Prevenar 13 Pediatric Objectives 2008-2010 - GLOBE Network · Modified from a slide prepared by Dr...

Dagan/Pnc/2016Slides prepared by Ron Dagan MD

Ron DaganThe Pediatric Infectious Disease Unit

Soroka University Medical Center

Ben-Gurion University

Beer-Sheva, Israel

Introduction of New Vaccines into

Vaccination Programs

Pneumococcal Conjugate Vaccines

(PCVs) - Overview


Pneumococcal Disease Endpoints

6A 6B 9V 14 19A 19F 23F


Pneumonia/LRI

Otitis media

Invasive Pneumococcal

disease

Meningitis

Bacteremia/sepsis

Bacteremic pneumonia


PCV7 4 6B 9V 14 18C 19F 23F

PCV13 4 6B 9V 14 18C 19F 23F 1 5 7F 3 6A 19A

PCV10 4 6B 9V 14 18C 19F 23F 1 5 7F

CRM197

conjugate

H. Influenzae Protein D (4, 6B, 9V, 14, 23F, 1, 5, 7F); Tetanus toxoid (18C); Diphtheria toxoid (19F)

Licensed PCVs

CRM197

conjugate


Goldblatt, Proceedings of the Ninth Global Vaccine Research Forum and Parallel Satellite Symposia, WHO. Bamako, Mali, 6-9

December 2009

IPD

Pneumonia

Otitis media

NP carriage

Vaccine efficacy

PCV Efficacy Against Various

Disease Endpoints (PCV Serotypes)

This image is courtesy of Prof. David Goldblatt


Perceived Efficacy of PCVs against IPD vs. Overall

Mucosal End-points

All-Cause

IPD

Alveolar

pneumonia

All-cause

pneumonia

All-cause

otitis media

Pe

rc

eive

d e

ffic

ac

y

10

20

30

40

50

60

70

80

90

100


Impact

of PCV

What Does Determine Impact?

Efficacy/effectiveness

against disease

Dependent on

- end-point measured (IPD vs mucosal disease)

- Specific vaccine (i.e. different carrier)

Local epidemiologic characteristics

- Serotype distribution before PCV introduction

- Immunodeficient population (i.e. HIV prevalence)

Vaccination

uptake

Efficacy/effectivenes

s against carriage

- Specific vaccine efficacy (i.e. effect of

carrier)

Indirect protection

(herd; societal protection)

Especially important for the unvaccinated including

prevention of early exposure to VT strains

Serotype coverage

of the vaccine

(PCV7, 10, 13)

Time after vaccine

introduction




Ra

te

ra

tio

re

la

tive

to

p

re

-P

CV

7 im

ple

me

nta

tio

n

PC

V7

typ

es

No

n-P

CV

7 typ

es*

All se

ro

typ

es

Years post PCV introduction

Feikin et al, PLOS Medicine, 9:e1001517, 2013

Post-PCV7 Introduction IPD -

Summary Rate Ratios

* Including PCV13 serotypes not in PCV7

6-7 yrs 6-7 yrs 6-7 yrs


Antibiotics

1 3 4 5

6B 6C 7F 9V 11A

12F 14 15 18C 19A

19F 22F 23F 33F

6A

35B

PCV7

1 3 4 5

6B 6C 7F 9V 11A

12F 14 15 18C 19A

19F 22F 23F 33F

6A

35B

15 19A

35B

11A

33F

Antibiotics + PCV7

Susceptible

Resistant

http://mirror-us-ga1.gallery.hd.org/_exhibits/medicine/pills-red-and-yellow-antibiotics-closeup-1-AJHD.jpg


IPD Incidence After PCV7 Introduction in US Population

Pilishvili et al, J Infect Dis, 201:32-41, 2010


0,0

10,0

20,0

30,0

40,0

50,0

60,0

90-91 92-93 94-95 96-97 98-99 00-01 02-03 04-05 06-07 08-09 10-11 12-1314-15

7VT 6A 1, 3, 5, 7F, 19A Non13VT

IPD Incidence in Children <24 Months,

Israel, 1989-2015

PCV7

NIP

PCV13

NIP

Ben-Shimol et al, Vaccine, 32:3452–3459, 2014 (updated)


Number of Invasive Pneumococcal Isolates in Children Among 8 Children

Hospitals by Study Years, 1994–2011

Kaplan et al, PIDJ; 32: 203–207, 20013


Incidence of IPD by Age Group,

Denmark, 2000–2013

Barrella Harboe et al, CID, 59:1066–73, 2014

<2 years

≥65 years

PCV7

Start PCV13

PCV7

Start PCV13


0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

11-12/09 1-6/10 7-12/10 1-6/11 7-12/11 1-6/12 7-12/12 1-6/13 7-12/13 1-6/14 7-12/14 1-6/15 7-12/15

VT7 6A 19A 1 3 5 7F Others Cx(-)

Pneumococcal Carriage in Children <5 Yrs Attending

Pediatric Emergency Room, Southern Israel

* For the period of 07-12/09, data for Jewish children are from Nov-Dec only and for Bedouin children for Dec only

713

8 children <5 yrs old seen each working day at the medical Pediatric ER since Nov 09

Ben Shimol et al, Human Vaccine and Immunotherapeutic http://dx.doi.org/10.1080/21645515.2015.1095414, 2015, updated

Dis

trib

uti

on

b

y s

ero

typ

e g

rou

p

n=635 n=694 n=708 n=762 n=599 n=740 n=754n=890n=176 n=875 n=779 n=919 n=650

PCV13 serotype carriage 2014-2015 vs 2009-2010: -72%

http://dx.doi.org/10.1080/21645515.2015.1095414


0

0,5

1

1,5

2

Pre-PCV PCV7 PCV13

<4m 4-11m 12-23m

0

5

10

15

20

25

30

Pre-PCV PCV7 PCV13

<4m 4-11m 12-23m

0

1

2

3

4

5

6

Pre-PCV PCV7 PCV13

<4m 4-11m 12-23m

PCV7 serotypes + 6A 5 additional PCV13 serotypes

0

2

4

6

8

10

Pre-PCV PCV7 PCV13

<4m 4-11m 12-23m

All pneumococcal OM

All-cause OM

In

cid

en

ce

(p

er 1

00

0 p

op

ula

tio

n)

98% (74-100)

88% (55-93)

90% (81-95)

79%% (73-84)

Incidence and Incidence Rate Reductions of Pneumococcal

and All-cause OM, Children <4, 4-11 and 12-23m,

in the pre-PCV7, PCV7 and PCV13 Periods

Pre-PCV: 2004-2008

PCV7: 2010-2011

PCV13: 2013-2015


9.1

10.2

7.2

-25%

Regev-Yochay, Dagan et al, data from the prospective surveillance on carriage in Southern Israel last (updated Jan/2016)

-68%

IPD Incidence among Individuals ≥18 yrs,

Israel July 2009 through June 2015


0

5

10

15

20

25

30

35

2009-10 2010-11 2011-12 2012-13 2013-14 2014-15

5-17 18-44 45-64 65+

Ra

te

IP

D p

er 1

00

,0

00

po

pu

latio

n

All Pneumococcal IPD Incidence Rates

in Individuals ≥5 Yrs in Israel: 2009-2015

Year

-69%

-55%

-19%

-18%

PCV7

PCV`13

Dagan et al, data from the prospective surveillance on carriage in Southern Israel last (updated 08/06/2015)


Annual Counts of Serotype-specific IPD in The Gambia

Mackenzie al, Lancet ID, http://dx.doi.org/10.1016/S1473-3099(16)00054-2, 2016

http://dx.doi.org/10.1016/S1473-3099(16)00054-2


Serotype 19A IPD Cases in Individuals <5 and ≥5 Yrs Old

in 6 Countries

1. Moore et Al, Lancet Infect Dis, 15:301-09, 2015 2. Dagan et al (data from the nationwide prospective surveillance on IPD in Israel)\

3. Finland Institute for Health and W elfare (THL) : http://www.thl.fi/en/web/thlfi-en/topics/information-packages/incid ence-of-invasive-pneumococcal-disease-in-finland

4. New Zealand Public Health Surveillance: institute of Environmental Science and Research Ltd (ESR); Accessed 13Feb2015 from https://surv.esr.cri.nz/surveillance/IPD.php5. www.ispch.cl/sites/default/files/Bolet%C3%ADn%20de%20Vigilancia%20de%20Laboratorio%20de%20Streptococcus%20pneumoniae.pdf accessed Oct 29, 30, 2015

6. For the UK: Prof Liz Miller, Personal Communication

- Some studies a year = Jan – Dec; in others July – June- In Chile – Individuals ≥2 years of age

<5 years old

≥5 years old

http://www.thl.fi/en/web/thlfi-en/topics/information-packages/incidence-of-invasive-pneumococcal-disease-in-finland

https://surv.esr.cri.nz/surveillance/IPD.php

http://www.ispch.cl/sites/default/files/Bolet%C3%ADn de Vigilancia de Laboratorio de Streptococcus pneumoniae.pdf


1. Moore et Al, Lancet Infect Dis, 15:301-09, 2015 2. Dagan et al (data from the nationwide prospective surveillance on IPD in Israel)\

3. Finland Institute for Health and W elfare (THL) : http://www.thl.fi/en/web/thlfi-en/topics/information-packages/incid ence-of-invasive-pneumococcal-disease-in-finland

4. New Zealand Public Health Surveillance: institute of Environmental Science and Research Ltd (ESR); Accessed 13Feb2015 from https://surv.esr.cri.nz/surveillance/IPD.php5. www.ispch.cl/sites/default/files/Bolet%C3%ADn%20de%20Vigilancia%20de%20Laboratorio%20de%20Streptococcus%20pneumoniae.pdf accessed Oct 29, 30, 2015

6. For the UK: Prof Liz Miller, Personal Communication

- In New Zeeland, serotypes 6A and 6C were only distinguished from 2010 onwards; they have been combined for this analysis- Some studies a year = Jan – Dec; in others July – June

- In Chile – Individuals ≥2 years of age

Serotype 6A IPD Cases in Individuals <5 and ≥5 Yrs Old

in 6 Countries

<5 years old <5 years old

http://www.thl.fi/en/web/thlfi-en/topics/information-packages/incidence-of-invasive-pneumococcal-disease-in-finland

https://surv.esr.cri.nz/surveillance/IPD.php

http://www.ispch.cl/sites/default/files/Bolet%C3%ADn de Vigilancia de Laboratorio de Streptococcus pneumoniae.pdf


Mucosal infections –

the probe studies re-discovered

Pneumonia

Otitis

Media

http://www.google.es/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://www.telegraph.co.uk/news/health/news/9795993/Warning-over-killer-pneumonia-linked-to-flu.html&ei=d-cPVarvB8KAU47ogKAI&bvm=bv.88528373,d.d24&psig=AFQjCNHgdDPuDnm1kRr5bEF3pnX2rInodw&ust=1427191963171754




Clinical diagnosis (WHO fast breathing? Febrile? Other clinical signs?)

Any severe pneumonia

Modified from a slide prepared by Dr Thomas Cherian, WHO

Any Chest X-ray

abnormality

Lobar consolidation/

pleural effusion

Defining Pneumococcal Pneumonia

Lobar consolidation/pleural

effusion or CRP >40 mg/L

Culture-positive

Pneumococcal pneumonia

Vaccine probe


All-Cause IPD Alveolar

pneumonia

All-cause

pneumonia

Pe

rc

eive

d e

ffic

ac

y

10

20

30

40

50

60

70

80

90

100

Perceived Efficacy of PCVs against Overall

Pneumonia /LRIs


0,0

5,0

10,0

15,0

20,0

25,0

0,0

1,0

2,0

3,0

4,0

5,0

6,0

7,0

8,0

7/0

2

9/0

2

11/

02

1/0

3

3/0

3

5/0

3

7/0

3

9/0

3

11/

03

1/0

4

3/0

4

5/0

4

7/0

4

9/0

4

11/

04

1/0

5

3/0

5

5/0

5

7/0

5

9/0

5

11/

05

1/0

6

3/0

6

5/0

6

7/0

6

9/0

6

11/

06

1/0

7

3/0

7

5/0

7

7/0

7

9/0

7

11/

07

1/0

8

3/0

8

5/0

8

7/0

8

9/0

8

11/

08

1/0

9

3/0

9

5/0

9

7/0

9

9/0

9

11/

09

1/1

0

3/1

0

5/1

0

7/1

0

9/1

0

11/

10

1/1

1

3/1

1

5/1

1

7/1

1

9/1

1

11/

11

1/1

2

3/1

2

5/1

2

7/1

2

9/1

2

11/

12

1/1

3

3/1

3

5/1

3

7/1

3

9/1

3

11/

13

1/1

4

3/1

4

5/1

4

7/1

4

9/1

4

11/

14

1/1

5

3/1

5

5/1

5

7/1

5

9/1

5

11/

15

1/1

6

3/1

6

5/1

6

Monthly Hospital Visits for Alveolar Pneumonia, Children <2 Years,

Southern Israel, Since July 2002

Year

Mo

nth

ly in

cid

en

ce

s p

er 1

,0

00

p

op

ula

tio

n

n=362n=631n=585 n=673 n=674 n=660 n=593n=576 n=386 n=351 n=390n=648 n=705

22.8

24.0

19.8

20.5

23.322.8

21.9

20.4

19.0

12.2

11.210.7

09-1004-05 05-06 06-07 07-08 08-09 10-11 11-12 12-13 13-1403-0402-03 14-15

An

nu

al in

cid

en

ce

p

er 1

,00

0 p

op

ula

tio

n

PCV7

Private market

PCV7

NIP

PCV7

PCV13

11.7

n=345

15-16

Updated 28-02-2016

A prospective population-based study to document hospital use for alveolar pneumonia in young children

-50%

Vs. 2002-2008

Greenberg et al, Vaccine, 33:4623–4629, 2015 (updated)Each study year is July through June



0

20

40

60

80

100

120

0

500

1000

1500

2000

2500

3000

Alveolar pneumonia, southern Israel IPD, nationwide incidence

In

cid

en

ce

, c

hild

re

n <

2 yrs p

er

10

0,0

00

PCV7

NIP PCV7

PCV13

PCV7

Private market

* Pediatric Emergency Room ambulatory visits and hospitalizations

Greenberg et al, Vaccine, 33:4623–4629, 2015 (updated)

-50%

Vs. 2002-2008

Each study year is July through June

Alveolar Pneumonia Hospital Visits* and IPD

Incidence Reduction in Children <2 Yrs Old,

2012-14 vs 2004-8


0

20

40

60

80

100

120

0

500

1000

1500

2000

2500

3000

Alveolar pneumonia, southern Israel IPD, nationwide incidence

In

cid

en

ce

, c

hild

re

n <

2 yrs p

er

10

0,0

00

PCV7

NIP PCV7

PCV13

Alveolar Pneumonia Hospital Visits* and IPD

Incidence Reduction in Children <2 Yrs Old,

2012-14 vs 2004-8

PCV7

Private market

-64%

Vs. 2004-2008

-1100

-61

x18

Greenberg et al, Vaccine, 33:4623–4629, 2015 (updated)

Ben-Shimol et al, Vaccine, 32:3452–3459, 2014 (updated)

-50%

Vs. 2002-2008

* Pediatric Emergency Room ambulatory visits and hospitalizations

Each study year is July through June


The Viral-Bacterial Interaction and Pneumonia

ColonizationViral URI


Virus PCV Placebo Efficacy 95% CI p value

Influenza A/B 31 56 45 14-64 0.01

PIV1-3 24 43 44 8-66 0.02

hMPV 26 62 58 34-73 0.001

RSV 90 115 22 -3-41 0.08

PCV Efficacy Against Viral-associated Pneumonia

Hospitalization in Children

Madhi & Klugman, Nature Med, 10:811-13, 2004

Madhi et al, J Infect Dis, 193:1236-43, 2006

• >1/3 of children hospitalized for pneumonia in whom a virus is identified

have concurrent infection due to pneumococcus included in the PCV

• Study provides a minimal estimate of contribution of pneumococcal co-

infection (role of serotypes not included in the PCV)


0

1000

2000

3000

4000

5000

6000

7000

2006-07 2007-08 2008-09 2009-10 2010-11 2011-12 2012-13 2013-14 2014-15

Alveolar Other LRIs All-cause LRIs

In

cide

nce

p

er 1

00,0

00 c

hild

re

n <2

yrs PCV7

Private marketPCV7

NIP

PCV7

PCV13

-40%

-21%

-25

-603

-905

-1508

Hospitalizations for Alveolar Pneumonia and

All-cause LRIs in Children <2 Years Old, Southern Israel:

Incidence Reduction 2012-15 vs 2006-8

Dagan et al, 55th

ICAAC, San Diego, CA, USA, Sept 2015 (Abst. # I-292).LRI = low er respiratory infections


Griffin et al, MMWR, 63:995-8, 2014

-72%

An

nu

alized

mo

nth

ly h

osp

ita

lizatio

ns p

er

1,0

00

Annualized Monthly All-cause Pneumonia Hospitalizations

Children <2 Yrs During Pre-PCV, PCV7, and PCV13 Years

Tennessee, USA


Evolution of Community-acquired Pneumonia Cases:

8 Pediatric Pediatric Emergency Department Visit, France

Pleuropneumonia

1, 3, 5, 7F, 14, 19A

- Pre-PCV13 (June 2009 - May 2010)

- Transitional (June 2010 – May 2011)

- Post PCV13 (June 2011 – May 2012)

Angoulvant et al, Clin Infect Dis, 58:918-24, 2014

8 Pediatric Emergency Departments, France



Involvement of S. pneumoniae and NTHi in Otitis Media Evolution:

the Disease Continuum Model of Pathogenesis

Dagan et al et al, Lancet Infect Dis, 16:480-92, 2016

Complex otitis media: any cases of recurrent, non responsive, and spontaneously

draining infections, and chronic disease with effusion (which is a long-term and recurrent infection and inflammation of the middle ear)


The Paradoxical Efficacy of PCVs Against Otitis Media

Dagan et al et al, Lancet Infect Dis, 16:480-92, 2016


Impact of PCV7/PCV13 Post Implementation on

OM-Associated Burden

Recurrence/

Complexity/

Chronicity

Chronicity

Ventilation tube

insertion

<12m

23%

(16–29)

Ventilation tube

insertion2

12-23m

16%

(13–19)

Hospitalization with

OM1

<24m

36.4%

(24.1–46.7)

<24m

42.7%

(42.4–43.1)

All OM-related

ambulatory

visits3

Presenting to ER with

OM complicated by

otorrhea5

<15yrs*

38%

P<0.001

* 75%

<36m

<24m

17%

(14-19)

<24m

28%

(23-33)

<24m

8%

(6-11)

<24m

33%

(28-38)

Development of Frequent

OM by age 2 yrs4

2000-2001 birth

cohort

2001-2002 birth

cohort

Tennesse

e

New

-Y

ork

<24m

16%

(11-21)

<24m

23%

(10-35)

<24m

3%

(-3-8)

<24m

21%

(6-33)

Ventilation tube insertion

by age 2 yrs4

2000-2001 birth

cohort

2001-2002 birth

cohortTennessee

New

-Y

ork

1Durando et al, Vaccine 27:3459–3462 2009

2Jardine et al, Pediatr Infect Dis J, 28:761–765, 2009

3Zhou et al, Pediatr. 121;253-260, 2008

4Poehling et al, Pediatrics, 119:707-15, 2007

5Stamboulidis et al, Pediatr Infect Dis J, 30: 551–555, 2011

6Marom et al, JAMA Pediatr, 168:68-75, 2014

37%

PCV7

PCV13

Recurrent-OM

USA 2001-20136


0,0

1,0

2,0

3,0

4,0

5,0

6,0

7,0

8,0

9,0

10,0

2004-2005 2005-2006 2006-2007 2007-2008 2008-2009 2009-2010 2010-2011 2011-2012 2012-2013 2013-2014 2014-2015

4 6B 9V 14 18C 23F 1 3 5 7F 6A 19F 19A

inc

ide

nc

ep

er

10

00

po

pu

lati

on

at

ris

k

Year

Serotype-specific Incidence (PCV7 and PCV13 Serotypes)

in Children <24m with MEF Culture, Southern Israel,

2004-2015*

* Each year is July 1st through June 30th

7.8 7.8

7.3

8.1

5.7

3.7 4.4

1.7

0.6

0.2

Ben-Shimol et al, CID, DOI 10.1093/cid/CIW347, 2016

0.4

-96%

Vaccination

HMO subsidized

Initiation of PCV7

NIP + catch-up

Initiation,

substitution

PCV7 by PCV13


9,8

8,7

9,3 9,4

7,2

5,6

6,7

4,4

2,5

1,9

1,2

0,0

1,0

2,0

3,0

4,0

5,0

6,0

7,0

8,0

9,0

10,0

All Pneumococcal OM

PCV7 in NIP*

An

nu

al

inc

ide

nc

e p

er

10

00

po

pu

lati

on

at

ris

kImpact of the Sequential PCV7/PCV13 Introduction to the NIP

on Pneumococcal OM, Children <24m

Initiation,

substitution

PCV7 by PCV13

87% (82 – 90%)

11,8

6,9

7,9

8,8

6,7

7,5 7,57,0

5,3

4,04,2

0,0

1,0

2,0

3,0

4,0

5,0

6,0

7,0

8,0

9,0

10,0

11,0

12,0

13,0PCV7 in Private

practice

Rate Reduction

2014-2015 vs. 2004-2008

12,0

10,0

12,1

10,9

9,5

8,7

10,4

8,8

4,7

3,12,4

0,0

1,0

2,0

3,0

4,0

5,0

6,0

7,0

8,0

9,0

10,0

11,0

12,0

13,0PCV7 in NIP*

Initiation,

substitution

PCV7 by PCV13

PCV7 in Private

practice

NTHi

78% (73 – 82%)

PCV7 in NIP*

Initiation,

substitution

PCV7 by PCV13

PCV7 in Private

practice

Culture-negative

53% ( 44 – 60%)

* Each study year is July 1st through June 30th Ben-Shimol et al, CID, DOI 10.1093/cid/CIW347, 2016


Overall OM (Pneumococcal and Non-pneumococcal) Incidence

in Children <24m with MEF Culture, Southern Israel, 2004-2015*

30,6

23,2

26,127,1

21,2 20,5

22,9

19,6

12,0

8,5

7,8

0,0

5,0

10,0

15,0

20,0

25,0

30,0

35,0

2004-05 2005-06 2006-07 2007-08 2008-09 2009-10 2010-11 2011-12 2012-13 2013-14 2014-15

PCV7 in Private

practice

PCV7 in NIP*

Initiation,

substitution

PCV7 by PCV13

An

nu

al in

cid

en

ce

pe

r 1

00

0 p

op

ula

tio

n a

t risk

* Each study year is July 1st through June 30th

Year

71% (59 – 74%)

Rate Reduction

2014-2015 vs. 2004-2008

- 1895

cases/100,000

Ben-Shimol et al, CID, DOI 10.1093/cid/CIW347, 2016


Children vs. Adults…

http://www.google.co.il/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://simpsons.wikia.com/wiki/Adults/Kids&ei=1NkrVeP9FYjdPYyUgKAF&bvm=bv.90491159,d.d2s&psig=AFQjCNHXUq2iWfahqcoDv9GsrMLpH4TKjQ&ust=1429023477477716


Antipneumococcal Polysaccharide Binding Antibody Responses

Elicited During the Immunization Series

de Roux A et al. Clin Infect Dis. 2008;46:1015-1023


Antipneumococcal OPA Responses

Elicited During the Immunization Series

de Roux A et al. Clin Infect Dis. 2008;46:1015-1023


OutcomeEfficacy

%95% CI

Primary outcome

• First episode of confirmed VT-CAP 45.6 21.8 – 62.5

Secondary outcomes

• First episode of non-bacteremic/non-invasive VT-CAP

• First episode of VT-IPD

• All-cause CAP

45.0

75.0

5.1

14.2 – 65.3

41.3 – 90.8

−5.1 – 14.2

CAPITA Study – Main Study Outcome Efficacies

Study group PCV13 Placebo

Death 3,006 (7.1%) 3,005 (7.1%)

Rapidly decreasing efficacy with age, especially after 75 years

Bonten et al. N Engl J Med, 372:1114-25, 2015


Should PCV13 Be Implemented in Adults

Beyond High Risk Indications?

• The study was conducted on relatively fit elderlies

– Many of the CAP cases in debilitated, compromised, high risk and institutionalized

• Population did not receive PPV23 (no reduced response to PCV13)

• Effect on all-cause pneumonia ~5% and not statistically significant

• No overall reduction of mortality

• No PCV13 in children – Most cases in Bonten’ s study were PCV13 serotypes

• Implemenation to the entire population will take years, meanwhile PCV13

serotypes may continue to decrease

However:

• Still a considerable number of elderly with pneumonia have urine

molecular tests suggesting PCV7/13 serotypes

• what about populations with− Low (or no) vaccination rate in infants?

− Started national campaigns only recently?

− Does it depend on which vaccine is used (PCV10, PCV13) in infants?


Antibiotic resistance


Nasopharyngeal and Otitis media Connection

and PCV Effect

PCV

Antibiotic resistance

Reduction in disease

caused by most

resistant serotypes

6B, 9V, 14, 19F, 23F, 6A, 19A

Reduction in

carriage most

resistant serotypes

Reduction in

antibiotic use


Pneumococcal Disease Endpoints

6A 6B 9V 14 19A 19F 23F

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