Factors affecting the antimicrobial changes during treatment for acute otitis media in Japan: A retrospective cohort study using classification and regression trees (CART) analysis.

OBJECTIVES: Factors that affect the change of first-line antimicrobial agents were investigated to further promote their appropriate use. METHODS: This descriptive study used an electronic medical records database. Total 16,353 of the 199,896 patients enrolled between 1996 and 2019 met the inclusion criteria and formed the overall pediatric acute otitis media (AOM) cohort. The factors leading to the change in first-line antimicrobial agents within 14 days were analyzed using classification and regression trees (CART) analysis. RESULTS: This antimicrobial treatment cohort, involved 4860 cases of AOM alone and 9567 cases of AOM with other diseases. The size of the medical facility based on number of beds and historical duration of patient registration impacted on antimicrobial changes. CONCLUSIONS: The current results show that hospital-wide or nation-wide antimicrobial stewardship promotion could be the most influencing factor for antimicrobial changes. Particularly in cases of AOM where other diseases coexist, a more accurate diagnosis and definition of treatment failure of first-line drug are suggested to be important while establishing future treatment strategies. The current study is important to promote appropriate antimicrobial use for AOM treatment.

The pneumococcal conjugate vaccine had a sustained effect on Swedish children 8 years after its introduction.

AIM: The pneumococcal conjugate vaccine, which covered seven serotypes of Streptococcus pneumoniae (PCV7), was introduced in Stockholm, Sweden, in 2007. It was replaced by a 13-valent vaccine (PCV13) in 2011. We previously reported a decreased incidence of pneumonia and sinusitis among young children 4 years after the introduction of the PCV7. This study followed the incidence of pneumonia, sinusitis, mastoiditis and meningitis for four more years. METHODS: We studied validated hospital registry data covering children up to 17 years of age, who were hospitalised in the Stockholm region from 2003 to 2016, when the child population peaked at 485 687. All 11 115 cases diagnosed with pneumonia, coded as bacterial pneumonia, sinusitis, mastoiditis, bacterial meningitis or empyema, were identified. The controls had viral pneumonia or pyelonephritis. RESULTS: The incidence rates for children under 2 years of age hospitalised for sinusitis, mastoiditis and meningitis decreased significantly by 61%-79% during the eight-year post-vaccination period. Hospitalisations for bacterial pneumonia decreased by 19%-25% in the same age group. These changes were probably due to both the vaccines and changes in diagnosis routines. CONCLUSION: The effect of vaccination on children under 2 years of age was sustained 8 years after the introduction of the pneumococcal conjugate vaccines.

Association of Pneumococcal Serotype With Susceptibility to Antimicrobial Drugs: A Systematic Review and Meta-analysis.

BACKGROUND: Pneumococcal serotypes differ in antimicrobial susceptibility. However, patterns and causes of this variation are not comprehensively understood. METHODS: We undertook a systematic review of epidemiologic studies of pneumococci isolated from carriage or invasive disease among children globally from 2000-2019. We evaluated associations of each serotype with nonsusceptibility to penicillin, macrolides, and trimethoprim/sulfamethoxazole. We evaluated differences in the prevalence of nonsusceptibility to major antibiotic classes across serotypes using random-effects meta-regression models and assessed changes in prevalence of nonsusceptibility after implementation of pneumococcal conjugate vaccines (PCVs). We also evaluated associations between biological characteristics of serotypes and their likelihood of nonsusceptibility to each drug. RESULTS: We included data from 129 studies representing 32 187 isolates across 52 countries. Within serotypes, the proportion of nonsusceptible isolates varied geographically and over time, in settings using and those not using PCVs. Factors predicting enhanced fitness of serotypes in colonization as well as enhanced pathogenicity were each associated with higher likelihood of nonsusceptibility to penicillin, macrolides, and trimethoprim/sulfamethoxazole. Increases in prevalence of nonsusceptibility following PCV implementation were evident among non-PCV serotypes, including 6A, 6C, 15A, 15B/C, 19A, and 35B; however, this pattern was not universally evident among non-PCV serotypes. Postvaccination increases in nonsusceptibility for serotypes 6A and 19A were attenuated in settings that implemented PCV13. CONCLUSIONS: In pneumococci, nonsusceptibility to penicillin, macrolides, and trimethoprim/sulfamethoxazole is associated with more frequent opportunities for antibiotic exposure during both prolonged carriage episodes and when serotypes cause disease. These findings suggest multiple pathways leading to resistance selection in pneumococci.

Invasive Pneumococcal Disease: Concerning Trends in Serotype 19A Notifications in New Zealand.

New Zealand (NZ) is one of few countries to shift from PCV13 to PCV10. The number of serotype 19A cases in young children and the proportions of isolates that are penicillin-resistant have been steadily increasing since. It is time for NZ to reconsider its choice of pneumococcal vaccine.

Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Medically Attended Lower Respiratory Tract Infection and Pneumonia Among Older Adults.

BACKGROUND: Among older adults, 13-valent pneumococcal conjugate vaccine (PCV13) has been found efficacious against nonbacteremic pneumonia associated with vaccine-serotype pneumococci. However, the burden of lower respiratory tract infection (LRTI) and pneumonia preventable by direct immunization of older adults continues to be debated. METHODS: We analyzed data from an open cohort of adults aged ≥65 years enrolled in Kaiser Permanente Southern California health plans from 2016 to 2019 who received PCV13 concordant with US Advisory Committee on Immunization Practices guidelines. We estimated PCV13 vaccine effectiveness (VE) via the adjusted hazard ratio for first LRTI and pneumonia episodes during each respiratory season, comparing PCV13-exposed and PCV13-unexposed time at risk for each participant using a self-matched inference framework. Analyses used Cox proportional hazards models, stratified by individual. RESULTS: Among 42 700 adults who met inclusion criteria, VE was 9.5% (95% confidence interval [CI], 2.2% to 16.3%) against all-cause medically attended LRTI and 8.8% (95% CI, -.2% to 17.0%) against all-cause medically attended pneumonia. In contrast, we did not identify evidence of protection against LRTI and pneumonia following receipt of the 23-valent pneumococcal polysaccharide vaccine. PCV13 prevented 0.7 (95% CI, .2 to 1.4) and 0.5 (95% CI, .0 to 1.0) cases of LRTI and pneumonia, respectively, per 100 vaccinated persons annually; over 5 years, 1 case of LRTI and 1 case of pneumonia were prevented for every 27 and 42 individuals vaccinated, respectively. CONCLUSIONS: PCV13 vaccination among older adults substantially reduced incidence of medically attended respiratory illness. Direct immunization of older adults is an effective strategy to combat residual disease burden associated with PCV13-type pneumococci.

The Burden of Invasive Bacterial Disease and the Impact of 10-Valent Pneumococcal Conjugate Vaccine in Children <5 years hospitalized for Meningitis in Lusaka, Zambia, 2010-2019.

BACKGROUND: Despite the availability of vaccines, invasive bacterial diseases remain a public health concern and cause childhood morbidity and mortality. We investigated the characteristics of etiological agents causing bacterial meningitis in children <5 years in the years pre- (2010-2012) and post- (2014-2019) 10-valent pneumococcal conjugate vaccine (PCV10) introduction in Zambia. METHODS: Streptococcus pneumoniae (Spn), Haemophilus influenzae (Hi), and Neisseria meningitidis (Nm) from cerebrospinal fluid (CSF) were identified by microbiological culture and/or real-time polymerase chain reaction. RESULTS: During the surveillance period, a total of 3811 children were admitted with suspected meningitis, 16% (598 of 3811) of which were probable cases. Bacterial meningitis was confirmed in 37% (221 of 598) of the probable cases. Spn pneumoniae, Hi, and Nm accounted for 67% (148 of 221), 14% (31 of 221), and 19% (42 of 221) of confirmed cases, respectively. Thirty-six percent of pneumococcal meningitis was caused by 10-valent pneumococcal conjugate vaccine (PCV10) serotypes, 16% 13-valent pneumococcal conjugate vaccine and 39% by nonvaccine serotype (NVS). There was an association between the introduction of PCV10 vaccination and a decrease in both Spn meningitis and the proportion of PVC10 serotypes in the postvaccination period. Antimicrobial susceptibility of 47 Spn isolates revealed 34% (16 of 47) penicillin resistance. The 31 serotyped Hi accounted for 74% type b (Hib) and 10% type a (Hia). All 42 serogrouped Nm belonged to serogroup W. CONCLUSIONS: There was a decline in pneumococcal meningitis and proportion of PCV10 serotypes in the postvaccination period. However, the serotype replacement with non-PCV10 serotypes and penicillin resistance warrant continued surveillance to inform policy.

Triumph of Pneumococcal Conjugate Vaccines: Overcoming a Common Foe.

Pneumococcal conjugate vaccine (PCV) has reduced the burden of pneumococcal disease by the near elimination of vaccine serotypes from countries giving a booster dose at >9 months of life. Herd protection, induced by interruption of pneumococcal vaccine type transmission has protected children too young to be immunized, children and adults with underlying risk conditions for invasive pneumococcal disease, and the elderly. PCV has rolled out in most poor countries, but millions of children remain un-immunized especially in middle income countries because of cost constraints. These are being met by considering fewer doses to maintain herd protection, and support for more affordable vaccine from developing country manufacturers. While 3rd generation PCV's with potential inclusion of 20+ serotypes are close to market in adults, it will be their introduction into childhood immunization and herd protection that is most likely to maximize the public health benefits of these vaccines.

Carrier-Induced Hyporesponsiveness to Pneumococcal Conjugate Vaccines: Unraveling the Influence of Serotypes, Timing, and Previous Vaccine Dose.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) elicit lower immune response against serotypes carried before or at the time of vaccination (hyporesponsiveness) in infants. The limited studies conducted to date did not permit comprehensive insights regarding this phenomenon. This study, the largest ever conducted with both carriage and serologic endpoints, attempted to add insight on serotype-specific hyporesponsiveness in relation to the number of PCV doses administered before carriage acquisition. METHODS: In a double-blind randomized clinical trial (n = 1754 infants), 7-valent or 13-valent PCV was administered at ages 2, 4, 6, and 12 months. New acquisition was defined based on nasopharyngeal swabs at ages 2, 4, 6, 7, and 12 months. Serotype-specific immunoglobulin G levels were obtained 1 month after the infant series and 1 month after the toddler dose. RESULTS: A lower immune response after the infant series and the toddler dose was consistently observed for carriers of serotypes 6A, 6B, 18C, and 19F at predefined time points, with a similar trend observed in carriers of serotype 23F. In contrast, carriage of serotypes 9V, 14, and 19A did not generally affect immune responses. For some but not all serotypes, hyporesponsiveness was decreased with an increased number of vaccine doses received before acquisition. A complex interrelationship between carriage and immune response was observed between cross-reacting serotypes. CONCLUSIONS: Carrier-induced hyporesponsiveness to PCVs is common, differs among serotypes, and depends on timing of carriage acquisition and prior number of administered PCV doses. CLINICAL TRIALS REGISTRATION: NCT00508742.

Invasive Disease Potential of Pneumococcal Serotypes in Children After PCV13 Implementation.

We aimed to assess the invasive disease potential of non-PCV13 serotypes after the implementation of this vaccine. Most non-PCV13 serotypes had low invasive disease potential. Among serotypes with the highest invasive disease potential (12F, 24F, 38, 8, 33F, 22F, and 10A), all but 24F and 38 were included in PCV20.

Dose-specific Effectiveness of 7- and 13-Valent Pneumococcal Conjugate Vaccines Against Vaccine-serotype Streptococcus pneumoniae Colonization in Children.

BACKGROUND: Reduced-dose pneumococcal conjugate vaccine (PCV) schedules are under consideration in countries where children are recommended to receive 3 doses. Whereas PCV-derived protection against vaccine-serotype colonization is responsible for herd effects of vaccination, dose-specific PCV effectiveness against colonization endpoints is not known. We aimed to assess the performance of differing PCV schedules against vaccine-serotype colonization in children. METHODS: From 2009-2016, we monitored pneumococcal carriage in southern Israel, where children should receive PCV at ages 2 months, 4 months, and 12 months (2 primary [p] +1 booster [b] schedule). We analyzed nasopharyngeal swabs and vaccination histories from 5928 children aged 0-59 months without symptoms of diseases potentially attributable to pneumococci. Matching individuals on age, sex, ethnicity, visit timing, and recent antibiotic receipt, we measured schedule-specific 7-valent PCV (PCV7) and 13-valent PCV (PCV13) effectiveness against vaccine-serotype colonization in a modified case-control framework. We sampled from the distribution of all possible case-control match assignments for statistical analyses. RESULTS: Receiving 2 primary-series PCV13 doses conferred 53% (95% confidence interval [CI], 32-67%) protection against PCV13-serotype colonization at ages ≤12 months; 1 primary-series dose was not protective. A 2p+1b PCV13 series conferred 40% (95% CI, 4-67%) and 62% (95% CI, 33-83%) protection against PCV13-serotype colonization at ages 13-24 months and 25-59 months, respectively. Estimates suggested greater PCV13-conferred protection against PCV7-targeted serotypes than the 6 PCV13-only serotypes. As compared to children receiving 2p+1b PCV13 dosing, those receiving 1p+1b and 2p+0b schedules experienced 2.05-fold (95% CI, 1.12-5.00) and 3.33-fold (95% CI, 2.28-4.93) greater odds, respectively, of vaccine-serotype pneumococcal colonization at ages 13-24 months. CONCLUSIONS: Our results demonstrate real-world effectiveness of 2p+1b PCV dosing against vaccine-serotype colonization. Reduced-dose schedules may confer lower protection against vaccine-serotype carriage during and beyond the first year of life.

Introduction of multi-dose PCV 13 vaccine in Benin: from the decision to vaccinators experience.

BACKGROUND: In 2011, Benin introduced the 13-valent pneumococcal conjugated vaccine (PCV13), in a single-dose vial, into its Expanded Programme for Immunisation (EPI) with support from Gavi. In April 2018, with the support of the Agence de Médecine Préventive Afrique (AMP) and other technical and financial partners, the single-dose vial was transitioned to a four-dose vial. Here we describe the decision-making process and the experience of the vaccinators during the change. METHODS: We carried out semi-structured, individual interviews with 61 participants individuals involved in the EPI: 7 from central level, 5 from regional level, 7 from township level and 42 from district level. The interviews were recorded and transcribed, and the information categorised, using Nvivo software, and then analysed. RESULTS: The Inter-agency Coordination Committee (ICC), the Benin National Advisory Committee for Vaccines and Vaccination, (BNACVV) and the World Health Organisation (WHO) (i.e., the traditional governance structures involved in vaccination decisions) were not involved in the decision to change to the four-dose vial for PCV13. The decision was taken by the EPI, supported by Gavi. The vaccination errors observed in the first months following the change in presentation were due to the absence of guidelines for changes in vaccine presentation and the central-level actors' perception that it was 'only a change in the vial', and therefore that the communication and training for a new vaccine were not required since the vaccine itself and its administration mode were unchanged. CONCLUSIONS: It is important that the other countries eligible for Gavi support that are about to change to the multi-dose vial PCV13 presentation learn from Benin's experience. The main lessons learned are that changes in the presentation of an established vaccine should follow the same process as the introduction of a new vaccine, and that all stakeholders involved in vaccines and vaccination should participate in the decision-making process and implementation.

[Expert consensus on immunoprophylaxis of pneumococcal disease (2020 version)].

Pneumococcal disease is a serious global public health problem and a leading cause of morbidity and mortality of children and adults in China. Antibiotics are commonly used to treat pneumococcal disease. However, antibiotic resistance to Streptococcus pneumoniae has become a severe problem around the world due to widespread antibiotic use. Immunoprophylaxis of pneumococcal disease with pneumococcal vaccines is therefore of great importance. In this article, we review the etiology, clinical presentation, epidemiology, and disease burden of pneumococcal disease and the vaccinology of pneumococcal vaccines. Our review is based on the Expert Consensus on Immunoprophylaxis of Pneumococcal Disease (2017 version), the Pneumococcal Vaccines WHO Position Paper (2019), and recent national and international scientific advances. This consensus article aims to provide public health and vaccination staff with appropriate evidence for pneumococcal vaccine use and to improve professional capacity for pneumococcal disease prevention and control.

Incorporating economies of scale in the cost estimation in economic evaluation of PCV and HPV vaccination programmes in the Philippines: a game changer?

BACKGROUND: Many economic evaluations ignore economies of scale in their cost estimation, which means that cost parameters are assumed to have a linear relationship with the level of production. Economies of scale is the situation when the average total cost of producing a product decreases with increasing volume caused by reducing the variable costs due to more efficient operation. This study investigates the significance of applying the economies of scale concept: the saving in costs gained by an increased level of production in economic evaluation of pneumococcal conjugate vaccines (PCV) and human papillomavirus (HPV) vaccinations. METHODS: The fixed and variable costs of providing partial (20% coverage) and universal (100% coverage) vaccination programs in the Philippines were estimated using various methods, including costs of conducting questionnaire survey, focus-group discussion, and analysis of secondary data. Costing parameters were utilised as inputs for the two economic evaluation models for PCV and HPV. Incremental cost-effectiveness ratios (ICERs) and 5-year budget impacts with and without applying economies of scale to the costing parameters for partial and universal coverage were compared in order to determine the effect of these different costing approaches. RESULTS: The program costs of the partial coverage for the two immunisation programs were not very different when applying and not applying the economies of scale concept. Nevertheless, the program costs for universal coverage were 0.26 and 0.32 times lower when applying economies of scale compared to not applying economies of scale for the pneumococcal and human papillomavirus vaccinations, respectively. ICERs varied by up to 98% for pneumococcal vaccinations, whereas the change in ICERs in the human papillomavirus vaccination depended on both the costs of cervical cancer screening and the vaccination program. This results in a significant difference in the 5-year budget impact, accounting for 30 and 40% of reduction in the 5-year budget impact for the pneumococcal and human papillomavirus vaccination programs. CONCLUSIONS: This study demonstrated the feasibility and importance of applying economies of scale in the cost estimation in economic evaluation, which would lead to different conclusions in terms of value for money regarding the interventions, particularly with population-wide interventions such as vaccination programs. The economies of scale approach to costing is recommended for the creation of methodological guidelines for conducting economic evaluations.

A pneumococcal conjugate vaccination programme reduced clinically suspected invasive disease in unvaccinated children.

AIM: The 10-valent pneumococcal conjugate vaccine was introduced to the Finnish national vaccination programme for children born since June 2010. We evaluated the changes in the rates of clinically suspected invasive pneumococcal disease (IPD) in unvaccinated children to estimate the indirect herd protection impact of the programme. METHODS: The target cohort for this ecological before and after comparison were unvaccinated children born from January 2008 to May 2010 and ineligible for the vaccination programme, who were followed up from 2011 to 2014. The reference cohort was age and season-matched children born in January 2003 to 2005 and followed up from 2006 to 2009. National data on hospital discharge codes compatible with IPD or unspecified sepsis were collected. RESULTS: We compared the follow-up periods of 2007-2009 in the reference cohort and 2012-2014 in the target cohort. The incidence of non-laboratory-confirmed IPD in unvaccinated children fell by 68%, from 47 to 15/100 000 person-years. When unspecified sepsis was added, the decrease was 39%, from 171 to 104/100 000 person-years. Laboratory confirmed IPD fell by 44%, from 15 to 8/100 000 person-years. CONCLUSION: The pneumococcal vaccination programme provided herd protection against clinically suspected IPD. The absolute reduction was almost 10-times higher than for just laboratory-confirmed disease.

A case report of parapneumonic pleural effusion caused by Streptococcus pneumoniae serotype 19A in a child immunized with 13-valent conjugate pneumococcal vaccine.

BACKGROUND: Simple parapneumonic effusion is a pleural effusion associated with lung infection (i.e., pneumonia). Streptococcus pneumoniae remains the most common pathogen causing parapneumonic effusions. In Morocco, the pneumococcal conjugate vaccine 13-valent (PCV13) was introduced in the national immunization program in October 2010 in 2 + 1 schedule for prevention of pneumococcal disease, and replaced by the PCV10 in July 2012 in the same schedule. We report a case of parapneumonic pleural effusions caused by S. pneumoniae serotype 19A in a child immunized with 3 doses of PCV13. CASE PRESENTATION: This is a 2.5 years old previously healthy Moroccan female, fully vaccinated by PCV13 and immunocompetent, admitted to a private medical clinic with a six months history of persistent asthma. On arrival (7 February 2015), she was febrile to 40.3 °C with a brutal flu syndrome, chills, dry cough and serous rhinitis, for which she received symptomatic treatment. A biological assessment was done that confirmed the clinical diagnosis of flu. Seven days after, she presented a progressive deterioration of its general condition and the onset of severe abdominal pain. She was hospitalized and a second biological assessment, computed tomography scans and chest radiography were done that confirmed a diagnosis of a pneumococcal parapneumonia with abscess of the left lower lobe with encysted empyema. Microbiological analysis of the pleural fluid showed a S. pneumoniae serotype 19A with susceptibility intermediate to penicillin. The patient was treated by antibiotics including amoxicillin, cefixime ceftriaxone and vancomycin. CONCLUSIONS: We reported a case of parapneumonic pleural effusions caused by a vaccine serotype pneumococcal 19A occurring in an immunocompetent child immunized with 3 doses of PCV13.

Measurement and valuation of health providers' time for the management of childhood pneumonia in rural Malawi: an empirical study.

BACKGROUND: Human resources are a major cost driver in childhood pneumonia case management. Introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in Malawi can lead to savings on staff time and salaries due to reductions in pneumonia cases requiring admission. Reliable estimates of human resource costs are vital for use in economic evaluations of PCV-13 introduction. METHODS: Twenty-eight severe and twenty-four very severe pneumonia inpatients under the age of five were tracked from admission to discharge by paediatric ward staff using self-administered timesheets at Mchinji District Hospital between June and August 2012. All activities performed and the time spent on each activity were recorded. A monetary value was assigned to the time by allocating a corresponding percentage of the health workers' salary. All costs are reported in 2012 US$. RESULTS: A total of 1,017 entries, grouped according to 22 different activity labels, were recorded during the observation period. On average, 99 min (standard deviation, SD = 46) were spent on each admission: 93 (SD = 38) for severe and 106 (SD = 55) for very severe cases. Approximately 40 % of activities involved monitoring and stabilization, including administering non-drug therapies such as oxygen. A further 35 % of the time was spent on injecting antibiotics. Nurses provided 60 % of the total time spent on pneumonia admissions, clinicians 25 % and support staff 15 %. Human resource costs were approximately US$ 2 per bed-day and, on average, US$ 29.5 per severe pneumonia admission and US$ 37.7 per very severe admission. CONCLUSIONS: Self-reporting was successfully used in this context to generate reliable estimates of human resource time and costs of childhood pneumonia treatment. Assuming vaccine efficacy of 41 % and 90 % coverage, PCV-13 introduction in Malawi can save over US$ 2 million per year in staff costs alone.

Introduction of the pneumococcal conjugate vaccine in humanitarian and fragile contexts: Perspectives from stakeholders in four African countries.

Childhood pneumonia causes a significant burden of preventable child morbidity and mortality in Chad, Guinea, Somalia/Somaliland, and South Sudan. Leaders from these countries have committed to reducing this burden and are preparing to introduce the pneumococcal conjugate vaccine (PCV) into their immunization programs. To support long-term sustainability for expected PCV introductions in settings afflicted by prolonged humanitarian crises this research explores national stakeholders' perspectives on contextual factors that may influence optimal vaccine implementation. This qualitative study used purposive sampling to identify and interview stakeholders involved in vaccine decision-making. Interview transcripts were analyzed through the framework method, an approach involving charting data into pre-populated matrices. Findings from interviews with 16 key informants from government, partner organizations, and international health agencies fit within the following four overarching themes: (1) population-level vulnerabilities to pneumonia, exacerbated by climatic risks and low levels of maternal education; (2) disease burden and the interest in enhancing surveillance to monitor vaccine impact and integrate disease control efforts; (3) policy processes, including formalizing vaccine decision-making; and (4) vaccine implementation preparation, including the conduct of robust communication campaigns, training, and cold chain upgrades. This research explores perspectives from leaders in these countries which are at pivotal moments in their journeys toward introducing PCV. Widespread commitment among leaders, in addition to financial support, will facilitate vaccine introduction. Further, fostering a shared understanding among partners about context-specific determinants of program success will help build tailored implementation strategies for each country.

PCV15, a pneumococcal conjugate vaccine, for the prevention of invasive pneumococcal disease in infants and children.

INTRODUCTION: Streptococcus pneumoniae is a causative agent of pneumonia and acute otitis media (AOM), as well as invasive diseases such as meningitis and bacteremia. PCV15 (V114) is a new 15-valent pneumococcal conjugate vaccine (PCV) approved for use in individuals ≥6 weeks of age for the prevention of pneumonia, AOM, and invasive pneumococcal disease. AREAS COVERED: This review summarizes the V114 Phase 3 development program leading to approval in infants and children, including pivotal studies, interchangeability and catch-up vaccination studies, and studies in at-risk populations. An integrated safety summary is presented in addition to immunogenicity and concomitant use of V114 with other routine pediatric vaccines. EXPERT OPINION: Across the development program, V114 demonstrated a safety profile that is comparable to PCV13 in infants and children. Immunogenicity of V114 is comparable to PCV13 for all shared serotypes except serotype 3, where V114 demonstrated superior immunogenicity. Higher immune responses were demonstrated for V114 serotypes 22F and 33F. Results of the ongoing study to evaluate V114 efficacy against vaccine-type pneumococcal AOM and anticipated real-world evidence studies will support assessment of vaccine effectiveness and impact, with an additional question of whether higher serotype 3 immunogenicity translates to better protection against serotype 3 pneumococcal disease.

Uptake of pneumococcal vaccines in older Australian adults before and after universal public funding of PCV13.

BACKGROUND: In 2020 Australia changed the funded universal older adult pneumococcal vaccination program from use of the 23-valent pneumococcal polysaccharide vaccine (PPV23) at age 65 to the 13-valent pneumococcal conjugate vaccine (PCV13) at age 70 years. We investigated uptake of both PCV13 and PPV23 in older adults before and after the program change. METHODS: We analysed a national dataset of records of patients attending general practices (GPs). We included regular attendees aged 65 or above in 2020. Cumulative uptake of PCV13 and monthly uptake of PPV23 was compared for the two periods before (January 2019 to June 2020) and after (July 2020 to May 2021) the program change on 1 July 2020, by age groups and presence of comorbid conditions. RESULTS: Our study included data from 192,508 patients (mean age in 2020: 75.1 years, 54.2 % female, 46.1 % with at least one comorbidity). Before July 2020, for all adults regardless of underlying comorbidities, the cumulative uptake of PCV13 was < 1 % but by May 2021, eleven months after the program changes, cumulative uptake of PCV13 had increased among those aged 70-79 years (without comorbidity: 16.3 %; with comorbidity: 21.1 %) and 80 + years (without comorbidity: 13.5 %; with comorbidity: 17.7 %), but not among those aged 65-69 years (without comorbidity: 1.3 %; with comorbidity: 3 %). Monthly uptake of PPV23 dropped following the program change across all age groups. CONCLUSIONS: Changes in uptake of PCV13 and PPV23 among those aged 70 + years were consistent with program changes. However, PCV13 uptake was still substantially lower in individuals aged 65-69 years overall and in those with comorbidities.