Invasive Pneumococcal Disease Cases Research Articles

Chemical Synthesis of Truncated Capsular Oligosaccharide of Serotypes 6C and 6D of Streptococcus pneumoniae with Their Immunological Studies.

Serotypes 6C and 6D of Streptococcus pneumoniae are two major variants that cause invasive pneumococcal disease (IPD) in serogroup 6 alongside serotypes 6A and 6B. Since the introduction of the pneumococcal conjugate vaccines PCV7 and PCV13, the number of cases of IPD caused by pneumococcus in children and the elderly population has greatly decreased. However, with the widespread use of vaccines, a replacement effect has recently been observed among different serotypes and lowered the effectiveness of the vaccines. To investigate protection against the original serotypes and to explore protection against variants and replacement serotypes, we created a library of oligosaccharide fragments derived from the repeating units of the capsular polysaccharides of serotypes 6A, 6B, 6C, and 6D through chemical synthesis. The library includes nine pseudosaccharides with or without exposed terminal phosphate groups and four pseudotetrasaccharides bridged by phosphate groups. Six carbohydrate antigens related to 6C and 6D were prepared as glycoprotein vaccines for immunogenicity studies. Two 6A and two 6B glycoconjugate vaccines from previous studies were included in immunogenicity studies. We found that the conjugates containing four phosphate-bridged pseudotetrasaccharides were able to induce good immune antibodies and cross-immunogenicity by showing superior activity and broad cross-protective activity in OPKA bactericidal experiments.

Invasive Pneumococcal Disease (IPD) epidemiology and serotype replacement after the introduction of the 13-valent pneumococcal conjugate vaccine in Ontario, Canada, 2007-2022

Abstract Introduction New vaccine products were recently authorized for protection against invasive pneumococcal disease (IPD) in Canada. Our aim was to determine age- and serotype-specific trends in IPD incidence and severity in Canada’s largest province, Ontario. Methods We included all confirmed IPD cases reported in Ontario and defined the pre-PCV13 era (01/2007 to 12/2010), post-PCV13 era (01/2011 to 12/2019), and COVID-19 pandemic era (01/2020 to 12/2022). We estimated incidence, hospitalization, and case fatality rate (CFR) by age. We grouped IPD cases by vaccine-specific serotypes (PCV13; PCV15-non-PCV13; PCV20-non-PCV13; PCV20-non-PCV15; PPV23-non-PCV20; and non-vaccine preventable [NVP]). We then compared incidence rates by age and serotype groups in the pre- and post-PCV13 era by calculating rate ratios (RR) and their 95% confidence intervals (CI). Results Incidence and hospitalizations declined from the pre- to post-PCV13 era in children aged <5 years (RR = 0.7, 95%CI = 0.6-0.8 and RR = 0.8, 95%CI = 0.7-0.9, respectively) but the CFR increased (1.4% to 2.3%). Other age groups saw smaller declines or more stable incidence rates across the years; hospitalizations increased in adults aged 50-64 years (RR = 1.2, 95%CI 1.1-1.4) and ≥65 years (RR = 1.1, 95%CI 1.0-1.1). For all ages, IPD cases and hospitalizations attributable to PCV13 serotypes declined and those attributable to PCV15-non-PCV13, PCV20-non-PCV-13, and NVP serotypes increased. IPD incidence declined during the COVID-19 era. Conclusions IPD incidence and hospitalizations due to PCV13 serotypes decreased after PCV13 introduction but increased for other serotypes. Continued surveillance is required to evaluate changes to pneumococcal vaccination programs and ongoing changes to the distribution of IPD-causing serotypes.

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.

Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease among children in the United States between 2010 and 2019: An indirect cohort study

BackgroundA U.S. case-control study (2010–2014) demonstrated vaccine effectiveness (VE) for ≥ 1 dose of the thirteen-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) invasive pneumococcal disease (IPD) at 86 %; however, it lacked statistical power to examine VE by number of doses and against individual serotypes. MethodsWe used the indirect cohort method to estimate PCV13 VE against VT-IPD among children aged < 5 years in the United States from May 1, 2010 through December 31, 2019 using cases from CDC’s Active Bacterial Core surveillance, including cases enrolled in a matched case-control study (2010–2014). Cases and controls were defined as individuals with VT-IPD and non-PCV13-type-IPD (NVT-IPD), respectively. We estimated absolute VE using the adjusted odds ratio of prior PCV13 receipt (1-aOR x 100 %). ResultsAmong 1,161 IPD cases, 223 (19.2 %) were VT cases and 938 (80.8 %) were NVT controls. Of those, 108 cases (48.4 %; 108/223) and 600 controls (64.0 %; 600/938) had received > 3 PCV13 doses; 23 cases (17.6 %) and 15 controls (2.4 %) had received no PCV doses. VE ≥ 3 PCV13 doses against VT-IPD was 90.2 % (95 % Confidence Interval75.4–96.1 %), respectively. Among the most commonly circulating VT-IPD serotypes, VE of ≥ 3 PCV13 doses was 86.8 % (73.7–93.3 %), 50.2 % (28.4–80.5 %), and 93.8 % (69.8–98.8 %) against serotypes 19A, 3, and 19F, respectively. ConclusionsAt least three doses of PCV13 continue to be effective in preventing VT-IPD among children aged < 5 years in the US. PCV13 was protective against serotypes 19A and 19F IPD; protection against serotype 3 IPD did not reach statistical significance.

Pneumococci isolated from children in community-based practice differ from isolates identified by population and laboratory-based invasive disease surveillance.

Characterizing strains causing noninvasive and invasive pneumococcal disease (IPD) may inform the impact of new pneumococcal conjugate vaccines (PCVs). During 2011-2019, among children aged 6-36 months, pneumococcal serotype distribution and antibiotic non-susceptibility of nasopharyngeal and middle ear fluid (MEF) isolates collected at onset of acute otitis media (AOM) in Rochester, New York were compared with IPD isolates from Active Bacterial Core surveillance (ABCs) across 10 U.S. sites. From Rochester, 400 (nasopharyngeal) and 156 (MEF) pneumococcal isolates were collected from 259 children. From ABCs, 907 sterile-site isolates were collected from 896 children. Non-PCV serotypes 35B and 21 were more frequent among the Rochester AOM cases, while serotypes 3, 19A, 22F, 33F, 10A, and 12F contained in PCVs were more frequent among ABCs IPD cases. The proportion of antibiotic non-susceptible pneumococcal isolates was generally more common among IPD cases. In 2015-2019, serotype 35B emerged as the most common serotype associated with multiclass antibiotic non-susceptibility for both the Rochester AOM and ABCs IPD cases. Pneumococcal isolates from children in Rochester with AOM differ in serotype distribution and antibiotic susceptibility compared to IPD cases identified through U.S. surveillance. Non-PCV serotype 35B emerged as a common cause of AOM and IPD.

Unveiling the role of preceding seasonal influenza in the development of bacteremic pneumococcal pneumonia in older adults before the COVID-19 pandemic in Japan

We aimed to investigate the impact of preceding seasonal influenza on the clinical characteristics of adult patients with invasive pneumococcal disease (IPD) in Japan. Data for 1722 adult patients with IPD were analyzed before (2017-2019) and during the COVID-19 pandemic (2020-2022). The seasonal influenza epidemic disappeared soon after the emergence of the pandemic. Compared with that before the pandemic (66.7%), we observed a lower bacteremic pneumonia proportion in patients with IPD during the pandemic (55.6%). The clinical presentations of IPD cases significantly differed between those with and without preceding influenza. The proportion of bacteremic pneumonia was higher in IPD patients with preceding influenza than in those without in both younger (44.9% vs 84.2%) and older adults (65.5% vs 87.0%) before the pandemic. The case fatality rate was significantly higher in IPD patients with preceding influenza (28.3%) than in those without (15.3%) in older adults before the pandemic (P = 0.020). Male and aging are high risk factors for death in older patients with IPD who had preceding influenza. Our study reveals that preceding seasonal influenza plays a role in the development of bacteremic pneumococcal pneumonia, increasing the risk of death in older adults.

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.

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

ABSTRACT 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.

Streptococcus pneumoniae serotype 3 population structure in the era of conjugate vaccines, 2001-2018.

Background. Despite use of highly effective conjugate vaccines, invasive pneumococcal disease (IPD) remains a leading cause of morbidity and mortality and disproportionately affects Indigenous populations. Although included in the 13-valent pneumococcal conjugate vaccine (PCV13), which was introduced in 2010, serotype 3 continues to cause disease among Indigenous communities in the Southwest USA. In the Navajo Nation, serotype 3 IPD incidence increased among adults (3.8/100 000 in 2001-2009 and 6.2/100 000 in 2011-2019); in children the disease persisted although the rates dropped from 5.8/100 000 to 2.3/100 000.Methods. We analysed the genomic epidemiology of serotype 3 isolates collected from 129 adults and 63 children with pneumococcal carriage (n=61) or IPD (n=131) from 2001 to 2018 of the Navajo Nation. Using whole-genome sequencing data, we determined clade membership and assessed changes in serotype 3 population structure over time.Results. The serotype 3 population structure was characterized by three dominant subpopulations: clade II (n=90, 46.9 %) and clade Iα (n=59, 30.7 %), which fall into Clonal Complex (CC) 180, and a non-CC180 clade (n=43, 22.4 %). The proportion of clade II-associated IPD cases increased significantly from 2001 to 2010 to 2011-2018 among adults (23.1-71.8 %; P<0.001) but not in children (27.3-33.3 %; P=0.84). Over the same period, the proportion of clade II-associated carriage increased; this was statistically significant among children (23.3-52.6 %; P=0.04) but not adults (0-50.0 %, P=0.08).Conclusions. In this setting with persistent serotype 3 IPD and carriage, clade II has increased since 2010. Genomic changes may be contributing to the observed trends in serotype 3 carriage and disease over time.

Impact of Demographic Developments and PCV13 Vaccination on the Future Burden of Pneumococcal Diseases in Germany—An Integrated Probabilistic Differential Equation Approach

Streptococcus pneumonia is the primary cause of morbidity and mortality in infants and children globally. Invasive pneumococcal disease (IPD) incidence is affected by various risk factors such as age and comorbidities. Additionally, this bacterium is a major cause of community-acquired pneumonia (CAP), leading to higher rates of hospitalization, especially among older adults. Vaccination with pneumococcal conjugate vaccines (PCVs) has proven effective, but the demographic transition in Germany poses a challenge. This study introduces a novel stochastic approach by integrating a population forecast model into a transmission dynamic model to investigate the future burden of pneumococcal diseases in three age groups (0–4, 5–59, and 60 and older). Our simulations, presented through mean predictions and 75% prediction intervals, indicate that implementing PCV13 (13-valent pneumococcal conjugate vaccine) until the year 2050 results in reduced cases of IPD and CAP in all age groups compared to scenarios without infant vaccination. However, cases with non-vaccine serotypes may persist at higher levels compared to scenarios without infant vaccination. Consequently, there may be a need for improvement in the current national vaccine policy, such as implementing the use of higher-valent PCVs and strengthening adult vaccination uptake.

Indirect impact of childhood 13-valent pneumococcal conjugate vaccine (PCV13) in Canadian older adults: a Canadian Immunization Research Network (CIRN) retrospective observational study

Background13-valent pneumococcal conjugate vaccine (PCV13) has been part of publicly funded childhood immunisation programmes in Ontario and British Columbia (BC) since 2010. We assessed the indirect impact of infant PCV13...

Mortality of Invasive Pneumococcal Disease following Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Greenland.

Before the incorporation of the 13-valent pneumococcal conjugate vaccine (PCV13) into the childhood vaccination regimen in Greenland in 2010, Inuit populations experienced a substantial prevalence of invasive pneumococcal disease (IPD). The PCV13 introduction has been shown to markedly reduce the incidence of IPD. This current study estimated the impact of PCV13 introduction on IPD mortality in Greenland. This was a nationwide register-based study using all available data on IPD cases 1995-2020 in Greenland. Thirty-one-day IPD case fatality rates (CFR), and all-cause and mortality rates associated with IPD during the period before the introduction of PCV13 (January 1995 to September 2010) were compared with those observed in the post-PCV13 era (September 2010 to October 2020). Standardized mortality ratios (SMRs) expressed differences in mortality by sex, age, region, ethnicity, comorbidity, and serotype. IPD CFR decreased with 24.5% from the pre- to the post-PCV13 period. SMR in IPD patients decreased by 57% (95% CI, 36-75%), and a reduction occurred in all age groups. While SMR in IPD persons ≥60 years remained virtually unchanged, there were no IPD-related deaths in persons ≤39 years in the post-PCV13 period. In conclusion, IPD-related mortality has decreased in Greenland following PCV13 introduction in 2010 in the country.

Invasive pneumococcal disease 3 years after introduction of a reduced 1 + 1 infant 13-valent pneumococcal conjugate vaccine immunisation schedule in England: a prospective national observational surveillance study

The UK transition from a 2 + 1 to a 1 + 1 infant immunisation schedule with the 13-valent pneumococcal conjugate vaccine (PCV13) on Jan 1, 2020, coincided with the start of the COVID-19 pandemic. We describe the epidemiology of invasive pneumococcal disease (IPD) in England over 6 financial years (April 1 to March 31) between 2017-18 and 2022-23. We used prospective national surveillance data, including serotyping and whole-genome sequencing of invasive isolates, to analyse IPD trends in England by age and financial year. We compared breakthrough infections and vaccine failure rates in 2022-23 among children eligible for the 1 + 1 schedule with rates in cohorts of children eligible for the 2 + 1 schedule between 2017-18 and 2019-20. We assessed genomic changes over time by comparing Global Pneumococcal Sequencing Clusters and multilocus sequence types among PCV13 serotypes causing IPD. There were 4598 laboratory-confirmed IPD cases in 2022-23, 3025 in 2021-22, 1240 in 2020-21, and 5316 in 2019-20. IPD incidence in 2022-23 was 14% lower than in 2019-20 (incidence rate ratio [IRR] 0·86, 95% CI 0·81-0·91; p<0·001). IPD incidence in 2022-23 compared with 2019-20 was 34% higher in children (aged <15 years) (378 cases vs 292 cases; IRR 1·34, 95% CI 1·08-1·68; p=0·009) and 17% lower in adults (aged 15 years and older; 4220 vs 5024; 0·83, 0·78-0·88; p<0·001). The proportion of PCV13-type IPD increased from 19·4% (95% CI 18·2-20·4; 957 of 4947) in 2019-20 to 29·7% (28·3-31·0; 1283 of 4326) in 2022-23, mainly due to serotype 3, but also serotypes 19F, 19A, and 4, alongside a decrease in non-PCV13 serotypes 8, 12F, and 9N. The increase in IPD incidence due to serotypes 3, 19A, and 19F was driven by clonal expansion of previously circulating strains, whereas serotype 4 expansion was driven by newer strains (ie, sequence types 801 and 15603). Breakthrough infections and vaccine failure rates were similar in children eligible for the 1 + 1 (1·08 per 100 000 person-years) and 2 + 1 (0·76 per 100 000 person-years; IRR 1·42, 95% CI 0·78-2·49; p=0·20) PCV13 schedules. Overall, IPD incidence in England was lower in 2022-23, 2 years after removal of pandemic restrictions, than in 2019-20. Breakthrough and vaccine failure rates were not significantly different between children who received the 1 + 1 compared with the 2 + 1 PCV13 immunisation schedule. The post-pandemic increase in childhood IPD incidence and especially PCV13-type IPD will require close monitoring. None.

Cost-effectiveness of the 20-valent pneumococcal conjugate vaccine versus the 23-valent pneumococcal polysaccharide vaccine for older adults in South Korea

BackgroundDespite the demonstrated immunogenicity and safety of the 20-valent pneumococcal conjugate vaccine (PCV20) in older adults, the cost-effectiveness of the PCV20 was not examined compared to the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in South Korea. Therefore, this study aimed to evaluate the cost-effectiveness of PCV20 compared with PPSV23 in adults aged 65 years and older in South Korea. MethodsWe constructed a Markov model that included susceptible states, invasive pneumococcal disease (IPD), non-bacteremic pneumonia (NBP), and death. The population was categorized by disease risk status (low risk, moderate risk, and high risk) and age group (65–74/75–84/85–99 years) at model entry. The annual incidence and mortality of IPD and NBP associated with PCV20 and PPSV23 were estimated based on serotype coverage, vaccine coverage, and vaccine effectiveness. The disease costs and utilities were obtained from previous studies. The incremental cost-effectiveness ratio (ICER) was used to evaluate cost-effectiveness within the threshold of 16,824 USD per quality-adjusted life-year (QALY). ResultsAmong the total population (n = 8,843,072), PCV20 prevented 1941 and 50,575 cases of IPDs and NBPs, respectively, and 898 and 8593 deaths due to IPDs and NBPs compared to PPSV23. The total medical cost per person was 12.11 USD higher in PCV20, with a gain of 0.0053 LYs and 0.0045 QALYs per person. The ICER for PCV20 and PPSV23 was 2270 USD/LY and 2677 USD/QALY. ConclusionsIn South Korea, PCV20 is a cost-effective option compared with PPSV23 for adults aged 65 years and older. These cost-effectiveness results provide evidence for decision-making regarding the approval and National Immunization Program implementation of PCV20.

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.

Invasive Pneumococcal Disease After 2 Decades of Pneumococcal Conjugate Vaccine Use.

We sought to describe the evolving epidemiology of invasive pneumococcal disease (IPD) among children in Massachusetts, United States, over the last 2 decades during which sequential 7-valent pneumococcal conjugate vaccines (PCV7) and 13-valent PCVs (PCV13) were implemented. Cases of IPD in children aged <18 years were detected between 2002 and 2021 through an enhanced population-based, statewide surveillance system. Streptococcus pneumoniae isolates from normally sterile sites were serotyped and evaluated for antimicrobial susceptibility. IPD incidence rates and rate ratios with 95% confidence intervals (CIs) were calculated. We identified 1347 IPD cases. Incidence of IPD in children aged <18 years declined 72% over 2 decades between 2002 and 2021 (incidence rate ratios 0.28, 95% CI 0.18-0.45). IPD rates continued to decline after replacement of PCV7 with PCV13 (incidence rate ratios 0.25, 95% CI 0.16-0.39, late PCV7 era [2010] versus late PCV13 era [2021]). During the coronavirus disease 2019 pandemic years, 2020 to 2021, the rate of IPD among children aged <18 years reached 1.6 per 100 000, the lowest incidence observed over the 20 years. In PCV13 era, approximately one-third of the IPD cases in children aged >5 years had at least 1 underlying condition (98, 30.3%). Serotypes 19A and 7F contributed 342 (48.9%) of all cases before implementation of PCV13 (2002-2010). Serotype 3 (31, 8.6%), and non-PCV13 serotypes 15B/C (39, 10.8%), 33F (29, 8.0%), 23B (21, 0.8%), and 35B (17, 4.7%) were responsible for 37.8% of cases in PCV13 era (2011-2021). Penicillin nonsusceptibility continued to decline (9.8% vs 5.3% in pre-/late PCV13 era, P = .003), however has become more common among non-PCV13 serotypes compared with vaccine serotypes (14.8% vs 1.4%, P < .001). Robust ongoing surveillance networks are critical for identifying emerging serotypes and development of next-generation vaccine formulations.

Effectiveness of ten-valent pneumococcal conjugate vaccine on invasive pneumococcal disease among children

The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in March 2015 in Bangladesh. In this study, we aimed to estimate the impact of PCV10 on invasive pneumococcal disease (IPD) identified by blood cultures and severe pneumonia identified clinically and its effectiveness on invasive disease caused by vaccine serotypes.We conducted population-based surveillance among children aged 2- <24 months between April 2012 through March 2019 in Mirzapur, a rural sub-district of Bangladesh. We compared incidence of IPD and severe pneumonia before (April 2012 to March 2015) and after (April 2015 to March 2019) the introduction of PCV10. Vaccine effectiveness was measured using an indirect cohort analysis of data from four sentinel sites in which PCV10 vaccination status was compared between children with IPD caused by vaccine serotype vs. non-vaccine serotypes.We identified 24 IPD cases by blood culture and 1,704 severe pneumonia hospitalizations during the surveillance period. IPD incidence in under-2-year-old children fell 25 % (95 % CI: −1.2 % to 76 %; p-value = 0.59) from 106 cases per 100,000 child-years at baseline to 79.3 in April 2018- March 2019. Vaccine serotype-IPD incidence was lower (77 % reduction, 95 % CI: −0.45 % to 96 %; p-value = 0.068) in April 2018 - March 2019 than in the pre-vaccine period (85.7 cases to 19.8/100,000 child-years). A significant decline of 54.0 % (95 % CI: 47.0 % to 59.0 %; p-value < 0.001) was observed in hospitalizations due to severe pneumonia. From indirect cohort analysis, the effectiveness of PCV10 against vaccine serotype IPD was 37 % (95 % CI: −141.0 % to 83.5 %; p = 0.5) after the 1st dose and 63.1 % (95 % CI: −3.3 % to 85.9 %, p = 0.0411) after the 2nd or the 3rd dose.This study demonstrates that PCV10 introduction prevented hospitalizations with severe pneumonia and provided individual protection against vaccine serotypes.

Potential Impact of Higher-Valency Pneumococcal Conjugate Vaccines Among Adults in Different Localities in Germany.

Next-generation pneumococcal conjugate vaccines (PCVs) have been approved for use. The serotype distribution of pneumococcal isolates can vary between regions. To understand the potential impacts of new PCVs, we evaluated trends in invasive pneumococcal disease (IPD) among adults in Germany at a local level using Bayesian hierarchical logistic regression. There was little spatial variation in IPD cases caused by PCV13 serotypes, which dropped from 60% of IPD cases in 2006 to 30% in 2018. Over half of IPD cases in 2018 were attributable to serotypes covered by new PCVs (PCV15, PCV20), which suggests they could further reduce the burden of IPD.

1735. Impact of Children Universal Pneumococcal Vaccination (PCV7v/PCV13v) on Pneumococcal Invasive Disease Hospitalizations in a Private General Hospital, Uruguay

Abstract Background In 2008 Uruguay included pneumococcal conjugate vaccine (PCV) 7valent in children´s vaccination program (2+1). In 2010 PCV13 replaced PCV7. Since 2015, adults at risk of invasive pneumococcal disease (IPD) may receive 23 valent polysaccharide vaccine (PV23) or combined schedule PCV13+PV23. Objective: to assess the impact of this strategy on IPD hospitalization. Methods Rates per 10,000 discharges (Confidence Interval 95 %), diseases and serotypes (ST) are described before PCV7 vaccination (2006-2007), the year of vaccine implementation (2008), early after implementation (2009-2015) and late after implementation (2016-2022), the last 3 years during COVID-19 pandemic. Results In 2006-2022 were 33 IPD cases in children and 88 in adults over 15 years old. Children´s hospitalization median annual rates were as follow 2006-2007: 50 (25-75); 2008: 18,5 (-2-39); 2009-2015: 8,5 (3-14); 2016-2022: 4 (0-8); percentages of rate reduction were 82,5% and 92% (p&amp;lt; 0.0000). In adults 2006-2007: 17 (10-25); 2008: 13,4 (4,62-22,1); 2009-2015: 6,6 (4,4-9); 2016-2022: 6 (3,5-8,5); percentages of rate reduction were 63,5% and 66 % (p= 0,0001). Pneumococcal pneumonia (PP) was the most frequent disease in children 22/33 (66,6%), followed by bacteremia 8/32. PP was also in adults 68/88 (77.2,7%), followed by meningitis (7/88). One non vaccinated child died in 2008. Case fatality rate in adults was 9% (8/88), 3 died in 2006-2007, 2 in 2009-20215 and 3 in 2016-2022. 24 different ST were isolated in adults. Most frequent ST were 12F(15), 7F(11), 1(8), 8(7), 3(6) and 5(6). PCV13 would cover 38/88 (43%). A significant decline in PCV13 serotypes (PCV13-ST) was observed comparing the period prior PCV 17/22 (77%) with the late period 8/24 (34%) (p&amp;lt; 0.0000). 15 different ST were isolated in children: 26 PCV13-ST. 16 prior 2008: most frequent ST 1(5), 14(4), 3(2) and 5(2). In 2009-2022 13 hospitalizations; PCV13-ST: 1(2), 19A(2), 14(1), 6B&amp;lt; (1), 9V(1), 3(1) and non PCV13-ST: 7B/C(1), 24F(1), 13(1), 15A(1), 15B(1). A significant decline of PCV13-ST was observed comparing the period prior PCV (15/16, 94%) with the late period (2/4, 50 %) (p&amp;lt; 0.0000). Conclusion There was a reduction in children’s discharge rates and in adults´ probably due to herd effect. Adult vaccination will improve individual immunization. Disclosures María Catalina Pírez, Pediatrician, Pediatric infectologist, microbiologist Professor of pediatric, Degree V, Merck, Pfizer: Expert Testimony|Merck, Pfizer: Honoraria

1737. Cost-Effectiveness Analysis of Catch-Up Vaccination with the 20-Valent Pneumococcal Conjugate Vaccine

Abstract Background A 20-valent pneumococcal vaccine (PCV20) was approved in April 2023 by the US FDA for use in children &amp;lt; 18 years of age. Routine use in infants consists of a 3-dose schedule followed by a booster dose between 12 and 15 months of age. In addition, a catch-up program for children previously vaccinated with PCV13 who remain at risk of disease associated with the 7 new covered serotypes in PCV20 can potentially improve direct protection and accelerate the onset of indirect effects in the population. This study evaluated the cost-effectiveness of a PCV20 catch-up program in US children aged 14– 59 months who previously completed the recommended PCV13 series. Methods A population-based, multi-cohort, decision-analytic Markov model was developed to estimate the public health impact and cost-effectiveness of a PCV20 catch-up program from both a societal (base-case) and health-care perspective over a 10-year time horizon. In the model a single supplemental dose was assumed to be given to 63% of children aged 14-59 months who had received a complete schedule of PCV13. Input parameters for costs, disutilities, and epidemiology of pneumonia and otitis media (OM) were extracted from published data sources. Data on invasive pneumococcal disease (IPD) were based on published and unpublished (ABC) data. PCV20 effectiveness estimates were based on PCV7/PCV13 studies. Results The direct and indirect effects of a PCV20 catch-up program was estimated to prevent an additional 5,500 invasive IPD cases, 270,000 pneumonia cases, 0.6 million OM cases, and 1800 deaths compared to a 3+1 PCV20 program without a PCV20 catch-up program. This corresponds to a net gain of 30,000 life years or 55,600 QALYs. Most health gains were achieved due to the assumed accelerated indirect effects because of the catch-up program. Acquisition costs for the PCV20 catch-up program were offset by monetary savings from averted disease cases resulting in $800 million net saving. The catch-up program was also dominant from the health-care perspective. Conclusion Implementation of a PCV20 catch-up program is expected to increase direct impact and accelerated indirect effects, more rapidly reducing pneumococcal disease burden and saving substantial health-care costs across the US population. Disclosures Mark Rozenbaum, Ph.D., M.B.A., Pfizer: Stocks/Bonds Liping Huang, MD, MA, MS, Pfizer Inc.: Stocks/Bonds Johnna Perdrizet, MPH, Pfizer Inc: Stocks/Bonds Alejandro D. Cane, MD, PhD, Pfizer: Stocks/Bonds Adriano Arguedas, Medical director, Pfizer: Emplyee|Pfizer: Stocks/Bonds Kyla hayford, PhD, Pfizer: Employee|Pfizer: Ownership Interest|Pfizer: Stocks/Bonds Maria J Tort, PhD, Pfizer Inc: Stocks/Bonds Ruth Chapman, MSc, PhD, Pfizer: Advisor/Consultant Vincenza Snow, MD, Pfizer Vaccines: employee|Pfizer Vaccines: Stocks/Bonds Erica Chilson, PharmD, Pfizer, Inc: Ownership Interest|Pfizer, Inc: Stocks/Bonds Ray Farkouh, PhD, Pfizer: Stocks/Bonds Desmond Dillon-Murphy, MSc, PhD, Pfizer: Advisor/Consultant