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Sasaki-Tanaka R, Kanda T, Yokoo T, Abe H, Hayashi K, Sakamaki A, Kamimura H, Terai S. Hepatitis A and E Viruses Are Important Agents of Acute Severe Hepatitis in Asia: A Narrative Review. Pathogens 2025; 14:454. [PMID: 40430774 PMCID: PMC12114595 DOI: 10.3390/pathogens14050454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2025] [Revised: 04/25/2025] [Accepted: 05/03/2025] [Indexed: 05/29/2025] Open
Abstract
Acute-on-chronic liver failure (ACLF) and acute liver failure (ALF) are severe hepatitis that occur in patients with and without chronic liver diseases and/or cirrhosis, respectively, and both often result in death. Hepatitis A virus (HAV) and hepatitis E virus (HEV) infection can cause these severe conditions. We reviewed the role of HAV and HEV, which infect humans through the fecal-oral route, in ALF and ACLF in Asian countries. This narrative review was the derived from a traditional non-systematic review. Hepatitis A should be recognized as one of the sexually transmitted infections, especially among men who have sex with men. HAV genotype IIIA infection seems to present a more severe clinical manifestation. Acute HEV-1 infection is associated with ALF in pregnant women in India. HEV-4, rather than HEV-3, was found in severe hepatitis in Japan. HEV also plays a role as a cause of acute insult and/or chronic liver disease in immunocompromised patients with ACLF. Further studies are needed for the development of vaccines and antivirals against HAV and HEV infections. Despite the limitations of the recording of cases and the extent of specific vaccinations, multidisciplinary cooperation, involving hepatologists, virologists, experts in public health, etc., may improve the treatment of HAV and HEV infection.
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Affiliation(s)
- Reina Sasaki-Tanaka
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8520, Japan; (R.S.-T.); (T.Y.); (H.A.); (K.H.); (A.S.); (H.K.); (S.T.)
| | - Tatsuo Kanda
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8520, Japan; (R.S.-T.); (T.Y.); (H.A.); (K.H.); (A.S.); (H.K.); (S.T.)
- Division of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Uonuma Kikan Hospital, Minami-Uonuma, Niigata 949-7302, Japan
| | - Takeshi Yokoo
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8520, Japan; (R.S.-T.); (T.Y.); (H.A.); (K.H.); (A.S.); (H.K.); (S.T.)
| | - Hiroyuki Abe
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8520, Japan; (R.S.-T.); (T.Y.); (H.A.); (K.H.); (A.S.); (H.K.); (S.T.)
| | - Kazunao Hayashi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8520, Japan; (R.S.-T.); (T.Y.); (H.A.); (K.H.); (A.S.); (H.K.); (S.T.)
| | - Akira Sakamaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8520, Japan; (R.S.-T.); (T.Y.); (H.A.); (K.H.); (A.S.); (H.K.); (S.T.)
| | - Hiroteru Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8520, Japan; (R.S.-T.); (T.Y.); (H.A.); (K.H.); (A.S.); (H.K.); (S.T.)
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8520, Japan; (R.S.-T.); (T.Y.); (H.A.); (K.H.); (A.S.); (H.K.); (S.T.)
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Kupke P, Kupke M, Borgmann S, Kandulski A, Hitzenbichler F, Menzel J, Geissler EK, Schlitt HJ, Wenzel JJ, Werner JM. Hepatitis E virus infection in immunosuppressed patients and its clinical manifestations. Dig Liver Dis 2025; 57:378-384. [PMID: 38997847 DOI: 10.1016/j.dld.2024.06.020] [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: 05/06/2024] [Revised: 06/04/2024] [Accepted: 06/24/2024] [Indexed: 07/14/2024]
Abstract
BACKGROUND & AIMS Hepatitis E virus (HEV) is a main cause of acute hepatitis globally. However, immunosuppressed patients regularly develop chronic courses. The aim of this study was to analyse the current status of HEV diagnostics, characterize clinical manifestations and identify risk factors for complicated HEV infections. METHODS In this retrospective study at two large hospitals, 512 patients with borderline and positive anti-HEV-IgM and 94 patients with positive HEV-PCR between January 1999 and May 2023 were included. RESULTS Detection by anti-HEV-IgM-ELISA led to a positive HEV-PCR in only 17.9 %. Amongst patients with positive HEV-PCR, 61 had underlying immunosuppression and 23 were patients after solid organ transplantation (SOT). All 13 patients with chronic HEV infections were immunosuppressed. Generally, immunosuppression led to higher HEV-RNA concentrations and a higher probability of receiving immediate treatment. However, all fulminant courses with liver failure happened in patients without immunosuppression. Immunocompetent patients showed symptoms more frequently and primarily had higher bilirubin levels indicating more severe liver damage. A risk factor for delayed or failed viral clearance after SOT was the administration of mTOR inhibitors. CONCLUSIONS Fulminant HEV infections happen primarily in immunocompetent patients. Nevertheless, immunosuppressed patients bear the risk of undetected, prolonged HEV infections, reflected by the rare occurrence of symptoms.
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Affiliation(s)
- Paul Kupke
- Department of Surgery, University Hospital Regensburg, 93053 Regensburg, Germany.
| | - Maximilian Kupke
- Department of Internal Medicine II, Hospital Ingolstadt, 85049 Ingolstadt, Germany
| | - Stefan Borgmann
- Department of Infectious Diseases and Infection Control, Hospital Ingolstadt, 85049 Ingolstadt, Germany
| | - Arne Kandulski
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Florian Hitzenbichler
- Department of Infection Prevention and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Josef Menzel
- Department of Internal Medicine II, Hospital Ingolstadt, 85049 Ingolstadt, Germany
| | - Edward K Geissler
- Department of Surgery, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Hans J Schlitt
- Department of Surgery, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Jürgen J Wenzel
- National Consultant Laboratory for HAV and HEV, Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Jens M Werner
- Department of Surgery, University Hospital Regensburg, 93053 Regensburg, Germany
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Lupulović D, Gnjatović M, Prodanov-Radulović J, Ćujić D, Gajdov V, Samojlović M, Petrović T. Seroepidemiological Survey of Hepatitis E Virus in Intensive Pig Farming in Vojvodina Province, Serbia. Animals (Basel) 2025; 15:151. [PMID: 39858151 PMCID: PMC11758650 DOI: 10.3390/ani15020151] [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: 12/08/2024] [Revised: 01/06/2025] [Accepted: 01/08/2025] [Indexed: 01/27/2025] Open
Abstract
Hepatitis E virus (HEV) is the causative agent of acute hepatitis E infection in humans. Two epidemiological patterns of the disease exist-endemic and sporadic. Genotypes 1 (HEV-1) and 2 (HEV-2) are transmitted through contaminated water and are responsible for the outbreaks of many large-scale epidemics in developing countries of Asia and Africa. Genotypes 3 (HEV-3) and 4 (HEV-4) have zoonotic potential and cause sporadic cases and small outbreaks in high-income countries. The first case of HEV infection in swine was confirmed in 1997 and later detected in other animal species. The aim of this study was to investigate the seroprevalence of HEV infection in pig farms in Vojvodina province, Serbia. Three hundred blood samples were collected from five different categories of pigs from 3 different farms on the territory of the South Bačka district in Vojvodina (Serbia). The analyses were conducted by in-house ELISA, while the western blot method was used as a confirmatory test for doubtful results. The presence of HEV IgG was detected on all three examined farms. The established seroprevalence in Farm A was 37%, 31% in Farm B, and 54% in Farm C. The mean seroprevalence for all farms was 40.66%. A higher seroprevalence was found in fatteners compared to younger categories of pigs. We concluded that HEV is widespread on pig farms with intensive management. Further analyses should be conducted with the aim of implementing a surveillance program to prevent possible human infection.
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Affiliation(s)
- Diana Lupulović
- Institute for the Application of Nuclear Energy INEP, Banatska 31b, 11080 Zemun, Serbia; (M.G.); (D.Ć.)
| | - Marija Gnjatović
- Institute for the Application of Nuclear Energy INEP, Banatska 31b, 11080 Zemun, Serbia; (M.G.); (D.Ć.)
| | - Jasna Prodanov-Radulović
- Scientific Veterinary Institute “Novi Sad”, Rumenački put 20, 21000 Novi Sad, Serbia; (J.P.-R.); (V.G.); (M.S.); (T.P.)
| | - Danica Ćujić
- Institute for the Application of Nuclear Energy INEP, Banatska 31b, 11080 Zemun, Serbia; (M.G.); (D.Ć.)
| | - Vladimir Gajdov
- Scientific Veterinary Institute “Novi Sad”, Rumenački put 20, 21000 Novi Sad, Serbia; (J.P.-R.); (V.G.); (M.S.); (T.P.)
| | - Milena Samojlović
- Scientific Veterinary Institute “Novi Sad”, Rumenački put 20, 21000 Novi Sad, Serbia; (J.P.-R.); (V.G.); (M.S.); (T.P.)
| | - Tamaš Petrović
- Scientific Veterinary Institute “Novi Sad”, Rumenački put 20, 21000 Novi Sad, Serbia; (J.P.-R.); (V.G.); (M.S.); (T.P.)
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Hofstetter J, Holcomb DA, Kahler AM, Rodrigues C, da Silva ALBR, Mattioli MC. Performance of Conditional Random Forest and Regression Models at Predicting Human Fecal Contamination of Produce Irrigation Ponds in the Southeastern United States. ACS ES&T WATER 2024; 4:5844-5855. [PMID: 39734778 PMCID: PMC11672865 DOI: 10.1021/acsestwater.4c00839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2024]
Abstract
Irrigating fresh produce with contaminated water contributes to the burden of foodborne illness. Identifying fecal contamination of irrigation waters and characterizing fecal sources and associated environmental factors can help inform fresh produce safety and health hazard management. Using two previously collected data sets, we developed and evaluated the performance of logistic regression and conditional random forest models for predicting general and human-specific fecal contamination of ponds in southwest Georgia used for fresh produce irrigation. Generic Escherichia coli served as a general fecal indicator, and human-associated Bacteroides (HF183), crAssphage, and F+ coliphage genogroup II were used as indicators of human fecal contamination. Increased rainfall in the previous 7 days and the presence of a building within 152 m (a proxy for proximity to septic systems) were associated with increased odds of human fecal contamination in the training data set. However, the models did not accurately predict the presence of human-associated fecal indicators in a second data set collected from nearby irrigation ponds in different years. Predictive statistical models should be used with caution to assess produce irrigation water quality as models may not reliably predict fecal contamination at other locations and times, even within the same growing region.
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Affiliation(s)
- Jessica Hofstetter
- Waterborne Disease Prevention Branch, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, United States; Chenega Enterprise Systems & Solutions, LLC, Chesapeake, Virginia 23320, United States; Department of Horticulture, Auburn University, Auburn, Alabama 36849, United States
| | - David A Holcomb
- Waterborne Disease Prevention Branch, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, United States
| | - Amy M Kahler
- Waterborne Disease Prevention Branch, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, United States
| | - Camila Rodrigues
- Department of Horticulture, Auburn University, Auburn, Alabama 36849, United States
| | | | - Mia C Mattioli
- Waterborne Disease Prevention Branch, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, United States
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Gong G, Xin J, Lou Y, Qiong D, Dawa Z, Gesang Z, Suolang S. Cell Culture of a Swine Genotype 4 Hepatitis E Virus Strain. J Med Virol 2024; 96:e70031. [PMID: 39530175 DOI: 10.1002/jmv.70031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 10/12/2024] [Accepted: 10/17/2024] [Indexed: 11/16/2024]
Abstract
HEV infection has become a global health concern. The study of HEV pathogenicity has been hindered by the lack of a suitable in vitro culture system. In the present research, we systematic demonstration of efficient replication of swine GT4 HEV in A549 cells, Huh-7 cells, and HepG2/C3A cell lines. The results of the immunofluorescence assay and immunofluorescence confocal assay showed that swine GT4 HEV is efficiently replicated in three cell lines at 72 h postinoculation. Meanwhile, we also detected the virus titer quantified were increased at 2-, 6,- and 11-days postinoculation. Moreover, we successfully observed HEV virus particles in the cell suspension at 6 days postinoculation. This finding holds significance for advancing in vitro HEV studies.
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Affiliation(s)
- Ga Gong
- Animal Science College, Xizang Agriculture and Animal Husbandry University, Nyingchi, China
| | - Jiaojiao Xin
- Animal Science College, Xizang Agriculture and Animal Husbandry University, Nyingchi, China
| | - Yongzhi Lou
- Animal Science College, Xizang Agriculture and Animal Husbandry University, Nyingchi, China
| | - Da Qiong
- Animal Science College, Xizang Agriculture and Animal Husbandry University, Nyingchi, China
| | | | - Zhuoma Gesang
- Animal Disease Prevention and Control Center of Xizang Autonomous Region, Lhasa, China
| | - Sizhu Suolang
- Animal Science College, Xizang Agriculture and Animal Husbandry University, Nyingchi, China
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Brüggemann Y, Klöhn M, Wedemeyer H, Steinmann E. Hepatitis E virus: from innate sensing to adaptive immune responses. Nat Rev Gastroenterol Hepatol 2024; 21:710-725. [PMID: 39039260 DOI: 10.1038/s41575-024-00950-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/29/2024] [Indexed: 07/24/2024]
Abstract
Hepatitis E virus (HEV) infections are a major cause of acute viral hepatitis in humans worldwide. In immunocompetent individuals, the majority of HEV infections remain asymptomatic and lead to spontaneous clearance of the virus, and only a minority of individuals with infection (5-16%) experience symptoms of acute viral hepatitis. However, HEV infections can cause up to 30% mortality in pregnant women, become chronic in immunocompromised patients and cause extrahepatic manifestations. A growing body of evidence suggests that the host immune response to infection with different HEV genotypes is a critical determinant of distinct HEV infection outcomes. In this Review, we summarize key components of the innate and adaptive immune responses to HEV, including the underlying immunological mechanisms of HEV associated with acute and chronic liver failure and interactions between T cell and B cell responses. In addition, we discuss the current status of vaccines against HEV and raise outstanding questions regarding the immune responses induced by HEV and treatment of the disease, highlighting areas for future investigation.
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Affiliation(s)
- Yannick Brüggemann
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
| | - Mara Klöhn
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Partner Sites Hannover-Braunschweig, Hannover, Germany
- Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
| | - Eike Steinmann
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany.
- German Center for Infection Research (DZIF), External Partner Site, Bochum, Germany.
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McSteen BW, Ying XH, Lucero C, Jesudian AB. Viral etiologies of acute liver failure. World J Virol 2024; 13:97973. [PMID: 39323454 PMCID: PMC11401000 DOI: 10.5501/wjv.v13.i3.97973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 08/07/2024] [Accepted: 08/19/2024] [Indexed: 08/29/2024] Open
Abstract
Acute liver failure (ALF) is a rare cause of liver-related mortality worldwide, with an estimated annual global incidence of more than one million cases. While drug-induced liver injury, including acetaminophen toxicity, is the leading cause of ALF in the Western world, viral infections remain a significant cause of ALF and the most common cause in many developing nations. Given the high mortality rates associated with ALF, healthcare providers should be aware of the broad range of viral infections that have been implicated to enable early diagnosis, rapid treatment initiation when possible, and optimal management, which may include liver transplantation. This review aims to provide a summary of viral causes of ALF, diagnostic approaches, treatment options, and expected outcomes.
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Affiliation(s)
- Brian W McSteen
- Department of Medicine, New York-Presbyterian/Weill Cornell Campus, New York, NY 10021, United States
| | - Xiao-Han Ying
- Department of Medicine, New York-Presbyterian/Weill Cornell Campus, New York, NY 10021, United States
| | - Catherine Lucero
- Department of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10021, United States
| | - Arun B Jesudian
- Department of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10021, United States
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Albert V, Ramamurthy T, Das S, G Dolma K, Majumdar T, Baruah PJ, Chaliha Hazarika S, Apum B, Das M. Comprehending the risk of foodborne and waterborne disease outbreaks: Current situation and control measures with Special reference to the Indian Scenario. Heliyon 2024; 10:e36344. [PMID: 39253199 PMCID: PMC11382067 DOI: 10.1016/j.heliyon.2024.e36344] [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: 10/11/2023] [Revised: 08/10/2024] [Accepted: 08/14/2024] [Indexed: 09/11/2024] Open
Abstract
Background Foodborne and waterborne diseases and outbreaks are a neglected public health issue worldwide. In developing countries, diarrheal disease caused by foodborne and waterborne infections is a major cause of ill health. There is a lack of information on foodborne pathogens, their transmission routes, outbreaks, and related mortalities, due to the absence of a robust disease surveillance system and adequately equipped laboratories. Although hygiene practices are much better in Western countries, the widespread use of preserved and raw food items is a cause of concern. Consequently, the occurrence of foodborne diseases is not rare in these countries either. WHO has recently released the 'Global Strategy for Food Safety 2022-2030', addressing the emerging challenges, new technologies, and innovative approaches to strengthen food safety systems and enhance laboratory capacity for foodborne disease surveillance. Foodborne outbreaks are a huge challenge in India. Malnutrition, anemia, hookworm and enteric infections, are the predominant cryptic health conditions among children in rural and tribal areas, leading to severe consequences, including death, and posing a substantial threat to public health. Combating such events with adequate food safety and hygiene practices is achievable. Systematic collection of data can help to develop food safety policies that could reduce the burden of foodborne diseases. Objective This review aims to examine the current situation of foodborne and waterborne diseases, identification of the factors contributing to their occurrence and outbreaks, and defining the gaps in control measures, challenges, and potential solutions in improving the public health system. Methods Strengths, weaknesses, opportunities, and threats (SWOT) analysis was made based on the literature review of foodborne and waterborne infections to assess the current situation and to identify knowledge gaps. Finding SWOT analysis showed the strength and gaps in the different national initiatives analogous to the global programs. Though, Integrated Disease Surveillance Programme (IDSP), Food Safety and Standards Authority of India (FSSAI), the core Government missions, independently generate substantial information, sporadic and outbreak cases of diarrhea still prevail in the country due to the absence of a systematic national surveillance system. Recently, many government initiatives have been made through Sustainable Development Goals (SDGs), G20 goals, etc. However, potential threats such as risk of zoonotic disease transmission to humans, emerging infections and antimicrobial resistance (AMR), and unauthorized activities in the food sector pose a big challenge in safeguarding the public health. Conclusion Maintenance of global food safety requires a systematic analysis of present situations, identification of existing shortcomings, and targeted efforts toward prevention of infections. The ongoing G20 mission and the SDGs for 2030 represent significant strides in this direction. To have pathogen-free animals and supply of contamination-free raw foods is impractical, but, mitigating the prevalence of zoonotic diseases can be accomplished by rigorously enforcing hygiene standards throughout the food production chain. A crucial requirement at present is the implementation of integrated laboratory surveillance for foodborne and waterborne infections, as this will provide policymakers and stakeholders all the evidence based scientific information. This system will facilitate efforts in minimizing the risks associated with foodborne and waterborne infections.
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Affiliation(s)
- Venencia Albert
- Indian Council of Medical Research, Ansari Nagar East, New Delhi-110029, India
| | - Thandavarayan Ramamurthy
- ICMR-National Institute for Research in Bacterial Infections (NIRBI), Kolkata, West Bengal 700010, India
| | - Samaresh Das
- Center for Development of Advanced Computing (CDAC), Kolkata, 700 091, West Bengal, India
| | - Karma G Dolma
- Department of Microbiology, Sikkim Manipal Institute of Medical Sciences (SMIMS), Sikkim Manipal University, Gangtok, Sikkim 737102, India
| | - Tapan Majumdar
- Department of Microbiology, Agartala Government Medical College, Agartala, Tripura 799006, India
| | | | | | - Basumoti Apum
- Department of Microbiology, Bankin Pertin General Hospital & Research Institute, Pasighat, Arunachal Pradesh 791102, India
| | - Madhuchhanda Das
- Division of Development Research, Indian Council of Medical Research, Department of Health Research (Ministry of Health & Family Welfare), P.O. Box No. 4911, Ansari Nagar East, New Delhi-110029 India
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Letafati A, Taghiabadi Z, Roushanzamir M, Memarpour B, Seyedi S, Farahani AV, Norouzi M, Karamian S, Zebardast A, Mehrabinia M, Ardekani OS, Fallah T, Khazry F, Daneshvar SF, Norouzi M. From discovery to treatment: tracing the path of hepatitis E virus. Virol J 2024; 21:194. [PMID: 39180020 PMCID: PMC11342613 DOI: 10.1186/s12985-024-02470-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Accepted: 08/14/2024] [Indexed: 08/26/2024] Open
Abstract
The hepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide. HEV is classified into eight genotypes, labeled HEV-1 through HEV-8. Genotypes 1 and 2 exclusively infect humans, while genotypes 3, 4, and 7 can infect both humans and animals. In contrast, genotypes 5, 6, and 8 are restricted to infecting animals. While most individuals with a strong immune system experience a self-limiting infection, those who are immunosuppressed may develop chronic hepatitis. Pregnant women are particularly vulnerable to severe illness and mortality due to HEV infection. In addition to liver-related complications, HEV can also cause extrahepatic manifestations, including neurological disorders. The immune response is vital in determining the outcome of HEV infection. Deficiencies in T cells, NK cells, and antibody responses are linked to poor prognosis. Interestingly, HEV itself contains microRNAs that regulate its replication and modify the host's antiviral response. Diagnosis of HEV infection involves the detection of HEV RNA and anti-HEV IgM/IgG antibodies. Supportive care is the mainstay of treatment for acute infection, while chronic HEV infection may be cleared with the use of ribavirin and pegylated interferon. Prevention remains the best approach against HEV, focusing on sanitation infrastructure improvements and vaccination, with one vaccine already licensed in China. This comprehensive review provides insights into the spread, genotypes, prevalence, and clinical effects of HEV. Furthermore, it emphasizes the need for further research and attention to HEV, particularly in cases of acute hepatitis, especially among solid-organ transplant recipients.
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Affiliation(s)
- Arash Letafati
- Department of Virology, Faculty of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran.
| | - Zahra Taghiabadi
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Mahshid Roushanzamir
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
- Department of Pharmacological and Biomolecular Science, University of Milan, Milan, Italy
| | - Bahar Memarpour
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
- Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Saba Seyedi
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | | | - Masoomeh Norouzi
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Saeideh Karamian
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Arghavan Zebardast
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Marzieh Mehrabinia
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Omid Salahi Ardekani
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Tina Fallah
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Fatemeh Khazry
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Samin Fathi Daneshvar
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Mehdi Norouzi
- Department of Virology, Faculty of Public Health, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
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Kupke P, Brucker J, Wettengel JM, Protzer U, Wenzel JJ, Schlitt HJ, Geissler EK, Werner JM. Cytokine Response of Natural Killer Cells to Hepatitis B Virus Infection Depends on Monocyte Co-Stimulation. Viruses 2024; 16:741. [PMID: 38793623 PMCID: PMC11125674 DOI: 10.3390/v16050741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 04/29/2024] [Accepted: 05/05/2024] [Indexed: 05/26/2024] Open
Abstract
Hepatitis B virus (HBV) is a major driver of chronic hepatic inflammation, which regularly leads to liver cirrhosis or hepatocellular carcinoma. Immediate innate immune cell response is crucial for the rapid clearance of the infection. Here, natural killer (NK) cells play a pivotal role in direct cytotoxicity and the secretion of antiviral cytokines as well as regulatory function. The aim of this study was to further elucidate NK cell responses triggered by an HBV infection. Therefore, we optimized HBV in vitro models that reliably stimulate NK cells using hepatocyte-like HepG2 cells expressing the Na+-taurocholate co-transporting polypeptide (NTCP) and HepaRG cells. Immune cells were acquired from healthy platelet donors. Initially, HepG2-NTCP cells demonstrated higher viral replication compared to HepaRG cells. Co-cultures with immune cells revealed increased production of interferon-γ and tumor necrosis factor-α by NK cells, which was no longer evident in isolated NK cells. Likewise, the depletion of monocytes and spatial separation from target cells led to the absence of the antiviral cytokine production of NK cells. Eventually, the combined co-culture of isolated NK cells and monocytes led to a sufficient cytokine response of NK cells, which was also apparent when communication between the two immune cell subpopulations was restricted to soluble factors. In summary, our study demonstrates antiviral cytokine production by NK cells in response to HBV+ HepG2-NTCP cells, which is dependent on monocyte bystander activation.
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Affiliation(s)
- Paul Kupke
- Department of Surgery, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Johanna Brucker
- Department of Surgery, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Jochen M. Wettengel
- Institute of Virology, School of Medicine and Health/Helmholtz Munich, Technical University of Munich, 81675 Munich, Germany
- German Center for Infection Research (DZIF), Munich Partner Site, 81675 Munich, Germany
| | - Ulrike Protzer
- Institute of Virology, School of Medicine and Health/Helmholtz Munich, Technical University of Munich, 81675 Munich, Germany
- German Center for Infection Research (DZIF), Munich Partner Site, 81675 Munich, Germany
| | - Jürgen J. Wenzel
- Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Hans J. Schlitt
- Department of Surgery, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Edward K. Geissler
- Department of Surgery, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Jens M. Werner
- Department of Surgery, University Hospital Regensburg, 93053 Regensburg, Germany
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11
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Plümers R, Dreier J, Knabbe C, Steinmann E, Todt D, Vollmer T. Kinetics of Hepatitis E Virus Infections in Asymptomatic Persons. Emerg Infect Dis 2024; 30:934-940. [PMID: 38666600 PMCID: PMC11060471 DOI: 10.3201/eid3005.231764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2024] Open
Abstract
To determine the kinetics of hepatitis E virus (HEV) in asymptomatic persons and to evaluate viral load doubling time and half-life, we retrospectively tested samples retained from 32 HEV RNA-positive asymptomatic blood donors in Germany. Close-meshed monitoring of viral load and seroconversion in intervals of ≈4 days provided more information about the kinetics of asymptomatic HEV infections. We determined that a typical median infection began with PCR-detectable viremia at 36 days and a maximum viral load of 2.0 × 104 IU/mL. Viremia doubled in 2.4 days and had a half-life of 1.6 days. HEV IgM started to rise on about day 33 and peaked on day 36; IgG started to rise on about day 32 and peaked on day 53. Although HEV IgG titers remained stable, IgM titers became undetectable in 40% of donors. Knowledge of the dynamics of HEV viremia is useful for assessing the risk for transfusion-transmitted hepatitis E.
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Gupta T, Dhiman S, Sharma A. Menace of hepatitis E in pregnancy: unleashing the threat of fulminant liver failure. BMJ Case Rep 2024; 17:e257234. [PMID: 38521515 PMCID: PMC10961495 DOI: 10.1136/bcr-2023-257234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/25/2024] Open
Abstract
This case report presents a primigravida in her 20s with a history of seizure disorder and chronic cholecystitis, who presented at 30 weeks and 6 days of gestation with upper abdominal pain, fever and vomiting. Initially diagnosed with acute calculous cholecystitis, the patient's condition rapidly deteriorated, resulting in fetal demise and the development of severe complications. Subsequent investigations revealed an enlarged fatty liver and signs of acute liver failure. The diagnosis of acute fatty liver of pregnancy was initially considered but later ruled out, and the patient was diagnosed with hepatitis E based on positive anti-hepatitis E virus IgM antibodies. Prompt termination of pregnancy was performed, followed by intensive care management. After a prolonged hospital stay, the patient recovered and was discharged in stable condition. This case emphasises the importance of considering hepatitis E as a potential cause of acute liver failure in pregnant women and the need for early recognition and multidisciplinary management to achieve favourable outcomes.
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Affiliation(s)
- Tanisha Gupta
- Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, Delhi, India
| | - Soniya Dhiman
- Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, Delhi, India
| | - Aparna Sharma
- Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, Delhi, India
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13
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Fatawou MA, Chavely MG, Henri MYM, Daniel KN, Claire EZM, Richard N. First Detection and Characterization of Hepatitis E Virus in Sewage Samples in Cameroon. FOOD AND ENVIRONMENTAL VIROLOGY 2023; 15:255-261. [PMID: 37553482 DOI: 10.1007/s12560-023-09562-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 07/26/2023] [Indexed: 08/10/2023]
Abstract
Hepatitis E virus (HEV) represents an important public health concern in many developing countries, including Africa. Transmission of HEV to humans by contaminated drinking water is the most important mode of transmission in low- and middle-income countries. This study aimed to assess the presence of HEV in the environment in Cameroon through molecular analysis of sewage samples. Retrospectively, a total of 157 sewage samples collected between January 2018 and December 2019 were randomly selected and analyzed by molecular techniques to detect and characterize the HEV followed by sequencing and phylogenetic analysis. Three samples (1.9%) collected from North, Far North, and Adamawa regions were positive by real-time reverse transcription polymerization chain reaction. Among these, 2 samples were positive for HEV ribonucleic acid by nested reverse transcription polymerization chain reaction and only one yielded a good sequencing product. Phylogenetic analysis of this unique HEV strain showed that this HEV strain belonged to genotype 3, subtype 3a, and clustered with swine HEV strains from Cameroon, Argentina, and the USA. This study provides preliminary data on the circulation of HEV in wastewater in Cameroon. Further studies will be needed to assess the overall situation in Cameroon.
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Affiliation(s)
| | | | | | | | | | - Njouom Richard
- Virology Department, Centre Pasteur of Cameroon, Yaoundé, Cameroon.
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14
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Songtanin B, Molehin AJ, Brittan K, Manatsathit W, Nugent K. Hepatitis E Virus Infections: Epidemiology, Genetic Diversity, and Clinical Considerations. Viruses 2023; 15:1389. [PMID: 37376687 DOI: 10.3390/v15061389] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 06/13/2023] [Accepted: 06/15/2023] [Indexed: 06/29/2023] Open
Abstract
According to the World Health Organization, approximately 20 million people worldwide are infected annually with the hepatitis E virus (HEV). There are four main genotypes of HEV. Genotype 1 and genotype 2 are common in developing countries and are transmitted by contaminated water from a fecal-oral route. Genotype 3 and genotype 4 are common in developed countries and can lead to occasional transmission to humans via undercooked meat. Hepatitis E virus 1 and HEV3 can lead to fulminant hepatitis, and HEV3 can lead to chronic hepatitis and cirrhosis in immunocompromised patients. The majority of patients with HEV infection are asymptomatic and usually have spontaneous viral clearance without treatment. However, infection in immunocompromised individuals can lead to chronic HEV infection. Both acute and chronic HEV infections can have extrahepatic manifestations. No specific treatment is required for acute HEV infection, no treatment has been approved in chronic infection, and no HEV vaccine has been approved by the (United States) Food and Drug Administration. This review focuses on the molecular virology (HEV life cycle, genotypes, model systems, zoonosis), pathogenesis, clinical manifestation, and treatment of chronic HEV infection, especially in immunocompromised patients, to provide clinicians a better understanding of the global distribution of these infections and the significant effect they can have on immunocompromised patients.
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Affiliation(s)
- Busara Songtanin
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Adebayo J Molehin
- Department of Microbiology & Immunology, College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USA
| | - Kevin Brittan
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Wuttiporn Manatsathit
- Department of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Kenneth Nugent
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
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15
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Mahsoub HM, Heffron CL, Hassebroek AM, Sooryanarain H, Wang B, LeRoith T, Rodríguez GR, Tian D, Meng XJ. Fetal Loss in Pregnant Rabbits Infected with Genotype 3 Hepatitis E Virus Is Associated with Altered Inflammatory Responses, Enhanced Virus Replication, and Extrahepatic Virus Dissemination with Positive Correlations with Increased Estradiol Level. mBio 2023; 14:e0041823. [PMID: 36939322 PMCID: PMC10128027 DOI: 10.1128/mbio.00418-23] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 02/24/2023] [Indexed: 03/21/2023] Open
Abstract
Hepatitis E virus (HEV) causes adverse clinical outcomes in pregnant women, but the underlying mechanisms remain poorly understood. To delineate the mechanisms of pregnancy-associated adverse effects during HEV infection, we utilized a genotype 3 HEV from rabbit (HEV-3ra) and its cognate host (rabbits) to systematically investigate the clinical consequences, viral replication dynamics, and host immune and hormonal responses of HEV infection during pregnancy. We found a significant fetal loss of 23% in HEV-infected pregnant rabbits, indicating an early-stage miscarriage. HEV infection in pregnant rabbits was characterized by higher viral loads in feces, intestinal contents, liver, and spleen tissues, as well as a longer and earlier onset of viremia than in infected nonpregnant rabbits. HEV infection altered the pattern of cytokine gene expressions in the liver of pregnant rabbits and caused a transient increase of serum interferon gamma (IFN-γ) shortly after a notable increase in viral replication, which may contribute to early fetal loss. Histological lesions in the spleen were more pronounced in infected pregnant rabbits, although moderate liver lesions were seen in both infected pregnant and nonpregnant rabbits. Total bilirubin was elevated in infected pregnant rabbits. The serum levels of estradiol (E2) in HEV-infected pregnant rabbits were significantly higher than those in mock-infected pregnant rabbits at 14 days postinoculation (dpi) and correlated positively with higher viral loads in feces, liver, and spleen tissues at 28 dpi, suggesting that it may play a role in extrahepatic virus dissemination. The results have important implications for understanding the severe diseases associated with HEV infection during pregnancy. IMPORTANCE HEV causes adverse pregnancy outcomes, with a mortality rate of >30% in pregnant women, but the underlying mechanisms are poorly understood. In this study, we utilized HEV-3ra and its cognate host (pregnant rabbit) to delineate the potential underlying mechanisms of pregnancy-associated adverse outcomes during HEV infection. We found that infected pregnant rabbits had a fetal loss of 23%, which coincided with enhanced viral replication and an elevated systemic IFN-γ response, followed by longer viremia duration and extrahepatic viral dissemination. Estradiol levels were increased in infected pregnant rabbits and correlated positively with higher fecal viral shedding and higher viral loads in liver and spleen tissues. Infected pregnant rabbits had more pronounced splenic lesions, higher serum total bilirubin, and an altered cytokine gene expression profile in the liver. The results will contribute to our understanding of the mechanisms of HEV-associated adverse pregnancy outcomes.
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Affiliation(s)
- Hassan M. Mahsoub
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Fralin Life Sciences Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - C. Lynn Heffron
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Fralin Life Sciences Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Anna M. Hassebroek
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Fralin Life Sciences Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Harini Sooryanarain
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Fralin Life Sciences Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Bo Wang
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Fralin Life Sciences Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Tanya LeRoith
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Fralin Life Sciences Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Guillermo Raimundi Rodríguez
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Fralin Life Sciences Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Debin Tian
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Fralin Life Sciences Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Xiang-Jin Meng
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Fralin Life Sciences Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
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16
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Ostankova YV, Shchemelev AN, Boumbaly S, Balde TAL, Zueva EB, Valutite DE, Serikova EN, Davydenko VS, Skvoroda VV, Vasileva DA, Semenov AV, Esaulenko EV, Totolian AA. Prevalence of HIV and Viral Hepatitis Markers among Healthcare Workers in the Republic of Guinea. Diagnostics (Basel) 2023; 13:diagnostics13030378. [PMID: 36766482 PMCID: PMC9914033 DOI: 10.3390/diagnostics13030378] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Revised: 01/12/2023] [Accepted: 01/14/2023] [Indexed: 01/20/2023] Open
Abstract
Healthcare workers are much more likely to be infected with HIV and hepatitis viruses compared to the general population. Although healthcare workers are more aware of HIV and hepatitis viruses, several countries in Africa lack a comprehensive grasp of disease routes and transmission risks. The aim of this study was to assess the prevalence of the serological and molecular biological markers of HIV and viral hepatitis among healthcare workers in the Republic of Guinea. The study material was 74 blood serum samples collected from healthcare workers who received additional training at the Institute of Applied Biological Research of Guinea (IRBAG, Kindia, Republic of Guinea). The markers examined included HBsAg, HBeAg, anti-HBs IgG, anti-HBcore IgG, anti-HCV qualitative determination, anti-HEV IgM and IgG, anti-HAV IgM and IgG, and anti-HIV. For viral DNA and RNA detection, nucleic acids were extracted from blood serum, and viral presence was inferred using real-time PCR with hybridization fluorescence detection. A high prevalence of viral hepatitis B markers was shown, and significantly fewer cases of viral hepatitis C and HIV were detected. Almost all examined medical workers had anti-HAV IgG antibodies, but no antibodies to hepatitis E virus. Apparently, the identified markers depend on the general prevalence of certain pathogens in the region and are associated with the traditions and characteristics of the country's residents.
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Affiliation(s)
- Yulia V Ostankova
- Saint Petersburg Pasteur Institut of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor), 197101 Saint Petersburg, Russia
| | - Alexander N Shchemelev
- Saint Petersburg Pasteur Institut of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor), 197101 Saint Petersburg, Russia
| | - Sanaba Boumbaly
- Institute of Applied Biological Research of Guinea (IRBAG), Kindia 100 BP 75, Guinea
- Centre International de Recherche sur les Infections Tropicales en Guinée, Nzerekore 400 BP, Guinea
| | - Thierno A L Balde
- Institute of Applied Biological Research of Guinea (IRBAG), Kindia 100 BP 75, Guinea
| | - Elena B Zueva
- Saint Petersburg Pasteur Institut of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor), 197101 Saint Petersburg, Russia
| | - Diana E Valutite
- Saint Petersburg Pasteur Institut of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor), 197101 Saint Petersburg, Russia
| | - Elena N Serikova
- Saint Petersburg Pasteur Institut of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor), 197101 Saint Petersburg, Russia
| | - Vladimir S Davydenko
- Saint Petersburg Pasteur Institut of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor), 197101 Saint Petersburg, Russia
| | - Vsevolod V Skvoroda
- Saint Petersburg Pasteur Institut of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor), 197101 Saint Petersburg, Russia
| | - Daria A Vasileva
- Saint Petersburg Pasteur Institut of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor), 197101 Saint Petersburg, Russia
| | - Alexander V Semenov
- Ekaterinburg Research Institute of Viral Infections, State Research Center of Virology and Biotechnology Vector of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor), 620030 Ekaterinburg, Russia
| | - Elena V Esaulenko
- Saint Petersburg Pasteur Institut of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor), 197101 Saint Petersburg, Russia
| | - Areg A Totolian
- Saint Petersburg Pasteur Institut of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor), 197101 Saint Petersburg, Russia
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17
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Samala N, Wang RY, Auh S, Balla AK, Dakhoul L, Alter HJ, Farci P, Ghabril M, Lucey MR, Rangnekar AS, Reddy KR, Ghany MG. Hepatitis E prevalence and infection in solid-organ transplant recipients in the United States. J Viral Hepat 2022; 29:1134-1142. [PMID: 36036116 DOI: 10.1111/jvh.13739] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 04/27/2022] [Accepted: 07/19/2022] [Indexed: 12/29/2022]
Abstract
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. An increased risk for HEV infection has been reported in organ-transplant recipients, mainly from Europe. Prospective data on HEV prevalence in the United States (U.S.) organ transplant population are limited. To determine the prevalence and factors associated with HEV infection among solid organ transplant-recipients, we conducted a prospective, cross-sectional, multicentre study among transplant-recipients and age- and organ-matched waitlist patients. Participants answered a risk-exposure questionnaire and were tested for HEV-RNA (in-house PCR), HEV-IgG, and IgM (ELISA, Wantai). Among 456 participants, 224 were transplant-recipients, and 232 were waitlist patients. The mean age was 58 years, 35% female, and 74% White. HEV seroprevalence of the entire cohort was 20.2% and associated with older age (p < 0.0001) and organ transplantation (p = 0.02). The HEV seropositivity was significantly higher among transplant-recipients compared with waitlist patients (24% vs. 16.4%, p = 0.042). Among transplant recipients, relative-risk of being HEV seropositive increased with older age (RR = 3.4 [1.07-10.74] in patients >70 years compared with ≤50 years, p = 0.037); history of graft hepatitis (2.2 [1.27-3.72], p = 0.005); calcineurin inhibitor use (RR = 1.9 [1.03-3.34], p = 0.02); and kidney transplantation (2.4 [1.15-5.16], p = 0.02). HEV-RNA, genotype 3 was detected in only two patients (0.4%), both transplant-recipients. HEV seroprevalence was higher among transplant-recipients than waitlist patients. HEV should be considered in transplant-recipients presenting with graft hepatitis. Detection of HEV-RNA was rare, suggesting that progression to chronic HEV infection is uncommon in transplant-recipients in the U.S.
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Affiliation(s)
- Niharika Samala
- Division of Gastroenterology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Richard Y Wang
- Department of Transfusion Medicine, National Institutes of Health, Bethesda, Maryland, USA
| | - Sungyoung Auh
- Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Abdalla Kara Balla
- MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Lara Dakhoul
- Division of Gastroenterology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Harvey J Alter
- Department of Transfusion Medicine, National Institutes of Health, Bethesda, Maryland, USA
| | - Patrizia Farci
- Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Marwan Ghabril
- Division of Gastroenterology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Michael R Lucey
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Amol S Rangnekar
- MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - K Rajender Reddy
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Marc G Ghany
- Liver Disease Branch (LDB), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
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18
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Thippornchai N, Leaungwutiwong P, Kosoltanapiwat N, Vuong C, Nguyen K, Okabayashi T, Lee A. Survey of hepatitis E virus in pork products and pig stools in Nakhon Pathom Province, Thailand. Vet Med Sci 2022; 8:1975-1981. [PMID: 35636430 PMCID: PMC9514495 DOI: 10.1002/vms3.854] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background Hepatitis E virus (HEV) is an important public health threat resulting in more than 3 million symptomatic cases and 70,000 deaths annually. HEV is classified into at least eight genotypes, and five are associated with human infection. Genotypes 1 and 2 primarily affect humans, whereas genotypes 3 and 4 circulate in both humans and swine and are considered zoonotic viruses. Previous studies in Central Thailand have reported human HEV isolates with high similarity to swine strains and high seroprevalence in pigs, suggesting the potential for pig‐to‐human transmission. Objectives This study aimed to detect and analyse HEV in pork products and pig stools collected from local markets and pig farms in Nakhon Pathom Province in Central Thailand. Methods A total of 177 pig stool and 214 pork product samples were detected for HEV by using RT–PCR amplification. Next, nucleotide sequencing and phylogenetic analysis were performed. Results We found one sample of pork products (1/214, 0.5%), which was a pig liver sample (1/51, 2.0%), and 49 HEV‐positive samples in pig stools (49/177, 27.7%). Phylogenetic analysis showed that all these HEV sequences belonged to genotype 3, with a high correlation between our samples and HEV from humans and swine was previously reported in Thailand. Conclusions This study suggested that the consumption of poorly sanitized or uncooked animal meat or food and frequent exposure to pig stools may be risk factors for HEV infections in humans.
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Affiliation(s)
- Narin Thippornchai
- Department of Microbiology and Immunology Faculty of Tropical Medicine Mahidol University Bangkok Thailand
| | - Pornsawan Leaungwutiwong
- Department of Microbiology and Immunology Faculty of Tropical Medicine Mahidol University Bangkok Thailand
| | - Nathamon Kosoltanapiwat
- Department of Microbiology and Immunology Faculty of Tropical Medicine Mahidol University Bangkok Thailand
| | - Cindy Vuong
- Department of Tropical Medicine Medical Microbiology and Pharmacology University of Hawaii at Manoa Honolulu Hawaii USA
| | - Kellyan Nguyen
- Department of Tropical Medicine Medical Microbiology and Pharmacology University of Hawaii at Manoa Honolulu Hawaii USA
| | - Tamaki Okabayashi
- Department of Veterinary Science Faculty of Agriculture University of Miyazaki Musashimurayama Japan
- Center for Animal Disease Control University of Miyazaki Musashimurayama Japan
- Mahidol Osaka Center for Infectious Diseases Osaka University Musashimurayama Japan
| | - Awapuhi Lee
- Department of Tropical Medicine Medical Microbiology and Pharmacology University of Hawaii at Manoa Honolulu Hawaii USA
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19
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Sanyal A, Agarwal S, Ramakrishnan U, Garg KM, Chattopadhyay B. Using Environmental Sampling to Enable Zoonotic Pandemic Preparedness. J Indian Inst Sci 2022; 102:711-730. [PMID: 36093274 PMCID: PMC9449264 DOI: 10.1007/s41745-022-00322-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 06/27/2022] [Indexed: 11/28/2022]
Abstract
The current pandemic caused by the SARS CoV-2, tracing back its origin possibly to a coronavirus associated with bats, has ignited renewed interest in understanding zoonotic spillovers across the globe. While research is more directed towards solving the problem at hand by finding therapeutic strategies and novel vaccine techniques, it is important to address the environmental drivers of pathogen spillover and the complex biotic and abiotic drivers of zoonoses. The availability of cutting-edge genomic technologies has contributed enormously to preempt viral emergence from wildlife. However, there is still a dearth of studies from species-rich South Asian countries, especially from India. In this review, we outline the importance of studying disease dynamics through environmental sampling from wildlife in India and how ecological parameters of both the virus and the host community may play a role in mediating cross-species spillovers. Non-invasive sampling using feces, urine, shed hair, saliva, shed skin, and feathers has been instrumental in providing genetic information for both the host and their associated pathogens. Here, we discuss the advances made in environmental sampling protocols and strategies to generate genetic data from such samples towards the surveillance and characterization of potentially zoonotic pathogens. We primarily focus on bat-borne or small mammal-borne zoonoses and propose a conceptual framework for non-invasive strategies to tackle the threat of emerging zoonotic infections.
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20
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Interplay between Hepatitis E Virus and Host Cell Pattern Recognition Receptors. Int J Mol Sci 2021; 22:ijms22179259. [PMID: 34502167 PMCID: PMC8431321 DOI: 10.3390/ijms22179259] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Revised: 08/02/2021] [Accepted: 08/06/2021] [Indexed: 11/23/2022] Open
Abstract
Hepatitis E virus (HEV) usually causes self-limiting acute hepatitis, but the disease can become chronic in immunocompromised individuals. HEV infection in pregnant women is reported to cause up to 30% mortality, especially in the third trimester. Additionally, extrahepatic manifestations like neuronal and renal diseases and pancreatitis are also reported during the course of HEV infection. The mechanism of HEV pathogenesis remains poorly understood. Innate immunity is the first line of defense triggered within minutes to hours after the first pathogenic insult. Growing evidence based on reverse genetics systems, in vitro cell culture models, and representative studies in animal models including non-human primates, has implicated the role of the host’s innate immune response during HEV infection. HEV persists in presence of interferons (IFNs) plausibly by evading cellular antiviral defense. This review summarizes our current understanding of recognizing HEV-associated molecular patterns by host cell Pattern Recognition Receptors (PRRs) in eliciting innate immune response during HEV infection as well as mechanisms of virus-mediated immune evasion.
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21
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Bari FD, Wodaje HB, Said U, Waktole H, Sombo M, Leta S, Chibsa TR, Plummer P. First molecular detection of hepatitis E virus genome in camel and pig faecal samples in Ethiopia. Virol J 2021; 18:160. [PMID: 34348751 PMCID: PMC8335859 DOI: 10.1186/s12985-021-01626-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 07/26/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Hepatitis E is an enteric and zoonotic disease caused by hepatitis E virus (HEV) that is mainly transmitted via the faecal-oral route through contaminated food or the environment. The virus is an emerging infectious agent causing acute human infection worldwide. A high seroprevalence of the disease was reported in pregnant women in Addis Ababa, Ethiopia, raising significant public health concern. The presence of HEV specific antibodies were also reported in dromedary camels in the country; however, the infectious virus and/or the viral genome have not been demonstrated to date in animal samples. METHODS To address this gap, a total of 95 faecal samples collected from both apparently healthy pigs of uncharacterised types (50 samples) in Burayu and Addis Ababa areas and camels (Camelus dromedarius, 45 samples) in west Hararghe were screened for the presence of HEV genome using universal primers in a fully nested reverse transcription polymerase chain reaction (nRT-PCR). The protocol is capable of detecting HEV in faecal samples from both pigs and camels. RESULTS The nRT-PCR detected HEV genes in six (12%) pig faecal samples and one camel sample (2.2%). Therefore, the results indicate that HEV is circulating in both pigs and camels in Ethiopia and these animals and their products could serve as a potential source of infection for humans. CONCLUSION The detection of HEV in both animals could raise another concern regarding its public health importance as both animals' meat and camel milk are consumed in the country. Further studies to determine the prevalence and distribution of the virus in different animals and their products, water bodies, food chain, and vegetables are warranted, along with viral gene sequencing for detailed genetic characterisation of the isolates circulating in the country. This information is critically important to design and institute appropriate control and/or preventive measures.
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Affiliation(s)
- Fufa Dawo Bari
- Department of Microbiology, Immunology and Veterinary Public Health, College of Veterinary Medicine and Agriculture, Addis Ababa University, Bishoftu, Ethiopia.
| | - Haimanot Belete Wodaje
- Department of Microbiology, Immunology and Veterinary Public Health, College of Veterinary Medicine and Agriculture, Addis Ababa University, Bishoftu, Ethiopia.,Assosa University, Assosa, Ethiopia
| | - Umer Said
- Department of Microbiology, Immunology and Veterinary Public Health, College of Veterinary Medicine and Agriculture, Addis Ababa University, Bishoftu, Ethiopia.,Oda Bultum University, West Hararge, Chiro, Ethiopia
| | - Hika Waktole
- Department of Microbiology, Immunology and Veterinary Public Health, College of Veterinary Medicine and Agriculture, Addis Ababa University, Bishoftu, Ethiopia
| | - Melaku Sombo
- National Animal Health Diagnostic and Investigation Center, Sebeta, Ethiopia
| | - Samson Leta
- Department of Biomedical Sciences, College of Veterinary Medicine and Agriculture, Addis Ababa University, Bishoftu, Ethiopia
| | | | - Paul Plummer
- Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.,Department of Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA
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22
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Hansen JD, Perri RE, Riess ML. Liver and Biliary Disease of Pregnancy and Anesthetic Implications: A Review. Anesth Analg 2021; 133:80-92. [PMID: 33687174 DOI: 10.1213/ane.0000000000005433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Liver and biliary disease complicates pregnancy in varying degrees of severity to the mother and fetus, and anesthesiologists may be asked to assist in caring for these patients before, during, and after birth of the fetus. Therefore, it is important to be familiar with how different liver diseases impact the pregnancy state. In addition, knowing symptoms, signs, and laboratory markers in the context of a pregnant patient will lead to faster diagnosis and treatment of such patients. This review article discusses changes in physiology of parturients, patients with liver disease, and parturients with liver disease. Next, general treatment of parturients with acute and chronic liver dysfunction is presented. The article progresses to specific liver diseases with treatments as they relate to pregnancy. And finally, important aspects to consider when anesthetizing parturients with liver disease are discussed.
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Affiliation(s)
- Jennette D Hansen
- From the Department of Anesthesiology, North Kansas City Hospital, North Kansas City, Missouri
| | - Roman E Perri
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Matthias L Riess
- From the Department of Anesthesiology, North Kansas City Hospital, North Kansas City, Missouri.,Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee.,Department of Pharmacology, Vanderbilt University, Nashville, Tennessee
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23
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Talapko J, Meštrović T, Pustijanac E, Škrlec I. Towards the Improved Accuracy of Hepatitis E Diagnosis in Vulnerable and Target Groups: A Global Perspective on the Current State of Knowledge and the Implications for Practice. Healthcare (Basel) 2021; 9:133. [PMID: 33572764 PMCID: PMC7912707 DOI: 10.3390/healthcare9020133] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/21/2021] [Accepted: 01/26/2021] [Indexed: 02/07/2023] Open
Abstract
The hepatitis E virus (HEV) is a positive single-stranded, icosahedral, quasi-enveloped RNA virus in the genus Orthohepevirus of the family Hepeviridae. Orthohepevirus A is the most numerous species of the genus Orthohepevirus and consists of eight different HEV genotypes that can cause infection in humans. HEV is a pathogen transmitted via the fecal-oral route, most commonly by consuming fecally contaminated water. A particular danger is the HEV-1 genotype, which poses a very high risk of vertical transmission from the mother to the fetus. Several outbreaks caused by this genotype have been reported, resulting in many premature births, abortions, and also neonatal and maternal deaths. Genotype 3 is more prevalent in Europe; however, due to the openness of the market, i.e., trade-in animals which represent a natural reservoir of HEV (such as pigs), there is a possibility of spreading HEV infections outside endemic areas. This problem is indeed global and requires increased hygiene measures in endemic areas, which entails special care for pregnant women in both endemic and non-endemic regions. As already highlighted, pregnant women could have significant health consequences due to the untimely diagnosis of HEV infection; hence, this is a population that should be targeted with a specific combination of testing approaches to ensure optimal specificity and sensitivity. Until we advance from predominantly supportive treatment in pregnancy and appraise the safety and efficacy of a HEV vaccine in this population, such screening approaches represent the mainstay of our public health endeavors.
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Affiliation(s)
- Jasminka Talapko
- Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, HR-31000 Osijek, Croatia;
| | - Tomislav Meštrović
- University Centre Varaždin, University North, HR-42000 Varaždin, Croatia;
- Clinical Microbiology and Parasitology Unit, Dr. Zora Profozić Polyclinic, HR-10000 Zagreb, Croatia
| | - Emina Pustijanac
- Faculty of Natural Sciences, Juraj Dobrila University of Pula, HR-52100 Pula, Croatia;
| | - Ivana Škrlec
- Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, HR-31000 Osijek, Croatia;
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24
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Laugel E, Hartard C, Jeulin H, Berger S, Venard V, Bronowicki JP, Schvoerer E. Full-length genome sequencing of RNA viruses-How the approach can enlighten us on hepatitis C and hepatitis E viruses. Rev Med Virol 2020; 31:e2197. [PMID: 34260779 DOI: 10.1002/rmv.2197] [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: 08/14/2020] [Revised: 11/04/2020] [Accepted: 11/04/2020] [Indexed: 12/09/2022]
Abstract
Among the five main viruses responsible for human hepatitis, hepatitis C virus (HCV) and hepatitis E virus (HEV) are different while sharing similarities. Both viruses can be transmitted by blood or derivatives whereas HEV can also follow environmental or zoonotic routes. These highly variable RNA viruses can cause chronic hepatitis potentially leading to hepatocarcinoma. HCV and HEV can develop new structures and functions under selective pressure to adapt to host immunity, human tissues, treatments or even various animal reservoirs. Elsewhere, with directly acting antiviral treatments, HCV can be eradicated whereas HEV is an emerging pathogen against which specific treatments have to be improved. As a unique molecular tool able to explore viral genomic plasticity, full-length genome (FLG) sequencing has become easier, faster and cheaper. The present review will show how FLG sequencing can explore these RNA viruses with the aim to investigate key genomics data to improve basic knowledge, patients' healthcare and preventive tools.
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Affiliation(s)
- Elodie Laugel
- Université de Lorraine, Vandœuvre-lès-Nancy, France.,Laboratoire de Virologie, CHRU de Nancy Brabois, Vandœuvre-lès-Nancy, France.,Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), UMR 7564 CNRS-UL, Vandœuvre-lès-Nancy, France
| | - Cédric Hartard
- Université de Lorraine, Vandœuvre-lès-Nancy, France.,Laboratoire de Virologie, CHRU de Nancy Brabois, Vandœuvre-lès-Nancy, France.,Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), UMR 7564 CNRS-UL, Vandœuvre-lès-Nancy, France
| | - Hélène Jeulin
- Université de Lorraine, Vandœuvre-lès-Nancy, France.,Laboratoire de Virologie, CHRU de Nancy Brabois, Vandœuvre-lès-Nancy, France.,Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), UMR 7564 CNRS-UL, Vandœuvre-lès-Nancy, France
| | - Sibel Berger
- Laboratoire de Virologie, CHRU de Nancy Brabois, Vandœuvre-lès-Nancy, France
| | - Véronique Venard
- Université de Lorraine, Vandœuvre-lès-Nancy, France.,Laboratoire de Virologie, CHRU de Nancy Brabois, Vandœuvre-lès-Nancy, France
| | - Jean-Pierre Bronowicki
- Université de Lorraine, Vandœuvre-lès-Nancy, France.,Service d'hépato-gastroentérologie, CHRU de Nancy Brabois, Vandœuvre-lès-Nancy, France
| | - Evelyne Schvoerer
- Université de Lorraine, Vandœuvre-lès-Nancy, France.,Laboratoire de Virologie, CHRU de Nancy Brabois, Vandœuvre-lès-Nancy, France.,Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), UMR 7564 CNRS-UL, Vandœuvre-lès-Nancy, France
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25
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Ghoshal UC, Ghoshal U, Dhiman RK. Gastrointestinal and Hepatic Involvement in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Review. J Clin Exp Hepatol 2020; 10:622-628. [PMID: 32837095 PMCID: PMC7287456 DOI: 10.1016/j.jceh.2020.06.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 06/03/2020] [Indexed: 01/08/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a pandemic coronavirus disease-19 (COVID-19) that began in Wuhan city, China, in December 2019. Till 14th April, 19,39,801 people have been affected by this virus, of whom 1,20,897 died. Though respiratory symptoms are the typical manifestation of this disease, gastrointestinal (GI) symptoms such as anorexia, nausea, vomiting, loss of taste sensation, diarrhea, abdominal pain, and discomfort have been reported. The pooled prevalence of GI symptom is 17.6% (95% confidence interval, 12.3%-24.5%), as indicated in a meta-analysis. A few studies suggested that the presence of GI symptoms is associated with poorer prognosis. The virus is excreted in feces during the acute disease, and even after, the nasopharyngeal swab has become negative for viral ribonucleic acid. Fecal viral excretion may have clinical significance because of possible feco-oral transmission of the infection. Nearly, 10.5%-53% of patients with COVID-19, particularly those with severe disease, have been shown to have an elevation of hepatic enzymes though biochemical and clinical jaundice are uncommon. Knowledge about this disease in general and GI involvement, in particular, is currently evolving.
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Affiliation(s)
- Uday C. Ghoshal
- Address for correspondence. Uday C. Ghoshal, Professor, Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226014, India.
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26
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Thakur V, Ratho RK, Kumar S, Saxena SK, Bora I, Thakur P. Viral Hepatitis E and Chronicity: A Growing Public Health Concern. Front Microbiol 2020; 11:577339. [PMID: 33133046 PMCID: PMC7550462 DOI: 10.3389/fmicb.2020.577339] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 09/03/2020] [Indexed: 12/15/2022] Open
Abstract
Hepatitis E viral infection recently emerges as a global health concern. Over the last decade, the understanding of hepatitis E virus (HEV) had changed with the discovery of new genotypes like genotype-7 and genotype-8 with associated host and mode of infection. Diversification in the mode of hepatitis E infection transmission through blood transfusion, and organ transplants in contrast to classical feco-oral and zoonotic mode is the recent medical concern. The wide spectrum of infection ranging from self-limiting to acute liver failure is now overpowered by HEV genotype-specific chronic infection especially in transplant patients. This concern is further escalated by the extra-hepatic manifestations of HEV targeting the central nervous system (CNS), kidney, heart, and pancreas. However, with the development of advanced efficient cell culture systems and animal models simulating the infection, much clarity toward understanding the pathogenetic mechanism of HEV has been developed. Also this facilitates the development of vaccines research or therapeutics. In this review, we highlight all the novel findings in every aspect of HEV with special emphasis on recently emerging chronic mode of infection with specific diagnosis and treatment regime with an optimistic hope to help virologists and/or liver specialists working in the field of viral hepatitis.
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Affiliation(s)
- Vikram Thakur
- Department of Virology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Radha Kanta Ratho
- Department of Virology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Swatantra Kumar
- Centre for Advanced Research, Faculty of Medicine, King George's Medical University, Lucknow, India
| | - Shailendra K Saxena
- Centre for Advanced Research, Faculty of Medicine, King George's Medical University, Lucknow, India
| | - Ishani Bora
- Department of Virology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Pryanka Thakur
- Department of Virology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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27
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Acute Liver Failure During Pregnancy: Happy to Recover from Hep E. Dig Dis Sci 2020; 65:2515-2517. [PMID: 32524414 DOI: 10.1007/s10620-020-06367-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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28
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Li Y, Long F, Yang C, Hao X, Wu J, Situ J, Chen S, Qian Z, Huang F, Yu W. BALB/c Mouse Is a Potential Animal Model System for Studying Acute and Chronic Genotype 4 Hepatitis E Virus Infection. Front Microbiol 2020; 11:1156. [PMID: 32612582 PMCID: PMC7308725 DOI: 10.3389/fmicb.2020.01156] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Accepted: 05/06/2020] [Indexed: 01/13/2023] Open
Abstract
Hepatitis E virus (HEV) is the main pathogen of hepatitis worldwide. However, its infection biology and pathogenesis remain largely unknown. Suitable small-animal models are required to advance the study of HEV infection. Although an efficient model of genotype 1 (gt1) and gt3 HEV infection has been established in human liver chimeric mice, the infectivity of gt4 HEV infection in mice has not been comprehensively characterized. In this study, immunocompromised BALB/c nude, immunocompetent BALB/c, and C57BL/6 mice were inoculated with either gt3 or gt4 HEV (19 HEV strains, including human, swine, macaque-adapted, and cow HEV strains). Infectivity was identified by viral RNA and antigen detection, inflammation, and histopathological analysis. Then, HEV-infected BALB/c mice were treated with antiviral drugs. Acute HEV infection was established in BALB/c mice inoculated with eight gt4 HEV strains. However, gt3 HEV strains failed to achieve active HEV infection. HEV infection was established in BALB/c nude and regular mice inoculated with gt4 HEV but not in C57BL/6 mice. Gt4 HEV infection resulted in rapid viremia and high titers in feces, sera, and replication sites. HEV infection in mice showed no gender preference. Furthermore, chronic gt4 HEV infection was well imitated in BALB/c mice for 32 weeks and caused liver fibrosis. CONCLUSION BALB/c mice have a great potential for reproducing the process of gt4 HEV infection. The successful establishment of a gt4 HEV small-animal model provides an opportunity to further understand HEV infection biology and zoonotic transmission and develop anti-HEV vaccine.
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Affiliation(s)
- Yunlong Li
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Feiyan Long
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Chenchen Yang
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Xianhui Hao
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Jian Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jianwen Situ
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Shuangfeng Chen
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Zhongyao Qian
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Fen Huang
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Wenhai Yu
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
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29
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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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30
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Nitta S, Takahashi K, Kawai-Kitahata F, Tsuchiya J, Sato A, Miyoshi M, Murakawa M, Itsui Y, Nakagawa M, Azuma S, Kakinuma S, Watanabe M, Asahina Y. Time course alterations of virus sequences and immunoglobulin titers in a chronic hepatitis E patient. Hepatol Res 2020; 50:524-531. [PMID: 31883166 DOI: 10.1111/hepr.13480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Revised: 12/04/2019] [Accepted: 12/23/2019] [Indexed: 02/08/2023]
Abstract
AIM Hepatitis E virus (HEV) can cause chronic infection in immunocompromised hosts. However, the dynamics of HEV during persistent infection is not well understood. To elucidate time course alterations in virus sequences and anti-HEV antibodies during persistent infection, we analyzed the HEV sequences and titers of anti-HEV antibodies from a chronic hepatitis E patient. METHODS Serum samples were obtained from a chronic hepatitis E patient under corticosteroid therapy for neurological disease. The titers of anti-HEV antibodies (immunoglobulin A, immunoglobulin M, and immunoglobulin G) in serum samples were detected by enzyme immunoassay. The full or near-full nucleotide sequences of HEV isolated from consecutive serum samples were identified and compared. Phylogenetic analysis was also performed. RESULTS Alterations of anti-HEV antibodies from a chronic hepatitis E patient were different from those previously reported in acute hepatitis E patients. The virus sequence was unchanged in the period without treatment, but nucleotide mutations were observed after ribavirin treatment was started. In addition, the sequence of this strain had extremely high identity to that isolated from swine liver in Japan. CONCLUSIONS Virus mutations in HEV emerged after ribavirin treatment was started. Sequence analysis may useful for deciding the treatment strategy for chronic hepatitis E patients who did not eliminate the virus with 3 months of RBV treatment and inferring the origin of the infection. This report provides insights into the chronicity of hepatitis E, and the impact of persistent infection and ribavirin treatment on the emergence of virus mutations.
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Affiliation(s)
- Sayuri Nitta
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kazuaki Takahashi
- Department of Medical Sciences, Tokyo-Shinagawa Hospital, Tokyo, Japan.,Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - Fukiko Kawai-Kitahata
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Jun Tsuchiya
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ayako Sato
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Masato Miyoshi
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Miyako Murakawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuhiro Itsui
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Mina Nakagawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Seishin Azuma
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Sei Kakinuma
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.,Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan
| | - Mamoru Watanabe
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.,TMDU Advanced Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuhiro Asahina
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.,Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan
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31
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Paul RC, Nazneen A, Banik KC, Sumon SA, Paul KK, Akram A, Uzzaman MS, Iqbal T, Tejada-Strop A, Kamili S, Luby SP, Gidding HF, Hayen A, Gurley ES. Hepatitis E as a cause of adult hospitalization in Bangladesh: Results from an acute jaundice surveillance study in six tertiary hospitals, 2014-2017. PLoS Negl Trop Dis 2020; 14:e0007586. [PMID: 31961861 PMCID: PMC6994197 DOI: 10.1371/journal.pntd.0007586] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 01/31/2020] [Accepted: 12/27/2019] [Indexed: 12/14/2022] Open
Abstract
In the absence of reliable data on the burden of hepatitis E virus (HEV) in high endemic countries, we established a hospital-based acute jaundice surveillance program in six tertiary hospitals in Bangladesh to estimate the burden of HEV infection among hospitalized acute jaundice patients aged ≥14 years, identify seasonal and geographic patterns in the prevalence of hepatitis E, and examine factors associated with death. We collected blood specimens from enrolled acute jaundice patients, defined as new onset of either yellow eyes or skin during the past three months of hospital admission, and tested for immunoglobulin M (IgM) antibodies against HEV, HBV and HAV. The enrolled patients were followed up three months after hospital discharge to assess their survival status; pregnant women were followed up three months after their delivery to assess pregnancy outcomes. From December’2014 to September’2017, 1925 patients with acute jaundice were enrolled; 661 (34%) had acute hepatitis E, 48 (8%) had hepatitis A, and 293 (15%) had acute hepatitis B infection. Case fatality among hepatitis E patients was 5% (28/589). Most of the hepatitis E cases were males (74%; 486/661), but case fatality was higher among females—12% (8/68) among pregnant and 8% (7/91) among non-pregnant women. Half of the patients who died with acute hepatitis E had co-infection with HAV or HBV. Of the 62 HEV infected mothers who were alive until the delivery, 9 (15%) had miscarriage/stillbirth, and of those children who were born alive, 19% (10/53) died, all within one week of birth. This study confirms that hepatitis E is the leading cause of acute jaundice, leads to hospitalizations in all regions in Bangladesh, occurs throughout the year, and is associated with considerable morbidity and mortality. Effective control measures should be taken to reduce the risk of HEV infections including improvements in water quality, sanitation and hygiene practices and the introduction of HEV vaccine to high-risk groups. In the absence of reliable surveillance data on the burden of hepatitis E in endemic countries, we conducted a hospital-based acute jaundice surveillance study over a two and a half year period in six tertiary hospitals in Bangladesh. The study confirms that HEV infections occur throughout the year, and is a major (34%) cause of acute jaundice in tertiary hospitals in Bangladesh. Three-quarters of the acute hepatitis E cases were male, and HEV infection was higher among patients residing in urban areas than patients in rural areas (41% vs 32%). The overall case fatality rate of acute HEV infections in hospitals was 5%, but was higher among pregnant women (12%). Hepatitis E patients who died were more likely to have co-infection with HAV or HBV than the HEV infected patients who did not die. Fifteen percent of HEV infected mothers had miscarriage/stillbirth. Of the children who were born alive, 19% died, all within one week of birth. Considering the high burden of hepatitis E among hospitalized acute jaundice patients, Bangladesh could take control measures to reduce this risk including improvements in water quality, sanitation and hygiene practices and the introduction of hepatitis E vaccine in high-risk areas.
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Affiliation(s)
- Repon C. Paul
- icddr,b, Dhaka, Bangladesh
- School of Public Health and Community Medicine, UNSW Medicine, Sydney, Australia
- * E-mail:
| | | | | | | | | | - Arifa Akram
- Institute of Epidemiology, Disease Control and Research, Government of the People’s Republic of Bangladesh
| | - M. Salim Uzzaman
- Institute of Epidemiology, Disease Control and Research, Government of the People’s Republic of Bangladesh
| | - Tahir Iqbal
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Alexandra Tejada-Strop
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Saleem Kamili
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Stephen P. Luby
- Infectious Diseases and Geographic Medicine, Stanford University, Stanford, California, United States of America
| | | | - Andrew Hayen
- Australian Centre for Public and Population Health Research, University of Technology Sydney, Sydney, Australia
| | - Emily S. Gurley
- icddr,b, Dhaka, Bangladesh
- Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
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Murata K, Kang JH, Nagashima S, Matsui T, Karino Y, Yamamoto Y, Atarashi T, Oohara M, Uebayashi M, Sakata H, Matsubayashi K, Takahashi K, Arai M, Mishiro S, Sugiyama M, Mizokami M, Okamoto H. IFN-λ3 as a host immune response in acute hepatitis E virus infection. Cytokine 2020; 125:154816. [PMID: 31465972 DOI: 10.1016/j.cyto.2019.154816] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 07/31/2019] [Accepted: 08/19/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM Hepatitis E virus (HEV) is mainly transmitted orally, either waterborne or zoonotic foodborne. Intestinal viruses such as rotavirus are known to induce type III interferon (IFN) in the gastrointestinal (GI) tract where type III IFN dominantly functions in comparison with type I IFN. Therefore, the aim of this study is to investigate the significance of type III IFN (IFN-λ3) in acute hepatitis E. METHODS IFN-λ3 and HEV RNA levels in the sera of patients with acute HEV infection and in the supernatant of HEV-inoculated cells were measured, using an in-house high-sensitivity method and reverse transcription-polymerase chain reaction, respectively. RESULTS High serum IFN-λ3 levels were found in the early phase of acute HEV infection, which normalized after resolution. Interestingly, serum IFN-λ3 levels correlated well with serum HEV RNA titers in the same sera, both of which showed the peak before the robust increase of transaminases. In vitro experiments demonstrated that HEV replicated well in the cells with little IFN-λ3 induction (Caco-2, A549) and recombinant IFN-λ3 inhibited HEV replication in a dose-dependent manner. In contrast, in HT-29 cells, a colon cancer cell line, HEV poorly replicated and induced IFN-λ3 in a titer-dependent manner. CONCLUSIONS These clinical and experimental observations suggest that HEV induced IFN-λ3 as a host innate immune response, which may play a protective role against HEV.
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Affiliation(s)
- Kazumoto Murata
- Department of Gastroenterology, Graduate School of Medical Sciences, International University of Health and Welfare, Nasushiobara, Japan; Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, Japan.
| | - Jong-Hon Kang
- Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Shigeo Nagashima
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Japan
| | - Takeshi Matsui
- Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Yoshiyasu Karino
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Yoshiya Yamamoto
- Department of Gastroenterology, Hakodate Municipal Hospital, Hakodate, Japan
| | - Tomofumi Atarashi
- Department of Gastroenterology, Obihiro Kosei Hospital, Obihiro, Japan
| | - Masatsugu Oohara
- Department of Gastroenterology and Oncology, Kitami Red Cross Hospital, Kitami, Japan
| | - Minoru Uebayashi
- Department of Gastroenterology and Oncology, Kitami Red Cross Hospital, Kitami, Japan
| | | | - Keiji Matsubayashi
- Central Blood Institute, Blood Service Headquarters, Japanese Red Cross Society, Tokyo, Japan
| | - Kazuaki Takahashi
- Department of Medical Sciences, Tokyo Shinagawa Hospital, Tokyo, Japan
| | - Masahiro Arai
- Department of Medical Sciences, Tokyo Shinagawa Hospital, Tokyo, Japan
| | - Shunji Mishiro
- Department of Medical Sciences, Tokyo Shinagawa Hospital, Tokyo, Japan
| | - Masaya Sugiyama
- Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, Japan
| | - Masashi Mizokami
- Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Japan
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Milojević L, Velebit B, Teodorović V, Kirbiš A, Petrović T, Karabasil N, Dimitrijević M. Screening and Molecular Characterization of Hepatitis E Virus in Slaughter Pigs in Serbia. FOOD AND ENVIRONMENTAL VIROLOGY 2019; 11:410-419. [PMID: 31243738 DOI: 10.1007/s12560-019-09393-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 06/20/2019] [Indexed: 05/25/2023]
Abstract
Hepatitis E virus (HEV) is a zoonotic virus that can cause acute hepatitis in humans. Besides the fecal-oral route, transmission can occur by consumption of undercooked pig liver. Genotype 3 is the most frequent genotype found in Europe. Studies on HEV in slaughter-age pigs have not been conducted in Serbia so far. Pork meat production and consumption in Serbia is on average, higher than in the rest of Europe. With the aim to identify the circulating HEV genotypes, pig livers and swab samples from three pig slaughterhouses located in three different sub-regions of Serbia were collected. A nested RT-PCR was used to amplify the hypervariable HEV ORF-1 region (334 bp). The amplicons yielded in this study were sequenced, and a molecular phylogeny analysis based on the maximum likelihood method, including HEV sequences reported in several other countries, was performed. The average prevalence of HEV genotype 3 in 3-month-old pigs was 34%. Phylogenetic analysis revealed the majority of HEV amplification fragments from Serbia were grouped in four clades within sub-genotype 3a and were also genetically related to German, Italian, Slovenian, and American HEV sequences. Sub-genotypes 3b and 3j were also found in a single pig each. This study provides the first analysis of the genetic diversity and circulation dynamics of HEV in pigs at slaughterhouses in Serbia.
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Affiliation(s)
- Lazar Milojević
- Institute of Meat Hygiene and Technology, Kaćanskog 13, Belgrade, 11040, Serbia
| | - Branko Velebit
- Institute of Meat Hygiene and Technology, Kaćanskog 13, Belgrade, 11040, Serbia.
| | - Vlado Teodorović
- Faculty of Veterinary Medicine, University of Belgrade, Bulevar Oslobođenja 18, Belgrade, 11000, Serbia
| | - Andrej Kirbiš
- Veterinary Faculty, University of Ljubljana, Gerbičeva 60, 1000, Ljubljana, Slovenia
| | - Tamaš Petrović
- Scientific Veterinary Institute "Novi Sad", Rumenački put 20, Novi Sad, 21000, Serbia
| | - Neđeljko Karabasil
- Faculty of Veterinary Medicine, University of Belgrade, Bulevar Oslobođenja 18, Belgrade, 11000, Serbia
| | - Mirjana Dimitrijević
- Faculty of Veterinary Medicine, University of Belgrade, Bulevar Oslobođenja 18, Belgrade, 11000, Serbia
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Tripathy AS, Sharma M, Deoshatwar AR, Babar P, Bharadwaj R, Bharti OK. Study of a hepatitis E virus outbreak involving drinking water and sewage contamination in Shimla, India, 2015-2016. Trans R Soc Trop Med Hyg 2019; 113:789-796. [PMID: 31647558 DOI: 10.1093/trstmh/trz072] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 05/15/2019] [Accepted: 07/17/2019] [Indexed: 01/02/2025] Open
Abstract
BACKGROUND Hepatitis E, caused by hepatitis E virus (HEV), accounts for 50% of acute hepatitis cases in India. We report an outbreak of hepatitis E in Shimla, India, in 2015-2016. METHODS ICMR-National Institute of Virology (NIV), Pune, received two batches of water samples from Shimla in January 2016 to test for the presence of enterically transmitted hepatitis viruses. Subsequently, 57 icterus patients were tested for various markers of hepatotropic viruses, i.e. anti-HEV IgM/IgG, anti-hepatitis A virus (anti-HAV) IgM/IgG antibodies and HEV RNA. Water samples were screened for HEV and HAV RNA followed by phylogenetic analysis. RESULTS Overall, 48/57 patients availing municipal water had evidence of HEV infection, detected by serology and RT-PCR. All the water samples tested positive for HEV and HAV RNA, while the patients were negative for anti-HAV IgM antibody, indicating no recent HAV infection. Phylogenetic analysis confirmed the aetiological agent of the current outbreak to be HEV genotype 1. CONCLUSIONS Serology and RT-PCR confirmed HEV as the aetiology of the outbreak. The absence of new cases of hepatitis A, despite the presence of HAV in the water supply, could be due to previously acquired immunity. Sewage contamination of water leading to faecal-oral transmission of HEV still remains a concern, thus emphasising the need for a vaccination/control strategy.
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Affiliation(s)
- Anuradha S Tripathy
- Hepatitis Group, ICMR-National Institute of Virology, Pune, 130/1, Sus Road, Pashan, Pune, Maharashtra, India
| | - Meenal Sharma
- Hepatitis Group, ICMR-National Institute of Virology, Pune, 130/1, Sus Road, Pashan, Pune, Maharashtra, India
| | - Avinash R Deoshatwar
- Epidemiology Group, ICMR-National Institute of Virology, Pune, 130/1, Sus Road, Pashan, Pune, Maharashtra, India
| | - Prasad Babar
- Hepatitis Group, ICMR-National Institute of Virology, Pune, 130/1, Sus Road, Pashan, Pune, Maharashtra, India
| | - Rakesh Bharadwaj
- Directorate of Health Services, Kasumpati, Shimla-171009, Himachal Pradesh, India
| | - Omesh Kumar Bharti
- Department of Epidemiology, Deen Dayal Upadhyay (DDU) Zonal Hospital, Shimla, Himachal Pradesh, India
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35
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Montone AMI, De Sabato L, Suffredini E, Alise M, Zaccherini A, Volzone P, Di Maro O, Neola B, Capuano F, Di Bartolo I. Occurrence of HEV-RNA in Italian Regional Pork and Wild Boar Food Products. FOOD AND ENVIRONMENTAL VIROLOGY 2019; 11:420-426. [PMID: 31512058 DOI: 10.1007/s12560-019-09403-2] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Revised: 08/28/2019] [Accepted: 08/30/2019] [Indexed: 06/10/2023]
Abstract
Hepatitis E is an emerging threat in industrialized countries. The foodborne transmission linked to consumption of pork and game meat is considered the main source of autochthonous infection. In Europe, small outbreaks have been reported linked to the consumption of pork liver sausages and wild boar meat. Based on previous findings and on increasing evidence of pork and game meat as a vehicle for HEV infections, the present study investigated the occurrence of HEV in 99 pork and 63 wild boar sausages and salami sold in Southern Italy. The HEV genome was detected in four wild boar sausages. Sequencing from 2 wild boar sausages confirmed that the HEV strains detected belonged to HEV-3 genotype, not assigned to any defined subtype. Data obtained confirmed the possible occurrence of HEV in pork products and in game. Although the detection rate is low, these products are frequently consumed raw after curing, whose effect on virus viability is still unknown.
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Affiliation(s)
| | - Luca De Sabato
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore Di Sanità, Viale Regina Elena 299, 00161, Rome, Italy
| | - Elisabetta Suffredini
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore Di Sanità, Viale Regina Elena 299, 00161, Rome, Italy
| | - Mosè Alise
- Istituto Zooprofilattico Sperimentale del Mezzogiorno, Via Salute 2, 80055, Portici, NA, Italy
| | - Alessandra Zaccherini
- Istituto Zooprofilattico Sperimentale del Mezzogiorno, Via Salute 2, 80055, Portici, NA, Italy
| | - Palmiero Volzone
- Istituto Zooprofilattico Sperimentale del Mezzogiorno, Via Salute 2, 80055, Portici, NA, Italy
| | - Orlandina Di Maro
- Istituto Zooprofilattico Sperimentale del Mezzogiorno, Via Salute 2, 80055, Portici, NA, Italy
| | - Benedetto Neola
- Istituto Zooprofilattico Sperimentale del Mezzogiorno, Via Salute 2, 80055, Portici, NA, Italy
| | - Federico Capuano
- Istituto Zooprofilattico Sperimentale del Mezzogiorno, Via Salute 2, 80055, Portici, NA, Italy
| | - Ilaria Di Bartolo
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore Di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
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36
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Hepatitis E Virus Shows More Genomic Alterations in Cell Culture than In Vivo. Pathogens 2019; 8:pathogens8040255. [PMID: 31766624 PMCID: PMC6963849 DOI: 10.3390/pathogens8040255] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 11/12/2019] [Accepted: 11/18/2019] [Indexed: 12/16/2022] Open
Abstract
Hepatitis E Virus (HEV) mutations following ribavirin treatment have been associated with treatment non-response and viral persistence, but spontaneous occurring genomic variations have been less well characterized. We here set out to study the HEV genome composition in 2 patient sample types and 2 infection models. Near full HEV genome Sanger sequences of serum- and feces-derived HEV from two chronic HEV genotype 3 (gt3) patients were obtained. In addition, viruses were sequenced after in vitro or in vivo expansion on A549 cells or a humanized mouse model, respectively. We show that HEV acquired 19 nucleotide mutations, of which 7 nonsynonymous amino acids changes located in Open Reading Frame 1 (ORF1), ORF2, and ORF3 coding regions, after prolonged in vitro culture. In vivo passage resulted in selection of 8 nucleotide mutations with 2 altered amino acids in the X domain and Poly-proline region of ORF1. Intra-patient comparison of feces- and serum-derived HEV gt3 of two patients showed 7 and 2 nucleotide mutations with 2 and 0 amino acid changes, respectively. Overall, the number of genomic alterations was up to 1.25× per 1000 nucleotides or amino acids in in vivo samples, and up to 2.84× after in vitro expansion of the same clinical HEV strain. In vitro replication of a clinical HEV strain is therefore associated with more mutations, compared to the minor HEV genomic alterations seen after passage of the same strain in an immune deficient humanized mouse; as well as in feces and blood of 2 immunosuppressed chronically infected HEV patients. These data suggest that HEV infected humanized mice more closely reflect the HEV biology seen in solid organ transplant recipients.
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Paul RC, Gidding HF, Nazneen A, Banik KC, Sumon SA, Paul KK, Luby SP, Gurley ES, Hayen A. A Low-Cost, Community Knowledge Approach to Estimate Maternal and Jaundice-Associated Mortality in Rural Bangladesh. Am J Trop Med Hyg 2019; 99:1633-1638. [PMID: 30298803 DOI: 10.4269/ajtmh.17-0974] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
In the absence of a civil registration system, a house-to-house survey is often used to estimate cause-specific mortality in low- and middle-income countries. However, house-to-house surveys are resource and time intensive. We applied a low-cost community knowledge approach to identify maternal deaths from any cause and jaundice-associated deaths among persons aged ≥ 14 years, and stillbirths and neonatal deaths in mothers with jaundice during pregnancy in five rural communities in Bangladesh. We estimated the method's sensitivity and cost savings compared with a house-to-house survey. In the five communities with a total of 125,570 population, we identified 13 maternal deaths, 60 deaths among persons aged ≥ 14 years associated with jaundice, five neonatal deaths, and four stillbirths born to a mother with jaundice during pregnancy over the 3-year period before the survey using the community knowledge approach. The sensitivity of community knowledge method in identifying target deaths ranged from 80% for neonatal deaths to 100% for stillbirths and maternal deaths. The community knowledge approach required 36% of the staff time to undertake compared with the house-to-house survey. The community knowledge approach was less expensive but highly sensitive in identifying maternal and jaundice-associated mortality, as well as all-cause adult mortality in rural settings in Bangladesh. This method can be applied in rural settings of other low- and middle-income countries and, in conjunction with hospital-based hepatitis diagnoses, used to monitor the impact of programs to reduce the burden of cause-specific hepatitis mortality, a current World Health Organization priority.
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Affiliation(s)
- Repon C Paul
- School of Public Health and Community Medicine, UNSW Medicine, Sydney, Australia.,International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Heather F Gidding
- School of Public Health and Community Medicine, UNSW Medicine, Sydney, Australia
| | - Arifa Nazneen
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Kajal C Banik
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Shariful A Sumon
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Kishor K Paul
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Stephen P Luby
- Infectious Diseases and Geographic Medicine, Stanford University, Stanford, California
| | - Emily S Gurley
- Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.,International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Andrew Hayen
- Australian Centre for Public and Population Health, Research, University of Technology Sydney, Sydney, Australia
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38
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Hoan NX, Huy PX, Sy BT, Meyer CG, Son TV, Binh MT, Giang DP, Tu Anh D, Bock CT, Wang B, Tong HV, Kremsner PG, Song LH, Toan NL, Velavan TP. High Hepatitis E virus (HEV) Positivity Among Domestic Pigs and Risk of HEV Infection of Individuals Occupationally Exposed to Pigs and Pork Meat in Hanoi, Vietnam. Open Forum Infect Dis 2019; 6:ofz306. [PMID: 31660396 PMCID: PMC6735913 DOI: 10.1093/ofid/ofz306] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Accepted: 06/25/2019] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) infection can occur through consumption of undercooked pork meat or exposure to animal feces. Because there are scarce data only in developing countries, we assessed whether pigs might be a potential source of human HEV infections in Vietnam. In addition, we determined anti-HEV seroprevalences in the general population and in individuals professionally exposed to pigs and pork meat. METHODS The study took place in Hanoi, Vietnam. Liver tissues from domestic pigs (n = 210) and serum samples obtained from individuals occupationally exposed to pigs and pork meat (n = 283) and from unexposed healthy controls (n = 168) were screened for HEV-ribonucleic acid (RNA) by reverse-transcription polymerase chain reaction. The exposed group was divided into pork meat vendors (n = 81), pig farmers (n = 96), and slaughterers (n = 106). Serum samples were subjected to HEV immunoglobulin (Ig)G and IgM enzyme-linked immunosorbent assays. The HEV genotypes were assessed by direct sequencing, followed by phylogenetic analyses. RESULTS Hepatitis E virus seroprevalence was higher among persons occupationally exposed to pigs/pork meat compared with unexposed individuals (anti-HEV IgM 11% vs 6%, P = .07; anti-HEV IgG 53% vs 31%, P < .0001). Positivity of anti-HEV IgG among slaughterhouse staff was 66%, followed by 51% in pig-farmers and 38% in pork meat vendors (P = .00073). A similar trend was observed for IgM positivity. Of the pig liver tissues, 26 of 210 (12.4%) were positive for HEV-RNA and assessed to be HEV genotype 3. CONCLUSIONS Hepatitis E virus circulates in domestic pigs in Hanoi and constitutes a permanent zoonotic disease risk. The high HEV seroprevalence among occupationally exposed individuals indicates an associated risk of HEV infection.
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Affiliation(s)
- Nghiem Xuan Hoan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Institute of Clinical Infectious Diseases, Hanoi, Vietnam
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
| | - Pham Xuan Huy
- Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam
| | - Bui Tien Sy
- Institute of Clinical Infectious Diseases, Hanoi, Vietnam
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
| | - Christian G Meyer
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
- Duy Tan University, Da Nang, Vietnam
| | - Trinh Van Son
- Institute of Clinical Infectious Diseases, Hanoi, Vietnam
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
| | - Mai Thanh Binh
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
| | - Dao Phuong Giang
- Institute of Clinical Infectious Diseases, Hanoi, Vietnam
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
| | - Dam Tu Anh
- Department of Immunology and Pathophysiology, Hanoi Medical University, Vietnam
| | - C-Thomas Bock
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
| | - Bo Wang
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
| | - Hoang Van Tong
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
- Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam
| | - Peter G Kremsner
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
| | - Le Huu Song
- Institute of Clinical Infectious Diseases, Hanoi, Vietnam
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
| | - Nguyen Linh Toan
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
- Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam
| | - Thirumalaisamy P Velavan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
- Duy Tan University, Da Nang, Vietnam
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Rogers E, Todd SM, Pierson FW, Kenney SP, Heffron CL, Yugo DM, Matzinger SR, Mircoff E, Ngo I, Kirby C, Jones M, Siegel P, Jobst P, Hall K, Etches RJ, Meng XJ, LeRoith T. CD8 + lymphocytes but not B lymphocytes are required for protection against chronic hepatitis E virus infection in chickens. J Med Virol 2019; 91:1960-1969. [PMID: 31317546 DOI: 10.1002/jmv.25548] [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: 05/13/2019] [Accepted: 07/09/2019] [Indexed: 12/12/2022]
Abstract
Hepatitis E is an important global disease, causing outbreaks of acute hepatitis in many developing countries and sporadic cases in industrialized countries. Hepatitis E virus (HEV) infection typically causes self-limiting acute hepatitis but can also progress to chronic disease in immunocompromised individuals. The immune response necessary for the prevention of chronic infection is T cell-dependent; however, the arm of cellular immunity responsible for this protection is not currently known. To investigate the contribution of humoral immunity in control of HEV infection and prevention of chronicity, we experimentally infected 20 wild-type (WT) and 18 immunoglobulin knockout (JH-KO) chickens with a chicken strain of HEV (avian HEV). Four weeks postinfection (wpi) with avian HEV, JH-KO chickens were unable to elicit anti-HEV antibody but had statistically significantly lower liver lesion scores than the WT chickens. At 16 wpi, viral RNA in fecal material and liver, and severe liver lesions were undetectable in both groups. To determine the role of cytotoxic lymphocytes in the prevention of chronicity, we infected 20 WT and 20 cyclosporine and CD8+ antibody-treated chickens with the same strain of avian HEV. The CD8 + lymphocyte-depleted, HEV-infected chickens had higher incidences of prolonged fecal viral shedding and statistically significantly higher liver lesion scores than the untreated, HEV-infected birds at 16 wpi. The results indicate that CD8 + lymphocytes are required for viral clearance and reduction of liver lesions in HEV infection while antibodies are not necessary for viral clearance but may contribute to the development of liver lesions in acute HEV infection.
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Affiliation(s)
- Eda Rogers
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | - Stephanie Michelle Todd
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | - Frank William Pierson
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | - Scott P Kenney
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | - Connie Lynn Heffron
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | - Danielle M Yugo
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | - Shannon R Matzinger
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | - Elena Mircoff
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | - Irene Ngo
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | - Charles Kirby
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | - Michaela Jones
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | - Paul Siegel
- Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | - Peter Jobst
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | - Karen Hall
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | | | - Xiang-Jin Meng
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | - Tanya LeRoith
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
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Kamar N, Pischke S. Acute and Persistent Hepatitis E Virus Genotype 3 and 4 Infection: Clinical Features, Pathogenesis, and Treatment. Cold Spring Harb Perspect Med 2019; 9:cshperspect.a031872. [PMID: 29735575 DOI: 10.1101/cshperspect.a031872] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Hepatitis E virus (HEV) genotype (gt)3 and 4 infections are prevalent in industrialized and high-income countries. Although most HEV gt3 and gt4 infections are clinically silent, acute infection may be symptomatic in some patients. In persons with underlying liver disease and in elderly men, HEV infections may present as acute or acute-on-chronic liver failure. Chronic hepatitis may develop in immunosuppressed individuals, including transplant recipients, human immunodeficiency virus (HIV)-infected patients, and persons with hematologic malignancy undergoing chemotherapy, and may progress to life-threatening liver cirrhosis. Extrahepatic manifestations of infection may include neurological and renal disease. Although there is no approved specific therapy for the treatment of acute or chronic HEV gt3 or gt4 infection, off-label use of ribavirin appears to be capable of eliminating chronic HEV infection, and may reduce disease severity in patients suffering from acute liver failure.
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Affiliation(s)
- Nassim Kamar
- Department of Nephrology and Organ Transplantation, Université Paul Sabatier, Toulouse 31059, France
| | - Sven Pischke
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany
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Dagnew M, Belachew A, Tiruneh M, Moges F. Hepatitis E virus infection among pregnant women in Africa: systematic review and meta-analysis. BMC Infect Dis 2019; 19:519. [PMID: 31195988 PMCID: PMC6567642 DOI: 10.1186/s12879-019-4125-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Accepted: 05/22/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND There have been a number of studies about seroprevalence of HEV among pregnant women in Africa. However, the finding of seroprevalence of HEV infection among pregnant women is variable and inconsistent. Therefore; this systematic review intended to provide the pooled seroprevalence of HEV among pregnant women in Africa. METHODS We searched, Pub Med, Science direct, African online journals and Google scholar electronic data bases and all available references until August 30, 2018. We included cross sectional studies and cohort studies. The search was further limited studies done in African pregnant women. Statistical analysis done by using Stata (version 11) software. The overall pooled prevalence of HEV presented by using the forest plot with 95% CI. The methodological qualities of included studies were assessed using Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instruments. RESULT The pooled seroprevalence of HEV among pregnant women in Africa was 29.13% (95% CI 14.63-43.63). The highest seroprevalence was 84.3% in Egypt and the lowest 6.6% reported in Gabon. There was highest heterogeneity level where I2 = 99.7%; P < 0.0001.The observed heterogeneity attributed to geographic location/ region, country, assay method used in each study and year of study published. Moreover, HEV seroprevalence varies between countries and within countries. The HEV infection among African pregnant women seems to have a decreasing trend over time. CONCLUSION The seroprevalence of HEV among pregnant women in Africa is high. The seroprevalence of HEV among pregnant women differ with geographic location and assay method. Therefore, it is recommended to conduct further research on commercial ELISA kit sensitivity and specificity, molecular tests, incidence, morbidity and mortality and vertical transmission of HEV from mother to infant in Africa. TRIAL REGISTRATION CRD42018084963 .
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Affiliation(s)
- Mulat Dagnew
- Department of Medical Microbiology, College of Medicine and Health Sciences, School of Biomedical and Laboratory Sciences, University of Gondar, Gondar, Ethiopia
| | - Amare Belachew
- College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia
| | - Moges Tiruneh
- Department of Medical Microbiology, College of Medicine and Health Sciences, School of Biomedical and Laboratory Sciences, University of Gondar, Gondar, Ethiopia
| | - Feleke Moges
- Department of Medical Microbiology, College of Medicine and Health Sciences, School of Biomedical and Laboratory Sciences, University of Gondar, Gondar, Ethiopia
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Yang C, Hao X, Li Y, Long F, He Q, Huang F, Yu W. Successful Establishment of Hepatitis E Virus Infection in Pregnant BALB/c Mice. Viruses 2019; 11:E451. [PMID: 31108901 PMCID: PMC6563234 DOI: 10.3390/v11050451] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Revised: 05/08/2019] [Accepted: 05/14/2019] [Indexed: 02/06/2023] Open
Abstract
Worldwide, the Hepatitis E virus (HEV) is the main pathogen of acute viral hepatitis, with an extremely high mortality in pregnant women. However, the pathogenesis of HEV infection in pregnant women remains largely unknown. We established an HEV-infected pregnant mice animal model to explore the adverse pregnancy outcomes of HEV infection. Mice were infected with HEV in their early, middle and late stages of pregnancy. HEV RNA was detected in the tissues (liver, spleen, kidney, colon, uterus and placenta) of pregnant mice. HEV antigens were also detected in these tissues of HEV-infected pregnant mice. Miscarriages (7/8, 87.5%) occurred in pregnant mice infected with HEV in the middle of pregnancy. Th1-biased immune status was found in these aborted mice. Vertical transmission was confirmed by HEV replication in the uterus and placenta, as well as in the positive HEV RNA and HEV antigen positive in fetal livers. The successful establishment of HEV infection in pregnant mice is beneficial for further study of HEV pathogenesis, especially the adverse pregnancy outcomes caused by HEV infection.
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Affiliation(s)
- Chenchen Yang
- Medical School, Kunming University of Science and Technology, Kunming 650500, China.
| | - Xianhui Hao
- Medical School, Kunming University of Science and Technology, Kunming 650500, China.
| | - Yunlong Li
- Medical School, Kunming University of Science and Technology, Kunming 650500, China.
| | - Feiyan Long
- Medical School, Kunming University of Science and Technology, Kunming 650500, China.
| | - Qiuxia He
- Medical School, Kunming University of Science and Technology, Kunming 650500, China.
| | - Fen Huang
- Medical School, Kunming University of Science and Technology, Kunming 650500, China.
| | - Wenhai Yu
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.
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Hudu SA, Niazlin MT, Nordin SA, Harmal NS, Tan SS, Omar H, Shahar H, Mutalib NA, Sekawi Z. Hepatitis E virus isolated from chronic hepatitis B patients in Malaysia: Sequences analysis and genetic diversity suggest zoonotic origin. ALEXANDRIA JOURNAL OF MEDICINE 2019. [DOI: 10.1016/j.ajme.2017.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Affiliation(s)
- Shuaibu Abdullahi Hudu
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra, Malaysia
- Department of Medical Microbiology and Parasitology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria
| | - Mohd Taib Niazlin
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra, Malaysia
| | - Syafinaz Amin Nordin
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra, Malaysia
| | - Nabil Saad Harmal
- Department of Microbiology, Faculty of Medicine, Asia Metropolitan University, 81750 Johor Bahru, Malaysia
| | - Soek Siam Tan
- Department of Hepatology, Selayang Hospital, Lebuh Selayang-Kepong , Batu Caves, 68100 Selangor Darul Ehsan, Malaysia
| | - Haniza Omar
- Department of Hepatology, Selayang Hospital, Lebuh Selayang-Kepong , Batu Caves, 68100 Selangor Darul Ehsan, Malaysia
| | - Hamiza Shahar
- Department of Hepatology, Selayang Hospital, Lebuh Selayang-Kepong , Batu Caves, 68100 Selangor Darul Ehsan, Malaysia
| | - Noor Aliza Mutalib
- Department of Hepatology, Selayang Hospital, Lebuh Selayang-Kepong , Batu Caves, 68100 Selangor Darul Ehsan, Malaysia
| | - Zamberi Sekawi
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra, Malaysia
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44
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Hepatitis E: Current Status in India and Other Asian Countries. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2019. [DOI: 10.22207/jpam.13.1.15] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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45
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Jemeršić L, Prpić J, Brnić D, Keros T, Pandak N, Đaković Rode O. Genetic diversity of hepatitis E virus (HEV) strains derived from humans, swine and wild boars in Croatia from 2010 to 2017. BMC Infect Dis 2019; 19:269. [PMID: 30890143 PMCID: PMC6425696 DOI: 10.1186/s12879-019-3906-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Accepted: 03/14/2019] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND To fulfill epidemiological data and investigate possible interspecies transmission, this study shall attempt to sequence representative HEV strains of human, swine and wild boar origin collected from 2010 to 2017 in Croatia. METHODS In total, 174 anti-HEV antibody positive human sera samples; 1419 blood or faeces samples of swine, as well as 720 tissue and/or blood samples of wild boar originating from different counties (18 in total) in Croatia were tested for the presence of HEV RNA. RESULTS HEV RNA was detected in 26 human sera samples (14.9%; 95% CI 10.4-21.0%). HEV RNA was detected in 216 tested swine (15.2%; 95% CI 13.5-17.1%), regardless of age, farm breeding system or geographical origin. Viral RNA was also detectable in faeces samples which prove that swine actively participate in shedding HEV into the environment. Of the total of 720 tested wild boar samples, 83 were HEV RNA positive (11.5, 95% CI 9.4-14.1%) originating from six counties. According to the sequence analysis all strains have shown to be members of Orthohepevirus A genotype HEV-3, regardless of host. The genotyping results confirm grouping of sequences into four subtypes of HEV strains of which subtypes 3a and 3c belong to the general cluster 3abchij, and were predominately detected during the study, while subtypes 3e and 3f fall within cluster 3efg. Strains within subtypes 3a and 3e were found in humans, swine and wild boars; subtype 3c strains were derived from humans and swine, whereas subtype 3f strains were found only in humans. Strains belonging to subtypes 3a and 3c were derived during the entire investigated period and may be considered endemic in Croatia, whereas strains within subtypes 3e and 3f were detected sporadically indicating the possibility of newly imported infections. CONCLUSIONS All detected strains show to be genetically highly related to strains found in humans and/or animals from other European Countries, indicating that trade of live animals or wild boar movement increases the risk of HEV infection spread. Furthermore, homologous strains found in different investigated species within this study indicate interspecies transmission of HEV and/or an existence of an accessible mutual source of infection.
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Affiliation(s)
- Lorena Jemeršić
- Croatian Veterinary Institute, Savska cesta 143, 10 000 Zagreb, Croatia
| | - Jelena Prpić
- Croatian Veterinary Institute, Savska cesta 143, 10 000 Zagreb, Croatia
| | - Dragan Brnić
- Croatian Veterinary Institute, Savska cesta 143, 10 000 Zagreb, Croatia
| | - Tomislav Keros
- Croatian Veterinary Institute, Savska cesta 143, 10 000 Zagreb, Croatia
| | - Nenad Pandak
- General Hospital “Josip Bencevic”, University of Osijek, Faculty of Medicine, Andrije Stampara 42, 35000 Slavonski Brod, Croatia
| | - Oktavija Đaković Rode
- University Hospital for Infectious Diseases “Dr. Fran Mihaljevic”, Mirogojska 8, 10 000 Zagreb, Croatia
- University of Zagreb School of Dental Medicine, Gundulićeva 5, 10000 Zagreb, Croatia
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46
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Lanford RE, Walker CM, Lemon SM. Nonhuman Primate Models of Hepatitis A Virus and Hepatitis E Virus Infections. Cold Spring Harb Perspect Med 2019; 9:a031815. [PMID: 29686041 PMCID: PMC6360867 DOI: 10.1101/cshperspect.a031815] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Although phylogenetically unrelated, human hepatitis viruses share an exclusive or near exclusive tropism for replication in differentiated hepatocytes. This narrow tissue tropism may contribute to the restriction of the host ranges of these viruses to relatively few host species, mostly nonhuman primates. Nonhuman primate models thus figure prominently in our current understanding of the replication and pathogenesis of these viruses, including the enterically transmitted hepatitis A virus (HAV) and hepatitis E virus (HEV), and have also played major roles in vaccine development. This review draws comparisons of HAV and HEV infection from studies conducted in nonhuman primates, and describes how such studies have contributed to our current understanding of the biology of these viruses.
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Affiliation(s)
- Robert E Lanford
- Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas 782227
| | - Christopher M Walker
- Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital and College of Medicine, The Ohio State University, Columbus, Ohio 43205
| | - Stanley M Lemon
- Departments of Medicine and Microbiology & Immunology, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7030
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47
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Zhou JH, Shang Y, Cao XA, Wang YN, Liu Y, Hu Y, Lan X. Potential effects of hepatitis E virus infection in swine on public health in China. INFECTION GENETICS AND EVOLUTION 2018; 68:113-118. [PMID: 30562577 DOI: 10.1016/j.meegid.2018.12.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 12/14/2018] [Accepted: 12/14/2018] [Indexed: 12/30/2022]
Abstract
Hepatitis E virus (HEV), a zoonotic pathogen, is the main cause of acute hepatitis worldwide. Swine serves as the main reservoir, and its infection is mainly transmitted via fecal-oral route. Due to huge consumption of pork in China, close human-swine interactions at pig farms likely contribute to high risk in zoonotic transmission of HEV. Thus, we aim to investigate the HEV prevalence in pig farm in seven provinces across the east to west China and estimate the potential effects of swine HEV on public health in China. In this study, serum samples of pig were collected for detection of anti-HEV antibodies from the seven provinces. A high seroprevalence of 67.1% was found, and no clear difference was observed among these regions. However, the age and the breeding purpose (for meat supplier or breeding offspring) play significant roles in the risk of swine HEV infection. In addition, sequence comparison of various HEV genomes isolated in China displayed that swine HEV posed obvious threats to ruminant breeding and public health. The high level of seroprevalence of swine HEV strongly plays an important role in cross-species of HEV infection. Therefore, effective measures should be performed to prevent HEV infection from infected pigs to human and other ruminants.
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Affiliation(s)
- Jian-Hua Zhou
- State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, PR China; College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu, PR China
| | - Youjun Shang
- State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, PR China
| | - Xiao-An Cao
- State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, PR China
| | - Yi-Ning Wang
- State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, PR China
| | - Yongsheng Liu
- State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, PR China
| | - Yonghao Hu
- State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, PR China; College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu, PR China.
| | - Xi Lan
- State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, PR China.
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48
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Antia RE, Adekola AA, Jubril AJ, Ohore OG, Emikpe BO. Hepatitis E Virus infection seroprevalence and the associated risk factors in animals raised in Ibadan, Nigeria. J Immunoassay Immunochem 2018; 39:509-520. [PMID: 30212262 DOI: 10.1080/15321819.2018.1514507] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Hepatitis E (HE) is an important viral hepatitis of global public and livestock health, and food security significance due to the ubiquitous distribution, multiple transmission route and zoonotic potentials. HE is also endemic in most developing countries including Nigeria. This study therefore investigates the seroprevalence and associated risk factors of HEV infection in pigs raised in Ibadan, Nigeria. Taking an analytical cross-sectional study design, 176 animals (comprising 120 pigs, 26 goats, and 30 cattle) were randomly sampled at the Bodija Municipal abattoir, Ibadan. Serum samples and demographic information were collected for HEV antibody detection (using a commercial recombinant genotype-3 antigen ELISA kit) and risk factors, respectively. A 57.5% (69/120) HEV seroprevalence was reported in the pigs while 0% prevalence was reported in the goats and cattle. In the pigs, a significant age-based HEV seropositivity difference (χ2 = 5.30; OR = 0.20-0.89; p = 0.02) with a higher seroprevalence in the < 6 months (68.42%; 39/57) compared to the > 6 months age group (47.62%; 20/63) was reported. No significant sex, breed and husbandry system effect on HEV seroprevalence was detected in the pigs. This study therefore underscores the high HEV seroprevalence and age-based odds of HEV-exposure in pigs in Ibadan, Nigeria.
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Affiliation(s)
- Richard Edem Antia
- a Department of Veterinary Pathology , University of Ibadan , Ibadan , Nigeria
| | | | - Afusat Jagun Jubril
- a Department of Veterinary Pathology , University of Ibadan , Ibadan , Nigeria
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Khounvisith V, Tritz S, Khenkha L, Phoutana V, Keosengthong A, Pommasichan S, Nouanthong P, Hübschen JM, Snoeck CJ, Reinharz D, Muller CP, Black AP, Pauly M. High circulation of Hepatitis E virus in pigs and professionals exposed to pigs in Laos. Zoonoses Public Health 2018; 65:1020-1026. [DOI: 10.1111/zph.12520] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Revised: 06/06/2018] [Accepted: 08/07/2018] [Indexed: 01/19/2023]
Affiliation(s)
- Vilaysone Khounvisith
- Lao-Lux-Laboratory; Institute Pasteur du Laos; Vientiane Lao People's Democratic Republic
- Institut de la Francophonie pour la Médecine Tropicale; Vientiane Lao People's Democratic Republic
| | - Silvia Tritz
- Lao-Lux-Laboratory; Institute Pasteur du Laos; Vientiane Lao People's Democratic Republic
- Department of Infection and Immunity; Luxembourg Institute of Health; Esch-sur-Alzette Luxembourg
| | - Latdavone Khenkha
- Lao-Lux-Laboratory; Institute Pasteur du Laos; Vientiane Lao People's Democratic Republic
| | - Vannaphone Phoutana
- The Faculty of Agriculture; National University of Laos; Xaythany, Vientiane People's Democratic Republic
| | - Amphone Keosengthong
- The Faculty of Agriculture; National University of Laos; Xaythany, Vientiane People's Democratic Republic
| | - Sisavath Pommasichan
- The Faculty of Agriculture; National University of Laos; Xaythany, Vientiane People's Democratic Republic
| | | | - Judith M. Hübschen
- Department of Infection and Immunity; Luxembourg Institute of Health; Esch-sur-Alzette Luxembourg
| | - Chantal J. Snoeck
- Department of Infection and Immunity; Luxembourg Institute of Health; Esch-sur-Alzette Luxembourg
| | - Daniel Reinharz
- Institut de la Francophonie pour la Médecine Tropicale; Vientiane Lao People's Democratic Republic
| | - Claude P. Muller
- Lao-Lux-Laboratory; Institute Pasteur du Laos; Vientiane Lao People's Democratic Republic
- Department of Infection and Immunity; Luxembourg Institute of Health; Esch-sur-Alzette Luxembourg
- Laboratoire National de Santé; Dudelange Luxembourg
| | - Antony P. Black
- Lao-Lux-Laboratory; Institute Pasteur du Laos; Vientiane Lao People's Democratic Republic
| | - Maude Pauly
- Lao-Lux-Laboratory; Institute Pasteur du Laos; Vientiane Lao People's Democratic Republic
- Department of Infection and Immunity; Luxembourg Institute of Health; Esch-sur-Alzette Luxembourg
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An Update on the Clinicopathologic Features and Pathologic Diagnosis of Hepatitis E in Liver Specimens. Adv Anat Pathol 2018; 25:273-281. [PMID: 29697415 DOI: 10.1097/pap.0000000000000195] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Infection with the hepatitis E virus (HEV) is globally seen a leading cause of hepatitis. Now increasingly recognized also in industrialized countries, hepatitis E constitutes a significant health problem worldwide. The patient's immune status determines the clinical course and histopathology of hepatitis E. In immunocompetent patients, hepatitis E usually follows an asymptomatic or subclinical course, but may also present with acute hepatitis. In contrast, immunocompromised patients may develop chronic hepatitis, and patients with preexisting liver diseases are at risk for liver decompensation with potentially fatal outcome. Whereas pathologists only occasionally encounter liver biopsies from immunocompetent individuals with hepatitis E, they are more likely exposed to biopsies from patients with preexisting liver disease or immunocompromised individuals. Histopathologic hallmarks of hepatitis E in immunocompetent patients comprise lobular disarray, lobular, and portal inflammation, as well as hepatocyte necrosis of varying extend and regeneration. Thus, it is similar to acute non-E viral hepatitis, yet further differential diagnoses include autoimmune hepatitis and drug-induced liver injury. Histopathologic findings of hepatitis E in preexisting liver disease are determined by the underlying pathology, but may be more severe. Histopathologic presentation of hepatitis E in immunocompromised patients is highly variable, ranging from minimal active hepatitis to chronic hepatitis with severe activity and progressive fibrosis. Taken together, the variability of the histologic features depending on the clinical context and the overlap with other liver diseases make the histopathologic diagnosis of hepatitis E challenging. Immunohistochemistry for HEV open reading frame 2 protein and molecular testing for HEV RNA are useful tissue-based ancillary tools.
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