High circulation of hepatitis E virus (HEV) in pigs from the central region of Argentina without evidence of virus occurrence in pork meat and derived products.

Hepatitis E virus (HEV) is an emerging cause of viral hepatitis and pigs are considered a reservoir for the virus. HEV genotype 3 (HEV-3) has been reported in pigs, environmental matrices, and sporadic human cases in Argentina. We aimed to investigate HEV circulation in pigs from central Argentina and to assess the virus presence in pork meat and food products. Four types of samples obtained or derived from pigs collected in Córdoba province (Argentina) between 2019 and 2022, were tested: 276 serum samples were analyzed for anti-HEV antibody detection; stool (n = 20), pork meat (n = 71), and salami (n = 76) samples were studied for RNA-HEV detection, followed by sequencing and phylogenetic analyses. The positivity rate for anti-HEV antibodies was 80.1% (221/276). Eleven fecal samples (11/20) tested positive for RNA-HEV, from animals under 120 days of age. Three samples could be sequenced, and phylogenetic analyses revealed that they belonged to HEV-3 clade abchijklm, clustering close to strains previously detected in wastewater from Córdoba. None of the muscle meat or salami samples tested positive. A high HEV circulation in pigs was found, showing that these animals may play a significant role in the viral maintenance in the region, becoming a potential risk to the exposed population. Despite not detecting RNA-HEV in pork meat and salami in our study, we cannot rule out the possibility of foodborne transmission in Córdoba province.

Hepatitis A virus monitoring in wastewater: A complementary tool to clinical surveillance.

Monitoring wastewater is an effective tool for tracking information on trends of enteric viral dissemination. This study aimed to perform molecular detection and genetic characterization of HAV in wastewater and to correlate the results with those obtained from clinical surveillance. Wastewater samples (n=811) of the second most populous city in Argentina were collected from the main wastewater treatment plant (BG-WWTP, n=261), and at 7 local neighborhood collector sewers (LNCS, n=550) during 2017-2022. Clinical samples of acute hepatitis A cases (HA, n=54) were also analyzed. HAV molecular detection was performed by real time RT-PCR, and genetic characterization by RT-Nested PCR, sequencing and phylogenetic analysis. RNA-HAV was detected in sewage samples throughout the entire period studied, and detection frequencies varied according to the location and year (2.9% - 56.5%). In BG-WWTP, 23% of the samples were RNA-HAV+. The highest detection rates were in 2017 (30.0%), 2018 (41.7%) and 2022 (56.5%), which coincides with the highest number of HA cases reported. Twenty-eight (28) sequences were obtained (from clinical and sewage samples), and all were genotype IA. Two monophyletic clusters were identified: one that grouped clinical and wastewater samples from 2017-2018, and another with specimens from 2022, evidencing that environmental surveillance might constitute a replica of viral circulation in the population. These findings evidence that WBE, in a centralized and decentralized sewage monitoring, might be an effective strategy to track HAV circulation trends over time, contributing to the knowledge of HAV in the new post-vaccination epidemiological scenarios in Argentina and in Latin America.

Hepatitis E virus in blood donors from Argentina: A possible source of viral infection?

BACKGROUND: The hepatitis E virus (HEV) causes acute hepatitis, which can progress to chronicity in immunosuppressed patients. It is transmitted mainly by the fecal-oral or zoonotic routes, but there is current evidence that it can be transmitted by blood transfusions. The objective of the study was to investigate HEV infections in blood donors in Argentina, within the framework of a hemovigilance program. METHODS: A total of 547 samples from Argentinean blood donors, collected in 2016, 2019 and 2020 was studied for IgG and IgM anti-HEV by ELISA (Diapro) and RNA HEV by RT-real time PCR and RT-Nested-PCR. RESULTS: The prevalence of IgG anti-HEV was 3.47% (19/547). No significant differences were registered according to the year studied, sex or age. The presence of RNA HEV was observed in 0.18% (1/547) of the donors studied without serological evidence of infection. CONCLUSIONS: This is the first molecular detection in blood donors from Argentina, showing a molecular prevalence within the range described for RNA-HEV in blood donors from other non-endemic countries, in which immunocompetent RNA-HEV positive donors without serological evidence of infection were identified. The presence of viraemic donors could imply transfusion transmission, which deserves further attention and study.

Rapid screening of SARS-CoV-2 infection: Good performance of nasopharyngeal and Nasal Mid-Turbinate swab for antigen detection among symptomatic and asymptomatic individuals.

Although the nasopharyngeal swab (NPS) is considered the gold standard for the diagnosis of the SARS-CoV-2 infection, the Nasal Mid-Turbinate swab (NMTS) is often used due to its higher tolerance among patients. We compared the diagnostic performance of the NPS and the NMTS for the Panbio™ COVID-19 antigen-detecting rapid diagnostic test (Ag-RDT). Two hundred and forty-three individuals were swabbed three times by healthcare professionals: a NMTS and a NPS specimen for the Ag-RDT and an oropharyngeal swab for real time RT-PCR. Forty-nine participants were RNA-SARS-CoV-2 positive by real time RT-PCR: 45 and 40 were positive by the Ag-RDT with NPS and NMTS, respectively. The overall sensitivity and specificity were 91.8% (95% CI: 83.2-100.0) and 99.5% (95% CI: 98.2-100.0) for Ag-RDT with NPS, and 81.6% (95% CI: 69.8-93.5) and 100.0% (95% CI: 99.7-100.0) for the Ag-RDT with NMTS. The Cohen's kappa index was 0.92 (95% CI: 0.85-0.98). Among asymptomatic individuals, the Ag-RDT with both sampling techniques showed a high sensitivity [100.0% (95% CI: 95.5-100.0) with NPS; 90.9% (95% CI: 69.4-100.0) with NMTS], while the performance of the test decreased in samples with Ct≥ 30 and in patients tested after the first 7 days from symptom onset. Although the NMTS yielded a lower sensitivity compared to NPS, it might be considered a reliable alternative, as it presents greater adherence among patients, enabling scaling of antigen testing strategies, particularly in countries with under-resourced health systems.

Hepatitis E virus infection in a patient with alcohol related chronic liver disease: a case report of acute-on-chronic liver failure.

BACKGROUND: The hepatitis E virus (HEV) infection has been described as a causing factor for acute-on-chronic-liver-failure (ACLF) in patients with underlying chronic liver disease (CLD), such as chronic hepatitis or cirrhosis, which could end in the failure of one or more organs and high short-term mortality. There are scarce data about the association of HEV in patients with chronic liver disorders in South America. CASE PRESENTATION: A 56-year-old hypertensive male with a history of type 2 diabetes was diagnosed with alcohol-related-liver cirrhosis in February 2019. A year later, the patient was admitted to hospital due to fatigue, jaundice and acholia. No evidence of hepatitis A virus, hepatitis B virus, hepatitis C virus, Epstein-Barr virus, herpes zoster virus and cytomegalovirus infections were found. Nevertheless, in February and March, 2020 the patient was positive for HEV-IgM and HEV-IgG, and HEV genotype 3 RNA was detected in sera. Afterwards, he presented grade I hepatic encephalopathy and, therefore, was diagnosed with acute hepatitis E-on-chronic liver disease. The patient reported a recent travel to the Argentine coast, where he consumed seafood. Besides, he reveled to have consumed pork meat and had no history of blood transfusion. CONCLUSION: This report describes a unique case of hepatitis E virus infection in a patient with alcohol-related cirrhosis. This is the first report of a patient with HEV-related ACLF in Argentina and it invokes the importance of HEV surveillance and treatment among patients with CLD, such as alcohol-related cirrhosis.

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.

Hepatitis E virus infection in pregnant women, Argentina.

BACKGROUND: Hepatitis E virus (HEV) infection is an important cause of acute hepatitis worldwide. In pregnant women, HEV can cause more severe symptoms, with high rates of fatal hepatic failure in endemic countries. However, HEV prevalence and circulation among pregnant women from South America is almost unknown. We aimed to investigate HEV infection in pregnant women for the first time in Argentina. METHODS: IgG and IgM anti-HEV antibodies and RNA-HEV were investigated (by ELISA assays and RT-Nested-PCR, respectively) in 202 serum samples from pregnant women collected in the central region of Argentina between 2015 and 2017. A control group of 155 non-pregnant women was included (year 2018). RESULTS: The IgG anti-HEV positivity rate was 8.4% (17/202), higher than the 2.6% (4/155) obtained for the non-pregnant women control group, and showing association between pregnancy and HEV infection (p = 0.023, OR = 3.5, CI95% = 1.1-10.5). Women younger than 25 years old presented higher levels of antibodies, and there were no differences in the prevalences between trimesters of pregnancy. Two samples were reactive for IgM anti-HEV, showing recent infections, although no symptoms were registered in these patients. All samples were negative for RNA-HEV amplification. CONCLUSIONS: HEV produces infections in pregnant women from Argentina, alerting health teams to consider it as a possible cause of liver disease.

Unexpected high seroprevalence of hepatitis E virus in patients with alcohol-related cirrhosis.

INTRODUCTION: Little is known about hepatitis E virus (HEV) infection in patients with cirrhosis. The aim of the present study was to describe the frequency of HEV infection and associated risk factors in patients with cirrhosis from Argentina. MATERIALS AND METHODS: We evaluated HEV seroprevalence (IgG anti-HEV) and acute infections (IgM and RNA) in patients with cirrhosis (n = 140) vs. healthy controls (n = 300). Additionally, we compared the same outcomes in individuals with alcohol-related cirrhosis (n = 43) vs. patients with alcohol use disorder (without cirrhosis, n = 72). RESULTS: The overall HEV seroprevalence in the cohort of subjects with cirrhosis was 25% (35/140), compared to 4% in the healthy control group [12/300; OR = 8; (95% CI = 4-15.99); p<0.05]. HEV seropositivity was significantly higher in alcohol-related cirrhosis compared to other causes of cirrhosis [39.5% vs. 12.4%; OR = 4.71; (95% CI = 1.9-11.6); p<0.05] and to healthy controls [OR = 15.7; (95% CI = 6.8-36.4); p = 0.0001]. The HEV seroprevalence in alcoholic-related cirrhosis vs. with alcohol use disorder was 39.5% vs. 12.5% [OR = 4.58; (95% CI = 1.81-11.58); p<0.001]. CONCLUSION: We found a high seroprevalence of HEV in patients with cirrhosis and in individuals with alcohol use disorder. The simultaneous presence of both factors (cirrhosis + alcohol) showed more association to HEV infection. Larger studies with prospective follow up are needed to further clarify this interaction.

Hepatitis A outbreak affecting men who have sex with men (MSM) in central Argentina, occurred in July 2017-April 2018, later than the European outbreak.

BACKGROUND: During June-2016-May-2017, several outbreaks of HA were recorded in Europe, especially described in MSM. In our area since July-2017, an increase of hepatitis A (HA) notification was reported. OBJECTIVE: In order to understand the unusual increase of cases occurred in the central region of Argentina, the aim of this study was to describe, characterize and contextualize epidemiologically the HA outbreak occurred this area, until April2018. STUDY DESIGN: HA cases (positive anti-HAV IgM) obtained from the calendar week 29/2017 in which the first case of MSM was recognized were included in our study. HAV RNA detection and molecular characterization was performed from serum samples and/or stool by RT - PCR of VP1/2A genomic region (360bp). RESULTS: Of the 32 cases notified, 87.5% of them were unvaccinated men and 69.6% were MSM (mean age 31.9 years). All MSM associated HAV sequences were genotyped as IA, and clustered with the VRD 521-2016 strain, responsible of causing outbreaks mostly in MSM in Europe since mid-2016. CONCLUSION: As a consequence of the implementation of immunization in children, and the improvement in socio-economic, hygienic and sanitation factors, young adults are becoming increasingly susceptible to HAV infections. Here we add evidence in South America to the HA outbreaks described worldwide among young MSM, demonstrating the need to reinforce official policy of vaccination, in this group and adjust epidemiological surveillance, catch-up vaccination for adolescents, young adults and immunosuppressed patients.

Hepatitis E virus in South America: The current scenario.

Hepatitis E virus (HEV) is one of the most frequent causes of acute viral hepatitis of enteric transmission worldwide. In South America the overall epidemiology has been little studied, and the burden of the disease remains largely unknown. A research of all scientific articles about HEV circulation in South America until November 2017 was carried out. Human seroprevalences of HEV varied according to the studied population: blood donors presented prevalence rates ranging from 1.8% to 9.8%, while reports from HIV-infected individuals, transplant recipients and patients on hemodialysis showed higher prevalence rates. Only 2 cases of chronic hepatitis in solid-organ transplant patients from Argentina and Brazil have been described. Detection of HEV in the swine population is widely prevalent in the region. Anti-HEV antibodies have also been recently documented in wild boars from Uruguay. Although scarce, studies focused on environmental and food HEV detection have shown viral presence in these kind of samples, highlighting possible transmission sources of HEV in the continent. HEV genotype 3 was the most frequently detected in the region, with HEV genotype 1 detected only in Venezuela and Uruguay. HEV is widely distributed throughout South America, producing sporadic cases of acute hepatitis, but as a possible agent of chronic hepatitis. Finding the virus in humans, animals, environmental samples and food, show that it can be transmitted through many sources, alerting local governments and health systems to improve diagnosis and for the implementation of preventive measures.