Cross-species transmission and histopathological variation in specific-pathogen-free minipigs infected with different hepatitis E virus strains.

Hepatitis E virus (HEV) is a major cause of viral hepatitis worldwide. Pigs are the natural host of HEV genotype 3 and the main reservoir of HEV. As the host range of HEV genotype 3 expands, the possibility that HEV from various species can be transmitted to humans via pigs is increasing. We investigated the potential cross-species transmission of HEV by infecting minipigs with swine HEV (swHEV), rabbit HEV (rbHEV), and human HEV (huHEV) and examining their histopathological characteristics and distribution in various organs. Fifteen specific-pathogen-free Yucatan minipigs were infected with swHEV, rbHEV, huHEV, or a mock control. In the present study, we analysed faecal shedding, viremia, and serological parameters over a seven-week period. Our results indicated that swHEV exhibited more robust shedding and viremia than non-swHEVs. Only swHEV affected the serological parameters, suggesting strain-specific differences. Histopathological examination revealed distinct patterns in the liver, pancreas, intestine, and lymphoid tissues after infection with each HEV strain. Notably, all three HEVs induced histopathological changes in the pancreas, supporting the association of HEVs with acute pancreatitis. Our results also identified skeletal muscle as a site of HEV antigen presence, suggesting a potential link to myositis. In conclusion, this study provides valuable insights into the infection dynamics of different HEV strains in minipigs, emphasizing the strain-specific variations in virological, serological, and histological parameters. The observed differences in infection kinetics and tissue tropism will contribute to our understanding of HEV pathogenesis and the potential for cross-species transmission.

Hepatitis E Virus in the United States and Canada: Is It Time to Consider Blood Donation Screening?

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the world and can lead to severe complications in immunocompromised individuals. HEV is primarily transmitted through eating pork, which has led to an increased in anti-HEV IgG seropositivity in the general population of Europe in particular. However, it can also be transmitted intravenously, such as through transfusions. The growing evidence of HEV contamination of blood products and documented cases of transmission have given rise to practice changes and blood product screening of HEV in many European countries. This review covers the abundant European literature and focuses on the most recent data pertaining to the prevalence of HEV RNA positivity and IgG seropositivity in the North American general population and in blood products from Canada and the United States. Currently, Health Canada and the Food and Drug Administration do not require testing of HEV in blood products. For this reason, awareness among blood product prescribers about the possibility of HEV transmission through blood products is crucial. However, we also demonstrate that the province of Quebec has a prevalence of anti-HEV and HEV RNA positivity similar to some European countries. In light of this, we believe that HEV RNA blood donation screening be reevaluated with the availability of more cost-effective assays.

Hepatitis E Virus: What More Do We Need to Know?

Hepatitis E virus (HEV) infection is typically a self-limiting, acute illness that spreads through the gastrointestinal tract but replicates in the liver. However, chronic infections are possible in immunocompromised individuals. The HEV virion has two shapes: exosome-like membrane-associated quasi-enveloped virions (eHEV) found in circulating blood or in the supernatant of infected cell cultures and non-enveloped virions ("naked") found in infected hosts' feces and bile to mediate inter-host transmission. Although HEV is mainly spread via enteric routes, it is unclear how it penetrates the gut wall to reach the portal bloodstream. Both virion types are infectious, but they infect cells in different ways. To develop personalized treatment/prevention strategies and reduce HEV impact on public health, it is necessary to decipher the entry mechanism for both virion types using robust cell culture and animal models. The contemporary knowledge of the cell entry mechanism for these two HEV virions as possible therapeutic target candidates is summarized in this narrative review.

The Full-Genome Analysis and Generation of an Infectious cDNA Clone of a Genotype 6 Hepatitis E Virus Variant Obtained from a Japanese Wild Boar: In Vitro Cultivation in Human Cell Lines.

Hepatitis E virus (HEV) can cause self-limiting acute and chronic hepatitis infections, particularly in immunocompromised individuals. In developing countries, HEV is mainly transmitted via drinking contaminated water, whereas zoonotic transmission dominates the route of infection in developed countries, including Japan. Pigs are an important reservoir for HEV infection. Wild boars, which share the same genus and species as domestic pigs, are also an HEV reservoir. During our nationwide study of HEV infection in wild boar populations in Japan, a genotype 6 (HEV-6) strain, wbJHG_23, was isolated in Hyogo Prefecture in 2023. The genomic length was 7244 nucleotides, excluding the poly(A) tract. The wbJHG_23 strain exhibited the highest nucleotide identity throughout its genome with two previously reported HEV-6 strains (80.3-80.9%). Conversely, it displayed lower similarity (73.3-78.1%) with the HEV-1-5, HEV-7, and HEV-8 strains, indicating that, although closely related, the wbJHG_23 strain differs significantly from the reported HEV-6 strains and might represent a novel subtype. The wbJHG_23 strain successfully infected the human-derived cancer cell lines, PLC/PRF/5 and A549 1-1H8 cells, suggesting that HEV-6 has the potential for zoonotic infection. An infectious cDNA clone was constructed using a reverse genetics system, and a cell culture system supporting the efficient propagation of the HEV-6 strain was established, providing important tools for further studies on this genotype. Using this cell culture system, we evaluated the sensitivity of the wbJHG_23 strain to ribavirin treatment. Its good response to this treatment suggested that it could be used to treat human infections caused by HEV-6.

The question of screening organ donors for hepatitis e virus: a case report of transmission by kidney transplantation in France and a review of the literature.

BACKGROUND: Hepatitis E is a potentially serious infection in organ recipients, with an estimated two-thirds of cases becoming chronic, and with a subsequent risk of cirrhosis and death. In Europe, transmission occurs most often through the consumption of raw or undercooked pork, more rarely through blood transfusion, but also after solid organ transplantation. Here we describe a case of Hepatitis E virus (HEV) infection transmitted following kidney transplantation and review the literature describing cases of HEV infection transmitted by solid organ transplantation. CASE PRESENTATION: Three weeks after kidney transplantation, the patient presented with an isolated minimal increase in GGT and hepatic cytolysis 6 months later, leading to the diagnosis of genotype 3c hepatitis E, with a plasma viral load of 6.5 log10IU/mL. In retrospect, HEV RNA was detected in the patient's serum from the onset of hepatitis, and in the donor's serum on the day of donation, with 100% identity between the viral sequences, confirming donor-derived HEV infection. Hepatitis E had a chronic course, was treated by ribavirin, and relapsed 10 months after the end of treatment. DISCUSSION: Seven cases of transmission of HEV by solid organ transplantation have been described since 2012 without systematic screening for donors, all diagnosed at the chronic infection stage; two patients died. HEV organ donor transmission may be underestimated and there is insufficient focus on immunocompromised patients in whom mild liver function test impairment is potentially related to hepatitis E. However, since HEV infection is potentially severe in these patients, and as evidence accumulates, we believe that systematic screening of organ donors should be implemented for deceased and living donors regardless of liver function abnormalities, as is already the case in the UK and Spain. In January 2024, the French regulatory agency of transplantation has implemented mandatory screening of organ donors for HEV RNA.

Hepatitis E Virus in Domestic Ruminants and Virus Excretion in Milk-A Potential Source of Zoonotic HEV Infection.

The hepatitis E virus is a serious health concern worldwide, with 20 million cases each year. Growing numbers of autochthonous HEV infections in industrialized nations are brought on via the zoonotic transmission of HEV genotypes 3 and 4. Pigs and wild boars are the main animal reservoirs of HEV and play the primary role in HEV transmission. Consumption of raw or undercooked pork meat and close contact with infected animals are the most common causes of hepatitis E infection in industrialized countries. However, during the past few years, mounting data describing HEV distribution has led experts to believe that additional animals, particularly domestic ruminant species (cow, goat, sheep, deer, buffalo, and yak), may also play a role in the spreading of HEV. Up to now, there have not been enough studies focused on HEV infections associated with animal milk and the impact that they could have on the epidemiology of HEV. This critical analysis discusses the role of domestic ruminants in zoonotic HEV transmissions. More specifically, we focus on concerns related to milk safety, the role of mixed farming in cross-species HEV infections, and what potential consequences these may have on public health.

Prevalence of Acute Hepatitis E Virus Infections in Swiss Blood Donors 2018-2020.

INTRODUCTION: Hepatitis E virus (HEV) genotype 3 is the major cause of acute viral hepatitis in several European countries. It is acquired mainly by ingesting contaminated pork, but has also been reported to be transmitted through blood transfusion. Although most HEV infections, including those via blood products, are usually self-limiting, they may become chronic in immunocompromised persons. It is thus essential to identify HEV-infected blood donations to prevent transmission to vulnerable recipients. AIMS: Prior to the decision whether to introduce HEV RNA screening for all Swiss blood donations, a 2-year nationwide prevalence study was conducted. METHODS: All blood donations were screened in pools of 12-24 samples at five regional blood donation services, and HEV RNA-positive pools were subsequently resolved to the individual donation index donation (X). The viral load, HEV IgG and IgM serology, and HEV genotype were determined. Follow-up investigations were conducted on future control donations (X + 1) and previous archived donations of the donor (X - 1) where available. RESULTS: Between October 2018 and September 2020, 541,349 blood donations were screened and 125 confirmed positive donations were identified (prevalence 1:4331 donations). At the time of blood donation, the HEV RNA-positive individuals were symptom-free. The median viral load was 554 IU/mL (range: 2.01-2,500,000 IU/mL). Men (88; 70%) were more frequently infected than women (37; 30%), as compared with the sex distribution in the Swiss donor population (57% male/43% female, p < 0.01). Of the 106 genotyped cases (85%), all belonged to genotype 3. Two HEV sub-genotypes predominated; 3h3 (formerly 3s) and 3c. The remaining sub-genotypes are all known to circulate in Europe. Five 3ra genotypes were identified, this being a variant associated with rabbits. In total, 85 (68%) X donations were negative for HEV IgM and IgG. The remaining 40 (32%) were positive for HEV IgG and/or IgM, and consistent with an active infection. We found no markers of previous HEV in 87 of the 89 available and analyzed archive samples (X - 1). Two donors were HEV IgG-positive in the X - 1 donation suggesting insufficient immunity to prevent HEV reinfection. Time of collection of the 90 (72%) analyzed X + 1 donations varied between 2.9 and 101.9 weeks (median of 35 weeks) after X donation. As expected, none of those tested were positive for HEV RNA. Most donors (89; 99%) were positive for anti-HEV lgG/lgM (i.e., seroconversion). HEV lgM-positivity (23; 26%) indicates an often-long persistence of lgM antibodies post-HEV infection. CONCLUSION: The data collected during the first year of the study provided the basis for the decision to establish mandatory HEV RNA universal screening of all Swiss blood donations in minipools, a vital step in providing safer blood for all recipients, especially those who are immunosuppressed.

Infectious hepatitis E virus is associated with the mature sperm head.

Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis worldwide. HEV associated pregnancy mortality has been reported as up to 30% in humans. Recent findings suggest HEV may elicit effects directly in the reproductive system with HEV protein found in the testis, viral RNA in semen, and viral replication occurring in placental cell types. Using a natural host model for HEV infection, pigs, we demonstrate infectious HEV within the mature spermatozoa and altered sperm viability from HEV infected pigs. HEV isolated from sperm remained infectious suggesting a potential transmission route via sexual partners. Our findings suggest that HEV should be explored as a possible sexually transmittable disease. Our findings propose that infection routes outside of oral and intravenous infection need to be considered for their potential to contribute to higher mortality in HEV infections when pregnancy is involved and in HEV disease in general.

Hepatitis E Virus Infection in Voluntary Blood Donors in the Russian Federation.

Transfusion-transmitted hepatitis E virus (HEV) infection is an increasing concern in many countries. We investigated the detection rate of HEV viremia in blood donors in Russia. A total of 20,405 regular repetitive voluntary non-renumerated blood donors from two regions (Moscow and Belgorod) were screened for HEV RNA using the cobas® HEV test in mini-pools of six plasma samples. Samples from each reactive pool were tested individually. The average HEV RNA prevalence was 0.024% (95% CI: 0.01-0.05%), or 1 case per 4081 donations. No statistically significant differences in HEV RNA prevalence were observed between the two study regions. The PCR threshold cycle (Ct) values ranged from 25.0 to 40.5 in reactive pools, and from 20.9 to 41.4 in reactive plasma samples when tested individually. The HEV viremic donors had different antibody patterns. Two donor samples were reactive for both anti-HEV IgM and IgG antibodies, one sample was reactive for anti-HEV IgM and negative for anti-HEV IgG, and two samples were seronegative. At follow-up testing 6 months later, on average, four donors available for follow-up had become negative for HEV RNA and positive for anti-HEV IgG. The HEV ORF2 sequence belonging to HEV-3 sub-genotype 3a was obtained from one donor sample. The sequencing failed in the other four samples from viremic donors, presumably due to the low viral load. In conclusion, the HEV RNA detection rate in blood donors in Russia corresponds with data from other European countries, including those that implemented universal donor HEV screening. These data support the implementation of HEV RNA donor screening to reduce the risk of transfusion-transmitted HEV infection in Russia.

An outbreak of hepatitis E virus genotype 4d caused by consuming undercooked pig liver in a nursing home in Zhejiang Province, China.

Hepatitis E infection is typically caused by contaminated water or food. In July and August 2022, an outbreak of hepatitis E was reported in a nursing home in Zhejiang Province, China. Local authorities and workers took immediate actions to confirm the outbreak, investigated the sources of infection and routes of transmission, took measures to terminate the outbreak, and summarized the lessons learned. An epidemiological investigation was conducted on all individuals in the nursing home, including demographic information, clinical symptoms, history of dietary, water intake and contact. Stool and blood samples were collected from these populations for laboratory examinations. The hygiene environment of the nursing home was also investigated. A case-control study was conducted to identify the risk factors for this outbreak. Of the 722 subjects in the nursing home, 77 were diagnosed with hepatitis E, for an attack rate of 10.66 %. Among them, 18 (23.38 %, 18/77) individuals had symptoms such as jaundice, fever, and loss of appetite and were defined as the population with hepatitis E. The average age of people infected with hepatitis E virus (HEV) was 59.96 years and the attack rate of hepatitis E among women (12.02 %, 59/491) was greater than that among men (7.79 %, 18/231). The rate was the highest among caregivers (22.22 %, 32/144) and lowest among logistics personnel (6.25 %, 2/32); however, these differences were not statistically significant (P > 0.05). Laboratory sequencing results indicated that the genotype of this hepatitis E outbreak was 4d. A case-control study showed that consuming pig liver (odds ratio (OR) = 7.50; 95 % confidence interval [CI]: 3.84-16.14, P < 0.001) and consuming raw fruits and vegetables (OR = 5.92; 95 % CI: 1.74-37.13, P = 0.017) were risk factors for this outbreak of Hepatitis E. Moreover, a monitoring video showed that the canteen personnel did not separate raw and cooked foods, and pig livers were cooked for only 2 min and 10 s. Approximately 1 month after the outbreak, an emergency vaccination for HEV was administered. No new cases were reported after two long incubation periods (approximately 4 months). The outbreak of HEV genotype 4d was likely caused by consuming undercooked pig liver, resulting in an attack rate of 10.66 %. This was related to the rapid stir-frying cooking method and the hygiene habit of not separating raw and cooked foods.

Repeated cross-sectional sampling of pigs at slaughter indicates varying age of hepatitis E virus infection within and between pig farms.

Humans can become infected with hepatitis E virus (HEV) by consumption of undercooked pork. To reduce the burden of HEV in humans, mitigation on pig farms is needed. HEV is found on most pig farms globally, yet within-farm seroprevalence estimates vary considerably. Understanding of the underlying variation in infection dynamics within and between farms currently lacks. Therefore, we investigated HEV infection dynamics by sampling 1711 batches of slaughter pigs from 208 Dutch farms over an 8-month period. Four farm types, conventional, organic, and two types with strict focus on biosecurity, were included. Sera were tested individually with an anti-HEV antibody ELISA and pooled per batch with PCR. All farms delivered seropositive pigs to slaughter, yet batches (resembling farm compartments) had varying results. By combining PCR and ELISA results, infection moment and extent per batch could be classified as low transmission, early, intermediate or late. Cluster analysis of batch infection moments per farm resulted in four clusters with distinct infection patterns. Cluster 1 farms delivered almost exclusively PCR negative, ELISA positive batches to slaughter (PCR-ELISA+), indicating relatively early age of HEV infection. Cluster 2 and 3 farms delivered 0.3 and 0.7 of batches with intermediate infection moment (PCR+ELISA+) respectively and only few batches with early infection. Cluster 4 farms delivered low transmission (PCR-ELISA-) and late infection (PCR+ELISA-) batches, demonstrating that those farms can prevent or delay HEV transmission to farm compartments. Farm type partly coincided with cluster assignment, indicating that biosecurity and management are related to age of HEV infection.

Nationwide survey of hepatitis E virus infection among wildlife in Japan.

In Japan, hepatitis E virus (HEV) causes hepatitis in humans through the consumption of raw or undercooked meat, including game meat. In the present study, nationwide surveillance of HEV infection among a total of 5,557 wild animals, including 15 species, was conducted in Japan. The prevalence of anti-HEV antibodies in wild boar was 12.4%, with higher positive rates in big boars (over 50 kg, 18.4%) than in small individuals (less than 30 kg, 5.3%). Furthermore, HEV RNA was more frequently detected in piglets than in older boars. Interestingly, the detection of HEV among wildlife by ELISA and RT-PCR suggested that HEV infection in Sika deer was a very rare event, and that there was no HEV infection among wild animals except for wild boar, Sika deer and Japanese monkeys. In conclusion, wild boar, especially piglets, are at high risk of HEV infection, while other wild animals showed less risk or no risk of HEV transmission.

Risk of transfusion-transmitted hepatitis E virus infection from pool-tested platelets and plasma.

BACKGROUND AND AIMS: Immunocompromised patients are at risk of chronic hepatitis E which can be acquired by blood transfusions. Currently, screening of blood donors (BDs) for HEV RNA with a limit of detection (LOD) of 2,000 IU/ml is required in Germany. However, this may result in up to 440,000 IU of HEV RNA in blood products depending on their plasma volume. We studied the residual risk of transfusion-transmitted (tt) HEV infection when an LOD of 2,000 IU/ml is applied. METHODS: Highly sensitive individual donor testing for HEV RNA on the Grifols Procleix Panther system (LOD 7.89 IU/ml) was performed. HEV loads were quantified by real-time PCR. RESULTS: Of 16,236 donors, 31 (0.19%) were HEV RNA positive. Three BDs had viral loads between 710 and 2,000 IU/ml, which pose a significant risk of tt hepatitis E with any type of blood product. Eight BDs had viral loads of >32 to 710 IU/ml, which pose a risk of tt hepatitis E with platelet or plasma transfusions because of their higher plasma volume compared to red blood cell concentrates. Eight of these 11 potentially infectious BDs were seronegative for HEV, indicating a recent infection. Only 8 of 31 donors had viral loads >2,000 IU/ml that would also have been detected by the required screening procedure and 12 had very low HEV loads (<32 IU/ml). CONCLUSIONS: Screening of BDs with an LOD of 2,000 IU/ml reduced the risk of tt HEV infection by about 73% for red blood cell concentrates but by just 42% for platelet and fresh frozen plasma transfusions. Single donor screening (LOD <32 IU/ml) should lead to an almost 100% risk reduction. LAY SUMMARY: Immunocompromised patients, such as solid organ or hematopoietic stem cell recipients, are at risk of chronic hepatitis E, which can be acquired via blood transfusions. The risk of transfusion-transmitted hepatitis E in these patients may not be sufficiently controlled by (mini-)pool hepatitis E virus RNA screening of blood donors. Single donor screening should be considered to improve the safety of blood products.

Hepatitis E Outbreak in the Central Part of Italy Sustained by Multiple HEV Genotype 3 Strains, June-December 2019.

In European countries, autochthonous acute hepatitis E cases are caused by Hepatitis E Virus (HEV) genotype 3 and are usually observed as sporadic cases. In mid/late September 2019, a hepatitis E outbreak caused by HEV genotype 3 was recognized by detection of identical/highly similar HEV sequences in some hepatitis E cases from two Italian regions, Abruzzo and Lazio, with most cases from this latter region showing a link with Abruzzo. Overall, 47 cases of HEV infection were finally observed with onsets from 8 June 2019 to 6 December 2019; they represent a marked increase as compared with just a few cases in the same period of time in the past years and in the same areas. HEV sequencing was successful in 35 cases. The phylogenetic analysis of the viral sequences showed 30 of them grouped in three distinct molecular clusters, termed A, B, and C: strains in cluster A and B were of subtype 3e and strains in cluster C were of subtype 3f. No strains detected in Abruzzo in the past years clustered with the strains involved in the present outbreak. The outbreak curve showed partially overlapped temporal distribution of the three clusters. Analysis of collected epidemiological data identified pork products as the most likely source of the outbreak. Overall, the findings suggest that the outbreak might have been caused by newly and almost simultaneously introduced strains not previously circulating in this area, which are possibly harbored by pork products or live animals imported from outside Abruzzo. This possibility deserves further studies in this area in order to monitor the circulation of HEV in human cases as well as in pigs and wild boars.

Hepatitis E Virus in People Who Use Crack-Cocaine: A Cross-Sectional Study in a Remote Region of Northern Brazil.

People who use crack-cocaine (PWUCC) have numerous vulnerabilities and pose a challenge to health and social assistance services. The exposure to pathogens and risk situations occur differently according to each individual, region and social group. This study identified the presence, genotypes and factors associated with hepatitis E virus (HEV) exposure among a community-recruited cohort of 437 PWUCC in northern Brazil. Epidemiological information was collected through community-based assessments and interviews. Thereafter, blood and fecal samples were collected and tested for HEV using an immunoenzymatic assay, and the genotype was identified by PCR. Logistic regressions were used to identify the risk factors independently associated with exposure to HEV. In total, 79 (18.1%) PWUCC were exposed to HEV: 73 (16.7%) for IgG and six for IgG + IgM. HEV RNA was detected in six fecal samples and in two blood samples from PWUCC with IgM + IgG. Subtype 3c was identified in all of the samples. The factors associated with exposure to HEV were low monthly income, unstable housing (e.g., homelessness), crack-cocaine use ≥40 months, and the shared use of crack-cocaine equipment. The current study provides unique initial insights into HEV status and risk factors among PWUCC in a remote area in Brazil, with diverse implications for urgently improved diagnosis, prevention, and treatment intervention needs.

Mechanism of Cross-Species Transmission, Adaptive Evolution and Pathogenesis of Hepatitis E Virus.

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.

Feasibility of controlling hepatitis E in Jiangsu Province, China: a modelling study.

BACKGROUND: Hepatitis E, an acute zoonotic disease caused by the hepatitis E virus (HEV), has a relatively high burden in developing countries. The current research model on hepatitis E mainly uses experimental animal models (such as pigs, chickens, and rabbits) to explain the transmission of HEV. Few studies have developed a multi-host and multi-route transmission dynamic model (MHMRTDM) to explore the transmission feature of HEV. Hence, this study aimed to explore its transmission and evaluate the effectiveness of intervention using the dataset of Jiangsu Province. METHODS: We developed a dataset comprising all reported HEV cases in Jiangsu Province from 2005 to 2018. The MHMRTDM was developed according to the natural history of HEV cases among humans and pigs and the multi-transmission routes such as person-to-person, pig-to-person, and environment-to-person. We estimated the key parameter of the transmission using the principle of least root mean square to fit the curve of the MHMRTDM to the reported data. We developed models with single or combined countermeasures to assess the effectiveness of interventions, which include vaccination, shortening the infectious period, and cutting transmission routes. The indicator, total attack rate (TAR), was adopted to assess the effectiveness. RESULTS: From 2005 to 2018, 44 923 hepatitis E cases were reported in Jiangsu Province. The model fits the data well (R2 = 0.655, P < 0.001). The incidence of the disease in Jiangsu Province and its cities peaks are around March; however, transmissibility of the disease peaks in December and January. The model showed that the most effective intervention was interrupting the pig-to-person route during the incidence trough of September, thereby reducing the TAR by 98.11%, followed by vaccination (reducing the TAR by 76.25% when the vaccination coefficient is 100%) and shortening the infectious period (reducing the TAR by 50.05% when the infectious period is shortened to 15 days). CONCLUSIONS: HEV could be controlled by interrupting the pig-to-person route, shortening the infectious period, and vaccination. Among these interventions, the most effective was interrupting the pig-to-person route.

The Foodborne Transmission of Hepatitis E Virus to Humans.

Globally, Hepatitis E virus (HEV) causes over 20 million cases worldwide. HEV is an emerging and endemic pathogen within economically developed countries, chiefly resulting from infections with genotype 3 (G3) HEV. G3 HEV is known to be a zoonotic pathogen, with a broad host range. The primary source of HEV within more economically developed countries is considered to be pigs, and consumption of pork products is a significant risk factor and known transmission route for the virus to humans. However, other foods have also been implicated in the transmission of HEV to humans. This review consolidates the information available regarding transmission of HEV and looks to identify gaps where further research is required to better understand how HEV is transmitted to humans through food.

An outbreak of hepatitis E in Yavatmal, India, 2019.

Hepatitis E, a public health concern in developing countries, frequently presents in epidemic, as well as in sporadic forms. This study investigated an outbreak of viral hepatitis at Yavatmal, Maharashtra, India in March 2019. Blood samples from 10 patients were received at Indian Council of Medical Research-National Institute of Virology, Pune to test for the presence of enterically transmitted hepatitis viruses. Subsequently, 49 suspected cases were screened for anti-hepatitis E virus (HEV)/hepatitis A virus (HAV) immunoglobulin M and immunoglobulin G (IgG) antibodies, alanine amino-transferase levels and HEV RNA. Water samples were screened for HEV and HAV RNA followed by phylogenetic analysis. Overall 32 of 49 (65.3%) suspected cases had recent acute HEV infection, while dual infection with HAV was noted in one case (2.04%). Forty-eight of 49 suspected cases were positive for anti-HAV IgG antibodies indicative of previously acquired immunity against HAV. Water samples had evidence of HEV contamination as detected by reverse transcription-polymerase chain reaction. Sequencing of HEV RNA from both patients (n = 2) and water samples (n = 5) indicated HEV genotype 1 to be the etiological agent of this outbreak. Serological and molecular evidence confirmed HEV as the etiology. Mixing of contaminated drain water with the domestic water supply may have triggered this outbreak. Subsequent changing of the defaulted water pipelines and its segregation from drain pipelines by the health authorities resulted in progressive decline of this outbreak. Despite the limitations, periodic surveillance of HEV exposure pattern and reporting of small outbreaks would supplement to the global disease burden data of hepatitis E.