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Pneumococcal Disease in Children: P.S. It Matters

Pneumococcal Disease in Children: P.S. It Matters

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Pneumococcal Disease in Children: P.S. It Matters. Learning Objectives. Describe the current burden of pneumococcal disease since the introduction of pneumococcal conjugate vaccines Discuss the current recommended immunization schedule in infants and children to prevent pneumococcal disease - PowerPoint PPT Presentation

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Page 1: Pneumococcal Disease in Children:  P.S. It Matters

Pneumococcal Disease in Children: P.S. It Matters

Page 2: Pneumococcal Disease in Children:  P.S. It Matters

Learning Objectives• Describe the current burden of pneumococcal disease

since the introduction of pneumococcal conjugate vaccines

• Discuss the current recommended immunization schedule in infants and children to prevent pneumococcal disease

• Review and implement strategies for improving immunization rates within one’s clinical practice, including being able to answer frequently encountered questions that involve safety, efficacy, and possible misinformation

Page 3: Pneumococcal Disease in Children:  P.S. It Matters

Streptococcus pneumoniae• A leading bacterial cause of serious illness

among children and adults worldwide• Gram-positive bacteria• Polysaccharide capsule important pathogenic

factor; prevents phagocytosis• Over 90 distinct capsular types identified• Protection is serotype specific; some cross

protection within serogroups

Lynch J, Zhanel G. Semin Respir Crit Care Med. 2009;30(2):189-209.

Page 4: Pneumococcal Disease in Children:  P.S. It Matters

Pneumococcal Disease• Influenza and pneumococcal disease are the most

common causes of vaccine-preventable disease and death in the US

• Major pneumococcal clinical syndromes include– Pneumonia– Bacteremia – Meningitis

• Invasive pneumococcal disease (IPD): isolation of S. pneumoniae from a normally sterile site (blood, CSF, pleural, pericardial, peritoneal, bone or joint fluid)

• Pneumococcal diseases encompass invasive and non-invasive syndromes

Adapted from CDC. http://www.cdc.gov/vaccines/pubs/pinkbook/pneumo.html. Accessed Nov 2011.

Page 5: Pneumococcal Disease in Children:  P.S. It Matters

Invasive Pneumococcal DiseaseClinical Syndromes

Active Bacterial Core Surveillance USA 2006–2007

< 5 yrs 18-64 yrs ≥ 65 yrs0

5

10

15

20

25

30

35Bacteremia without focus

Invasive Pneumonia

Meningitis

Age Group

Cas

es (o

r Dea

ths)

per

100

,000

Po

pula

tion

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

Page 6: Pneumococcal Disease in Children:  P.S. It Matters

< 1 1 2-4 5-17 18-34 35-49 50-64 ≥ 650

5

10

15

20

25

30

35

40

45

CasesDeaths

Age (years)

Cas

es p

er 1

00,0

00 P

opul

atio

n pe

r Ye

arS. Pneumoniae ABCs Data USA: 2009

Invasive Pneumococcal Disease (Inpatient and Outpatient)

CDC ABC Surveillance report. http://www.cdc.gov/abcs/reports-findings/survreports/spneu09.html. Accessed Nov 2011.

Page 7: Pneumococcal Disease in Children:  P.S. It Matters

S. Pneumoniae ABCs Data–2009All Age Groups

Meningitis4.8%

Bacteremia without Focus19.2%Pneumonia with

Bacteremia70.4%

Not Categorized5.6%

CDC ABC Surveillance report. http://www.cdc.gov/abcs/reports-findings/survreports/spneu09.html. Accessed Nov 2011.

Based on a total of 4,166 IPD cases

Page 8: Pneumococcal Disease in Children:  P.S. It Matters

S. pneumoniae Carriage and Infection

• Nasopharyngeal carriage of S. pneumoniae necessary for transmission of bacteria and invasive disease

• Person-to-person contact; respiratory droplets• Autoinoculation• Seasonal patterns• S. pneumoniae can be present in the

nasopharynx commensally and not cause disease

Pneumococcal disease. http://www.cdc.gov/vaccines/pubs/pinkbook/pneumo.html. Accessed Nov 2011.

Page 9: Pneumococcal Disease in Children:  P.S. It Matters

Pneumococcal Disease in Children• Bacteremia without known site of infection most

common clinical presentation• Bacteremic pneumonia accounts for 12–16% of

IPD among children 2 years and younger• S. pneumoniae leading cause of bacterial

meningitis among children 2 months to 10 years– Group B streptococcus leading cause of meningitis in

children < 2 months • Common cause of acute otitis media

Pneumococcal disease. http://www.cdc.gov/vaccines/pubs/pinkbook/pneumo.html. Accessed Nov 2011.Thigpen M, et al. N Engl J Med. 2011;364:2016-2025.

Page 10: Pneumococcal Disease in Children:  P.S. It Matters

Pneumococcal Acute Otitis Media (AOM)

• Most common reason for physician office visits among pre-school aged children in the US

• 83% of children experience ≥ 1 episode of AOM before 36 months of age

• S. pneumoniae most common bacterial cause of AOM (30–50% of episodes)

• AOM most common reason for antibiotic prescriptions among US children

Zhou F, et al. Pediatrics. 2008;121:253-260.

Page 11: Pneumococcal Disease in Children:  P.S. It Matters

Annual Global Pneumococcal Deaths in Children#1 Vaccine-Preventable Cause of Death in Children < 5 Years Worldwide

Deaths per 100,000 children < 5 years

O’Brien K, et al. Lancet. 2009;374:893-902.

Page 12: Pneumococcal Disease in Children:  P.S. It Matters

Risk Factors for Pneumococcal Diseases or Complications

• Immunocompetent children– Chronic heart disease– Chronic lung disease – Diabetes mellitus– Cerebrospinal fluid leaks– Cochlear implant

• Children with functional or anatomic asplenia– Sickle cell disease and other hemoglobinopathies– Congenital or acquired asplenia, or splenic dysfunction

• Children with immunocompromising conditions– HIV infection– Chronic renal failure and nephrotic syndrome– Diseases associated with treatment with immunosuppressive

drugs or radiation therapy; or solid organ transplantation– Congenital immunodeficiency

CDC. MMWR Recomm Rep. 2010;59(RR-11):1-18.

Page 13: Pneumococcal Disease in Children:  P.S. It Matters

Vaccines for Invasive Pneumococcal Disease (before PCV-13)

PPSV23 PCV7Year introduced 1983 2000

Vaccine constituents Mixture of 23 purified capsular polysaccharides; phenol preservative

Mixture of 7 purified capsular polysaccharides conjugated to nontoxic diphtheria toxin (CRM197); aluminum phosphate adjuvant

Immune responseT-cell independent response; poor inducer of immunologic memory; poorly immunogenic in children ≤ 2 years

T-cell response; immunologic priming and memory response; good antibody response in infants/young children

RecommendationsAll adults ≥ 65 years; high-risk individuals ages 2-64 years; adults 19-64 years with asthma or smokers; single dose

Routine vaccination of children < 24 months and high risk children 24-59 months; doses at 2, 4, 6 months of age; booster at 12-15 months

Duration of protection

High antibody titers for 1-2 years; wane over 5-10 years At least 2-3 years

Revaccination 5 years after the 1st dose for individuals at high risk

Not recommended following an age-appropriate primary series

Pneumococcal disease. http://www.cdc.gov/vaccines/pubs/pinkbook/pneumo.html. Accessed Nov 2011.Lynch J, Zhanel G. Sem Respir Crit Care Med. 2009;30(2):189-209.

Page 14: Pneumococcal Disease in Children:  P.S. It Matters

Changes in Overall Invasive Pneumococcal Disease, 1998–2007

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

Cas

es/1

00,0

00 p

opul

atio

n

0

20

40

60

100

80

120

1998 1999 20012000 2002 2003 2004 2005 2006 2007Year

PCV7 introduced Age Group 2007 vs baseline* (years) (% reduction)

< 55–1718–4950–64≥ 65

7643401837

*Baseline is 1998-1999

Page 15: Pneumococcal Disease in Children:  P.S. It Matters

Direct Effect of Vaccination: Invasive Pneumococcal Disease Among Children < 5 Years, 1998/99–2007

Cas

es/1

00,0

00 p

opul

atio

n

0

10

20

30

40

50

60

7080

90

1998 1999 20012000 2002 2003 2004 2005 2006 2007Year

PCV7 introduced

Serotype group

PCV7 typeNon-PCV7 type19A

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

Page 16: Pneumococcal Disease in Children:  P.S. It Matters

Redelings MD, et al. Arch Pediatr Adolesc Med. 2005;159:195-196.

Invasive Pneumococcal Disease (IPD) Mortalityin Children < 2 Years; Vital Records USA

1995 1996 1997 1998 1999 2000 20010

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0M

orta

lity

Rat

e pe

r 100

,000

Pop

ulat

ion

Overall IPD MortalityPneumococcal Meningitis MortalityPneumococcal Septicemia Mortality

Page 17: Pneumococcal Disease in Children:  P.S. It Matters

Herd Immunity: Invasive Pneumococcal Disease Among Adults ≥ 65 Years, 1998/99–2007

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

Cas

es/1

00,0

00 P

opul

atio

n

0

5

10

15

20

25

30

35

40

1998 1999 20012000 2002 2003 2004 2005 2006 2007Year

PCV7 introduced

Serotype group

PCV7 typeNon-PCV7 type19A

*92% reduction in PCV7 serotypes, 2007 vs baseline

*

*Baseline is 1998-1999

Page 18: Pneumococcal Disease in Children:  P.S. It Matters

Herd Immunity: Invasive Pneumococcal Disease in Infants 0 to 90 days,1997–2004

Poehling K, et al. JAMA. 2006;295:1668-1674.

Page 19: Pneumococcal Disease in Children:  P.S. It Matters

Rates of Invasive Pneumococcal DiseaseMetropolitan Atlanta, Georgia

Albrich WC, et al. Clin Infect Dis. 2007;44:1569-1576.

Cas

es p

er 1

00,0

00 P

erso

ns

Adults ≥ 18 yearsChildren < 18 years

Bacteremia BacteremiaMeningitis MeningitisPneumonia Pneumonia

*

*

*

**

2000/01 2001/02 2002/03 2003/04

02468

10121416

18

*Clinical syndromes with significant trends over time 2000/2001 to 2003/2004; P ≤ 0.05

Page 20: Pneumococcal Disease in Children:  P.S. It Matters

ABC Incidence of Pneumococcal Meningitis by PCV7 ST Group Over Time: All Ages

Hsu HE, et al. N Engl J Med. 2009;360:244-256.

Men

ingi

tis C

ases

/100

,000

Per

sons

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1998–1999 2000–2001 2002–2003 2004–2005

Non-PCV7 STs

PCV7-related STs

PCV7 STs

Page 21: Pneumococcal Disease in Children:  P.S. It Matters

ABC Incidence of Pneumococcal Meningitis by PCV7 ST Group Over Time: < 2 Years

Hsu HE, et al. N Engl J Med. 2009;360:244-256.

1998-1999 2000-2001 2002-2003 2004-20050

2

4

6

8

10

12

Non-PCV7 SerotypesPCV7-related SerotypesPCV7 Serotypes

Men

ingi

tis C

ases

/100

,000

Per

sons

Page 22: Pneumococcal Disease in Children:  P.S. It Matters

South Africa (Urban) PCV-9 DBRCTHIV-infected childrenVE: 9% (95%CI -15 to 27)

HIV non-infected childrenVE: 25% (95%CI 4 to 41)

Northern California, USAPCV-7 DBRCTVE: 30%; 95%CI 11, 46% Philippines (Rural)

PCV-11 DBRCTVE: 22.9; 95%CI -1, 41

Navajo, USA (Rural)American IndiansPCV-7 Cluster randomizedVE: -2%; P > 0.05

Black S, et al. Pediatr Infect Dis J. 2001;20:1105-1107.Hansen J, et al. Pediatr Infect Dis J. 2006;25:779-781.Klugman KP, et al. N Engl J Med. 2003;349:1341-1348. Cutts F, et al. Lancet. 2005;365:1139-1146.Lucero MG, et al. Pediatr Infect Dis J. 2009;28:455-462.

PCV Efficacious in Reducing Radiologically Confirmed Pneumonia in Children

VE: vaccine effectiveness

The GambiaPCV-9 DBRCTVE: 37%; 95%CI 27, 45%

Page 23: Pneumococcal Disease in Children:  P.S. It Matters

Efficacy of PCV in Children < 2 Years

• 11 publications of 6 randomized controlled trials• N = 57,015 children received PCV; N = 56,029 received

placebo or another vaccine• Vaccine-serotype IPD; RR = 0.20 (0.10-0.42); P

< 0.0001• All serotypes IPD; RR = 0.42 (0.25-0.71); P = 0.001• WHO X-ray defined pneumonia; RR = 0.73 (0.64-0.85);

P < 0.0001• Clinical pneumonia; RR = 0.94 (0.91-0.98); P = 0.0006• All-cause mortality; RR = 0.91 (0.81-1.01); P = 0.07

Lucero M, et al. Cochrane Database Syst Rev. 2009;4:CD004977.

Page 24: Pneumococcal Disease in Children:  P.S. It Matters

National Estimated Changes in Rates of Pneumonia Hospitalizations Post PCV7

Grijalva C, et al. Lancet. 2007;369:1179-1186.Grijalva C, Griffin M. Expert Rev Vaccines. 2008;7:83-95. *Statistically significant decline

All-cause Pneumonia; Nationwide Inpatient Sample

Change comparing 2004 data with pre-PCV7 years after trend adjustment

Page 25: Pneumococcal Disease in Children:  P.S. It Matters

PCV7 and Community Acquired PneumoniaRetrospective Cohort of Children and Adults–Washington State HMO

Nelson J, et al. Vaccine. 2008;26:4947-4954.

< 1 1-2 65-74 > 750

5

10

15

20

25

Confirmed Hospitalized

Before (1998-2000) During (2001-2002) After (2003-2004)

Age (years)

Rate

per

100

0 Pe

rson

Yea

rs

< 1 1-2 65-74 > 750

5

10

15

20

25

Confirmed Outpatient

Before (1998-2000) During (2001-2002) After (2003-2004)

Age (years)

Rat

e pe

r 100

0 Pe

rson

Yea

rs

Page 26: Pneumococcal Disease in Children:  P.S. It Matters

Estimated PCV7-Associated Reductions in US Burden of Hospitalizations, 2000–2006

IPDNonbacteremic

Pneumococcal Pneumonia (ICD9 481 with no IPD codes)

Age Group Estimate 95% CI Estimate 95% CI

< 2 8,440 8,101-8,752 3,399 4,119-2,592

2-4 2,025 1,766-2,244 934 1,590-188

5-17 1,528 1,257-1,772 3,977 4,595-3,305

18-39 8,592 7,658-9,432 21,808 23,411-20,094

40-64 7,270 5,428-9,004 24,614 26,976-22,169

65+ 20,046 16,851-23,014 99,415 110,428-87,565

Total 47,899 41,060-54,218 154,147 171,118-135,893

% Adults 75% 95%

Simonsen L, et al. mBio. 2011;2:e00309-e00310.

Page 27: Pneumococcal Disease in Children:  P.S. It Matters

Efficacy of PCV7 for Acute Otitis Media (AOM)Kaiser Permanente Randomized Double-Blind Trial

Analysis Vaccine Efficacy (%)

AOM Visits 8.9AOM Episodes 7.0Frequent AOM Episodes (3/4)* 9.3Frequent AOM Episodes (5/6)* 22.8Ventilatory Tube Placement 20.1AOM PCV7 Serotypes 66.7

Black S, et al. Pediatr Infect Dis. 2000;19:187-195.

N = 37,868 infants; vaccine at 2, 4, 6, and 12 to 15 months of age;meningococcal vaccine as control

*number of episodes in 6months/number of episodes in 1 year

Page 28: Pneumococcal Disease in Children:  P.S. It Matters

Analysis Vaccine Efficacy (%)AOM Any Cause 6AOM PCV7 Serotypes 57AOM Cross-reactive Serotypes 511st Episode AOM, PCV7 Serotypes 52Subsequent Episodes AOM, PCV7 Serotypes 45

Efficacy of PCV7 for Acute Otitis Media (AOM)Finnish Otitis Media Vaccine Trial

Eskola J, et al. N Engl J Med. 2001;344:403-409.

N = 1662 infants; vaccine at 2, 4, 6, and 12 months of age; Hepatitis B vaccine as control

Page 29: Pneumococcal Disease in Children:  P.S. It Matters

Ambulatory Visits for Acute Otitis Media and Antibiotic Prescriptions

1997–2004 MarketScan Databases

Zhou F, et al. Pediatrics. 2008;121:253-260.

Rat

e (p

er 1

000

pers

on-y

ears

) 2500

2000

1500

1000

500

0

Year1997 1998 1999 2000 2001 2002 2003 2004

Ambulatory visits for AOM

Non-AOM ARI visits

Antibiotic prescriptions for non-AOM ARI visitsAntibiotic prescriptions for AOM visits

AOM: acute otitis media; ARI: acute respiratory infection

Page 30: Pneumococcal Disease in Children:  P.S. It Matters

Impact of PCV7 on Otitis MediaReduction in Antibiotic Use

Fireman B, et al. Pediatr Infect Dis J. 2003;22:10-16.

Endpoint Change Following PCV7Antibiotic prescriptions after the primary series ↓ by 5.7% (95% CI 4.2–7.2)

Second-line antibiotics ↓ by 13.3% (95% CI 9.9–16.5)Number of antibiotic prescriptions prevented per 100 children vaccinated (from dose 1 to 3.5 years)

35

Page 31: Pneumococcal Disease in Children:  P.S. It Matters

Black S, et al. Pediatr Infect Dis J. 2004;23:485-489.

Penicillin Resistance in PCV7 Serotypes Northern California Kaiser Permanente (All ages)

1994 1995 1996 1997 1998 1999 2000 2001 2002 20030

2

4

6

8

10

12

14

16

3

5

11

1314

11

15

98

5

Isol

ates

Res

ista

nt to

Pen

icill

in (%

)

PCV7 Introduced

Page 32: Pneumococcal Disease in Children:  P.S. It Matters

Invasive Pneumococcal Disease in Children < 2 Years Active Bacterial Core Surveillance (ABCs) Data

Kyaw M, et al. N Engl J Med. 2006;354:1455-1463.

Page 33: Pneumococcal Disease in Children:  P.S. It Matters

Invasive Pneumococcal Disease Penicillin Non-susceptible (≥ 2 years) ABCs Data

Kyaw M, et al. N Engl J Med. 2006;354:1455-1463.

Page 34: Pneumococcal Disease in Children:  P.S. It Matters

Effect of Introduction of PCV-7 on Drug-Resistant S. pneumoniae

Kyaw M, et al. N Engl J Med. 2006;354:1455-1463.                  

Page 35: Pneumococcal Disease in Children:  P.S. It Matters

Invasive Pneumococcal Disease Serotype 19A

Moore M, et al. J Infect Dis. 2008;197:1016-1027.

Page 36: Pneumococcal Disease in Children:  P.S. It Matters

Trends in Antibiotic Resistance: Serotype 19A Children < 5 Years

Moore M, et al. J Infect Dis. 2008;197:1016-1027.

Page 37: Pneumococcal Disease in Children:  P.S. It Matters

IPD and S. pneumoniae Serotypes

White bars: penicillin susceptible; gray bars: penicillin intermediate; black bars: penicillin resistant

Children < 5 years Adults > 50 years

Moore M, et al. J Infect Dis. 2008;197:1016-1027.

Page 38: Pneumococcal Disease in Children:  P.S. It Matters

Hicks L, et al. Clin Infect Dis. 2011;53:631-639.

Outpatient Antibiotic Prescribing and S. pneumoniae Serotype 19A IPD Isolates

Antibiotic Parameter 1996–1999 (n = 11,264)

2000–2003 (n = 10,811)

1996–2003 (n = 22,075)

Cephalosporin

Proportion, % High-prescribing sites 3.4 6.8 4.9

Low-prescribing sites 2.6 4.2 3.5

P-value 0.32 0.03 0.03

Logistic regression Point estimate (β1) 0.26 0.51 0.36

Odds Ratio (95% CI) 1.30 (1.04-1.62) 1.67 (1.41-1.98) 1.43 (1.25-1.64)

P-value 0.02 < 0.001 < 0.001

Macrolides

Proportion, % High-prescribing sites 3.4 6.8 4.9

Low-prescribing sites 2.6 4.2 3.5

P-value 0.32 0.03 0.03

Logistic regression Point estimate (β1) 0.26 0.51 0.36

Odds Ratio (95% CI) 1.30 (1.04-1.62) 1.67 (1.41-1.98) 1.43 (1.25-1.64)

P-value 0.02 < 0.001 < 0.001

Page 39: Pneumococcal Disease in Children:  P.S. It Matters

Children With New Acquisition of Serotype 19A After Finishing Primary Series PCV7

van Gils E, et al. JAMA. 2010;304:1099-1106.

Page 40: Pneumococcal Disease in Children:  P.S. It Matters

Antibiotic Use and PCV7 in Children with AOMFrench Prospective Study

Cohen R, et al. Pediatr Infect Dis J. 2006;25:1001-1007.

Vaccine (+

), Antib

iotics (

-)

Vaccine (+

), Antib

iotics (+

)

Vaccine (

-), Antib

iotics (-)

Vaccine (

-), Antib

iotics (+

)02468

1012141618

4.2

8.610.3

16.2

Ris

k fo

r Pen

icill

in R

esis

tant

St

rain

s (%

)

Antibiotics (+): Antibiotic use within the last 3 months

Page 41: Pneumococcal Disease in Children:  P.S. It Matters

Gertz R, et al. J Infect Dis. 2010;201:770-775.

11%, 8%, 8%, 5%Total = 32%

Distribution of Penicillin Non-Susceptible Invasive Pneumococcal Isolates–ABCs 2007 (all age groups)

Serotype 19A(n = 478)

Serotypes 15A, 35B, 23A, 6C (n = 287)

Serotype 6A (n = 38)

Others (n = 32)[13 serotypes, 2 isolates nontypeable]

PCV7 Serotypes (n = 61)

25.6% of 3,511 total isolates were penicillin non-susceptible

Page 42: Pneumococcal Disease in Children:  P.S. It Matters

Expanded Serotype Coverage with PCV13

Page 43: Pneumococcal Disease in Children:  P.S. It Matters

13-Valent Pneumococcal Conjugate Vaccine (PCV13)

• Licensed by FDA on February 24, 2010• Serotypes in PCV13

– PCV7 types: 4, 6B, 9V, 14, 18C, 19F, 23F– Additional serotypes: 1, 3, 5, 6A, 7F, 19A

• Approved for use in children 6 weeks through 5 years (before the 6th birthday) – 4-dose series at ages 2, 4, 6, and 12-15 months

• Indications– Prevention of invasive pneumococcal disease (IPD) caused by

the 13 vaccine serotypes– Prevention of otitis media caused by PCV7 serotypes

CDC. MMWR Morb Mortal Wkly Rep. 2010;59(9):258-261.

Page 44: Pneumococcal Disease in Children:  P.S. It Matters

2012 Child Immunization Schedule

ACIP Schedules. http://www.cdc.gov/vaccines/recs/schedules/default.htm. Accessed Feb 2012.

Page 45: Pneumococcal Disease in Children:  P.S. It Matters

PCV13 Recommended Schedules for Children < 24 Months

CDC. MMWR Recomm Rep. 2010;59(RR-11):1-18.

Age at Examination (mos)

Vaccination History: Total PCV7 and/or PCV13 Doses

Received PreviouslyRecommended PCV13 Regimen

2 through 6 mos

0 doses 3 doses, 8 wks apart; 4th dose at age 12-15 mos

1 dose 2 doses, 8 wks apart; 4th dose at age 12-15 mos

2 doses 1 dose, 8 wks after the most recent dose; 4th dose at age 12-15 mos

7 through 11 mos0 doses 2 doses, 8 wks apart; 3rd dose at 12-15 mos

1 or 2 doses before age 7 mo 1 dose at age 7-11 mos, 2nd dose at 12-15 mos, ≥ 8 wks later

12 through 23 mos

0 doses 2 doses, ≥ 8 wks apart

1 dose before age 12 mo 2 doses, ≥ 8 wks apart

1 dose at ≥ 12 mo 1 dose, ≥ 8 wks after the most recent dose

2 or 3 doses before age 12 mo 1 dose, ≥ 8 wks after the most recent dose

4 doses of PCV 7 or other age-appropriate, complete PCV7 schedule

1 supplemental dose, ≥ 8 wks after the most recent dose

Page 46: Pneumococcal Disease in Children:  P.S. It Matters

Transition from PCV7 to PCV13 Accordingto Number of Doses Previously Received

Primary Infant Series Booster Dose Supplemental PCV13 Dose

2 mos 4 mos 6 mos ≥ 12 mos* 14-59 mos**

PCV7 PCV13 PCV13 PCV13 --

PCV7 PCV7 PCV13 PCV13 --

PCV7 PCV7 PCV7 PCV13 --

PCV7 PCV7 PCV7 PCV7 PCV13

*No additional PCV13 doses are indicated for children 12-23 months who received 2 or 3 doses or PCV7 before age 12 months and at least 1 dose of PCV13 at age ≥ 12months**For children with underlying medical conditions, a supplemental PCV13 dose is recommended through 71 months of age

CDC. MMWR Morb Mortal Wkly Rep. 2010;59(9):258-261.

Page 47: Pneumococcal Disease in Children:  P.S. It Matters

PCV13 Recommended Schedules for Children ≥ 24 Months

Age at Examination (mos)

Vaccination History: Total PCV7 and/or PCV13 Doses Received

PreviouslyRecommended PCV13 Regimen

Healthy children 24 through 59 mos

Unvaccinated or any incomplete schedule 1 dose, ≥ 8 wks after the most recent dose

4 doses of PCV7 or other age-appropriate, complete PCV7 schedule

1 supplemental dose, ≥ 8 wks after the most recent dose

Children 24 through 71 mos with

underlying medical conditions

Unvaccinated or any incomplete schedule of < 3 doses

2 doses, one ≥ 8 wks after the most recent dose and another dose ≥ 8 wks later

Any incomplete schedule of 3 doses 1 dose, ≥ 8 wks after the most recent dose

4 doses of PCV7 or other age-appropriate, complete PCV7 schedule

1 supplemental dose, ≥ 8 wks after the most recent dose*

*For children who have underlying medical conditions, a supplemental PCV13 dose is recommended through 71 months of age

CDC. MMWR Recomm Rep. 2010;59(RR-11):1-18.

Page 48: Pneumococcal Disease in Children:  P.S. It Matters

Invasive Pneumococcal Disease Caused by Serotype 19A: A Preventable Death?

• June 2011, a 2-year-old girl in California died from IPD caused by serotype 19A

• Serotype 19A is included in PCV13, but not PCV7• The child had received 3 doses of PCV7, but had NOT

received PCV13• California Dept. of Public Health identified an additional

30 PCV-13 eligible children who had developed nonfatal IPD caused by serotypes not included in PCV7

CDC. MMWR Wkly Rep. 2011;60:1477-1481.

Page 49: Pneumococcal Disease in Children:  P.S. It Matters

Coverage with PCV13, Immunization Information System (IIS) Sentinel Sites, US

March 12, 2010–June 30, 2011

Age Group(months)

Enrolled in IIS in Birth Range

(number)

Completed PCV7 Series Did Not Complete PCV7 Series

NumberReceived

PCV13 (%)* NumberReceived

PCV13 (%)*

0–11 288,671 --- --- 288,671 71

12–23 297,285 160,565 58 136,720 45

24–59 953,295 694,135 32 259,160 14

CDC. MMWR Wkly Rep. 2011;60:1477-1481.

*On or after March 12, 2010; unweighted average across sites

• During 2010 and 2011, evaluated PCV13-type IPD cases and vaccine coverage in children ≤ 59 months

• Among ~850,000 children aged 12 through 59 months with a complete PCV7 series as of March 2010, 37% received the supplemental dose as of June 30, 2011

• CDC PCV13 Vaccine Effectiveness Evaluation– 68% of cases of IPD due to the new serotypes in PCV13 were among vaccine-eligible

children 24–59 months

Page 50: Pneumococcal Disease in Children:  P.S. It Matters

2010 CDC ABC Data–IPD Rates All Serotypes and PCV13 Serotypes Children < 2 Years

Moore M, et al. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy; Chicago, IL 2011: G1-538.

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Frequency of Adverse Events Following Administration of PCV13 or PCV7

Adverse EventPercent

PCV13 (n = 4,729) PCV7 (n = 2,760)Injection-site reaction

Pain/tenderness 48.8 54.4Erythema (any) 46.6 46.6Induration/swelling 35.3 37.1

Irritability 70.0 68.4Drowsiness/increased sleep 59.2 58.3Decreased appetite 38.7 48.0Fever 36.9 46.7Restless sleep/decreased sleep

36.0 34.4

Fever > 39°C 5.3 7.4Diarrhea 3.1 3.0Vomiting 1.8 2.0Rash 1.1 1.6

CDC. MMWR Recomm Rep. 2010;59(RR-11):1-18. Data from 13 combined clinical trials

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PPSV23 After PCV13 for Children ≥ 2 Years of Age with Underlying Medical Conditions

Group Schedule for PPSV23 Revaccination with PPSV23

Children who have sickle cell disease, functional or anatomic asplenia, HIV-infection, or other immunocompromising condition

1 dose of PPSV23 administered at age ≥ 2 years and ≥ 8 weeks after last indicated dose of PCV13

1 dose 5 years after the 1st dose of PPSV23

Immunocompetent children with chronic illness

1 dose of PPSV23 administered at age ≥ 2 yrs and ≥ 8 weeks after last indicated dose of PCV13

Not recommended

Doses of PCV13 should be completed before PPSV23 is given. No more than 2 PPSV23 doses are recommended.

CDC. MMWR Recomm Rep. 2010;59(RR-11):1-18.

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PCV10

Rodgers G, Klugman K. Vaccine. 2011;29S:C43-C48.

• Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, 23F• First approved by the European Commission in March

2009– For active immunization against invasive pneumococcal disease

and acute otitis media in infants and children 6 weeks up to 2 years of age

– Licensed globally, indications vary for countries outside of Europe

– European label has been updated to include use in preterm infants

– Not licensed in USA– Placebo-controlled efficacy study in Argentina, Columbia,

and Panama (COMPAS)– 22% reduction in community-acquired pneumonia

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Future Developments: Pneumococcal Vaccines for Children

• 15-valent pneumococcal conjugate vaccine (PCV)• Continue to further expand valency of PCVs• Protein vaccines alone (protection independent of serotype)• Addition of pneumococcal proteins to conjugate vaccines• Innovative whole-cell killed pneumococci as a vaccine

Adapted from Rodgers G, Klugman K. Vaccine. 2011;29S:C43-C48.

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Estimated PCV Vaccination Coverage Children 19–35 months; NIS, 2006–2010

2006 2007 2008 2009 20100

102030405060708090

100

PCV ≥ 3 doses PCV ≥ 4 doses

Vacc

inat

ion

Cov

erag

e (%

)

CDC. MMWR Wkly Rep. 2011;60:1157-1163. NIS: National Immunization Survey

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Vaccine Concerns–Parents of Children Age 6 or Younger, 2010 Survey

Vaccine Concern Parents Reporting Concern (%)

Painful for children to receive so many shots during 1 doctor’s visit 38

Child is getting too many vaccines in 1 doctor’s visit 36

Children get too many vaccines during the first 2 years of life 34

Vaccines may cause fevers 32

Vaccines may cause learning disabilities such as autism 30

Ingredients in vaccines are unsafe 26

Vaccines are not tested enough for safety 17

Vaccines may cause chronic disease 16

Vaccines are given to children for diseases they are not likely to get 11

Vaccine shortages will contribute to incomplete vaccinations 9

Vaccines are given to children to prevent diseases that are not serious 8

No concerns 23

Kennedy A, et al. Health Affairs. 2011;30:1151-1159.

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Barriers to Adequate Childhood Immunization

Patient /Parent Barriers

• Lack of knowledge about immunizations• Fears about vaccine safety• Logistical problems that limit access to immunization services

Provider Barriers

• Providers may be uninformed about immunization indications and contraindications, especially due to frequent changes/updates

• Logistical issues– Cost of immunizations– Vaccine storage– Vaccine availability– Lack of access to prior immunization records

• Missed opportunities to vaccinate• Missed visits• Limited time for communication about vaccine risks and benefits

Systems Barriers• Disruption of vaccine supply• Children may qualify to receive vaccines through Vaccines for

Children (VFC) program, but VFC does not reimburse providers for administration costs

Burns I, Zimmerman R. J Fam Pract. 2005;54:S58-S62.AAP. Pediatrics. 2010;125:1295-1304.

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Improving Vaccination Rates:Provider Issues

• Know the facts – ACIP: http://www.cdc.gov/vaccines/recs/default.htm

• Recommend vaccinations to your patients • Address questions and concerns about vaccine safety• Get organized and use systems approaches

– Ensure offering and administration of vaccine Automatic processes that empower nurses are effective Address convenience, efficiency, durability

• Evaluate and provide feedback• Consider new paradigms

– New venues – Extend vaccination season

• Practice what we preach – Get vaccinated/get your own children vaccinated!

Adapted from Nichol KL. Cleve Clin J Med. 2006;73:1009-1015.

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Strategies to Improve Immunization Rates

• Client reminder and recall systems • Vaccination requirements for child care and school• Parent/patient education• Reducing client out-of-pocket costs • Vaccination programs in schools• Vaccination programs in WIC settings • Standing orders• Computerized record reminders• Chart reminders• Drop-in vaccination services• Expanding access in health care settings• Personal health records• Office-based quality improvement activities

CDC. http://www.cdc.gov/vaccines/recs/default.htm. Accessed Nov 2011.AAP. Pediatrics. 2010;125:1295-1304.

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Summary• Pneumococcal disease is a common cause of morbidity and

mortality in children worldwide

• In the US, routine immunization with PCV7 resulted in a dramatic reduction in disease caused by vaccine serotypes, with benefits in very young children and older adults through herd immunity

• Invasive pneumococcal disease due to non-PCV7 serotypes increased in the years following implementation of PCV7; particularly serotype 19A

• PCV13 (with expanded serotype coverage) has replaced PCV7, but PCV13 coverage remains suboptimal in certain age groups

• Identify and address any barriers to recommended childhood immunizations

• Implement strategies for improving immunization rates