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 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.

Phylogeography and evolutionary history of hepatitis E virus genotype 3 in Argentina.

BACKGROUND: Few studies about the evolutionary history of the hepatitis E virus (HEV) have been conducted. The aim of our work was to investigate and make inferences about the origin and routes of dispersion of HEV-3 in Argentina. METHODS: Phylogenetic, coalescent and phylogeographic analyses were performed using a 322-bp ORF2 genomic fragment of all HEV-3 sequences with known date and place of isolation published at GenBank until May 2018 (n=926), including 16 Argentinian sequences (isolated from pigs, water and humans). RESULTS: Phylogenetic analysis revealed two clades within HEV-3: abchij and efg. All Argentinian samples were grouped intermingled within clade 3abchij. The coalescent analysis showed that the most recent common ancestor for the clade 3abchij would have existed around the year 1967 (95% highest posterior density (HPD): 1963-1970). The estimated substitution rate was 1.01×10-2 (95%HPD: 9.3×10-3-1.09×10-2) substitutions/site/y, comparable with the rate previously described. The phylogeographic approach revealed a correspondence between phylogeny and place of origin for Argentinian samples, suggesting many HEV introductions in the country, probably from Europe and Japan. CONCLUSIONS: This is the first evolutionary inference of HEV-3 that includes Argentinian strains, showing the circulation of many HEV-3 subtypes, obtained from different sources and places, with recent diversification processes. ACCESSION NUMBERS: [KX812460], [KX812461], [KX812462], [KX812465], [KX812466], [KX812467], [KX812468], [KX812469].

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.

New pieces in the transmission cycle of the hepatitis E virus in South America: first viral detection in wild boars from Argentina.

BACKGROUND: The hepatitis E virus (HEV) causes hepatitis worldwide. In Europe, wild boars are known to be viral reservoirs and sources of infection. In South America, there is a lack of information about HEV in these animals. METHODS: A total of 102 wild boar serum samples from Argentina (2014-2017) were studied for serological and molecular HEV detection. RESULTS: We obtained a seroprevalence of 19.6%, similar to that recently described in Uruguay (the only antecedent in South America). HEV ribonucleic acid (RNA) was amplified in two anti-HEV-positive samples. CONCLUSIONS: This is the first report of HEV circulation in wild boars from Argentina, adding evidence to the findings obtained in Uruguay indicating that wild boars could be viral reservoirs in South America.

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.

Environmental hepatitis E virus detection supported by serological evidence in the northwest of Argentina.

Background: Hepatitis E virus (HEV) is an emergent cause of acute hepatitis worldwide. Water contamination is a possible source of viral infection. In South America, particularly in Argentina, little is known about environmental HEV circulation, including recreational water. The aim of this work was to provide evidence of current environmental and human circulation of HEV in northern Argentina. Methods: Molecular detection of HEV in water samples from the Arias-Arenales River in the city of Salta by nested polymerase chain reaction (ORF2 region) and anti-HEV immunoglobulin G (IgG) and IgM detection in the general population by enzyme-linked immunosorbent assay was carried out. Results: HEV RNA was detected in 1.6% (3/189) of the environmental samples. All sequences belonged to HEV genotype 3 and were very similar to those previously detected in the country. The prevalence of IgG anti-HEV was 9% (13/143) and three samples were positive for specific IgM. Conclusions: Circulation of HEV in the northwest of Argentina was demonstrated for the first time, showing viral presence in environmental samples and infections in people who attended health care centres for routine control. These findings show that recreational waters are a possible source of virus and highlight the need to carry out HEV detection when a case of hepatitis occurs.

Increased Hepatitis E Virus Seroprevalence Correlates with Lower CD4+ Cell Counts in HIV-Infected Persons in Argentina.

Hepatitis E virus (HEV) is a single-stranded RNA virus that can cause hepatitis in an epidemic fashion. HEV usually causes asymptomatic or limited acute infections in immunocompetent individuals, whereas in immunosuppressed individuals such as transplant recipients, HEV can cause chronic infections. The risks and outcomes of HEV co-infection in patients infected with human immunodeficiency virus (HIV) are poorly characterized. We used a third generation immunoassay to measure serum IgG antibodies specific for HEV in 204 HIV-infected individuals from Argentina and a control group of 433 HIV-negative individuals. We found 15 of 204 (7.3%, 95%CI 3.74-10.96%) individuals in the HIV-positive group to have positive HEV IgG levels suggestive of previous infection, compared to 19 of 433 (4.4%, 95% CI 2.5-6.3%) individuals in the HIV-negative control group (p = 0.12). Among HIV-positive individuals, those with HEV seropositivity had lower CD4 counts compared to those that were HEV seronegative (average CD4 count of 234 vs 422 mm3, p = 0.01), indicating that patients with lower CD4 counts were more likely to be HEV IgG positive. Moreover, HEV seropositivity in patients with CD4 counts <200 mm3 was 16%, compared to 4.5% in those with CD4 counts >200 mm3 (p = 0.012). We found a positive PCR result for HEV in one individual. Our study found that increased seroprevalence of HEV IgG correlated with lower CD4 counts in HIV-infected patients in Argentina.

First detection of hepatitis E virus in Central Argentina: environmental and serological survey.

BACKGROUND: The hepatitis E virus (HEV) is an emergent causative agent of acute hepatitis worldwide, transmitted by fecal-oral route. In Argentina it is considered rare, so differential laboratory testing is not routinely performed. Besides, in Argentina's central area epidemiological and molecular characteristics of HEV are still unknown. OBJECTIVES: Provide evidence of local circulation of HEV by molecular detection on environmental samples and by serological survey in healthy adult population of Córdoba city, Argentina. STUDY DESIGN: Environmental surveillance was conducted in river and sewage samples collected between 2007 and 2009-2011. Viral detection was performed by RT-Nested PCR of ORF-1 and ORF-2 partial regions. Anti-HEV IgG was determined by EIA in 433 serum samples collected between 2009 and 2010. RESULTS: HEV was detected in 6.3% of raw sewage samples and in 3.2% of riverine samples. Nucleotide sequencing analyses revealed that all isolates belonged to genotype 3, subtypes a, b and c. The prevalence of IgG anti-HEV was 4.4%. Seroprevalence increased with the age of the individuals (OR: 3.50; 95% CI 1.39-8.87; p=0.0065) and, although the prevalence was higher in low income population, no statistical relation was found between anti-HEV and socioeconomic level. CONCLUSIONS: The environmental findings added to serological results, demonstrate that HEV circulates in central Argentina. Contamination of water with HEV could represent a route of transmission for local populations, which have a high number of susceptible individuals. This fact alerts local health care systems in order to include detection of HEV in the diagnostic algorithm of viral hepatitis.

Molecular epidemiology of hepatitis B virus in Córdoba, Argentina.

BACKGROUND: The analysis of the genomes of hepatitis B virus (HBV) identifies phylogenetic variants called genotypes, which may lead to distinct biological and clinical behaviors. OBJECTIVES: The aim of this study was to describe the current molecular epidemiology and genetic diversity of HBV in Córdoba, Argentina. STUDY DESIGN: A total of 52 HBV samples, 40 from HBV mono-infected and 12 from human immunodeficiency virus (HIV)-HBV co-infected patients, were sequenced in the S gene and in the basal core promoter-precore (BCP-pC) region. RESULTS: Presence of subgenotypes F1b (35%) and F4 (17.5%), subgenotype A2 (37.5%), C (5.0%) (subgenotype could not be defined) and D (5.0%) (subgenotype D2, and the other could not be defined) were observed among mono-infected patients. The co-infected individuals displayed a different genotype distribution: sub-genotype A2 was the most common (75.0%), followed by subgenotype F1b (25.0%). CONCLUSIONS: These results showed two epidemiologic scenarios: the mono-infected population may represent the ethnic composition of the current human population of Córdoba, where the Amerindian (genotype F) and European origins (subgenotype A2) account for the 90% of the samples; for the co-infected patients, the high prevalence of subgenotype A2 resemble previous analyses from Buenos Aires. In addition, mutations in hepatitis B surface antigen (HBsAg), polymerase and BCP-pC regions were identified, mainly in chronic or co-infected patients.