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Background: Kenya introduced Synflorix™ (GlaxoSmithKline, PCV10-GSK), a 10-valent pneumococcal conjugate vaccine, in 2011, using three primary doses and, in select areas, catch-up campaigns. Surveys conducted 1-2 years post-introduction showed a stable prevalence of pneumococcal colonization, with declines in vaccine-type carriage. However, little is known about the long-term impact of PCV10-GSK in Kenya., Methods: We conducted a cross-sectional survey of pneumococcal carriage among children aged <5 years in November-December 2017 in Kibera (Nairobi informal settlement, no catch-up) and Asembo (rural western Kenya, 2-dose catch-up for children 1-4 years), using the same methods and settings as prior annual surveys from 2009 to 2013. Participants were randomly selected from an ongoing population-based surveillance platform. Nasopharyngeal swabs were frozen in skim milk-tryptone-glucose-glycerin media within 4 h and underwent culture with broth enrichment for pneumococcus. Isolates were serotyped by polymerase chain reaction and Quellung., Results: We enrolled 504 children, including 252 from each site; >90 % of participants had received 3 doses of PCV10-GSK. Pneumococcal colonization was detected in 210 (83.3 %) participants in Kibera and 149 (59.1 %) in Asembo, which was significantly lower than the prevalence observed in 2013 (92.9 % and 85.7 %, respectively). PCV10-GSK serotypes were detected in 35/252 (13.9 %) participants in Kibera and 23/252 (9.1 %) in Asembo, respectively; these prevalences were lower, but not statistically different, from vaccine-type carriage prevalences in 2013 (17.3 % and 13.3 %, respectively). In 2017 in both sites, serotypes 3, 6A, 19A, 19F, and 35B were among the most common serotypes., Conclusion: Six years post-PCV10-GSK introduction, the prevalence of pneumococcal carriage among children has decreased, and the impact of PCV10-GSK on vaccine-type carriage has plateaued. Kenya recently changed from PCV10-GSK to Pneumosil™ (Serum Institute of India), a 10-valent PCV that includes serotypes 6A and 19A; these data provide historical context for interpreting changes in vaccine-type carriage following the PCV formulation switch., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Despite current polysaccharide and conjugate vaccine use, pneumococcal diseases remain prevalent in older adults. VAX-24 is a 24-valent pneumococcal conjugate vaccine (PCV) containing eCRM, a proprietary carrier protein with non-native amino acids (para-azidomethyl-L-phenylalanine) that undergo site-specific conjugation to pneumococcal polysaccharides that have been activated with a small-molecule linker (dibenzocyclooctyne). Site-specific conjugation utilizing click chemistry enables consistent exposure of T-cell epitopes, reduction in carrier protein to pneumococcal polysaccharide ratio, and enhances manufacturing process consistency to improve PCVs by increasing serotype coverage while minimizing carrier suppression. Healthy adults aged 65 or older were randomized in a 1:1:1:1 ratio to receive a single injection of VAX-24 at 1 of 3 dose levels (1.1, 2.2, or a mixed dose of 2.2 or 4.4 mcg) or Prevnar 20® (PCV20) in a phase 2, blinded study. Primary outcome measures were solicited local and systemic events within 7 days post-vaccination, unsolicited adverse events (AEs) within 1 month, and serious AEs, medically attended AEs, or new onset of chronic disease within 6 months of vaccination. Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) were measured pre-vaccination and at 1 month post-vaccination. Of 207 participants enrolled, 200 completed the trial. Safety profiles were comparable across the three VAX-24 doses and PCV20. Robust OPA and IgG immune responses were seen for all 24 serotypes. On average, immune responses to VAX-24 2.2 mcg dose were similar or higher compared to PCV20. In adults ≥ 65 years, VAX-24 had a safety profile similar to PCV20 through six months post-vaccination and induced robust OPA and IgG responses to all 24 serotypes, supporting prior data showing that site-specific conjugation allows for increased serotype coverage with similar or higher immune response vs other PCVs. The outcome of this phase 2 study further supports use of VAX-24 2.2 mcg dose in phase 3 trials. Clinicaltrials.gov: NCT05297578., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J. Wassil, M. Sisti, J. Fairman, D. Johnson, T.-S. Migone, K. Nguyen, A. Paschenko, P. Sauer, S. Iki, M.E. Hanson, J.K. Simon are employees of Vaxcyte and may own stock or hold stock options in the company. S. Bennett is a contractor employee of Vaxcyte. B. Rankin and J. Clark are clinical trial investigators involved in Vaxcyte studies., (Copyright © 2024 Vaxcyte, Inc. Published by Elsevier Ltd.. All rights reserved.)

Background: Effective strategies are needed to improve vaccine acceptance. This study sought to determine if a peer-led vaccine education intervention embedded within community medical practices increases parental acceptance of pediatric pneumococcal conjugate vaccination., Methods: From March 2022-July 2023, we conducted a randomized trial at three pediatric health practices in predominantly Hasidic Jewish neighborhoods in New York, where vaccine deferral is common. Parents of children up to 18 months due/overdue for routine pneumococcal vaccination were randomized (1:1) to receive routine care alone or routine care plus a peer educational intervention. Peer educators trained in motivational interviewing and vaccine science provided counseling at enrollment and follow-up telephone engagement in the intervention arm at day 30 and 60. Primary outcome was child's pneumococcal immunization status by allocation arm expressed as at least one dose received between enrollment and 90 days post-enrollment., Results: 144 parent-child dyads were eligible for outcome analysis. Participants in the group receiving routine care along with peer-led vaccine counseling were significantly more likely to have their child receive at least 1 vaccine dose between enrollment and 90 days compared to the group who received routine care alone (28.4 % vs 12.9 %, risk ratio [RR] 2.21, confidence interval [CI] 1.09-4.49, p = 0.022). The effect of peer education was greatest in dyads with children less than 1 year old at enrollment (34 % vs 12.7 %, RR 2.67, CI (1.22-5.86), p = 0.009)., Conclusions: Peer vaccine education can increase vaccine acceptance compared to routine care alone and may be particularly valuable in decreasing vaccination delays for younger infants. (Funded by EGL Charitable Foundation, ClinicalTrials.gov NCT05875779)., Competing Interests: Declaration of competing interest The authors have no relevant conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pneumococcus is a common cause of pneumonia, meningitis, and other serious infections in children. The previous study has proved that the 13-valent pneumococcal conjugate vaccine (PCV13) has sufficient immunogenicity in children. The data on long-term persistence of immunity will help the follow-up development work of pneumococcal vaccines., Methods: Children who received the full vaccination course of the tested PCV13 in the previous clinical trial were enrolled again, and these who received other pneumococcal vaccines, or were infected with one or more serotypes of S. pneumoniae corresponding to PCV13 before enrollment were excluded. Participants were divided into four groups by age which is same as that of previous trial. The study lasted for 5 years, during which we measured pneumococcal antibodies of 13 serotypes included in PCV13 at particular points in time. Geometric mean concentrations (GMCs) and seropositive rates (the rate of IgG concentration ≥0.35 μg/mL) of antibodies against 13 serotypes were calculated., Results: For the participants aged 2 months, five years after primary vaccination, except for serotypes 3 and 4, seropositive rates were 100%. GMCs of IgG antibodies against 13 serotypes ranged from 0.733 to 15.160 μg/mL. All of the participants aged 7-11 months had the serotype-specific IgG concentration ≥0.35 μg/mL four years after primary vaccination with the exception of serotypes 3, 4, 6 A and 9 V. IgG GMCs were 0.753-11.031 μg/mL. All participants aged 12-23 months and 2-5 years old had the serotype-specific IgG concentration ≥0.35 μg/mL three or two years after primary vaccination respectively, except for serotype 3. IgG GMCs ranged from 0.815 to 13.111 μg/mL, and 0.684 to 12.282 μg/mL respectively., Conclusion: PCV13 was applied to the population aged 2 months and 7 months - 5 years old with a good immune persistence, providing more extensive evidence of long-term efficacy for that vaccine., Trial Registration: The trial was registered with ClinicalTrials.gov, number NCT06210737., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The World Health Organization (WHO) encourages countries to provide appropriate vaccinations for children, adolescents, and relevant adult populations. Childhood programme have been the focus of global investments, but recent pandemics have increasingly demonstrated the value of life course vaccination. Our objective is to compare national life course immunization programmatic maturity prior to mass COVID-19 vaccine introduction, the largest adult vaccination programme, globally. As coverage estimates (typically used to assess childhood programmes) are not available for adult vaccinations, this analysis pilots a standardized quantitative metric of programmatic maturity., Methods: Through consultation with vaccination experts, we developed a standardized approach to assess national immunization programme maturity across the life course. In accordance with expert input, five vaccines were selected to represent delivery across the life course: diphtheria tetanus toxoid and pertussis (DTP); measles (MCV) second dose; human papillomavirus (HPV) final dose; pneumococcal conjugate (PCV) final dose; and seasonal influenza annual dose. Experts recommended inclusion of the following indicators for each vaccine: a legal mandate (national policy), experience delivering the vaccine (programme duration), and vaccine use (uptake for relevant populations). We developed a metric accordingly that provides up to 5 points per vaccine ("vaccine specific maturity score") which when summed forms the "life course maturity score", with a maximum score of 25. We analysed the prevalence of national policies, experience, and use by region and World Bank income group., Results: More than 55% of the 194 WHO Member States had childhood vaccine policies for all three of the vaccines considered (DTP, MCV, and PCV) compared to 60% for HPV (proxy for adolescent vaccination programme) and 52% for seasonal influenza (proxy for adult vaccination programme). Childhood vaccination programmes (e.g., MCV and DTP) had the highest vaccine specific maturity scores, while seasonal influenza and HPV vaccination programmes had much lower scores. The national life course maturity scores ranged from 1 to 23, with a global median of 12 (IQR: 8; 16)., Discussion: The piloted metric provides an overview of the maturity of life course immunization programmes. The metric is structured to be a flexible, rapid resource that can be used to assess other combinations of vaccines across the life course. The findings from this paper provide a baseline of immunization programme maturity for childhood, adolescent, and adult vaccination programmes immediately prior to the COVID-19 vaccine introduction. This maturity score, or adaptations of this approach, could be used to monitor the trajectory of national immunization programme maturity across the life course in the years ahead., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: In early 2021, the 10-valent Pneumococcal conjugate vaccine (PCV10) was replaced with 13-valent (PCV13) by the federal directorate of immunization (FDI), Pakistan. We assessed the impact of a higher valent vaccine, PCV13, on the serotype distribution of nasopharyngeal carriage in rural Pakistan., Methods: Children <2 years were randomly selected from two rural union councils of Matiari, Sindh in Pakistan between September-October,2022. Clinical, sociodemographic and vaccination histories were recorded. Nasopharyngeal swabs were collected and processed at Infectious Disease Research Laboratory, Aga Khan University, Karachi. Whole genome sequencing was performed on the culture positive isolates., Results: Of the 200 children enrolled, pneumococcus was detected in 140(70 %) isolates. Majority of age-eligible children (60.1 %,110/183) received 3 PCV13 doses. PCV10 carriage declined from 13.2 %(78/590) in 2017/18 to 7.2 % (10/140) in 2022, additional PCV13 serotypes (3, 6A/6C and 19A) decreased from 18.5 %(109/590) to 11.4 %(16/140) while non-PCV13 serotypes increased from 68.3 %(403/590) to 81.4 %(114/140). There were 88.5 %(n = 124), 80.7 %(n = 113), 55.0 %(n = 77), and 46.0 %(n = 65) isolates predicted to be resistant to cotrimoxazole, penicillin(meningitis cut-off), tetracycline, and erythromycin respectively., Conclusion: Replacing PCV10 with PCV13 rapidly decreased prevalence of PCV13 carriage among vaccinated children in Matiari, Pakistan. Vaccine-driven selection pressure may have been responsible for the increase of non-PCV13 serotypes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended for infants in Argentina's national immunization program (NIP) in a 2 + 1 schedule since 2012. Licensure of the 15-valent vaccine (PCV15) is anticipated soon, and the 20-valent vaccine (PCV20) recently received regulatory approval. This cost-effectiveness analysis examined the public health and economic implications of transitioning from PCV13 to either PCV15 or PCV20 in Argentina's pediatric NIP., Methods: A decision-analytic Markov model was used with a 10-year time horizon and a 3.0% annual discount rate for costs and benefits. Vaccine effectiveness estimates were derived from Argentinian surveillance data, PCV13 clinical effectiveness and impact studies, and PCV7 efficacy studies. Population, epidemiologic, and economic inputs were obtained from literature and Argentinian-specific data. The study adopted a healthcare system perspective; sensitivity and scenario analyses were conducted to assess input parameters and structural uncertainty., Results: Compared with PCV13, PCV20 was estimated to avert an additional 7,378, 42,884, and 172,389 cases of invasive pneumococcal disease (IPD), all-cause pneumonia, and all-cause otitis media (OM), respectively, as well as 3,308 deaths, resulting in savings of United States Dollars (USD) 50,973,962 in direct medical costs. Compared with PCV15, PCV20 was also estimated to have greater benefit, averting an additional 6,140, 35,258, and 142,366 cases of IPD, pneumonia, and OM, respectively, as well as 2,624 deaths, resulting in savings of USD 37,697,868 in direct medical costs. PCV20 was associated with a higher quality-adjusted life year gain and a lower cost (i.e., dominance) versus both PCV13 and PCV15. Results remained robust in sensitivity analyses and scenario assessments., Conclusion: Over a 10-year horizon, vaccination with PCV20 was expected to be the dominant, cost-saving strategy versus PCV13 and PCV15 in children in Argentina. Policymakers should consider the PCV20 vaccination strategy to achieve the greatest clinical and economic benefit compared with lower-valent options., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Lucila Rey-Ares reports a relationship with Pfizer Inc that includes: employment. An Ta reports a relationship with Cytel Inc that includes: employment. An Ta reports a relationship with Pfizer Inc that includes: consulting or advisory. Donata Freigofaite reports a relationship with Cytel Inc that includes: employment. Sophie Warren reports a relationship with Pfizer Inc that includes: employment. Mercedes Mac Mullen reports a relationship with Pfizer Inc that includes: employment. Carolina Carballo reports a relationship with Pfizer Inc that includes: employment. Liping Huang reports a relationship with Pfizer Inc that includes: employment. The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: LRA, CC, and LH are employees of Pfizer Inc. SW and MM were employed by Pfizer Inc. at the time of manuscript development. AT received consulting fees from Pfizer Inc. for the study and manuscript development and is an employee of Cytel Inc. DF was employed by Cytel Inc. at the time of manuscript development. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Streptococcus pneumoniae carriage studies are crucial to monitor changes induced by use of pneumococcal conjugate vaccines and inform vaccination policies. In this cross-sectional study, we examined changes within the pneumococcal population following introduction of PCV13 in 2015 in the National Immunization Program (NIP), in Portugal. In 2018-2020 (NIP-PCV13), we obtained 1450 nasopharyngeal samples from children ≤6 years attending day-care. We assessed serotypes, antimicrobial resistance, and genotypes (MLST and GPSC) and compared findings with earlier periods: 2009-2010 (pre-PCV13), 2011-2012 (early-PCV13), and 2015-2016 (late-PCV13). Pneumococcal carriage prevalence remained stable at 60.2 %. Carriage of PCV13 serotypes was 10.7 %, markedly reduced compared to pre-PCV13 period (47.6 %). The most prevalent PCV13 serotypes were 19F, 3, and 19A all showing a significant decreasing trend compared to the pre-PCV13 period (from 7.1 % to 4.7 %, 10.1 % to 1.8 %, and 14.1 % to 1.8 %, respectively), a notable observation given the described limited effectiveness of PCV13 against serotype 3. Non-vaccinated children and children aged 4-6 years were more likely to carry PCV13 serotypes (2.5-fold, 95 %CI [1.1-5.6], and 2.9-fold, 95 %CI [1.3-6.8], respectively). The most prevalent non-PCV13 serotypes were 15B/C, 11A, 23B, 23A, and NT, collectively accounting for 51.9 % of all isolates. In total, 30.5 % of all pneumococci were potentially covered by PCV20. Resistance to penicillin (low-level) and macrolides increased significantly, from 9.3 % and 13.4 %, respectively, in the late-PCV13 period, to approximately 20 % each, mostly due to lineages expressing non-PCV13 serotypes, nearing pre-PCV13 levels. An expansion of lineages traditionally associated with PCV13 serotypes, like CC156-GPSC6 (serotype 14) and CC193-GPSC11 (serotype 19F), but now predominantly expressing non-PCV13 serotypes (11A, 15B/C, and 24F for GPSC6; and 15A and 21 for GPSC11) was noted. These findings indicate that the pneumococcal population is adapting to the pressures conferred by PCV13 and antimicrobial use and indicate the need to maintain close surveillance., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RSL has received consulting and speaking fees from Pfizer and Merck Sharp & Dome. RSL has received funds for unrestricted research grants from Pfizer and Merck Sharp & Dome, paid directly to her institution. ABA has received consulting and speaking fees from Pfizer and Merck Sharp & Dome. All other authors declare they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pneumococcal disease in older adults in the United Kingdom is rising despite immunisation. A key gap in the literature is the clinical effectiveness of revaccination with the pneumococcal polysaccharide vaccine (PPV23)., Methods: A cohort study was performed in England, using electronic medical records in the Clinical Practice Research Datalink. Individuals aged ≥64 years and vaccinated with PPV23 were included. Rates of hospitalised pneumonia (HP) and invasive pneumococcal disease (IPD) were compared between individuals receiving a single PPV23 dose versus those receiving two doses using multi-level Cox proportional hazards models. Propensity score weighting was performed to minimise the effect of confounding covariates across the comparison groups., Results: Between 2006 and 2019, there were 462 505 eligible participants. Of those, 6747 (1·5 %) received revaccination. Two doses compared to one dose was associated with an increased risk of HP (adjusted Hazard Ratio [aHR] 1·95; 95 %CI 1·74-2·20) and IPD (aHR 1·44; 95 %CI 1·41-1·46). In participants aged 64-74 years PPV23 revaccination was associated with more IPD (aHR 2·02; 95 %CI 1·75-2·33) and HP (aHR 1·46; 95 %CI 1·42-1.49). In those aged ≥75 years PPV23 revaccination was associated with more HP (aHR 1·12; 95 %CI 1·08-1·16) with no statistically significant difference detected in risk of IPD (aHR 1·20; 95 %CI 0·94-1·52)., Conclusions: No clear benefit of PPV23 revaccination was measured in older adults in this observational study. The small proportion of revaccinated subjects limits the strength of the conclusions. Further research evaluating the clinical effectiveness of PPV23 revaccination is required., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: NF and DH are currently in receipt of grant support from Seqirus UK Ltd. for the evaluation of influenza vaccines in the UK. NF and DH have previously received research-initiated and industry-initiated research grant support from GlaxoSmithKline (GSK) Biologicals for evaluation of rotavirus vaccination in the UK. DH has also received grants from GSK, Sanofi Pasteur, and Merck & Co (Kenilworth, New Jersey, USA) for rotavirus strain surveillance. KD, VD, LB, SA, NB and KF have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Immunogenicity of influenza and pneumococcal vaccines varies and requires further elucidation in patients with multiple sclerosis (MS) under treatment with disease-modifying therapies (DMTs)., Methods: Adult MS patients who consented with vaccination after standard-of-care consultation by their treating physicians were enrolled. All received a single dose of an inactivated quadrivalent influenza vaccine and of the 23-valent pneumococcal vaccine. A blood sample was collected before and after four weeks of vaccination for measurement of antibodies against Influenza A, B and S. pneumoniae. Patients were followed-up for adverse events and MS relapse for 12 months., Results: One hundred and seventy-two patients (65.7 % female, mean age 42 ± 13 years old, mean MS duration 7.6 ± 7.2 years, 81.4 % under DMTs) were enrolled from November 2019 to March 2020. Antibody measurements were available for 151 patients. Seropositivity for anti-PPSV23 did not differ between baseline and at 4 weeks of follow-up (n = 56, 37.1 %). There was a significant increase of absolute antibody titers post-vaccination for both influenza A and B (p < 0.001). For Influenza A, seropositivity was evident for 57 (37.7 %) patients at 4 weeks compared to 19 (12.6 %) patients at baseline (p McNemar  < 0.001). For Influenza Β, 110 (72.8 %) seroconverted 4 weeks after vaccination compared to 12 (7.9 %) at baseline (p McNemar  < 0.001). Interferon and fumarate did not affect influenza seroconversion while rituximab was associated with lower titers. Mild local AEs (pain, edema) were observed in 23.8 %; no severe AE was reported. Thirty-four patients (19.8 %) had a relapse during the 12-month follow-up; none was attributed to the vaccination., Conclusions: Seroconversion in MS patients on treatment was more frequent following influenza compared to PPSV23 vaccination. Rituximab had an effect on the height of the immune response. Better immunization coverage as well as future evaluation of the breadth of immune response elicited by immunization is necessary for these patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Cardiovascular disease (CVD) is the leading cause of death and illness globally. Influenza, pneumococcal disease and herpes zoster infection may trigger acute cardiovascular events or cause complications among cardiac patients. Vaccination is recommended for adults with CVD. There is a gap in research evidence around determinants and uptake of influenza, pneumococcal and zoster vaccines in adults with CVD., Objective: The aim of this study is to examine the rate of the uptake of influenza, zoster and pneumococcal vaccines, factors associated with the uptake of influenza vaccine, and the perceptions of influenza and pneumococcal vaccination among people with CVD in the community., Method: Cross-sectional survey data was analysed from three separate surveys carried out in Australia between October 2019 and September 2020 of 972 adults with CVD. We used descriptive statistics to describe data. Thematic analysis examined the reasons for taking influenza vaccine. Multivariable analysis was used to identify independent predictors of the influenza vaccine uptake and perceptions associated with the uptake of influenza and pneumococcal vaccines., Results: Out of 972 participants, a total of 661 (68 %) people said they had received influenza vaccine in the last 12 months; 361 (37 %) had ever received pneumococcal vaccine; 196 (20 %) had ever received zoster vaccine. Among 661 participants who said they received influenza vaccine within the 12 months prior to the study, 543 (82 %) participants received it from doctors or general practitioners (GPs) offices. Age 65 and older, being born in Australia, being employed or retired and having comorbidity were positive predictors of influenza vaccination. Doctors' recommendations to take the vaccine and awareness of free vaccines positively predicted influenza and pneumococcal vaccine uptake., Conclusion: The uptake of recommended pneumococcal and zoster vaccines is low in people with CVD. Doctors' recommendations, targeted health promotion programs in general practice, and easy access to vaccination may optimise vaccination uptake in patients with CVD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Co author C Raina Macintyre has received funding from Sanofi and Seqirus for investigator driven research on influenza If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Vaccinations are important for informal caregivers and their care recipients. Mental health problems are common among care givers. The aim of this study was to investigate vaccination readiness in informal caregivers and associations with mental health issues. Associations between vaccination readiness in informal caregivers and the vaccination status of their aged care recipients were examined., Methods: Within the multicenter prospective registry study 'Bavarian ambulatory Covid-19 Monitor (BaCoM) ', informal caregivers were asked for symptoms of depression (PHQ-9), burden of caretaking (BSFC-s), psychological antecedents of vaccination readiness (5C model) and previous Covid-19 infections of their care recipients. The vaccination status against Covid-19, seasonal influenza and pneumococcal disease was determined via vaccination certificates. Data analysis was performed using ordinal regressions and Mann-Whitney-U tests., Results: Data of n = 91 informal caregivers, associated with n = 84 care recipients were collected. Symptoms of depression were associated with reduced vaccination readiness (Calculation: p = 0.026, OR = 1.18), as well as the perceived burden of caretaking (Confidence: p = 0.006, OR = 0.88). A previous Covid-19 infection of the care recipients was associated with decreased vaccination readiness of informal caregivers (Median (Q1-Q3) Confidence: 5.0 (4.5-6.0) vs. 4.0 (3.0-5.0); Calculation: 5.0 (3.0-6.0) vs. 4.0 (1.0-5.0)). The vaccination status of the care recipients interrelated significantly with vaccination readiness of their informal caregivers (Confidence: p < 0.001; Complacency: p < 0.01; Constraints p < 0.05). No significant interrelations between vaccination readiness and the vaccination status against seasonal influenza or pneumococcal disease occurred., Conclusion: Mental health issues of informal caregivers seem to be associated with the actual vaccination status against Covid-19 in their care recipients. Target group specific counselling as well as an active involvement of informal caregivers in shared decision-making processes can be of relevance, but even more attention should be paid to the protection of mental health for informal caregivers., Trial Registration Number: German Register of Clinical Studies DRKS 26039., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To evaluate the cost-effectiveness of the 20-valent pneumococcal conjugate vaccine (PCV20) compared to 13-valent pneumococcal conjugate vaccine (PCV13) for the pediatric population in Korea, where the four-dose vaccine coverage rate is over 97%., Methods: We constructed a Markov model to calculate the cost and quality-adjusted life-years (QALYs) over 10 years. The health states were susceptible states; disease states, which included invasive pneumococcal diseases such as meningitis, bacteremia, pneumonia, and acute otitis media; and death attributable to pneumococcal disease. The annual incidence and mortality due to pneumococcal diseases were estimated based on the serotypes covered by PCV13 and PCV20, vaccine coverage rate, vaccine effectiveness, and population size. Vaccine, administration, and disease costs were included in the model., Results: In the total population (n = 51,431,305), PCV20 prevented more pneumococcal diseases and deaths, resulting in a gain of 74,855 QALY over PCV13. Meanwhile, the PCV20 group spent $275,136,631 less than the PCV13 group. As PCV20 gained more QALYs but spent less on total medical costs than PCV13, PCV20 was dominant over PCV13., Conclusions: In the Korean population, PCV20 is a cost-effective and dominant option over PCV13. Our findings provide evidence for decision-making regarding the introduction of PCV20 in countries with high vaccine coverage., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sun-Kyeong Park reports financial support was provided by Pfizer Korea Ltd. Young June Choe reports financial support was provided by Pfizer Korea Ltd. Ju-Yeon Lee reports financial support was provided by Pfizer Korea Ltd. In-Ae Suk reports financial support was provided by Pfizer Korea Ltd. Young-Soo Kim reports financial support was provided by Pfizer Korea Ltd. Hak-Yeon Kim reports financial support was provided by Pfizer Korea Ltd. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pneumonia is one of the main contributors to non-cancer mortality among patients with head and neck cancer (HNC). This study aimed to determine the vaccine uptake for pneumococcal polysaccharide and conjugate vaccines, quadrivalent influenza vaccines, and mRNA COVID-19 vaccines before and after an HNC diagnosis. Furthermore, the study investigated the timing of vaccination after a cancer diagnosis., Materials & Methods: This register based multicentre study included Danish patients ≥ 18y diagnosed with HNC between 2018 and 2021. The vaccine uptake was assessed by calculating cumulative incidence (CI), while the timing of vaccination after an HNC diagnosis was explored by calculating incidence rates of vaccination the first and second half year after a cancer diagnosis., Results: The cumulative incidence of vaccine uptake for pneumococcal vaccines was estimated to be 8 % and 16 % one year before and after an HNC diagnosis, respectively. The CIs were 36 % and 38 % for quadrivalent influenza vaccines, respectively, whereas the CIs of vaccine uptake for mRNA COVID-19 vaccines were 60 % and 89 %. The IR of mRNA COVID-19 vaccinations the first half year after HNC diagnosis were 273 per 1000 person-months of follow-up (PMFU) and 111 per 1000 PMFU the second half year, respectively (IRR: 0.38, p < 0.001). Comparing the same periods, the IR of quadrivalent influenza vaccination was 28 per 1000 PMFU and 51 per 1000 PMFU (IRR: 1.95, 0 < 0.001). The IRs of pneumococcal vaccinations were 11 per 1000 PMFU and 14 per 1000 PMFU (IRR 1.28, p = 0.21)., Conclusions: Although our study shows a significant increase in pneumococcal and COVID-19 vaccine uptake after HNC diagnosis, a gap remains in vaccine uptake before diagnosis, underscoring the need for increased awareness of vaccination options and recommendations. Our findings could serve as a reference for future recommendations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mads Frederik Eiberg reports financial support was provided by Danish Cancer Society. Zitta Barrella Harboe reports financial support was provided by Independent Research Fund Denmark. Zitta Barrella Harboe reports financial support was provided by Lundbeck Foundation. Zitta Barrella Harboe reports financial support was provided by Danish Cancer Society. Omid Rezahosseini reports financial support was provided by A.P. Møllers fonden. Omid Rezahosseini reports financial support was provided by Research Foundation of Rigshospitalet. Zitta Barrella Harboe reports a relationship with The Danish Vaccination Council that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Pneumococcal meningitis outbreaks occur sporadically in the African meningitis belt. Outbreak control guidelines and interventions are well established for meningococcal but not pneumococcal meningitis. Mathematical modelling is a useful tool for assessing the potential impact of different pneumococcal control strategies. This work aimed to estimate the impact of reactive vaccination with pneumococcal conjugate vaccine (PCV) had it been implemented in past African meningitis belt outbreaks and assess their efficiency relative to existing routine infant immunisation with PCV., Methods & Results: Using recent pneumococcal meningitis outbreaks in Burkina Faso, Chad, and Ghana as case studies, we investigated the potential impact of reactive vaccination. We calculated the number needed to vaccinate to avert one case (NNV) in each outbreak setting and over all outbreaks and compared this to the NNV for existing routine infant vaccination. We extended previous analyses of reactive vaccination by considering longer-term protection in vaccinees over five years, incorporating a proxy for indirect effects. We found that implementing reactive vaccination in previous pneumococcal meningitis outbreaks could have averted up to 10-20 % of outbreak cases, with the biggest potential impact in Brong Ahafo, Ghana (2015-2016) and Goundi, Chad (2009). The NNV, and hence the value of reactive vaccination, varied greatly. 'Large' (80 + cumulative modelled cases per 100,000 population) and/or 'prolonged' (exceeding a response threshold of 10 suspected cases per 100,000 per week for four weeks or more) outbreaks had NNV estimates under 10,000. For routine infant vaccination with PCV, the estimated NNV ranged from 3,100-5,600 in Burkina Faso and 1,500-2,600 in Ghana., Implications: This analysis provides evidence to inform the design of pneumococcal meningitis outbreak response guidelines. Countries should consider reactive vaccination in each outbreak event, together with maintaining routine infant vaccination as the primary intervention to reduce pneumococcal disease burden and outbreak risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Various vaccinations are recommended for older adults; however, unlike childhood immunization programs, there is often no systematic immunization schedule for older adults, and management of the immunization schedule is the responsibility of the individuals. Self-managing immunization status can be challenging and potentially lead to missed vaccinations. This study aimed to describe the statuses and patterns of indicated vaccine uptake among older adults. This descriptive study utilized data from a large-scale nationwide internet survey in Japan (n = 6,828). Participants aged 65 years and older were asked about their immunization status for four vaccines in Japan: coronavirus disease 2019, influenza, pneumococcal, and herpes zoster vaccines. Overall, 6.8 % of the participants received all four vaccines, whereas 9.5 % had not received any of four vaccines. Many participants received one to three types of vaccinations (one type: 24.7 %, two types: 30.8 %, three types: 28.1 %). Attention should be focused on vaccine uptake among older adults., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Otitis media (OM) is a prevalent respiratory disease in children and poses significant public health challenges due to its impact on child health and economic burdens. However, there have no nationwide epidemiological studies conducted in Japan. This study investigates the epidemiological trends of OM in Japan, taking into account the impact of the 7-valent pneumococcal conjugate vaccine (PCV7) introduction., Method: This study was retrospective cohort study using secondary data on the nationwide longitudinal birth cohort. This survey followed two cohorts born in 2001 (pre-PCV era) and 2010 (post-PCV era) until the age of 9. Every year, parents were surveyed about their children's health status, including occurrences of OM. The annual period prevalence and cumulative incidence of OM were assessed in this study, and the two cohorts were compared using a modified Poisson regression model adjusted environmental factors with the 2001 cohort as reference., Result: The study included 47,015 children from the 2001 cohort and 38,554 from the 2010 cohort. Peak annual period prevalence of OM varied by era. Cumulative incidence was 13.8 % for the 2001 cohort and 18.5 % for the 2010 cohort by 1.5 years of age and 28.9 % and 33.3 %, respectively, by 3.5 years of age. In particular, from the fourth survey onward, covering ages 2.5-3.5 years, a shift was observed from an increased risk to a decreased risk of OM., Conclusion: This nationwide longitudinal study emphasizes variations in OM epidemiology across Japan over time, with changes potentially influenced by the introduction of PCV7. In this study, due to the absence of individual PCV7 vaccination data, the effect of PCV7 was estimated based on the vaccination rate at the population level. The results suggest a notable decrease in the incidence of OM in later years, aligning with the increased uptake of PCV7., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Carriage studies are an efficient means for assessing pneumococcal conjugate vaccine effect in settings where pneumococcal disease surveillance programmes are not well established. In this study the effect of 10-valent pneumococcal conjugate vaccine (PCV10) introduction on pneumococcal carriage and density among Nepalese children using a bacterial microarray and qPCR was examined., Methods: PCV10 was introduced into the Nepalese infant immunisation schedule in August 2015. Nasopharyngeal swabs were collected from healthy Nepalese children in Kathmandu between April 2014 and December 2021. Samples were plated on blood agar, incubated overnight, and DNA extracted from plate sweeps. Pneumococcal serotyping was done using the Senti-SPv1.5 microarray (BUGS Bioscience, UK). DNA was extracted from swab media and qPCR performed for pneumococcal autolysin (lytA)., Results: A significant decline in prevalence of PCV10 serotypes was observed when comparing pre-PCV10 with post-PCV10 collection periods (36.5 %, 454/1244 vs 10.3 %, 243/2353, p < 0.0001). Multiple-serotype carriage was also observed to significantly decline when comparing pre-PCV10 with post-PCV10 periods (31.4 %, 390/1244 vs 22.2 %, 522/2353, p < 0.0001). Additionally, a significant decline in median pneumococcal density was observed when comparing pre-PCV10 with post-PCV10 periods (3.3 vs 3.25 log10 GE/ml, p = 0.0196)., Conclusions: PCV10 introduction was associated with reduced, prevalence of all PCV10 serotypes, multiple serotype carriage, and pneumococcal carriage density., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andrew J Pollard reports financial support was provided by GAVI Alliance. Rama Kandasamy reports a relationship with National Health and Medical Research Council that includes: funding grants. Rama Kandasamy reports a relationship with Sanofi that includes: funding grants. AJP is chair of the UK Joint Committee on Vaccination and Immunisation and was a member of WHOs SAGE while this study was being conducted. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Large health insurance claims databases can be used to estimate rates of rare safety outcomes. We measured incidence rates of rare outcomes that could be used to contextualize adverse events among people receiving pneumococcal vaccines in clinical trials or clinical practice. However, algorithms used to identify outcomes in administrative databases are subject to error. Using two algorithms for each outcome, we assessed the influence of algorithm choice on the rates of the outcomes., Methods: We used closed administrative medical and pharmacy claims in the Healthcare Integrated Research Database SM (HIRD) to construct a broad cohort of individuals less than 100 years old (i.e., the target cohort) and a trial-similar cohort of individuals resembling those potentially eligible for a vaccine clinical trial (e.g., for a pneumococcal vaccine). We stratified by age and sex and used specific and sensitive algorithms to estimate rates of 39 outcomes including cardiac/cerebrovascular, metabolic, allergic/autoimmune, neurological, and hematologic outcomes. Specific algorithms intended to reduce false positive errors, while sensitive algorithms intended to reduce false negative errors, thereby providing lower and upper bounds for the "true" rates., Results: We followed approximately 40 million individuals in the target cohort for an average of 3 years. Of 39 outcomes, 14 (36 %) had a rate from the specific algorithm that was less than half the rate from the sensitive algorithm. Rates of cardiac/cerebrovascular outcomes were most consistent (mean ratio of rates from specific algorithms compared to rates from sensitive algorithms = 0.76), while the rates of neurological and hematologic outcomes were the least consistent (mean ratio of rates = 0.33 and 0.36, respectively)., Conclusions: For many cardiac/cerebrovascular outcomes, rates were similar regardless of the algorithm. For other outcomes, rates varied substantially by algorithm. Using multiple algorithms to ascertain outcomes in claims data can be informative about the extent of uncertainty due to outcome misclassification., Competing Interests: Declaration of competing interest This study was sponsored by Pfizer. CLC and SL are employees of Carelon Research (formerly HealthCore, Inc.), which received funding from Pfizer in connection with the development of this manuscript. HC was an employee of Carelon Research at the time the study was conducted. JD and WW are employees and shareholders of Pfizer, Inc., (Copyright © 2024. Published by Elsevier Ltd.)

Pneumococcal disease, presenting as invasive pneumococcal disease (IPD) or community-acquired pneumonia (CAP) is an important cause of illness and hospitalisation in the elderly. To reduce pneumococcal burden, since 2003, 65-year-olds in England have been offered a 23-valent pneumococcal polysaccharide vaccine (PPV23). This study compares the impact and cost-effectiveness (CE) of vaccination with the existing PPV23 vaccine to the new 15-and 20-valent pneumococcal conjugate vaccines (PCV15 and PCV20), targeting adults aged 65 or 75 years old. We developed a static Markov model for immunisation against pneumococcal disease, capturing different vaccine effectiveness and immunity waning assumptions, projecting the number of IPD/CAP cases averted over the thirty years following vaccination. Using an economic model and probabilistic sensitivity analysis we evaluated the CE of the different immunisation strategies at current vaccine list prices and the willingness-to-pay at a median threshold of £20,000/QALY and an uncertainty threshold of 90% of simulations below £30,000/QALY. PCV20 averted more IPD and CAP cases than PCV15 or PPV23 over the thirty years following vaccination: 353(360), 145(159) and 150(174) IPD and 581(673), 259(485) and 212(235) CAP cases at a vaccination age of 65(75) under base vaccine effectiveness assumptions. At the listed prices of PCV20 and PPV23 vaccines as of May 2023, both vaccines were cost-effective when vaccinating 65- or 75-year-olds with an ICER threshold of £20,000 per QALY. To achieve the same cost-effectiveness as PPV23, the additional cost of PCV20 should be less than £44(£91) at an ICER threshold of £20,000/QALY (£30,000/QALY) if vaccination age is 65 (or £54(£103) if vaccination age is increased to 75). We showed that both PPV23 and PCV20 were likely to be cost-effective. PCV20 was likely to avert more cases of pneumococcal disease in elderly adults in England than the current PPV23 vaccine, given input assumptions of a higher vaccine effectiveness and slower waning for PCV20., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: A U.S. case-control study (2010-2014) demonstrated vaccine effectiveness (VE) for ≥ 1 dose of the thirteen-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) invasive pneumococcal disease (IPD) at 86 %; however, it lacked statistical power to examine VE by number of doses and against individual serotypes., Methods: We used the indirect cohort method to estimate PCV13 VE against VT-IPD among children aged < 5 years in the United States from May 1, 2010 through December 31, 2019 using cases from CDC's Active Bacterial Core surveillance, including cases enrolled in a matched case-control study (2010-2014). Cases and controls were defined as individuals with VT-IPD and non-PCV13-type-IPD (NVT-IPD), respectively. We estimated absolute VE using the adjusted odds ratio of prior PCV13 receipt (1-aOR x 100 %)., Results: Among 1,161 IPD cases, 223 (19.2 %) were VT cases and 938 (80.8 %) were NVT controls. Of those, 108 cases (48.4 %; 108/223) and 600 controls (64.0 %; 600/938) had received > 3 PCV13 doses; 23 cases (17.6 %) and 15 controls (2.4 %) had received no PCV doses. VE ≥ 3 PCV13 doses against VT-IPD was 90.2 % (95 % Confidence Interval75.4-96.1 %), respectively. Among the most commonly circulating VT-IPD serotypes, VE of ≥ 3 PCV13 doses was 86.8 % (73.7-93.3 %), 50.2 % (28.4-80.5 %), and 93.8 % (69.8-98.8 %) against serotypes 19A, 3, and 19F, respectively., Conclusions: At least three doses of PCV13 continue to be effective in preventing VT-IPD among children aged < 5 years in the US. PCV13 was protective against serotypes 19A and 19F IPD; protection against serotype 3 IPD did not reach statistical significance., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Lee Harrison provides service on advisory boards (Pfizer, Sanofi, GSK) and a DSMB (Merck); while LH does not receive any fees for this work he is reimbursed for occasional travel. Tamara Pilishvili reports a relationship with GSK that includes: employment. During data collection, analysis, and write-up, TP was employed by CDC. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Globally, cardiovascular disease (CVD) is the leading cause of death and illness. Vaccine-preventable infections may increase acute coronary vascular disease events and the risk of complications. Low vaccine coverage has been reported among adults at high risk of complications from vaccine-preventable infections. There is a gap in research evidence around determinants of uptake of vaccines among adults with CVD. This study examined the uptake of influenza, pneumococcal and zoster vaccines and the determinants of uptake of the vaccines among cardiac patients., Method: A prospective cross-sectional study was carried out among hospitalised cardiac patients through an interviewer-administered questionnaire. Descriptive statistics were used to investigate self-reported uptake of influenza, pneumococcal and zoster vaccines. Univariate and multivariate analyses of participants' social demographic and clinical characteristics were conducted to identify factors for receiving influenza vaccine., Results: Low vaccination rates among 104 participants were found for influenza (45.2%), pneumococcal (13.5%) and zoster (5.8%) vaccines. The most common reason for not receiving influenza vaccine was concern about side effects. Lack of awareness about the pneumococcal and zoster vaccines was the main reason for the poor uptake of these vaccines. Australia-born participants were more likely to receive influenza vaccine than overseas-born participants. Working-age participants and, interestingly, people living with a current smoker were less likely to receive influenza vaccine., Conclusion: Influenza, pneumococcal and zoster vaccine uptake among cardiac patients was low. Encouraging physician recommendations for vaccination for cardiac patients under 65 years of age and addressing vaccination challenges among people from culturally and linguistically diverse backgrounds and pharmacy, workplace, and hospital vaccination may help increase vaccination uptake among cardiac patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Has received funding from Sanofi and Seqirus for investigator driven research on influenza - C Raina MacIntyre]., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: We explored the role of metabolic hormones and the B-cell repertoire in the association between nutritional status and vaccine responses., Methods: In this prospective cohort study, nested within a larger randomized open-label trial, 211 South African children received two doses of measles vaccine and two or three doses of pneumococcal conjugate vaccine (PCV). Metabolic markers (leptin, ghrelin and adiponectin) and distribution of B-cell subsets (n = 106) were assessed at 18 months of age., Results: Children with a weight-for-height z-score (WHZ) ≤ -1 standard deviation (SD) at booster vaccination had a decreased mean serotype-specific PCV IgG response compared with those with WHZ > -1 and <+1 SD or WHZ ≥ +1 SD at 9 months post-booster (18 months of age). (Naive) pre-germinal center B-cells were associated with pneumococcal antibody decay between one to nine months post-booster. Predictive performance of elastic net models for the combined effect of B-cell subsets, metabolic hormones and nutritional status (in addition to age, sex, and randomization group) on measles and PCV vaccine response had an average area under the receiver operating curve of 0.9 and 0.7, respectively., Conclusions: The combined effect of B-cell subsets, metabolic hormones and nutritional status correlated well with the vaccination response for measles and most PCV serotypes., Clinicaltrials: gov registration of parent studies: NCT02943902 and NCT03330171., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Vaccination against pneumococci is currently the most effective method of protection against pneumococcal infections. The aim of the study was to analyse changes in hospitalisations and in-hospital deaths due to pneumonia before (2009-2016) and after (2017-2020) the introduction of PCV 10 vaccinations in the National Immunisation Programme in Poland., Methods: Data on hospitalisations related to community acquired pneumonia (CAP) in the years 2009-2020 were obtained from the Nationwide General Hospital Morbidity Study. Analyses were made in the age groups: <2, 2-3, 4-5, 6-19, 20-59, 60+ years in 2009-2016 and 2017-2020., Results: Overall, there were 1,503,105 CAP-related hospitalisations in 2009-2020, 0.7% of which were caused by Streptococcus pneumoniae infections. Children <2 years of age were the most frequently hospitalised for CAP per 100,000 population, followed by patients aged 2-3, 4-5 and 60+ years. In the years 2009-2016, the percentage of CAP hospital admissions increased significantly, and after the year 2017, it decreased significantly in each of the age groups (p<0.001). In the years 2009-2016, a significant increase in hospitalisations for Streptococcus pneumoniae infections was observed in the age groups <2, 2-3 and 4-5 years (p<0.05). A significant reduction in hospitalisations was observed in the age groups <2, 20-59 and 60+ in 2017-2020 (p<0.05). In the years 2009-2020, there were 84,367 in-hospital deaths due to CAP, 423 (0.5%) of which due to Streptococcus pneumoniae, with patients mainly aged 60+., Conclusions: Implementation of the PCV vaccination programme has effectively decreased the incidence of CAP hospitalisations, including children <2 years of age. The group that is most at risk of death are persons aged 60+. The results of our study can be useful in evaluating the vaccine efficacy and benefits, and they can be an essential part of public health policy. Effective prevention strategies for CAP should be implemented in different age groups., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier India Pvt Ltd. All rights reserved.)

Objective: To assess the health and economic outcomes of a PCV13 or PCV15 age-based (65 years-and-above) vaccination program in Switzerland., Interventions: The three vaccination strategies examined were:Target population: All adults aged 65 years-and-above. Perspective(s): Switzerland health care payer., Time Horizon: 35 years. Discount rate: 3.0%. Costing year: 2023 Swiss Francs (CHF)., Study Design: A static Markov state-transition model., Data Sources: Published literature and publicly available databases or reports., Outcome Measures: Pneumococcal diseases (PD) i.e., invasive pneumococcal diseases (IPD) and non-bacteremic pneumococcal pneumonia (NBPP); total quality-adjusted life-years (QALYs), total costs and incremental cost-effectiveness ratios (CHF/QALY gained)., Results: Using an assumed coverage of 60%, the PCV15 strategy prevented a substantially higher number of cases/deaths than the PCV13 strategy when compared to the No vaccination strategy (1,078 IPD; 21,155 NBPP; 493 deaths). The overall total QALYs were 10,364,620 (PCV15), 10,364,070 (PCV13), and 10,362,490 (no vaccination). The associated overall total costs were CHF 741,949,814 (PCV15), CHF 756,051,954 (PCV13) and CHF 698,329,579 (no vaccination). Thus, the PCV13 strategy was strongly dominated by the PCV15 strategy. The ICER of the PCV15 strategy (vs. no vaccination) was CHF 20,479/QALY gained. In two scenario analyses where the vaccine effectiveness for serotype 3 were reduced (75% to 39.3% for IPD; 45% to 23.6% for NBPP) and NBPP incidence was increased (from 1,346 to 1,636/100,000), the resulting ICERs were CHF 29,432 and CHF 13,700/QALY gained, respectively. The deterministic and probabilistic sensitivity analyses demonstrated the robustness of the qualitative results-the estimated ICERs for the PCV15 strategy (vs. No vaccination) were all below CHF 30,000/QALYs gained., Conclusions: These results demonstrate that using PCV15 among adults aged 65 years-and-above can prevent a substantial number of PD cases and deaths while remaining cost-effective over a range of inputs and scenarios., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [This study was performed by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Kwame Owusu-Edusei and Nicole Cossrow are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may hold stock or stock options in Merck & Co., Inc., Rahway, NJ, USA. Andrea-Favre-Bulle and Thomas Mutschler are employees of MSD, Lucerne, Switzerland and may hold stock or stock options in Merck & Co., Inc., Rahway, NJ, USA. Eleana Tsoumani is an employee of MSD, Athens, Greece and may hold stock or stock options in Merck & Co., Inc., Rahway, NJ, USA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in—or financial conflict with—the subject matter or materials discussed in this manuscript apart from those disclosed herewith]., (Copyright © 2024. Published by Elsevier India Pvt Ltd.)

Background: The current recommendation for the elderly is to receive both a single dose 23-valent pneumococcal polysaccharide vaccine (PPSV-23) and an annual inactivated influenza vaccine. There is a lack of post-marketing safety studies on concomitant vaccination using real-world data. We aimed to evaluate the safety of administering PPSV-23 and influenza vaccine concomitantly versus sequentially., Methods: We performed a retrospective cohort study using a linked database that combines vaccination registry from the Korea Disease Control and Prevention Agency and claims data from the National Health Insurance Service. The study population included all those aged over 65 who received PPSV-23 at least once from Jan 1, 2016, to Dec 31, 2020. This study evaluated the 16 prespecified events of interest. Concomitant vaccination was defined as receiving both PPSV-23 and influenza vaccine on the same day. For sequential vaccination, we defined it as receiving influenza vaccination during the period from 30 to 365 days prior to the date of PPSV-23 injection. We performed 1:4 propensity score matching and estimated adjusted incidence rate ratio (aIRR) with a 95 % confidence interval (CI) using conditional Poisson regression., Results: Of the 2,885,144 elderly patients who received PPSV-23 vaccination at least once from Jan 1, 2016, to Dec 31, 2020, a total 87,899 were included in the concomitant vaccination group and 1,200,091 were included in the sequential vaccination group. After adjusting for confounders, the concomitant group exhibited a significantly lower risk of allergic reactions (aIRR: 0.71, 95 % CI: 0.58-0.87), neuritis (aIRR: 0.72, 95 % CI: 0.57-0.91), and pneumonia (aIRR: 0.85, 95 % CI: 0.80-0.90), while demonstrating significantly higher risks of paralysis (aIRR: 1.63, 95 % CI: 1.05-2.52) compared to the sequential group., Conclusions: Concomitant administration of PPSV-23 and influenza vaccine in the elderly was not associated with a higher risk of most prespecified adverse events (AEs) compared to sequential vaccination. This study supports the safety of concomitant administration of PPSV-23 and influenza vaccine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Introduction of pneumococcal conjugate vaccines (PCVs) reduced the number of cases of pneumococcal disease (PD). However, there is an increase in clinical and economic burden of PD from serotypes that are not part of the existing pneumococcal vaccines, particularly impacting pediatric and elder population. In addition, the regions where the PCV is not available, the disease burden remains high. In this study, immunogenicity and safety of the BE's 14-valent PCV (PNEUBEVAX 14™; BE-PCV-14) containing two additional epidemiologically important serotypes (22F and 33F) was evaluated in infants in comparison to licensed vaccine, Prevenar-13 (PCV-13)., Methods: This is a pivotal phase-3 single blind randomized active-controlled study conducted at 12 sites across India in 6-8 weeks old healthy infants at 6-10-14 weeks dosing schedule to assess immunogenic non-inferiority and safety of a candidate BE-PCV-14. In total, 1290 infants were equally randomized to receive either BE-PCV-14 or PCV-13. Solicited local reactions and systemic events, adverse events (AEs), serious AEs (SAEs), and medically attended AEs (MAAEs) were recorded. Immunogenicity was assessed by measuring anti-PnCPS (anti-pneumococcal capsular polysaccharide) IgG concentration and functional antibody titers through opsonophagocytic activity (OPA), one month after completing three dose schedule. Cross protection to serotype 6A offered by serotype 6B was also assessed in this study., Findings: The safety profile of BE-PCV-14 was comparable to PCV-13 vaccine. Majority of reported AEs were mild in nature. No severe or serious AEs were reported in both the treatment groups. For the twelve common serotypes and for the additional serotypes (22F and 33F) in BE-PCV-14, NI criteria was demonstrated as defined by WHO TRS-977. Primary immunogenicity endpoint was met in terms of IgG immune responses for all 14 serotypesof BE-PCV-14. Moreover, a significant proportion of subjects (69%) seroconverted against serotype 6A, even though this antigen was not present in BE-PCV-14. This indicates that serotype 6B of BE-PCV-14 cross protects serotype 6A. BE-PCV-14 also elicited comparable serotype specific functional OPA immune responses to all the serotypes common to PCV-13., Interpretations: BE-PCV-14 was found to be safe and induced robust and functional serotype specific immune responses to all 14 serotypes. It also elicited cross protective immune response against serotype 6B.These findings suggest that BE-PCV-14 can be safely administered to infants and achieve protection against pneumococcal disease caused by serotypes covered in the vaccine. The study was prospectively registered with clinical trial registry of India - CTRI/2020/02/023129., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘RVM, ST, SG, VY, RM, KT and PP are employees of Biological E Limited and they do not have any stock options or incentives. All the other participating authors declare no conflicts of interest.’., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The cross-protection of pneumococcal conjugate vaccines (PCV) against serotype 6C is not clearly documented, although 6C represents a substantial burden of pneumococcal disease in recent years. A systematic review by the World Health Organization that covered studies through 2016 concluded that available data were insufficient to determine if either PCV10 (which contains serotype 6B but not 6A) or PCV13 (containing serotype 6A and 6B) conferred protection against 6C., Methods: We performed a systematic review of randomized controlled trials and observational studies published between January 2010 - August 2022 (Medline/Embase), covering the direct, indirect, and overall effect of PCV10 and PCV13 against 6C invasive pneumococcal disease (IPD), non-IPD, nasopharyngeal carriage (NPC), and antimicrobial resistance (AMR)., Results: Of 2548 publications identified, 112 were included. Direct vaccine effectiveness against 6C IPD in children ranged between 70 and 85 % for ≥ 1 dose PCV13 (n = 3 studies), was 94 % in fully PCV13 vaccinated children (n = 2), and -14 % for ≥ 1 dose of PCV10 (n = 1). Compared to PCV7, PCV13 efficacy against 6C NPC in children was 66 % (n = 1). Serotype 6C IPD rates or NPC prevalence declined post-PCV13 in most studies in children (n = 5/6) and almost half of studies in adults (n = 5/11), while it increased post-PCV10 for IPD and non-IPD in all studies (n = 6/6). Changes in AMR prevalence were inconsistent., Conclusions: In contrast to PCV10, PCV13 vaccination consistently protected against 6C IPD and NPC in children, and provided some level of indirect protection to adults, supporting that serotype 6A but not 6B provides cross-protection to 6C. Vaccine policy makers and regulators should consider the effects of serotype 6A-containing PCVs against serotype 6C disease in their decisions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GH, IS, and MB are employees of P95 Epidemiology & Pharmacovigilance, which was contracted by Pfizer to conduct the research described in this manuscript. GH has also received personal fees from MSD, Sanofi Pasteur, Janssens, SNB, and Pfizer as speaker at international meetings and as a member of advisory boards, outside the scope of the submitted work. LRG, CT, LJ, and BDG are employees of Pfizer, Inc. and may hold stocks or stock options. MS has received personal fees from GSK, Pfizer, AstraZeneca, and Sanofi Pasteur as a speaker at international meetings and as a member of advisory boards (outside the scope of the submitted work). She has also worked as a contractor for Pfizer., (Copyright © 2024. Published by Elsevier India Pvt Ltd.)

The spleen is responsible for blood filtration and mounting an immune response against pathogens. In some people the spleen must be surgically removed because of traumatic events or oncological and hematological conditions. These patients are at higher risk of developing diseases caused by encapsulated bacteria throughout their lives. Thus, immunisations are advised for splenectomised persons to prevent infection caused by Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b (Hib). This study assessed vaccination coverage (VC) among Norwegian patients with surgical asplenia. Using the Nomesco Classification of Surgical Procedures codes, patient information (age, sex, date of initial diagnosis and date of surgery) was acquired from the Norwegian Patient Registry. The National Immunization Register provided information on vaccination status and data of any subsequent invasive bacterial infections were obtained from the Norwegian Surveillance System for Communicable Diseases. From the total population of Norway, 3155 patients who had undergone complete splenectomy were identified. Of these, 914 (29.0%) had received at least one dose of pneumococcal conjugate vaccine (PCV), 1324 (42.0%) at least one dose of pneumococcal polysaccharide vaccine and 589 (18.7%) had received both. Only 4.2% of the patients had received two doses of a meningococcal ACWY conjugate vaccine, while 8.0% of 1467 patients splenectomised after 2014 had received at least two doses of a serogroup B meningococcal vaccine. The VC for Hib was 18.7%. Nearly all splenectomised children under the age of 10 were vaccinated with Hib and PCV as these vaccines are included in the childhood immunisation program. For all vaccines, VC decreased with age. Twenty-nine invasive bacterial infections were registered post-splenectomy in 25 patients. Vaccination according to national recommendations could have prevented at least 8 (28%) of these infections. Our study showed that efforts are required to increase VC of splenectomised individuals in Norway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: V114 (15-valent pneumococcal conjugate vaccine [PCV]) contains all serotypes in 13-valent PCV (PCV13) and additional serotypes 22F and 33F. This study evaluated safety and immunogenicity of V114 compared with PCV13 in healthy infants, and concomitant administration with DTPa-HBV-IPV/Hib and rotavirus RV1 vaccines., Methods: V114 and PCV13 were administered in a 2+1 schedule at 2, 4, and 11-15 months of age. Adverse events (AEs) were collected on Days 1-14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-primary series (PPS), immediately prior to a toddler dose, and 30 days post-toddler dose (PTD). Primary objectives included non-inferiority of V114 to PCV13 for 13 shared serotypes and superiority of V114 to PCV13 for the two additional serotypes., Results: 1184 healthy infants 42-90 days of age were randomized 1:1 to V114 (n = 591) or PCV13 (n = 593). Proportions of participants with solicited AEs and serious AEs were comparable between vaccination groups. V114 met pre-specified non-inferiority criteria for all 13 shared serotypes, based on the difference in proportions of participants with serotype-specific IgG concentrations ≥0.35 μg/mL (response rate; lower bound of two-sided 95% confidence interval [CI] >-10.0) and IgG geometric mean concentration (GMC) ratios (lower bound of two-sided 95% CI >0.5), and pre-specified superiority criteria for serotypes 22F and 33F (lower bound of two-sided 95% CI >10.0 for response rates and >2.0 for GMC ratios). Antibody responses to DTPa-HBV-IPV/Hib and RV1 vaccines met pre-specified non-inferiority criteria, based on antigen-specific response rates to DTPa-HBV-IPV/Hib and anti-rotavirus IgA geometric mean titers., Conclusions: After a 2+1 schedule, V114 elicited non-inferior immune responses to 13 shared serotypes and superior responses to the two additional serotypes compared with PCV13, with comparable safety profile. These results support the routine use of V114 in infants., Trial Registration: ClinicalTrials.gov: NCT04031846; EudraCT: 2018-003787-31., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SM, CC, RL, RTW, and JP are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and may own stock and/or stock options in Merck & Co., Inc., Rahway, NJ, USA. RM, LM, and KB were employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA at the time of this study. JK is an employee of MSD (UK) Limited, London, UK and may hold stock and/or stock options in Merck & Co., Inc., Rahway, NJ, USA. MCT is an employee of Merck Canada Inc., Kirkland, QC, Canada and may hold stock and/or stock options in Merck & Co., Inc., Rahway, NJ, USA. HG is an employee of MSD B.V., Netherlands and may hold stock and/or stock options in Merck & Co., Inc., Rahway, NJ, USA. FM-T has received honoraria from GSK group of companies, Pfizer Inc, Sanofi Pasteur, MSD, Seqirus, Biofabri, and Janssen for taking part in advisory boards and expert meetings and for acting as a speaker in congresses outside the scope of the submitted work. FM-T has also acted as principal investigator in randomized controlled trials of the above-mentioned companies as well as Ablynx, Gilead, Regeneron, Roche, Abbott, Novavax, and MedImmune, with honoraria paid to his institution. RD has received grants from Pfizer, MSD, and MedImmune/AstraZeneca. He serves as scientific consultant on the review/board/advisory committee of Pfizer, and MSD. He is also part of the speakers’ bureaus of Pfizer, MSD, Sanofi Pasteur, and GSK. PR has participated in scientific advisory boards for Merck & Co., Pfizer and GSK and has received institutional funding for investigator-initiated research from GlaxoSmithKline Biologicals and Merck & Co. All other authors report no potential conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Introduction: Pneumococcus is an important respiratory pathogen. The 10-valent pneumococcal vaccine (PHiD-CV) was introduced into the Icelandic vaccination programme in 2011. The aim was to estimate the impact of PHiD-CV on paediatric hospitalisations for respiratory tract infections and invasive disease., Methods: The 2005-2015 birth-cohorts were followed until three years of age and hospitalisations were recorded for invasive pneumococcal disease (IPD), meningitis, sepsis, pneumonia and otitis media. Hospitalisations for upper- and lower respiratory tract infections (URTI, LRTI) were used as comparators. The 2005-2010 birth-cohorts were defined as vaccine non-eligible cohorts (VNEC) and 2011-2015 birth-cohorts as vaccine eligible cohorts (VEC). Incidence rates (IR) were estimated for diagnoses, birth-cohorts and age groups, and incidence rate ratios (IRR) between VNEC and VEC were calculated assuming Poisson variance. Cox regression was used to estimate the hazard ratio (HR) of hospitalisation between VNEC and VEC., Results: 51,264 children were followed for 142,315 person-years, accumulating 1,703 hospitalisations for the respective study diagnoses. Hospitalisations for pneumonia decreased by 20% (HR 0.80, 95%CI:0.67-0.95) despite a 32% increase in admissions for LRTI (HR 1.32, 95%CI:1.14-1.53). Hospital admissions for culture-confirmed IPD decreased by 93% (HR 0.07, 95%CI:0.01-0.50) and no hospitalisations for IPD with vaccine-type pneumococci were observed in the VEC. Hospitalisations for meningitis and sepsis did not change. A decrease in hospital admissions for otitis media was observed, but did not coincide with PHiD-CV introduction., Conclusion: Following the introduction of PHiD-CV in Iceland, hospitalisations for pneumonia and culture confirmed IPD decreased. Admissions for other LRTIs and URTIs increased during this period., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Nasopharyngeal carriage (NPC) of Streptococcus pneumoniae is a precondition for pneumococcal disease and a source of transmission. This trial evaluated NPC of S. pneumoniae and other pathogens post-vaccination with the pneumococcal non-typeable Haemophilus influenzae (NTHi) protein D conjugate vaccine (PHiD-CV) in human immunodeficiency virus (HIV)-infected (HIV+), HIV-exposed-uninfected (HEU), and HIV-unexposed-uninfected (HUU) South African children., Methods: In this phase III, open, single-centre, controlled study (ClinicalTrials.gov: NCT00829010), 484 children were stratified by HIV status: 83 HIV+, 101 HEU, and 300 HUU. HIV+ and HEU children received a 3 + 1 PHiD-CV vaccination schedule: primary vaccination, age 6/10/14 weeks, and booster dose, age 9-10 months. HUU infants were randomised (1:1:1) to 3-dose priming and booster (HUU/3+1); 3-dose priming without booster (HUU/3+0); or 2-dose priming and booster (HUU/2+1). Bacterial NPC was assessed 8 times up to 24-27 months of age., Results: Overall pneumococcal carriage rates were similar across 3+1 groups irrespective of HIV status; trends towards higher carriage rates in the HIV+ than HEU and HUU/3+1 groups were observed at 24-27 months of age. In HUU children, carriage of any pneumococcal serotype was similar for the three different dosing schedules at all timepoints; carriage of vaccine-type pneumococci tended to be lower at 16-19 months and 24-27 months of age in children who had received a booster dose (HUU/2+1 and HUU/3+1 groups) than in the HUU/3+0 group. Carriage rates of NTHi, Staphylococcus aureus and Moraxella catarrhalis were comparable between all groups., Conclusions: HIV infection or exposure did not seem to alter the effect of PHiD-CV on pneumococcal NPC in children during their first 2 years of life. NPC prevalence of vaccine-type pneumococci following vaccination series tended to be lower in children who had received a booster dose in comparison to those who had not., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DB, JPY, JRG, LS, NF and SS are employees of the GSK group of companies and MM was an employee of the GSK group of companies. DB, JPY, JRG, LS, MM and SS own shares of the GSK group of companies. SAM’s institution received grants from the Bill & Melinda Gates Foundation, the GSK group of companies, Novartis and Minervax and personal consulting fees for advisory boards and/or speaker’s bureaus from the GSK group of companies, Medimmune, Pfizer and Sanofi Pasteur. All other authors declare no conflict of interest., (Copyright © 2020 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd.. All rights reserved.)

Background: Most of the available data on invasive pneumococcal disease in Latin America are derived from laboratory-based surveillance systems. There is a lack of epidemiological data on the disease severity and mortality from hospitalized patients with pneumococcal infection., Methods: In this hospital-based retrospective historical series of hospitalized children with laboratory-confirmed IPD, we evaluated changes in disease episodes, in-hospital fatality rates, and need for intensive care unit admission after the inclusion of PCV10 in the Brazilian vaccination schedule. Invasive pneumococcal strains isolated by culture were serotyped. Changes over time were assessed, and pre-vaccination (2005-2009) to post-vaccination (2011-2015) disease rates and serotypes were compared., Results: 260 patients with IPD and positive pneumococcal isolates were identified (198 during the pre-PCV10 period). When comparing both periods, hospitalizations were reduced from 20 cases to 5 cases per 10,000 pediatric admissions (p < 0.0001). Likewise, fatalities reduced from 6.6 to 2.0 cases per 10,000 pediatric admissions (p < 0.0001). Pneumonia was the most frequent clinical diagnosis (58%) - of which 49.6% had pleural effusion - followed by meningitis (22%) and bacteremia (15.9%). Overall 30% of cases were sent to ICU, with no percentual changes after PCV10. Additional PCV13 serotypes increased from 7% before vaccine introduction to 21% after PCV10 use. Similarly, serotypes not included in PCV13 increased from 11% to 29%., Conclusions: There was a significant reduction in the hospitalizations rates, ICU admissions, and fatalities due to IPD after PCV10 introduction in Brazil. Cases due to PCV10 serotypes were reduced, while infections rates caused by non-PCV10 serotypes increased., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Streptococcus pneumoniae is still one of the major causes of morbidity and mortality worldwide. In Japan, pneumococcal conjugate vaccine (PCV)7 and PCV13 were licensed in 2010 and 2013, respectively. We conducted a nationwide paediatric invasive pneumococcal disease (IPD) and non-IPD surveillance study in Japan between 2015 and 2017. We collected 498 IPD isolates and 231 non-IPD isolates from a total of 187 medical institutions in Japan. We performed serotyping, antimicrobial susceptibility testing and multi-locus sequencing typing (MLST) for the collected isolates. Among the 498 IPD isolates, the most prevalent serotype was 24F, followed by 12F, 15A and 15B/C. However, 12F increased and 24F significantly decreased during the study period (p < 0.001), resulting in 12F becoming the most prevalent serotype in 2017. Among the IPD isolates, the PCV7 and PCV13 coverage rates were 0.8% and 9.2%, respectively. The most prevalent serotype among the non-IPD isolates was 15A, followed by 35B, 15B/C and 19A. The overall resistance rates to penicillin (PG), cefotaxime (CTX), meropenem (MEM), erythromycin (EM) and levofloxacin (LFX) were 40.5%, 12.2%, 19.4%, 91.8% and 0.5%, respectively. PG, CTX and MEM resistance rates were significantly higher in non-IPD isolates than in IPD isolates (p < 0.001). Serotype 15A-CC63 and serotype 35B-CC558 tended to be multi-drug resistant. In conclusion, the PCV13 coverage rate was significantly lower than that in a previous surveillance study in Japan between 2012 and 2014, and IPD cases attributable to serotype 19A also decreased. We should note the rapid increase in the prevalence of serotype 12F in IPD cases and the spread of the multi-drug resistant serotype 15A-CC63 and 35B-CC558 lineages., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Takao Fujisawa was supported by a research grant through his institution from Pfizer Inc. Yutaka Ito and Satoshi Nakano were supported by research funding from Pfizer for the surveillance study. Satoshi Nakano was supported by Japan Society for the Promotion of Science (19K16637)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The findings and conclusions in this report are those of the authors and do not necessarily represent the official positon of the Centers for Disease Control and Prevention., Background: Continued indirect effects provided by the childhood pneumococcal conjugate vaccine (13-valent pneumococcal conjugate vaccine [PCV13]) program in the United States have decreased disease in the adult population, reducing the potential direct effects of vaccinating older adults., Objective: We examined the incremental cost-effectiveness of continuing to recommend PCV13 in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) at age 65 compared to a strategy that only included a recommendation for PPSV23 at age 65., Methods: We used a probabilistic model following a cohort of 65 year olds in 2019. We used vaccination coverage and disease incidence estimates for healthy adults and adults with chronic medical conditions. We incorporated continued indirect effects from the childhood PCV13 program on adult disease incidence., Results: In the base case scenario, continuing to recommend PCV13 at age 65 cost $561,682 per quality-adjusted life year (QALY) gained. In a scenario where PPSV23 provided modest protection against non-invasive pneumococcal pneumonia, costs increased to $2.3 million per QALY. These estimates are larger than our prior estimates for cost-effectiveness of this recommendation in the context of predicted indirect effects due to new data indicating PCV13 provided limited impact on serotype 3, the major cause of the remaining PCV13-type disease. Under our prior assumptions about PCV13 effectiveness against serotype 3 disease, the cost of continuing the recommendation is $207,607 per QALY., Conclusion: Indirect effects from the childhood PCV13 program have dramatically increased the cost per QALY of continuing to recommend PCV13 at age 65 after only a few years., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier Ltd.)

Pathogenic bacteria, such as Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Moraxella catarrhalis, are important vaccine targets. The 10-valent pneumococcal conjugate vaccine (PCV10) acts on 10 differents S. pneumoniae serovars. However, this vaccine could also act on other bacteria genera, leading to dysbiosis. Moreover, the vaccination has also been associated with imbalances in the ratio between commensal and potentially pathogenic bacteria. Despite the wealth of studies assessing the influence of the microbiome on vaccine effects, how vaccination can influence the microbiome remains poorly understood. Herein, we assessed the effects of PCV10 on infant nasopharyngeal microbiome composition. Nasopharyngeal aspirates were collected from children with acute respiratory infection (ARI) aged 6-23 months. Two groups were composed of 48 vaccinated and 36 unvaccinated subjects. 16S ribosomal RNA sequencing was performed to assess bacterial composition and results were analyzed with QIIME. Similar bacterial compositions were observed in the unvaccinated and vaccinated samples. Principal component analysis also indicated a similar bacterial composition between the groups. In addition, bacterial diversity was not different between the vaccinated and unvaccinated samples. Accordingly, our results suggest that PCV10 vaccination promotes a specific response against its targets, thereby preserving the nosocomial microbiome. Although not statistically significant, Streptococcus and Haemophilus genera were increased in the vaccinated group, while Moraxella was decreased. Increases in Streptococcus may be associated with vaccine-target taxa replacement by non-pathogenic species. In sum, we observed that PCV10 vaccination acts by promoting a target-specific action against pathogenic bacteria and also induces commensal bacteria colonization without substantially changing the nasopharyngeal microbiome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Pediatric pneumococcal pneumonia complicated by parapneumonic pleural effusion/empyema (PPE/PE) remains a major concern despite general immunization with pneumococcal conjugate vaccines (PCVs)., Methods: In a nationwide pediatric hospital surveillance study in Germany we identified 584 children <18 years of age with bacteriologically confirmed PPE/PE from October 2010 to June 2018. Streptococcus pneumoniae was identified by culture and/or PCR of blood samples and/or pleural fluid and serotyped., Results: S. pneumoniae was identified in 256 of 584 (43.8%) children by culture (n = 122) and/or PCR (n = 207). The following pneumococcal serotypes were detected in 114 children: serotype 3 (42.1%), 1 (25.4%), 7F (12.3%), 19A (7.9%), other PCV13 serotypes (4.4%) and non-PCV13 serotypes (7.9%). Between October 2010 and June 2014 serotype 1 (38.1%) and serotype 3 (25.4%) were most prevalent, whereas between July 2014 and June 2018 serotype 3 (62.7%) and non-PCV13 serotypes (15.7%) were dominant. Compared to children with other pneumococcal serotypes, children with serotype 3 associated PPE/PE were younger (median 3.2 years [IQR 2.1-4.3 years] vs. median 5.6 years [IQR 3.8-8.2 years]; p < 0.001) and more frequently admitted to intensive care (43 [89.6%] vs. 48 [73.8%]; p = 0.04). Seventy-six of 114 (66.7%) children with pneumococcal PPE/PE had been vaccinated with pneumococcal vaccines. Thirty-nine of 76 (51.3%) had received a vaccine covering the serotype detected. Thirty of these 39 breakthrough cases were age-appropriately vaccinated with PCV13 and considered vaccine failures, including 26 children with serotype 3, three children with serotype 19A and one child with serotype 1., Conclusion: Following the introduction of PCV13 in general childhood vaccination we observed a strong emergence of serotype 3 associated PPE/PE in the German pediatric population, including a considerable number of younger children with serotype 3 vaccine breakthrough cases and failures. Future PCVs should not only cover newly emerging serotypes, but also include a more effective component against serotype 3., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: This study aimed to investigate whether systemic immunization with a 13-valent pneumococcal conjugate vaccine (PCV13) followed by intranasal (IN) immunization with phosphorylcholine (PC) can boost immune response against Streptococcus pneumoniae., Materials and Methods: Two weeks after the intraperitoneal (IP) injection of PCV13, mice were divided into two groups (mice requiring another IP injection of PCV13 and mice requiring PC-keyhole limpet hemocyanin IN immunization in combination with cholera toxin as a mucosal adjuvant) to compare the magnitude of systemic and mucosal immune responses against S. pneumoniae and PC., Results: Serum immunoglobulin (Ig) G antibody titer against the vaccine strains of S. pneumoniae was similar between the PCV13 systemic immunization group and PC IN immunization group, while the serum IgG antibody titer against PC was significantly higher in the PC IN immunization group. PC-specific IgA antibody titer in the nasal lavage and PC-specific IgA-producing cell number in the nasal mucosa were also significantly higher in the PC IN immunization group. Induction of PC-specific IgA in the PC IN immunization group enhanced the clearance of bacteria from the middle ear., Conclusion: Additional IN immunization with PC after PCV13 immunization, which is currently conducted under a periodic vaccination program, can produce a booster effect comparable to that achieved by additional systemic immunization as well as PC-specific mucosal immune response, thereby providing protection against S. pneumoniae serotypes not contained in PCV13., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Pneumococcal carriage is a prerequisite for pneumococcal disease. Little is known about whether social contact frequency and intensity are associated with pneumococcal carriage. In Fiji, indigenous iTaukei have higher prevalence of pneumococcal carriage compared with Fijians of Indian Descent (FID). We hypothesised that contact differences may contribute to ethnic differences in pneumococcal carriage prevalence and density., Methods: In 2015, young infants (5-8 weeks), toddlers (12-23 months), children (2-6 years), and caregivers from Suva and surrounding areas, participated in a cross-sectional survey (n = 2014), three years post pneumococcal conjugate vaccine introduction. Demographic and contact data, and nasopharyngeal swabs were collected. Pneumococci were detected, and quantified using quantitative real-time PCR, with molecular serotyping by microarray. Associations between ethnicity, contact, and pneumococcal carriage and density were estimated using multivariable generalised estimating equation regression models., Results: iTaukei participants had larger household sizes, higher pneumococcal carriage rates, more contacts, and more frequent contacts of longer duration, compared with FID. The odds of vaccine-type carriage increased by 28% (95% CI 8-53%) P < 0.01 in association with physical contact with 7-14 year old children. iTaukei ethnicity was associated with vaccine-type carriage (aOR) 1.73; 95% CI 1.06-2.82, P = 0.03) and non-vaccine type carriage (aOR 5.98; 95% CI 4.47-8.00, P < 0.01). Ethnicity and contact were not associated with pneumococcal density., Conclusions: iTaukei had greater frequency and intensity of contact compared with FID. Physical contact was associated with pneumococcal carriage. Observed differences in pneumococcal nasopharyngeal carriage prevalence between iTaukei and FID were not explained by differences in social contact patterns by ethnicity., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Community-acquired pneumonia (CAP) is a common infection with significant morbidity and mortality. In January 2017, Poland introduced pneumococcal conjugate vaccine (PCV) into their national immunisation programme to protect children against invasive pneumococcal disease. This study was designed to investigate pneumonia-related hospitalisation rates and trends from 2009 to 2016 prior to the introduction of nationally funded PCV vaccination., Methods: Using national public statistic data available from the National Institute of Public Health - National Institute of Hygiene, annual hospitalisation rates for pneumonia were analysed, categorised by aetiology and age (<2, 2-3, 4-5, 6-19, 20-59, 60+ years). Trends over time were assessed, as well as in-hospital mortality., Results: The overall hospitalisation rate due to pneumonia varied between 325.9 and 372.2/100,000 population. Higher rates of hospitalisation were seen in older adults and children ≤5 years. Trends were observed when analysing hospitalisations by pneumonia aetiology within age groups: between 2009 and 2016, Streptococcus pneumoniae hospitalisations significantly increased for children aged <2, 2-3, and 4-5 years, from 5.3 to 12.4, 5.2 to 8.2, and 1.9 to 4.6/100,000 population respectively. Whereas hospitalisations due to Haemophilus influenzae pneumonia decreased significantly from 7.8 to 1.8 and 4.8 to 1.9/100,000 children aged <2 and 2-3 years respectively. The numbers of in-hospital deaths increased from 5578 in 2009 to 8149 in 2016, with >85% of deaths in the 60+ age group., Conclusions: This is the first national study of pneumonia hospitalisations in Poland, providing the baseline data from which to investigate the impact of the change in vaccination policy on pneumonia hospitalisations in Poland., (Copyright © 2019 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd.. All rights reserved.)

Background: A more affordable pneumococcal conjugate vaccine (PCV) that provides comparable protection to current PCVs is needed to ensure sustainable access in resource-limited settings. Serum Institute of India Pvt. Ltd.'s PCV candidate (SIIPL-PCV) has the potential to meet this need as manufacturing efficiency has been optimized and the vaccine targets the most prevalent disease-causing serotypes in Africa and Asia. We report SIIPL-PCV's safety, tolerability, and immunogenicity in adults, toddlers, and infants in The Gambia., Methods: This phase 1/2, randomized, double-blind trial sequentially enrolled 34 PCV-naive adults (18-40 years old), 112 PCV (Prevenar 13® [PCV13])-primed toddlers (12-15 months old), and 200 PCV-naive infants (6-8 weeks old), who were randomized (1:1) to receive SIIPL-PCV or a licensed comparator vaccine. Infants received three-doses of SIIPL-PCV or PCV13 at 6, 10, and 14 weeks of age co-administered with routine Expanded Program on Immunization (EPI) vaccines. Reactogenicity was solicited through seven-days post-vaccination; unsolicited adverse events (AEs) were assessed throughout the study. The safety and immunogenicity of a matching booster at 10-14 months of age were evaluated in a subset of 96 infants. Immune responses were evaluated post-primary and pre- and post-booster vaccinations., Results: Reactogenicity was primarily mild-to-moderate in severity. In infants, the most common solicited reactions were injection-site tenderness and fever, with no meaningful treatment-group differences. There were no serious or severe vaccine-related AEs and no meaningful trends in SAEs, vaccine-related AEs, or overall AEs. Infant post-primary seroresponse rates (IgG level ≥ 0.35 µg/mL) were ≥89% for all serotypes except 6A (79%) in the SIIPL-PCV group. IgG GMCs were >1 µg/mL for all serotypes in both SIIPL-PCV and PCV13 groups. Post-booster GMCs were comparable between groups., Conclusion: SIIPL-PCV was well-tolerated, had an acceptable safety profile, and was immunogenic for all vaccine serotypes. Results support the evaluation of SIIPL-PCV in a phase 3 non-inferiority trial. Clinicaltrials.gov: NCT02308540., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Vaccination coverage among older adults is low in the United States. A recommendation from a provider is a strong predictor of vaccine receipt. Using Medicare Fee-For-Service data (2015-2017) this study characterized providers by the number of influenza and pneumococcal vaccines administered in physician offices, age, gender, and professional specialty to determine the volume of vaccines provided by individual providers and characteristics of these providers. Half of all vaccinations were provided by 10% of providers. The mean age of 224,483 and 165,710 unique influenza and pneumococcal providers respectively was 49 years (SD: 12 years) with males and females equally distributed. The highest vaccinating quartile of providers tended to be older, more likely male and more likely general physicians. Those who administered a high volume of one vaccine were likely to administer a high volume of the other. Providers administering vaccines in office-based settings can do more to increase vaccination coverage rates., (Published by Elsevier Ltd.)

Background: Native American populations experience a substantial burden of pneumococcal disease despite use of highly effective pneumococcal conjugate vaccines (PCVs). Protein-based pneumococcal vaccines may extend protection beyond the serotype-specific protection elicited by PCVs., Methods: In this phase IIb, double-blind, controlled trial, 6-12 weeks-old Native American infants randomized 1:1, received either a protein-based pneumococcal vaccine (dPly/PhtD) containing pneumolysin toxoid (dPly, 10 µg) and pneumococcal histidine triad protein D (PhtD, 10 µg) or placebo, administered along with 13-valent PCV (PCV13) at ages 2, 4, 6 and 12-15 months. Other pediatric vaccines were given per the routine immunization schedule. We assessed vaccine efficacy (VE) against acute otitis media (AOM) and acute lower respiratory tract infection (ALRI) endpoints. Immunogenicity, reactogenicity and unsolicited adverse events were assessed in a sub-cohort and serious adverse events were assessed in all children., Results: 1803 infants were randomized (900 dPly/PhtD; 903 Control). VE against all episodes of American Academy of Pediatrics (AAP)-defined AOM was 3.8% (95% confidence interval: -11.4, 16.9). Point estimates of VE against other AOM outcomes ranged between 2.9% (-9.5, 14.0) and 5.2% (-8.0, 16.8). Point estimates of VE against ALRI outcomes ranged between -4.4% (-39.2, 21.8) and 2.0% (-18.3, 18.8). Point estimates of VE tended to be higher against first than all episodes but the confidence intervals included zero. dPly/PhtD vaccine was immunogenic and had an acceptable reactogenicity and safety profile after primary and booster vaccination in Native American infants., Conclusions: The dPly/PhtD vaccine was immunogenic and well tolerated, however, incremental efficacy in preventing AAP-AOM over PCV13 was not demonstrated., Clinical Trials Registration: NCT01545375 (www.clinicaltrials.gov)., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Invasive pneumococcal disease (IPD) is a significant cause of morbidity and mortality among children worldwide. In April 2013, Mozambique introduced 10-valent PCV (PCV10) into the National Expanded Program on immunization using a three-dose schedule at 2, 3, and 4 months of age. We aimed to evaluate the invasive disease potential of pneumococcal serotypes among children in our region before and after PCV10 introduction., Methods: We used data from ongoing population-based surveillance for IPD and cross-sectional pneumococcal carriage surveys among children aged <5 years in Manhiҫa, Mozambique. To determine the invasive disease potential for each serotype pre- and post-PCV10 introduction, odds ratios (OR) and 95% confidence intervals (95% CI) were calculated comparing serotype-specific prevalence in IPD and in carriage. For each serotype, OR and 95% CI > 1 indicated high invasive disease potential and OR and 95% CI < 1 indicated low invasive disease potential., Results: In the pre-PCV10 period, 524 pneumococcal isolates were obtained from 411 colonized children and IPD cases were detected in 40 children. In the post-PCV10 period, 540 pneumococcal isolates were obtained from 507 colonized children and IPD cases were detected in 30 children. The most prevalent serotypes causing IPD pre-PCV10 were 6A (17.5%), 6B (15.0%), 14 (12.5%), 23F (10.0%) and 19F (7.5%), and post-PCV10 were 6A (36.7%), 13 (10%), 1 (10.0%), 6B (6.7%) and 19A (6.7%). Serotypes associated with high invasive disease potential pre-PCV10 included 1 (OR:22.3 [95% CI 2.0; 251.2]), 6B (OR:3.1 [95% CI 1.2; 8.1]), 14 (OR: 3.4 [95% CI 1.2; 9.8]) and post-PCV10 included serotype 6A (OR:6.1[95% CI 2.7; 13.5])., Conclusion: The number of serotypes with high invasive disease potential decreased after PCV10 introduction. Serotype 6A, which is not included in PCV10, was the most common cause of IPD throughout the study and showed a high invasive potential in the post-PCV10 period., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Immunodeficient patients are recommended to receive pneumococcal vaccination. However, there is limited evidence showing effectiveness of the polysaccharide vaccine. Polysaccharide vaccination has shown an association with cardiovascular event risk reduction. We assessed the efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in relation to the risk of hospitalization and death due to pneumonia and acute cardiac events., Methods: The medical records of all dialysis patients attending our 8 study centers in 2010 were studied, and we selected 1038 consecutive patients. One-to-one propensity score matching was used to correct for potential selection bias in a PPSV23-vaccinated group versus a non-vaccinated group, and a total of 510 patients were identified for outcome analysis. Time to first admission, or deaths due to all-cause pneumonia or cardiac events until 2015 were compared between both groups., Results: The all-cause death rate was significantly decreased in the PPSV23-vaccinated group, (hazard ratio [HR] 0.62, 95% confidence interval [CI]; 0.46-0.83, P = 0.002). All-cause death was considered to be a competing risk for the other outcomes. Further outcomes were evaluated by competing risk analysis adjusting for mortality. There was no statistically significant difference in the hospitalization rate for pneumonia; however, the hospitalization rate due to cardiac events was significantly lower in the PPSV23-vaccinated group than in the non-vaccinated group (HR 0.44, 95% CI; 0.20-0.96, P = 0.040). There was no statistically significant difference in the death rate due to pneumonia; however, the rate of cardiac death was significantly lower in the PPSV23-vaccinated group than in the non-vaccinated group (HR 0.36, 95% CI; 0.18-0.71, P = 0.003)., Conclusions: The PPSV23 vaccination is associated with a good prognosis and a low-risk of cardiac events in dialysis patients; however, there was no evidence indicating enhanced protective efficacy against pneumonia, suggesting the PPSV23 vaccination might improve the prognosis by directly preventing cardiovascular events., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Serotype 3 pneumococcal disease has not substantially declined at the population level after the routine introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into pediatric immunization programs across the globe. This epidemiological finding has generated debate regarding the effectiveness of PCV13 against serotype 3 disease. Evaluating PCV13 effectiveness against serotype 3 is especially critical in adults, where serotype 3 makes up an important amount of remaining pneumococcal disease., Methods: We performed a systematic review of the published literature to assess the direct effectiveness of PCV13 against serotype 3 community-acquired pneumonia (CAP) among adults. We then estimated overall vaccine effectiveness (VE) using a pooled analysis of the individual-level, raw data., Results: Two published studies met inclusion criteria. One was a randomized controlled trial conducted in the Netherlands and published in 2014. The other was a recently-published case-control study conducted in Louisville, Kentucky that used a test-negative design (TND). We also identified a third TND study conducted in Argentina that was recently presented as a conference abstract but is not yet published. All three studies were conducted in adults aged ≥65 years. PCV13 VE against serotype 3 hospitalized CAP was 52.5% (95%CI: 6.2-75.9%) from the pooled analysis of individual-level data from all three studies. Results were similar if the unpublished estimate was excluded (serotype 3 VE = 53.6% [95%CI: 6.7-76.9%]). No heterogeneity was observed., Conclusions: Currently-available evidence, although limited to three studies, suggests that PCV13 provides direct protection against serotype 3 hospitalized CAP in adults aged ≥65 years., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recently, the Dutch Health Council advised on elderly pneumococcal vaccination favouring the conventional polysaccharide vaccine over the novel conjugated vaccine. This advice was strongly inspired by a cost-effectiveness analysis considered to show favourable outcomes for the polysaccharide but not for the conjugated vaccine. We argue that using the same data and methods as presented by the Health Council, a different perspective on the results leads to a conclusion that not only the polysaccharide but also the conjugated pneumococcal vaccine is cost-effective. Our alternative perspective concerns the use of realistic vaccine prices, and applying an adequate time horizon for cost-effectiveness modelling. Notably, for one-off vaccination of 65-years old elderly, in all investigated analyses, also the conjugated vaccine seems cost-effective; i.e. well below the threshold of €20,000 per quality-adjusted life year, reflecting the most stringent threshold used for vaccines in the Netherlands., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pneumococcal disease is a leading cause of childhood mortality, globally. The pneumococcal conjugate vaccine (PCV) has been introduced to many countries worldwide. However there are few studies evaluating PCV impacts in low- and middle-income countries (LMIC) because measuring the impact of PCV on pneumococcal disease in LMICs is challenging. We review the role of pneumococcal carriage studies for the evaluation of PCVs in LMICs and discuss optimal methods for conducting these studies. Fifteen carriage studies from 13 LMICs quantified the effects of PCV on carriage, and identified replacement carriage serotypes in the post-PCV era. Ten studies reported on the indirect effects of PCV on carriage. Results can be used to inform cost-effectiveness evaluations, guide policy decisions on dosing and product, and monitor equity in program implementation. Critically, we highlight gaps in our understanding of serotype replacement disease in LMICs and identify priorities for research to address this gap., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: We conducted a post-hoc analysis of a double blind, randomized, placebo-controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) among adults aged 65 years or older to assess public health impact., Methods: For all outcomes, we included all randomized subjects, using a modified intention-to-treat (mITT) approach to determine vaccine efficacy (VE), vaccine preventable disease incidence (VPDI) defined as control minus vaccinated group incidence, and numbers needed to vaccinate (NNV) (based on a five-year duration of protection)., Results: Results are reported for, in order, clinical, adjudicated (clinical plus radiologic infiltrate determined by committee), pneumococcal, and vaccine-type pneumococcal (VT-Sp) community-acquired pneumonia; invasive pneumococcal disease (IPD) and VT-IPD. VEs (95% CI) for all hospital episodes were 8.1% (-0.6%, 16.1%), 6.7% (-4.1%, 16.3%), 22.2% (2.0%, 38.3%), 37.5% (14.3%, 54.5%), 49.3% (23.2%, 66.5%), and 75.8% (47.6%, 88.8%). VPDIs per 100,000 person-years of observation (PYOs) were 72, 37, 25, 25, 20, and 15 with NNVs of 277, 535, 816, 798, 1016, and 1342. For clinical CAP, PCV13 was associated with a reduction of 909 (-115, 2013) hospital days per 100,000 PYOs translating to a reduction over 5 years of one hospital day for every 22 people vaccinated. When comparing at-risk persons (defined by self-report of diabetes, chronic lung disease, or other underlying conditions) to not at-risk persons, VEs were similar or lower, but because baseline incidences were higher the VPDIs were approximately 2-10 times higher and NNVs 50-90% lower., Conclusion: A public health analysis of pneumonia and IPD outcomes in a randomized controlled trial found substantial burden reduction following adult PCV13 immunization implemented in a setting with an ongoing infant PCV7-PCV10 program. VPDIs were higher among at-risk adults., Funding: The original study and the current analysis were funded by Pfizer., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)