Carlos G. Grijalva, MD MPH Department of Preventive Medicine Vanderbilt University School of...

Effectiveness of the US pneumococcal conjugate vaccination program on preventing pneumonia hospitalizations

Carlos G. Grijalva, MD MPHDepartment of Preventive Medicine

Vanderbilt University School of Medicine

Nashville, Tennessee

Overview Pneumococcal diseases

Importance of pneumonia

PCV7 efficacy against pneumonia

Study design considerations

PCV7 uptake & secular trends

Population-based changes after PCV7

introduction

0

50

100

150

200

250

<1 1 2-4 5-17 18-34 35-49 50-64 >65 Total

Age

Rat

e / 1

00,0

00Invasive pneumococcal diseases Active Bacterial Core Surveillance System, 1999

http://www.cdc.gov/ncidod/dbmd/abcs/survreports/spneu99.pdf

http://www.cdc.gov/ncidod/dbmd/abcs/survreports/spneu99.pdf

Pneumococcal-related Diseases

Study focus Invasive PneumococcalDisease (IPD)

Meningitis

Bacteremia

Pneumonia

Otitis media/Sinusitis

More severe

More common

Polysaccharide vs. Conjugate vaccines

Property Polysaccharide Conjugate

Immunogenicity children <2 years NO YES

B cell dependent immune response YES YES

T cell dependent immune response NO YES

Immune memory NO YES

Booster effect NO YES

Long term protection NO YES

Reduction of carriage NO YES

Herd immunity NO YES

Adapted from Granoff DM. Vaccines. 2004

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

0

50

100

150

200

250

<112-4

Year

IPD

rat

e /

100

000

Impact of PCV7 on IPD, US

Active Bacterial Core Surveillance (ABCs) Report, Emerging Infections Program Network, Streptococcus pneumoniae, 1997-2009, Centers for Disease Control and Prevention. http://www.cdc.gov/ncidod/dbmd/abcs/survreports.htm. Accessed Sep 16th, 2010. 6

PCV7

http://www.cdc.gov/ncidod/dbmd/abcs/survreports.htm

Bryce J, et al. Lancet. 2005;365:1147-1152

Pneumonia 19%

Injuries 3%

Other 10%

Neonatal 37%

HIV/AIDS 3%

Diarrhea 17%

Measles 4%

Malaria 8%

Preterm 28%

Congenital 8%

Asphyxia 23%

Sepsis or pneumonia 26%

Diarrhea 3%

Tetanus 7%Other 7%

Causes of neonatal deaths

WHO: Major Causes of Death in Children <5 Years

Pneumonia is the leading killer of children

Pneumonia Leading infectious cause of death

3% to 18% of all childhood hospitalizations

Streptococcus pneumoniae is the leading bacterial cause of pneumonia

17–44% pneumonia admissions in children

13–34% pneumonia admissions in adults

Marston BJ, et al. Arch Intern Med. 1997;157:1709-1718Farha T, Thomson AH. Paediatr Respir Rev. 2005;6:76-82

Michelow I, et al. Pediatrics. 2004;113:701-707Drummond P, et al. Arch Dis Child. 2000; 83:408-412

The British Thoracic Society and the Public Health Laboratory Service. Q J Med. 1987; 62:195-220

PCV7 Efficacy (Pneumonia) : NCKP

Black et al. PIDJ. 2002;21:810–15 Hansen et al. PIDJ. 2006;25:779–81

ControlRate / 1000

PCV7Rate / 1000

Vaccine Efficacy

(%)95% CI

Clinical pneumonia 55.9 53.4 4.3 –3.5 to 11.5

Chest X-ray obtained 34.2 30.9 9.8 0.1 to 18.5

Positive chest X-ray 11.0 8.7 20.5 4.4 to 34.0

WHO consolidation 30.3 10.7 to 45.7

Objectives

To estimate the impact of PCV7 Pneumonia hospitalization rates in

children aged <2 years (target population)

To evaluate indirect effects

Annual No. of PCV7 Doses (millions)Coverage with 3 or more doses

0

2

4

6

8

10

12

14

16

18

20

2000 2001 2002 2003 2004 2005

Nu

mb

er o

f va

ccin

e d

ose

s d

istr

ibu

ted

x m

illi

on

0

10

20

30

40

50

60

70

80

90

100

Per

cen

t w

ith

3+

do

ses

(ch

ild

ren

19-

35 m

on

ths)

CDC. Biosurveillance 2000–2005 and National Immunization SurveyGrijalva CG, et al. Expert Rev Vaccines. 2008;7:83–95

Source of Information: NIS

HCUP: Nationwide Inpatient Sample Sponsored by AHRQ

Largest inpatient database publicly available

~20% of US hospital discharges

Discharge level information De-identified data, diagnoses, procedures, no lab, no chest x-

rays

Complex sampling design

Methods

Monthly hospitalization rates (annualized): All-cause pneumonia

Pneumococcal pneumonia

Dehydration (control condition) Segmented regression analysis: ITS Log-transformed rates as outcomes Quantified vaccine effect by end of 2004

Grijalva CG, et al. Lancet. 2007;369:1179–1186

Interrupted Time-series Analysis

Quasi-experimental design

Wagner AK, et al. J Clin Pharm Therap. 2002;27:299–309

Impact of an Intervention:Before and After Comparison

Evaluate longitudinal effects of time-delimited interventions Account for seasonal and secular trends

With a control group can assess non-specific changes


0

50

100

150

200

250

300

350

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

Year

Rat

e p

er 1

00,0

00

Intervention(2000)


0

50

100

150

200

250

300

350

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

Rat

e p

er 1

00,0

00

Year

Intervention(2000)

Overestimation of

Effect


0

50

100

150

200

250

300

350

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

Rat

e p

er 1

00,0

00

Year

Intervention(2000)


0

50

100

150

200

250

300

350

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

Rat

e p

er 1

00,0

00

Year

Intervention(2000)

Underestimation of Effect

1997 1998 1999 2000 2001 2002 2003 20040

25

50

75

100Pre-PCV7 Post-PCV7

Years

Ho

spit

aliz

atio

ns

per

100

,000


Pneumococcal Pneumonia Rates/100,000 US Children <2 Years

∆–65% (–47, –77)

1997 1998 1999 2000 2001 2002 2003 20040

25

50

75

100Pre-PCV7 Post-PCV7

Years

Ho

spit

aliz

atio

ns

per

100

,000


Pneumococcal Pneumonia Rates/100,000 US Children <2 Years

∆–39% (–22, –52)

Pre-PCV7 Post-PCV7

1997 1998 1999 2000 2001 2002 2003 20040

500

1000

1500

2000

2500

3000

Years

Ho

spit

aliz

atio

ns

per

100

,000


All-cause pneumonia Rates/100,000 US Children <2 Years

∆–0%Pre-PCV7 Post-PCV7

1997 1998 1999 2000 2001 2002 2003 20040

500

1000

1500

2000

2500

3000

Years

Ho

spit

aliz

atio

ns

per

100

,000


Dehydration Rates/100,000 US Children <2 Years

<2 2-4 5-17 18-39 40-64 >64

-100

-80

-60

-40

-20

0

Per

cen

t (%

) ch

ang

e

Grijalva CG, et al. Expert Rev Vaccines. 2008 Feb;7(1):83-95

Pneumococcal Pneumonia Hospitalizations

All-cause Pneumonia Hospitalizations

20<2 2-4 5-17 18-39 40-64 >64

-100

-80

-60

-40

-20

0

Per

cen

t (%

) ch

ang

e

Grijalva CG, et al. Expert Rev Vaccines. 2008 Feb;7(1):83-95

Age groupRate

difference per 100,000

US population

Annual pneumonia admissions prevented

<2 years –505.9 8 million 41,287

18–39 years –27.4 90 million 24,743


Estimated Absolute Declines in Pneumonia Hospitalizations

Hospitalizations Ambulatory Hospitalizations Ambulatory

-100

-80

-60

-40

-20

0

All-cause pneumonia Pneumococcal pneumonia

11.5 vs 5.5 per1000 pers-yrs




Per

cen

t (%

) ch

ang

e

Zhou F, et al. Arch Pediatr Adolesc Med. 2007;161:1162–1168

Healthcare Use for Pneumonia; US Children <2 Years, 1997–1999 vs 2004

Changes in Non-pneumonia ARI hospitalizations, US 1997-2006

0

10

20

30

40

<2 years old

2-4 years old

1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

Introduction ofPneumococcal

conjugate vaccine

Year

An

nu

al

ho

sp

ita

liza

tio

ns

/ 1

,00

0 c

hil

dre

n

Grijalva et al, 2009 MMWR 58(1): 1-4

↓22%

NC

0

200

400

600

800

1000

1200

1400

1600

1800Pre - PCV7 Post - PCV7

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Ho

spit

ali

za

tio

n r

ate

pe

r 1

00

,00

0

Grijalva et al. Clin Infect Dis. 2010; 50(6):805-13

All-cause pneumonia Rates/100,000 US Children <2 Years

Conclusions

♦ Major declines in all-cause and pneumococcal pneumonia after PCV7 program introduction

♦ Sustained declines consistently observed in different studies/settings

♦ Large national database (HCUP NIS) allowed detection and monitoring of direct and indirect effects

Acknowledgement

♦ Marie R. Griffin, MD MPH

♦ Professor of Medicine and Preventive Medicine. VUMC

♦ J. Pekka Nuorti, MD DSc

♦ Epidemiologist, CDC

Carlos G. Grijalva, MD MPH Department of Preventive Medicine Vanderbilt University School of...

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