The emergent invasive serotype 4 ST10172 strain acquires vanG type vancomycin-resistance element: A case of a 66-year-old with bacteremic pneumococcal pneumonia.

We report a single case of invasive pneumococcal disease (IPD) by serotype 4, multilocus sequence type 10172 (serotype 4/ST10172) isolate with vanG-type resistance genes and reduced vancomycin susceptibility. The isolate was recovered during 2022 from a 66-year-old resident with bacteremic pneumococcal pneumonia within a CDC Active Bacterial Core surveillance (ABCs) site hospital. The patient had received 23-valent pneumococcal polysaccharide vaccine and there was no evidence of concurrent or prior receipt of vancomycin in the previous year. Serotype 4/ST10172 IPD has shown increases within western ABCs sites and the recent acquisition of a vanG element warrants close monitoring of this lineage.

Genetic characteristics of invasive pneumococcal disease-derived Streptococcus pneumoniae of serogroup 24 isolated in Tokyo, Japan.

BACKGROUND: Since the introduction of the national routine vaccination program against Streptococcus pneumoniae in Japan from the early 2010s, the incidence of invasive pneumococcal disease (IPD) caused by non-vaccine serotypes has increased. This study focused on non-vaccine serogroup 24 strains derived from IPD and aimed to clarify their genetic characteristics. METHODS: Between 2013 and 2022, 121 strains identified as serogroup 24 in patients with IPD were collected and applied to multilocus sequence typing and next-generation sequencing. Whole-genome data were used to delineate phylogenetic relationships and to identify virulence and antimicrobial resistance-associated genes. RESULTS: Recent trends in sequence types (STs) were characterized by an increase in the proportion of ST162 and ST2754 for 24F and 24B, respectively, after 2018. Whole-genome phylogenetic analysis demonstrated that serogroup 24 strains were organized into three clades, closely related to STs but not with serotypes. All ST162 strains were classified as Global Pneumococcal Sequence Cluster (GPSC) 6 and harbored the virulence-associated rlrA islet, with co-trimoxazole-resistance mutations in folA and folP genes. Two ST162 strains with different serotypes 24F and 24B from the same patient were phylogenetically indistinguishable, showing that these strains were derived by serotype conversion during infection. CONCLUSION: The recent changes in predominant STs were similar to those previously reported throughout Japan, except Tokyo. Little correlation between whole-genome phylogeny and serotypes and the observed serotype conversion in one patient indicate potentially variable immunogenicity of this serogroup.

Assessing the Impact of Pneumococcal Conjugate Vaccine Immunization Schedule Change From 3+0 to 2+1 in Australian Children: A Retrospective Observational Study.

BACKGROUND: In mid-2018, the Australian childhood 13-valent pneumococcal conjugate vaccine schedule changed from 3+0 to 2+1, moving the third dose to 12 months of age, to address increasing breakthrough cases of invasive pneumococcal disease (IPD), predominantly in children aged >12 months. This study assessed the impact of this change using national IPD surveillance data. METHODS: Pre- and postschedule change 3-dose 13-valent pneumococcal conjugate vaccine breakthrough cases were compared by age group, serotype, and clinical syndrome. Annual rates of breakthrough cases were calculated (per 100 000) using respective birth cohort sizes and 3-dose vaccine coverage. Using time-series modelling, observed IPD rates in children aged <12 years were compared to that expected if the 3+0 schedule were continued. FINDINGS: Over 2012-2022, rate of 3-dose breakthrough cases in children aged >12 months was 2.8 per 100 000 (n = 557; 11 birth cohorts). Serotype 3 replaced 19A as predominant breakthrough serotype (respectively, 24% and 65% in 2013 to 60% and 20% in 2022) followed by 19F. In breakthrough cases, the most frequent clinical phenotype was bacteremic pneumonia (69%), with meningitis accounting for 3%-4%. In cohorts eligible for 2+1 versus 3+0 schedules, rate of breakthrough cases was lower for all vaccine serotypes, except type 3 (incidence rate ratio, 0.50 [95% confidence interval, .28-.84] and 1.12 [0.71-1.76], respectively). Observed compared to expected IPD was 51.7% lower (95% confidence interval, -60.9 to -40.7%) for vaccine serotypes, but the change for nonvaccine types was not significant 12% (-9.6 to 39.7). INTERPRETATIONS: The 2+1 schedule is likely superior to 3+0 for overall IPD control, a finding that may be worth consideration for other countries considering or using 3+0 PCV schedules.

Hospital Burden of All-Cause Pneumonia and Nonbacteremic Pneumococcal Pneumonia in Adults in France Between 2013 and 2019.

Background: Community-acquired pneumonia (CAP) is associated with significant morbidity and mortality. The study objective was to describe the hospital burden of pneumonia in the adult population in France. Methods: This retrospective study was conducted from the National Health Insurance Database. All hospitalizations for pneumonia (all-cause) between 2013 and 2019 were included. Different risk categories for patients were established based on pneumococcal vaccine recommendations by French health authorities. Results: A total of 2 199 240 episodes of CAP were registered over the study period (annual mean, 314 177 [standard deviation, 17 818.6]); 75% occurred in patients aged ≥65 years, among whom 47% were not classified in the moderate- or high-risk categories recommended for French pneumococcal vaccination. The incidence of CAP increased with age (117.9, 395.3, and 1916.7 per 100 000 for the age groups 18-49, 50-64, and ≥65 years, respectively, in 2019). Furthermore, being at risk of pneumococcal disease resulted in more severe outcomes, including longer episode duration (mean, 14 days in low-risk vs 17 days in high-risk patients) and higher risk of referral to critical care units (from 20% to 27%), of rehospitalization up to 180 days (from 39% to 67%), of in-hospital death (from 12% to 19%), and of 1-year mortality (from 26% to 49%). Conclusions: This study establishes the incidence of CAP in adults in France, describes the significant burden of disease, and highlights the need for better prevention policies.

Pneumococcal carriage and disease in adults in England 2011-2019: the importance of adults as a reservoir for pneumococcus in communities.

BACKGROUND: Pneumococcal carriage in children has been extensively studied, but carriage in healthy adults and its relationship to invasive pneumococcal disease (IPD) is less understood. METHODS: Nasal wash samples from adults without close contact with young children (Liverpool, UK), 2011-2019, were cultured, and culture-negative samples tested by PCR. Pneumococcal carriage in adults 18-44 years was compared with carriage among PCV-vaccinated children 13-48 months (nasopharyngeal swabs, Thames Valley, UK) and IPD data for England for the same ages for 2014-2019. Age-group specific serotype invasiveness was calculated and used with national IPD data to estimate carriage serotype distributions for adults aged 65+ years. RESULTS: In total 98 isolates (97 carriers) were identified from 1,631 adults aged 18+ years (age and sex standardized carriage prevalence 6.4%), with only three identified solely by PCR. Despite different carriage and IPD serotype distributions between adults and children, serotype invasiveness was highly correlated (R=0.9). Serotypes 3, 37 and 8 represented a higher proportion of adult carriage than expected from direct low-level transmission from children to adults. The predicted carriage serotype distributions for 65+ years aligned more closely with the carriage serotype distribution for young adults than young children. CONCLUSIONS: The nasal wash technique is highly sensitive; additional benefit of PCR is limited. Comparison of carriage serotype distributions suggests some serotypes may be circulating preferentially within these specific young adults. Our data suggest that for some serotypes carried by adults 65+ years, other adults may be an important reservoir for transmission. Age groups such as older children should also be considered.

Serotype distribution of invasive pneumococcal disease from countries of the WHO Africa, Americas, Eastern Mediterranean, South-East Asia, and Western Pacific regions: a systematic literature review from 2010 to 2021.

Background: Most publications on invasive pneumococcal disease (IPD) serotype distribution are from about 20 countries (Australia, Canada, China, European Union members, Japan, New Zealand, South Korea, and USA). Here, we reviewed the literature among underrepresented countries in the Americas (AMRO), Africa (AFRO), Eastern Mediterranean (EMRO), South-East Asia (SEARO), and Western Pacific (WPRO) WHO regions. Methods: We performed a systematic review of the most recent IPD serotype surveillance publications (from 01/01/2010 to 31/12/2021, Medline/Embase) in those WHO regions. Selection criteria were delineated by contemporality, within-country geographical scope, and number of samples. Reported serotype distributions for each country were stratified by age group, pneumococcal conjugate vaccine (PCV) serotype category (considering undifferentiated serotypes), and PCV program period (pre-PCV, intermediate, or PCVhv [higher valency PCV formulation]). Pre-PCV period pooled data estimated PCV serotype category distribution by age group across WHO regions, while for the PCVhv period, country-level dataset tables were prepared. Results: Of 2,793 publications screened, 107 were included (58 pediatric, 11 adult, 37 all ages, and one comprising every age group). One-third of eligible countries (51/135) published serotype distribution, ranging from 30 to 43% by WHO region. Considering number of samples per WHO region, a few countries prevailed: AMRO (Brazil), AFRO (South Africa, Malawi, and Burkina Faso), and WPRO (Taiwan). In the pre-PCV period, PCV13 formulation serotypes predominated: ranging from 74 to 85% in children and 58-86% in adults in the different WHO regions. The PCVhv period represented half of the most recent IPD surveillance by countries (26/51). Undifferentiated serotypes represented >20% of IPD from most countries (34/51). Conclusion: Ubiquity of undifferentiated serotypes among the publications could constrain estimates of PCV program impact and of serotype coverage for newer PCVhv formulations; consequently, we recommend that countries favor techniques that identify serotypes specifically and, rather than reporting PCV formulation serotype distributions, provide serotype results individually. Systematic review registration: The protocol has been prospectively registered at PROSPERO, identifier: CRD42021278501. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278501.

Cardiovascular events after invasive pneumococcal disease: a retrospective cohort study.

OBJECTIVES: This study aims to understand the magnitude of and mechanisms underlying the development of cardiovascular events (CVEs) in patients with invasive pneumococcal disease (IPD). We aimed to identify factors that contribute to the occurrence of CVEs within 1 year after admission and discuss implications for patient care. METHODS: A multicentered cohort study included adult patients from four Dutch hospitals who had a positive blood culture for Streptococcus pneumoniae and any type of clinical manifestation between 2012 and 2020. Disease characteristics and microbiological data were systematically collected from electronic patient files. The main outcome measures were the occurrence of stroke and acute coronary syndromes (ACS). RESULTS: Of 914 eligible patients, 4.2% experienced a CVE within 1 year after admission for IPD. ACS mainly occurred in the first 2 weeks, whereas stroke developed throughout follow-up. Although ACS was positively associated with disease severity, the sole independent predictor was alcohol abuse (odds ratio [OR] 3.840, 95% confidence interval [CI] 1.108-13.303). Although stroke occurred in 6.3% of meningitis cases, the best clinical predictor of stroke was a body temperature >39.5 °C at admission (OR 3.117 [1.154-8.423]). In the adult IPD population aged <70 years, pneumococcal serotypes were the primary predictors of ACS (7F; OR 15.733 [1.812-136.632]) and stroke (22F; OR 7.320 [1.193-44.903]). CONCLUSIONS: Adverse CVEs were not uncommon after IPD diagnosis and deserve attention, especially in the high-risk groups we identified in our study population. Whether specific serotypes play a role in the development of CVE requires substantiation in further research.

Cost-effectiveness analysis of the 20-valent pneumococcal conjugate vaccine for the pediatric population in South Korea.

OBJECTIVES: To evaluate the cost-effectiveness of the 20-valent pneumococcal conjugate vaccine (PCV20) compared to 13-valent pneumococcal conjugate vaccine (PCV13) for the pediatric population in Korea, where the four-dose vaccine coverage rate is over 97%. METHODS: We constructed a Markov model to calculate the cost and quality-adjusted life-years (QALYs) over 10 years. The health states were susceptible states; disease states, which included invasive pneumococcal diseases such as meningitis, bacteremia, pneumonia, and acute otitis media; and death attributable to pneumococcal disease. The annual incidence and mortality due to pneumococcal diseases were estimated based on the serotypes covered by PCV13 and PCV20, vaccine coverage rate, vaccine effectiveness, and population size. Vaccine, administration, and disease costs were included in the model. RESULTS: In the total population (n = 51,431,305), PCV20 prevented more pneumococcal diseases and deaths, resulting in a gain of 74,855 QALY over PCV13. Meanwhile, the PCV20 group spent $275,136,631 less than the PCV13 group. As PCV20 gained more QALYs but spent less on total medical costs than PCV13, PCV20 was dominant over PCV13. CONCLUSIONS: In the Korean population, PCV20 is a cost-effective and dominant option over PCV13. Our findings provide evidence for decision-making regarding the introduction of PCV20 in countries with high vaccine coverage.

Cost-effectiveness analysis of the pediatric 20-valent pneumococcal conjugate vaccine compared with lower-valent alternatives in Argentina.

OBJECTIVES: The 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended for infants in Argentina's national immunization program (NIP) in a 2 + 1 schedule since 2012. Licensure of the 15-valent vaccine (PCV15) is anticipated soon, and the 20-valent vaccine (PCV20) recently received regulatory approval. This cost-effectiveness analysis examined the public health and economic implications of transitioning from PCV13 to either PCV15 or PCV20 in Argentina's pediatric NIP. METHODS: A decision-analytic Markov model was used with a 10-year time horizon and a 3.0% annual discount rate for costs and benefits. Vaccine effectiveness estimates were derived from Argentinian surveillance data, PCV13 clinical effectiveness and impact studies, and PCV7 efficacy studies. Population, epidemiologic, and economic inputs were obtained from literature and Argentinian-specific data. The study adopted a healthcare system perspective; sensitivity and scenario analyses were conducted to assess input parameters and structural uncertainty. RESULTS: Compared with PCV13, PCV20 was estimated to avert an additional 7,378, 42,884, and 172,389 cases of invasive pneumococcal disease (IPD), all-cause pneumonia, and all-cause otitis media (OM), respectively, as well as 3,308 deaths, resulting in savings of United States Dollars (USD) 50,973,962 in direct medical costs. Compared with PCV15, PCV20 was also estimated to have greater benefit, averting an additional 6,140, 35,258, and 142,366 cases of IPD, pneumonia, and OM, respectively, as well as 2,624 deaths, resulting in savings of USD 37,697,868 in direct medical costs. PCV20 was associated with a higher quality-adjusted life year gain and a lower cost (i.e., dominance) versus both PCV13 and PCV15. Results remained robust in sensitivity analyses and scenario assessments. CONCLUSION: Over a 10-year horizon, vaccination with PCV20 was expected to be the dominant, cost-saving strategy versus PCV13 and PCV15 in children in Argentina. Policymakers should consider the PCV20 vaccination strategy to achieve the greatest clinical and economic benefit compared with lower-valent options.

Elixhauser comorbidity method in predicting death of Spanish inpatients with asplenia and pneumococcal pneumonia.

BACKGROUND: Pneumococcal pneumonia (PP) is a serious infection caused by Streptococcus pneumoniae (pneumococcus), with a wide spectrum of clinical manifestations. The aim of this study was to analyze the comorbidity factors that influenced the mortality in patients with asplenia according to PP. METHODS: Discharge reports from the Spanish Minimum Basic Data Set (MBDS) was used to retrospectively analyze patients with asplenia and PP, from 1997 to 2021. Elixhauser Comorbidity Index (ECI) was calculated to predict in-hospital mortality (IHM). RESULTS: 97,922 patients with asplenia were included and 381 cases of PP were identified. The average age for men was 63.87 years and for women 65.99 years. In all years, ECI was larger for splenectomized than for non-splenectomized patients, with men having a higher mean ECI than women. An association was found between risk factors ECI, splenectomy, age group, sex, pneumococcal pneumonia, and increased mortality (OR = 0.98; 95% CI: 0.97-0.99; p < 0.001). The IHM increased steadily with the number of comorbidities and index scores in 1997-2021. CONCLUSIONS: Asplenia remain a relevant cause of hospitalization in Spain. Comorbidities reflected a great impact in patients with asplenia and PP, which would mean higher risk of mortality.

Pneumococcal and Influenza Vaccination Coverage in Patients with Heart Failure: A Systematic Review.

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.

Adult Pneumococcal Vaccination in Ghana: Current Status and Future Recommendations - Expert Opinion.

Vaccination programs have proven successful in the prevention and control of infectious diseases among children on a global scale, but the majority of adult populations remain unvaccinated. immunocompromised adults as well as older adults aged low-income countries as Streptococcus pneumoniae infections are associated with substantial morbidity and mortality among 65 years and above. Despite the introduction of pneumococcal conjugate vaccines (PCVs), the burden of vaccine-type serotypes remains high in there are no clear policies for adult vaccination. As per the Global Burden of Disease 2019 report, about 120,000 individuals aged 70 years and older died as a result of LRTIs) in sub-Saharan Africa. A medical advisory board meeting was conducted in April 2022 to discuss the burden of pneumococcal diseases in adults, the current status of policies and practices of adult vaccination, unmet needs, and challenges in Ghana. This expert opinion paper outlines the pneumococcal epidemiology and burden of disease in Ghana, as well as the rationale for adult pneumococcal vaccination. It also highlights the potential barriers to adult vaccination and offers recommendations to overcome these obstacles and enhance vaccine acceptance in Ghana.

Les programmes de vaccination ont prouvé leur succès dans la prévention et le contrôle des maladies infectieuses chez les enfants à l'échelle mondiale, mais la majorité des populations adultes restent non vaccinées. Les infections à Streptococcus pneumoniae sont associées à une morbidité et une mortalité substantielles chez les adultes immunodéprimés ainsi que chez les personnes âgées de 65 ans et plus. Malgré l'introduction des vaccins conjugués contre le pneumocoque (VCP), la charge des sérotypes vaccinaux reste élevée dans les pays à faible revenu car il n'existe pas de politiques claires en matière de vaccination des adultes. Selon le rapport sur la charge mondiale de morbidité de 2019, environ 120 000 personnes âgées de 70 ans et plus sont décédées des suites d'infections des voies respiratoires inférieures (IVRI) en Afrique subsaharienne. Une réunion du conseil consultatif médical a eu lieu en avril 2022 pour discuter du fardeau des maladies pneumococciques chez les adultes, de l'état actuel des politiques et pratiques de vaccination des adultes, des besoins non satisfaits et des défis au Ghana. Cet article d'opinion d'experts présente l'épidémiologie pneumococcique et le fardeau de la maladie au Ghana, ainsi que les arguments en faveur de la vaccination pneumococcique des adultes. Il met également en lumière les obstacles potentiels à la vaccination des adultes et propose des recommandations pour surmonter ces obstacles et améliorer l'acceptation des vaccins au Ghana. MOTS-CLÉS: Maladie pneumococcique, Fardeau de la maladie, Vaccin conjugué contre le pneumocoque, Vaccination des adultes, Streptococcus pneumoniae, Ghana, Défis de la vaccination, Immunisation des adultes, VCP-13, Pneumonie acquise en communauté.

Invasive pneumococcal disease surveillance in Canada, 2021-2022.

Background: Invasive pneumococcal disease (IPD, Streptococcus pneumoniae) has been a nationally notifiable disease in Canada since 2000. The use of conjugate vaccines has caused a shift in the distribution of serotypes over time. This report is a summary of the demographics, serotypes and antimicrobial resistance of IPD isolates collected in Canada in 2021 and 2022. Methods: The National Microbiology Laboratory (NML) of the Public Health Agency of Canada in Winnipeg, Manitoba collaborates with provincial and territorial public health laboratories to conduct national surveillance of IPD. There were 1,999 isolates reported in 2021 and 3,775 isolates in 2022. Serotype was determined by the Quellung reaction or whole-genome sequencing (WGS). Antimicrobial susceptibilities were determined by WGS methods, broth microdilution, or data shared by collaborators in the Canadian Antimicrobial Resistance Alliance program at the University of Manitoba. Population-based IPD incidence rates were obtained through the Canadian Notifiable Disease Surveillance System. Results: The incidence of IPD in Canada was 5.62 cases per 100,000 population in 2021, decreasing from the peak of 10.86 cases per 100,000 population in 2018. Serotypes with increasing trends (p<0.05) between 2018 and 2022 included: 4 (6.1%-12.4%), 9V (1.0%-5.1%) and 12F (4.8%-5.4%). The overall prevalence of PCV13 serotypes increased over the same period (31.2%-41.5%, p<0.05) while the prevalence of non-vaccine types decreased significantly (27.3%-21.5%, p<0.0001). The highest rates of antimicrobial resistance in 2021 and 2022 were seen with clarithromycin (21%, 2021; 24%, 2022) and erythromycin (22%, 2021; 24%, 2022). Multidrug-resistant IPD continued to increase from 2018 to 2022 (6.7%-12.6%, p<0.05). Conclusion: The number of cases of IPD continued to decrease in 2021 in comparison to previous years, however, 2022 saw a return to pre-COVID-19 levels. Disease due to PCV13 serotypes 3, 4, 9V and 19F, as well as non-PCV13 serotypes 12F and 20, is increasing in prevalence. Surveillance of IPD to monitor changing serotype distribution and antimicrobial resistance is essential.

Invasive Pneumococcal Disease Epidemiology and Serotype Replacement After the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Ontario, Canada, 2007-2022.

Background: 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-pneumococcal 13-valent conjugate vaccine (PCV13) era (01/2007 to 12/2010), post-PCV13 era (01/2011 to 12/2019), and coronavirus disease 2019 (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; polysaccharide 23-valent vaccine-non-PCV20; and non-vaccine-preventable [NVP]). We then compared incidence rates by age and serotype group in the pre- and post-PCV13 eras by calculating rate ratios (RRs) and their 95% CIs. 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-PCV13, 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.

Vaccines for the Elderly and Vaccination Programs in Europe and the United States.

The share of the elderly population is growing worldwide as life expectancy increases. Immunosenescence and comorbidities increase infectious diseases' morbidity and mortality in older adults. Here, we aimed to summarize the latest findings on vaccines for the elderly against herpes zoster, influenza, respiratory syncytial virus (RSV), COVID-19, and pneumococcal disease and to examine vaccine recommendation differences for this age group in Europe and the United States. PubMed was searched using the keywords "elders" and "vaccine" alongside the disease/pathogen in question and paraphrased or synonymous terms. Vaccine recommendations were also sought in the European and US Centers for Disease Control and Prevention databases. Improved vaccines, tailored for the elderly, mainly by using novel adjuvants or by increasing antigen concentration, are now available. Significant differences exist between immunization policies, especially between European countries, in terms of the recipient's age, number of doses, vaccination schedule, and implementation (mandatory or recommended). Understanding the factors that influence the immune response to vaccination in the elderly may help to design vaccines that offer long-term protection for this vulnerable age group. A consensus-based strategy in Europe could help to fill the gaps in immunization policy in the elderly, particularly regarding vaccination against RSV and pneumococcus.

New Vaccines for Chronic Respiratory Patients.

Chronic respiratory diseases (CRD) are responsible for more than four million deaths worldwide and have become especially prevalent in developed countries. Although the current therapies help manage daily symptoms and improve patients' quality of life, there is a major need to prevent exacerbations triggered mainly by respiratory infections. Therefore, CRD patients are a prime target for vaccination against infectious agents. In the present manuscript we review the state of the art of available vaccines specifically indicated in patients with CRDs. In addition to pneumococcus, influenza, pertussis, and SARS-CoV-2 vaccines, recently added immunization options like vaccines and monoclonal antibodies against respiratory syncytial virus, are particularly interesting in CRD patients. As new products reach the market, health authorities must be agile in updating immunization recommendations and in the programming of the vaccination of vulnerable populations such as patients with CRDs. Organizational and educational strategies might prove useful to increase vaccine uptake by CRD patients.

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.

BACKGROUND: A 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. METHODS: We 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 %). RESULTS: Among 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. CONCLUSIONS: At 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.

Lifetime Health and Economic Burden of Invasive Pneumococcal Diseases Attributable to V116 Serotypes Among Adults in the United States.

INTRODUCTION: This study aimed to estimate and compare the lifetime clinical and economic burden of invasive pneumococcal diseases (IPD) attributable to the serotypes contained in a new 21-valent pneumococcal conjugate vaccine (V116) vs. the 20-valent pneumococcal conjugate vaccine (PCV20) among adults aged 18 years and above in the USA. METHODS: A state-transition Markov model was used to track IPD cases and deaths as well as the associated direct medical costs (in 2023 US dollars) from a US healthcare payer perspective at 3% annual discount rate. The results were summarized for V116, PCV20, and eight unique serotypes contained in V116. A sensitivity analysis was conducted to determine the most influential inputs on the overall total direct lifetime cost. RESULTS: For the total population of US adults aged 18 years and above in 2021 (approx. 258 million residents), the estimated lifetime numbers of cases of IPD, post-meningitis sequelae (PMS), and IPD-related deaths attributable to the serotypes contained in V116 were approximately 1.4 million, 17,608, and 186,200, respectively, with a total discounted lifetime direct cost of $32.6 billion. A substantial proportion (approx. 31%) of those were attributable to the unique eight serotypes. The corresponding estimates for PCV20 were approximately 35% lower-934,000, 11,500, and 120,000, respectively-with a total discounted direct lifetime cost of $21.9 billion. CONCLUSION: These results show that V116 serotypes (compared to PCV20) are associated with substantially higher clinical and economic burden of IPD. The addition of V116 to vaccination recommendations can help to reduce the residual burden of IPD in US adults.

Follow-Up Study of Effectiveness of 23-Valent Pneumococcal Polysaccharide Vaccine Against All-Type and Serotype-Specific Invasive Pneumococcal Disease, Denmark.

As a follow-up to a previous study, we investigated vaccine effectiveness (VE) of 23-valent pneumococcal polysaccharide vaccine (PPSV23) against invasive pneumococcal disease (IPD) among 1,254,498 persons >65 years of age as part of a vaccination program in Denmark during April 2020-January 2023. We assessed VE by using a Cox regression model and adjusted for age, sex, and underlying conditions. Using nationwide data, we estimated a VE of PPSV23 against all-type IPD of 32% and against PPSV23-serotype IPD of 41%. Because this follow-up study had more statistical power than the original study, we also estimated VE against IPD caused by PPSV23-serotypes excluding serotype 3; serotype 3; serotype 8; serotype 22F; PPSV23 non-PCV15 serotypes; PPSV23 non-PCV20 serotypes; and IPD over time. Our findings suggest PPSV23 vaccination can protect persons >65 years of age against IPD caused by all serotypes or serotype groupings, except serotype 3.

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

INTRODUCTION: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Pneumococcal diseases (e.g., ear infections, pneumonia, bloodstream infections) are among the leading causes of illness and death in children worldwide. The pneumococcal conjugate vaccine protects against pneumococcal diseases and has significantly reduced the number of newly diagnosed cases. Higher-valent vaccines (which provide coverage for a greater number of disease-causing serotypes) have recently received European Commission approval for use in adults and  children. This study examined costs and health benefits associated with the 20-valent pneumococcal conjugate vaccine (PCV20) under a 3+1 (i.e., three primary doses and one booster dose) schedule in Germany's childhood vaccination program compared with 13-valent pneumococcal conjugate vaccine (PCV13) and the 15-valent pneumococcal conjugate vaccine (PCV15), both under a 2+1 (two primary doses, one booster) schedule. PCV20 was estimated to result in greater health benefits from avoiding more cases in pneumococcal diseases and lower costs compared with both PCV13 and PCV15. PCV20, therefore, is considered the best option among the three vaccines for children in Germany.