Impact of 13V pneumococcal vaccine on invasive pneumococcal disease and meningitis in the UK http://www.meningitis.org/conference2015

1. Impact of 13V pneumococcal vaccine on
invasive pneumococcal disease and
meningitis in the UK
Liz Miller
Public Health England UK
MRF meeting London
November 4th 2015

2. 2
Bacteraemia
Soft Tissue Infection (rare)
Arthritis (rare)
Sinusitis
(common)
Otitis Media 1 in 3 children
each year, 25-30% pneumococcal
Meningitis
Pneumonia, most common
cause of Community Acquired
Pneumonia
Peritonitis (rare)
The Clinical Spectrum of Pneumococcal Infection

3. 0
10
20
30
40
50
60
0-2
m
ths
3-5
m
ths
6-11
m
ths
12-23
m
ths
24-35
m
ths
36-47
m
ths
48-59
m
ths5-9
yrs
10-14
yrs
15-19
yrs
20-24
yrs
25-29
yrs
30-34
yrs
35-39
yrs
40-44
yrs
45-49
yrs
50-54
yrs
55-59
yrs
60-64
yrs
65-69
yrs
70-74
yrs
75+
yrs
1996
1997
1998
1999
2000
Annual incidence per 100,000 of invasive pneumococcal infection, E&W, by age
group and year
Inability to mount immune
response to capsule
Waning immunity
Non-immune factors

4. Case fatality rate within 7 days of IPD
4
0
5
10
15
20
25
<2yr 2to4 5to14 15to44 45to64 ≥65
CRF
Age
1997/1998 1998/1999 1999/2000 2000/2001 2001/2002 2002/2003 2003/2004 2004/2005
2005/2006 2006/2007 2007/2008 2008/2009 2009/2010 2010/2011 2011/2012

5. PNEUMOCOCCAL VACCINES
Serotype composition of pneumococcal vaccines in the UK
schedule
•
• The polysaccharide vaccine (Pneumovax ™ ) covers 23 of the
most common serotypes
•7 valent conjugate vaccine (Prevenar™ ) contains serotypes
4 6B 9V 14 18C 19F 23F
• 10 valent conjugate (Synflorix ™ )* also contains 1, 5 and 7F
• 13 valent conjugate (Prevenar13™ )* also contains 3, 6A, 19A
*no efficacy data obtained prior to use, licensed on immunogenicity data

6. Evolution of Pneumococcal Vaccination
Policy: E&W
•1992 PPV23 (23 valent pneumococcal polysaccharide vaccine)
for ≥2 years of age at increased risk of IPD.
•2002 PCV7 for children < 2 years of age at increased risk of IPD.
•2003 PPV23 for ≥ 80 years of age.
•2004 PPV23 for ≥ 75 years of age.
•2005 PPV23 for ≥ 65 years of age.
•2006 From September, PCV7 as a 2 + 1 schedule in infant
immunisation schedule. Catch- up to 2 years of age.
•2010 From April, PCV13 replaced PCV7, no catch-up.

7. PHE Enhanced Surveillance of IPD
Microbiology
Labs in England
and Wales
S pneumoniae cultures sent for
serotyping to reference lab at
Colindale
Reports of S. pneumoniae isolates
sent to Colindale electronically into
national database
Joint data set held in Immunisation department
reconciled annually 6 months after end of epi year (July to June)
to generate incidence rates
Real time data from
serotyped isolates
on PHE website

8. Direct and herd immunity impact of PCV7 offset by serotype
replacement: From Miller et al Lancet ID 2011
Age
years
Type of
IPD
Incidence rate ratio (95% CI) % reduction
2009-10 vs 2000-2006
<2 Vaccine Type 0.02 (0.01-0.05) 98% reduction
Non PCV7 1.68 (1.37-2.06)
All IPD 0.44 (0.39-0.49) 56% reduction
≥65 Vaccine Type 0.19 (0.14-0.25) 81% reduction
Non PCV7 1.48 (1.32-1.65)
All IPD 0.81 (0.75-0.88) 19% reduction
8

9. Impact of PCV7 on pneumococcal meningitis
Age group
(years)
Type of
pneumococcal
meningitis
Average
adjusted
incidence 2000-
2006
Average adjusted
incidence 2008-10
IRR (95% CI)
2008-10 vs 2000-2006
<5 VT 2.43 0.12 0.05 (0.02-0.15)
NVT 0.75 1.32 1.77 (1.27-2.47)
All 3.18 1.44 0.56 (0.36-0.89)
≥65 VT 0.18 0.05 0.30 (0.10-0.96)
NVT 0.25 0.30 1.19 (0.84-1.69)
All 0.43 0.35 0.82 (0.57-1.19)

10. Figure 3. Post-PCV7 introduction invasive pneumococcal disease summary rate ratios.
Feikin DR, Kagucia EW, Loo JD, Link-Gelles R, Puhan MA, et al. (2013) Serotype-Specific Changes in Invasive Pneumococcal Disease after
Pneumococcal Conjugate Vaccine Introduction: A Pooled Analysis of Multiple Surveillance Sites. PLoS Med 10(9): e1001517.
doi:10.1371/journal.pmed.1001517
http://journals.plos.org/plosmedicine/article?id=info:doi/10.1371/journal.pmed.1001517

11. •PCV7 was replaced by
PCV13 in April 2010 with
no catch up

12. Vaccine effectiveness estimates to December 2014: additional
PCV13 serotypes: ≥2 dose under 12m or 1 dose aged 12+m
Serotype Cases vaccinated :
unvaccinated
Controls* vaccinated
: unvaccinated
Adjusted VE
(95% CI)
1 14:31 486:93 77.6 (47.1-90.5)
3 41:23 486:93 33.5 (-38.5-68.1)
6A 1:7 486:93 97.2 (60.4-99.8)
7F 6:41 486:93 93.8 (81.0-98.0)
19A 39:56 486:93 70.7 (43.7-84.7)
Controls are age matched IPD cases infected with a non-vaccine serotype

13. Impact of PCV13 on vaccine type IPD
children <5 years to June 2014 from Waight et al
Lancet ID 2015
0
5
10
15
20
25
30
35
40
45
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
CorrectedIPDincidenceper105
<2
PCV7
PCV13 only
PCV7 PCV13
0
2
4
6
8
10
12
14
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
CorrectedIPDincidenceper105
2 to 4
PCV7 PCV13

14. Impact of PCV13 on vaccine type IPD
adults aged 45+ years to June 2014
0
1
2
3
4
5
6
7
8
9
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
CorrectedIPDincidenceper105
45 to 64
PCV7 PCV13
0
2
4
6
8
10
12
14
16
18
20
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
CorrectedIPDincidenceper105
≥65
PCV7
PCV13

15. Data to Sept 2015

16. 0
10
20
30
40
50
60
70
80
26 28 30 32 34 36 38 40 42 44 46 48 50 52 01 03 05 07 09 11 13 15 17 19 21 23 25
CumulativeNumberofReports
Week
06/07 07/08 08/09 09/10 10/11
11/12 12/13 13/14 14/15 15/16
Introduction of Prevenar™
GREEN LINE Week 36 2006
Cumulative weekly number of reports of Invasive Pneumococcal Disease due to serotype 19A:
Children aged <2 years in England and Wales by epidemiological year July-June (2006 – to Sept 2015))
Introduction of Prevenar13™
RUST LINE Week 13 2010

17. Data to Sept 2015

18. 0
50
100
150
200
250
300
350
26 28 30 32 34 36 38 40 42 44 46 48 50 52 01 03 05 07 09 11 13 15 17 19 21 23 25
CumulativeNumberofReports
Week
06/07 07/08 08/09 09/10 10/11
11/12 12/13 13/14 14/15 15/16
Introduction of Prevenar™
GREEN LINE Week 36 2006
Cumulative weekly number of reports of Invasive Pneumococcal Disease due to serotype 19A :
Persons aged ≥65 years in England and Wales by epidemiological year July-June (2006 - to Sept 2015))
Introduction of Prevenar13™
RUST LINE Week 13 2010

19. 2008/2009
Carriage IPD
PCV13 27.6% 63.6%
Rest 72.4% 36.4%
• Post PCV13 carriage study in 2012/13 showed full serotype replacement in
the nasopharynx (van Hoek Vaccine 2014)
• Impact on overall IPD depends on whether replacing serotypes are more
or less invasive than the vaccine types (case:carrier ratio)
• Carriage study from 2008/09 (Flasche et al PLoS Med 2011) together with
IPD surveillance allowed estimation of average invasiveness of PCV13 VT
and NVT
Predicting serotype replacement with PCV13
•Non PCV13 serotypes overall appear less invasive – less potential
for replacement disease predicted despite full serotype
replacement in carriage

20. From
Waight
et al LID
2015 to
end June
2014

21. Change from pre-PCV7 baseline by end
June 2014
Age Serotype 2000-06
incidence per
105
2013/14
incidence
per 105
IRR
2013/14:
2000-6
95% CI *
<2 All 51.81 12.03 0.23 0.46-0.59
PCV7 39.05 0.38 0.01 0.00-0.03
PCV13only 7.49 1.43 0.19 0.10-0.37
NVT 5.27 10.23 1.94 1.42-2.63
≥65 All 34.13 20.58 0.60 0.56-0.64
PCV7 17.89 0.53 0.03 0.02-0.04
PCV13only 7.02 3.72 0.53 0.43-0.61
NVT 9.22 16.33 1.77 1.62-1.95
All ages All 15.63 6.85 0.44
(56% reduction)
0.43-0.47
PCV7 7.73 0.20 0.03 0.02-0.04
PCV13only 3.80 1.40 0.37 0.33-0.41
NVT 4.10 5.25 1.28 1.20-1.35

22. Data to end September 2015

23. 0
200
400
600
800
1000
1200
1400
1600
1800
2000
26 28 30 32 34 36 38 40 42 44 46 48 50 52 01 03 05 07 09 11 13 15 17 19 21 23 25
CumulativeNumberofReports
Week
06/07 07/08 08/09 09/10 10/11
11/12 12/13 13/14 14/15 15/16
Introduction of Prevenar™
GREEN LINE Week 36 2006
Cumulative weekly number of reports of Invasive Pneumococcal Disease due to any of the serotypes
NOT in Prevenar13™ : Persons aged ≥65 years in England and Wales
by epidemiological year July-June (2006 - to date)
Introduction of Prevenar13™
RUST LINE Week 13 2010

24. 24
0
10
20
30
40
50
60
70
80
90
100Proportionofnon-PCV13IPDcases
Serotype
Distribution of NVT IPD serotypes 2014/15

25. Conclusions
• PCV7 and 13 have had profound impacts on the
incidence and serotype distribution of IPD in England
and Wales
• By end June 2014 there was an overall reduction in IPD
compared with pre PCV7 baseline of 56%
• However this reduction is now being eroded by
progressive increases in non-PCV13 serotypes and a
recent increase in 19A
• A variety of non-PCV13 are increasing with 22F and 33F
(15 valent candidates) covering less than 20% of NVTs
• Do we need even higher valency PCVs or a new type
of vaccine?

26. Acknowledgements
PHE Colleagues:
Immunisation Department:
Sarah Collins, Nick Andrews, Shamez Ladhani, Pauline Kaye (nee
Waight), Rashmi Malkani
Respiratory and Vaccine Preventable Bacteria Reference Unit:
Carmen Sheppard, David Litt, Norman Fry
Microbiology Laboratories who send isolates for serotyping and
electronic reports of IPD cases
GPs who provide clinical information and vaccination histories for
their patients
Risk of
narcolepsy after
AS03
adjuvanted
pandemic
A/H1N1 2009
influenza