BACKGROUND: Although pneumococcal vaccine is recommended for everyone 65 years of age and older, only 58% of Canadians in this age group have been vaccinated, well below the Public Health Agency of Canada\'s target of 80%. To improve uptake, a stepped-wedge cluster randomized trial testing the effectiveness of a community pharmacist intervention was developed.
OBJECTIVE: This pre-specified sub-study aimed to uncover and quantify factors contributing to vaccine hesitancy by exploring the nature of patient-pharmacist conversations about pneumococcal vaccine.
METHODS: Beginning each month (April to August 2023), participating pharmacies were randomly selected to receive an education package designed to enhance pharmacists\' knowledge, skills, and abilities in promoting pneumococcal vaccination. Pharmacists provided usual care (control stage) until they received the educational package and transitioned to the intervention stage. Weekly scorecards tracked patient-pharmacist conversations about pneumococcal vaccination. Chi-squared tests compared time taken for each conversation and patient-reported reason(s) for refusal between control and intervention stages.
RESULTS: Thirteen pharmacies from across Alberta were included in the analysis, reporting 656 patient-pharmacist conversations (control stage n=271, intervention stage n=385). Time taken for pneumococcal vaccine conversations decreased after pharmacies received the education package (65% of conversations resulting in vaccination took <20 minutes in the control stage, compared to 88% in the intervention stage (p=0.004)). The most common patient-reported reason for refusal, needing more time to think about the vaccine, remained similar between stages (p=0.23). However, during the intervention stage, fewer patients refused vaccination due to lack of time to receive it today (p=0.016) and perceived lack of benefit (p=0.035), but more patients refused vaccination due to cost barriers (p=0.026).
CONCLUSIONS: The education provided in this study changed the reasons for refusing vaccines, suggesting the nature of patient-pharmacist conversations became more efficient and informed. Similar interventions could be adopted across Canada and the US to help combat vaccine hesitancy.

BACKGROUND: Pneumococcal diseases (PD) cause considerable morbidity and mortality in adults. V116 is an investigational 21-valent pneumococcal conjugate vaccine (PCV) specifically designed to protect adults from pneumococcal serotypes responsible for the majority of residual PD. This phase 3 study evaluated safety, tolerability, and immunogenicity of V116 in pneumococcal vaccine-experienced adults ≥50 years.
METHODS: A total of 717 adults were enrolled to receive a single dose of pneumococcal vaccine as follows: Cohort 1 (n=350) previously received PPSV23 and were randomized 2:1 to receive V116 or PCV15, respectively; Cohort 2 (n=261) previously received PCV13 and were randomized 2:1 to receive V116 or PPSV23, respectively; Cohort 3 (n=106) previously received PPSV23+PCV13, PCV13+PPSV23, PCV15+PPSV23, or PCV15 and all received open-label V116. Immunogenicity was evaluated 30 days postvaccination using opsonophagocytic activity (OPA) geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) for all V116 serotypes. Safety was evaluated as the proportion of participants with adverse events (AEs).
RESULTS: V116 was immunogenic across all 3 cohorts as assessed by serotype-specific OPA GMTs and IgG GMCs postvaccination for all 21 serotypes. V116 elicited comparable immune responses to serotypes shared with PCV15 (Cohort 1) or PPSV23 (Cohort 2), and higher immune responses to serotypes unique to V116. The proportions of participants with solicited AEs were generally comparable across cohorts.
CONCLUSIONS: V116 is well tolerated with a safety profile comparable to currently licensed pneumococcal vaccines and generates IgG and functional immune responses to all V116 serotypes, regardless of prior pneumococcal vaccine received.

BACKGROUND: Pneumococcal carriage in children has been extensively studied, but carriage in healthy adults and its relationship to invasive pneumococcal disease (IPD) is less understood.
METHODS: Nasal wash samples from adults without close contact with young children (Liverpool, UK), 2011-2019, were cultured, and culture-negative samples tested by PCR. Pneumococcal carriage in adults 18-44 years was compared with carriage among PCV-vaccinated children 13-48 months (nasopharyngeal swabs, Thames Valley, UK) and IPD data for England for the same ages for 2014-2019. Age-group specific serotype invasiveness was calculated and used with national IPD data to estimate carriage serotype distributions for adults aged 65+ years.
RESULTS: In total 98 isolates (97 carriers) were identified from 1,631 adults aged 18+ years (age and sex standardized carriage prevalence 6.4%), with only three identified solely by PCR. Despite different carriage and IPD serotype distributions between adults and children, serotype invasiveness was highly correlated (R=0.9). Serotypes 3, 37 and 8 represented a higher proportion of adult carriage than expected from direct low-level transmission from children to adults. The predicted carriage serotype distributions for 65+ years aligned more closely with the carriage serotype distribution for young adults than young children.
CONCLUSIONS: The nasal wash technique is highly sensitive; additional benefit of PCR is limited. Comparison of carriage serotype distributions suggests some serotypes may be circulating preferentially within these specific young adults. Our data suggest that for some serotypes carried by adults 65+ years, other adults may be an important reservoir for transmission. Age groups such as older children should also be considered.

BACKGROUND: Streptococcus pneumoniae (Spn) has been a leading cause of bacterial meningitis in children. The most recent estimation of the global burden of Spn meningitis indicates a positive trajectory in eliminating Spn through the implementation of pneumococcal conjugate vaccines. However, continuous monitoring and assessment of the disease burden are necessary due to the evidence of serotype replacement, antibiotic resistance, and the impact of the recent COVID-19 pandemic.
OBJECTIVE: The aim of this systematic review is to provide an updated and focused assessment of the global and regional burden of Spn meningitis in children, which can guide policies and strategies to reduce the disease burden.
METHODS: Population-based studies published from January 1, 2000, to January 1, 2022, were preliminarily searched from the electronic databases PubMed, Embase, Global Health (CABI), and CINAHL Plus without any language restrictions. Studies were included if they reported the incidence, prevalence, mortality, or case-fatality ratio (CFR) for Spn meningitis in children aged 0-4 years; meningitis was confirmed by cerebrospinal fluid culture; the study period was a minimum of 1 year; the number of reported cases was at least 10; and the study had no methodological ambiguities. The article screening process follows the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Characteristics including study period, setting, World Health Organization region, income level, vaccination information, and participant data (age, number of cases, deaths, sequelae, and risk factors) will be extracted from the included studies. Search results will be updated and incorporated into our review prior to finalizing the extraction of data. Generalized linear mixed models meta-analysis will be performed to estimate the pooled incidence and CFR. We will further assess the risk of bias and heterogeneity, and will perform subgroup and sensitivity analyses to provide a meaningful interpretation of the current burden and literature for pneumococcal meningitis.
RESULTS: Our preliminary search in December 2021 yielded 9295 articles. Out of 275 studies that were assessed with our eligibility criteria, 117 articles were included. Data extraction and analysis are expected to be complete by January 2025. We plan to publish the results from the full study, including an updated search in 2024, by March 2025.
CONCLUSIONS: Given that the major burden of Spn meningitis affects children under the age of 5 years, this systematic review will provide a thorough understanding of the global burden of Spn meningitis in this vulnerable population over a span of 2 decades. Insights into incidence trends, geospatial distribution, risk factors, and sequelae will be valuable for stakeholders, policy makers, and the academic community. This information will aid in the ongoing monitoring of the disease and in enhancing targeted vaccine programs to further mitigate the impact of the disease on children worldwide.
BACKGROUND: PROSPERO CRD42021293110; https://tinyurl.com/kc3j5k4m.
UNASSIGNED: DERR1-10.2196/50678.

In patients with cancer, tumor- and treatment-induced immunosuppression are responsible for a four-fold increase in morbidity and mortality caused by influenza and invasive Streptococcus pneumoniae infections compared to the general population. The main oncology societies strongly recommend vaccination in patients with cancer to prevent these infections. However, vaccine hesitancy is a main concern in this population. The aim of this study was to assess the feasibility of in-hospital vaccination for patients under anticancer treatment and their family members (FMs) against influenza and pneumococcal infections during the COVID-19 pandemic in order to increase vaccine coverage. This was a single-center, prospective, observational study conducted at the Department of Oncology of Luigi Sacco University Hospital (Milan, Italy) between October 2020 and April 2021. The main primary outcome was the incidence of influenza-like illness (ILI) and pneumococcal infections. The main secondary outcome was safety. A total of 341 subjects were enrolled, including 194 patients with cancer and 147 FMs. The incidence of ILI was higher among patients than among FMs (9% vs. 2.7%, OR 3.92, p = 0.02). Moreover, two subjects were diagnosed with pneumococcal pneumonia. The most frequent vaccine-related AEs were pain in the injection site (31%) and fatigue (8.7%). In conclusion, this hospital-based vaccination strategy was feasible during the COVID-19 pandemic, representing a potential model to maximize vaccine coverage during a public health emergency.

BACKGROUND: In 2023 in France, 15 valent- pneumococcal conjugate vaccines (PCV15) have been recommended as alternatives to PCV13 for children < 2 years. PCV20 has been recommended for at-risk adults but not yet for infants, while PCV21 targets older adults. We endeavored to estimate the potential benefit of new pneumococcal vaccines in preventing invasive pneumococcal infections by comparing serotype extension to PCV13.
METHODS: The National Reference Centre for Pneumococci distributed S. pneumoniae IPD serotypes from children and adults.
RESULTS: In 2022, for children under 24 months, PCV15 and PCV20 ensured 10 % and 36 % more coverage against IPD than PCV13. For adults, PCV15, PCV20, and PCV21 covered up to 3 %, 26 %, and 50 % more IPD cases than PCV13.
CONCLUSIONS: The new generation of pneumococcal vaccines could reduce the burden of invasive pneumococcal infections through serotype extension. Additional studies are needed in parallel to optimize their utilization and improve vaccine coverage in France.

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BACKGROUND: 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.
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.
CONCLUSIONS: 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.

BACKGROUND: The effectiveness of immunisation with pneumococcal conjugate vaccine (PCV) has been demonstrated in many countries. However, the global impact of PCV is limited by its cost, which has prevented its introduction in some countries. Reducing the cost of PCV programmes will facilitate further vaccine introductions and improve the sustainability of PCV in low-income countries when they transition from subsidised vaccine supply. We are conducting a large, population-level, cluster-randomised field trial (PVS) of an alternative reduced-dose schedule of PCV compared to the standard schedule. We are also conducting a nested sub-study at the individual level to investigate the immunogenicity of the two schedules and their effects on pneumococcal carriage acquisition (PVS-AcqImm).
METHODS: PVS-AcqImm is a prospective, cluster-randomised trial of an alternative schedule of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months compared to the standard of three primary doses scheduled at 6, 10, and 14 weeks of age. Sub-groups within the alternative schedule group receive yellow fever vaccine separately or co-administered with PCV at 9 months of age. The primary endpoints are (a) concentrations of vaccine-type anti-pneumococcal IgG at 18 months of age, (b) proportions with yellow fever neutralising antibody titre ≥ 1:8 4 weeks after separate or co-administration of PCV and yellow fever vaccines, and (c) rate of nasopharyngeal vaccine-type pneumococcal acquisition from 10-14 months of age. Participants and field staff are not masked to group allocation while measurement of the laboratory endpoints is masked. Approximately equal numbers of participants are resident in each of 28 randomly allocated geographic clusters (14 clusters in each group); 784 enrolled for acquisition measurements and 336 for immunogenicity measurements.
OBJECTIVE: This statistical analysis plan (SAP) describes the PVS-AcqImm cohort and follow-up criteria to be used in different analyses. The SAP defines the endpoints and describes how adherence to the interventions will be presented. We describe the approach to analyses and how we will account for the effect of clustering. Defining the SAP prior to the conduct of analysis will avoid bias in analyses that may arise from prior knowledge of trial findings.
BACKGROUND: ISRCTN, ISRCTN7282161328. Registered on 28 November 2019. https://www.isrctn.com/ISRCTN72821613 .
METHODS: MRCG SCC number 1670, LSHTM Ref 17683. Current protocol version: 6.0, 24 May 2021. Version: 1.0 (5 April 2023); SAP revisions-none.

BACKGROUND: The introduction of pneumococcal conjugate vaccines (PCV) has reduced carriage of vaccine-type (VT) pneumococci in many settings. We determined the impact of The Gambia\'s national PCV programme on carriage of VT pneumococci in the population.
METHODS: Seven-valent PCV (PCV7) was introduced in August 2009 without catch-up and with doses scheduled at 2, 3, 4 months of age; it was replaced by PCV13 in May 2011. We did cross-sectional carriage surveys in 2009, 2015, and 2017 in age-stratified, population-based samples. Nasopharyngeal specimens were collected and processed according to WHO guidelines. We calculated observed and adjusted prevalence ratios (PR) of VT carriage before and after PCV introduction.
RESULTS: We enrolled 2988, 3162, and 2709 participants in 2009, 2015, and 2017 respectively. The baseline (2009) prevalence of VT pneumococcal carriage among children aged 0-4 years was 42.6 %, which declined to 14.9 % and 17.5 % in 2015 and 2017 respectively (adjPR 0.32 [95 % CI 0.27, 0.38] and 0.38 [0.31, 0.46] respectively). VT prevalence among children aged 5-14 years was 16.6 %, 15.1 %, and 15.8 % in the three surveys (2017 vs 2009, adjPR 0.70 [0.58, 0.83]). VT prevalence among 15-44 year-olds was 6.4 %, 5.7 %, and 7.1 % in the three surveys (2017 vs 2009, adjPR 0.59 [0.46, 0.75]), while in those aged ≥ 45 years it was 4.5 %, 6.5 %, and 4.5 % respectively. Non-VT carriage increased in all age-groups. Prevalent residual serotypes were 34 and 15B (age 0-4 years), 3 and 34 (age 5-14 years), and 3 and 16F (age ≥ 15 years).
CONCLUSIONS: Introduction of PCV was associated with reduced VT pneumococcal carriage in young, and older children, although with substantial residual prevalence. Persisting VT, and non-VT, carriage indicate significant, persistent transmission of pneumococci in the population.