Infection dynamics and persistence of hepatitis E virus on pig farms – a review

Abstract Background Hepatitis E virus (HEV) genotype 3 and 4 is a zoonosis that causes hepatitis in humans. Humans can become infected by consumption of pork or contact with pigs. Pigs are the main reservoir of the virus worldwide and the virus is present on most pig farms. Main body Though HEV is present on most farms, the proportion of infected pigs at slaughter and thus the level of exposure to consumers differs between farms and countries. Understanding the cause of that difference is necessary to install effective measures to lower HEV in pigs at slaughter. Here, HEV studies are reviewed that include infection dynamics of HEV in pigs and on farms, risk factors for HEV farm prevalence, and that describe mechanisms and sources that could generate persistence on farms. Most pigs become infected after maternal immunity has waned, at the end of the nursing or beginning of the fattening phase. Risk factors increasing the likelihood of a high farm prevalence or proportion of actively infected slaughter pigs comprise of factors such as farm demographics, internal and external biosecurity and immunomodulating coinfections. On-farm persistence of HEV is plausible, because of a high transmission rate and a constant influx of susceptible pigs. Environmental sources of HEV that enhance persistence are contaminated manure storages, water and fomites. Conclusion As HEV is persistently present on most pig farms, current risk mitigation should focus on lowering transmission within farms, especially between farm compartments. Yet, one should be aware of the paradox of increasing the proportion of actively infected pigs at slaughter by reducing transmission insufficiently. Vaccination of pigs may aid HEV control in the future.

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Hepatitis E virus infection in 6-month-old pigs in Taiwan

Scientific Reports ◽

10.1038/s41598-020-74034-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Ming-Hui Liao ◽

Fang-Tzy Wu ◽

Huimin Bai ◽

Yen Hai Doan ◽

Jyh-Yuan Yang ◽

...

Keyword(s):

Hepatitis E Virus ◽

Phylogenetic Analyses ◽

Hepatitis E ◽

Limited Information ◽

Genotype 3 ◽

Entire Genome ◽

Entire Genome Sequence ◽

Detection Frequency ◽

Pig Farms ◽

Acute Hepatitis E

Abstract Hepatitis E virus (HEV) is the causative agent of acute hepatitis E. Genotype 3 (G3) and 4 (G4) HEV have recently been identified in and isolated from swine as the main HEV genotypes worldwide. However, there is limited information on HEV infection status among pigs in Taiwan, especially pigs in the stage before transportation to the slaughterhouse. To determine the frequency of HEV infection among pigs in Taiwan, we detected and quantified HEV RNA contained in 295 fecal specimens collected from 6-month-old pigs bred in 30 pig farms located in 8 counties. We found that 25.1% (74/295) of the fecal specimens were positive for HEV RNA by a quantitative real-time reverse transcription-polymerase chain reaction, and the copy number ranged from 2.3 × 103 to 2.08 × 107 copies/g. Amplification of a 338 bp sequence in ORF2 was achieved in 16 of 74 HEV RNA-positive samples, and their nucleotide sequences were determined. Two HEV sequences appeared to belong to subtype 3a of G3 and the remaining 14 HEV sequences belonged to subtype 4b of G4 (G4b). The entire genome sequence of two G4b HEVs was obtained by next-generation sequence analyses, and the phylogenetic analyses indicated that unique G4b HEVs were circulating in pig farms in Taiwan. In the present study, we found that both G3 and G4 HEVs were circulating in Taiwanese pig farms and G4b was the predominant subtype. In addition, the relatively high detection frequency of HEV RNA in the 6-month-old pigs indicated that Taiwanese pigs just before transportation to the slaughterhouse are at risk of carrying HEVs, and thus thorough cooking or heating of pork meat or organs is needed before consumption in Taiwan and possibly in other countries as well.

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A26 Molecular epidemiology of hepatitis E virus in Ireland 2016

Virus Evolution ◽

10.1093/ve/vez002.025 ◽

2019 ◽

Vol 5 (Supplement_1) ◽

Author(s):

Charlene Bennett ◽

Linda Dunford ◽

Suzie Coughlan ◽

Cillian De Gascun ◽

Joanne O’Gorman

Keyword(s):

Molecular Epidemiology ◽

Foodborne Pathogens ◽

Hepatitis E Virus ◽

Risk Mitigation ◽

Hepatitis E ◽

Mitigation Measures ◽

Clinical Samples ◽

Bootstrap Support ◽

Genotype 3 ◽

Pork Products

Abstract Foodborne viruses such as hepatitis E virus (HEV) pose an increasing risk to public health and to confidence in Irish food. Hepatitis E has been acknowledged as a significant pathogen of likely zoonotic transmission, with pork products and shellfish being implicated as potential sources. The European Food Safety Authority has recommended that systematic strain typing of viruses in humans, animals, and food commodities is needed to improve understanding of etiological agents and foodborne transmission pathways, in particular for HEV. The dominant autochthonous genotype of HEV in Europe is genotype 3, thought to be associated with consumption of contaminated food, specifically pork products. However, little is known about the epidemiology of HEV in Ireland. In 2016, HEV became a notifiable disease in Ireland. Following this, as part of the Department of Agriculture, Food and the Marine-funded FoVIRA study, the molecular epidemiology of HEV in Irish clinical samples has been characterized for the first time. HEV RNA-positive clinical specimens from 2016 were genetically characterized (n = 14). A 450 nucleotide fragment of the ORF2 region of the HEV genome was amplified, with contiguous sequence assembly performed using DNA Lasergene v14. Sequences were aligned with ClustalW implemented in Bioedit v7.1.9 and compared to reference strains from GenBank. A maximum likelihood phylogenetic tree was constructed using the Hasegawa–Kishino–Yano model and a discrete gamma distribution to model evolutionary rate distances between sites. Evolutionary analyses were conducted in MEGA7. Statistical support was provided by bootstrapping with 1,000 replicates. Fourteen strains belonged to genotype 3 and were classified as the following subtypes: 3c (n = 7), 3e (n = 4), 3f (n = 1), 3 untyped (n = 1), and 1 untyped. Phylogenetic analysis showed the formation of two distinct clusters of genotype 3:3abchij and 3efg, with strong bootstrap support. A genotype 1 was detected and found to be associated with travel. Data generated from this research will contribute to a risk exposure assessment and will be used to identify potential control points and risk mitigation measures for viral foodborne pathogens. This study will provide a unique opportunity to build national capability in the area of food testing within Irish public laboratories.

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Screening of Swiss Pig Herds for Hepatitis E Virus: A Pilot Study

Animals ◽

10.3390/ani11113050 ◽

2021 ◽

Vol 11 (11) ◽

pp. 3050

Author(s):

Julia Lienhard ◽

Isabelle Vonlanthen-Specker ◽

Xaver Sidler ◽

Claudia Bachofen

Keyword(s):

Hepatitis E Virus ◽

Screening Tool ◽

Hepatitis E ◽

Genotype 3 ◽

Sequence Collection ◽

Pig Farms ◽

Industrialised Countries ◽

Fattening Pigs ◽

Subtype 3 ◽

Specific Cluster

Hepatitis E virus (HEV) is an important cause of acute hepatitis in humans worldwide. In industrialised countries, most infections are caused by the zoonotic genotype 3. The main reservoir was found in pigs, with fattening pigs as the main shedders. The aim of this study was to establish a screening tool to detect HEV in pig farms. HEV-positive samples were sequenced using Sanger sequencing. First, different sample materials, including floor swabs, slurry, dust swabs and faeces were tested for HEV. Floor swabs turned out to give the best results and, in the form of sock swabs, were used for the screening of Swiss pig herds. A total of 138 pig farms were tested, with a focus on fattening pigs. Overall, 81 farms (58.8%) were HEV positive. Most sequences belonged to subtype 3h, in which they formed a specific cluster (Swiss cluster). In addition, subtype 3 l and two unassigned sequences were detected. As a conclusion, sock swabs were found to be a helpful tool to screen pig herds for HEV and establish a sequence collection that may enable molecular epidemiology and support outbreak investigation and prevention.

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Seroprevalence of Hepatitis E Virus in Pigs from Different Farming Systems in The Netherlands

Journal of Food Protection ◽

10.4315/0362-028x.jfp-13-302 ◽

2014 ◽

Vol 77 (4) ◽

pp. 640-642 ◽

Cited By ~ 24

Author(s):

S. A. RUTJES ◽

M. BOUWKNEGT ◽

J. W. van der GIESSEN ◽

A. M. de RODA HUSMAN ◽

C. B. E. M. REUSKEN

Keyword(s):

The Netherlands ◽

Hepatitis E Virus ◽

Transmission Rate ◽

Hepatitis E ◽

Pig Manure ◽

Organic Farms ◽

Specific Antibodies ◽

Free Range ◽

Contact Frequency ◽

Pig Farms

Sporadic nontravel-related hepatitis E virus (HEV) infections have been reported in industrialized countries. These infections are caused by zoonotic HEV genotypes 3 and 4 that circulate in swine, wild boar, and deer. In The Netherlands, HEV RNA has been detected in > 50% of the pig farms, and HEV-specific antibodies were detected in ~70% of the slaughter pigs. In the current study, HEV seroprevalences were investigated in pigs raised on conventional, free-range, and organic farms in The Netherlands. Differences in seroprevalence may indicate different exposure routes or transmission dynamics within pig herds for HEV. In 2004, serum samples of 846 fattening pigs were obtained from farms that applied conventional (265 pigs at 24 farms), organic (417 pigs at 42 farms), and free-range (164 pigs at 12 farms) farming. HEV-specific antibodies were detected in samples from all conventional and free-range pig farms and in 41 of 42 organic pig farms, indicating that the probability of introducing HEV on a farm appeared to be equal for the different farming types. The estimated average within-herd seroprevalence was significantly higher for pigs raised on organic farms (89%) than for pigs raised on conventional farms (72%, P = 0.04) and nearly significant for pigs raised on free-range farms (76%, P = 0.06). Six of ten organic farms were estimated to have a within-herd seroprevalence of > 95%, compared with 1 of 10 and 4 of 10 of the free-range and conventional pig farms, respectively. This suggests a higher force of infection with HEV for pigs reared on organic farms compared with pigs reared on conventional or free-range farms. This may be due to repetitive exposure to HEV caused by farming system–specific housing conditions, such as a greater contact frequency between pigs and more exposure to pig manure, increasing the transmission rate.

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Advances in Hepatitis E Virus Biology and Pathogenesis

Viruses ◽

10.3390/v13020267 ◽

2021 ◽

Vol 13 (2) ◽

pp. 267

Author(s):

Shaoli Lin ◽

Yan-Jin Zhang

Keyword(s):

Pregnant Women ◽

Hepatitis E Virus ◽

Case Fatality ◽

Hepatitis E ◽

Host Cells ◽

High Rate ◽

Rapid Progression ◽

Genotype 1 ◽

Genotype 3 ◽

Zoonotic Infections

Hepatitis E virus (HEV) is one of the causative agents for liver inflammation across the world. HEV is a positive-sense single-stranded RNA virus. Human HEV strains mainly belong to four major genotypes in the genus Orthohepevirus A, family Hepeviridae. Among the four genotypes, genotype 1 and 2 are obligate human pathogens, and genotype 3 and 4 cause zoonotic infections. HEV infection with genotype 1 and 2 mainly presents as acute and self-limiting hepatitis in young adults. However, HEV infection of pregnant women with genotype 1 strains can be exacerbated to fulminant hepatitis, resulting in a high rate of case fatality. As pregnant women maintain the balance of maternal-fetal tolerance and effective immunity against invading pathogens, HEV infection with genotype 1 might dysregulate the balance and cause the adverse outcome. Furthermore, HEV infection with genotype 3 can be chronic in immunocompromised patients, with rapid progression, which has been a challenge since it was reported years ago. The virus has a complex interaction with the host cells in downregulating antiviral factors and recruiting elements to generate a conducive environment of replication. The virus-cell interactions at an early stage might determine the consequence of the infection. In this review, advances in HEV virology, viral life cycle, viral interference with the immune response, and the pathogenesis in pregnant women are discussed, and perspectives on these aspects are presented.

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Epidemiology of Hepatitis E in 2017 in Bavaria, Germany

Food and Environmental Virology ◽

10.1007/s12560-021-09474-0 ◽

2021 ◽

Author(s):

K. Hriskova ◽

D. Marosevic ◽

A. Belting ◽

J. J. Wenzel ◽

A. Carl ◽

...

Keyword(s):

Risk Factors ◽

Hepatitis E ◽

Food Samples ◽

Healthy Population ◽

Genotype 3 ◽

Human Samples ◽

Multivariable Analyses ◽

Upper Abdominal ◽

Undercooked Meat

AbstractIn the last decade, the number of reported hepatitis E virus (HEV) infections in Germany, including Bavaria, has continued to rise. In order to identify risk factors associated with HEV infection, we investigated notified hepatitis E cases from Bavaria during 2017. The project “Intensified Hepatitis E Surveillance in Bavaria” included interviews with questionnaires, collection and genotyping of stool, serum and food samples. In addition, certain risk factors were examined in a sample comparison with healthy population using univariable analysis and logistic regression. In total, 135 hepatitis E cases from Bavaria were included in the analysis. Mean age for women was 46 (range 20–74) years and 47.5 (range 20–85) for men. 56 of the cases (41.5%) were asymptomatic. Among the symptomatic cases, both men and women were equally affected with symptoms like fever (16.3%), jaundice (18.8%) and upper abdominal pain (28.2%). 145 human samples (serum, stool) and 6 food samples were collected. 15.9% of the human samples (n = 23) were positive for HEV RNA by reverse-transcription quantitative real-time PCR (RT-qPCR). Identified risk factors significantly associated with hepatitis E were sausage consumption with odds ratio 9.6 (CI 1.3–70.1), fish with OR 2.2 (CI 1.1–4.4) and cat ownership with OR 1.9 (CI 1.3–3.0) in multivariable analyses. Further investigation is needed to confirm the role of fish in HEV transmission. Autochthonous HEV genotype 3 is prevalent in Bavaria and there could be more transmission routes contributing to the spread of HEV than previously known. Undercooked meat, offal, sausages, fish, shellfish and contact with animals and pets are possible sources for infection.

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Hepatitis E Virus Occurrence in Pigs Slaughtered in Italy

Animals ◽

10.3390/ani11020277 ◽

2021 ◽

Vol 11 (2) ◽

pp. 277

Author(s):

Eleonora Chelli ◽

Elisabetta Suffredini ◽

Paola De Santis ◽

Dario De Medici ◽

Santina Di Bella ◽

...

Keyword(s):

Hepatitis E Virus ◽

Phylogenetic Analyses ◽

Hepatitis E ◽

Rt Pcr ◽

High Seroprevalence ◽

Genotype 3 ◽

Sporadic Cases ◽

Wild Boar Meat ◽

Small Clusters ◽

Frequent Exposure

In Europe, foodborne transmission has been clearly associated to sporadic cases and small clusters of hepatitis E in humans linked to the consumption of contaminated pig liver sausages, raw venison, or undercooked wild boar meat. In Europe, zoonotic HEV-genotype 3 strains are widespread in pig farms but little information is available on the prevalence of HEV positive pigs at slaughterhouse. In the present study, the prevalence of HEV-RNA positive pigs was assessed on 585 animals from 4 abattoirs located across Italy. Twenty-one pigs (3.6%) tested positive for HEV in either feces or liver by real-time RT-PCR. In these 21 pigs, eight diaphragm muscles resulted positive for HEV-RNA. Among animals collected in one abattoir, 4 out of 91 plasma tested positive for HEV-RNA. ELISA tests for the detection of total antibodies against HEV showed a high seroprevalence (76.8%), confirming the frequent exposure of pigs to the virus. The phylogenetic analyses conducted on sequences of both ORF1 and ORF2 fragments, shows the circulation of HEV-3c and of a novel unclassified subtype. This study provides information on HEV occurrence in pigs at the slaughterhouse, confirming that muscles are rarely contaminated by HEV-RNA compared to liver, which is the most frequently positive for HEV.

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Hepatitis E Virus in Croatia in the “One-Health” Context

Pathogens ◽

10.3390/pathogens10060699 ◽

2021 ◽

Vol 10 (6) ◽

pp. 699

Author(s):

Anna Mrzljak ◽

Lorena Jemersic ◽

Vladimir Savic ◽

Ivan Balen ◽

Maja Ilic ◽

...

Keyword(s):

Hepatitis E Virus ◽

Current Knowledge ◽

Hepatitis E ◽

Human Case ◽

Interspecies Transmission ◽

Genotype 3 ◽

Chronic Patients ◽

Indirect Contact ◽

The One ◽

Foodborne Infection

Hepatitis E virus (HEV) is the most common cause of viral hepatitis globally. The first human case of autochthonous HEV infection in Croatia was reported in 2012, with the undefined zoonotic transmission of HEV genotype 3. This narrative review comprehensively addresses the current knowledge on the HEV epidemiology in humans and animals in Croatia. Published studies showed the presence of HEV antibodies in different population groups, such as chronic patients, healthcare professionals, voluntary blood donors and professionally exposed and pregnant women. The highest seroprevalence in humans was found in patients on hemodialysis in a study conducted in 2018 (27.9%). Apart from humans, different studies have confirmed the infection in pigs, wild boars and a mouse, indicating the interspecies transmission of HEV due to direct or indirect contact or as a foodborne infection. Continued periodical surveys in humans and animals are needed to identify the possible changes in the epidemiology of HEV infections.

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