Pneumococcal Disease In Adults Research Articles

Estimates of the Health and Economic Burden of Pneumococcal Infections Attributable to the 15-Valent Pneumococcal Conjugate Vaccine Serotypes in the USA.

IntroductionDespite the availability of vaccines, pneumococcal disease (PD) is associated with high clinical and economic burden, mainly caused by non-vaccine serotypes and certain vaccine-type serotypes. V114 is a 15-valent pneumococcal conjugate vaccine (PCV) that contains two epidemiologically important serotypes, 22F and 33F, in addition to the 13 serotypes in 13-valent PCV (PCV13). This study quantified the epidemiologic and economic burden of PD attributable to V114 serotypes among adults in the USA.MethodsA Markov model was used to estimate the burden of V114 serotypes in a hypothetical, non-vaccinated cohort of US adults ≥ 19 years of age who were tracked from 2019 until death. The model calculated all the invasive pneumococcal disease (IPD) and non-bacteremic pneumococcal pneumonia (NBPP) cases, deaths, and costs. Economic burden was estimated from a healthcare payer perspective (2019 US dollars) and discounted at 3%.ResultsThe model estimated 415,229 and 10.3 million lifetime cases of V114-type IPD and NBPP, respectively. Serotypes 22F and 33F caused approximately 33% of IPD cases and 20% of NBPP cases, while serotype 3 accounted for approximately 36% of IPD cases and 13% of NBPP cases. V114 serotypes caused 472,063 total lifetime deaths. Total discounted lifetime costs attributable to V114 serotypes were $44.8 billion US dollars.ConclusionsIn this hypothetical model of a non-vaccinated cohort of US adults, V114 serotypes were associated with a substantial health and economic burden, the majority of which was attributable to serotypes 3, 22F, and 33F. The addition of V114 to the national vaccination recommendations may help to reduce the epidemiologic and economic burden associated with PD in adults ≥ 19 years of age in the USA by providing increased coverage of these serotypes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-022-00588-x.

Recent Topics of Pneumococcal Vaccination: Indication of Pneumococcal Vaccine for Individuals at a Risk of Pneumococcal Disease in Adults.

Pneumococcal disease is one of the most common and severe vaccine-preventable diseases (VPDs). Despite the advances in antimicrobial treatment, pneumococcal disease still remains a global burden and exhibits a high mortality rate among people of all ages worldwide. The immunization program of the pneumococcal conjugate vaccine (PCV) in children has decreased pneumococcal disease incidence in several countries. However, there are several problems regarding the pneumococcal vaccine, such as indications for immunocompetent persons with underlying medical conditions with a risk of pneumococcal disease, the balance of utility and cost, i.e., cost-effectiveness, vaccine coverage rate, serotype replacement, and adverse events. Especially for individuals aged 19–64 at risk of pneumococcal disease, physicians and vaccine providers should make a rational decision whether the patients should be vaccinated or not, since there is insufficient evidence supporting it. We describe this review regarding topics and problems regarding pneumococcal vaccination from the clinician’s point of view.

Effectiveness of 23-Valent Pneumococcal Polysaccharide Vaccine Against Pneumococcal Diseases Among the Elderly Aged 60 Years or Older: A Matched Test Negative Case-Control Study in Shanghai, China.

Background:Streptococcus pneumoniae infection among adults, especially in adults over 60 years old in China results in a large number of hospitalizations and a substantial financial burden. This study assessed the vaccine effectiveness (VE) of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal diseases among the elderly aged 60 years or older in Shanghai, China.Methods: We conducted a test-negative case–control study among the elderly aged 60 years or older who sought care at hospitals in 13 districts of Shanghai from September 14, 2013 to August 31, 2019. A case was defined as pneumococcal disease and testing positive for Streptococcus pneumoniae. Controls had symptoms congruent with pneumococcal disease but were negative for Streptococcus pneumoniae. We conducted 1:2 matching by gender, age, hospital and admission date. Vaccination status was verified from the immunization system database. VE was calculated with conditional logistic regression according to the formula (1–OR) ×100%.Results: Overall, 603 adults aged 60 years or older with pneumococcal disease and positive for Streptococcus pneumoniae were included as cases, and 19.6% (118 persons) had a recorded PPV23 vaccination. The controls included 1,206 adults, whose vaccination rate was 23.8% (287 persons). The VE against pneumococcal diseases among the whole population was 24% (95% CI: 2%, 40%) and among women 44% (95% CI: 6%, 67%). After adjusting for multiple variables, the effectiveness of PPV23 against pneumococcal diseases was still statistically significant with VE for all of 25% (95% CI: 3%, 42%) and VE for women of 49% (95% CI: 11%, 71%).Conclusion: PPV23 was effective against pneumococcal diseases in adults aged 60 years or older in Shanghai, China. Its relatively high effectiveness among women warrants this group to be particularly targeted for vaccination, with further research on why vaccination effectiveness is less among men.

Persistence of Pneumococcal Serotype 3 in Adult Pneumococcal Disease in Hong Kong.

The epidemiology of hospitalised pneumococcal disease in adults following the introduction of universal childhood pneumococcal immunisation in 2009 was assessed. Culture-confirmed Streptococcus pneumoniae (SP) from adults hospitalised between 2009 to 2017 were examined. The cases were categorised into invasive pneumococcal disease (IPD) and pneumonia (bacteraemic, non-bacteraemic, and that associated with other lung conditions). The isolates were serotyped and antimicrobial susceptibilities were determined by microbroth dilution. Patient characteristics, comorbidities, and outcomes were analysed. Seven hundred and seventy-four patients (mean age, 67.7 years, SD ± 15.6) were identified, and IPD was diagnosed in 110 (14.2%). The most prevalent serotype, 19F, was replaced by serotype 3 over time. Penicillin and cefotaxime non-susceptibilities were high at 54.1% and 39.5% (meningitis breakpoints), 19.9% and 25.5% (non-meningitis breakpoints), respectively. The overall 30-day mortality rate was 7.8% and 20.4% for IPD. Age ≥ 75 years (OR:4.6, CI:1.3–17.0, p < 0.02), presence of any complications (OR:4.1, CI:1.02–16.3, p < 0.05), pleural effusion (OR:6.7, CI:1.2–39.4, p < 0.03) and intensive care unit (ICU) admission (OR:9.0, CI:1.3–63.4, p < 0.03) were independent predictors of 30-day mortality. Pneumococcal disease by PCV 13 covered serotypes; in particular, 19F and 3 are still prominent in adults. Strengthening targeted adult vaccination may be necessary in order to reduce disease burden.

Should older adult pneumococcal vaccination recommendations change due to decreased vaccination in children during the pandemic? A cost-effectiveness analysis

BackgroundThe COVID-19 pandemic is causing declines in childhood immunization rates. We examined potential COVID-19-related changes in pediatric 13-valent pneumococcal conjugate vaccine (PCV13) use, subsequent impact on childhood and adult pneumococcal disease rates, and how those changes might affect the favorability of PCV13 use in non-immunocompromised adults aged ≥65 years. MethodsA Markov model estimated pediatric disease resulting from decreased PCV13 use in children aged <5 years; absolute decreases from 10 to 50% for 1–2 years duration were examined, assuming no catch-up vaccination and that decreased vaccination led to proportionate increases in PCV13 serotype pneumococcal disease in children and seniors. Integrating pediatric model output into a second Markov model examining 65-year-olds, we estimated the cost effectiveness of older adult pneumococcal vaccination strategies while accounting for potential epidemiologic changes from decreased pediatric vaccination. ResultsOne year of 10–50% absolute decreases in PCV13 use in <5-year-olds increased pneumococcal disease by an estimated 4–19% in seniors; 2 years of decreased use increased senior rates by 8–38%. In seniors, a >53% increase in pneumococcal disease was required to favor PCV13 use in non-immunocompromised seniors at a $200,000 per quality-adjusted life-year gained threshold, which corresponded to absolute decreases in pediatric PCV13 vaccination of >50% over a 2-year period. In sensitivity analyses, senior PCV13 vaccination was unfavorable if absolute decreases in pediatric PCV13 receipt were within plausible ranges, despite model assumptions favoring PCV13 use in seniors. ConclusionCOVID-19-related decreases in pediatric PCV13 use would need to be both substantial and prolonged to make heightened PCV13 use in non-immunocompromised seniors economically favorable.

Invasive Pneumococcal Disease in Adults in Portugal: The Importance of Serotypes 8 and 3 (2015-2018).

Increasing the uptake of the 13-valent pneumococcal conjugate vaccine (PCV13) in children is expected to alter the serotypes causing invasive pneumococcal disease (IPD) in adults due to herd protection. We characterized 2172 cases of adult IPD in 2015–2018 in Portugal after the introduction of PCV13 in the national immunization plan of 2015. Among the 58 detected serotypes, serotypes 8 (n = 413; 19%), 3 (n = 334; 15%), 22F (n = 148; 7%), 14 (n = 138; 6%), and 19A (n = 116; 5%) were the most frequent. Among PCV13 serotypes, 7F and 19A IPD decreased, but serotype 3 IPD remained stable. The non-PCV13 serotypes were a heterogeneous group, with serotypes 23A and 23B enriched among CSF cases; serotype 8 associated with younger patients; and serotypes 22F, 6C, and 31 associated with older patients. The continued increase of serotype 8 IPD was one of the drivers for the increased coverage of the 23-valent pneumococcal polysaccharide vaccine (PPV23; 80% in 2015–2018). Antimicrobial resistance was associated with older age and serotypes 6C, 11A, 14, 15A, 19A, and 19F. Three years after the introduction of PCV13 in the NIP with an uptake of >95%, the proportion of PCV13 serotypes causing IPD in adults stabilized in Portugal. The direct vaccination of adults may be important in preventing IPD in this age group.

295. Is Herd Immunity from Pneumococcal Conjugate Vaccines Changing the Clinical Features of Invasive Pneumococcal Disease in Adults?

BackgroundNumerous factors that affect the presentation and severity of pneumococcal disease. Several studies in the pre-PCV era demonstrated that organism characteristics, including serotype, are associated with variability in disease presentation and severity. We undertook an analysis of population based surveillance for invasive pneumococcal disease (IPD) to assess whether herd immunity from PCVs will change the presentation and severity of IPD in adultsMethodsTIBDN has performed population-based surveillance for IPD in Toronto and Peel region (pop’n 4.5M) since 1995. All sterile site isolates of S. pneumoniae are reported to a central study laboratory, isolates are serotyped, and clinical and vaccination data are collected via patient and physician interview and chart review. Population data are obtained from Statistics Canada. Backwards stepwise logistic regression assessed patient characteristics, illness features, and isolate factors associated with clinical presentation and case fatality.ResultsBetween 1995 and 2018, 8815 episodes of IPD were identified in adults. Patients infected with PCV10not7 serotypes were younger, more likely male and without underlying illness. Patients with infections due to non-vaccine types were more likely to be immunocompromised. Case fatality in IPD declined from 177/754 in 1995/6 to 113/554 in 2017/8; OR 0.67, 95%CI0.51-0.86, P< .0001) and in all serotype groups (Figure). In multivariable models adjusted for host factors, relative to infections caused PCV7 serotypes, those caused by PCV10not7 were less likely to be fatal (OR 0.65, 95%CI 0.46–0.91); those caused by PCV13not10 were more likely to be fatal (OR 1.6, 95%CI 1.3–1.9). Bacteremic pneumonia as a proportion of presentations is highest in IPD due to PCV10not7 and PCV13not10 serotypes (85% and 83%, respectively), and lowest in IPD due to non-vaccine serotypes and PCV20not15 (59% and 68%, P< .0001). Meningitis is least common in IPD due to PCV10not7 serotypes (2.6%), and highest in cases due to non-vaccine types and PCV20not15 (9.0% and 8.0%, respectively, P< .0001).FIgure ConclusionIn our population, herd immunity from PCVs will result in a higher proportion of adult IPD occurring in immunocompromised cases, and a shift from bacteremic pneumonia to bacteremia without focus and meningitis.Disclosures Allison McGeer, MD, FRCPC, GlaxoSmithKline (Advisor or Review Panel member, Research Grant or Support)Merck (Advisor or Review Panel member, Research Grant or Support)Pfizer (Research Grant or Support)

1240. Persistence of Circulating Antibody Through 12 Months Following Vaccination With a 20-Valent Pneumococcal Conjugate Vaccine in Adults 60–64 Years of Age

BackgroundWhile widespread use of pneumococcal conjugate vaccines (PCVs) has reduced disease burden, expanding serotype coverage remains an unmet need in disease prevention. The 20-valent PCV (PCV20) contains capsular polysaccharide conjugates from serotypes included in the 13-valent PCV (PCV13; Prevnar 13®) as well as 7 additional serotypes. In a phase 2 study of PCV20 in adults 60–64 years of age, robust immune responses were observed at 1 month after vaccination; antibody persistence up to 12 months after vaccination from that study is described herein.MethodsIn this randomized, active-controlled, double-blind study (ClinicalTrials.gov NCT03313037), adults aged 60–64 years received a single PCV20 dose followed 1 month later by saline placebo or PCV13 followed 1 month later by 23-valent pneumococcal polysaccharide vaccine (PPSV23), which provided benchmarks for all PCV20 serotypes. Immunogenicity was assessed at baseline and at 1 and 12 months after vaccination as serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) and immunoglobulin G (IgG) geometric mean concentrations (GMCs). OPA and IgG geometric mean fold rises (GMFRs) from baseline to 12 months after vaccination were assessed.ResultsIn the PCV20 group, OPA GMTs (n=185–200 at Month 12) for all PCV20 serotypes increased substantially from baseline to 1 month after vaccination and then declined by Month 12 but remained elevated above baseline. OPA GMFRs from baseline to Month 12 after PCV20 vaccination were 1.9–15.0 for the serotypes in common with PCV13 and 5.6–15.6 for the 7 additional serotypes. Similar results were observed for IgG concentrations, with GMFRs of 2.4–9.4 for the PCV13 serotypes and 3.0–15.5 for the 7 additional serotypes. At Month 12, 11 months after PPSV23 vaccination (n=162–195), OPA GMFRs were 5.3–11.5 for the 7 additional serotypes; IgG GMFRs were 5.0–10.4. Benchmarking to PCV13 serotypes in the control group was not appropriate as these subjects received both PCV13 and PPSV23, which overlap in polysaccharide composition for 12 serotypes.ConclusionImmune responses induced by PCV20 persisted at 12 months after vaccination in adults 60–64 years of age, further supporting the potential of PCV20 to expand serotype protection against adult pneumococcal disease.DisclosuresMariano Young Jr., MD, Pfizer Inc (Employee, Shareholder) Daniel Scott, MD, Pfizer (Employee, Shareholder) Michael W. Pride, PhD, Pfizer (Employee, Shareholder) Ingrid L. Scully, PhD, Pfizer Inc (Employee, Shareholder) John Ginis, BS, Pfizer Inc (Employee, Shareholder) Yahong Peng, PhD, Pfizer (Employee, Shareholder) Kathrin U. Jansen, PhD, Pfizer (Employee, Shareholder) William C. Gruber, MD, Pfizer (Employee, Shareholder) Wendy Watson, MD, Pfizer (Employee, Shareholder)

Effectiveness of 23-Valent Pneumococcal Polysaccharide Vaccine against Invasive Pneumococcal Disease in Adults, Japan, 2013-2017.

The decline in the proportion of pneumococcal conjugate vaccine (PCV)–covered serotypes among adult invasive pneumococcal disease (IPD) patients might change the overall effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) because its effectiveness differs according to serotype. Using the indirect cohort method, we calculated the effectiveness of PPSV23 against IPD among adults in Japan to assess the impact of the national pediatric PCV program. Clinical and epidemiologic information and pneumococcal isolates were collected from IPD patients >20 years of age through enhanced IPD surveillance during April 2013–December 2017. Adjusted effectiveness against PPSV23-serotype IPD was 42.2%. Despite a substantial decline in the proportion of 13-valent PCV serotypes during the study period (45% to 31%), the change in effectiveness for PPSV23-serotype IPD was limited (47.1% to 39.3%) and only marginal in the elderly population (39.9% to 39.4%). The pediatric PCV program had limited impact on PPSV23 effectiveness against IPD in adults.

Serotype Patterns of Pneumococcal Disease in Adults Are Correlated With Carriage Patterns in Older Children.

The importance of specific serotypes causing invasive pneumococcal disease (IPD) differs by age. Data on pneumococcal carriage in different age groups, along with data on serotype-specific invasiveness, could help explain these age-related patterns and their implications for vaccination. Using pneumococcal carriage and disease data from Israel, we evaluated the association between serotype-specific IPD in adults and serotype-specific carriage prevalence among children in different age categories, while adjusting for serotype-specific invasiveness. We estimated carriage prevalence using different age groupings that were selected a priori. The Deviance Information Criterion was used to determine which age groupings of carriage data best fit the adult IPD data. Serotype-specific disease patterns were further evaluated by stratifying IPD data by comorbidity status. The relative frequency of serotypes causing IPD differed between adults and children, and also differed between older and younger adults and between adults with and without comorbidities. Serotypes overrepresented as causes of IPD in adults were more commonly carried in older children compared with younger children. In line with this, the serotype-specific frequency of carriage in older children, rather than infants, best correlated with serotype-specific IPD in adults. These analyses demonstrate that the serotype patterns in carriage in older children, rather than infants, are best correlated with disease patterns in adults. This might suggest these older children are more influential for disease patterns in adults. These insights could help in optimizing vaccination strategies to reduce disease burden across all ages.

Impact of pneumococcal conjugate vaccine on pneumonia hospitalization and mortality in children and elderly in Ecuador: Time series analyses

BackgroundPneumococcal conjugate vaccines (PCV) reduce the burden of invasive pneumococcal disease and pneumonia hospitalizations. However, there is limited evidence of the effect of PCVs on pneumonia mortality in children. It is anticipated that indirect effects resulting from PCV use among children might further reduce the remaining burden of adult pneumococcal disease caused by pneumococcal serotypes contained in PCV. Whether this will result in reduced pneumonia mortality in children and adults is still not known. MethodsWe investigated the impact of PCV on pneumonia hospitalization and mortality in in Ecuador, where PCV was introduced in 2010, considering national data from secondary data sources from 2005 to 2015. Time series analysis using regression models were used to evaluate the decline in the number of all-cause pneumonia hospitalizations and deaths in the period post-PCV introduction. The target populations were children under 5 years and adults aged 50 years and over. Outcomes of interest were hospitalizations and mortality in which the main cause of hospital admission and death, respectively, were coded as ICD10 codes J12-18 (pneumonia). Three different models were fitted. ResultsWe demonstrate a sizeable impact of PCV in pneumonia hospitalization in children < 1 year (27% reduction, 95%CI 12–42%), and < 5 years of age (33% reduction, 95%CI 11–43%). The estimated impact of PCV in pneumonia mortality was a reduction of 14% in < 1 year (95%CI 0–33%), 10% in < 5 years (95%CI 0–25%), and 22% (95%CI 7–34%) in adults aged 50–64 years. Little evidence of a change was detected in elderly ≥ 65 years. ConclusionThis study is the first to report on the impact of PCV in pneumonia morbidity and mortality in children and older adults, being relevant to policy makers and global donors. Findings were consistent when using different models. Additional studies on the indirect effect of PCV in older adults are needed.

Effectiveness of 23-valent pneumococcal polysaccharide vaccine on adult pneumococcal disease

Streptococcus pneumoniae (Spn) will cause various pneumococcal diseases when host has a weak immune system. The World Health Organization ranks it as one of the 12 key pathogens causing heavy burden of disease. At present, the drug resistance of Spn is rising, and vaccination is an important and effective strategy to decrease the burden of disease. The 23-valent pneumococcal polysaccharide vaccine (PPV23) is a preventive vaccine for adults that covers 65% to 91% of Spn isolates worldwide. Accumulating evidence have confirmed the effectiveness of PPV23 in decreasing the incidence, hospitalization, mortality, and economic burden of pneumococcal diseases in adults. The burden of pneumococcal diseases in China is heavy, but the adult vaccination rate is low. Here, we review the prevalence of adult pneumococcal diseases, the preventive and protective effects and benefits of PPV23 vaccine on high-risk population, especially the elderly individuals. We hope this review can provide references and new ideas for adult PPV23 vaccination programs in China.

Dynamics of Pneumococcal Carriage in Adults: A New Look at an Old Paradigm

Limited information is available on pneumococcal colonization among adults. We studied pneumococcal carriage dynamics in healthy adults using high-sensitivity approaches. Eighty-seven adults (25-50 years old) were followed for 6 months in Portugal. Nasopharyngeal, oropharyngeal, and saliva samples were obtained monthly; pneumococcal carriers were also sampled weekly. Carriage was investigated by quantitative polymerase chain reaction (targeting lytA and piaB) and culture. Positive samples were serotyped. Approximately 20% of the adults were intermittent carriers; 10% were persistent carriers (>4 months). Pneumococcal acquisition and clearance rates were 16.5 (95% confidence interval [CI], 11.2-24.2) and 95.9 (95% CI, 62.3-145.0) cases/1000 person-weeks, respectively. Living with children increased pneumococcal acquisition (hazard ratio, 9.7 [95% CI, 2.6-20.5]; P < .001). Median duration of carriage was 7 weeks and did not depend on regular contact with children. The pneumococcal carrier state in healthy adults is more dynamic than generally assumed: Acquisition is frequent and duration of carriage is often long. This suggests that some adults may act as reservoirs of pneumococci and hence, depending on the social structure of a community, the magnitude of herd effects potentially attainable through children vaccination may vary. These findings are important when designing strategies to prevent pneumococcal disease in adults.

Impact of population aging on the burden of vaccine-preventable diseases among older adults in the United States

ABSTRACT Despite vaccination recommendations, the burden of vaccine-preventable diseases remains high in older adults in the United States (US), contributing to substantial morbidity, mortality, and health care resource use and costs. To adequately plan for health care resource needs and to help inform vaccination policies, burden of disease projections that account for population aging over the coming decades are needed. As a first step, this exploratory study projects the burden of influenza, pertussis, herpes zoster, and pneumococcal disease in adults aged 50 y and older in the US, using a population-based modeling framework with separate decision trees for each vaccine-preventable disease. The model uses projected population estimates from the US Census Bureau to account for changes in the US population over time and then calculates expected numbers of cases and associated costs for each disease, keeping current estimates of age-specific disease incidence, vaccine coverage, and efficacy constant over time. This approach was used to focus the exploratory analysis on the burden of disease that may be expected due to population changes alone, assuming that all else remains unchanged. Due to population growth and the shifting age distribution over the next 30 y, the annual societal economic burden for the four vaccine-preventable diseases is projected to increase from approximately $35 billion to $49 billion, resulting in cumulative costs of approximately $1.3 trillion, as well as more than 1 million disease-related deaths. Given such notable burden, further efforts to increase vaccination coverage and effectiveness in older adults are needed.

Differences and Temporal Changes in Risk of Invasive Pneumococcal Disease in Adults with Hematological Malignancies: Results from a Nationwide 16-Year Cohort Study.

Patients with hematological malignancies (HM) are known to carry an increased risk of invasive pneumococcal disease (IPD). However, temporal variations in IPD risks following a cancer diagnosis remain poorly characterized. To inform vaccine guidelines and patient management, we assessed the IPD incidence among patients with HM and other malignancies. The study population included all individuals aged ≥15 years during 2000-2016 in Denmark. Variations in incidences of IPD over time and between different types of hematological malignancies and diagnoses were assessed by Poisson regression. During 85 002 224 person-years of observation, 13 332 episodes of a first IPD were observed, of which 765 (5.7%) occurred among individuals with HM. Among HM patients, the IPD incidence rate decreased continuously during the study period (rate ratio per year, 0.91; 95% confidence interval, .90-.92). The risk of IPD in patients with HM was up to 39 times higher when compared to the background population and was highest for multiple myeloma, acute lymphoblastic leukemia, and chronic lymphocytic leukemia. Unlike other malignancies, the increased IPD risk did not wane with the time since HM diagnosis. We found a vaccination uptake of only ≤2% in patients with HM and ≤1% for those with other types of malignancies. Adults with HM in general and patients with lymphoid malignancies in particular have an increased risk for IPD, compared with patients with other types of cancer and with individuals free of cancer. The pneumococcal vaccination uptake is extremely low in this at risk-population. Efforts to prevent IPD in HM patients are continuously warranted.

A Systematic Review of Studies Published between 2016 and 2019 on the Effectiveness and Efficacy of Pneumococcal Vaccination on Pneumonia and Invasive Pneumococcal Disease in an Elderly Population.

Adult vaccination is high on the agenda in many countries. Two different vaccines are available for the prevention of pneumococcal disease in adults: a 23-valent polysaccharide vaccine (PPV23), and a 13-valent conjugated vaccine (PCV13). The objective of this review is to update the evidence base for vaccine efficacy and effectiveness of PPV23 and PCV13 against invasive pneumococcal disease and pneumonia among an unselected elderly population. We systematically searched for clinical trials and observational studies published between January 1 2016 and April 17 2019 in Pubmed, Embase, Cinahl, Web of Science, Epistemonikos and Cochrane databases. Risk of bias was assessed using Cochrane Risk of Bias tool for and the Newcastle–Ottawa Scale. Results were stratified by vaccine type and outcome. We identified nine studies on PCV13 and six on PPV23. No new randomized clinical trials were identified. Due to different outcomes, it was not possible to do a meta-analysis. New high-quality observational studies indicate protective vaccine effectiveness for both vaccines against vaccine type pneumonia. Our estimates for the protective vaccine efficacy and effectiveness (VE) of PPV23 on pneumonia and pneumococcal pneumonia overlap with results from previously published reviews. Some of the results indicate that the effectiveness of the PPV23 is best in younger age groups, and that it decreases over time.

Indirect costs of adult pneumococcal disease and the productivity-based rate of return to the 13-valent pneumococcal conjugate vaccine for adults in Turkey

ABSTRACT Productivity benefits of health technologies are ignored in typical economic evaluations from a health payer’s perspective, risking undervaluation. We conduct a productivity-based cost-benefit analysis from a societal perspective and estimate indirect costs of adult pneumococcal disease, vaccination benefits from the adult 13-valent pneumococcal conjugate vaccine (PCV13 Adult), and rates of return to PCV13 Adult for a range of hypothetical vaccination costs. Our context is Turkey’s funding PCV13 for the elderly and for non-elderly adults with select comorbidities within the Ministry of Health’s National Immunization Program. We use a Markov model with one-year cycles. Indirect costs from death or disability equal the expected present discounted value of lifetime losses in the infected individual’s paid and unpaid work and in caregivers’ paid work. Vaccination benefits comprise averted indirect costs. Rates of return equal vaccination benefits divided by vaccination costs, minus one. Input parameters are from public data sources. We model comorbidities’ effects by scalar multiplication of the parameters of the general population. Indirect costs per treatment episode of inpatient community-acquired pneumonia (CAP), bacteremia, and meningitis – but not for outpatient CAP – approach or exceed Turkish per capita gross domestic product. Vaccination benefits equal $207.02 per vaccination in 2017 US dollars. The rate of return is positive for all hypothetical costs below this. Results are sensitive to herd effects from pediatric vaccination and vaccine efficacy rates. For a wide range of hypothetical vaccination costs, the rate of return compares favorably with those of other global development interventions with well-established strong investment cases.

Evaluating the cost-effectiveness of a sequential pneumococcal vaccination compared to single-dose vaccination strategy for adults in Hong Kong

ABSTRACT Two vaccines, 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13), are widely available for the prevention of pneumococcal disease in adults. However, it is unclear how cost-effective these pneumococcal vaccine choices are in the Hong Kong healthcare environment. We aimed to assess the cost-effectiveness of a sequential administration of PCV13 followed by PPSV23 compared to a single dose of PPSV23 vaccination for pneumococcal disease control in Hong Kong adults aged ≥65 years and individuals aged 20–64 years with immunocompromising and chronic conditions. A previously developed deterministic cohort sequential model was applied to compare the outcomes of two vaccination strategies from a societal perspective. Population-specific model input, including incidence, mortality, case-fatality, risk group distribution, vaccination costs, disease management, and productivity loss, was estimated from a Hong Kong-wide electronic medical database. Costs were valued in US$ in 2017. Vaccination strategies with an incremental cost-effectiveness ratio (ICER, defined as incremental cost per QALY saved) less than one local GDP per capita ($46,193 in 2017) were defined as highly cost-effective. Deterministic sensitivity analyses (SA) were conducted. Compared with single-dose PPSV23, sequential vaccination of PCV13 followed by PPSV23 was cost-saving for adults aged ≥20 years. In the deterministic SA, the base-case results were robust for tested parameter uncertainties. Future vaccination policies should consider the cost-effectiveness of a sequential vaccination strategy as a measure to reduce the vaccine-preventable pneumococcal disease burden in Hong Kong.

Distribution of PCV13 and PPSV23 Streptococcus pneumoniae serotypes in Argentinean adults with invasive disease, 2013–2017

Streptococcus pneumoniae is a major cause of severe invasive disease associated with high mortality and morbidity worldwide. To identify the serotypes most commonly associated with infection in adults in Argentina, 791 pneumococcal isolates from 56 hospitals belonging to 16 provinces and Buenos Aires city were serotyped. The isolates were submitted as part of a National Surveillance Program for invasive pneumococcal disease in adults, which started in 2013. Serotypes 3, 8, 12F, 7F and 1 were the most prevalent among adult patients. During the study period there was no significant difference in serotype distribution between the age groups studied (18–64 and ≥65 years old), except for serotype 1, 3 and 23A. Most prevalent serotypes in pneumonia were serotype 7F, 1, 12F, 8, and 3. When the clinical diagnosis was meningitis, serotype 3 and 12F were the most prevalent, whereas when the diagnosis was sepsis/bacteremia the most prevalent was serotype 8. In this work, for the 18–64-year-old group, PPSV23 and PCV13 serotypes accounted for 74.56% and 44.54% respectively of the cases in the studied period. On the other hand, for the ≥65-year-old group, these serotypes represented 72.30% and 41.42% respectively. The aim of this work was to establish the knowledge bases of the serotypes that cause invasive pneumococcal diseases in the adult population in Argentina and to be able to detect changes in their distribution over time in order to explore the potential serotype coverage of the vaccines in current use.

Factors Associated With Severe Nonmeningitis Invasive Pneumococcal Disease in Adults in France.

BackgroundIn France, pneumococcal vaccination in adults is recommended for risk groups (chronic conditions/immunosuppression). We conducted a study on invasive pneumococcal disease (IPD) in adults to identify factors associated with disease severity and death.MethodsWe included IPD cases, excluding meningitis, from 25 acute care hospitals in 6 regions. We defined severe cases as those with shock or severe sepsis or intensive care unit admission/mechanical ventilation. We included deaths occurring within 30 days of hospitalization. Infectious disease specialists collected clinical/microbiological data on cases.ResultsDuring 2014–2017, 908 nonmeningitis IPD cases were diagnosed; 48% were severe, 84% had comorbidities, 21% died. Ninety percent of cases with comorbidities who previously sought health care were not vaccinated against pneumococcus. Compared with previously healthy cases, the risk of severe IPD increased from 20% (adjusted risk ratio [aRR], 1.2; 95% confidence interval [CI], 1.0–1.4) in cases with 1–2 chronic diseases to 30% (aRR, 1.3; 95% CI, 1.0–7.0) in those with >2 chronic diseases. Among risk groups, 13-valent pneumococcal conjugate vaccine (PCV13) serotypes and 23-valent pneumococcal polysaccharide vaccine (PPSV23) nonPCV13 serotypes were more likely to induce severe IPD compared with nonvaccine serotypes (aRR, 1.5; 95% CI, 1.3–1.9; aRR, 1.3; 95% CI, 1.0–1.5, respectively).ConclusionsWe observed a cumulative effect of concurrent comorbidities on severe IPD. Vaccine serotypes were more likely to induce severe IPD among risk groups. The missed opportunities for vaccination underscore the need to enhance vaccination in risk groups.