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.

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.

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.

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.

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.

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.

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.

Hepatitis E Virus (HEV) Spread and Genetic Diversity in Game Animals in Northern Italy.

Hepatitis E virus (HEV) is the causative agent of hepatitis E, an emerging public health infection which has an increasing incidence across Europe. Because of the apparent lack of species barriers, HEV was characterized as a zoonotic agent. Swine are recognized as the main reservoir, but HEV is also found in wild animals such as ungulates, lagomorphs, and bats. Our work aimed at detecting the HEV presence in wild fauna in two hunting areas of Northern Italy (Parma and Sondrio areas) with different environmental and anthropic characteristics to investigate its possible role as reservoir. Liver samples were collected from wild boars, red deer, roe deer and chamois, and viral identification was carried out by One-Step RT Real-time PCR. Positive samples were genotyped, and phylogenetic analysis was performed. The virus was found only in the wild boar population, with different prevalence and subtypes in the two areas (14% HEV3a and 1.2% close to HEV3f in Parma and Sondrio, respectively). Wild ruminants seem otherwise to pose a marginal risk. Given the high pig farm density in the Parma area, and expansion of the wild boar population, continuous monitoring of the strains circulating in wildlife is crucial.

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.

Stability of hepatitis E virus at high hydrostatic pressure processing.

Hepatitis E virus (HEV) is the causative agent of acute and chronic hepatitis in humans. The zoonotic HEV genotype 3 is the main genotype in Europe. The foodborne transmission via consumption of meat and meat products prepared from infected pigs or wild boars is considered the major transmission route of this genotype. High hydrostatic pressure processing (HPP) is a technique, which can be used for inactivation of pathogens in food. Here, preparations of a cell culture-adapted HEV genotype 3 strain in phosphate-buffered saline (PBS) were subjected to HPP and the remaining infectivity was titrated in cell culture by counting fluorescent foci of replicating virus. A gradual decrease in infectivity was found by application of 100 to 600 MPa for 2 min. At 20 °C, infectivity reduction of 0.5 log10 at 200 MPa and 1 log10 at 400 MPa were observed. Slightly higher infectivity reduction of 1 log10 at 200 MPa and 2 log10 at 400 MPa were found by application of the pressure at 4 °C. At both temperatures, the virus was nearly completely inactivated (>3.5 log10 infectivity decrease) at 600 MPa; however, low amounts of remaining infectious virus were observed in one of three replicates in both cases. Transmission electron microscopy showed disassembled and distorted particles in the preparations treated with 600 MPa. Time-course experiments at 400 MPa showed a continuous decline of infectivity from 30 s to 10 min, leading to a 2 log10 infectivity decrease at 20 °C and to a 2.5 log10 infectivity decrease at 4 °C for a 10 min pressure application each. Predictive models for inactivation of HEV by HPP were generated on the basis of the generated data. The results show that HPP treatment can reduce HEV infectivity, which is mainly dependent on pressure height and duration of the HPP treatment. Compared to other viruses, HEV appears to be relatively stable against HPP and high pressure/long time combinations have to be applied for significant reduction of infectivity.

A systematic review of the epidemiology of Hepatitis E virus infection in South - Eastern Asia.

Hepatitis E virus (HEV) infection is an emerging zoonotic viral disease, with an increasingly international public health challenge. Despite the concerns that the global disease burden may be underestimated. Therefore, evaluation of the disease epidemiology in South - eastern Asia through a systematic review will assist in unraveling the burden of the disease in the subregion. A priori protocol was prepared for the systematic review and followed by a literature search involving five electronic databases. Identified publications were screened for high quality studies and the elimination of bias and relevant data extracted. A total of 4157 citations were captured, and only 35 were included in the review. A wide range of HEV seroprevalence was recorded from 2% (urban blood donors in Malaysia) to 77.7% (lowland communities in Lao PDR). Sporadic HEV infection and epidemics were also detected in the subregion. Indicating hyperendemicity of the disease in South - eastern Asia.

Foodborne transmission of hepatitis A and hepatitis E viruses: A literature review.

Foodborne viruses have been recognized as a growing concern to the food industry and a serious public health problem. Hepatitis A virus (HAV) is responsible for the majority of viral outbreaks of food origin worldwide, while hepatitis E virus (HEV) has also been gaining prominence as a foodborne viral agent in the last years, due to its zoonotic transmission through the consumption of uncooked or undercooked infected meat or derivatives. However, there is a lack of scientific reports that gather all the updated information about HAV and HEV as foodborne viruses. A search of all scientific articles about HAV and HEV in food until March 2020 was carried out, using the keywords "HAV", "HEV", "foodborne", "outbreak" and "detection in food". Foodborne outbreaks due to HAV have been reported since 1956, mainly in the USA, and in Europe in recent years, where the number of outbreaks has been increasing throughout time, and nowadays it has become the continent with the highest foodborne HAV outbreak report. Investigation and detection of HAV in food is more recent, and the first detections were performed in the 1990s decade, most of them carried out on seafood, first, and frozen food, later. On the other hand, HEV has been mainly looked for and detected in food derived from reservoir animals, such as meat, sausages and pate of pigs and wild boars. For this virus, only isolated cases and small outbreaks of foodborne transmission have been recorded, most of them in industrialized countries, due to HEV genotype 3 or 4. Virus detection in food matrices requires special processing of the food matrix, followed by RNA detection by molecular techniques. For HAV, a real-time PCR has been agreed as the standard method for virus detection in food; in the case of HEV, a consensus assay for its detection in food has not been reached yet. Our investigation shows that there is still little data about HAV and HEV prevalence and frequency of contamination in food, prevalent viral strains, and sources of contamination, mainly in developing countries, where there is no research and legislation in this regard. Studies on these issues are needed to get a better understanding of foodborne viruses, their maintenance and their potential to cause diseases.

Transmission of Rat Hepatitis E Virus Infection to Humans in Hong Kong: A Clinical and Epidemiological Analysis.

BACKGROUND AND AIMS: Hepatitis E virus (HEV) variants causing human infection predominantly belong to HEV species A (HEV-A). HEV species C genotype 1 (HEV-C1) circulates in rats and is highly divergent from HEV-A. It was previously considered unable to infect humans, but the first case of human HEV-C1 infection was recently discovered in Hong Kong. The aim of this study is to further describe the features of this zoonosis in Hong Kong. APPROACH AND RESULTS: We conducted a territory-wide prospective screening study for HEV-C1 infection over a 31-month period. Blood samples from 2,860 patients with abnormal liver function (n = 2,201) or immunosuppressive conditions (n = 659) were screened for HEV-C1 RNA. In addition, 186 captured commensal rats were screened for HEV-C1 RNA. Sequences of human-derived and rat-derived HEV-C1 isolates were compared. Epidemiological and clinical features of HEV-C1 infection were analyzed. HEV-C1 RNA was detected in 6/2,201 (0.27%) patients with hepatitis and 1/659 (0.15%) immunocompromised persons. Including the previously reported case, eight HEV-C1 infections were identified, including five in patients who were immunosuppressed. Three patients had acute hepatitis, four had persistent hepatitis, and one had subclinical infection without hepatitis. One patient died of meningoencephalitis, and HEV-C1 was detected in cerebrospinal fluid. HEV-C1 hepatitis was generally milder than HEV-A hepatitis. HEV-C1 RNA was detected in 7/186 (3.76%) rats. One HEV-C1 isolate obtained from a rat captured near the residences of patients was closely related to the major outbreak strain. CONCLUSIONS: HEV-C1 is a cause of hepatitis E in humans in Hong Kong. Immunosuppressed individuals are susceptible to persistent HEV-C1 infection and extrahepatic manifestations. Subclinical HEV-C1 infection threatens blood safety. Tests for HEV-C1 are required in clinical laboratories.

Prevalence of hepatitis E virus in children from Northeast of Argentina.

The aim of this study was to assess the prevalence of hepatitis E virus (HEV) in a young population from the Northeast region of Argentina. Four hundred and twelve patients under 18 years old, from rural areas of Chaco Province, were tested for anti-HEV immunoglobulin G (IgG) using enzyme-linked immunosorbent assay. Anti-HEV IgG antibodies were detected in 7 out of 412 patients, accounting for an overall 1.7% prevalence. HEV infection in developing countries is associated to lack of clean drinking water. Consequently, the seroprevalence observed in children in rural areas of Chaco, Argentina, where the access to tap water is less than 15%, was unexpectedly low.