B cells in the pneumococcus-infected lung are heterogeneous and require CD4+ T cell help including CD40L to become resident memory B cells.

Recovery from respiratory pneumococcal infections generates lung-localized protection against heterotypic bacteria, mediated by resident memory lymphocytes. Optimal protection in mice requires re-exposure to pneumococcus within days of initial infection. Serial surface marker phenotyping of B cell populations in a model of pneumococcal heterotypic immunity revealed that bacterial re-exposure stimulates the immediate accumulation of dynamic and heterogeneous populations of B cells in the lung, and is essential for the establishment of lung resident memory B (BRM) cells. The B cells in the early wave were activated, proliferating locally, and associated with both CD4+ T cells and CXCL13. Antagonist- and antibody-mediated interventions were implemented during this early timeframe to demonstrate that lymphocyte recirculation, CD4+ cells, and CD40 ligand (CD40L) signaling were all needed for lung BRM cell establishment, whereas CXCL13 signaling was not. While most prominent as aggregates in the loose connective tissue of bronchovascular bundles, morphometry and live lung imaging analyses showed that lung BRM cells were equally numerous as single cells dispersed throughout the alveolar septae. We propose that CD40L signaling from antigen-stimulated CD4+ T cells in the infected lung is critical to establishment of local BRM cells, which subsequently protect the airways and parenchyma against future potential infections.

Streptococcus pneumoniae among the children of Aden, Yemen: a cross-sectional report of post-pneumococcal conjugate vaccine.

INTRODUCTION: Streptococcus pneumoniae cause a significant global health challenge. We aimed to determine nasopharyngeal carriage, serotypes distribution, and antimicrobial profile of pneumococci among the children of Aden. METHODOLOGY: A total of 385 children, aged 2-17 years, were included. Asymptomatic samples were randomly collected from children in selected schools and vaccination centers. Symptomatic samples were obtained from selected pediatric clinics. The nasopharyngeal swabs were tested for pneumococci using culture and real time polymerase chain reaction (RT-PCR). Serotyping was done with a pneumotest-latex kit and antimicrobial susceptibility was tested by disc diffusion and Epsilometer test. RESULTS: The total pneumococcal carriage was 44.4% and 57.1% by culture and RT-PCR, respectively. There was a statistically significant association between carriage rate and living in single room (OR = 7.9; p = 0.00001), sharing a sleeping space (OR = 15.1; p = 0.00001), and low monthly income (OR = 2.02; p = 0.007). The common serotypes were 19, 1, 4, 5, 2, and 23. The proportion of non-pneumococcal conjugate vaccine (non-PCV13) serotypes was 24%. Pneumococci were resistant to penicillin (96.5%), cefepime (15.8%), ceftriaxone (16.4%), and amoxicillin-clavulanate (0%). Erythromycin, azithromycin, and doxycycline had resistance rates of 48%, 31%, and 53.3%, respectively. CONCLUSIONS: A high pneumococcal carriage rate was observed in Yemeni children, particularly in low-income households and shared living conditions. There was significant penicillin resistance at meningitis breakpoint. Furthermore, non-PCV13 serotypes were gradually replacing PCV13 serotypes. The findings underscore the urgent need for enhanced surveillance and stewardship to improve vaccination and antibiotic policies in Yemen.

Posibilities for use of whole genome sequencing (WGS) for the analysis of Streptococcus pneumoniae isolates.

Streptococcus pneumoniae (pneumococcus) is a Gram-positive coccus causing both non-invasive and invasive infectious diseases. Pneumococcal diseases are vaccine preventable. Invasive pneumococcal diseases (IPD) meeting the international case definition are reported nationally and internationally and are subject to surveillance programmes in many countries, including the Czech Republic. An important part of IPD surveillance is the monitoring of causative serotypes and their frequency over time and in relation to ongoing vaccination programmes. In the world and in the Czech Republic, whole genome sequencing (WGS) is increasingly used for pneumococci, which allows for serotyping from sequencing data, precise analysis of their genetic relationships, and the study of genes present in their genome. Whole-genome sequencing enables the generation of reliable and internationally comparable data that can be easily shared. Sequencing data are analysed using bioinformatics tools that require knowledge in the field of natural sciences with an emphasis on genetics and expertise in bioinformatics. This publication presents some options for pneumococcal analysis, i.e., serotyping, multilocus sequence typing (MLST), ribosomal MLST (rMLST), core genome MLST (cgMLST), whole genome MLST (wgMLST), single nucleotide polymorphism (SNP) analysis, assignment to Global Pneumococcal Sequence Cluster (GPSC), and identification of virulence genes and antibiotic resistance genes. The WGS strategies and applications for Europe and WGS implementation in practice are presented. WGS analysis of pneumococci allows for improved IPD surveillance, thanks to molecular serotyping, more detailed typing, generation of internationally comparable data, and improved evaluation of the effectiveness of vaccination programmes.

The Effectiveness of 23-valent Pneumococcal Polysaccharide Vaccine on Elderly Colorectal Cancer Long-Term Survivors: A population-based exact-matched cohort study.

Colorectal cancer (CRC) long-term survivor is a rapid enlarging group. However, the effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPSV23) on this group is unknown. This nationwide population-based study in Taiwan was designed to examine the effect of PPSV23 on incidence rate ratio (IRR) of pneumonia hospitalization, cumulative incidence, and overall survival rate for these long-term CRC survivors. This cohort study was based on the Taiwan Cancer Registry and Taiwan National Health Insurance Research Database from 2000-2017. After individual exact matching to covariates with 1:1 ratio, there were a total of 1,355 vaccinated and 1,355 unvaccinated survivors. After adjusted by multivariate Poisson regression model, vaccinated group had a non-significantly lower pneumonia hospitalization risk than unvaccinated, with an adjusted IRR of 0.879 (p = .391). Besides, vaccinated group had both lower cumulative incidence rate and higher overall survival time than unvaccinated.

Unswitched memory B cell deficiency in children with sickle cell disease and response to pneumococcal polysaccharide vaccine.

Early mortality in sickle cell disease (SCD) is attributed to increased infections due to loss of splenic function. Marginal zone B cells are important for initial opsonization of pathogens and can be absent in spleen histopathology in SCD. The frequency of unswitched memory B cells (UMBC), the circulating correlate of marginal zone B cells, reflects the immunologic function of the spleen. We hypothesized that asplenia in SCD is associated with alterations in the peripheral blood lymphocyte population and explored whether UMBC deficiency was associated with a clinical phenotype. We analyzed B cell subsets and clinical history for 238 children with SCD and 63 controls. The median proportion of UMBCs was lower in children with SCD compared with controls (4.7% vs. 6.6%, p < .001). Naïve B cells were higher in SCD compared with controls (80.6 vs. 76.3%, respectively, p = .02). UMBC frequency declined by 3.4% per year increase in age in SCD (95% CI: 2%, 4.7%, p < .001), but not in controls. A majority of children in all cohorts had an IgM concentration in the normal range for age and there were no differences between groups (p = .13). Subjects developed titers adequate for long-term protection to fewer serotypes in the polysaccharide vaccine than controls (14.7 vs. 19.4, p < .001). In this cohort, bacteremia was rare and specific clinical complications were not associated with UMBC proportion. In summary, UMBC deficiency occurs in SCD and is associated with age. Future studies should investigate B cell subsets prospectively and identify the mechanism of B cell loss in the spleen.

Impaired upper respiratory tract barrier function during postnatal development predisposes to invasive pneumococcal disease.

Infants are highly susceptible to invasive respiratory and gastrointestinal infections. To elucidate the age-dependent mechanism(s) that drive bacterial spread from the mucosa, we developed an infant mouse model using the prevalent pediatric respiratory pathogen, Streptococcus pneumoniae (Spn). Despite similar upper respiratory tract (URT) colonization levels, the survival rate of Spn-infected infant mice was significantly decreased compared to adults and corresponded with Spn dissemination to the bloodstream. An increased rate of pneumococcal bacteremia in early life beyond the newborn period was attributed to increased bacterial translocation across the URT barrier. Bacterial dissemination in infant mice was independent of URT monocyte or neutrophil infiltration, phagocyte-derived ROS or RNS, inflammation mediated by toll-like receptor 2 or interleukin 1 receptor signaling, or the pore-forming toxin pneumolysin. Using molecular barcoding of Spn, we found that only a minority of bacterial clones in the nasopharynx disseminated to the blood in infant mice, indicating the absence of robust URT barrier breakdown. Rather, transcriptional profiling of the URT epithelium revealed a failure of infant mice to upregulate genes involved in the tight junction pathway. Expression of many such genes was also decreased in early life in humans. Infant mice also showed increased URT barrier permeability and delayed mucociliary clearance during the first two weeks of life, which corresponded with tighter attachment of bacteria to the respiratory epithelium. Together, these results demonstrate a window of vulnerability during postnatal development when altered mucosal barrier function facilitates bacterial dissemination.

Cost-effectiveness analysis of adult pneumococcal conjugate vaccines for pneumococcal disease in Japan.

BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is used in the Japanese National Immunization Program for older adults and adults with increased risk for pneumococcal disease, however, disease incidence and associated burden remain high. We evaluated the cost-effectiveness of pneumococcal conjugate vaccines (PCVs) for adults aged 65 years and high-risk adults aged 60-64 years in Japan. RESEARCH DESIGN AND METHODS: Using a Markov model, we evaluated lifetime costs using societal and healthcare payer perspectives and estimated quality-adjusted life-years (QALYs), and number of prevented cases and deaths caused by invasive pneumococcal disease (IPD) and non-IPD. The base case analysis used a societal perspective. RESULTS: In comparison with PPSV23, the 20-valent PCV (PCV20) prevented 127 IPD cases 10,813 non-IPD cases (inpatients: 2,461, outpatients: 8,352) and 226 deaths, and gained more QALYs (+0.0015 per person) with less cost (-JPY22,513 per person). All sensitivity and scenario analyses including a payer perspective analysis indicated that the incremental cost-effectiveness ratios (ICERs) were below the cost-effectiveness threshold value in Japan (JPY5 million/QALY). CONCLUSIONS: PCV20 is both cost saving and more effective than PPSV23 for adults aged 65 years and high-risk adults aged 60-64 years in Japan.

Lipidation of pneumococcal proteins enables activation of human antigen-presenting cells and initiation of an adaptive immune response.

Streptococcus pneumoniae remains a significant global threat, with existing vaccines having important limitations such as restricted serotype coverage and high manufacturing costs. Pneumococcal lipoproteins are emerging as promising vaccine candidates due to their surface exposure and conservation across various serotypes. While prior studies have explored their potential in mice, data in a human context and insights into the impact of the lipid moiety remain limited. In the present study, we examined the immunogenicity of two pneumococcal lipoproteins, DacB and MetQ, both in lipidated and non-lipidated versions, by stimulation of primary human immune cells. Immune responses were assessed by the expression of common surface markers for activation and maturation as well as cytokines released into the supernatant. Our findings indicate that in the case of MetQ lipidation was crucial for activation of human antigen-presenting cells such as dendritic cells and macrophages, while non-lipidated DacB demonstrated an intrinsic potential to induce an innate immune response. Nevertheless, immune responses to both proteins were enhanced by lipidation. Interestingly, following stimulation of dendritic cells with DacB, LipDacB and LipMetQ, cytokine levels of IL-6 and IL-23 were significantly increased, which are implicated in triggering potentially important Th17 cell responses. Furthermore, LipDacB and LipMetQ were able to induce proliferation of CD4+ T cells indicating their potential to induce an adaptive immune response. These findings contribute valuable insights into the immunogenic properties of pneumococcal lipoproteins, emphasizing their potential role in vaccine development against pneumococcal infections.

Immunogenicity and safety of a 14-valent pneumococcal polysaccharide conjugate vaccine (PNEUBEVAX 14™) administered to 6-8 weeks old healthy Indian Infants: A single blind, randomized, active-controlled, Phase-III study.

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.

Pneumococcal vaccination and primary care presentations for acute respiratory tract infection and antibiotic prescribing in older adults.

BACKGROUND: While the 23-valent pneumococcal polysaccharide vaccine (PPV23) has demonstrated its role in preventing severe pneumococcal disease, its impact on more non-specific conditions like acute respiratory tract infection (ARI) and lower respiratory tract infections (LRTI) remains unclear. We aimed to investigate the role of PPV23 in prevention of presentations for ARI and LRTI and related antibiotic prescriptions among older adults in primary care. METHODS: Using a nationwide general practice dataset, we followed a cohort of regularly attending patients aged ≥65 years from 1 January 2014 until 31 December 2018 for presentations for ARI, LRTI, and related antibiotic prescriptions. Associations between PPV23 receipt and each outcome were assessed using a multiple failures survival model to estimate hazard ratios (HR) adjusted for age, sex, socioeconomic status, and various health measures. RESULTS: A cohort of 75,264 patients aged ≥65 years (mean 75.4, 56% female) in 2014 was followed. The incidence of presentations for ARI, ARI-related antibiotic prescription, LRTI, and LRTI-related antibiotic prescription was 157.6, 76.0, 49.6, and 24.3 per 1000 person-years, respectively. Recent PPV23 vaccine receipt was associated with a small reduction in ARI presentations (adjusted HR vaccinated vs. unvaccinated 0.96; 95%CI 0.94-0.98; p = 0.002); however, there was no reduction in ARI-related antibiotic prescription, LRTI presentation, nor LRTI-related antibiotic prescription (adjusted HR were 0.99[95%CI 0.96-1.03], 1.04[95%CI 0.99-1.09], 1.07[95%CI 1.00-1.14]). CONCLUSION: PPV23 vaccination in older adults may result in a small reduction in the incidence of total ARI presentations in primary care. However, the effect is small and residual confounding cannot be excluded.

Evaluating the health and economic outcomes of a PCV15 vaccination program for adults aged 65 years-and-above in Switzerland.

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.

Effect of the PCV 10 vaccination on community-acquired pneumonia hospitalisations after four years of its introduction into the Polish National Immunisation Programme: Follow-up study.

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.

Invasive pneumococcal diseases in Chinese children: a multicentre hospital-based active surveillance from 2019 to 2021.

This study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of Streptococcus pneumoniae isolates from paediatric patients in China. We conducted a multi-centre prospective study for IPD in 19 hospitals across China from January 2019 to December 2021. Data of demographic characteristics, risk factors for IPD, death, and disability was collected and analysed. Serotypes, antibiotic susceptibility, and multi-locus sequence typing (MLST) of pneumococcal isolates were also detected. A total of 478 IPD cases and 355 pneumococcal isolates were enrolled. Among the patients, 260 were male, and the median age was 35 months (interquartile range, 12-46 months). Septicaemia (37.7%), meningitis (32.4%), and pneumonia (27.8%) were common disease types, and 46 (9.6%) patients died from IPD. Thirty-four serotypes were detected, 19F (24.2%), 14 (17.7%), 23F (14.9%), 6B (10.4%) and 19A (9.6%) were common serotypes. Pneumococcal isolates were highly resistant to macrolides (98.3%), tetracycline (94.1%), and trimethoprim/sulfamethoxazole (70.7%). Non-sensitive rates of penicillin were 6.2% and 83.3% in non-meningitis and meningitis isolates. 19F-ST271, 19A-ST320 and 14-ST876 showed high resistance to antibiotics. This multi-centre study reports the clinical features of IPD and demonstrates serotype distribution and antibiotic resistance of pneumococcal isolates in Chinese children. There exists the potential to reduce IPD by improved uptake of pneumococcal vaccination, and continued surveillance is warranted.

Retrospective study on the health and economic burden of hospitalized patients due to pneumonia and invasive pneumococcal infections in Belgium settings.

INTRODUCTION: pneumococcal infections are associated with high morbidity, hospitalisation and mortality. The objective of this study was to investigate the health and economic burden of all-cause pneumonia and invasive pneumococcal disease in Belgian hospital settings, by patient's age and risk profile. METHODS: This descriptive retrospective study was conducted in 17 Belgian hospitals. Univariate and multivariate logistic linear regression models were performed. The Health Insurance and patient's cost perspectives were considered because a few studies report these costs. RESULTS: The analysis has included 4,712 hospital admissions over the year 2018. Median hospitalization costs were higher for invasive pneumococcal infection diagnosis than for all-cause pneumonia (p < 0,001), respectively 4,051€ and 3,362€. Other factors associated with higher hospitalization cost were patient's high-risk profile, admission to emergency unit, transfer from nursing home, admission to intensive care unit and length of stay. CONCLUSION: Streptococcus pneumoniae infections remain a public health problem with significant cost for the Health Insurance and poor prognosis. Invasive pneumococcal infections are associated with longer hospital stays and required more intensive care than all other causes of pneumonia, in addition to be more costly, which justifies more attention for vaccination. This study also suggests an increase of economic and health burden with age and presence of underlying conditions.

Cost-effectiveness and impact on infections and associated antimicrobial resistance of 20-valent pneumococcal conjugate vaccine in US children previously immunized with PCV13.

AIM: The US Food and Drug Administration approved the 20-valent pneumococcal conjugate vaccine (PCV20) to prevent pneumococcal disease. In the context of routine PCV20 vaccination, we evaluated the cost-effectiveness and public health and economic impact of a PCV20 catch-up program and estimated the number of antibiotic prescriptions and antibiotic-resistant infections averted. MATERIALS AND METHODS: A population-based, multi-cohort, decision-analytic Markov model was developed using parameters consistent with previous PCV20 cost-effectiveness analyses. In the intervention arm, children aged 14-59 months who previously completed PCV13 vaccination received a supplemental dose of PCV20. In the comparator arm, no catch-up PCV20 dose was given. The direct and indirect benefits of vaccination were captured over a 10-year time horizon. RESULTS: A PCV20 catch-up program would prevent 5,469 invasive pneumococcal disease cases, 50,286 hospitalized pneumonia cases, 218,240 outpatient pneumonia cases, 582,302 otitis media cases, and 1,800 deaths, representing a net gain of 30,014 life years and 55,583 quality-adjusted life years. Furthermore, 720,938 antibiotic prescriptions and 256,889 antibiotic-resistant infections would be averted. A catch-up program would result in cost savings of $800 million. These results were robust to sensitivity and scenario analyses. CONCLUSIONS: A PCV20 catch-up program could prevent pneumococcal infections, antibiotic prescriptions, and antimicrobial-resistant infections and would be cost-saving in the US.

Cost-effectiveness of an in-development adult-formulated 21-valent pneumococcal conjugate vaccine in US adults aged 50 years or older.

Indirect effects of childhood pneumococcal conjugate vaccines (PCV) have diminished the cost-effectiveness of current adult vaccine recommendations. An in-development adult-formulated 21-valent pneumococcal conjugate vaccine (PCV21) may play a critical role in reducing pneumococcal illness by targeting a larger number of serotypes responsible for adult pneumococcal infections. This study assesses the cost-effectiveness of PCV21 in US adults aged 50 years or older compared with currently recommended pneumococcal vaccines, from both the societal and healthcare perspectives. A Markov model evaluated the lifetime cost-effectiveness of PCV21 (given at age 50 years only, at ages 50/65 years, and risk-based at ages < 65 years plus age-based at age 65 years) compared to no vaccination and to currently recommended pneumococcal vaccines given either as currently recommended or routinely at ages 50/65 years. The analysis was conducted in hypothetical Black and non-Black cohorts aged 50 years or older, with and without considering childhood pneumococcal vaccination indirect effects. Model parameters were based on US data. Parameter uncertainty was assessed using 1-way and probabilistic sensitivity analyses. From the societal perspective, PCV21 at ages 50/65 years compared to PCV21 at age 50 years cost $7,410 per quality adjusted life year (QALY) gained in Black cohort analyses and $85,696/QALY gained in the non-Black cohort; PCV21 at ages 50/65 years had the most favorable public health outcomes. From the healthcare perspective, compared to no vaccination, PCV21 at age 50 years cost $46,213/QALY gained in the Black cohort and $86,629/QALY in non-Blacks. All other strategies were dominated in both cohorts and from both perspectives. When considering childhood pneumococcal vaccination indirect effects, costs of PCV21 at ages 50/65 years remained less than $140,000/QALY gained from the societal perspective in both populations. PCV21 is potentially cost-effective compared to currently approved pneumococcal vaccines in adults aged 50 years or older from both the societal and healthcare perspectives.

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.

Protective effect of PCV13 against all-cause hospitalized pneumonia in children in Beijing, China: real-world evidence.

BACKGROUND: The study evaluated the protective effect of 13-valent pneumococcal polysaccharide conjugate vaccine (PCV13) against all-cause hospitalized pneumonia in children in Beijing. METHODS: Based on the vaccination record and inpatient medical record database of Beijing, children born in 2017 in Beijing, matched by age, gender, and district of the children with the ratio of 1:4, were selected as the vaccinated and unvaccinated groups according whether if vaccinated with PCV13. The incidence rate and 95 % confidence interval (95 %CI), vaccine effectiveness (VE) and direct medical costs of all-cause hospitalized pneumonia were calculated and compared within the same period of 12 months, 18 months, 24 months and 30 months after the birth of the child. RESULTS: The decreased incidence rates of all-cause hospitalized pneumonia were observed at the four points in the PCV13 vaccinated group compared to the unvaccinated group, which were significant at the points of 12 months (0.42 % vs. 0.72 %, P = 0.001), 18 months (0.90 % vs. 1.26 %, P = 0.002) and 24 months (1.37 % vs. 1.65 %, P = 0.046). The VE of PCV13 against all-cause hospitalized pneumonia within 12 months was the highest as 41.9 % (95 % CI 19.6 %, 58.0 %), followed by 29.3 % (95 % CI 11.4 %, 43.5 %) within 18 months, 17.1 % (95 % CI 0.3 %, 31.1 %) within 24 months and it almost disappeared within 30 months. The VE of 4-dose vaccination within 18 months and 24 months were 39.9 % (95 % CI 20.3 %, 54.7 %) and 27.2 % (95 % CI 8.6 %, 42.0 %), respectively. The median hospitalization cost of the children in the vaccinated group was higher at the four points but without significance. CONCLUSIONS: PCV13 had a certain protective effect on all-cause hospitalized pneumonia, and the booster immunization strategy had the best protective effect with great public health significance to enter the immunization program.