A trial to evaluate the safety and immunogenicity of a 20-valent pneumococcal conjugate vaccine in populations of adults ≥65 years of age with different prior pneumococcal vaccination

IntroductionA 20-valent pneumococcal conjugate vaccine, PCV20, was developed to expand protection against vaccine-preventable pneumococcal disease. PCV20 contains the components of the 13-valent pneumococcal conjugate vaccine, PCV13, and includes capsular polysaccharide conjugates for 7 additional serotypes. Thus, PCV20 may cover those additional serotypes in individuals previously vaccinated with PCV13 or provide benefits of immunization with a conjugate vaccine to individuals previously immunized with a pneumococcal polysaccharide vaccine. This study described the safety and immunogenicity of PCV20 in adults ≥65 years of age with prior pneumococcal vaccination.MethodsThis phase 3, multicenter, randomized, open-label study was conducted in the United States and Sweden. Adults ≥65 years of age were enrolled into 1 of 3 cohorts based on their prior pneumococcal vaccination history (23-valent pneumococcal polysaccharide vaccine [PPSV23], PCV13, or both PCV13 and PPSV23). Participants were randomized 2:1 within their cohort to receive a single dose of PCV20 or PCV13 in those with prior PPSV23 only, and PCV20 or PPSV23 in those with prior PCV13 only; all participants with prior PCV13 and PPSV23 received PCV20. Safety was assessed by prompted local reactions within 10 days, systemic events within 7 days, adverse events (AEs) within 1 month, and serious AEs (SAEs) and newly diagnosed chronic medical conditions (NDCMCs) within 6 months after vaccination. Immune responses 1 month after PCV20 were assessed.ResultsThe percentages of participants reporting local reactions, systemic events, and AEs after PCV20 administration were similar across cohorts and comparable with the PCV13 and PPSV23 control groups. SAE and NDCMC rates were low in all groups. Robust immune responses, including opsonophagocytic antibody responses, to the 20 vaccine serotypes were observed 1 month after PCV20 regardless of prior pneumococcal vaccination.ConclusionsPCV20 was well tolerated and immunogenic in adults ≥65 years of age previously vaccinated with different pneumococcal vaccine regimens.Clinicaltrials.gov NCT03835975.     

Pneumococcal vaccination in older adults: An initial analysis of social determinants of health and vaccine uptake

ObjectivesTo examine the potential influence of social determinants of health on pneumococcal vaccination in older American adults.MethodsThis study used nationwide, US Medicare claims data from 2013 to 2016 to assess uptake of pneumococcal vaccination among adults in the first year after turning age 65. Patients were followed from the point of being 65 years of age and initially enrolled in traditional fee-for-service Medicare or a Medicare Advantage plan through the subsequent year and observed for pneumococcal vaccination in outpatient clinics and pharmacies. Publicly-available data on select social determinants of health were incorporated and guided by the World Health Organization vaccine hesitancy matrix. Logistic regression determined predictors of vaccination while controlling clinical and demographic characteristics.ResultsA total of 307,488 and 74,995 adults aged 65 years were identified from Medicare Advantage and Medicare fee-for-service claims, respectively, and 21.1% of Medicare Advantage and 38.2% of Medicare fee-for-service patients received a pneumococcal vaccine in the first year after turning 65. Those residing in urban areas had a higher likelihood of pneumococcal vaccination in both the Medicare Advantage (OR: 1.31; 95% CI: 1.267–1.344) and Medicare fee-for-service (OR: 1.53; 95% CI: 1.450–1.615) cohorts. Additionally, residing in areas of higher health literacy or communities with more democratic voters were consistently associated with a higher odds of pneumococcal vaccination regardless of Medicare type. Results also pointed to a synergistic relationship between receiving the influenza vaccine and also being vaccinated against pneumococcal disease.ConclusionSocial determinants of health, including local health literacy, poverty, residing in more liberal areas, and access to information, may be influencing the pneumococcal vaccine-related decisions of older adults. However, additional factors associated with the vaccine hesitancy matrix and more granular data (e.g., zip code-level) are needed to fully determine the impact in this and other vaccines recommended in older adults.     

Compliance to Advisory Committee on Immunization Practices recommendations for pneumococcal vaccination

We evaluated compliance to the ACIP pneumococcal vaccination recommendations issued in 2014 for adults aged ≥ 65 years and in 2012 for adults with high-risk (HR) conditions. The MarketScan® Commercial and Medicare Supplemental databases (January 2007-June 2019) were used to identify the cohorts of interest. Analyses for adults aged ≥ 65 years were adjusted to account for missing vaccination history. Two HR cohorts were identified. The HR1 cohort included patients with immunocompromising conditions, functional or anatomic asplenia, cerebrospinal fluid leak, or cochlear implant. The HR2 cohort included patients with chronic heart, lung, or liver disease; diabetes mellitus; alcoholism; cirrhosis; or cigarette smoking. Full compliance for those aged ≥ 65 years or in the HR1 cohort was defined as receipt of PCV13 and PPSV23, and partial compliance was defined as receipt of PCV13 or PPSV23. For those in the HR2 cohort, full compliance was defined as receipt of PPSV23. Annual compliance rates were estimated using the Kaplan–Meier method.Among those aged ≥ 65 years, partial compliance at 4 years post index was 53% and full compliance was 17% in adjusted analyses. In subjects ≥ 65 years receiving the first vaccination, 42% received the second vaccination by year 4. For the HR1 cohort, partial compliance was 19% and full compliance was 5% at 6 years post index date. For the HR2 cohort, full compliance was 20% at 6 years, with the highest rate in patients with diabetes (27%) and the lowest rate in patients with alcoholism (8%).Additional efforts are needed to maximize compliance to the ACIP pneumococcal vaccine recommendations among adults ≥ 65 years of age and adults with HR conditions including streamlined recommendations and single-dose vaccines. These efforts may subsequently reduce the incidence and burden of pneumococcal disease.     

Associations of influenza and pneumococcal vaccinations with burdens of older family caregivers: The Japan Gerontological Evaluation study (JAGES) cross-sectional study

BackgroundInfluenza and pneumonia tend to be severe in older adults; thus, vaccination is necessary to prevent these illnesses. Vaccination is especially important for older family caregivers (OFCs) not only to prevent them from becoming ill, but also to prevent secondary infections in the family care receivers (FCRs), who are mostly frail older adults and have a higher risk of severe illness. Thus, we investigated whether caregiving burdens were associated with the vaccinations among older adults.MethodsWe used cross-sectional data from the Japan Gerontological Evaluation Study (JAGES), which was conducted in 64 Japanese municipalities from November 2019 to January 2020. The target population consisted of 26,177 individuals aged 65 years or older who were independent and did not need public long-term care. The primary outcome was the uptakes of either or both influenza and pneumococcal vaccinations. Multinomial logistic regressions were performed, setting those who underwent neither vaccinations as the reference group.ResultsAmong the participants, 23.3 %, 25.8 %, 9.4 %, or 41.5 % underwent neither, only influenza, only pneumococcal, or the both vaccinations, respectively. The caregiving frequency, time length in a day, or dementia of FCR were negatively associated with influenza vaccination (caregiving almost every day: relative risk ratio {RRR}: 0.39, 95 % confident interval {95 % CI} [0.24–0.63]; caregiving almost all day: 0.44, 95 % CI: 0.23–0.85; caregiving for FCR: RRR:0.55, 95 % CI: 0.34–0.91). On the other hand, those caregiving burdens were not associated with pneumococcal only or the both vaccinations. Having a family physician mitigated all the negative effect of the caregiving burdens on the vaccinations.ConclusionOur results suggest that the caregiving burden is a barrier to influenza vaccination but not to pneumococcal vaccination and that having a physician mitigates the negative effect regardless of the burden kind.     

The adult vaccination landscape in the United States during the Affordable Care Act era: Results from a large retrospective database analysis

BackgroundEarly provisions of the Affordable Care Act (ACA) reduced financial barriers to preventive care, including routinely recommended vaccines; however, vaccination coverage remains suboptimal. This study examined characteristics of routine adult vaccinations and potential missed opportunities for vaccinations through the lens of healthcare resource utilization among adults in the ACA era.MethodsThis was a retrospective analysis of healthcare claims from the Truven Health MarketScan Commercial Claims and Encounters (CCAE), Medicare Supplemental (MS), and Multi-State Medicaid databases among adults aged 19 years or older. Influenza, Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis), herpes zoster (HZ), and pneumococcal vaccinations were identified between 2011 and 2016. Potential missed opportunities were defined as well-visits at which individuals were age-eligible for vaccination but did not receive it, assessed during recommended windows for each vaccine. Missed encounters were defined as having no well-visits. Multivariable logistic regression was used to identify factors associated with vaccination and potential missed opportunities.ResultsFamily/internal medicine and unknown/other providers administered most influenza, Tdap, and pneumococcal vaccinations, for the CCAE/MS and Medicaid cohorts, respectively. HZ vaccinations were primarily administered through pharmacies. The proportion of vaccination events increased in the pharmacy setting between 2011 and 2016. Having preventive care visits, non-well-visits, and receiving most care from a family/internal medicine practitioner were associated with increased odds of vaccination. Missed encounters were common in Medicaid enrollees. Potential missed opportunities were more prevalent in the CCAE/MS cohort than among Medicaid enrollees. Having non-well-visits was associated with a reduced likelihood of having a missed opportunity.ConclusionSince the ACA implementation, preventive care among adults was sporadic. Many adults had limited opportunities for vaccination. The large prevalence of missed opportunities suggests vaccination uptake could be improved. Better support for vaccination or referrals for providers who may not traditionally vaccinate could improve vaccine uptake.     

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.     

A phase 3, randomized,double-blind study to evaluate the immunogenicity and safety of 3 lots of 20-valent pneumococcal conjugate vaccine in pneumococcal vaccine-naive adults 18 through 49 years of age

IntroductionIntroduction of pneumococcal conjugate vaccines (PCVs), including the 13-valent PCV (PCV13), has considerably reduced pneumococcal disease burden. However, additional serotypes not in PCV13 continue to present a substantial disease burden. The 20-valent PCV (PCV20) was developed to expand protection against pneumococcal disease beyond PCV13. As part of the phase 3 clinical development program, the current study assessed consistency of immune responses across 3 lots of PCV20 and described the safety profile of PCV20.MethodsThis phase 3, randomized, multicenter, double-blind study of pneumococcal vaccine-naive adults 18–49 years of age randomized 1710 participants in a 2:2:2:1 ratio to receive 1 of 3 lots of PCV20 or PCV13. Immunogenicity was assessed through serotype-specific opsonophagocytic activity (OPA) titers before and approximately 1 month (28–42 days) after vaccination. Reported local reactions within 10 days, systemic events within 7 days, adverse events (AEs) within 30 days, and serious AEs (SAEs) and newly diagnosed chronic medical conditions (NDCMCs) within 6 months after vaccination were evaluated.ResultsEquivalence in immune responses (OPA geometric mean titers) for all 20 vaccine serotypes was demonstrated across the 3 PCV20 lots. Robust responses, assessed by OPA geometric mean fold rises, percentage of participants achieving ≥4-fold rises, and percentage of participants with OPA titers ≥lower limit of quantitation, were observed after PCV20. Reported rates of local reactions, systemic events, and AEs were similar between the pooled PCV20 lots and PCV13; most events were mild or moderate. Reported rates of SAEs and NDCMCs were low and similar between the PCV20 and PCV13 groups.ConclusionsThree different lots of PCV20 demonstrated robust and consistent immunogenicity. The safety and tolerability of PCV20 was acceptable and similar to that of PCV13. (Clinicaltrials.gov: NCT03828617).     

Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against community-acquired pneumonia in older individuals after the introduction of childhood 13-valent pneumococcal conjugate vaccine: A multicenter hospital-based case-control study in Japan

BackgroundIn the era of childhood pneumococcal conjugate vaccine (PCV) immunization, especially 13-valent pneumococcal conjugate vaccine (PCV13) immunization, serotype replacement of Streptococcus pneumoniae and herd immunity in adults have been reported worldwide. Therefore, continuous evaluation of the effectiveness of the pneumococcal vaccine in adults is crucial because vaccine effectiveness may change owing to these factors. The purpose of this study was to evaluate the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against all-cause pneumonia and pneumococcal pneumonia in older individuals with community-acquired pneumonia (CAP) after the introduction of childhood PCV13 in Japan, a topic that has remained largely unexplored.MethodsWe evaluated pneumococcal vaccine effectiveness in this multicenter, matched case-control study conducted in hospitals and clinics. Cases included patients (aged ≥ 65 years) newly diagnosed with CAP between October 2016 and September 2019. A maximum of five non-pneumonia control patients matched for sex, school grade, date of outpatient visit, and medical institution were selected for each case. Conditional logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of pneumococcal vaccines for the occurrence of all-cause CAP and pneumococcal CAP.ResultsThe analysis included 740 individuals (142 patients and 598 controls). The median age of participants was 75 years (men: 54%). The adjusted OR for pneumococcal vaccination against all-cause CAP was 1.31 (95% CI: 0.84–2.06), while that for PPSV23 vaccination in the previous 5 years was 1.33 (95% CI: 0.85–2.09). The adjusted OR for PPSV23 vaccination in the previous 5 years against pneumococcal CAP was 0.93 (95% CI: 0.35–2.50).ConclusionsThis study was unable to demonstrate the effectiveness of PPSV23 against all-cause and pneumococcal pneumonia after the introduction of childhood PCV13 in Japan. Nonetheless, additional studies are needed to validate these results.     

Recalibrated estimates of non-bacteremic and bacteremic pneumococcal community acquired pneumonia in hospitalized Canadian adults from 2010 to 2017 with addition of an extended spectrum serotype-specific urine antigen detection assay

Objective(s)In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in hospitalized adults from 2010 to 2017.MethodsS. pneumoniae was detected using culture (blood and sputum), and urine antigen detection (UAD). Serotyping was performed with Quellung, PCR, or using the PCV13- and PPV23 (non-PCV13)-specific UADs. Laboratory results, demographic, and outcome data were categorized by age (16–49, 50–64, and 65 + ) and by disease [non-bacteremic pCAP, bacteremic pCAP, and IPD(non-CAP)].Results11,129 CAP cases and 216 cases of IPD (non-CAP) were identified. Laboratory testing for S. pneumoniae was performed in 8912 CAP cases, identifying 1264 (14.2%) as pCAP. Of pCAP cases, 811 (64.1%) were non-bacteremic and 455 (35.9%) were bacteremic. Adults 65 + years represented 54.5% of non-bacteremic pCAP, 41.4% of bacteremic pCAP, and 48.6% of IPD cases. Adults 50–64 years contributed 30.3%, 33.1%, and 29.9%, respectively. In pCAP, PCV13 serotypes declined between 2010 and 2014 due to declines in serotypes 7F and 19A, then plateaued from 2015 to 2017 with persistence of serotype 3. In later study years, non-bacteremic pCAP was predominant, and PPV23 (non-PCV13) serotypes increased from 2015 to 2017, with serotypes 22F, 11A, and 9 N being most frequently identified. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These outcomes and mortality were more common in bacteremic pCAP and IPD, versus non-bacteremic pCAP.Conclusion(s)Along with IPD, pCAP surveillance (bacteremic and non-bacteremic) is important as their trends may differ over time. With insufficient herd protection from PCV13 childhood immunization, or use of PPV23 in adults, this study supports direct adult immunization with PCV13 or higher valency conjugate vaccines to reduce the residual burden of pCAP and IPD.     

Distribution of serotypes causing invasive pneumococcal disease in older adults from high-income countries and impact of pediatric and adult vaccination policies

BackgroundNeither indirect protection through use of 13-valent and 10-valent pneumococcal conjugate vaccines (PCV13 and PCV10) in pediatric National Immunization Programs (NIPs) nor direct vaccination with the 23-valent polysaccharide vaccine have eliminated vaccine serotype invasive pneumococcal disease (IPD) in older adults. Vaccinating older adults with higher-valency PCV15 and PCV20 could address remaining IPD due to pediatric PCV serotypes plus additional IPD due to serotypes included in these vaccines.MethodsWe collected serotype-specific IPD data in older adults (≥65 years in most countries), from national or regional surveillance systems or hospital networks of 33 high-income countries. Data were from official government websites, online databases, surveillance system reports, published literature, and personal communication with in-country investigators. Average percentages of IPD serotypes were calculated.ResultsAmong 52,905 cases of IPD with a serotype identified, PCV13 serotypes accounted for 33.7% of IPD (55.8% and 30.6% for countries with PCV10 and PCV13 in the pediatric NIP), most commonly serotypes 3 (14.9%) and 19A (7.0%). PCV15 and PCV20 would cover an additional 10.4% and 32.9% of older adult IPD beyond PCV13 serotypes (PCV10 countries: 7.7% and 23.3%; PCV13 countries: 10.6% and 34.6%). The most common of these additional serotypes were 8 (9.9%), 22F (7.9%), 12F (4.6%), and 11A (3.3%). PPSV23 policies for older adults were not correlated with lower IPD percentages due to PPSV23 serotypes.ConclusionsVaccinating older adults with higher-valency PCVs, especially PCV20, could substantially reduce the remaining IPD burden in high-income countries, regardless of current PCV use in pediatric NIPs and adult PPSV23 policies.     

Long-term impact of pneumococcal conjugate vaccines for children on adult pneumococcal pneumonia in Japan: Two multicenter observational studies from 2011 to 2020

BackgroundPediatric pneumococcal conjugate vaccines (PCVs) introduction has directly and indirectly reduced pneumococcal pneumonia and invasive disease caused by PCV-covered serotypes among children and adults globally. In Japan, both PCV7 and PCV13 were introduced into the national immunization program (NIP) for children in 2013. However, the long-term impact of PCV use in children on adult pneumococcal pneumonia in Japan remains unclear.MethodsWe assessed serotypes isolated from adult pneumococcal pneumonia patients (in- and outpatients) in two multicenter observational studies in Japan: 2011–2014 and 2016–2020. The latter study period was divided into two periods to evaluate changes after PCV introduction in children. The Quellung reaction was used to determine serotypes. We evaluated trends of individual and vaccine-covered serotypes over three periods and assessed the difference in changes by patient group before and after the introduction of pediatric PCVs.ResultsA total of 650 patients were enrolled: 224, 322, and 104 in 2011–2014, 2016–2017, and 2018–2020, respectively. The median age was 73 years; 59.7% (388/650) were male; 86.9% (565/650) had comorbidities; and 10.2% (66/650) were nursing-home residents. The proportion of PCV13 serotypes decreased from 52.7% in 2011–2014 to 30.4% in 2016–2017 (p <0.001) after PCV13 introduction for children. However, PCV13, PCV15, and PCV20 serotypes still accounted for 38.5, 43.3, and 59.6% of total pneumococcal pneumonia in 2018–2020, respectively. Decline of PCV13 serotypes was more marked in patients aged ≥65 (-23.5%; p <0.001) than those aged <65 (-12.3%; p = 0.104) from 2011–2014 to 2016–2020. The proportion of PPSV23 non-PCV13 serotypes didn’t change over time.ConclusionsThe proportion of adult pneumococcal pneumonia caused by PCV13 serotypes in Japan declined after pediatric PCVs introduction into NIP, possibly due to indirect effects of pediatric PCVs. However, use of new PCVs in Japanese adults may potentially prevent additional pneumococcal pneumonia cases. Now, pneumococcal vaccination strategy for older adults requires discussion.     

Epidemiology of community-acquired pneumonia in the era of extended serotype-covering multivalent pneumococcal conjugate vaccines

BackgroundSouth Korea has been providing 10-valent pneumococcal conjugate vaccine/(PCV10)/13-valent pneumococcal conjugate vaccine (PCV13) to children and 23-valent pneumococcal polysaccharide vaccine (PPSV23) to older adults as part of a national immunization program.MethodsFrom September 2015 to August 2017, a prospective cohort study was conducted for adults aged ≥19 years with community-acquired pneumonia (CAP) at four university hospitals. All-cause and pneumococcal CAP incidence and mortality rates were evaluated on the basis of hospital catchment population. Serotype distribution of pneumococcal CAP was also evaluated.ResultsAmong 2669 patients with CAP, 252 cases (9.4%) were pneumococcal CAP cases. The annual incidences of all-cause and pneumococcal CAP were 194.3 cases and 18.3 cases respectively, per 100,000 persons. Serotyped Streptococcus pneumoniae was identified in 107 cases (42.5%) through culture or a serotype-specific urinary antigen detection assay. Pneumococcal CAP caused by the PCV13 and PPSV23 serotypes were 50 cases (46.7% of serotyped pneumococcal CAP and 19.8% of pneumococcal CAP), and 83 cases (77.6% of serotyped pneumococcal CAP and 32.9% of pneumococcal CAP), respectively. The most prevalent serotype was 3 (n = 21, 19.6% of serotyped pneumococcal CAP), followed by 19A (n = 10, 9.3% of serotyped pneumococcal CAP) and 11A (n = 10, 9.3% of serotyped pneumococcal CAP). Compared with non-pneumococcal CAP patients, pneumococcal CAP patients were more likely to have a higher CURB-65 scores (P = 0.002). The overall 30-day mortality rate of pneumococcal CAP was higher than that of non-pneumococcal CAP (6.3% versus 5.6%; odds ratio [OR], 1.15; 95% confidence interval [CI], 0.67–1.96), but this trend was reversed in patients aged 65–74 years (4.2% versus 8.6%; OR, 0.47; 95% CI, 0.14–1.54).ConclusionsThe disease burden of PCV13-serotype pneumococcal CAP remains significantly high in Korean adults, particularly among elderly people, even after a high uptake of pediatric PCVs.     

Identification of subgroups in the Danish population for targeted human papillomavirus vaccination efforts

BackgroundIn the Danish childhood vaccination program, the human papillomavirus (HPV) vaccination coverage is lower than for other vaccines. To tailor a targeted HPV vaccination effort, we aimed to identify girls in Denmark with lower first dose HPV vaccination coverage than girls in general.MethodsA population-based retrospective cohort study was performed of girls born in 2001–2004, residing in Denmark in September 2019 (N = 128,351). Data from the Danish Vaccination Register was linked to sociodemographic data from the Danish Civil Registration System and Statistics Denmark. Cox's proportional hazard regression models were used to compare vaccination uptake rates between subgroups of girls.ResultsHPV vaccination coverage at 14 years of age varied widely by municipality (53.4–80.6%). Girls living with neither of their parents had a lower chance of being vaccinated compared to girls living with both their parents (HR 0.43; 95% CI 0.41–0.46), likewise for girls attending special need education compared with girls attending public schools (HR 0.50; 95% CI 0.42–0.59). The vaccination uptake among immigrants was lower compared to Danish-born girls (HR 0.51; 95% CI 0.49–0.54), especially among immigrant girls whose parents had not passed any Danish exams. Finally, girls who were DTaP-IPV revaccinated had a 50% greater chance of being HPV vaccinated compared to girls who were not (HR 1.61; 95% CI 1.58–1.64).ConclusionTo increase the HPV vaccination uptake, we recommend vaccination efforts targeting girls living without any of their parents, girls attending special need education, immigrants, and girls who are not DTaP-IPV revaccinated. When targeting immigrants, the effort should focus on disseminating sufficient and understandable information about the Danish childhood vaccination program to the parents.     

Vaccination rates and adherence in premature infants before and after pneumococcal conjugate vaccine schedule change for term infants – A claims database analysis in Germany

BackgroundIn 2015, the German Standing Committee on Vaccination (STIKO) changed the pneumococcal conjugate vaccination (PCV) schedule for mature infants from a 3+1 scheme (2, 3, 4, and 11–14 months of age) to a 2+1 scheme (2, 4, and 11–14 months of age). For premature infants, the 3+1 scheme remained. The aim of this study was to assess vaccination rates, completeness, and timeliness for PCV in premature infants before and after the modified recommendation.MethodsA retrospective claims data analysis using the “Institut für angewandte Gesundheitsforschung Berlin” Research Database was conducted. Premature infants born in 2013 and 2016 with an individual follow-up of 24 months were included. Hexavalent combination (HEXA) vaccination with a consistent 3+1 recommendation for mature and premature infants was analyzed as reference vaccination.ResultsAfter 24 months, the PCV rate for at least one dose remained stable in premature newborns of 2016 compared to 2013, while the HEXA vaccination rate increased slightly. However, a significant decrease of a completed PCV schedule (4 doses) in premature infants was noted, whereas the completeness of HEXA vaccination did not change. The timeliness of PCV in premature newborns increased for the first and the booster PCV, while the timeliness of HEXA immunization did not change from 2013 to 2016.ConclusionAlthough STIKO still recommends a 3+1 PCV schedule for premature infants in Germany, premature infants were vaccinated according to the changed recommendations for mature born infants. A substantial share of premature infants remained unvaccinated, and their vaccinations were often delayed.     

Parental and provider vaccine hesitancy and non-timely childhood vaccination in Switzerland

ObjectiveAlthough medical providers are a trusted vaccination information source for parents, they do not universally support vaccination. Complementary medicine (CM) providers are particularly likely to hold vaccine hesitant (VH) views, and VH parents often consult with them. Little research compares VH of parents and providers, and if and how each is associated with uptake of recommended childhood vaccines.MethodsWe defined non-timely receipt as recommended vaccines given > 1 month later than officially recommended, based on vaccination records. We administered versions of the Parent Attitudes about Childhood Vaccines (PACV) 5-item survey instrument to 1256 parents and their children’s pediatricians (N = 112, 40 CM-oriented, 72 biomedical [not CM-oriented]) to identify moderately (PACV-score 5–6) and highly (PACV-score 7+) hesitant providers/parents. We obtained multivariable adjusted odds ratios to test relationships between parental VH and provider type/VH, and between non-timely receipt of selected childhood vaccines and parental VH and provider type/VH.ResultsNo biomedical providers were VH, 9 CM providers were moderately VH, and 17 were highly VH. Parents seeing moderately and highly hesitant providers had adjusted odds ratio (AOR) for being VH = 6.6 (95% confidence interval (CI), 3.1–14.0) and AOR = 31.3 (95% CI 16.8–58.3), respectively. Across all vaccine uptake endpoints, children of moderately and highly hesitant parents had 1.9–3.8 and 7.1–12.3 higher odds of non-timely vaccination, and children seeing highly hesitant CM providers had 4.9–9.4 higher odds. Children seeing moderately hesitant CM providers had 3.3 higher odds of non-timely vaccination for the 1st dose of measles and 3.5 higher odds for 1st dose of polio/pertussis/tetanus.ConclusionVH by both parents and providers each is associated with non-timely childhood vaccination. As VH parents are more likely to consult with VH providers, interventions aimed at increasing timely vaccination need to primarily target VH providers and their clients.     

Duration of influenza vaccine effectiveness in the elderly in Japan: A retrospective cohort study using large-scale population-based registry data

BackgroundThe immune response to influenza vaccination in the elderly is likely to be lower than that in young adults. Clinical protection may not persist year-round in the elderly. However, the effectiveness of influenza vaccine in the elderly has not been adequately studied, especially in terms of the duration of effectiveness.MethodsWe used a linked database of healthcare administrative claims data and vaccination records maintained by the municipality of a city in Kanto region of Japan. We studied individuals who were aged 65 years or older at baseline and were followed up between April 1, 2014 to March 31, 2020. The duration of influenza vaccine effectiveness by age category was analyzed using a time-dependent piecewise Cox proportional hazard model with time-dependent vaccine status, prior season vaccination and covariates confirmed in the baseline period (age, sex, cancer, diabetes, chronic obstructive pulmonary diseases, asthma, chronic kidney diseases, and cardiovascular diseases).ResultsWe identified an analysis population of 83,146 individuals, of which 7,401 (8.9%) had experienced influenza and 270 (0.32%) underwent influenza-related hospitalization. Individuals who were vaccinated during the first season (n = 47,338) were older than non-vaccinated individuals (n = 35,808) (average age, 75.8 vs. 74.1 years, respectively). The multivariable analysis showed a lower incidence of influenza in vaccinated individuals (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.43–0.51; P < 0.001), while the incidence of hospitalization for influenza did not differ significantly by vaccination status (HR, 0.79; 95% CI, 0.53–1.18; P = 0.249). Protective effectiveness against incidence was maintained for 4 or 5 months after vaccination in those aged 65–69 and 80-years, 5 months in 70–79 years.ConclusionsOur study identified moderate vaccine effectiveness in preventing the incidence of influenza in the Japanese elderly. Vaccine effectiveness showed a trend of gradual attenuation. Clinicians should suspect influenza infection even in those vaccinated, especially in elderly individuals who had received vaccination more than 4 or 5 months previously.     

Survey of influenza vaccine knowledge,attitudes, and beliefs among pregnant women in the 2016–17 season

ObjectivesInfluenza vaccination coverage among pregnant women in the United States is suboptimal. We surveyed women who were pregnant during the 2016–17 influenza season to assess knowledge and attitudes regarding influenza vaccination.MethodsWe identified and sampled pregnant women to include approximately equal numbers of vaccinated and unvaccinated women from strata defined by vaccination status and trimester from four integrated health systems in the Vaccine Safety Datalink (VSD). Potential participants were contacted via mail and telephone to complete a standardized survey. Characteristics and responses of women vaccinated and unvaccinated during pregnancy were compared.ResultsThe survey was completed by 510 (48%) of 1062 contacted women; 500 were included in the analysis. Vaccine receipt while pregnant was associated with primigravida status (p = 0.02), college degree (p = 0.01), employment in health care (p < 0.01), and history of routine annual influenza vaccination (p < 0.01). Among 330 vaccinated women, the primary reasons for vaccination included protection of self and baby from influenza (n = 233, 71%), and medical professional recommendation (n = 46, 14%). Multiple reasons were given for nonvaccination, but concern about ‘negative effects’ was cited most often (n = 44, 29%). Vaccinated women were significantly more likely to believe that influenza vaccines are safe and effective, and to recognize the potential for harm from influenza infection. Nearly all women reported receiving at least one influenza vaccination recommendation from a healthcare provider.ConclusionsVaccinated pregnant women were more likely to receive routine annual influenza vaccine compared to those not vaccinated. Recommendations by obstetric providers should be supplemented with efforts to encourage women of childbearing age to receive annual vaccination.