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1.
Gastroenterol Hepatol ; 45(2): 99-105, 2022 Feb.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34023475

RESUMO

BACKGROUND: Acute hepatitis A is usually a self-limited viral disease but can be severe and even fatal in special groups of patients including those with chronic liver disease and recipients of liver transplantation. To take appropriate preventive measures, it is important to determine the immune status against the hepatitis A virus in patients at risk of grave clinical outcomes following infection. To assess the need for immunization against hepatitis A, we aimed to determine the immune status against hepatitis A in a population of liver transplant recipients. We also investigated the association between hepatitis A immune status and demographic factors such as age and sex, underlying liver disease, source of drinking water, geographical area of residence and socioeconomic status. METHODS: This cross-sectional study was performed on 242 recipients of allogenic liver transplants at Abu Ali Sina Organ Transplant Hospital in Shiraz, Iran, between January 2017 and April 2017. The level of immunity was assessed using hepatitis A antibody detection kits. RESULTS: The rate of immunity against hepatitis A was detected as 88.8% in our study population. In the multivariable logistic regression model, younger age (OR=1.175, P<0.001) and higher education level (OR=2.142, P=0.040) were the main determinants of non-immune status. However, hepatitis A immunity was independent of gender, monthly family income, water supply source, residential area and underlying liver disorder. CONCLUSION: Although a significant proportion of liver transplant recipients in this study showed evidence of natural immunity to hepatitis A, a considerable proportion of younger patients and those with a higher level of education were non-immune. The results of this study signify the importance of screening for hepatitis A immunity in this at-risk population of patients and the need for vaccinating non-immune patients.


Assuntos
Vírus da Hepatite A/imunologia , Hepatite A/imunologia , Transplante de Fígado , Transplantados , Doença Aguda , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Estudos Transversais , Escolaridade , Feminino , Anticorpos Anti-Hepatite A/análise , Humanos , Irã (Geográfico) , Transplante de Fígado/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Características de Residência , Fatores Sexuais , Classe Social , Abastecimento de Água , Adulto Jovem
2.
Cell Rep ; 36(4): 109438, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34320338

RESUMO

During microbial infection, bystander CD8+ T cells that are not specific to infecting pathogens can be activated by interleukin (IL)-15. However, the tissue-homing properties of bystander-activated CD8+ T cells have not been elucidated. Here, we examine the effects of IL-15 on the expression of chemokine receptors on CD8+ T cells and their migration. IL-15 upregulates CCR5 in memory CD8+ T cells in the absence of T cell receptor (TCR) stimulation and enhances CCR5-dependent migration. IL-15-induced CCR5 upregulation is abrogated by TCR stimulation, indicating that CCR5 is upregulated in bystander-activated CD8+ T cells. Moreover, CCR5 signals increase proliferation and cytotoxic protein expression in IL-15-treated memory CD8+ T cells, although the increase has a small extent. CCR5 upregulation in bystander-activated CD8+ T cells is associated with severe liver injury in patients with acute hepatitis A. Altogether, the results indicate that CCR5 upregulation by IL-15 mediates the migration of bystander-activated CD8+ T cells.


Assuntos
Linfócitos T CD8-Positivos/metabolismo , Movimento Celular , Memória Imunológica , Interleucina-15/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores CCR5/genética , Doença Aguda , Adulto , Animais , Morte Celular/genética , Proliferação de Células/genética , Feminino , Hepatite A/complicações , Hepatite A/genética , Hepatite A/imunologia , Humanos , Inflamação/complicações , Inflamação/imunologia , Inflamação/patologia , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Receptores CCR5/metabolismo , Receptores CCR7/metabolismo , Regulação para Cima/genética , Adulto Jovem
3.
Viruses ; 13(5)2021 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-34066709

RESUMO

Hepatitis A virus (HAV) infection is a common cause of acute viral hepatitis worldwide. Despite decades of research, the pathogenic mechanisms of hepatitis A remain incompletely understood. As the replication of HAV is noncytopathic in vitro, a widely accepted concept has been that virus-specific cytotoxic T cells are responsible for liver injury. However, accumulating evidence suggests that natural killer (NK) cells, NKT cells, and even non-HAV-specific CD8+ T cells contribute to liver damage during HAV infection. In addition, intrinsic death of virus-infected hepatocytes has been implicated as a cause of liver injury in a murine model of hepatitis A. Furthermore, genetic variations in host factors such as T cell immunoglobulin-1 (TIM1) and IL-18 binding protein (IL-18BP) have been linked to hepatitis A severity. This review summarizes the current knowledge of the mechanisms of hepatocellular injury in hepatitis A. Different mechanisms may be involved under different conditions and they are not necessarily mutually exclusive. A better understanding of these mechanisms would aid in diagnosis and treatment of diseases associated with HAV infection.


Assuntos
Vírus da Hepatite A/patogenicidade , Hepatite A/complicações , Hepatócitos/patologia , Fígado/lesões , Fígado/virologia , Animais , Carcinoma Hepatocelular/patologia , Hepatite A/imunologia , Hepatite A/fisiopatologia , Vírus da Hepatite A/imunologia , Hepatócitos/virologia , Humanos , Fígado/citologia , Neoplasias Hepáticas/patologia , Camundongos
4.
Nat Commun ; 12(1): 1439, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33664251

RESUMO

Treatment of advanced melanoma with combined PD-1/CTLA-4 blockade commonly causes serious immune-mediated complications. Here, we identify a subset of patients predisposed to immune checkpoint blockade-related hepatitis who are distinguished by chronic expansion of effector memory CD4+ T cells (TEM cells). Pre-therapy CD4+ TEM cell expansion occurs primarily during autumn or winter in patients with metastatic disease and high cytomegalovirus (CMV)-specific serum antibody titres. These clinical features implicate metastasis-dependent, compartmentalised CMV reactivation as the cause of CD4+ TEM expansion. Pre-therapy CD4+ TEM expansion predicts hepatitis in CMV-seropositive patients, opening possibilities for avoidance or prevention. 3 of 4 patients with pre-treatment CD4+ TEM expansion who received αPD-1 monotherapy instead of αPD-1/αCTLA-4 therapy remained hepatitis-free. 4 of 4 patients with baseline CD4+ TEM expansion given prophylactic valganciclovir and αPD-1/αCTLA-4 therapy remained hepatitis-free. Our findings exemplify how pathogen exposure can shape clinical reactions after cancer therapy and how this insight leads to therapeutic innovations.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Infecções por Citomegalovirus/tratamento farmacológico , Hepatite A/prevenção & controle , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Antivirais/uso terapêutico , Linfócitos T CD4-Positivos/transplante , Linfócitos T CD8-Positivos/imunologia , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/imunologia , Hepatite A/imunologia , Hepatite A/virologia , Humanos , Memória Imunológica/imunologia , Melanoma/tratamento farmacológico , Valganciclovir/uso terapêutico , Carga Viral
5.
Sci Rep ; 11(1): 4778, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637853

RESUMO

This study determined the prevalence of total hepatitis A antibody (anti-HAV) among 5-7 years old children and their mothers in the whole Cambodia, using a nationwide study, and examined the differences between the two cohorts. A total of 4535 dried blood spot-driven (DBS) samples (2021 mothers and their 2514 children of 5-7 years old) and the concomitant 922 whole blood samples (subset of the whole participants) were collected using a multistage random sampling strategy throughout Cambodia in 2017. Total anti-HAV was detected using the chemiluminescence enzyme immunoassay method. Compared to gold standard whole blood samples, the sensitivity and specificity of DBS mediated anti-HAV detection were 94.8% and 98%, respectively. Total anti-HAV prevalence among mothers was 91.2% (95%CI: 90.0-92.5%), and that of their children was 31.5% (95%CI: 29.7-33.3%). In our study, the low prevalence of total anti-HAV among children indicates the country's improvement of safe water and food supply, hygiene and sanitation. If the hygiene and sanitation are consistently improved in Cambodia, the prevalence might be no longer increased when the children become adults.


Assuntos
Anticorpos Anti-Hepatite A/sangue , Vírus da Hepatite A Humana/isolamento & purificação , Hepatite A/sangue , Camboja/epidemiologia , Criança , Pré-Escolar , Feminino , Hepatite A/epidemiologia , Hepatite A/imunologia , Anticorpos Anti-Hepatite A/imunologia , Vírus da Hepatite A Humana/imunologia , Humanos , Masculino , Prevalência , Estudos Soroepidemiológicos
6.
J Med Virol ; 93(6): 3991-3994, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33448443

RESUMO

The hepatitis A vaccine is recommended for all children greater than or equal to 1 year of age, however, the duration of vaccine protection is unknown and protection through adulthood is crucial to prevent symptomatic hepatitis later in life. We report on 25 years of follow-up of a cohort of Alaska Native individuals who were vaccinated in early childhood. We assessed the duration of vaccine protection by calculating the geometric mean concentration and proportion of participants with protective levels of IgG antibody to hepatitis A virus (anti-HAV) (≥20 mIU/mL) every 2 to 3 years. We estimated the amount of time until the anti-HAV dropped below protective levels using survival analyses. At 25 years, 43 of the original 144 participants were available, mean anti-HAV levels were 91.5 mIU/mL, and 35 (81.4%) had protective levels of anti-HAV. Using data from all persons and all time points, a survival analysis estimated 78.7% of participants had protective levels of anti-HAV at 25 years. The high level of protective antibodies in this cohort indicate that supplemental doses of hepatitis A vaccine are not needed 25 years after completion of the vaccine series.


Assuntos
Anticorpos Anti-Hepatite A/sangue , Vacinas contra Hepatite A/imunologia , Hepatite A/imunologia , Hepatite A/prevenção & controle , Imunogenicidade da Vacina , Alaska/epidemiologia , Nativos do Alasca/estatística & dados numéricos , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Hepatite A/sangue , Hepatite A/epidemiologia , Vacinas contra Hepatite A/administração & dosagem , Humanos , Imunização Secundária , Imunoglobulina G/sangue , Masculino , Fatores de Tempo , Vacinação/estatística & dados numéricos
7.
Turk J Med Sci ; 51(1): 382-384, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-32718125

RESUMO

Background/aim: COVID-19 has become the biggest health problem of this century. It has been hypothesized that immunity against hepatitis A virus (HAV) may provide protection from COVID- 19. Materials and methods: As of 10June 2020, the infection had spread to 213 countries, with 7.3 million people infected and 413,733 dead. This data was combined with the World Health Organization susceptibility classification on the worldwide prevalence of HAV, and the relationship between HAV susceptibility and COVID-19 mortality were analyzed. Results: When the data from 213 countries were analyzed, it was found that there was a significant increasing trend in COVID-19 mortality rates by HAV susceptibility (P <0.001). Using a cut-off of 200/million population, the mortality risk associated with living in a more susceptible country (medium/high) was 27.8 times higher (95% CI for OR: 3.6­213.2) Conclusion: The results of this study showed that, despite confounding factors in different countries, hepatitis A susceptibility of the population may have been correlated with COVID-19 mortality. This observation needs to be confirmed by further studies.


Assuntos
COVID-19/mortalidade , Suscetibilidade a Doenças/imunologia , Hepatite A/imunologia , COVID-19/imunologia , Suscetibilidade a Doenças/epidemiologia , Hepatite A/epidemiologia , Vírus da Hepatite A/imunologia , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Navios
8.
Hepatology ; 73(4): 1251-1260, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32592242

RESUMO

BACKGROUND AND AIMS: China has conducted surveillance for hepatitis A since 1990, and hepatitis A was highly-to-intermediately endemic in 1992 when a Chinese hepatitis A vaccine (HepA) was licensed and introduced as a family-pay vaccine. In 2008, HepA was introduced into the Expanded Program on Immunization as a free childhood vaccine. APPROACH AND RESULTS: Three nationally representative surveys conducted in 1992, 2006, and 2014 assessed hepatitis B serology. The 1992 survey included hepatitis A virus (HAV) serology, and we tested sera from the 2006 and 2014 surveys for HAV antibodies. We used surveillance, seroprevalence, and vaccination status data to describe the changing epidemiology of hepatitis A in China from 1990 through 2014. Before HepA licensure, anti-HAV seroprevalence was 60% at 4 years of age, 70% at 10 years, and 90% at 59 years; incidence was 52/100,000 and peaked at 4 years. In 2006, after >10 years of private sector vaccination, HepA coverage was <30% among children <5 years, and incidence was 5.4/100,000 with a peak at 10 years. In 2014, coverage was >90% among children under 5 years; incidence was 1.9/100,000. Individuals born before the national introduction of HepA (1988-2004) had lower anti-HAV seroprevalence than earlier and later birth cohorts. CONCLUSIONS: The incidence of hepatitis A declined markedly following HepA introduction and improvement of sanitation and hygiene. The emerging epidemiology is consistent with disease-induced immunity having been replaced by vaccine-induced immunity, resulting in a low incidence of hepatitis A. Catch-up HepA campaigns to close the immunity gap among the 1998-2004 birth cohorts should be considered.


Assuntos
Vacinas contra Hepatite A/uso terapêutico , Vírus da Hepatite A Humana/imunologia , Hepatite A/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , China/epidemiologia , Notificação de Doenças/estatística & dados numéricos , Feminino , Hepatite A/imunologia , Hepatite A/prevenção & controle , Anticorpos Anti-Hepatite A/imunologia , Humanos , Incidência , Lactente , Masculino , Vacinação em Massa/estatística & dados numéricos , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Estudos Soroepidemiológicos , Adulto Jovem
9.
J Med Virol ; 93(6): 3666-3671, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32986240

RESUMO

Hepatitis A infections still represent a major global health concern. During the past years, a transition pattern of the hepatitis A epidemiology was noted in many parts of the world. In Tunisia, there is not a recent survey on age-specific hepatitis A virus seroprevalence. This study aimed to investigate the seroprevalence of hepatitis A virus infection in Central-West Tunisia, representative of regions with lowest socioeconomic level in the country, before vaccine implementation. Sera obtained from the blood samples of subjects were screened for the detection of hepatitis A virus. The seroprevalence was evaluated by detection of total antibodies to hepatitis A virus using commercially available immunoassay kits. A total of 1379 subjects, aged 5-75 years (mean age: 29.0 ± 17.3 years) were studied. The global anti-hepatitis A virus seroplevalence was 84.7% (95% confidence interval: [82.6-86.5]). A higher hepatitis A virus seroprevalence was showed in subjects aged 10-14 years compared to those aged less than 10 years (50.0% vs. 31.0%). In subjects aged 20-29 years, a rapid increase in the hepatitis A virus prevalence was noted; it reached 97.0%. The seroprevalence of anti-hepatitis A virus differed by zone of residence (81.1% in rural area vs. 72.4% in urban area, p = .005) and increased significantly with lower level of education (p = .019). There was no statistical significant seroprevalence difference between male and female: 84.2% versus 85.2%, respectively. Our study confirm the transition pattern of the hepatitis A virus endemicity in Tunisia from high to intermediate and provide an evaluation of the hepatitis A virus epidemiological situation before vaccine implementation.


Assuntos
Vírus da Hepatite A/imunologia , Hepatite A/epidemiologia , Hepatite A/imunologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Hepatite A/sangue , Anticorpos Anti-Hepatite A/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Tunísia/epidemiologia , Adulto Jovem
10.
Infect Dis Now ; 51(1): 94-96, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33022294

RESUMO

OBJECTIVES: We aimed to evaluate the immune response of HIV-1 positive patients to a single injection of HAV vaccine in a context of vaccine shortage during the 2017 European outbreak. METHODS: We retrospectively enrolled all HIV-1 positive patients vaccinated by a single injection of HAV vaccine Vaqta 50®. HAV serology was performed before and>30 days after the vaccine injection. RESULTS: Among the 73 patients, HIV-1 viral load was≤50 copies/mL in 93.2% of the cases. Medians of CD4 and median ratio of T CD4/CD8 cells were 658/mm3 and 0.9, respectively. A low immune response rate (59.7%) was observed among the patients. Responders had a significantly higher CD4/CD8 cell ratio than non-responders. CONCLUSIONS: A serologic control should be recommended in this population in the event of a single injection vaccination schedule. During routine follow-up, and prior to any untoward event, physicians should assess the vaccination coverage of HIV-infected patients.


Assuntos
Infecções por HIV/imunologia , Vacinas contra Hepatite A/imunologia , Hepatite A/prevenção & controle , Adulto , Contagem de Linfócito CD4/métodos , Relação CD4-CD8/métodos , Surtos de Doenças , Hepatite A/epidemiologia , Hepatite A/imunologia , Anticorpos Anti-Hepatite A/sangue , Vacinas contra Hepatite A/administração & dosagem , Humanos , Imunidade/imunologia , Esquemas de Imunização , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Viral
11.
Int J STD AIDS ; 32(3): 276-279, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33334270

RESUMO

Within the UK, the majority of hepatitis A occurs in high risk groups such as men who have sex with men (MSM). It has been estimated that 70% of MSM need immunity to provide adequate herd immunity. We aimed to estimate the proportion of hepatitis A susceptibility in MSM throughout a 10-year period (2010-2019), and explore associated demographic factors. Using our Electronic Patient Record system, we extracted anonymous clinical data between for MSM at their first attendance; including hepatitis A IgG result, age, country of birth and diagnosis of an STI. Overall, 1401/6884(20%) were tested for hepatitis A IgG at their first attendance, with 626/1401 (45%, 95% CI = 42%-47%) showing susceptibility. Testing rates increased between 2010-2019 (OR = 67.79, 95%CI = 39.09-117.60, p = <0.0001); however, susceptibility remained similar (OR = 0.98, 95%CI = 0.33-2.89, p = 0.98). MSM aged 35 and under had significantly higher susceptibility vs MSM aged over 35 (OR 3.4176, 95%CI = 2.71-4.31, p = <0.0001). UK-born had significantly higher susceptibility vs non-UK born (OR 1.5, 95%CI = 1.2147-1.8618, p = 0.0002). Susceptibility of hepatitis A in MSM may be higher than necessary to control future outbreaks. It is important that effective targeting of MSM, particularly young MSM, occur at all levels of healthcare and not solely rely on opportunistic presentation at a sexual health clinic.


Assuntos
Hepatite A/diagnóstico , Hepatite A/imunologia , Homossexualidade Masculina/estatística & dados numéricos , Programas de Rastreamento/métodos , Adulto , Idoso , Infecções por HIV/epidemiologia , Hepatite A/epidemiologia , Anticorpos Anti-Hepatite A/sangue , Humanos , Imunidade Coletiva , Masculino , Pessoa de Meia-Idade , Comportamento Sexual , Saúde Sexual , Reino Unido/epidemiologia , Vacinação
12.
J Med Virol ; 93(6): 3656-3665, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32975838

RESUMO

Fulminant hepatic failure (FHF) is a lethal manifestation of hepatitis A virus (HAV) infection, whose underlying mechanisms are poorly understood. We aimed to evaluate the importance of the modulation of the RANTES-chemokine receptor type 5 (CCR5) signaling axis and its immunomodulatory effects in directing hepatitis A disease pathogenesis using an in silico, in vitro and patient cohort-based approach. In silico interaction studies were performed using computation approaches with suitable software. Differential expression of relevant cytokines and immune cell markers were studied using real-time quantitative reverse transcription PCR (qRT-PCR), enzyme-linked immunosorbent assay, and flow-cytometry-based methods. In the HepG2 cell line, we studied inflammatory responses and susceptibility to HAV infection following RANTES stimulation and antibody blockade of CCR5. The HAV-VP3 region exhibited high interaction in CCR5: HAV complexes. RANTES levels were significantly increased in FHF cases. Reduced monocyte and T-cell activation were observed in FHF cases. RANTES expression inversely correlated with viremia but positively correlated with proinflammatory responses. Hyper Th1-biased immune responses, marked by high interleukin (IL)-12/IL-10 ratio were observed in FHF cases, which were also characterized by upregulated tumor necrosis factor-alpha (TNF-α) expression and reduced interferon-gamma expression. In vitro, RANTES was protective against HAV infection but resulted in upregulated TNF-α expression. Although viral load increased upon the regulation of inflammatory responses by CCR5 blocking, it was still significantly lower compared to control HAV-infected cells. Our study suggests the importance of RANTES-CCR5 signaling and linked-immunomodulation in HAV disease pathogenesis, as well as highlights the utility of CCR5 antagonists as a risk-reduction strategy in FHF patients. Our findings, therefore, have important implications for the management of high-risk HAV infections.


Assuntos
Quimiocina CCL5/genética , Quimiocina CCL5/imunologia , Vírus da Hepatite A/imunologia , Hepatite A/imunologia , Receptores CCR5/genética , Receptores CCR5/imunologia , Adulto , Quimiocina CCL5/farmacologia , Estudos de Coortes , Simulação por Computador , Feminino , Células Hep G2 , Hepatite A/virologia , Hepatócitos/efeitos dos fármacos , Humanos , Imunomodulação , Falência Hepática Aguda , Masculino , Pessoa de Meia-Idade , Prognóstico , Carga Viral
13.
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
14.
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
16.
J Viral Hepat ; 27(11): 1234-1242, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32564517

RESUMO

Although a high seroprevalence of antibodies against hepatitis A virus (HAV) has been estimated in Central Africa, the current status of both HAV infections and seroprevalence of anti-HAV antibodies remains unclear due to a paucity of surveillance data available. We conducted a serological survey during 2015-2017 in Gabon, Central Africa, and confirmed a high seroprevalence of anti-HAV antibodies in all age groups. To identify the currently circulating HAV strains and to reveal the epidemiological and genetic characteristics of the virus, we conducted molecular surveillance in a total of 1007 patients presenting febrile illness. Through HAV detection and sequencing, we identified subgenotype IIA (HAV-IIA) infections in the country throughout the year. A significant prevalence trend emerged in the young child population, presenting several infection peaks which appeared to be unrelated to dry or rainy seasons. Whole-genome sequencing and phylogenetic analyses revealed local HAV-IIA evolutionary events in Central Africa, indicating the circulation of HAV-IIA strains of a region-specific lineage. Recombination analysis of complete genome sequences revealed potential recombination events in Gabonese HAV strains. Interestingly, Gabonese HAV-IIA possibly acquired the 5'-untranslated region (5'-UTR) of the rare subgenotype HAV-IIB in recent years, suggesting the present existence of HAV-IIB in Central Africa. These findings indicate a currently stable HAV-IIA circulation in Gabon, with a high risk of infections in children aged under 5 years. Our findings will enhance the understanding of the current status of HAV infections in Central Africa and provide new insight into the molecular epidemiology and evolution of HAV genotype II.


Assuntos
Vírus da Hepatite A , Hepatite A , África Central , Criança , Feminino , Gabão , Genótipo , Hepatite A/imunologia , Anticorpos Anti-Hepatite A , Vírus da Hepatite A/isolamento & purificação , Humanos , Masculino , Filogenia , Estudos Soroepidemiológicos
17.
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 , Proteína C1 de Niemann-Pick , Transcriptoma , Proteínas Virais de Fusão/metabolismo , Vírion/metabolismo , Internalização do Vírus
18.
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
19.
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
20.
Ann Glob Health ; 86(1): 29, 2020 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-32211299

RESUMO

Background: Hepatitis A virus (HAV) and hepatitis E virus (HEV) are transmitted by the fecal-oral route and are responsible for epidemic and sporadic outbreaks of acute hepatitis in low-income countries like Bangladesh. Objective: The purpose of this study was to describe the seroprevalence of acute hepatitis due to HAV and HEV infection in Bangladesh. Methods: The nationwide food-borne illness surveillance started in 2014 at 10 different hospitals which covered seven divisions of Bangladesh. Blood samples were collected from suspected acute hepatitis cases and screened for the anti-HAV IgM and anti-HEV IgM using enzyme-linked immunosorbent assay (ELISA). Participants' socioeconomic status, clinical, sanitation and food history were recorded. Multivariate logistic regression was performed to determine the risk factors associated with HAV and HEV infection. Findings: A total of 998 patients were enrolled and tested for both HAV and HEV. Among these, 19% (191/998) were identified as HAV positive and 10% (103/998) were HEV positive. The median age was 12 years and 25 years for HAV and HEV positive patients, respectively. The prevalence of HAV was higher among the females (24.9%), whereas HEV was higher among males (11.2%). The highest occurrence of HAV was observed among children while HEV was most prevalent in the 15-60 years age group (12.4%). Conclusion: Through our nationwide surveillance, it is evident that hepatitis A and hepatitis E infection is common in Bangladesh. These data will be useful towards planning preventive and control measures by strengthening the sanitation programs and vaccination strategies in Bangladesh.


Assuntos
Hepatite A/epidemiologia , Hepatite E/epidemiologia , Doença Aguda , Adolescente , Adulto , Distribuição por Idade , Bangladesh/epidemiologia , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Hepatite A/imunologia , Anticorpos Anti-Hepatite A/imunologia , Anticorpos Anti-Hepatite/imunologia , Hepatite E/imunologia , Humanos , Imunoglobulina M/imunologia , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Estudos Soroepidemiológicos , Distribuição por Sexo , Adulto Jovem
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