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7/8/2013
1
Pneumococcal Immunization
Update
Stephan L. Foster, Pharm.D., FAPhA, FNAP
Professor and Vice-Chair
College of Pharmacy
University of Tennessee Health Science Center, Memphis, TN
Liaison Member, CDC Advisory Committee on Immunization Practices
(ACIP)
RxVaccinate
This webinar is provided as part of RxVaccinate –
an educational research project being conducted
by the American Pharmacists Association (APhA)
to help pharmacists and pharmacies expand their
pneumococcal immunization services.
For information about how you can be part of this
project, please visit:
www.pharmacist.com/rxvaccinate
Support
Supported by an independent
educational grant from Pfizer
Medical Education Group
Disclosures
Stephan L. Foster, PharmD, FAPhA, FNAP, is on the
speakers bureau for Merck Vaccine.
APhA’s educational and editorial staff declare no conflicts of
interest or financial interests in any product or service
mentioned in this activity, including grants, employment, gifts,
stock holdings, and honoraria.
The American Pharmacists Association is accredited
by the Accreditation Council for Pharmacy Education
as a provider of continuing pharmacy education.
Target Audience: Pharmacists
ACPE#: 0202-0000-13-155-L01-P
Activity Type: Knowledge-based
Objectives
At the end of this session, the participant will
be able to:
1. Describe pneumococcal disease
2. Recall current CDC recommendations for
pneumococcal vaccination
3. Discuss benefits and risks associated with
pneumococcal vaccination
4. Answer frequently asked questions by
patients and prescribers
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2
Streptococcus pneumoniae
Gram-positive coccobacillus with a polysaccharide cellular capsule Colonizes upper respiratory tract as part of normal flora
Disseminated Disease Bacteremia
Meningitis
Arthritis
Peritonitis
Lower Respiratory Tract Pneumonia
Upper Respiratory Tract Sinusitis
Otitis Media
>90 serotypes based upon polysaccharide capsules
Incidence in U.S.- 2000
Prior to conjugate vaccine introduction Meningitis
3300 cases
Invasive Disease 60,000 cases
Pneumonia 100,000 – 135,000 hospitalizations
Death 14% of hospitalized adults
Adults - CFR 15-20%
Elderly - CFR 30-40%
http://www.cdc.gov/ncidod/dbmd/diseaseinfo/streppneum_t.htm
Invasive Pneumococcal Disease (IPD)
in Adults with Chronic Disease
8.8 51.4 62.9 93.7 100.4
300.4
422.9 503.1
0
100
200
300
400
500
600
IPD
IPD
Cases/1
00,0
00
Kyaw MH, Rose CE, Fry AM, et.al. J Infect Dis.2005;192:377-86
Changes 2005 - 2012
503
422
186 173
0
100
200
300
400
500
600
Hematological Cancer HIV
2005
2012
2012 data unpublished from CDC
Cases /
100,0
00
Healthy People 2020 Goals Immunization and Infectious Diseases
IID-4 Reduce Invasive Pneumococcal Infections
IID-4.1 Reduce new invasive pneumococcal
infections among children under age 5 years
Baseline: 20.3 cases/100,000
Goal: 12 cases/100,000
IID-4.2 Reduce new invasive pneumococcal
infections among adults aged 65 years and older
Baseline: 40.4 new cases/100,000
Goal: 31 new cases/100,000
http://www.healthypeople.gov/2020/topicsobjectives2020/objectiveslist.aspx?topicId=23#565
All baseline date from 2008
Healthy People 2020 Goals
IID-4 Reduce Invasive Pneumococcal
Infections
IID-4.3 Reduce invasive antibiotic-resistant
pneumococcal infections among children
under age 5 years
Baseline: 4.3 cases/100,000
Goal: 3.0 cases/100,000
IID-4.4 Reduce invasive antibiotic-resistant
pneumococcal infections among adults aged
65 years
Baseline: 2.6 cases/100,000
Goal: 2 cases/100,000
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3
Healthy People 2020 Goals
IID-7 Achieve and maintain effective vaccination
coverage levels for universally recommended
vaccines among young children
IID-7.7 Achieve and maintain an effective coverage
level of 4 doses of pneumococcal conjugate vaccine
(PCV) among children by age 19 to 35 months
Baseline: 80.1%
Target: 90%
Healthy People 2020 Goals IID-13 Increase the number of adults who
are vaccinated against pneumococcal
disease
IID-13.1 Increase the percentage of
noninstitutionalized adults aged 65 years and
older who are vaccinated against
pneumococcal disease
Baseline: 60.1% (2009 data)
Target 90%
Healthy People 2020 Goals
IID-13 Increase the number of adults who
are vaccinated against pneumococcal
disease
IID-13.2 Increase the percentage of
noninstitutionalized high-risk adults aged 18-
64 years who are vaccinated against
pneumococcal disease
Baseline: 16.6% (2009 data)
Target: 60%
Healthy People 2020 Goals
IID-13 Increase the number of adults who
are vaccinated against pneumococcal
disease
IID-13.2 Increase the percentage of
institutionalized adults (persons aged 18
years and older in long-term or nursing
homes) who are vaccinated against
pneumococcal disease
Baseline: 66.4% (2005-2006 data)
Target: 90%
History
1881 – Pasteur, Steinberg isolate and grow pneumococcus Gram-stain discovered 1884
33% CFR for untreated pneumonia
1920’s – 1930’s – Antisera – 18% mortality
1930’s – Sulfapyridine
1941 – Sulfadiazine – 8% mortality
1940’s – Penicillin 1970’s – Penicillin resistance
1980’s – 44% resistant to penicillin
1990’s – Fluoroquinolone resistance
Mechanism of Resistance
Beta-lactams bind active enzyme needed for
synthesis of cell wall
Genes encoding the protein enzymes alter the affinity
for penicillins, cephalosporins, lincosamides
(clindamycin)
Macrolides inhibit protein synthesis in ribosome
Site of attachment altered to resist
Efflux pump excludes macrolides
Fluoroquinolones bind topoisomerase enzymes
to inhibit DNA synthesis
Mutations reduce binding of drugs
Pneumococcus resistant increasing
NEJM 2002;346:722
7/8/2013
4
Strategies for Minimizing
Antimicrobial Resistance
Proper antibiotic use
Patient Education
Clinician education and guidelines
Formulary management
Surveillance
Infection control practices
Vaccination
ASHP. Therapeutic position statement on strategies for identifying
and preventing pneumococcal resistance. Am J Health-Syst Pharm.
2004;61:2430-35
History of Pneumococcal Vaccination
1911 – Gold miners in South Africa
Attack rate 100/1000 persons with CFR 25%
Sir Almroth Wright – developer of typhoid vaccine
Vaccine containing heat-killed pneumococci
Left before trials completed
Stated after published results
“the comparative statistics which have been sent forth testify…in every
case to a reduction in the incidence-rate and death-rate of pneumonia in
the inoculated…Where in comparative statistics we find the difference
between the inoculated and the uninoculated is diminishing is after a
certain time effaced, this does not necessarily indicate that the immunity
of the inoculated is diminishing. We may be witnessing, instead of a
descent of the level of the inoculated to the level of the inoculated, an
assent of the uninoculated to the level of the inoculated…We
recommend that the prophylactic inoculation should…be applied as a
routine measure to every native on recruitment.”
History of Pneumococcal Vaccination F. Spencer Lister –
Left to compete work in South Africa
Discovered 8 different serotypes
Trials of polyvalent whole bacteria
Efficacy debated due to trial flaws
Suspected Wright’s vaccine was not potent enough
1927 Schiemann and Casper (Germany) discovered
immunogenicity of capsular polysaccharide
1930 polysaccharide vaccine with serotypes 1,2,3
Inconclusive results
1936 Type-specific antisera reduced mortality to 18%
1940’s WWII Air Force pilot training base outbreak
Tetravalent vaccine types 1,2,5,7
Demonstrated
Efficacy if not another serotype
Effective if not a carrier
Did not eliminate carrier state
1940 Penicillin Discovered
Vaccination Abandoned
History of Pneumococcal
Polysaccharide Vaccine (PPSV)
1950’s licenses withdrawn
1970’s new studies on polysaccharide
demonstrated clinical efficacy (60-70%)
Increasing resistance noted
1977 14-valent PPSV
Studies in children disappointing
History of Pneumococcal Conjugate
Vaccine (PCV) 1937 reported lack of responsiveness in
infants 2 to 14 months of age (both PPSV
and whole cell vaccine)
Linked polysaccharide to horse serum was
effective in rabbits
Noticed lack of response to Haemophillus
influenza type b (Hib) vaccine in infants
1990 studies with conjugation to protein
1993 conjugate Hib licensed
Pneumococcal conjugate licensed in 2000
7/8/2013
5
Licensed Vaccines
14 Serotype Pneumococcal
Polysaccharide Vaccine
Introduced 1977
Products Pneumovax®14 – (Merck & Co.)
Pnu-Imune 14® (Lederle, Inc.)
14 Serotypes
1, 2, 3, 4, 5,6A, 7F, 8, 9N, 12F, 18C, 19F, 23F, 25F
68 - 80% that cause invasive disease
Included 1 serotypes that cause most drug-resistant infections
Replaced in 1983
23 Serotype Pneumococcal
Polysaccharide Vaccine
Introduced 1983
Products Pneumovax®23 – (Merck & Co.)
Pnu-Imune 23® (Lederle, Inc.) – ended production 2002
23 Serotypes
1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F
85-90% that cause invasive disease
7 Serotype Pneumococcal
Conjugate vaccine
Licensed in 2000
Product
Prevnar 7 (Wyeth)
7 serotypes
4, 6B, 9V, 14,18C, 19F, 23F
When introduced, covered 80% of serotypes
causing invasive pneumococcal disease
(IPD) in children
50-60% older children and adults
13 Serotype Pneumococcal
Conjugate vaccine
Licensed in 2010
Product
Prevnar 13 (Pfizer)
13 serotypes
1,3,4,5,6A,6B,7F,9V,14,18C,19A,19F, 23F
Additional serotypes caused 61% of IPD cases
in children <5 years (before introduction of
vaccine)
Approved based upon safety and non-
inferiority immunogenicity data compared to
these serotypes in PPSV23
Rates of Pneumococcal Disease are Decreasing ABC Surveillance
0
20
40
60
80
100
120
140
160
180
200
<1 1 2-4 5-17 18-34 35-49 50-64 > 65
1997
2005
2011
Cases p
er
100,0
00
Age in years
7/8/2013
6
Not Optimal
CDC National Estimates (ABC Surveillance)
36,850 cases per year
4,250 deaths per year
Pneumococcal Vaccination Rate 2011
19-35 Months (PCV)
93.6% (3 doses)
84.4% (4 doses)
19-49 years high-risk (PPSV)
20.1% (18.5% in 2010)
> 65 years (PPSV)
62.3% (59.7% in 2010)
Vaccines are underused!
Non-influenza Vaccination Rates 2011
Vaccine % 2010 %
PPSV23 (19-64 y/o high-risk) 20.1 18.5
PPSV23 (>65 y/o) 62.3 59.7
Tetanus in past 5 years (19-49 years) 64.5 52.3
Tdap in past 6 years (19-64 years) 12.5 8.5
Tdap living with infants <1 y/o (19-49 years) 21.5 10.6
Tdap in past 5 years (HCP) – not including unknown 37.3
Hepatitis A (19-49 years) 12.5 10.7
Hepatitis B (19-49 years) 35.9 33.8
Hepatitis B with Diabetes (19-49 years) 26.9 22.7
Zoster (>60 years) 15.8 14.4
HPV Females (19-26 years) 21.5 16.5
HPV Males (19-21 years) 2.8 0.3
http://www.cdc.gov/mmwr/pdf/wk/mm62e0129.pdf
Changes in invasive pneumococcal disease (IPD) incidence by serotype group among
children aged <5 years (A) and adults aged ⩾65 years (B) 1998–2007. *Seven-valent
pneumococcal conjugate vaccine (PCV7) was introduced in the United States for routine use
among young children and infants in the second half of 2000.
Pilishvili T et al. J Infect Dis. 2010;201:32-41
© 2010 by the Infectious Diseases Society of America
Trends due to PCV7
Decrease in IPD in children by 79%
Overall rates leveled off – all ages
IPD by Penicillin resistant strains decreased
57% overall
81% children
IPD by non-PCV7 serotypes increased
Mostly type 19A
Hospitalizations for pneumonia in children
decreased 35%
Decrease in otitis media
Herd Effects of PCV7
Rates/ incidence of IPD in older children and
adults have decreased:
34% age 18-49 years
14% age 50-64 years
37% age > 65 years
IPD due to 7 serotypes decreased 90-93%
Decrease in all-cause pneumonia
hospitalizations among young adults
No benefit for adults with high-risk conditions
MMWR 2010;59 (RR-11):1-19
Comparison of Serotypes Pneumovax 23 (Merck) Prevnar 13 (Pfizer)
1
2
3
4
5
6B
7F
8
9N
9V
10A
11A
12F
14
15B
17F
18C
19A
19F
20
22F
23F
33F
1
3
4
5
6A
6B
7F
9V
14
18C
19A
19F
23F
Red indicates serotypes unique to vaccine
7/8/2013
7
IPD Caused by Vaccine
Serotypes, 2008
MMWR 2010;59 (RR-11):1-19
Differences between PPSV23 and PCV13
Immune Response
PPSV23 – T-independent antigen
Stimulates mature B lymphocytes
Not T lymphocytes
Response is not long lasting nor creates an
anamnestic (memory) response to rechallenge
No boosting effect
Infants and small children respond poorly
PCV13 – T-dependent antigen
Changed due to protein conjugate
Stimulates a T helper cell response
Strong memory response on rechallenge
Good response in infants and small children.
Decreases nasopharyngeal carriage
Differences between PPSV23 and PCV13
Adverse reactions
Similar in both
Mostly local (redness, induration, pain)
Mild and self limiting
PPSV23 more local effects with revaccination
Difficult to evaluate due to variety of vaccines given at
the same time.
Systemic
Myalgia and fever infrequent
Febrile seizures with PCV and TIV in 2010-11
season
Risk: 1 in 1640 vaccinees
Serious – rare (similar to other vaccines)
Hyporesponsiveness
Repeated doses of bacterial polysaccharide vaccines may induce
immune tolerance
Most data from meningococcal polysaccharide vaccines (serotype C)
Antibody concentrations lower than primary immunization
Lower immune (antibody) response
May relate to existing memory B cells overwhelmed by large dose of
antigen
May depend upon existing antibody concentration
Limited number of studies on pneumococcal vaccines have shown
varied results.
Many are short-term studies
Many different variables involved (i.e. serotypes, measurement of
immunogenicity, base-line titers)
ACIP Decision PCV13 not for routine use in adults
Awaiting more evidence
High risk groups
Pneumococcal vaccine-naïve person
Give PCV13 first
Give PPSV23 at least 8 weeks later
Repeat PPSV23 5 years later
Previous vaccination with PPSV23
Give PCV13 8 weeks after last PPSV23.
If second dose of PPSV23 is needed
No sooner than 8 weeks after PCV13
No sooner than 5 years after PPSV23
Over 65
One additional dose of PPSV23
If 5 years since last PPSV23
If 8 weeks after PCV13
ACIP.MMWR 2012;61(40):816-819
7/8/2013
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Footnotes
Childhood Indications
Routine for all Children (PCV13)
Ages 2,4,6 months booster 12-15 months
Ages 14-59 months who completed PCV7 series, single
dose
High-risk children
24-71 months, 1 dose if 3 PCV13 doses previously given
2 doses 8 weeks apart if fewer doses given
6-18 years, single dose PCV13 to previously unvaccinated
children
2 years or older, PPSV 8 weeks after last PCV13
Additional PPSV after 5 years to patients with asplenia
and immunocompromising conditions
High-Risk Conditions
MMWR 2010;59 (RR-11):1-19
7/8/2013
9
1.Pneumococcal polysaccharide (PPSV23) vaccination
1. Vaccinate all persons with the following indications:
1. all adults aged 65 years and older;
2. adults younger than age 65 years with chronic lung disease (including
chronic obstructive pulmonary disease, emphysema, and asthma);
chronic cardiovascular diseases; diabetes mellitus; chronic renal failure;
nephrotic syndrome; chronic liver disease (including cirrhosis);
alcoholism; cochlear implants; cerebrospinal fluid leaks;
immunocompromising conditions; and functional or anatomic asplenia
(e.g., sickle cell disease and other hemoglobinopathies, congenital or
acquired asplenia, splenic dysfunction, or splenectomy [if elective
splenectomy is planned, vaccinate at least 2 weeks before surgery]);
3. residents of nursing homes or long-term care facilities; and
4. adults who smoke cigarettes.
2. Persons with immunocompromising conditions and other selected conditions
are recommended to receive PCV13 and PPSV23 vaccines. See footnote #10
for information on timing of PCV13 and PPSV23 vaccinations.
3. Persons with asymptomatic or symptomatic HIV infection should be vaccinated
as soon as possible after their diagnosis.
4. When cancer chemotherapy or other immunosuppressive therapy is being
considered, the interval between vaccination and initiation of
immunosuppressive therapy should be at least 2 weeks. Vaccination during
chemotherapy or radiation therapy should be avoided.
5. Routine use of PPSV23 is not recommended for American Indians/Alaska
Natives or other persons younger than age 65 years unless they have
underlying medical conditions that are PPSV23 indications. However, public
health authorities may consider recommending PPSV23 for American
Indians/Alaska Natives who are living in areas where the risk for invasive
pneumococcal disease is increased.
6. When indicated, PPSV23 should be administered to patients who are uncertain
of their vaccination status and there is no record of previous vaccination. When
PCV13 is also indicated, a dose of PCV13 should be given first (see footnote
#10).
Footnotes Adult Indications (PPSV23)
All adults aged 65 years and older
Only one dose….do not repeat
All adults younger than 65 years with high-
risk conditions (immunocompetent)
One time revaccination 5 years after the first
dose with the following conditions:
Chronic renal failure or nephrotic syndrome
Functional or anatomic asplenia
Immunosuppressed
One dose after age 65 if one or two doses
were received before and it has been at least
5 years since the last dose.
Adult High-Risk Conditions Adult Indications (PCV13)
Approved for adults 50 years and older for
the prevention of pneumococcal pneumonia
and invasive disease caused by the 13
vaccine strains
PPSV23 and PCV13
Contraindications
Severe allergic reaction after previous dose
Precautions
Moderate or severe acute illness with or
without fever
PPSV23 Vaccine Effectiveness Cochrane Collaboration Review
25 studies met inclusion criteria
18 RCTs with 64,852 participants
Strong evidence of efficacy against IPD (reduced
disease by 74%)
Efficacy against all cause pneumonia in low
income countries (46%)
No reduction in all-cause mortality
Efficacy poorer in adults with chronic illness
7 non-RCTs with 62,294 participants
Protection against IPD (reduced disease by 52%) Moberley s, Holden J, Tatham DP, Andrews RM. Vaccines for preventing pneumococcal infection in
adults.Cochrane Database of Systematic Reviews 2013.
http://summaries.cochrane.org/CD000422/vaccination-for-preventing-pneumococcal-infection-in-adults
7/8/2013
10
Studies in HIV patients
PPSV23
No effect on infection or death
All-cause pneumonia higher in vaccine group French N, et al. 23-valent polysaccharide vaccine in HIV-1 infected Ugandan adults:double-
blind, randomised and placebo controlled trial. Lancet 2000;355:2106-11
PCV7
Vaccine efficacy of 74% against serotypes in vaccine French, et al. A trial of 7-valent pneumococcal conjugate vaccine in HIV-infected adults. N
Engl J Med. 2010;362;812-22
Herd Effect of PCV7
Reduction in IPD
Mortality still high (40 times higher than non-HIV)
Need more intervention in this population Cohen,et al. Prevention of invasive pneumococcal disease among HIV-infected adults in the
era of childhood pneumococcal infection. AIDS 2010;24:2253-62
PCV13 for use in adults
PCV 13 (Prevnar® – Pfizer) FDA approval in
Adults > 50 years (December 30, 2011)
Accelerated Approval Pathway
Approved based upon immunogenicity data
Indication
Prevention of disease against types in vaccine
Approval based upon immunogenicity data
Evidence not available
Efficacy against pneumonia
Study in Netherlands to be completed 2013
No evidence of indirect (herd) effect due to use in
children
ACIP recommendations for PCV13 in adults
June 2012 ACIP meeting
PPSV23
Limited efficacy in immunocompromised
Safe and covers 70% of serotypes of IPD
Continue use (2 or 3 doses in very high risk)
PCV13
No recommendation for routine use in adults
Potential benefit seen in previous studies
Herd effect in children unlikely to contribute
Add one dose to high-risk adults
PCV 1 year after PPSV
PPSV 8 weeks after PCV
NOTE: The dose recommendations for PCV-13 noted on
this slide are correct
High-Risk Conditions
MMWR.2012;61(40) accessed at http://www.cdc.gov/mmwr/pdf/wk/mm6140.pdf
Pneumococcal Vaccine Decision Tree for Adults
19 - 64 Years Old with Select Conditions
ACIP. MMWR. 2012; 61 (40): 816-819
Pneumococcal Vaccine Decision Tree for Adults
≥ 65 Years Old with Select Conditions
ACIP. MMWR. 2012; 61 (40): 816-819
7/8/2013
11
Roles of Health-care Providers
Get vaccinated yourself!
Dispel myths and educate the public
Screen patients
Keep records - document
Have all immunizations available
Use Immunization Information Systems
Registries
Communicate with other providers
Participate in health fairs and community events
Develop policies/procedures
Involve all personnel in your practice
Addressing Concerns
Discussion with patient / parent or guardian
Factual
Appropriate language
Simple, easy to understand
Communicate with empathy
Use strong language
“You should get this vaccine today!”
Reinforce key points
Safety
Risks for disease
State laws
Show where patient can get good information
Immunization resources
Communication Tips
Talk about impact of pneumococcal
disease
Explain methods of payments available
Use Vaccine Information Statement (VIS)
If refused, offer at next visit.
If one vaccine refused, give others if
acceptable
Talking Points
Vaccination can help protect against a
serious disease
Pneumococcal infection can be deadly
You are at increased risk
Over 65 years
High-risk medical conditions
Smoker
Vaccination is safe
“May I administer this vaccine to you today?”
.......any questions?
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