New ACIP recommendations for use of pneumococcal polysaccharide vaccine in adults

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New ACIP recommendations for use of pneumococcal
polysaccharide vaccine in adults

• Pekka Nuorti, MD, DSc
• Centers for Disease Control and Prevention
• Current Issues in Immunization
• March 12, 2009

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Presentation outline

• Currently available pneumococcal vaccines
• Changes in invasive pneumococcal disease (IPD)
  burden in adults after routine use of childhood
  pneumococcal conjugate vaccine (PCV7)
• New guidelines from the Advisory Committee on
  Immunization practices (ACIP) for use of
  pneumococcal polysaccharide vaccine (PPSV23)
• adults who have asthma
• cigarette smokers
• Remaining questions and challenges

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Currently available pneumococcal vaccines
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Invasive
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Evaluating the need to change vaccine
recommendations key factors

• Disease burden
• Vaccine efficacy and effectiveness
• serotype coverage, duration of protection
• Vaccine safety
• adverse events
• Program issues
• feasibility of implementation
• acceptability and demand
• Cost-effectiveness
• Achievable incremental public health impact of
  proposed policy compared with current policy

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Changing epidemiology of pneumococcal disease in
adults after routine childhood PCV7 use
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Active Bacterial Core surveillance (ABCs) methods

• IPD case definition pneumococcus isolated from
  normally sterile site in a surveillance area
  resident
• Chart review for clinical information
• Active contact with clinical laboratories to
  identify cases
• Audits ensure completeness of reporting
• Isolates serotyped at reference laboratories (CDC
  and MDH)

Total population 18.5 million
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Rates of invasive pneumococcal disease among
adults, by age,1998/99-2006 All serotypes
2006 vs. baseline 65 -38 (-34,-41) 50-64
-16 (-14,-19) 18-49 -38 (-41,-34)
PCV7 intro-duction
CDC, Active Bacterial Core surveillance,
unpublished
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Rates of invasive pneumococcal disease among
adults, by age,1998/99-2006 PCV7 serotypes
2006 vs. baseline 65 -89 (-86,-91) 50-64
-84 (-80,88) 18-49 -88 (-85,-91)
PCV7 intro-duction
CDC, Active Bacterial Core surveillance,
unpublished
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Underlying medical conditions and risk for
invasive pneumococcal disease
Estimated using data from the CDCs ABCs
surveillance and National Health Interview
Survey (NHIS)
Kyaw, JID 2005192377-86
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Rates of IPD among persons with and without ACIP
indications for PPSV23
Persons aged 50-64 years CDC Active Bacterial
Core surveillance, unpublished
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Proportion of remaining cases of IPD by
age-group, 2007
N 42.000 cases 85 are in adults
CDC, Active Bacterial Core surveillance,
unpublished
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Summary of indirect effects of childhood PCV7 on
adult IPD

• After childhood PCV7 introduction, rates of IPD
  in adult age-groups have decreased significantly
• gt half of the prevented cases are among adults
• Despite major indirect PCV7 effects, remaining
  disease burden in adults is substantial
• about 36,000 remaining IPD cases annually
• 4500 deaths due to IPD

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New ACIP indications for PPSV23 in adults
asthma and cigarette smoking
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Persons at increased risk for severe
disease include those with chronic illness such
aschronic pulmonary disease (e.g., COPD or
emphysema, but not asthma)
Recommendations of the ACIP. MMWR 199746(No.
RR-8).
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Risk of pneumococcal disease among persons with
asthma

• Asthma is an independent risk-factor for invasive
  pneumococcal disease
• The risk among persons with asthma was at least
  double that among controls.

Talbot et al. N Engl J Med 2005 352(20) 2082-90
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The ACIPs rationale for making asthma an
indication for PPSV23

• Whether or not asthma is an indication for PPSV23
  has been an area of confusion among health care
  providers
• Asthma is already an indication for influenza
  vaccine
• New information suggests that asthma is an
  independent risk factor for IPD
• Including asthma in the chronic lung disease
  category consistent with the current clinical
  practice of many adult immunization providers
• Most adult asthmatics who develop IPD already
  have another condition for which PPSV23 is
  recommended

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ACIP recommendation, June 2008

• Asthma is an independent risk factor for IPD
• The ACIP recommends that asthma should be
  included among the chronic pulmonary diseases
  (such as COPD and emphysema) that are indications
  for PPSV23 in adults aged 19 through 64 years.
• Wording of the revised recommendation Persons
  aged 19 through 64 years who have asthma should
  receive a single dose of PPSV23.

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Why are persons with asthma at increased risk for
pneumococcal disease?

• Exact mechanism for increased susceptibility
  unknown. Hypotheses
• Effect of respiratory infections on triggering
  asthma exacerbations?
• Persons with asthma may have
• disrupted physical barrier of the airway lining
• increased mucous production
• alterations in immune response
• Asthma medications (corticosteroids) may suppress
  the immune system

Hartert T. J Allergy Clin Immunol 2008
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Prevalence of current and former smoking among
IPD cases by age, 2001-2003
N1878
CDC. Active Bacterial Core surveillance,
unpublished
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Association of cigarette smoking and IPD

• Strongest independent risk-factor in
  immunocompetent, non-elderly adults1
• Adjusted population attributable risk 51
• Dose response relations
• Association also subsequently confirmed in
  immunocompromised groups2,3

1. Nuorti et al. N Engl J Med 2000342681-9 2.3.
Breiman Arch Int Med 2000, Grau Arch Int Med 2005
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Number of cigarettes smoked daily and risk of IPD
aOR 2.3 3.7
5.5
Nuorti et al. N Engl J Med 2000342681-9
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The ACIPs rationale for making cigarette smoking
an indication for PPSV23

• Approximately half of adults aged lt65 years who
  develop severe pneumococcal disease are smokers
• Cigarette smoking is a particularly strong risk
  factor for severe pneumococcal disease
• Cigarette smoking is a risk behavior that is easy
  to identify among patients in clinical practice
• Many adults who smoke cigarettes and develop
  pneumococcal disease also have another condition
  for which PPSV23 is already recommended
• Smoking cessation should be part of the
  therapeutic plan regardless of immunization

Greene et al CID 2006.
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Quitting smoking and risk of IPD
aOR 3.5 3.7
0.6
Nuorti et al. N Engl J Med 2000342681-9
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IDSA / American Thoracic Society guidelines on
the management of community-acquired pneumonia in
adults
Mandell LA, et al. Infectious Diseases Society of
America/American Thoracic Society Guidelines on
the Management of Community-Acquired Pneumonia in
Adults. CID 200744S27S72
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ACIP recommendation, October 2008

• Adults who smoke cigarettes are at substantially
  increased risk for IPD
• The ACIP recommends that cigarette smoking should
  be added to the list of indications for PPSV23 in
  adults aged 19 through 64 years.
• Wording of the recommendation Persons aged 19
  through 64 years who smoke cigarettes should
  receive a single dose of PPSV23 and smoking
  cessation counseling.

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Why are cigarette smokers at increased risk of
IPD?

• Specific biologic mechanisms poorly understood
• Cigarette smoke
• impairs mucociliary clearance in the respiratory
  tract
• disrupts respiratory epithelium
• enhances bacterial attachment
• Smokers may have
• more frequent (viral) respiratory infections
• higher rates of pneumococcal colonization
• lower immunoglobulin levels?

Nuorti et al. N Engl J Med 2000342681-9
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Comparison of estimated IPD rates among
asthmatics and smokers with rates among persons
with established PPSV23 indications
Kyaw JID 2005, ages 18-64 years Talbot NEJM 2005,
ages 2-49 years Nuorti NEJM 2000, ages 18-64
years
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Current and new PPSV23 target groups and
self-reported coverage, adults aged 19-64 years,
U.S. 2007
Diabetes, heart diseases, bronchitis, emphysema,
kidney disease, liver diseases and cancer
National Health Interview Survey, 2007 U.S.
Census Interim Population Projections, 2008
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Remaining questions and challenges

• About one-fifth of U.S. adults smoke cigarettes
• Although most smokers have another PPSV23
  indication, targeting this group may
  substantially increase the number of vaccines
  required
• As with other risk-based indications, determining
  optimal timing of vaccination with PPSV23 is
  challenging
• Most smokers begin in adolescence or early
  adulthood but risk of IPD increases with
  increasing pack-years
• Among IPD cases, smoking prevalence is high from
  early adulthood
• Using indicators such as pack-years smoked may
  not be feasible in clinical practice

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Conclusions

• Despite dramatic reductions in pneumococcal
  disease due to childhood PCV7, substantial
  disease burden remains in adults, particularly
  among those with risk factors
• Adults who have asthma or who smoke cigarettes
  are at increased risk for invasive pneumococcal
  disease
• Vaccinating individuals who have established and
  new high risk conditions with PPSV23 and efforts
  to increase coverage continue to be an important
  prevention strategy

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Additional resources

• Additional recommendations for use of PPSV23 and
  PCV7 can be found in the following documents
• 1997 ACIP recommendations for prevention of
  pneumococcal disease. Available at
• http//www.cdc.gov/mmwr/PDF/rr/rr4608.pdf
• 2000 ACIP recommendations for preventing
  pneumococcal disease among infants and young
  children. Available at http//www.cdc.gov/mmwr/PD
  F/rr/rr4909.pdf
• 2009 Adult immunization Schedule. Available at
• http//www.cdc.gov/mmwr/PDF/wk/mm5753-Immunizatio
  n.pdf

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Acknowledgements

• CDC
• Matthew Moore
• Cynthia Whitney
• Jessica Henry
• Jennifer Rosen
• James Singleton
• Peng-Jun Lu
• Riyadh Muhammad
• Tamara Pilishvili
• Chris Van Beneden
• Bernard Beall
• Elizabeth Zell
• Carolyn Wright

• ABCs sites
• Monica Farley
• Wendy Baughman
• David Stephens
• Nana Bennett
• Shelley Zansky
• Zack Fraser
• Jim Hadler
• Lee Harrison
• Lauri Thompson Sanza
• Ann Thomas
• Art Reingold
• Pam Daily
• Ruth Lynfield
• Catherine Lexau
• Anita Glennen

Sue Johnson Pam Gahr Allen Craig Bill
Schaffner Brenda Barnes Steve Burnite Ken
Gershman B. Koziol B. Juni UTHSC San Antonio Jim
Jorgensen Lettie McElmeel Sharon Crawford
Vanderbilt University Carlos Grijalva Marie
Griffin Patrick Arbogast Kathy Edwards
The findings and conclusions in this presentation
are those of the speaker and do not necessarily
represent the views of the Centers for Disease
Control and Prevention.
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Questions?