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1.
Biomed Environ Sci ; 33(7): 484-492, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32807267

RESUMO

Objective: Long-term seroprotection via the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus (HAV). Due to documented difficulties during decade-long follow-ups after receiving vaccines, statistical-modeling approaches have been applied to predict the duration of immune protection. Methods: Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children (1-8 years old) following a 0, 6 months vaccination schedule, a power-law model accounting for the kinetics of B-cell turnover, as well as a modified power-law model considering a memory-B-cell subpopulation, were fitted to predict the long-term immune responses induced by HAV vaccination (Healive or Havrix). Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were predicted. Results: A total of 375 participants who completed the two-dose vaccination were included in the analysis. Both models predicted that, over a life-long period, participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with Havrix. Additionally, consistent with previous studies, more than 90% of participants were predicted to maintain seroconversion for at least 30 years. Moreover, the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years post-vaccination. Conclusions: Based on the results of our modeling, Healive may adequately induce long-term immune responses following a 0, 6 months vaccination schedule in children via induction of memory B cells to provide stable and durable immune protection.


Assuntos
Anticorpos Anti-Hepatite A/sangue , Vacinas contra Hepatite A/administração & dosagem , Hepatite A/imunologia , Imunidade Ativa , Vacinação , Adolescente , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Masculino , Modelos Estatísticos , Vacinação/estatística & dados numéricos
2.
Sci Rep ; 10(1): 11834, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32678281

RESUMO

Aluminium hydroxide is a well-known adjuvant used in vaccines. Although it can enhance an adaptive immune response to a co-administered antigen, it causes adverse effects, including macrophagic myofasciitis (MMF), subcutaneous pseudolymphoma, and drug hypersensitivity. The object of this study is to demonstrate pediatric cases of aluminium hydroxide-induced diseases focusing on its rarity, under-recognition, and distinctive pathology. Seven child patients with biopsy-proven MMF were retrieved from the Seoul National University Hospital (SNUH) pathology archives from 2015 to 2019. The medical records and immunisation history were reviewed, and a full pathological muscle examination was carried out. The mean age was 1.7 years (8.9-40 months), who had records of vaccination against hepatitis B, hepatitis A, and tetanus toxoid on the quadriceps muscle. The chief complaints were muscle weakness (n = 6), delayed motor milestones (n = 6), instability, dysarthria, and involuntary movement (n = 1), swallowing difficulty (n = 1), high myopia (n = 1), and palpable subcutaneous nodules with skin papules (n = 1). Muscle biopsy showed MMF (n = 6) and pseudolymphoma (n = 1) with pathognomic basophilic large macrophage infiltration, which had distinctive spiculated inclusions on electron microscopy. The intracytoplasmic aluminium was positive for PAS and Morin stains. Distinctive pathology and ultrastructure suggested an association with aluminium hydroxide-containing vaccines. To avoid misdiagnosis and mistreatment, we must further investigate this uncommon condition, and pharmaceutical companies should attempt to formulate better adjuvants that do not cause such adverse effects.


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Hidróxido de Alumínio/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Fasciite/induzido quimicamente , Miosite/induzido quimicamente , Pseudolinfoma/induzido quimicamente , Vacinação/efeitos adversos , Vacinas Virais/efeitos adversos , Pré-Escolar , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/imunologia , Fasciite/diagnóstico , Fasciite/imunologia , Feminino , Hepatite A/imunologia , Hepatite A/prevenção & controle , Hepatite A/virologia , Hepatite B/imunologia , Hepatite B/prevenção & controle , Hepatite B/virologia , Humanos , Lactente , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Debilidade Muscular/induzido quimicamente , Debilidade Muscular/diagnóstico , Debilidade Muscular/imunologia , Miosite/diagnóstico , Miosite/imunologia , Pseudolinfoma/diagnóstico , Pseudolinfoma/imunologia , Tela Subcutânea , Tétano/imunologia , Tétano/prevenção & controle , Tétano/virologia , Vacinas Virais/administração & dosagem
4.
Nat Microbiol ; 5(9): 1096-1106, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32541946

RESUMO

Cell-to-cell communication by exosomes controls normal and pathogenic processes1,2. Viruses can spread in exosomes and thereby avoid immune recognition3. While biogenesis, binding and uptake of exosomes are well characterized4,5, delivery of exosome cargo into the cytoplasm is poorly understood3. We report that the phosphatidylserine receptor HAVCR1 (refs. 6,7) and the cholesterol transporter NPC1 (ref. 8) participate in cargo delivery from exosomes of hepatitis A virus (HAV)-infected cells (exo-HAV) by clathrin-mediated endocytosis. Using CRISPR-Cas9 knockout technology, we show that these two lipid receptors, which interact in the late endosome9, are necessary for the membrane fusion and delivery of RNA from exo-HAV into the cytoplasm. The HAVCR1-NPC1 pathway, which Ebola virus exploits to infect cells9, mediates HAV infection by exo-HAV, which indicates that viral infection via this exosome mimicry mechanism does not require an envelope glycoprotein. The capsid-free viral RNA in the exosome lumen, but not the endosomal uncoating of HAV particles contained in the exosomes, is mainly responsible for exo-HAV infectivity as assessed by methylene blue inactivation of non-encapsidated RNA. In contrast to exo-HAV, infectivity of HAV particles is pH-independent and requires HAVCR1 or another as yet unidentified receptor(s) but not NPC1. Our findings show that envelope-glycoprotein-independent fusion mechanisms are shared by exosomes and viruses, and call for a reassessment of the role of envelope glycoproteins in infection.


Assuntos
Endossomos/metabolismo , Exossomos/metabolismo , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Vírus da Hepatite A/metabolismo , Hepatite A/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Sistemas CRISPR-Cas , Proteínas de Transporte/metabolismo , Linhagem Celular , Ebolavirus , Endocitose , Endossomos/virologia , Exossomos/virologia , Técnicas de Inativação de Genes , Células HEK293 , Hepatite A/imunologia , Hepatite A/virologia , Receptor Celular 1 do Vírus da Hepatite A/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Glicoproteínas de Membrana , Transcriptoma , Proteínas Virais de Fusão/metabolismo , Vírion/metabolismo , Internalização do Vírus
5.
Adv Ther ; 37(5): 2373-2389, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32301062

RESUMO

BACKGROUND: Analytical data suggesting that immunoglobulin given intramuscularly (IGIM) may have reduced protection against hepatitis A virus (HAV) infection led to an update in the recommended IGIM dose (0.2 ml/kg). METHODS: This prospective, open-label, single-arm clinical study evaluated whether a single 0.2 ml/kg dose of IGIM provided protective levels of anti-HAV antibodies (≥ 10 mIU/ml for up to 60 days) in HAV-seronegative healthy adults. RESULTS: Of the 28 subjects enrolled and dosed, 26 (93%) completed the study. Mean uncorrected anti-HAV antibody titers peaked at 109 mIU/ml on day 5 and stayed above 10 mIU/ml through day 60 (N = 26). The mean uncorrected anti-HAV antibody titers had a median Tmax of 95.33 h, a mean Cmax of 118 mIU/ml, and a mean observed Thalf of 63.3 days; baseline-corrected titers had a median Tmax of 95.33 h, a mean Cmax of 114 mIU/ml, and a mean observed Thalf of 47.1 days (N = 27). All subjects (28/28) experienced at least 1 treatment-emergent adverse event (TEAE), with a total of 83 TEAEs reported; none was serious, and 96% (80/83) resolved without sequelae. Most (63%) events judged definitely and possibly related to study treatment involved localized pain due to intramuscular injections. There were no serious adverse events and no deaths or discontinuations due to TEAEs. CONCLUSIONS: A single 0.2 ml/kg dose of IGIM provided protective anti-HAV levels for at least 60 days, with acceptable safety and tolerability profiles in healthy subjects. Uncorrected and baseline-corrected pharmacokinetic findings were similar and consistent with the corresponding sampling points in previous research. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT03351933.


Assuntos
Anticorpos Anti-Hepatite A/imunologia , Hepatite A/prevenção & controle , Imunoglobulina G/administração & dosagem , Imunoglobulina G/imunologia , Adulto , Relação Dose-Resposta a Droga , Feminino , Voluntários Saudáveis , Hepatite A/imunologia , Vírus da Hepatite A/imunologia , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Projetos de Pesquisa
6.
Am J Trop Med Hyg ; 103(1): 164-168, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32342836

RESUMO

Despite several recent reports of outbreaks of hepatitis A, little is known about the disease burden in Lao People's Democratic Republic (PDR). We conducted a cross-sectional age-stratified seroprevalence study of anti-hepatitis A virus (HAV) IgG and risk factors in a rural province (Xiengkhouang) and Vientiane capital in Lao PDR. Overall, 62% of participants were anti-HAV positive in Xiengkhouang Province compared with 45.5% in Vientiane capital. In Xiengkhouang, 23.7% of 5- to 10-year-olds were already seropositive compared with 5% in Vientiane. A dramatic increase in seroprevalence occurred between 15- to 20-year and 21- to 30-year age-groups (35.7-62.4%, Xiengkhouang, and 11.5-69.7%, Vientiane) until essentially all older adults were positive in both locations. The main risk factors for HAV antibodies were age, non-Lao-Tai ethnicity, and food-related risk factors. In conclusion, Lao children seem to be exposed very early to HAV, particularly in rural settings, and exposure continues throughout their lives, mostly without being reported. In the older birth cohorts, the high seroprevalence may largely reflect poor sanitation and exposure during childhood. In Vientiane capital, the lower seroprevalence at young ages may reflect better water sanitation since the late 1990s. A comparison with neighboring Thailand indicates that the impact of improved sanitation in Lao PDR began only two decades later. Further improvements in water sanitation, in particular in the rural districts, and better food hygiene are warranted. Our study also suggests that HAV infections are underreported. Improved reporting would provide guidance for targeted interventions to further reduce HAV infections.


Assuntos
Anticorpos Antivirais/sangue , Surtos de Doenças , Vírus da Hepatite A/imunologia , Hepatite A/epidemiologia , Imunoglobulina G/sangue , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Notificação de Doenças/estatística & dados numéricos , Feminino , Hepatite A/sangue , Hepatite A/imunologia , Hepatite A/virologia , Humanos , Laos/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , População Rural , Saneamento/métodos , Estudos Soroepidemiológicos , Abastecimento de Água
7.
Sex Transm Infect ; 96(4): 265-270, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32169881

RESUMO

BACKGROUND: Outbreaks of hepatitis A are being reported more commonly among men who have sex with men (MSM) globally. Australia has also reported a sharp increase in the number of cases of hepatitis A in 2017. This study aimed to determine the level of immunity to hepatitis A among MSM attending a large urban sexual health clinic in Victoria in the lead up to recent outbreak. METHODS: This was a retrospective audit of serological testing data from first-time MSM attendees at Melbourne Sexual Health Centre (MSHC) in Australia from 1 January 2012 to 31 December 2018. We determined the proportion of MSM who were tested and who had serological detection of hepatitis A IgG, stratified by age and calendar year. We used univariable and multivariable logistic regression to investigate factors associated with testing for and detection of hepatitis A IgG. RESULTS: There were 16 609 first-time MSM attendees at MSHC over the 7-year period, of which 9718 (59%, 95% CI 58% to 60%) were tested for hepatitis A IgG. There was a 2% annual increase in the proportion of men tested (from 60% in 2012 to 69% in 2018; OR=1.02, 95% CI 1.00 to 1.03, p=0.025). Men born outside of Australia/New Zealand, and younger men <30 years had higher odds of being tested. Of those tested, 44% (n=4304, 95% CI 43% to 45%) had hepatitis A IgG detected at their first visit, with no change over time (OR=1.01, 95% CI 0.99 to 1.03, p=0.210). Detection of hepatitis A IgG was associated with being aged 30 years or older (adjusted OR=2.06, 95% CI 1.89 to 2.24, p<0.001) or being born overseas versus Australia/New Zealand (AOR=1.21, 95% CI 1.11 to 1.31, p<0.001). CONCLUSION: Hepatitis A immunity among MSM remains below the estimated 70% required to prevent outbreaks. Measures including increased testing and higher vaccination coverage are needed to prevent outbreaks and to limit the number of cases and deaths.


Assuntos
Anticorpos Anti-Hepatite A/sangue , Hepatite A/imunologia , Homossexualidade Masculina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos Soroepidemiológicos , Vitória , Adulto Jovem
8.
Yonsei Med J ; 61(1): 100-102, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31887806

RESUMO

To evaluate the pathophysiology of autoimmune hepatitis (AIH) following acute hepatitis A (AHA) in immunologic aspects, we performed multi-color flow cytometry with peripheral blood mononuclear cells of a patient who underwent liver transplantation due to AIH-induced liver failure. Unlike general AHA patients, the proportion of tumor necrosis factor-α-producing Treg cells remained high for 6 months after diagnosis of AHA until she underwent a liver transplantation. The conversion of Treg cells into mediators of inflammation may have played a role in the autoimmune pathogenesis following AHA.


Assuntos
Hepatite A/complicações , Hepatite Autoimune/etiologia , Hepatite Autoimune/imunologia , Inflamação/patologia , Falência Hepática/etiologia , Falência Hepática/imunologia , Linfócitos T Reguladores/imunologia , Idoso , Feminino , Hepatite A/imunologia , Hepatite A/fisiopatologia , Hepatite Autoimune/fisiopatologia , Humanos , Fígado/patologia , Fígado/fisiopatologia , Falência Hepática/patologia , Falência Hepática/fisiopatologia , Testes de Função Hepática
9.
PLoS One ; 14(6): e0216033, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31242191

RESUMO

INTRODUCTION: South Africa is considered highly endemic for hepatitis A virus (HAV) although few seroprevalence studies have been conducted over the past two decades. The World Health Organization recommends integrating HAV vaccination into national childhood immunization schedules where there is transition from high to intermediate endemicity. As a means of gauging age-specific rates of infection, we report HAV seroprevalence rates among specimens tested for HAV serology within South Africa's public health sector from 2005-2015. MATERIALS AND METHODS: Hepatitis A serology results (Anti-HAV IgM, IgG and total antibody) from 2005-2015 were extracted from South Africa's National Health Laboratory Service's Corporate Data Warehouse (NHLS CDW), the central data repository of all laboratory test-sets within the public health sector. Results were extracted according to test-set, result, date of testing, health facility, name, surname, age, and sex. Anti-HAV IgG results were merged with total antibody results to reflect anti-HAV seroprevalence. Testing volume, positivity rates and age-specific anti-HAV seroprevalence rates by year and geographic distribution are described. RESULTS AND DISCUSSION: A total of 501 083 HAV IgM results were retrieved, of which 16 423 (3.3%) were positive, 484 259 (96.6%) negative and 401 (0.1%) equivocal; and 34 710 HAV total antibody/IgG tests of which 30 675 (88.4%) were positive, 4 020 (11.6%) negative and 15 equivocal. Whereas IgM positivity was highest among the 1-4 year age group (33.5%) and lowest among patients >45 years (<0.5%), total antibody positivity ranged from its lowest level of 52.7% in the 1-4 year age group increasing to levels of >90% only after 25 years of age. CONCLUSION: Anti-HAV total antibody testing within the South African public health sector demonstrates seroprevalence rates reach levels >90% only in adulthood, suggesting South Africa could be in transition from high to intermediate endemicity. Prospective studies with geographically representative sampling are required to confirm these findings and evaluate provincial and urban/rural heterogeneity.


Assuntos
Anticorpos Anti-Hepatite A/sangue , Vírus da Hepatite A/imunologia , Hepatite A/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Hepatite A/imunologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , África do Sul/epidemiologia , Adulto Jovem
10.
Bull Hosp Jt Dis (2013) ; 77(2): 146-152, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31128586

RESUMO

INTRODUCTION: Autoimmune hepatitis (AIH) is a cause of chronic liver disease. It is usually suspected based on clinical presentation and laboratory findings, but the diagnosis relies on the presence of specific autoantibodies and characteristic histology. Other unexplained findings should always prompt investigation for coexisting syndromes. CASE PRESENTATION: The patient is a 60-year-old Hispanic female with a history of mild asthma presented with exertional and pleuritic chest pain with weight loss, arthralgia, subjective fever, and night sweats for the last 3 months. Given the nonspecific nature of the presentation, further workup was pursued. Laboratory results indicated pancytopenia, elevated INR, and positive autoimmune panel including ANA, anti-chromatin, anti-histone, and rheumatoid factor as well as abnormal C3 and C4. Subsequent liver biopsy with interface hepatitis lead to a diagnosis of AIH with concurrent systemic lupus erythematosus suspected. CONCLUSION: The diagnostic work up for AIH is multimodal and aims to differentiate other etiologies such as congestive hepatopathy, iron overload, viral hepatitis, and other autoimmune liver diseases. In this particular case, unusual clinical and laboratory findings led to diagnosis of the overlap syndrome. Treatment for both was necessary to prevent further progression of disease.


Assuntos
Autoanticorpos , Hepatite A , Hepatite Autoimune , Hidroxicloroquina/administração & dosagem , Fígado/patologia , Lúpus Eritematoso Sistêmico , Prednisona/administração & dosagem , Fator Reumatoide/sangue , Antirreumáticos/administração & dosagem , Artralgia/diagnóstico , Artralgia/etiologia , Autoanticorpos/sangue , Autoanticorpos/classificação , Biópsia/métodos , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Diagnóstico Diferencial , Feminino , Hepatite A/diagnóstico , Hepatite A/imunologia , Hepatite A/fisiopatologia , Hepatite A/terapia , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/imunologia , Hepatite Autoimune/fisiopatologia , Hepatite Autoimune/terapia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/terapia , Pessoa de Meia-Idade , Administração dos Cuidados ao Paciente/métodos , Resultado do Tratamento
11.
BMC Infect Dis ; 19(1): 443, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113369

RESUMO

BACKGROUND: Hepatitis A Virus (HAV) is one of the most common food and water borne infectious disease prevailing globally. The objective of the study was to determine sero-prevalence of HAV infection in a district of Sri Lanka. METHODS: This was a descriptive cross sectional study conducted on 1403 participants aged 1 year and above selected by multistage stratified (for age group and area of residence) cluster sampling from September 2015 to December, 2016. An interviewer-administered questionnaire was used to collect data and Anti-IgG testing was done to determine sero-positivity. The overall, the age and sex specific sero-prevalence of HAV were calculated with 95% confidence intervals (CI). RESULTS: Of the 1403 participants 1132 were anti HAV IgG positive. Therefore the overall sero-prevalence of HAV infection was 80.7% (95%CI: 78.64-82.76). There were 283 (20.2%) individuals below the age group of 14 years and below and out of them, 204 had anti HAV IgG, therefore sero-prevalence was 72.1% for that age group. The age group 15 years and aboe comprised of 1120 (79.8%) participants and of them 928 had anti HAV IgG, making sero-prevalence 82.9%. The lowest sero-prevalence (66.9%, n = 232) was observed in the age group of 11-20 years followed by 21-30 age group. From age 31 years onwards, the sero-prevalence exceeded 90%, reaching 100% after 71 years. The urban population showed a sero-prevalence of 83% (n = 195) and 80.2% (n = 937) for the rural sector while females had a sero-prevalence of 82.2% (n = 766) and it was 77.7% (n = 366) for males. Thirty-four (3.0%) participants who had sero-positive results (n = 1132) claimed that they have had HAV in the past. CONCLUSIONS: Overall, four fifth of the population was immune to HAV infection in the district of Gampaha.


Assuntos
Vírus da Hepatite A/isolamento & purificação , Hepatite A/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos Transversais , Feminino , Hepatite A/sangue , Hepatite A/imunologia , Hepatite A/virologia , Anticorpos Anti-Hepatite A/sangue , Anticorpos Anti-Hepatite A/imunologia , Vírus da Hepatite A/genética , Vírus da Hepatite A/imunologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , População Rural/estatística & dados numéricos , Estudos Soroepidemiológicos , Sri Lanka/epidemiologia , População Urbana/estatística & dados numéricos , Adulto Jovem
12.
Zhonghua Gan Zang Bing Za Zhi ; 27(4): 241-243, 2019 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-31082332

RESUMO

The mechanism of innate and adaptive immune responses to chronic infections with hepatotropic viruses (HBV, HCV) was studied in 2018. Its mechanism elucidated the dysregulation of natural killer (NK) cells, monocytes, B cells and T cells. In addition, a new target for immune regulation of HBV infection (TLR3/OX40L) was introduced. The discovery of new NK cell immune checkpoints, the involvement of mononuclear macrophages in liver failure and inflammation, sex hormone affecting intrahepatic-resistant bacterial infection through the regulation of humoral immunity, and the communication mechanism between liver and other immune organs have enriched people's understanding of liver immunology and its clinical significance.


Assuntos
Hepatite A/imunologia , Hepatovirus/imunologia , Células Matadoras Naturais , Fígado/imunologia , Humanos , Linfócitos T
13.
Viruses ; 11(3)2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30897727

RESUMO

Hepatitis A virus (HAV) outbreaks among men who have sex with men (MSM) have been reported worldwide and associated primarily with sexual transmission through oral-anal sex. Here, we provide the molecular and evolutionary description of a European strain, linked to HAV outbreaks among MSM, detected in a Brazilian homosexual couple. Bayesian analysis provided evidence that the viral isolates were introduced in Brazil from Spain between the end of 2016 and the beginning of 2017.


Assuntos
Surtos de Doenças , Vírus da Hepatite A/genética , Hepatite A/transmissão , Homossexualidade Masculina , Adulto , Anticorpos Antivirais/sangue , Teorema de Bayes , Brasil , Evolução Molecular , Hepatite A/diagnóstico , Hepatite A/imunologia , Vírus da Hepatite A/imunologia , Humanos , Masculino , Fatores de Risco , Espanha/epidemiologia
14.
Future Microbiol ; 14: 247-258, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30663895

RESUMO

AIM: We evaluated the accuracy of a commercial rapid immunochromatographic test (rapid test [RT]) for hepatitis A (HA) diagnosis and epidemiological studies. MATERIALS & METHODS: The accuracy of a RT was evaluated in laboratory and in field conditions. Predictive modeling estimated the test performance in a hypothetical population. RESULTS: The RT showed sensitivities of 66-86%, and specificities of 21-100%, depending on the antibody isotype (IgM or IgG) analyzed and prevalence of infection. CONCLUSION: The RT is a good alternative for diagnostic in HA outbreaks. The predictive model indicates that it should not be used alone for HA diagnosis in low prevalence populations. These data can be used in the future to strengthen decision-making during the implementation of rapid diagnostic methods in health services.


Assuntos
Anticorpos Antivirais/sangue , Cromatografia de Afinidade/métodos , Testes Diagnósticos de Rotina/métodos , Hepatite A/diagnóstico , Hepatite A/imunologia , Adolescente , Adulto , Idoso , Brasil , Tomada de Decisão Clínica , Reações Cruzadas , Surtos de Doenças , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Serviços de Saúde , Hepatite A/epidemiologia , Vacinas contra Hepatite A , Humanos , Imunoglobulina G/sangue , Isotipos de Imunoglobulinas , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Sensibilidade e Especificidade , Estudos Soroepidemiológicos , Adulto Jovem
16.
EBioMedicine ; 39: 348-357, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30472089

RESUMO

BACKGROUND: A huge outbreak in the men-having-sex-with-men (MSM) has hit Europe during the years 2016-2018. Outbreak control has been hampered by vaccine shortages in many countries, and to minimize their impact, reduction of antigen doses has been implemented. However, these measures may have consequences on the evolution of hepatitis A virus (HAV), leading to the emergence of antigenic variants. Cases in vaccinated MSM patients have been detected in Barcelona, opening the possibility to study HAV evolution under immune pressure. METHODS: We performed deep-sequencing analysis of ten overlapping fragments covering the complete capsid coding region of HAV. A total of 14578255 reads were obtained and used for the analysis of virus evolution in vaccinated versus non-vaccinated patients. We estimated maximum and minimum mutation frequencies, and Shannon entropy in the quasispecies of each patient. Non-synonymous (NSyn) mutations affecting residues exposed in the capsid surface were located, with respect to epitopes, using the recently described crystal structure of HAV, as an indication of its potential role in escaping to the effect of vaccines. FINDINGS: HAV evolution at the quasispecies level, in non-vaccinated and vaccinated patients, revealed higher diversity in epitope-coding regions of the vaccinated group. Although amino acid replacements occurring in and around the epitopes were observed in both groups, their abundance was significantly higher in the quasispecies of vaccinated patients, indicating ongoing processes of fixation. INTERPRETATION: Our data suggest positive selection of antigenic variants in some vaccinated patients, raising concerns for new vaccination polices directed to the MSM group.


Assuntos
Proteínas do Capsídeo/genética , Vírus da Hepatite A/imunologia , Hepatite A/epidemiologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Adulto , Proteínas do Capsídeo/imunologia , Surtos de Doenças , Europa (Continente)/epidemiologia , Evolução Molecular , Hepatite A/imunologia , Hepatite A/virologia , Antígenos da Hepatite A/genética , Antígenos da Hepatite A/metabolismo , Vírus da Hepatite A/genética , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , Quase-Espécies , Análise de Sequência de RNA/métodos , Vacinação
17.
Saudi J Gastroenterol ; 25(1): 67-70, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30117491

RESUMO

Acute hepatitis A viral (HAV) infection is rare in the liver transplant population due to recommended pre-transplant vaccinations. We report a case of acute hepatitis A infection in a liver transplant recipient. This individual had immunity to hepatitis A with protective IgG antibodies and presented with abnormal liver biochemistry in the post-transplant in-patient setting. Hepatitis A infection was confirmed by positive HAV IgM whereas other etiologies, including acute cellular rejection, were ruled out by laboratory tests and liver biopsies. He was treated conservatively with supportive care and liver enzymes recovered to normal baseline. Despite adequate pre-transplant immunity, in the post-transplant setting there may be loss of protective immunity due to profound immunosuppression and hence hepatitis A should remain an important differential diagnosis in the setting of acute hepatitis.


Assuntos
Vírus da Hepatite A Humana/imunologia , Hepatite A/imunologia , Transplante de Fígado/efeitos adversos , Fígado/virologia , Doença Aguda , Diagnóstico Diferencial , Hepatite A/epidemiologia , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Imunossupressão/efeitos adversos , Fígado/química , Fígado/enzimologia , Transplante de Fígado/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/métodos , Resultado do Tratamento , Vacinação/normas , Cobertura Vacinal/normas
18.
Hum Vaccin Immunother ; 15(2): 420-425, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30260275

RESUMO

Backgroud: Beijing was hyper-endemic for hepatitis A until the 1990s and has been vaccinating against hepatitis A since 1994. The objective is to study the epidemiology and changes of antibody level of hepatitis A from 1990 to 2017. METHODS: A multistage randomized cluster sampling serological cross-sectional study was conducted in individuals over one year old in 1992, 2006 and 2014 in Beijing. Venous blood samples were collected to test anti-HAV antibody. The incidence data of hepatitis A were obtained from National Notifiable Disease Reporting System (NNDRS) and CDC statistics in Beijing. The vaccination data of hepatitis A immunization were acquired from Beijing Immune Information System. RESULTS: From 1990 to 2017, the reported incidence rate of HAV in Beijing declined from 59.41/100,000 in 1990 to 0.80/100,000 in 2017. The average age of HAV infection was postponed from individuals under 20 years old to individuals over 20 years old. After hepatitis A vaccine was introduced to Beijing, the outbreak of hepatitis A decreased sharply. Adjusted anti-HAV positive rate in general population was 68.23%, 81.73% and 82.47% respectively in 1992, 2006 and 2014. Due to hepatitis A vaccination conducted in children, the anti-HAV positive rate in individuals under 20 years old increased from 1992 to 2014, while in individuals over 20, this rate was barely changed. The coverage rate in target population was higher than 99% after hepatitis A vaccine was integrated into Expanded Program on Immunization (EPI). CONCLUSION: Incidence rate of hepatitis A in Beijing has decreased dramatically from 1990 to 2017. Hepatitis A vaccine plays an important role in protecting individuals under 20 years old. A higher proportion of adults will be susceptible to hepatitis A virus due to the decay of antibodies as they grow up from childhood to adulthood, which may result in possible outbreak of hepatitis A.


Assuntos
Anticorpos Anti-Hepatite A/sangue , Hepatite A/epidemiologia , Hepatite A/imunologia , Programas de Imunização , Adolescente , Adulto , Pequim/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Vírus da Hepatite A , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Vacinação/estatística & dados numéricos , Vacinas contra Hepatite Viral/imunologia , Adulto Jovem
19.
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
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