Public health impact and cost-effectiveness of 15-valent pneumococcal conjugate vaccine use among the pediatric population of the United States

BackgroundAlthough use of the 13-valent pneumococcal conjugate vaccine (PCV13) among children has reduced incidence of pneumococcal disease, a considerable burden of disease remains. PCV15 is a new vaccine that contains pneumococcal serotypes 22F and 33F in addition to serotypes contained in PCV13. To inform deliberations by the Advisory Committee on Immunization Practices on recommendations for PCV15 use among U.S. children, we estimated the health impact and cost-effectiveness of replacing PCV13 with PCV15 within the routine infant immunization program in the United States. We also assessed the impact and cost-effectiveness of a supplementary PCV15 dose among children aged 2–5 years who have already received a full PCV13 series.MethodsWe estimated the incremental number of pneumococcal disease events and deaths averted, costs per quality adjusted life-year (QALY) gained, and costs per life-year gained under different vaccination strategies using a probabilistic model following a single birth cohort of 3.9 million individuals (based on 2020 U.S. birth cohort). We assumed that vaccine effectiveness (VE) of PCV15 against the two additional serotypes was the same as the VE of PCV13. The cost of PCV15 use among children was informed from costs of PCV15 use among adults and from discussions with the manufacturer.ResultsOur base case results found that replacing PCV13 with PCV15 prevented 92,290 additional pneumococcal disease events and 22 associated deaths, while also saving $147 million in costs. A supplementary PCV15 dose among children aged 2–5 years who were fully vaccinated with PCV13 prevented further pneumococcal disease events and associated deaths but at a cost of more than $2.5 million per QALY gained.ConclusionsA further decrease in pneumococcal disease in conjunction with considerable societal cost savings could be expected from replacing PCV13 with PCV15 within the routine infant immunization program in the United States.     

PCV13 serotype decrease in Italian adolescents and adults in the post-PCV13 era: Herd protection from children or secular trend?

Background and aim of the workIn 2010 PCV13 replaced PCV7 in the pediatric vaccination schedule for Italian children. While a strong herd effect was demonstrated for PCV7, a possible herd effect due to PCV13 is still under debate. Our aim was to evaluate differences in the distribution of pneumococcal serotypes between the pre and post-PCV13 eras in unvaccinated Italian adolescents and adults with laboratory-confirmed pneumococcal infection from 3 Italian Regions with a high rate of PCV13 vaccination of children.Patients and methodsAdolescents and adults admitted with laboratory-confirmed pneumococcal infection in the hospitals of 3 Italian Regions (Friuli-Venezia Giulia, Emilia Romagna, and Tuscany) between April 2006 and June 2016 were included in the study. Diagnosis of pneumococcal infection and serotyping were performed with Real Time PCR directly on normally sterile fluids or on culture isolates.Results523 patients with laboratory-confirmed pneumococcal infection were enrolled (Male/Female ratio was 300/223, 1.3; median age 67.1, IQR 53.4–74.9). None of the patients had been vaccinated with any pneumococcal vaccine; 96.4% were serotyped. Overall, the most frequent serotypes were 3 (67/504, 13.3%), 8 (43/504, 8.5%), and 19A (38/504, 7.5%). Serotype distribution differed among age classes and clinical presentations.Overall, PCV13 serotypes accounted for 47.6% of cases: 62.3% in the pre-PCV13 era and 45.0% in the post-PCV13 era; (p = 0.005 OR = 2.03; CL 95%: 1.2–3.3). Serotype 7F accounted for 12/77 (15.6%) of all serotypes in the pre-PCV13 period and for 12/427 (2.8%) in the post-PCV13 period and was the only serotype significantly contributing to the difference in percentage between pre and post-PCV13 eras.ConclusionOur study demonstrated a difference in percentage in serotype distribution in adolescents and adults laboratory-confirmed pneumococcal infection between the pre and post-PCV13 eras. This difference is mainly due to the decrease of serotype 7F. Thus, in order to decrease disease burden, adults and in particular the elderly should be offered a specific vaccination program.     

A population-based analysis to determine the impact of the 13-valent pneumococcal conjugate vaccine on community-acquired pneumonia in British Columbia,Canada

BackgroundPneumonia is a leading cause of morbidity and mortality globally. We determined the impact of 13-valent pneumococcal conjugate vaccine (PCV13) use on community-acquired pneumonia (CAP) rates eight years after the vaccine was introduced in the infant immunization program.MethodsUsing diagnostic codes from administrative databases, we calculated the overall and age-specific CAP incidence per month (2000–2018). Changes in the CAP incidence before and after the PCV13 vaccine program introduction were evaluated using negative binomial regression model adjusting for 7-valent pneumococcal conjugate vaccine program.ResultsThe PCV13 vaccine infant immunization program was associated with declining CAP incidence among children aged 0–2 years (adjusted Incidence Rate Ratio (aIRR): 0.91; 95% CI: 0.87–0.96). Overall CAP incidence did not decrease in those aged 3–5 years (0.98; 95% CI: 0.93–1.04), 6–17 years (1.02; 95% CI: 0.97–1.08), 18–49 years (1.02; 95% CI:0.98–1.05), 50–64 years (1.07; 95% CI: 1.04–1.11), ≥65 years (1.05; 95% CI:1.02–1.08).ConclusionsThe PCV13 infant immunization program is temporally associated with a reduction in CAP incidence in vaccine target age group. However, no significant decrease in CAP incidence in other age groups warrants further study of the etiology of CAP to develop and implement effective prevention programs.     

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.     

Changes in empyema among U.S. children in the pneumococcal conjugate vaccine era

BackgroundParapneumonic empyema, a serious complication of pneumonia, started increasing among U.S. children before the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2000, and continued afterwards. This increase was due in part to pneumococcal serotypes not included in PCV7 that were included in the new 13-valent (PCV13) vaccine introduced in 2010. We assessed changes in the incidence of empyema hospitalizations among U.S. children after PCV13 introduction.MethodsWe calculated annualized empyema hospitalization rates among U.S. children <18 years using Nationwide Inpatient Sample and Census data (1997–2013) for four periods based on PCV7 and PCV13 introductions. Relative rates (RR) and 95% confidence intervals (CI) were calculated by age group and sex, comparing PCV7 [early-PCV7 (2001–2005) and late-PCV7 (2006–2009)] and PCV13 (2011–2013) periods with the pre-PCV7 period (1997–1999). Secondary analyses examined changes in pneumococcal, streptococcal, staphylococcal and unspecified empyema.ResultsAmong children <18 years of age, annualized empyema hospitalization rates peaked at 3.6 per 100,000 in the late-PCV7 period compared with 2.1 per 100,000 in the pre-PCV7 period [RR: 1.70 (95% CI: 1.11–2.60)]. However, annualized rates in the post-PCV13 period declined to 2.0 per 100,000, similar to rates in the pre-PCV7 period. Empyema rates among children <2 years were lower in the post-PCV13 period compared to the pre-PCV7 period [RR: 0.77 (95% CI: 0.61–0.96)], but rates in the two periods among children 2–4 and 5–17 years were similar. Most empyema were of unspecified etiology. Pneumococcal and unspecified empyema declined after PCV13 introduction.ConclusionsAlthough empyema hospitalization rates among U.S. children peaked after PCV7 introduction, rates decreased substantially following the introduction of PCV13.     

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

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

Pneumococcal meningitis in Greece: A retrospective serotype surveillance study in the post-PCV13 era (2010–2020)

BackgroundAs Greece is a country which has introduced the 13-valent pneumococcal conjugate vaccine (PCV13) both in the infant and in the adult immunization programs, the aim of the study was to investigate age-specific and serotype-specific trends of pneumococcal meningitis over an 11-year period (2010–2020).Materials and MethodsData are reported from pneumococcal meningitis cases [notified to the National Public Health Organization (NPHO)], with clinical samples and bacterial isolates sent for pneumococcal identification and serotyping at the National Meningitis Reference Laboratory (NMRL). Pneumococcal identification was performed directly on clinical samples or bacterial isolates by multiplex PCR (mPCR) assay, while serotyping was carried out by application of the Capsular Sequence Typing (CST) method with the combination of single tube PCR assays.ResultsA total of 427 pneumococcal meningitis cases were notified to the NPHO between 2010 and 2020. Among those, 405 (94.8%) were microbiologically confirmed, while samples from 273 patients were sent to the NMRL for identification and/or further typing. The annual notification rate peaked at 0.47/100,000 in 2016 and since then has been decreasing. The incidence was highest in infants and in older adults. Pneumococcal serotypes were identified in 260/273 (95.2%) cases, where clinical samples were sent to the NMRL. The most prevalent serotypes (≥5%) were 3, 19A, 23B, 15B/C, 11A/D, 23A, 22F. During the study period there has been a decrease of PCV13 serotypes combined with an increase of non-PCV13 serotypes (p = 0.0045).ConclusionsThis is the first study to report serotypes for pneumococcal meningitis across all ages in the post-PCV13 era in Greece. There is a need to enhance surveillance, by close monitoring of the emerging serotypes and the impact of vaccination programs. Higher-valency PCVs may help to improve the coverage of pneumococcal disease.     

Association of infant pneumococcal vaccination with pneumococcal pneumonia among mothers: A nested case–control study using the GPRD

Since implementation of infant immunization with 7-valent pneumococcal conjugate vaccine (PCV7), increased rates of pneumococcal pneumonia have been reported among adults. Using a cohort of mother–infant pairs identified from the General Practice Research Database in the UK we found that from 2006 to 2010 the annual incidence rate of pneumococcal pneumonia among mothers increased from 61/100,000 to 81/100,000. We identified 43 cases of pneumococcal pneumonia in mothers and 430 control mother–infant pairs. The conditional odds ratio of pneumococcal pneumonia in mothers whose infants received a three-dose series of PCV7 compared to mothers whose infants received zero, one, or two doses was 4.0 (95% confidence interval [95%CI]: 1.0–15.8), and 11.0 (95%CI: 1.2–98.6) when compared with mothers whose infants received no vaccinations. The incidence of pneumococcal pneumonia may have increased in mothers following the introduction of PCV7, possibly because mothers whose infants received PCV7 are at increased risk for pneumococcal pneumonia. Though there is a chance of bias inherent to observational studies, the study findings support close monitoring of adult pneumococcal disease and potential role of adult vaccination needs to be explored.     

Distribution of invasive Streptococcus pneumoniae serotypes before and 5 years after the introduction of 10-valent pneumococcal conjugate vaccine in Brazil

BackgroundIn March 2010, the 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the routine immunization program in Brazil. We describe the pneumococcal serotypes that caused invasive pneumococcal diseases (IPD) before and after the introduction of PCV10 using data from a national laboratory-based surveillance system.MethodWe compared the prevalence of vaccine types (VT) and non-vaccine types (NVT) of Streptococcus pneumoniae in three periods, pre-PCV10 (January/2005-December/2009), early post-PCV10 (January/2010-December/2013), and late post-PCV10 (January/2014-December/2015), by episode in meningitis and non-meningitis cases and by age group. Changes in serotype prevalence in the early and late post-PCV10 periods were determined using pre-PCV10 period as a reference.ResultsA total of 8971 IPD isolates from patients aged 2 months to 99 years were analyzed. In the late post-PCV10 period, the VT-IPD reduction in the 2-month to 4-year age group was 83.4% for meningitis and 87.4% for non-meningitis cases; in the age groups 5–17 years, 18–64 years, and ≥65 years, VT declined by 56.1%, 54.1%, and 47.4%, respectively, in meningitis cases, and by 60.9%, 47.7%, and 53.4%, respectively, in non-meningitis cases. NVT-IPD increased throughout the study period, driven mainly by serotypes 3, 6C, and 19A, which remained the predominant types causing IPD in the late post-PCV10 period.ConclusionWe observed direct and indirect PCV10 protection against IPD caused by VT and a shift in the distribution of serotypes 5 years after the introduction of PCV10. Continued IPD surveillance is needed to evaluate the sustainability of the high prevalence of serotypes 3, 6C, and 19A, which were not included in PCV10.     

Comparative effectiveness of individual pneumococcal vaccines with dual pneumococcal vaccination in older United States Veterans

IntroductionPneumococcal vaccination recommendations are constantly evolving. Recent pneumococcal vaccination guidelines have been updated to recommend pneumococcal conjugate vaccines in older adults. However, the clinical benefits of protein conjugate vaccine (PCV 13), pneumococcal polysaccharide vaccine (PPSV 23) and dual vaccination when compared to each other remain unclear.MethodsA retrospective cohort study conducted between 2014 and 2016 conducted at the Veterans Health administration (VHA) (N = 1,277,575). Primary outcomes were pneumococcal pneumonia and pneumococcal meningitis. Secondary outcomes were “other” pneumonia and “other” meningitis. “Other” referred to episodes of pneumonia and meningitis without an identified etiological agent.ResultsPCV 13 was associated with decreased risk of pneumococcal pneumonia (Adjusted HR 0.69; 95 % CI 0.51 to 0.93) and “other” pneumonia (Adjusted HR 0.74; 95 % CI 0.64 to 0.86) when compared to PPSV 23. No significant difference was found between PCV 13 and PPSV 23 in terms of pneumococcal meningitis (Adjusted HR 3.98; 95 % CI 0.74 to 21.32; P = 0.12) and “other” meningitis (Adjusted HR 0.81; 95 % CI 0.33 to 2.03; P = 0.66). Dual vaccination was also associated with a decrease in the rate of pneumococcal pneumonia (Adjusted HR 0.88; 95 % CI 0.77 to 0.99; P = 0.03) and “other” pneumonia (Adjusted HR 0.90; 95 % CI 0.85 to 0.95; P < 0.01) in comparison to PPSV 23.ConclusionsPCV 13 was associated with a 31% decrease in the rate of pneumococcal pneumonia in comparison to PPSV 23 in older adult Veterans. Our results demonstrating clinical benefit with PCV 13 vaccination are in alignment with the latest pneumococcal vaccination guidelines that recommend routine vaccination with pneumococcal conjugate vaccines in all older adults.     

Use of administrative records to assess pneumococcal conjugate vaccine impact on pediatric meningitis and pneumonia hospitalizations in Rwanda

BackgroundOngoing surveillance is critical to assessing pneumococcal conjugate vaccine (PCV) impact over time. However, robust prospective studies are difficult to implement in resource-poor settings. We evaluated retrospective use of routinely collected data to estimate PCV impact in Rwanda.MethodsWe collected data from admission registers at five district hospitals on children age <5 years admitted for suspected meningitis and pneumonia during 2002–2012. We obtained clinical and laboratory data on meningitis from sentinel surveillance at the national reference hospital in Kigali. We developed multivariable logistic regression models to estimate PCV effectiveness (VE) against severe pneumonia and probable bacterial meningitis and Poisson models to estimate absolute rate reductions. Haemophilus influenzae type b vaccine was introduced in January 2002, PCV7 in April 2009 and PCV13 in August 2011.ResultsAt the district hospitals, the severe pneumonia and suspected meningitis hospitalization rates decreased by 70/100,000 and 11/100,000 children for 2012 compared to baseline, respectively. VE against severe pneumonia calculated from logistic regression was 54% (95% CI 42–63%).In Kigali, from 2002 to 2012, annual suspected meningitis cases decreased from 170 pre-PCV7 to 40 post-PCV13 and confirmed pneumococcal meningitis cases from 7 to 0. VE against probable bacterial meningitis was 42% (95% CI −4% to 68%).ConclusionIn a resource-poor African setting, analysis of district hospital admission logbooks and routine sentinel surveillance data produced results consistent with more sophisticated impact studies conducted elsewhere. Our findings support applying this methodology in other settings and confirm the benefits of PCV in Rwanda.     

Comparative incidence dynamics and serotypes of meningitis,bacteremic pneumonia and other-IPD in young children in the PCV era: Insights from Israeli surveillance studies

IntroductionWidespread introduction of pneumococcal conjugated vaccines (PCVs) impacted on invasive pneumococcal disease (IPD). However, IPD reduction may not be similar in all outcomes within IPD.We assessed PCV7/PCV13 impact on pneumococcal meningitis, bacteremic pneumonia (BP) and other (non-meningitis, non-pneumonia) IPD episodes in children <5 years in Israel.MethodsA prospective, population-based, active nationwide surveillance.All pneumococcal invasive episodes with positive blood/CSF cultures, July 2000 through June 2016, were included. Three sub-periods were defined: pre-PCV (2000–2008), PCV7 (2009–2011) and PCV13 (2014–2016). Incidence rate ratios (IRRs) were calculated.ResultsOverall, 4321 episodes were recorded; 456 (10.6%) meningitis, 1478 (34.2%) pneumonia and 2387 (55.2%) other-IPD.In the pre-PCV period, proportion of serotypes in PCV13, but not in PCV7 (mainly serotypes 1, 5 and 19A) was higher in BP (43.3%) compared with other-IPD episodes (32.8%, p < 0.001) and similar to that of meningitis (37.6%, p = 0.1). The proportion of episodes in children <12 months was higher in meningitis (52.1%) compared with pneumonia (23.2%) and other-IPD episodes (39.5%; p < 0.001 for both).The declines of the 3 entities were not similar; Meningitis rate non-significantly declined by 24% (IRR = 0.76; 95% CI 0.57–1.01), while BP and other-IPD rates significantly declined by 57% and 70%, respectively. In contrast to other entities, BP did not decline significantly after PCV7 introduction but started to decline only after PCV13 introduction.Rates of meningitis, pneumonia and other-IPD caused by PCV13-serotypes (VT13) substantially declined by 88%, 95% and 97%, respectively, comparing PCV13 and the pre-PCV periods. However, diseases caused by non-VT13 increased by 256%, 302% in meningitis and pneumonia, respectively, but only 116% in other-IPD.ConclusionsFollowing PCV7/PCV13 introduction, rates of episodes caused by VT13 were substantially reduced in all 3 groups. However, differences in age distribution, serotype replacement and specific serotype decrease suggest different pathogenesis and host susceptibility between the 3 entities.     

Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against community-acquired pneumonia in older individuals after the introduction of childhood 13-valent pneumococcal conjugate vaccine: A multicenter hospital-based case-control study in Japan

BackgroundIn the era of childhood pneumococcal conjugate vaccine (PCV) immunization, especially 13-valent pneumococcal conjugate vaccine (PCV13) immunization, serotype replacement of Streptococcus pneumoniae and herd immunity in adults have been reported worldwide. Therefore, continuous evaluation of the effectiveness of the pneumococcal vaccine in adults is crucial because vaccine effectiveness may change owing to these factors. The purpose of this study was to evaluate the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against all-cause pneumonia and pneumococcal pneumonia in older individuals with community-acquired pneumonia (CAP) after the introduction of childhood PCV13 in Japan, a topic that has remained largely unexplored.MethodsWe evaluated pneumococcal vaccine effectiveness in this multicenter, matched case-control study conducted in hospitals and clinics. Cases included patients (aged ≥ 65 years) newly diagnosed with CAP between October 2016 and September 2019. A maximum of five non-pneumonia control patients matched for sex, school grade, date of outpatient visit, and medical institution were selected for each case. Conditional logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of pneumococcal vaccines for the occurrence of all-cause CAP and pneumococcal CAP.ResultsThe analysis included 740 individuals (142 patients and 598 controls). The median age of participants was 75 years (men: 54%). The adjusted OR for pneumococcal vaccination against all-cause CAP was 1.31 (95% CI: 0.84–2.06), while that for PPSV23 vaccination in the previous 5 years was 1.33 (95% CI: 0.85–2.09). The adjusted OR for PPSV23 vaccination in the previous 5 years against pneumococcal CAP was 0.93 (95% CI: 0.35–2.50).ConclusionsThis study was unable to demonstrate the effectiveness of PPSV23 against all-cause and pneumococcal pneumonia after the introduction of childhood PCV13 in Japan. Nonetheless, additional studies are needed to validate these results.     

Invasive pneumococcal disease: Clinical outcomes and patient characteristics 2–6 years after introduction of 7-valent pneumococcal conjugate vaccine compared to the pre-vaccine period,the Netherlands

BackgroundImplementation of 7-valent pneumococcal conjugate vaccine (PCV7) in the Dutch national immunization program for infants led to a shift from vaccine to non-vaccine serotypes in invasive pneumococcal disease (IPD) in all age groups. We studied the impact of the serotype shift on clinical syndromes and outcomes.MethodsPneumococcal isolates from hospitalized IPD patients obtained from nine sentinel microbiology laboratories, covering 25% of the Dutch population, were serotyped. Clinical syndromes, outcomes and patient characteristics in the post-PCV7 (2008–2012) period were compared with the pre-PCV7 period (2004–2006). Serotype specific propensity of the association with empyema, meningitis and death was calculated.ResultsInvasive pneumonia incidence significantly decreased in children <5 years and elderly ≥65 years, but increased in 5–64 years old from 4.92 to 5.58 cases/100.000/year (RR 1.13 95% CI 0.99–1.29). Empyema incidence significantly increased in elderly 65 years and older from 0.61 to 2.60 cases/100.000/year (RR 4.28 95% CI 1.97–9.33), mainly due to serotype 1. The incidence of meningitis only declined significantly in children <5 years. IPD case-fatality decreased in children <5 years from 5% to 3%, in 5–64 years old from 9% to 7% and in elderly ≥65 years significantly from 22% to 17%, due to lower case-fatality rates for most emerging non-PCV7 serotypes.ConclusionsAn increase in empyema incidence was observed in persons ≥65 years old in the post-PCV7 era, mainly due to the emergence of serotype 1, although overall IPD case-fatality decreased. Extended conjugate vaccines that target serotype 1 or serotypes with high case-fatality may offer further reduction of pneumococcal disease burden.     

Pneumococcal epidemiology among us adults hospitalized for community-acquired pneumonia

BackgroundFew studies have measured the burden of adult pneumococcal disease after the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the US infant vaccination schedule. Further, most data regarding pneumococcal serotypes are derived from invasive pneumococcal disease (IPD), which represents only a fraction of all adult pneumococcal disease burden. Understanding which pneumococcal serotypes cause pneumonia in adults is critical for informing current immunization policy. The objective of this study was to measure the proportion of radiographically-confirmed (CXR+) community-acquired pneumonia (CAP) caused by PCV13 serotypes in hospitalized US adults.MethodsThis observational, prospective surveillance study recruited hospitalized adults aged ≥18 years from 21 acute care hospitals across 10 geographically-dispersed cities in the United States between October 2013 and September 2016. Clinical and demographic data were collected during hospitalization. Vital status was ascertained 30 days after enrollment. Pneumococcal serotypes were detected via culture from the respiratory tract and normally-sterile sites (including blood and pleural fluid). Additionally, a novel, Luminex-based serotype-specific urinary antigen detection (UAD) assay was used to detect serotypes included in PCV13.ResultsOf 15,572 enrolled participants, 12,055 eligible patients with CXR+CAP were included in the final analysis population. Mean age was 64.1 years and 52.7% were aged ≥65 years. Common comorbidities included chronic obstructive pulmonary disease (43.0%) and diabetes mellitus (28.6%). PCV13 serotypes were detected in 552/12,055 (4.6%) of all patients and 265/6347 (4.2%) of those aged ≥65 years. Among patients aged 18–64 years PCV13 serotypes were detected in 3.8–5.3% of patients depending on their risk status.ConclusionsAfter implementation of a pneumococcal conjugate vaccination program in US children, and despite the herd protection observed in US adults, a persistent burden of PCV13-type CAP remains in this population.     

Cost-effectiveness of 13-valent pneumococcal conjugate vaccination in Mongolia

ObjectiveThe Ministry of Health (MOH), Mongolia, is considering introducing 13-valent pneumococcal conjugate vaccine (PCV13) in its national immunization programme to prevent the burden of disease caused by Streptococcus pneumoniae. This study evaluates the cost-effectiveness and budget impact of introducing PCV13 compared to no PCV vaccination in Mongolia.MethodsThe incremental cost-effectiveness ratio (ICER) of introducing PCV13 compared to no PCV vaccination was assessed using an age-stratified static multiple cohort model. The risk of various clinical presentations of pneumococcal disease (meningitis, pneumonia, non-meningitis non-pneumonia invasive pneumococcal disease and acute otitis media) at all ages for thirty birth cohorts was assessed. The analysis considered both health system and societal perspectives. A 3 + 0 vaccine schedule and price of US$3.30 per dose was assumed for the baseline scenario based on Gavi, the Vaccine Alliance’s advance market commitment tail price.ResultsThe ICER of PCV13 introduction is estimated at US$52 per disability-adjusted life year (DALY) averted (health system perspective), and cost-saving (societal perspective). Although indirect effects of PCV have been well-documented, a conservative scenario that does not consider indirect effects estimated PCV13 introduction to cost US$79 per DALY averted (health system perspective), and US$19 per DALY averted (societal perspective). Vaccination with PCV13 is expected to cost around US$920,000 in 2016, and thereafter US$820,000 every year. The programme is likely to reduce direct disease-related costs to MOH by US$440,000 in the first year, increasing to US$510,000 by 2025.ConclusionIntroducing PCV13 as part of Mongolia’s national programme appears to be highly cost-effective when compared to no vaccination and cost-saving from a societal perspective at vaccine purchase prices offered through Gavi. Notwithstanding uncertainties around some parameters, cost-effectiveness of PCV introduction for Mongolia remains robust over a range of conservative scenarios. Availability of high-quality national data would improve future economic analyses for vaccine introduction.     

Invasive disease potential of Streptococcus pneumoniae serotypes before and after 10-valent pneumococcal conjugate vaccine introduction in a rural area,southern Mozambique

BackgroundInvasive pneumococcal disease (IPD) is a significant cause of morbidity and mortality among children worldwide. In April 2013, Mozambique introduced 10-valent PCV (PCV10) into the National Expanded Program on immunization using a three-dose schedule at 2, 3, and 4 months of age. We aimed to evaluate the invasive disease potential of pneumococcal serotypes among children in our region before and after PCV10 introduction.MethodsWe used data from ongoing population-based surveillance for IPD and cross-sectional pneumococcal carriage surveys among children aged <5 years in Manhiҫa, Mozambique. To determine the invasive disease potential for each serotype pre- and post-PCV10 introduction, odds ratios (OR) and 95% confidence intervals (95% CI) were calculated comparing serotype-specific prevalence in IPD and in carriage. For each serotype, OR and 95% CI > 1 indicated high invasive disease potential and OR and 95% CI < 1 indicated low invasive disease potential.ResultsIn the pre-PCV10 period, 524 pneumococcal isolates were obtained from 411 colonized children and IPD cases were detected in 40 children. In the post-PCV10 period, 540 pneumococcal isolates were obtained from 507 colonized children and IPD cases were detected in 30 children. The most prevalent serotypes causing IPD pre-PCV10 were 6A (17.5%), 6B (15.0%), 14 (12.5%), 23F (10.0%) and 19F (7.5%), and post-PCV10 were 6A (36.7%), 13 (10%), 1 (10.0%), 6B (6.7%) and 19A (6.7%). Serotypes associated with high invasive disease potential pre-PCV10 included 1 (OR:22.3 [95% CI 2.0; 251.2]), 6B (OR:3.1 [95% CI 1.2; 8.1]), 14 (OR: 3.4 [95% CI 1.2; 9.8]) and post-PCV10 included serotype 6A (OR:6.1[95% CI 2.7; 13.5]).ConclusionThe number of serotypes with high invasive disease potential decreased after PCV10 introduction. Serotype 6A, which is not included in PCV10, was the most common cause of IPD throughout the study and showed a high invasive potential in the post-PCV10 period.     

Trends in pneumococcal meningitis hospitalizations following the introduction of the 13-valent pneumococcal conjugate vaccine in the United States

BackgroundThe 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in 2010 in the U.S. and its impact on pneumococcal meningitis (PM) is unknown. We assessed the impact of PCV13 on PM hospitalization rates 4 years after the vaccine was introduced.MethodsThis was a retrospective analysis of the National Inpatient Sample from 2008–2014. Patients with an ICD-9-CM code for PM (320.1) were identified and rates calculated using US Census data as the denominator. Data weights were used to derive national estimates. We examined three time periods: 2008–2009 (late post-PCV7), 2010 (transition year), and 2011–2014 (post-PCV13).ResultsDuring the study period, there were 10,493 hospitalizations due to PM in the U.S. Overall, PM incidence decreased from 0.62 to 0.38 cases per 100,000 over this time (39% decrease; P < 0.01). Among children <2 years, the average annualized PM rate decreased by 45% from 2.19 to 1.20 per 100,000 (P = 0.10). Annual PM rates decreased in those aged 18–39 years (0.25–0.15 cases per 100,000; P = 0.02) and 40–64 years (0.95–0.54 cases per 100,000; P = 0.03). A total of 1016 deaths were due to PM, and the case fatality rate was variable over the study period (8.3%–11.2%; P = 0.96).ConclusionFollowing the introduction of PCV13, hospitalization rates for PM decreased significantly with no subsequent improvements in case-fatality rate.     

Pneumococcal conjugate serotype distribution and predominating role of serotype 3 in German adults with community-acquired pneumonia

IntroductionImplementation of the 7-valent pneumococcal conjugate vaccine (PCV7) in infant vaccination programs has substantially reduced the burden of PCV7 serotypes also in adult community-acquired pneumonia (CAP). Currently, it is unclear, if this extensive herd protection effect can be extrapolated to the additional 6 serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13), which replaced PCV7 in Germany in 2010.ObjectivesWe investigated changing trends for PCV13 serotypes in adult CAP patients between three to seven years after implementation of PCV13 infant immunization in Germany.MethodsBetween December 2012 and January 2017, urine samples from German adult patients with radiologically confirmed CAP were prospectively collected by the multi-center cohort study CAPNETZ and analyzed by the serotype-specific multiplex urinary antigen detection assay (SSUAD) allowing for the detection of PCV13 serotypes.ResultsPCV13 serotypes were found in 59 of 796 (7.4%) patients with all-cause CAP, most prevalent was serotype 3 (30 of 59 patients, 50.8%). All patients with serotype 3-CAP were admitted to hospital and the majority required oxygen at admission (83.3% of patients with serotype 3-CAP versus 50.9% of patients with pneumococcal CAP by other serotypes, p = 0.005). Compared to SSUAD testing, conventional microbiological workup missed 27 of 30 (90.0%) serotype 3-CAP cases. We could not observe a time trend in the proportions of PCV13 serotypes and serotype 3 in all-cause CAP between 2013 and 2016 (OR trend per year 0.84, 95% CI 0.64–1.11 for PCV13 serotypes and OR trend per year 0.95, 95% CI 0.70–1.28 for serotype 3). Conclusions: Conventional methods underestimate serotype 3-CAP that can cause severe disease. Changes in overall PCV13 coverage were not detected during the years 2013 to 2016, mostly driven by a high proportion of serotype 3.     

Cost-effectiveness of continuing pneumococcal conjugate vaccination at age 65 in the context of indirect effects from the childhood immunization program

The findings and conclusions in this report are those of the authors and do not necessarily represent the official positon of the Centers for Disease Control and Prevention.BackgroundContinued indirect effects provided by the childhood pneumococcal conjugate vaccine (13-valent pneumococcal conjugate vaccine [PCV13]) program in the United States have decreased disease in the adult population, reducing the potential direct effects of vaccinating older adults.ObjectiveWe examined the incremental cost-effectiveness of continuing to recommend PCV13 in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) at age 65 compared to a strategy that only included a recommendation for PPSV23 at age 65.MethodsWe used a probabilistic model following a cohort of 65 year olds in 2019. We used vaccination coverage and disease incidence estimates for healthy adults and adults with chronic medical conditions. We incorporated continued indirect effects from the childhood PCV13 program on adult disease incidence.ResultsIn the base case scenario, continuing to recommend PCV13 at age 65 cost $561,682 per quality-adjusted life year (QALY) gained. In a scenario where PPSV23 provided modest protection against non-invasive pneumococcal pneumonia, costs increased to $2.3 million per QALY. These estimates are larger than our prior estimates for cost-effectiveness of this recommendation in the context of predicted indirect effects due to new data indicating PCV13 provided limited impact on serotype 3, the major cause of the remaining PCV13-type disease. Under our prior assumptions about PCV13 effectiveness against serotype 3 disease, the cost of continuing the recommendation is $207,607 per QALY.ConclusionIndirect effects from the childhood PCV13 program have dramatically increased the cost per QALY of continuing to recommend PCV13 at age 65 after only a few years.