ABSTRACT
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.
Subject(s)
Hepatitis A/epidemiology , Female , Hepatitis A Antibodies/analysis , Hepatitis A Antibodies/immunology , Hepatitis A virus/immunology , Humans , Longitudinal Studies , Male , Republic of Korea/epidemiology , Seroepidemiologic StudiesABSTRACT
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.
Subject(s)
Hepatitis A Antibodies/blood , Hepatitis A Virus, Human/isolation & purification , Hepatitis A/blood , Cambodia/epidemiology , Child , Child, Preschool , Female , Hepatitis A/epidemiology , Hepatitis A/immunology , Hepatitis A Antibodies/immunology , Hepatitis A Virus, Human/immunology , Humans , Male , Prevalence , Seroepidemiologic StudiesABSTRACT
Hepatitis A virus (HAV) is able to cause a spectrum of illnesses ranging from no symptom to fulminant hepatitis which may lead to acute kidney injury. Although hepatitis A vaccine is recommended in non-immune solid organ transplant recipients who live in or travel to endemic areas, the standard 2-dose vaccination regimen demonstrated less favorable immunogenicity among these population. The 3-dose regimen showed higher response rate and immune durability in patients with human immunodeficiency virus. However, this strategy has never been studied in solid organ transplant recipients. A single-center, open-labeled, computer-based randomized controlled trial (RCT) with a 2:1 allocation ratio was conducted from August 2017 to December 2018. The study compared the seroconversion rate after receiving 2- or 3-dose regimen of hepatitis A vaccine at 0, 6 and 0, 1, 6 months, respectively, in non-immune kidney transplant recipients. A total of 401 adult kidney transplant recipients were screened for anti-HAV IgG and 285 subjects had positive results so the seroprevalence was 71.1%. Of 116 seronegative recipients, 93 (80.2%) completed vaccination; 60 and 33 participants completed 2- and 3-dose vaccination, respectively. The baseline characteristics were comparable between both groups. The seroconversion rate at 1 month after vaccination was 51.7% in the standard 2-dose regimen and 48.5% in the 3-dose regimen (p = 0.769). Overall, the seroconversion rate appeared to be associated with high estimated glomerular infiltration rate, high serum albumin, and low intensity immunosuppressive regimen. Seroconversion rate after hepatitis A vaccination in kidney transplant recipients was less favorable than healthy population. Three-dose regimen did not show superior benefit over the standard 2-dose regimen. Other strategies of immunization may increase immunogenicity among kidney transplant recipients.
Subject(s)
Hepatitis A Vaccines/administration & dosage , Kidney Transplantation/adverse effects , Adolescent , Adult , Aged , Dose-Response Relationship, Immunologic , Drug Administration Schedule , Female , Hepatitis A/prevention & control , Hepatitis A Antibodies/immunology , Hepatitis A Vaccines/therapeutic use , Humans , Male , Middle Aged , Young AdultABSTRACT
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.
Subject(s)
Hepatitis A Vaccines/therapeutic use , Hepatitis A Virus, Human/immunology , Hepatitis A/epidemiology , Adolescent , Adult , Child , Child, Preschool , China/epidemiology , Disease Notification/statistics & numerical data , Female , Hepatitis A/immunology , Hepatitis A/prevention & control , Hepatitis A Antibodies/immunology , Humans , Incidence , Infant , Male , Mass Vaccination/statistics & numerical data , Middle Aged , Public Health Surveillance , Seroepidemiologic Studies , Young AdultABSTRACT
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.
Subject(s)
Hepatitis A Antibodies/immunology , Hepatitis A/prevention & control , Immunoglobulin G/administration & dosage , Immunoglobulin G/immunology , Adult , Dose-Response Relationship, Drug , Female , Healthy Volunteers , Hepatitis A/immunology , Hepatitis A virus/immunology , Humans , Injections, Intramuscular , Male , Middle Aged , Prospective Studies , Research DesignABSTRACT
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.
Subject(s)
Hepatitis A/epidemiology , Hepatitis E/epidemiology , Acute Disease , Adolescent , Adult , Age Distribution , Bangladesh/epidemiology , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Female , Hepatitis A/immunology , Hepatitis A Antibodies/immunology , Hepatitis Antibodies/immunology , Hepatitis E/immunology , Humans , Immunoglobulin M/immunology , Infant , Infant, Newborn , Logistic Models , Male , Middle Aged , Multivariate Analysis , Prevalence , Seroepidemiologic Studies , Sex Distribution , Young AdultABSTRACT
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.
Subject(s)
Hepatitis A virus/isolation & purification , Hepatitis A/epidemiology , Adolescent , Adult , Aged , Child , Child, Preschool , Cross-Sectional Studies , Female , Hepatitis A/blood , Hepatitis A/immunology , Hepatitis A/virology , Hepatitis A Antibodies/blood , Hepatitis A Antibodies/immunology , Hepatitis A virus/genetics , Hepatitis A virus/immunology , Humans , Infant , Male , Middle Aged , Prevalence , Rural Population/statistics & numerical data , Seroepidemiologic Studies , Sri Lanka/epidemiology , Urban Population/statistics & numerical data , Young AdultABSTRACT
Hepatitis A virus (HAV) is the most common cause of acute viral hepatitis worldwide. The virus is mainly transmitted via the fecaloral route and, the incidence of infection is closely related to low socioeconomic conditions and poor sanitation. Mexico, previously categorized an area of high endemicity for HAV infection, is undergoing epidemiological transition. However, a limited number of HAV-related scientific reports regarding to virus burden is available. According to the local government health agency (Secretarla de Salud, SSA in Spanish), from 1994 to 2017 a reduction in the incidence of hepatitis related to HAV has been reported. However, HAV is still the most common cause of viral hepatitis in the country, and the pediatric population is the most prone to be infected with this virus. The analysis of the SSA data reveals that most of the reported cases from 1994 to 2017 were found in highly industrialized states. This information contradicts the documented relationship between the highest prevalence of infection and the lowest socio-economic status, and supports the necessity of viral detection and notification of HAV cases. Moreover, in spite that four HAV vaccines are available in Mexico and universal vaccination has been shown to be beneficial in developing countries in terms of declining endemicity, HAV vaccination is not mandatory in Mexico. In this review, preventive strategies including appropriate diagnosis, vaccination and public health policies on the basis of the epidemiologic status of HAV in Mexico are discussed.
Subject(s)
Hepatitis A Antibodies/immunology , Hepatitis A Vaccines/therapeutic use , Hepatitis A virus/immunology , Hepatitis A/epidemiology , Vaccination/methods , Hepatitis A/therapy , Humans , Incidence , Mexico/epidemiology , Prevalence , Seroepidemiologic StudiesABSTRACT
Since the early 21st century, almost all developed countries have had a very low hepatitis A virus antibody (anti-HAV) sero-prevalence profile, as sanitation conditions and health care facilities have been optimized to a universal standard. There has not been a report on anti-HAV prevalence among a large scale population in Japan since 2003. Therefore, this study aimed to investigate the current HAV status among the general population in Hiroshima. From each age and sex specific group, a total of 1,200 samples were randomly selected from 7,682 stocked serum samples from residents' and employees' annual health check-ups during 2013-2015. Total anti-HAV was detected using Chemiluminescent Enzyme Immunoassay. The overall anti-HAV sero-prevalence was 16.8%. In both males and females, anti-HAV prevalence among individuals between 20-59 years of age was as low as 0.0-2.0%, whilst that among 70 s was as high as 70.0-71.0%. A large number of residents aged under 60 are now susceptible to HAV infection. The cohort reduction trend of anti-HAV in Japan exposes the high possibility of mass outbreak in the future. HAV vaccine especially to younger generation and high risk population may prevent outbreak in Japan.
Subject(s)
Hepatitis A Antibodies/analysis , Hepatitis A Virus, Human/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Disease Outbreaks , Female , Hepatitis A/epidemiology , Hepatitis A Antibodies/immunology , Hepatitis A virus/immunology , Hepatitis A virus/pathogenicity , Humans , Japan/epidemiology , Male , Middle Aged , Prevalence , Risk Factors , Seroepidemiologic Studies , Serologic Tests/methodsABSTRACT
The European Pharmacopoeia (Ph. Eur.) standard ELISA method for determination of antigen content of hepatitis A vaccines (HAV) requires specific coating and detection Biological Reference Reagents (BRRs). The 4th batch of detection antibodies BRRs was established in 2017 for use in conjunction with the Ph. Eur. General Chapter 2.7.14 Assay of hepatitis A vaccine. Stocks of these BRRs were running low and therefore the European Directorate for the Quality of Medicines and HealthCare (EDQM) organised a collaborative study to qualify replacement batches. The candidate BRR antibodies batch 5 were prepared under appropriate conditions from starting materials similar to previous batches to ensure continuity. Prior to the study, a low level of detection was obtained with new batches of the HRPO-GAM provided by the established supplier, supposedly due to a manufacturing issue in the conjugation step. Several other batches procured from the same supplier were tested without any success. Consequently HRPO-GAM batches from 3 other suppliers were tested and one batch was chosen to be included as a BRR based on its suitable characteristics. During the collaborative study, the new batches of antibodies were compared to previous batches of BRRs. Results confirmed that they were suitable to be used for the intended purpose, and could be used at the same final concentrations as the previous batch, i.e. 1:500 for the primary antibody and 1:400 for the conjugated secondary antibody. A higher background OD than in previous batches was observed, so it is recommended to subtract the background from the OD values obtained in the test in order to plot the sigmoid curve and calculate the titre of test samples. Moreover it is recommended that the first dilutions used for the IS and BRP2 should be 1:2 and 1:20, respectively, in order to achieve the same ODmax as for the previous BRRs batches. The BRRs were adopted by correspondence in October 2018 by the Ph. Eur. Commission and are presented as a set containing Hepatitis A virus primary detection antibody BRR batch 5 and Conjugated secondary detection antibody BRR batch 5. They are available from the EDQM as Hepatitis A vaccine ELISA detection antibodies set BRR batch 5.
Subject(s)
Hepatitis A Antibodies/immunology , Hepatitis A Vaccines/standards , Antibodies , Biological Assay , Enzyme-Linked Immunosorbent Assay , Europe , Hepatitis A Vaccines/immunology , Humans , International Cooperation , Reference Standards , Vaccines, InactivatedABSTRACT
BACKGROUND: With the improvement in sanitation and hygiene, the incidence of hepatitis A virus (HAV) infection has declined, and its seroprevalence among Japanese people has been reduced. Universal HAV vaccination is yet to be implemented in Japan, and the healthcare workers (HCWs) are at higher risks of acquiring this infection. We herein report the seroepidemiology of HAV infection among HCWs at Osaka University Hospital. METHODS: Between September and October 2017, we collected serum samples submitted to our laboratory for HCWs health examination and tested for the anti-HAV antibody. RESULTS: Overall HAV seropositivity rate was 5.1% (22/436 samples). The seroprevalence was higher among those in the twenties (6.0%) and thirties (8.0%), compared to older age groups. CONCLUSIONS: In this age of internationalization, the decreasing immunity for HAV places HCWs at risk of developing the disease. As a preventive measure against occupational infection, HAV vaccination may be needed for Japanese HCWs.
Subject(s)
Health Personnel/statistics & numerical data , Hepatitis A Antibodies/blood , Hepatitis A/blood , Occupational Diseases/blood , Adult , Female , Hepatitis A/epidemiology , Hepatitis A/virology , Hepatitis A Antibodies/immunology , Hepatitis A virus/immunology , Hepatitis A virus/physiology , Humans , Japan/epidemiology , Male , Middle Aged , Occupational Diseases/epidemiology , Occupational Diseases/virology , Prevalence , Risk Factors , Seroepidemiologic Studies , Young AdultABSTRACT
We describe a rare case of hepatitis A virus (HAV) replication in feces despite presence of hepatitis A antibodies in an acute myeloid leukemia (AML) patient after transfusion with HAV contaminated platelets. The patient has been vaccinated against HAV years before the AML diagnosis. Transient infection and reshedding should thus be considered in antibody-positive hematological patients. Transfusion associated HAV transmission is rare, and little evidence exists on the clinical consequences and possible effect of treatment with immunoglobulin. Further reporting on fecal shedding despite antibodies are needed, as HAV antibody levels are used as course of action for post-exposure prophylaxis and infection control.
Subject(s)
Feces/virology , Hepatitis A virus/isolation & purification , Hepatitis A/transmission , Transfusion Reaction/virology , Adult , Blood Transfusion/methods , Female , Hepatitis A/immunology , Hepatitis A/virology , Hepatitis A Antibodies/immunology , Hepatitis A Vaccines/immunology , Hepatitis A virus/immunology , Humans , Leukemia, Myeloid, Acute/immunology , Leukemia, Myeloid, Acute/virology , Post-Exposure Prophylaxis/methods , Vaccination/methodsABSTRACT
BACKGROUND: Worldwide about 1.5 million clinical cases of hepatitis A virus (HAV) infections occur every year and increasingly countries are introducing HAV vaccination into the childhood immunization schedule with a single dose instead of the originally licenced two dose regimen. Diagnosis of acute HAV infection is determined serologically by anti-HAV-IgM detection using ELISA. Additionally anti-HAV-IgG can become positive during the early phase of symptoms, but remains detectable after infection and also after vaccination against HAV. Currently no serological marker allows the differentiation of HAV vaccinated individuals and those with a past infection with HAV. Such differentiation would greatly improve evaluation of vaccination campaigns and risk assessment of HAV outbreaks. Here we tested the HAV non-structural protein 2A, important for the capsid assembly, as a biomarker for the differentiation of the immune status in previously infected and vaccinated individuals. METHODS: HAV antigens were recombinantly expressed as glutathione-S-transferase (GST) fusion proteins. Using glutathione tagged, magnetic fluorescent beads (Luminex®), the proteins were affinity purified and used in a multiplex serological assay. The multiplex HAV assay was validated using 381 reference sera in which the immune status HAV negative, vaccinated or infected was established using the Abbott ARCHITECT® HAVAb-IgM or IgG, the commercial HAV ELISA from Abnova and documentation in vaccination cards. RESULTS: HAV multiplex serology showed a sensitivity of 99% and specificity of 95% to detect anti-HAV IgG/IgM positive individuals. HAV biomarker 2A allowed the differentiation between previously infected and vaccinated individuals. HAV vaccinated individuals and previously infected individuals could be identified with 92% accuracy. CONCLUSION: HAV biomarker 2A can be used to differentiate between previously HAV-vaccinated and naturally infected individuals. Within a multiplex serological approach this assay can provide valuable novel information in the context of outbreak investigations, longitudinal population based studies and evaluations of immunization campaigns.
Subject(s)
Biomarkers/blood , Cysteine Endopeptidases/blood , Hepatitis A virus/immunology , Hepatitis A/blood , Hepatitis A/diagnosis , Viral Proteins/blood , Adolescent , Adult , Capsid Proteins/blood , Capsid Proteins/immunology , Child , Child, Preschool , Cysteine Endopeptidases/immunology , Hepatitis A/immunology , Hepatitis A/virology , Hepatitis A Antibodies/blood , Hepatitis A Antibodies/immunology , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Infant , Infant, Newborn , Vaccination/methods , Viral Proteins/immunologyABSTRACT
OBJECTIVES: To describe the immunogenicity and side effects of immunisation against hepatitis A virus (HAV) in JIA patients on methotrexate treatment, who have not been previously exposed to HAV. METHODS: Case-control study performed in JIA patients and healthy controls matched on age and gender. The subjects received two doses of inactivated anti-HAV vaccine (720 mIU/ml) intramuscularly at 0 and 6 months. Seroconversion, seroprotection rates and anti-HAV-IgG titres were measured at 1, 7 and 18 months. Children were monitored for adverse events. RESULTS: 83 JIA patients and 76 controls were enrolled in the study. At one month, seroprotection rates were lower in children with, as compared to those without JIA (48.2% vs. 65%; p=0.05). At 7 and 18 months, rates of seroprotection rose significantly and were similar in both groups. The titre of anti-HAV-IgG was lower in children with JIA than healthy children at all time points (p<0.001). Vaccines were well tolerated. CONCLUSIONS: Two doses of inactivated HAV vaccine were well tolerated and immunogenic in most immunosuppressed children with JIA; however, a single dose of HAV vaccine was insufficient to induce seroprotection in half of the patients. Further studies are required to analyse the long-term immunity against HAV in this population and optimal HAV immunisation regimen.
Subject(s)
Arthritis, Juvenile/drug therapy , Hepatitis A Antibodies/immunology , Hepatitis A Vaccines/therapeutic use , Hepatitis A/prevention & control , Immunogenicity, Vaccine/immunology , Immunoglobulin G/immunology , Immunosuppressive Agents/therapeutic use , Methotrexate/therapeutic use , Arthritis, Juvenile/immunology , Case-Control Studies , Child , Child, Preschool , Female , Hepatitis A Vaccines/immunology , Humans , Male , Vaccines, Inactivated/immunology , Vaccines, Inactivated/therapeutic useABSTRACT
Vaccination is the most effective and well-tolerated method of conferring long-term protection against hepatitis A and B viruses (HAV; HBV). Long-term studies are required to characterize the duration of protection and need for boosters. Following primary immunization of 150 and 157 healthy adults with 3-doses of combined hepatitis A/hepatitis B vaccine (HAB; Twinrix™, GSK Vaccines, Belgium) at 0-1-6 months in 2 separate studies, we measured vaccine-induced antibody persistence against HAV and HBV annually for 20 y (Study A: NCT01000324; Study B: NCT01037114). Subjects with circulating anti-HAV antibodies < 15 mIU/mL or with anti-hepatitis B surface antigen < 10 mIU/mL were offered an additional monovalent hepatitis A and/or B vaccine dose (Havrix™/Engerix™-B, GSK Vaccines, Belgium). Applying the immunogenicity results from these studies, mathematical modeling predicted long-term persistence. After 20 y, 18 and 25 subjects in studies A and B, respectively, comprised the long-term according-to-protocol cohort for immunogenicity; 100% and 96.0% retained anti-HAV antibodies ≥ 15 mIU/mL, respectively; 94.4% and 92.0% had anti-HBs antibodies ≥ 10 mIU/mL, respectively. Between Years 16-20, 4 subjects who received a challenge dose of monovalent hepatitis A vaccine (N = 2) or hepatitis B vaccine (N = 2), all mounted a strong anamnestic response suggestive of immune memory despite low antibody levels. Mathematical modeling predicts that 40 y after vaccination ≥ 97% vaccinees will maintain anti-HAV ≥ 15 mIU/mL and ≥ 50% vaccinees will retain anti-HBs ≥ 10 mIU/mL. Immunogenicity data confirm that primary immunization with 3-doses of HAB induces persisting anti-HAV and anti-HBs specific antibodies in most adults for up to 20 y; mathematical modeling predicts even longer-term protection.
Subject(s)
Hepatitis A Antibodies/blood , Hepatitis A Vaccines/immunology , Hepatitis B Antibodies/blood , Hepatitis B Vaccines/immunology , Immunogenicity, Vaccine , Immunologic Memory , Adult , Belgium/epidemiology , Cohort Studies , Female , Follow-Up Studies , Hepatitis A/epidemiology , Hepatitis A/prevention & control , Hepatitis A Antibodies/immunology , Hepatitis A Antibodies/isolation & purification , Hepatitis A Vaccines/administration & dosage , Hepatitis B/epidemiology , Hepatitis B/prevention & control , Hepatitis B Antibodies/immunology , Hepatitis B Antibodies/isolation & purification , Hepatitis B Vaccines/administration & dosage , Humans , Immunization, Secondary , Male , Middle Aged , Time Factors , Vaccination/methods , Vaccines, Combined/administration & dosage , Vaccines, Combined/immunologyABSTRACT
Sri Lanka is one of the intermediate-endemic areas for hepatitis A virus (HAV), and concerns exist about the increasing HAV-susceptible population. In fact, Sri Lanka recorded a large hepatitis outbreak, possibly hepatitis A, around the end of the Sri Lankan war. It included more than 14,000 patients consisting of local residents, internally displaced personnel, and military personnel in the main combat zone. The outbreak had slowed down by October 2009; however, acute viral hepatitis continued to occur sequentially among military personnel. We obtained clinical information and serum samples from 222 patients with acute hepatitis who visited the Military Hospital Anuradhapura between January and September 2010. Samples were subjected to laboratory testing including HAV-immunoglobulin M and genotyping. Most patients (98.2%) were confirmed as having hepatitis A belonging to two subgenotypes: IA and IIIA. We did not observe any differences in clinical or biochemical features among patients with subgenotypes IA and IIIA except for pale stools and upper abdominal discomfort. During the investigation period, we observed a serial outbreak caused by identical HAV strains with an interval in line with that of typical HAV incubation periods. Most patients in the first outbreak were found in the training center, and patients in the second outbreak were found in multiple places where soldiers were assigned after the training center. These findings indicate that a strain of HAV diffused from one place to another along with movement of infected persons among the HAV-susceptible population. HAV vaccination for high-risk groups, such as young soldiers, is necessary.
Subject(s)
Disease Outbreaks , Hepatitis A virus/genetics , Hepatitis A/virology , Military Personnel/statistics & numerical data , Abdominal Pain/epidemiology , Adolescent , Adult , Anorexia/epidemiology , Fever/epidemiology , Genotype , Hepatitis A/epidemiology , Hepatitis A/immunology , Hepatitis A/transmission , Hepatitis A Antibodies/immunology , Humans , Immunoglobulin M/immunology , Male , Nausea/epidemiology , Polymerase Chain Reaction , RNA, Viral/blood , Sri Lanka , Young AdultABSTRACT
Purpose - The environmental and demographic characteristics of closed institutions, particularly prisons, precipitate morbidity during hepatitis A virus (HAV) outbreaks. Given the high prevalence of chronic liver disease and other risk factors in the prison setting, the purpose of this paper is to examine HAV-immunity and its associated factors in this population. Design/methodology/approach - The cross-sectional study was conducted in 2009: a serology screening for HAV IgG was carried out among 116 inmates in Switzerland's largest pre-trial prison. Other participant characteristics were collected through a structured face-to-face questionnaire with a physician. Findings - In terms of significant demographics, Africa (53.5 percent) and the Balkans/Eastern Europe (36.2 percent) were the main regions of origin; a minority of inmates were from Western Europe (6.9 percent), Latin America (2.6 percent) or Asia (0.9 percent). The authors identified hepatitis A antibody-negative serology (lack of immunity) in five out of 116 prisoners (4.3 percent, 95 percent CI 1.4-9.7). Among participants of European origin alone, five out of 50 inmates were hepatitis A antibody-negative (10 percent, 95 percent CI 3.3-21.8), whereas the 66 inmates from other all continents were hepatitis A antibody-positive (immune) (p=0.026). Originality/value - In this prison population composed of mostly African migrants, hepatitis A immunity was high. This reaffirms that region of origin is highly associated with childhood immunity against HAV. HAV vaccination should take into account a patient's area of origin and his/her risk factors for systemic complications, if ever infected. This targeted strategy would offer herd immunity, and seek out the most vulnerable individuals who are potentially at risk of new exposure in this precarious setting.
Subject(s)
Hepatitis A Vaccines/administration & dosage , Hepatitis A/ethnology , Prisoners/statistics & numerical data , Adult , Black People/statistics & numerical data , Cross-Sectional Studies , Emigrants and Immigrants/statistics & numerical data , Harm Reduction/drug effects , Health Status , Hepatitis A/blood , Hepatitis A/immunology , Hepatitis A Antibodies/blood , Hepatitis A Antibodies/immunology , Hepatitis A Vaccines/immunology , Humans , Male , Middle Aged , Prevalence , Seroepidemiologic Studies , Switzerland/epidemiology , Young AdultABSTRACT
We previously observed 80.7% seropositivity and a significant interaction between gender and hepatitis A virus (HAV) vaccine type (Havrix vs. Epaxal) on the seropositivity approximately 11 months after single-dose HAV vaccinations in Korean young adults. Our objective was to evaluate seropositivity approximately 2 years after a single-dose HAV vaccination and the influence of demographic characteristics on seropositivity, including the interaction between gender and vaccine type. Seronegative medical school students were randomly vaccinated with Havrix or Epaxal. Based on a total serum anti-HAV antibody titer cutoff of 20 IU/mL, 338 participants (76.0%) of the 445 vaccinees were seropositive 20-25 months after a single-dose HAV vaccination. The seropositive rates were similar after vaccination with Havrix (77.0%) and Epaxal (74.9%). Univariate analysis indicated that female (p = 0.052) and less obese (p < 0.001) participants had a higher seropositive rate, whereas other characteristics such as age, alcohol use, smoking history, vaccine type, and follow-up duration were not associated with seropositivity. Multivariate analysis indicated that women (p = 0.026) and participants with moderate alcohol use (p < 0.001) showed significantly higher seropositive rates than men and participants with no or low alcohol use, respectively. The seropositive rates after vaccination with Havrix and Epaxal were 70.9% and 67.5% in men and 87.7% and 91.3% in women, respectively (p for interaction = 0.304). Compared with the seropositive rate approximately 11 months after vaccination, the seropositive rate decreased substantially only in men in the Havrix group (11.0% points), and consequently, the interaction between gender and vaccine type disappeared while seropositivity remained high (87.7% and 91.3% in Havrix and Epaxal groups, respectively) among women approximately 2 years after vaccination. Further studies are needed to assess whether the seropositive rate would be maintained in all groups more than 2 years after a single-dose HAV vaccination.
Subject(s)
Hepatitis A Virus, Human/immunology , Hepatitis A/immunology , Viral Vaccines/immunology , Adolescent , Adult , Female , Hepatitis A Antibodies/immunology , Hepatitis A Vaccines/immunology , Humans , Immunization, Secondary/methods , Korea , Male , Vaccination/methods , Young AdultABSTRACT
An increasing amount of research has been conducted on immunoglobulin Y (IgY) because the use of IgY offers several advantages with respect to diagnostic testing, including its easy accessibility, low cost and translatability to large-scale production, in addition to the fact that it can be ethically produced. In a previous work, immunoglobulin was produced and purified from egg yolks (IgY) reactive to hepatitis A virus (HAV) antigens. In the present work, this anti-HAV-specific IgY was used in an indirect immunofluorescence assay to detect viral antigens in liver biopsies that were obtained from experimentally infected cynomolgus monkeys. Fields that were positive for HAV antigen were detected in liver sections using confocal microscopy. In conclusion, egg yolks from immunised hens may be a reliable source for antibody production, which can be employed for immunological studies.