Background/Objectives: As heart failure (HF) patients face increased vulnerability to respiratory infections, optimizing pneumococcal and influenza vaccination coverage becomes pivotal for mitigating additional health risks and reducing hospitalizations, morbidity, and mortality rates within this population. In this specific subpopulation of patients, vaccination coverage for pneumococcal and influenza holds heightened significance compared to other vaccines due to their susceptibility to respiratory infections, which can exacerbate existing cardiovascular conditions and lead to severe complications or even death. However, despite the recognized benefits, vaccination coverage among HF patients remains below expectations. The aim of the present systematic review was to assess the vaccination coverage for influenza and pneumococcus in HF patients from 2005 to 2023 and the vaccination\'s effects on survival and hospitalizations. Methods: The authors developed the protocol of the review in accordance with the PRISMA guidelines, and the search was performed in databases including PubMed and Scopus. After the initial search, 851 studies were found in PubMed Library and 1961 in Scopus (total of 2812 studies). Results: After the initial evaluation, 23 publications were finally included in the analysis. The total study population consisted of 6,093,497 participants. Regarding the influenza vaccine, vaccination coverage ranged from low rates of 2.5% to very high rates of 97%, while the respective pneumococcal vaccination coverage ranged from 20% to 84.6%. Most studies demonstrated a beneficial effect of vaccination on survival and hospitalizations. Conclusions: The present systematic review study showed a wide variety of vaccination coverage among patients with heart failure.

Vaccination can prevent bacterial and viral infections that could otherwise increase the chances of receiving (unnecessary) antibiotic treatment(s). As a result, vaccination may provide an important public health intervention to control antimicrobial resistance (AMR).
Perform a systematic literature review to better understand the impact of influenza, pneumococcal and COVID-19 vaccination on antibiotic use, and to identify differences in effect between world regions and study designs.
We performed a systematic literature review and meta-analysis which updated previous literature reviews with new data from 1 October 2018 to 1 December 2021. The study focuses on randomised controlled trials (RCTs) and observational studies. Results from the meta-analysis of RCTs were stratified by WHO region and age group. Vote counting based on the direction of effect was applied to synthesize the results of the observational studies.
Most studies are performed in the WHO European Region and the Region of the Americas in high-income countries. RCTs show that the effect of influenza vaccination on the number of antibiotic prescriptions or days of antibiotic use (Ratio of Means (RoM) 0.71, 95% CI 0.62-0.83) is stronger compared to the effect of pneumococcal vaccination (RoM 0.92, 95% CI 0.85-1.00). These studies also confirm a reduction in the proportion of people receiving antibiotics after influenza vaccination (Risk Ratio (RR) 0.63, 95% CI 0.51-0.79). The effect of influenza vaccination in the European and American regions ranged from RoM 0.63 and 0.87 to RR 0.70 and 0.66, respectively. The evidence from observational studies supports these findings but presents a less consistent picture. No COVID-19 studies were identified.
We find that both RCTs and observational studies show that influenza vaccination significantly reduces antibiotic use, while the effect of pneumococcal vaccination is less pronounced. We were unable to study the effect of COVID-19 vaccination and no clear regional patterns were found due to the high heterogeneity between studies. Overall, our data supports the use of influenza vaccination as an important public health intervention to reduce antibiotic use and possibly control AMR.

OBJECTIVE: Cost-effectiveness analysis (CEA) is the standard framework for informing the efficient allocation of scarce healthcare resources. The importance of considering all relevant intervention strategies and appropriate incremental comparisons have both long been recognized in CEA. Failure to apply methods correctly can lead to suboptimal policies. Our objective is to assess if CEAs of infant pneumococcal vaccination apply appropriate methods with respect to the completeness of strategies assessed and incremental comparisons between them.
METHODS: We conducted a systematic search of the PubMed, Scopus, Embase, and Web of Science databases and performed a comparative analysis of the retrieved pneumococcal vaccination CEAs. We checked the appropriateness of the incremental analyses by attempting to replicate the published incremental cost-effectiveness (CE) ratios from the reported costs and health effects.
RESULTS: Our search returned twenty-nine eligible articles. Most studies failed to recognize one or more intervention strategies (n = 21). Incremental comparisons were questionable in four CEAs and insufficient reporting of cost and health effect estimates was identified in three studies. Overall, we only found four studies that made appropriate comparisons between all strategies. Lastly, study findings appear to be strongly associated with manufacturer sponsorship.
CONCLUSIONS: We found considerable scope for improvement regarding strategy comparison in the infant pneumococcal vaccination literature. To prevent overestimation of the CE of new vaccines, we urge greater adherence to existing guidelines recommending that all available strategies are evaluated to capture relevant comparators for CE evaluation. Closer adherence to existing guidelines will generate better evidence, leading to more effective vaccination policies.

Pneumococcal disease is a major cause of morbidity/mortality worldwide, and vaccination is an important measure in its prevention. Despite European children being vaccinated with pneumococcal conjugate vaccines (PCVs), pneumococcal infections are still a major cause of morbidity/mortality in adults with risk conditions and their vaccination might be an important prevention strategy. New PCVs have been approved, but information is lacking on their potential impact in European adults. In our review, we searched PubMed, MEDLINE, and Embase for studies on the additional PCV20 serotypes (concerning incidence, prevalence, disease severity, lethality, and antimicrobial resistance) in European adults, between January 2010 and April 2022, having included 118 articles and data from 33 countries. We found that these serotypes have become more prevalent in both invasive and non-invasive pneumococcal disease (IPD and NIPD), representing a significant proportion of cases (serotypes 8, 12F, 22F) and more serious disease and/or lethality (10A, 11A, 15B, 22F), showing antimicrobial resistance (11A, 15B, 33F), and/or affecting more vulnerable individuals such as the elderly, immunocompromised patients, and those with comorbidities (8, 10A, 11A, 15B, 22F). The relevance of pneumococcal adult carriers (11A, 15B, 22F, and 8) was also identified. Altogether, our data showed an increase in the additional PCV20 serotypes\' prevalence, accounting for a proportion of approximately 60% of all pneumococcal isolates in IPD in European adults since 2018/2019. Data suggest that adults, as older and/or more vulnerable patients, would benefit from vaccination with higher-coverage PCVs, and that PCV20 may address an unmet medical need.

BACKGROUND: Pneumococcal diseases (PDs) are among the leading causes of mortality and morbidity worldwide. However, the evidence on epidemiology, health economic, and patient-reported outcomes has not been systematically reviewed and published in Japan. This study aimed to assess the burden, treatment adherence and compliance, and serotype distribution associated with PDs in Japan.
METHODS: One hundred and eight studies were identified between January 2005 and June 2020. The identified studies were mostly regional and with a limited scale, clinical settings, and populations.
RESULTS: In 2013-2017, invasive PD incidence rates were 4.98-9.47/100,000 in <4-year-olds, 0.36/100,000 in 5-14-year-olds, 0.46/100,000 in 15-64-year-olds, and 1.50-5.38/100,000 in the elderly. The incidence of invasive PDs in children decreased from 24.6/100,000 in 2008 to 10.7/100,000 in 2013 after the introduction of PCV7 and further declined to 10.3/100,000 in 2014 after PCV13 was introduced. From 2014, the prevalence of PCV13 serotypes decreased across all age groups along with a decrease of PPV23 serotypes, but an increase of PPV23 serotypes not included in PCV13 among adults and the elderly. No study reported health-related quality-of-life data for PDs. In children, direct costs were 340,905-405,978 JPY (3,099-3,691 USD) per pneumococcal bacteraemia, 767,447-848,255 JPY (6,977-7,711 USD) per pneumococcal meningitis, and 79,000 JPY (718 USD) per pneumococcal acute otitis media episodes. In adults and the elderly, the direct cost of pneumococcal pneumonia was 348,280-389,630 JPY (3,166-3,542 USD). The average hospital stay length was 7.2-31.9 days in children, 9.0 days in adults and 9.0-28.7 days in adults and the elderly.
CONCLUSIONS: The epidemiological burden of PDs remains high in Japan, especially among children and the elderly with invasive PDs accounting for a very small proportion of all PDs. A significant impact of the PCV13 vaccine program was reported, while the PPV23\'s impact remains unclear. A substantial decrease in quality-adjusted life years in adults and the elderly and a high economic burden may exist.

UNASSIGNED: Modeling analyses have attempted to quantify the global impact of pneumococcal conjugate vaccines (PCVs) on pneumococcal disease (PD), however these pediatric models face several challenges in obtaining comprehensive impact measurements.
UNASSIGNED: We present several measurement challenges and discuss examples from recently published pediatric modeling evaluations. Challenges include estimating the number of infants fully or partially vaccinated with PCVs, inclusion of indirect effects of vaccination, accounting for various dosing schedules, capturing effect of PCVs on nonspecific, noninvasive PD, and inclusion of adult PCV use.
UNASSIGNED: The true impact of PCVs has been consistently underestimated in published analyses due to multiple measurement challenges. Nearly 100 million adults are estimated to have received PCV13 over the last decade globally, potentially preventing up to 662 thousand cases of PD. Approximately 4.1 million cases of invasive PD alone may have been averted through indirect protection. Estimates of PCV impact on noninvasive PD remain a challenge due to altered epidemiology. Program switches, incomplete vaccination, and private market uptake among children also confound PD impact estimates. Taken together, the number of averted PD cases from PCV use in the last ten years may be up to three times higher than estimated in previous studies.

BACKGROUND: Vaccine regulatory decision-making is based on vaccine efficacy against etiologically confirmed outcomes; however, these outcomes may underestimate the preventable disease burden. To quantify this underestimation, we compared vaccine-preventable disease incidence (VPDI) of clinically defined outcomes to radiologically/etiologically confirmed outcomes.
METHODS: We performed a systematic review of efficacy trials for several vaccines (1997-2019) and report results for pneumococcal conjugate vaccines [CRD42019145268]. Data were extracted for outcomes within a clinical syndrome, organized from most sensitive to most specific. VPDI was determined for each outcome, and VPDI ratios were calculated, with a clinically defined outcome (numerator) and a radiologically/etiologically confirmed outcome (denominator).
RESULTS: Among 9 studies, we calculated 27 VPDI ratios; 24 had a value >1. Among children, VPDI ratios for clinically defined versus vaccine serotype otitis media were 0.6 [95%CI not calculable], 2.1 [95%CI: 1.5;3.0], and 3.7 [95%CI: 1.0;10.2]; the VPDI ratios comparing clinically defined to radiologically confirmed pneumonia ranged from not calculable to 2.7 [95%CI: 1.2;10.4]; the VPDI ratio comparing clinically suspected invasive pneumococcal disease (IPD) to laboratory confirmed IPD was 3.8 [95%CI not calculable]. Among adults, the ratio comparing clinically defined to radiologically confirmed pneumonia was 1.9 [95%CI: -6.0;9.1] and to vaccine serotype confirmed pneumonia was 2.9 [95%CI: 0.5;7.8].
CONCLUSIONS: While there is substantial uncertainty around individual point estimates, there is a consistent trend in VPDI ratios, most commonly showing under-ascertainment of 1.5- to 4-fold, indicating that use of clinically defined outcomes is likely to provide a more accurate estimate of a pneumococcal conjugate vaccine\'s public health value.

OBJECTIVE: Streptococcus pneumoniae infections remain a significant source of morbidity and mortality worldwide. The purpose of this review was to summarize the impact of pneumococcal disease on health state utilities (HSU) in the acute phase of illness.
METHODS: We searched MEDLINE, EMBASE, EconLit, the Health Technology Assessment Database, the National Health Economic Evaluation Database, and Tufts Cost-Effectiveness Registry (up to January 2020) for primary studies. Eligible studies elicited HSU estimates using preference-based instruments for the acute phase of infection of pneumococcal syndromes including acute otitis media, pneumonia/lower respiratory tract infections, bacteremia/sepsis, and meningitis. Two reviewers independently conducted screening, data extraction and quality appraisal.
RESULTS: We screened 10,178 studies, of which 26 met our inclusion criteria. Cohort sizes ranged from 8 to 2060 respondents. The most frequently studied syndrome was pneumonia (n = 17), followed by acute otitis media (n = 9), meningitis (n = 7) and bacteremia/sepsis (n = 4). Overall, each syndrome was associated with a substantial impact on HSU. Bacteremia/sepsis (range: - 0.331 to 0.992) and meningitis (range: - 0.330 to 0.977) were generally associated with the lowest HSU, followed by pneumonia (range: - 0.054 to 0.998) and acute otitis media (range: 0.064 to 0.970). HSU estimates varied considerably by treatment setting, elicitation method and type of respondent. The only study to compare pneumococcal infections to non-pneumococcal infections in the same population revealed significantly lower HSU estimates among pneumococcal infections.
CONCLUSIONS: Pneumococcal syndromes are associated with decreased HSU estimates. Given the considerable heterogeneity in methods and source populations as well as study quality, care should be taken to select the most appropriate estimates.

BACKGROUND: Estimates in the research literature on the health-related quality of life (QOL) associated with pneumococcal disease exhibit variation. It complicates the selection of estimates in modeling projects that evaluate the health impact and economic value of the prevention and treatment. This study reviewed the literature and developed pooled QOL estimates associated with pneumococcal disease states.
METHODS: We searched peer-reviewed literature for studies that reported pneumococcal disease-related QOL estimates. For each study, we extracted QOL estimates and categorized by age group and disease state. QOL estimates were converted to quality-adjusted life-years (QALYs). Pooled QALY estimates were calculated using simple average, sample-size weighting and inverse-variance weighting.
RESULTS: From 18 studies, we organized QOL estimates into 20 groups based on age and disease state. We observed the largest within-disease state variations of QALY estimates in meningitis-related disease states compared to other disease states. Across all age-disease state categories, the pooled QALY estimates ranged from 0.39 for meningitis with long-term sequelae among 0- to 18-year-olds, to 1.00 for non-inpatient pneumonia among 0- to 18-year-olds.
CONCLUSIONS: Our results indicated disparities in QOL estimates associated with pneumococcal disease from the literature. Pooled estimates provided a source of consistency that can be used in future modeling efforts.

This narrative review describes the epidemiology of invasive pneumococcal diseases, nasopharyngeal carriage, and antibiotic resistance of Streptococcus pneumoniae serotypes, and vaccination coverage in children in the Philippines. Epidemiological data show that, despite the availability of the free-of-cost 13-valent pneumococcal conjugate vaccine for infants as part of the National Immunization Program, the burden of pneumococcal disease in young children remains high in the Philippines. The significant variability in data reported between studies highlights an urgent need for active and comprehensive disease surveillance for more accurate estimates of pneumococcal disease in the country. Although data from 2001 to 2013 show high rates of pneumococcal carriage in children in the Philippines aged < 5 years, contemporary data are lacking, again emphasizing the need for active surveillance programs. The introduction of pneumococcal conjugate vaccines has resulted in substantial declines in disease caused by pneumococcal serotypes included in the vaccines, but the emergence of pneumococcal disease due to nonvaccine serotypes is an ongoing concern. Surveillance of actively circulating serotypes is critical to better understand vaccine coverage. Antimicrobial resistance of S. pneumoniae remains a significant threat to public health worldwide; data regarding antibiotic resistance in young children in the Philippines are limited, but reports generally show low rates of antibiotic resistance in this group. National immunization rates have increased in recent years, yet many individuals are still unprotected from pneumococcal disease. Overall, there is a critical need for contemporary and accurate disease surveillance in the Philippines. Such data would provide better estimates of pneumococcal disease incidence, serotype distribution, and antibiotic resistance to better inform vaccination strategies and to ensure that children in the Philippines are best protected against pneumococcal disease.