Feasibility of age- and gestation-based routine universal influenza vaccines schedules for children aged 6 months − 2 years and pregnant women

BackgroundHong Kong’s seasonal influenza schedule follows the World Health Organization’s northern hemisphere vaccine composition recommendations but with year-round influenza activity there is the potential to implement routine age- and gestation-based schedules utilising both northern and southern hemisphere vaccines for children aged 6 months to 2 years and for pregnant women. This study assessed the potential feasibility of such schedules.MethodsA literature review was conducted and in-depth interviews with vaccine experts, policy makers and nurses were undertaken.ResultsThe following schedules were proposed and assessed for perceived feasibility: 1) a four-dose schedule in the first two years of life requiring an additional unscheduled clinic visit at 7 months; 2) a three-dose schedule excluding the 4-week booster after the first dose; 3) a two-dose schedule for pregnant women involving a dose at the booking visit and a dose with pertussis vaccine at 7 months gestation; and 4) a one-dose schedule at 7 months gestation.ConclusionsAge- and gestation-based routine influenza vaccination schedules are theoretically feasible for both young children and pregnant women. The three-dose paediatric and one-dose obstetric schedules were assessed in interviews with vaccine experts, policy makers and nurses to be most acceptable. Further clinical studies are required to determine whether such schedules are non-inferior to current seasonal-based schedules in terms of vaccine effectiveness and vaccine uptake.     

Hepatitis A antibody persistence 8 and 10 years after 1-dose and 2-dose vaccination in children from Panama

BackgroundHepatitis A virus (HAV) remains a global public health concern, which is potentially growing in Latin America, due to an expected shift from high to intermediate endemicity levels. The use of HAV vaccines in pediatric national immunization programs (NIPs), either as a 2-dose or a 1-dose schedule, has been explored in Latin American countries; however, evidence demonstrating long-term protection in this population is limited in the region. We evaluated long-term antibody persistence following a 1-dose partial series and the recommended 2-dose schedule used in Panama’s pediatric NIP.MethodsTwo independent cross-sectional serological surveys were conducted at year 8 (Y8) and Y10 following vaccination under the NIP with 1 or 2 doses of an inactivated HAV vaccine (Havrix, GSK). Seropositivity (anti-HAV antibody concentration ≥ 15 mIU/mL) rates and antibody geometric mean concentrations (GMCs) were assessed at each serosurvey. Non-inferiority of 1 dose versus 2 doses was also explored.ResultsThis study (NCT02712359) included 600 and 599 children at Y8 and Y10 post-vaccination, respectively. Seropositivity rates were 74.3% (95% confidence interval [CI]: 69.0; 79.2) and 97.7% (95% CI: 95.3; 99.1) at Y8 and 71.9% (95% CI: 66.4; 76.9) and 96.3% (95% CI: 93.5; 98.2) at Y10, in the 1-dose and 2-dose groups, respectively. Antibody GMCs were lower in the 1-dose versus the 2-dose group in both surveys. Non-inferiority was not demonstrated since the lower limit of the 2-sided 95% CI for the between-group difference in seropositivity rates (1-dose minus 2-dose) was < ?10%.ConclusionAnti-HAV antibody persistence was observed in lower percentages of children receiving 1 dose versus 2 doses of Havrix, at 8 and 10 years post-vaccination in Panama. Further investigations are needed to confirm antibody persistence and conclude on the protection afforded beyond 10 years in the pediatric population in Latin America.     

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

BackgroundVaccination 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.MethodsParticipants 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.Results900 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.ConclusionImmune 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.     

Vaccine coverage among children with epilepsy in two Canadian provinces: A Canadian immunization research network study

ObjectivesChildren with epilepsy are at increased risk of complications from vaccine-preventable infections, yet information on vaccine coverage in these children is scarce. We aimed to compare vaccine coverage among children with epilepsy to children without epilepsy.Study designWe conducted a retrospective cohort study including all 2005–2013 births in Manitoba and Ontario, Canada, creating two cohorts: 2-year-olds and 7-year-olds (followed to age 2 and 7 years). We split each cohort into epilepsy and non-epilepsy subcohorts. We assessed vaccination coverage based on provincial schedules and determined timeliness of MMR (measles, mumps, rubella) dose 1 (recommended at 12 months) and DTaP (diphtheria, tetanus, pertussis) dose 4 (recommended at 18 months). We used logistic regression to calculate adjusted odds ratios (aORs) of the association between epilepsy and vaccination, combining both provincial estimates using random effects meta-analysis.ResultsWe included 16,558 2-year-olds (Manitoba, 653; Ontario, 15,905) and 13,004 7-year-olds (Manitoba, 483; Ontario, 12,521) with epilepsy. At age 2 years, the aOR for up-to-date vaccination among children with versus without epilepsy was 0.9 (95% confidence interval 0.8–1.1); at age 7 years it was 1.0 (0.9–1.1). Infants diagnosed with epilepsy before age 6 months were less likely to be up-to-date at age 2 years (0.9; 0.8–0.9), although this difference disappeared by age 7 years. Vaccine timeliness was similar between children with and without epilepsy for MMR dose 1 and DTaP dose 4.ConclusionsOverall, this study suggests that children with epilepsy are not significantly under-vaccinated compared to their peers without epilepsy. As children with epilepsy are at a higher risk of complications from vaccine-preventable diseases, vaccination in children with epilepsy should be optimized, especially early in life, as these children may not be able to rely on herd protection.     

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

BackgroundDespite 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.MethodsWe 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.FindingsCompared 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%).InterpretationHepA 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.     

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.     

Immunogenicity and safety of an egg culture-based quadrivalent inactivated non-adjuvanted subunit influenza vaccine in subjects ≥3 years: A randomized,multicenter, double-blind,active-controlled phase III,non-inferiority trial

Subunit influenza vaccine only formulated with surface antigen proteins has better safety profiles relative to split-virion influenza vaccine. Compared to the traditional quadrivalent split-virion influenza vaccine, a novel quadrivalent subunit influenza vaccine is urgently needed in China. We completed a phase 3, randomized, double-blind, active-controlled, non-inferiority clinical study at two sites in Henan Province, China. Eligible volunteers were split into four age cohorts (3–8 years, 9–17 years, 18–64 years, and ≥ 65 years, based on their dates of birth) and randomly assigned (1:1) to the subunit and the split-virion ecNAIIV4 groups. All volunteers were intramuscularly administered a single vaccine dose at baseline, and children aged 3–8 years received a boosting dose at day 28. And the immune response was evaluated by measuring hemagglutinin-inhibition antibody titers against the four vaccine strains in blood samples. Safety profiles had nonsignificant differences between the study groups in ≥ 3 years cohort. Most adverse reactions post-vaccination, both local and systemic, were mild to moderate and resolved within 3 days. And no serious adverse events occurred. The immunogenicity of the trial vaccine was non-inferior to the comparator. Further, a two-dose vaccine series can provide better seroprotection than that of a one-dose series in children aged 3–8 years, with clinically acceptable safety profiles.Clinical Trials Registration. ChiCTR2100049934.     

Long-term effectiveness of pentavalent and monovalent rotavirus vaccines against hospitalization in Taiwan children

BackgroundTwo rotavirus vaccines (RV1 and RV5) are available on the private market in Taiwan, not included in national immunization program. Scanty reports evaluated the rotavirus vaccine effectiveness (VE) in Asian countries.MethodsFrom February 2014-July 2017, we conducted a prospective case-control study in ten hospitals in Taiwan. Case-patients included children aged 8–59 months, and hospitalized with laboratory-confirmed rotavirus acute gastroenteritis (AGE). For each case patient, up to four controls, rotavirus-negative AGE or non-AGE illnesses, respectively, were matched by gender, age and enrolled date. Vaccination history was confirmed through vaccination card or hospital record. VE was calculated as (1 − odds ratio of vaccination) × 100%.ResultsTotally 4248 AGE patients and 2242 non-AGE controls were enrolled. A total of 330 case-patients with rotavirus AGE, 1226 rotavirus-negative AGE controls and 1122 non-AGE controls were included for analysis. Unvaccinated rate was 85.15% for rotavirus-positive cases, 42.9% for rotavirus-negative controls, and 34.31% for non-AGE controls. VE of two-dose RV1 was 84.9% (95% confidence interval [CI]:77.7%, 90.1%) for rotavirus-negative AGE and 88.9% (95% CI: 83.4%, 92.8%) for non-AGE controls, while VE of three-dose RV5 was 92.5% (95% CI: 85.1%, 96.7%) and 96.4% (95% CI: 91.9%, 98.6%), respectively. For respective vaccine, VEs were not significantly different in term of rotavirus genotypes. VEs of both vaccines declined <80% in children aged three years by combined controls.ConclusionsBoth vaccines provided excellent and sustained protection against rotavirus AGE hospitalization in children in Taiwan, but the effectiveness declined slightly in children aged three years.     

Impact of the National Perinatal Hepatitis B Prevention Programme in the Republic of Korea: A retrospective registry-based cohort study

IntroductionHepatitis B is a major preventable cause of morbidity and mortality from chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. We aimed to evaluate the performance and outcomes of the Korean Perinatal Hepatitis B Prevention Programme (PHBPP) and to investigate the impact of the current post-exposure immunoprophylaxis protocol.MethodsA retrospective cohort study was performed based on electronic data registry of infants born to hepatitis B virus (HBV)-infected mothers between July 2002 and 2013.ResultsDuring the study period, 159,983 Korean infants were registered with the PHBPP, with an overall programme coverage of 92.8%. Despite receiving timely post-exposure immunoprophylaxis, 8.6% of infants born to mothers aged <25 years and hepatitis B e antigen (HBeAg)-positive, and 0.7% of infants born to mothers aged ≥25 years and HBeAg-negative were infected. An estimated 14,123 infants were directly protected from perinatal HBV transmission by the PHBPP during the 11.5-year period, at a cost of 1157 US dollars per case averted. The incidence of paediatric hepatocellular carcinoma declined dramatically during the period.ConclusionsA substantial number of infants have been prevented from hepatitis B since the PHBPP was launched in the Republic of Korea. Continued efforts to promote the programme, an integrated approach to maximising its coverage, a risk-stratified strategy, and innovations in logistics could further reduce perinatal HBV transmission.     

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.     

Adult immunization against hepatitis B: Does the number of jabs matter?

BackgroundAt least one-half of adults beginning an immunization series with a three-dose hepatitis B virus (HBV) vaccine (ENGERIX-B, RECOMBIVAX-B) have been reported not to receive the third dose. Use of a two-dose vaccine may improve adherence and lead to greater overall levels of seroprotection.ObjectiveTo examine expected levels of adherence and overall seroprotection at one year among adults in routine clinical settings beginning an immunization series with either ENGERIX-B or the two-dose HBV vaccine, HEPLISAV-B.MethodsDecision-analytic model comparing expected levels of adherence and overall seroprotection at one year among a hypothetical cohort of one million previously unvaccinated adults aged ≥ 30 years receiving first doses of either ENGERIX-B or HEPLISAV-B in a routine clinical setting. We stratified the population by age (30–49 years vs ≥ 50 years) to allow for possible differences in adherence and seroprotection. We estimated our model using published adherence rates for HBV vaccines, and reported seroprotection rates by number of doses administered. We also compared total expected costs of HBV immunization with each vaccine.ResultsUse of a two-dose rather than three-dose HBV vaccine would increase the expected number of adults seroprotected at one year by 275,000 per one million persons beginning immunization series, largely reflecting a gain of 290,000 in the expected number of persons fully vaccinated. Results were similar for the two age groups. While the cost per dose of HEPLISAV-B exceeds that of ENGERIX-B, its estimated mean cost per person seroprotected at one year is $50-$70 (～15%) lower.ConclusionsUse of a two-dose HBV vaccine would increase the number of adults fully seroprotected at one year compared with the number expected with a three-dose vaccine. Notwithstanding its higher unit cost, mean expected cost per person seroprotected is substantially lower for HEPLISAV-B than ENGERIX-B as a result of much higher levels of seroprotection.     

Immunogenicity and safety of a two-dose regimen with hepatitis E virus vaccine in healthy adults in rural Bangladesh: A randomized,double-blind,controlled, phase 2/pilot trial

BackgroundHepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide and it contributes to considerable maternal and neonatal mortality and morbidity in many low-income countries like Bangladesh. A three-dose regimen of a vaccine against HEV (HEV 239) has shown promising results in China. The effects and safety of this vaccine in other populations and with different dosing regimens remains uncertain.ObjectivesInvestigate the immune response and safety of a two-dose regimen with the HEV 239 vaccine among healthy adults. Examine the feasibility of conducting a larger HEV 239 vaccine trial in rural Bangladesh.MethodsOne-hundred healthy men and non-pregnant women 16–39 years old were randomized in a 1:1 ratio to receive two doses of either the study (HEV) or control (Hepatitis B virus, HBV) vaccine (at 0, 1 month). Blood samples were collected at day 0, day 60 and 2 years after vaccination. The primary endpoints were the proportion and severity of adverse events up to 2 months after dose one and the longitudinal shift in anti-HEV IgG levels from day 0 to day 60 and 2 years after vaccination.ResultsAdverse events to HEV 239 were comparable to the control vaccine, mild in severity and resolved within one to nine days. All participants in the study group seroconverted and achieved high levels of HEV IgG antibodies that remained positive for two years in all but one. A T-cell response was detected one month after HEV 239 vaccination.ConclusionOur results show that two doses of the HEV 239 vaccine produces broad and likely functional immune responses against HEV that remain for at least two years. The safety profile was acceptable and a phase four study of HEV 239 in rural Bangladesh is feasible.ClinicalTrials.gov Identifier: NCT02759991.     

Incidence of herpes zoster among varicella-vaccinated children,by number of vaccine doses and simultaneous administration of measles,mumps, and rubella vaccine

IntroductionChildren may receive measles-mumps-rubella (MMR) and varicella (VAR) vaccines separately or as measles-mumps-rubella-varicella (MMRV). We examined whether pediatric herpes zoster (HZ) incidence varied by pattern of varicella vaccine administration.MethodsIn six integrated health systems, we examined HZ incidence among children turning 12 months old during 2003–2008. All received varicella and MMR vaccines on recommended schedules. Cases were identified through 2014 using ICD-9 codes. Incidence was examined by number of varicella vaccine doses and same-day MMR.ResultsAmong 199,797 children, overall HZ incidence was 18.6/100,000 person-years in the first-dose MMR + VAR group, 17.9/100,000 person-years in the MMRV group, and 7.5/100,000 person-years in the VAR-alone group. HZ incidence was lower following the second dose than before the second dose in all first-dose groups.ConclusionsHZ incidence was not meaningfully different between the MMRV and MMR + VAR first-dose groups. Overall and within first-dose groups, HZ incidence was lower among children receiving two varicella vaccine doses.     

Reduction of HPV16/18 prevalence in young women after eight years of three- and two-dose vaccination schemes

BackgroundRecommendations for human papillomavirus vaccination have relied on immunogenicity studies and efficacy results derived from adult women. Insufficient information exists regarding HPV effectiveness in vaccinated girls as they become sexually active, regardless of dose scheme. We aimed to compare the prevalence of high-risk HPV between unvaccinated and vaccinated young women eight years after immunization.MethodsAfter eight years, we recontacted women who received two-dose of bivalent or three-dose—either bivalent or quadrivalent—, HPV vaccine when aged 9–10 years-old as part of a clinical trial. Additionally, we recruited a contemporaneous unvaccinated woman group for comparison. Only those sexually active were included. High-risk HPV DNA was determined in urine samples and compared across groups.ResultsThe prevalence of HPV16/18 types was 6.8% (95 %CI 3.2–14.1%) in the unvaccinated (n = 6/88), 1.1% (95 %CI 0.2–5.8%) in the three-dose (n = 1/93), and 0.0% (95 %CI 0.0–7.0%) in the two-dose group (n = 0/51).ConclusionHPV vaccination, with two-dose of bivalent or three-dose schemes—either with the bivalent or quadrivalent vaccine—, was associated with a lower prevalence of HPV16/18 types eight years after primary immunization.     

Empowering Health Workers to Build Public Trust in Vaccination: Experience from the International Pediatric Association’s Online Vaccine Trust Course, 2020–2021

BackgroundThe quality of interactions between health workers (HWs) and caregivers is key in vaccine acceptance. To optimize this, HWs need knowledge about best vaccine communication practices in person and on social media. Most pre-service curricula do not include such approaches. COVID-19 necessitated the International Pediatric Association (IPA) to shift from in-person train the trainer workshops to developing an online Vaccine Trust Course to address these gaps.MethodThe seven-module, 8-hour Vaccine Trust Course was offered online in seven languages and promoted globally. Course outcomes for participants between September 1, 2020 and September 30, 2021 were assessed using enrollment, participation, and completion data; pre-and post-training surveys of attitudes, knowledge, and practice skills; and follow-up practice surveys 3 months post course completion.ResultsOf the 4,926 participants across 137 countries who registered; 2,381 (48.3 %) started the course, with 1,217 (51.1 %) completing. The majority were 25 – 39 years (57 %), female (57 %), and in pediatrics (70 %); 31 % came from India. 62 % of completers rated course structure/design as excellent, 36 % as good. Over 80 % rated the content as the most valuable aspect. Three months post training, 61 % HWs reported increased empathy towards caregivers, confidence while counseling and increased vaccine acceptance amongst their patients. 21 % identified the course as the only factor in these positive changes.ConclusionShifting from face-to-face to online training due to the COVID-19 pandemic helped increase the global reach of HWs course engagement and uptake. Trained HWs reported increased empathy towards caregivers and confidence while counseling and increased patient vaccine acceptance.     

Incidence trends of parapneumonic pleural effusions/empyema in children 2009 to 2018 from health insurance data: Only temporal reduction after the introduction of PCV13

BackgroundRecently, emergence of a higher proportion of serotype 3 in children with parapneumonic pleural effusion/empyema (PPE/PE) were observed in Germany despite general immunization with 13-valent pneumococcal conjugate vaccine (PCV13) since 2009. The impact of PCV13 on the overall incidence of PPE/PE in children is unclear.MethodsAnnual incidence of PPE/PE in children were determined using secondary health care data for 2009–2018, provided by the Barmer statutory health insurer, serving about 11% of the German population. Temporal trends of the annual incidence were modelled applying generalized additive models.ResultsOverall incidence of PPE/PE in children ( ≤18 years) in the ten-year observation period was 18.17 per 100,000. The 0–1 year olds showed the highest incidence (43.09 per 100 000). PPE/PE incidence decreased from 2009 until 2013 (nadir 2013 was 15.36; 95% CI: 13.41–17.31). Since 2013, the data show an annual increase. The nadir of incidence for the 2–5 year olds (15.85; 95% CI: 11.27–20.43) and the 6–18 year olds (12.29; 95% CI: 10.23–14.36) was also in 2013, whereas for the 0–1 year olds it was found in 2014 (32.66; 95% CI: 23.79–41.54). The GAM across all age groups showed a nearly U-shaped curve between time and incidence of PPE/PE by calendar year (p-non-linear = 0.0017). The model confirms the nadir in the year 2013.DiscussionWe found a nonlinear temporal trend of PPE/PE incidence in children with a decrease from 2009 to 2013 and a subsequent increase until 2018. The former might be explained by a quasi elimination of serotype 1, the latter by an increase in the proportion of serotype 3 as demonstrated in German surveillance data of pediatric PPE/PE cases generated during the same observation period.     

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).     

Number needed to immunize to prevent RSV with extended half-life monoclonal antibody

BackgroundRespiratory syncytial virus (RSV) is one of the most important respiratory pathogens in young children. Infants <6 months of age and infants and young children with extreme pre-term birth, and cardiac and pulmonary co-morbidities experience the highest incidence of severe RSV disease. There are no licensed vaccines; immunoprophylaxis is recommended for the highest risk children. Extended half-life RSV monoclonal antibodies (EHL-mAbs) are under development intended for immunization of all infants and high-risk children <2 years of age. We modeled the anticipated public health benefits of RSV EHL-mAb immunization using the number needed to immunize (NNI).MethodsWe combined RSV hospitalization, outpatient and outpatient lower respiratory tract infection (LRI) incidence estimates and a range of immunization efficacies to estimate the annual NNI. We calculated the absolute incidence rate reduction (ARR) by multiplying the incidence rates by immunization efficacy. NNI was calculated as the reciprocal of the ARR.ResultsFor an RSV EHL-mAb with 70% efficacy, 6–18 infants would need to be immunized to prevent one RSV-associated outpatient visit, and 13–33 infants would need to be immunized to prevent one RSV-associated LRI outpatient visit. To prevent one RSV-associated hospitalization, 37–85 infants 0–5 months of age, and 107–280 infants 6–11 months of age would need to be immunized.ConclusionsPublic health benefits, such as disease cases averted due to immunization, are essential elements in consideration of candidate vaccines for a national immunization program. An RSV EHL-mAb of moderate efficacy could have high impact. These data provide an additional perspective for public health decision making.     

Predictors of antibody persistence to the 7-valent pneumococcal conjugate vaccine in healthy Fijian infants at 12 months of age

Little is known about the predictors of antibody persistence to pneumococcal conjugate vaccines (PCV) in the context of reduced dose schedules. In Fiji, an RCT investigated 0, 1, 2 and 3 dose schedules of 7-valent PCV administered at 6, 10 and 14 weeks of age in 364 healthy infants. This study was a post-hoc analysis of the predictors of poor antibody persistence at 12 months, prior to a booster, using univariable and multivariable analyses.The strongest predictors of poor antibody persistence as measured by serotype-specific immunoglobulin G (IgG) and opsonophagocytosis (OI) assays were being of Indigenous Fijian ethnicity (IgG: adjusted odds ratio (aOR) 3.43, p < 0.001; OI: aOR 1.96, p = 0.013) and receipt of fewer than 3 doses of PCV.These findings may help to identify which children may be at an increased risk of pneumococcal disease in the context of reduced dose primary series PCV schedules.     

Motivational interviewing and vaccine acceptance in children: The MOTIVE study

Background and ObjectiveVaccine coverage have been less than desired in young children in part due to parental vaccine hesitancy. Addressing health beliefs through patient-centered communication approaches such as motivational interviewing (MI) may improve vaccine confidence. Thus, the objective of this study was to determine the difference in paediatric vaccination coverage rates based on the Advisory Committee on Immunization Practices (ACIP) and Centers for Disease Control and Prevention (CDC) recommended schedule in children 0–6 years of age after an educational intervention for providers and integration of an MI-based communication tool, MOTIVE (MOtivational Interviewing Tool to Improve Vaccine AcceptancE).MethodsPaediatric and family practice providers in a federally qualified health center in the United States completed an educational intervention regarding vaccine hesitancy and use of the MOTIVE tool. Providers then implemented the MOTIVE tool to address common health beliefs using strong, presumptive vaccine recommendations and an MI framework during encounters with patients 0–6 years of age. Data were collected from 1-year pre-educational intervention (July 2018-June 2019, N = 2504) and post-intervention (July 2019-March 2020, N = 1954) to examine differences in vaccination coverage rates and documented vaccine refusals.ResultsUse of the MOTIVE tool was associated with a statistically significant increase in IIV vaccination coverage rate in children 6 months to 6 years of age (32.4% versus 43.9%, p < 0.01). A significantly increased Hib vaccination coverage rate was observed in children 0–18 months of age. Patients with commercial insurance also had significantly higher vaccination coverage rates for the DTaP, IPV, and VAR vaccines during the intervention period. Use of the MOTIVE tool was associated with a decrease in documented vaccine refusals per 100 patients in children 0–6 years of age (31.5 versus 17.6, p < 0.01).ConclusionUse of an MI-based communication tool may decrease vaccine refusals and improve childhood vaccination coverage rates, particularly for IIV.Clinical Trial Registration: ClinicalTrials.gov, NCT03934008, https://clinicaltrials.gov/ct2/show/NCT03934008, deidentified individual participant data will not be made available.