Invasive pneumococcal disease in Latin America and the Caribbean: Serotype distribution, disease burden, and impact of vaccination. A systematic review and meta-analysis.

BACKGROUND: Invasive pneumococcal diseases (IPD) are associated with high morbidity, mortality, and health costs worldwide, particularly in Latin America and the Caribbean (LAC). Surveillance about the distribution of serotypes causing IPD and the impact of pneumococcal vaccination is an important epidemiological tool to monitor disease activity trends, inform public health decision-making, and implement relevant prevention and control measures. OBJECTIVES: To estimate the serotype distribution for IPD and the related disease burden in LAC before, during, and after implementing the pneumococcal vaccine immunization program in LAC. METHODS: Systematic literature review following Cochrane methods of studies from LAC. We evaluated the impact of the pneumococcal vaccine on hospitalization and death during or after hospitalizations due to pneumococcal disease and serotype-specific disease over time. We also analyzed the incidence of serotyped IPD in pneumococcal conjugate vaccine PCV10 and PCV13. The protocol was registered in PROSPERO (ID: CRD42023392097). RESULTS: 155 epidemiological studies were screened and provided epidemiological data on IPD. Meta-analysis of invasive diseases in children <5 years old found that 57%-65% of causative serotypes were included in PCV10 and 66%-84% in PCV13. After PCV introduction, vaccine serotypes declined in IPD, and the emergence of non-vaccine serotypes varied by country. CONCLUSIONS: Pneumococcal conjugate vaccines significantly reduced IPD and shifted serotype distribution in Latin America and the Caribbean. PCV10/PCV13 covered 57-84% of serotypes in children under 5, with marked decline in PCV serotypes post-vaccination. Continuous surveillance remains crucial for monitoring evolving serotypes and informing public health action.

Vacina pneumocócica 23-valente (polissacarídica) para imunização da população de idosos (60 anos ou mais) contra a doença pneumocócica / 23-valent pneumococcal (polysaccharide) vaccine for immunization of the elderly population (60 years and older) against pneumococcal disease

INTRODUÇÃO: A doença pneumocócica (DP), causada pelo Streptococcus pneumoniae, também denominado de pneumococo, é uma condição de elevada incidência na população mundial e brasileira. Ela compreende uma gama de infecções em que se destacam a pneumonia adquirida na comunidade, otite média aguda, sinusite bacteriana e meningite bacteriana aguda. Sua manifestação mais grave ocorre nos quadros de infecção secundária de corrente sanguínea pelo pneumococo, em geral por uma pneumonia primária, e nas meningites, condições definidas como doença pneumocócica invasiva (DPI) e que apresentam elevado risco de óbito. A doença pneumocócica está entre as principais causas de internação no Brasil e também de óbito. Certas condições de base aumentam muito o risco de desenvolvimento de DP e DPI, bem como elevam sua letalidade, das quais se destaca a população idosa. A presença de comorbidades tais como doença pulmonar obstrutiva crônica, insuficiência cardíaca, asma, doença renal ou hepática crônica, diabete mélito e tabagismo, associados a redução do movimento mucociliar na mucosa respiratória e a imunossenescência tornam a população idosa muito vulnerável a DP e DPI. Além disso, é crescente a resistência bacteriana do pneumococo incrementando as taxas de mortalidade por esta condição. A prevenção da DP

Cost-effectiveness of introducing a domestic pneumococcal conjugate vaccine (PCV7-TT) into the Cuban national immunization programme.

OBJECTIVES: To evaluate the cost-effectiveness of introducing a domestic pneumococcal conjugate vaccine (PCV7-TT) into the Cuban National Immunization Program (NIP). METHODS: We compared PCV7-TT given at two, four and six months of age to a scenario without PCV7-TT, over a ten-year period (2020-2029). We calculated the cost (Cuban pesos - CUP) per Disability Adjusted Life Year (DALY) averted from a Government perspective. We compared results from a static cohort model and a parsimonious prediction model informed by the serotype distribution among pneumococcal carriers and cases. We ran probabilistic and deterministic uncertainty analyses. RESULTS: PCV7-TT could prevent 6897 (95% uncertainty interval, 4344-8750) hospitalizations and 189 (115-253) deaths in children <5 years of age, over the period 2020-2029. This could cost around 25 million (20-31) discounted CUP but would be offset by treatment cost savings of around 23 million (14-31). A parsimonious model predicted less favourable impact and cost-effectiveness but the cost per DALY averted was still less than 0.4 times the current GDP per capita. CONCLUSIONS: PCV7-TT is likely to be cost-effective in Cuba. The impact of the vaccine would need to be carefully monitored following its introduction into the NIP.

An updated cost-effectiveness analysis of pneumococcal conjugate vaccine among children in Thailand.

BACKGROUND: A previous cost-effectiveness analysis (CEA) showed that Pneumococcal Conjugate Vaccine (PCV) 10 and PCV13 were not cost-effective for universal immunization among children in Thailand. Given recent changes in the evidence of efficacy, herd effects and price, a CEA of PCVs should be revisited. This study aimed to determine the cost-effectiveness of PCV10 and PCV13 compared to no PCV vaccination in Thai children. MATERIAL AND METHODS: A Markov model was developed under a societal perspective with a lifetime horizon. Inputs were derived from a comprehensive literature review. Costs were calculated using the Thai National Electronic Database and converted to the year 2017 value. All costs and outcomes were discounted at a rate of 3%. The findings were reported as incremental cost-effectiveness ratios (ICERs) in Thai Baht (THB) per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed. A cost-effectiveness acceptability curve was generated with the cost-effectiveness threshold of 160,000 THB/QALY. RESULTS: Base-case analysis of 2 + 1 dose schedule and five-year protection, with no consideration of herd effect showed that ICER for PCV10 was 170,437 THB/QALY, while ICER for PCV13 was 73,674 THB/QALY. With consideration of herd effect, both PCV10 and PCV13 had lower costs and higher QALYs compared to no PCV vaccination. Based on our probabilistic sensitivity analysis at willingness-to-pay of 160,000 THB/QALY, PCV13 had 93% of being cost-effective, while 4.7% and 2.3%, for PCV10 and no PCV vaccination, respectively. CONCLUSION: At current prices, PCV13 is cost-effective, while PCV10 is not cost-effective in Thailand. When considering herd-effect, both PCV10 and PCV13 are cost-effective.

Environmental factors which can affect the burden of pneumococcal disease and the immune response to pneumococcal vaccines: the need for more precisely delineated vaccine recommendations.

Introduction: Precision medicine describes the customization of healthcare tailored to the individual patient. Generally, vaccines are considered as public health tools rather than from the individual patient perspective. However, adult vaccination programs in particular should consider many different factors, at the individual level and also from societal, cultural and country-specific perspectives. Currently, most immunization programs, including those for pneumococcal vaccines, have only been adopted on the basis of age or medical risk. Areas covered: Based on a broad literature search, this review addresses possible environmental factors which can affect the burden of pneumococcal disease and the immune response to pneumococcal vaccines. Expert opinion: Factors which influence the incidence of pneumococcal disease and the reaction against pneumococcal vaccination, including personal conditions, geographic/ethnic factors and social risks, are diverse. To maximize the effects of pneumococcal vaccination, not only for public health but also to induce optimal effects at the individual level, vaccines need to be verified under diverse situations and with collaboration among relevant medical societies, governments, and the pharmaceutical industry. Whereas vaccines are generally considered only from the public health perspective, flexible, comprehensive and tailored pneumococcal immunization programs, with appropriate policy support, can generate a greater positive impact on public health.

Cost-Effectiveness Comparison of Pneumococcal Conjugate Vaccines in Turkish Children.

BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) is used for universal infant vaccination in Turkey. OBJECTIVES: To assess the cost effectiveness of replacing PCV13 with pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). METHODS: A Markov cohort model with monthly cycles following 1 cohort of infants over a 10-year time horizon was used. Local input parameters were obtained from published sources and expert consultation whenever possible. The model was adapted to estimate the health benefits and economic impact of each vaccine on invasive pneumococcal disease, pneumonia, and acute otitis media (AOM). An annual discount rate of 3% was used for benefits and costs (2016 euros). RESULTS: Under base-case assumptions, vaccinating 1 birth cohort of 1 325 783 infants with PHiD-CV instead of PCV13 was predicted to have the same impact on meningitis and pneumonia, a similar impact on bacteremia (+30 cases), but greater reductions in AOM-related general practitioner visits (-34 955) and hospitalizations (-624). Assuming equal vaccine prices, PHiD-CV was predicted to be dominant over PCV13 (176 additional quality-adjusted life-years while saving €635 330 [discounted]). One-way sensitivity analysis indicated that varying the vaccine price differential had the largest effect on the incremental cost-effectiveness ratio, and then AOM parameters. Probabilistic sensitivity analysis predicted PHiD-CV to be dominant over PCV13 in 92.4% of simulations. CONCLUSIONS: Any difference in price between PHiD-CV and PCV13 is expected to be the key driver of vaccine choice for preventing childhood pneumococcal disease in Turkey. At price parity, PHiD-CV use is likely to be a dominant strategy over the use of PCV13.

Overview of antibody-mediated immunity to S. pneumoniae: pneumococcal infections, pneumococcal immunity assessment, and recommendations for IG product evaluation.

Streptococcus pneumoniae (S. pneumoniae) strains colonize the nasopharynx and can cause mucosal infections in the upper airway and middle ear, pneumonias, and invasive infections like bacteremia, sepsis, and meningitis. Over 90 serotypes, defined by the structure of their capsular polysaccharides, are known. Twenty-three of these serotypes cause most infections and several of these serotypes can develop antibiotic resistance. Susceptibility factors that increase the susceptibility to S. pneumoniae mucosal and invasive infections include all forms of primary and secondary antibody deficiencies. Many patients affected by one of these deficiencies benefit from the regular administration of human gamma globulin (IgG) preparations. Donors of plasma units used to prepare human IgG have varying concentrations of IgG antibodies against relevant S. pneumoniae serotypes. These antibodies are developed in response to colonization and common subclinical infections and by routine vaccination with S. pneumoniae polysaccharide vaccines. The presence of an adequate concentration of these protective antibodies against all prevalent serotypes needs to be determined to assure the effectiveness of human IgG. All presently available methods to assess IgG antibodies against S. pneumoniae capsular polysaccharides have advantages and pitfalls that are analyzed in this review. In vitro testing does not provide a complete or necessarily accurate measurement of the effectiveness of antibodies in vivo. For regulatory purposes, caution needs to be used in the interpretation of currently available assays that measure pneumococcal antibody levels. Monitoring S. pneumoniae infections in patients treated with IgG and tracing information about IgG lots used to treat these patients should be encouraged.

Cost-Utility Study of PCV13 Versus PPSV23 in Adults in Chile.

INTRODUCTION: Pneumococcal infections are a public health problem in older adults. In Chile there are two vaccines at this time, PPSV23 and PCV13. The first has lower immunogenicity and effectiveness in preventing pneumococcal pneumonia and a lower cost than PCV13. OBJECTIVE: To determine the cost-effectiveness of PCV13 versus PPSV23 in adults 18 years old and over in the Chilean Health System. MATERIAL AND METHOD: A cost-utility study was performed using the Markov model (population data for a time horizon of 10 years). Utilities and epidemiological data were obtained from the literature and costs from the Chilean Public sector. Vaccine's costs and quality-adjusted life years (QALYs) were determined and compared. RESULTS: PCV13 vaccination program in adults (≥18 years), generated savings of $42,195 USD and an increase of 6,820 QALYs, avoiding 107 cases of bacteremia, 13 meningitis, 6,706 inpatient pneumonia, 4,509 outpatient pneumonia and 1,189 deaths compared to PPSV23 without variation on sensitivity analysis on high impact variables. For the subgroup of patients over 65 years old PCV13 generates savings of $ 32,105.94USD and produces 5,430 QALYs more compared to PPSV23. CONCLUSION: PCV13 is dominant. A PCV13 vaccination program saves costs to the public system, reduces mortality and morbidity; these results are robust.

Burden of pneumococcal community-acquired pneumonia in adults across Europe: A literature review.

BACKGROUND: The burden of community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae (pneumococcus) among adults in Europe is poorly defined. METHODS: Structured searches of PubMed were conducted to identify the incidence of pneumococcal CAP among adults across Europe. RESULTS: The overall incidence rates for CAP was 68-7000 per 100,000 and the incidence in hospitalised CAP cases of all causes was 16-3581 per 100,000. In general the incidence of CAP increased consistently with age. Available data indicated higher burdens of pneumococcal CAP caused in groups with more comorbidities. Most cases of pneumococcal CAP (30%-78%) were caused by serotypes covered by PCV13 vaccine; the incidence of PCV13-related pneumonia decreased after the introduction of childhood vaccination. CONCLUSIONS: We observed a high burden adult pneumococcal CAP in Europe despite use of the 23-valent pneumococcal polysaccharide vaccine, particularly in elderly patients with comorbidities. CAP surveillance presented wide variations across Europe. Pneumococcal CAP has to be monitored very carefully due to the possible effect of current vaccination strategies.

Pneumococcal Vaccine Coverage in Adults Aged 19-64 Years, Newly Diagnosed With Chronic Conditions in the U.S.

INTRODUCTION: This study examined pneumococcal vaccine coverage in adults aged 19-64 years newly diagnosed with diabetes, chronic heart, lung, or liver disease. These conditions are indicated for pneumococcal vaccination by the Advisory Committee on Immunization Practices. METHODS: A retrospective cohort analysis was conducted in 2016 using the Truven Health MarketScan® database. The study population was adults aged 19-64 years with at least one new chronic condition during 2009-2013 and continuous health plan enrolment for 2 years before and 1 year after the initial diagnosis. Vaccine coverage by length of follow-up since diagnosis (ranging from 1 to 5 years) was summarized. Multivariate analyses were performed to understand factors associated with vaccination. RESULTS: A total of 552,942 adults aged 19-64 years with chronic conditions were identified. There were 8% of adults newly diagnosed with one of four chronic conditions that received a pneumococcal vaccination after 1 year of follow-up; the proportion increased to 20.1% among those with 5 years of follow-up data. Adults aged 50-64 years were more likely to be vaccinated than those aged 19-49 years. Adults with diabetes were more likely to be vaccinated than adults with chronic heart, lung, or liver disease. Adults enrolled in HMO plans were more likely to be vaccinated than adults in other plan types. A higher number of healthcare encounters increased the likelihood of vaccination. Adults who received influenza vaccination were also more likely to receive a pneumococcal vaccination. CONCLUSIONS: Vaccine coverage remains well below Healthy People 2020 targets. A substantial number of adults with chronic conditions remain unvaccinated and at risk for pneumococcal disease.

Assessment of Postvaccine Immunity against Streptococcus pneumoniae in Patients with Asplenia, including an Analysis of Its Impact on Bacterial Flora of the Upper Respiratory Tract and Incidence of Infections.

S. pneumoniae is a microorganism that may cause a serious threat in postsplenectomy patients due to a potentially invasive course of infection. In order to assess a protective activity after vaccination with the 23-valent vaccine, we made an analysis of the level of antibodies in patients with asplenia compared to a control group of healthy donors. Additionally, colonization by potentially pathogenic microorganisms of the upper respiratory tract was analyzed to determine the carrier state by strains with vaccine serotype. No such strains were found in the research, yet three non-vaccine-serotype strains were found. Colonization of the upper respiratory tract by potentially pathogenic microorganisms may be connected with increased susceptibility observed and incidence of infections in patients with asplenia. However, colonization by S. pneumoniae may not have an effect on the level of specific antibodies with the 23-valent vaccine against S. pneumoniae (PPV23) in postsplenectomy patients and healthy people. The response to vaccination against S. pneumoniae showed a lower level of specific antibodies in patients with splenectomy performed more than 2 years before the test than in patients with a recently removed spleen, i.e., from 1 month to 2 years before the test. Vaccination against pneumococci also has positive effects on incidence of other etiology infections, which is of high significance in the prophylaxis of infectious diseases in this group of patients.

The utility of saliva for the assessment of anti-pneumococcal antibodies: investigation of saliva as a marker of antibody status in serum.

CONTEXT: Salivary antibodies may act as non-invasive marker of systemic immunity enabling assessment of vaccination and protection against bacterial infections. OBJECTIVE: To assess if levels of anti-pneumococcal (Pn) antibodies in saliva reflect concentrations in serum and determine whether saliva can accurately identify protective concentrations in serum. METHODS: IgG, IgA and IgM antibody levels in paired saliva and serum samples were measured against 12 Pn polysaccharide antigens in 72 healthy adults. RESULTS: Antibody levels in saliva correlated positively with serum across immunoglobulin classes, most strongly for IgA. Individuals who had protective antibody levels in serum demonstrated significantly higher IgG and IgA salivary antibody concentrations/secretion rates. Salivary IgG and IgA Pn antibodies were able to distinguish between those with/without protective levels in serum for the majority of serotypes. Salivary IgM antibodies were not able to differentiate protective status. Median IgG and IgA Pn salivary parameters were able to identify individuals who had protective levels in serum on ≥8/12 serotypes with moderate accuracy: median IgA secretion rates provided the best sensitivity (73%) and specificity (71%). CONCLUSIONS: These findings suggest that IgG and IgA Pn specific antibodies in saliva may be useful surrogate markers of antibody status in serum.

Cost effectiveness of pneumococcal urinary antigen in Emergency Department: a pragmatic real-life study.

Community-acquired pneumonia (CAP) is frequent and can be life-threatening. Streptococcus pneumoniae is the main bacteria involved, and is susceptible to penicillin A. Rapid microbiological diagnosis could then help reduce the antimicrobial spectrum. The pneumococcal urinary antigen (PUA) test is fast and easy to perform, but its impact on antimicrobial prescription and cost-effectiveness in emergency departments (ED) is not well known. We performed a pragmatic real life retrospective study in an adult ED to assess its usefulness: proportion of positive results, impact on antimicrobial prescriptions and cost-effectiveness. Over 3 years (from January 1st 2012 to December 31st 2014), 979 PUA tests were reutilized in our ED among 1224 patients who consulted for CAP; 51 (5.2%) were positive. Among them, 10 led to a modification of the antimicrobial treatment, but only 7 (14.3%) were in accordance with the results. The total cost of a PUA test is 27€. As only 7 PUA tests led to appropriate antimicrobial modification, we deemed that 972 had no impact, and the potential cost savings, if the test had not been used, would have been 26,244 € (972 × 27) during 3 years, that is 8748 € per year. Thus, it seems that the PUA test should not be generally used in the ED considering its low rate of positivity and the difficulties for physicians to adapt antibiotic treatment accordingly. This attitude change in utilization would lead to substantial cost savings.

The full benefits of adult pneumococcal vaccination: A systematic review.

BACKGROUND: Pneumococcal disease causes substantial morbidity and mortality, including among adults. Adult pneumococcal vaccines help to prevent these burdens, but they are underused. Accounting for the full benefits of adult pneumococcal vaccination may promote more rational resource allocation decisions with respect to adult pneumococcal vaccines. OBJECTIVES: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic review to assess the extent to which the literature has empirically captured (e.g., through measurement or modeling) the full benefits of adult pneumococcal vaccination. METHODS: We systematically searched PubMed and Embase to identify studies published between January 1, 2010 and April 10, 2016 that examine adult pneumococcal vaccination. We included articles if they captured any health or economic benefit of an adult pneumococcal vaccine administered to adults age ≥ 50 or ≥ 18 in risk groups. Finally, we summarized the literature by categorizing the types of benefits captured, the perspective taken, and the strength of the evidence presented. Our protocol is number 42016038335 in the PROSPERO International prospective register of systematic reviews. RESULTS: We identified 5,857 papers and included 150 studies for analysis. While most capture health gains and healthcare cost savings, far fewer studies consider additional benefit categories, such as productivity gains. However, the studies with a broader approach still exhibit significant limitations; for example, many present only abstracts, while others offer no new measurements. Studies that examine the 13-valent pneumococcal conjugate vaccine focus more on broad economic benefits, but still have limitations. CONCLUSIONS: This review highlights the need for more robust empirical accounting of the full benefits of adult pneumococcal vaccination. Literature outside this realm indicates that these broad benefits may be substantial. Failing to investigate the full benefits may lead society to undervalue vaccines' contributions and therefore underinvest in their development and adoption.

Comparison of the Impact of Pneumococcal Conjugate Vaccine 10 or Pneumococcal Conjugate Vaccine 13 on Invasive Pneumococcal Disease in Equivalent Populations.

Background: Pneumococcal conjugate vaccine 10 (PCV10) and pneumococcal conjugate vaccine 13 (PCV13), are used in childhood immunization programs worldwide, but direct comparisons of impacts against invasive pneumococcal disease (IPD) in equivalent populations have not been performed. We compared the vaccines (prevaccination 2007-2009 vs postvaccination 2013-2016) in Sweden, where the 21 counties use either PCV10 or PCV13 (introduced 2009-2010). Methods: All IPD episodes (n = 16992) were recorded in Sweden during 2005-2016. Of 14 186 isolates from 2007-2016, 13 468 (94.9%) were characterized with serotyping and 12 235 (86.2%) with antibiotic susceptibility. Poisson models assessed changes in incidence over time. Results: Invasive pneumococcal disease incidences decreased between 2005 and 2016 in vaccinated children (by 68.5%), and in the whole population (by 13.5%), but not among the elderly (increased by 2%) due to a substantial increase in nonvaccine types (NVTs). In 2016, NVTs constituted 72% of IPD cases in the elderly. Serotype 6A declined in PCV10 and PCV13 counties, whereas serotype 19A increased in PCV10 counties. There was no effect against serotype 3. Cross-protection was found between 6B and 6A but not between 19F and 19A. Serotype 6C increased in PCV10 counties, but not in PCV13 counties, suggesting cross-protection with 6A, which is included in PCV13. In the elderly, the increase in NVTs, excluding 6C, was more pronounced in PCV13 counties. Conclusions: The overall impact of IPD incidences was not statistically different irrespective of vaccine used. The incidence of serotypes, where the effect of the vaccines differed, will influence the cost-effectiveness of which vaccine to use in immunization programs. The dominance of NVTs suggests a limited effect of current pediatric PCVs against IPD in the elderly.

Streptococcus pneumoniae serotype 19A: worldwide epidemiology.

INTRODUCTION: Streptococcus pneumoniae causes mucosal and invasive diseases with high morbidity and mortality. Introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) into routine infant immunization programs worldwide resulted in serotype 19A becoming a leading cause of the remaining pneumococcal disease burden in vaccinated and nonvaccinated individuals. This article reviews the impact of the latest generation PCVs (10-valent PCV, PCV10, and 13-valent PCV, PCV13) on serotype 19A. Areas covered: This article covers immune responses elicited by PCV7, PCV10 and PCV13 against serotype 19A and their impact on nasopharyngeal (NP) carriage and disease in vaccinated and unvaccinated populations using data from surveillance systems, randomized controlled trials, and observational studies. Expert commentary: As expected from a PCV containing serotype 19A, PCV13 elicits significantly higher functional immune responses against serotype 19A than PCV7 and PCV10. Higher responses are likely to be linked to both direct impact in vaccinated populations and reductions in 19A NP carriage in children, thus inducing herd protection and reducing 19A invasive pneumococcal disease (IPD) in nonvaccinated children and adults. In contrast, PCV7 and PCV10 have shown mixed evidence of direct short-lived cross-protection and little to no impact on 19A carriage, resulting in continued transmission and disease.

Overall effectiveness of pneumococcal conjugate vaccines: An economic analysis of PHiD-CV and PCV-13 in the immunization of infants in Italy.

Pneumococcal diseases are associated with a significant clinical and economic burden. The 7-valent pneumococcal conjugate vaccine (PCV-7) has been used for the immunization of newborns against invasive pneumococcal diseases (IPD) in Italy while now, the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) and the 13-valent pneumococcal conjugate vaccine (PCV-13) are available. The aim of this analysis was to compare the estimated health benefits, cost and cost-effectiveness of immunization strategies vs. non-vaccination in Italy using the concept of overall vaccine effectiveness. A published Markov model was adapted using local data wherever available to compare the impact of neonatal pneumococcal vaccination on epidemiological and economic burden of invasive and non-invasive pneumococcal diseases, within a cohort of newborns from the Italian National Health Service (NHS) perspective. A 18-year and a 5-year time horizon were considered for the base-case and scenario analysis, respectively. PHiD-CV and PCV-13 are associated with the most important reduction of the clinical burden, with a potential marginal advantage of PHiD-CV over PCV-13. Compared with no vaccination, PHiD-CV is found on the higher limit of the usually indicated willingness to pay range (30,000 - 50,000€/quality-adjusted life year [QALY] gained), while the incremental cost-effectiveness ratio (ICER) for PCV-13 is slightly above. Compared with PCV-13, PHiD-CV would provide better health outcomes and reduce costs even at parity price, solely due to its differential effect on the incidence of NTHi acute otitis media (AOM). The analysis on a shorter time horizon confirms the direction of the base-case.