking differences that remain difficult to understand with the current knowledge of transmission pathways.
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19
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Al-Absi ES, Al- Sadeq DW, Younis MH, Yassine HM, Abdalla OM, Mesleh AG, Hadwan TA, Amimo JO, Thalib L, Nasrallah GK. Performance evaluation of five commercial assays in assessing seroprevalence of HEV antibodies among blood donors. J Med Microbiol 2018; 67:1302-1309. [DOI: 10.1099/jmm.0.000807] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Enas S. Al-Absi
- 1Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
- 2Biomedical Research Center, Qatar University, Doha, Qatar
| | - Duaa W. Al- Sadeq
- 1Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Manaf H. Younis
- 3Department of Public Health, College of Health Sciences, Qatar University, Doha, Qatar
| | | | - Omnya M. Abdalla
- 1Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Areej G. Mesleh
- 1Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Tameem A. Hadwan
- 1Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Joshua O. Amimo
- 4Department of Animal Production, Faculty of Veterinary Medicine University of Nairobi, Nairobi, Kenya
- 5Bioscieces of Eastern and Central Africa-International Livestock Research Institute (BecA-ILRI), Nairobi, Kenya
| | - Lukman Thalib
- 5Bioscieces of Eastern and Central Africa-International Livestock Research Institute (BecA-ILRI), Nairobi, Kenya
| | - Gheyath K. Nasrallah
- 1Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
- 2Biomedical Research Center, Qatar University, Doha, Qatar
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20
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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: 55] [Impact Index Per Article: 7.9] [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.
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Affiliation(s)
- Duaa W Al-Sadeq
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Amin F Majdalawieh
- Department of Biology, Chemistry and Environmental Sciences, College of Arts and Sciences, American University of Sharjah, Sharjah, 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
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Abstract
Hepatitis E virus (HEV) is globally prevalent with relatively high percentages of anti-HEV immunoglobulin G-positive individuals in the populations of developing and developed countries. There are two distinct epidemiologic patterns of hepatitis E. In areas with high disease endemicity, primarily developing countries in Asia and Africa, this disease is caused mainly by genotype 1 or 2 HEV, both of which transmit predominantly through contaminated water and occur as either outbreaks or as sporadic cases of acute hepatitis. The acute hepatitis caused by either of these two genotypes has the highest attack rate in young adults, and the disease is particularly severe among pregnant women. In developed countries, sporadic cases of locally acquired genotype 3 or 4 HEV infection are observed. The reservoir of genotype 3 and 4 HEV is believed to be animals, such as pigs, with zoonotic transmission to humans. The affected persons are often elderly, and persistent infection has been well documented among immunosuppressed persons. A subunit vaccine has been shown to be effective in preventing clinical disease and has been licensed in China.
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Affiliation(s)
- Yansheng Geng
- School of Public Health, Hebei University, No. 342 Yuhuadonglu, Baoding, 071000, China.
| | - Youchun Wang
- Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, No. 2 Tiantanxili, Dongcheng District, Beijing, 100050, China
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22
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Al-Sadeq DW, Majdalawieh AF, Nasrallah GK. Seroprevalence and incidence of hepatitis E virus among blood donors: A review. Rev Med Virol 2017; 27:e1937. [PMID: 28876496 DOI: 10.1002/rmv.1937] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 07/16/2017] [Accepted: 07/18/2017] [Indexed: 12/19/2022]
Abstract
Hepatitis E virus (HEV) is an RNA virus with 4 main genotypes. HEV-1 and HEV-2 infect solely humans, while HEV-3 and HEV-4 infect humans and various animals such as pigs, deer, and rabbits. HEV-5 and HEV-6 infect mainly wild boar. Recently, new genotypes, known as HEV-7 and HEV-8, were found to infect camels and humans. HEV is globally distributed into different epidemiological patterns based on socioeconomic factors and ecology. Although HEV is mainly transmitted through the fecal-oral route, it was also recognized as a transfusion-transmitted virus. Transmission through blood donation was documented worldwide with rising annual observations, accounting for more than 2.5% of all transmissions. HEV infection is usually asymptomatic or subclinical in immunocompetent individuals, so it remains questionable whether there is an urgent need to screen for HEV prior to blood transfusion. Moreover, recent studies conducted in the Middle East and North Africa (MENA) region indicate that HEV is highly endemic. Here, we provide a review on HEV epidemiology, transmission, and laboratory diagnosis, giving special emphasis to the newly discovered genotypes, HEV-7 and HEV-8. Furthermore, we underscore the findings of recent HEV seroprevalence and viremia studies among blood donors worldwide. We also shed light on similar studies performed among blood donors in the MENA region.
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Affiliation(s)
- Duaa W Al-Sadeq
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Amin F Majdalawieh
- Department of Biology, Chemistry, and Environmental Sciences, College of Arts and Sciences, American University of Sharjah, Sharjah, United Arab Emirates
| | - Gheyath K Nasrallah
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
- Biomedical Research Center, Qatar University, Doha, Qatar
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23
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Larralde O, Petrik J. Phage-displayed peptides that mimic epitopes of hepatitis E virus capsid. Med Microbiol Immunol 2017; 206:301-309. [PMID: 28434129 DOI: 10.1007/s00430-017-0507-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Accepted: 04/17/2017] [Indexed: 12/17/2022]
Abstract
Hepatitis E is an emerging zoonotic infection of increasing public health threat for the UK, especially for immunosuppressed individuals. A human recombinant vaccine has been licensed only in China and is not clear whether it protects against hepatitis E virus (HEV) genotype 3, the most prevalent in Europe. The aim of this study was to use phage display technology as a tool to identify peptides that mimic epitopes of HEV capsid (mimotopes). We identified putative linear and conformational mimotopes using sera from Scottish blood donors that have the immunological imprint of past HEV infection. Four mimotopes did not have homology with the primary sequence of HEV ORF2 capsid but competed effectively with a commercial HEV antigen for binding to anti-HEV reference serum. When the reactivity profile of each mimotope was compared with Wantai HEV-IgG ELISA, the most sensitive HEV immunoassay, mimotopes showed 95.2-100% sensitivity while the specificity ranged from 81.5 to 95.8%. PepSurf algorithm was used to map affinity-selected peptides onto the ORF2 crystal structure of HEV genotype 3, which predicted that these four mimototopes are clustered in the P domain of ORF2 capsid, near conformational epitopes of anti-HEV neutralising monoclonal antibodies. These HEV mimotopes may have potential applications in the design of structural vaccines and the development of new diagnostic tests.
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Affiliation(s)
- Osmany Larralde
- Microbiology RDI, Scottish National Blood Transfusion Service, NHS National Services Scotland, 21 Ellen's Glen Road, Edinburgh, EH17 7QT, UK.
| | - Juraj Petrik
- Microbiology RDI, Scottish National Blood Transfusion Service, NHS National Services Scotland, 21 Ellen's Glen Road, Edinburgh, EH17 7QT, UK
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24
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Seroprevalence and Risk Factors of Hepatitis E in Eastern Iran. IRANIAN RED CRESCENT MEDICAL JOURNAL 2017. [DOI: 10.5812/ircmj.41644] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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25
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Kodani M, Kamili NA, Tejada-Strop A, Poe A, Denniston MM, Drobeniuc J, Kamili S. Variability in the performance characteristics of IgG anti-HEV assays and its impact on reliability of seroprevalence rates of hepatitis E. J Med Virol 2016; 89:1055-1061. [DOI: 10.1002/jmv.24741] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Revised: 10/26/2016] [Accepted: 12/02/2016] [Indexed: 12/27/2022]
Affiliation(s)
- Maja Kodani
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STDs, and TB Prevention; Centers for Disease Control and Prevention; Atlanta Georgia
| | - Nourine A. Kamili
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STDs, and TB Prevention; Centers for Disease Control and Prevention; Atlanta Georgia
| | - Alexandra Tejada-Strop
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STDs, and TB Prevention; Centers for Disease Control and Prevention; Atlanta Georgia
| | - Amanda Poe
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STDs, and TB Prevention; Centers for Disease Control and Prevention; Atlanta Georgia
| | - Maxine M. Denniston
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STDs, and TB Prevention; Centers for Disease Control and Prevention; Atlanta Georgia
| | - Jan Drobeniuc
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STDs, and TB Prevention; Centers for Disease Control and Prevention; Atlanta Georgia
| | - Saleem Kamili
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STDs, and TB Prevention; Centers for Disease Control and Prevention; Atlanta Georgia
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26
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A Comparative Study of Assay Performance of Commercial Hepatitis E Virus Enzyme-Linked Immunosorbent Assay Kits in Australian Blood Donor Samples. JOURNAL OF BLOOD TRANSFUSION 2016; 2016:9647675. [PMID: 27891290 PMCID: PMC5116528 DOI: 10.1155/2016/9647675] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Accepted: 10/19/2016] [Indexed: 01/07/2023]
Abstract
Hepatitis E virus (HEV) is transfusion-transmissible and therefore poses a risk to blood transfusion safety. Seroprevalence studies are useful for estimating disease burden and determining risk factors. Considerable variability in the sensitivity of HEV antibody detection assays exists. This study aimed to compare the performances of commercially available HEV enzyme-linked immunosorbent assays (ELISA) in Australian blood donor samples. Plasma samples that tested positive (n = 194) or negative (n = 200) for HEV IgG (Wantai HEV IgG ELISA) were selected. Of the 194 HEV IgG positive samples, 4 were positive for HEV IgM (Wantai HEV IgM ELISA). All samples were tested with the MP Diagnostics: HEV IgG ELISA, total (IgG, IgM, and IgA) HEV antibody ELISA, and HEV IgM ELISA. Of the 194 Wantai HEV IgG positive samples, 92 (47%) tested positive with the MP Diagnostics HEV IgG ELISA (κ = 0.47) and 126 (65%) with MP Diagnostics total HEV antibody assay (κ = 0.65). There was poor agreement between Wantai and MP Diagnostics HEV IgM assays. This study demonstrated poor agreement between the assays tested. These observations are consistent with previous reports demonstrating significant variability between HEV ELISAs, highlighting that results of HEV serology should be interpreted with caution.
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27
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Petrik J, Lozano M, Seed CR, Faddy HM, Keller AJ, Prado Scuracchio PS, Wendel S, Andonov A, Fearon M, Delage G, Zhang J, Shih JWK, Gallian P, Djoudi R, Tiberghien P, Izopet J, Dreier J, Vollmer T, Knabbe C, Aggarwal R, Goel A, Ciccaglione AR, Matsubayashi K, Satake M, Tadokoro K, Jeong SH, Zaaijer HL, Zhiburt E, Chay J, Teo D, Chua SS, Piron M, Sauleda S, Echevarría JM, Dalton H, Stramer SL. Hepatitis E. Vox Sang 2016; 110:93-130. [PMID: 26198159 DOI: 10.1111/vox.12285] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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28
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[Hepatitis E virus: opinions of the Working Group of the Federal Ministry of Health Blood]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2015; 58:198-218. [PMID: 25608627 DOI: 10.1007/s00103-014-2103-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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29
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Koning L, Charlton MR, Pas SD, Heimbach JK, Osterhaus ADME, Watt KD, Janssen HLA, de Knegt RJ, van der Eijk AA. Prevalence and clinical consequences of Hepatitis E in patients who underwent liver transplantation for chronic Hepatitis C in the United States. BMC Infect Dis 2015; 15:371. [PMID: 26328802 PMCID: PMC4557757 DOI: 10.1186/s12879-015-1103-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2015] [Accepted: 08/12/2015] [Indexed: 12/31/2022] Open
Abstract
Background Infection with hepatitis E virus (HEV) in immunocompromised patients can lead to severe liver disease. Treatment options for HEV include peginterferon or ribavirin, routinely also used for the treatment of hepatitis C virus (HCV) infection. We determined the prevalence and clinical consequences of HEV in United States (US) based patients who underwent liver transplantation (LT) for chronic HCV. Methods Seroprevalence of HEV in 145 US LT recipients with a history of chronic HCV was determined pre-LT, 1, 3 and 5 years post-LT. All last available samples and all samples in IgM positive patients and post-LT IgG seroconverters were tested for HEV RNA. Results Overall anti-HEV seroprevalence was 42 %. Five patients were HEV IgM positive pre-LT, one patient had IgM seroconversion post-LT and eight patients had IgG seroconversion post-LT. None of the tested samples were positive for HEV RNA. Eight out of nine of the post-LT seroconverters had been treated for HCV recurrence before or at the moment of seroconversion. Conclusions LT recipients in the US are at risk of acquiring HEV. Post-LT HCV treatment with interferons and/or ribavirin may have protected patients against chronic HEV. With the arrival of new direct antiviral agents for the treatment of HCV and the elimination of peginterferon and ribavirin from HCV treatment regimens, the prevalence of chronic HEV in this population may rise again.
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Affiliation(s)
- Ludi Koning
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands. .,Mayo Clinic Transplant Center, Rochester, MN, USA.
| | - Michael R Charlton
- Intermountain Medical Center, Transplant Center, Salt Lake City, UT, USA.
| | - Suzan D Pas
- Department of Viroscience, Erasmus University Medical Center, room NA-1019, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
| | | | - Albert D M E Osterhaus
- Department of Viroscience, Erasmus University Medical Center, room NA-1019, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
| | | | - Harry L A Janssen
- Toronto Centre for Liver Disease, Toronto Western & General Hospital, University Health Network, Toronto, Canada.
| | - Robert J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
| | - Annemiek A van der Eijk
- Department of Viroscience, Erasmus University Medical Center, room NA-1019, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
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30
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Farshadpour F, Taherkhani R, Makvandi M. Prevalence of Hepatitis E Virus among Adults in South-West of Iran. HEPATITIS RESEARCH AND TREATMENT 2015; 2015:759589. [PMID: 26199756 PMCID: PMC4493289 DOI: 10.1155/2015/759589] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/01/2015] [Accepted: 06/14/2015] [Indexed: 12/22/2022]
Abstract
Background. Knowledge regarding prevalence of HEV in general population can be an indicator of the public health and hygiene. Therefore, this study was conducted to evaluate the prevalence of HEV among adults in South-West of Iran. Methods. Blood samples were taken from 510 participants, 206 (40.4%) males and 304 (59.6%) females from February to July 2014. Detection of anti-HEV IgG and IgM antibodies was carried out by ELISA test. Results. The overall anti-HEV IgG and IgM prevalence rates were 46.1% and 1.4%, respectively. Anti-HEV IgG and IgM seropositivity were not statistically associated with gender and race/ethnicity. Meanwhile, there were significant differences between the age groups regarding HEV IgG and IgM seropositivity. HEV IgG seroprevalence increased with age from 14.3% in subjects aged 18-30 years to 71.4% in persons over 71 years old, and considerably individuals aged 61 to 70 years had the highest HEV prevalence (90.9%). Also, 5.7% in the age group 18-30 years and 2.2% in the age group 31-40 years were positive for anti-HEV IgM antibodies and the highest rate was observed in subjects aged 18-30 years. Conclusion. In conclusion, high HEV IgG seroprevalence of 46.1% was observed among adults in South-West of Iran.
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Affiliation(s)
- Fatemeh Farshadpour
- Department of Microbiology and Parasitology, School of Medicine, Bushehr University of Medical Sciences, Bushehr 7514633341, Iran
- Persian Gulf Tropical Medicine Research Center, Bushehr University of Medical Sciences, Bushehr 7514633341, Iran
| | - Reza Taherkhani
- Department of Microbiology and Parasitology, School of Medicine, Bushehr University of Medical Sciences, Bushehr 7514633341, Iran
- Persian Gulf Biomedical Research Center, Bushehr University of Medical Sciences, Bushehr 7514633341, Iran
| | - Manoochehr Makvandi
- Health Research Institute, Infectious and Tropical Disease Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 6135715794, Iran
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31
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Pauli G, Aepfelbacher M, Bauerfeind U, Blümel J, Burger R, Gärtner B, Gröner A, Gürtler L, Heiden M, Hildebrandt M, Jansen B, Offergeld R, Schlenkrich U, Schottstedt V, Seitz R, Strobel J, Willkommen H, Baylis SA. Hepatitis E Virus. Transfus Med Hemother 2015; 42:247-65. [PMID: 26557817 DOI: 10.1159/000431191] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2015] [Accepted: 02/10/2015] [Indexed: 12/12/2022] Open
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Kim BS, Lim HS, Lee K, Min YS, Yoon YS, Jeong HS. A survey on the status of hepatitis e virus infection among slaughterhouse workers in South Korea. J Prev Med Public Health 2015; 48:53-61. [PMID: 25652711 PMCID: PMC4322518 DOI: 10.3961/jpmph.14.048] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2014] [Accepted: 12/24/2014] [Indexed: 12/19/2022] Open
Abstract
Objectives: The seroprevalence of hepatitis E virus (HEV) among high-risk groups overseas is high, but studies in these groups are rare in South Korea. We conducted the present study from April to November 2012 to obtain data on the seroprevalence and associated risk factors for HEV among slaughterhouse workers in South Korea. Methods: Slaughterhouse workers from 80 workplaces nationwide were surveyed in South Korea in 2012. The subjects comprised 1848 cases: 1434 slaughter workers and 414 residual products handlers. By visiting 80 slaughterhouses, which were mixed with 75 of which also performed residual products handling, we conducted a questionnaire survey for risk factors and obtained blood samples in order to determine the seropositivity and seroprevalence of HEV. Anti-HEV IgG and IgM were measured using HEV IgG and IgM enzyme-linked immunospecific assay kits and HEV antigen was measured by reverse transcription polymerase chain reaction (RT-PCR). Results: The seropositivity of anti-HEV IgG was 33.5% (slaughter workers 32.8% and residual products handlers 36.2%), and among the seropositive individuals the seroprevalence of anti-HEV IgM was 0.5% (slaughter workers 0.5%, residual products handlers 0.7%). The response rate of HEV-antigen as measured by RT-PCR was 0.2%. Risk factors significantly related to anti-HEV IgG seropositivity were age, sex , and working duration (slaughter workers only). Conclusions: There were significant risk factors (sex, age, and working duration) for HEV identified in our study. All three positive cases for HEV-antigen by RT-PCR were related to pig slaughter but without statistical significance. To prevent HEV, an educational program and working guidelines may be needed for high risk groups.
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Affiliation(s)
- Byung-Seok Kim
- Department of Preventive Medicine, Dongguk University College of Medicine, Gyeongju, Korea
| | - Hyun-Sul Lim
- Department of Preventive Medicine, Dongguk University College of Medicine, Gyeongju, Korea
| | - Kwan Lee
- Department of Preventive Medicine, Dongguk University College of Medicine, Gyeongju, Korea
| | - Young-Sun Min
- Department of Preventive Medicine, Dongguk University College of Medicine, Gyeongju, Korea
| | - Young-Sil Yoon
- Division of Vaccine Research, Korea Centers for Disease Control and Prevention, Cheongju, Korea
| | - Hye-Sook Jeong
- Division of Vaccine Research, Korea Centers for Disease Control and Prevention, Cheongju, Korea
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Yoon Y, Jeong HS, Yun H, Lee H, Hwang YS, Park B, Lee CJ, Lee S, Hyeon JY. Hepatitis E Virus (HEV) seroprevalence in the general population of the Republic of Korea in 2007-2009: a nationwide cross-sectional study. BMC Infect Dis 2014; 14:517. [PMID: 25248488 PMCID: PMC4262127 DOI: 10.1186/1471-2334-14-517] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2014] [Accepted: 09/18/2014] [Indexed: 01/28/2023] Open
Abstract
Background Hepatitis E virus (HEV) is an emerging pathogen associated with endemic and acute viral hepatitis. In this study, we investigate the HEV seroprevalence and putative risk factors by a nationwide cross-sectional study in the Republic of Korea. Methods The prevalence of anti-HEV antibody was investigated in 2,450 serum samples collected in fourth Korea National Health and Nutrition Examination Survey. In addition, epidemiological information on possible risk factors including gender, age, education, occupation, and residence location for exposure to HEV was obtained. Results The frequency of anti-EIA reactive sample was 5.9% (144/2450). The individuals in groups with male, older age, low education level and living in rural or coastal regions had high seroprevalence estimates (P ≤ 0.001). In addition, seroprevalence was significantly higher among individuals with self-identified skilled agricultural, forestry, and fishery workers (31.3%, P < 0.001). Conclusions This study provides valuable data that could be used to investigate associations of HEV seroprevalence and putative risk factors by a nationwide cross-sectional study. The high HEV seroprevalence of skilled agricultural, forestry, and fishery workers and individuals lived in coastal and rural area indicated that zoonotic transmission is an important risk factor for HEV infection in the republic of Korea. Further studies that include detailed and continuous nationwide surveys are required to identify unrecognized risk factors and to monitor the HEV infection prevalence. Electronic supplementary material The online version of this article (doi:10.1186/1471-2334-14-517) contains supplementary material, which is available to authorized users.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Ji-Yeon Hyeon
- Division of Vaccine Research, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Osong-eup, CheongJu, Chungcheongbuk-do 363-951, Republic of Korea.
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34
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Poovorawan K, Jitmitrapab S, Treeprasertsuk S, Thongmee T, Theamboonlers A, Tangkijvanich P, Komolmit P, Poovorawan Y. Risk factors and molecular characterization of acute sporadic symptomatic hepatitis E virus infection in Thailand. ASIAN PAC J TROP MED 2014; 7:709-714. [DOI: 10.1016/s1995-7645(14)60121-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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35
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Zhuang W, Ding X, Lyu C, Xiang L, Teng H, Li J. Hepatitis E virus seroprevalence among blood donors in Jiangsu Province, East China. Int J Infect Dis 2014; 26:9-11. [PMID: 24981426 DOI: 10.1016/j.ijid.2014.04.022] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Revised: 04/12/2014] [Accepted: 04/21/2014] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE Hepatitis E virus (HEV) infection is responsible for over 50% of acute viral hepatitis cases, and the blood transfusion route has emerged as a possible means of sporadic HEV infection. The aim of this study was to determine the seroprevalence of HEV among blood donors in East China. METHODS Blood samples were collected consecutively between January and June 2011 from 486 blood donors living in Jiangsu Province, East China. Anti-HEV IgG was tested by ELISA. RESULTS One hundred and thirteen blood donors developed HEV IgG antibody, indicating the prevalence of HEV IgG seropositivity to be 23.3%. HEV IgG seropositivity was 25.3% (90/356) in the male group, significantly higher than that in the female group (17.7%, 23/130) (p<0.05). The donors who had donated more than 10 times had significantly higher HEV IgG seropositivity than the other groups (p<0.05). Furthermore, donors aged 50-55 years had significantly higher HEV IgG seropositivity than the other age groups (p<0.05). CONCLUSIONS We investigated HEV seroprevalence among blood donors in East China. Our data will help identify the risk factors for HEV infection and provide guidance on controlling the safety of blood transfusions in the clinical setting.
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Affiliation(s)
- Wanchuan Zhuang
- Department of Hematology, Lianyungang Second People's Hospital affiliated to Bengbu Medical College, Lianyungang, China
| | - Xian Ding
- Department of Pediatrics, Huai'an Second People's Hospital affiliated to Xuzhou Medical College, Huai'an, China
| | - Chun Lyu
- Department of Hepatology, Huai'an Fourth People's Hospital, Huai'an, China
| | - Leilei Xiang
- Department of Pediatrics, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, 223300, China
| | - Hairong Teng
- Department of Radiotherapy, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China
| | - Jiaxin Li
- Department of Pediatrics, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, 223300, China.
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Gajjar MD, Bhatnagar NM, Sonani RV, Gupta S, Patel T. Hepatitis E seroprevalence among blood donors: A pilot study from Western India. Asian J Transfus Sci 2014; 8:29-31. [PMID: 24678170 PMCID: PMC3943141 DOI: 10.4103/0973-6247.126685] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background: Hepatitis E virus (HEV) is emerging as a potential threat to blood safety after several cases of transmission by transfusion or transplantation have been described. Currently, blood donors in India are not screened for HEV. The studies conducted on HEV in recent times in India have focused on epidemiology and future perspectives, but there is no published study on blood donors. To address possible issues surrounding blood safety and risk of HEV transmission within the Indian blood supply, HEV seroprevalence study was conducted in blood donors at our center. Materials and Methods: A total of 460 male voluntary blood donors were selected for the study and after taking their written consent. Serum anti-HEV IgM was detected by Dia.Pro HEV kit (Diagnostic Bioprobes Srl, Milano, Italy). Results: The study population was composed of 460 male voluntary blood donors and their age ranged from 18 to 60 years with a mean age of 30.48 years. Out of 460 donors, 22 (4.78%) donors were tested positive for IgM anti-HEV and the mean value alanine aminotransferase (ALT) was 26.06 IU/L, the highest being 93.5 IU/L. Normal reference value of ALT in our center was 40 IU/L. Out of 22 anti-HEV positive donors, 19 (86.36%) had ALT values above 40 IU/L. Conclusion: HEV seroprevalence of 4.78% in our center. Though reports of HEV transmission through blood has been reported from various parts of the world, before making it as a mandatory screening test among blood donors in India, further studies with confirmatory assay of HEV need to be done.
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Affiliation(s)
- Maitrey D Gajjar
- Department of Immunohaematology and Blood Transfusion, B. J. Medical College and Civil Hospital, Ahmedabad, Gujarat, India
| | - Nidhi M Bhatnagar
- Department of Immunohaematology and Blood Transfusion, B. J. Medical College and Civil Hospital, Ahmedabad, Gujarat, India
| | - Rajesh V Sonani
- Department of Immunohaematology and Blood Transfusion, B. J. Medical College and Civil Hospital, Ahmedabad, Gujarat, India
| | - Shweta Gupta
- Department of Immunohaematology and Blood Transfusion, B. J. Medical College and Civil Hospital, Ahmedabad, Gujarat, India
| | - Tarak Patel
- Department of Immunohaematology and Blood Transfusion, B. J. Medical College and Civil Hospital, Ahmedabad, Gujarat, India
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Liang H, Su S, Deng S, Gu H, Ji F, Wang L, Liang C, Wang H, Zhang G. The prevalence of hepatitis E virus infections among swine, swine farmers and the general population in Guangdong Province, China. PLoS One 2014; 9:e88106. [PMID: 24520348 PMCID: PMC3919735 DOI: 10.1371/journal.pone.0088106] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2013] [Accepted: 01/07/2014] [Indexed: 12/28/2022] Open
Abstract
Hepatitis E virus (HEV) infection is widespread in China, but few studies have been carried out in Guangdong Province. This study aimed to characterize the prevalence of HEV infections among swine, swine farmers and the general population in Guangdong Province. We conducted an epidemiological study that included swine, swine farmers and health examination attendees in Guangdong from 2011 to 2013. The overall seroprevalence of anti-HEV antibodies in swine was 64.7%. The results revealed that growing pigs, sows and boars (OR ranges from 3.5 to 21.5) have a higher risk than nursery pigs. HEV RNA in swine bile showed that HEV is epidemic in swine in the Pearl River Delta, with the highest prevalence of 22.73% in Foshan. Some genomes of HEV strains from each district were sequenced. Phylogenetic analysis of partial open reading frame 2 (ORF2) shows that they belong to genotype IV and are most closely related to isolates from China. In total, 307 participants were enrolled in the study, including 114 swine farmers and 193 attendees from hospitals. IgG anti-HEV was detected in 48.25% of swine farmers and in 38.34% of the general population. Seroprevalence rates were almost stratified by age, with a higher positive rate for males compared to females across all age groups. Women on swine farms appeared to have a lower risk of infection compared to the general population, revealing that the risk factors for HEV infection are not unique. The results suggested that there were other risk factors for HEV infection. HEV infection is prevalent in Guangdong, but due to the small sample sizes, more investigations are needed to assess the potential impact of HEV infection, and many additional risk factors should be considered.
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Affiliation(s)
- Huanbin Liang
- MOA Key Laboratory of Animal Vaccine Development, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Shuo Su
- MOA Key Laboratory of Animal Vaccine Development, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Shengchao Deng
- MOA Key Laboratory of Animal Vaccine Development, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Honglang Gu
- MOA Key Laboratory of Animal Vaccine Development, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Fangxiao Ji
- MOA Key Laboratory of Animal Vaccine Development, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Lifang Wang
- MOA Key Laboratory of Animal Vaccine Development, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Chumin Liang
- MOA Key Laboratory of Animal Vaccine Development, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Heng Wang
- MOA Key Laboratory of Animal Vaccine Development, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Guihong Zhang
- MOA Key Laboratory of Animal Vaccine Development, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- * E-mail:
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Wu WC, Su CW, Yang JY, Lin SF, Chen JY, Wu JC. Application of serologic assays for diagnosing acute hepatitis E in national surveillance of a nonendemic area. J Med Virol 2014; 86:720-8. [DOI: 10.1002/jmv.23785] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/03/2013] [Indexed: 12/27/2022]
Affiliation(s)
- Wen-Chieh Wu
- Division of Gastroenterology; Department of Medicine; Taipei Veterans General Hospital; Taipei Taiwan
| | - Chien-Wei Su
- Division of Gastroenterology; Department of Medicine; Taipei Veterans General Hospital; Taipei Taiwan
- Faculty of Medicine; School of Medicine; National Yang-Ming University; Taipei Taiwan
- Institute of Clinical Medicine; School of Medicine; National Yang-Ming University; Taipei Taiwan
| | - Jyh-Yuan Yang
- Research and Diagnostic Center; Centers for Disease Control; Taipei Taiwan
| | - Szu-Fong Lin
- Research and Diagnostic Center; Centers for Disease Control; Taipei Taiwan
| | - Jen-Yu Chen
- Institute of Clinical Medicine; School of Medicine; National Yang-Ming University; Taipei Taiwan
| | - Jaw-Ching Wu
- Institute of Clinical Medicine; School of Medicine; National Yang-Ming University; Taipei Taiwan
- Department of Medical Research and Education; Taipei Veterans General Hospital; Taipei Taiwan
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Echevarría JM. Light and Darkness: Prevalence of Hepatitis E Virus Infection among the General Population. SCIENTIFICA 2014; 2014:481016. [PMID: 24672733 PMCID: PMC3941225 DOI: 10.1155/2014/481016] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/07/2013] [Accepted: 12/25/2013] [Indexed: 05/05/2023]
Abstract
Human hepatitis E virus (HHEV) spreads early in life among the population in areas endemic for genotype 1 and infects mainly adults in areas endemic for genotype 3, where it would be responsible for about 10% of cases of suspected acute viral hepatitis of unknown etiology and for a number of subclinical, unrecognized infections. The overall prevalence of antibody to HHEV is high in most of the former areas and low in most of the later ones, but wide regional differences have been recorded in both cases. "Hot spots" of HHEV infection would exist for both types of strains in particular regions or among particular populations of the world. Studies on pork derivatives, shellfish bivalves, and vegetables for HHEV contamination at the sale point need to be extended for evaluating the impact of the agent on food safety, and the meaning of the finding of HHEV genotype 1 genomes in urban sewage from developed countries should be established through active surveillance. Consensus about technical issues in regard to anti-HEV testing would improve the knowledge of the HHEV epidemiology. Studies in particular regions and populations, and introduction of molecular diagnosis in the clinical setting as a routine tool, would also be required.
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Affiliation(s)
- José-Manuel Echevarría
- Department of Virology, National Centre of Microbiology, Instituto de Salud Carlos III, Road Majadahonda-Pozuelo, Km2, Majadahonda, 28220 Madrid, Spain
- *José-Manuel Echevarría:
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Lee WJ, Shin MK, Cha SB, Yoo HS. Development of a novel enzyme-linked immunosorbent assay to detect anti-IgG against swine hepatitis E virus. J Vet Sci 2013; 14:467-72. [PMID: 24421718 PMCID: PMC3885741 DOI: 10.4142/jvs.2013.14.4.467] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2012] [Revised: 02/16/2013] [Accepted: 02/19/2013] [Indexed: 11/20/2022] Open
Abstract
Swine hepatitis E virus (HEV) is widespread throughout pigs in both developing and industrialized countries. This virus is an important zoonotic agent and a public concern worldwide. Infected pigs are asymptomatic, so diagnosing swine HEV relies on detection of the virus or antibodies against the virus. However, several obstacles need to be overcome for effective and practical serological diagnosis. In this study, we developed an enzyme-linked immunosorbent assay (ELISA) that used a purified recombinant capsid protein of swine HEV. The potential clinical use of this assay was evaluated by comparing it with a commercial kit (Genelabs Technologies, Diagnostics, Singapore). Results of the ELISA were highly correlated with those of the commercial kit with a sensitivity of 97% and specificity of 95%. ROC (receiving operator characteristic) analysis of the ELISA data produced a value of 0.987 (95% CI, 0.977~0.998, p < 0.01). The cut-off value for the ELISA was also determined using negative pig sera. In summary, the HEV-specific ELISA developed in the present study appears to be both practical and economical.
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Affiliation(s)
- Won Jung Lee
- Department of Infectious Diseases, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea
| | - Min Kyoung Shin
- Department of Infectious Diseases, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea
| | - Seung Bin Cha
- Department of Infectious Diseases, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea
| | - Han Sang Yoo
- Department of Infectious Diseases, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea
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Pas SD, Streefkerk RHRA, Pronk M, de Man RA, Beersma MF, Osterhaus ADME, van der Eijk AA. Diagnostic performance of selected commercial HEV IgM and IgG ELISAs for immunocompromised and immunocompetent patients. J Clin Virol 2013; 58:629-34. [PMID: 24210958 DOI: 10.1016/j.jcv.2013.10.010] [Citation(s) in RCA: 141] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2013] [Revised: 09/08/2013] [Accepted: 10/06/2013] [Indexed: 12/15/2022]
Abstract
BACKGROUND Hepatitis E virus (HEV) genotype 3 is recognised as an emerging pathogen in industrialised countries. The currently commercially available HEV-specific enzyme linked immunosorbent assays (ELISAs) are primarily designed for the detection of antibodies against genotypes 1 (Burma) and 2 (Mexico) and may not sensitively detect HEV genotypes 3 or 4. OBJECTIVES This study aimed to evaluate the analytical and clinical performances of eight commercially available HEV serum antibody immunoglobulin M (IgM)- and immunoglobulin G (IgG)-specific ELISAs for genotype 1 and 3 HEV infections in a clinical setting and to study the antibody responses against HEV of immunocompromised versus immunocompetent patient groups. STUDY DESIGN Analytical performance and diagnostic sensitivity and specificity were assessed using well-defined reference samples and samples from patients with polymerase chain reaction (PCR)-confirmed HEV infection (n=88) and a specificity panel (n=98). RESULTS Limiting dilutions indicated that the highest analytical sensitivity in head-to-head comparison was measured for the Mikrogen_new IgG assay. Taking the serum working dilutions of each assay into account, the Wantai IgG assay was the most sensitive assay. Receiver operator curve (ROC) analysis showed area under the curve (AUC) values of 0.943, 0.964, 0.969, 0.971, 0.974 and 0.994 for the DSI, Mikrogen_old, MP Diagnostics, Mikrogen_new, Wantai and DiaPro anti-HEV IgM assays, respectively. The highest specificity of currently available assays was found for the IgM Wantai assay (>99%). If anti-HEV IgM and IgG results from each supplier were combined, DSI and Wantai assays were able to detect the highest number of (passed) HEV infections. CONCLUSIONS Our study showed that current commercial HEV ELISAs could be used to diagnose HEV genotype 3 infection adequately in a clinical setting.
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Affiliation(s)
- Suzan D Pas
- Department of Viroscience, Erasmus MC, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands
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Xu C, Wang RY, Schechterly CA, Ge S, Shih JW, Xia NS, Luban NLC, Alter HJ. An assessment of hepatitis E virus (HEV) in US blood donors and recipients: no detectable HEV RNA in 1939 donors tested and no evidence for HEV transmission to 362 prospectively followed recipients. Transfusion 2013; 53:2505-11. [PMID: 23829163 DOI: 10.1111/trf.12326] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2013] [Revised: 05/28/2013] [Accepted: 05/28/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatitis E virus (HEV) infection has become relevant to blood transfusion practice because isolated cases of blood transmission have been reported and because HEV has been found to cause chronic infection and severe liver disease in immunocompromised patients. STUDY DESIGN AND METHODS We tested for immunoglobulin (Ig)G and IgM antibodies to the HEV and for HEV RNA in 1939 unselected volunteer US blood donors. Subsequently, we tested the same variables in pre- and serial posttransfusion samples from 362 prospectively followed blood recipients to assess transfusion risk. RESULTS IgG anti-HEV seroprevalence in the total 1939 donations was 18.8%: 916 of these donations were made in 2006 at which time the seroprevalence was 21.8% and the remaining 1023 donations were in 2012 when the seroprevalence had decreased to 16.0% (p < 0.01). A significant (p < 0.001) stepwise increase in anti-HEV seroprevalence was seen with increasing age. Eight of 1939 donations (0.4%) tested anti-HEV IgM positive; no donation was HEV RNA positive. Two recipients had an apparent anti-HEV seroconversion, but temporal relationships and linked donor testing showed that these were not transfusion-transmitted HEV infections. CONCLUSION No transfusion-transmitted HEV infections were observed in 362 prospectively followed blood recipients despite an anti-HEV seroprevalence among donations exceeding 16%.
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Affiliation(s)
- Chenyu Xu
- Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland; National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen, Fujian, China; Department of Laboratory Medicine, Center for Cancer and Blood Diseases, Children's National Medical Center; Department of Pediatrics, School of Medicine and Health Sciences, George Washington University, Washington, DC
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Lee JT, Shao PL, Chang LY, Xia NS, Chen PJ, Lu CY, Huang LM. Seroprevalence of Hepatitis E Virus Infection among Swine Farmers and the General Population in Rural Taiwan. PLoS One 2013; 8:e67180. [PMID: 23840620 PMCID: PMC3694024 DOI: 10.1371/journal.pone.0067180] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2013] [Accepted: 05/15/2013] [Indexed: 12/13/2022] Open
Abstract
Objectives Hepatitis E virus (HEV) is an emerging pathogen. We evaluated the seroprevalence of HEV infection among swine farmers and the general population in Taiwan, a nonendemic country. Methods We conducted a cross-sectional seroepidemiologic study in rural Taiwan in 2012 and 2013. The study included swine farmers, health examination attendees, pregnant women, and students. A commercial enzyme-linked immunosorbent assay was used to detect immunoglobulin G (IgG) and IgM against HEV. Pertinent information was collected using a questionnaire. Results In total, 660 participants were enrolled in the study, including 156 swine farmers, 314 health examination attendees, 100 pregnant women, and 90 students. IgG anti-HEV was detected in 29.5% of swine farmers, 11.5% of health examination attendees, 2% of pregnant women, and 1.1% of students. Two subjects were positive for IgM anti-HEV. Logistic regression analysis revealed that swine farmers had an approximately 3.5-fold increased risk (odds ratio [OR], 3.46; 95% confidence interval [CI], 1.91–6.27; p<0.0001) for being seropositive for IgG anti-HEV as compared to the general population. Age was positively associated with seropositive rate (OR, 1.07 per year; 95% CI, 1.05–1.09; p<0.0001). Conclusion HEV infection is prevalent in Taiwan. The seroprevalence of HEV infection is high in swine farmers and in the elderly population.
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Affiliation(s)
- Jian-Te Lee
- Department of Pediatrics, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan
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Affiliation(s)
- Naveen Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Abstract
Hepatitis E, caused by infection with hepatitis E virus (HEV), is a common cause of enterically-transmitted acute hepatitis in developing countries. Occasional cases of sporadic hepatitis E have been increasingly recognized in developed countries over the past decade. These cases differ from those in developing countries in being possibly caused by zoonotic transmission, often affecting people with a suppressed immune system and occasionally leading to persistent HEV infection. The commonly used tests for HEV infection include detection of IgM and IgG anti-HEV antibodies and detection of HEV RNA. IgM anti-HEV antibodies can be detected during the first few months after HEV infection, whereas IgG anti-HEV antibodies represent either recent or remote exposure. The presence of HEV RNA indicates current infection, whether acute or chronic. Although several diagnostic assays for anti-HEV antibodies are available, they have undergone fairly limited testing and often provide discordant results, particularly for IgG antibodies. Thus, although the available antibody assays might be useful for case diagnosis in areas with high disease endemicity, their use for case diagnosis in areas with low endemicity and for seroprevalence studies remains problematic. Improved validation of existing anti-HEV antibody assays or development of new assays with superior performance characteristics is urgently needed.
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Affiliation(s)
- Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.
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Chiu DMY, Chan MCW, Yeung ACM, Ngai KLK, Chan PKS. Seroprevalence of hepatitis E virus in Hong Kong, 2008-2009. J Med Virol 2012; 85:459-61. [PMID: 23239426 DOI: 10.1002/jmv.23429] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/22/2012] [Indexed: 01/05/2023]
Abstract
The public health impact of hepatitis E virus (HEV) infection varies across the world. An HEV vaccine has been recently approved for clinical use in China. Population-specific seroprevalence data are essential for cost-effective assessment of vaccination programs. Here, a cross-sectional study was performed to provide an update on the local seroprevalence of HEV. An archive of serum samples submitted for virological investigation between 2008 and 2009 to a general hospital was used. A total of 450 samples with equal numbers from each gender covering the age groups from 1-10 to >80 years (25 samples per group) were tested for HEV immunoglobulin G (IgG) by enzyme-linked immunoassay. Age- and gender-specific seroprevalence were determined. The HEV IgG positive rate increased from 8% among 1-10 years to 56% among >80 years. The increase in prevalence was constant throughout all age groups without a steeper slope or plateau observed from any age group. The overall positive rate among males was significantly higher than among females (32.9% vs. 24.4%, P = 0.048). The best-fitted seroprevalence curves also suggested a higher positive rate for males across all age groups. Increased HEV IgG positivity was noted in comparison with historical local studies. Collectively, the prevalence of HEV in Hong Kong has increased over the past decade. A large proportion of the population is still susceptible to infection, and all age groups are at risk. Territory-wide vaccination program should be considered.
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Affiliation(s)
- Diana M Y Chiu
- Virology Division, Public Health Laboratory Services Branch, Centre for Health Protection, Department of Health, Government of Hong Kong Special Administrative Region, China
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