Update on the use of pneumococcal vaccines in adults 65 years of age and older – A Public Health Perspective

An Advisory Committee Statement (ACS) National Advisory Committee on Immunization (NACI) 

Preamble

The National Advisory Committee on Immunization (NACI) provides the Public Health Agency of Canada (hereafter referred to as the PHAC) with ongoing and timely medical, scientific, and public health advice relating to immunization. PHAC acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge and is disseminating this document for information purposes. People administering the vaccine should also be aware of the contents of the relevant product monograph(s). Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) of the Canadian manufacturer(s) of the vaccine(s). Manufacturer(s) have sought approval of the vaccine(s) and provided evidence as to its safety and efficacy only when it is used in accordance with the product monographs. NACI members and liaison members conduct themselves within the context of PHAC's Policy on Conflict of Interest, including yearly declaration of potential conflict of interest.

Summary of information contained in this NACI statement

The following highlights key information for immunization providers. Please refer to the remainder of the Statement for details.

1. What

Streptococcus pneumoniae (S. pneumoniae) is a bacterium that can cause many types of diseases including invasive pneumococcal disease (IPD), and community-acquired pneumonia (CAP).

For the prevention of diseases caused by S. pneumoniae in adults, two types of vaccines are available in Canada: pneumococcal 23-valent polysaccharide (PNEU-P-23) vaccine containing 23 pneumococcal serotypes and pneumococcal 13-valent conjugate (PNEU-C-13) vaccine containing 13 pneumococcal serotypes.

NACI has been tasked with providing a recommendation from a public health perspective on the use of pneumococcal vaccines in adults who are 65 years of age and older, following the implementation of routine childhood pneumococcal vaccine programs in Canada.

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Organization: Public Health Agency of Canada

Published: November 2018
Cat.: HP40-221/2018E-PDF
ISBN: 978-0-660-27296-2
Pub.: 180186

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2. Who

Information in this statement is intended for provinces and territories (P/Ts) making decisions for publicly funded, routine, immunization programs for adults who are 65 years of age and older without risk factors increasing their risk of IPD. These recommendations supplement the recent NACI recommendations on this topic that were issued for individual-level decision making in 2016.

3. How

For routine, publicly funded, immunization programs for adults 65 years of age without other risk factors increasing their risk of IPD, NACI does not recommend the inclusion of PNEU-C-13 vaccine at its current price. One dose of PNEU-P-23 vaccine is recommended for all adults 65 years of age and older, regardless of risk factors or previous pneumococcal vaccination. Individual-level recommendations for PNEU-C-13 vaccine have been discussed in the 2016 NACI recommendations.

4. Why

The programmatic recommendation for adults age 65 years and older is based on the epidemiology of circulating S. pneumoniae serotypes causing IPD and CAP in Canada and the evidence of changing incidence of pneumococcal disease following the implementation of childhood PNEU C vaccination programs. Although there is clinical trial evidence for PNEU-C-13 vaccine efficacy in older adults for preventing IPD and CAP, currently within the Canadian context, such a publicly funded program would not significantly decrease the disease burden in a cost-effective manner.

I. Introduction

The objective of this Statement Update is to provide evidence and recommendations, from a public health perspective, for the use of pneumococcal vaccines for the prevention of community-acquired pneumonia (CAP) and invasive pneumococcal disease (IPD) in adults 65 years of age and older, without other risk factors increasing their risk of IPD.

This statement:

Updates the epidemiology of pneumococcal disease in those 65 years of age and older in Canada with regards to serotypes included in PNEU-P-23 and PNEU-C-13 using the most recently available national surveillance data (2015);

  • Provides an update to the review of the literature on the use of PNEU-P-23 in adults;
  • Provides an overview of the available literature on the changes observed internationally following the implementation of childhood PNEU-C programs on the general population of adults;
  • Provides an economic analysis of pneumococcal vaccination for adults over 65 years of age; and
  • Provides updated programmatic, population-level, recommendations for the use of pneumococcal vaccines in adults who are 65 years of age and older without other risk factors increasing their risk of IPD.

PNEU-P-23 vaccine is recommended for use in Canada for the prevention of IPD in adults who are 65 years of age and older. Since July 2015, PNEU-C-13 vaccine has been authorized for the prevention of IPD and CAP caused by the serotypes included in the vaccine, for all adults 18 years of age and older.

In 2016, in addition to recommending the use of PNEU-P-23 vaccine for all adults 65 years of age and older, NACI has recommended the use of PNEU-C-13 vaccine to individuals desiring additional protection against strains contained in the vaccine.(1) In addition to the individual-level recommendations that were developed in consideration of the existing evidence on vaccine safety, immunogenicity and efficacy, as part of its expanded mandate, NACI has also been tasked to provide a public health-level recommendation based on a comprehensive evaluation of programmatic factors including vaccine program cost-effectiveness and the impact on disease burden. The intent of the public-health level guidance is to support P/Ts in developing programmatic recommendations concerning the inclusion of PNEU-C-13 vaccine into the existing pneumococcal programs for adults 65 years of age and older. Previously published NACI Statements are available on the Government of Canada website.

National Vaccine Coverage Goals and Disease Reduction Targets have been set and endorsed by the Public Health Network council. For IPD, in individuals over the age of 65 years, a disease reduction target to less than 23.5 cases per 100,000 population per year (P-Y) by 2025 has been set(2).

II. Methods

NACI reviewed the key questions for the literature review, as proposed by the Pneumococcal Working Group (PWG), including such considerations as the burden of disease to be prevented and the target population(s), safety, immunogenicity, efficacy, effectiveness of the vaccine(s), vaccine schedules, indirect effects of concurrent vaccination program, and other aspects of the overall immunization strategy. Knowledge review and synthesis of studies published until April 10, 2017 was performed by two graduate students and technical advisors at PHAC, and supervised by the NACI PWG Chair.

The national surveillance data on IPD came from the Canadian Notifiable Disease Surveillance System (CNDSS). Data from 8 jurisdictions (BC, AB, SK, ON, QC, PEI, YK and NU) representing 90% of the Canadian population were used to perform the analyses. All cases were presumed to meet the national case definition for IPD. CNDSS data are limited by the lack of information on cases' risk factors, including immuno-competence and vaccination status; other data limitations are provided on the Government of Canada website.

The CNDSS cases and the National Microbiology Laboratory (NML) specimen data are not linked and have therefore been reported separately. To enhance comparability, only the NML serotype data for specimens submitted by 8 jurisdictions that provide national line level surveillance data (namely BC, AB, SK, ON, QC, PEI, YK and NU) were analyzed. The exception is the antimicrobial resistance data, for which specimens from all jurisdictions have been reported. The NML data are limited by reporting differences between jurisdictions and the availability of bacterial isolates submitted for testing; other NML data limitations are provided on the Government of Canada website. The following overall limitations of existing surveillance programs in Canada are noted:

  • Nationally representative data are not currently available on the burden of all-cause CAP and vaccine type (VT) CAP in Canada;
  • National surveillance data on vaccination status or additional risk factors (e.g. comorbidities) are not available for identified cases of IPD and VT IPD in Canada;
  • Missing data are present within both the CNDSS and NML datasets.

The systematic review and meta-analysis by Kraicer-Melamed et al., 2016 (3, 4) was developed in consultation with the PWG and was used as the evidence base for decision-making by NACI. Since the publication of the systematic review by Kraicer-Melamed et al., a similar systematic review and meta-analysis was published by Falkenhorst et al., 2017(5), to examine the efficacy or effectiveness of PPV23 to prevent IPD and pneumococcal pneumonia (PP) in individuals aged 60 years and older. Further to this, a systematic review and meta-analysis by Htar et al., 2017, also assessed the vaccine efficacy of PNEU-P-23 and PNEU-C-13 against CAP. For comparative purposes, all systematic reviews and meta-analyses were appraised by the PWG using the AMSTAR measurement tool for the assessment of the methodological quality of systematic reviews. (6-8)

A narrative literature review on the indirect effects of routinely administered pneumococcal infant immunization programs on the incidence of pneumococcal disease in adults was also performed.

To guide protection against pneumococcal disease at the population level, recommendations were made in consideration of the Erickson-De Wals framework for immunization programs in Canada.(9) Following thorough review of the evidence and consultation at the NACI meetings of September 27-28, 2017 and February 7-8, 2018, the committee voted on specific recommendations. The description of relevant considerations, rationale for specific decisions, and knowledge gaps are described in the text.

III. Epidemiology

S. pneumoniae can spread from person to person via droplets from the nose or mouth, by sneezing or coughing. Although asymptomatic upper respiratory tract colonization is common, infection with S. pneumoniae can cause many types of diseases, with IPD and non-invasive pneumococcal community acquired pneumonia (NIpCAP) being the most common in adults. IPD is a severe form of infection that occurs when the bacteria invade normally sterile sites, such as the bloodstream or central nervous system, leading to bacteremia and meningitis. Certain conditions predispose individuals to diseases that are caused by S. pneumoniae, including sickle-cell disease and other hemoglobinopathies, chronic renal failure, chronic liver disease, immunosuppression, anatomic or functional asplenia, cerebrospinal fluid leaks, diabetes mellitus, and HIV infection. There are currently over 90 serotypes recognized worldwide, 15 of which are known to cause the majority of pneumococcal disease. (10-12)

National surveillance data on cases meeting the national IPD case definition are routinely collected through CNDSS. The NML provides data for isolates submitted by provincial and territorial public health laboratories including Laboratoire de santé publique du Québec (LSPQ), the Alberta Provincial Laboratory for Public Health (ProvLab) and the Toronto Invasive Bacterial Diseases Network (TIBDN). Though national laboratory and epidemiologic data are not linked at the case level, it is estimated that approximately 75% of specimens from cases reported through CNDSS are provided to NML for testing. Information about IPD and CAP in hospitalized adults 65 years of age and older, including vaccination history and immune status, is collected through the Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN).

Detailed epidemiological information on IPD in Canada is provided on the Government of Canada website.

III.1 Disease distribution by age group

Following the initial NACI recommendation in 1989, all Canadian provinces and territories have implemented PNEU-P-23 vaccination programs for adults who are 65 years of age and older. In addition, all Canadian provinces and territories have implemented routine childhood PNEU-C vaccination programs between 2002 and 2006 (Table 1), with the majority of P/Ts currently using a 3-dose PNEU-C-13 vaccination schedule.(13-27) PNEU-C-13 vaccine has been recommended by NACI as a preferred product for childhood programs since 2010, and was included in all provincial and territorial (P/T) pediatric vaccination programs by 2011.

Table 1: Routine childhood conjugate pneumococcal vaccine program introduction by province and territory

P/T Year of routine PNEU-C-7 program introduction Year of routine PNEU-C-10 program introduction Year of routine PNEU-C-13 program introduction
BC September 2003 N/A June 2010
AB September 2002 N/A July 2010
SK April 2005 N/A July 2010
MB October 2004 N/A July 2010
ON January 2005 December 2009 November 2010
QC December 2004 June 2009 January 2011
NL March 2005 October 2009 September 2010
NB April 2005 N/A July 2010
NS January 2005 N/A July 2010
PE June 2003 N/A September 2010
YT June 2005 N/A May 2011
NT January 2006 September 2009 September 2010
NU April 2002 N/A September 2010

Since the introduction of pediatric PNEU-C programs in Canada, a 2.6-fold decrease in IPD incidence was observed in children less than 5-years-old between 2002 and 2006 (from 39.1 to 15.3 cases per 100,000 population), followed by an additional 1.6-fold reduction between 2010 and 2015 (17.7 to 10.8 cases per 100,000 population). Among older age groups, the impact of routine pediatric immunization programs on IPD has been more modest, with reductions in PNEU-C-13 serotypes being offset by an increase in non-vaccine serotypes and serotypes that are unique to the PNEU-P-23 vaccine (Figure 1, Figure 3).

Figure 1: Incidence of IPD by age group, 2001-2015, CNDSS

Figure 1.

Figure 1 shows incidence rate of IPD (vertical axis) in cases per 100,000 population with respect to year (horizontal axis) in shown yearly increments from years 2001 to 2015. Text boxes provide additional timeline information concerning Health Canada's PNEU-C-7 NOC issuance (2001), implementation (2002-2006) and PNEU-C-13 implementation (2010-2012). Data points are based on Canadian Notifiable Disease Surveillance System data.

Surveillance results are plotted in distinct individual colors, differentiating between age brackets. Age brackets are represented as: < 5 (purple), 5 to 17 (light blue); 18 to 49 (teal); 50 to 64 (green) and > 65 (red).

The age bracket with the highest incidence rate variance is shown to be the < 5 bracket. This plot exhibits concave properties during its first five years (2001-2005) with an incidence rate of ~29 cases per 100,000 population (2001), increasing to a global maximum of ~42 cases per 100,000 population (2003). The incidence rate then decreases steadily down to a local minimum of ~16 cases per 100,000 population (2006), bouncing back to a local maximum of ~21 cases per 100,000 population (2009), to finally progressively decrease toward its global minimum of ~11 cases per 100,000 population.

Both 50 to 64 and > 65 age brackets exhibit similar trends, although the > 65 bracket's incidence rate hovers ~12.5 cases per 100,000 population higher than the 50-64 age bracket. The 50-64 age bracket display a slow but steady increasing trend from ~6 to ~14 cases per 100,000 population (2001 to 2007), stabilizing around ~12.5 cases per 100,000 population during the following years. The > 65 age bracket display a somewhat steeper increase in incidence rate from ~13 to ~25 cases per 100,000 population (2001 to 2004), stabilizing around ~25 cases per 100,000 population during the following years.

The two lowest incidence age brackets are shown to be the 5 to 17 and 18 to 49 brackets, which exhibit rates < 5 cases per 100,000 population, with the exception of years 2006 to 2008, where the 18 to 49 age bracket displayed slightly higher incidenceincidence rate (~6 cases per 100,000 population).

In adults 65 years of age and older, the annual incidence rate of IPD has decreased non-significantly from 25.1 cases per 100,000 population (pop.) in 2011 to 23.6 cases per 100,000 pop. in 2015 (p>0.05). In this age group, the largest decrease has been observed in adults 85 years of age and older, while in other age groups incidence has remained unchanged. (Figure 2)

Figure 2. Incidence of IPD, adults 65 years of age and older, 2011-2015, CNDSS
Figure 2.

Figure 2 shows incidence rate of IPD (vertical axis) in cases per 100,000 population with respect to year (horizontal axis) in shown yearly increments from year 2011 to 2015 Data points are based on Canadian Notifiable Disease Surveillance System data.

Surveillance results are plotted in distinct individual colors, differentiating between age brackets. Age brackets are represented as: 65-74 (yellow), 75 to 84 (green) and 85+ (red). In 85 years and older age group, the largest decrease has been observed (~50 to ~42 cases per 100,000 population), while other age groups display incidence rate stability: ~18.5 cases per 100,000 population among 65-74 age bracket; ~28 cases per 100,000 population among 85+ age bracket.

III.2 Disease distribution by serotype

Based on the data from isolates submitted to NML, the proportion of PNEU-C-13 vaccine serotypes has been decreasing in all age groups since the introduction of routine pediatric programs.(28) When comparing the number of specimens containing PNEU-C-13 vaccine serotypes in 2011 with the number in 2015, a reduction of approximately 30% has been observed in adults 65 years of age and older (Figure 3).

Figure 3: Proportion of specimens from IPD cases corresponding to PNEU-C-13, unique PNEU-P-23 and non-vaccine (NVT) serotypes for individuals 65 years and older, 2011-2015, NML
Figure 3.

Figure 3 depicts the proportion of specimens from IPD cases corresponding to PNEU-C-13, unique PNEU-P-23 and non-vaccine (NVT) serotypes for individuals 65 years and older during the years 2011-2015, data from NML.

YEAR PNEU-C-13 (Number; % of total) PNEU-P-23* (Number; % of total) NVT (Number; % of total) Total (Number)
2011 357; 43% 196; 24% 268; 33% 821
2012 327; 40% 240; 29% 250; 30% 818
2013 300; 34% 309; 35% 285; 32% 895
2014 230; 27% 297; 35% 326; 38% 855
2015 245; 27% 309; 34% 340; 38% 896
Total 1459; 34% 1351; 31% 1469; 34% 4285

*excluding serotypes contained in PNEU-C-13 XXX

Table 2: Number of specimens from IPD cases corresponding to PNEU-C-13, unique PNEU-P-23 and NVT serotypes for individuals 65 years and older, 2011-2015, NML

YEAR PNEU-C-13 PNEU-P-23* NVT Total
2011 357 196 268 821
2012 327 240 250 818
2013 300 309 285 895
2014 230 297 326 855
2015 245 309 340 896
Total 1459 1351 1469 4285

During the same period, there has been an approximately 50% observed increase in the number of specimens with unique serotypes contained in PNEU-P-23 and a 25% increase in NVT serotypes. Detailed information about IPD specimens by serotype for adults 65 to 74 years of age is provided in Table 3.

Table 3. Number of IPD specimens by serotype, adults 65 to 74 years of age, 2011-2015, NML

Vaccine product Serotype 2011 2012 2013 2014 2015
PNEU-C-13 19A 116 107 98 67 67
3 88 85 86 76 89
7F 85 63 63 46 26
19F 15 8 9 11 19
4 11 17 12 6 11
6A 14 14 7 8 6
14 7 7 6 4 7
6B 7 7 8 3 4
23F 4 6 5 7 7
18C 2 5 4 2 3
9V 7 4 2 0 2
1 1 2 0 0 2
5 0 2 0 0 2
PNEU-P-23
(*excluding serotypes
contained in PNEU-C-13)
22F 84 106 116 111 103
11A 23 30 33 39 48
9N 22 15 40 30 30
8 15 22 35 25 32
15B 10 11 16 14 27
12F 15 9 13 14 19
20 4 8 16 21 20
10A 6 13 13 11 15
17F 7 9 3 12 5
2 0 0 0 0 0
NVT 15A 36 48 54 58 73
23A 44 44 41 51 50
6C 52 45 46 39 35
16F 12 26 24 35 22
23B 18 19 16 31 26
35B 18 13 29 21 29
35F 13 14 14 24 26
31 10 9 12 20 14
38 14 6 18 7 14
15C 9 11 8 8 6
34 12 4 5 3 13
Others† 30 11 18 29 32

In adults 65 years of age and older, among serotypes that are contained in the conjugate vaccines, the most prevalent were those unique to the PNEU-C-13 vaccine (i.e. 3, 7F and 19A). With the exception of serotype 3 (ST3), a declining trend for serotypes contained in the PNEU-C-13 vaccine has been observed since 2011. (Table 3, Figure 4). Similar trends have also been reported by other international jurisdictions that have implemented routine pediatric PNEU-C vaccine programs. (29-35)

Figure 4: Proportion of specimens with serotypes included in PNEU-C-13 vaccine in adults 65 years of age and older, 2011-2015, NML
Figure 4.

Figure 4 shows proportion of specimens with serotypes included in PNEU-C-13 vaccine in adults 65 years of age and older, from years 2011-2015. Data from NML.

YEAR 19A 3 7F Others
2011 32% 25% 24% 19%
2012 33% 26% 19% 22%
2013 33% 29% 21% 18%
2014 29% 33% 20% 18%
2015 27% 36% 11% 26%

III.3 Disease distribution by antimicrobial resistance (AMR)

Following the introduction of PNEU-C vaccine programs in Canada, an overall decline in AMR pneumococci has been observed concomitant with the decline in PNEU-C vaccine contained serotypes, including the multi-drug resistant serotype 19A.(12, 36) Between 2011 and 2014, resistance of S. pneumoniae to penicillin decreased from 12% to 9% and resistance to clindamycin declined from 7% to 4%. Over the same period, resistance to three or more classes of antimicrobials has also declined from 8% to 5%. Resistance to clarithromycin, which can be used in community-acquired pneumonia (CAP), decreased from 25% in 2012/13 to 22% in 2014. Resistance to doxycycline and trimethoprim/sulfamethoxazole has remained relatively stable around 8% and 6%, respectively (Figure 5). All isolates tested between 2011 and 2014 have shown susceptibility to vancomycin, ertapenem, linezolid, and tigecycline.

Figure 5: Antimicrobial resistance trends among isolates of S. pneumoniae submitted to NML, 2011 - 2015
Figure 5.

Figure 5 (clustered bar graph) shows the percentage of antimicrobial resistance (AMR) from isolates of S. pneumonia submitted to NML from 2011 (dark blue), 2012 (orange); 2013 (green); 2014 (purple) and 2015 (teal). The different clusters are identified as such: AUG = amoxicillin/clavulanic acid; PENm = penicillin using the parenteral meningitis CLSI interpretive standard;; PENn = penicillin using the parenteral non-meningitis interpretive standard; PENo = penicillin using the oral penicillin V interpretive standard; LEV = levofloxacin; MOX = moxifloxacin; AXOm = ceftriaxone using the parenteral meningitis interpretive standard; AXOn = ceftriaxone using the parenteral non-meningitis interpretative standard; FURo = cefuroxime using the oral interpretative standard; FURp = cefuroxime using the parenteral interpretative standard; ETP = ertapenem; IMI = imipenem; MER = meropenem; CLA = clarithromycin; CLI = clindamycin; CHL = chloramphenicol; DOX = doxycycline; SXT = trimethoprim/sulfamethoxazole.

Between 2011 and 2014, resistance of S. pneumoniae to penicillin decreased from 12% to 9% and resistance to clindamycin declined from 7% to 4%. Over the same period, resistance to three or more classes of antimicrobials has also declined from 8% to 5%. Resistance to clarithromycin, which can be used in community-acquired pneumonia (CAP), decreased from 25% in 2012/13 to 22% in 2014. Resistance to doxycycline and trimethoprim/sulfamethoxazole has remained relatively stable around 8% and 6%, respectively. All isolates tested between 2011 and 2014 have shown susceptibility to vancomycin, ertapenem, linezolid, and tigecycline.

*Data from NML. The data is limited by reporting differences between jurisdictions; variability in sample sizes amongst the smaller jurisdictions that result in small counts representing large relative proportions; and the availability of bacterial isolates submitted for testing; other data limitations of NML are provided at https://www.canada.ca/en/public-health/services/publications/drugs-health-products/national-laboratory-surveillance-invasive-streptococcal-disease-canada-annual-summary-2014.html.

III.4 CAP

Using SOS Network data from five provinces, Leblanc et al.(37) reported on CAP incidence in hospitalized adults from December 2010 to December 2013. CAP caused by S. pneumoniae was identified through sputum culture, commercial pan-pneumococcal urine antigen detection (UAD) or a serotype-specific UAD. Over the course of the study, 14.3% (549/3851) of all-cause CAP was found to be caused by S. pneumoniae when any of the diagnostic tests were used. Among serotypable specimens (384/549), 70.1% (269/384) were serotypes included in the PNEU-C-13 vaccine. Of all S. pneumoniae CAP captured during the study period, there was an observed decline in the proportion of PNEU-C-13 serotypes from 72.9% in 2011 to 63.5% in 2013. In adults 65 years of age and older, the proportion of all-cause CAP that was caused by serotypes contained in PNEU-C-13 vaccine decreased from 15.5% in 2011 to 10.8% in 2013. Among individuals included in the study, approximately a third had an immunocompromising condition.

III.5 Immunization coverage

In 2014, national immunization coverage for PNEU-P-23 among immunocompetent adults 65 years of age and older was estimated to be 36.5% (95% CI: 32.7 - 40.3).(38)

For 2015, national immunization coverage for PNEU-C in children at the age of 2 years was estimated to be 80.3% (95% CI: 75.1 - 84.7).(39)

IV. Vaccine

IV.1 Preparations authorized for use in Canada

Two preparations of pneumococcal vaccine for use in adults are available in Canada and are described in past NACI statements.(1, 40-42)

PNEU-P-23 (Pneumovax®23) is a sterile solution of 23 highly purified capsular polysaccharides (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F). PNEU-P-23 is available as a 3 ml single-dose vial containing 0.5 ml dose of liquid vaccine and a 1.5 ml prefilled syringe containing 0.5 ml dose of liquid vaccine.

PNEU-C-13 (Prevnar®13) is a sterile solution of polysaccharide capsular antigen of 13 serotypes of S. pneumoniae (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F). The antigens are individually conjugated to a diphtheria CRM197 protein carrier. The CRM197 protein carrier is adsorbed on aluminum phosphate as an adjuvant. Each dose of vaccine contains 4.4 mcg of the 6B polysaccharide, and 2.2 mcg each of the remaining polysaccharides. PNEU-C-13 is marketed in a single dose, prefilled 1ml syringe containing 0.5mL of vaccine.

A comprehensive list of vaccine contents is available online within the Canadian Immunization Guide.

IV.2a Efficacy - Direct

PNEU-P-23 vaccine

IPD

A Cochrane review of studies published up to June 2012 identified 5 RCTs that recruited 27,886 otherwise healthy adults living in high-income countries. The study authors reported evidence of protective efficacy against IPD for <2 to 6 years following immunization, with a vaccine efficacy of 80% odds ratio (OR: 0.20; 95% CI 0.10 to 0.39; random-effects model, I2 = 0%).(7) An additional trial conducted by Hönkanen et al.in Finland estimated PNEU-P-23's efficacy in preventing IPD among individuals 65 years of age and older to be 60% risk ratio (RR: 0.40; 95% CI: 0.10 - 1.90).(98)

CAP

A Cochrane review of 6 RCTs published up to June 2012 and involving 29,186 adults from high-income countries found a pooled estimated vaccine efficacy against all cause pneumonia of 29% (OR: 0.71; 95% CI 0.45 to 1.12; I2=93). The systematic review analysis conducted by Kraicer-Melamed et al.(4, 44) was similarly not able to find conclusive evidence for vaccine efficacy of PNEU-P-23 in preventing CAP, reporting a pooled vaccine efficacy of three trials to be -10% (95% CI: -36% - 12).

PNEU-C-13 vaccine

Vaccine efficacy was reported for a mean follow-up time of 3.97 years(45). For overall VT CAP, vaccine efficacy was estimated to be 45.6% (95% CI: 21.8, 62.5) and for non-bacteremic VT CAP 45.0% (95% CI: 14.2, 65.3). For VT IPD vaccine efficacy was estimated to be 75.0% (95% CI: 41.4, 90.8). Please refer to the previous NACI statement for additional information on PNEU-C-13 efficacy in the general population of adults who are 65 years of age and older.(1)

IV.2b Effectiveness - Direct and Indirect

The effectiveness of PNEU-P-23 and PNEU-C-13 vaccines in preventing pneumococcal disease (IPD and CAP) was evaluated on the basis of data obtained from published systematic reviews(4, 5, 7, 8, 44) and a review of studies summarized in a previous NACI statement.(46) The following table (Appendix A) summarizes the AMSTAR score for each systematic review assessed.

Several differences in study inclusion and exclusion criteria resulted in different summary estimates for PNEU-P-23 vaccine effectiveness against IPD. Most notably, Kraicer-Melamed et al.(4) excluded studies of patients with significant underlying immunocompromising medical conditions or residents of nursing homes or assisted living settings as these were not considered a reasonable representation of disease transmission and health outcomes for the general population. Kraicer-Melamed et al. did not exclude studies with observational designs, and they did not include populations <50 years old. Inclusion and exclusion criteria for the referenced systematic reviews are detailed in Appendix B.

Direct effects

PNEU-P-23 vaccine

IPD

The review of data from eight cohort and four case-control studies conducted by Kraicer-Melamed et al. estimated pooled vaccine effectiveness for IPD to be 50% (95% CI: 21%-69%) for cohort studies and 54% (95% CI: 32%-69%) for case-control studies.(4) Stratification by method of diagnosis, time since vaccination (2 weeks up to 5 years), and quality indicated that estimates were largely unaffected by these additional factors.

In addition, a Cochrane review(47-51) of 5 non-RCT studies that included adults over 55 years of age reported a vaccine effectiveness of 68% for all IPD (OR: 0.32; 95% CI 0.22 to 0.47; random-effects model; I2 =18%, P = 0.30).(47-51) However, the pooled analysis included data from trials that used polysaccharide vaccines of lower valency (i.e. 14-valent vaccines) or vaccines for which valency was not specified.

The literature search also found three recently conducted systematic reviews. A meta-analysis by Falkenhorst et al.(5) reported PNEU-P-23's vaccine effectiveness against all IPD of 58% (OR: 0.42; 95% CI: 0.28 to 0.62; I2 =11%) based on data from 5 cohort studies and of 45% (OR: 0.55; 95% CI: 0.35 to 0.85 I2 =0%) when two cohort studies with high risk of bias were excluded. For case-control studies vaccine effectiveness was reported at 59% (OR: 0.41; 95% CI: 0.26 to 0.65; I2=60%) for all pneumococcus and 73% (OR: 0.27; 95% CI: 0.16 to 0.44; I2 =0%) for VT IPD based on pooled data from 3 and 2 studies, respectively. Data from four indirect cohort studies was also analyzed by the study authors, who estimated vaccine effectiveness against VT IPD at 37% (OR: 0.63; 95%CI 0.55 to 0.73; I2 =0%).

CAP

The literature search identified three recently published systematic reviews. The analysis conducted by Kraicer-Melamed et al.(3) provided pooled vaccine effectiveness estimates for all cause CAP. Based on data from nine cohort studies(48, 49, 52-58) and seven case-control studies(47, 59-64), pooled vaccine effectiveness for all-cause CAP was estimated at 17% (95% CI: -26%-45%) and 7% (95% CI: -10%-21%), respectively. Additional stratifications by method of diagnosis, time since vaccination, and study quality did not affect the overall conclusion of no statistically significant effect of PNEU-P-23 vaccination on the prevention of CAP.

A study by Falkenhorst et al. provided a pooled estimate for vaccine effectiveness in preventing pneumococcal pneumonia(PP) based on two cohort studies to be 48% [95% CI: 25-63%, I2 = 0%]) and one case-control study with a vaccine effectiveness against PP of 53% (95% CI 33-68%).(5) Htar et al.(65) also conducted a systematic review of 33 observational studies that reported vaccine effectiveness results on the protection for any clinically relevant outcome other than IPD. Depending on the conducted analysis, in adults 65 years of age and older, the study authors reported wide ranges of vaccine effectiveness (-143% to 60%). Presence of pediatric PNEU-C vaccine programs and time since vaccination were found to significantly (p<0.01) influence PNEU-P-23 vaccine effectiveness, with diversity of study populations, circulation of S. pneumoniae serotypes and case definition further explaining very high between-study heterogeneity (I2 = 99.24%, p < 0.01). The reported meta-analyzed vaccine effectiveness estimate for any-CAP requiring hospitalization in the general population was 10.2% (95%CI: -12.6; 33.0) and -6.31 (95% CI: -15.78; 3.17, I2 = 60%) in countries with a national childhood PNEU-C immunization program. In the stratified meta-analysis by maximum time since vaccination, vaccine effectiveness was 32.6% (95%CI: -5.9; 71.1, I2 = 99%) and 2.4% (95%CI: -5.4; 10.1, I2 = 65%) when the time since vaccination was less than 60 months and 60 months or more, respectively.

PNEU-C-13 vaccine

There were no publications identified describing direct effectiveness of PNEU-C-13 at the time of the literature search. With the ACIP's recommendation to use PNEU-C-13 in all adults aged 65 years and older, vaccine effectiveness data should become available in the future as the effect of vaccine in that population is analysed. (1)

Indirect effects of routinely administered infant immunization programs with PNEU-C vaccine on pneumococcal disease

There is evidence that the use of conjugate vaccines in children can generate herd effects in adults. As demonstrated through the evaluation of mass meningococcal vaccine programs, such an effect has been observed for meningococcal conjugate vaccines, but not for polysaccharide vaccines.

To better understand prospective changes in IPD, VT IPD, CAP, and VT CAP in individuals 50 years of age and older, a narrative review of the literature describing incidences prior to and following the implementation of childhood PNEU-C programs was conducted by the PWG.

IPD

Changes in adult (18 years of age and older) IPD incidence following infant PNEU-C program introduction in unvaccinated populations were recently reported in a systematic review and meta-analysis of 142 studies published between January 1994 and Jan 2016.(66) Data were available from 27 high-income and seven middle-income countries, including studies that reported on the impact of infant PNEU-C immunization programs in Canada. Using a random-effects model to estimate vaccine effectiveness over time, the authors predicted a 90% reduction in 8.5 years (95% CI 5.7- 19.7) for the additional 6 serotypes following a switch from PNEU-C-7 to PNEU-C-13 vaccine programs. The model showed similar decreases in IPD due to PNEU-C vaccine serotypes in adults aged 19-64 years and adults aged 65 years and older.

The PWG also conducted a review of 10 Canadian studies that reported on serotype specific IPD incidence in immunocompetent adults after PNEU-C infant program introduction in Alberta, Ontario, British Columbia and Quebec, including data from the CIRN SOS Network, which included 45 hospitals (18,000 beds) in 7 provinces. Based on empirical evidence (period 2000-2014) and theoretical considerations, Zhou et al.(67) predicted future trends in IPD rates in Quebec adults 65-74 years of age in the context of childhood PNEU-C vaccine programs. According to the multivariate Poisson regression model, proportion of PNEU-C-13 serotypes (including ST3) in IPD cases was expected to reach 20% (95% CI: 15% to 28%) in 2024. The study authors also conducted a sensitivity analysis in which, depending on the impact of PNEU-C-13 vaccine on ST3 IPD, the proportion of PNEU-C-13 types in overall IPD was expected to range from 23% [8% to 52%] to 18% [6% to 49%].

Kellner et al. analyzed over 1,150 IPD samples from adults 65 years of age and older in Calgary following the initiation of the provincial infant PNEU-C-7 program in 2002 (68). From the1998/2001 to 2003/2007 period, there was an observed 78% reduction in PNEU-C-7 serotypes in the 65-85 year-old age group (22.1 to 4.8/100,000 P-Y). The trend of decreasing IPD incidence among Calgary adults in the same age group was further documented by Leal et al. based on over 1,400 IPD cases reported from 1998 through 2010. (69) The authors observed a near eradication (2.2/100,000 P-Y) of PNEU-C-7 serotype IPD cases in the 65 years of age and older age group, with no reported PNEU-C-7 serotype cases in individuals 85 years and over in 2010. Sahni et al. reported similar trends following the introduction of PNEU-C-7 in British Columbia. (70) The proportion of PNEU-C-7 serotypes in samples submitted to the BC Centre for Disease Control from 2002 through 2010 significantly decreased by 94% (2.7 to 0.1 per 100,000 P-Y, p<0.01) in the 17-64 age group and by 91% (9.6 to 0.7 per 100,000 P-Y, p<0.01) in persons over 64 years of age. The most recent regional data analysis by Cabaj et al. (71) showed marked declines in adult IPD rates 10 years following the childhood PNEU-C program introduction. Compared to the pre-introduction rates (2000-2002 vs. 2010-2013), there was a 36% reduction in IPD in adults 65-84 years of age, and a 42% reduction in adults 85 years of age and older. The study authors noted a near-elimination of PCV7-serotype IPD in adults 65 years of age and older, particularly in immunocompetent individuals.

Two studies using TIBDN data from 1995 to 2011 reported consistent decreases in adult IPD after childhood PNEU-C program implementation.(72, 73) Rudnick et al., and Lim et al. reported an 88% reduction (95% CI, 93-78%) in IPD due to PNEU-C-7 serotypes among adults 15-64 years of age and an 89% reduction (95% CI, 94-80%) in adults over 65 years of age. During the same period, the incidence of IPD due to serotypes included in PNEU-P-23 but not in PNEU-C-13 remained stable. Desai et al.(74) also reported on IPD surveillance data from Ontario between 2007 and 2014. Based on data from over 3,800 adults aged 65 years and over, there was a 20% annual decrease in the incidence of PNEU-C-7 serotypes (from 3.0 to 0.7 cases per 100,000). A significant decrease (p < 0.001) in incidence was also observed for PNEU-C-13 serotypes 4 years after its introduction into the routine childhood program (9.8 to 5.3 per 100,000). For serotypes unique to PNEU-P-23, the study authors observed a significant increase (p < 0.001) in incidence over the study period, from 2.3 cases per 100 000 in 2007 to 5.8 cases per 100,000 in 2014.

Decreases in the proportion of IPD cases attributable to PNEU-C VT serotypes in Quebec were reported by LSPQ.(75) Based on the data from 21 sentinel hospitals which report approximately a third of all IPD cases among children < 5 years of age in Quebec, only one case (1.2% of total cases) of PNEU-C-7 and 10 cases (12.3% of all cases) of PNEU-C-13-unique serotype were reported in 2014, compared to 20 cases (26.3%) of PNEU-C-7 and 23 cases (30.3%) of PNEU-C-13-unique serotype reported in 2006.

National data from IPD samples submitted to the NML three years after the introduction of the PNEU-C-13 vaccine programs in Canada were reported by Demczuk et al. In this time period, the study authors observed an overall PNEU-C-13 serotype decrease from 50% to 39% among individuals 65 years of age and older (p<0.001).(76)

CAP

The literature search identified fourteen studies that reported on CAP incidence rates among adults following the implementation of childhood PNEU-C programs. A decrease in CAP incidence was observed in all studies beginning three years after program initiation.

A study by Nelson et al.(77) from the Group Health Cooperative in Washington State evaluated the impact of infant PNEU-C-7 immunization on pneumonia in approximately 800,000 members in the first 2 years post-childhood PNEU-C program introduction in year 2000. Pneumonia episodes were identified in 17,513 outpatient and 6,318 hospitalized events using diagnostic codes and confirmed chest radiograph reports or hospitalization records.

For the 65-74 year age group, study authors observed an increase in incidence rate ratios of confirmed hospitalized pneumonia (IRR 1.3; 95%CI: 1.12-1.5) and decrease in confirmed outpatient pneumonia (IRR 0.97; 95%CI: 0.88-1.08). Using the clinical discharge diagnosis from approximately 20% of all US hospital admissions, Grijalva et al.(78) compared the impact of PNEU-C-7 program during the 4 years after its introduction in the US. For the 65 years of age and older individuals, the study authors estimated a 20% hospital admission rate reduction for PP (from 73.9 to 59.3/100,00; 14.6/100,000 [95% CI: 2.0-27.6]) and a 15% hospital admission rate reduction for all-cause pneumonia (from 2,559 to 2,162/100,000; 396.5/100,000 [95% CI: 60.9-774.1]).

Simonson et al.(79) used Healthcare Cost and Utilization Project State Inpatient Databases from 10 states to evaluate the impact of PNEU-C-7 infant program introduction on PP hospitalizations. Compared to a pre-program baseline incidence, the authors observed a 54% (95% CI: 53-56) reduction in non-bacteremic PP in adults ≥ 65 years of age, six years after program implementation.

Griffin et al.(80) also analyzed the impact of PNEU-C-7 introduction on hospitalization for all cause pneumonia in the Nationwide Inpatient Sample database. The authors reported a 6.6% (95% CI: 0.5-12.7) reduction in all cause pneumonia in the 65-74-year-old age group 7 to 9 years after the infant PNEU-C-7 program introduction. Simonsen et al.(81) also used the IMS Charge Data Master hospital database that collects information from approximately 500 non-federal, short-stay hospitals (20% of all US hospital admissions) to analyze the impact of the infant PNEU-C-13 program introduction on non-invasive pneumococcal or lobar pneumonia two years following the PNEU-C-13 infant program introduction. For adults 65 years of age and older, the study authors estimated a 34% (95% CI: 27-41) decline in hospital admissions.

Decreasing incidence was also observed among individuals over 65 years of age in two studies in the UK and one study from Australia. Rodrigo et al.(82) reported on differences in VT PP 3 to 5 years following PNEU-C-13 childhood program introduction. An observed decrease in incidence of PNEU-C-13 VT CAP was reported in individuals aged 65-74 years of age (23.2 to 12.5 per 100,000) 3 years following PNEU-C-13 adoption. In this age group, the study authors estimated the annual change in rate ratio for pneumococcal CAP, CAP due to serotypes contained in PNEU-C-7 and CAP due to additional serotypes contained in PNEU-C-13 to be 0.84 (0.80-0.89), 0.52 (0.43-0.62) and 0.87 (0.80-0.95), respectively. Nair et al.(83) analyzed hospital records and death certification datasets from Scotland for the three-year period following PNEU-C-13 introduction in 2010. Compared to the incidence pre PNEU-C-7 program introduction in 2006, study authors found a 21.4% (95%CI: 42.9-7.1) decrease in hospital admissions for PP in the 65-74-year age group. Menzies et al.(84) evaluated the impact of infant PNEU-C-7 program on adult pneumonia hospitalization up to 6.5 years following program introduction, analyzing the Institute of Health and Welfare National Hospital Morbidity Database. For pneumococcal and lobar pneumonia in individuals 65-74 years of age, the study authors reported a post (2005-2011) vs. pre (1998-2004) program implementation incidence rate ratio of 0.86 (95% CI: 0.74-0.99).

Decrease in adult CAP following infant PNEU-C program introduction was also reported in studies from Japan, Nicaragua, Taiwan, Germany and Poland(85). In a single hospital study in Taiwan, among adults over 65 years of age, Lin et al.(86) observed a 64.1% reduction (95% CI: 13.3-115%) in non-bacteremic PP hospitalizations within three years of childhood program implementation (from 51 to 18 cases per 100,000 hospitalizations, p=0.009).

In a study from Poland, Patrzalek et al.(87)reported on the changes of all-cause pneumonia incidence among individuals 65 years of age and older following the implementation of a national childhood PNEU-C-7 program. The study authors reported a 56% reduction in incidence four years after the program (from 1,939 to 1,095 cases per 100,000 population). Katoh et al.(88) reported on the changes in the incidence of PP in Japan using data polled through a systematic review. In comparison to pre-program period, one to three years following the childhood PNEU-C-7 program implementation, study authors found an 18.1% decrease (95% CI: 24.6, 11.5%) in the total proportion of PNEU-C-7 serotypes.

Akata et al. also reported changes in PP rates from 2011 to 2015. During this period, there was a significant decrease in vaccine serotypes from 46.4% to 8.3% (p < 0.05) for PNEU-C-7 serotypes and from 71.4% to 33.3% (p < 0.05) for PNEU-C-13 serotypes. Pletz et al..(85), using the data from the CAPNETZ study in Germany, studied the impact of PNEU-C-7 program introduction in 2007 on the incidence of adult CAP (mean age, 58 years). The proportion of patients with PNEU-C-7 serotype non-bacteremic PP decreased from 31.3% to 14.8% in the four years following PNEU-C-7 program implementation. Becker-Dreps(89) reported changes (pre/post introduction) due to pneumonia two years after PNEU-C-13 program introduction in Nicaragua as IRR of 0.81 (95% CI: 0.61-1.06) for ambulatory visits and 2.07 (95% CI: 1.84-2.33) for hospitalizations.

In the Netherlands, van Werkoven et al.(90) reported incidence trends for non-IPD pneumococcal CAP caused by PNEU-C-13 types and non-PNEU-C-13 serotypes among patients 65 years of age and older who were recruited into the CAP-pilot and CAPITA studies. In 270 samples that were available for analysis, the proportion of PNEU-C-7 serotypes in non-IPD PP decreased linearly from 28% in 2008/2009 to 7% in 2012/2013 (p<0.001), 7 years after PNEU-C-7 childhood program introduction.

No statistically significant changes in the proportion of additional strains contained in PNEU-C-10 or PNEU-C-13 were observed over this time period.

Information on the impact of infant PNEU-C program introduction was also available from Shigayeva et al.(91)who analyzed the Ontario TIBDN data for non-bacteremic PP six years following the implementation of the provincial childhood PNEU-C-7 immunization program. The median age of adults included in the study was 64 years, with 46.6% being 65 years of age and older. The study authors reported a 24.6% (95% CI: 15-35.2%) reduction in non-bacteremic PP between 2003 and 2011.

IV.3 Immunogenicity

Information on PNEU-P-23 and PNEU-C-13 vaccine immunogenicity has previously been detailed in the NACI statement on PNEU-C-13 for individuals(41).

IV.4 Vaccine administration and schedule

Detailed information on PNEU-P-23 and PNEU-C-13 vaccine administration and recommended schedules is available in the Pneumococcal vaccine chapter of the Canadian Immunization Guide.

IV.5 Serological testing

Routine pre- or post-immunization serology for pneumococcal vaccines is not indicated.

IV.6 Storage requirements

Please refer to the Pneumococcal vaccine chapter of the Canadian Immunization Guide for information regarding storage of pneumococcal vaccines.

IV. 7 Simultaneous administration with other vaccines

Please refer to the Pneumococcal vaccine chapter of the Canadian Immunization Guide for information regarding simultaneous administration of pneumococcal vaccines with other vaccines.

IV.8 Adverse events

Adverse events (AE) following administration of PNEU-P-23 and PNEU-C-13 have been reported in previous NACI statements on PNEU-C-13(1, 40, 41) and in the Pneumococcal vaccine chapter of the Canadian Immunization Guide.

A recently published study by Miller et al.(92) evaluated the post-licensure safety of PNEU-P-23 (Pneumovax®23 only) using data from the US Vaccine Adverse Event Reporting System from 1990-2013. The authors identified injection site erythema, pain, and swelling as the most commonly reported adverse events among adults 18 years of age and older following administration of PNEU-P-23 and concluded that the evaluation revealed no novel or surprising results.

IV.9 Contraindications and precautions

Please refer to the previous statement and the Canadian Immunization Guide for more information on contraindications and precautions for PNEU-P-23 and PNEU-C-13.

IV.10 Economic analysis

Under the Erickson-De Wals framework, PWG evaluated a static model from previous work that was developed to simulate IPD and non-invasive pneumococcal community-acquired pneumonia (NIpCAP) epidemiology in the age-group 65 to 74 years of age.(93) PWG compared two different strategies:(i) one dose of PNEU-P-23 at age 65 years, and (ii) PNEU-C-13 at age 65 years followed by PNEU-P-23 one year later. Program costs included vaccine and administration costs, with the vaccine price differential in the base model set at $55 per dose, in favor of PNEU-P-23. Demographic and epidemiological parameters used in the model were extracted from published studies, surveillance and administrative databases originating from Quebec and Ontario.

Future trends in IPD and NIpCAP incidence and serotype distribution (2015-2024) were modelled using surveillance data from Quebec and considering the assumed serotype replacement and the indirect effects of PNEU-C-13 vaccine use in children. Benefits of vaccination included reduction in outpatient and emergency room visits, hospitalizations, long-term sequelae from meningitis and mortality, as well as improvement in quality of life. Direct disease costs to the healthcare system, including costs to individuals for treatment of disease were considered, but not indirect costs resulting from work absenteeism and productivity losses. All benefits and costs were discounted at a 3% annual rate with a lifetime horizon and incremental cost-effective ratios (ICER) expressed as $CAD/QALY.

The reference population was 100,000 persons 65 to 74 years of age, followed over a lifetime, with mutually exclusive outcomes associated with pneumococcal infections including IPD (meningitis, bacteremia-septicemia, bacteremic pneumonia, and other clinical presentations) and NIpCAP. PNEU-C-13 effectiveness values against VT-IPD and VT-NIpCAP in the 65-74 years age group were derived from results of the CAPITA trial in the Netherlands and PNEU-P-23 effectiveness values against VT-IPD were derived from the Cochrane review of randomized clinical trials and from a case-control study in the US. PNEU-P-23 effectiveness against NIpCAP was assumed to be zero. Forecasted changes in serotype distribution were based on Quebec LSPQ (Laboratoire de Sante Publique du Quebec) data (using 2000-2014 data to predict serotype distribution until 2024), which predicted the continued shifting of IPD burden from PNEU-C vaccine towards non-vaccine serotypes. Information on input parameters used in the base-case and sensitivity analyses is provided in Table 4 and Table 5.

Table 4: Input parameters used in the base-case and sensitivity analyses

Model parameters Base-case Sensitivity analyses References
Epidemiology      
IPD incidence 22.2/100,000 p-y x 0.5 to x 2 MED-ECHO Quebec(1-5)
Hospitalized CAP incidence 333.4/ 100,000 p-y x 0.5 to x 2 MED-ECHO Quebec(1-5)
Proportion of CAP non- hospitalized 40% 20% to 70%  
Vaccine      
PNEU-C-13 effectiveness Table 5 x 0.8 to x 1.2 (limit=100%) (6)
PNEU-P-23 effectiveness against IPD Table 5 x 0.8 to x 1.2 (limit=100%) (8, 7)
PNEU-P-23 effectiveness against NIpCAP Table 5 Table 5 (8, 7, 9)
Economics      
Vaccine price difference PNEU-C-13 (minus) PNEU-P-23 $55 $0 to $55 Quebec Ministry of Health and Social Services, written communication, 2016
Administration cost $16 $0 to $30 (10)
Discounting rate annual 3% 0 to 6% (11)
  1. M. Jackson, O. Yu, C.G. Whitney, L. Bounds, R. Bittner, et coll. « Impact of the introduction of pneumococcal conjugate vaccine on rates of community acquired pneumonia in children and adults », Vaccine, 2008, 26(38) : 4947-54.
  2. Morrow, A., De Wals P., Petit G., Guay M. et L.J. Erickson. « The burden of pneumococcal disease in the Canadian population before routine use of the seven-valent pneumococcal conjugate vaccine », Canadian Journal of Infectious Diseases and Medical Microbiology, 2007, 18(2) : 121-7.
  3. JOKINEN, C., L. HEISKANEN, H. JUVONEN, S. KALLINEN, K. KARKOLA, M. KORPPI, et coll. « Incidence of community-acquired pneumonia in the population of four municipalities in Eastern Finland », American Journal of Epidemiology, 1993, 137(9) : 977-88.
  4. JOKINEN, C., L. HEISKANEN, H. JUVONEN, S. KALLINEN, M. KLEEMOLA, M. KOSKELA, et coll. « Microbial etiology of community-acquired pneumonia in the adult population of 4 municipalities in eastern Finland », Clinical Infectious Diseases, 2001, 32(8) : 1141-54.
  5. MARRIE, T.J., D.E. LOW, E. DE CAROLIS, R. DUPERVAL, S. FIELD, T. LOUIE, et coll. « A comparison of bacteremic pneumococcal pneumonia with nonbacteremic community-acquired pneumonia of any etiology - Results from a Canadian multicentre study », Canadian Respiratory Journal, 2003, 10(7) : 368-74.
  6. CCNI. Une déclaration du comité consultatif (DCC). Déclaration sur l'utilisation du vaccin conjugué contre le pneumocoque 13-valent chez l'adulte (Pneu-C-13). RMTC, 2013, 39 (DCC -5) : 1-52.
  7. Honkanen, P.O., T. Keistinen, L. Miettinen, E. Herva, U. Sankilampi, E. Läärä, et coll. « Incremental effectiveness of pneumococcal vaccine on simultaneously administered influenza vaccine in preventing pneumonia and pneumococcal pneumonia among persons aged 65 years or older », Vaccine, 1999, 17(20-21) : 2493-500.
  8. Mise à jour sur l'utilisation des vaccins conjugués contre le pneumocoque chez les enfants [Internet], Canada, ASPC, 2010 [mis à jour en nov. 2010; recensé le 2 nov. 2017]. Disponible à l'adresse https://www.canada.ca/fr/sante-publique/services/rapports-publications/releve-maladies-transmissibles-canada-rmtc/numero-mensuel/2010-36/releve-maladies-transmissibles-canada-3.html.
  9. Menzies, R.I., S.H. Jayasinghe, V.L. Krause, C.K. Chiu et P.B. McIntyre. « Impact of pneumococcal polysaccharide vaccine in people aged 65 years or older », Medical Journal of Australia, 2014, 200(2) : 112-5.
  10. Link-Gelles, R., T. Taylor et M.R. Moore. « Forecasting invasive pneumococcal disease trends after the introduction of 13-valent pneumococcal conjugate vaccine in the United States, 2010-2020 », Vaccine, 2013, 31(22) : 2572-7.
  11. Pneumococcal Polysaccharide (PNEUMO-P) Vaccine [Internet], Alberta, Canada, Alberta Health Services, 2016 [mis à jour le 6 juillet 2017; recensé le 6 déc. 2017]. Disponible à l'adresse https://myhealth.alberta.ca/Alberta/Pages/immunization-pneumococcal-polysaccharide.aspx

Table 5: Vaccine effectiveness against VT IPD and VT NIpCAP since vaccine administration

Years since vaccination 0 1 2 3 4 5 6 7 8 9
VT-IPD
PNEU-C-13< 76% 76% 76% 76% 76% 63% 51% 38% 25% 13%
PNEU-P-23 72% 72% 72% 64% 64% 64% 51% 38% 26% 13%
PNEU-P-23 (sensitivity analysis) 72% 72% 72% 64% 64% 0% 0% 0% 0% 0%
VT-NIpCAP
PNEU-C-13 46% 46% 46% 46% 46% 38% 31% 23% 15% 8%
PNEU-P-23 (base-case model) 0% 0% 0% 0% 0% 0% 0% 0% 0% 0%
PNEU-P-23 (sensitivity analysis) 30% 24% 18% 12% 6% 0% 0% 0% 0% 0%
Figure 6: Incremental cost-effectiveness ratio of combined PNEU-C-13 and PNEU-P-23 vaccination versus PNEU-P-23 only vaccination in univariate sensitivity analyses, health care perspective
Figure 6.

Figure 6 displays a tornado diagram representing the incremental cost-effectiveness ratio of combined PNEU-C-13 and PNEU-P-23 vaccination versus PNEU-P-23 only vaccination in univariate sensitivity analyses from a health care perspective, the base case for estimated ICER $60,977/QALY.

Variable/Uncertainty Low Up
% S. pneumonia among NIpCAP [0.5; 0] $39,005.00 $231,535.00
CAP incidence [x2 to x0.5] $32,599.00 $98,836.00
Discount rate [0%; 6%] $45,571.00 $77,288.00
Ratio of PCV13-types in NIpCAP/IPD [1.0 to 0.6] $54,931.00 $81,017.00
IPD incidence [x2 to 0.5] $46,645.00 $71,720.00
Administration cost [$0 to $30] $48,107.00 $72,873.00
PCV13 effectiveness against VT-NIpCAP [x1.2 to x0.8] $52,462.00 $72,332.00
PPV23 effectiveness against VT-IPD [x0.8 to x1.2] $54,919.00 $70,048.00
PPV23 effectiveness against VT-NIpCAP [not; effective] $60,977.00 $68,597.00
Case-fatality outcomes [x1.2 to x0.8] $57,765.00 $64,568.00
Figure 7: Univariate sensitivity analysis of the impact of price differential between PNEU-C-13 and PNEU-P-23 on incremental cost-effectiveness ratio of the PNEU-C-13 and PNEU-P-23 versus PNEU-P-23 only scenario, healthcare system perspective
Figure 7.

Figure 7 (line graph) shows a univariate sensitivity analysis of the impact of price differential between PNEU-C-13 and PNEU-P-23 on incremental cost-effectiveness ratio of the PNEU-C-13 and PNEU-P-23 versus PNEU-P-23 only scenario, from a healthcare system perspective.

ICER ($/QALY-gained) Price Differential ($)
$15,020.00 $0.00
$23,275.00 $10.00
$31,531.00 $20.00
$39,786.00 $30.00
$48,041.00 $40.00
$56,296.00 $50.00
$64,552.00 $60.00

IV.11 Summary considerations

In adults 65 years of age and older, following the introduction of routine pediatric PNEU-C programs, the proportion of CAP and IPD caused by serotypes that are contained in PNEU-C-7 and PNEU-C-13 vaccines have been decreasing. The PNEU-C-7 vaccine strains in IPD have almost disappeared in the elderly population, with the similar trend being observed for PNEU-C-13; a 30% reduction has been observed in the first five years following pediatric PNEU-C-13 program implementation, with a more than 90% reduction in PNEU-C-13 vaccine containing strains expected to occur by 2019(66).

The only exception is ST3, persisting with approximately 180 cases per year in adults over 65 years of age. This is likely a result of greater circulation in this age group, in part due to decreased effectiveness of PNEU-C-13 in children against carriage and the low effectiveness of PNEU-P-23 vaccine against ST3. Among adults 65 years of age and older, serotypes not contained in the currently available vaccines as well as those unique to PNEU-P-23 vaccine continue to be the most important contributors to the IPD burden of illness in Canada.

NACI has therefore continued to recommend one dose of PNEU-P-23 vaccine for all adults 65 years of age and older. Comprehensive recommendations for the use of PNEU-P-23 are provided in the CIG.

According to 2015 data, in adults 65 years of age and older, approximately 30% of IPD cases and 10% of all-cause CAP requiring hospitalization are caused by PNEU-C-13 serotypes.

In immunocompetent adults aged 65 years and older, both PNEU-C-13 and PNEU-P-23 vaccines have been shown to be safe, immunogenic and effective against IPD. Comparative immunogenicity studies between PNEU-C-13 and PNEU-P-23 vaccine have indicated that antibody levels are higher in elderly subjects vaccinated with PNEU-C-13 for 8 serotypes that are common to both vaccines, but the clinical and population-level implications associated with this improved immunogenicity remain unclear.(102, 103) PNEU-C-13 vaccine has also been shown to be moderately efficacious against NIpCAP caused by the serotypes included in the vaccine.

Based on the model that was developed by De Wals et al. and with an assumed 50% vaccine coverage, introducing the PNEU-C-13 vaccine at 65 years of age could potentially annually prevent up to 35 cases of IPD and up to 250 cases of community-acquired pneumonia, of which 150 are hospitalized (Table 6). At the current price, adding PNEU-C-13 vaccine to routine immunization programs for adults 65 years and older was not found to be cost effective, despite the likely overestimates in the vaccine-preventable pneumococcal disease burden that was used in the De Wals et al. model (Table 6). At a stable vaccine cost, given the declining incidence of PNEU-C-13 serotypes in IPD and CAP as a result of pediatric PNEU-C-13 vaccine programs, the cost-effectiveness of PNEU-C-13 program in adults will likely decline over time. Despite the reduction in the proportion of PNEU-C-13 vaccine types, the IPD burden is likely to remain stable or increase over time as a result of replacement. The effect on overall NIpCAP remains unknown due to the lack of nationally representative data on outpatient CAP.

Table 6: Estimated impact of pneumococcal vaccine programs on pneumococcal disease in Canada
Program options Considerations (N=100,000)
PNEU-P-23 only at 65 years
of age versus no vaccination
Number (percentage) of IPD cases averted= 85 (33.8%)
Number (percentage) of IPD deaths averted= 18 (33.8%)
Number (percentage) of CAP cases averted= 0 (0%)
Number (percentage) of CAP hospitalizations averted= 0 (0%)
Number (percentage) of CAP deaths averted= 0 (0%)
(0%)
Program cost = $2.7 M
Estimated cost savings to health system (medical cost only)= $688,391
Incremental Cost Effectiveness Ratio= $10,148/QALY saved
PNEU-C-13 and PNEU-P-23
(1 year apart) at 65 years of
age versus PNEU-P-23 at
65 years of age
Number (percentage) of IPD cases averted= 17 (9.9%)
Number (percentage) of IPD deaths averted= 3 (9.9%)
Number (percentage) of CAP cases averted= 125 (8.1%)
Number (percentage) of CAP hospitalizations averted= 76 (8.1%)
Number (percentage) of CAP deaths averted= 8 (8.1%)
Difference in program cost = $8.1 M
Estimated cost savings to health system (medical cost only)= $710,717
Incremental Cost Effectiveness Ratio= $63,318/QALY saved

Table 7: Option management

Options
PNEU-P-23 vs.
PNEU-C-13 and
PNEU-P-23
Considerations Decision Points
PNEU-P-23 alone Epidemiology:
  • IPD incidence in adults is
    stable, but increasing proportion
    of IPD specimens with serotypes unique to PNEU-P-23
    by 5%
Vaccine efficacy:
  • IPD: 80% (61 - 90%)
  • CAP all-cause: 29% (-12 - 55%)
Vaccine effectiveness:
  • IPD: 45 - 68% (depending on
    studies and stratified by study
    design)
  • PNEU-P-23 serotypes IPD:
    73% (56 - 84%)
  • CAP (all cause):
    • Worst-case: 7% (-12 - 21%)
    • Best-case: 48% (25 - 63%)
Economics:
  • ICER: ~$10 000/QALY
    compared to no vaccination
    program

Epidemiology
Decrease in circulating PNEU-C-13
serotypes - except serotype 3 (ST3);
burden of illness of PNEU-P-23 (not 13)
serotypes still present

Vaccine Efficacy and Effectiveness
PNEU-C-13 has better vaccine efficacy
against IPD/CAP for PNEU-C-13
serotypes, including serotype 3
compared to PNEU-P-23;
PNEU-P-23 has possible vaccine
efficacy and effectiveness against CAP,
but not shown consistently.

Safety
Both vaccines are safe with no
associated SAE reported

Feasibility/Acceptability
Vaccination with PNEU-C-13 cannot
replace PNEU-P-23 - need 2 vaccines;
given one year apart is acceptable

Ethics/Equity:
PNEU-C-13 available on private
market - if not publicly funded -
potential inequity

Economics:
PNEU-C-13 and PNEU-P-23 more
expensive than PNEU-P-23 with ICER
from ~$49,000 to $63 000/QALY in
two Canadian studies.

PNEU-C-13 and
PNEU-P-23
Epidemiology:
  • IPD incidence in adults is stable
    but the proportion of PNEU-C-13
    serotypes is decreasing in all
    age groups, including in 65
    years and over (30% reduction);
    except for ST3.
  • This decrease in the incidence
    of IPD and CAP has been seen
    following the implementation of
    childhood pneumococcal
    vaccination programs
  • S. pneumoniae CAP in SOS:
    decline in proportion of PNEU-
    C-13 serotypes CAP from 73%
    in 2011 to 64% in 2013. In adults
    65-74 years: the proportion
    of all-cause CAP that was
    caused by PNEU-C-13 serotypes
    decreased from 15.5% in
    2011 to 10.8% in 2013 - this
    is only 3 years after PNEU-
    C-13 introduction in children.
Vaccine Efficacy:
  • Against PNEU-C-13
    serotypes CAP: 45.6% (21.8
    - 62.5%)
  • Against non-bacteremic
    PNEU-C-13 serotypes CAP:
    45.0% (14.2 - 65.3%)
  • Against PNEU-C-13 serotypes
    IPD: 75.0% (41.4 - 90.8%)
Ethics:
  • If PNEU-C-13 only available
    on private market: potential
    inequity
Economics
ICER: ~$49,000/QALY to $63 000/QALY,
compared to PNEU-P-23 only;
using the epidemiology from
2015 - increasing ICER with
decrease in circulating PNEU-C-
13 serotypes.

V. Recommendations

In summary, based on the review of the literature and Canadian epidemiological data, PNEU-P-23 vaccine is a safe and effective tool in preventing IPD in immunocompetent adults over 65 years of age, while evidence on the effectiveness in preventing CAP remains inconclusive. The available Canadian epidemiological data indicate that the burden of IPD among individuals 65 years of age due to PNEU-C-13 serotypes is decreasing, but the burden of IPD caused by unique PNEU-P-23 serotypes and those not included in any currently available vaccine remains substantial.

Further studies on PNEU-P-23 and PNEU-C-13 vaccine effectiveness, the Canadian burden of S. pneumoniae disease, the impacts of childhood PNEU-C programs, and the burden of CAP in Canada will be needed to guide future recommendations for adults over 50 years of age.

Recommendation 1:

NACI recommends that PNEU-P-23 vaccine should be offered in routine immunization programs for all adults age 65 years and older for the prevention of IPD (Strong NACI recommendation).

NACI concludes that there is good evidence to recommend immunization (Grade B Evidence)

This recommendation is based on the results of the systematic review on PNEU-P-23 vaccine efficacy and effectiveness in preventing IPD, incidence of circulating IPD serotypes in Canada, and the evidence of changing incidence of pneumococcal disease following the implementation of childhood PNEU-C vaccination programs. The current IPD epidemiology and the results from systematic reviews and meta-analyses suggest that PNEU-P-23 may be as effective as PNEU-C-13 in preventing IPD in the general population of adults 65 years of age and older.

The evidence for the effectiveness of PNEU-P-23 in the prevention of CAP is however conflicting. Findings from systematic reviews and meta-analyses indicate that PNEU-P-23 may or may not be effective in preventing CAP in the general population of adults over 65 years of age.

Recommendation 2:

NACI recommends that PNEU-C-13 vaccine should not be publicly funded in routine immunization programs for adults 65 years of age and older without other risk factors increasing their risk of IPD (Strong NACI recommendation), unless PNEU-C-13 price decreases. NACI considered disease burden, herd immunity effects and the results of economic evaluation.

NACI concludes that there is fair evidence to recommend against immunization (Grade D Evidence)

This recommendation for adults aged 65 years and older, without other risk factors increasing their risk of IPD is based on the epidemiology of circulating serotypes causing IPD and CAP in Canada and the evidence of changing incidence of pneumococcal disease following the implementation of childhood PNEU C vaccination programs. Although there is clinical trial evidence for PNEU-C-13 vaccine efficacy in older adults for preventing CAP, within the Canadian context, such a publicly funded program would not significantly decrease the disease burden in a cost- effective manner.

IV. Research priorities

  • Direct comparison of vaccine efficacy of PNEU-P-23 and PNEU-C-13 via randomized controlled trial among the general population of adults 65 years of age and older looking at the outcomes of IPD, VT IPD, CAP, and VT CAP
  • Assessment of the herd effects of PNEU-C childhood programs over time on the incidence of IPD, VT IPD, CAP, and VT CAP and on carriage within the Canadian population of individuals 65 years of age and older
  • Estimates of the vaccine effectiveness of PNEU-C-13 in the general population of individuals 65 years of age and older
  • Assessment of program PNEU-C-13 vaccine effectiveness in additional specific population groups (e.g. Indigenous populations)

IIV. Surveillance issues

  • Nationally representative data is not currently available on the burden of CAP and VT CAP in Canada
  • National surveillance data on vaccination status are not available for identified cases of IPD and VT IPD in Canada, which limits extension of findings
  • Additional risk factors (e.g. comorbidities) are not available for identified cases of IPD and VT-IPD, which limits extensions of findings to high-risk groups due to underlying health conditions

Missing data was present within both the CNDSS and NML datasets.

Tables

Table 8. Ranking Individual Studies: Levels of Evidence Based on Research Design

Level Description
I Evidence from randomized controlled trial(s).
II-1 Evidence from controlled trial(s) without randomization.
II-2 Evidence from cohort or case-control analytic studies, preferably from more than one center or research group using clinical outcome measures of vaccine efficacy.
II-3 Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of the introduction of penicillin treatment in the 1940s) could also be regarded as this type of evidence.
III Opinions of respected authorities, based on clinical experience, descriptive studies and case reports, or reports of expert committees.

Table 9. Ranking Individual Studies: Quality (internal validity) Rating of Evidence

Quality
Rating
Description
Good A study (including meta-analyses or systematic reviews) that meets all design- specific criteria* well.
Fair A study (including meta-analyses or systematic reviews) that does not meet (or it is not clear that it meets) at least one design-specific criterion* but has no known "fatal flaw".
Poor A study (including meta-analyses or systematic reviews) that has at least one design-specific* "fatal flaw", or an accumulation of lesser flaws to the extent that the results of the study are not deemed able to inform recommendations.

General design specific criteria are outlined in Harris RP, Helfand M, Woolf SH, et al. Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med 2001;20:21-35.

Return to footnote * referrer

Table 10. NACI Recommendations: Strength of Recommendation and Strength of Evidence

STRENGTH OF NACI
RECOMMENDATION
STRENGTH OF EVIDENCE
Based on factors not isolated to
strength of evidence (e.g. public health need)
Based on assessment of the body of evidence
Strong
"should/should not be offered"
  • Known advantages outweigh known disadvantages ("should"),
OR known disadvantages outweigh known advantages ("should not")
  • Implication: A strong recommendation applies to most populations/patients and should be followed unless a clear and compelling rationale for an alternative approach is present
A - good evidence to recommend
B - fair evidence to recommend
C - conflicting evidence, however other factors may influence decision-making
D - fair evidence to recommend against
E - good evidence to recommend against
I - insufficient evidence (in quality or quantity), however other factors may influence decision-making
Discretionary
"may be considered"
  • Known advantages closely balanced with known disadvantages, OR uncertainty in the evidence of advantages and disadvantages exists
  • Implication: A discretionary recommendation may be considered for some populations/patients in some circumstances. Alternative approaches may be reasonable.
A - good evidence to recommend
B - fair evidence to recommend
C - conflicting evidence, however other factors may influence decision-making
D - fair evidence to recommend against
E - good evidence to recommend against
I - insufficient evidence (in quality or quantity), however other factors may influence decision-making

Table 11 Summary of Safety Evidence for NACI Recommendations

Evidence for Safety for PNEU-P-23
STUDY DETAILS SUMMARY
Study Vaccine Study
Design
Number of
Participants
Summary of Key Findings
Using Text or Data
Level of
Evidence
Quality
Miller et al.,
20161
PPVS23 (Pneumovax®23)n Case-series: surveillance system of AEs Vaccine AE Reporting System (VAERS) in the USA received 25168 reports of AEs among individuals of all ages, between 1990-2013. Among adults ≥19 years of age (21586 reports), injection site erythema (n=6119 [31%]), injection site pain (n=5161 [26%]), and erythema (n=4498 [23%]) were the most commonly reported non-serious AEs. The most commonly reported serious AEs among individuals who were ≥19 were pyrexia (770 [44%]), injection site erythema (520 [30%]), and cellulitis (515 [29%]). Level III N/A - data from a surveillance system

Miller ER, Moro PL, Cano M, Lewis P, Bryant-Genevier M, Shimabukuro TT. Post-licensure safety surveillance of 23-valent pneumococcal polysaccharide vaccine in the Vaccine Adverse Event Reporting System (VAERS), 1990-2013. Vaccine. 2016 May 27;34(25):2841-6

Return to footnote 1 referrer

Table 12. Summary of evidence on PNEU-P-23 efficacy

Evidence for efficacy for PNEU-P-23 in preventing IPD
STUDY DETAILS SUMMARY
Study Vaccine Study
Details
Participants Summary of Key Findings
Using Text or Data
Level of
Evidence
Quality
Honkanen et al., 19991 Pneu-P-23 Influenza RCT Finland, initiated in 1992 Study open to all persons living in 35 northern districts Participant follow-up (vaccinated) 38,037 person years Individuals with immunocompromising conditions not excluded IPD reported as bacteraemia, with cases identified from the national register Group 1: 13,980 individuals ≥65 years of age immunized with Pneu-P-23 and influenza vaccine; mean age 73.3 years Group 2: 12,945 individuals ≥65 years of age immunized with influenza vaccine; mean age 73.7 years Efficacy: 63% (95% CI: -91 to 93); based on 2 cases in Group 1 and 5 cases in Group 2 Level I Poor - no allocation concealment
Maruyama2 Pneu-P-23 RCT, placebo controlled, double blind Japan, initiated in 2006 Participants recruitment in hospital affiliated nursing homes Participant follow-up (vaccinated) 1,140 person years IPD reported as bacteremic pneumonia Group 1: 502 immunocompetent individuals ≥55 years of age immunized with Pneu-P-23 vaccine; mean age 84.7 years Group 2: 504 immunocompetent individuals ≥55 years of age not immunized with Pneu-P-23 vaccine; mean age 84.8 years Efficacy: 86% (95% CI: -277 to 99); based on 0 cases in Group 1 and 3 cases in Group 2 Level I Fair
Ortqvist et al., 19983 Pneu-P-23 RCT, placebo controlled, double blind Sweden, initiated in 1991 Participants former CAP inpatients; recruitment done in infectious disease departments of 6 university hospitals Participant follow-up (vaccinated) 793 person years IPD reported as bacteremic pneumonia Group 1: 339 immunocompetent individuals ≥50 years of age immunized with Pneu-P-23 vaccine; mean age 69.4 years Group 2: 352 immunocompetent individuals ≥50 years of age not immunized with Pneu-P-23 vaccine; mean age 69.1 years Efficacy: 79% (95% CI: -77 to 98); based on 1 case in Group 1 and 5 cases in Group 2 Level I Good
Alfageme4 Pneu-P-23 RCT Spain, initiated in 1999 Participant recruitment done in one university hospital; all participants with confirmed COPD, primarily male (>93%) Participant follow-up (vaccinated): 2.7 years Group 1: 298 immunocompetent individuals ≥60 years of age immunized with Pneu-P-23 vaccine; mean age 69 years Group 2: 298 immunocompetent individuals ≥60 years of age not immunized with Pneu-P-23 vaccine; mean age 69.1 years No cases of bacteremic pneumococcal infection were observed during the study period Level I Fair
Evidence for efficacy for PNEU-P-23 in preventing CAP
STUDY DETAILS SUMMARY
Study Vaccine Study
Details
Participants Summary of Key Findings
Using Text or Data
Level of
Evidence
Quality
Ortqvist et al., 1998 3 Pneu-P-23 RCT, placebo controlled, double blind Sweden, initiated in in 1991 Participants former CAP inpatients; recruitment done in infectious disease departments of 6 university hospitals Participant follow-up (vaccinated) 793 person years Diagnosis: clinical and radiological for CAP; positive culture from pleural fluid or sputum or a positive pneumococcal (pneumolysin) antibody test for PP Group 1: 339 immunocompetent individuals ≥50 years of age immunized with Pneu-P-23 vaccine; mean age 69.4 years Group 2: 352 immunocompetent individuals ≥50 years of age not immunized with Pneu-P-23 vaccine; mean age 69.1 years Efficacy CAP: -18% (95% CI: -75 to 20), Efficacy PP: -25% (95% CI: -147 to 36) Group 1: 63 (19%) individuals diagnosed with CAP, of which 19 were pneumococcal pneumonia (PP) Group 2: 57 (5.6%) individuals diagnosed with CAP, of which 16 were with PP CAP was diagnosed in 120 (17%) study participants on 177 occasions; 84 individuals had one episode of pneumonia, 24 had two, and 12 had three or more. Level I Good
Honkanen et al., 19991 Pneu-P-23 Influenza RCT Finland, initiated in 1992 Study open to all persons living in 35 northern districts Participant follow-up (vaccinated) 38,037 person years Individuals with immunocompromising conditions not excluded Diagnosis: clinical and radiological for CAP; positive pneumococcal (pneumolysin) antibody test for PP Group 1: 13,980 individuals ≥65 years of age immunized with Pneu-P-23 and influenza vaccine; mean age 73.3 years Group 2: 12,945 individuals ≥65 years of age immunized with influenza vaccine; mean age 73.7 years Efficacy CAP: -20% (95% CI: -50 to 10) Efficacy PP: -20% (95% CI: -90 to 20) During the influenza season, the relative risk of CAP in Group 1 was 1.2 (95% CI 0.7±1.9) and for PP 2.1 (95% CI 0.8±5.4); in non-influenza seasons relative risks were 1.2 (95% CI 0.9±1.6) for CAP and 1.2 (95% CI 0.8±1.9) for PP. Level I Poor - no adjustment for confounders and allocation
Alfageme4 Pneu-P-23 RCT Spain, initiated in 1999 Participant recruitment done in one university hospital; all participants with confirmed COPD Participant follow-up (vaccinated): 2.7 years Diagnosis: clinical and radiological for CAP; positive culture from pleural fluid, bronchial aspirate or sputum for PP Group 1: 207 immunocompetent individuals ≥65 years of age immunized with Pneu-P-23 vaccine Group 2: 182 immunocompetent individuals ≥65 years of age not immunized with Pneu-P-23 vaccine Efficacy CAP: -14% (95% CI: -107 to 38) Group 1: 22 individuals diagnosed with CAP Group 2: 17 individuals diagnosed with CAP Level I Fair
Maruyama5 Pneu-P-23 RCT, placebo controlled, double blind Japan, initiated in 2006 Participants recruitment in hospital affiliated nursing homes Participant follow-up (vaccinated) 1,140 person years Diagnosis: clinical and radiological for CAP; positive culture from pleural fluid or sputum, or a positive urine test for PP Group 1: 502 immunocompetent individuals ≥55 years of age immunized with Pneu-P-23 vaccine; mean age 84.7 years Group 2: 504 immunocompetent individuals ≥55 years of age not immunized with Pneu-P-23 vaccine; mean age 84.8 years Efficacy CAP: 45% (95% CI: 22 to 61) Efficacy PP: 64% (95% CI: 32 to 81) Group 1: 63 individuals diagnosed with CAP, of which 14 with PP Group 2: 104 individuals diagnosed with CAP, of which 37 with PP Level I Fair
Kawakami et al., 20105 Pneu-P-23 Influenza RCT Japan, initiated in 2005 Participants recruitment in hospitals and private clinics Participants followed-up for 2 years Diagnosis: clinical and radiological for CAP Group 1: 391 immunocompetent individuals ≥65 years of age immunized with Pneu-P-23 and influenza vaccine; mean age 78.5 yearsGroup 2: 387immunocompetent individuals ≥65 years of age immunized with influenza vaccine; mean age 77.7 years HR: 0.82 95% CI (0.55-1.23) Efficacy CAP, ≥65: 22% (95% CI: -12 to 45) Efficacy CAP, 65-75: -54% (95% CI: -239 to 30) Group 1: 67 individuals ≥65 with CAP; 16 in 127 individuals 65-75 years of age Group 2: 81 individuals ≥65 with CAP; 12 in 140 individuals 65-75 years of age Level I Fair - adjusted for some confounders and concealment allocation

Honkanen PO, Keistinen T, Miettinen L, Herva E, Sankilampi U, Läärä E, et al. Incremental effectiveness of pneumococcal vaccine on simultaneously administered influenza vaccine in preventing pneumonia and pneumococcal pneumonia among persons aged 65 years or older. Vaccine. 1999;17(20-21):2493-500

Return to footnote 1 referrer

Maruyama T., O. Taguchi, M.S. Niederman, J. Morser, H. Kobayashi, T. Kobayashi, et coll. « Efficacy of 23-valent pneumococcal vaccine in preventing pneumonia and improving survival in nursing home residents: Double blind, randomised and placebo controlled trial », BMJ (en ligne), 2010, 340(7746) : 579.

Return to footnote 2 referrer

Ortqvist A, Hedlund J, Burman L-, Elbel E, Hofer M, Leinonen M, et al. Randomised trial of 23-valent pneumococcal capsular polysaccharide vaccine in prevention of pneumonia in middle-aged and elderly people. Lancet. 1998;351(9100):399-403

Return to footnote 3 referrer

Alfageme I, Vazquez R, Reyes N, Muñoz J, Fernández A, Hernandez M, et al. Clinical efficacy of anti-pneumococcal vaccination in patients with COPD. Thorax. 2006;61(3):189-95

Return to footnote 4 referrer

Kawakami K, Ohkusa Y, Kuroki R, Tanaka T, Koyama K, Harada Y, et al. Effectiveness of pneumococcal polysaccharide vaccine against pneumonia and cost analysis for the elderly who receive seasonal influenza vaccine in Japan. Vaccine. 2010;28(43):7063-9

Return to footnote 5 referrer

Table 13 Summary of PNEU-P-23 effectiveness

Evidence for Effectiveness for PNEU-P-23 in Preventing IPD
STUDY DETAILS SUMMARY
Study Study Details Number of
Participants
Summary of Key
Findings Using Text
or Data
Level of
Evidence
Quality
Andrews et al., 2012 1 Indirect cohort UK Serotyped IPD cases (diagnosed between November 2003 and December 2010) with data on vaccination history, underlying risk factors and outcome of infection Group 1: 1,272 Pneu-P-23 vaccine type IPD cases ≥65 years of age matched for age and time period Group 2: 1,270 non-Pneu-P-23 IPD cases ≥65 years of age Effectiveness, non-immunocompromised individuals 65 to 74 years of age::
  • <2 years since vaccination: 67% (95% CI: 41 to 82)
  • 2 to <5 years since vaccination: 36% (95% CI: -9 to 62)
Effectiveness, all individuals, serotypes in Pneu-P-23 and not in Pneu-C-7: 49% (95% CI: 30 to 63)
II-2 Fair - adjusted but with potential exposure bias
Wright et al. 20132 Indirect cohort UK HPA database of IPD cases in the North East of England (diagnosed between April 2006 and July 2012) Group 1: 555 Pneu-P-23 vaccine type IPD cases ≥65 years of age matched for age and time period Group 2: 106 non-Pneu-P-23 IPD cases ≥65 years of age Effectiveness, individuals 65-74 years of age vaccinated less than 5 years prior to diagnosis: 55.2% (95% CI: -18.6 to 82.8) Effectiveness, immunocompetent individuals 65-74 years of age: 70.3% (95% CI: -6.2 to 91.7) II-2 Good
Leventer-Roberts et al., 20153 Case-Control Israel IPD cases extracted from health records of the Clalit Health Services database (diagnosed between January 2007 through December 2010) with over 470,000 adults 65 years of age and older Group 1: 212 IPD cases ≥65 Group 2: 848 matched controls ≥65 years of age Effectiveness, all individuals, all serotypes, immunization at less than 5 years since vaccination: 42% (95% CI: 19 to 59) II-2 Good
Rudnick et al, 20134 Indirect cohort Canada IPD cases from Toronto Invasive Bacterial Diseases Network (TIBDN) database (diagnosed between 1995 to 2011) Group 1: 1,461 Pneu-P-23 vaccine type IPD cases ≥65 years of age matched for age and time period Group 2: 234 non-Pneu-P-23 IPD cases ≥65 years of age Effectiveness, all individuals, immunization <5years: 42.6% (95% CI; 26 to 55.5). Effectiveness, individuals ≥65, immunization <5years: 36.9% (95% CI: 12.7 to 54.4) Effectiveness, individuals ≥65 with no underlying conditions, immunization <5years: 51.1% (95% CI: -6.4 to 77.6) Effectiveness, all individuals, serotypes in Pneu-P-23 and not in Pneu-C-13: 45.2% (95% CI: 27.5 to 58.6) II-2 Good
Dominguez et al., 20055 Case-Control Spain IPD cases in 12 hospitals (diagnosed between January 2001 through March 2002) matched with 2 hospital and 1 outpatient control subject on the basis of age and underlying medical conditions Group 1: 149 IPD cases ≥65 Group 2: 447 matched controls ≥65 years of age Effectiveness, non-immunocompromised individuals, all serotypes: 76% (95% CI: 51 to 88) Effectiveness, non-immunocompromised, vaccine serotypes: 78% (95% CI, 50 to 90) 131 IPD cases caused by vaccine or vaccine-related serotypes II-2 Good
Gutierez et al. 20146 Indirect cohort Spain IPD cases registered in the Surveillance System of the Region of Madrid (diagnosed between 2008 and 2011) 18.6% of cases with immunodeficiency and/or cancer ion Group 1: 588 Pneu-P-23 vaccine type IPD cases ≥6o years of age matched for age and time period Group 2: 211 non-Pneu-P-23 IPD cases ≥60 years of age Effectiveness, all individuals, immunization at less than 5 years since vaccination: 44.5% (95% CI: 19.4 to 61.8) Effectiveness, individuals 60-69 years of age: 54.2% (95% CI: 15.3 to 75.2) Effectiveness, individuals 70-79 years of age: 54.1% (95% CI: 19.2 to 73.9) Effectiveness, all individuals, serotypes in Pneu-P-23 and not in Pneu-C-13: 46.8% (95% CI: 45.2 to 76.8) II-2 Fair
Vila-Corcoles et al., 20107 Case-Control Spain IPD cases identified using an active surveillance system of 3 reference hospitals (diagnosis made between January 2002 and April 2007) Group 1: 88 IPD cases ≥60 years of age Group 2: 176 matched controls ≥65 years of age Effectiveness, all serotypes: 72% (95% CI: 46 to 85) Effectiveness, all serotypes, adults 60-79 years of age: 68% (95% CI: 26 to 86) Effectiveness, Pneu-P-23 serotypes: 77% (95% CI: 40 to 92) II-2 Good
Vila-Corcoles et al., 20068 Cohort Spain Study conducted from January 2002 through April 2005; hospital records of reference used to identify IPD cases 11,241 individuals aged ≥65 years assigned to one primary care center; immunized individuals follow-up for 17,401 person-years Effectiveness, all serotypes, <5.5 years since immunization: 40% (95% CI: -65 to 78) Effectiveness, vaccine serotypes, <5.5 years since immunization: 39% (95% CI: -176 to 87) II-2 Good
Ochoa-Gondar et al. 20149 Cohort Spain Hospital records of the 2 reference hospitals in the study area used to identify IPD cases (December 2008 to November 2011) 27,204 individuals aged ≥60 years assigned to 9 primary care centers; immunized individuals follow-up for 29,065 person-years Effectiveness, all serotypes, <5 years since immunization: 62% (95% CI: -68 to 91) II-2 Good
Hechter et al., 201210 Cohort USA Participants of the longitudinal California Men's Health Study; mean follow-up period 6.4 years 3,962 individuals immunized at age ≥65 years; mean follow-up period 7.3 years Effectiveness, all serotypes, vaccination at age ≥65 years: 65% (95% CI: -91 to 94); only 3 cases of pneumococcal bacteremia during study period II-2 Poor - no noted adjustment
Jackson et al., 2003 11 Cohort USA Members of the Group Health Cooperative; study period 2.7 years 47,365 adults ≥65 years of age were followed for 84,203 person-years for pneumococcal vaccination. Of 26,313 individuals who were vaccinated before the beginning of the study, 91% received the vaccine ≥ 65 years of age and 81% were vaccinated <5 years before the beginning of the study. Of the 21,052 persons who had not received pneumococcal vaccine before study entry, 52% were vaccinated during the study period. There were 38,207 non-immunocompromised individuals. Effectiveness, all serotypes, immunocompetent adults ≥65 years of age: 54% (95% CI: 13 to 76); estimate based on 39 cases of pneumococcal bacteremia II-2 Good
Tsai et al., 2015 12 Cohort Taiwan Data extracted from the IPD notification database of Taiwan's Ministry of Health and Welfare Cohort of 458,362 propensity score matched individuals ≥75 years of age with and without Pneu-P-23 immunization, (229,181in each group, mean age 81.7 years) Effectiveness, all serotypes, <1 year since immunization: 76% (95% CI: 54 to 88) II-2 Good
Evidence for Effectiveness for PNEU-P-23 in Preventing CAP
STUDY DETAILS SUMMARY
Study Study Details Number of Participants Summary of Key Findings Using Text or Data Level of Evidence Quality
Dominguez et al., 201013 Case-Control Spain Hospitalized patients with CAP admitted through the emergency department; diagnosis based on clinical and radiological findings; mean age (cases) 77.2 years Study conducted from May 2005 through January 2007. Similar proportion of individuals in both groups immunized with influenza vaccine Group 1: 489 cases ≥65 years of age Group 2: 1,467 hospital patients matched for sex, age, date of hospitalisation and underlying disease Effectiveness, all CAP, immunocompetent adults ≥65 years of age, <5 years since immunization: 23.6 % (-7.2 to 45.6) II-2 Good
Dominguez et al., 201714 Case-Control Spain Hospitalized patients with CAP; diagnosis based on clinical and radiological findings Study conducted from September 2013 to June 2015. Similar proportion of individuals in both groups immunized with influenza vaccine Group 1: 1,895 cases ≥65 years of age Group 2: 1,895 hospital patients matched for sex, age and date of hospitalisation Effectiveness, all CAP, adults ≥65-74 years of age, <5 years since immunization: 23.6% (-3 to 43.3) II-2 Good
Jackson et al., 200915 Case-Control USA Members of the Group Health Cooperative; study period 3 years CAP identified according to diagnosis codes assigned to outpatient and inpatient encounters, and validated by review of chest radiograph reports or medical records; data on CAP collected over three seasons between the date influenza vaccine first became available and the end of influenza season 38% of cases <75 years of age Group 1: 1,173 immunocompetent adults ≥65 years of age with CAP Group 2: 2,346 age- and sex-matched controls Effectiveness, all CAP, immunocompetent adults ≥65 years of age: 0% (95% CI: -30 to 20) II-2 Fair - adjusted for some potential confound-ers
Leventer-Roberts et al., 201516 Case-Control Israel Data on hospital treated CAP cases extracted from health records of the Clalit Health Services database (diagnosed between January 2007 through December 2010) with over 470,000 adults 65 years of age and older Group 1: 23, 441 CAP cases ≥65 Group 2: 46,882 matched controls ≥65 years of age Effectiveness, all CAP, individuals 65-74 years of age, immunization at less than 5 years since vaccination: -12% (95% CI: -21 to -3) II-2 Good
Loeb et al., 200917 Case-Control Canada CAP patients presenting to emergency departments of two hospitals; diagnosis based on clinical and radiological findings; mean age of cases 79.1 years (controls 74.4 years) Cases had a significantly higher proportion of comorbidities, including those associated with immunosuppression (cancer 27.1% vs. 18.1% and transplant 1.6% vs. 0.8%) Recruitment from September 2002 to April 2005 Group 1: 717 CAP cases ≥65 Group 2: 867 controls ≥65 years of age from the same community Effectiveness, all CAP: -45% (95% CI: -78 to -19) II-2 Poor - no adjustment for confound-ers
Skull et al., 200718 Case-Control Australia Hospitalized CAP patients; diagnosis based on clinical and radiological findings; mean age of cases 78.4 years (controls 76.1 years) Approximately ¼ of individuals with immunosuppression Recruitment from April 2000 to March 2002 Group 1: 1,952 CAP cases ≥65 Group 2: 2,927 controls ≥65 years of age. Effectiveness, all CAP: -1% (95% CI: -16 to 13) II-2 Good
Vila-Corcoles et al., 2009 19 Case-Control Spain Data collected from 19 primary health care centres and 3 reference hospitals PP confirmed on the basis of clinical and radiological findings, and culture or urine antigen testing Study conducted from January 2002 to April 2007. Group 1: 210 patients ≥ 50 years of age with non-bacteremic pneumococcal pneumonia Group 2: 420 outpatient controls matched by age,, sex and chronic medical condition Effectiveness, all non-bacteremic PP, all individuals ≥50 years of age: 42% (14-61) Effectiveness, all PP with or without bacteremia, individuals 65-79 years of age: 48% (19-66) Effectiveness, all PP with or without bacteremia, all non-immunocompromised individuals ≥50 years of age: 45% (95% CI: 20 to 62) II-2 Good
Vila-Corcoles et al., 201220 Case-Control Spain Data collected from 19 primary health care centres and 2 reference hospitals PPa confirmed on the basis of clinical and radiological findings, and culture or urine antigen testing Study conducted from January 2002 to April 2007. Group 1: 77 patients with chronic pulmonary disease (chronic bronchitis, emphysema and/or asthma) ≥ 60 years of age with non-bacteremic pneumococcal pneumonia Group 2: 98 outpatient controls matched by age,, sex and chronic medical condition Average age of study participants was 73 years Effectiveness, all non-bacteremic PP, all individuals ≥60 years of age: 34% (-34-67) II-2 Fair
Wiemken et al., 201421 Case-Control International Data extracted from the Community-Acquired Pneumonia Organization (CAPO) cohort study of adult hospitalized patients with CAP; PP diagnosis based on positive culture or urinary antigen test Mean age of cases, 79 years Group 1: 279 individuals ≥65 years of age with pneumococcal. pneumonia; 35% with bacteremia Group 2: individuals with CAP of any other or unknown etiology Effectiveness, PP: 37% (95% CI 16 to 60) Effectiveness,PP, males: 34% (95% CI: −1% to 57) Effectiveness, PP, females: 68% (95% CI 40-83). II-2 Good
Ansaldi et al., 200522 Cohort Italy   RR: 0.72 95% CI (0.57 - 0.93) II-2 Good
Suzuki et al, 201723 Cohort Japan Inpatients and outpatients of 4 community hospitals screened for CAP from September 2011 through Aug 2014. CAP diagnosed based on clinical and radiological findings; PP confirmed with culture and urine antigen testing. Group 1: 419 individuals ≥ 65 years of age with PP with or without bacteremia Group 2: 1,617 individuals with NIpCAP with or without bacteremia Effectiveness, all PP, individuals 65-74 years of age, immunized <5 years prior to diagnosis: 32.2% (-20.7 to 61.9) Effectiveness, Pneu-P-23 type PP, individuals 65-74 years of age, immunized <5 years prior to diagnosis: 39.8% (-15.5 to 68.6) Effectiveness, Pneu-P-23 and non-Pneu-C-13 type PP, all adults ≥65 years of age, immunized <5 years prior to diagnosis: 12.0% (-62.8 to 52.4) II-2 Fair
Hechter et al., 201224 Cohort USA Participants of the longitudinal California Men's Health Study; mean follow-up period 6.4 years Cases identified on the basis of ICD codes for pneumonia in hospital electronic medical records. 3,962 individuals immunized at age ≥65 years Effectiveness (hospitalization), all-cause CAP, immunization at or after 65 years of age: 5% (95% CI: -17 to 22) II-2 Poor - no adjustment for confound-ers
Jackson et al., 200325 Cohort USA Members of the Group Health Cooperative; study period 3 years Outpatient and hospital records for CAP 47,365 adults ≥65 years of age were followed for 84,203 person-years for pneumococcal vaccination. Of 26,313 individuals who were vaccinated before the beginning of the study, 91% received the vaccine ≥ 65 years of age and 81% were vaccinated <5 years before the beginning of the study. Of the 21,052 persons who had not received pneumococcal vaccine before study entry, 52% were vaccinated during the study period. Effectiveness (hospitalization), immunocompetent individuals, all-cause CAP: -14% (95% CI: -31 to 1) Effectiveness (hospitalization), immunocompetent individuals, all-cause CAP, individuals immunized with influenza vaccine: -5% (-29 to 14) Effectiveness, all-cause CAP: -7% (95% CI: -14 to 1) No differences in risk found in time since vaccination II-2 Good
Ochoa-Gondar et al., 200826 Cohort Spain Data extracted from electronic medical records from 8 primary care centres and regional reference hospitals PP diagnosis based on sputum culture or urinary antigen testing 1,298 individuals with a diagnosis of chronic respiratory disease (chronic bronchitis, emphysema and asthma) aged ≥65 701 immunized individuals followed-up for 2,278 person-years 601 individuals immunized in prior 2 years and 98 in prior 3-5 years Effectiveness, all CAP, outpatient: -15% (95% CI: 52 to -1.72) Effectiveness, all CAP, hospitalization: 30% (95% CI: 52 to 0) II-2 Good
Ochoa-Gondar et al., 2014 27 Cohort Spain Hospital records of the 2 reference hospitals in the study Area; PP diagnosis based on sputum culture or urinary antigen testing 27,204 individuals aged ≥60 years assigned to 9 primary care centers; immunized individuals follow-up for 29,065 person-years Effectiveness, immunocompetent, PP: 7% (95% CI: -42 to 40) Effectiveness, immunocompetent, all CAP: 11% (95% CI: -9 to 18) Effectiveness, non-bacteremic PP, immunized <5 years prior to diagnosis: 48% (95% CI: 8 to 71) Effectiveness, all CAP, immunized <5 years prior to diagnosis: 25% (95% CI: 2 to 42) II-2 Good
Tsai et al., 2015 29 Cohort Taiwan Data extracted from the Taiwan National Health Insurance Research Database (NHIRD) Proportion of participants who received the seasonal influenza vaccine similar in the Pneu-P-23 vaccinated and non-vaccinated group Cohort of 458,362 propensity score matched individuals ≥75 years of age with and without Pneu-P-23 immunization, (229,181in each group, mean age 81.7 years) Effectiveness (hospitalization), immunization <1 year prior to diagnosis: 60% (95% CI: 58 to 60) II-2 Good
Vila-Corcoles et al., 2006 30 Cohort Spain Study conducted from January 2002 through April 2005 Over 85% of individuals received Pneu-P-23 vaccine within 2 years prior to study recruitment; PP diagnosed with urinary antigen testing 11,241 individuals aged ≥65 years assigned to one primary care center; immunized individuals follow-up for 17,401 person-years Effectiveness, non-bacteremic PP, immunized <5 years from diagnosis: 39% (95% CI: -6 to 65) Effectiveness (hospitalization), all CAP, immunized <5 years from diagnosis: 21% (95% CI: 2 to 36) II-2 Good
Rodriguez-Barradas et al. 200831 Cohort USA Members of the Veterans Aging Cohort 5-Site Study; study period up to 3 years Outpatient and hospital records of Veterans Affairs (VA) medical centers 692 individuals without HIV average age 55.5 years Effectiveness, all cause CAP, <3 years since immunization: 15% (95% CI: -1.95 to 75) II-2 Good
Hung et al. 201032 Cohort China (Hong Kong) 1,875 immunocompetent individuals aged ≥65 years with chronic illness who attended the outpatient clinics in the Hong KongWest Cluster (HKWC) Study participants followed for 64 weeks Effectiveness, hospitalization from all cause CAP: 23% (95% CI: 7 to 37%) Effectiveness, hospitalization from PP: 38% (95% CI: -5 to 70%) II-2 Fair

Andrews NJ, Waight PA, George RC, Slack MPE, Miller E. Impact and effectiveness of 23-valent pneumococcal polysaccharide vaccine against invasive pneumococcal disease in the elderly in England and Wales. Vaccine. 2012;30(48):6802-8

Return to footnote 1 referrer

Wright LB, Hughes GJ, Chapman KE, Gorton R, Wilson D. Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against invasive pneumococcal disease in people aged 65 years and over in the North East of England, April 2006-July 2012. Trails Vaccinology. 2013;2(1):45-8

Return to footnote 2 referrer

Leventer-Roberts M, Feldman BS, Brufman I, Cohen-Stavi CJ, Hoshen M, Balicer RD. Effectiveness of 23-valent pneumococcal polysaccharide vaccine against invasive disease and hospital-treated pneumonia among people aged ≤ 65 years: A retrospective case-control study. Clin Infect Dis. 2015;60(10):1472-80

Return to footnote 3 referrer

Rudnick W, Liu Z, Shigayeva A, Low DE, Green K, Plevneshi A, et al. Pneumococcal vaccination programs and the burden of invasive pneumococcal disease in Ontario, Canada, 1995-2011. Vaccine. 2013;31(49):5863-71

Return to footnote 4 referrer

Domínguez À, Salleras L, Fedson DS, Izquierdo C, Ruíz L, Ciruela P, et al. Effectiveness of pneumococcal vaccination for elderly people in Catalonia, Spain: A case-control study. Clin Infect Dis. 2005;40(9):1250-7

Return to footnote 5 referrer

Gutiérrez Rodríguez MA, Ordobás Gavín MA, García-Comas L, Sanz Moreno JC, CóRdoba Deorador E, Lasheras Carbajo MD, et al. Effectiveness of 23-valent pneumococcal polysaccharide vaccine in adults aged 60 years and over in the region of Madrid, Spain, 2008–2011. Eurosurveillance. 2014;19(40)

Return to footnote 6 referrer

Vila-Corcoles A., O. Ochoa-Gondar, J.A. Guzmán, T. Rodriguez-Blanco, E. Salsench et C.M. Fuentes. « Effectiveness of the 23-valent polysaccharide pneumococcal vaccine against invasive pneumococcal disease in people 60 years or older », BMC Infect Dis, 2010, 10.

Return to footnote 7 referrer

8. Vila-Córcoles, A., O. Ochoa-Gondar, I. Hospital, X. Ansa, A. Vilanova, T. Rodríguez, et coll. « Protective effects of the 23-valent pneumococcal polysaccharide vaccine in the elderly population: The EVAN-65 study », Clinical Infectious Diseases, 2006, 43(7) : 860-8.

Return to footnote 8 referrer

Ochoa-Gondar O, Vila-Corcoles A, Rodriguez-Blanco T, Gomez-Bertomeu F, Figuerola-Massana E, Raga-Luria X, et al. Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against community-acquired pneumonia in the general population aged =60 years: 3 years of follow-up in the CAPAMIS study. Clin Infect Dis. 2014;58(7):909-17

Return to footnote 9 referrer

Hechter RC, Chao C, Jacobsen SJ, Slezak JM, Quinn VP, Van Den Eeden SK, et al. Clinical effectiveness of pneumococcal polysaccharide vaccine in men: California Men's Health Study. Vaccine. 2012;30(38):5625-30

Return to footnote 10 referrer

Jackson LA, Neuzil KM, Yu O, Benson P, Barlow WE, Adams AL, et al. Effectiveness of pneumococcal polysaccharide vaccine in older adults. New Engl J Med. 2003;348(18):1747-55

Return to footnote 11 referrer

Tsai Y-, Hsieh M-, Chang C-, Wen Y-, Hu H-, Chao Y-, et al. The 23-valent pneumococcal polysaccharide vaccine is effective in elderly adults over 75 years old-Taiwan's PPV vaccination program. Vaccine. 2015;33(25):2897-902

Return to footnote 12 referrer

Domínguez, A., C. Izquierdo, L. Salleras, L. Ruiz, D. Sousa, J- Bayas, et coll. « Effectiveness of the pneumococcal polysaccharide vaccine in preventing pneumonia in the elderly », European Respiratory Journal, 2010, 36(3) : 608-14.

Return to footnote 13 referrer

Domínguez, À., N. Soldevila, D. Toledo, N. Torner, L. Force, M.J. Pérez, et coll. « Effectiveness of 23-valent pneumococcal polysaccharide vaccination in preventing community-acquired pneumonia hospitalization and severe outcomes in the elderly in Spain », PLoS ONE, 2017, 12(2).

Return to footnote 14 referrer

Jackson ML, Nelson JC, Jackson LA. Risk factors for community-acquired pneumonia in immunocompetent seniors. J Am Geriatr Soc. 2009;57(5):882-8

Return to footnote 15 referrer

Leventer-Roberts, M., B.S. Feldman, I. Brufman, C.J. Cohen-Stavi, Hoshen M et R.D. Balicer. « Effectiveness of 23-valent pneumococcal polysaccharide vaccine against invasive disease and hospital-treated pneumonia among people aged ≤ 65 years: A retrospective case-control study », Clinical Infectious Diseases, 2015, 60(10) : 1472-80.

Return to footnote 16 referrer

Loeb M, Neupane B, Walter SD, Hanning R, Carusone SC, Lewis D, et al. Environmental risk factors for community-acquired pneumonia hospitalization in older adults. J Am Geriatr Soc. 2009;57(6):1036-40

Return to footnote 17 referrer

Skull SA, Andrews RM, Byrnes GB, Kelly HA, Nolan TM, Brown GV, et al. Prevention of community-acquired pneumonia among a cohort of hospitalized elderly: Benefit due to influenza and pneumococcal vaccination not demonstrated. Vaccine. 2007;25(23):4631-40

Return to footnote 18 referrer

Vila-Corcoles A, Ochoa-Gondar O, Rodriguez-Blanco T, Gutierrez-Perez A, Vila-Rovira A, Group ES. Clinical effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumonia in patients with chronic pulmonary diseases. Human Vaccines & Immunotherapeutics. 2012 05/01;8(5):639-44

Return to footnote 19 referrer

Vila-Corcoles, A., O. Ochoa-Gondar, T. Rodriguez-Blanco, A. Gutierrez-Perez, A. Vila-Rovira et E.S. Group. « Clinical effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumonia in patients with chronic pulmonary diseases », Human Vaccines & Immunotherapeutics, 2012 05/01; 8(5) : 639-44.

Return to footnote 20 referrer

Wiemken TL, Carrico RM, Klein SL, Jonsson CB, Peyrani P, Kelley RR, et al. The effectiveness of the polysaccharide pneumococcal vaccine for the prevention of hospitalizations due to Streptococcus pneumoniae community-acquired pneumonia in the elderly differs between the sexes: RESULTS from the Community-Acquired Pneumonia Organization (CAPO) international cohort study. Vaccine. 2014;32(19):2198-203

Return to footnote 21 referrer

Ansaldi F, Turello V, Lai P, Batone G, De Luca S, Rosselli R, et al. Effectiveness of a 23-valent polysaccharide vaccine in preventing pneumonia and non-invasive pneumococcal infection in elderly people: A large-scale retrospective cohort study. J Int Med Res. 2005;33(5):490-500.

Return to footnote 22 referrer

Suzuki M, Dhoubhadel BG, Ishifuji T, Yasunami M, Yaegashi M, Asoh N, et al. Serotype-specific effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumococcal pneumonia in adults aged 65 years or older: a multicentre, prospective, test-negative design study. Lancet Infect Dis. 2017;17(3):313-21

Return to footnote 23 referrer

Hechter RC, Chao C, Jacobsen SJ, Slezak JM, Quinn VP, Van Den Eeden SK, et al. Clinical effectiveness of pneumococcal polysaccharide vaccine in men: California Men's Health Study. Vaccine. 2012;30(38):5625-30

Return to footnote 24 referrer

Jackson, L.A., K.M. Neuzil, O. Yu, P. Benson, W.E. Barlow, A.L. Adams, et coll. « Effectiveness of pneumococcal polysaccharide vaccine in older adults », New England Journal of Medicine, 2003, 348(18) : 1747-55.

Return to footnote 25 referrer

Ochoa-Gondar O, Vila-Corcoles A, Ansa X, Rodriguez-Blanco T, Salsench E, de Diego C, et al. Effectiveness of pneumococcal vaccination in older adults with chronic respiratory diseases: results of the EVAN-65 study. Vaccine. 2008 Apr 7;26(16):1955-62

Return to footnote 26 referrer

Ochoa-Gondar, O., A. Vila-Corcoles, T. Rodriguez-Blanco, F. Gomez-Bertomeu, E. Figuerola-Massana, X. Raga-Luria, et coll. « Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against community-acquired pneumonia in the general population aged =60 years: 3 years of follow-up in the CAPAMIS study », Clinical Infectious Diseases, 2014, 58(7) : 909-17.

Return to footnote 27 referrer

Rodriguez-Barradas MC, Goulet J, Brown S, Goetz MB, Rimland D, Simberkoff MS, et al. Impact of Pneumococcal Vaccination on the Incidence of Pneumonia by HIV Infection Status among Patients Enrolled in the Veterans Aging Cohort 5-Site Study. Clin Infect Dis. 2008 Apr 1;46(7):1093-100

Return to footnote 28 referrer

TSAI, Y.H., M.J. HSIEH, C.J. CHANG, Y.W. WEN, H.C. HU, Y.N. CHAO, et coll. « The 23-valent pneumococcal polysaccharide vaccine is effective in elderly adults over 75 years old-Taiwan's PPV vaccination program », Vaccine, 2015, 33(25) : 2897-902.

Return to footnote 29 referrer

Vila-Córcoles, A., O. Ochoa-Gondar, I. Hospital, X. Ansa, A. Vilanova, T. Rodríguez, et coll. « Protective effects of the 23-valent pneumococcal polysaccharide vaccine in the elderly population: The EVAN-65 study », Clinical Infectious Diseases, 2006, 43(7) : 860-8.

Return to footnote 30 referrer

Rodriguez-Barradas, M.C., J. Goulet, S. Brown, M.B. Goetz, D. Rimland, M.S. Simberkoff, et coll. « Impact of pneumococcal vaccination on the incidence of pneumonia by HIV infection status among patients enrolled in the veterans aging cohort 5-site study », Clinical Infectious Diseases, 1er avril 2008, 46(7) : 1093-100.

Return to footnote 31 referrer

Hung IF, Leung AY, Chu DW, Leung D, Cheung T, Chan CK, et al. Prevention of acute myocardial infarction and stroke among elderly persons by dual pneumococcal and influenza vaccination: a prospective cohort study. Clin Infect Dis. 2010 Nov 1;51(9):1007-16

Return to footnote 32 referrer

Table 14 Summary of Canadian studies reporting on indirect effects of childhood PNEU-C programs in IPD

Changes in Pneumococcal Disease correlated to childhood PNEU-C programs in Canada*
Study Surveillance systems used Incidence of Overall IPD pre-program Incidence of Overall IPD post-program Incidence of Vaccine-Type IPD pre-program Incidence of Vaccine-Type IPD post-program STUDY DETAILS
Desai et al.1 Data from 3,825 laboratory confirmed IPD cases reported by hospital and private laboratories to public health units from the integrated Public Health Information System were obtained for the period between Jan. 1, 2007, and Dec. 31, 2014. N/A N/A Between 2007 and 2014 the incidence of Pneu-C-7 included serotypes decreased from 3.0 to 0.7 cases per 100, 000. Between 2010 and 2014, there was also a significant decrease in Pneu-C-13 cases from 12 to 5.3 per 100 000. Decrease was observed in Pneu-C-13 unique serotypes (i.e., serotypes 1, 3, 5, 6A, 7F and 19A) showed a similar trend, with decrease in rates from 9.8 cases per 100 000 in 2010 to 4.6 cases per 100 000 in 2014. Further serotype specific analysis showed that within those serotypes included in PCV13, from 2011 to 2014 there was a significant decrease in the incidence per year caused by serotypes 7F (27.9% decrease), 19A (23.0% decrease) and 3 (12.7% decrease). Pneu-P-23 incidence increased from 2.3 cases per 100 000 in 2007 to 5.8 cases per 100 000 in 2014. All studies NACI Evidence Level: III)
Lefebvre et al, 2016 2 21 sentinel hospitals that provided 318/891 (35.7%) of laboratory-confirmed IPD case samples in the province of Quebec in 2014 N/A N/A 2006 (n = 76) : Pneu-C-7 serotypes 20 (26.3%) Additional Pneu-C-10 serotypes 10 (13.2%) Additional Pneu-C-013 serotypes 23 (30.3%) Non-Pneu-C serotypes 23 (30.3%) 2014 (n = 81) : Pneu-C-7 serotypes 1 (1.2%) Additional Pneu-C-10 serotypes 1(1.2%) Additional Pneu-C-013 serotypes 10 (12.3%) Non-Pneu-C serotypes 69 (85.2%)
Kellner et al., 20093 Active, population-based laboratory surveillance from Calgary, Alberta and surrounding area from 1998 - 2007 were reported and analysed. 1998-2001: 65-84: 36.2 per 100,000 P-Y 85+: 55.0 per 100,000 P-Y 2003-2007: 65-84: 23.9 per 100,000 P-Y 85+: 60.1 per 100,000 P-Y PCV7: 1998-2001: 65-84: 22.1 per 100,000 P-Y 85+: 29.1 per 100,000 P-Y PCV7: 2003-2007: 65-84: 4.8 per 100,000 P-Y 85+: 22.5 per 100,000 P-Y
Leal et al, 20124 Active, population-based laboratory surveillance from Calgary, Alberta and surrounding area from 1998 - 2007 were reported and analysed. 1998-2001: 65-84: 36.2 per 100,000 P-Y 85+: 55.0 per 100,000 P-Y 2007-2010: 65-84: 20.8 per 100,000 P-Y 85+: 25.3 per 100,000 P-Y PCV7: 1998-2001: 65-84: 22.1 per 100,000 P-Y 85+: 29.1 per 100,000 P-Y PCV7: 2007-2010: 65-84: 2.2 per 100,000 P-Y 85+: 0 per 100,000 P-Y
Rudnick et al., 20135 Active, population-based surveillance of laboratory data from Toronto, Ontario and surrounding area from 1995 - 2011 were reported and analysed. 1995/1996: 57.1 per 100,000 2001: 30.6 per 100,000 2005: 22.2 per 100,000 Between 2001 and 2011, an 88% reduction (95% CI, 93-78%) in IPD due to Pneu-C-7 serotypes occurred among adults 15-64 years old and an 89% reduction (95% CI, 94-80%) occurred among adults over 65 years of age
Lim et al. 20136 Active, population-based surveillance of laboratory data from Toronto, Ontario and surrounding area from 1995 - 2011 were reported and analysed. 2001: 30.6 per 100,000 2008/2010: 23.6 per 100,000 N/A 2008/2010: 13.3 per 100,000
Demczuk et al, 20137 Data on 8,047 serotyped isolates submitted to the National Microbiology Laboratory (Public Health Agency of Canada) from 2010-2012; 4,040 cultures submitted from all Canadian provincial and territorial public health and regional hospital laboratories except for the provinces of Alberta and Quebec and greater metropolitan Toronto region; 1,366 isolates were typed by Laboratoire de santé publique du Québec; 1260 isolates typed by the Toronto Invasive Bacterial Diseases Network (TIBDN); and 1381 isolates typed by the Provincial Laboratory for Public Health, Edmonton, Alberta. 2,818 (35% of total number of samples) from adults ≥65 years of age     Overall Pneu-C-13 serotypes decreased significantly (p<0.001) over the 3-year period in the ≥65-year-old age groups, from 50% (487/967) to 39% (369/937), respectively.
Sahni et al., 20128 Data were collected from all confirmed cases of IPD that were reported to the BC Centre for Disease Control between 2002 and 2010. N/A N/A PCV7: 2002: 9.6 per 100,000 PCV7: 2010: 0.7 per 100,000

Desai S, Policarpio ME, Wong K, Gubbay J, Fediurek J, Deeks S. The epidemiology of invasive pneumococcal disease in older adults from 2007 to 2014 in Ontario, Canada: a population-based study. CMAJ Open. 2016 Sep 29;4(3):E545-50

Return to footnote 1

Programme de surveillance du pneumocoque: rapport 2014 [Internet]. Québec, Canada: Laoratoire de santé publique du Québec; 2016 [updated Feb 4, 2016; cited Dec 6, 2017]. Available from: https://www.inspq.qc.ca/en/node/4680

Return to footnote 2

Kellner JD, Vanderkooi OG, MacDonald J, Church DL, Tyrrell GJ, Scheifele DW. Changing epidemiology of invasive pneumococcal disease in Canada, 1998-2007: Update from the calgary-area Streptococcus pneumoniae research (Casper) study. Clin Infect Dis. 2009;49(2):205-12.

Return to footnote 3

Leal J, Vanderkooi OG, Church DL, MacDonald J, Tyrrell GJ, Kellner JD. Eradication of invasive pneumococcal disease due to the seven-valent pneumococcal conjugate vaccine serotypes in Calgary, Alberta. Pediatr Infect Dis J. 2012;31(9).

Return to footnote 4

Rudnick W, Liu Z, Shigayeva A, Low DE, Green K, Plevneshi A, et al. Pneumococcal vaccination programs and the burden of invasive pneumococcal disease in Ontario, Canada, 1995-2011. Vaccine. 2013;31(49):5863-71.

Return to footnote 5

Lim GH, Wormsbecker AE, McGeer A, Pillai DR, Gubbay JB, Rudnick W, et al. Have changing pneumococcal vaccination programmes impacted disease in Ontario? Vaccine. 2013;31(24):2680-5.

Return to footnote 6

Demczuk W.H.B., Martin I, Griffith A., Lefebvre B., McGeer A., Lovgren M., et al. Serotype distribution of invasive Streptococcus pneumoniae in Canada after the introduction of the 13-valent pneumococcal conjugate vaccine, 2010-2012. Can J Microbiol. 2013;59:778-88.

Return to footnote 7

Sahni V, Naus M, Hoang L, Tyrrell GJ, Martin I, Patrick DM. The epidemiology of invasive pneumococcal disease in British Columbia following implementation of an infant immunization program: Increases in herd immunity and replacement disease. Can J Public Health. 2012;103(1):29-33.

Return to footnote 8

Notes: All data is for individuals 65+ unless otherwise noted

P-Y = Person-Years

Data collected from Rudnick et al., 2013 compares pre-licensing to post-licensing due to data availability

* PCV7 programs were implemented variably across Canada. Three doses of PCV 7 were recommended in Quebec in 2004 followed by a switch to PCV10 in 2010 and four doses were recommended in Alberta in 2002, in Ontario in 2001, with a publicly funded program beginning in 2005, and in British Columbia in 2003, which changed to a 3-dose schedule in 2007 and PCV-13 in 2010. Vaccination coverage was approximately 70-95%.

Table 15. Summary of studies reporting on indirect effects of childhood PNEU-C programs in CAP and pneumococcal pneumonia

Changes in Pneumococcal Disease correlated to childhood PNEU-C programs
STUDY DETAILS (All studies NACI Evidence Level: III)
Details of childhood PNEU-C programsa Adult PNEU-P-23 vaccination programsa Study Surveillance systems used Incide
nceb of Vaccine-Type CAP pre-program

Incide
nceb of Vaccine-Type CAP post-program

Incidence of Overall CAP pre-program Incidence of Overall CAP post-program
Australia (n=1)
In 2005, three doses of PCV7 were recommended for infants in Australia reaching approximately 91% coverage. In 2005, Pneu-P-23 was introduced for all adults 65 years of age and older. Menzies et al., 20151 Data were collected from a national database (Australian Institute of Health and Welfare National Hospital Morbidity Database) of electronic records and ICD-10-AM codes in Australia between 1998 and 2011; contains data from >99% of public and private hospitals In Australia Incidence was not provided. Effect estimates (IRRs) were reported comparing 2005-2011 to 1998-2004. Pneumococcal and lobar pneumonia: 65-74: 0.86 (95% CI: 0.74 - 0.99) 75-84: 0.86 (95% CI: 0.76 - 0.98) 85+: 0.91 (95% CI: 0.77 - 1.09) Unspecified cause of pneumonia: 65-74: 0.95 (95% CI: 0.88 - 1.01) 75-84: 0.96 (95% CI: 0.90 - 1.03) 85+: 0.96 (95% CI: 0.89 - 1.02) All cause pneumonia: 65-74: 0.96 (95% CI: 0.90 - 1.04) 75-84: 0.98 (95% CI: 0.91 - 1.04) 85+: 0.97 (95% CI: 0.90 - 1.03)
Canada (n=1)
PCV7 programs were implemented variably across Canada. Three doses of PCV 7 were recommended in Quebec in 2004 followed by a switch to PCV10 in 2010 and four doses were recommended in Alberta in 2002, in Ontario in 2001, with a publicly funded program beginning in 2005, and in British Columbia in 2003, which changed to a 3-dose schedule in 2007 and PCV-13 in 2010. Vaccination coverage was approximately 70-95%. PPV23 was suggested for all individuals 65 years of age and older throughout all study periods. Shigayeva et al. 20162 Data from the Toronto Invasive Bacterial Dis-eases Network (TIBDN) IPD surveillance database (2003 to 2011); median age of adults 64 years(46.6% >65). 24.6% (95% CI: 15-35.2%) reduction in non-bacteremic PP between 2003 and 2011    
United Kingdom (n=2)
In 2006, childhood vaccination with 3 doses of PCV7 was introduced. Coverage reached approximately 90%d. PCV13 replaced PCV7 by 2010. By 2005, PPV23 vaccination was recommended for all individuals 65 years of age and older. Nair et al. 20163 Data collected from hospital records for the entire Scottish population for the period 2000 to 2012 N/A N/A Annual hospitalization rate for all-cause pneumonia 2000-2005 (per 100,000 persons): 65-74 years: 373 (365-380 75-84 years: 875 (861-889) ≥85 years: 1909 (1872-1946) Annual hospitalization rate for PP 2000-2006 65-74 age group: 205.2 Annual hospitalization rate for all-cause pneumonia 2010-2012 (per 100,000 pop.): 65-74 years: 634 (621-647 75-84 years: 1426 (1402-1451 ≥85 years: 2785 (2728-2842) Annual hospitalization rate for PP 2010-2012 65-74 age group: 155 -21.4% (-42.9, -7.1) hospital admissions for PP in the 65-74 age group
Rodrigo et al., 20154 Data collected from hospital records of all individuals admitted to a hospital with CAP between 2008 and 2013; from 383 adults in the study diagnosed with pneumococcal pneumonia by urine antigen testing, 56% had received Pneu-P-23 Additional PCV13 serotypes 2008-2009: VT CAP: 65-74: 23.2 (95% CI: 12.3 - 39.6) per 100,000 75-84: 44.7 (95% CI: 25.6 - 72.6) per 100,000 85+: 104.2 (95% CI: 50.0 - 191.6) per 100,000 Additional PCV13 serotypes 2010-2011: VT CAP: 65-74: 17.8 (95% CI: 8.6 - 32.8) per 100,000 75-84: 11.2 (95% CI: 3.0 - 28.6) per 100,000 85+: 52.1 (95% CI: 16.9 - 121.6) per 100,000 2011-2012: 65-74: 23.2 (95% CI: 12.3 - 39.6) per 100,000 75-84: 19.6 (95% CI: 7.9 - 40.3) per 100,000 85+: 52.1 (95% CI: 16.9 - 121.6) per 100,000 2012-2013: 65-74: 12.5 (95% CI: 5.0 - 25.7) per 100,000 75-84: 22.3 (95% CI: 9.6 - 44.0) per 100,000 85+: 20.8 (95% CI: 2.5 - 75.3) per 100,000 2008-2009: Overall CAP: 65-74: 201.4 (95% CI: 166.0 - 242.2) per 100,000 75-84: 360.3 (95% CI: 300.8 - 428.1) per 100,000 85+: 1052.1 (95% CI: 856.9 - 1278.4) per 100,000 Pneumo-coccal CAP: 65-74: 69.5 (95% CI: 49.4 - 95.0) per 100,000 75-84: 136.9 (95% CI: 101.3 - 181.0) per 100,000 85+: 416.7 (95% CI: 297.7 - 567.4) per 100,000 2010-2011: Overall CAP: 65-74: 137.2 (95% CI: 108.3 - 171.6) per 100,000 75-84: 254.2 (95% CI: 204.7 - 312.1) per 100,000 85+: 489.6 (95% CI: 359.7 - 651.0) per 100,000 Pneumo-coccal CAP: 65-74: 39.2 (95% CI: 24.6 - 59.4) per 100,000 75-84: 50.3 (95% CI: 29.8 - 79.5) per 100,000 85+: 114.6 (95% CI: 57.2 - 205.0) per 100,000 2011-2012: Overall CAP: 65-74: 190.7 (95% CI: 156.3 - 230.5) per 100,000 75-84: 413.4 (95% CI: 349.5 - 485.6) per 100,000 85+: 937.5 (95% CI: 753.9 - 1152.3) per 100,000 Pneumo-coccal CAP: 65-74: 35.6 (95% CI: 21.8 - 55.1) per 100,000 75-84: 67.0 (95% CI: 43.0 - 99.8) per 100,000 85+: 156.2 (95% CI: 87.4 - 257.7) per 100,000 2012-2013: Overall CAP: 65-74: 137.2 (95% CI: 108.3 - 171.6) per 100,000 75-84: 245.8 (95% CI: 197.2 - 302.8) per 100,000 85+: 427.1 (95% CI: 306.5 - 579.4) per 100,000 Pneumococcal CAP: 65-74: 41.0 (95% CI: 26.0 - 61.5) per 100,000 75-84: 69.8 (95% CI: 45.2 - 103.1) per 100,000 85+: 166.7 (95% CI: 95.3 - 270.7) per 100,000 Change in rate ratios for pneumococcal CAP = 0.84 (0.80-0.89), CAP due to serotypes contained in Pneu-C-7 = 0.52 (0.43-0.62) and CAP due to additional serotypes contained in Pneu-C-13 = 0.87 (0.80-0.95)
Poland (n=1)
In 2006, 3 doses of PCV7 were introduced in Kielce, Poland. Coverage reached approximately 99%. There was no publicly funded PPV23 program for 65+ in Poland at the time of publication. Patrzalek et al., 20125 Data were collected in the form of ICD-10 codes from the provincial division of the National Health Fund in Kielce between 2005 and 2010. N/A N/A All cases of pneumonia 2006: 1939 per 100,000 All cases of pneumonia 2007: 2049 per 100,000 2008: 1692 per 100,000 2009: 1061 per 100,000 2010: 1095 per 100,000
Nicaragua (n=1)
In 2010 the pediatric pneumococcal immunization program with Pneu-C-13 was added to the g National Immunization Schedule; coverage between 60 and 65% Pneu-P-23 was provided to adults aged 50 years and older since 2010; coverage approximately 25% Becker-Dreps et al., 20156 Hospital data from a single public referral hospital in one region of Nicaragua were analyzed from 2008 to 2012. Adjusted incidence rate ratios (IRR) based on the total number of ambulatory visits for pneumonia and pneumonia hospitalizations were provided for pre and post vaccine periods     IRR in ambulatory visits, individuals ≥65 years of age: 0.81 (95% CI: 0.61 to 1.06) IRR in pneumonia hospitalizations, individuals ≥65 years of age 2.07 (95% CI: 1.84, 2.33
Germany (n=1)
Routine immunization of children was initiated in 2007 with Pneu-C-7 vaccine, which was replaced by Pneu-C-13 in 2010   Pletz et al, 20167 Data on the distribution of the vaccine-serotypes covered by Pneu-C vaccines in adult patients with CAP was obtained from a CAPNETZ, a German multicenter prospective cohort study for periods 2002-2006 and 2007-2011 using a serotype-specific multiplex urinary antigen detection assay; mean age, pre Pneu-C introduction 63 and post Pneu-C introduction 57.7 Pneumococcal serotypes in non-bacteremic pneumococcal pneumonia 2002-2006, proportion Pneu-C-7 serotypes: 57/182 Pneumococcal serotypes in non-bacteremic pneumococcal pneumonia 2007-2011, proportion Pneu-C-7 serotypes: 26/176
Japan (n=1)
PCV7 became commercially available in February 2010 and was widely employed through a subsidiary from the local government, which increased the estimated vaccination rate among infants to over 80% in 2012; PCV13 was incorporated into the routine immunization schedule in November 2013 Routine PPV23 for adults aged 65 or older in troduced in October 2014; prior to that coverage approximately 25% Katoh et al. 20178 Systematic literature search conducted for studies reporting CAP incidence in Japan; pooled analysis of studies provided estimates on incidence pre and post Pneu-C-7 introduction Proportion of vaccine-covered serotypes 2001-2006: Pneu-C-7: 44.7% Pneu-P-23 but not Pneu-C-7: 32.6% Non-VT: 11.1% Proportion of vaccine-covered serotypes 2011-2013 Pneu-C-7: 26.6% Pneu-P-23 but not Pneu-C-7: 42% Non-VT: 15.7%    
Taiwan (n=1)
In 2005, PCV7 became available in Taiwan. Less than 20% of children were vaccinated by 2007.f PPV23 is recommended for all individuals aged 65 years of age and older. Lin et al., 20109 Data collected from one hospital's records between 2000 and 2008 were analyzed. N/A N/A 2004-2005: Non-bacteremicPP: 51 per 100,000 hospital-izations 2006-2008: Non-bacteremic PP: 18 per 100,000 hospital-izations 64.1% reduction, (95% CI 13.3-115.0%) - adults 65 years of age and older
The Netherlands (n=1)
In 2006, 4 doses of PCV7 were added to the national infant immunization program. The program attained approximately 95% coverage. PCV7 was replaced by PCV10 in 2011 No national recommendation for PPV23 for the general population 65+. Van Werkhoven et al, 201510 Post-hoc analysis of two studies : the CAP-pilot study (prospective study of 1095 patients hospitalized with CAP between January2008 and April 2009) and the CAPiTA trial (double-blind randomized placebo-controlled trial evaluating the efficacy of Pneu-C-13 in 84,496 community-dwelling immunocompetent adults ≥65 years and older.) A total of 288 unimmunized individuals were diagnosed with non-bacteremic pneumococcal CAP between 2009 and 2013. Proportion of Pneu-P-7 isolates in total reported NIpCAPsamples: 2008: 34/118 2009: 11/37 2010: 3/23 2011: 5/32 2012: 1/37 2013: 3/23 Proportion of Pneu-P-10 - Pneu-C-7 isolates in total reported NIpCAP samples: 2008: 22/118 2009: 4/37 2010: 5/23 2011: 6/32 2012: 10/37 2013: 5/23    
United States of America (n=5)
In 2000, 3 doses of PCV7 were recommended for use in all children younger than 2 years of age in the U.S.A. PCV13 replaced PCV7 in 2010. Coverage has remained at approximately 90% since 2009.g PPV23 was recommended for all adults 65 years of age and older until 2014. In 2014, PCV13 was recommended for this age group. Griffin et al., 201311 Data were collected between 1994 and 2012 from the National Inpatient Sample, which is comprised of 20% of all discharge diagnoses in U.S. hospitals across 44 states. N/A N/A All cause pneumonia hospitaliza-tion: 1997-1999: 65-74:1293 per 100,000 75-84:2758 per 100,000 85+: 5697 per 100,000 All cause pneumonia hospitaliza-tion: 2001-2006: 65-74: 1268 per 100,000 75-84:2615 per 100,000 85+: 5209 per 100,000 2007-2009: 65-74: 1208 per 100,000 75-84:2398 per 100,000 85+: 4396 per 100,000 6.6% (95% CI: 0.5-12.7) reduction in all cause pneumonia in the 65-74 year age group
Simonsen et al., 201412 N/A N/A 2007-2009: All cause pneumonia: 1438.4 per 100,000 Non-invasive pneumococcal or lobar pneumonia: 48.4 per 100,000 2011-2012: All cause pneumonia: 1375.2 per 100,000 Non-invasive pneumococcal or lobar pneumonia: 32.7 per 100,000 34% (95% CI: 27-41) decline in hospital admissions,non-invasive pneumococcal or lobar pneumonia
Nelson et al., 200813 Data were collected from the ICD-9 diagnostic codes from the Group Health study population in Washington state between 1998 and 2004. N/A N/A 1998-2000: Hospitalized pneumonia: 65-74: 490 per 100,000 P-Y 75+: 1530 per 100,000 P-Y Confirmed outpatient pneumonia: 65-74: 1230 per 100,000 P-Y 75+: 2170 per 100,000 P-Y 2003-2004: Hospitalized pneumonia: 65-74: 640 per 100,000 P-Y 75+: 2250 per 100,000 P-Y Confirmed outpatient pneumonia: 65-74: 1200 per 100,000 P-Y 75+: 2190 per 100,000 P-Y IRR for 65-74 pre/post program implementation: 1.3 [95%CI: 1.12-1.5]) for hospitalization and 0.97 [95%CI: 0.88-1.08] for outpatient pneumonia
Simonsen et al., 201114 Data was collected from the Health Case Utilization Project State Inpatient Databases between 1996 and 2006. The databases include all ICD-9 coded discharge diagnoses from 10 states; diagnosis by X-ray in the majority of cases N/A N/A 1996-1999: Lobar PP: 144.9 per 100,000 Non-bacteremic PP: 126.1 per 100,000 All cause pneumonia: 1875.2 per 100,000 2005-2006: Lobar PP: 64.7 per 100,000 Non-bacteremic PP: 55.9 per 100,000 All cause pneumonia: 1672.6 per 100,000 54% (95% CI: 53-56) reduction in non-bacteremic PP in adults ≥65 years of age
Grijalva et al. 200715 Data from the Nationwide Inpatient Sample, the largest inpatient database available in the USA, were analyzed with an interrupted time-series analysis that used pneumonia (all-cause and pneumococcal) admission rates PP admissions 1997-1999, persons ≥65 years of age: 73.9/100,000 PP admissions 2001-2004, persons ≥65 years of age: 59.3/100,000 All cause pneumonia admissions 1997-1999, persons ≥65 years of age: 2,559.2/100,000 All cause pneumonia admissions 2001-2004, persons ≥65 years of age: 2,162.7/100,000

Menzies RI, Jardine A, McIntyre PB. Pneumonia in Elderly Australians: Reduction in Presumptive Pneumococcal Hospitalizations but No Change in All-Cause Pneumonia Hospitalizations Following 7-Valent Pneumococcal Conjugate Vaccination. Clin Infect Dis. 2015;61(6):927-33.

Return to footnote 1 referrer

Shigayeva A, Rudnick W, Green K, Tyrrell G, Demczuk WH, Gold WL, et al. Association of serotype with respiratory presentations of pneumococcal infection, Ontario, Canada, 2003-2011. Vaccine. 2016 Feb 3;34(6):846-53.

Return to footnote 2 referrer

Nair H, Watts AT, Williams LJ, Omer SB, Simpson CR, Willocks LJ, et al. Pneumonia hospitalisations in Scotland following the introduction of pneumococcal conjugate vaccination in young children. BMC Infect Dis. 2016;16(1).

Return to footnote 3 referrer

Rodrigo, C., T. Bewick, C. Sheppard, S. Greenwood, T.M. Mckeever, C.L. Trotter, et coll. « Impact of infant 13-valent pneumococcal conjugate vaccine on serotypes in adult pneumonia », European Respiratory Journal, 2015, 1er juin 2015, 45(6) : 1632-41.

Return to footnote 4 referrer

Patrzalek M, Gorynski P, Albrecht P. Indirect population impact of universal PCV7 vaccination of children in a 2 + 1 schedule on the incidence of pneumonia morbidity in Kielce, Poland. Eur J Clin Microbiol Infect Dis. 2012;31(11):3023-8.

Return to footnote 5 referrer

Becker-Dreps S, Amaya E, Liu L, Rocha J, Briceño R, Moreno G, et al. Impact of a combined pediatric and adult pneumococcal immunization program on adult pneumonia incidence and mortality in Nicaragua. Vaccine. 2015;33(1):222-7.

Return to footnote 6 referrer

Pletz MW, Ewig S, Rohde G, Schuette H, Rupp J, Welte T, et al. Impact of pneumococcal vaccination in children on serotype distribution in adult community-acquired pneumonia using the serotype-specific multiplex urinary antigen detection assay. Vaccine. 2016;34(20):2342-8.

Return to footnote 7 referrer

Katoh S, Suzuki M, Ariyoshi K, Morimoto K. Serotype replacement in adult pneumococcal pneumonia after the introduction of seven-valent pneumococcal conjugate vaccines for children in Japan: a systematic literature review and pooled data analysis. Jpn J Infect Dis. 2017 Mar 28.

Return to footnote 8 referrer

Lin SH, Tan CK, Lai CC, Wang CY, Hsueh PR. Declining incidence of nonbacteremic pneumococcal ppneumonia in hospitalized elderly patients at a tertiary care hospital after the introduction of pneumococcal vaccines in Taiwan, 2004 to 2008. J Am Geriatr Soc. 2010 Jan;58(1):195,196 Erratum in J.Am.Geriatr.Soc 2010, 58, 4, 810.

Return to footnote 9 referrer

van Werkhoven CH, Hollingsworth RC, Huijts SM, Bolkenbaas M, Webber C, Patterson S, et al. Pneumococcal conjugate vaccine herd effects on non-invasive pneumococcal pneumonia in elderly. Vaccine. 2016;34(28):3275-82.

Return to footnote 10 referrer

Griffin MR, Zhu Y, Moore MR, Whitney CG, Grijalva CG. U.S. hospitalizations for pneumonia after a decade of pneumococcal vaccination. New Engl J Med. 2013;369(2):155-63.

Return to footnote 11 referrer

Footnote 12

Simonsen L, Taylor RJ, Schuck-Paim C, Lustig R, Haber M, Klugman KP. Effect of 13-valent pneumococcal conjugate vaccine on admissions to hospital 2 years after its introduction in the USA: A time series analysis. Lancet Respir Med. 2014;2(5):387-94.

Return to footnote 12 referrer

Nelson JC, Jackson M, Yu O, Whitney CG, Bounds L, Bittner R, et al. Impact of the introduction of pneumococcal conjugate vaccine on rates of community acquired pneumonia in children and adults. Vaccine. 2008;26(38):4947-54.

Return to footnote 13 referrer

Simonsen L, Taylor RJ, Young-Xu Y, Haber M, May L, Klugman KP. Impact of pneumococcal conjugate vaccination of infants on pneumonia and influenza hospitalization and mortality in all age groups in the United States. mBio. 2011;2(1).

Return to footnote 14 referrer

Nelson JC, Jackson M, Yu O, Whitney CG, Bounds L, Bittner R, et al. Impact of the introduction of pneumococcal conjugate vaccine on rates of community acquired pneumonia in children and adults. Vaccine. 2008;26(38):4947-54.

Return to footnote 15 referrer

List of abbreviations

Abbreviation Term
AE Adverse event
AMR

Antimicrobial resistance

CAP

Community-acquired pneumonia

CI Confidence Interval
CIRN Canadian Immunization Research Network
CNDSS

Canadian Notifiable Disease Surveillance System

HIV Human Immunodeficiency Virus
HSCT Hematopoetic Stem Cell Transplant
ICD International Classification of Diseases
ICER

Incremental cost-effective ratio

IM Intramuscularly
IPD Invasive pneumococcal disease
IRR

Incidence rate ratio

LSPQ Laboratoire de santé publique du Québec
MED-ECHO Maintenance et exploitation des données pour l'étude de la clientèle hospitalière

NACI

National Advisory Committee on Immunization

NIpCAP

Non-invasive pneumococcal community-acquired pneumonia
NML National Microbiology Laboratory
NOC Notice of compliance
NVT Non-vaccine type
NWT Northwest Territories
OR Odds ratio
Pop, Population
PP Pneumococcal pneumonia
P-Y Population per year
PHAC

Public Health Agency of Canada

PNEU-C Pneumococcal conjugate vaccine
PNEU-C-7 7-valent pneumococcal conjugate vaccine
PNEU-C-10 10-valent pneumococcal conjugate vaccine
PNEU-C-13 13-valent pneumococcal conjugate vaccine
PNEU-P Pneumococcal polysaccharide vaccine
PNEU-P-23 23-valent pneumococcal polysaccharide vaccine
PWG Pneumococcal Working Group
QALY Quality adjusted life-years
RCT Randomized controlled trial
RR Risk ratio
SAE Serious adverse events
SC Subcutaneously
SOS

Serious Outcome Surveillance

ST3 Serotype 3
TIBDN Toronto Invasive Pneumococcal Burden of Disease Network
UAD Urine antigen detection
US United States of America
UK United Kingdom
VT Vaccine type

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