RxVaccinate - American Pharmacists Associationelearning.pharmacist.com/.../Pneumococcal_slides... · Invasive Pneumococcal Disease (IPD) in Adults with Chronic Disease 8.8 2012 51.4

7/8/2013

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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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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


Goal: 3.0 cases/100,000

IID-4.4 Reduce invasive antibiotic-resistant

pneumococcal infections among adults aged

65 years


Goal: 2 cases/100,000

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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%


IID-13 Increase the number of adults who


disease


noninstitutionalized high-risk adults aged 18-

64 years who are vaccinated against


Baseline: 16.6% (2009 data)

Target: 60%


IID-13 Increase the number of adults who


disease


institutionalized adults (persons aged 18

years and older in long-term or nursing

homes) who are vaccinated against


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

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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

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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


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


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


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

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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

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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

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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

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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

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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

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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?

Documents

RxVaccinate - American Pharmacists Associationelearning.pharmacist.com/.../Pneumococcal_slides... · Invasive Pneumococcal Disease (IPD) in Adults with Chronic Disease 8.8 2012 51.4