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1.
Rev. clín. esp. (Ed. impr.) ; 220(7): 400-408, oct. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-199639

RESUMO

ANTECEDENTES Y OBJETIVOS: Desde junio de 2016 se han producido brotes de hepatitis A en diversos países europeos, afectando principalmente a hombres que tienen sexo con hombres (HSH). El objetivo del presente trabajo fue valorar su impacto clínico y epidemiológico en Cantabria. MATERIAL Y MÉTODOS: Se recogieron retrospectivamente todos los casos de hepatitis A diagnosticados en Cantabria entre enero de 2013 y septiembre de 2018. Se compararon dos periodos (enero 2013-mayo 2016 y junio 2016-septiembre 2018). RESULTADOS: Se diagnosticaron un total de 156 casos, objetivándose un aumento de la incidencia a partir de octubre de 2016. Con respecto al periodo 2013-2016, se observó una mayor proporción de varones (50,0 vs. 84,5%; p = 0,012) con una predominancia de la orientación sexual homosexual (80,6%) y una mayor frecuencia de transmisión sexual (0 vs. 48,3%; p = 0,061) en los pacientes del periodo 2016-2018. Desde el punto de vista clínico destacó que todos los casos de hepatitis grave ocurrieron en este último periodo. CONCLUSIONES: Nuestros resultados reafirman el elevado impacto clínico y epidemiológico del brote epidémico en Cantabria y ponen de relieve la necesaria optimización de las actuales medidas de prevención contra la hepatitis A


BACKGROUND AND OBJECTIVES: Since June 2016, there have been outbreaks of hepatitis A in various European countries, mainly affecting men who have sex with men (MSM). The aim of this study was to assess their clinical and epidemiological impact in Cantabria, Spain. MATERIAL AND METHODS: We retrospectively collected all cases of hepatitis A diagnosed in Cantabria between January 2013 and September 2018. We compared 2 periods: January 2013-May 2016 and June 2016-September 2018. RESULTS: A total of 156 cases were diagnosed, observing an increase in the incidence starting in October 2016. With regard to 2013-2016, we observed a higher proportion of men (50.0% vs. 84.5%; p=.012) with a predominance of the homosexual orientation (80.6%) and a higher rate of sexual transmission (0% vs. 48.3%; p=.061) for the patients in the 2016-2018 period. From the clinical standpoint, all cases of severe hepatitis occurred during this latter period. CONCLUSIONS: Our results reaffirm the high clinical and epidemiological impact of the epidemic outbreak in Cantabria and emphasizes the need for optimising the current prevention measures against hepatitis A


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Vírus da Hepatite A/patogenicidade , Hepatite A/epidemiologia , Homossexualidade Masculina/estatística & dados numéricos , Espanha/epidemiologia , Surtos de Doenças/prevenção & controle , Controle de Doenças Transmissíveis/métodos , Fatores de Risco , Doenças Sexualmente Transmissíveis/epidemiologia , Estudos Retrospectivos
3.
J Public Health Manag Pract ; 26(2): 176-179, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995548

RESUMO

CONTEXT: While the New York City Department of Health and Mental Hygiene (DOHMH) can use agency-wide emergency activation to respond to a hepatitis A virus-infected food handler, there is a need to identify alternative responses that conserve scarce resources. OBJECTIVE: To compare the costs incurred by DOHMH of responding to a hepatitis A case in restaurant food handlers using an agency-wide emergency activation (2015) versus the cost of collaborating with a private network of urgent care clinics (2017). DESIGN: We partially evaluate the costs incurred by DOHMH of responding to a hepatitis A case in a restaurant food handler using agency-wide emergency activation (2015) with the cost of collaborating with a private network of urgent care clinics (2017) estimated for a scenario in which DOHMH incurred the retail cost of services rendered. RESULTS: Costs incurred by DOHMH for emergency activation were $65 831 ($238 per restaurant employee evaluated) of which DOHMH personnel services accounted for 85% ($55 854). Costs of collaboration would have totaled $50 914 ($253 per restaurant employee evaluated) of which personnel services accounted for 6% ($3146). CONCLUSIONS: Accounting for incident size, collaborating with the clinic network was more expensive than agency-wide emergency activation, though required fewer DOHMH personnel services.


Assuntos
Custos e Análise de Custo/métodos , Hepatite A/economia , Saúde Pública/economia , Custos e Análise de Custo/estatística & dados numéricos , Surtos de Doenças/estatística & dados numéricos , Manipulação de Alimentos , Hepatite A/epidemiologia , Vírus da Hepatite A/patogenicidade , Humanos , Cidade de Nova Iorque/epidemiologia , Saúde Pública/métodos , Saúde Pública/estatística & dados numéricos , Restaurantes/organização & administração , Restaurantes/estatística & dados numéricos
4.
Rev. esp. salud pública ; 94: 0-0, 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-193573

RESUMO

OBJETIVO: En Galicia, la incidencia (I) de hepatitis A (HA) es baja y la susceptibilidad es del 51% en adultos (18-64 años). Entre 2016 y 2018 se incrementaron los casos, fundamentalmente en hombres. El objetivo de este estudio fue describir los casos de HA en Galicia en este periodo de brote (PB), compararlos con el periodo pre-brote (PPB), y describir las intervenciones realizadas. METODOS: Se realizó un estudio descriptivo de los casos de HA declarados entre 2016-2018 (PB), comparados con los del periodo previo (2010-2015, PPB). Se incluyeron los casos del Sistema de Notificación Obligatoria (por atención primaria, hospitalaria y microbiología) de 2010 a 2018. Se calculó el canal epidémico para el PPB, como media de casos/cuatrisemana para comparar casos observados/esperados. La incidencia (I) [casos por cada 100.000 habitantes (c/105h)] por sexo y edad se comparó con el PPB mediante el Riesgo Relativo (RR). Se enviaron mensajes con recomendaciones específicas a través de webs de referencia para hombres que tenían sexo con hombres (HSH). RESULTADOS: El brote duró 20 cuatrisemanas (septiembre de 2016 a marzo de 2018). La incidencia fue de 3 casos por cada 100.000 habitantes en hombres y 0,5 casos por cada 100.000 habitantes en mujeres. Frente al PPB, el RR-PB en hombres fue 4,8 (IC95%=4-7) y 20,4 (IC95%=5-87) entre 40 y 44 años. El 42% de los hombres respondieron tener relaciones con otros hombres (el 57% entre 20 y 30 años). A finales de 2016 se envió a través de Wapo (una de las webs de referencia de HSH) un mensaje con recomendaciones (fundamentalmente sobre vacunación), registrándose 331 entradas. CONCLUSIONES: La incidencia de HA aumenta en Galicia en el período 2016-2018 por un brote en HSH. La susceptibilidad se incrementa entre jóvenes, lo que hace necesario insistir en la vacunación de los grupos de riesgo


OBJECTIVE: In Galicia, the incidence (I) of hepatitis A (HA) is low and the susceptibility is 51% in adults (18-64 years). Between 2016 and 2018 the cases increased, mainly in men. We intend to describe the cases of HA in Galicia during this outbreak period (PB), compare them with the pre-outbreak period (PPB), and the interventions performed. METHODS: Descriptive study of the cases of HA declared between 2016-18 (PB), compared to those from the previous period (2010-2015, PPB). Cases recorded in the mandatory notification system (general practice, hospitalization and microbiology) from 2010 to 2018 were included. For the pre-outbreak period 2010-2015 (PPB) it was calculated the average of cases/four-week period to compare observed/expected cases; the incidence (I) [cases/100,000 inhabitants (c/105h)] by sex and age was compared with the PPB through the Relative Risk (RR). It were sent messages with recommendations through men who have sex with men (MSM) reference websites. RESULTS: The outbreak lasted 80 weeks (september of 2016 to march of 2018). The incidence was 3 cases/105h in men and 0.5 cases/105h in women. Compared to the PPB, the RR-PB in men was 4.8 (95%CI=4-7) and 20.4 (95%CI=5-87) in 40-44 years. 42% of men declared to have relationships with other men (57% in 20-30 years). At the end of 2016, a message with recommendations (specially vaccination) was sent via Wapo (promoted to MSM through one of its reference websites), where 331 entries were registered. CONCLUSIONS: HA's incidence, in Galicia, increased in 2016-2018 by an outbreak in MSM. We found an increased susceptibility among young people which makes necessary to insist on the vaccination of groups at risk


Assuntos
Humanos , Masculino , Feminino , Vírus da Hepatite A/patogenicidade , Hepatite A/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Homossexualidade Masculina/estatística & dados numéricos , Epidemiologia Descritiva , Espanha/epidemiologia , Suscetibilidade a Doenças/epidemiologia , Fatores de Risco , Incidência
5.
Int J Med Sci ; 16(10): 1366-1370, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692913

RESUMO

Hepatitis A virus (HAV) infection is a major cause of acute hepatitis including acute liver failure. Hepatitis B infection (HBV) occurs worldwide, with the highest rates in Asian and African countries, and there are several reports that HAV infection may have a more severe clinical course in patients with chronic HBV infection. We previously demonstrated that Japanese miso extracts have inhibitory effects on HAV replication. In the present study, we examined the replication of HAV and HBV in a hepatocyte superinfection model and the inhibitory effects of Japanese miso extracts on both viruses. According to the results, HAV infection inhibited HBV replication in superinfected hepatocytes, and Japanese rice-koji miso extracts had inhibitory effects on HAV replication. Our findings provide useful information for clinicians in managing HAV infection in patients with chronic HBV infection.


Assuntos
Hepatite A/tratamento farmacológico , Hepatite B Crônica/tratamento farmacológico , Extratos Vegetais/farmacologia , Superinfecção/tratamento farmacológico , Replicação Viral/efeitos dos fármacos , Linhagem Celular , Hepatite A/complicações , Hepatite A/virologia , Vírus da Hepatite A/efeitos dos fármacos , Vírus da Hepatite A/patogenicidade , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/complicações , Hepatite B Crônica/virologia , Hepatócitos/virologia , Humanos , Oryza/química , Extratos Vegetais/uso terapêutico , Soja/química , Superinfecção/complicações , Superinfecção/virologia
6.
Vaccine ; 37(30): 4111-4117, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31196682

RESUMO

BACKGROUND: While the hepatitis A virus (HAV) vaccine is recommended for United States (US) travelers to endemic regions, vaccination rates are lower among non-US-born adults and some racial minority groups. PURPOSE: We aimed to examine the relationship between birthplace, race and their interaction as predictors of self-reported HAV vaccination among adult travelers to high-risk countries (HRCs) through analysis of the National Health Interview Survey (NHIS), 2012-2015. METHODS: The study included 36,872 US adult participants in the 2012-2015 NHIS who traveled to countries where HAV is endemic. The main outcome was self-reported HAV vaccination (≥2 doses). Complex survey methods were applied to all models to provide statistical estimates that were representative of US adults. Multivariable logistic regression models adjusting for demographic, socioeconomic, medical, and access-to-care characteristics were fitted to examine the association between birthplace, race, race-by-birthplace (for interaction) and vaccination status. RESULTS: For adult travelers to HRCs, the adjusted odds ratio (AOR) of HAV vaccination was lower for non-US-born compared to US-born adults, AOR 0.86 (95% CI; 0.76, 0.98). For Hispanics, the AOR of HAV vaccination was 0.80 (95% CI; 0.70, 0.91) as compared to non-Hispanic-Whites. Furthermore, a significant qualitative interaction between birthplace and race was found (P-value 0.0005). Among non-Hispanic Blacks, the adjusted odds of HAV vaccination for non-US-born adults were 1.35 (95% CI; 1.06, 1.72) times the odds for US-born adults. In contrast, the AORs of HAV vaccination of non-US-born versus US-born adults were 36% (95% CI; 17%, 51%) and 30% (95% CI; 12%, 44%), lower for Asians and Hispanics, respectively. CONCLUSIONS: The association between birthplace and HAV vaccination status differs by race among travelers to HRCs, with US-born non-Hispanic Black and non-US-born Asian and Hispanic adults having lower odds of vaccination. Health care resources should be focused on these target populations to improve travel vaccination compliance.


Assuntos
Vírus da Hepatite A/imunologia , Vírus da Hepatite A/patogenicidade , Vacinação/estatística & dados numéricos , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Hepatite A/epidemiologia , Hepatite A/virologia , Humanos , Hepatopatias/epidemiologia , Hepatopatias/virologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Autorrelato , Medicina de Viagem , Cobertura Vacinal/estatística & dados numéricos , Adulto Jovem
7.
Bioorg Med Chem Lett ; 29(13): 1614-1619, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31054861

RESUMO

Synthesized 3-benzyl(phenethyl)benzo[g]quinazolines (1-17) were evaluated in vitro to determine their effects against the anti-hepatitis A virus (HAV) using a cytopathic effect inhibition assay. Of the synthesized compounds, 16 and 17 showed considerably high anti-HAV activity, as indicated by their EC50 values of 27.59 and 18 µM, respectively, when compared to that of amantadine (37.3 µM), the standard therapeutic agent. In addition, they exhibited low cytotoxicity as indicated by their CC50 values, 290.63 and 569.45 µM, respectively. Compounds 1, 2, and 5 exhibited remarkable activity compared to the active compounds (16, 17) and amantadine. The selectivity index (SI) values were calculated and applied as a parameter for classifying the activity of the targets. In addition, molecular docking was performed to rationalize the SAR of the target compounds and analyze the binding modes between the docked-selected compounds and amino acid residues in the active site of the HAV-3C proteinase enzyme.


Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite A/patogenicidade , Quinazolinas/uso terapêutico , Antivirais/farmacologia , Humanos , Simulação de Acoplamento Molecular , Quinazolinas/farmacologia , Relação Estrutura-Atividade
8.
PLoS Biol ; 17(4): e3000229, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31039149

RESUMO

Hepatitis A virus (HAV), an enigmatic and ancient pathogen, is a major causative agent of acute viral hepatitis worldwide. Although there are effective vaccines, antivirals against HAV infection are still required, especially during fulminant hepatitis outbreaks. A more in-depth understanding of the antigenic characteristics of HAV and the mechanisms of neutralization could aid in the development of rationally designed antiviral drugs targeting HAV. In this paper, 4 new antibodies-F4, F6, F7, and F9-are reported that potently neutralize HAV at 50% neutralizing concentration values (neut50) ranging from 0.1 nM to 0.85 nM. High-resolution cryo-electron microscopy (cryo-EM) structures of HAV bound to F4, F6, F7, and F9, together with results of our previous studies on R10 fragment of antigen binding (Fab)-HAV complex, shed light on the locations and nature of the epitopes recognized by the 5 neutralizing monoclonal antibodies (NAbs). All the epitopes locate within the same patch and are highly conserved. The key structure-activity correlates based on the antigenic sites have been established. Based on the structural data of the single conserved antigenic site and key structure-activity correlates, one promising drug candidate named golvatinib was identified by in silico docking studies. Cell-based antiviral assays confirmed that golvatinib is capable of blocking HAV infection effectively with a 50% inhibitory concentration (IC50) of approximately 1 µM. These results suggest that the single conserved antigenic site from complete HAV capsid is a good antiviral target and that golvatinib could function as a lead compound for anti-HAV drug development.


Assuntos
Anticorpos Neutralizantes/ultraestrutura , Desenho de Fármacos , Vírus da Hepatite A/imunologia , Aminopiridinas/metabolismo , Aminopiridinas/farmacologia , Anticorpos Monoclonais , Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais , Antígenos Virais , Capsídeo/metabolismo , Simulação por Computador , Epitopos , Antígenos da Hepatite A/metabolismo , Antígenos da Hepatite A/ultraestrutura , Vírus da Hepatite A/patogenicidade , Vírus da Hepatite A/ultraestrutura , Humanos , Piperazinas/metabolismo , Piperazinas/farmacologia , Ligação Proteica
9.
Sci Rep ; 9(1): 1493, 2019 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-30728377

RESUMO

Since the early 21st century, almost all developed countries have had a very low hepatitis A virus antibody (anti-HAV) sero-prevalence profile, as sanitation conditions and health care facilities have been optimized to a universal standard. There has not been a report on anti-HAV prevalence among a large scale population in Japan since 2003. Therefore, this study aimed to investigate the current HAV status among the general population in Hiroshima. From each age and sex specific group, a total of 1,200 samples were randomly selected from 7,682 stocked serum samples from residents' and employees' annual health check-ups during 2013-2015. Total anti-HAV was detected using Chemiluminescent Enzyme Immunoassay. The overall anti-HAV sero-prevalence was 16.8%. In both males and females, anti-HAV prevalence among individuals between 20-59 years of age was as low as 0.0-2.0%, whilst that among 70 s was as high as 70.0-71.0%. A large number of residents aged under 60 are now susceptible to HAV infection. The cohort reduction trend of anti-HAV in Japan exposes the high possibility of mass outbreak in the future. HAV vaccine especially to younger generation and high risk population may prevent outbreak in Japan.


Assuntos
Anticorpos Anti-Hepatite A/análise , Vírus da Hepatite A Humana/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Surtos de Doenças , Feminino , Hepatite A/epidemiologia , Anticorpos Anti-Hepatite A/imunologia , Vírus da Hepatite A/imunologia , Vírus da Hepatite A/patogenicidade , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Testes Sorológicos/métodos
10.
Indian J Med Res ; 150(5): 508-511, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31939396

RESUMO

Background & objectives: Humans are considered to be the principal host for hepatitis A virus (HAV) infection. In India, heterogeneous groups of susceptible individuals coexist in different regions. There has been a decline in antibody titres to HAV among young adults which may pose a major public health problem. The objective of this study was to assess the IgG anti-HAV level among healthcare workers (HCWs) in the age group of 20-60 yr and its association with the socio-demographic variables. Methods: Blood sample (2 ml) was collected under aseptic conditions from each participant followed by the preparation of serum and storing at -20°C. ELISA-based kits were used for the determination of IgG antibodies to HAV in the human serum samples. Results: Two hundred and fifty four HCWs were enrolled. IgG anti-HAV antibodies were detected in 97.2 per cent of the samples analyzed. No differences were observed in the levels of IgG anti-HAV antibody and education, income, occupation and socio-economic classes of the HCWs. A seropositivity rate of over 90 per cent was seen amongst all the socio-economic classes. Interpretation & conclusions: High levels of IgG protective antibodies were seen among the studied HCWs, hence HAV vaccination may not be required. It will be advisable to do a cost-benefit analysis of vaccination for HAV.


Assuntos
Pessoal de Saúde , Vírus da Hepatite A/isolamento & purificação , Hepatite A/epidemiologia , Estudos Soroepidemiológicos , Adulto , Feminino , Hepatite A/sangue , Hepatite A/virologia , Vírus da Hepatite A/imunologia , Vírus da Hepatite A/patogenicidade , Humanos , Imunoglobulina G/sangue , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Centros de Atenção Terciária , Vacinação
11.
Artigo em Inglês | MEDLINE | ID: mdl-29712682

RESUMO

Disease outbreaks resembling hepatitis A have been known since antiquity. However, it was not until World War II when two forms of viral hepatitis were clearly differentiated. After the discovery of Australia antigen and its association with hepatitis B, similar methodologies were used to find the hepatitis A virus. The virus was ultimately identified when investigators changed the focus of their search from serum to feces and applied appropriate technology.


Assuntos
Vírus da Hepatite A/isolamento & purificação , Hepatite A/história , Animais , Fezes/virologia , Hepatite A/transmissão , Hepatite A/virologia , Vírus da Hepatite A/patogenicidade , Hepatite B/história , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/história , Antígenos de Superfície da Hepatite B/isolamento & purificação , História do Século XX , História do Século XXI , Humanos
12.
Artigo em Inglês | MEDLINE | ID: mdl-29712684

RESUMO

There are many similarities in the epidemiology and transmission of hepatitis A virus (HAV) and hepatitis E virus (HEV) genotype (gt)3 infections in the United States. Both viruses are enterically transmitted, although specific routes of transmission are more clearly established for HAV than for HEV: HAV is restricted to humans and primarily spread through the fecal-oral route, while HEV is zoonotic with poorly understood modes of transmission in the United States. New cases of HAV infection have decreased dramatically in the United States since infant vaccination was recommended in 1996. In recent years, however, outbreaks have occurred among an increasingly susceptible adult population. Although HEV is the most common cause of acute viral hepatitis in developing countries, it is rarely diagnosed in the United States.


Assuntos
Hepatite A/epidemiologia , Hepatite A/transmissão , Hepatite E/epidemiologia , Hepatite E/transmissão , Animais , Hepatite A/prevenção & controle , Vírus da Hepatite A/patogenicidade , Hepatite E/prevenção & controle , Vírus da Hepatite E/patogenicidade , Humanos , Estados Unidos/epidemiologia , Vacinas contra Hepatite Viral/uso terapêutico , Zoonoses/virologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-29661811

RESUMO

Mechanistic analyses of hepatitis A virus (HAV)-induced pathogenesis have long been thwarted by the lack of tractable small animal models that recapitulate disease observed in humans. Several approaches have shown success, including infection of chimeric mice with human liver cells. Other recent studies show that HAV can replicate to high titer in mice lacking expression of the type I interferon (IFN) receptor (IFN-α/ß receptor) or mitochondrial antiviral signaling (MAVS) protein. Mice deficient in the IFN receptor show critical features of type A hepatitis in humans when challenged with human HAV, including histological evidence of liver damage, leukocyte infiltration, and the release of liver enzymes into blood. Acute pathogenesis is caused by MAVS-dependent signaling that leads to intrinsic apoptosis of hepatocytes.


Assuntos
Modelos Animais de Doenças , Hepatite A/imunologia , Fígado/virologia , Transdução de Sinais/fisiologia , Proteínas Adaptadoras de Transdução de Sinal , Animais , Vírus da Hepatite A/patogenicidade , Hepatócitos , Humanos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL
14.
Sci Rep ; 8(1): 16696, 2018 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-30420608

RESUMO

Hepatitis A is a vaccine-preventable disease with a global distribution. It predominantly occurs in regions with inadequate living conditions, but also affects populations in industrialised countries. Children are frequently involved in the transmission of hepatitis A virus (HAV) and thus play a central role in the epidemiology of hepatitis A. Here, we investigated HAV infections, immunisations, and associated demographic determinants in a nationwide, population-based, cross-sectional survey conducted in Germany from 2003-2006. Out of 17,640 children and adolescents, complete data sets (HAV serology, demographic information and vaccination card) were available for 12,249 (69%), all aged 3-17 years. We found protective antibody levels (>=20 IU/L) in 1,755 (14%) individuals, 1,395 (11%) were vaccinated against hepatitis A, 360 (3%) individuals were HAV seropositive without prior hepatitis A vaccination, thus indicating a previous HAV infection. Antibody prevalence (attributable to vaccination or infection) increased significantly with age. Multivariate logistic regression revealed that predominantly children and adolescents with migration background-even if they were born in Germany-are affected by HAV infections. Our results provide a rationale to emphasise existing vaccination recommendations and, moreover, to consider additional groups with a higher risk of infection for targeted vaccination, especially children with a migration background.


Assuntos
Vírus da Hepatite A/patogenicidade , Hepatite A/epidemiologia , Hepatite A/prevenção & controle , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Alemanha/epidemiologia , Vírus da Hepatite A/imunologia , Humanos , Modelos Logísticos , Masculino , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Vacinação
15.
Ann Hepatol ; 17(4): 561-568, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29893695

RESUMO

INTRODUCTION AND AIM: HAVCR1 protein is the cellular receptor for hepatitis A virus (HAV). Genetic polymorphism in this gene may alter the outcome of HAV infection. In a previous study, a 6-amino acid insertion (157insMTTTVP) in HAVCR1 gene was associated with more severe disease. We decided to investigate this association further. MATERIAL AND METHODS: We sequenced exon 4 of the HAVCR1 gene in patients with clinical hepatitis A attending our institution, and a group of healthy controls in a disease-endemic setting in India. Frequencies of different haplotypes of a genomic region with two overlapping insertion-deletion polymorphisms (indels; rs141023871 and rs139041445) were compared between patients and controls, as well as between patients with and without a severe form of disease (liver failure). RESULTS: The gene had three haplotypes in the region of interest - a short form, an intermediate-form with a 5-amino acid 157insMTTVP insertion and a long-form with a 6-amino acid 157insMTTTVP insertion. The allele frequency (29/150 [19%] vs. 43/146 [29%]; p = ns) and haplotype frequency (29/75 [39%] vs. 39/73 [53%]; p = ns) of the 157insMTTTVP variant were similar in hepatitis A patients and healthy controls (30%). Further, the allele frequency (12/58 [21%] vs. 17/92 [18%]; p = ns) and haplotype frequency (12/29 [41%] vs.17/46 [37%]; p = ns) of the longest variant were also similar in patients with severe and mild disease. DISCUSSION: In the study population, the 157insMTTTVP variant of HAVCR1 gene was not associated with more severe outcome of HAV infection. Further studies in other populations around the world are needed to assess the relation of this genetic variation with disease outcome.


Assuntos
Receptor Celular 1 do Vírus da Hepatite A/genética , Hepatite A/genética , Mutação INDEL , Polimorfismo Genético , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Doenças Endêmicas , Éxons , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Hepatite A/diagnóstico , Hepatite A/epidemiologia , Hepatite A/virologia , Vírus da Hepatite A/patogenicidade , Interações Hospedeiro-Patógeno , Humanos , Índia/epidemiologia , Lactente , Masculino , Fenótipo , Fatores de Risco , Índice de Gravidade de Doença
16.
Laeknabladid ; 104(3): 127-131, 2018.
Artigo em Islandês | MEDLINE | ID: mdl-29493530

RESUMO

INTRODUCTION: Hepatitis A virus (HAV) epidemics occurred repeatedly in Iceland in the early 20th century, but since then few cases have been reported and no epidemics since 1952. The latest Icelandic studies on HAV from around 1990 showed low incidence of infection and de-- creasing prevalence of antibodies. The objective of this study was to determine the incidence, clinical presentation and origin of HAV, abroad or in Iceland. MATERIAL AND METHODS: A retrospective search was undertaken on all patients with positive anti-HAV IgM during the 11 years period of 2006-2016 in the virological database of the National University Hospital of Iceland. Clinical data was collected from medical records on symptoms at diagnosis, blood test results and possible route of transmission. RESULTS: A total of 12 individuals were diagnosed with acute hepatitis A during the period and 6691 HAV total andibody tests and 1984 HAV IgM antibody tests were performed. Nine (75%) had been abroad within 7 weeks from initial symptoms. The most common symptoms were jaundice (83%), fever (67%) and nausea and/or vomiting (58%). 50% were admitted to a hospital. 42% had elevated INR/PT. Everyone sur-vived without complications. CONCLUSION: Annually, approximately one case of acute hepatitis A was diagnosed in Iceland during the study period but a very high number of antibody tests were performed. The majority of cases occurred among individuals who had recently been abroad. If patients have jaundice, fever and nausea, testing for HAV infection should be undertaken. HAV is not endemic in Iceland.


Assuntos
Vírus da Hepatite A/patogenicidade , Hepatite A/epidemiologia , Biomarcadores/sangue , Bases de Dados Factuais , Hepatite A/diagnóstico , Hepatite A/transmissão , Hepatite A/virologia , Anticorpos Anti-Hepatite A/sangue , Vírus da Hepatite A/imunologia , Hospitais Universitários , Humanos , Islândia/epidemiologia , Imunoglobulina M/sangue , Incidência , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Viagem
17.
Arch Virol ; 163(5): 1187-1193, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29387970

RESUMO

To establish an animal model for the newly identified Marmota Himalayana hepatovirus, MHHAV, so as to develop a better understanding of the infection of hepatitis A viruses. Five experimental woodchucks (Marmota monax) were inoculated intravenously with the purified MHHAV from wild woodchuck feces. One animal injected with PBS was defined as a control. Feces and blood were routinely collected. After the animals were subjected to necropsy, different tissues were collected. The presence of viral RNA and negative sense viral RNA was analyzed in all the samples and histopathological and in situ hybridization analysis was performed for the tissues. MHHAV infection caused fever but no severe symptoms or death. Virus was shed in feces beginning at 2 dpi, and MHHAV RNA persisted in feces for ~2 months, with a biphasic increase, and in blood for ~30 days. Viral RNA was detected in all the tissues, with high levels in the liver and spleen. Negative-strand viral RNA was detected only in the liver. Furthermore, the animals showed histological signs of hepatitis at 45 dpi. MHHAV can infect M. monax and is associated with hepatic disease. Therefore, this animal can be used as a model of HAV pathogenesis and to evaluate antiviral and anticancer therapeutics.


Assuntos
Modelos Animais de Doenças , Vírus da Hepatite A/patogenicidade , Hepatite A , Hepatite Viral Animal , Marmota , Animais , Fezes/virologia , Hepatite A/patologia , Hepatite A/fisiopatologia , Hepatite A/virologia , Vírus da Hepatite A/genética , Vírus da Hepatite A/isolamento & purificação , Vírus da Hepatite A/fisiologia , Hepatite Viral Animal/patologia , Hepatite Viral Animal/fisiopatologia , Hepatite Viral Animal/virologia , Fígado/patologia , Fígado/virologia , RNA Viral/isolamento & purificação , Baço/patologia , Baço/virologia
18.
Gastroenterology ; 154(4): 1047-1060, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29229400

RESUMO

BACKGROUND AND AIMS: CD4+CD25+Foxp3+ T-regulatory (Treg) cells control immune responses and maintain immune homeostasis. However, under inflammatory conditions, Treg cells produce cytokines that promote inflammation. We investigated production of tumor necrosis factor (TNF) by Treg cells in patients with acute hepatitis A (AHA), and examined the characteristics of these cells and association with clinical factors. METHODS: We analyzed blood samples collected from 63 patients with AHA at the time of hospitalization (and some at later time points) and 19 healthy donors in South Korea. Liver tissues were collected from patients with fulminant AHA during liver transplantation. Peripheral blood mononuclear cells were isolated from whole blood and lymphocytes were isolated from liver tissues and analyzed by flow cytometry. Cytokine production from Treg cells (CD4+CD25+Foxp3+) was measured by immunofluorescence levels following stimulation with anti-CD3 and anti-CD28. Epigenetic stability of Treg cells was determined based on DNA methylation patterns. Phenotypes of Treg cells were analyzed by flow cytometry and an RORγt inhibitor, ML-209, was used to inhibit TNF production. Treg cell suppression assay was performed by co-culture of Treg-depleted peripheral blood mononuclear cells s and isolated Treg cells. RESULTS: A higher proportion of CD4+CD25+Foxp3+ Treg cells from patients with AHA compared with controls produced TNF upon stimulation with anti-CD3 and anti-CD28 (11.2% vs 2.8%). DNA methylation analysis confirmed the identity of the Treg cells. TNF-producing Treg cells had features of T-helper 17 cells, including up-regulation of RORγt, which was required for TNF production. The Treg cells had reduced suppressive functions compared with Treg cells from controls. The frequency of TNF-producing Treg cells in AHA patients' blood correlated with their serum level of alanine aminotransferase. CONCLUSIONS: Treg cells from patients with AHA have altered functions compared with Treg cells from healthy individuals. Treg cells from patients with AHA produce higher levels of TNF, gain features of T-helper 17 cells, and have reduced suppressive activity. The presence of these cells is associated with severe liver injury in patients with AHA.


Assuntos
Hepatite A/metabolismo , Fígado/metabolismo , Linfócitos T Reguladores/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Doença Aguda , Antígenos CD/imunologia , Antígenos CD/metabolismo , Apirase/imunologia , Apirase/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Metilação de DNA , Epigênese Genética , Fatores de Transcrição Forkhead/imunologia , Fatores de Transcrição Forkhead/metabolismo , Hepatite A/diagnóstico , Hepatite A/imunologia , Hepatite A/virologia , Vírus da Hepatite A/imunologia , Vírus da Hepatite A/patogenicidade , Interações Hospedeiro-Patógeno , Humanos , Subunidade alfa de Receptor de Interleucina-2/imunologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Fígado/imunologia , Fígado/patologia , Fígado/virologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/imunologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Fenótipo , Índice de Gravidade de Doença , Transdução de Sinais , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/virologia , Células Th17/imunologia , Células Th17/metabolismo , Células Th17/virologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/imunologia
19.
mBio ; 8(5)2017 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-28874468

RESUMO

Receptor molecules play key roles in the cellular entry of picornaviruses, and TIM1 (HAVCR1) is widely accepted to be the receptor for hepatitis A virus (HAV), an unusual, hepatotropic human picornavirus. However, its identification as the hepatovirus receptor predated the discovery that hepatoviruses undergo nonlytic release from infected cells as membrane-cloaked, quasi-enveloped HAV (eHAV) virions that enter cells via a pathway distinct from naked, nonenveloped virions. We thus revisited the role of TIM1 in hepatovirus entry, examining both adherence and infection/replication in cells with clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-engineered TIM1 knockout. Cell culture-derived, gradient-purified eHAV bound Huh-7.5 human hepatoma cells less efficiently than naked HAV at 4°C, but eliminating TIM1 expression caused no difference in adherence of either form of HAV, nor any impact on infection and replication in these cells. In contrast, TIM1-deficient Vero cells showed a modest reduction in quasi-enveloped eHAV (but not naked HAV) attachment and replication. Thus, TIM1 facilitates quasi-enveloped eHAV entry in Vero cells, most likely by binding phosphatidylserine (PtdSer) residues on the eHAV membrane. Both Tim1-/-Ifnar1-/- and Tim4-/-Ifnar1-/- double-knockout mice were susceptible to infection upon intravenous challenge with infected liver homogenate, with fecal HAV shedding and serum alanine aminotransferase (ALT) elevations similar to those in Ifnar1-/- mice. However, intrahepatic HAV RNA and ALT elevations were modestly reduced in Tim1-/-Ifnar1-/- mice compared to Ifnar1-/- mice challenged with a lower titer of gradient-purified HAV or eHAV. We conclude that TIM1 is not an essential hepatovirus entry factor, although its PtdSer-binding activity may contribute to the spread of quasi-enveloped virus and liver injury in mice.IMPORTANCE T cell immunoglobulin and mucin-containing domain protein 1 (TIM1) was reported more than 2 decades ago to be an essential cellular receptor for hepatitis A virus (HAV), a picornavirus in the Hepatovirus genus, resulting in its designation as "hepatitis A virus cellular receptor 1" (HAVCR1) by the Human Genome Organization Gene Nomenclature Committee. However, recent studies have shown that HAV exists in nature as both naked, nonenveloped (HAV) virions and membrane-cloaked, quasi-enveloped infectious virus (eHAV), prompting us to revisit the role of TIM1 in viral entry. We show here that TIM1 (HAVCR1) is not an essential cellular receptor for HAV entry into cultured cells or required for viral replication and pathogenesis in permissive strains of mice, although it may facilitate early stages of infection by binding phosphatidylserine on the eHAV surface. This work thus corrects the published record and sets the stage for future efforts to identify specific hepatovirus entry factors.


Assuntos
Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Vírus da Hepatite A/fisiologia , Hepatite A/virologia , Interações Hospedeiro-Patógeno , Internalização do Vírus , Animais , Sistemas CRISPR-Cas , Carcinoma Hepatocelular , Linhagem Celular Tumoral , Chlorocebus aethiops , Receptor Celular 1 do Vírus da Hepatite A/deficiência , Receptor Celular 1 do Vírus da Hepatite A/genética , Vírus da Hepatite A/metabolismo , Vírus da Hepatite A/patogenicidade , Humanos , Fígado/patologia , Fígado/fisiopatologia , Fígado/virologia , Camundongos , Receptor de Interferon alfa e beta/deficiência , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/metabolismo , Células Vero , Vírion/metabolismo , Vírion/patogenicidade , Vírion/fisiologia , Ligação Viral , Replicação Viral
20.
BMC Infect Dis ; 17(1): 561, 2017 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-28800730

RESUMO

BACKGROUND: Hepatitis A virus (HAV) is a food and water-borne virus causing clinical (mainly hepatitis) and subclinical disease in humans. It is important to characterize circulating strains of HAV in order to prevent HAV infections using efficacious vaccines. The aim of this study was the detection and characterization of the circulating strains of HAV in Turkey by performing serology, RT-PCR, sequencing and phylogenetic analysis. METHODS: In this study, 355 HAV suspected cases were analysed by ELISA for the presence of antibodies to HAV. RNA was extracted from 54 HAV IgM positive human sera. None of the suspect cases were vaccinated against HAV and they never received blood transfusions. Samples found positive by RT-PCR using primers targeting the VP1/VP2A junction and VP1/VP3 capsid region of HAV, were subjected to sequencing and phylogenetic analyses. RESULTS: IgM type antibodies to HAV were detected in 54 patients. Twenty one of them were students. The age of IgM positive cases was between 3 and 60 years. IgM positivity differed in age groups and was higher in the age group 3 to 10 years. Phylogenetic analysis showed that the majority of HAV strains detected in this study belong to the "HAV 1B" cluster. In addition, the HAV sub-genotypes IA (KT874461.1) and IIIA (KT222963.1) were found in 2 children. These sub-genotypes were not previously reported in Turkey. The child who carried sub-genotype IIIA travelled to Afghanistan and presented with abdominal pain, icterus and vomitus. He was positive for anti-HAV IgM and IgG but negative for hepatitis B and C. Liver enzymes like aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase and lactate dehydrogenase were severely elevated. Bilirubin levels were also increased. White blood cells, neutrophils and hemoglobin were decreased while lymphocytes and monocytes were increased. Similar clinical signs and laboratory findings were reported for the child infected with sub-genotype IA but aspartate aminotransferase and alanine aminotransferase were not severely elevated. CONCLUSIONS: The results indicate that molecular studies determining the HAV genotype variation in Turkey are timely and warranted. The majority of IgM positive cases in 3-10 year old patients indicate that childhood vaccination is important. Sub-genotype IB is the most prevalant genotype in Turkey. Surprisingly, sub-genotype IA and IIIA are also present in Turkey; future diagnostic efforts need to include diagnostic methods which can identify this emerging HAV genotypes. Our results also show that one important risk factor for contracting hepatitis A virus is international travel since genotype IIIA was detected in a child who had travelled to Afghanistan.


Assuntos
Vírus da Hepatite A/genética , Hepatite A/etiologia , Filogenia , Adolescente , Adulto , Afeganistão , Criança , Pré-Escolar , Feminino , Genótipo , Hepatite A/virologia , Anticorpos Anti-Hepatite A/sangue , Vírus da Hepatite A/isolamento & purificação , Vírus da Hepatite A/patogenicidade , Humanos , Fígado/enzimologia , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Turquia , Proteínas Estruturais Virais/genética , Adulto Jovem
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