Impact of 13V pneumococcal vaccine on invasive pneumococcal disease and

meningitis in the UK

Liz MillerPublic Health England UK

MRF meeting LondonNovember 4th 2015

2

Bacteraemia

Soft Tissue Infection (rare)

Arthritis (rare)

Sinusitis (common)

Otitis Media 1 in 3 childreneach year, 25-30% pneumococcal

Meningitis

Pneumonia, most common cause of Community AcquiredPneumonia

Peritonitis (rare)

The Clinical Spectrum of Pneumococcal Infection

0

10

20

30

40

50

601996

1997

1998

1999

2000

Annual incidence per 100,000 of invasive pneumococcal infection, E&W, by age group and year

Inability to mount immuneresponse to capsule

Waning immunityNon-immune factors

4

Case fatality rate within 7 days of IPD

<2yr 2to4 5to14 15to44 45to64 ≥650

5

10

15

20

25

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

Age

CRF

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

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.

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 departmentreconciled annually 6 months after end of epi year (July to June)

to generate incidence rates

Real time data from serotyped isolates

on PHE website

Direct and herd immunity impact of PCV7 offset by serotype replacement: From Miller et al Lancet ID 2011

Ageyears

Type of IPD

Incidence rate ratio (95% CI) % reduction2009-10 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

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)

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.1001517http://journals.plos.org/plosmedicine/article?id=info:doi/10.1371/journal.pmed.1001517

•PCV7 was replaced by PCV13 in April 2010 with

no catch up

Vaccine effectiveness estimates to December 2014: additional PCV13 serotypes: ≥2 dose under 12m or 1 dose aged 12+m

Serotype Cases vaccinated :

unvaccinatedControls* vaccinated

: unvaccinatedAdjusted 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

Impact of PCV13 on vaccine type IPD children <5 years to June 2014 from Waight et al

Lancet ID 201520

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/201

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/201

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/201

40

5

10

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30

35

40

45

<2PCV7

PCV13 only

Corr

ecte

d IP

D in

ciden

ce p

er 1

05

PCV7 PCV13

2000

/200

1

2001

/200

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/200

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/200

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2004

/200

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/200

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2006

/200

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/200

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/200

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/201

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2010

/201

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/201

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/201

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/201

40

2

4

6

8

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12

14

2 to 4

Corr

ecte

d IP

D in

ciden

ce p

er 1

05

PCV7 PCV13

Impact of PCV13 on vaccine type IPD adults aged 45+ years to June 2014

2000

/200

1

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/200

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/200

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/200

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/200

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/200

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/200

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/200

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9

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/201

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/201

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2011

/201

2

2012

/201

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2013

/201

40

1

2

3

4

5

6

7

8

9

45 to 64

Corr

ecte

d IP

D in

ciden

ce p

er 1

05

PCV7 PCV13

2000

/200

1

2001

/200

2

2002

/200

3

2003

/200

4

2004

/200

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/200

8

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/200

9

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/201

0

2010

/201

1

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/201

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/201

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2013

/201

40

2

4

6

8

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12

14

16

18

20

≥65

Corr

ecte

d IP

D in

ciden

ce p

er 1

05

PCV7 PCV13

Data to Sept 2015

0

10

20

30

40

50

60

70

8006/07 07/08 08/09 09/10 10/1111/12 12/13 13/14 14/15 15/16

Week

Cum

ulat

ive

Num

ber o

f Rep

orts

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

Data to Sept 2015

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50

100

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350

06/07 07/08 08/09 09/10 10/1111/12 12/13 13/14 14/15 15/16

Week

Cum

ulat

ive

Num

ber o

f Rep

orts

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

2008/2009Carriage 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

From Waight et al LID 2015 to end June 2014

Change from pre-PCV7 baseline by end June 2014

Age Serotype 2000-06 incidence per 105

2013/14 incidenceper 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

Data to end September 2015

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 23 250

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06/07 07/08 08/09 09/10 10/11 11/12 12/1313/14 14/15 15/16

Week

Cum

ulat

ive

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f Rep

orts

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

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0

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70

80

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100Distribution of NVT IPD serotypes 2014/15

Serotype

Prop

ortio

n of

non

-PCV

13 I

PD c

ases

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?

AcknowledgementsPHE 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

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