Evolutionary study of potentially zoonotic hepatitis E virus genotype 3 from swine in Northeast Brazil

Hepatitis E virus (HEV), an emerging virus associated with acute hepatic disease, leads to thousands of deaths worldwide. HEV has already been reported in Brazil; however, there is a lack of epidemiological and molecular information on the genetic variability, taxonomy, and evolution of HEV. It is thus unclear whether hepatitis E is a neglected disease in Brazil or it has low relevance for public health in this country. Here, for the first time, we report the presence of HEV in Northeast Brazil. A total of 119 swine faecal samples were screened for the presence of HEV RNA using real-time polymerase chain reaction (RT-PCR) and further confirmed by conventional RT-PCR; among these, two samples were identified as positive. Molecular evolution analyses based on capsid sequences revealed that the samples had close proximities to HEV sequences belonging to genotype 3 and were genetically related to subtype 3f isolated in humans. Parsimony ancestral states analysis indicated gene flow events from HEV cross-species infection, suggesting an important role of pig hosts in viral spillover. HEV's ability for zoonotic transmission by inter-species host switching as well as its possible adaptation to new animal species remain important issues for human health.

Seroprevalence of hepatitis E virus infection in domestic pigs in the Federal District, Brazil / Soroprevalência da infecção pelo vírus da hepatite E em suínos domésticos no Distrito Federal, Brasil

Hepatitis E is caused by the hepatitis E virus (HEV) which is currently known to be a zoonotic pathogen transmitted by pigs. In Brazil, there is no information about the circulation of HEV in the swine herd of the Federal District. Therefore, a cross-sectional study was performed with sera from 449 domestic pigs, provided by the Secretary of Agriculture of the Federal District. Blood samples were collected between June and September 2014. A commercially available ELISA kit was used for the detection of IgG antibodies. High seroprevalence of antibodies to HEV was found, since 304 animals showed anti-HEV positive reactions (67.7%; 95% CI = 63.2%, 71.9%). The seropositivity presented no difference by gender or age. The results suggest that HEV circulates among domestic pigs in the Federal District and it can serve as a warning to the local public health system due to their possible involvement in human infections.(AU)

A hepatite E é causada pelo vírus da hepatite E (HEV), considerado um patógeno de transmissão zoonótica que tem suínos como reservatórios. No Brasil, não há informações a respeito da circulação do HEV no rebanho suíno do Distrito Federal. Por isso, foi conduzido um estudo transversal com amostras de soro de 449 suínos domésticos provenientes de 234 propriedades, cedidas pela Secretaria de Agricultura do Distrito Federal. As amostras sanguíneas foram coletadas entre junho e setembro de 2014. Um kit de ELISA comercialmente disponível foi utilizado para a detecção sorológica de anticorpos IgG contra o HEV. Foi encontrada uma alta soroprevalência de anticorpos contra o HEV, uma vez que 304 animais apresentaram amostras reagentes (67,7%, IC 95% = 63,2%, 71,9%). A soropositividade não variou com relação ao gênero ou à idade. Os resultados sugerem que o HEV circula entre os suínos domésticos no Distrito Federal, e isso pode servir como um alerta para o sistema de saúde pública da região devido ao possível envolvimento desses animais em infecções humanas.(AU)

High frequency of hepatitis E virus infection in swine from South Brazil and close similarity to human HEV isolates

Abstract Hepatitis E virus is responsible for acute and chronic liver infections worldwide. Swine hepatitis E virus has been isolated in Brazil, and a probable zoonotic transmission has been described, although data are still scarce. The aim of this study was to investigate the frequency of hepatitis E virus infection in pigs from a small-scale farm in the rural area of Paraná State, South Brazil. Fecal samples were collected from 170 pigs and screened for hepatitis E virus RNA using a duplex real-time RT-PCR targeting a highly conserved 70 nt long sequence within overlapping parts of ORF2 and ORF3 as well as a 113 nt sequence of ORF2. Positive samples with high viral loads were subjected to direct sequencing and phylogenetic analysis. hepatitis E virus RNA was detected in 34 (20.0%) of the 170 pigs following positive results in at least one set of screening real-time RT-PCR primers and probes. The swine hepatitis E virus strains clustered with the genotype hepatitis E virus-3b reference sequences in the phylogenetic analysis and showed close similarity to human hepatitis E virus isolates previously reported in Brazil.

Acute Hepatitis E Mimicking a Flare of Disease in a Patient with Chronic Autoimmune Hepatitis

Abstract: Acute hepatitis E is becoming increasingly recognised in Europe with up to 40% of the population in Southern France being exposed to the virus, which is harboured in pigs. Patients with known liver disease may present with acute hepatitis E and present a diagnostic challenge. For example patients with autoimmune hepatitis (AIH) who are immunosuppressed and contract hepatitis E may be at increased risk of developing chronicity due to concurrent immunosuppression. Importantly, the diagnosis may be missed with the infection misdiagnosed as an autoimmune flare, and immunosuppression increased by the attending physician, thus enhancing the risk of chronicity of infection leading to progressive liver injury in immunocompromised patients. We report a case of acute hepatitis E in a patient with AIH and discuss the features that helped us differentiating it from an autoimmune flare.

High Clinical Manifestation Rate in an Imported Outbreak of Hepatitis E Genotype 1 Infection in a German Group of Travellers Returning from India

Abstract: Background. There are only few reports about travel-associated, imported tropical hepatitis E virus (HEV) genotype 1 infections within Western travellers. We describe the clinical course of a single outbreak of hepatitis E in a German travellers group returning from India and compare the results of two commercial HEV-seroassays. Material and methods. After identifying hepatitis E in an index patient returning from a journey to India all 24 members of this journey were tested for anti-HEV-IgG and IgM using two commercial seroassays (Wantai and Mikrogen), for HEV-RNA by PCR and HEV-Ag by an antigen-assay (Wantai). Results. 5/24 (21%) individuals were viraemic with viral loads between 580-4,800,000 IU/mL. Bilirubin and ALT levels in these patients ranged from 1.3-14.9 mg/dL (mean 7.3 mg/dL, SD 5.6 mg/dL) and 151-4,820 U/L (mean 1,832U/L, SD 1842U/L), respectively and showed significant correlations with viral loads (r = 0.863, p < 0.001; r = 0.890, p < 0.001). No risk factor for food-borne HEV-transmission was identified. All viraemic patients (5/5) tested positive for anti-HEV-IgG and IgM in the Wantai-assay but only 4/5 in the Mikrogen-assay. Wantai-HEV-antigen-assay was negative in all patients. Six months later all previously viraemic patients tested positive for anti-HEV-IgG and negative for IgM in both assays. However, two non-viremic individuals who initially tested Wantai-IgM-positive stayed positive indicating false positive results. Conclusions. Despite the exact number of exposed individuals could not be determined HEV genotype 1 infections have a high manifestation rate of more than 20%.The Wantai-antigen-test failed, the Wantai-IgMrapid-test and the Mikrogen-IgM-recomblot showed a better performance but still they cannot replace real-time PCR for diagnosing ongoing HEV-infections.

Concomitant Outbreaks of Yellow Fever and Hepatitis E Virus in Darfur States; Sudan; 2012

Introduction: Yellow fever (YF) is a vector-borne disease transmitted to humans by infected Aedes mosquitoes; while hepatitis E virus (HEV) is a waterborne disease that is transmitted through the fecal-oral route. Both diseases have very close clinical presentation; namely fever; jaundice; malaise; and dark urine; they differ in severity and outcome.Methodology: In this cross-sectional; laboratory-based study; an attempt was made to measure the correlation of concomitant YF and HEV infection in Darfur States during the previous YF outbreak in 2012.Results: Results found concomitant outbreaks of YF and HEV at the same time with very weak statistical correlation between the two infections during the outbreak period; with Cramer's V correlation 0.05 and insignificant p value of 0.86.Conclusions: This correlation indicates that clinicians and care providers in tropical areas have to deal with clinical case definitions used for disease surveillance very carefully since prevalence of HEV infection is relatively common and this increases the possibility of misclassification and missing YF cases; particularly initial index cases; in a season or outbreak

Hepatitis E: un virus infrecuente o un agente infrecuentemente pensado? / [Hepatitis E: an infrequent virus or an unfrecuently investigated agent?].

Two cases of hepatitis E that were assisted in our Unit of Hepatology and Liver Transplantation are described in this article. The first patient had prior hepatic involvement and therefore a more severe course, whereas the second case, with normal liver function, only developed a self-limited acute hepatitis.

Hepatitis E en niños / Hepatitis E in children

La hepatitis E, conocida previamente como hepatitis no A, no B, de transmisión enteral, es una infección causada por el virus de la hepatitis E (VHE), cuyas características clínicas y epidemiológicas son las de una hepatitis aguda. Pertenece a la familia Hepaviridae. El VHE setransmite principalmente por la vía fecal-oral, la mayoría de las epidemias se pueden asociar conbrotes que tienen su origen en el agua, alta densidad de población y deficientes condiciones sanitarias. El cuadro clínico es el de una hepatitis aguda típica, sin embargo, tiene un amplio espectro de presentación clínica. Es común encontrar marcadores serológicos para VHE positivos en niños con hepatitis viral aguda por otros virus hepatótropos, especialmente el virus B y C. El diagnóstico de infección por VHE se puede hacer por detección serológica y/o molecular. La teórica viabilidad de una vacuna frente alVHEestá basada en diversas evidencias.

Hepatitis E, formerly known as hepatitis non A, non B, enteral transmission, is an infection causedby the hepatitis E virus (HEV), clinical and epidemiological characteristics are those of acute hepatitis. Hepaviridae belongs to the family. HEV is transmitted primarily through fecal-oral route,most outbreaks have been associated with outbreaks that have their origin in water, high population density and poor sanitation. The clinical picture is that of a typical acute hepatitis, however, has a broad spectrum of clinical presentation. Commonly found positive for HEV serological markers in children with acute viral hepatitis other hepatotropic viruses, especially viruses B and C. The diagnosis of HEV infectionan be done by serological detection and/or molecular. The theoretical feasibility of a vaccineagainstHEVis based on different evidence.

Revisión actualizada sobre el virus de la hepatitis E / Update on information regarding hepatitis E virus

La hepatitis E ha sido considerada desde su primera descripción como una enfermedad con un patrón epidemiológico vinculado con el consumo de agua y alimentos contaminados, de modo similar a la hepatitis A, y con una prevalencia superior en zonas geográficas con condiciones sociosanitarias deficientes. La introducción de técnicas moleculares aportó los datos necesarios para demostrar que en los países desarrollados la infección por el virus de la hepatitis E es frecuente, tiene carácter autóctono y un patrón epidemiológico distinto, asociada al contacto con animales domésticos, especialmente el cerdo. La consideración de la hepatitis E en los países desarrollados como una zoonosis supone un giro conceptual interesante que hace necesario revisar esta entidad clínica desde una perspectiva distinta de la que se venía utilizando. Esta revisión resume el conocimiento actual en la biología, la estructura y la transmisión del virus, así como el diagnóstico de la infección, y describe el estado actual en áreas con una incidencia baja de hepatitis aguda E y el papel de los animales como vectores potenciales del virus

Presencia de anti-VHE en un estudio de cohorte de porcinos ¿reservorio animal de hepatitis E en Chile? / Presence of anti hepatitis E virus antibodies in swine

Background: Swine hepatitis E virus (HEV) has a cross-reaction with human anti-HEV antibodies. Therefore, pigs could be an animal reservoir, rendering hepatitis E as a zoonosis. The spread of this infection among infected pigs across countries would be possible through trading. Previously, using an anti-human conjugate, we detected anti-HEV antobodies in adult pigs in Chile. Aim: To detect anti-HEV (ELISA) in a cohort of swine at different ages. Material and Methods: Two hundred pigs aged 42 to 360 days, divided in 20 groups of 10 animals were tested. Anti-HEV was detected by ELISA using anti-pig IgG horseradish peroxidase instead of anti-human conjugates. Results: Anti-HEV were detected in one animal aged 90 days, two animals aged 120 days, one animal aged 260 days and 2 animals aged 360 days, five pregnant sows and two old hogs. This represents a total of 14 animals or 7 percent of the sample. Conclusions: There is a significant prevalence of anti-HEV in pigs from 90 days of birth, suggesting that these swine are aprobable reservoir.

Hepatitis E

La hepatitis viral es una de las enfermedades más viejas del hombre y así aparece en los escritos hipocráticos. Observaciones epidemiológicas y estudios experimentales iniciales confirman la existencia de dos formas de la enfermedad producidas por diferentes agentes etiológicos. La primera forma se denominó hepatitis A, tenía periodo de incubación de tres a cinco semanas y se transmitía por vía oral-fecal. La segunda forma se denominó hepatitis B, tenía un período de incubación de tres a seis meses y se transmitia por vía parenteral. La aplicación de pruebas serológicas específicas para diagnosticar estos dos agentes virales rapidamente demostró que existían otras hepatitis virales no producidas por estos dos agentes que se denominaron hepatitis no A no B. En los últimos cinco años la investigación clínica sobre las hepatitis no A no B, han logrado identificar dos de los tres potenciales agentes causantes de esta forma de hepatitis. Uno de ellos denominado virus de la hepatitis C, que es la principal causa de la hepatitis transfusional, se ha podido aislar y clonar recientemente. El otro agente denominado virus E por sus características epidemiológicas endémicas y de transmisión enteral, fue la causa principal de la hepatitis que causó varios brotes epidemiológicos en la decada de los 50 en la India y en Rusia y que se ha identificado como el agente causal de hepatitis en Mexico y en algunos paises de América Central. Este virus pertenece a la familia calcivirus, esta constituido por una cadena simple de RNA, se transmite por vía oral-fecal, tiene un período de incubación de 20 a 40 días e induce una enfermedad clínica similar a la producida por el virus de la hepatitis A, siendo más letal en mijeres embarazadas y no produce complicaciones crónicas. El descubrimiento de este agente facilitará diseñar estrategias de sanidad y vacunación, que permitan controlar cabalmente la presencia de un virus capaz de generar brotes epidémicos responsables de muchas suertes.