Increase in Hepatitis A Cases Linked to Imported Strains to Rio de Janeiro, Brazil: A Cross-Sectional Study.

This study aims to evaluate the epidemiological and molecular features associated with HAV transmission in adults in Rio de Janeiro during a period of increased registered cases of HAV (2017-2018). Socio-epidemiological data and serum samples from anti-HAV IgM+ individuals were obtained. HAV RNA was RT-PCR amplified and sequenced for further phylogenetic and phylogeographic analyses. From fifty-two HAV IgM+ individuals, most were men (78.85%; p = 0.024), aged 20-30 years old (84.61%; p < 0.001), resided in the Rio de Janeiro north zone (31/52; 59.62%; p = 0.001), and are men who have sex with men (MSM) (57.69%; p = 0.002). Sexual practices were more frequent (96%) than others risk factors (food-borne (44%), water-borne (42.31%), and parenteral (34.62%)). Individuals who traveled to endemic regions had a 7.19-fold (1.93-36.04; p < 0.01) increased risk of HAV. Phylogenetic analysis revealed four distinct clades of subgenotype IA, three of them comprised sequences from European/Asian MSM outbreaks and one from Brazilian endemic strains. Bayesian Inference showed that the imported strains were introduced to Brazil during large mass sportive events. Sexual orientation and sexual practices may play a role in acquiring HAV infection. Public policies targeting key populations must be implemented to prevent further dissemination of HAV and other STIs.

Immunity to hepatitis A virus in liver transplant recipients: A population-based study in Iran / Inmunidad al virus de la hepatitis A en receptores de trasplante de hígado: un estudio poblacional en Irán

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.

Antecedentes: La hepatitis A aguda suele ser una enfermedad viral autolimitada, pero puede ser grave e incluso mortal en grupos especiales de pacientes, incluidos aquellos con enfermedad hepática crónica y los receptores de un trasplante de hígado. Para tomar las medidas preventivas adecuadas, es importante determinar el estado inmunológico frente al virus de la hepatitis A en pacientes con riesgo de sufrir resultados clínicos graves después de la infección. Para evaluar la necesidad de inmunización contra la hepatitis A, nuestro objetivo fue determinar el estado inmunológico contra la hepatitis A en una población de receptores de trasplante de hígado. También investigamos la asociación entre el estado inmunológico de la hepatitis A y factores demográficos como la edad y el sexo, la enfermedad hepática subyacente, la fuente de agua potable, el área geográfica de residencia y el nivel socioeconómico.Métodos: este estudio transversal se realizó en 242 receptores de trasplantes de hígado alogénicos en el hospital de trasplantes de órganos “Abu Ali Sina” en Shiraz, Irán, entre enero de 2017 y abril de 2017. El nivel de inmunidad se evaluó mediante kits de detección de anticuerpos contra la hepatitis A.Resultados: La tasa de inmunidad contra la hepatitis A se detectó como 88,8% en nuestra población de estudio. En el modelo de regresión logística multivariable, la edad más joven (OR=1,175, p<0,001) y el nivel de educación superior (OR=2,142, p=0,040) fueron los principales determinantes del estado no inmunitario. Sin embargo, la inmunidad contra la hepatitis A fue independiente del sexo, el ingreso familiar mensual, la fuente de suministro de agua, el área residencial y la enfermedad hepática subyacente.

Immunity to hepatitis A virus in liver transplant recipients: A population-based study in Iran.

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.

Eficacia, seguridad y recomendaciones de uso de vacunas contra hepatitis A en niños expuestos e infectados por virus de inmunodeficiencia humana (VIH) / Efficacy, safety and usage recommendations of vaccines against hepatitis A in children exposed and infected by the immunodeficiency virus human (HIV)

ANTECEDENTES: La inmunización de niños infectados o expuestos al VIH representa una estrategia fundamental para reducir la morbilidad y mortalidad por enfermedades infecciosas prevenibles por vacunación, cuyo riesgo es marcadamente elevado en esta población debido al compromiso del sistema inmune. Sin embargo, una menor cantidad de niños con VIH logran inmunidad protectora y aquellos que lo hacen pueden experimentar una disminución mayor y más rápida de la inmunidad. La importancia de prevenir la infección por el virus de la hepatitis A (VHA) en el contexto de la coinfección con VIH radica en que la inmunosupresión asociada al VIH puede incrementar la duración, virulencia y patogenicidad del VHA, a su vez que la infección por VHA puede afectar el curso de la enfermedad por VIH. OBJETIVO: Describir la evidencia científica disponible en relación a la eficacia, seguridad y recomendaciones de uso de vacunas contra hepatitis A en niños expuestos e infectados por virus de inmunodeficiencia humana (VIH). OBJETIVO: Describir la evidencia científica disponible en relación a la eficacia, seguridad y recomendaciones de uso de vacunas contra hepatitis A en niños expuestos e infectados por virus de inmunodeficiencia humana (VIH). MÉTODO: Búsqueda electrónica de estudios publicados en español o inglés en PubMed, Cochrane Library, Web of Science y LILACS hasta el 27 de noviembre de 2021. Adicionalmente, se realizó una búsqueda en PubMed y repositorios de organismos elaboradores de Guías de Práctica Clínica. La selección de estudios fue desarrollada por un solo revisor. RESULTADOS: Se incluyeron diez estudios para la evaluación de la eficacia y seguridad y cuatro documentos para la evaluación de las recomendaciones de uso de vacunas contra hepatitis A en niños expuestos e infectados por virus de inmunodeficiencia humana (VIH). Seroprevalencia contra VHA al inicio del estudio: El porcentaje de participantes con presencia de anticuerpos contra VHA al inicio de estudio fue generalmente bajo (mediana: 12.2%; rango: 2.9% a 48.3%). Inmunogenicidad de las vacunas contra VHA: Tras una primera dosis de inmunización contra el VHA, la seroconversión se produjo en un 68.6% a 87.1% de participantes (mediana: 76.7%). Tras una segunda dosis, el porcentaje de seroconversión se ubicó en el rango de 84.5% a 100% (mediana: 98%). El porcentaje o recuento inicial de CD4 fue un importante predictor de la concentración de anticuerpos. Un único estudio evaluó el efecto de una tercera dosis de vacuna contra el VHA aplicada 18 meses después de la segunda dosis, obteniendo seropositividad de 97%, con un 76% con altos títulos de anticuerpos (≥ 250 mIU/mL). El título medio de anticuerpos fue mayor con tres dosis, comparado con dos dosis de vacuna (602 vs. 287 mUI / ml; p< 0,0001). Eventos adversos asociados a la vacunación: La vacunación contra el VHA en niños infectados o expuestos al VIH produjo eventos adversos leves y en su mayoría autolimitados. La carga viral media de VIH no varió en los niños con VIH vacunados. Duración de la protección después de la inmunización: Se evaluó la presencia de anticuerpos contra el VHA habiendo transcurrido 18 meses después de la aplicación de la segunda dosis de la vacuna. De 120 participantes, 108 (90%) tenían títulos de anticuerpos protectores persistentes, mientras que 12 (10%) no los tenían. Entre quienes no los tenían, dos participantes nunca presentaron respuesta protectora, nueve tuvieron títulos de anticuerpos de ≥ 20 a ≤ 250 mUI/mL tras la segunda dosis, y uno tuvo títulos de anticuerpos de 329 mUI/mL tras la segunda dosis. Los sujetos con bajas respuestas de anticuerpos después de dos dosis de la vacuna contra el VHA tuvieron menor probabilidad de mantener seropositividad 18 meses después que aquellos con altas respuestas de anticuerpos (p= 0.0003). Recomendaciones sobre la vacunación contra VHA en niños con VIH: El NIH de Estados Unidos, y el Ministerio de Salud y Protección Social de Colombia recomiendan dos dosis de vacunas contra VHA en niños con VIH a los 12 y 18 meses. El Ministerio de Salud Pública de Ecuador recomienda solo una dosis a los 12 meses. La Organización Mundial de la Salud recomienda la inmunización contra VHA con un esquema de dos dosis en grupos de riesgo de contraer hepatitis A e inmunodeprimidos. CONCLUSIONES: En los diferentes estudios, la seroprevalencia inicial de anticuerpos contra el virus de la hepatitis A (VHA) fue muy baja, con una mediana de 12.2%, lo cual indica una gran proporción de niños infectados o expuestos a VIH susceptibles a infección por VHA. La aplicación de una primera dosis de vacuna contra VHA produjo una mediana de seroconversión de 76.7%, mientras que una segunda dosis alcanzó una mediana de seroconversión del 98%. El estado inicial de linfocitos T CD4+ fue un importante predictor de la concentración de anticuerpos contra el VHA tras la inmunización. Un mayor recuento o porcentaje inicial de CD4 se asoció con mayor seroconversión, títulos de anticuerpos más altos y mayor probabilidad de mantener seropositividad 18 meses después de la segunda dosis. Resultados de un único estudio muestran que 18 meses después de la aplicación de la segunda dosis de la vacuna contra VHA, un 8.3% de niños dejaron de tener anticuerpos protectores contra el VHA. Resultados de un único estudio muestran que la aplicación de una tercera dosis de vacuna contra VHA 18 meses después de la segunda dosis no alteró el porcentaje personas con seroconversión, pero produjo mayores concentraciones de anticuerpos que quienes solo recibieron dos dosis. La vacunación contra el VHA en niños infectados o expuestos al VIH produjo eventos adversos leves y en su mayoría autolimitados. La carga viral media de VIH no varió en los niños con VIH vacunados. El NIH de Estados Unidos y el Ministerio de Salud y Protección Social de Colombia recomiendan dos dosis de vacunas contra VHA en niños con VIH a los 12 y 18 meses. El Ministerio de Salud Pública de Ecuador recomienda solo una dosis a los 12 meses. La Organización Mundial de la Salud recomienda la inmunización contra VHA con un esquema de dos dosis en grupos de riesgo de contraer hepatitis A e inmunodeprimidos.

Plasmonic Metasurfaces Based on Pyramidal Nanoholes for High-Efficiency SERS Biosensing.

An inverted pyramidal metasurface was designed, fabricated, and studied at the nanoscale level for the development of a label-free pathogen detection on a chip platform that merges nanotechnology and surface-enhanced Raman scattering (SERS). Based on the integration and synergy of these ingredients, a virus immunoassay was proposed as a relevant proof of concept for very sensitive detection of hepatitis A virus, for the first time to our best knowledge, in a very small volume (2 µL), without complex signal amplification, allowing to detect a minimal virus concentration of 13 pg/mL. The proposed work aims to develop a high-flux and high-accuracy surface-enhanced Raman spectroscopy (SERS) nanobiosensor for the detection of pathogens to provide an effective method for early and easy water monitoring, which can be fast and convenient.

Mechanisms of Hepatocellular Injury in Hepatitis A.

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.

Nationwide seroprevalence of hepatitis A in South Korea from 2009 to 2019.

Hepatitis A, an acute type of hepatitis caused by the hepatitis A virus, occurs worldwide. Following the 2009 hepatitis A epidemic in South Korea, patient outbreak reports were collectively converted to an "all-patient report" in 2011, and national immunization programs were introduced for children in 2015. In this study, we aimed to analyze the changes and characteristics of hepatitis A antibody titers in South Korea following the epidemic. The results of hepatitis A antibody tests performed at clinical laboratories from 2009 to 2019 were analyzed based on year, age, region, sex, and medical institution. The average 2009-2018 positive anti-hepatitis A virus immunoglobulin G rate was 51.8%, but it increased (56.06%) in 2019. Significantly different antibody-positive rates were observed based on age: <10 years, 54.5%; 20-29 years, 19.5%; ≥50 years, almost 100%. The positive rate of individuals in their teens and 20s gradually increased, whereas that of those in their 30s and 40s gradually decreased. Males had higher antibody-positive rates than females, and samples from higher-level general hospitals exhibited higher antibody rates. The positive anti-hepatitis A virus immunoglobulin M rates gradually decreased after 2009 and were <1% after 2012. However, a high positive rate of 3.69% was observed in 2019 when there was an epidemic. Anti-hepatitis A virus immunoglobulin G-positive rates were similar throughout the year, but the anti-hepatitis A virus immunoglobulin M-positive rates increased from January, peaked in April, and decreased from July, exhibiting distinct seasonality. This is considered to be related to groundwater pollution during the spring drought season. The introduction of the "all-patient report" and national vaccination program for children has had an effective influence on hepatitis A management. However, for hepatitis A prevention, policy considerations for high-risk age groups with low antibody-positive rates will be necessary.

Seroprevalence of hepatitis A virus infection in Central-West of Tunisia.

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.

Prognostic, clinical, and therapeutic importance of RANTES-CCR5 axis in hepatitis A infection: A multiapproach study.

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.

Hepatitis A susceptibility parallels high COVID-19 mortality.

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.

Potentially Infectious Novel Hepatitis A Virus Strains Detected in Selected Treated Wastewater Discharge Sources, South Africa.

Hepatitis A virus (HAV) is a waterborne pathogen of public health importance. In South Africa (SA), unique HAV subgenotype IB strains have been detected in surface and wastewater samples, as well as on fresh produce at the point of retail. However, due to the use of molecular-based assays, the infectivity of the detected strains was unknown. Considering the potential shift of HAV endemicity from high to intermediate, which could increase the risk of severe symptomatic disease, this study investigated the identity of HAV strains detected before and after viability treatment of selected wastewater discharge samples. For one year, 118 samples consisting of sewage, treated wastewater discharge and downstream dam water were collected from five wastewater treatment plants (WWTP 1, 2, 3, 4 and 5). Unique HAV IB strains were detected in samples from all five WWTPs, with 11 of these strains carrying amino acid mutations at the immunodominant and neutralisation epitopes. A quasispecies dynamic of HAV has also been detected in sewage samples. The subsequent application of viability PCR revealed that potentially infectious HAV strains were discharged from WWTP 1, 2, 4 and 5 into the dam. Therefore, there is a potential risk of HAV exposure to communities using water sources downstream the WWTPs.

Declining prevalence of hepatitis A and silent circulation of hepatitis E virus infection in southeastern Brazil.

OBJECTIVES: Hepatitis A virus (HAV) infection is considered highly endemic in Brazil, especially in low-income areas. In contrast, only a few human cases of hepatitis E have been reported. This study aimed to estimate the prevalence and potential risk factors of HAV and hepatitis E virus (HEV) infections in an adult population from a rural township of southeastern Brazil. METHODS: We conducted a cross-sectional survey using serum samples from urban and rural residents of Cássia dos Coqueiros, São Paulo state. A total of 990 samples were tested for anti-HAV IgG by chemiluminescent microparticle immunoassay, and a subset of 248 samples tested for anti-HEV IgG, using two commercial ELISA. Variables associated with anti-HAV and anti-HEV positivity were assessed by a multivariate analysis using a binomial logistic regression model. RESULTS: Seroprevalence of HAV and HEV was 89.1% and 20.7%, respectively. Age was significantly associated with HAV infection. Wantai and Mikrogen ELISA yielded comparable HEV seroprevalence results. CONCLUSIONS: Anti-HAV seroprevalence has declined and correlates with age, whereas anti-HEV was significantly higher than that found in previous population-based studies. These results indicate a need for further investigations of the magnitude of HEV infection in Brazil using the currently available, more sensitive diagnostic methods.

Is there a higher risk of a complicated course of hepatitis A in kidney transplant patients?

BACKGROUND: We describe a patient who was planned to receive a kidney transplant from his wife. Both were infected with Hepatitis A virus (HAV) two weeks prior to the planned transplantation. Due to prolonged shedding of HAV (up until 126 days) we decided to postpone the kidney transplant in order to prevent long term complications. OBJECTIVES: The main question in this case was is there a higher risk of a complicated course of HAV-infection after kidney transplantation? We discuss the need for upscale of preventative measures of HAV infections in solid organ transplant candidates. STUDY DESIGN: We performed a literature study on risks of a complicated course of HAV in solid organ transplant recipients and performed a seroprevalence study on anti-HAV in a cohort of 106 hemodialysis patients. RESULTS: Little is known whether HAV infection in solid organ transplant patients causes a more aggressive course of diseases. However, HAV infections in these populations are associated with increased risk of liver failure. CONCLUSIONS: This case highlights the need of scaling up preventative measures against HAV infections in solid organ transplant candidates.

Hepatitis a virus infection in Central-West Tunisia: an age structured model of transmission and vaccination impact.

BACKGROUND: The epidemiological pattern of hepatitis A infection has shown dynamic changes in many parts of the world due to improved socio-economic conditions and the accumulation of seronegative subjects, which leads to possible outbreaks and increased morbidity rate. In Tunisia, the epidemiological status of hepatits A virus is currently unknown. However, over the past years higher numbers of symptomatic hepatitis A virus infection in school attendants and several outbreaks were reported to the Ministry of Health, especially from regions with the lowest socio-economic levels in the country. The aim of this study was to investigate the current seroprevalence of hepatitis A virus antibodies in central-west Tunisia and assess the impact of hepatitis A virus vaccination on hepatitis A epidemiology. METHODS: Serum samples from 1379 individuals, aged 5-75 years, were screened for hepatitis A virus antibodies. Adjusted seroprevalence, incidence and force of infection parameters were estimated by a linear age structured SEIR (Susceptible-Exposed-Infectious-Recovered) compartmental model. A vaccine model was then constructed to assess the impact on hepatitis A virus epidemiology of 3 scenarios of vaccination strategies: one dose at 12-months of age, one dose at 6-years and one dose at 12-months and another at 6-years of age during 6 years. RESULTS: A rapid increase in anti-hepatitis A virus seroprevalence was noted during infancy and adolescence: 47% of subjects under 10-years-old are infected; the prevalence increases to 77% at 15-years and reaches 97% in subjects aged 30-years. The force of infection is highest between 10 and 30-years of age and the incidence declines with increasing age. The vaccine model showed that the 3-scenarios lead to a significant reduction of the fraction of susceptibles. The two doses scenario gives the best results. Single-dose vaccination at 6-years of age provides more rapid decrease of disease burden in school-aged children, as compared to single-dose vaccination at 12-months, but keeps with a non-negligible fraction of susceptibles among children < 6-years. CONCLUSIONS: Our study confirms the epidemiological switch from high to intermediate endemicity of hepatitis A virus in Tunisia and provides models that may help undertake best decisions in terms of vaccinations strategies.

Hepatitis A, B and C seropositivity among first-year healthcare students in western Turkey: a seroprevalence study.

BACKGROUND: The risk of viral hepatitis among healthcare students (HCSs) is greater than that among the general population. Therefore, this study was conducted to investigate the seroprevalence of the hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) among first-year HCSs at a university in Turkey and as a secondary objective, to determine the factors associated with HAV and HBV seropositivity. METHODS: This cross-sectional study was performed in first-year HCSs in Izmir, western Turkey. Data were collected using a self-administered questionnaire including items on sociodemographic characteristics, medical history, and hygiene. A total of 650 HCSs were tested for the HAV, HBV and HCV markers. Categorical variables were compared using the chi-square test. The association between independent variables and anti-HAV seropositivity and anti-HBs seropositivity was assessed by multinomial logistic regression analysis. RESULTS: The overall frequency of total anti-HAV seropositivity was 34.9%. HBsAg, total anti-HBc and anti-HBs seropositivity were found in 0.3, 1.2 and 93.7% of samples, respectively. All of the HCSs were negative for anti-HCV. Total anti-HAV seropositivity was found to be 1.73 times higher in those ≥21 years old, and it was 1.61 times higher in those who perceived their economic status to be average and 2.75 times higher in those who perceived their economic status to be low. Total anti-HAV seropositivity was found to be 4.37 times higher in those who lived in provinces with intermediate human development index levels. Total anti-HBs seropositivity was found to be 2.48 times higher in those ≤20 years old, and it was 2.13 times higher in those who perceived their economic status to be average. CONCLUSIONS: Approximately two out of three HCSs were susceptible to HAV infection. Since HCSs are at high risk for HAV infection, they should be vaccinated before medical clerkships begin. Our results indicate that there is a high prevalence of anti-HBs seropositivity among HCSs. This result may be largely attributed to the implementation of a successful vaccination program in Turkey since 1998.

Cell Culture Systems and Drug Targets for Hepatitis A Virus Infection.

Hepatitis A virus (HAV) infection is one of the major causes of acute hepatitis, and this infection occasionally causes acute liver failure. HAV infection is associated with HAV-contaminated food and water as well as sexual transmission among men who have sex with men. Although an HAV vaccine has been developed, outbreaks of hepatitis A and life-threatening severe HAV infections are still observed worldwide. Therefore, an improved HAV vaccine and anti-HAV drugs for severe hepatitis A should be developed. Here, we reviewed cell culture systems for HAV infection, and other issues. This review may help with improving the HAV vaccine and developing anti-HAV drugs.

Polyvalent Human Immune Globulin: A Prospective, Open-Label Study Assessing Anti-Hepatitis A Virus (HAV) Antibody Levels, Pharmacokinetics, and Safety in HAV-Seronegative Healthy Subjects.

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.

Hepatitis A Virus in Lao People's Democratic Republic: Seroprevalence and Risk Factors.

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.

Hepatitis A virus and hepatitis E virus prevalence relates to human immunodeficiency virus infection in Japanese male blood donors.

Hepatitis A virus (HAV) has begun to spread globally among men who have sex with men (MSM). Hepatitis E virus (HEV) also may be transmitted through sexual contact among MSM. To assess the current status of these viruses among MSM in Japan, the seroprevalence of both viruses using 503 plasma samples collected between 2009 and 2018 from human immunodeficiency virus (HIV)-positive male donors who were presumed to be mainly MSM was investigated. Our results suggested that HAV may be spreading within this population, as reported elsewhere. By contrast, the spread of HEV was confirmed only among younger HIV-positive donors.

The impact of universal live attenuated hepatitis A vaccines in Henan, China, 2005-2018.

OBJECTIVES: To analyze the effects of one dose of live attenuated hepatitis A vaccine in a developing country. METHODS: The reported cases of hepatitis A virus (HAV) infection from 2005 to 2018 in Henan province, China, were analyzed. Data of vaccinated children were assessed on the childhood immunization information management system. Questionnaire survey and blood sample collection were randomly conducted in six counties and districts of Henan province to analyze the prevalence of HAV lgG among the population aged 0-70 years. RESULTS: In 2008, Henan province began to expand its program on immunization, and children aged 18 months were given one dose of live attenuated hepatitis A vaccine (HepA-L). From 2005 to 2007, the HAV incidence remained steady at above 5000 cases per year and increased to 7489 in 2007. Since 2008, the HAV incidence decreased cumulatively from 4576 to 237 in 2018, indicating a 94.8% decrease, which was particularly pronounced among adolescents (98.2%). The proportion of hepatitis A cases in patients younger than 10 years continually decreased from 41.6% in 2012 to 3.8% in 2018. The reduction of reported cases older than 40 years was slower than that of children. In 2012, the proportion of hepatitis A cases older than 40 years was 27.6%, and continually increased to 69.2% (164/237) in 2018. The results of serological investigation showed that the 0-1.5-year age group had the lowest anti-HAV IgG prevalence (38.6%), which increased to 75.0% in the 4-6-year age group, covered by this immunization program. CONCLUSIONS: The data indicated a large decrease in HAV infections in Henan province from 2008 onward in response to the introduction of a planned immunization program of HepA-L.