Clinical and economic burden of acute otitis media caused by Streptococcus pneumoniae in European children, after widespread use of PCVs-A systematic literature review of published evidence.

BACKGROUND: Acute otitis media (AOM) is a common childhood disease frequently caused by Streptococcus pneumoniae. Pneumococcal conjugate vaccines (PCV7, PCV10, PCV13) can reduce the risk of AOM but may also shift AOM etiology and serotype distribution. The aim of this study was to review estimates from published literature of the burden of AOM in Europe after widespread use of PCVs over the past 10 years, focusing on incidence, etiology, serotype distribution and antibiotic resistance of Streptococcus pneumoniae, and economic burden. METHODS: This systematic review included published literature from 31 European countries, for children aged ≤5 years, published after 2011. Searches were conducted using PubMed, Embase, Google, and three disease conference websites. Risk of bias was assessed with ISPOR-AMCP-NPC, ECOBIAS or ROBIS, depending on the type of study. RESULTS: In total, 107 relevant records were identified, which revealed wide variation in study methodology and reporting, thus limiting comparisons across outcomes. No homogenous trends were identified in incidence rates across countries, or in detection of S. pneumoniae as a cause of AOM over time. There were indications of a reduction in hospitalization rates (decreases between 24.5-38.8% points, depending on country, PCV type and time since PCV introduction) and antibiotic resistance (decreases between 14-24%, depending on country), following the widespread use of PCVs over time. The last two trends imply a potential decrease in economic burden, though this was not possible to confirm with the identified cost data. There was also evidence of an increase in serotype distributions towards non-vaccine serotypes in all of the countries where non-PCV serotype data were available, as well as limited data of increased antibiotic resistance within non-vaccine serotypes. CONCLUSIONS: Though some factors point to a reduction in AOM burden in Europe, the burden still remains high, residual burden from uncovered serotypes is present and it is difficult to provide comprehensive, accurate and up-to-date estimates of said burden from the published literature. This could be improved by standardised methodology, reporting and wider use of surveillance systems.

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

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

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

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

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

BACKGROUND: Despite 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. METHODS: We 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). RESULTS: Among 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. CONCLUSIONS: In 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.

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.

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

Objective: 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. Methods: 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. 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. Conclusion: 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.

Cost-effectiveness of use of 20-valent pneumococcal conjugate vaccine among adults in Germany.

OBJECTIVES: Despite national recommendations for use of pneumococcal vaccines, rates of community-acquired pneumonia (CAP) and invasive pneumococcal disease (IPD) remain high in Germany. New pneumococcal conjugate vaccines (PCVs) with expanded coverage have the potential to reduce the pneumococcal disease burden among adults. METHODS: Using a Markov model, we evaluated the lifetime outcomes/costs comparing 20-valent PCV (PCV20) with standard of care (SC) vaccinations for prevention of CAP and IPD among adults aged ≥60 years and at-risk adults aged 18-59 years in Germany. PCV20 also was compared with sequential vaccination with 15-valent PCV (PCV15) followed by PPSV23 in a scenario analysis. RESULTS: Over the course of a lifetime (82 years), use of PCV20vs. SC would prevent 54,333 hospitalizations, 26368 outpatient CAP cases, 10946 disease-related deaths yield 74,694 additional life-years (LYs), while lowering total medical costs by 363.2 M €. PCV20 remained cost saving (i.e. dominant) versus SC even in numerous sensitivity analyses, including a sensitivity analysis assuming moderate effectiveness of the SC pneumococcal polysaccharide vaccine against noninvasive pneumococcal CAP. In several scenario analyses and a probabilistic sensitivity analysis, PCV20 was also cost-saving compared toPCV15 PPSV23 vaccination. CONCLUSIONS: One dose of PCV20 among adults aged ≥60 years and adults aged 18-59 years with moderate- and high-risk conditions wouldsubstantially reduce pneumococcal disease, save lives, and be cost saving compared with SC.

Cost-effectiveness analysis of pediatric immunization program with 15-valent pneumococcal conjugate vaccine in Japan.

BACKGROUND: The 15-valent pneumococcal conjugate vaccine (PCV15 or V114) has recently been approved for pediatric vaccination against pneumococcal diseases (PDs) in Japan. The study aims to evaluate the cost-effectiveness of pediatric vaccination with V114 versus 13-valent PCV (PCV13) in Japan. METHODS: The study used a decision analytical Markov model to estimate the cost and effectiveness outcomes for a birth cohort in Japan over a 10-year time horizon. The model tracked the occurrences of acute PD events, including invasive PD (IPD), non-bacteremic pneumococcal pneumonia (NBPP) and pneumococcal acute otitis media (AOM) and the long-term impact of post-meningitis sequalae. Vaccine effectiveness was estimated based on literature and assumptions, and accounted for indirect effects and vaccine waning. The base case took the societal perspective, including both direct and indirect costs, while a healthcare payer perspective was modeled in a scenario analysis. Additional scenario analyses and sensitivity analyses were conducted. RESULTS: In the base case, V114 was associated with an incremental gain of 24 quality-adjusted life years and a reduction of ¥365,610,955 in total costs compared to PCV13. It was expected to reduce the number of pneumococcal AOM, NBPP, and IPD cases by 1,832, 1,333 and 25, respectively. All scenario analyses and most sensitivity analyses showed that V114 was a dominant strategy compared to PCV13. CONCLUSIONS: Pediatric vaccination with V114 is expected to lead to cost savings and more health benefits compared to PCV13 in Japan from both societal and healthcare payer perspectives. The findings are robust under plausible assumptions and inputs.

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.

Economic burden of acute otitis media, pneumonia, and invasive pneumococcal disease in children in the United States after the introduction of 13-valent pneumococcal conjugate vaccines during 2014-2018.

BACKGROUND: Streptococcus pneumoniae remains a leading cause of morbidity, mortality, and healthcare resource utilization (HRU) among children. This study quantified HRU and cost of acute otitis media (AOM), pneumonia, and invasive pneumococcal disease (IPD). METHODS: The IBM MarketScan® Commercial Claims and Encounters and Multi-State Medicaid databases from 2014 to 2018 were analyzed. Children with AOM, all-cause pneumonia, or IPD episodes were identified using diagnosis codes in inpatient and outpatient claims. HRU and costs were described for each condition in the commercial and Medicaid-insured populations. National estimates of the number of episodes and total cost ($US 2019 for each condition were extrapolated using data from the US Census Bureau. RESULTS: Approximately 6.2 and 5.6 million AOM episodes were identified in commercial and Medicaid-insured children, respectively, during the study period. Mean cost per AOM episode was $329 (SD $1505) for commercial and $184 (SD $1524) for Medicaid-insured children. A total of 619,876 and 531,095 all-cause pneumonia cases were identified among commercial and Medicaid-insured children, respectively. Mean cost per all-cause pneumonia episode was $2304 (SD $32,309) in the commercial and $1682 (SD $19,282) in the Medicaid-insured population. A total of 858 and 1130 IPD episodes were identified among commercial and Medicaid-insured children, respectively. Mean cost per IPD episode was $53,213 (SD $159,904) for commercial and $23,482 (SD $86,209) for the Medicaid-insured population. Nationally, there were over 15.8 million cases of AOM annually, with total estimated cost of $4.3 billion, over 1.5 million cases of pneumonia annually, with total cost of $3.6 billion, and about 2200 IPD episodes annually, for a cost of $98 million. CONCLUSIONS: The economic burden of AOM, pneumonia, and IPD among US children remains substantial. IPD and its manifestations were associated with higher HRU and costs per episode, compared to AOM and all-cause pneumonia. However, owing to their higher frequencies, AOM and all-cause pneumonia were the main contributors to the economic burden of pneumococcal disease nationally. Additional interventions, such as the development of pneumococcal conjugate vaccinees with sustained protection of existing vaccine type serotypes as well as broader inclusion of additional serotypes, are necessary to further reduce the burden of disease caused by these manifestations.

Cost-effectiveness of pneumococcal vaccines among adults aged 65 years and older in China: A comparative study.

We aimed to assess the cost-effectiveness and health benefits of 23-valent pneumococcal polysaccharide vaccine (PPSV23), 13-valent pneumococcal conjunctive vaccine (PCV13), and PCV13-PPSV23 sequential vaccination strategies in preventing pneumonia and other pneumococcal diseases among the senior citizens (≥ 65 years) in China. The cost-effectiveness of pneumococcal vaccines compared to no vaccination was estimated using a decision-tree Markov model from a societal perspective. Parameters including epidemiological data, vaccine efficacy and cost data were obtained from previous studies. Cases and deaths averted, quality-adjusted life years (QALYs) gained, and incremental cost-effectiveness ratios (ICERs) were presented as outcomes. Sensitivity analyses were performed to explore the uncertainty in the model. In the base-case analysis, compared with no pneumococcal vaccination, the ICERs of PPSV23, PCV13 and PCV13-PPSV23 are US$10,776.7/QALY, $9,193.2/QALY, and $15,080.0/QALY, respectively. PCV13 is the most cost-effective strategy and the only cost-effective strategy based on a threshold of the one-time national GDP per capita, whereas PPSV23 vaccine strategy is provided with the lowest cost, and PCV13-PPSV23 demonstrates the greatest impact on pneumococcal disease burden. Sensitivity analyses reveal that the results are greatly influenced by serotype coverage, vaccine efficacy, CAP incidence and vaccine prices. The PCV13 vaccination for Chinese seniors is more cost-effective than PPSV23 vaccination and PCV13-PPSV23 sequential vaccination.

Association of Pneumococcal Conjugate Vaccine Use With Hospitalized Pneumonia in Medicare Beneficiaries 65 Years or Older With and Without Medical Conditions, 2014 to 2017.

Importance: The association of 13-valent pneumococcal conjugate vaccine (PCV13) use with pneumonia hospitalization in older adults, especially those with underlying medical conditions, is not well described. Objective: To evaluate the association of PCV13 use with pneumonia, non-health care-associated (non-HA) pneumonia, and lobar pneumonia (LP) hospitalization among US Medicare beneficiaries 65 years or older. Design, Setting, and Participants: This cohort study with time-varying exposure assignment analyzed claims data from US Medicare beneficiaries 65 years or older enrolled in Parts A/B with a residence in the 50 US states or the District of Columbia by September 1, 2014. New Medicare Parts A/B beneficiaries within 6 months after their 65th birthday were continuously included in the cohort after September 1, 2014, and followed through December 31, 2017. Participants were censored if they died, changed enrollment status, or developed a study outcome. Most of the analyses were conducted from 2018 to 2019, and additional analyses were performed from 2021 to 2022. Exposures: Use of PCV13 vaccination 14 days or more before pneumonia hospitalization. Main Outcomes and Measures: Discrete-time survival models were used to estimate the incidence rate ratio (IRR) and number of pneumonia hospitalizations averted through PCV13 use. The adjusted IRR for the association of PCV13 vaccination with pneumonia hospitalization was used to estimate vaccine effectiveness (VE). Results: At the end of follow-up (December 2017), 24 121 625 beneficiaries (13 593 975 women [56.4%]; 418 005 [1.7%] Asian, 1 750 807 [4.8%] Black, 338 044 [1.4%] Hispanic, 111 508 [0.5%] Native American, and 20 700 948 [85.8%] White individuals) were in the cohort; 4 936 185 (20.5%) had received PCV13 only, and 10 646 220 (79.5%) had not received any pneumococcal vaccines. More than half of the beneficiaries in the cohort were younger than 75 years, White, and had either immunocompromising or chronic medical conditions. Coverage with PCV13 increased from 0.8% (September 2014) to 41.5% (December 2017). The VE for PCV13 was estimated at 6.7% (95% CI, 5.9%-7.5%) for pneumonia, 4.7% (95% CI, 3.9%-5.6%) for non-HA pneumonia, and 5.8% (95% CI, 2.6%-8.9%) for LP. From September 2014 through December 2017, an estimated 35 127 pneumonia (95% CI, 33 011-37 270), 24 643 non-HA pneumonia (95% CI, 22 761-26 552), and 1294 LP (95% CI, 797-1819) hospitalizations were averted through PCV13 use. Conclusions and Relevance: The study results suggest that PCV13 use was associated with reduced pneumonia hospitalization among Medicare beneficiaries 65 years or older, many of whom had underlying medical conditions. Increased PCV13 coverage and use of recently approved higher-valent pneumococcal conjugate vaccines may avert additional pneumonia hospitalizations in adults.

Cost-effectiveness of 20-valent pneumococcal conjugate vaccine in Denmark compared with PPV23.

BACKGROUND: A new 20-valent pneumococcal conjugate vaccine (PCV20) provides protection against 20 pneumococcal serotypes. The vaccine has the potential to decrease the impact of pneumococcal diseases in society and to increase health among vulnerable persons. AIM: This study investigates the cost-effectiveness of vaccinating Danish adults in different age groups and risk of pneumococcal disease with PCV20 compared to the 23-valent pneumococcal polysaccharide vaccine (PPV23) - either as PCV20 compared to PPV23 or as PPV23 followed by PCV20 compared to PPV23. METHODS: A Markov model adapted to the Danish setting was developed to estimate clinical outcomes and costs of vaccinating the Danish population in specific age and risk groups. The model used a restricted societal perspective and estimated outcomes and costs using a lifetime time horizon. To estimate the clinical outcomes and costs, inputs on vaccine effectiveness and waning were retrieved from other studies whereas data on risk groups, coverage and costs were based on real-world data. RESULTS: The results showed that in all scenarios the incidence and mortality of pneumococcal disease were reduced when vaccinating with PCV20, resulting in lower costs. For the vaccine target group of adults aged ≥18 years at moderate or high risk and all adults aged ≥65 years both in the case of PPV23+PCV20 compared to PPV23 and in case of PCV20 compared to PPV23 vaccination with PCV20 was found to be a dominant strategy gaining 1,350 or 5,821 quality-adjusted life years (QALYs), respectively, and reducing total costs by 60 or 396 million EUR, respectively, as compared to PPV23 vaccination alone. Similar results of dominant PCV20 strategy were found for other age and risk group comparisons. Both deterministic and probabilistic sensitivity analyses confirmed the results being robust to changes in input parameters and applied assumptions. LIMITATIONS: Like other modelling studies, this analysis has limitations such as lack of detailed data for some inputs. CONCLUSION: Vaccination with PCV20 reduced the incidence and mortality of pneumococcal diseases in Danish adults compared to PPV23. This reduction has the potential to reduce the financial burden related to managing diseases while also increasing public health.

Return on Investment of 10-Valent Pneumococcal Conjugate Vaccine in Ecuador From 2010 to 2030.

OBJECTIVES: Ecuador introduced the pneumococcal conjugate vaccine in 2010. A recent time series analysis has demonstrated the impact of 10-valent pneumococcal conjugate vaccine (PCV10) on hospitalized pneumococcal disease in children. We leveraged these estimates to calculate the return on investment (ROI) of PCV10 in Ecuador from 2010 to 2030 at the national and regional levels. METHODS: We used 2 approaches to estimate the economic benefits: (1) cost of illness, which includes treatment, transportation, and productivity loss averted, (2) and the value of statistical life, which reflects society's average willingness to pay to save one life. Costs of the immunization program include vaccine costs (doses, syringes, injection supplies) and immunization delivery costs (personnel, cold chain equipment and maintenance, transportation, distribution services, and other recurrent costs). We estimated the ROI by dividing the net benefits by costs. RESULTS: The ROI using the cost-of-illness approach was slightly negative in the introduction year. From 2011 to 2020, we estimated the ROI to be 0.45 (0.15-0.73). For the future decade, the ROI is estimated at 0.37 (-0.03 to 1.03). Using the value-of-statistical-life approach, the ROI was 1.46 (0.82-2.17) in the introduction year. In the first decade, the ROI was 1.01 (0.49-1.60); in the second decade, the ROI fell to 0.83 (0.23-1.78). CONCLUSIONS: The results of this study demonstrate the total economic benefits of PCV10 in Ecuador exceed immunization program costs after the introduction year. Estimates from this study will inform country policy makers and will contribute to efforts to mobilize resources for immunization.

Healthcare Costs for Pneumococcal Disease in the Era of Infant Immunization With 13-Valent Pneumococcal Conjugate Vaccine: A Population-Based Study.

OBJECTIVES: Invasive pneumococcal disease (IPD) and a variety of clinical syndromes caused by pneumococci, such as acute otitis media (AOM), acute sinusitis (AS), and community-acquired pneumonia (CAP), cause a substantial burden on healthcare systems. Few studies have explored the short-term financial burden of pneumococcal disease after the 13-valent pneumococcal conjugate vaccine (PCV13) introduction in the infant immunization programs. This population-based study evaluated changes in costs associated with healthcare utilization for pneumococcal disease after the PCV13 introduction in the infant immunization program in British Columbia, Canada. METHODS: Individuals with pneumococcal disease were identified using provincial administrative data for the 2000 to 2018 period. Total direct healthcare costs were determined using case-mix methodology for hospitalization and fee-for-service codes for outpatient visits and medications dispensed. Costs were adjusted to 2018 Canadian dollars. Changes in the annual healthcare costs were evaluated across vaccine eras (pre-PCV13, 2000-2010; PCV13, 2011-2018) using generalized linear models, adjusting for the 7-valent pneumococcal conjugate vaccine program (2004-2010). RESULTS: During the 19-year study period, pneumococcal disease resulted in 6.3 million cases among 85 million total patient-years, resulting in total healthcare costs of $7.9 billion. More than 6.2 million cases were treated in outpatient setting, costing $0.65 billion (8% of total costs associated with pneumococcal disease treatment), whereas 370 000 hospitalized cases were 3% of all cases, which accrued $7.25 billion (92% of total costs) in costs. Healthcare costs for all studied infections nearly doubled over the study period from $248 million in 2000 to $476 million in 2018 (P = .003). In contrast, there were large declines in total annual costs in the PCV13 era for IPD (adjusted relative rate (aRR) 0.73; 95% confidence interval [CI] 0.56-0.95; P = .032), AOM (aRR 0.70; 95% CI 0.59-0.83; P = .001), and AS (aRR 0.68; 95% CI 0.54-0.85; P = .004) compared with the pre-PCV13 era. Total costs increased marginally in the PCV13 era for all-cause CAP (aRR 1.04; 95% CI 0.94-1.15; P = .484). CONCLUSIONS: This study confirms a temporal association in declining economic burden for IPD, AOM, and AS after the PCV13 introduction. Nevertheless, the total economic burden continues to be high in the PCV13 era, mainly driven by increasing CAP costs.

Cost-effectiveness of the 15-valent pneumococcal conjugate vaccine for high-risk adults in Switzerland.

BACKGROUND: Vaccination against pneumococcal disease (PD) has shown a favorable cost-effectivenessprofile for many national immunization programs. While vaccination efforts have concentrated on children, many adults with underlying illnesses face elevated risks of PD and death. A 15-valent pneumococcal conjugate vaccine (V114) is currently available offering protection against 15 different serotypes and can be used in adults. RESEARCH DESIGN AND METHODS: We examined the cost-effectiveness of V114 vaccination in high-risk adults, aged 18+, in Switzerland. To this end, a Markov model was constructed estimating the lifetime direct medical costs and clinical effectiveness of V114 vaccination on invasive pneumococcal disease (IPD) and non-bacteremic pneumococcal pneumonia (NBPP). RESULTS: Considering 60% vaccine uptake and direct effects of vaccination, in total 760 IPD and 4,396 NBPP in- and outpatient cases could be prevented. Vaccinating high-risk adults with V114 led to CHF 37.4 million additional vaccination costs but saved CHF 14.4 million of medical treatment costs. V114 vaccination produced a gain of 2,095 QALYs and 6,320 LYs compared with no vaccination, leading to incremental cost-effectiveness ratios of CHF 17,866/QALY and CHF 15,616/QALY gained from a health care payer and societal perspective, respectively. CONCLUSIONS: This evidence justifies the implementation of V114 vaccination among high-risk adults in Switzerland.

Cost-Effectiveness of Pneumococcal Vaccines for Adults Aged 65 Years and Older in Argentina.

OBJECTIVES: In 2017, the Argentine Ministry of Health incorporated a sequential 13-valent pneumococcal conjugate vaccine (PCV13)-23-valent pneumococcal polysaccharide vaccine (PPSV23) regimen for adults aged ≥65 years to reduce pneumococcal disease burden. Cost-effectiveness analysis of PCV13-PPSV23 schedule for adults aged ≥65 years in Argentina was performed compared with PPSV23 only. METHODS: Markov model was developed. Local data were incorporated for costs and disease burden analysis. Vaccine efficacy or effectiveness was obtained from a systematic review adjusted to current local vaccine serotype circulation and vaccines coverage. A total of 3 scenarios were evaluated: main scenario according to published literature of pneumonia incidence, epidemiologic surveillance scenario based on Argentine Ministry of Health data, and an alternative scenario assuming a 50% hypothetical pneumonia incidence reduction resulting from herd immunity induced by childhood vaccination. Sensitivity analyses were done. RESULTS: Sequential PCV13-PPSV23 schedule showed cost-savings results in the main scenario with -$1 667 742.23 saved and 716 life-years gained (LYG). The epidemiologic surveillance scenario showed an incremental cost-effectiveness ratio of $2141.92 per LYG and an alternative scenario with $3740.30 per LYG. Tornado diagram shows widest bars related to adjustment for vaccine-type pneumococcal pneumonia (urine analysis) pneumonia at risk cost and pneumonia incidence rate. Monte Carlo simulation shows that >98% of simulations were cost-saving for the main scenario. CONCLUSIONS: In the main scenario, cost-saving results were obtained considering only reduction of vaccine serotype coverage after the introduction of childhood PCV13 vaccination. In the epidemiologic surveillance and alternative scenarios, assuming a hypothetical incidence reduction, highly cost-effective results were observed.

Incidence and disease burden of community-acquired pneumonia in southeastern China: data from integrated medical resources.

Community-acquired pneumonia (CAP) is a lower respiratory tract infection. It is one of the commonest infectious diseases and the third leading cause of death worldwide. However, the epidemiological profiles of CAP in southeastern China are unknown. Data of inpatients and outpatients diagnosed with CAP from January 1, 2015 to December 31, 2020 were obtained from the National Healthcare Big Data in Fuzhou (Fuzhou Database). This database covers medical data from 37 hospitals and 159 community health service stations. The incidence rate, treatment pattern, and direct medical costs of CAP were assessed using clinical data. A total of 8,156,237 patients were enrolled, with a mean age of 33.72 ± 20.88 years. The overall incidence rate of CAP was 3.13 (95% confidence interval [CI]: 3.11-3.15) per 1000 person-years (PY), with 15.97 (95% CI: 15.85-16.08) per 1000 PY in children below 5 years old and 2.62 (95% CI: 2.57-2.66) per 1000 PY in the elderly ≥60 years. The cost per outpatient was $242.83 ± 341.62, and the cost per inpatient was $4,530.4 ± 9,151.68. The three most used therapeutic drugs in patients with CAP are cefotaxime, moxifloxacin, and azithromycin. In addition, despite the ability of both imported and domestic pneumococcal conjugate vaccines to reduce the incidence rate of CAP, the current vaccination coverage rates were relatively low. We suggest that more attention should be paid to the disease burden of CAP, especially due to its great economic burden in China.

Age-stratified burden of pneumococcal community acquired pneumonia in hospitalised Canadian adults from 2010 to 2015.

BACKGROUND: In Canada, 13-valent pneumococcal conjugate vaccine (PCV13) is recommended in childhood, in individuals at high risk of invasive pneumococcal disease (IPD) and in healthy adults aged ≥65 years for protection against vaccine-type IPD and pneumococcal community-acquired pneumonia (pCAP). Since vaccine recommendations in Canada include both age-based and risk-based guidance, this study aimed to describe the burden of vaccine-preventable pCAP in hospitalised adults by age. METHODS: Surveillance for community-acquired pneumonia (CAP) in hospitalised adults was performed prospectively from 2010 to 2015. CAP was radiologically confirmed, and pCAP was identified using blood and sputum culture and urine antigen testing. Patient demographics and outcomes were stratified by age (16-49, 50-64, ≥65 and ≥50 years). RESULTS: Of 6666/8802 CAP cases tested, 830 (12.5%) had pCAP, and 418 (6.3%) were attributed to a PCV13 serotype. Of PCV13 pCAP, 41% and 74% were in adults aged ≥65 and ≥50 years, respectively. Compared with non-pCAP controls, pCAP cases aged ≥50 years were more likely to be admitted to intensive care units (ICUs) and to require mechanical ventilation. Older adults with pCAP were less likely to be admitted to ICU or required mechanical ventilation, given their higher mortality and goals of care. Of pCAP deaths, 67% and 90% were in the ≥65 and ≥50 age cohorts, respectively. CONCLUSIONS: Adults hospitalised with pCAP in the age cohort of 50-64 years contribute significantly to the burden of illness, suggesting that an age-based recommendation for adults aged ≥50 years should be considered in order to optimise the impact of pneumococcal vaccination programmes in Canada.

The cost-effectiveness of using pneumococcal conjugate vaccine (PCV13) versus pneumococcal polysaccharide vaccine (PPSV23), in South African adults.

Streptococcus pneumoniae (pneumococcus) remains an important cause of morbidity and mortality. Pneumococcal vaccination is part of the South African pediatric public immunization program but the potential cost-effectiveness of such an intervention for adults is unknown. This study aimed to compare the cost-effectiveness of two widely used pneumococcal vaccines: pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide vaccine (PPSV23) in South African adults, 18 years and older. Four analyses were carried out in a) both the private and public health care sectors; and b) for the HIV-infected population alone and for the total mixed population (all HIV-infected and -uninfected people). A previously published global pharmacoeconomic model was adapted and populated to represent the South African adult population. The model utilized a Markov-type process to depict the lifetime clinical and economic outcomes of patients who acquire pneumococcal disease in 2015, from a societal perspective. Costs were sourced in South African rand and converted to US dollar (USD). The incremental cost divided by the incremental effectiveness (expressed as quality-adjusted life years gained) represented the incremental cost-effectiveness ratio for PCV13 compared to PPSV23. Results indicated that the use of PCV13 compared to PPSV23 is highly cost-effective in the public sector cohorts with incremental cost-effectiveness ratios of $771 (R11,106)/quality-adjusted life year and $956 (R13,773)/quality-adjusted life year for the HIV-infected and mixed populations, respectively. The private sector cohort showed similar highly cost-effective results for the mixed population (incremental cost-effectiveness ratio $626 (R9,013)/quality-adjusted life year) and the HIV-infected cohort (dominant). In sensitivity analysis, the model was sensitive to vaccine price and effectiveness. Probabilistic sensitivity analyses found predominantly cost-effective ICERs. From a societal perspective, these findings provide some guidance to policy makers for consideration and implementation of an immunization strategy for both the public and private sector and amongst different adult patient pools in South Africa.