Meningococcal vaccination in patients with newly diagnosed asplenia in the United States

BackgroundPatients with asplenia are recommended to receive meningococcal ACWY (MenACWY) and B (MenB) vaccines in the United States (US).ObjectivesTo examine uptake and time to receipt of meningococcal vaccines in newly diagnosed asplenia patients, and identify factors associated with vaccination.MethodsFor this retrospective database analysis, patients were identified from 1/1/2010 (MenACWY) or 1/1/2015 (MenB) through 3/31/2018 from an administrative claims database including commercially insured US patients with ≥1 inpatient or ≥2 outpatient claims with evidence of a new asplenia diagnosis (sickle cell disease was excluded); continuous enrollment for ≥12 months before and ≥6 months after the index date; and age ≥2 (MenACWY) or ≥10 (MenB) years. Co-primary outcomes were uptake and time to receipt of ≥1 dose, separately for MenACWY and MenB, by Kaplan–Meier analysis. Cox proportional hazards regression models were used to identify characteristics associated with vaccination.ResultsAmong 2,273 and 741 patients eligible for the MenACWY and MenB analyses, respectively, 28.1% and 9.7% received MenACWY and MenB in the first 3 years after a new asplenia diagnosis. Patients were more likely to receive meningococcal vaccines if they had received pneumococcal vaccines (MenACWY: hazard ratio [HR] 26.02; 95% confidence interval [CI] 21.01–32.22; MenB: HR 3.89; 95% CI 2.07–7.29) or attended ≥1 well-care visit (MenACWY: HR 6.63; 95% CI 4.84–9.09; MenB: HR 11.17; 95% CI 3.02–41.26).ConclusionsMeningococcal vaccination rates among newly diagnosed asplenia patients were low, highlighting the need to educate providers about the recommendations for high-risk conditions and ensure healthcare access for vulnerable patients.     

Persistence of hSBA titers elicited by the meningococcal serogroup B vaccine menB-FHbp for up to 4 years after a 2- or 3-dose primary series and immunogenicity,safety, and tolerability of a booster dose through 26 months

BackgroundTo demonstrate extended protection against meningococcal serogroup B (MenB) disease after MenB-FHbp (bivalent rLP2086) vaccination, this study evaluated immunopersistence through 26 months following MenB-FHbp boosting after 2 or 3 primary doses in adolescents.Study designThis phase 3, open-label study was an extension of 3 phase 2 studies with participants aged 11–18 years randomized to receive primary MenB-FHbp vaccination following 1 of 5 dosing schedules or control. A booster dose was administered 48 months after the primary series. Immunopersistence through 48 months after the last primary dose (persistence stage) and 26 months postbooster (booster stage) was determined by serum bactericidal assays using human complement (hSBAs) against 4 vaccine-heterologous test strains. Safety evaluations included adverse events (AEs) and local and systemic reactions.ResultsOverall, 698 and 304 subjects enrolled in the persistence and booster stages, respectively. hSBA titers declined in all groups during 12 months postprimary vaccination, then remained stable through 48 months. One month postbooster, 93.4–100.0% of subjects achieved hSBA titers ≥ lower limit of quantitation against each test strain; percentages at 12 and 26 months postbooster were higher than at similar time points following primary vaccination. Primary and booster MenB-FHbp vaccinations were well tolerated, with ≤ 12.5% of subjects reporting AEs during each stage. The most common local (reported by 84.4–93.8% of subjects) and systemic (68.8–76.6%) reactions to the booster were injection site pain and fatigue and headache, respectively; ≤ 3.7% of subjects reported severe systemic events.ConclusionProtective hSBA titers initially declined but were retained by many subjects for 4 years irrespective of primary MenB-FHbp vaccination schedule. Boosting at 48 months after primary vaccination was safe, well tolerated, and induced immune responses indicative of immunological memory that persisted through 26 months. Booster vaccination during late adolescence may prolong protection against MenB disease.     

Meningococcal B vaccination coverage among older adolescents in the United States

BackgroundSerogroup B meningococcal (MenB) vaccination recommendations for adolescents in the United States (US) include routine vaccination for all individuals at increased risk and vaccination for individuals not at increased risk aged 16–23 years (preferred age 16–18 years) based on shared clinical decision-making. The two licensed MenB vaccines require administration of ≥2 doses.MethodsThis cross-sectional study analyzed 2017–2018 National Immunization Survey-Teen (NIS-Teen) data to evaluate ≥1 dose and ≥2 dose MenB vaccination coverage among adolescents aged 17 years. Multivariable logistic regression was used to further evaluate determinants of MenB vaccination.ResultsNationally, MenB vaccination coverage among 17-year-olds increased from 14.5% in 2017 to 17.2% in 2018 for ≥1 dose and from 6.3% to 8.4% for ≥2 doses. MenB vaccination coverage (2017–2018) was the lowest in the South (≥1 dose: 14.6%; ≥2 doses: 6.3%) and highest in the Northeast region (18.3% and 9.3%), with variation observed by census division. Adolescents were more likely to have received ≥1 dose of MenB vaccine if they had any Medicaid insurance (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.32–2.39) or had received human papillomavirus (OR, 1.94; 95% CI, 1.41–2.67) or meningococcal A, C, W, and Y (OR, 4.03; 95% CI, 2.92–5.56) vaccinations.ConclusionsMenB first-dose coverage in the US is low, and even lower for a second dose, with regional variation. Being up to date with other routinely administered vaccines increased the likelihood of receiving MenB vaccination.     

Persistence of bactericidal antibodies following primary and booster MenACWY-TT vaccination of toddlers: A review of clinical studies

The long-term persistence of antibody responses following primary vaccination with quadrivalent conjugate vaccines targeting meningococcal serogroups A, C, W, and Y (MenACWY) and the duration of protection following a booster dose have not been fully elucidated, particularly in children who received primary dosing as toddlers. This review summarizes the findings of one phase 3 and three phase 2 open-label, randomized clinical studies that assessed the long-term antibody persistence of MenACWY conjugated to tetanus toxoid as a carrier protein (MenACWY-TT) in toddlers. Following primary vaccination, antibody responses persisted for approximately 2–3 years and then decreased up to 5 years after vaccination. Geometric mean titers remained elevated for all serogroups up to 5 years after primary vaccination. In children who received a booster dose of MenACWY-TT at 4–5 years after primary dosing as toddlers, antibody responses were documented in >99% of subjects across all serogroups, with minimal decreases in antibody persistence from 2–6 years after booster vaccination. The persistence of meningococcal serogroup C (MenC) antibody responses was similar between MenACWY-TT and MenC vaccine recipients after primary and booster dosing. Together, these findings indicate that antibody responses to primary MenACWY-TT vaccination persist for 2–3 years. Additionally, these findings indicate that in subjects who receive primary MenACWY-TT vaccination as toddlers, the antibody response to booster MenACWY-TT vaccination lasts for up to 6 years and suggest that immune memory is afforded at least into early adolescence, which is an age group at increased risk of invasive meningococcal disease.     

Cost of illness of invasive meningococcal disease caused by serogroup B Neisseria meningitidis in Spain

IntroductionInvasive meningococcal disease (IMD) is a severe infectious disease, mainly affecting children under 5 years, associated with long-term physical, neurological and psychological sequelae. In Spain, most IMD cases are caused by meningococcal serogroup B (MenB). This study estimates its economic burden from a societal perspective in Spain.MethodsA previously published bottom-up, model-based incidence costing approach by Scholz et al. (2019) to estimate the economic burden of MenB in Germany was adapted to the Spanish setting. Diagnosis and age-related costs for a hypothetical Spanish cohort were calculated over a lifetime horizon. Official Spanish databases, literature and expert opinion were used as data sources. The costs were updated to 2019 prices, and a 3% discount rate was applied. Direct costs related to the acute IMD phase, long-term sequelae, rehabilitation and public health response were considered. Indirect costs included productivity losses and premature mortality and were calculated using the human-capital approach (HCA) and friction-cost approach (FCA). Deterministic and probabilistic sensitivity analyses were also performed.ResultAt base-case, the total cost for a cohort of 142 patients (2017–2018 period) was €4.74 million (€33,484/case) using the FCA and €13.14 million (€92,768/case) using the HCA. Direct costs amounted to €4.65 million (€32,765/case). Sequelae costs represented 62.46% of the total cost using the FCA and 77.63% using the HCA. Deterministic sensitivity analysis showed that variation of ± 20% in the input parameter values (population, epidemiology, productivity, costs) had the greatest influence on the base-case results, and the probabilistic sensitivity analysis showed the probability of fitting base-case estimates was > 99%, both for FCA and HCA.DiscussionMenB IMD is an uncommon but severe disease, with a high economic burden for Spanish society. The elevated costs per IMD case reflect its severity in each patient suffering this disease, especially due to the development of sequelae.     

A phase 3, randomized,controlled, open-label study to evaluate the persistence up to 5 years of 1 or 2 doses of meningococcal conjugate vaccine MenACWY-TT given with or without 13-valent pneumococcal conjugate vaccine in 12–14-month-old children

BackgroundImmunogenicity and safety up to 5 years after administration of 1 or 2 doses of quadrivalent meningococcal serogroup A, C, W, and Y tetanus toxoid conjugate vaccine (MenACWY-TT) given alone or with 13-valent pneumococcal conjugate vaccine (PCV13) in children was investigated.MethodsThis phase 3 study randomized healthy 12–24-month-olds to MenACWY-TT at Month 0 (ACWY1d), MenACWY-TT at Months 0 and 2 (ACWY2d), MenACWY-TT and PCV13 at Month 0 (Co-Ad), or PCV13 at Month 0 and MenACWY-TT at Month 2 (PCV13/ACWY). Immune responses 1, 3, and 5 years after primary vaccination were evaluated with serum bactericidal activity using rabbit complement (rSBA) titers ≥ 1:8 and geometric mean titers (GMTs). Evaluation of serious adverse events up to 5 years after primary vaccination are reported.ResultsOf the 802 children randomized in the study, 619 completed the study through Year 5. Immune responses after vaccination declined over time but were higher 5 years after vaccination compared with levels before vaccination. At Year 5, the percentages of children with rSBA titers ≥ 1:8 across all serogroups were 20.5 %?58.6 %, 28.4 %?65.8 %, 23.9 %?52.8 %, and 19.4 %?55.8 % in the ACWY1d, ACWY2d, Co-Ad, and PCV13/ACWY groups, respectively. Comparable antibody persistence at Year 5 was observed for participants receiving 1 or 2 doses of MenACWY-TT, although GMTs were elevated in those who received 2 versus 1 dose. The percentage of children with protective antibody titers at Year 5 was similar in participants who received PCV13 and MenACWY-TT compared with that observed for participants who only received 1 or 2 MenACWY-TT doses. No new safety concerns were identified during the study period.ConclusionAntibody responses persisted in the majority of children up to 5 years after primary vaccination with MenACWY-TT administered in a 1- or 2-dose regimen with or without PCV13, with no new safety concerns identified.ClinicalTrials.gov Identifier NCT01939158; EudraCT number 2013–001083-28.     

MenACWY-CRM conjugate vaccine booster dose given 4–6 years after priming: Results from a phase IIIb,multicenter, open label study in adolescents and adults

BackgroundVaccination strategies against bacterial meningitis vary across countries. In the United States, a single dose of quadrivalent meningococcal conjugate vaccine (MenACWY) is recommended at 11–12 years of age, with a booster dose approximately 5 years later. We assessed immune responses to a booster dose of MenACWY-CRM vaccine after priming with MenACWY-CRM or MenACWY-D vaccines in adolescents and adults.MethodsIn this phase IIIb, multicenter, open-label study, healthy 15–55-year-olds, who received MenACWY-CRM (N = 301) or MenACWY-D (N = 300) 4–6 years earlier or were meningococcal vaccine-naïve (N = 100), received one MenACWY-CRM vaccine dose. Immunogenicity was evaluated pre-vaccination, 3 or 5 days post-vaccination (sampling subgroups), and 28 days post-vaccination by serum bactericidal activity assay using human complement (hSBA). After vaccination, participants were monitored for 7 days for reactogenicity, 29 days for unsolicited adverse events (AEs), and 181 days for serious AEs and medically-attended AEs.ResultsSufficiency of the immune response to a MenACWY-CRM booster dose was demonstrated; the lower limit of the 1-sided 97.5% confidence interval for percentages of participants with hSBA seroresponse at 28 days post-vaccination was >75% for each serogroup in those primed with either the MenACWY-CRM or MenACWY-D vaccine. Seroresponse was observed in ≥93.24% of primed participants and ≥35.87% of naïve participants 28 days post-vaccination. At 5 days post-booster, among primed participants, hSBA titers ≥1:8 were achieved in ≥47.14% of participants for MenA and in ≥85.52% of participants for MenC, MenW and MenY, and 3.25- to 8.59-fold increases in hSBA geometric mean titers against each vaccine serogroup were observed. No safety concerns were raised throughout the 6-month follow-up period.ConclusionsA booster dose of the MenACWY-CRM vaccine induced a robust and rapid anamnestic response in adolescents and adults, irrespectively of either MenACWY-CRM or MenACWY-D vaccine administered 4–6 years earlier, with an acceptable clinical safety profile.ClinicalTrials.gov registration: NCT02986854.An Audio Summary linked to this article that can be found on Figshare https://figshare.com/articles/MenACWY-CRM_conjugate_vaccine_booster_dose_given_4_6_years_after_priming_Results_from_a_phase_IIIb_multicenter_open_label_study_in_adolescents_and_adults_mp4/11823048     

Effect of provider recommendation style on the length of adolescent vaccine discussions

ObjectiveTo determine whether providers’ vaccine recommendation style affects length of the adolescent vaccine discussions.MethodsWe analyzed vaccine discussions using audio-recordings of clinical encounters where adolescents were eligible for HPV vaccines ± meningococcal vaccines. We measured length of vaccine discussions, the provider’s use of an “indicated” (vaccination due at visit) or “elective” (vaccination is optional) recommendation style, and vaccine receipt. Parent and child demographics, parental vaccination intentions, and parental satisfaction with vaccine discussion were collected from pre- and post-visit surveys. We used linear and logit regressions with random effects to estimate recommendation style’s association with discussion length and with vaccine receipt, respectively.ResultsWe analyzed 106 vaccine discussions (82 HPV; 24 meningococcal) across 82 clinical encounters and 43 providers. Vaccine discussions were longer when providers presented vaccination as elective versus indicated (140 vs. 74 s; p-value < 0.001). Controlling for vaccine type, parental vaccination intent, and patient characteristics, an elective style was associated with 41 seconds longer vaccine discussion (p-value < 0.05). Providers used the indicated style more frequently with the meningococcal vaccine than with the HPV vaccine (96% vs. 72%; p-value < 0.05). Parents’ odds of vaccinating were 9.3 times higher following an indicated versus an elective presentation (p-value < 0.05). Vaccine discussion length and presentation style were not associated with parental satisfaction.ConclusionsOur results suggest that using an indicated recommendation improves vaccine discussions’ efficiency and effectiveness, but this style is used more often with meningococcal than HPV vaccines. Increasing providers’ use of indicated styles for HPV vaccines has the potential to increase vaccination rates and save time during medical visits.     

An innovative housing-related measure for individual socioeconomic status and human papillomavirus vaccination coverage: A population-based cross-sectional study

BackgroundHuman papillomavirus (HPV) is a known cause of anogenital (eg, cervical) and oropharyngeal cancers. Despite availability of effective HPV vaccines, US vaccination-completion rates remain low. Evidence is conflicting regarding the association of socioeconomic status (SES) and HPV vaccination rates. We assessed the association between SES, defined by an individual validated Housing-based Index of Socioeconomic Status (HOUSES), and HPV vaccination status.MethodsWe conducted a cross-sectional study of children/adolescents 9–17 years as of December 31, 2016, living in southeastern Minnesota by using a health-record linkage system to identify study-eligible children/adolescents, vaccination dates, and home addresses matched to HOUSES data. We analyzed the relationship between HPV vaccination status and HOUSES using multivariable Poisson regression models stratifying by age, sex, race, ethnicity, and county.ResultsOf 20,087 study-eligible children/adolescents, 19,363 (96.4%) were geocoded and HOUSES measures determined. In this cohort, 57.9% did not receive HPV vaccination, 15.8% initiated (only), and 26.3% completed the series. HPV vaccination-initiation and completion rates increased over higher SES HOUSES quartiles (P < .001). Rates of HPV vaccination initiation versus unvaccinated increased across HOUSES quartiles in multivariable analysis adjusted for age, sex, race, ethnicity, and county (1st quartile, referent; 2nd quartile, 0.97 [0.87–1.09]; 3rd quartile, 1.05 [0.94–1.17]; 4th quartile, 1.15 [1.03–1.28]; test for trend, P = .002). HOUSES was a stronger predictor of HPV vaccination completion versus unvaccinated (1st quartile referent; 2nd quartile, 1.06 [0.96–1.16]; 3rd quartile, 1.12 [1.03–1.23]; 4th quartile, 1.32 [1.21–1.44]; test for trend, P < .001). Significant interactions were shown for HPV vaccination initiation by HOUSES for sex (P = .009) and age (P = .006).ConclusionThe study showed disparities in HPV vaccination by SES, with the highest HOUSES quartiles associated with increased rates of initiating and even greater likelihood of completing the series. HOUSES data may be used to target and tailor HPV vaccination interventions to undervaccinated populations.     

Addressing logistical barriers to childhood vaccination using an automated reminder system and online resource intervention: A randomized controlled trial

BackgroundAs the rates of vaccination decline in children with logistical barriers to vaccination, new strategies to increase vaccination are needed. The goal of this study was to develop and evaluate the effectiveness of the Vaccines For Babies (VFB) intervention, an automated reminder system with online resources to address logistical barriers to vaccination in caregivers of children enrolled in an integrated healthcare system. Effectiveness was evaluated in a randomized controlled trial.MethodsQualitative interviews were conducted with parents of children less than two years old to identify logistical barriers to vaccination that were used to develop the VFB intervention. VFB included automated reminders to schedule the 6- and 12-month vaccine visit linking caregivers to resources to address logistic barriers, sent to the preferred mode of outreach (text, email, and/or phone). Parents of children between 3 and 10 months of age with indicators of logistical barriers to vaccination were randomized to receive VFB or usual well child care (UC). The primary outcome was percentage of days undervaccinated at 2 years of life. A difference in differences analysis was conducted.ResultsQualitative interviews with 6 parents of children less than 2 years of age identified transportation, scheduling challenges, and knowledge of vaccine timing as logistical barriers to vaccination. We enrolled 250 participants in the trial, 45% were loss to follow-up. There were no significant differences in vaccination uptake between those enrolled in UC or the VFB intervention (0.51%, p = 0.86). In Medicaid enrolled participants, there was a modest decrease in percentage of days undervaccinated in the VFB intervention compared to UC (6.3%, p = 0.07).ConclusionAutomated Reminders and with links to heath system resources was not shown to increase infant vaccination uptake demonstrating additional resources are needed to address the needs of caregivers experiencing logistical barriers to vaccination.     

Immunogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) administered concomitantly with the meningococcal serogroup B (4CMenB) vaccine in infants: A post-hoc analysis in a phase 3b,randomised, controlled trial

BackgroundNo data are currently available on immunogenicity of higher-valent pneumococcal conjugate vaccines when co-administered with a 4-component meningococcal serogroup B vaccine (4CMenB).MethodsPost-hoc analysis of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) immunogenicity when co-administered with 4CMenB (2 + 1 schedule) and/or a CRM-conjugated meningococcal serogroup C vaccine (MenC-CRM) in a trial assessing 4CMenB reduced schedules and co-administration with MenC-CRM (NCT01339923). Infants were randomized to receive 4CMenB and MenC-CRM (Group 1) or MenC-CRM (Group 2) at 3, 5, and 12 months (M) of age. Both groups received PHiD-CV (3 + 1 schedule) as part of the Brazilian national immunisation programme at 3 M, 5 M, 7 M, and 12 M of age. Antibody responses were assessed pre-vaccination, 1 M post-dose 2, pre-booster, and 1 M post-booster.ResultsAnti-pneumococcal antibody responses were in similar ranges in the two study groups.Conclusions4CMenB co-administration did not seem to impact antibody responses to PHiD-CV in infants.     

Equity of the Meningitis B vaccination programme in England, 2016–2018

In England, the Meningitis B (MenB) vaccine is scheduled at eight and 16 weeks with a booster dose at one year of age and protects children against invasive bacterial meningococcal disease caused by Neisseria meningitidis serogroup B. Coverage of the second dose of MenB vaccine at 12 months was >92% in 2017/18, but this may mask inequalities in coverage in particular population groups.MenB vaccination records for children aged six, 12 and 18 months of age from December 2016 to May 2018 were routinely extracted from GP patient management systems every month in England via a web-based platform for national monitoring of vaccine coverage. We determined the association between ethnicity, deprivation and area of residence, vaccine coverage and drop-out rates (between dose one and dose two), using binomial regression.After adjusting for other factors, ethnic groups with lowest dose one coverage (Black or Black British-Caribbean, White-Any other White background, White-Irish) also had lowest dose two coverage, but in addition, these ethnic groups also had the largest drop-out rates between dose one and dose two. The drop-out rate for Black or Black British-Caribbean children was 5.7 percentage points higher than for White-British children. Vaccine coverage decreased with increasing deprivation quintile, and this was most marked for the booster coverage (6.2 percentage points lower in the most deprived compared to least deprived quintile, p < 0.001).To achieve high coverage for completed courses across all ethnic groups and deprivation quintiles both high initiation rates and a reduction in drop-out rates for ethnic groups with lowest coverage is necessary. A qualitative approach to better understand reasons behind lower coverage and higher drop-out rates in the most underserved ethnic groups is required to develop tailored approaches addressing these inequalities.     

Anti-varicella-zoster virus antibody titers and seroprotection status from before the first dose of varicella vaccination to before entering elementary school in one region in Japan

ObjectiveWe aimed to examine changes in anti-varicella-zoster virus (VZV) antibody titers and seroprotection status from before the first dose of vaccination to before 7 years old entering elementary school in children who received the routine two-dose varicella vaccination.MethodsParticipants were 37 healthy children who received the routine two-dose varicella vaccination at our hospital. A total of five serum samples per child were collected immediately before and 4–6 weeks after each dose of the vaccination and in the year before entry to elementary school. We measured anti-VZV antibody titers by immune adherence hemagglutination (IAHA) method and glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). A positive antibody titer and the seroprotection level were set as ≥2-fold and ≥16-fold, respectively, for IAHA antibody and as ≥50 units and ≥105 units, respectively, for gpELISA-IgG antibody.ResultsThe rates of IAHA antibody positivity in the five samples (in order of collection) were 0%, 65%, 38%, 100%, and 59%, and the rates of seroprotection were 0%, 43%, 8%, 100%, and 43%. The rates of gpELISA-IgG antibody positivity were 8%, 81%, 89%, 100%, and 100%, and the rates of seroprotection were 5%, 54%, 70%, 100%, and 89%. The mean IAHA antibody titer and mean gpELISA-IgG antibody titer before entering elementary school were both lower than the respective titers obtained after the second vaccination (both p < 0.01).ConclusionsRoutine two-dose varicella vaccination leads to good antibody production, but titers of acquired antibodies decrease before children enter elementary school.     

Safety data from the MenB-FHbp clinical development program in healthy individuals aged 10 years and older

BackgroundThe MenB-FHbp vaccine (Trumenba®) is licensed in various countries for the prevention of meningococcal serogroup B disease in individuals ≥ 10 years of age. The clinical development program included 11 completed trials where, in each trial, MenB-FHbp had an acceptable safety profile after a primary vaccination series was administered to individuals 10–65 years of age. However, the detection of potential rare events was limited because of individual clinical trial size. The current safety analysis evaluates pooled reactogenicity and other adverse events (AEs) reported in these trials to identify new safety signals not detectable in individual trials.MethodsEleven trials contributed safety data, of which 10 recorded local and systemic reactogenicity events; 8 of the trials were controlled, and reactogenicity data were pooled for 7 of these 8 trials. Additional AE evaluations included immediate AEs (IAEs), medically attended AEs (MAEs), serious AEs (SAEs), newly diagnosed chronic medical conditions (NDCMCs), and autoimmune or neuroinflammatory conditions.ResultsLocal and systemic reactions were more frequent in the MenB-FHbp group (n = 15,294) compared with controls (n = 5509), although most reactions were transient and mild to moderate in severity. Frequencies of IAEs, SAEs, MAEs, NDCMCs, and autoimmune or neuroinflammatory conditions were similar between the MenB-FHbp and control groups.ConclusionsMenB-FHbp demonstrated a favorable safety and tolerability profile in the clinical development program of > 15,000 vaccine recipients ≥ 10 years of age. No new safety signals were identified in the pooled analysis compared with data from the individual trials. Continued postmarketing safety surveillance is important for the identification of rare events.Clinicaltrials.gov: NCT01299480; NCT000808028; NCT00879814; NCT00780806; NCT01352845; NCT01352793; NCT01461993; NCT01323270; NCT01830855; NCT01461980; NCT01768117.     

Safety of meningococcal B vaccine (4CMenB) in adolescents in Australia

BackgroundFour-component meningococcal B (4CMenB) vaccine is licensed in many countries but has had limited use in adolescents despite this age group being at increased risk of meningococcal disease.ObjectivesTo assess the safety profile of two doses of 4CMenB in adolescents.MethodsCluster randomised controlled trial of senior school students in South Australia (SA) with participating schools randomised to intervention (4CMenB) or control. Vaccine safety was monitored using the South Australian Vaccine Safety Surveillance System (SAVSS), a spontaneous reporting system for adverse events following immunisation (AEFI) with enhanced follow-up of AEFI.Results58,637 doses of 4CMenB vaccine were administered to 30,522 students (median age 16 years) during 2017–2018. Of 18,348 and 12,174 students vaccinated in 2017 and 2018, 97.3% and 84.3%, respectively, received both scheduled doses (N = 28,115). 193 AEFI in 187 students were reported with a reporting rate of 0.32% (95%CI: 0.28–0.39%). Seventy individuals sought medical review, including nine serious adverse events. 98% (166/169) of those who were contactable for AEFI follow-up (87.6% 169/193) reported resolution of the event. Most common AEFI were injection site reaction (126/193), headache (99/193) and nausea (61/193). AEFI were more frequently reported in females (aOR = 1.409 (95%CI: 1.002, 1.980)), schools with high level of educational advantage (adjusted Odds Ratio (aOR) = 1.515 (95%CI: 1.005, 2.284)), following first dose (aOR = 1.619 (95%CI: 1.168, 2.244)), and in 2017 (aOR = 1.437 (95%CI: 1.001, 2.064)). Reported AEFI declined with increasing age (aOR = 0.771 (95%CI: 0.673, 0.883)).ConclusionIn this largest post-licensure use of 4CMenB in adolescents, the low AEFI reporting rate provides real-world evidence of 4CMenB safety in this age group.(ClinicalTrials.gov number: NCT03089086).     

Developing communication tools on rotavirus vaccination to support family paediatricians in Italy

BackgroundUniversal rotavirus (RV) vaccination for newborns was introduced in Italy in 2018, but national vaccination coverage is still suboptimal. Effective communication between the family paediatrician (FP) and parents/caregivers is essential to promote vaccination acceptance. This project aimed to support FPs in communicating RV vaccination to parents/caregivers through the development and implementation of demonstrative videos and training modules.MethodsA working group composed of two FPs, two communication professionals, a medical expert from GSK and a clinical psychologist, was formed to establish the key scientific information to be communicated to parents/caregivers and develop the demonstrative videos. Four videos depicting four communication styles (I to IV) were developed based on the Social Styles Theory. Thirty FPs were then asked to pilot test the videos and provide feedback. In addition, two training modules with scientific information were developed to learn how to respond to parents’/caregivers’ objections.ResultsA total of 23 FPs provided feedback after using one or more videos at least five times. Twenty FPs (87.0 %) used mostly-one style, and most (60.0 %) used Style IV. Overall, the feedback was positive, as the majority of FPs (82.6 %, n = 19/23) indicated that the proposed videos were ‘useful’ or ‘extremely useful’ for introducing the RV vaccination to parents/caregivers in their actual practice. Based on this feedback, shorter versions of each video were also produced, and two training modules were developed to support FPs in responding to parental objections. Most FPs 75 % (n = 9/12) found Module 1 ‘very useful’, and all found Module 2 ‘very useful’ (100 %, n = 12/12).ConclusionsThe communication tools developed were well appreciated by the FPs and are expected to support FPs in communicating RV vaccination thereby increasing its coverage. Practicing RV communication may also prove beneficial for FPs to communicate other critical topics to parents/caregivers.     

Hepatitis A incidence,seroprevalence, and vaccination decision among MSM in Amsterdam,the Netherlands

BackgroundSeveral outbreaks of Hepatitis A virus (HAV) were recently documented among men who have sex with men (MSM) in Europe. We investigated the HAV incidence among MSM in Amsterdam, the Netherlands; and HAV seroprevalence and HAV vaccination decision among MSM visiting the Sexually Transmitted Infection (STI) clinic in Amsterdam.MethodsUsing surveillance data from 1992 to 2017 of MSM with acute HAV in Amsterdam, we estimated the incidence by calendar year and age. We explored HAV seroprevalence by calendar year and age, determinants for HAV seropositivity, and opting-in/out for HAV vaccination using data collected among MSM that visited the STI clinic between 2006 and 2017 and were included in a nationwide Hepatitis B virus (HBV) vaccination programme. Offering HAV vaccination at the STI clinic differed over three consecutive periods: not offered, offered for free, or offered for 75 euros. Logistic regression analyses were used to explore determinants.ResultsHAV incidence increased in 2016/17 after 4 years of absence and peaked in MSM around 35 years of age. Among MSM visiting the STI clinic, HAV seroprevalence was 37% (95%CI = 35–40%), which was constant over the period 2006–2017, and increased with age (p < 0.001). Determinants for HAV seropositivity in multivariable analysis were: older age (p < 0.001), originating from an HAV endemic country (p < 0.001), and being HBV seropositive (p = 0.001). MSM opted-in more frequently when HAV vaccination was offered for free versus paid (89% versus 11%, respectively; p < 0.001). Younger MSM were less inclined to vaccinate when payment was required (p = 0.010). Post-hoc analyses showed that 98% versus 46% of MSM visiting the Amsterdam STI clinic would be protected against HAV infection if HAV vaccination was offered for free or for 75 euros, respectively.ConclusionsThe MSM population of Amsterdam is vulnerable to a new HAV outbreak. We strongly recommend that MSM have access to free hepatitis A vaccination.     

The effects of parent’s health literacy and health beliefs on vaccine hesitancy

Parental vaccine hesitancy is a key factor influencing children’s vaccination against infectious diseases such as the COVID-19. The current study aims to investigate how parent’s health literacy and health belief affect parental hesitancy toward the COVID-19 vaccination, and navigate effective measures to help parents make vaccination decision for children. A mixed-mode web survey was conducted among parents of children aged 3–11 years. Parental vaccine hesitancy, health literacy, and health beliefs were assessed. Parallel mediation model examined whether the association between parent's health literacy and vaccine hesitancy was mediated by health beliefs. In total, 11.3% of the 346 participants reported vaccine hesitancy. Hesitant parents were more likely to be he mother (Father: 4.5%; Mother: 12.9%) and with children having allergic issues (Allergic: 18.3%; Non-allergic: 9.8%). Meanwhile, parents with lower health literacy were more likely to show hesitancy towards vaccinating their children (β = −6.87, 95% CI = [−10.50, −3.11]). This relationship was partially mediated by more perceived barriers in vaccination (β = −2.53, 95%CI = [−4.09, −1.02]), but not other health beliefs. In other words, parents with better health literacy may perceive fewer barriers in making vaccination decision for their children, thus being less hesitant. Accordingly, healthcare professionals and policy makers could design education service to promote parents’ health literacy, and remove the perceived barriers as well as increase their confidence in following the COVID-19 vaccine guidance for children.