PCV13 effectiveness and overall effect of PCV10/13 vaccination programmesin children under five years of age

SpIDnet multicentre studies

Camelia Savulescu, Germaine Hanquet on behalf of the SpIDnet group

ESCAIDENovember 2016

SpIDnet projectBackground and aim

Active Invasive Pneumococcal Disease (IPD) surveillance

Since 2012

>6 mil. children <5 years

Objectives To measure PCV13

vaccine effectiveness

To measure the impact of vaccination programmes

2+1 (9 sites)/ 3+1 (4 sites)

VC>90% (8 sites) /VC=50-78% (4 sites)/ VC<50% (1 site)

PCV13 effectiveness against IPD Methods

Prospective dataset: individual data 2012-15 (10 sites)

Study design Indirect cohort (Broome method): common protocol

Cases: vaccine serotypes IPD

Controls: nonPCV13 and nonPCV13-related serotypes (VRT) IPD

Exposure At least one dose PCV13

Fully vaccinated >12mo (according to recommendations on site)

Analysis VE=(1-OR)*100; site as fixed effect

Adjusted PCV13 VE against IPD serotype categories by vaccination status, SpIDnet multicentre study, 2012-15

87 86 84 80

93 95

5752

-20

0

20

40

60

80

100

951/875 487/451 951/875 458/425 826/756 430/395 951/875 467/431

367/168 235/88 265/140 170/76 102/28 65/12 142/120 77/65

at least onedose

fullyvaccinated

at least onedose

fullyvaccinated

at least onedose

fullyvaccinated

at least onedose

fullyvaccinated

10 sites 10 sites 10 sites 9 sites 7 sites 7 sites 10 sites 9 sites

PCV13st PCV13non7st PCV7st VRTst

vacc

ine

eff

ect

ive

ne

ss (%

)

Adjusted for site, age, sex, underlying conditions, year of notification

Adjusted PCV13 VE against PCV13 serotype specific IPDby vaccination status, SpIDnet multicentre study, 2012-15

8694

70

57

86 84

95 97

-20

0

20

40

60

80

100

908/833 345/318 908/833 423/390 819/753 396/365 748/682 237/214

89/50 47/20 79/50 57/34 54/23 48/19 36/15 14/3

at least onedose

fullyvaccinated

at least onedose

fullyvaccinated

at least onedose

fullyvaccinated

at least onedose

fullyvaccinated

9 sites 6 sites 9 sites 7 sites 6 sites 5 sites 7 sites 5 sites*

Serotype 19A Serotype 3 Serotype 1 Serotype 7F

vaccin

e e

ffecti

ven

ess (

%)

Adjusted for site, age, sex, underlying conditions, year of notification *Adjusted for site, age, sex and year of notification

Adjusted PCV13 VE against serotype specific IPDby vaccination status, SpIDnet multicentre study, 2012-15

96 98

8895 93

97 94

-20

0

20

40

60

80

100

757/693 385/354 763/698 321/294 557/502 171/154 616/560

43/6 32/2 20/10 8/3 16/5 7/1 10/2

at least onedose

fully vaccinated at least onedose

fully vaccinated at least onedose

fully vaccinated at least onedose

5 sites 5 sites 5 sites 4 sites 4 sites* 3 sites* 3 sites

Serotype 14 Serotype 19F Serotype 6A/B Serotype 9V

vaccin

e e

ffecti

ven

ess (

%)

Adjusted for site, age, sex, underlying conditions, year of notification *Adjusted for site, age, sex and year of notification

PCV10/13 impact on IPD incidence: Methods

Study design Before/after study: aggregated retrospective data (12 sites)

Cases: Confirmed IPD in <5 years by serotype categories

Denominators: Population by site and year

Analysis

IPD incidence/site: Imputed for missing serotyping (12 sites) and adjusted for surveillance sensitivity (three sites)

Incidence rate ratios (IRR): post PCV10/13 years vs the 2009 incidence /site

Summary IRR, heterogeneity (I2): random effects meta-analysis

0.01

0.10

1.00

10.00

20

11

20

12

2013

20

14

20

15

2011

20

12

2013

20

14

20

15

2011

20

12

*

2013

*

2014

*

20

15

*

2011

20

12

20

13

2014

20

15

All type IPD PCV7 IPD 1,3,5,6A,7F,19A IPD NonPCV13 IPD

po

ole

d I

RR

(lo

gari

thm

ic s

cale

)

*I2>75%; IRR= incidence rate ratio;

Ratio of IPD incidence in children <5 years compared to 2009 (n=12 sites)

-44%

-72%-84%

+72%

0.01

0.10

1.00

10.00

2011

2012

2013

2014

2015

2011

2012

*

2013

*

2014

2015

2011

2012

2013

2014

2015

2011

2012

*

2013

*

2014

2015

*

1,5,7F IPD 3,6A,19A IPD St3 IPD St19A IPD

pool

ed IR

R(lo

gari

thm

ic s

cale

)

*I2>75%, IRR= incidence rate ratio

Ratio of IPD incidence in children <5 years compared to 2009 (n=12 sites)

-95%

-46%

-70%-76%

0.01

0.10

1.00

10.00

20

11

20

12

2013

20

14

20

15

2011

20

12

2013

20

14

20

15

2011

20

12

*

2013

*

2014

20

15

*

2011

*

20

12

20

13

2014

20

15

All type IPD PCV7 IPD 1,3,5,6A,7F,19A IPD NonPCV13 IPD

po

ole

d IR

R (

loga

rith

mic

sca

le)

*I2>75%; IRR= incidence rate ratio;

Ratio of IPD incidence in children <5 years compared to 2009 in PCV13 sites (n=8 sites)

-42%

-89%-73%

+97%

0.01

0.10

1.00

10.00

2011

2012

2013

2014

2015

2011

2012

2013

2014

2015

*

2011

2012

2013

2014

2015

2011

2012

*

2013

2014

2015

*

1,5,7F IPD 3,6A,19A IPD St3 IPD St19A IPD

pool

ed IR

R (lo

gari

thm

ic s

cale

)

*I2>75%, IRR= incidence rate ratio

Ratio of IPD incidence in children <5 years compared to 2009 in PCV13 sites (n=8 sites)

-96%

-64%

-79%-80%

Conclusions and recommendations

PCV13 effectiveness study

High PCV13 effectiveness overall and for most specific serotypes

Serotype 3 VE is lower than the other serotypes

Need for additional years to increase the sample size PCV13 effectiveness in vulnerable populations,

clinical manifestations, severe outcomes

PCV10/13 impact study

PCV7 and additional six vaccine serotypes still decrease as compared to 2009

NonPCV13 IPD increase due to serotype replacement

All type IPD still below the level of 2009

More years needed to study serotypes trends over time

SpIDnet teamAt the surveillance sites: Professionals from participating hospitals and laboratories in each site

Czech Republic: P. Krizova, J. Kozakova, H. Sebestova, M. Maly

Denmark: P. Valentiner-Branth, L. Espenhain, T. Dalby, Z. Harboe, HC Slotved, VF. de Casadevante, K. Fuursted

France: A. Lepoutre, E. Belchior, C. Levy, R. Cohen, E. Varon, M.C. Ploy, J. Gaillat, D. Levy‐Bruhl

Ireland: J. Mereckiene, S. Cotter, M.A. Fitzgerald, M. Corcoran, R. Cunney, H. Humphries

Netherlands: M. Knol, L. Mollema, A. Van der Ende, W. van der Hoek, G. Berbers, H. de Melker, E. Sanders

Norway: D. Vestrheim, B. Winje, M. Bergsaker

Romania: M. Pana, D. Craciun, I. Codita, V. Alexandrescu

Sweden: B. Henriques Normark, E. Morfeldt, J. Darenberg, T. Lepp, A. Lindstrand

Scotland, UK: E. McDonald, A. Smith Palmer, C. Cameron, A. Smith, B. Denham, B. Jones, J. McMenamin

England and Wales, UK: S. Ladhani, S. Collins, N. Fry

Spain: M. Viarce Torres (national level)

• Catalonia: P. Ciruela, C. Izquierdo, C. Muñoz‐Almagro, S. Broner, R. Pallarés

• Madrid: L. Garcia, P. Latasa, J. Carlos Sanz, M. Ordobas

• Navarre: M. Guevara, J. Castilla, C. Ezpeleta, A. Gil-Setas

At the ECDC: R. Whittaker, L. Pastore Celentano

At the coordination: C. Savulescu (c.savulescu@epiconcept.fr), G. Hanquet, M. Valenciano, A. Moren – EpiConcept

Thank you!

Děkuji!

Merci!

Takk!

Tak!

Bedankt!

Multumesc!

Gracias!Tack!