Healthcare and Epidemiological Surveillance Costs of Hepatitis A Outbreaks in Spain in Regions with and without Universal Hepatitis A Vaccination of Children during 2010-2018.

The aim of this study was to evaluate and compare hepatitis A outbreak-associated healthcare and epidemiological surveillance costs in Spain in two types of autonomous regions during 2010-2018: (1) regions with a prevention strategy based on universal hepatitis A vaccination of children and vaccination of high-risk population groups (Catalonia) and (2) regions with a prevention strategy based on vaccinating high-risk population groups (Castile and Leon, Murcia, Navarra, Community of Madrid, Community of Valencia). Healthcare costs were determined based on the resources used to treat hepatitis A outbreak-associated cases and hospitalizations. Epidemiological surveillance costs were calculated from the resources used during surveillance activities. The ratios for total, healthcare and epidemiological surveillance costs (regions without universal hepatitis A vaccination of children vs. Catalonia) were used to compare the two hepatitis A prevention strategies. From 2010 to 2018, the total, healthcare and epidemiological surveillance costs per million population were 1.75 times (EUR 101,671 vs. EUR 58,032), 1.96 times (EUR 75,500 vs. EUR 38,516) and 1.34 times greater (EUR 26,171 vs. EUR 19,515) in regions without universal hepatitis A vaccination of children than in Catalonia, respectively. The ratios tended to increase over time during 2010-2018. In 2015-2018, total, healthcare and epidemiological surveillance costs per million population were 2.68 times (EUR 69,993 vs. EUR 26,158), 2.86 times (EUR 53,807 vs. EUR 18,825) and 2.21 times greater (EUR 16,186 vs. EUR 7333) in regions without universal hepatitis A vaccination of children than in Catalonia, respectively. These findings suggest that universal hepatitis A vaccination of children could reduce hepatitis A outbreak-associated costs.

Modelling the Cost-Effectiveness of Hepatitis A in South Africa.

The World Health Organization (WHO) recommends the consideration of introducing routine hepatitis A vaccination into national immunization schedules for children ≥ 1 years old in countries with intermediate HAV endemicity. Recent data suggest that South Africa is transitioning from high to intermediate HAV endemicity, thus it is important to consider the impact and cost of potential routine hepatitis A vaccination strategies in the country. An age-structured compartmental model of hepatitis A transmission was calibrated with available data from South Africa, incorporating direct costs of hepatitis A treatment and vaccination. We used the calibrated model to evaluate the impact and costs of several childhood hepatitis A vaccination scenarios from 2023 to 2030. We assessed how each scenario impacted the burden of hepatitis A (symptomatic hepatitis A cases and mortality) as well as calculated the incremental cost per DALY averted as compared to the South African cost-effectiveness threshold. All costs and outcomes were discounted at 5%. For the modelled scenarios, the median estimated cost of the different vaccination strategies ranged from USD 1.71 billion to USD 2.85 billion over the period of 2023 to 2030, with the cost increasing for each successive scenario and approximately 39-52% of costs being due to vaccination. Scenario 1, which represented the administration of one dose of the hepatitis A vaccine in children < 2 years old, requires approximately 5.3 million vaccine doses over 2023-2030 and is projected to avert a total of 136,042 symptomatic cases [IQR: 88,842-221,483] and 31,106 [IQR: 22,975-36,742] deaths due to hepatitis A over the period of 2023 to 2030. The model projects that Scenario 1 would avert 8741 DALYs over the period of 2023 to 2030; however, it is not cost-effective against the South African cost-effectiveness threshold with an ICER per DALY averted of USD 21,006. While Scenario 3 and 4 included the administration of more vaccine doses and averted more symptomatic cases of hepatitis A, these scenarios were absolutely dominated owing to the population being infected before vaccination through the mass campaigns at older ages. The model was highly sensitive to variation of access to liver transplant in South Africa. When increasing the access to liver transplant to 100% for the baseline and Scenario 1, the ICER for Scenario 1 becomes cost-effective against the CET (ICER = USD 2425). Given these findings, we recommend further research is conducted to understand the access to liver transplants in South Africa and better estimate the cost of liver transplant care for hepatitis A patients. The modelling presented in this paper has been used to develop a user-friendly application for vaccine policy makers to further interrogate the model outcomes and consider the costs and benefits of introducing routine hepatitis A vaccination in South Africa.

Coadministered pneumococcal conjugate vaccine decreases immune response to hepatitis A vaccine: a randomized controlled trial.

OBJECTIVES: We explored the influence of coadministration on safety and immunogenicity of the most common travellers' vaccine hepatitis A (HepA) and the pneumococcal conjugate vaccine (PCV) increasingly used both at home and before travel. METHODS: Volunteers aged ≥18 years (n = 305) were randomly assigned 1:1:1 into three groups receiving: 13-valent PCV (PCV13) + HepA, PCV13, or HepA. Anti-pneumococcal IgG concentrations, opsonophagocytic activity (OPA) titres, and total hepatitis A antibody (anti-HAV) concentrations were measured before and 28 ± 3 days after vaccination. Adverse events (AEs) were recorded over 4 weeks. RESULTS: After vaccination, the anti-HAV geometric mean concentration was significantly lower in the PCV13+HepA than the HepA group: 34.47 mIU/mL (95% CI: 26.42-44.97 mIU/mL) versus 72.94 mIU/mL (95% CI: 55.01-96.72 mIU/mL), p < 0.001. Anti-HAV ≥10 mIU/mL considered protective was reached by 71 of 85 (83.5%) in the PCV13+HepA group versus 76 of 79 (96.2%) in the HepA group, p 0.008. The increases in anti-pneumococcal IgG and OPA levels were comparable in the PCV13+HepA and PCV13 groups, apart from a bigger rise in the PCV13+HepA group for serotype 3 (one-way ANOVA: serotype 3 IgG p 0.010, OPA p 0.002). AEs proved more frequent among those receiving PCV13 than HepA, but simultaneous administration did not increase the rates: ≥one AE was reported by 45 of 56 (80.4%) PCV13, 43 of 54 (79.6%) PCV13+HepA, and 25 of 53 (47.2%) HepA recipients providing structured AE data. DISCUSSION: Coadministration of HepA and PCV13 did not cause safety concerns, nor did it impact the patients' response to PCV13, apart from serotype 3. However, coadministered PCV13 significantly impaired antibody responses to HepA.

Trends and Opportunities: Hepatitis A Virus Infection, Seroprevalence, and Vaccination Coverage-United States, 1976-2020.

OBJECTIVES: The incidence of hepatitis A declined in the United States following the introduction of hepatitis A vaccines, before increasing in the setting of recent widespread outbreaks associated with person-to-person transmission. We describe the hepatitis A epidemiology in the United States, identify susceptible populations over time, and demonstrate the need for improved hepatitis A vaccination coverage, especially among adults at increased risk for hepatitis A. METHODS: We calculated the hepatitis A incidence rates for sociodemographic characteristics and percentages for risk factors and clinical outcomes for hepatitis A cases reported to the National Notifiable Diseases Surveillance System during 1990-2020. We generated nationally representative estimates and 95% CIs of hepatitis A seroprevalence during 1976-March 2020 and self-reported hepatitis A vaccination coverage during 1999-March 2020 for the noninstitutionalized civilian US population using data from the National Health and Nutrition Examination Survey. RESULTS: Overall, the rate per 100 000 population of reported cases of hepatitis A virus infection in the United States declined 17.3-fold, from 10.4 during 1990-1998 to 0.6 during 2007-2015, and then increased to 2.8 during 2016-2020. The overall hepatitis A seroprevalence in the United States increased from 38.2% (95% CI, 36.2%-40.1%) during 1976-1980 to 47.3% (95% CI, 45.4%-49.2%) during 2015-March 2020. The prevalence of self-reported hepatitis A vaccination coverage in the United States increased more than 2.5-fold, from 16.3% (95% CI, 15.0%-17.7%) during 1999-2006 to 41.9% (95% CI, 40.2%-43.7%) during 2015-March 2020. CONCLUSIONS: Hepatitis A epidemiology in the United States changed substantially during 1976-2020. Improved vaccination coverage, especially among adults recommended for vaccination by the Advisory Committee on Immunization Practices, is vital to stop current hepatitis A outbreaks associated with person-to-person transmission in the United States and prevent similar future recurrences.

Immunogenicity persistence of hepatitis A vaccines Healive® and Havrix® among children:15 years follow-up and long-term prediction.

Healive® was the only Chinese WHO-prequalified inactivated vaccine for the hepatitis A virus, which has been widely used in national immunization programs in China. Long-term follow-up studies are needed to estimate the persistence of vaccine-induced antibody levels and the necessity for booster vaccines. During the trial, geometric mean concentrations (GMCs) and seroconversion rates (SRs) of anti-HAV antibodies were compared based on two different inactivated hepatitis A vaccines, Healive® and Havrix®. Four hundred children were randomly assigned to receive two doses of Healive® or Havrix® at 0 and 6 months. The current study assessed antibody persistence for both vaccines 15 years post-immunization. A mixed linear model was used to predict long-term antibody persistence. The GMCs were significantly higher for Healive® compared to Havrix® at 1, 6, 7, 66, 138 months (P < .001) and 186 months (P = .004 < .05) post-vaccination. Healive® and Havrix® reached a GMC of 164.8 mIU/ml and 105.7 mIU/ml post-15 years of vaccination, respectively. The seroconversion rates of both vaccines showed no statistically significant differences (97.9% for Healive® and 94.7% for Havrix®, P = .20). The prediction showed that Healive® would provide protection for a minimum of 30 years following immunization, with a lower limit of the 95% confidence intervals for GMCs greater than 20mIU/mL. Compared to Havrix®, the vaccine Healive® showed a stronger protective effect and better persistence among children at 15 years post-full immunization. Prediction indicated at least 30 years of antibody persistence for Healive® and at least 25 years for Havrix®.

Delaying the third dose of Japanese aluminum-free hepatitis A vaccine Aimmugen elicits effective immune responses against hepatitis A in adults.

Inactivated aluminum-adsorbed hepatitis A vaccines such as Havrix, Vaqta, and Avaxim are commonly used worldwide. These vaccines are typically administered in a two-dose series (at 0 and 6-12 months). However, a lyophilized inactivated aluminum-free hepatitis A vaccine, Aimmugen, which is approved in Japan, is typically administered in a three-dose series (at 0, 2-4, and 24 weeks). Hence, individuals visiting endemic hepatitis A areas receive the primary two doses of Aimmugen before traveling and the third booster dose much later. It is currently uncertain whether boosting with a delayed third dose of Aimmugen is effective, or whether a new vaccination schedule should instead be initiated. Therefore, we investigated the anti-hepatitis-A viral immune response of adult travelers who received the third dose of Aimmugen more than 24 weeks after the first dose. Participants were vaccinated with the third dose of Aimmugen more than 2 years after the first two doses. Antibody titers were measured at Day 0 (prevaccination) and at 28-42 days after the third dose of Aimmugen. Twenty-nine adult participants were enrolled in the study (14 men and 15 women; mean age ± standard deviation age, 36.2 ± 8.1 years). The interval between the first two doses and the third dose was 3-14 years. The seroprotection rate (i.e., the percentage of participants with anti-hepatitis A virus antibody titers ≥ 10 mIU/mL) was 96.6 % (28/29) at Day 0 and increased to 100 % (29/29) at Days 28-42. Geometric mean concentration increased from 105 to 4,013 mIU/mL. We demonstrated that delaying the third dose of Aimmugen still elicited effective immune responses after priming with two doses of the vaccine. Trial registration: UMIN Clinical Trials Registry (UMIN-CTR): MIN000013624. Registered 03 April 2014. https://center6.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000015906.

Safety of concomitant administration of inactivated hepatitis A vaccine with other vaccines in children under 16 years old in post-marketing surveillance.

BACKGROUND: Concomitant administration refers to the receipt of two or more vaccines during a single healthcare encounter, which is an efficient way to increase vaccination coverage in children. However, the post-marketing safety studies of concomitant administration are scarce. Inactivated hepatitis A vaccine (Healive®) has been used widely in China and other countries for more than a decade. We aimed to explore the safety of Healive® co-administered with other vaccines compared to Healive® alone in children under 16 years old. METHODS: We retrieved Adverse Events Following Immunization (AEFI) cases and vaccination doses of Healive® during 2020-2021 in Shanghai, China. The AEFI cases were divided into concomitant administration group and Healive® alone group. We used administrative data on vaccine doses as denominators to calculate and compare crude reporting rates between groups. We also compared baseline gender and age distribution, clinical diagnoses, and time interval from vaccination to onset of symptoms between groups. RESULTS: A total 319,247 doses of inactivated hepatitis A vaccine (Healive®) were used and 1,020 AEFI cases (319.50 per million doses) associated with Healive® were reported during 2020-2021 in Shanghai. There were 259,346 doses concomitantly administered with other vaccines and 830 AEFI cases (320.04 per million doses) were reported. There were 59,901 doses of Healive® that vaccinated alone, with 190 AEFI cases (317.19 per million doses). There was only one case with serious AEFI in concomitant administration group, with a rate of 0.39 per million doses. Reported rates of AEFI cases were similar between groups in general (p > 0.05). CONCLUSION: Concomitant administration of inactivated hepatitis A vaccine (Healive®) with other vaccines has a similar safe profile as Healive® alone.

Persistence of immunity against hepatitis A in Brazilian children vaccinated with a single dose of inactivated virus vaccine.

In 2014, the Brazilian National Immunization Program implemented the universal vaccination against the hepatitis A virus (HAV) for children aged 12 months and older, applying a single dose of the inactivated virus vaccine. It is essential to carry out follow-up studies in this population, aiming to verify the longevity of HAV immunological memory. This study evaluated the humoral and cellular immune response of a cohort of children vaccinated between 2014 and 2015, and further investigated between 2015 and 2016, and who had their initial antibody response assessed after the single dose. A second evaluation took place in January 2022. We examined 109 children out of the 252 that took part in the initial cohort. Seventy (64.2%) of them had anti-HAV IgG antibodies. Cellular immune response assays were performed in 37 anti-HAV-negative and 30 anti-HAV-positive children. Production of interferon-gamma (IFN-y) stimulated with the VP1 antigen was demonstrated in 34.3% of these 67 samples. Of the 37 negative anti-HAV samples, 12 (32.4%) produced IFN-y. Among the 30 anti-HAV-positive, 11 (36.7%) produced IFN-y. In total, 82 (76.6%) children presented some type of immune response against HAV. These findings demonstrate the persistence of immunological memory against HAV in the majority of children vaccinated between 6 and 7 years with a single dose of the inactivated virus vaccine.

Immunogenicity and safety of a live attenuated varicella vaccine co-administered with inactive hepatitis A vaccine: A phase 4, single-center, randomized, controlled trial.

Co-administration of vaccines can facilitate the introduction of new vaccines in immunization schedules. This study aimed to evaluate the immunogenicity and safety of co-administration with live attenuated varicella vaccine (VarV) and inactivated hepatitis A vaccine (HepA) among children aged 12 ~ 15 months. In this phase 4 clinical trial, 450 children were randomized with a ratio of 1:1 to receive VarV and Hep A simultaneously (Group A) or separately (Group B). The primary endpoints were the seroconversion rate of anti-varicella-zoster virus (VZV) antibodies 42 days after vaccination of VarV and the seroconversion rate of anti-Hepatitis A virus (HAV) antibodies 30 days after two-dose vaccination of HepA. After full immunization, the seroconversion rates of anti-VZV antibodies were 91.79% in Group A and 92.15% in Group B; the geometric mean titers (GMTs) were 11.80 and 12.19, respectively. The seroconversion rates of anti-HAV antibodies were 99.48% in Group A and 100.0% in Group B; the geometric mean concentrations (GMCs) reached 9499.11 and 9528.36 mIU/ml, respectively. The lower limits of the 95% CI for the seroconversion difference of anti-VZV antibodies and anti-HAV antibodies were -5.86% and -2.90%, which greater than the predefined non-inferiority margin (-10%). The incidence rate of adverse reactions in Group A was lower than Group B (9.33% vs 16.22%), and only one serious adverse event was reported in Group B, which was unrelated to the study vaccine. In conclusion, the co-administration of VarV with HepA has non-inferior immunogenicity and safety profiles were quite comparable with the separate administration of both vaccines.Trial registration number: NCT05526820 (ClinicalTrials.gov).

A randomized phase 3 trial of the immunogenicity and safety of coadministration of a live-attenuated tetravalent dengue vaccine (TAK-003) and an inactivated hepatitis a (HAV) virus vaccine in a dengue non-endemic country.

BACKGROUND: Vaccination against hepatitis A virus (HAV) is largely recommended for travelers worldwide. Concurrent dengue and HAV vaccination may be desired in parallel for travelers to countries where both diseases are endemic. This randomized, observer-blind, phase 3 trial evaluated coadministration of HAV vaccine with tetravalent dengue vaccine (TAK-003) in healthy adults aged 18-60 years living in the UK. METHODS: Participants were randomized (1:1:1) to receive HAV vaccine and placebo on Day 1, and placebo on Day 90 (Group 1), TAK-003 and placebo on Day 1, and TAK-003 on Day 90 (Group 2), or TAK-003 and HAV vaccine on Day 1, and TAK-003 on Day 90 (Group 3). The primary objective was non-inferiority of HAV seroprotection rate (anti-HAV ≥ 12.5 mIU/mL) in Group 3 versus Group 1, one month post-first vaccination (Day 30) in HAV-naïve and dengue-naïve participants. Sensitivity analyses were performed on combinations of baseline HAV and dengue serostatus. Secondary objectives included dengue seropositivity one month post-second vaccination (Day 120), HAV geometric mean concentrations (GMCs), and safety. RESULTS: 900 participants were randomized. On Day 30, HAV seroprotection rates were non-inferior following coadministration of HAV and TAK-003 (Group 3: 98.7 %) to HAV administration alone (Group 1: 97.1 %; difference: -1.68, 95 % CI: -8.91 to 4.28). Sensitivity analyses including participants who were neither HAV-naïve nor DENV-naïve at baseline supported this finding. Anti-HAV GMCs on Day 30 were 82.1 (95 % CI: 62.9-107.1) mIU/mL in Group 1 and 93.0 (76.1-113.6) mIU/mL in Group 3. By Day 120, 90.9-96.8 % of TAK-003 recipients were seropositive (neutralizing antibody titer > 10) to all four dengue serotypes. Coadministration of HAV vaccine and TAK-003 was well tolerated, with no important safety risks identified. CONCLUSION: Immune responses following coadministration of HAV vaccine and TAK-003 were non-inferior to administration of HAV vaccine alone. The results support the coadministration of HAV vaccine and TAK-003 with no adverse impact on immunogenicity, safety, and reactogenicity of either vaccine. CLINICALTRIALS: gov registration: NCT03525119.

Hepatitis A and B vaccination in adults at risk: A survey of US healthcare providers' attitudes and practices.

This study aimed to evaluate the attitudes and practices of US healthcare professionals (HCPs) regarding the Advisory Committee on Immunization Practices (ACIP) vaccination recommendations on HepA and HepB for adult patients at risk of contracting these infections or experiencing complications of hepatitis disease. This cross-sectional, web-based survey of 400 US HCPs, which included nurse practitioners and family medicine, internal medicine, infectious disease, emergency department, and gastroenterology physicians, assessed HCPs' attitudes and practices regarding the ACIP recommendations for adult patients at risk for hepatitis disease. HCP participants were identified via a survey research panel. A recruitment quota of 400 HCPs was set, including 50 NPs, 100 FMs, 100 IMs, 50 GIs, 50 EDs, and 50 IDs. The most frequently reported reasons for not recommending either HepA or HepB vaccines were "I think the risk of HepA infection is low in this patient population" and "I am uncertain about what the guidelines say about vaccinating this population." The most reported factors considered when determining eligibility for either vaccine were medical history and the patient's willingness/motivation to be vaccinated. Most reported it was extremely or moderately important to prevent hepatitis disease by vaccinating adult patients at risk, and most also reported recommending a HepA vaccine or HepB vaccine to patients at risk. Although most HCPs reported recommending HepA and HepB vaccines to patients at risk, these findings contrast with the low reported vaccination rates among these populations, and improved awareness of the ACIP recommendations among HCPs is needed.

Although hepatitis A and hepatitis B are vaccine-preventable diseases, not enough adults at risk are vaccinated in the United States (US). The Advisory Committee on Immunization Practices (ACIP) makes recommendations on the use of vaccines in the US. The ACIP recommendations identify groups of people at risk of contracting hepatitis A infection or experiencing complications of hepatitis A disease (e.g., people with chronic liver disease) and hepatitis B infection or its related complications (e.g., people with diabetes).To identify potential barriers to vaccination, we surveyed 400 US healthcare professionals to evaluate their views about the ACIP recommendations on hepatitis A and hepatitis B vaccination for patients at risk of infection or complications. Most reported it was extremely or moderately important to prevent hepatitis A or hepatitis B infection by vaccinating these adult patients. The most commonly reported reasons for not recommending either vaccine were "I am uncertain about what the guidelines say about vaccinating this population" and "I think the risk of hepatitis A or hepatitis B infection is low in this patient population".Our findings show that improved awareness of the guidelines among healthcare professionals is needed, particularly of the importance of hepatitis A vaccination, and hepatitis B vaccination in adults with diabetes. In addition to helping the ongoing multi-state hepatitis A outbreaks, this could aid in the successful implementation of the recent ACIP recommendation for hepatitis B vaccination in all adults that is expected to reduce barriers to vaccination.

Erythema Multiforme Following Hepatitis A and Pneumococcal Vaccinations.

Erythema multiforme (EM) is a rare cell-mediated immune response characterized by target or iris patches or plaques that present symmetrically on the extremities. This condition may be associated with pruritus but is usually self-limited and spontaneously resolves within 5 weeks of onset; prodromal symptoms are rare. Several known cases have been linked to vaccination, but many vaccines used in pediatric care have been reported as causative agents of EM. This case study offers an association of EM following administration of the hepatitis A and pneumococcal vaccines.

Acute hepatitis A in international travellers: a GeoSentinel analysis, 2008-2020.

BACKGROUND: Non-immune international travellers are at risk of acquiring hepatitis A. Although hepatitis A vaccination is recommended for unvaccinated travellers to high or intermediate hepatitis A virus endemicity, compliance with this recommendation is not universal.The main objective was to describe the demographic and travel characteristics of international travellers infected with hepatitis A during travel. METHODS: Available data on travellers with confirmed (positive molecular test) or probable (symptomatic individuals with a single positive IgM test) hepatitis A diagnosed during and after travel from January 2008 to December 2020 were obtained from the GeoSentinel Surveillance Network database. We analysed demographic and travel characteristics of infected travellers. RESULTS: Among 254 travellers with hepatitis A (185 confirmed and 69 probable), the median age was 28 years (interquartile range: 19-40), 150 (59%) were male, and among 54 travellers with information available, 53 (98%) were unvaccinated. The most common reasons for travel included tourism (n = 120; 47%) and visiting friends or relatives (VFR; n = 72; 28%). About two-thirds of VFR travellers with hepatitis A (n = 50; 69%) were younger than 20 years old. Hepatitis A was acquired most frequently in South-Central Asia (n = 63; 25%) and sub-Saharan Africa (n = 61; 24%), but 16 travellers (6%) acquired hepatitis A in regions with low endemicity including Western Europe (n = 7; 3%), the Caribbean (n = 6; 2%) and North America (n = 3; 1%). Median duration from illness onset to GeoSentinel site presentation was ~7 days (interquartile range : 4-14 days). Among 88 travellers with information available, 59% were hospitalized. CONCLUSIONS: Despite availability of highly effective vaccines, travellers still acquire hepatitis A, even when traveling to low-endemicity destinations. Providing pre-departure hepatitis A vaccine to susceptible travellers is crucial to reducing travel-associated hepatitis A and should be offered to all travellers as part of the pre-travel consultation, regardless of destination.

Epidemiologic patterns of hepatitis A infection during the pre-vaccination era: A population-based survey in Tunisia in 2015.

BACKGROUND: In the 1980s, Tunisia was considered a country of high endemicity for hepatitis A virus (HAV). Since 2000, an epidemiologic shift has led to an increased incidence of symptomatic and severe forms of HAV infection. OBJECTIVES: In 2015, we conducted a cross-sectional nationwide household-based hepatitis A virus (HAV) seroprevalence study in the total population regardless of age, sex, or geographic origin using a stratified sampling design to make an overview of the HAV epidemiologic situation in Tunisia before vaccine implementation. RESULTS: A total of 6,322 individuals were enrolled. The HAV prevalence was 78.8%. The anti-HAV IgG seropositivity rate increased from 16% for ages 5-9 years to 45% for ages 10-14 years, 67% for ages 15-19 years, 87% for ages 20-24 years, and >90% for older age groups, which suggested an age at midpoint of population immunity (AMPI) in late adolescence. It was significantly higher in rural areas (P < 10-3) and varied significantly between and within regions (P < 10-4). CONCLUSIONS: In this study, although the overall AMPI suggestsintermediate endemicity, the regional AMPI varies from intermediate to very high endemicity profiles attributable to different socioeconomic determinants and conditions of sanitation and hygiene. In addition, it provides insights for the best decisions in terms of vaccination strategies.

One or two doses of hepatitis A vaccine in universal vaccination programs in children in 2020: A systematic review.

BACKGROUND: Hepatitis A virus (HAV) is a global health concern as outbreaks continue to occur. Since 1999, several countries have introduced universal vaccination (UV) of children against HAV according to approved two-dose schedules. Other countries have implemented one-dose UV programs since 2005; the long-term impact of this schedule is not yet known. METHODS: We conducted a systematic literature search in four electronic databases for data published between January 2000 and July 2019 to assess evidence for one-dose and two-dose UV of children with non-live HAV vaccines and describe their global impact on incidence, mortality, and severity of hepatitis A, vaccine effectiveness, vaccine efficacy, and antibody persistence. RESULTS: Of 3739 records screened, 33 peer-reviewed articles and one conference abstract were included. Rapid declines in incidence of hepatitis A and related outcomes were observed in all age groups post-introduction of UV programs, which persisted for at least 14 years for two-dose and six years for one-dose programs according to respective study durations. Vaccine effectiveness was ≥95% over 3-5 years for two-dose programs. Vaccine efficacy was >98% over 0.1-7.5 years for one-dose vaccination. Antibody persistence in vaccinated individuals was documented for up to 15 years (≥90%) and ten years (≥74%) for two-dose and one-dose schedules, respectively. CONCLUSION: Experience with two-dose UV of children against HAV is extensive, demonstrating an impact on the incidence of hepatitis A and antibody persistence for at least 15 years in many countries globally. Because evidence is more limited for one-dose UV, we were unable to draw conclusions on immune response persistence beyond ten years or the need for booster doses later in life. Ongoing epidemiological monitoring is essential in countries implementing one-dose UV against HAV. Based on current evidence, two doses of non-live HAV vaccines are needed to ensure long-term protection.

Predictors associated with a better response to the Japanese aluminum-free hepatitis A vaccine, Aimmugen® , for people living with HIV.

AIM: After the hepatitis A virus (HAV) outbreak among men who have sex with men (MSM) around 2018, the importance of HAV vaccination was emphasized, especially for MSM-living with human immunodeficiency virus (MSM-LWHIV). Aimmugen® is licensed and distributed exclusively in Japan. While administration of three doses is recommended, 85% of recipients in the general population were reported to acquire seroprotection after the second dose. In this study, we evaluated the efficacy of two or three vaccine doses along with predictors associated with the response to Aimmugen® in MSM-LWHIV. METHODS: We retrospectively examined anti-HA-IgG titers of MSM-LWHIV vaccinated with Aimmugen® in our hospital. Patients' data were collected from medical records. RESULTS: Between January 2018 and October 2019, 141 subjects whose median age was 46 years old, were examined. All the subjects were on antiretroviral therapy (ART) and the median CD4 count was 615/µL. The acquisition rate of protectable anti-HA-IgG titers after the second and third dose was 71.1% and 98.6%, respectively. In 114 subjects whose anti-HA-IgG titers were tested after the second-dose, factors significantly associated with better response were prolonged ART duration and higher CD4 count. The titers of anti-HA-IgG after the third dose were higher in those who became seropositive after the second-dose than those who did not. CONCLUSIONS: Three-dose of Aimmugen® for MSM-LWHIV was effective while two-dose was less effective compared to non-HIV-infected people. People-LWHIV with shorter duration of ART and lesser CD4 cell count achieved lower titers of anti-HA-IgG and might require an additional vaccination.

Organ transplantation and vaccination / 器官移植

Organ transplant recipients are at a high risk of infection with high hospitalization rate, critical rate and fatality, due to low immune function caused by taking immunosuppressants for a period of long time after organ transplantation. Currently, vaccination is recognized as an effective approach to prevent infection. Organ transplant recipients may be vaccinated according to individual conditions. However, the sensitivity to vaccines may decline in organ transplant recipients. The types, methods and timing of vaccination have constantly been the hot spots of clinical trials. In this article, the general principles, specific vaccines and SARS-CoV-2 vaccines of vaccination in organ transplant recipients were briefly reviewed, aiming to provide reference for the vaccination of organ transplant recipients. Moreover, current status of SARS-CoV-2 vaccination for organ transplant recipients was illustrated under the global outbreak of novel coronavirus pneumonia pandemic.

A single blind randomized phase 3 study to evaluate safety and immunogenicity of inactivated hepatitis A vaccine (HAPIBEVTM) in 1-15 years-old healthy hepatitis A vaccine-naïve children.

The Biological E inactivated hepatitis A (HAPIBEV™) vaccine was developed by importing the Healive® vaccine bulk from China and fill-finish it in India. Healive® vaccine is approved in China for both children and adults. This study assessed the safety and immunogenicity of HAPIBEV™ vaccine as compared to the Havrix 720® vaccine of GlaxoSmithKline (GSK) pharmaceuticals when administered intramuscularly (IM) 6 months apart in 1-15 years old hepatitis A virus (HAV) vaccine naive children in India. This Phase 3, single blind, parallel, randomized, active-controlled, two-arm study was conducted at 8 centers in India in healthy HAV vaccine-naive children. Subjects were stratified into 2 age subsets (1-7 and 8-15 years) and randomly assigned to either BE-HAPIBEV™ or GSK's Havrix® vaccine and administered 2 IM injections 6 months apart. The immunogenicity evaluations included: (1) proportion of subjects who achieved the following at Day 210 from baseline: (a) seroconversion (≥20 mIU/mL) with anti-HAV immunoglobulin G (IgG) antibodies, (b) ≥4-fold increase in anti-HAV IgG antibodies, and (c) ≥2-fold increase in anti-HAV IgG antibodies concentration who were already seroconverted at baseline and (2) geometric mean concentrations (GMC) of anti-HAV IgG antibodies at baseline and Day 210. Safety was evaluated throughout the study. A total of 467 (89.8%) subjects completed the study. The non-inferiority criterion was met by HAPIBEV™ vaccine as seroconversion rates in both vaccine groups were 100%. Overall, other immunogenicity evaluations were either similar in both vaccine groups or higher in the HAPIBEV™ group compared with the Havrix® group. The safety profile was also comparable between HAPIBEV™ and Havrix® groups. The most common adverse event (AE) was injection site pain, and the majority of AEs were mild in severity. The HAPIBEV™ vaccine demonstrated an immunological and safety profile on par with Havrix® in 1-15 years old healthy HAV vaccine-naive Indian children. This study is registered with clinical trial registry of India bearing no: CTRI/2019/04/018384 on 02 Apr 2019.

Cost-effectiveness of routine catch-up hepatitis a vaccination in the United States: Dynamic transmission modeling study.

BACKGROUND: Despite routine vaccination of children against hepatitis A (HepA), a large segment of the United States population remains unvaccinated, imposing a risk of hepatitis A virus (HAV) to adolescents and adults. In July of 2020, the Advisory Committee on Immunization Practices recommended that all children and adolescents aged 2-18 years who have not previously received a HepA vaccine be vaccinated. We evaluated the public health impact and cost-effectiveness of this HepA catch-up vaccination strategy. METHODS: We used a dynamic transmission model to compare adding a HepA catch-up vaccination of persons age 2-18 years to a routine vaccination of children 12-23 months of age with routine vaccination only in the United States. The model included various health compartments: maternal antibodies, susceptible, exposed, asymptomatic infectious, symptomatic infectious (outpatient, hospitalized, liver transplant, post- liver transplant, death), recovered, and vaccinated with and without immunity. Using a 3% annual discount rate, we estimated the incremental cost per quality-adjusted life year (QALY) gained from a societal perspective over a 100-year time horizon. All costs were converted into 2020 US dollars. FINDINGS: Compared with the routine vaccination policy at 12-23 months of age over 100 years, the catch-up program for unvaccinated children and adolescents aged 2-18 years, prevented 70,072 additional symptomatic infections, 51,391 outpatient visits, 16,575 hospitalizations, and 413 deaths. The catch-up vaccination strategy was cost-saving when compared with the routine vaccination strategy. In scenario analysis allowing administering a second dose to partially vaccinated children, the cost-effectiveness of was not favorable at a higher vaccination coverage ($196,701/QALY at 5% and $476,241/QALY at 50%). INTERPRETATION: HepA catch-up vaccination in the United States is expected to reduce HepA morbidity and mortality and save cost. The catch-up program would be optimized when focusing on unvaccinated children and adolescents and maximizing their first dose coverage.