2. Outline Background Licensed pneumococcal conjugate vaccines
Effectiveness of PCV 13
Reduction in Nasopharyngeal carriage

3. Streptococcus pneumoniae: The bacterium responsible for pneumococcal disease
Major clinical syndromes are pneumonia, meningitis and bacteremia1
Organism has an outer polysaccharide layer1, 2
Defines the serotype
Functions as virulence factor
Is a vaccine target
More than 90 serotypes of S. pneumoniae have been identified.1, 2
Serotypes are not equally pathogenic
Last serotypes reported are 6C, 6D and 11E
Antibiotic resistance in S. pneumoniae is a global concern.1, 2
Exclusively human pathogen commonly carried in the nasopharynx1
Serotype 19F; Photograph courtesy of Robert P. Smith MS, MS Senior Research Scientist, Wyeth Vaccines.
1. Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases. In: Hamborsky J, Kroger A, Wolfe S, eds. 13th ed. Washington D.C. Public Health Foundation, World Health Organization. Initiative for Vaccine Research. Acute respiratory infections. Updated September Available from: Accessed July 21, 2015.

4. Noninvasive (mucosal)
Pneumococcal disease can be broadly grouped into categories of invasive and non-invasive (mucosal) disease
Pneumococcal disease1
Invasive
Noninvasive (mucosal)
Meningitis
Bacteraemia
Pneumonia
Acute otitis media
Sinusitis
~25% invasive2
~75% non-invasive
Non-invasive forms may become invasive (e.g. pneumonia when accompanied by bacteremia)1
Disease severity and invasiveness differ based on serotype3
1. World Health Organization (WHO). Wkly Epidemiol Rec. 2012;87(14): Said MA, et al. PLoS One. 2013;8:e Jansen AG, et al. Clin Infect Dis. 2009;49(2):e23-e29.

6. Deaths from vaccine-preventable diseases in children worldwide1−3
Pneumonia is a leading killer of children worldwide3
Hib, Haemophilus influenzae Type b.
1. World Health Organization. Global immunization data. July Available from: Accessed July 21, World Health Organization. Wkly Epidemiol Rec. 2012;87(14): ; 3. UNICEF/World Health Organization. Pneumonia: The forgotten killer of children, Available from: Last Accessed July 21, 2015.

7. Licensed pneumococcal conjugate vaccines
CRM 4 6B 9V 14
18C
19F
23F
PCV71
Development and licensure of expanded-valent vaccines were based on serology of the expanded-valent vaccine compared with PCV7.1−3
PCV102
Protein D 4 6B 9V 14
18C
19F
23F 1 5 7F TT DT
PCV10 is conjugated to a Haemophilus influenzae‒derived protein D, carrier for all serotypes except 18C (tetanus toxoid) and 19F (diphtheria toxoid).2
PCV134 4 6B 9V 14
18C
19F
23F 1 5 7F 3 6A
19A
PCV7 and PCV13 are conjugated to CRM197.1,4
CRM
DT, diphtheria toxoid; PCV, pneumococcal conjugate vaccine (7-valent [PCV7], 10-valent [PCV10] or 13-valent [PCV13]); TT, tetanus toxoid.
1. Prevenar13 vaccine NEAR Local Product Document (LPD) version 4 effective September Vesikari T, et al. Pediatr Infect Dis J. 2009;28(4 suppl):S66-S World Health Organization. Recommendations for the production and control of pneumococcal conjugate vaccines. WHO Technical Report Series, No. 927, 2005, Annex. Available from: Last Accessed July 22, Prevenar 13 [abbreviated summary of product characteristics]. GLM ex Iraq: Pfizer Limited.

8. Clinical relevance of the 6 additional serotypes in PCV 13
Clinical relevance of the 6 additional serotypes in Prevenar 13
Serotype
Clinical implications
Serotype 1
Associated with many IPD cases in children worldwide1
One of the most common serotypes causing pediatric IPD2
Associated with complicated pneumonia2
Serotype 3
An important cause of invasive disease and is associated with complicated 2-4
Among the most common isolates in AOM globally5,6
Serotype 5
Serotype 6A
Is multidrug-resistant7
Among the most common isolates in AOM globally5
Commonly found in nasopharyngeal isolates7,8
Serotype 7F
One of the most common serotypes causing IPD and pneumonia in children2-4
High case-fatality rate compared with other serotypes9
Serotype 19A
A leading cause of serious pneumococcal disease worldwide (including
complicated pneumonia (empyema)2−4
The most common serotype in pneumococcal carriage7,8
Among the most common isolates in AOM globally4-6,10
Multidrug resistance2,7,10−12
Complicated pneumonia
Common cause of AOM
Very multidrug resistant
Is common in AOM
Hausdorff WP. Vaccine. 2007;25:
Weil-Olivier C. BMC Infect Dis. 2012;12:207.
Kaplan SL. Pediatrics. 2010;125(3):
Pilishvili T. J Infect Dis. 2010;201:32-41.
Ruckinger S, et al. Pediatr Infect Dis J. 2009;28:
Rodgers GL, et al. Vaccine. 2009;27:
Alonso M, et al. PLoS ONE. 2013;8(1):e54333.
Cho EY. J Korean Med Sci. 2012;27:
Chappuy H, et al. BMC Infect Dis ;13:357.
Pichichero ME, Casey JR. JAMA. 2007;298:
Ma X. PLoS ONE. 2013;8(6):e67507.
Wroe PC. Pediatr Infect Dis. 2012;31(3):
Common in NPC
Multidrug resistant
Global cause of IPD and complicated pneumonias
1. Hausdorff WP. Vaccine. 2007;25(13): Weil-Olivier C, et al. BMC Infect Dis. 2012;12: Pilishvili T, et al. J Infect Dis. 2010;201(1): Kaplan SL. Pediatrics. 2010;125(3): Rodgers GL, et al. Vaccine. 2009;27(29): Alonso M, et al. PLoS ONE. 2013;8(1):e Cho EY, et al. J Korean Med Sci. 2012;27(7): Chappuy H, et al. BMC Infect Dis. 2013;13: Ruckinger S, et al. Pediatr Infect Dis J. 2009;28(2): Pichichero ME, Casey JR. JAMA. 2007;298(15): Ma X, et al. PLoS ONE. 2013;8(6):e Wroe PC et al. Pediatr Infect Dis J. 2012;31(3):

9. Pivotal non-inferiority study (2, 3, 4 and 11–12 months), post-infant series OPA GMTs1
Comparable functional activity
for the 7 shared serotypes:
10- to 100-fold higher functional activity for the 6 additional serotypes in the PCV13 group:
Serotype
PCV13
PCV7
Ratio* 4
1573
1861
0.85 6B
744
1161
0.64 9V
4938
5380
0.92 14
2140
3345
18C
1510
1780
19F
150
166
0.90
23F
1090
1071
1.02
Serotype
PCV13
PCV7
Ratio* 1 50 4
12.50 3
251 6
41.83 5
162
32.40 6A
1228
122
10.07 7F
11,545
115
100.39
19A
442 7
63.14
References
Gavi Alliance Progress Report Accessed from
Pfizer, data on file, Oct 2016.
*GMT of PCV13 versus PCV7.
GMT, geometric mean titer; OPA, opsonophagocytosis assay
1. Adapted from: Kieninger DM, et al. Vaccine. 2010;28(25):

10. Immunogenicity of licensed PCVs against serotype 19A functional antibody activity (OPA)
Functional antibody levels (OPA)
Serotype 19A
(potentially cross-reactive)
(contained in the vaccine)
PCV71
PCV101
PCV132
Geometric mean titers*
4.5 (3.9–5.3)
8.6 (7.1–10.5)
442 (361–543)
% Achieving >1:8*
3.4 (0.7–9.5)
19.6 (15.0–25.0)
100 (96.2–100)
PCV7 did not have any impact on serotype 19A IPD.3
The % of subjects achieving a ≥1:8 functional antibody response is at least 5x greater in PCV13 recipients than that of PCV7 or PCV10.1, 2
*Post-primary dosing in a 3+1 schedule
References
Gavi Alliance Progress Report Accessed from
Pfizer, data on file, Oct 2016.
Comparison of studies with different vaccines, with immunologic assays performed at different laboratories
OPA, opsonophagocytosis assay
1. Vesikari T, et al. Pediatr Infect Dis J. 2009;28(4 Suppl):S66-S Kieninger DM et al. Vaccine 2010;28(25): Pilishvili T, et al. J Infect Dis. 2010;201(1): Prevenar13 [Summary of Product Characteristics]. GLM ex Iraq: Pfizer Limited. 5. Synflorix [Summary of Product Characteristics]. Belgium: GlaxoSmithKline Biologicals

11. PCV13 effectiveness Data demonstrating the impact of PCVs
Reductions in IPD
Reductions in pneumonia
Reductions in acute otitis media
Key Point
We will start with IPD. While this represents a smaller proportion of disease than mucosal infections, invasive pneumococcal diseases are the most serious.

12. United Kingdom: Incidence of IPD in children <2 years1
IPD incidence* in children <2 years of age, from epidemiological year 2000–2001 to 2013–2014, United Kingdom 60 50 40 30 20 10
Corrected Incidence per 100,000
2000/2001
2001/2002
2002/2003
2003/2004
2004/2005
2005/2006
2006/2007
2007/2008
2008/2009
2009/2010
2010/2011
2011/2012
2012/2013
2013/2014
Year
All
PCV7
PCV13 only
NVT
PCV13
Serotype % change
2008‒2010 vs. 2013‒2014
46%
All type
76%
PCV7 type
89%
PCV13 type only
28%
NVT
Note to Speaker: This data is included in the EU SmPC; however, the slide is referenced to the published literature.
Key Points
The overall incidence of IPD due to the 6 additional serotypes in PCV13 continued to decrease following the introduction of PCV13 in 2009/2010 in children <2 years of age
A 46% reduction in IPD due to any serotype was observed in the incidence of IPD in children <2 years of age in 2013/2014 compared to the pre-PCV13 baseline average from 2008– Additionally, a 76% reduction was observed for PCV7 serotypes, and a 89% reduction was observed for serotypes only found in PCV13. Conversely, a 28% increase was observed for nonvaccine serotypes (NVT)
Compared with the pre-PCV7 period (2000–2006), the overall incidence of IPD in 2013/2014 was reduced 56%, and the incidence of PCV7-type IPD was reduced by 97%
Notes
PCV7 was introduced in the UK in September 2006, and was replaced by PCV13 in April 2010
The Public Health England Centre for Infectious Disease Surveillance and Control maintains a central database of IPF reports, which have been required since 2010, and are obtained from diagnostic microbiology laboratories in England and Wales
Electronic reports of IPD cases in England and Wales are matched with serotype reports of the isolates and analyzed by the Public Health England Respiratory and Vaccine Preventable Bacteria Reference Unit
The corrected incidence of IPD accounted for the proportion of samples serotyped, missing age, and for the trend in total IPD up to 2009/2010 (after which no trend correction was applied)
The incidence rate ratio (IRR) for IPD was calculated by comparing the incidence in 2013–2014 relative to the average incidence of IPD in the 2 years pre-PCV13 introduction (2008–2010) and during the pre-PCV7 years (2000–2006) using a Poisson regression
The incidence of nonvaccine serotypes found in cases of IPD in children <5 years increased relative to vaccine serotypes
Reference
Waight PA, Andrews NJ, Ladhani SN, et al. Effect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction: an observational cohort study. Lancet Infect Dis. 2015;15(5):
PCV=pneumococcal conjugate vaccine; PCV7=serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. PCV13 only=only serotypes 1, 3, 5, 6A, 7F, and 19A.
*Corrected for proportion of samples serotyped, missing age, denominator compared with 2009–2010, and trend in total IPD up to 2009–2010 (after which no trend correction was applied). NVT, non-vaccine serotypes; PCV13 only, serotypes in the PCV13 vaccine but not in the PCV7 vaccine.
1. Adapted from: Waight PA, et al. Lancet Infect Dis. 2015;15(5):

13. Vaccine effectiveness* (%) Vaccine effectiveness* (%)
PCV13 2+1
South Africa: Vaccine effectiveness* of PCV13 against IPD in children not infected with HIV aged ≥16 weeks in a case-control study1
Effectiveness of 2 or more doses of PCV13 versus no doses against IPD during PCV13 period†
Effectiveness of 2 or more doses of PCV7 or PCV13 versus no doses against PCV7-type IPD over full study period‡ %
(95% CI) %
(95% CI)
92%
(40–99)
90%
(53–98)
85% (37–96)
87%
(38–97)
The overall effectiveness of 2 or more doses of PCV7 or PCV13 against PCV7-type IPD in children aged ≥16 weeks not infected with HIV over the full study period was 78% [95% CI: 46%–91%].
82%
(44–94)
74%
( -183–98)
77%
(17–94)
52%
(-12%–79%)
Vaccine effectiveness* (%)
Vaccine effectiveness* (%)
PCV13 serotypes (all)§
PCV13 serotypes (additional)‖
PCV7 serotypes
All serotypes
Exposed to HIV
Not exposed to HIV
Malnourished
Not malnourished
*Vaccine effectiveness was adjusted for malnutrition, for diphtheria, tetanus, and pertussis vaccination status at 16 weeks (3 doses received or not), and for maternal education level. †Enrolled children born during or after August ‡Children born from February 2009 through July 2011.§PCV13 serotypes included: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. ‖Serotypes included in PCV13 but not in PCV7 were 1, 3, 5, 6A, 7F, and 19A. CI, confidence interval
1. Adapted from: Cohen C, et al. Lancet Glob Health. 2017;5(3):e359-e369.

14. Incidence (cases per 100,000 population)
South Africa: Age-specific incidence rates* for laboratory-confirmed IPD reported to GERMS-SA, 2009–20151
PCV7 introduced April 2009
PCV13 introduced June 2011
Incidence (cases per 100,000 population)
Age category (years)
Following the introduction of PCV7/PCV13 in South Africa, the incidence of IPD was significantly reduced between 2009 and 2015 in infants <1 year of age (p<0.001).
*Incidence rates were determined based on population figures obtained from Statistics South Africa.
2009: N=4,765, age unknown for n=163; 2010: N=4,199, age unknown for n=142; 2011: N=3,804, age unknown for n=219; 2012: N=3,222, age unknown for n=253; 2013: N=2,866, age unknown for n=142; 2014: N=2,734, age unknown for n=162; 2015: N=2,640, age unknown for n=158.
GERMS-SA, Group for Enteric, Respiratory and Meningeal Disease Surveillance in South Africa.1
1. GERMS-SA Annual Report Available from: Accessed March 28, 2017.

15. England and Wales: IPD cases due to Serotype 3 in children <5 years of age1
PCV13
68% reduction* (vs. 2008–2010)
Number of cases
*Not statistically significant.
1. Adapted from: Waight PA, et al. Lancet Infect Dis. 2015;15(5):

16. United States: Cases of IPD due to Serotype 6A in children ≤5 years of age1
PCV7
PCV13
97% reduction (vs. 1999–2000)
Number of cases
1. Adapted from: Richter SS, et al. Emerg Infect Dis. 2013;19(7):

17. Corrected incidence per 100,000
England and Wales: IPD incidence due to serotype 19A in children <15 years of age1
Serotype 19A
Corrected incidence per 100,000
<2 years of age
2–4 years of age
5–14 years of age
PCV7
PCV13
0.0
1.0
2.0
3.0
4.0
5.0
6.0
2000/2001
2001/2002
2002/2003
2003/2004
2004/2005
2005/2006
2006/2007
2007/2008
2008/2009
2009/2010
2010/2011
2011/2012
2012/2013
2013/2014
91% reduction in children <5 years of age (vs. 2008–2010)
1. Adapted from: Waight PA, et al. Lancet Infect Dis. 2015;15(5):

18. New Zealand: 19A IPD cases in children <5 years of age1
19A IPD cases in New Zealand
<5 years of age
PCV7
PCV10
PCV13
No overall change in 19A IPD was observed in vaccinated children (children <5 years) in New Zealand while PCV10 was in the NIP.
Number of IPD cases
1. Adapted from: Institute of Environmental Science and Research Limited Surveillance Report. Invasive pneumococcal disease in New Zealand Available from: Accessed 1 March 2018.

19. Pneumococcal CAP (children 1 month–15 years of age)
France: Pneumococcal CAP*† cases in children 1 month–15 years of age in 8 pediatric hospitals1
Pneumococcal CAP (children 1 month–15 years of age)
Pneumococcal CAP
63% reduction vs. pre-PCV13
Number of cases
Pre-PCV13 (June 2009–May 2010)
Transition (June 2010–May 2011)
Post-PCV13 (June 2011–May 2012)
*X-ray confirmed; laboratory-confirmed P-CAP defined by positive blood or pleural culture, positive pleural PCR, or positive pneumococcal antigen detection in pleural sample. Microbiologically confirmed.
CAP, community-acquired pneumonia; P-CAP, pneumococcal CAP; PCR, polymerase chain reaction
1. Adapted from: Angoulvant F, et al. Clin Infect Dis. 2014;58(7):

20. PCV 13 introduction in NIP PCV 13 withdrawal from NIP
Madrid, Spain: Incidence of bacteremic pneumonia before and after withdrawal of PCV13 from public vaccination program1
Incidence of bacteremic pneumonia in children <14 years of age, Madrid, Spain, January 1, 2009−June 1, 2014
S. pneumoniae incidence
PCV 13 introduction in NIP
PCV 13 withdrawal from NIP
Withdrawal of government subsidy of PCV13
Introduction of universal PCV13
1. Tagarro A, et al. J Pediatr. 2016;171:111-5.e1-3.

21. New Zealand: Frequency of S
New Zealand: Frequency of S. pneumoniae serotypes from middle ear fluid (MEF) in children <3 years of age undergoing tube insertion1 30 25 20 15 10 5
Percent
11A
10A
23A
33F
22F 6C
16F
15B
19A
23B
15C 9N
35B 3
35F
19F 31 38
23F
Phase 1* (PCV7†); N=25
Phase 2* (PCV10†); N=25
Compared with Phase 1, S. pneumoniae serotype 19A became the most commonly isolated serotype from MEF during phase 2.
Key Point
S pneumoniae serotype 19A was the most commonly isolated serotype from MEF in children <3 years of age undergoing ventilation tube (VT) insertion during phase 2 of the study
Notes
In New Zealand, PCV7 was introduced in the national immunization schedule in 2008 and was replaced with PCV10 in July 2011 (PCV13 was added for high-risk children at that time as well), but PCV7 continued to be used until stock was depleted in late 2011
Opportune timing related to the changing pneumococcal vaccine schedule in New Zealand allowed Best et al to study the etiology of otitis media (OM), specifically changes in the microbiology of MEF and nasopharyngeal (NP) carriage (including S pneumoniae serotypes and H influenzae), before and after the introduction of the PCV10 vaccine in late 2011
This large, multicenter, multiphase study also aimed to document and compare NP carriage and antibiotic susceptibility of OM-causing organisms in children with or without a history of recurrent acute otitis media (rAOM) or otitis media with effusion (OME) during the time periods when PCV7 (3+1 schedule) or PCV10 (3+1 schedule) were on the vaccine schedule
Phase 1 (N=325) of this study was conducted from May to November in 2011, 3 years after the introduction of PCV7 in New Zealand. Phase 2 (N=319) of the study was conducted from May to November in Children in this study were <3 years of age undergoing ventilation tube insertion for rAOM or OME. At enrollment, 96% of children in phase 1 had received 3 or more doses of PCV7; in phase 2, 94% of children who received 3 or more doses of PCV10. Non-otitis prone children <3 years of age who were eligible for vaccination comprised the seasonally matched comparison group
A total of 32 S pneumoniae isolates from MEF obtained from 25 children were serotyped in phase 1, and 29 isolates from 25 children were serotyped in phase 2
In phase 1 of the study, serotypes 35F and 19F were the most common serotypes isolated. However, in phase 2, 19A was the most common serotype isolated, followed by 11A
References
Best EJ, Walls T, Souter M, et al. Pneumococcal vaccine impact on otitis media microbiology: a New Zealand cohort study before and after the introduction of PHiD-CV10 vaccine. Vaccine. 2016;34(33):
Ministry of Health Immunisation Handbook 2014 (2nd edn). Wellington: Ministry of Health. Accessed October 27, 2016.
Institute of Environmental Science and Research Ltd (ESR). Invasive pneumococcal disease in New Zealand, Porirua: ESR; 2016.
Serotypes
*Phase 1 conducted from May to November 2011; Phase 2 conducted from May to November 2014.
†PCV7 was introduced in the New Zealand national immunization schedule in 2008 and replaced with PCV10 in late 2011.
1. Adapted from: Best EJ, et al. Vaccine. 2016;34(33):

22. United States: Rates of otitis media in children <2 years of age1
PCV13
Otitis media visit rate/child-year, <2 years of age
51% reduction
Key Point
In children <2 years of age in the United States, the rate for OM visits fell by 40.6% between 2009 and 2011, from 1.38 OM visits per child-year in 2009 to 0.82 OM visits per child-year in 2011
Notes
PCV7 was introduced into the NIP in the United States in 2000 and was replaced by PCV13 in 2010
De-identified records from a US managed health insurance claims database, Clinformatics Data Mart (Ingenix, Eden Prairie, MN), were analyzed to identify primary OM diagnoses in children ≤6 years of age from outpatient, inpatient, and enrollment data sets that included ~48 million individuals from 2001–2011
Nearly 7.82 million ≤6 years of age were identified, contributing nearly 5.51 million child-years. Children <2 years of age made up 48% of the study population
A total of 6.21 million visits with a primary diagnosis of OM were identified
In children aged <2 years of age, visits for OM decreased at a rate of 0.03/child-year annually from 2001 to 2009 however, a more drastic decrease was observed in 2010–2011 at 0.27/child-year annually (P<0.001) following the introduction of PCV13
By end of the study period, the rate for OM visits had fallen by 40.6% from 1.38 OM visits per child-years in 2009 to 0.82 OM visits per child-years in 2011
Reference
Marom T, Tan A, Wilkinson GS, Pierson KS, Freeman JL, Chonmaitree T. Trends in otitis media–related health care use in the United States, 2001–2011. JAMA Pediatr. 2014;168(1):68-75.
1. Marom TM, et al. JAMA Pediatr. 2014;168(1):68-75.

23. Introduction of PCV13 in pediatric populations has had an indirect impact on IPD in adults
Children are a primary reservoir for pneumococci.1
Relationship of carriage to development of natural immunity is not clearly understood.
Pneumococcal conjugate vaccines (PCVs) have been shown to reduce the carriage of vaccine-type strains in vaccinated children, thus reducing opportunities for transmission.1, 2
Decreased transmission of pneumococci from children to adults has led to the observed reduction in rates of IPD in adults since the introduction of PCV.3
Key Points
The introduction of PCV13 into the routine pediatric vaccination schedule in the United States has had an indirect impact on IPD in adults.1
As children are the primary reservoir of Streptococcus pneumoniae, the reduction in nasopharyngeal carriage of vaccine-type strains in vaccinated individuals results in subsequent decreased transmission to unvaccinated populations.2
Notes
Children in day care spend many hours each day together in crowded conditions, which likely facilitates the transmission of S pneumoniae.2
Pneumococcal conjugate vaccines such as PCV7and PCV13, have reduced nasopharyngeal carriage of S pneumoniae strains contained in the respective vaccines in children, and this may have contributed to decreased rates of IPD by reducing opportunities for transmission among children, and between children and adults.1-3
The indirect effect of PCVs is evidence of herd protection, not herd immunity, because no transfer of immunity occurs and individuals protected by the herd remain susceptible to colonization and infection.4
References
Davis SM, Deloria-Knoll M, Kassa HT, O’Brien KL. Impact of pneumococcal conjugate vaccines on nasopharyngeal carriage and invasive disease among unvaccinated people: Review of evidence on indirect effects. Vaccine. 2013;32(1):
Dagan R, Givon-Lavi N, Zamir O, et al. Reduction of nasopharyngeal carriage of Streptococcus pneumoniae after administration of a 9-valent pneumococcal conjugate vaccine to toddlers attending day care centers. J Infect Dis. 2002;185(7):
Cohen R, Levy C, Bingen E, et al. Impact of 13-valent pneumococcal conjugate vaccine on pneumococcal nasopharyngeal carriage in children with acute otitis media. Pediatr Infect Dis J. 2012;31(3):
Clemens J, Shin S, Ali M. New approaches to the assessment of vaccine herd protection in clinical trials. Lancet Infect Dis. 2011;11(6):
IPD, invasive pneumococcal disease; PCV, pneumococcal polysaccharide vaccine
1. Dagan R, et al. J Infect Dis. 2002;185(7): ; 2. Cohen R, et al. Pediatr Infect Dis J. 2012;31(3): ; 3. Davis SM, et al. Vaccine. 2014;32(1):

24. Proportion of nasopharyngeal swabs (%)
France: Carriage of overall six additional serotypes in children 6–24 months with acute otitis media1,2
NPC of S. pneumoniae (Sp) Serotypes, PCV7 Serotype (ST), and 6 Additional Plus 6C Serotypes as well as Antibiotic Resistance From 2001 to 2014
Period 1 (Oct 2001–Jun 2006)
Period 2 (Oct 2006–Jun 2010)
Period 3 (Oct 2010– Jun 2011)
Period 4 (Oct 2011– Jun 2014) Sp
PCV7 ST
ST 6 additional* + 6C
Penicillin intermediate
Penicillin resistant
PCV7 80 50 20 60 40 10 70 30
Recommendation
for high-risk infants
for all infants
PCV13
Implementation
Proportion of nasopharyngeal swabs (%)
Vaccine coverage: 96% in 2012
(≥1 dose, 6 months old).²
Adapted from Cohen et al
From 2001 to 2010, carriage of 6 additional* PCV13 serotypes plus 6C increased from 17.2% to 24.3% (P<0.001) and decreased from 2011 to after PCV13 implementation from 21.4% to 3.5% (P<0.001).
Penicillin-intermediate-resistant pneumococcal strains decreased from 65.8% in 2001 to 32.2% in 2014.†
Penicillin-resistant pneumococcal strains decreased from 1.3% in 2001 to 1% in 2014.†
Between 2001 and 2014, 121 paediatricians obtained nasopharyngeal swabs from children with acute otitis media aged 6–24 months. The swabs were analysed by the French National Reference Centre for Pneumococci. A total of 7991 patients were enrolled.
*Serotypes 1, 3, 5, 6A, 7F, 19A. † 95% CIs and p-values not available; no conclusion can be drawn regarding statistical significance.
NIP, National immunisation programme; NPC, nasopharyngeal carriage, PCV7, 7-valent pneumococcal conjugate vaccine;
PCV13, 13-valent pneumococcal conjugate vaccine.
1. Adapted from: Cohen R, et al. Vaccine. 2015;33(39): INVS. Available from: Accessed February 25, 2016. 24

25. Proportions of pneumococcal serotypes/serogroups isolated (%)
Switzerland: Pneumococcal carriage and serotype Distribution in AOM patients pre- and post-PCV introduction1
Variation of pneumococcal serotypes isolated from nasopharyngeal swabs of AOM patients during PCV vaccination periods
PCV13 serotypes
PCV7 (p<0.001)
PCV13-PCV7-Serotype 3-
Serotype 19A (p=0.002)
Serotype 19A (p=0.001)
Serotype 3 (p=0.013)
PCV13
Proportions of pneumococcal serotypes/serogroups isolated (%)
Time (Year)
A decrease in PCV13 serotypes was observed following PCV13 introduction, with the exception of serotype 3 increasing from 8.5% in 2004 to 11.1% in (2 test for trend: P=0.013).
The proportion of serotype 19A isolates increased post-PCV7, then decreased significantly in the PCV13 era (2 test for trend: P=0.001).
The proportion of non-PCV13 serotypes increased following PCV introduction, increasing from 26.1% in 2004 to 85.2% in 2015 (2 test for trend: P<0.001).
AOM, acute otitis media.
1. Allemann A, et al. Vaccine. 2017;35(15):

26. Prevention 1. Vaccination
CDC recommends administering PCV13 as a four-dose series at 2, 4, 6, and 12 through 15 months of life
Research shows that this vaccine is very effective at preventing infection resulting from the serotypes contained in the vaccine
PCV13 should also be administered to all adults 65 years or older and to some adults 19 through 64 years of age with conditions that put them at increased risk for pneumococcal disease

27. 2. OTHER PREVENTIVE MEASURES.
Nutritional support
Chemoprophylaxis – oral Pen V for those at risk e.g functional/anatomical asplenia.
Rational use of antibiotics
Reduction of the Environmental risks- Air pollution, overcrowding.

28. New vaccine in future? A 72- valent pneumococcal vaccine is under development. Hoped to offer ‘most comprehensive coverage’. THANK YOU.