Cases Of Pneumococcal Disease Research Articles

Cost-Effectiveness Analysis of Routine Childhood Immunization with 20-Valent versus 15-Valent Pneumococcal Conjugate Vaccines in Germany.

This study aimed to evaluate the cost-effectiveness of routine childhood immunization with the 20-valent pneumococcal conjugate vaccine (PCV20) in a four-dose regimen (3 + 1 schedule) versus the 15-valent PCV (PCV15/V114) in a three-dose regimen (2 + 1) in Germany. The study utilized a decision-analytic Markov model to estimate lifetime costs and effectiveness outcomes for a single birth cohort in Germany. The model tracked the incidence of acute pneumococcal infections and long-term pneumococcal meningitis sequelae for both vaccination strategies. The vaccine effectiveness data were derived from published clinical trials and observational studies of PCV7 and PCV13. Indirect effects, such as herd protection and serotype replacement, were included in the model. The model adopted a societal perspective, including direct medical, direct non-medical, and indirect costs. Scenario and sensitivity analyses were performed. In the base case, PCV20 prevented more pneumococcal disease cases and deaths, with an expected gain of 96 quality-adjusted life years (QALYs) compared to V114. However, PCV20 was associated with a total incremental cost of EUR 48,358,424, resulting in an incremental cost-effectiveness ratio (ICER) of EUR 503,620/QALY. Most of the scenario and sensitivity analyses estimated that the ICER for PCV20 exceeded EUR 150,000/QALY. Routine childhood immunization with PCV20 instead of V114 may not be an economically efficient use of healthcare resources in Germany.

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

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). 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. 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). Expansion and increased transmission of serotypes 4 and 12F among adults potentially led to recent genesis of an impactful hybrid "serotype-switch" variant.

Re-evaluating the impact and cost-effectiveness of pneumococcal conjugate vaccine introduction in 112 low-income and middle-income countries in children younger than 5 years: a modelling study

Streptococcus pneumoniae has been estimated to cause 9·18 million cases of pneumococcal pneumonia, meningitis, and invasive non-pneumonia non-meningitis disease and 318 000 deaths among children younger than 5 years in 2015. We estimated the potential impact and cost-effectiveness of pneumococcal conjugate vaccine (PCV) introduction. We updated our existing pseudodynamic model to estimate the impact of 13-valent PCV (PCV13) in 112 low-income and middle-income countries by adapting our previously published pseudodynamic model with new country-specific evidence on vaccine coverage, burden, and post-introduction vaccine impact from WHO-UNICEF estimates of national immunisation coverage and a global burden study. Deaths, disability-adjusted life-years (DALYs), and cases averted were estimated for children younger than 5 years born between 2000 and 2030. We used specific PCV coverage in each country and a hypothetical scenario in which coverage increased to diphtheria-tetanus-pertussis (DTP) levels. We conducted probabilistic uncertainty analyses. Using specific vaccine coverage in countries, we estimated that PCV13 could prevent 697 000 (95% credibility interval 359 000-1 040 000) deaths, 46·0 (24·0-68·9) million DALYs, and 131 (89·0-172) million cases in 112 countries between 2000 and 2030. PCV was estimated to prevent 5·3% of pneumococcal deaths in children younger than 5 years during 2000-30. The incremental cost of vaccination would be I$851 (510-1530) per DALY averted. If PCV coverage were increased to DTP coverage in 2020, PCV13 could prevent an additional 146 000 (75 500-219 000) deaths. The inclusion of real-world evidence from lower-income settings revealed that delays in PCV roll-out globally and low PCV coverage have cost many lives. Countries with delays in vaccine introduction or low vaccine coverage have experienced many PCV-preventable deaths. These findings underscore the importance of rapidly scaling up PCV to achieve high coverage and maximise vaccine impact. Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance.

Cost-effectiveness of PCV20 to Prevent Pneumococcal Disease in the Pediatric Population: A German Societal Perspective Analysis.

Since 2009, a pneumococcal conjugate vaccine (PCV) covering 13 serotypes (PCV13) has been included by Germany's Standing Committee on Vaccinations for infants, resulting in major reductions in pneumococcal disease (PD). Higher-valent vaccines may further reduce PD burden. This cost-effectiveness analysis compared 20-valent PCV (PCV20) under a 3+1 schedule with 15-valent PCV (PCV15) and PCV13, both under 2+1 schedule, in Germany's pediatric population. A Markov model with annual cycles over a 10-year time horizon was adapted to simulate the clinical and economic impact of pediatric vaccination with PCV20 versus lower-valent PCVs in Germany. The model used PCV13 clinical effectiveness and impact studies as well as PCV7 efficacy studies for vaccine direct and indirect effect estimates. Epidemiologic, utility, and medical cost inputs were obtained from published sources. Benefits and costs were discounted at 3% from a German societal perspective. Outcomes included PD cases, deaths, costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). In the base case, PCV20 provided greater health benefits than PCV13, averting more cases of invasive pneumococcal disease (IPD; 15,301), hospitalized and non-hospitalized pneumonia (460,197 and 472,365, respectively), otitis media (531,634), and 59,265 deaths over 10 years. This resulted in 904,854 additional QALYs and a total cost saving of €2,393,263,611, making PCV20 a dominant strategy compared with PCV13. Compared to PCV15, PCV20 was estimated to avert an additional 11,334 IPD, 704,948 pneumonia, and 441,643 otitis media cases, as well as 41,596 deaths. PCV20 was associated with a higher QALY gain and lower cost (i.e., dominance) compared with PCV15. The robustness of the results was confirmed through scenario analyses as well as deterministic and probabilistic sensitivity analyses. PCV20 3+1 dominated both PCV13 2+1 and PCV15 2+1 over 10 years. Replacing lower-valent PCVs with PCV20 would result in greater clinical and economic benefits, given PCV20's broader serotype coverage.

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

BackgroundIntroduction 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). MethodsThis 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. FindingsThe 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. InterpretationsBE-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.

Estimated population-level impact of pneumococcal conjugate vaccines against all-cause pneumonia mortality among unvaccinated age groups in five Latin American countries.

Pneumococcal conjugate vaccines (PCVs) provide strong direct protection in children, while limited data are available on their indirect effect on mortality among older age groups. This multi-country study aimed to assess the population-level impact of pediatric PCVs on all-cause pneumonia mortality among ≥5 years of age, and invasive pneumococcal disease (IPD) cases in Chile. Demographic and mortality data from Argentina, Brazil, Chile, Colombia, and Mexico were collected considering the ≥ 5-year-old population, from 2000-2019, with 1,795,789 deaths due to all-cause pneumonia. IPD cases in Chile were also evaluated. Time series models were employed to evaluate changes in all-cause pneumonia deaths during the post-vaccination period, with other causes of death used as synthetic controls for unrelated temporal trends. No significant change in death rates due to all-cause pneumonia was detected following PCV introduction among most age groups and countries. The proportion of IPD cases caused by vaccine serotypes decreased from 29% (2012) to 6% (2022) among ≥65 years in Chile. While an effect of PCV against pneumonia deaths (a broad clinical definition that may not be specific enough to measure indirect effects) was not detected, evidence of indirect PCV impact was observed among vaccine-type-specific IPD cases.

Cost-Effectiveness of 20-Valent Pneumococcal Conjugate Vaccine Among US Children with Underlying Medical Conditions.

A 20-valent pneumococcal conjugate vaccine (PCV20) was recently recommended for use among US children. We evaluated the cost-effectiveness of PCV20 among children aged 6years with chronic medical conditions (CMC+) and children aged 6years with immunocompromising conditions (IC) versus one and two doses of 23-valent pneumococcal polysaccharide vaccine (PPSV23), respectively. A probabilistic model was employed to depict 10-year risk of clinical outcomes and economic costs of pneumococcal disease, reduction in life years from premature death, and expected impact of vaccination among one cohort of children with CMC+ and IC aged 6years. Vaccine uptake was assumed to be 20% for both PCV20 and PPSV23. Cost per quality-adjusted life year (QALY) gained was evaluated from the US societal and healthcare system perspectives; deterministic and probabilistic sensitivity analyses (DSA/PSA) were also conducted. Among the 226,817 children with CMC+ aged 6 years in the US, use of PCV20 (in lieu of PPSV23) was projected to reduce the number cases of pneumococcal disease by 5203 cases, medical costs by US$8.7 million, and nonmedical costs by US$6.2 million. PCV20 was the dominant strategy versus PPSV23 from both the healthcare and societal perspectives. In the PSA, 99.9% of the 1000 simulations yielded a finding of dominance for PCV20. Findings in analyses of children with IC aged 6years in the USA were comparable (i.e., PCV20 was the dominant vaccination strategy). Scenario analyses showed that increasing PCV20 uptake to 100% could potentially prevent > 22,000 additional cases of pneumococcal disease and further reduce medical and nonmedical costs by US$70.0 million among children with CMC+ and IC. Use of PCV20 among young children with CMC+ and IC in the USA would reduce the clinical burden of pneumococcal disease and yield overall cost savings from both the US healthcare system and societal perspectives. Higher PCV20 uptake could further reduce the number of pneumococcal disease cases in this population.

In Vitro Evaluation of Effect of Storage Time on Immunogenicity of the 10-Valent Pneumococcal Conjugate Vaccine Using Baby Rabbit Complement &amp; HL-60 Cells

Background: The efficacy and effectiveness of a vaccine is influenced by several factors including storage duration. Additionally, vaccines may be sufficiently administered but functionality of antibody generated may be hampered with by other factors such as nutritional status of the patient. As such, one of the ways of assessing vaccine efficacy is assessing the functionality of the antibodies generated. The 10v-PCV is a highly effective vaccine used to prevent invasive pneumococcal diseases in children. However, here in Kenya, cases of pneumococcal diseases are high and challenging to treat. This study thus aimed to evaluate the effect of storage of PCV-10 storage time on the functionality of Abs generated. Methodology; An in vitro experimental research design was employed for this study. opsonophagocytic activity assay using HL-60 Cells &amp; Baby rabbit complement was used to assess whether or not the Pneumococci Serotype IgG antibodies elicited following administration with 10v-PCV vaccine are functional. Only 10v-PCV vaccine with same production date were procured. Twenty experimental rabbits of same gender were procured and used injected intraperitoneally with 3 doses of 100µl (0.34g) of 10v-PCV vaccine after every four weeks. Antibody functionality was then assessed using the opsonophagocytic activity assay method. Results: An average of 28.9% of pneumococcus exposed to the vaccine-induced secreted antibodies were killed by the pneumococcal IgG antibody. The highest percentage of number of bacteria killed was achieved after the 3rd dose of vaccination. There was no significant influence of storage duration on opsonophagocytic activity of generated antibodies. Conclusion: Storing of 10v-PCV vaccine up to 12 weeks does not significantly affect the opsonophagocytic activity of pneumococcal IgG antibodies.

Serotype, antibiotic susceptibility and whole-genome characterization of Streptococcus pneumoniae in all age groups living in Southwest China during 2018-2022.

Streptococcus pneumoniae is a common pathogen that colonizes the human upper respiratory tract, causing high morbidity and mortality worldwide. This study aimed to investigate the prevalence status of S. pneumoniae isolated from patients of all ages in Southwest China, including serotype, antibiotic susceptibility and other molecular characteristics, to provide a basis for clinical antibiotic usage and vaccine development. This study was conducted from January 2018 to March 2022 at West China Hospital, West China Second University Hospital, First People's Hospital of Longquanyi District (West China Longquan Hospital), Meishan Women and Children's Hospital (Alliance Hospital of West China Second University Hospital) and Chengdu Jinjiang Hospital for Women and Children Health. Demographic and clinical characteristics of 263 pneumococcal disease (PD) all-age patients were collected and analyzed. The serotypes, sequence types (STs), and antibiotic resistance of the strains were determined by next-generation sequencing, sequence analysis and the microdilution broth method. The most common pneumococcal serotypes were 19F (17.87%), 19A (11.41%), 3 (8.75%), 23F (6.46%) and 6A (5.70%). Coverage rates for PCV10, PCV13, PCV15, PCV20 and PCV24 were 36.12, 61.98, 61.98, 63.12 and 64.26%, respectively. Prevalent STs were ST271 (12.55%), ST320 (11.79%), ST90 (4.18%), ST876 (4.18%) and ST11972 (3.42%). Penicillin-resistant S. pneumoniae (PRSP) accounted for 82.35 and 1.22% of meningitis and nonmeningitis PD cases, respectively. Resistance genes msrD (32.7%), mefA (32.7%), ermB (95.8%), tetM (97.3%) and catTC (7.6%) were found among 263 isolates. Most isolates showed high resistance to erythromycin (96.96%) and tetracycline (79.85%), with more than half being resistant to SXT (58.94%). A few isolates were resistant to AMX (9.89%), CTX (11.03%), MEN (9.13%), OFX (1.14%), LVX (1.14%) and MXF (0.38%). All isolates were susceptible to vancomycin and linezolid. Our study provides reliable information, including the prevalence, molecular characterization and antimicrobial resistance of S. pneumoniae isolates causing pneumococcal diseases in Southwest China. The findings contribute to informed and clinical policy decisions for prevention and treatment.

Etiologic Profile of the Pneumococcus in Ghana: A Systematic Review.

Objective: To describe the profile of Streptococcus pneumoniae, identify research gaps, and provide in-depth insights into various aspects related to the pathogen. Methods: Google Scholar, PubMed, and ScienceDirect were searched for all studies on the pneumococcus in Ghana that reported on specimen collected, population and sample size, carriage prevalence, incidence of pneumococcal diseases, age of the study population, types of test performed, serotypes identified, antimicrobial susceptibilities, or molecular analysis on the pneumococci for data extraction. Results: Overall, a total of 7954 results were obtained from the three-database search, and of this, 24 articles were selected after screening. A total of 924 isolates were accounted for by serotyping/serogrouping. The prevalence of pneumococcal carriage in Ghana ranges from 11.0% to 51.4% in the population depending on the age (≤ 24-80 years), sickle cell disease (SCD), human immunodeficiency virus (HIV) status, or health of the study population, and penicillin (Pen)-nonsusceptible isolates ranged from 17% to 63%. The prevalence of pneumococci found as the etiologic agent of diseases among Ghanaians ranges from 3.4% for otitis media to 77.7% for meningitis. Overall, the 13-valent pneumococcal conjugate vaccine (PCV) (PCV-13) carriage serotypes accounted for 28.4% of the reported pneumococcal isolates. PCV-13 invasive serotypes accounted for 22.4% of the reported isolates. The non-PCV-13 carriage serotypes accounted for most (43.9%) of the reported isolates. In the pre-PCV-13 era, the nontypeable (NT) (5.5%) and other nonvaccine types (NVTs) (6.4%) were reported as being predominant. The non-PCV-13 serotypes accounted for 4.4% of the reported isolates in invasive pneumococcal disease (IPD) cases. Multidrug resistance (MDR) ranged from 7.8% to 100%. Conclusion: Predicting the invasiveness of pneumococci using molecular typing is the way to go in the future as this will provide answers to the extent to which capsular switching is contributing to the pneumococcal disease burden in Ghana almost a decade after introducing PCV-13. Continuous monitoring of antibiotic resistance patterns at both phenotypic and genotypic levels, along with serotyping and molecular typing, should be a standard practice in the surveillance of pneumococcal disease burden in Ghana.

Cost-effectiveness of 20-valent pneumococcal conjugate vaccine in US infants

BackgroundAs of June 2023, two pneumococcal conjugate vaccines, 20- (PCV20) and 15- (PCV15) valent formulations, are recommended for US infants under a 3 + 1 schedule. This study evaluated the health and economic impact of vaccinating US infants with a new expanded valency PCV20 formulation. MethodsA population-based, multi cohort, decision-analytic Markov model was developed to estimate the public health impact and cost-effectiveness of PCV20 from both societal and healthcare system perspectives over 10 years. Epidemiological data were based on published studies and unpublished Active Bacterial Core Surveillance System (ABCs) data. Vaccine effectiveness was based on PCV13 effectiveness and PCV7 efficacy studies. Indirect impact was based on observational studies. Costs and disutilities were based on published data. PCV20 was compared to both PCV13 and PCV15 in separate scenarios. ResultsReplacing PCV13 with PCV20 in infants has the potential to avert over 55,000 invasive pneumococcal disease (IPD) cases, 2.5 million pneumonia cases, 5.4 million otitis media (OM) cases, and 19,000 deaths across all ages over a 10-year time horizon, corresponding to net gains of 515,000 life years and 271,000 QALYs. Acquisition costs of PCV20 were offset by monetary savings from averted cases resulting in net savings of $20.6 billion. The same trend was observed when comparing PCV20 versus PCV15, with a net gain of 146,000 QALYs and $9.9 billion in net savings. A large proportion of the avoided costs and cases were attributable to indirect effects in unvaccinated adults and elderly. From a health-care perspective, PCV20 was also the dominant strategy compared to both PCV13 and PCV15. ConclusionsInfant vaccination with PCV20 is estimated to further reduce pneumococcal disease and associated healthcare system and societal costs compared to both PCV13 and PCV15.

Health and economic outcomes of 20-valent pneumococcal conjugate vaccine compared to 15-valent pneumococcal conjugate vaccine strategies for adults in Greece.

Higher valency pneumococcal conjugate vaccines (PCVs) are expected to improve protection against pneumococcal disease through coverage of additional serotypes. The aim of the present study was to evaluate the cost-effectiveness of 20-valent pneumococcal conjugate vaccine (PCV20) compared to 15-valent pneumococcal conjugate vaccine (PCV15) alone or followed by 23-valent polysaccharide vaccine (PPV23) for adults in Greece. A published Markov model was adapted to simulate lifetime risk of clinical and economic outcomes from the public payer's perspective. The model population was stratified based on age and risk profile (i.e., low, moderate, or high-risk of developing pneumococcal disease). Epidemiologic parameters, serotype coverage and vaccines' effectiveness were based on published literature, while direct medical costs (prices €, 2022) were obtained from official sources. Main model outcomes were projected number of invasive pneumococcal disease (IPD) and all-cause non-bacteremic pneumonia (NBP) cases and attributable deaths, costs and quality-adjusted life-years (QALY) for each vaccination strategy. Sensitivity analyses were performed to ascertain the robustness of model results. Over the modeled time horizon, vaccination with PCV20 compared to PCV15 alone or PCV15 followed by PPV23 prevents an additional 747 and 646 cases of IPD, 10,334 and 10,342 cases of NBP and 468 and 455 deaths respectively, resulting in incremental gain of 1,594 and 1,536 QALYs and cost savings of €11,183 and €48,858, respectively. PSA revealed that the probability of PCV20 being cost-effective at the predetermined threshold of €34,000 per QALY gained was 100% compared to either PCV15 alone or the combination of PCV15 followed by PPV23. PCV20 is estimated to improve public health by averting additional pneumococcal disease cases and deaths relative to PCV15 alone or followed by PPV23, and therefore translates to cost-savings for the public payer. Overall results showed that vaccination with PCV20 was estimated to be a dominant vaccination strategy (improved health outcomes with reduced costs) over PCV15 alone or followed by PPV23 for prevention of pneumococcal disease in adults in Greece.

Health Care Provider Knowledge and Attitudes Regarding Adult Pneumococcal Conjugate Vaccine Recommendations - United States, September 28-October 10, 2022.

Despite the availability of effective vaccines against pneumococcal disease, pneumococcus is a common bacterial cause of pneumonia, causing approximately 100,000 hospitalizations among U.S. adults per year. In addition, approximately 30,000 invasive pneumococcal disease (IPD) cases and 3,000 IPD deaths occur among U.S. adults each year. Previous health care provider surveys identified gaps in provider knowledge about and understanding of the adult pneumococcal vaccine recommendations, and pneumococcal vaccine coverage remains suboptimal. To assess the feasibility and acceptability domains of the Advisory Committee on Immunization Practices (ACIP) Evidence to Recommendations (EtR) framework, a health care provider knowledge and attitudes survey was conducted during September 28-October 10, 2022, by the Healthcare and Public Perceptions of Immunizations Survey Collaborative before the October 2022 ACIP meeting. Among 751 provider respondents, two thirds agreed or strongly agreed with the policy option under consideration to expand the recommendations for the new 20-valent pneumococcal conjugate vaccine (PCV20) to adults who had only received the previously recommended 13-valent pneumococcal conjugate vaccine (PCV13). Gaps in providers' knowledge and perceived challenges to implementing recommendations were identified and were included in ACIP's EtR framework discussions in late October 2022 when ACIP updated the recommendations for PCV20 use in adults. Currently, use of PCV20 is recommended for certain adults who have previously received PCV13, in addition to those who have never received a pneumococcal conjugate vaccine. The survey findings indicate a need to increase provider awareness and implementation of pneumococcal vaccination recommendations and to provide tools to assist with patient-specific vaccination guidance. Resources available to address the challenges to implementing pneumococcal vaccination recommendations include the PneumoRecs VaxAdvisor mobile app and other CDC-developed tools, including summary documents and overviews of vaccination schedules and CDC's strategic framework to increase confidence in vaccines and reduce vaccine-preventable diseases, Vaccinate with Confidence.

Cost-Effectiveness of Pneumococcal Vaccination in Adults in Italy: Comparing New Alternatives and Exploring the Role of GMT Ratios in Informing Vaccine Effectiveness.

In Italy, a sequential pneumococcal vaccination with conjugate vaccine (PCV) and polysaccharide vaccine (PPSV23) is recommended for individuals aged ≥ 65 years and those at risk for pneumococcal disease (PD) aged ≥ 6 years. The aim of this study was to assess the cost-effectiveness of the new vaccines, i.e., approved 15-valent and 20-valent PCVs. A published Markov model was adapted to evaluate the lifetime cost-effectiveness of vaccination with PCV15 + PPSV23 versus PCV13 + PPSV23, PCV20 alone, PCV20 + PPSV23, and No Vaccination. Simulated cohorts representing the Italian population, including individuals aged ≥ 65 years, those at risk aged 50-100 years, and those deemed high risk aged 18-100 years were assessed. Outcomes were accrued in terms of incremental PD cases, costs, quality-adjusted life years, life years, and the cost-utility ratio relative to PCV13 + PPSV23. The conservative base case analysis, including vaccine efficacy based on PCV13 data, showed that sequential vaccination with PCV15 or PCV20 in combination with PPSV23 is preferred over sequential vaccination with PCV13 + PPSV23. Especially in the high-risk group, PCV15 + PPSV23 sequential vaccination was dominant over No Vaccination and resulted in an ICUR of €3605 per QALY gained. Including PCV20 + PPSV23 into the comparison resulted in the domination of the PCV15 + PPSV23 and No Vaccination strategies. Additionally, explorative analysis, including the geometric mean titer (GMT) informed vaccine effectiveness (VE) was performed. In the low-risk and high-risk groups, the results of the GMT scenarios showed PCV15 + PPSV23 to be dominant over the other sequential vaccines. These findings suggest that if real-world studies would confirm a difference in vaccine effectiveness of PCV15 and PCV20 versus PCV13 based on GMT ratios, PCV15 + PPSV23 could prove a highly immunogenic and effective vaccination regime for the Italian adult population.

Assessing Public Health Impact of Four Pediatric Pneumococcal Conjugate Vaccination Strategies in the Netherlands.

The 10-valent pneumococcal conjugate vaccine (PCV10, Synflorix) was introduced into the Dutch pediatric national immunization program (NIP) starting in 2011. However, there is substantial pneumococcal disease burden due to increases in non-PCV10 covered serotypes. Higher-valent vaccines for pediatrics (PCV13, PCV15, and PCV20) may alleviate much of the remaining disease burden upon implementation through broader serotype coverage. This article assesses the public health impact of different pediatric vaccination strategies (switching to PCV13, PCV15 or PCV20) versus maintaining PCV10 at different time intervals in the Netherlands. A population-based, decision-analytic model was developed using historical pneumococcal disease surveillance data to forecast future invasive pneumococcal disease (IPD), pneumonia, and otitis media (OM) cases over a 7-year period (2023-2029) under the following strategies: continued use of PCV10, switching to PCV13 in 2023, switching to PCV15 in 2023, and switching to PCV20 in 2024. Scenario analyses were performed to account for uncertainties in future serotype distributions, disease incidence reductions, and epidemiologic parameters. Switching to PCV13 in 2023 was found to avert 26,666 cases of pneumococcal disease compared to continuing PCV10 over a 7-year period (2023-2029). Switching to PCV15 in 2023 was found to avert 30,645 pneumococcal cases over the same period. Switching to PCV20 once available in 2024 was estimated to avert 45,127 pneumococcal cases from 2024-2029. Overall conclusions were maintained after testing uncertainties. For the Dutch pediatric NIP, switching to PCV13 in 2023 would be an effective strategy compared with continued use of PCV10 for averting pneumococcal disease cases. Switching to PCV20 in 2024 was estimated to avert the most pneumococcal disease cases and provide the highest protection. However, in the face of budget constraints and the undervaluation of prevention strategies, it remains challenging to implement higher valent vaccines. Further research is needed to understand the cost-effectiveness and feasibility of a sequential approach.

Serotypes and antimicrobial resistance of Streptococcus pneumoniae in children under 5 years of age pre- and post-pneumococcal conjugate vaccine introduction in Paraguay.

Introduction. Streptococcus pneumoniae remains a major cause of mortality and morbidity worldwide in children <5 years of age, even with advances in vaccination programmes.Hypothesis/Gap Statement. Reviewing and reporting trends in the distribution of pneumococcal serotypes and antimicrobial resistance in Paraguay will be useful for decision-making in public health.Aim. This study analysed the serotype distribution and antimicrobial resistance of S. pneumoniae and the characteristics of pneumococcal disease in children <5 years old before and after the introduction of pneumococcal conjugate vaccines (PCVs).Methodology. A total of 885 isolates and 278 S. pneumoniae PCR-positive clinical specimens were referred to the Central Laboratory of Public Health (LCSP) within the meningitis and pneumonia laboratory based-surveillance network in the period 2006-2020. Conventional and molecular microbiological techniques were used for confirmation and characterization.Results. We identified 563 cases of pneumococcal disease in the pre-vaccination period, 325 cases in the post-PCV10 period and 275 cases in the post-PCV13 period. The serotypes covered by PCV10 decreased from 78.6-6.5 %. However, additional serotypes covered by PCV13 increased from 6.6-57.5% and non-PCV13 serotypes increased from 14.8-36.0 % (P<0.001) in the post-PCV13 period. In cases of meningitis, the rate of resistance to penicillin decreased after the introduction of conjugate vaccines. No resistance to ceftriaxone was found in any period. In cases without meningitis, the rate of resistance to penicillin and ceftriaxone decreased slightly. However, the rate of resistance to erythromycin and tetracycline increased and that to trimethoprim-sulfamethoxazole (SXT) decreased in the post-PCV13 period compared to the pre-PCV period. The multidrug resistance rate was 8.5 %.Conclusion. A change in the circulating serotypes and antimicrobial resistance to certain antibiotics was observed. Non-vaccine serotype circulation and multidrug resistance may compromise the success of the conjugate vaccines.

Cost-Effectiveness Analysis of the South African Infant National Immunization Program for the Prevention of Pneumococcal Disease.

Pneumococcal disease, which presents a substantial health and economic burden, is prevented through pneumococcal vaccination programs. We assessed the impact of switching from a 13-valent-based (PCV13) to lower 10-valent-based (PCV10-GlaxoSmithKline [GSK] or PCV10-Serum Institute of India [SII]) or higher-valent (PCV15 or PCV20) vaccination programs in South Africa. A previously published decision-analytic model was adapted to a South African setting. Historical invasive pneumococcal disease (IPD) incidence data were used to project IPD incidence over time for each vaccination program on the basis of serotype coverage. Historical incidence (IPD, pneumonia, otitis media), mortality, costs, and utilities were obtained from the published literature. Cases of disease, direct medical costs (i.e., vaccination, IPD, pneumonia, and otitis media costs) (in 2022 South African rands), life-years, quality-adjusted life-years (QALY), and incremental cost per QALY were estimated over a 5- and 10-year horizon for PCV13 and the PCV10 vaccines. Additionally, a public health impact analysis was conducted comparing PCV13, PCV15, and PCV20. Continuing use of PCV13 would substantially reduce disease incidence over time compared with switching to either of the PCV10 lower-valent vaccines. Cases of IPD were reduced by 4.22% and 34.70% when PCV13 was compared to PCV10-GSK and PCV10-SII, respectively. PCV13 was also found to be cost saving over 5- and 10-year time horizons compared with PCV10-SII and to be cost-effective over a 5-year time horizon and cost-saving over a 10-year time horizon compared with PCV10-GSK. PCV20 was consistently estimated to prevent more cases than the PCV10 vaccines, PCV13, or PCV15. Switching from a higher-valent to a lower-valent vaccine may lead to disease incidence re-emergence caused by previously covered serotypes. Maintaining PCV13 was estimated to improve public health further by averting additional pneumococcal disease cases and saving more lives and also to reduce total costs in most scenarios. Higher-valent PCVs can achieve the greatest public health impact in the pediatric vaccination program in South Africa.

578. Cost-effectiveness of Infant Vaccination with PCV15 Compared to PCV13 in the United States

Abstract Background Streptococcus pneumoniae is a major cause of mortality and morbidity in young children. The 13-valent pneumococcal conjugate vaccine (PCV13) has been in routine use in children in the United States (US) since 2010. An investigational 15-valent vaccine (PCV15) that protects against two additional serotypes is currently under review by the FDA. This study aimed to evaluate the clinical and economic impact of routine infant vaccination with PCV15 compared with PCV13 from a US societal perspective. Methods A Markov decision-analytic model was developed to estimate the impact of PCV15 vs. PCV13 on pneumococcal disease incidence, post meningitis sequalae, and deaths. The model followed the entire US population over a 100-year time horizon, taking herd immunity effects into account. Each vaccination program comprised 3 primary doses and one booster for the new birth cohorts. Model inputs were obtained from the published literature, online databases, and unpublished data. PCV15 effectiveness was extrapolated from observed PCV13 data and PCV7 clinical trials. Costs (in 2021 USD) and quality-adjusted life years (QALYs) were discounted at 3% per year. Because the price for PCV15 in the pediatric indication is currently unknown, an analysis was conducted to determine the threshold price, which was defined as the maximum price for PCV15 to remain cost-saving. A series of sensitivity analyses were performed to test the robustness of model results. Results The base case results projected that PCV15 prevented 185,711 more invasive pneumococcal disease cases, 987,727 all-cause pneumonia cases and 11,151,473 pneumococcal acute otitis media and tube-replacement cases compared with PCV13. This resulted in an expected gain of 96,056 QALYs and total reduction of $7 billion in direct medical costs (excluding vaccine costs), and $4 billion in direct non-medical and indirect costs in the US population over the 100-year time horizon. The threshold price per dose for PCV15 was $28 higher than PCV13’s price. Sensitivity analyses showed the results to be robust over plausible values of key model inputs and assumptions. Conclusion Infant vaccination with PCV15 is projected to provide both clinical benefits and cost-savings compared with PCV13. Disclosures Min Huang, PhD, Merck &amp; Co., Inc.: full-time employee Tianyan Hu, Ph.D., Merck &amp; Co., Inc.: full time employee Jessica Weaver, PhD, MPH, Merck &amp; Co., Inc.: Employee Kwame Owusu-Edusei, Ph.D., Merck &amp; Co., Inc.: full time employee Elamin Elbasha, Ph.D., Merck &amp; Co., Inc.: full time employee.

576. Burden of Pneumococcal Disease Due to Serotypes Covered by the 13-Valent and New Higher-Valent Pneumococcal Conjugate Vaccines in All Children and Children at Risk in the United States

Abstract Background Routine vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) in infants along with a catch-up option with PCV13/PPSV23 in children with underlying medical conditions (UMC) have considerably reduced invasive pneumococcal disease (IPD) and non-invasive pneumococcal disease (PD), including community acquired pneumonia (CAP) and acute otitis media (AOM), in the United State (US). However, a rise in IPD and non-invasive PD caused by non-PCV13 serotypes has been observed. A 15-valent PCV (PCV15) and 20-valent PCV (PCV20), containing additional serotypes to PCV13, are anticipated for children soon. The objective of the study was to estimate the annual cases, deaths, and economic burden of disease attributable to PCV13, PCV15, and PCV20 serotypes in children &amp;lt; 18 years old overall and those with UMC in the US. Methods Estimated annual cases, deaths and direct medical costs associated with PD caused by PCV13, PCV15 and PCV20 serotypes were calculated based on published incidence rates of IPD, CAP, and AOM, along with age-group specific serotype coverage, case fatality rates, and disease-related costs (Table 1). The PD burden in those with UMC were extrapolated based on incidence rate ratios of those with UMC vs. those without UMC. The results were reported for 0-17 years and were further stratified into 2 age groups: 0-4 and 5-17 years. Table 1:Source Data for the Calculation Results The estimated annual PD cases attributable to PCV13, PCV15, and PCV20 serotypes in those 0-17 years were 768,301, 1,275,187, and 1,656,716 and in those with UMC were 23,209, 43,579, 63,949 (Table 2.1), respectively. The estimated direct medical costs were $494, $833, $1,103 million in those 0-17 years, and $76, $127, and $186 million in those with UMC, respectively (Table 3.1). The total estimated IPD cases in children with UMC were 18% (PCV13), 20% (PCV15) and 23% (PCV20) of all estimated IPD cases in all children. Conclusion This study demonstrates that the clinical and economic burden associated with new serotypes included in higher valent PCVs are substantial and higher in children with UMCs. The result shows that PCV20 will offer broader PCV coverage in the prevention of PD in ages &amp;lt; 18 years overall and those specifically with UMC. Disclosures Alejandro D. Cane, MD, PhD, Pfizer: Full time employee|Pfizer: Stocks/Bonds Johnna Perdrizet, MPH, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Adriano Arguedas, Medical director, Pfizer: Stocks/Bonds.

Estimated public health impact of human rotavirus vaccine (HRV) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV) on child morbidity and mortality in Gavi-supported countries

ABSTRACT Vaccine impact models against rotavirus disease (RD) and pneumococcal disease (PD) in low- and middle-income countries assume vaccine coverage based on other vaccines. We propose to assess the impact on severe disease cases and deaths avoided based on vaccine doses delivered by one manufacturer to Gavi-supported countries. From the number of human rotavirus vaccine (HRV) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV) doses delivered, we estimated the averted burden of disease 1) in a specific year and 2) for all children vaccinated during the study period followed-up until 5 years (y) of age. Uncertainty of the estimated impact was assessed in a probabilistic sensitivity analysis using Monte-Carlo simulations to provide 95% confidence intervals. From 2009 to 2019, approximately 143 million children received HRV in 57 Gavi-supported countries, avoiding an estimated 18.7 million severe RD cases and 153,000, deaths. From 2011 to 2019, approximately 146 million children received PHiD-CV in 36 countries, avoiding an estimated 5.0 million severe PD cases and 587,000 deaths. The number of severe cases and deaths averted for all children vaccinated during the study period until 5 years of age were about 23.2 million and 190,000, respectively, for HRV, and 6.6 million and 749,000, respectively, for PHiD-CV. Models based on doses delivered help to assess the impact of vaccination, plan vaccination programs and understand public health benefits. In 2019, HRV and PHiD-CV doses delivered over a 5-y period may have, on average, averted nine severe disease cases every minute and one child death every 4 min.