PCV7 Effect on Invasive Disease in the U.S. Update from ABCs

1
PCV7 Effect on Invasive Disease in the
U.S.Update from ABCs

• Cynthia Whitney
• Centers for Disease Control and Prevention
• Atlanta, GA
• Netspear Meeting
• November 2005

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Prevnar (Wyeth Lederle)7-valent Pneumococcal
Conjugate Vaccine

• Poly- or oligosaccharides of serotypes 4, 6B,
  9V, 14, 18C, 19F, 23F
• Conjugated to CRM197
• In US, 7 vaccine serotypes caused gt80 of
  invasive disease in children and 50 in adults

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Pneumococcal Conjugate Vaccine Introduction in
the U.S.
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U.S. Recommendations for Use of Pneumococcal
Conjugate Vaccine

• All children lt2 years
• Children 2-4 years with
• Certain chronic illnesses
• Immunocompromising conditions
• Consider for all children 2-4 with priority to
  those
• 24-35 months
• Alaska Native, American Indian, African American
• Attending day care

Shortage
Advisory Committee on Immunization Practices.
MMWR 2000
5
Receipt of PCV7 Among Children 19-35 Months,
U.S, 2003
86.0
N21,310
National Immunization Survey, Q1-Q4, 2003
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Active Bacterial Core Surveillance for
Pneumococcal Disease,1998-2004
ABCs areas OR (3 counties) CA (1 county) MN (7
counties) GA (20 counties) MD (6 counties) CT
(entire state) NY (7 counties) TN (5 counties)
Total surveillance population 19.0 million
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Effect in Target Age GroupInvasive Pneumococcal
Disease Rates in Children lt5 Years, ABCs,
1998-2004
1 yr
2004 vs baseline
lt1 yr
- 77 (lt1 yr)
- 83 (1 yr)
- 73 (2 yr)
2 yrs
- 61 (3 yr)
3 yrs
- 49 (4 yr)
4 yrs
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Relative Magnitude of Changes by Serotype in lt2
year olds, ABCs 1998/1999 (Baseline) vs. 2004
Same serogroup as vaccine type
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Invasive Pneumococcal Disease Children lt5 years
of age, 1998-2004
PCV-7 introduced
PCV-7 types
2004 vs baseline
Non-vaccine types
24
-96
baseline
LA Hicks et al IDSA 2005
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What is Herd Immunity?
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Susceptible Population
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Herd Immunity Partially Vaccinated Population
x
x
x
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Evidence of herd effects reducing disease among
children

• Drop in VT disease in children outside vaccinated
  age group (50 reduction in infants lt2 mos and
  children 5-17 years)
• Observed reduction in VT disease in children lt5
  yrs (97) gtgt expected (67)
• Expected reduction vaccine coverage (73 3
  doses) X vaccine efficacy (92)

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What Weve LearnedPCV7 Effects in Children

• Disease caused by vaccine types plummeted in
  young children following conjugate vaccine
  introduction
• Herd immunity appears to be protecting
  unvaccinated children
• Magnitude of replacement disease small

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Conjugate Vaccine Effect on Carriage

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Transmission from Children to Adults

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Herd Effect in AdultsInvasive Pneumococcal
Disease Rates over TimeABCs, 1998-2004
65 years
2004 vs. baseline
- 36
40-64 yrs
- 26
18-39 yrs
- 53
Lexau et al. JAMA 2005 and unpublished data
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Invasive Pneumococcal Disease Adults 65 years and
older, 1998-2004
PCV-7 introduced
PCV-7 types
2003 vs baseline
10
Non-vaccine types
-76
baseline
LA Hicks et al IDSA 2005
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Trends in Invasive Pneumococcal Disease in Adults
18-64 years with HIV/AIDS
Vaccine introduction
- 9 (-22 6)
Baseline
- 21 (-33 -7)
Flannery B et al Annals Int Med 2006 in press
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What Weve Learned PCV7 effect on disease in
adults

• Large herd immunity effect in adults
• Replacement disease small in most adults
  substantial in highly susceptible hosts (eg,
  HIV/AIDS)
• Giving PCV7 to children effective means for
  preventing disease in adults

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Vaccine-type invasive pneumococcal disease
prevented by direct and indirect effects of the
pneumococcal conjugate vaccine -- ABCs 2003
Direct VT IPD cases prevented in 2003 1998/99
average number of VT IPD cases in children lt 5
years of age x 2003 PCV7 coverage with
three doses (68.1) x PCV7 effectiveness for VT
IPD (93.9). Indirect VT IPD cases prevented in
2003 (1998/99 average number of VT IPD cases
across all ages 2003 number of VT IPD
cases across all ages) 2003 direct VT IPD cases
prevented. Note Calculation of
indirect cases prevented does not account for
replacement disease.
CDC. MMWR Sep 16, 2005
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Distribution of Pneumococcal Serotypes by
Frequency and Penicillin ResistanceChildren lt2
years, ABCs, 1999
Conjugate vaccine
Not in vaccine
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Invasive disease caused by pneumococci
nonsusceptible and susceptible to penicillin in
children lt2 years, 1996-2004
Vaccine introduced
Pen S
Pen NS
Kyaw M et al, ABCs unpublished data
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Rates of Invasive Pneumococcal Disease Caused by
Penicillin-Nonsusceptible Strains by Age
GroupABCs 1998/1999 and 2004
55 reduction
CDC unpublished data
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Summary PCV7 Effect on Resistance

• Large reduction in resistant infections in
  children
• Herd immunity effects preventing resistant
  infections in unvaccinated children and adults

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Remaining Questions

• Will replacement disease become more of a
  problem?
• Is there herd effect with pneumonia?
• Optimal schedule/dosing
• Coverage needed for herd immunity
• How will results in other settings compare?
• How quickly can we introduce PCV into other
  countries?

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AcknowledgementsABCs Surveillance

• CDC
• Chris Van Beneden
• Anne Schuchat
• Elizabeth Zell
• Tamara Pilishvili
• Moe Kyaw
• Katherine Robinson
• Tami Skoff
• Carolyn Wright
• Brendan Noggle
• John Walls
• Dick Facklam
• LaShondra Shealey
• Dee Jackson

• ABCs sites
• Monica Farley
• Wendy Baughman
• David Stephens
• Nana Bennett
• Shelley Zansky
• Nancy Barrett
• Jim Hadler
• Lee Harrison
• Lauri Thompson Sanza
• Karen Stefonek
• Paul Cieslak
• Art Reingold
• Pam Daily
• Ruth Lynfield
• Catherine Lexau
• John Besser

Sue Johnson Pam Gahr Allen Craig Bill
Schaffner Brenda Barnes Matt Finke Ken
Gershman B. Koziol B. Juni UTHSC San Antonio Jim
Jorgensen Lettie McElmeel Sharon Crawford Emory
University Keith Klugman