RESUMO
Whether waste pickers are a risk group for hepatitis E virus (HEV) infection is largely unknown. This study aimed to determine the association between HEV exposure and the occupation of waste pickers and the work characteristics of waste pickers. An age-and gender-matched case-control seroprevalence study of 86 waste pickers and 86 control subjects of the general population was performed. We determined anti-HEV IgG antibodies in sera of cases and controls using a commercially available enzyme-linked immunoassay. The McNemar's test was used to assess the association between HEV seropositivity and the occupation of waste picker. The association between HEV seropositivity and work characteristics of waste pickers was assessed by bivariate and logistic regression analyses. Anti-HEV IgG antibodies were detected in 14 (16.3%) of the 86 waste pickers and in 8 (9.3%) of the 86 control subjects (McNemar's pair test: odds ratio (OR) = 13.0; 95% confidence interval (CI): 0.73-230.77; p = .02). Bivariate analysis showed that HEV exposure was associated with an ill status (p = .01) and reflexes impairment (p = .009). Logistic regression analysis showed that HEV seropositivity was associated with increasing age (OR = 6.52; 95% CI: 1.95-21.78; p = .002) and raising pigs (OR = 12.01; 95% CI: 1.48-97.26; p = .02). This is the first age- and gender-matched case-control study on the association between HEV infection and the occupation of waste picker. Waste pickers represent a risk group for HEV infection. Factors associated with HEV seropositivity found in this study may help in the design of optimal planning to avoid HEV infection.
Assuntos
Anticorpos Anti-Hepatite/sangue , Vírus da Hepatite E/imunologia , Hepatite E/imunologia , Doenças Profissionais/virologia , Reciclagem , Eliminação de Resíduos , Recursos Humanos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Vírus da Hepatite E/patogenicidade , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/etiologia , Razão de Chances , Fatores de Risco , Estudos Soroepidemiológicos , Recursos Humanos/classificação , Adulto JovemRESUMO
Hepatitis E virus genotype 3 (HEV-3) is an emerging zoonotic pathogen, responsible for sporadic cases of acute hepatitis E worldwide. Primate models have proven to be an essential tool for the study of HEV pathogenesis. Here we describe the outcomes of HEV infection in Macaca fascicularis (cynomolgus) inoculated experimentally with genotype 3. Eight adult cynomolgus macaques were inoculated intravenously with HEV-3 viral particles isolated from swine and human samples. Liver, spleen, duodenum, gallbladder and bile were sequential assessed up to the end-point of this study, 67 days post-inoculation (dpi). Our previously published findings showed that biochemical parameters return gradually to baseline levels at 55 dpi, whereas anti-HEV IgM and HEV RNA become undetectable in the serum and feces of all animals, indicating a non-viremic phase of recovery. Nevertheless, at a later stage during convalescence (67 dpi), the presence of HEV-3 RNA and antigen persist in central organs, even after peripheral viral clearance. Our results show that two cynomolgus inoculated with swine HEV-3 (animals I3 and O1) presented persistence of HEV RNA low titers in liver, gallbladder and bile. At this same stage of infection, HEV antigen (HEV Ag) could be detected in all infected animals, predominantly in non-reactive Kupffer cells (CD68+iNOS-) and sinusoidal lining cells. Simultaneously, CD4+, CD3+CD4+, and CD3+CD8+ immune cells were identified in hepatic sinusoids and small inflammatory clusters of lobular mononuclear cells, at the end-point of this study. Inability of HEV clearance in humans can result in chronic hepatitis, liver cirrhosis, with subsequent liver failure requiring transplantation. The results of our study support the persistence of HEV-3 during convalescence at 67 dpi, with active immune response in NHP. We alert to the inherent risk of viral transmission through liver transplantation, even in the absence of clinical and biochemical signs of acute infection. Thus, besides checking conventional serological markers of HEV infection, we strongly recommend HEV-3 RNA and antigen detection in liver explants as public health measure to prevent donor-recipient transmission and spread of hepatitis E.
Assuntos
Vírus da Hepatite E/genética , Hepatite E/genética , Fígado/virologia , Macaca fascicularis/virologia , Animais , Modelos Animais de Doenças , Duodeno/patologia , Duodeno/virologia , Fezes/virologia , Vesícula Biliar/patologia , Vesícula Biliar/virologia , Genótipo , Anticorpos Anti-Hepatite/genética , Anticorpos Anti-Hepatite/imunologia , Hepatite E/imunologia , Hepatite E/patologia , Hepatite E/virologia , Vírus da Hepatite E/imunologia , Vírus da Hepatite E/patogenicidade , Humanos , Fígado/patologia , Macaca fascicularis/imunologia , Tecido Parenquimatoso/patologia , Tecido Parenquimatoso/virologia , Baço/patologia , Baço/virologia , Suínos/virologia , Vírion/genética , Vírion/imunologia , Vírion/patogenicidadeRESUMO
Based on high seroprevalence, null surveillance, and lack of diagnostics, Mexico is a high-risk region for hepatitis E Virus (HEV) infection. However, few local news on infection are available. Clinicians and general population are in need of increasing awareness, and preventive measures should be emphasized.
Assuntos
Vírus da Hepatite E/patogenicidade , Hepatite E/virologia , Zoonoses/virologia , Animais , Genótipo , Hepatite E/epidemiologia , Hepatite E/terapia , Hepatite E/transmissão , Vírus da Hepatite E/genética , Humanos , México/epidemiologia , Prognóstico , Medição de Risco , Fatores de Risco , Zoonoses/epidemiologia , Zoonoses/terapia , Zoonoses/transmissãoRESUMO
Hepatitis E virus (HEV) is a common etiology of acute viral hepatitis worldwide. Recombinant HEV vaccines have been developed, but only one is commercially available and licensed in China since 2011. Epidemiological studies have identified genotype 3 as the major cause of chronic infection in immunocompromised individuals. Ribavirin has been shown to be effective as a monotherapy to induce HEV clearance in chronic patients who have undergone solid organ transplant (SOT) under immunosuppressive therapy. Efforts and improvements in prevention and control have been made to reduce the instances of acute and chronic hepatitis E in endemic and nonendemic countries. However, this review shows that further studies are required to demonstrate the importance of preventive vaccination and treatment worldwide, with emphasis on hepatitis E infection in the public health system.
Assuntos
Vírus da Hepatite E/efeitos dos fármacos , Hepatite E/prevenção & controle , Ribavirina/uso terapêutico , Vacinas Sintéticas/uso terapêutico , China/epidemiologia , Genótipo , Hepatite E/epidemiologia , Hepatite E/imunologia , Vírus da Hepatite E/imunologia , Vírus da Hepatite E/patogenicidade , HumanosRESUMO
Hepatitis E in industrialized countries is mainly associated with genotype 3 hepatitis E virus (HEV) and normally causes a sporadic self-limiting disease in immunocompetent individuals. Unlike genotype 3, genotypes 1 and 2 circulate in developing countries, produce severe disease and occur in the epidemic form. Hepatitis E occurring in travellers returning from endemic areas in developing countries is not a novel epidemiological occurrence, however the vast majority of cases remain to be genetically studied. The present study describes two cases of severe acute hepatitis E that required hospitalization for 6 and 9 days in two individuals of Indian nationality that had recently migrated to Portugal to work. The retrieved HEV sequences both belonged to genotype 1 and had a high degree of nucleotide sequence identity, clustering with strains isolated in India and Nepal, in 2013 and 2014. Confirmed HEV genotypes of increased pathogenicity like genotype 1 are being introduced into otherwise naïve populations of industrialized countries such as European countries with consequences difficult to predict. As far as we know the present study is the first in Portugal to describe and genetically characterize imported cases of hepatitis E infection caused by HEV genotype 1.
Assuntos
DNA Viral/genética , Vírus da Hepatite E/genética , Hepatite E/virologia , Adulto , Emigrantes e Imigrantes , Emigração e Imigração , Genótipo , Hepatite E/diagnóstico , Hepatite E/terapia , Vírus da Hepatite E/patogenicidade , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Portugal , Índice de Gravidade de Doença , Resultado do TratamentoAssuntos
Vírus da Hepatite E/patogenicidade , Hepatite E/epidemiologia , Transplante de Rim , Infecções Oportunistas/epidemiologia , Anticorpos Anti-Hepatite/sangue , Hepatite E/diagnóstico , Hepatite E/imunologia , Hepatite E/virologia , Vírus da Hepatite E/genética , Vírus da Hepatite E/imunologia , Interações Hospedeiro-Patógeno , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia , Infecções Oportunistas/virologia , Prevalência , Estudos Prospectivos , RNA Viral/genética , Estudos Soroepidemiológicos , Resultado do Tratamento , Estados Unidos/epidemiologia , Carga ViralRESUMO
Epidemiological studies found that hepatitis E virus genotype 3 (HEV-3) infection was associated with chronic hepatitis and cirrhosis in immunocompromised patients. Our study aimed to investigate the relationship between the host immunosuppressive status and the occurrence of HEV-related chronic hepatitis. Here we describe a successful experimental study, using cynomolgus monkeys previously treated with tacrolimus, a potent calcineurin inhibitor immunosuppressant, and infected with a Brazilian HEV-3 strain isolated from naturally infected pigs. HEV infected monkeys were followed up during 160 days post infection (dpi) by clinical signs; virological, biochemical and haematological parameters; and liver histopathology. The tacrolimus blood levels were monitored throughout the experiment. Immunosuppression was confirmed by clinical and laboratorial findings, such as: moderate weight loss, alopecia, and herpes virus opportunistic infection. In this study, chronic HEV infection was characterized by the mild increase of liver enzymes serum levels; persistent RNA viremia and viral faecal shedding; and liver histopathology. Three out of four immunosuppressed monkeys showed recurrent HEV RNA detection in liver samples, evident hepatocellular ballooning degeneration, mild to severe macro and microvesicular steatosis (zone 1), scattered hepatocellular apoptosis, and lobular focal inflammation. At 69 dpi, liver biopsies of all infected monkeys revealed evident ballooning degeneration (zone 3), discrete hepatocellular apoptosis, and at most mild portal and intra-acinar focal inflammation. At 160 dpi, the three chronically HEV infected monkeys showed microscopic features (piecemeal necrosis) corresponding to chronic hepatitis in absence of fibrosis and cirrhosis in liver parenchyma. Within 4-months follow up, the tacrolimus-immunosuppressed cynomolgus monkeys infected with a Brazilian swine HEV-3 strain exhibited more severe hepatic lesions progressing to chronic hepatitis without liver fibrosis, similarly as shown in tacrolimus-immunosuppressed solid organ transplant (SOT) recipients. The cause-effect relationship between HEV infection and tacrolimus treatment was confirmed in this experiment.
Assuntos
Vírus da Hepatite E/patogenicidade , Imunossupressores/imunologia , Macaca fascicularis/imunologia , Macaca fascicularis/virologia , Animais , Brasil , Feminino , Genótipo , Anticorpos Anti-Hepatite/imunologia , Hepatite E/imunologia , Hepatite E/virologia , Vírus da Hepatite E/genética , Vírus da Hepatite E/imunologia , Terapia de Imunossupressão/métodos , Fígado/imunologia , Fígado/virologia , Cirrose Hepática/imunologia , Cirrose Hepática/virologia , Testes de Função Hepática/métodos , Masculino , RNA Viral/genética , Eliminação de Partículas Virais/imunologiaRESUMO
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.
Assuntos
Humanos , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Viagem , Surtos de Doenças , Vírus da Hepatite E/genética , Hepatite E/virologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , RNA Viral/genética , Testes Sorológicos , Biomarcadores/sangue , Anticorpos Anti-Hepatite/sangue , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Risco , Vírus da Hepatite E/imunologia , Vírus da Hepatite E/patogenicidade , Hepatite E/diagnóstico , Hepatite E/transmissão , Hepatite E/epidemiologia , Carga Viral , Reações Falso-Positivas , Reação em Cadeia da Polimerase em Tempo Real , Genótipo , Alemanha/epidemiologia , Índia/epidemiologiaRESUMO
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.
Assuntos
Surtos de Doenças , Vírus da Hepatite E/genética , Hepatite E/virologia , Viagem , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Reações Falso-Positivas , Feminino , Genótipo , Alemanha/epidemiologia , Anticorpos Anti-Hepatite/sangue , Hepatite E/diagnóstico , Hepatite E/epidemiologia , Hepatite E/transmissão , Vírus da Hepatite E/imunologia , Vírus da Hepatite E/patogenicidade , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Fatores de Risco , Testes Sorológicos , Carga Viral , Adulto JovemRESUMO
BACKGROUND AND AIM: Hepatitis E virus (HEV) infection represents a risk for mortality in pregnant women. The seroepidemiology of HEV infection in rural pregnant women in the Americas is largely unknown. The aim of the study was to determine the seroepidemiology of anti-HEV IgG antibodies in rural pregnant women in Durango, Mexico. MATERIALS AND METHODS: The presence of anti-HEV IgG antibodies was determined in 439 pregnant women in rural Durango, Mexico using an enzyme-linked immunoassay. Seroprevalence association with socio-demographic, clinical and behavioral characteristics of the women was also investigated. RESULTS: Twenty five (5.7%; 95% CI: 3.88-8.27) of the 439 women (mean age: 24.53 ± 6.1 years) had anti-HEV antibodies. Multivariate analysis showed that HEV seropositivity was associated with increasing age (OR = 1.11; 95% CI: 1.03-1.20; P = 0.004), consumption of unpasteurized cow milk (OR = 5.37; 95% CI: 1.17-24.63; P = 0.03), and overcrowding at home (OR = 2.36; 95% CI: 1.13-4.92; P = 0.02). In contrast, the variables educational level, occupation, socio-economic status, foreign travel, consumption of untreated water and raw or undercooked meat, and raising animals did not show associations with HEV seropositivity. Exposure to HEV was associated with the number of deliveries but not with the number of cesarean sections or miscarriages. CONCLUSIONS: This is the first report of seroprevalence and contributing factors for HEV infection in rural pregnant women in the Americas, and of an association of the consumption of unpasteurized cow milk with HEV exposure. Results of this study should be useful for designing optimal preventive measures against HEV infection. vg