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1
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Memon MS, Kadir B, Kamani L, Chandio AA. Seroprevalence of Hepatitis-E Virus-Immunoglobulin G and its association with Chronic Liver Disease. Pak J Med Sci 2024; 40:1011-1016. [PMID: 38827844 PMCID: PMC11140340 DOI: 10.12669/pjms.40.5.8448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 01/22/2024] [Accepted: 02/18/2024] [Indexed: 06/05/2024] Open
Abstract
Background & Objective Viral hepatitis is a major public health concern in low-middle income countries. Hepatitis-E infection (HEV) is found globally but most prevalent in low-income countries especially those with poor sanitation systems, access to clean drinking water and health services. Superinfection with HEV in patients with chronic liver disease (CLD) can cause severe hepatic decompensation leading to increased morbidity and mortality. To determine the frequency of seroprevalence of Hepatitis-E virus Immunoglobulin g (IgG) and its association with chronic liver disease. Methods A cross-sectional study was conducted in Asian Institute of Medical Sciences, Hyderabad, Pakistan from January till May 2022. A total of 196 patients of aged ≥ 18 years, presenting in gastroenterology clinics were included in the study after informed consent. Result Among 196 patients, one third of patient were male (73.5%). Out of which 162 (82.7%) had liver disease and 34 (17.3%) were without liver disease. The median age of patient was 45 (33-51) years. The overall seroprevalence of HEV IgG among study population was 69.4%. HEV IgG was present in 114 and 22 in CLD and non CLD patients respectively. Multivariable regression shows no association between seroprevalence of HEV in CLD and non-CLD patient (AOR 1.02, 95% CI 0.45-2.313). Conclusion Our study showed high frequency of HEV seropositivity. No difference was observed in HEV seropositivity among CLD and non-CLD patients.
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Affiliation(s)
- Muhammad Sadik Memon
- Muhammad Sadik Memon, Professor, Asian Institute of Medical Sciences (AIMS) Hospital, Hyderabad, Pakistan
| | - Bushra Kadir
- Bushra Kadir, Consultant Gastroenterologist, Asian Institute of Medical Sciences (AIMS) Hospital, Hyderabad, Pakistan
| | - Lubna Kamani
- Lubna Kamani, Professor & Director GI Residency Program, Liaquat National Hospital, Karachi, Pakistan
| | - Ayaz Ahmed Chandio
- Ayaz Ahmed Chandio, Biostatician, Asian Institute of Medical Sciences (AIMS) Hospital, Hyderabad, Pakistan
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Ejaz M, Zohaib A, Usman M, Anwar MM, Khan HS, Ammar M, Saqib M, Khan SG, Athar MA, Mansoor MK, Ullah A, Naseem M, Hussain MH, Javed A. Genotypic analysis of hepatitis E virus (HEV) from sporadic symptomatic cases in Pakistan. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2024; 118:105567. [PMID: 38342162 DOI: 10.1016/j.meegid.2024.105567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 02/07/2024] [Accepted: 02/08/2024] [Indexed: 02/13/2024]
Abstract
Pakistan is the fifth most populous nation in the world and faces several challenges, including devastating floods, sub-optimal sanitary conditions, clustered accommodations, and unregulated cross-border movements. These drastic population shifts make it vulnerable to the efficient spread of the Hepatitis E virus (HEV). The current study analyzed the genotypic characteristics and variants of the Hepatitis E virus circulating in the population of Pakistan. A total of 75 ELISA-IgM positive samples were collected from three metropolitan cities: Lahore, Peshawar, and Karachi, and subjected to viral RNA extraction. The amplification of the HEV RNA-dependent RNA polymerase (RdRp) region was done using Nested PCR and degenerate primers. Out of the total, 40% of the samples were positive for HEV RNA. Sequencing and phylogenetic analysis identified the new HEV isolates as Subtype 1 g, a subtype within an existing HEV genotype 1. This shift warrants investigation into its impact on clinical manifestation and disease severity. Importantly, this study marks the first HEV subtype analysis in Pakistan, contributing valuable insights into subtype diversity and prevalence in the region.
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Affiliation(s)
- Momina Ejaz
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology, Islamabad, Pakistan
| | - Ali Zohaib
- Department of Microbiology, Faculty of Veterinary & Animal Sciences, The Islamia University of Bahawalpur, Pakistan
| | - Muhammad Usman
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology, Islamabad, Pakistan
| | - Muhammad Moaaz Anwar
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology, Islamabad, Pakistan
| | | | - Muhammad Ammar
- Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
| | - Muhammad Saqib
- Department of Clinical Medicine & Surgery, Faculty of Veterinary Science, University of Agriculture Faisalabad, Pakistan
| | - Sadia Ghani Khan
- Chemical Pathology Department, Dr. Ziauddin University Hospital, Clifton, Karachi, Pakistan
| | - Muhammad Ammar Athar
- Department of Molecular Pathology, National Medical Center DHA Phase 1, Karachi, Pakistan
| | - Muhammad Khalid Mansoor
- Department of Microbiology, Faculty of Veterinary & Animal Sciences, The Islamia University of Bahawalpur, Pakistan
| | - Ahsaan Ullah
- Department of Pathology, Faculty of Veterinary & Animal Sciences, The Islamia University of Bahawalpur, Pakistan
| | - Mehvish Naseem
- Department of Biotechnology, The Islamia University of Bahawalpur, Pakistan
| | - Muhammad Hammad Hussain
- Department of Animal and Veterinary Sciences, College of Agricultural and Marine Sciences, Sultan Qaboos University, Oman
| | - Aneela Javed
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology, Islamabad, Pakistan.
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Shafat Z, Islam A, Parveen S. Amino acid pattern reveals multi-functionality of ORF3 protein from HEV. Bioinformation 2024; 20:121-135. [PMID: 38497081 PMCID: PMC10941781 DOI: 10.6026/973206300200121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 02/29/2024] [Accepted: 02/29/2024] [Indexed: 03/19/2024] Open
Abstract
The smallest open reading frame (ORF) encoded protein ORF3 of hepatitis E virus (HEV), recently, has been demonstrated to perform multiple functions besides accessory roles. ORF3 could act as a target for vaccine against HEV infections. The IDR (intrinsically disordered region); IDP (ID protein)/IDPR (ID protein region), plays critical role in various regulatory functions of viruses. The dark proteome of HEV-ORF3 protein including its structure and function was systematically examined by computer predictors to explicate its role in viral pathogenesis and drug resistance beyond its functions as accessory viral protein. Amino acid distribution showed ORF3 enrichment with disorder-promoting residues (Ala, Pro, Ser, Gly) while deficiency in order-promoting residues (Asn, Ile, Phe, Tyr and Trp). Initial investigation revealed ORF3 as IDP (entirely disordered protein) or IDPR (proteins consisting of IDRs with structured globular domains). Structural examination revealed preponderance of disordered regions interpreting ORF3 as moderately/highly disordered protein. Further disorder predictors categorized ORF3 as highly disordered protein/IDP. Identified sites and associated-crucial molecular functions revealed ORF3 involvement in diverse biological processes, substantiating them as targets of regulation. As ORF3 functions are yet to completely explored, thus, data on its disorderness could help in elucidating its disorder related functions.
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Affiliation(s)
- Zoya Shafat
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
| | - Asimul Islam
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
| | - Shama Parveen
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
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Salgado CRS, Silva ADNE, Arruda IF, Millar PR, Amendoeira MRR, Leon LAA, Teixeira RBC, de Lima JTB, Chalhoub FLL, Bispo de Filippis AM, Fonseca ABM, de Oliveira JM, Pinto MA, Figueiredo AS. Serological Evidence of Hepatitis E Virus Infection in Brazilian Equines. Microorganisms 2023; 11:2743. [PMID: 38004754 PMCID: PMC10673136 DOI: 10.3390/microorganisms11112743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 09/08/2023] [Accepted: 09/11/2023] [Indexed: 11/26/2023] Open
Abstract
Hepatitis E virus (HEV) infection has been demonstrated in various animal species; those recognized as potential zoonotic reservoirs pose a considerable risk to public health. In Brazil, HEV-3 is the only genotype identified in humans and swine nationwide, in a colony-breeding cynomolgus monkey and, recently, in bovines and capybara. There is no information regarding HEV exposure in the equine population in Brazil. This study aimed to investigate anti-HEV antibodies and viral RNA in serum samples from horses slaughtered for meat export and those bred for sport/reproduction purposes. We used a commercially available ELISA kit modified to detect species-specific anti-HEV, using an anti-horse IgG-peroxidase conjugate and evaluating different cutoff formulas and assay precision. Serum samples (n = 257) were tested for anti-HEV IgG and HEV RNA by nested RT-PCR and RT-qPCR. The overall anti-HEV seroprevalence was 26.5% (68/257) without the detection of HEV RNA. Most municipalities (53.3%) and farms (58.8%) had positive horses. Animals slaughtered for human consumption had higher risk of HEV exposure (45.5%) than those bred for sports or reproduction (6.4%) (p < 0.0001). The statistical analysis revealed sex and breeding system as possible risk-associated factors. The first serological evidence of HEV circulation in Brazilian equines reinforces the need for the surveillance of HEV host expansion in a one-health approach.
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Affiliation(s)
- Caroline Roberta Soares Salgado
- Laboratório de Desenvolvimento Tecnológico em Virologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz—Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil; (C.R.S.S.); (J.M.d.O.)
| | - Aldaleia do Nascimento e Silva
- Laboratório de Desenvolvimento Tecnológico em Virologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz—Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil; (C.R.S.S.); (J.M.d.O.)
| | - Igor Falco Arruda
- Laboratório de Toxoplasmose e outras Protozooses, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz—Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil; (I.F.A.)
| | - Patrícia Riddell Millar
- Laboratório de Toxoplasmose e outras Protozooses, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz—Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil; (I.F.A.)
| | - Maria Regina Reis Amendoeira
- Laboratório de Toxoplasmose e outras Protozooses, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz—Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil; (I.F.A.)
| | - Luciane Almeida Amado Leon
- Laboratório de Desenvolvimento Tecnológico em Virologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz—Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil; (C.R.S.S.); (J.M.d.O.)
| | | | - Jorge Tiburcio Barbosa de Lima
- Departamento de Clínica e Cirurgia Veterinárias, Universidade Federal de Minas Gerais—UFMG, Belo Horizonte 31270-901, MG, Brazil
| | - Flávia Löwen Levy Chalhoub
- Laboratório de Arbovírus e Vírus Hemorrágicos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz—Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil
| | - Ana Maria Bispo de Filippis
- Laboratório de Arbovírus e Vírus Hemorrágicos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz—Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil
| | - Ana Beatriz Monteiro Fonseca
- Departamento de Estatística, Instituto de Matemática e Estatística, Universidade Federal Fluminense—UFF, Niterói 24210-346, RJ, Brazil
| | - Jaqueline Mendes de Oliveira
- Laboratório de Desenvolvimento Tecnológico em Virologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz—Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil; (C.R.S.S.); (J.M.d.O.)
| | - Marcelo Alves Pinto
- Laboratório de Desenvolvimento Tecnológico em Virologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz—Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil; (C.R.S.S.); (J.M.d.O.)
| | - Andreza Soriano Figueiredo
- Laboratório de Desenvolvimento Tecnológico em Virologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz—Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil; (C.R.S.S.); (J.M.d.O.)
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Melchert J, Radbruch H, Hanitsch LG, Baylis SA, Beheim-Schwarzbach J, Bleicker T, Hofmann J, Jones TC, Drosten C, Corman VM. Whole genome sequencing reveals insights into hepatitis E virus genome diversity, and virus compartmentalization in chronic hepatitis E. J Clin Virol 2023; 168:105583. [PMID: 37716229 PMCID: PMC10643812 DOI: 10.1016/j.jcv.2023.105583] [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: 06/15/2023] [Revised: 08/24/2023] [Accepted: 09/11/2023] [Indexed: 09/18/2023]
Abstract
BACKGROUND Hepatitis E virus (HEV) is a leading cause of acute hepatitis and can cause chronic infections in immunocompromised patients. Although HEV infections can be treated with ribavirin, antiviral efficacy is hampered by resistance mutations, normally detected by virus sequencing. OBJECTIVES High-throughput sequencing (HTS) allows for cost-effective complete viral genome sequencing. This enables the discovery and delineation of new subtypes, and revised the recognition of quasispecies and putative resistance mutations. However, HTS is challenged by factors including low viral load, sample degradation, high host background, and high viral diversity. STUDY DESIGN We apply complete genome sequencing strategies for HEV, including a targeted enrichment approach. These approaches were used to investigate sequence diversity in HEV RNA-positive animal and human samples and intra-host diversity in a chronically infected patient. RESULTS Here, we describe the identification of potential novel subtypes in a blood donation (genotype 3) and in an ancient livestock sample (genotype 7). In a chronically infected patient, we successfully investigated intra-host virus diversity, including the presence of ribavirin resistance mutations. Furthermore, we found convincing evidence for HEV compartmentalization, including the central nervous system, in this patient. CONCLUSIONS Targeted enrichment of viral sequences enables the generation of complete genome sequences from a variety of difficult sample materials. Moreover, it enables the generation of greater sequence coverage allowing more advanced analyses. This is key for a better understanding of virus diversity. Investigation of existing ribavirin resistance, in the context of minorities or compartmentalization, may be critical in treatment strategies of HEV patients.
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Affiliation(s)
- Julia Melchert
- Institute of Virology, Charité--Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany; German Centre for Infection Research (DZIF), Partner Site Charité, Berlin, Germany
| | - Helena Radbruch
- Department of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Leif G Hanitsch
- Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany
| | - Sally A Baylis
- Viral Safety Section, Paul-Ehrlich-Institut, Langen, Germany
| | - Jörn Beheim-Schwarzbach
- Institute of Virology, Charité--Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany
| | - Tobias Bleicker
- Institute of Virology, Charité--Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany
| | - Jörg Hofmann
- Labor Berlin - Charité Vivantes GmbH, Berlin 13353, Germany
| | - Terry C Jones
- Institute of Virology, Charité--Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany; German Centre for Infection Research (DZIF), Partner Site Charité, Berlin, Germany; Centre for Pathogen Evolution, Department of Zoology, University of Cambridge, Downing St., Cambridge, CB2 3EJ, UK
| | - Christian Drosten
- Institute of Virology, Charité--Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany; German Centre for Infection Research (DZIF), Partner Site Charité, Berlin, Germany
| | - Victor M Corman
- Institute of Virology, Charité--Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany; German Centre for Infection Research (DZIF), Partner Site Charité, Berlin, Germany; Labor Berlin - Charité Vivantes GmbH, Berlin 13353, Germany.
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6
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Primadharsini PP, Nagashima S, Nishiyama T, Okamoto H. Three Distinct Reporter Systems of Hepatitis E Virus and Their Utility as Drug Screening Platforms. Viruses 2023; 15:1989. [PMID: 37896767 PMCID: PMC10611241 DOI: 10.3390/v15101989] [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: 09/09/2023] [Revised: 09/20/2023] [Accepted: 09/22/2023] [Indexed: 10/29/2023] Open
Abstract
The hepatitis E virus (HEV) is increasingly acknowledged as the primary cause of acute hepatitis. While most HEV infections are self-limiting, cases of chronic infection and fulminant hepatitis necessitate the administration of anti-HEV medications. However, there is a lack of specific antiviral drugs designed for HEV, and the currently available drug (ribavirin) has been associated with significant adverse effects. The development of innovative antiviral drugs involves targeting distinct steps within the viral life cycle: the early step (attachment and internalization), middle step (translation and RNA replication), and late step (virus particle formation and virion release). We recently established three HEV reporter systems, each covering one or two of these steps. Using these reporter systems, we identified various potential drug candidates that target different steps of the HEV life cycle. Through rigorous in vitro testing using our robust cell culture system with the genotype 3 HEV strain (JE03-1760F/P10), we confirmed the efficacy of these drugs, when used alone or in combination with existing anti-HEV drugs. This underscores their significance in the quest for an effective anti-HEV treatment. In the present review, we discuss the development of the three reporter systems, their applications in drug screening, and their potential to advance our understanding of the incompletely elucidated HEV life cycle.
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Affiliation(s)
- Putu Prathiwi Primadharsini
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke 329-0498, Tochigi, Japan; (P.P.P.); (S.N.)
| | - Shigeo Nagashima
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke 329-0498, Tochigi, Japan; (P.P.P.); (S.N.)
| | - Takashi Nishiyama
- Laboratory of Membrane Proteins, Research Division for Quantitative Life Sciences, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan;
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke 329-0498, Tochigi, Japan; (P.P.P.); (S.N.)
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Agabou A, Benaissa MH, Bouasla I, De Sabato L, Hireche S, Ianiro G, Monini M, Di Bartolo I. First serological and molecular investigation of hepatitis E virus infection in dromedary camels in Algeria. Front Vet Sci 2023; 10:1272250. [PMID: 37795011 PMCID: PMC10546018 DOI: 10.3389/fvets.2023.1272250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 08/31/2023] [Indexed: 10/06/2023] Open
Abstract
Hepatitis E is an acute self-limited or fulminant infection in humans, caused by the hepatitis E virus (HEV). This member of the Hepeviridae family has been identified in a wide range of domestic and wild animals all over the world, with a possible transmission to humans through fecal oral route, direct contact and ingestion of contaminated meat products, making it one of the global zoonotic and public health major concerns. Since there is no monitoring program and a lack of data on HEV in animals in Algeria, the current preliminary survey has been undertaken to elucidate the exposure to the virus in camels at abattoirs of six southern provinces of Algeria. Two-hundred and eight sera/plasma were collected and analyzed (by double antigen sandwich ELISA) for the presence of total anti-HEV antibodies, among which 35.1% were positive, but no HEV RNA could be isolated from them (by two pan-HEV nested RT-PCR and broad range real-time reverse transcription RT-PCR). The univariate analysis showed significant associations (p < 0.05) between HEV seroprevalence and province of origin, age, and sex of camels, whereas the multivariable logistic regression analysis revealed a negative impact of camels' age on it. The obtained results confirm that HEV infection is widespread established in the camelid population of Algeria.
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Affiliation(s)
- Amir Agabou
- PADESCA Research Laboratory, Institute of Veterinary Sciences, University Frères Mentouri Constantine 1, Constantine, Algeria
| | | | - Ilyes Bouasla
- PADESCA Research Laboratory, Institute of Veterinary Sciences, University Frères Mentouri Constantine 1, Constantine, Algeria
| | - Luca De Sabato
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Rome, Italy
| | - Sana Hireche
- PADESCA Research Laboratory, Institute of Veterinary Sciences, University Frères Mentouri Constantine 1, Constantine, Algeria
| | - Giovanni Ianiro
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Rome, Italy
| | - Marina Monini
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Rome, Italy
| | - Ilaria Di Bartolo
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Rome, Italy
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8
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Santos-Silva S, Hemnani M, Lopez-Lopez P, Gonçalves HMR, Rivero-Juarez A, Van der Poel WHM, Nascimento MSJ, Mesquita JR. A Systematic Review of Hepatitis E Virus Detection in Camels. Vet Sci 2023; 10:323. [PMID: 37235406 PMCID: PMC10222403 DOI: 10.3390/vetsci10050323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 04/19/2023] [Accepted: 04/26/2023] [Indexed: 05/28/2023] Open
Abstract
Hepatitis E virus (HEV) represents a major cause of acute hepatitis and is considered an emerging public health problem around the world. In the Middle East's and Africa's arid regions, where camels frequently interact with human populations and camel-derived food products are a component of the food chain, camel-borne zoonotic HEV infection is a potential threat. To date, no review paper has been published on HEV in camels. As such, the purpose of the current work is to provide a scientific review of the identification of HEV genotypes seven and eight in camels worldwide to have a better understanding of the current status of this topic and to identify gaps in the current knowledge. Searches were carried out in the electronic databases PubMed, Mendeley, Web of Science, and Scopus, including studies published until 31 December 2022 (n = 435). Once the databases were checked for duplicate papers (n = 307), the exclusion criteria were applied to remove any research that was not relevant (n = 118). As a result, only 10 papers were found to be eligible for the study. Additionally, in eight of the ten studies, the rates of HEV infection were found to be between 0.6% and 2.2% in both stool and serum samples. Furthermore, four studies detected HEV genotype seven in dromedary camels, and two studies have shown HEV genotype eight in Bactrian camels. Interestingly, these genotypes were recently reported in camels from the Middle East and China, where one human infection with HEV genotype seven has been associated with the consumption of contaminated camel meat and milk. In conclusion, more research will be needed to determine the prevalence of HEV infection in camels around the world as well as the risk of foodborne transmission of contaminated camel products. As camels are utility animals in several countries, HEV in these animals may pose a potential risk to public health.
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Affiliation(s)
- Sérgio Santos-Silva
- ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal; (S.S.-S.); (M.H.)
| | - Mahima Hemnani
- ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal; (S.S.-S.); (M.H.)
| | - Pedro Lopez-Lopez
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Reina Sofía, Universidad de Córdoba, 14004 Córdoba, Spain; (P.L.-L.); (A.R.-J.)
- CIBER de Enfermedades Infecciosas (CIBERINFEC) Instituto de Salud Carlos III, 28220 Madrid, Spain
| | - Helena M. R. Gonçalves
- Biosensor Ntech-Nanotechnology Services, Lda, Avenida da Liberdade, 249, 1° Andar, 1250-143 Lisboa, Portugal;
- REQUIMTE, Instituto Superior de Engenharia do Porto, 4200-072 Porto, Portugal
| | - António Rivero-Juarez
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Reina Sofía, Universidad de Córdoba, 14004 Córdoba, Spain; (P.L.-L.); (A.R.-J.)
- CIBER de Enfermedades Infecciosas (CIBERINFEC) Instituto de Salud Carlos III, 28220 Madrid, Spain
| | - Wim H. M. Van der Poel
- Quantitative Veterinary Epidemiology Group, Wageningen University, 6708 PB Wageningen, The Netherlands;
- Department Virology & Molecular Biology, Wageningen Bioveterinary Research, 8200 AB Lelystad, The Netherlands
| | | | - João R. Mesquita
- ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal; (S.S.-S.); (M.H.)
- Epidemiology Research Unit (EPIUnit), Instituto de Saúde Pública da Universidade do Porto, 4050-600 Porto, Portugal
- Laboratório Para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), 4050-600 Porto, Portugal
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9
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Shafat Z, Ahmed A, Parvez MK, Parveen S. Intrinsic disorder in the open reading frame 2 of hepatitis E virus: a protein with multiple functions beyond viral capsid. J Genet Eng Biotechnol 2023; 21:33. [PMID: 36929465 PMCID: PMC10018590 DOI: 10.1186/s43141-023-00477-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 01/31/2023] [Indexed: 03/18/2023]
Abstract
BACKGROUND Hepatitis E virus (HEV) is the cause of a liver disease hepatitis E. The translation product of HEV ORF2 has recently been demonstrated as a protein involved in multiple functions besides performing its major role of a viral capsid. As intrinsically disordered regions (IDRs) are linked to various essential roles in the virus's life cycle, we analyzed the disorder pattern distribution of the retrieved ORF2 protein sequences by employing different online predictors. Our findings might provide some clues on the disorder-based functions of ORF2 protein that possibly help us in understanding its behavior other than as a HEV capsid protein. RESULTS The modeled three dimensional (3D) structures of ORF2 showed the predominance of random coils or unstructured regions in addition to major secondary structure components (alpha helix and beta strand). After initial scrutinization, the predictors VLXT and VSL2 predicted ORF2 as a highly disordered protein while the predictors VL3 and DISOPRED3 predicted ORF2 as a moderately disordered protein, thus categorizing HEV-ORF2 into IDP (intrinsically disordered protein) or IDPR (intrinsically disordered protein region) respectively. Thus, our initial predicted disorderness in ORF2 protein 3D structures was in excellent agreement with their predicted disorder distribution patterns (evaluated through different predictors). The abundance of MoRFs (disorder-based protein binding sites) in ORF2 was observed that signified their interaction with binding partners which might further assist in viral infection. As IDPs/IDPRs are targets of regulation, we carried out the phosphorylation analysis to reveal the presence of post-translationally modified sites. Prevalence of several disordered-based phosphorylation sites further signified the involvement of ORF2 in diverse and significant biological processes. Furthermore, ORF2 structure-associated functions revealed its involvement in several crucial functions and biological processes like binding and catalytic activities. CONCLUSIONS The results predicted ORF2 as a protein with multiple functions besides its role as a capsid protein. Moreover, the occurrence of IDPR/IDP in ORF2 protein suggests that its disordered region might serve as novel drug targets via functioning as potential interacting domains. Our data collectively might provide significant implication in HEV vaccine search as disorderness in viral proteins is related to mechanisms involved in immune evasion.
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Affiliation(s)
- Zoya Shafat
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
| | - Anwar Ahmed
- Centre of Excellence in Biotechnology Research, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Mohammad K. Parvez
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Shama Parveen
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
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10
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Geng Y, Shi T, Wang Y. Epidemiology of Hepatitis E. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:33-48. [PMID: 37223857 DOI: 10.1007/978-981-99-1304-6_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Hepatitis E virus (HEV) is globally prevalent with relatively high percentages of anti-HEV immunoglobulin G-positive individuals in the populations of developing and developed countries. There are two distinct epidemiological patterns of hepatitis E. In areas with high disease endemicity, primarily developing countries in Asia and Africa, this disease is caused mainly by genotypes HEV-1 or HEV-2; both genotypes transmit predominantly through contaminated water and occur as either outbreaks or sporadic cases of acute hepatitis. The acute hepatitis has the highest attack rate in young adults and is particularly severe among pregnant women. In developed countries, sporadic cases of locally acquired HEV-3 or HEV-4 infection are observed. The reservoir of HEV-3 and HEV-4 is believed to be animals, such as pigs, with zoonotic transmission to humans. The affected persons are often elderly, and persistent infection has been well documented among immunosuppressed persons. A subunit vaccine has been shown to be effective in preventing clinical disease and has been licensed in China.
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Affiliation(s)
- Yansheng Geng
- Key Laboratory of Public Health Safety of Hebei Province, School of Public Health, Hebei University, Baoding, China
| | - Tengfei Shi
- Key Laboratory of Public Health Safety of Hebei Province, School of Public Health, Hebei University, Baoding, China
| | - Youchun Wang
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, China.
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11
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Caballero-Gómez J, García-Bocanegra I, Cano-Terriza D, Beato-Benítez A, Ulrich RG, Martínez J, Guerra R, Martínez-Valverde R, Martínez-Nevado E, Ángel Quevedo-Muñoz M, Sierra-Arqueros C, Planas J, de Castro-García N, Rivero A, Rivero-Juarez A. Monitoring of hepatitis E virus in zoo animals from Spain, 2007-2021. Transbound Emerg Dis 2022; 69:3992-4001. [PMID: 36083467 PMCID: PMC10087427 DOI: 10.1111/tbed.14702] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 08/24/2022] [Accepted: 09/04/2022] [Indexed: 02/07/2023]
Abstract
Hepatitis E virus (HEV, family Hepeviridae) is an important emerging and zoonotic pathogen. In recent decades, the number of human cases of zoonotic hepatitis E has increased considerably in industrialized countries and HEV has been detected in an expanding range of mammal species. Although domestic pigs and wild boar are considered the main reservoirs of zoonotic HEV genotypes, the role of other susceptible animals in the epidemiology of the virus is still poorly understood. A large-scale, long-term study was carried out (1) to assess HEV exposure in captive zoo animals in Spain and (2) to determine the dynamics of seropositivity in individuals that were sampled longitudinally during the study period. Between 2007 and 2021, serum samples from 425 zoo animals belonging to 109 animal species (including artiodactyls, carnivores, perissodactyls, proboscideans and rodents) were collected from 11 different zoological parks in Spain. Forty-six of these animals at seven of these zoos were also longitudinally sampled. Anti-HEV antibodies were detected in 36 (8.5%; 95% CI: 5.8-11.1) of 425 sampled zoo animals. Specific antibodies against HEV-3 and HEV-C1 antigens were confirmed in ELISA-positive animals using western blot assay. Two of 46 longitudinally surveyed animals seroconverted during the study period. Seropositivity was significantly higher in carnivores and perissodactyls than in artiodactyls, and also during the period 2012-2016 compared with 2007-2011. HEV RNA was not detected in any of the 262 animals that could be tested by RT-PCR. To the best of the author's knowledge, this is the first large-scale, long-term surveillance on HEV in different orders of zoo mammals. Our results indicate exposure to HEV-3 and HEV-C1 in zoo animals in Spain and confirm a widespread but not homogeneous spatiotemporal circulation of HEV in captive species in this country. Further studies are required to determine the role of zoo species, particularly carnivores and perissodactyls, in the epidemiology of HEV and to clarify the origins of infection in zoological parks.
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Affiliation(s)
- Javier Caballero-Gómez
- Departamento Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, Córdoba, España.,Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain.,CIBERINFEC, ISCIII - CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Spain
| | - Ignacio García-Bocanegra
- Departamento Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, Córdoba, España.,CIBERINFEC, ISCIII - CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Spain
| | - David Cano-Terriza
- Departamento Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, Córdoba, España.,CIBERINFEC, ISCIII - CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Spain
| | - Adrián Beato-Benítez
- Departamento Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, Córdoba, España
| | - Rainer G Ulrich
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany.,German Centre for Infection Research (DZIF), partner site Hamburg-Lübeck-Borstel-Riems, Greifswald-Insel Riems, Germany
| | | | | | | | | | | | | | | | | | - Antonio Rivero
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain.,CIBERINFEC, ISCIII - CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Spain
| | - Antonio Rivero-Juarez
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain.,CIBERINFEC, ISCIII - CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Spain
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12
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Karamendin K, Seidalina A, Sabyrzhan T, Nuralibekov S, Kasymbekov Y, Suleimenova S, Khan E, Alikhanov O, Narsha U, Erkekulova K, Kydyrmanov A. Serological Screening for Middle East Respiratory Syndrome Coronavirus and Hepatitis E Virus in Camels in Kazakhstan. Pathogens 2022; 11:1224. [PMID: 36364975 PMCID: PMC9692571 DOI: 10.3390/pathogens11111224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 10/18/2022] [Accepted: 10/21/2022] [Indexed: 09/10/2024] Open
Abstract
After the recent Middle East Respiratory Syndrome coronavirus (MERS-CoV) pandemic in 2013, more attention has been paid to the camel as an important source of zoonotic viral infections. Almost simultaneously, in 2013, new genotypes 7 and 8 of the hepatitis E virus (HEV) were discovered in dromedary and Bactrian camels, respectively. HEV 7 was further shown to be associated with chronic viral hepatitis in a transplant recipient. In this study, serological screening for antibodies to MERS-CoV and hepatitis E virus was carried out on large camel farms in the south and west of Kazakhstan. 6.42% of the tested camels were found to be positive for antibodies to the hepatitis E virus, which indicates its circulation in local camel population. For the first time, antibodies to the hepatitis E virus were found in Bactrians, which have been little studied to date. Antibodies to MERS-CoV were not found in the camel sera.
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Affiliation(s)
- Kobey Karamendin
- Laboratory of Viral Ecology, Department of Virology, Scientific Production Center of Microbiology and Virology, 105 Bogenbay batyr Str., Almaty A25K1G0, Kazakhstan
| | - Aigerim Seidalina
- Laboratory of Viral Ecology, Department of Virology, Scientific Production Center of Microbiology and Virology, 105 Bogenbay batyr Str., Almaty A25K1G0, Kazakhstan
| | - Temirlan Sabyrzhan
- Laboratory of Viral Ecology, Department of Virology, Scientific Production Center of Microbiology and Virology, 105 Bogenbay batyr Str., Almaty A25K1G0, Kazakhstan
| | - Sardor Nuralibekov
- Laboratory of Viral Ecology, Department of Virology, Scientific Production Center of Microbiology and Virology, 105 Bogenbay batyr Str., Almaty A25K1G0, Kazakhstan
| | - Yermukhammet Kasymbekov
- Laboratory of Viral Ecology, Department of Virology, Scientific Production Center of Microbiology and Virology, 105 Bogenbay batyr Str., Almaty A25K1G0, Kazakhstan
| | - Symbat Suleimenova
- Laboratory of Viral Ecology, Department of Virology, Scientific Production Center of Microbiology and Virology, 105 Bogenbay batyr Str., Almaty A25K1G0, Kazakhstan
| | - Elizaveta Khan
- Laboratory of Viral Ecology, Department of Virology, Scientific Production Center of Microbiology and Virology, 105 Bogenbay batyr Str., Almaty A25K1G0, Kazakhstan
| | - Oralbek Alikhanov
- Department of Veterinary Medicine, Agrarian Faculty, M. Auezov South Kazakhstan State University, 9th Corpus, 198 M.Kh. Dulati Str., Shymkent 160013, Kazakhstan
| | - Uldana Narsha
- Department of Veterinary Medicine, Agrarian Faculty, M. Auezov South Kazakhstan State University, 9th Corpus, 198 M.Kh. Dulati Str., Shymkent 160013, Kazakhstan
| | - Kalya Erkekulova
- Department of Veterinary Medicine, Agrarian Faculty, M. Auezov South Kazakhstan State University, 9th Corpus, 198 M.Kh. Dulati Str., Shymkent 160013, Kazakhstan
| | - Aidyn Kydyrmanov
- Laboratory of Viral Ecology, Department of Virology, Scientific Production Center of Microbiology and Virology, 105 Bogenbay batyr Str., Almaty A25K1G0, Kazakhstan
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13
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Genomic Characterization and Antimicrobial Susceptibility of Dromedary-Associated Staphylococcaceae from the Horn of Africa. Appl Environ Microbiol 2022; 88:e0114622. [PMID: 36226992 DOI: 10.1128/aem.01146-22] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Members of the Staphylococcaceae family, particularly those of the genus Staphylococcus, encompass important human and animal pathogens. We collected and characterized Staphylococcaceae strains from apparently healthy and diseased camels (n = 84) and cattle (n = 7) in Somalia and Kenya. We phenotypically characterized the strains, including their antimicrobial inhibitory concentrations. Then, we sequenced their genomes using long-read sequencing, closed their genomes, and subsequently compared and mapped their virulence- and resistance-associated gene pools. Genome-based phylogenetics revealed 13 known Staphylococcaceae and at least two novel species. East African strains of different species encompassed novel sequence types and phylogenetically distant clades. About one-third of the strains had non-wild-type MICs. They were resistant to at least one of the following antimicrobials: tetracycline, benzylpenicillin, oxacillin, erythromycin, clindamycin, trimethoprim, gentamicin, or streptomycin, encoded by tet(K), blaZ/blaARL, mecA/mecA1, msrA/mphC, salA, dfrG, aacA-aphD, and str, respectively. We identified the first methicillin- and multidrug-resistant camel S. epidermidis strain of sequence type (ST) 1136 in East Africa. The pool of virulence-encoding genes was largest in the S. aureus strains, as expected, although other rather commensal strains contained distinct virulence-encoding genes. We identified toxin-antitoxin (TA) systems such as the hicA/hicB and abiEii/abiEi families, reported here for the first time for certain species of Staphylococcaceae. All strains contained at least one intact prophage sequence, mainly belonging to the Siphoviridae family. We pinpointed potential horizontal gene transfers between camel and cattle strains and also across distinct Staphylococcaceae clades and species. IMPORTANCE Camels are a high value and crucial livestock species in arid and semiarid regions of Africa and gain importance giving the impact of climate change on traditional livestock species. Our current knowledge with respect to Staphylococcaceae infecting camels is very limited compared to that for other livestock species. Better knowledge will foster the development of specific diagnostic assays, guide promising antimicrobial treatment options, and inform about potential zoonotic risks. We characterized 84 Staphylococcaceae strains isolated from camels with respect to their antimicrobial resistance and virulence traits. We detected potentially novel Staphylococcus species, resistances to different classes of antimicrobials, and the first camel multidrug-resistant S. epidermidis strain of sequence type 1136.
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14
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Ma Z, de Man RA, Kamar N, Pan Q. Chronic hepatitis E: Advancing research and patient care. J Hepatol 2022; 77:1109-1123. [PMID: 35605741 DOI: 10.1016/j.jhep.2022.05.006] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 05/08/2022] [Accepted: 05/10/2022] [Indexed: 12/15/2022]
Abstract
The hepatitis E virus (HEV) was initially thought to exclusively cause acute hepatitis. However, the first diagnosis of chronic hepatitis E in transplant recipients in 2008 profoundly changed our understanding of this pathogen. We have now begun to understand that specific HEV genotypes can cause chronic infection in certain immunocompromised populations. Over the past decade, dedicated clinical and experimental research has substantiated knowledge on the epidemiology, transmission routes, pathophysiological mechanisms, diagnosis, clinical features and treatment of chronic HEV infection. Nevertheless, many gaps and major challenges remain, particularly regarding the translation of knowledge into disease prevention and improvement of clinical outcomes. This article aims to highlight the latest developments in the understanding and management of chronic hepatitis E. More importantly, we attempt to identify major knowledge gaps and discuss strategies for further advancing both research and patient care.
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Affiliation(s)
- Zhongren Ma
- Biomedical Research Center, Northwest Minzu University, Lanzhou, China
| | - Robert A de Man
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands
| | - Nassim Kamar
- Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Disease (Infinity), University Paul Sabatier, Toulouse, France
| | - Qiuwei Pan
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
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15
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Seroprevalence of Hepatitis E Virus Antibodies (IgG) in the Community of Rawalpindi. LIVERS 2022. [DOI: 10.3390/livers2030009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Knowledge regarding the prevalence of the hepatitis E virus (HEV) in the general population can indicate public health and personal hygiene practices in a community. HEV spreads through the fecal-oral route and contaminates drinking water through sewage. Moreover, poverty also contributes to its prevalence in developing countries, including Pakistan. A cross-sectional study was conducted on 650 blood samples taken from suspected patients of HEV in the Rawalpindi cantonment area (Pakistan) from April to November 2019 at the Department of Virology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan. Out of them, 444 (68.15%) were male and 206 (31.85%) were female; the detection of anti-HEV IgG antibodies was carried out using a commercial Anti-Hepatitis E virus antibody (IgG) ELISA Kit. The overall anti-HEV IgG prevalence percentages were 19.23% and 4.77% in males and females, respectively. Patients were categorized into eight groups with ages ranging between 1 and 90 years. HEV IgG seroprevalence was the highest in ages 31–40 (6.46%). The study concluded that males aged 40 or above were susceptible and infected with hepatitis E.
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16
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El-Kafrawy SA, Hassan AM, El-Daly MM, Al-Hajri M, Farag E, Elnour FA, Khan A, Tolah AM, Alandijany TA, Othman NA, Memish ZA, Corman VM, Drosten C, Zumla A, Azhar EI. Genetic diversity of hepatitis E virus (HEV) in imported and domestic camels in Saudi Arabia. Sci Rep 2022; 12:7005. [PMID: 35487943 PMCID: PMC9054814 DOI: 10.1038/s41598-022-11208-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 04/08/2022] [Indexed: 11/09/2022] Open
Abstract
Camels gained attention since the discovery of MERS-CoV as intermediary hosts for potentially epidemic zoonotic viruses. DcHEV is a novel zoonotic pathogen associated with camel contact. This study aimed to genetically characterize DcHEV in domestic and imported camels in Saudi Arabia. DcHEV was detected by RT-PCR in serum samples, PCR-positive samples were subjected to sequencing and phylogenetic analyses. DcHEV was detected in 1.77% of samples with higher positivity in domestic DCs. All positive imported dromedaries were from Sudan with age declining prevalence. Domestic DcHEV sequences clustered with sequences from Kenya, Somalia, and UAE while imported sequences clustered with one DcHEV isolate from UAE and both sequences clustered away from isolates reported from Pakistan. Full-genome sequences showed 24 amino acid difference with reference sequences. Our results confirm the detection of DcHEV in domestic and imported DCs. Further investigations are needed in human and camel populations to identify DcHEV potential zoonosis threat.
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Affiliation(s)
- Sherif A El-Kafrawy
- Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ahmed M Hassan
- Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mai M El-Daly
- Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | | | | | | | - Anas Khan
- The Global Centre for Mass Gatherings Medicine, Public Health Directorate, Ministry of Health, Riyadh, Saudi Arabia
| | - Ahmed M Tolah
- Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Rabigh, Saudi Arabia
| | - Thamir A Alandijany
- Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Noura A Othman
- Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ziad A Memish
- King Saud Medical City, Ministry of Health, Riyadh, Saudi Arabia.,Al-Faisal University, Riyadh, Saudi Arabia.,Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Victor M Corman
- Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin, Germany.,Berlin Institute of Health, Institute of Virology, Berlin, Germany
| | - Christian Drosten
- Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin, Germany.,Berlin Institute of Health, Institute of Virology, Berlin, Germany
| | - Alimuddin Zumla
- Department of Infection, Division of Infection and Immunity, Centre for Clinical Microbiology, University College London, London, UK.,NIHR Biomedical Research Centre, University College London Hospitals, London, UK
| | - Esam I Azhar
- Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. .,Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
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17
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Shafat Z, Ahmed A, Parvez MK, Parveen S. Decoding the codon usage patterns in Y-domain region of hepatitis E viruses. J Genet Eng Biotechnol 2022; 20:56. [PMID: 35404024 PMCID: PMC9001762 DOI: 10.1186/s43141-022-00319-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 02/17/2022] [Indexed: 12/17/2022]
Abstract
BACKGROUND Hepatitis E virus (HEV) is a positive-sense RNA virus belonging to the family Hepeviridae. The genome of HEV is organized into three open-reading frames (ORFs): ORF1, ORF2, and ORF3. The ORF1 non-structural Y-domain region (YDR) has been demonstrated to play an important role in the HEV pathogenesis. The nucleotide composition, synonymous codon usage bias in conjunction with other factors influencing the viral YDR genes of HEV have not been studied. Codon usage represents a significant mechanism in establishing the host-pathogen relationship. The present study for the first time elucidates the detailed codon usage patterns of YDR among HEV and HEV-hosts (Human, Rabbit, Mongoose, Pig, Wild boar, Camel, Monkey). RESULTS The overall nucleotide composition revealed the abundance of C and U nucleotides in YDR genomes. The relative synonymous codon usage (RSCU) analysis indicated biasness towards C and U over A and G ended codons in HEV across all hosts. Codon frequency comparative analyses among HEV-hosts showed both similarities and discrepancies in usage of preferred codons encoding amino acids, which revealed that HEV codon preference neither completely differed nor completely showed similarity with its hosts. Thus, our results clearly indicated that the synonymous codon usage of HEV is a mixture of the two types of codon usage: coincidence and antagonism. Mutation pressure from virus and natural selection from host seems to be accountable for shaping the codon usage patterns in YDR. The study emphasised that the influence of compositional constraints, codon usage biasness, mutational alongside the selective forces were reflected in the occurrence of YDR codon usage patterns. CONCLUSIONS Our study is the first in its kind to have reported the analysis of codon usage patterns on a total of seven different natural HEV hosts. Therefore, knowledge of preferred codons obtained from our study will not only augment our understanding towards molecular evolution but is also envisaged to provide insight into the efficient viral expression, viral adaptation, and host effects on the HEV YDR codon usage.
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Affiliation(s)
- Zoya Shafat
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
| | - Anwar Ahmed
- Centre of Excellence in Biotechnology Research, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Mohammad K. Parvez
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Shama Parveen
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
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18
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El-Kafrawy SA, El-Daly MM. Hepatitis E virus in Saudi Arabia: more surveillance needed. Future Virol 2022. [DOI: 10.2217/fvl-2021-0320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Hepatitis E virus (HEV) is a small quasi-enveloped ssRNA causing acute hepatitis. HEV is the leading cause of intermittent acute hepatitis and fulminant hepatic failure. Risk factors include drinking contaminated water in developing countries and consumption of infected animal products in developed countries. Previous reports on HEV prevalence in Saudi Arabia had small sample sizes. Nationwide systematic seroprevalence studies are needed to investigate risk factors and annual incidence. Camels play a cultural and economic role in the life of Saudi citizens with frequent human contact and potential role in zoonotic transmission. Future research needs to include larger sample-sizes and nationwide studies. Future studies should also focus on raising awareness of HEV infection and the need for wider population testing and screening.
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Affiliation(s)
- Sherif Aly El-Kafrawy
- Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
| | - Mai Mohamed El-Daly
- Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
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Fanelli A, Tizzani P, Buonavoglia D. A systematic review and meta-analysis of hepatitis E virus (HEV) in wild boars. Res Vet Sci 2021; 142:54-69. [PMID: 34864434 DOI: 10.1016/j.rvsc.2021.11.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 05/02/2021] [Accepted: 11/26/2021] [Indexed: 12/19/2022]
Abstract
This systematic review and meta-analysis summarize the available information on Hepatitis E virus (HEV) -specific antibody seroprevalence and HEV RNA prevalence in wild boar, one of the most abundant game species worldwide. A literature search (CAB Abstracts, Web of Science, Embase and Scopus) was performed to find relevant peer-reviewed works published during the period 1990-2020. A random-effect model was carried out to calculate the pooled HEV-specific antibody seroprevalence and HEV RNA prevalence estimates with 95% confidence intervals, and I2 statistic was used to assess the heterogeneity of the data. Values by subgroups were compared according to the geographical area, age class (≤ 12 months old and > 12 months old), and sample type (bile, faeces, liver, meat/muscle, serum). Sixty-nine publications were selected, with the majority of the studies from Southern Europe (n = 27). The pooled HEV-specific antibody seroprevalence in wild boar was 28% (CI95% 23-34) and the HEV RNA prevalence 8% (CI95% 6-10). The analysis highlighted a significant heterogeneity among the estimates from the included studies (I2 = 98% and I2 = 95% for HEV-specific antibody seroprevalence and viral prevalence respectively). The moderator analysis indicated a statistically significant difference (p-value = 0.03) for the HEV RNA prevalence according to the sample type, with the highest value in bile (17%, CI95% 9-27), followed by liver (10%, CI95% 7-14), serum (7%, CI95% 4-10), faeces (5%, CI95% 2-9), and meat/muscle (3%, CI95% 0.04-10). Finally, the HEV RNA prevalence in Europe (8.7, CI95% 6.7-11) was significantly (p-value = 0.04) higher than in Asia (4, CI95% 0.6-8). The analysis highlights the important role of wild boar in the epidemiology of HEV.
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Affiliation(s)
- Angela Fanelli
- Department of Veterinary Medicine, University of Bari, Valenzano, Bari, Italy.
| | - Paolo Tizzani
- Department of Veterinary Sciences, University of Turin, Grugliasco, Turin, Italy
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Shafat Z, Ahmed A, Parvez MK, Parveen S. Role of "dual-personality" fragments in HEV adaptation-analysis of Y-domain region. J Genet Eng Biotechnol 2021; 19:154. [PMID: 34637041 PMCID: PMC8511232 DOI: 10.1186/s43141-021-00238-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 08/30/2021] [Indexed: 01/06/2023]
Abstract
BACKGROUND Hepatitis E is a liver disease caused by the pathogen hepatitis E virus (HEV). The largest polyprotein open reading frame 1 (ORF1) contains a nonstructural Y-domain region (YDR) whose activity in HEV adaptation remains uncharted. The specific role of disordered regions in several nonstructural proteins has been demonstrated to participate in the multiplication and multiple regulatory functions of the viruses. Thus, intrinsic disorder of YDR including its structural and functional annotation was comprehensively studied by exploiting computational methodologies to delineate its role in viral adaptation. RESULTS Based on our findings, it was evident that YDR contains significantly higher levels of ordered regions with less prevalence of disordered residues. Sequence-based analysis of YDR revealed it as a "dual personality" (DP) protein due to the presence of both structured and unstructured (intrinsically disordered) regions. The evolution of YDR was shaped by pressures that lead towards predominance of both disordered and regularly folded amino acids (Ala, Arg, Gly, Ile, Leu, Phe, Pro, Ser, Tyr, Val). Additionally, the predominance of characteristic DP residues (Thr, Arg, Gly, and Pro) further showed the order as well as disorder characteristic possessed by YDR. The intrinsic disorder propensity analysis of YDR revealed it as a moderately disordered protein. All the YDR sequences consisted of molecular recognition features (MoRFs), i.e., intrinsic disorder-based protein-protein interaction (PPI) sites, in addition to several nucleotide-binding sites. Thus, the presence of molecular recognition (PPI, RNA binding, and DNA binding) signifies the YDR's interaction with specific partners, host membranes leading to further viral infection. The presence of various disordered-based phosphorylation sites further signifies the role of YDR in various biological processes. Furthermore, functional annotation of YDR revealed it as a multifunctional-associated protein, due to its susceptibility in binding to a wide range of ligands and involvement in various catalytic activities. CONCLUSIONS As DP are targets for regulation, thus, YDR contributes to cellular signaling processes through PPIs. As YDR is incompletely understood, therefore, our data on disorder-based function could help in better understanding its associated functions. Collectively, our novel data from this comprehensive investigation is the first attempt to delineate YDR role in the regulation and pathogenesis of HEV.
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Affiliation(s)
- Zoya Shafat
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
| | - Anwar Ahmed
- Centre of Excellence in Biotechnology Research, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Mohammad K. Parvez
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Shama Parveen
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
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21
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Cellular Organelles Involved in Hepatitis E Virus Infection. Pathogens 2021; 10:pathogens10091206. [PMID: 34578238 PMCID: PMC8469867 DOI: 10.3390/pathogens10091206] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 09/16/2021] [Accepted: 09/16/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatitis E virus (HEV), a major cause of acute hepatitis worldwide, infects approximately 20 million individuals annually. HEV can infect a wide range of mammalian and avian species, and cause frequent zoonotic spillover, increasingly raising public health concerns. To establish a successful infection, HEV needs to usurp host machineries to accomplish its life cycle from initial attachment to egress. However, relatively little is known about the HEV life cycle, especially the functional role(s) of cellular organelles and their associated proteins at different stages of HEV infection. Here, we summarize current knowledge regarding the relation of HEV with the different cell organelles during HEV infection. Furthermore, we discuss the underlying mechanisms by which HEV infection is precisely regulated in infected cells and the modification of host cell organelles and their associated proteins upon HEV infection.
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Casares-Jimenez M, Lopez-Lopez P, Caballero-Gomez J, Frias M, Perez-Hernando B, Oluremi AS, Risalde MA, Ruiz-Caceres I, Opaleye OO, Garcia-Bocanegra I, Rivero-Juarez A, Rivero A. Global molecular diversity of Hepatitis E virus in wild boar and domestic pig. One Health 2021; 13:100304. [PMID: 34466650 PMCID: PMC8385159 DOI: 10.1016/j.onehlt.2021.100304] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 08/06/2021] [Accepted: 08/06/2021] [Indexed: 01/05/2023] Open
Abstract
Our study aim was to describe and characterize the global Hepatitis E virus (HEV) molecular and genotype geographical distribution in domestic pig and wild boar, which could facilitate the traceability of human cases. We performed a systematic sequence search for HEVs identified in domestic pig and wild boar from the available data in GenBank. Only sequences with lengths greater than 300 nt were included. For all sequences, the sequence length, host (i.e., domestic pig or wild boar), country of origin, and HEV genotype/subtype were recorded. Genotypes were assigned by the HEVnet typing tool. The genotype distributions were described by country and host. In countries with sequences available for both species, the genotype coincidences between both animal populations were analyzed. A total of 1404 viral sequences were included: 32.6% from wild boar and 67.4% from domestic pig. Most sequences were consistent with HEV genotype 3 (n = 1165). Genotype 4 was represented by 193 sequences, while genotypes 5 and 6 were represented by only 6 sequences. Sequences were identified in 39 countries, which included all continents except Antarctica. The genotypes with a wide distribution were 3a and 3f. Twenty-five countries had sequences that were found only in domestic pig, three countries only in wild boar, and 11 countries had sequences in both populations. In all countries with available sequences in both populations, the same viral genotype was identified. Our study shows that the number of swine HEV sequences is small, which limits direct comparisons with the sequences identified in humans. The global distribution of genotype 3, together with the wide distribution of genotype 4 in Asia, strongly limits the interpretation of the molecular analysis in the absence of an epidemiological survey of the cases. Increased HEV sequencing in swine should be a priority.
Our study shows that the number of swine HEV sequences is small. The global distribution of genotype 3 strongly limits the interpretation of the molecular analysis. Increased HEV sequencing in swine should be a priority.
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Affiliation(s)
- Maria Casares-Jimenez
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Pedro Lopez-Lopez
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Javier Caballero-Gomez
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain.,Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Mario Frias
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Belen Perez-Hernando
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Adeolu Sunday Oluremi
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain.,Department of Medical Microbiology and Parasitology, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - Maria A Risalde
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain.,Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), Departamento de Anatomía y Anatomía Patológica Comparadas y Toxicología, Facultad de Veterinaria, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Inmaculada Ruiz-Caceres
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Oluyinka Oladele Opaleye
- Department of Medical Microbiology and Parasitology, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - Ignacio Garcia-Bocanegra
- Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Antonio Rivero-Juarez
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Antonio Rivero
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
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23
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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: 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: 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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24
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Mrzljak A, Balen I, Barbic L, Ilic M, Vilibic-Cavlek T. Hepatitis E virus in professionally exposed: A reason for concern? World J Hepatol 2021; 13:723-730. [PMID: 34367494 PMCID: PMC8326162 DOI: 10.4254/wjh.v13.i7.723] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 03/31/2021] [Accepted: 06/25/2021] [Indexed: 02/06/2023] Open
Abstract
The zoonotic risk of hepatitis E virus (HEV) is well established. The HEV seroprevalence rates vary according to geographical region, assays used, and study cohorts. HEV infection is still underdiagnosed, implying the need to evaluate the disease's burden in the general population and specific risk groups, such as professionally exposed. Close contact with various animal reservoirs such as pigs, rabbits, sheep, dogs, wild boars, and deer has been associated with higher anti-HEV seroprevalence as a part of occupational exposure. While exact transmission routes remain to be determined, some general preventive measures such as proper hand hygiene, the usage of personal protective equipment, and the thermal processing of food before consumption should be followed. A "One-Health" multisectoral approach should be implemented to achieve optimal health and well-being outcomes, recognizing the interconnections between humans, animals, plants, and their shared environment, in which a vaccine against the zoonotic genotypes 3 and 4 and swine vaccination should be considered as a possible public health measure. This opinion review comprehensively addresses the HEV burden of professional exposure for butchers, slaughterhouse workers, veterinarians, farmers, hunters, and forestry workers delineates the current limits of protective work measures, and tackles future directions.
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Affiliation(s)
- Anna Mrzljak
- Department of Gastroenterology and Hepatology, University Hospital Centre Zagreb, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia.
| | - Ivan Balen
- Department of Gastroenterology and Endocrinology, General Hospital “Dr. Josip Bencevic”, Slavonski Brod 35000, Croatia
| | - Ljubo Barbic
- Faculty of Veterinary Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Maja Ilic
- Department of Epidemiology, Croatian Institute of Public Health, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Tatjana Vilibic-Cavlek
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Virology, Croatian Institute of Public Health, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
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25
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Velavan TP, Pallerla SR, Johne R, Todt D, Steinmann E, Schemmerer M, Wenzel JJ, Hofmann J, Shih JWK, Wedemeyer H, Bock CT. Hepatitis E: An update on One Health and clinical medicine. Liver Int 2021; 41:1462-1473. [PMID: 33960603 DOI: 10.1111/liv.14912] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 03/09/2021] [Accepted: 04/08/2021] [Indexed: 12/12/2022]
Abstract
The hepatitis E virus (HEV) is one of the main causes of acute hepatitis and the de facto global burden is underestimated. HEV-related clinical complications are often undetected and are not considered in the differential diagnosis. Convincing findings from studies suggest that HEV is clinically relevant not only in developing countries but also in industrialized countries. Eight HEV genotypes (HEV-1 to HEV-8) with different human and animal hosts and other HEV-related viruses are in circulation. Transmission routes vary by genotype and location, with large waterborne outbreaks in developing countries and zoonotic food-borne infections in developed countries. An acute infection can be aggravated in pregnant women, organ transplant recipients, patients with pre-existing liver disease and immunosuppressed patients. HEV during pregnancy affects the fetus and newborn with an increased risk of vertical transmission, preterm and stillbirth, neonatal jaundice and miscarriage. Hepatitis E is associated with extrahepatic manifestations that include neurological disorders such as neuralgic amyotrophy, Guillain-Barré syndrome and encephalitis, renal injury and haematological disorders. The risk of transfusion-transmitted HEV is increasingly recognized in Western countries where the risk may be because of a zoonosis. RNA testing of blood components is essential to determine the risk of transfusion-transmitted HEV. There are currently no approved drugs or vaccines for HEV infections. This review focuses on updating the latest developments in zoonoses, screening and diagnostics, drugs in use and under development, and vaccines.
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Affiliation(s)
- Thirumalaisamy P Velavan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Vietnamese-German Center for Medical Research, VG-CARE, Hanoi, Vietnam
- Faculty of Medicine, Duy Tan University, Da Nang, Vietnam
| | - Srinivas R Pallerla
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Vietnamese-German Center for Medical Research, VG-CARE, Hanoi, Vietnam
| | - Reimar Johne
- German Federal Institute for Risk Assessment, Berlin, Germany
| | - Daniel Todt
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
- European Virus Bioinformatics Center (EVBC), Jena, Germany
| | - Eike Steinmann
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
| | - Mathias Schemmerer
- Institute of Clinical Microbiology and Hygiene, National Consultant Laboratory for HAV and HEV, University Medical Center Regensburg, Regensburg, Germany
| | - Jürgen J Wenzel
- Institute of Clinical Microbiology and Hygiene, National Consultant Laboratory for HAV and HEV, University Medical Center Regensburg, Regensburg, Germany
| | - Jörg Hofmann
- Institute of Virology, Charité Universitätsmedizin Berlin, Labor Berlin-Charité-Vivantes GmbH, Berlin, Germany
| | | | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research, Partner Hannover-Braunschweig, Braunschweig, Germany
| | - Claus-Thomas Bock
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Division of Viral Gastroenteritis and Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
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26
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Corman VM, Nagy P, Ostermann S, Arloth J, Liljander A, Barua R, Das Gupta A, Hakimuddin F, Juhasz J, Wernery U, Drosten C. Hepatitis E Virus Genotype 7 RNA and Antibody Kinetics in Naturally Infected Dromedary Calves, United Arab Emirates. Emerg Infect Dis 2021; 26:2214-2217. [PMID: 32818408 PMCID: PMC7454054 DOI: 10.3201/eid2609.191758] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Orthohepevirus A genotype 7 is a novel zoonotic variant of hepatitis E virus. To clarify infection in the animal reservoir, we virologically monitored 11 dromedary dam–calf pairs. All calves became infected during the first 6 months of life and cleared the virus after an average of 2 months. Dams did not become infected.
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27
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Mechanism of Cross-Species Transmission, Adaptive Evolution and Pathogenesis of Hepatitis E Virus. Viruses 2021; 13:v13050909. [PMID: 34069006 PMCID: PMC8157021 DOI: 10.3390/v13050909] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 05/12/2021] [Accepted: 05/13/2021] [Indexed: 12/17/2022] Open
Abstract
Hepatitis E virus (HEV) is the leading cause of acute hepatitis worldwide. While the transmission in developing countries is dominated by fecal-oral route via drinking contaminated water, the zoonotic transmission is the major route of HEV infection in industrialized countries. The discovery of new HEV strains in a growing number of animal species poses a risk to zoonotic infection. However, the exact mechanism and the determinant factors of zoonotic infection are not completely understood. This review will discuss the current knowledge on the mechanism of cross-species transmission of HEV infection, including viral determinants, such as the open reading frames (ORFs), codon usage and adaptive evolution, as well as host determinants, such as host cellular factors and the host immune status, which possibly play pivotal roles during this event. The pathogenesis of hepatitis E infection will be briefly discussed, including the special forms of this disease, including extrahepatic manifestations, chronic infection, and fulminant hepatitis in pregnant women.
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28
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Nishizawa T, Takahashi M, Tsatsralt-Od B, Nyamdavaa K, Dulmaa N, Osorjin B, Tseren-Ochir EO, Sharav T, Bayasgalan C, Sukhbaatar B, Nagashima S, Murata K, Okamoto H. Identification and a full genome analysis of novel camel hepatitis E virus strains obtained from Bactrian camels in Mongolia. Virus Res 2021; 299:198355. [PMID: 33662492 DOI: 10.1016/j.virusres.2021.198355] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 02/24/2021] [Accepted: 02/24/2021] [Indexed: 12/27/2022]
Abstract
Hepatitis E virus (HEV) infects humans and a wide variety of other mammalian hosts. Recently, HEV strains belonging to genotype 8 (G8) within the Orthohepevirus A species of the Hepeviridae family, were identified in Bactrian camels (Camelus bactrianus) in China. The Bactrian camel (also known as the Mongolian camel) is native to the steppes of Central Asia. However, the HEV strains of Mongolian camels have not been examined. Among 200 serum samples from domestic Bactrian camels raised on 6 farms, in 6 soums in 3 provinces; 71 (35.5 %) were positive for anti-HEV IgG, with prevalence differing by farm (soum) (4.2-75.0 %); and 2 camels (1.0 %) that had been raised in Bogd, Bayankhongor Province, which had the highest seroprevalence among the six studied areas, were positive for HEV RNA. The two HEV strains (BcHEV-MNG140 and BcHEV-MNG146) obtained from the viremic camels in the present study shared 97.7 % nucleotide identity. They were closest to the reported G8 Chinese camel HEV strains but differed from them by 13.9-14.3 % over the entire genome, with a nucleotide difference of 24.0-26.5 % from the reported G1-G7 HEV strains. A phylogenetic tree indicated that the BcHEV-MNG140 and BcHEV-MNG146 strains were located upstream of a clade consisting of the Chinese camel HEV strains and formed a cluster with them, with a bootstrap value of 100 %, suggesting that they may represent a novel subtype within G8. These results indicate a high prevalence of HEV infection in Mongolian camels and suggest that the variability of camel HEV genomes is markedly high.
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Affiliation(s)
- Tsutomu Nishizawa
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, 329-0498, Japan
| | - Masaharu Takahashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, 329-0498, Japan
| | - Bira Tsatsralt-Od
- National Center for Communicable Diseases, Ministry of Health Mongolia, Ulaanbaatar, 210648, Mongolia
| | | | - Nyamkhuu Dulmaa
- National Center for Communicable Diseases, Ministry of Health Mongolia, Ulaanbaatar, 210648, Mongolia
| | | | - Erdene-Ochir Tseren-Ochir
- Department of Infectious Diseases and Microbiology, School of Veterinary Medicine, Mongolian University of Life Sciences, Ulaanbaatar, 17024, Mongolia
| | - Tumenjargal Sharav
- Department of Infectious Diseases and Microbiology, School of Veterinary Medicine, Mongolian University of Life Sciences, Ulaanbaatar, 17024, Mongolia
| | - Chimedtseren Bayasgalan
- Department of Infectious Diseases and Microbiology, School of Veterinary Medicine, Mongolian University of Life Sciences, Ulaanbaatar, 17024, Mongolia
| | - Boldbaatar Sukhbaatar
- Sector of Surveillance and Diagnosis of Infectious Diseases, State Central Veterinary Laboratory, Ulaanbaatar, 17024, Mongolia
| | - Shigeo Nagashima
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, 329-0498, Japan
| | - Kazumoto Murata
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, 329-0498, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, 329-0498, Japan.
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Modiyinji AF, Bigna JJ, Kenmoe S, Simo FBN, Amougou MA, Ndangang MS, Nola M, Njouom R. Epidemiology of hepatitis E virus infection in animals in Africa: a systematic review and meta-analysis. BMC Vet Res 2021; 17:50. [PMID: 33494758 PMCID: PMC7831161 DOI: 10.1186/s12917-021-02749-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2019] [Accepted: 01/06/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) is a major cause of acute hepatitis in humans worldwide and have high burden in the resource-limited countries. Better knowledge of the epidemiology of hepatitis in animals in Africa can help to understand the epidemiology among humans. The objective of this study was to summarize the prevalence of HEV infection and distribution of HEV genotypes among animals in Africa. METHODS In this systematic review and meta-analysis, we comprehensively searched PubMed, EMBASE, African Journals Online, and Africa Index Medicus from January 1st, 2000 to March 22th, 2020 without any language restriction. We considered cross-sectional studies of HEV infection in animals in Africa. Study selection, data extraction, and methodological quality of included studies were done independently by two investigators. Prevalence data were pooled using the random-effects meta-analysis. This review was registered in PROSPERO, CRD42018087684. RESULTS Twenty-five studies (13 species and 6983 animals) were included. The prevalence (antibodies or ribonucleic acid [RNA]) of HEV infection in animals varied widely depending on biological markers of HEV infection measured: 23.4% (95% confidence interval; 12.0-37.2) for anti-HEV immunoglobulins G, 13.1% (3.1-28.3) for anti-HEV immunoglobulins M, and 1.8% (0.2-4.3) for RNA; with substantial heterogeneity. In subgroup analysis, the immunoglobulins G seroprevalence was higher among pigs 37.8% (13.9-65.4). The following HEV genotypes were reported in animals: Rat-HEV genotype 1 (rats and horses), HEV-3 (pigs), HEV-7 (dromedaries), and Bat hepeviruses (bats). CONCLUSIONS We found a high prevalence of HEV infection in animals in Africa and HEV genotypes close to that of humans. Some animals in Africa could be the reservoir of HEV, highlighting the need of molecular epidemiological studies for investigating zoonotic transmission.
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Affiliation(s)
- Abdou Fatawou Modiyinji
- Department of Virology, Centre Pasteur of Cameroon, Yaoundé, Cameroon
- Department of Biology and Animal Physiology, Faculty of Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Jean Joel Bigna
- Department of Epidemiology and Public Health, Centre Pasteur of Cameroon, Yaoundé, Cameroon
- School of Public Health, Faculty of Medicine, University of Paris Sud, Le Kremlin-Bicêtre, France
| | - Sebastien Kenmoe
- Department of Virology, Centre Pasteur of Cameroon, Yaoundé, Cameroon
| | - Fredy Brice N. Simo
- Department of Virology, Centre Pasteur of Cameroon, Yaoundé, Cameroon
- Department of Epidemiology and Public Health, Centre Pasteur of Cameroon, Yaoundé, Cameroon
| | - Marie A. Amougou
- Department of Virology, Centre Pasteur of Cameroon, Yaoundé, Cameroon
- Department of Epidemiology and Public Health, Centre Pasteur of Cameroon, Yaoundé, Cameroon
| | - Marie S. Ndangang
- Department of Medical Information and Informatics, Rouen University Hospital, Rouen, France
| | - Moise Nola
- Department of Biology and Animal Physiology, Faculty of Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Richard Njouom
- Department of Virology, Centre Pasteur of Cameroon, Yaoundé, Cameroon
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Jing W, Liu J, Liu M. The global trends and regional differences in incidence of HEV infection from 1990 to 2017 and implications for HEV prevention. Liver Int 2021; 41:58-69. [PMID: 33025620 DOI: 10.1111/liv.14686] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 09/14/2020] [Accepted: 09/29/2020] [Indexed: 02/13/2023]
Abstract
BACKGROUND/AIMS Hepatitis E virus (HEV) infection is an important cause of acute viral hepatitis worldwide, but it is long-neglected. We aimed to understand the global trends and regional differences in the incidence of HEV infection, thereby making global tailored prevention strategies. METHODS This study is a post-hoc analysis of the data from Global Burden of Disease Study 2017. Annual HEV incident cases and incidence rates from 1990 to 2017 were collected. Changes in incident cases and estimated annual percentage changes (EAPCs) of age-standardized incidence rates (ASRs) were calculated to quantify the temporal trends of HEV infection. RESULTS Globally, HEV ASRs decreased by an average 0.16% (95% CI: 0.14%-0.17%) per year from 279.79 per 100 000 in 1990 to 269.70 per 100 000 in 2017; however, the number of HEV incident cases increased by 17.63% from 16.53 million in 1990 to 19.44 million in 2017. Against the global trend of ASR falling, an increasing trend was reported in Oceania (EAPC = 0.03; 95% CI: 0.03-0.04) and Western Europe (EAPC = 0.02; 95% CI: 0.01-0.03). The number of HEV incident cases increased remarkably in low (63.07%) and low-middle (37.46%) Socio-Demographic Index (SDI) regions between 1990 and 2017. Additionally, the number of HEV incident cases increased by 4.63% in high SDI regions, mainly in 40 plus age group. Surprisingly, more than 40% of HEV incident cases in Western Europe in 2017 were over 40 years old. CONCLUSIONS HEV is still pending in hyperendemic regions, and it is emerging in low endemic regions, suggesting more efforts should be done to make targeted prevention strategies.
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Affiliation(s)
- Wenzhan Jing
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Jue Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Min Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
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31
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Clinical Characteristics of Acute Hepatitis E and Their Correlation with HEV Genotype 3 Subtypes in Italy. Pathogens 2020; 9:pathogens9100832. [PMID: 33050666 PMCID: PMC7650787 DOI: 10.3390/pathogens9100832] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 10/04/2020] [Accepted: 10/09/2020] [Indexed: 02/08/2023] Open
Abstract
Genotype 3 (GT3) is responsible for most European autochthonous hepatitis E virus (HEV) infections. This study analyzed circulating genotypes and GT3 subtypes in the Lazio region, Italy, between 2011 and 2019, as well as their pathogenic characteristics. Of the 64 evaluable HEV GT3 patient-derived sequences, identified subtypes included GT3f (n = 36), GT3e (n = 15), GT3c (n = 9), GT3a (n = 1) and three unsubtyped GT3 sequences. GT3c strains were similar to Dutch sequences (96.8–98.1% identity), GT3e strains showed high similarity (96.8%) with a United Kingdom sequence, while the most related sequences to GT3f Italian strains were isolated in France, Belgium and Japan. One sequence was closely related to another Italian strain isolated in raw sewage in 2016. The liver functioning test median values for 56 evaluable GT3 patients were: alanine aminotransferase (ALT), 461 (range 52–4835 U/L); aspartate aminotransferase (AST), 659 (range 64–6588 U/L); and total bilirubin, 3.49 (range 0.4–33 mg/dL). The median HEV RNA viral load for 26 evaluable GT3 patients was 42,240 IU/mL (range 5680–895,490 IU/mL). Of the 37 GT3 patients with available clinical information, no correlation was observed between HEV clinical manifestations and GT3 subtype. HEV symptoms were comparable among GT3c/e/f patients across most analyzed categories except for epigastric pain, which occurred more frequently in patients with HEV GT3e (75%) than in patients with GT3c (50%) or GT3f (19%) (p = 0.01). Additionally, patients with HEV GT3c exhibited significantly higher median international normalized ratio (INR) than patients with GT3e and GT3f (p = 0.033). The severity of GT3 acute hepatitis E was not linked to HEV RNA viral load or to the GT3 subtype.
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32
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Aslan AT, Balaban HY. Hepatitis E virus: Epidemiology, diagnosis, clinical manifestations, and treatment. World J Gastroenterol 2020; 26:5543-5560. [PMID: 33071523 PMCID: PMC7545399 DOI: 10.3748/wjg.v26.i37.5543] [Citation(s) in RCA: 107] [Impact Index Per Article: 21.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 08/11/2020] [Accepted: 09/09/2020] [Indexed: 02/06/2023] Open
Abstract
The hepatitis E virus (HEV) is the fifth known form of viral hepatitis and was first recognized as the cause of an epidemic of unexplained acute hepatitis in the early 1980s. Globally, it is one of the most frequent causes of acute viral hepatitis. The majority of HEV infections are asymptomatic and lead to the spontaneous clearance of the virus. Among the eight different genotypes identified to date, HEV genotype 1 (HEV1), HEV2, HEV3, and HEV4 are the most frequent genotypes causing infections in humans. HEV1 and HEV2 are prevalent in developing regions and able to result in large-scale outbreaks originating from contaminated water supplies. They are also responsible for severe hepatitis in pregnant patients and infants. In contrast, HEV3 and HEV4 are zoonotic, and the transmission of these genotypes to humans occurs mainly through the fecal contamination of water and consumption of contaminated meat from infected animals. Their main reservoir is the pig, and they are mostly encountered in developed countries. The major risk groups for HEV infection and its ensuing adverse consequences are pregnant women, infants, older people, immunocompromised individuals, patients with underlying chronic liver diseases, and workers that come into close contact with HEV-infected animals. In the clinical perspective, HEV infections have diverse clinical manifestations including acute and self-limiting hepatitis, acute-on-chronic liver disease, chronic hepatitis, cirrhosis, and liver failure. Although HEV mainly results in acute self-limiting infection, chronic HEV infection may occur among immunocompromised patients (e.g., solid-organ transplant recipients). Additionally, HEV-associated extrahepatic manifestations involving various organs have been reported in the last decade, although the causal link for many of them still needs to be proven. Ribavirin and interferon-alpha are the most widely used agents for the treatment of HEV infections with a certain level of success. However, ribavirin is contraindicated in pregnant patients, and interferon-alpha cannot be used in most transplant recipients. Therefore, there is an urgent need for novel antiviral compounds that are safe and effective particularly for patients having contraindications for ribavirin or interferon-alpha and infected by the ribavirin-resistant HEV. In this review article, a literature search using PubMed and MEDLINE databases was performed, up to March 2020. Only the articles published in English were reviewed.
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Affiliation(s)
| | - Hatice Yasemin Balaban
- Department of Gastroenterology, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey
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Guo Y, Yang F, Xu X, Feng M, Liao Y, He Z, Takeda N, Muramatsu M, Li Q, Li TC. Immunization of human hepatitis E viruses conferred protection against challenge by a camel hepatitis E virus. Vaccine 2020; 38:7316-7322. [PMID: 32980200 DOI: 10.1016/j.vaccine.2020.09.036] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 09/04/2020] [Accepted: 09/13/2020] [Indexed: 12/27/2022]
Abstract
Dromedary camel hepatitis E virus is a novel HEV that belongs to the family Hepeviridae, and is classified as genotype 7 HEV (HEV-7). Since HEV-7 is transmitted from camels to humans and causes acute hepatitis E, this virus is a non-negligible pathogen for zoonosis, and a vaccine against HEV-7 infection is urgently needed. Here, we first intravenously inoculated HEV-7 to rhesus monkeys to explore the susceptibility, and we established an animal model. We then used virus-like particles (VLPs) of HEV-1 (HEV-1 VLPs) and HEV-3 (HEV-3 VLPs), a candidate hepatitis E vaccine, to intramuscularly inoculate rhesus monkeys. The monkeys elicited IgG antibody titers as high as >1:102,400 against heterologous HEV-7 without any adjuvants. The HEV-1 VLPs and HEV-3 VLPs-immunized monkeys were challenged intravenously with HEV-7, and they were protected completely from the infection, demonstrating that these VLPs could be a usable vaccine against HEV-7 infection. We also observed that HEV-7-infected rhesus monkeys did not show any liver damage during these experiments. Further efforts are necessary to establish an animal model for investigation of the pathogenesis of hepatitis E caused by HEV-7 infection.
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Affiliation(s)
- Yingqiu Guo
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan Province 650118, China
| | - Fengmei Yang
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan Province 650118, China
| | - Xingli Xu
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan Province 650118, China
| | - Min Feng
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan Province 650118, China
| | - Yun Liao
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan Province 650118, China
| | - Zhanlong He
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan Province 650118, China
| | - Naokazu Takeda
- Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0781, Japan
| | - Masamichi Muramatsu
- Department of Virology II, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashi-murayama, Tokyo 208-0011, Japan
| | - Qihan Li
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan Province 650118, China.
| | - Tian-Cheng Li
- Department of Virology II, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashi-murayama, Tokyo 208-0011, Japan.
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Olayinka A, Ifeorah IM, Omotosho O, Faleye TOC, Odukaye O, Bolaji O, Ibitoye I, Ope-Ewe O, Adewumi MO, Adeniji JA. A possible risk of environmental exposure to HEV in Ibadan, Oyo State, Nigeria. J Immunoassay Immunochem 2020; 41:875-884. [PMID: 32787711 DOI: 10.1080/15321819.2020.1804933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Hepatitis E virus (HEV) infection is both a major public health concern and emerging global health concern, with a documented incidence of 20 million, 3.4 million clinical cases, 70,000 deaths, and 3,000 stillbirths. The aetiologic agent, HEV is a primarily enterally transmitted hepatotropic virus. Fecal samples were collected from three selected pig farms across Ibadan, South-west Nigeria. Randomly picked samples were pooled per unit pen and fecal suspensions prepared were subjected to HEV Antigen (Ag) enzyme-linked immunosorbent assay. Molecular probing was done by Reverse Transcription and nested polymerase reaction (RT-nPCR) and deep sequencing. Sequencing was done paired-end for 300 cycles using the HiSeq system. Overall farm prevalence of 66.7% (2/3) and prevalence at individual level of 13.2% (9/68) were recorded. All nine samples positive for the ELISA screen were negative when subjected to RT-nPCR assays. Further, on deep sequencing, no HEV genomic fragment was found in the sample using de-novo assembly. Findings suggest possibly inapparent HEV in the pigs studied or a yet to be identified protein with HEV-Ag cross-reactivity ability on ELISA, thus constituting a possible risk of exposure to HEV infection in the population. Consequently, we recommend prompt intervention to unravel the mystery and break the chain of transmission.
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Affiliation(s)
- Adebowale Olayinka
- Department of Virology, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - I M Ifeorah
- Department of Medical Laboratory Sciences, Faculty of Health Sciences and Technology, University of Nigeria, Nsukka, Nigeria
| | - Oladipo Omotosho
- Department of Veterinary Medicine, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria
| | - T O C Faleye
- Department of Virology, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.,Centre for Human Virology and Genomics, Department of Microbiology, Nigerian Institute for Medical Research, Lagos, Nigeria
| | - Oladapo Odukaye
- Department of Veterinary Medicine, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria
| | - Oluremi Bolaji
- Department of Pharmaceutical Microbiology, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria 6. Infectious Disease Institute, College of Medicine, University of Ibadan, Ibadan, NigeriaInfectious Disease Institute, College of Medicine, Unive
| | - Ibipeju Ibitoye
- Department of Virology, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Oludayo Ope-Ewe
- Department of Virology, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - M O Adewumi
- Department of Virology, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.,WHO National Polio Laboratory, University of Ibadan, Ibadan, Nigeria
| | - J A Adeniji
- Department of Virology, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.,WHO National Polio Laboratory, University of Ibadan, Ibadan, Nigeria
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Monini M, Ostanello F, Dominicis A, Tagliapietra V, Vaccari G, Rizzoli A, Trombetta CM, Montomoli E, Di Bartolo I. Seroprevalence of Hepatitis E Virus in Forestry Workers from Trentino-Alto Adige Region (Northern Italy). Pathogens 2020; 9:pathogens9070568. [PMID: 32674277 PMCID: PMC7399850 DOI: 10.3390/pathogens9070568] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 07/02/2020] [Accepted: 07/10/2020] [Indexed: 12/15/2022] Open
Abstract
People with some occupational or recreational activities, such as hunters and veterinarians, may have increased risk to be infected by the hepatitis E virus (HEV). The aim of the present study was to establish whether forestry workers could be considered at a higher risk of HEV infection than a control group. One hundred and fifty sera from forestry workers and a control group of 85 sera were analysed by anti-HEV IgG antibodies detection using a commercial ELISA kit. The anti-HEV IgG seroprevalence was 14% for forestry workers and 9.4% for the control group. Comparing the risk of HEV infection in the two groups, there was no difference in the odds ratio. However, the seroprevalence in older subjects was higher in the forestry workers than in the control group. Two sera from forestry workers were also positive for anti-HEV IgM, and, in one of them, HEV-RNA was detected. Our findings showed an increase of seroprevalence with age, which is likely to reflect cumulative exposure to HEV over time. The occupation of forestry workers did not seem to be associated with a higher risk of HEV infection. The study provided new insights into the risk of acquiring HEV in occupational exposure workers with open-air activities.
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Affiliation(s)
- Marina Monini
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy; (A.D.); (G.V.); (I.D.B.)
- Correspondence: ; Tel.: +39-0649902787
| | - Fabio Ostanello
- Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra, 50, 40064 Ozzano dell’Emilia (BO), Italy;
| | - Alessandra Dominicis
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy; (A.D.); (G.V.); (I.D.B.)
| | - Valentina Tagliapietra
- Department of Biodiversity and Molecular Ecology, Research and Innovation Centre, Fondazione Edmund Mach, Via E. Mach, 1, 38098 San Michele all’Adige (TN), Italy; (V.T.); (A.R.)
| | - Gabriele Vaccari
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy; (A.D.); (G.V.); (I.D.B.)
| | - Annapaola Rizzoli
- Department of Biodiversity and Molecular Ecology, Research and Innovation Centre, Fondazione Edmund Mach, Via E. Mach, 1, 38098 San Michele all’Adige (TN), Italy; (V.T.); (A.R.)
| | - Claudia M. Trombetta
- Department of Molecular and Developmental Medicine, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy; (C.M.T.); (E.M.)
| | - Emanuele Montomoli
- Department of Molecular and Developmental Medicine, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy; (C.M.T.); (E.M.)
- VisMederi S.r.l., Strada del Petriccio e Belriguardo, 35, 53100 Siena, Italy
| | - Ilaria Di Bartolo
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy; (A.D.); (G.V.); (I.D.B.)
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El-Kafrawy SA, Hassan AM, El-Daly MM, Qadri I, Tolah AM, Al-Subhi TL, Alzahrani AA, Alsaaidi GA, Al-Abdullah N, Kaki RM, Li TC, Azhar EI. Seroprevalence of Dromedary Camel HEV in Domestic and Imported Camels from Saudi Arabia. Viruses 2020; 12:553. [PMID: 32443401 PMCID: PMC7290434 DOI: 10.3390/v12050553] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Revised: 04/27/2020] [Accepted: 05/05/2020] [Indexed: 12/12/2022] Open
Abstract
Hepatitis E Virus (HEV) imposes a major health concern in areas with very poor sanitation in Africa and Asia. The pathogen is transmitted mainly through ingesting contaminated water or food, coming into contact with affected people, and blood transfusions. Very few reports including old reports are available on the prevalence of HEV in Saudi Arabia in humans and no reports exist on HEV prevalence in camels. Dromedary camel trade and farming are increasing in Saudi Arabia with importation occurring unidirectionally from Africa to Saudi Arabia. DcHEV transmission to humans has been reported in one case from the United Arab Emeritus (UAE). This instigated us to perform this investigation of the seroprevalence of HEV in imported and domestic camels in Saudi Arabia. Serum samples were collected from imported and domestic camels. DcHEV-Abs were detected in collected sera using ELISA. The prevalence of DcHEV in the collected samples was 23.1% with slightly lower prevalence in imported camels than domestic camels (22.4% vs. 25.4%, p value = 0.3). Gender was significantly associated with the prevalence of HEV in the collected camels (p value = 0.015) where males (31.6%) were more infected than females (13.4%). This study is the first study to investigate the prevalence of HEV in dromedary camels from Saudi Arabia. The high seroprevalence of DcHEV in dromedaries might indicate their role as a zoonotic reservoir for viral infection to humans. Future HEV seroprevalence studies in humans are needed to investigate the role of DcHEV in the Saudi human population.
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Affiliation(s)
- Sherif Aly El-Kafrawy
- Department of Biological Science, Division of Microbiology, Faculty of science, King Abdulaziz University, PO Box 80216, Jeddah 21859, Saudi Arabia; (S.A.E.-K.); (A.M.H.); (I.Q.)
- Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia; (M.M.E.-D.); (A.M.T.); (T.L.A.-S.); (N.A.-A.); (R.M.K.)
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80205, Jeddah 21589, Saudi Arabia
| | - Ahmed Mohamed Hassan
- Department of Biological Science, Division of Microbiology, Faculty of science, King Abdulaziz University, PO Box 80216, Jeddah 21859, Saudi Arabia; (S.A.E.-K.); (A.M.H.); (I.Q.)
- Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia; (M.M.E.-D.); (A.M.T.); (T.L.A.-S.); (N.A.-A.); (R.M.K.)
| | - Mai Mohamed El-Daly
- Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia; (M.M.E.-D.); (A.M.T.); (T.L.A.-S.); (N.A.-A.); (R.M.K.)
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80205, Jeddah 21589, Saudi Arabia
| | - Ishtiaq Qadri
- Department of Biological Science, Division of Microbiology, Faculty of science, King Abdulaziz University, PO Box 80216, Jeddah 21859, Saudi Arabia; (S.A.E.-K.); (A.M.H.); (I.Q.)
| | - Ahmed Majdi Tolah
- Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia; (M.M.E.-D.); (A.M.T.); (T.L.A.-S.); (N.A.-A.); (R.M.K.)
| | - Tagreed Lafi Al-Subhi
- Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia; (M.M.E.-D.); (A.M.T.); (T.L.A.-S.); (N.A.-A.); (R.M.K.)
| | - Abdulrahman A. Alzahrani
- Directorate of Agriculture, Ministry of Environment Water and Agriculture, Makkah Region, Saudi Arabia; (A.A.A.); (G.A.A.)
| | - Ghaleb A. Alsaaidi
- Directorate of Agriculture, Ministry of Environment Water and Agriculture, Makkah Region, Saudi Arabia; (A.A.A.); (G.A.A.)
| | - Nabeela Al-Abdullah
- Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia; (M.M.E.-D.); (A.M.T.); (T.L.A.-S.); (N.A.-A.); (R.M.K.)
- Department of Public Health, College of Nursing, King Abdulaziz University, Jeddah 21859, Saudi Arabia
- Department of Infection Control and Environmental Health, King Abdulaziz University Hospital, King Abdulaziz University, Jeddah 21859, Saudi Arabia
| | - Reham Mohammed Kaki
- Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia; (M.M.E.-D.); (A.M.T.); (T.L.A.-S.); (N.A.-A.); (R.M.K.)
- Department of Infection Control and Environmental Health, King Abdulaziz University Hospital, King Abdulaziz University, Jeddah 21859, Saudi Arabia
- Department of Infectious Diseases, Internal Medicine, Faculty of Medicine King Abdulaziz University, Jeddah 21859, Saudi Arabia
| | - Tian-Cheng Li
- Department of Virology II, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashi-murayama, Tokyo 208-0011, Japan;
| | - Esam Ibraheem Azhar
- Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia; (M.M.E.-D.); (A.M.T.); (T.L.A.-S.); (N.A.-A.); (R.M.K.)
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80205, Jeddah 21589, Saudi Arabia
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Seroprevalence of hepatitis E virus in dromedary camels, Bedouins, Muslim Arabs and Jews in Israel, 2009-2017. Epidemiol Infect 2020; 147:e92. [PMID: 30869027 PMCID: PMC6518832 DOI: 10.1017/s0950268819000062] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Hepatitis E virus (HEV) is an emerging cause of viral hepatitis worldwide. Recently, HEV-7 has been shown to infect camels and humans. We studied HEV seroprevalence in dromedary camels and among Bedouins, Arabs (Muslims, none-Bedouins) and Jews and assessed factors associated with anti-HEV seropositivity. Serum samples from dromedary camels (n = 86) were used to determine camel anti-HEV IgG and HEV RNA positivity. Human samples collected between 2009 and 2016 from >20 years old Bedouins (n = 305), non-Bedouin Arabs (n = 320) and Jews (n = 195), were randomly selected using an age-stratified sampling design. Human HEV IgG levels were determined using Wantai IgG ELISA assay. Of the samples obtained from camels, 68.6% were anti-HEV positive. Among the human populations, Bedouins and non-Bedouin Arabs had a significantly higher prevalence of HEV antibodies (21.6% and 15.0%, respectively) compared with the Jewish population (3.1%). Seropositivity increased significantly with age in all human populations, reaching 47.6% and 34.8% among ⩾40 years old, in Bedouins and non-Bedouin Arabs, respectively. The high seropositivity in camels and in ⩾40 years old Bedouins and non-Bedouin Arabs suggests that HEV is endemic in Israel. The low HEV seroprevalence in Jews could be attributed to higher socio-economic status.
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Obaidat MM, Roess AA. Individual animal and herd level seroprevalence and risk factors of Hepatitis E in ruminants in Jordan. INFECTION GENETICS AND EVOLUTION 2020; 81:104276. [PMID: 32147473 DOI: 10.1016/j.meegid.2020.104276] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Revised: 03/03/2020] [Accepted: 03/04/2020] [Indexed: 01/09/2023]
Abstract
OBJECTIVES Hepatitis E virus (HEV) is zoonotic and endemic in several countries. There are no data on the farm level-prevalence and risk factors of HEV in ruminant farms in Jordan or elsewhere. This study aimed to estimate the seroprevalence and risk factors of HEV in ruminant farms in all regions of Jordan. MATERIAL AND METHODS A total of 460 apparently healthy ruminants from 115 (31 cow, 51 sheep and 33 goat) farms were tested for HEV antibodies using a double antigen sandwich enzyme linked immunosorbent test. A validated questionnaire was used to collect data on animal health and husbandry practices. RESULTS The results showed that 37.4% of the dairy farms under study (51.6%, 37.2% and 24.2% of dairy cow, sheep and goat farms; respectively) had at least one HEV seropositive animal. At the individual animal level, 12.1% of the tested animals were HEV positive; 14.5% (n = 18), 12.7% (n = 26) and 8.3% (n = 11) of cows, sheep and goats; respectively. Infrequent cleaning of feeders was associated with a significantly greater odds of HEV seropositivity in both large and small dairy ruminant farms (AOR = 16.0, p-val = 0.03, AOR = 3.4, p-val = 0.02, respectively). Farms which reported that small ruminants (sheep and goats) were mixed together had a greater odds of farm-level HEV seroprevalence (AOR = 3.1, p-val = 0.04). CONCLUSIONS This study shows widespread and high farm-level HEV seroprevalence in dairy farms in Jordan. Husbandry practices and off-abattoir carcass processing in Jordan could amplify emergence and transmission of zoonotic HEV. Future studies should include HEV genotyping in ruminants, their products and humans to better understand HEV epidemiology in Jordan.
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Affiliation(s)
- Mohammad M Obaidat
- Department of Veterinary Pathology and Public Health, Faculty of Veterinary Medicine, Jordan University of Science and Technology, Irbid, Jordan.
| | - Amira A Roess
- Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington, DC, USA; Department of Global and Community Health, College of Health and Human Services, George Mason University, Fairfax, VA, USA
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Nüesch-Inderbinen M, Kindle P, Baschera M, Liljander A, Jores J, Corman VM, Stephan R. Antimicrobial resistant and extended-spectrum ß-lactamase (ESBL) producing Escherichia coli isolated from fecal samples of African dromedary camels. SCIENTIFIC AFRICAN 2020; 7:e00274. [PMID: 34171008 PMCID: PMC7148658 DOI: 10.1016/j.sciaf.2020.e00274] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 11/07/2019] [Accepted: 01/22/2020] [Indexed: 12/02/2022] Open
Abstract
This study was conducted to determine the distribution of antimicrobial resistance among Escherichia coli isolated from feces of healthy dromedary camels in Kenya. A total of 162 fecal samples were cultivated for E. coli. Samples were also subcultivated to detect E. coli with extended-spectrum ß-lactamases (ESBLs). Antimicrobial susceptibility testing (AST) was performed by disk diffusion using a panel of 16 antimicrobials. In addition, isolates were screened for the presence of the plasmid-mediated colistin resistance genes mcr-1 to mcr-5. Samples from 20 (12.4%) of the camels contained antimicrobial resistant (AMR) E. coli, and 85% of the AMR isolates were multidrug resistant (MDR). The highest frequency of resistance was observed to tetracycline (11.7%), followed by ampicillin and streptomycin (both 10.5%), and sulfamethoxazole/trimethoprim (9.9%). Two (1.2%) of the isolates showed intermediate resistance to cefazolin and streptomycin, respectively. All the isolates were susceptible to amoxycillin/clavulanic acid, ciprofloxacin, fosfomycin, aztreonam and kanamycin, and 86.4% of the isolates were susceptible to all 16 antimicrobials used in this study. The prevalence of fecal carriage of ESBL producing E. coli was 0.6%. PCR and amplicon sequencing showed that the ESBL producer belonged to E. coli phylogenetic group A, sequence type (ST) 48, and harbored blaCTX-M-15. None of the isolates contained mcr genes. The results indicate that dromedary camels in Kenya may be reservoirs of AMR E. coli, including ESBL producers, that could potentially be transmitted to humans by direct contact or via the food chain.
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Affiliation(s)
| | - Patrick Kindle
- Institute for Food Safety and Hygiene, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
| | - Melinda Baschera
- Institute for Food Safety and Hygiene, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
| | - Anne Liljander
- International Livestock Research Institute, PO Box 30709, 00100 Nairobi, Kenya
| | - Jörg Jores
- Institute for Veterinary Bacteriology, Vetsuisse Faculty, University of Bern, Switzerland
| | - Victor Max Corman
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany.,German Centre for Infection Research, Berlin, Germany
| | - Roger Stephan
- Institute for Food Safety and Hygiene, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
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Caballero-Gómez J, García Bocanegra I, Gómez-Guillamón F, Camacho-Sillero L, Zorrilla I, Lopez-Lopez P, Cano-Terriza D, Jiménez-Ruiz S, Frias M, Rivero-Juarez A. Absence of Hepatitis E virus circulation in wild rabbits (Oryctolagus cuniculus) and Iberian hares (Lepus granatensis) in Mediterranean ecosystems in Spain. Transbound Emerg Dis 2020; 67:1422-1427. [PMID: 31930690 DOI: 10.1111/tbed.13478] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 12/30/2019] [Accepted: 01/06/2020] [Indexed: 01/13/2023]
Abstract
In recent decades, cases of autochthonous hepatitis E (HE) have sharply increased in European countries where foodborne transmission is considered the main route of HE virus (HEV) transmission. Although rabbits are considered the main reservoir of the zoonotic HEV-3ra subtype, information on the role of wild lagomorphs in the epidemiology of HEV remains scarce. The aim of this study therefore was to assess the circulation of HEV in European wild rabbits (Oryctolagus cuniculus) and Iberian hares (Lepus granatensis), the most important lagomorph species in Spanish Mediterranean ecosystems. Liver samples from 372 wild rabbits and 78 Iberian hares were analysed using a broad-spectrum RT-PCR that detects HEV genotypes 1-8. None of the 450 lagomorphs tested were positive for HEV infection. To the best of our knowledge, this is the first study to assess HEV circulation in wild rabbits in Spain and the first to evaluate HEV infection in Iberian hares. Our results indicate absence of HEV circulation in wild rabbits and Iberian hares in southern Spain during the study period, which suggests that the risk of transmission of HEV from wild lagomorphs to other species, including humans, is low.
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Affiliation(s)
- Javier Caballero-Gómez
- Departamento de Sanidad Animal, Universidad de Córdoba (UCO), Córdoba, Spain.,Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
| | | | - Félix Gómez-Guillamón
- Programa de Vigilancia Epidemiológica de la Fauna Silvestre (PVE), Consejería de Agricultura, Ganadería, Pesca y Desarrollo Sostenible, Junta de Andalucía, Málaga, Spain
| | - Leonor Camacho-Sillero
- Programa de Vigilancia Epidemiológica de la Fauna Silvestre (PVE), Consejería de Agricultura, Ganadería, Pesca y Desarrollo Sostenible, Junta de Andalucía, Málaga, Spain
| | - Irene Zorrilla
- Centro de Análisis y Diagnóstico de la Fauna Silvestre en Andalucía (CAD), Agencia de Medio Ambiente y Agua (AMAYA), Junta de Andalucía, Málaga, Spain
| | - Pedro Lopez-Lopez
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
| | - David Cano-Terriza
- Departamento de Sanidad Animal, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Saúl Jiménez-Ruiz
- Departamento de Sanidad Animal, Universidad de Córdoba (UCO), Córdoba, Spain.,Grupo de Sanidad y Biotecnología, Instituto de Investigación en Recursos Cinegéticos, Universidad de Castilla la Mancha, (SaBio-IREC, UCLM-CSIC-JCCM), Ciudad Real, Spain
| | - Mario Frias
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Antonio Rivero-Juarez
- Unidad de Enfermedades Infecciosas, Grupo de Virología Clínica y Zoonosis, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
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Modesto P, Maniaci MG, Cavallazzi U, Acutis PL, Peletto S. Evaluation of a molecular method for hepatitis E virus (HEV) detection in pancreatin of porcine origin. J Virol Methods 2019; 276:113790. [PMID: 31770544 DOI: 10.1016/j.jviromet.2019.113790] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 11/22/2019] [Accepted: 11/22/2019] [Indexed: 12/12/2022]
Abstract
Pancreatin is a combination of enzymes, principally amylase, lipase, and protease, used in the treatment of pancreatic endocrine insufficiency in humans. Pancreatin manufactured from imported porcine pancreas carries the risk of hepatitis E virus (HEV) contamination. About 1 % of the starting material for pancreatin manufacture is invariably constituted of the small intestine, which is known to be a major extrahepatic site of HEV replication in pigs. The aim of this study was to evaluate a method to detect and quantify HEV in pancreatin of porcine origin. Because HEV cannot be easily grown by conventional cell culture, an approach based on an established quantitative RT-PCR (RT-qPCR) was selected. This entailed the use of a non-HEV internal control to monitor RNA extraction efficacy and the production of HEV synthetic RNA as a reference to account for the efficacy of reverse-transcription. The method was evaluated by experiments in which HEV (from naturally infected pigs) was spiked in both the starting material (i.e., porcine pancreas homogenate for industrial production) and in the pancreatin itself. A laboratory protocol matching the industrial production workflow was set up and RT-qPCR experiments were carried out to evaluate the method's ability to detect HEV in pancreatin made from HEV-contaminated porcine tissues. The results showed that the method may be employed in two different strategies: to test the porcine pancreas homogenate (quantitative performance) or directly on pancreatin (qualitative assay). While the risk of HEV contamination in pancreatin may be low, it cannot be completely ruled out. Testing for HEV based on the precautionary principle ought to be the guiding rule.
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Affiliation(s)
- Paola Modesto
- Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, 10154 Torino, Italy
| | - Maria Grazia Maniaci
- Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, 10154 Torino, Italy
| | | | - Pier Luigi Acutis
- Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, 10154 Torino, Italy
| | - Simone Peletto
- Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, 10154 Torino, Italy.
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Teng JLL, Wernery U, Lee HH, Joseph S, Fung J, Elizabeth SK, Yeong KY, Kinne J, Chan KH, Lau SKP, Woo PCY. First Isolation and Rapid Identification of Newcastle Disease Virus from Aborted Fetus of Dromedary Camel Using Next-Generation Sequencing. Viruses 2019; 11:v11090810. [PMID: 31480604 PMCID: PMC6783818 DOI: 10.3390/v11090810] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 08/23/2019] [Accepted: 08/30/2019] [Indexed: 02/07/2023] Open
Abstract
Newcastle disease virus (NDV) causes morbidities and mortalities in wild and domestic birds globally. For humans, exposure to infected birds can cause conjunctivitis and influenza-like symptoms. NDV infections in mammals are rarely reported. In this study, using next-generation sequencing, an NDV was identified and isolated from Vero cells inoculated with the nasal swab of an aborted dromedary fetus in Dubai, during the time when an NDV outbreak occurred in a pigeon farm located in close proximity to the dairy camel farm where the mother of the aborted dromedary fetus resided, and there were a lot of pigeons in the camel farm. Genome analysis revealed that the structurally and functionally important features of other NDVs were also present in this dromedary NDV genome. Phylogenetic analysis based on the nucleotide sequences of fusion protein (F), hemagglutinin-neuraminidase protein (HN) and complete polyprotein showed that the virus belonged to sub-genotype VIg of class II NDV and is most closely related to pigeon NDVs in Egypt in the same year. The present study is the first that demonstrated isolation of NDV in dromedaries. Further study is warranted to investigate the relationship between NDV infection and abortion.
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Affiliation(s)
- Jade Lee Lee Teng
- Department of Microbiology, The University of Hong Kong, Hong Kong, China
- State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China
- Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China
| | - Ulrich Wernery
- Central Veterinary Research Laboratory, Dubai 00000, United Arab Emirates.
| | - Hwei Huih Lee
- Department of Microbiology, The University of Hong Kong, Hong Kong, China
| | - Sunitha Joseph
- Central Veterinary Research Laboratory, Dubai 00000, United Arab Emirates
| | - Joshua Fung
- Department of Microbiology, The University of Hong Kong, Hong Kong, China
| | | | - Kai Yan Yeong
- Department of Microbiology, The University of Hong Kong, Hong Kong, China
| | - Joerg Kinne
- Central Veterinary Research Laboratory, Dubai 00000, United Arab Emirates
| | - Kwok-Hung Chan
- Department of Microbiology, The University of Hong Kong, Hong Kong, China
| | - Susanna Kar Pui Lau
- Department of Microbiology, The University of Hong Kong, Hong Kong, China
- State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China
- Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong, China
| | - Patrick Chiu Yat Woo
- Department of Microbiology, The University of Hong Kong, Hong Kong, China.
- State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.
- Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China.
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong, China.
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Mrzljak A, Dinjar-Kujundzic P, Jemersic L, Prpic J, Barbic L, Savic V, Stevanovic V, Vilibic-Cavlek T. Epidemiology of hepatitis E in South-East Europe in the "One Health" concept. World J Gastroenterol 2019; 25:3168-3182. [PMID: 31333309 PMCID: PMC6626717 DOI: 10.3748/wjg.v25.i25.3168] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 05/16/2019] [Accepted: 05/31/2019] [Indexed: 02/06/2023] Open
Abstract
The significance of hepatitis E virus (HEV) as an important public health problem is rising. Until a decade ago, cases of HEV infection in Eur-ope were mainly confined to returning travelers, but nowadays, hepatitis E represents an emerging zoonotic infection in many European countries. The aim of this manuscript is to perform a systematic review of the published literature on hepatitis E distribution in humans, animals and environmental samples ("One Health" concept) in the South-Eastern European countries. Comparison of the available data showed that the anti-HEV seroprevalence in the South-Eastern Europe varies greatly, depending on the population studied, geographical area and methods used. The IgG seroprevalence rates in different population groups were found to be 1.1%-24.5% in Croatia, up to 20.9% in Bulgaria, 5.9-%17.1% in Romania, 15% in Serbia, up to 9.7% in Greece and 2%-9.7% in Albania. Among possible risk factors, older age was the most significant predictor for HEV seropositivity in most studies. Higher seroprevalence rates were found in animals. HEV IgG antibodies in domestic pigs were detected in 20%-54.5%, 29.2%-50%, 38.94%-50% and 31.1%-91.7% in Serbia, Bulgaria, Romania and Croatia, respectively. In wild boars seroprevalence rates were up to 10.3%, 30.3% and 31.1% in Romania, Slovenia and Croatia, respectively. A high HEV RNA prevalence in wild boars in some countries (Croatia and Romania) indicated that wild boars may have a key role in the HEV epidemiology. There are very few data on HEV prevalence in environmental samples. HEV RNA was detected in 3.3% and 16.7% surface waters in Slovenia and Serbia, respectively. There is no evidence of HEV RNA in sewage systems in this region. The available data on genetic characterization show that human, animal and environmental HEV strains mainly belong to the genotype 3.
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Affiliation(s)
- Anna Mrzljak
- Department of Medicine, Merkur University Hospital; School of Medicine, University of Zagreb, Zagreb 10000, Grad Zagreb, Croatia
| | | | - Lorena Jemersic
- Croatian Veterinary Institute, Zagreb 10000, Grad Zagreb, Croatia
| | - Jelena Prpic
- Croatian Veterinary Institute, Zagreb 10000, Grad Zagreb, Croatia
| | - Ljubo Barbic
- Faculty of Veterinary Medicine, University of Zagreb, Zagreb 10000, Grad Zagreb, Croatia
| | - Vladimir Savic
- Croatian Veterinary Institute, Zagreb 10000, Grad Zagreb, Croatia
| | - Vladimir Stevanovic
- Faculty of Veterinary Medicine, University of Zagreb, Zagreb 10000, Grad Zagreb, Croatia
| | - Tatjana Vilibic-Cavlek
- Department of Virology, Croatian Institute of Public Health; School of Medicine, University of Zagreb, Zagreb 10000, Grad Zagreb, Croatia
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Baschera M, Cernela N, Stevens MJ, Liljander A, Jores J, Corman VM, Nüesch-Inderbinen M, Stephan R. Shiga toxin-producing Escherichia coli (STEC) isolated from fecal samples of African dromedary camels. One Health 2019; 7:100087. [PMID: 30911597 PMCID: PMC6416407 DOI: 10.1016/j.onehlt.2019.100087] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Revised: 03/06/2019] [Accepted: 03/06/2019] [Indexed: 12/29/2022] Open
Abstract
Shiga toxin-producing Escherichia coli (STEC) cause gastrointestinal illnesses including non-bloody or bloody diarrhoea, haemorrhagic colitis (HC), and the haemolytic uremic syndrome (HUS). To investigate the occurrence of STEC among grazing dromedaries from Kenya, E. coli isolated from fecal matter collected from 163 dromedaries on a large ranch were screened for the presence of stx1 and stx2. STEC strains were isolated and serotyped. Isolates were subjected to PCR for the subtyping of stx genes and for the detection of eae and ehx. In addition, whole genome sequencing (WGS) was carried out to detect further virulence genes and to determine the multilocus sequence types (MLST). Antimicrobial resistance profiles were determined by disk diffusion. STEC was isolated from 20 (12.3%) of the fecal samples. Thereof, nine (45%) isolates were STEC O156:H25, three (15%) isolates typed STEC O43:H2. The remaining isolates occurred as single serotypes or were O non-typeable. Eleven (55%) of the isolates harboured stx2a, nine (45%) eae, and 14 (70%) ehx, respectively. WGS revealed the presence of iss in 16 (80%), subAB in four (20%) and astA in two (10%) of the isolates, Furthermore, espA, tccP, nleA, nleB, tccP, and tir were found exclusively among STEC O156:H25. Eleven different sequence types (ST) were detected. The most prominent was ST300/ST5343, which comprised STEC O156:H25. All STEC isolates were pan susceptible to a panel of 16 antimicrobial agents. Overall, the results indicate that dromedary camels in Kenya may be reservoirs of STEC, including serotypes possessing virulence markers associated to disease in humans, such as STEC O156:H25. STEC in camels may represent a health hazard for humans with close contact to camels or to consumers of camel derived foodstuffs, such as unpasteurised camel milk.
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Affiliation(s)
- Melinda Baschera
- Institute for Food Safety and Hygiene, Vetsuisse Faculty, University of Zurich, Switzerland
| | - Nicole Cernela
- Institute for Food Safety and Hygiene, Vetsuisse Faculty, University of Zurich, Switzerland
| | - Marc J.A. Stevens
- Institute for Food Safety and Hygiene, Vetsuisse Faculty, University of Zurich, Switzerland
| | - Anne Liljander
- International Livestock Research Institute, PO Box 30709, 00100 Nairobi, Kenya
| | - Jörg Jores
- Institute for Veterinary Bacteriology, Vetsuisse Faculty, University of Bern, Switzerland
| | - Victor Max Corman
- Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Institute of Virology, Berlin, Germany
- German Centre for Infection Research, Berlin, Germany
| | | | - Roger Stephan
- Institute for Food Safety and Hygiene, Vetsuisse Faculty, University of Zurich, Switzerland
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Zhu S, Zimmerman D, Deem SL. A Review of Zoonotic Pathogens of Dromedary Camels. ECOHEALTH 2019; 16:356-377. [PMID: 31140075 PMCID: PMC7087575 DOI: 10.1007/s10393-019-01413-7] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 03/12/2019] [Accepted: 03/12/2019] [Indexed: 06/09/2023]
Abstract
Dromedary, or one-humped, camels Camelus dromedarius are an almost exclusively domesticated species that are common in arid areas as both beasts of burden and production animals for meat and milk. Currently, there are approximately 30 million dromedary camels, with highest numbers in Africa and the Middle East. The hardiness of camels in arid regions has made humans more dependent on them, especially as a stable protein source. Camels also carry and may transmit disease-causing agents to humans and other animals. The ability for camels to act as a point source or vector for disease is a concern due to increasing human demands for meat, lack of biosafety and biosecurity protocols in many regions, and a growth in the interface with wildlife as camel herds become sympatric with non-domestic species. We conducted a literature review of camel-borne zoonotic diseases and found that the majority of publications (65%) focused on Middle East respiratory syndrome (MERS), brucellosis, Echinococcus granulosus, and Rift Valley fever. The high fatality from MERS outbreaks during 2012-2016 elicited an immediate response from the research community as demonstrated by a surge of MERS-related publications. However, we contend that other camel-borne diseases such as Yersinia pestis, Coxiella burnetii, and Crimean-Congo hemorrhagic fever are just as important to include in surveillance efforts. Camel populations, particularly in sub-Saharan Africa, are increasing exponentially in response to prolonged droughts, and thus, the risk of zoonoses increases as well. In this review, we provide an overview of the major zoonotic diseases present in dromedary camels, their risk to humans, and recommendations to minimize spillover events.
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Affiliation(s)
- Sophie Zhu
- Graduate Group in Epidemiology, University of California, Davis, CA, 95616, USA.
| | - Dawn Zimmerman
- Global Health Program, Smithsonian Conservation Biology Institute, Washington, DC, 20008, USA
| | - Sharon L Deem
- Institute for Conservation Medicine, Saint Louis Zoo, Saint Louis, MO, 63110, USA
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Primadharsini PP, Nagashima S, Okamoto H. Genetic Variability and Evolution of Hepatitis E Virus. Viruses 2019; 11:E456. [PMID: 31109076 PMCID: PMC6563261 DOI: 10.3390/v11050456] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 05/15/2019] [Accepted: 05/16/2019] [Indexed: 12/16/2022] Open
Abstract
Hepatitis E virus (HEV) is a single-stranded positive-sense RNA virus. HEV can cause both acute and chronic hepatitis, with the latter usually occurring in immunocompromised patients. Modes of transmission range from the classic fecal-oral route or zoonotic route, to relatively recently recognized but increasingly common routes, such as via the transfusion of blood products or organ transplantation. Extrahepatic manifestations, such as neurological, kidney and hematological abnormalities, have been documented in some limited cases, typically in patients with immune suppression. HEV has demonstrated extensive genomic diversity and a variety of HEV strains have been identified worldwide from human populations as well as growing numbers of animal species. The genetic variability and constant evolution of HEV contribute to its physiopathogenesis and adaptation to new hosts. This review describes the recent classification of the Hepeviridae family, global genotype distribution, clinical significance of HEV genotype and genomic variability and evolution of HEV.
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Affiliation(s)
- Putu Prathiwi Primadharsini
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi 329-0498, Japan.
| | - Shigeo Nagashima
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi 329-0498, Japan.
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi 329-0498, Japan.
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The Current Host Range of Hepatitis E Viruses. Viruses 2019; 11:v11050452. [PMID: 31108942 PMCID: PMC6563279 DOI: 10.3390/v11050452] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 05/08/2019] [Accepted: 05/14/2019] [Indexed: 01/01/2023] Open
Abstract
Hepatitis E virus (HEV) is an emerging zoonotic pathogen transmitting both human to human via the fecal oral route and from animals to humans through feces, direct contact, and consumption of contaminated meat products. Understanding the host range of the virus is critical for determining where potential threats to human health may be emerging from and where potential reservoirs for viral persistence in the environment may be hiding. Initially thought to be a human specific disease endemic to developing countries, the identification of swine as a primary host for genotypes 3 and 4 HEV in industrialized countries has begun a long journey of discovering novel strains of HEV and their animal hosts. As we continue identifying new strains of HEV in disparate animal species, it is becoming abundantly clear that HEV has a broad host range and many of these HEV strains can cross between differing animal species. These cross-species transmitting strains pose many unique challenges to human health as they are often unrecognized as sources of viral transmission.
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Transmission of a Novel Genotype of Hepatitis E Virus from Bactrian Camels to Cynomolgus Macaques. J Virol 2019; 93:JVI.02014-18. [PMID: 30700602 DOI: 10.1128/jvi.02014-18] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Accepted: 01/18/2019] [Indexed: 12/15/2022] Open
Abstract
Hepatitis E virus (HEV) is zoonotic and a major cause of acute viral hepatitis worldwide. Recently, we identified a novel HEV genotype 8 (HEV8) in Bactrian camels in Xinjiang, China. However, the epidemiology, pathogenicity, and zoonotic potential of HEV8 are unclear. Here, we present the prevalence of HEV8 in China and investigate its pathogenicity and cross-species transmission in cynomolgus macaques. Fresh fecal and milk samples from Bactrian camels collected from four provinces/regions in China were screened for HEV RNA by reverse transcriptase PCR (RT-PCR). An HEV8-positive sample was used to inoculate two cynomolgus macaques to examine the potential for cross-species infection. The pathogenicity of HEV8 was analyzed by testing HEV markers and liver function during the study period and histopathology of liver biopsy specimens at 3, 13, and 25 weeks postinoculation. Extrahepatic replication was tested by using reverse transcriptase quantitative PCR (RT-qPCR) and immunofluorescence assays. The overall prevalence of HEV8 RNA in Chinese Bactrian camels was 1.4% (4/295), and positive samples were found in three different provinces/regions in China. Histopathology confirmed acute and chronic HEV8 infections in the two monkeys. Multiple tissues were positive for HEV RNA and ORF2 proteins. Renal pathology was observed in the monkey with chronic hepatitis. Whole-genome sequencing showed only 1 to 3 mutations in the HEV8 in the fecal samples from the two monkeys compared to that from the camel. HEV8 is circulating in multiple regions in China. Infection of two monkeys with HEV8 induced chronic and systemic infections, demonstrating the high potential zoonotic risk of HEV8.IMPORTANCE It is estimated that one-third of the world population have been exposed to hepatitis E virus (HEV). In developed countries and China, zoonotic HEV strains are responsible for almost all acute and chronic HEV infection cases. It is always of immediate interest to investigate the zoonotic potential of novel HEV strains. In 2016, we discovered a novel HEV genotype, HEV8, in Bactrian camels, but the epidemiology, zoonotic potential, and pathogenicity of the virus were unknown. In the present study, we demonstrated that HEV8 was circulating in multiple regions in China and was capable of infecting cynomolgus macaques, a surrogate for humans, posing high risk of zoonosis. Chronic hepatitis, systemic infection, and renal pathology were observed. Collectively, these data indicate that HEV8 exhibits a high potential for zoonotic transmission. Considering the importance of Bactrian camels as livestock animals, risk groups, such as camelid meat and milk consumers, should be screened for HEV8 infection.
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Rasche A, Sander AL, Corman VM, Drexler JF. Evolutionary biology of human hepatitis viruses. J Hepatol 2019; 70:501-520. [PMID: 30472320 PMCID: PMC7114834 DOI: 10.1016/j.jhep.2018.11.010] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Revised: 11/09/2018] [Accepted: 11/10/2018] [Indexed: 02/06/2023]
Abstract
Hepatitis viruses are major threats to human health. During the last decade, highly diverse viruses related to human hepatitis viruses were found in animals other than primates. Herein, we describe both surprising conservation and striking differences of the unique biological properties and infection patterns of human hepatitis viruses and their animal homologues, including transmission routes, liver tropism, oncogenesis, chronicity, pathogenesis and envelopment. We discuss the potential for translation of newly discovered hepatitis viruses into preclinical animal models for drug testing, studies on pathogenesis and vaccine development. Finally, we re-evaluate the evolutionary origins of human hepatitis viruses and discuss the past and present zoonotic potential of their animal homologues.
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Affiliation(s)
- Andrea Rasche
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, 10117 Berlin, Germany,German Center for Infection Research (DZIF), Germany
| | - Anna-Lena Sander
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, 10117 Berlin, Germany
| | - Victor Max Corman
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, 10117 Berlin, Germany,German Center for Infection Research (DZIF), Germany
| | - Jan Felix Drexler
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, 10117 Berlin, Germany; German Center for Infection Research (DZIF), Germany.
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Yang F, Duan S, Guo Y, Li Y, Yoshizaki S, Takeda N, Wakita T, Muramatsu M, Zhao Y, He Z, Li TC. Current status of hepatitis E virus infection at a rhesus monkey farm in China. Vet Microbiol 2019; 230:244-248. [DOI: 10.1016/j.vetmic.2019.01.021] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Revised: 01/09/2019] [Accepted: 01/27/2019] [Indexed: 10/27/2022]
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