Twenty-Year Public Health Impact of 7- and 13-Valent Pneumococcal Conjugate Vaccines in US Children.

Pneumococcal conjugate vaccines (PCVs) have been used in the United States since 2000. To assess the cumulative 20-year effect of PCVs on invasive pneumococcal disease (IPD) incidence among children <5 years of age, we analyzed Active Bacterial Core Surveillance data, conducted a literature review, and modeled expected and observed disease. We found that PCVs have averted >282,000 cases of IPD, including ≈16,000 meningitis, ≈172,000 bacteremia, and ≈55,000 bacteremic pneumonia cases. In addition, vaccination has prevented 97 million healthcare visits for otitis media, 438,914-706,345 hospitalizations for pneumonia, and 2,780 total deaths. IPD cases declined 91%, from 15,707 in 1997 to 1,382 in 2019. Average annual visits for otitis media declined 41%, from 78 visits/100 children before PCV introduction to 46 visits/100 children after PCV13 introduction. Annual pneumonia hospitalizations declined 66%-79%, from 110,000-175,000 in 1997 to 37,000 in 2019. These findings confirm the substantial benefits of PCVs for preventing IPD in children.

Estimating the Population Newly Eligible for the Pneumococcal Conjugate Vaccine.

INTRODUCTION: Recommendations for adult pneumococcal vaccination in the U.S. were revised in 2022 after the introduction of 15- and 20-valent pneumococcal conjugate vaccines (PCV15 and PCV20) to call for routine PCV use among immunocompetent adults with risk conditions aged 19-64 years. The present study estimated the size of this newly recommended population. METHODS: A retrospective cohort study was conducted using the Optum de-identified electronic health record (EHR) dataset. Patients who were active in the EHR between January 2016 and June 2021 and had ≥1 condition included in the current pneumococcal recommendation without an immunocompromising condition were included. Data were weighted to account for potential differences between the EHR and U.S. POPULATION: Data analyses were conducted in 2022. RESULTS: Of 45.6 million adults aged 19-64 years in the database, 12.5 million met inclusion criteria and had ≥1 qualifying condition, primarily smoking, with chronic lung disease/asthma and/or diabetes also common. After weighting, the U.S. population aged 19-64 years newly eligible for PCVs was approximately 56 million. CONCLUSIONS: Approximately one in four U.S. adults aged <65 years is now recommended to receive PCV15 or PCV20, which highlights the need for providers to assess vaccination status, administer the vaccine, or refer patients as appropriate, as well as the need for tools to facilitate patient identification and vaccination.

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

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

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

INTRODUCTION: 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 6 years with chronic medical conditions (CMC+) and children aged 6 years with immunocompromising conditions (IC) versus one and two doses of 23-valent pneumococcal polysaccharide vaccine (PPSV23), respectively. METHODS: 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 6 years. 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. RESULTS: 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 6 years 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. CONCLUSIONS: 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.

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

BACKGROUND: As 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. METHODS: A 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. RESULTS: Replacing 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. CONCLUSIONS: Infant vaccination with PCV20 is estimated to further reduce pneumococcal disease and associated healthcare system and societal costs compared to both PCV13 and PCV15.

Pneumococcal vaccine uptake among Medicare Beneficiaries aged ≥65 years following the shared clinical decision-making recommendation for 13-valent pneumococcal conjugate vaccine in 2019.

BACKGROUND: In November 2019, the US Advisory Committee on Immunization Practices recommended shared clinical decision-making (SCDM) for use of 13-valent pneumococcal conjugate vaccine (PCV13) among immunocompetent elderly adults. The impact of SCDM on PCV13 use in this population, immunocompromised persons, and vulnerable subgroups has not been well documented. METHODS: Using Medicare Research Identifiable Files (01/2018 - 09/2020), monthly uptake of pneumococcal vaccine (PCV13, 23-valent pneumococcal polysaccharide vaccine [PPSV23]) was identified among fee-for-service beneficiaries aged ≥ 65 years with Part B coverage and no evidence of prior PCV13. Uptake was stratified by vaccine, risk profile, and demographics. RESULTS: Among the > 12 M beneficiaries included each month, PCV13 uptake declined from > 70% of pneumococcal vaccinations before SCDM to < 60% after SCDM (02/2020). Reductions in PCV13 uptake were consistent across vulnerable subgroups as well as immunocompromised persons. CONCLUSIONS: PCV13 use decreased among immunocompetent and immunocompromised persons alike, despite continued routine PCV13 recommendation for the latter group.

Risk of Pneumococcal Disease in US Adults by Age and Risk Profile.

Background: Older age and certain medical conditions are known to modify the risk of pneumococcal disease among adults. We quantified the risk of pneumococcal disease among adults with and without medical conditions in the United States between 2016 and 2019. Methods: This retrospective cohort study used administrative health claims data from Optum's de-identified Clinformatics Data Mart Database. Incidence rates of pneumococcal disease-all-cause pneumonia, invasive pneumococcal disease (IPD), and pneumococcal pneumonia-were estimated by age group, risk profile (healthy, chronic, other, and immunocompromising medical condition), and individual medical condition. Rate ratios and 95% CIs were calculated comparing adults with risk conditions with age-stratified healthy counterparts. Results: Among adults aged 18-49 years, 50-64 years, and ≥65 years, the rates of all-cause pneumonia per 100 000 patient-years were 953, 2679, and 6930, respectively. For the 3 age groups, the rate ratios of adults with any chronic medical condition vs healthy counterparts were 2.9 (95% CI, 2.8-2.9), 3.3 (95% CI, 3.2-3.3), and 3.2 (95% CI, 3.2-3.2), while the rate ratios of adults with any immunocompromising condition vs healthy counterparts were 4.2 (95% CI, 4.1-4.3), 5.8 (95% CI, 5.7-5.9), and 5.3 (95% CI, 5.3-5.4). Similar trends were observed for IPD and pneumococcal pneumonia. Persons with other medical conditions, such as obesity, obstructive sleep apnea, and neurologic disorders, were associated with increased risk of pneumococcal disease. Conclusions: The risk of pneumococcal disease was high among older adults and adults with certain risk conditions, particularly immunocompromising conditions.

Incidence and clinical outcomes of pneumonia in persons with down syndrome in the United States.

BACKGROUND: Persons with Down syndrome (DS) experience an increased risk of pneumonia. We determined the incidence and outcomes of pneumonia and relationship to underlying comorbidities in persons with and without DS in the United States. METHODS: This retrospective matched cohort study used de-identified administrative claims data from Optum. Persons with DS were matched 1:4 to persons without DS on age, sex, and race/ethnicity. Pneumonia episodes were analyzed for incidence, rate ratios and 95 % confidence intervals, clinical outcomes, and comorbidities. RESULTS: During 1-year follow-up among 33796 persons with and 135184 without DS, the incidence of all-cause pneumonia (pneumonia) was substantially higher among people with DS than those without DS (12427 vs. 2531 episodes/100000 person-years; 4.7-5.7 fold increase). Persons with DS and pneumonia were more likely to be hospitalized (39.4 % vs. 13.9 %) or admitted to the ICU (16.8 % vs. 4.8 %). Mortality was higher 1 year after first pneumonia (5.7 % vs. 2.4 %; P < 0.0001). Results were similar for episodes of pneumococcal pneumonia. Specific comorbidities were associated with pneumonia, particularly heart disease in children and neurologic disease in adults, which only partially mediated the effect of DS on pneumonia. CONCLUSIONS: Among persons with DS, incidence of pneumonia and associated hospitalizations were increased; mortality among those with pneumonia was comparable at 30 days, but higher at 1 year. DS should be considered an independent risk condition for pneumonia.

Burden of pneumococcal disease due to serotypes covered by the 13-valent and new higher-valent pneumococcal conjugate vaccines in the United States.

The addition of pneumococcal conjugate vaccines (PCVs) to the United States (US) national immunization program led to significant reductions in incidence, mortality, and associated sequelae caused by pneumococcal disease (PD) in children and adults through direct and indirect protection. However, there remains clinical and economic burden due to PD caused by serotypes not included in the current 13-valent PCV (PCV13) formulation. To address this unmet need, 15-valent PCV (PCV15) and 20-valent PCV (PCV20), containing additional serotypes to PCV13, were recently approved in the US for adults and are anticipated for pediatrics in the near future. The study objective was to estimate the annual number of cases, deaths, and economic burden of PD due to serotypes included in PCV13, PCV15, and PCV20 for both US pediatric and adult populations. An Excel-based model was developed to calculate clinical and economic outcomes using published age-group specific serotype coverage; incidence of invasive PD, community-acquired pneumonia, and acute otitis media; case fatality rates; and disease-related costs. The results showed that across all age groups, the estimated annual PD cases and associated deaths covered by PCV13 serotypes were 914,199 and 4320, respectively. Compared with PCV13 serotypes, the additional 2 and 7 serotypes covered by PCV15 and PCV20 were attributed with 550,475 and 991,220 annual PD cases, as well as 1425 and 3226 annual deaths, respectively. This clinical burden translates into considerable economic costs ranging from $903 to $1,928 million USD that could be potentially addressed by PCV15 and PCV20. The additional serotypes included in PCV20 contribute substantially to the clinical and economic PD burden in the US pediatric and adult populations. Despite the success of the PCV13 pediatric national immunization program and increased adult uptake of PCV13 and 23-valent polysaccharide vaccine, broader PCV serotype coverage is needed across all ages to further reduce pneumococcal disease burden.

Hospital discharge diagnosis position: impact on adult pneumonia burden estimates.

OBJECTIVES: Pneumonia hospitalization studies using administrative claims rely on pneumonia coded in the first discharge diagnosis field over pneumonia in any coded field, and few have evaluated disposition following discharge. This study reports the total disease burden and discharge disposition among patients with pneumonia coded in any diagnosis field. STUDY DESIGN: Retrospective database review. METHODS: Data from the 2014 National Inpatient Sample of the Healthcare Cost and Utilization Project, a population-weighted, 20% sample of all US community hospitalizations, were analyzed for all pneumonia hospitalizations in adults aged 18 to 64 years and 65 years or older. Number of hospitalizations, hospital stay length, direct medical costs, in-hospital mortality, patient discharge disposition, illness severity, and likelihood of dying were evaluated based on the diagnosis field of pneumonia as a discharge diagnosis (eg, first, second, third, or further). RESULTS: In 2014, an estimated 2.4 million US adult hospitalizations were associated with pneumonia in any of the discharge diagnosis positions (33%-35% in first, 33%-36% in second, and 29%-34% in further positions). When estimates were based only on hospitalizations with pneumonia in the first diagnosis field, approximately 66% of hospitalizations, 78% of hospital days, 87% of in-hospital deaths, 76% and 73% of transfers to short-term hospitals and skilled nursing facilities, 68% of discharges with home health care services, and 82% of direct medical costs were excluded. CONCLUSIONS: Pneumonia hospitalizations were associated with substantial health care resource utilization and in-hospital mortality. Relying only on pneumonia in the first hospital diagnosis field may potentially underestimate the burden associated with pneumonia hospitalizations.

Uptake of 13-Valent Pneumococcal Conjugate Vaccine among US Adults Aged 19 to 64 Years with Immunocompromising Conditions.

The CDC Advisory Committee on Immunization Practices (ACIP) recommended immunization with the recently licensed 13-valent pneumococcal conjugate vaccine (PCV13) for high-risk (immunocompromised) adults aged ≥19 years in 2012. This was in addition to the 23-valent pneumococcal polysaccharide vaccine (PPSV23). Data on vaccine-specific uptake among these individuals were previously unavailable. This retrospective observational study analyzed PCV13 uptake in immunocompromised patients aged 19-64 years. Data were acquired from insurance claims (N = 267,022) and electronic health records (EHR; N = 572,055) from October 2011-October 2016. Descriptive statistics were provided. Demographics were similar across the two database cohorts: mean age 49.7-51.0 years, 57-62% female, and >70% white. Iatrogenic immunosuppression was the most common high-risk category (33.3-44.2%). PCV13 uptake was 7.3% (95% CI: 7.25-7.45) in insurance claims and 9.9% (95% CI: 9.80-9.96) in EHR. Patients with HIV had the highest rate of PCV13 uptake; patients with multiple risk factors were above the mean in both cohorts. A Kaplan-Meier analysis was conducted to include patients lost to follow-up, with 441,657 and 722,071 patients for insurance claims and EHR, respectively. PCV13 uptake was only slightly higher: 9.3% (95% CI: 9.14-9.47) and 13.1% (95% CI: 12.93-13.19) for insurance claims and EHR, respectively. Four years after the ACIP 2012 recommendation, PCV13 uptake in high-risk adults aged19-64 years was low at <15% in all overall analyses. Clinicians caring for these patients should ensure adherence to the ACIP recommendation to minimize the risk of pneumococcal disease.

Immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine in patients with immunocompromising conditions: a review of available evidence.

Immunocompromising conditions increase the risk of invasive pneumococcal disease (IPD). Vaccine uptake in patients with these conditions may be low in part because of concerns about decreased immunogenicity and safety in these high-risk groups. We conducted a literature search to identify publications describing antibody responses to 13-valent pneumococcal conjugate vaccine (PCV13) in immunocompromised individuals recommended for PCV13 vaccination by the US Advisory Committee on Immunization Practices (ACIP). This review summarizes immunogenicity data from 30 publications regarding the use of PCV13 comprising 2406 individuals considered at high risk for IPD by the ACIP. Although antibody responses to PCV13 in individuals with immunocompromising and high-risk conditions were variable and generally lower compared with healthy controls, the vaccine was immunogenic and was largely well tolerated. Based on these findings, concerns regarding immunogenicity and safety of PCV13 are not supported and should not be barriers to vaccination in high-risk populations.