Study of pediatric invasive pneumococcal disease in the 13-pneumococcal conjugated vaccine era.

BACKGROUND: Invasive pneumococcal disease (IPD) remains a significant concern among children under 5, despite vaccination efforts. This study assessed IPD prevalence and associated risks in pediatric population. METHODS: An observational, retrospective, multicenter study in Comunidad Valenciana, Spain, of IPD cases in children under 13 from January 2012 to September 2022. Data from the CV Microbiology Surveillance Network (RedMIVA) and medical records were reviewed. RESULTS: A total of 379 IPD cases in 377 patients were analyzed, predominantly males (54.11 %) under 5 (81.17 %). PCV13 vaccination notably reduced PCV13-serotypes IPD (p=0.0002), except serotype 3. Pneumonia was common, with half having underlying conditions (50.40 %). Worse outcomes occurred in patients with neurological disorders (ANOVA, p=0.57). Vaccine failures often involved underlying conditions (63 %) and serotypes 3 and 19A. Immunodeficiencies may relate to recurrent IPD, but evidence is limited. CONCLUSION: Despite vaccination, IPD still impacts children, influenced by immunological status, affecting severity and mortality.

An economic evaluation of pneumococcal conjugate vaccines, PCV20 versus PCV15, for the prevention of pneumococcal disease in the Swedish pediatric population.

In September 2023, 10-valent pneumococcal conjugate vaccine (PCV) was replaced by 15-valent PCV (PCV15) in Sweden's pediatric national immunization program. Following European approval of 20-valent PCV (PCV20) in March 2024, we assessed the cost-effectiveness of PCV20 versus PCV15, both under 2 + 1 schedule, among Sweden's pediatric population. A Markov state-transition model evaluated the economic and health benefits of PCV20 versus PCV15 among all ages over a 10-year time horizon. The base case adopted a Swedish payer perspective with an annual cycle length and 3.0% discount rate for costs and outcomes. Country-specific data informed population size, epidemiology, costs, and quality of life estimates. PCV15/PCV20 effect estimates were informed by PCV13 clinical effectiveness and impact studies plus PCV7 efficacy studies. Sensitivity analyses evaluated model robustness, including PCV20 under a 3 + 1 schedule. PCV20 was associated with higher quality-adjusted life year gains versus PCV15, averting an estimated 3,116 invasive pneumococcal disease cases 21,109 inpatient pneumonia cases, 6,618 outpatient pneumonia cases, and 36,209 otitis media cases, plus 3,281 pneumococcal disease-related deaths. PCV20 yielded substantial cost savings exceeding 5.4 billion SEK over a 10-year time horizon, primarily attributed to reduced direct medical costs due to improved health outcomes compared with PCV15. The findings confirmed the dominance of PCV20 in the base case, which remained robust across deterministic and probabilistic sensitivity analyses as well as scenario assessments. PCV20 was the dominant strategy versus PCV15 over 10 years. The broader serotype coverage of PCV20 suggests superior clinical and economic advantages over PCV15, warranting inclusion in Sweden's pediatric immunization program.

Health-economic burden attributable to novel serotypes in candidate 24- and 31-valent pneumococcal conjugate vaccines.

INTRODUCTION: Next-generation pneumococcal vaccines currently in clinical trials include 24- and 31-valent pneumococcal conjugate vaccines (PCV24, PCV31), which aim to prevent upper-respiratory carriage and disease involving the targeted serotypes. We aimed to estimate the comprehensive health-economic burden associated with acute respiratory infections (ARIs) and invasive pneumococcal disease (IPD) attributable to PCV24- and PCV31-additional (non-PCV20) serotypes in the United States. MATERIAL AND METHODS: We multiplied all-cause incidence rate estimates for acute otitis media (AOM), sinusitis, and non-bacteremic pneumonia by estimates of the proportions of each of these conditions attributable to pneumococci and the proportions of pneumococcal infections involving PCV24- and PCV31-additional serotypes. We estimated serotype-specific IPD incidence rates using US Active Bacterial Core surveillance data. We accounted for direct medical and non-medical costs associated with each condition to estimate resulting health-economic burden. Non-medical costs included missed work and lost quality-adjusted life years due to death and disability. RESULTS: The health-economic burden of PCV24-additional serotypes totaled $1.3 ($1.1-1.7) billion annually in medical and non-medical costs, comprised of $0.9 ($0.7-1.2) billion due to ARIs and $0.4 ($0.3-0.5) billion due to IPD. For PCV31-additional serotypes, medical and non-medical costs totaled $7.5 ($6.6-8.6) billion annually, with $5.5 ($4.7-6.6) billion due to ARIs and $1.9 ($1.8-2.1) billion due to IPD. The largest single driver of costs was non-bacteremic pneumonia, particularly in adults aged 50-64 and ≥65 years. CONCLUSIONS: Additional serotypes in PCV24 and PCV31, especially those included in PCV31, account for substantial health-economic burden in the United States.

Increased proportions of invasive pneumococcal disease cases amongs adults experiencing homelessness sets stage for new serotype 4 capsular-switch recombinant.

BACKGROUND: The Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs) identified increased serotype 4 invasive pneumococcal disease (IPD), particularly among adults experiencing homelessness (AEH). METHODS: We quantified IPD cases during 2016-2022. Employing genomic-based characterization of IPD isolates, we identified serotype-switch variants. Recombinational analyses were used to identify the genetic donor and recipient strains that generated a serotype 4 progeny strain. We performed phylogenetic analyses of the serotype 4 progeny and serotype 12F genetic recipient to determine genetic distances. RESULTS: We identified 30 inter-related (0-21 nucleotide differences) IPD isolates recovered during 2022-2023, corresponding to a serotype 4 capsular-switch variant. This strain arose through a multi-fragment recombination event between serotype 4/ST10172 and serotype 12F/ST220 parental strains. Twenty-five of the 30 cases occurred within Oregon. Of 29 cases with known residence status, 16 occurred in AEH. Variant emergence coincided with a 2.6-fold increase (57 to 148) of cases caused by the serotype 4/ST10172 donor lineage in 2022 compared to 2019 and its first appearance in Oregon. Most serotypes showed sequential increases of AEH IPD/all IPD ratios during 2016-2022 (for all serotypes combined, 247/2198, 11.2% during 2022 compared to 405/5317, 7.6% for 2018-2019, p<0.001). Serotypes 4 and 12F each caused more IPD than any other serotypes in AEH during 2020-2022 (207 combined reported cases primarily in 4 western states accounting for 38% of IPD in AEH). CONCLUSION: Expansion and increased transmission of serotypes 4 and 12F among adults potentially led to recent genesis of an impactful hybrid "serotype-switch" variant.

Effectiveness of the ten- and thirteen-valent pneumococcal conjugate vaccines to prevent serotype 19A invasive pneumococcal disease in Quebec, Canada. A Canadian immunization research network (CIRN) study.

In the province of Quebec, Canada, a 2 + 1 dose pneumococcal conjugate vaccine (PCV) program for children was implemented in 2004. PCV7, PCV10, PCV13 and a mixed PCV10/PCV13 schedule were sequentially used without catch-up. The effectiveness of vaccination schedules to prevent serotype 19A invasive pneumococcal disease (IPD) in <5-year-old children was estimated by the indirect cohort method during 2009-2023. A total of 248 19A IPD cases and 457 IPD controls were included in the analysis. Adjusted vaccine effectiveness (VEa) for ≥1 dose was 57 % [95 %CI: -1 %,82 %] for PCV10 and 62 % [16 %,83 %] for PCV13. VEa for 3 doses was 69 % [17 %,88 %] for PCV10, 76 % [39 %,90 %] for PCV13 and 86 % [64 %,95 %] for the 2PCV10 + 1PCV13 schedule. Protection provided by the PCV10-only schedule tended to be of lower magnitude compared to the two other schedules. The mixed PCV10 + PCV13 schedule showed a protection against 19A IPD at least comparable to that of 3 PCV-13 doses.

Pneumococcal serotypes missing prespecified efficacy threshold in immunogenicity trials: real-world evidence from national immunization programs.

OBJECTIVES: The 13-valent (PCV13) and 10-valent (PCV10) pneumococcal conjugate vaccines missed non-inferiority for certain 7-valent (PCV7) serotypes in immunogenicity trials. This study examines the population-level IPD case trends for these serotypes. METHODS: We identified six countries with national IPD surveillance data that introduced PCV13 (Canada, Germany, Israel, Italy, South Africa, and the United States) and three with PCV10 (Finland, Brazil, and the Netherlands). We extracted country-specific annual IPD case counts for serotypes that met non-inferiority (4, 14, 18C, 19F, 9 V [PCV10 only]) and missed non-inferiority (6B, 23F, 9 V [PCV13 only]) for different age groups (<5 and ≥5 years) for eight years following PCV13/PCV10 introduction. RESULTS: For all ages and countries, IPD cases due to PCV7 serotypes that missed non-inferiority either decreased or remained suppressed following PCV13/PCV10 introduction. Similar trends were found for PCV7 serotypes that met non-inferiority in those <5 years. Paradoxically, cases increased in those ≥5 years in Canada, Italy, and the US, primarily driven by increases in serotypes 4 and 19F disease. CONCLUSIONS: Despite missing non-inferiority for serotypes in immunogenicity trials, higher-valent PCVs effectively suppressed these serotypes across all ages. Non-inferiority criteria from immunogenicity trials may not fully predict real-world disease impact after PCV implementation.

National recommendations for adult pneumococcal vaccination in countries of the WHO regions of Americas, Africa, Eastern Mediterranean, South East Asia, and Western Pacific.

BACKGROUND: Adults who are elderly or who have underlying health conditions are at particular risk of Streptococcus pneumoniae infections, and pneumococcal vaccines are available. Nonetheless, only national recommendations from countries of North America and Europe have been previously reviewed in the literature. METHODS: Consequently, we aimed to collate national guidelines for adult pneumococcal immunization across the 161 countries within the World Health Organization (WHO) regions-the Americas (except Canada and the United States of America), Africa, Eastern Mediterranean, South East Asia, and Western Pacific-from country-level official websites and documents, from the WHO portal, and from direct contact with public health officials, pertinent governmental sources, or local vaccination experts. RESULTS: For 40.4 % (65/161) of these countries, adult pneumococcal vaccination information was available. Among these 65 with available information, 63.1 % (41/65) include adult pneumococcal vaccination in the national vaccination schedule: 58.5 % (24/41) recommend vaccination both for older adults and for risk groups, while 9.8 % (4/41) recommend it only for older adults, and 31.7 % (13/41) only for risk groups. Of note, among the 13 national risk based-only recommendations, 30.8 % (4/13) are age-dependent and strictly reserved for older adults. The regions where age-based adult pneumococcal vaccination recommendations seem to predominate are South East Asia, Western Pacific, and the Americas. The threshold for age-based pneumococcal vaccination recommendations varies between 50 and 70 years of age. The Americas has the highest proportion of countries with risk-based recommendations. Three-quarters of these countries include PCV and PPV23 in the recommendations, most often given in sequence. CONCLUSIONS: Less than half of countries of the five WHO regions analyzed have accessible information on adult pneumococcal vaccination, and only 25.5 % (41/161) of all countries reviewed recommend adult pneumococcal immunization within the national vaccination schedule. Policymakers should consider extending pneumococcal vaccination guidelines-adapted to national priorities for adult healthcare-as based on local age demographics and risk factor predominance.

Effect of Childhood Pneumococcal Conjugate Vaccination on Invasive Disease Serotypes in Serbia.

In Serbia, PCV10 was introduced into the routine immunization for children under 2 in 2018 and replaced by PCV13 in 2022. We evaluated their impact on the distribution of invasive pneumococcal disease (IPD) serotypes across all age groups. Overall, 756 isolates were obtained from patients with IPD between 2010 and 2023 through laboratory surveillance. In the post-vaccination period, serotypes 14, 19F, 23F, and 6A significantly declined, while 3 and 19A considerably increased. This was especially evident in the ≤2 years group, making these serotypes the most prevalent among them. Serotype 3 dominated, representing 19.1% of all invasive isolates prior to 2018 and 33.1% thereafter. While serotype coverage of PCV10 has significantly decreased in the ≤2 years group (from 74.2% before 2018 to 29.5% after 2018), PCV13 coverage was 63.9% after 2018. In the post-PCV period, non-PCV13 serotypes, such as 9N, 10A, 15A, 15B, 15C, 22F, 6C, 6D, and 7C, increased across all isolates. Antibiotic non-susceptibility considerably decreased after 2018. MLST analysis showed shifts in sequence type prevalence, with pre-PCV lineages replaced and ongoing serotype 3 persistence, alongside potential capsule-switching events. These findings emphasize a noticeable shift in the distribution of serotypes and adaptability of pneumococcal populations, highlighting the importance of ongoing surveillance and the requirement for the urgent introduction of higher valent vaccines into the National Immunization Program.

The emergent invasive serotype 4 ST10172 strain acquires vanG type vancomycin-resistance element: A case of a 66-year-old with bacteremic pneumococcal pneumonia.

We report a single case of invasive pneumococcal disease (IPD) by serotype 4, multilocus sequence type 10172 (serotype 4/ST10172) isolate with vanG-type resistance genes and reduced vancomycin susceptibility. The isolate was recovered during 2022 from a 66-year-old resident with bacteremic pneumococcal pneumonia within a CDC Active Bacterial Core surveillance (ABCs) site hospital. The patient had received 23-valent pneumococcal polysaccharide vaccine and there was no evidence of concurrent or prior receipt of vancomycin in the previous year. Serotype 4/ST10172 IPD has shown increases within western ABCs sites and the recent acquisition of a vanG element warrants close monitoring of this lineage.

Assessing the Impact of Pneumococcal Conjugate Vaccine Immunization Schedule Change From 3+0 to 2+1 in Australian Children: A Retrospective Observational Study.

BACKGROUND: In mid-2018, the Australian childhood 13-valent pneumococcal conjugate vaccine schedule changed from 3+0 to 2+1, moving the third dose to 12 months of age, to address increasing breakthrough cases of invasive pneumococcal disease (IPD), predominantly in children aged >12 months. This study assessed the impact of this change using national IPD surveillance data. METHODS: Pre- and postschedule change 3-dose 13-valent pneumococcal conjugate vaccine breakthrough cases were compared by age group, serotype, and clinical syndrome. Annual rates of breakthrough cases were calculated (per 100 000) using respective birth cohort sizes and 3-dose vaccine coverage. Using time-series modelling, observed IPD rates in children aged <12 years were compared to that expected if the 3+0 schedule were continued. FINDINGS: Over 2012-2022, rate of 3-dose breakthrough cases in children aged >12 months was 2.8 per 100 000 (n = 557; 11 birth cohorts). Serotype 3 replaced 19A as predominant breakthrough serotype (respectively, 24% and 65% in 2013 to 60% and 20% in 2022) followed by 19F. In breakthrough cases, the most frequent clinical phenotype was bacteremic pneumonia (69%), with meningitis accounting for 3%-4%. In cohorts eligible for 2+1 versus 3+0 schedules, rate of breakthrough cases was lower for all vaccine serotypes, except type 3 (incidence rate ratio, 0.50 [95% confidence interval, .28-.84] and 1.12 [0.71-1.76], respectively). Observed compared to expected IPD was 51.7% lower (95% confidence interval, -60.9 to -40.7%) for vaccine serotypes, but the change for nonvaccine types was not significant 12% (-9.6 to 39.7). INTERPRETATIONS: The 2+1 schedule is likely superior to 3+0 for overall IPD control, a finding that may be worth consideration for other countries considering or using 3+0 PCV schedules.

Genetic characteristics of invasive pneumococcal disease-derived Streptococcus pneumoniae of serogroup 24 isolated in Tokyo, Japan.

BACKGROUND: Since the introduction of the national routine vaccination program against Streptococcus pneumoniae in Japan from the early 2010s, the incidence of invasive pneumococcal disease (IPD) caused by non-vaccine serotypes has increased. This study focused on non-vaccine serogroup 24 strains derived from IPD and aimed to clarify their genetic characteristics. METHODS: Between 2013 and 2022, 121 strains identified as serogroup 24 in patients with IPD were collected and applied to multilocus sequence typing and next-generation sequencing. Whole-genome data were used to delineate phylogenetic relationships and to identify virulence and antimicrobial resistance-associated genes. RESULTS: Recent trends in sequence types (STs) were characterized by an increase in the proportion of ST162 and ST2754 for 24F and 24B, respectively, after 2018. Whole-genome phylogenetic analysis demonstrated that serogroup 24 strains were organized into three clades, closely related to STs but not with serotypes. All ST162 strains were classified as Global Pneumococcal Sequence Cluster (GPSC) 6 and harbored the virulence-associated rlrA islet, with co-trimoxazole-resistance mutations in folA and folP genes. Two ST162 strains with different serotypes 24F and 24B from the same patient were phylogenetically indistinguishable, showing that these strains were derived by serotype conversion during infection. CONCLUSION: The recent changes in predominant STs were similar to those previously reported throughout Japan, except Tokyo. Little correlation between whole-genome phylogeny and serotypes and the observed serotype conversion in one patient indicate potentially variable immunogenicity of this serogroup.

Pneumococcal carriage and disease in adults in England 2011-2019: the importance of adults as a reservoir for pneumococcus in communities.

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.

Cardiovascular events after invasive pneumococcal disease: a retrospective cohort study.

OBJECTIVES: This study aims to understand the magnitude of and mechanisms underlying the development of cardiovascular events (CVEs) in patients with invasive pneumococcal disease (IPD). We aimed to identify factors that contribute to the occurrence of CVEs within 1 year after admission and discuss implications for patient care. METHODS: A multicentered cohort study included adult patients from four Dutch hospitals who had a positive blood culture for Streptococcus pneumoniae and any type of clinical manifestation between 2012 and 2020. Disease characteristics and microbiological data were systematically collected from electronic patient files. The main outcome measures were the occurrence of stroke and acute coronary syndromes (ACS). RESULTS: Of 914 eligible patients, 4.2% experienced a CVE within 1 year after admission for IPD. ACS mainly occurred in the first 2 weeks, whereas stroke developed throughout follow-up. Although ACS was positively associated with disease severity, the sole independent predictor was alcohol abuse (odds ratio [OR] 3.840, 95% confidence interval [CI] 1.108-13.303). Although stroke occurred in 6.3% of meningitis cases, the best clinical predictor of stroke was a body temperature >39.5 °C at admission (OR 3.117 [1.154-8.423]). In the adult IPD population aged <70 years, pneumococcal serotypes were the primary predictors of ACS (7F; OR 15.733 [1.812-136.632]) and stroke (22F; OR 7.320 [1.193-44.903]). CONCLUSIONS: Adverse CVEs were not uncommon after IPD diagnosis and deserve attention, especially in the high-risk groups we identified in our study population. Whether specific serotypes play a role in the development of CVE requires substantiation in further research.

Hospital Burden of All-Cause Pneumonia and Nonbacteremic Pneumococcal Pneumonia in Adults in France Between 2013 and 2019.

Background: Community-acquired pneumonia (CAP) is associated with significant morbidity and mortality. The study objective was to describe the hospital burden of pneumonia in the adult population in France. Methods: This retrospective study was conducted from the National Health Insurance Database. All hospitalizations for pneumonia (all-cause) between 2013 and 2019 were included. Different risk categories for patients were established based on pneumococcal vaccine recommendations by French health authorities. Results: A total of 2 199 240 episodes of CAP were registered over the study period (annual mean, 314 177 [standard deviation, 17 818.6]); 75% occurred in patients aged ≥65 years, among whom 47% were not classified in the moderate- or high-risk categories recommended for French pneumococcal vaccination. The incidence of CAP increased with age (117.9, 395.3, and 1916.7 per 100 000 for the age groups 18-49, 50-64, and ≥65 years, respectively, in 2019). Furthermore, being at risk of pneumococcal disease resulted in more severe outcomes, including longer episode duration (mean, 14 days in low-risk vs 17 days in high-risk patients) and higher risk of referral to critical care units (from 20% to 27%), of rehospitalization up to 180 days (from 39% to 67%), of in-hospital death (from 12% to 19%), and of 1-year mortality (from 26% to 49%). Conclusions: This study establishes the incidence of CAP in adults in France, describes the significant burden of disease, and highlights the need for better prevention policies.

Serotype distribution of invasive pneumococcal disease from countries of the WHO Africa, Americas, Eastern Mediterranean, South-East Asia, and Western Pacific regions: a systematic literature review from 2010 to 2021.

Background: Most publications on invasive pneumococcal disease (IPD) serotype distribution are from about 20 countries (Australia, Canada, China, European Union members, Japan, New Zealand, South Korea, and USA). Here, we reviewed the literature among underrepresented countries in the Americas (AMRO), Africa (AFRO), Eastern Mediterranean (EMRO), South-East Asia (SEARO), and Western Pacific (WPRO) WHO regions. Methods: We performed a systematic review of the most recent IPD serotype surveillance publications (from 01/01/2010 to 31/12/2021, Medline/Embase) in those WHO regions. Selection criteria were delineated by contemporality, within-country geographical scope, and number of samples. Reported serotype distributions for each country were stratified by age group, pneumococcal conjugate vaccine (PCV) serotype category (considering undifferentiated serotypes), and PCV program period (pre-PCV, intermediate, or PCVhv [higher valency PCV formulation]). Pre-PCV period pooled data estimated PCV serotype category distribution by age group across WHO regions, while for the PCVhv period, country-level dataset tables were prepared. Results: Of 2,793 publications screened, 107 were included (58 pediatric, 11 adult, 37 all ages, and one comprising every age group). One-third of eligible countries (51/135) published serotype distribution, ranging from 30 to 43% by WHO region. Considering number of samples per WHO region, a few countries prevailed: AMRO (Brazil), AFRO (South Africa, Malawi, and Burkina Faso), and WPRO (Taiwan). In the pre-PCV period, PCV13 formulation serotypes predominated: ranging from 74 to 85% in children and 58-86% in adults in the different WHO regions. The PCVhv period represented half of the most recent IPD surveillance by countries (26/51). Undifferentiated serotypes represented >20% of IPD from most countries (34/51). Conclusion: Ubiquity of undifferentiated serotypes among the publications could constrain estimates of PCV program impact and of serotype coverage for newer PCVhv formulations; consequently, we recommend that countries favor techniques that identify serotypes specifically and, rather than reporting PCV formulation serotype distributions, provide serotype results individually. Systematic review registration: The protocol has been prospectively registered at PROSPERO, identifier: CRD42021278501. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278501.

Vaccines for the Elderly and Vaccination Programs in Europe and the United States.

The share of the elderly population is growing worldwide as life expectancy increases. Immunosenescence and comorbidities increase infectious diseases' morbidity and mortality in older adults. Here, we aimed to summarize the latest findings on vaccines for the elderly against herpes zoster, influenza, respiratory syncytial virus (RSV), COVID-19, and pneumococcal disease and to examine vaccine recommendation differences for this age group in Europe and the United States. PubMed was searched using the keywords "elders" and "vaccine" alongside the disease/pathogen in question and paraphrased or synonymous terms. Vaccine recommendations were also sought in the European and US Centers for Disease Control and Prevention databases. Improved vaccines, tailored for the elderly, mainly by using novel adjuvants or by increasing antigen concentration, are now available. Significant differences exist between immunization policies, especially between European countries, in terms of the recipient's age, number of doses, vaccination schedule, and implementation (mandatory or recommended). Understanding the factors that influence the immune response to vaccination in the elderly may help to design vaccines that offer long-term protection for this vulnerable age group. A consensus-based strategy in Europe could help to fill the gaps in immunization policy in the elderly, particularly regarding vaccination against RSV and pneumococcus.

Cost-effectiveness analysis of the pediatric 20-valent pneumococcal conjugate vaccine compared with lower-valent alternatives in Argentina.

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.

Cost-effectiveness analysis of the 20-valent pneumococcal conjugate vaccine for the pediatric population in South Korea.

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.

New Vaccines for Chronic Respiratory Patients.

Chronic respiratory diseases (CRD) are responsible for more than four million deaths worldwide and have become especially prevalent in developed countries. Although the current therapies help manage daily symptoms and improve patients' quality of life, there is a major need to prevent exacerbations triggered mainly by respiratory infections. Therefore, CRD patients are a prime target for vaccination against infectious agents. In the present manuscript we review the state of the art of available vaccines specifically indicated in patients with CRDs. In addition to pneumococcus, influenza, pertussis, and SARS-CoV-2 vaccines, recently added immunization options like vaccines and monoclonal antibodies against respiratory syncytial virus, are particularly interesting in CRD patients. As new products reach the market, health authorities must be agile in updating immunization recommendations and in the programming of the vaccination of vulnerable populations such as patients with CRDs. Organizational and educational strategies might prove useful to increase vaccine uptake by CRD patients.

Invasive pneumococcal disease surveillance in Canada, 2021-2022.

Background: Invasive pneumococcal disease (IPD, Streptococcus pneumoniae) has been a nationally notifiable disease in Canada since 2000. The use of conjugate vaccines has caused a shift in the distribution of serotypes over time. This report is a summary of the demographics, serotypes and antimicrobial resistance of IPD isolates collected in Canada in 2021 and 2022. Methods: The National Microbiology Laboratory (NML) of the Public Health Agency of Canada in Winnipeg, Manitoba collaborates with provincial and territorial public health laboratories to conduct national surveillance of IPD. There were 1,999 isolates reported in 2021 and 3,775 isolates in 2022. Serotype was determined by the Quellung reaction or whole-genome sequencing (WGS). Antimicrobial susceptibilities were determined by WGS methods, broth microdilution, or data shared by collaborators in the Canadian Antimicrobial Resistance Alliance program at the University of Manitoba. Population-based IPD incidence rates were obtained through the Canadian Notifiable Disease Surveillance System. Results: The incidence of IPD in Canada was 5.62 cases per 100,000 population in 2021, decreasing from the peak of 10.86 cases per 100,000 population in 2018. Serotypes with increasing trends (p<0.05) between 2018 and 2022 included: 4 (6.1%-12.4%), 9V (1.0%-5.1%) and 12F (4.8%-5.4%). The overall prevalence of PCV13 serotypes increased over the same period (31.2%-41.5%, p<0.05) while the prevalence of non-vaccine types decreased significantly (27.3%-21.5%, p<0.0001). The highest rates of antimicrobial resistance in 2021 and 2022 were seen with clarithromycin (21%, 2021; 24%, 2022) and erythromycin (22%, 2021; 24%, 2022). Multidrug-resistant IPD continued to increase from 2018 to 2022 (6.7%-12.6%, p<0.05). Conclusion: The number of cases of IPD continued to decrease in 2021 in comparison to previous years, however, 2022 saw a return to pre-COVID-19 levels. Disease due to PCV13 serotypes 3, 4, 9V and 19F, as well as non-PCV13 serotypes 12F and 20, is increasing in prevalence. Surveillance of IPD to monitor changing serotype distribution and antimicrobial resistance is essential.