ByAhmed KhaledVaccine team

Pfizer KSAAhmed.khaled@pfizer.com

In the Year 2000,Prevenar was the first PCV to be licensed for the prevention of PD in children.

For more than 9 years Prevenar had significantly reduced the incidence of PD in children and adult through direct and Indirect Effect.

In 2009,Prevenar 13 was licensed to provide the broadest coverage of any PCV.

Why children need Broadest coverage

0

2

4

6

8

10

12

14

16

18

14 1 6B 5 23F 19F 6A 19A 9V 18C 2 4 3 7F 12F 8 12A 15A 9N 290

1020

30

4050

60

70

8090

100

Global IPD serotype distribution among children <5 years – before pneumococcal conjugate vaccination

*Weighted by regional disease burden

Serotype

Ser

oty

ped

iso

late

s (%

)

Cu

mu

lati

ve d

istr

ibu

tio

n (

%)

Serotypes by rank order and cumulative serotype distribution

Pneumococcal Global Serotype Project (version 2), 30 November 2008. Prepared by GAVI’s PneumoADIP

Serotypes covered by Prevenar(PCV7)

0

2

4

6

8

10

12

14

16

18

14 1 6B 5 23F 19F 6A 19A 9V 18C 2 4 3 7F 12F 8 12A 15A 9N 290

1020

30

4050

60

70

8090

100

Global IPD serotype distribution among children <5 years

*Weighted by regional disease burden

Serotype

Ser

oty

ped

iso

late

s (%

)

Cu

mu

lati

ve d

istr

ibu

tio

n (

%)

Serotypes by rank order and cumulative serotype distribution

Pneumococcal Global Serotype Project (version 2), 30 November 2008. Prepared by GAVI’s PneumoADIP

Important serotypes not covered by Prevenar (PCV7)

0

2

4

6

8

10

12

14

16

18

14 1 6B 5 23F 19F 6A 19A 9V 18C 2 4 3 7F 12F 8 12A 15A 9N 290

1020

30

4050

60

70

8090

100

Global IPD serotype distribution among children <5 years – before pneumococcal conjugate vaccination

*Weighted by regional disease burden

Serotype

Ser

oty

ped

iso

late

s (%

)

Cu

mu

lati

ve d

istr

ibu

tio

n (

%)

Serotypes by rank order and cumulative serotype distribution

Pneumococcal Global Serotype Project (version 2), 30 November 2008. Prepared by GAVI’s PneumoADIP

Prevenar 13 contains the 13 serotype causing most of IPD in children < 5 years.

7

Rationale for inclusion of additional serotypes in PCV13

Serotype 1 •Important cause of pneumococcal disease in many regions•Cause of epidemic disease•Important cause of pneumococcal pneumonia, predominant serotype in empyema in children

Serotype 5 •Cause epidemic disease•Among the leading serotypes in Africa and South America

Serotype 7F •Important cause of pneumococcal disease globally, increasing in many European countries •Higher case fatality reported from Germany

Serotype 3 •Important cause of pneumococcal disease including pneumonia and AOM•Increasingly reported in IPD in Europe•Among the leading serotypes in CAP and IPD in adults

Serotype 6A •Commonly found in carriage and frequently antibiotic resistant•Important cause of pneumococcal disease, particularly AOM•Decrease in 6A pediatric IPD following use of PCV7, remaining disease may be mostly 6C

Serotype 19A •Commonly found in carriage and frequently antibiotic resistant•Significantly increased in IPD globally•Commonly found in AOM•19F antibodies from PCV7 vaccination do not cross-protect for 19A infection

Dagan et al. J Infect Dis 2008;197(8):1094-102. Dagan et al. Clin Infect Dis 2000;30(2):319-21. Brueggemann et al. Journal of Clinical Microbiology 2003;41(11):4966-70, Gratten Med J Aust 1993;158(5):340-2, Nunes et al. Clin Microbiol Infect 2008;14(1):82-4, Romney et al. Clin Infect Dis 2008;47(6):768-74, Ruckinger et al. Pediatr Infect Dis J 2009;28(2):118-22, Whitney et al. Lancet 2006;368(9546):1495-502, Dagan & Klugman Lancet Infect Dis, 8(12), 785-795 (2008), Byington et al. Pediatr Infect Dis J, 25(3), 250-254 (2006), Fletcher et al. Pediatr Infect Dis J, 25(6), 559-560 (2006), Cohen et al. Vaccine, (2009) in press, Hausdorff WP, Vaccine, 25(13), 2406-2412 (2007), Imohl et alClin Microbiol Infect, (2009), in press)

Summary for the 6 additional serotypes

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

Age group Above 2 Years Below 2 Years

IPD/NIPD Mainly IPD Both IPD/NIPD

Colonization Rarely colonized Commonly Colonized

AB resistance AB resistance is low AB resistance is high

Serotype 19A :in USA

Hicks LA, Harrison LH, Flannery B, et al; for the Active Bacterial Core Surveillance Program of the Emerging Infections Program Network. Incidence of pneumococcal disease due to non–pneumococcal conjugate vaccine (PCV7) serotypes in the United States during the era of widespread PCV7 vaccination, 1998–2004. J Infect Dis. 2007;196:1346-1354

8. Lepoutre A, Varon E, Georges S,et al. Impact of infant pneumococcal vaccination on invasive pneumococcal diseases in France, 2001-2006. Euro Surveill. 2008;13:1-6. 9. Aguiar SI, Serrano I, Pinto FR, et al; on behalf of Portuguese SurveillanceGroup for the Study of Respiratory Pathogens. Changes in Streptococcus pneumoniae serotypes causing invasive disease with non-universal vaccination coverage of the seven-valent conjugate vaccine. Clin MicrobiolInfect. 2008;14:835-843. 10. Barricarte A, Castilla J, Gil-Setas A, et al. Effectiveness of the 7-valent pneumococcal conjugate vaccine: a population-based case-control study. Clin Infect Dis. 2007;44:1436-1441. 11. Centers for Disease Control and Prevention. Invasive pneumococcal disease in children 5 years after conjugate vaccine introduction—eight states, 1998–2005. MMWR. 2008;57:144-148.12. Bekri H, Cohen R, Varon E, et al. Streptococcus pneumoniae serotypes involved in children with pleural empyemas in France. Arch Pediatr. 2007;14:239-243. 13. Cliff D, Spencer DA, Paton JY, et al. Thefirst year of enhanced surveillance of pneumococcal empyema in UK children. Poster presented at: 26th Annual Meeting of ESPID; May 13-17, 2008; Graz, Austria.

9. Dagan R, Givon-Lavi N, Leibovitz E, et al. Introduction and expansion of multidrug-resistant Streptococcus pneumoniae serotype 19A clones causing acute otitis media in an unvaccinated population. J Infect Dis. In press.

Distribution of serotypes in KSA 2000-2004

0

20

40

60

80

100

7V

13V

7V 83 62.3 62

13V 88.1 71.7 72

>2 Years 2-5 Years >5 Years

Shibl AM. Clin Microbiol Infect 2008; 14 (9): 876-879

Antibiotic resistance in children <5 years 2000-2004

0

20

40

60

80

100

7V

13V

7V 71.4 76.9 76.1

13V 90 87.9 95.2

Penicillin Resist Eryth Resisit Cefotax. Resist

Shibl AM. Clin Microbiol Infect 2008; 14 (9): 876-879

PCV7PCV7 44 6B6B 9V9V 1414 18C18C 19F19F 23F23F

PCV7 13 4 6B 9V 14 18C 19F 23F 1 3 5 6A 7F 19A

With six additional serotypes PCV7 13 offers the broadest serotype coverage against pneumococcal disease

PCV13 contains the same carrier protein – CRMPCV13 contains the same carrier protein – CRM197,197,

a carrier protein used in bacterial conjugate vaccines for more than 20 years

Why selecting CRM197 as a carrier for Prevenar 13

Experience with Carrier Protein – CRM 197

Carrier Protein - CRM197

Non-toxic variant of diphtheria toxin

Over 300M doses delivered in conjugate vaccines for past 20 years

Used in HibTITER, Meningitec, and Prevenar

Over 75 clinical studies of vaccines containing CRM197

Can be administered concomitantly with other routine pediatric vaccines .

More Immunogenic than Protein D carrier used in PCV10

18

Total levels of antibodies (GMC values)elicited - post primary series (2, 3, 4 mos)*

Prevenar (CRM 197 based) elicited significantly higher levels of antibodies (ELISA GMCs) for all 7 common serotypes

0.00.5

1.01.52.0

2.53.03.54.0

4.55.0

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

PCV10( Non-CRM 197) (n = 1107) Prevenar(CRM197 conjugated) (n = 375)

GM

C (

µg

/mL

)

*only 7 common serotypes shown, † n indicates number of subjects with available results for at least one serotype

††

Vesikari T et al. Pediatr Infect Dis J 2009;28(4):S66-76

19

Total levels of antibodies (GMC values) - post booster* (2, 3, 4 & 12-18 mos), 4 doses of either PCV10 or PCV7

**Prevenar elicited significantly higher GMCs for 5(conjugated to Protein D) of 7 common serotypes

^PCV10 elicited significantly higher ELISA GMCs for serotype 19F

012

34567

89

10

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

PCV10 (Non-CRM197 based)(n = 347) Prevenar(CRM197 based) (n = 89)

**

**

**

**

**^

GM

C (

µg

/mL

)

*only 7 common serotypes shown, † n indicates number of subjects with available results for at least one serotype

††

Vesikari T et al. Pediatr Infect Dis J 2009;28(4):S66-76

Total levels of antibodies (GMC Levels )Post Booster* (2, 3, 4 & 12-18 mos)- 4 doses of either PCV10 or PCV7

012

34567

89

10

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

PCV10 (n = 347) Prevenar (n = 89)

Vesikari T et al. Pediatr Infect Dis J 2009;28(4):S66-76

GM

C (

µg

/mL

)

Protein D is a less immunogenic carrier than CRM197

*only 7 common serotypes shown, † n indicates number of subjects with available results for at least one serotype

††

Prevenar 13

Therapeutic indications– Active immunization for the prevention of invasive disease, pneumonia and acute otitis

media caused by Streptococcus pneumoniae in infants and children from 6 weeks to 5 years of age.

Prevenar 13 is Indicated for Active immunisation for the prevention of invasive disease, pneumonia & acute otitis media caused by Streptococcus pneumoniae in infants & children from 6 weeks to 5 years of age (SMPC Section 4.1)

Prevenar 13 SmPC 2009 and adapted from Bogaert D, et al. The Lancet Infectious Diseases. 2004;4(3):144-154.

Pneumonia is the Leading Killer of Children Worldwide

WHO, Pneumonia: The Forgotten Killer of Children, 2006

Pneumonia is the Leading Killer of Children Worldwide

WHO, Pneumonia: The Forgotten Killer of Children, 2006

Prevenar 13 has the Broadest Serotype Coverageof any PCV

Based on serotype surveillance in Europe performed before the introduction of Prevenar, Prevenar 13 is estimated to cover 73-100 % (depending on the country) of serotypes causing invasive pneumococcal disease (IPD) in children less than 5 years of age. (SMPC Section 5.1)

In this age group, serotypes 1, 3, 5, 6A, 7F, and 19A account for 15.6 % to 59.7 % of invasive disease, depending on the country the time period studied, and the use of Prevenar1 . (SMPC Section 5.1)

1Prevenar 13 SmPC 2009

Prevenar 13 Dosing

Prevenar 13 vaccine schedule for infants and children previously vaccinated with Prevenar (7-valent)

Transition from Prevenar to Prevenar 13 at any point during the schedule

Dose 1 Dose 2 Dose 3 Booster

Child 1 PREVENAR PREVENAR PREVENAR Prevenar 13

(1 or 2 doses)*

Child 2 PREVENAR PREVENAR Prevenar 13 Prevenar 13

(1 or 2 doses)*

Child 3 PREVENAR Prevenar 13 Prevenar 13 Prevenar 13

Child 4 Prevenar 13 Prevenar 13 Prevenar 13 Prevenar 13

ACIP recommendation for Children completely vaccinated with PCV7

ACIP recommendation for High risk children >24 months

NB:Prevenar 13 is approved in EMEA only up to 5 years

It is recommended that infants who receive a first dose of Prevenar 13 complete the vaccination coursewith Prevenar 13.

Method of administration

The vaccine should be given by intramuscular injection. The preferred sites are the anterolateral aspect of the thigh (vastus lateralis muscle) in infants or the deltoid muscle of the upper arm in young children.

Contraindications

Hypersensitivity to the active substances, to any of the excipients (see section 6.1), or to diphtheriatoxoid.

As with other vaccines, the administration of Prevenar 13 should be postponed in subjects suffering from acute, severe febrile illness. However, the presence of a minor infection, such as a cold, should not result in the deferral of vaccination.

Special precautions for storage

Store in a refrigerator (2°C–8°C).

Do not freeze.

Concomitant vaccine conclusions

PCV13 can be given with any of the following vaccine antigens, either as monovalent or combination vaccines:

– Diphtheria– Tetanus– Acellular or whole cell pertussis– Haemophilus influenzae type b– Inactivated poliomyelitis– Hepatitis B– Meningococcal serogroup C– Measles, mumps, rubella and varicella– Rotavirus vaccine (safety evaluation)– Hepatitis A (safety evaluation)

Safety Conclusions

The safety profile of PCV13 is comparable to that of PCV7

The most commonly reported adverse reactions were– Injection-site reactions– Fever– Irritability– Decreased appetite– Increased and/or decreased sleep

Scientific foundation of Prevenar 13

Study Sample Size Efficacy in ITT, %, (95% CI)

United States1

(1995-1998, PCV7, 4 doses)37,868 94% (80-99)

United States

(American Indians)2

(1997-2000, PCV7, 4 doses)

8,292 83% (21-96)

South Africa(1998-20013, PCV9*, 3 doses)

39,836

HIV-negative83% (39-97)

HIV-positive65% (24-86)

The Gambia(2000-20044, PCV9, 3 doses)

17,437 71% (46-86)

Efficacy of Prevenar (PCV7) Clinical Studies of PCV in IPD: Summary

1. Black S, et al. Pediatr Infect Dis J. 2000;19:187-195. 3. Klugman KP, et al. N Engl J Med. 2003;349:1341-1348. 2. O’Brien KL, et al. Lancet. 2003;362:355-361. 4. Cutts FT, et al. Lancet. 2005;365:1139-1146.

*Investigational vaccine, not available commercially†IPD included culture-confirmed pneumonia, meningitis, or bacteremia

Evaluation of Efficacy of PCV in Infants Against IPD1-4

Efficacy studies have demonstrated PCV7 and investigational PCV9 decreases incidence of vaccine serotype-specific IPD1-4†

Efficacy of Prevenar (PCV7)Clinical Studies of PCV in CXR-positive Pneumonia

1. Black SB, et al. Pediatr Infect Dis J. 2002;21:810-815.2. Hansen J, et al. Pediatr Infect Dis J. 2006;25:779-781.

Study Efficacy (95% CI)[CXR-positive Pneumonia† (ITT)]

PCV7

United States—NCKP1 18% (5-29)

Re-analysis of NCKP (WHO criteria)2 26% (7-41)

Investigational PCV9*

South Africa3

Total population 17% (4-28)

HIV-negative 20% (2-35)

HIV-positive 13% (-7-29)

The Gambia4 36% (27-43)

*Investigational 9-valent pneumococcal conjugate vaccine †All-cause hospitalization and mortality reduced by 15% and 16%, respectively CXR=chest x-ray; NCKP=Northern California Kaiser Permanente

3. Klugman KP, et al. New Engl J Med. 2003;349:1341-1348.4. Cutts F, et al. Lancet. 2005;365:1139-1146.

Efficacy of PCV7 and PCV9* in Radiologically Confirmed Pneumonia1-4

PCV decreases radiologically documented alveolar pneumonia1-4

Efficacy of Prevenar (PCV7)Clinical Study of PCV in AOM/OM (Finland, U.S.)

Finnish Trial, Follow-up1,2

n=1,662Age <2 yrs

NCKP Trial, Follow-up3,4

n=37,868Age <2 yrs

All AOM/OM episodes 6% 7%

OM visits -- 9%

Recurrent OM episodes Range, 16%-18% Range, 9%-26%

Tympanostomy tube placement* 39%2 24%4

All pneumococcal AOM episodes 34% --

All vaccine-serotype AOM episodes 57% --

1. Eskola J, et al. N Engl J Med. 2001;344:403-409.2. Palmu AA, et al. Pediatr Infect Dis J. 2004;23:732-738.3. Black S, et al. Pediatr Infect Dis J. 2000:19:187-195. 4. Fireman B, et al, Pediatr Infect Dis J. 2003; 22:10-16.

PCV7 Efficacy Results for OM Outcomes—Per-Protocol Analysis

PCV7 significantly decreases otitis media and associated outcomes at follow-up

*Tympanostomy tube placement is a marker of more severe AOM

What is the safety profile of the vaccine shown in clinical trials

and real world use?

What is the ability of the vaccine to reduce the incidence of

disease shown in real world use?

What is the ability of the vaccine to reduce the incidence of

disease shown in clinical trials?

Is the vaccine able to produce the protective level of antibodies?

What is the Percentage of IPD cases in certain population that

is caused by the vaccine serotypes?

Criteria for evaluating PCVs:

Epidemiology

Immunogenicity

Efficacy

Effectiveness

Safety

S. pneumoniae Disease Burden in Children

Otitis media

Pneumonia

Bacteremia

Meningitis

Dis

eas

e s

eve

rity

For each case of pneumococcal meningitis in a

year:

X 1000 to 10,000

X 100 to 1000

X 10

Pre

vale

nc

e

Invasive

Non-invasive

Adapted from: American Academy of Pediatrics. Pediatrics. 2000;106:367-376 & MMWR. 1997;46:1-24

Effectivness of Prevenar (PCV7)

PCV Effectiveness

AOM

Antibiotic resistance

Herd immunity

Pneumonia

IPD

Effectivness of PCV

PCV Effectivness

AOM

Antibiotic resistance

Herd immunity

Pneumonia

IPD

Adapted from Hicks LA, et al. J Infect Dis. 2007;196:1346-1354.

Effectiveness of PREVENAR*

IPD (U.S.)

PREVENAR introduced

baseline

Cas

es/1

00,0

00

po

pu

lati

on

Design: U.S. study in children <5 years of age. Latest published data from U.S. CDC’s Active Bacterial Core surveillance

Rates of IPD Among Children <5 Years of Age

Year

• Because PREVENAR was first studied and licensed in the U.S., much effectiveness data come from there• IPD significantly declined in the U.S. since the introduction of PREVENAR in 2000

*Trademark

0

10

20

30

40

50

60

70

80

90

100

1998 1999 2000 2001 2002 2003 2004

All serotypes (PCV7 + nonvaccine)

PCV7 serotypes

0

20

40

60

80

100

120

140

1998 1999 2000 2001 2002 2003 2004

All serotypes

PCV7 serotypes

PCV7 and related serotypes

Non-PCV7 or related

Effectiveness of PREVENAR*

IPD (Canada)C

ases

of

infe

ctio

n/1

00,0

00

Adapted from Kellner JD, et al. CMAJ. 2005;173:1149-1151.

Year

81.6% decrease in IPD (all serotypes)

(p=0.02)

93.4% decrease in IPD (PREVENAR and

related serotypes) (p<0.001)

Cases of Pneumococcal Infection per 100,000 in Children <2 Years of Age

PREVENAR introduced

In Canada, rates of pneumococcal infection in children aged ≤23 months declined 81.6%

*Trademark

Effectiveness of PREVENAR*

IPD (Australia)

1. Roche PW, et al. Commun Dis Intell. 2006;30:80-92.2. Roche PW, et al. Commun Dis Intell. 2008;32:18-30.

0

50

100

150

200

250

2001 2002 2003 2004 2005 2006

Indigenous population

Non-indigenous population

Rat

e/10

0,00

0 p

op

ula

tio

n

PREVENAR recommended for all indigenous children

Universal PREVENARvaccination

Year

Rate of IPD Following Vaccination of Indigenous Children Beginning in 2001, Universal Vaccination Beginning in 2004 (Children <2 Years of Age)1,2

• As more regions study the effects of routine PREVENAR vaccination, similar outcomes to the U.S. studies are being realized

• The rate of IPD caused by vaccine serotypes in Australia decreased by 74% between 2001 and 20041

*Trademark

Adapted from Dubos F, et al. Arch Dis Child. 2007;92:1009-1012.

Effectiveness of PREVENAR*

Pneumococcal Meningitis (France)

As PREVENAR vaccine use increased, pneumococcal meningitis cases decreased

0

2

4

6

8

10

12

14

16

18

2001 2002 2003 2004 2005

0

20,000

40,000

60,000

80,000

100,000

120,000

140,000

160,000

180,000Pneumococcal meningitis cases(all serotypes)Vaccine doses sold

Est

ima

ted

pn

eum

oco

ccal

m

enin

git

is c

ase

s (a

ll s

ero

typ

es)

Vac

cine d

oses so

ld

Year

Relationship Between Number of Meningitis Cases† (Children <18 Years of Age) and Distributed Vaccine Doses

†Estimated cases of pneumococcal meningitis

*Trademark

PREVENARintroduced

PREVENARintroduced

Adapted from Tsai CJ, et al. Clin Infect Dis. 2008;46:1664-1672.

Effectiveness of PREVENAR*

Pneumococcal Meningitis (U.S.)

Trends in Hospitalizations for Pneumococcal Meningitis (All Ages) and Mortality Rates in the U.S., 1994 to 2004

Bars represent 95% CIs

Ho

spit

aliz

atio

n r

ate/

100,

000

Year

Mo

rtal

ity

rate

/100

,000

Year

Hospitalizations In-hospital deaths

After the introduction of PREVENAR, annual rates for pneumococcal meningitis hospitalizations and mortality decreased and then remained relatively stable during following years

33% decrease

33% decrease

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1994 1996 1998 2000 2002 2004

0.0

0.2

0.4

0.6

1994 1996 1998 2000 2002 2004

*Trademark

PREVENARintroduced

PREVENARintroduced

Adapted from Tsai CJ, et al. Clin Infect Dis. 2008;46:1664-1672.

Effectiveness of PREVENAR*

Pneumococcal Meningitis (U.S.)

Trends in Hospitalizations for Pneumococcal Meningitis (All Ages) and Mortality Rates in the U.S., 1994 to 2004

Bars represent 95% CIs

Ho

spit

aliz

atio

n r

ate/

100,

000

Year

Mo

rtal

ity

rate

/100

,000

Year

Hospitalizations In-hospital deaths

After the introduction of PREVENAR, annual rates for pneumococcal meningitis hospitalizations and mortality decreased and then remained relatively stable during following years

33% decrease

33% decrease

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1994 1996 1998 2000 2002 2004

0.0

0.2

0.4

0.6

1994 1996 1998 2000 2002 2004

*Trademark

Effectivness of PCV

PCV Effectiveness

AOM

Antibiotic resistance

Herd immunity

Pneumonia

IPD

PREVENAR introduced into routine vaccination schedules in the U.S.

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

Effectiveness of PREVENAR*

Pneumococcal Pneumonia-related Health Care Utilization

Hospitalization rates for pneumococcal pneumonia declined 57.6%

Hospitalizations (Cases per 1,000 Person-years) for Pneumococcal Pneumonia(Children <2 Years of Age)

Year

Hospitalizations ↓ 57.6% (p<0.001)†

†p-values for 2004 vs 1997

Ho

spit

aliz

atio

ns/

1,00

0 p

erso

n-y

ears

*Trademark

0.0

0.5

1.0

1997 1998 1999 2000 2001 2002 2003 2004

Effectiveness of PREVENAR*

Pneumonia (U.S.)

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

† Design: Interrupted time-series analysis comparing admission rates for 2001 to 2004 (years following PREVENAR introduction) to expected rates calculated for 1997 to 1999‡p<0.0001

Estimated % Reduction in U.S. Admission Rates for All-cause and Pneumococcal Pneumonia, 2004†

Age (yrs) All-cause Pneumonia

Reduction (CI)

Pneumococcal Pneumonia

Reduction (CI)

<2 39%‡

(22-52)

65%‡ (47-77)

*Trademark

After the introduction of PREVENAR, there was a 39% annual decline in all-cause pneumonia admissions—representing ~41,000 fewer pneumonia admissions in 2004

in children <2 years of age

Effectivness of PCV

PCV Effectivness

AOM

Antibiotic resistance

Herd immunity

Pneumonia

IPD

Effectivness of PCV

PCV Effectivness

AOM

Antibiotic resistance

Herd immunity

Pneumonia

IPD

0

20

40

60

80

100

<5 5–17 18–39 40–64 ≥65

1998 to 1999 2000 2001 2002 2003

Effectiveness of PREVENAR*

Indirect Effect—IPD (U.S.)

†Active Bacterial Core surveillance, United States, 1998 to 2003‡p<0.05, 2003 vs 1998-1999

Rate of Vaccine-type (VT) IPD Before and After Introduction of PREVENAR,

by Age Group and Year†

94% reduction

65% reduction

Routine childhood immunization programs

Unvaccinated population

Adapted from CDC. Morb Mortal Wkly Rep. 2005;54:893-897.

PREVENAR vaccination was associated with a reduction in IPD in vaccinated and unvaccinated populations

‡

Rat

e/10

0,00

0

Age group (y)

*Trademark

‡

20,459

9,140

Direct effects Indirect effects

Effectiveness of PREVENAR*

Indirect Effect (U.S.)

The CDC Surveillance System has reported an increased incidence of IPD due to nonvaccine serotypes in children <5 and in adults ≥40 years of age. It is unknown whether these effects would be observed in other populations. †Direct VT IPD cases prevented in 2003 = 1998/1999 average number of VT IPD cases in children <5 years of age x 2003 PREVENAR coverage with 3 doses (68.1%) x PREVENAR effectiveness for VT IPD (93.9%)‡Indirect VT IPD cases prevented in 2003 = (1998/1999 average number of VT IPD cases across all ages – 2003 number of VT IPD cases across all ages) – 2003 direct VT IPD cases preventedNote: Calculation of indirect cases prevented does not account for replacement diseaseAdapted from CDC. MMWR. 2005;54:893-897.

Estimated Vaccine-type Cases Averted by Direct† and Indirect Effects‡ of PREVENAR: U.S., 2003

Est

ima

ted

ca

ses

pre

ven

ted

(n

o.)

25,000

20,000

15,000

10,000

5,000

0

*Trademark

Effectivness of PCV

PCV Effectivness

AOM

Antibiotic resistance

Herd immunity

Pneumonia

IPD