pneumococcal disease in children: p.s. it matters
DESCRIPTION
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 PresentationTRANSCRIPT
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
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.
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.
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.
< 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.
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
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.
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.
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.
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.
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.
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.
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
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.
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
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
Herd Immunity: Invasive Pneumococcal Disease in Infants 0 to 90 days,1997–2004
Poehling K, et al. JAMA. 2006;295:1668-1674.
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
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
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
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%
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.
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
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
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.
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
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
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
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
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
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.
Invasive Pneumococcal Disease Penicillin Non-susceptible (≥ 2 years) ABCs Data
Kyaw M, et al. N Engl J Med. 2006;354:1455-1463.
Effect of Introduction of PCV-7 on Drug-Resistant S. pneumoniae
Kyaw M, et al. N Engl J Med. 2006;354:1455-1463.
Invasive Pneumococcal Disease Serotype 19A
Moore M, et al. J Infect Dis. 2008;197:1016-1027.
Trends in Antibiotic Resistance: Serotype 19A Children < 5 Years
Moore M, et al. J Infect Dis. 2008;197:1016-1027.
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.
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
Children With New Acquisition of Serotype 19A After Finishing Primary Series PCV7
van Gils E, et al. JAMA. 2010;304:1099-1106.
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
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
Expanded Serotype Coverage with PCV13
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.
2012 Child Immunization Schedule
ACIP Schedules. http://www.cdc.gov/vaccines/recs/schedules/default.htm. Accessed Feb 2012.
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
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.
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.
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.
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
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.
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
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.
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
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.
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
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.
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.
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.
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.
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