Immunization UpdateImmunization Update

Doug Stewart, DO, MPHDoug Stewart, DO, MPHAssociate Professor of PediatricsAssociate Professor of Pediatrics

University of Oklahoma - TulsaUniversity of Oklahoma - Tulsa

OutlineOutline• OutcomeOutcome• Options, Guidelines, and StandardsOptions, Guidelines, and Standards• Advisory Committee on Immunization Advisory Committee on Immunization

Practices (ACIP)Practices (ACIP)• Current guideline for childrenCurrent guideline for children

– Important pointsImportant points– Recent changesRecent changes– Anticipated changesAnticipated changes

• Current guideline for adultsCurrent guideline for adults– Recent changesRecent changes– Anticipated changesAnticipated changes

Comparison of 20Comparison of 20thth Century Annual Century Annual Morbidity and Current Morbidity, Morbidity and Current Morbidity,

Vaccine-Preventable Diseases (pre-1990 Vaccines)Vaccine-Preventable Diseases (pre-1990 Vaccines)

DiseaseDisease20th Century20th Century

Annual MorbidityAnnual Morbidity†† 2004*2004*Percent Percent DecreaseDecrease

SmallpoxSmallpox 48,16448,164 00 100%100%

DiphtheriaDiphtheria 175,885175,885 0 0 100%100%

MeaslesMeasles 503,282503,282 3737 99.99%99.99%

MumpsMumps 152,209152,209 236236 99.84%99.84%

PertussisPertussis 147,271147,271 18,95718,957 87.13%87.13%

Polio (paralytic)Polio (paralytic) 16,31616,316 00 100%100%

RubellaRubella 47,74547,745 1212 99.97%99.97%

Congenital Rubella SyndromeCongenital Rubella Syndrome 823823 00 100%100%

TetanusTetanus 1,3141,314 2727 97.95%97.95%

† Source: CDC. MMWR April 2, 1999. 48: 242-264 * Provisional 2004 Data

Numbers in yellow indicate at or near record lows in 2004

Comparison of Pre-Vaccine EraComparison of Pre-Vaccine EraEstimated Annual Morbidity and Current Morbidity,Estimated Annual Morbidity and Current Morbidity,

Vaccine-Preventable Diseases (post-1990 Vaccines)Vaccine-Preventable Diseases (post-1990 Vaccines)

DiseaseDisease

Pre-Vaccine Era Pre-Vaccine Era Estimated Annual Estimated Annual

MorbidityMorbidity 20032003Percent Percent DecreaseDecrease

Hepatitis AHepatitis A 117,333117,333 32,71132,711 72.1%72.1%

Hepatitis B (acute)Hepatitis B (acute) 66,23266,232 21,03021,030 68.2%68.2%

Hib (invasive)Hib (invasive) 20,00020,000 4040 99.8%99.8%

Pneumococcus (invasive)Pneumococcus (invasive) 63,06763,067 39,80039,800 36.9%36.9%

VaricellaVaricella 4,085,1204,085,120 817,024817,024 80.0%80.0%

Influenza (<5 years)Influenza (<5 years) N/AN/A N/AN/A ------

Meningococcus (invasive)Meningococcus (invasive) 2,1832,183 N/AN/A ------

N/A = not available

Outcomes known?

No

Preferences known?

Unanimous Standard

Guideline

Option with preference indifferent

Option with preferences

unknown

Option with outcomes unknown

Yes

No

Yes

Majority

Evenly split

Indifferent

Strongly divided

Option with preferences

split

Degree of unanimity?

Type of ambivalence?

Taxonomy of Degrees of Flexibility

From Eddy, D. A Manual for Assessing Health Practices & Designing Practice Policies: The Explicit Approach . Philadelphia: American College of Physicians;1992.

Standard

Guideline

OptionBoundary

Pathway

Advise

physicia

ns

Prece

rtifica

tion

Utiliza

tion

revie

wCove

rage

Credentia

ling

Three Dimensions of Practice Policies

From Eddy, D. A Manual for Assessing Health Practices & Designing Practice Policies: The Explicit Approach . Philadelphia: American College of Physicians;1992.

Guideline for ChildrenGuideline for Children

Guideline for AdultsGuideline for Adults

ACIPACIP

• Advisory panel to HHS and CDCAdvisory panel to HHS and CDC• Statutory authority from CongressStatutory authority from Congress• Advise on communicable disease control, Advise on communicable disease control,

emphasis on vaccinesemphasis on vaccines• Route, dose, schedule, special populationsRoute, dose, schedule, special populations• 15 members plus non-voting liaison members15 members plus non-voting liaison members• Terminates April 2006Terminates April 2006

Status of New VaccinesStatus of New Vaccines

Table updated 11/15/05 http://aapredbook.aappublications.org/news/vaccstatus.shtml

VaccineVaccine ManufacturerManufacturer BLA to FDABLA to FDA BLA age BLA age indicationsindications

FDA license FDA license statusstatus

ACIP statusACIP status

MCV4MCV4 sanofi pasteursanofi pasteur Dec 2003Dec 2003 11-55 yrs11-55 yrs Lic 1/14/05Lic 1/14/05 See MMWRSee MMWR

VZ 2VZ 2ndnd dose dose MerckMerck Supp to Supp to originaloriginal

12 mo – 12 yr12 mo – 12 yr Lic 4/5/05Lic 4/5/05 Not rec June Not rec June 20052005

TdapTdap GSKGSK July 2004July 2004 10-18 yrs10-18 yrs Lic 5/3/05Lic 5/3/05 See ACIPSee ACIP

TdapTdap sanofi pasteursanofi pasteur Aug 2004Aug 2004 11-64 yrs11-64 yrs Lic 6/10/05Lic 6/10/05 See ACIPSee ACIP

MMRVMMRV MerckMerck Aug 2004Aug 2004 Same as Same as MMRMMR

9/6/059/6/05 Rec Oct-05 to Rec Oct-05 to be postedbe posted

HAVHAV Merck & GSKMerck & GSK Supp to Supp to originaloriginal

12 mo12 mo 8/15/05 & 8/15/05 & 10/18/0510/18/05

Rec Oct-05 to Rec Oct-05 to be postedbe posted

RotavirusRotavirus MerckMerck April 2005April 2005 2,4, & 6 mo2,4, & 6 mo To be To be reviewedreviewed

Pending Pending licensurelicensure

Zoster Zoster vaccinevaccine

MerckMerck April 2005April 2005 Older adultsOlder adults To be To be reviewedreviewed

Pending Pending licensurelicensure

InfluenzaInfluenza GSKGSK 5/25/055/25/05 18 yrs18 yrs 8/31/058/31/05 See MMWRSee MMWR

Hib/DTaP/IPVHib/DTaP/IPV sanofi pasteursanofi pasteur 7/25/057/25/05 2,4,6, and 15 2,4,6, and 15 to 18 mos.to 18 mos.

To be To be reviewedreviewed

Pending Pending licensurelicensure

Status of New VaccinesStatus of New Vaccines

Table updated 11/15/05 http://aapredbook.aappublications.org/news/vaccstatus.shtml

VaccineVaccine ManufacturerManufacturer BLA to FDABLA to FDA BLA age BLA age indicationsindications

FDA license FDA license statusstatus

ACIP statusACIP status

MCV4MCV4 sanofi pasteursanofi pasteur Dec 2003Dec 2003 11-55 yrs11-55 yrs Lic 1/14/05Lic 1/14/05 See MMWRSee MMWR

VZ 2VZ 2ndnd dose dose MerckMerck Supplement Supplement to originalto original

12 mo – 12 yr12 mo – 12 yr Lic 4/5/05Lic 4/5/05 NotNot rec June rec June 20052005

TdapTdap GSKGSK July 2004July 2004 10-18 yrs10-18 yrs Lic 5/3/05Lic 5/3/05 See ACIPSee ACIP

TdapTdap sanofi pasteursanofi pasteur Aug 2004Aug 2004 11-64 yrs11-64 yrs Lic 6/10/05Lic 6/10/05 See ACIPSee ACIP

MMRVMMRV MerckMerck Aug 2004Aug 2004 Same as Same as MMRMMR

Lic 9/6/05Lic 9/6/05 Rec Oct-05 Rec Oct-05 to be postedto be posted

HAVHAV Merck & GSKMerck & GSK Supplement Supplement to originalto original

12 mo12 mo 8/15/05 & 8/15/05 & 10/18/0510/18/05

Rec Oct-05 Rec Oct-05 to be postedto be posted

RotavirusRotavirus MerckMerck April 2005April 2005 2,4, & 6 mo2,4, & 6 mo To be To be reviewedreviewed

Pending Pending licensurelicensure

Zoster Zoster vaccinevaccine

MerckMerck April 2005April 2005 Older adultsOlder adults To be To be reviewedreviewed

Pending Pending licensurelicensure

InfluenzaInfluenza GSKGSK 5/25/055/25/05 18 yrs18 yrs Lic 8/31/05Lic 8/31/05 See MMWRSee MMWR

Hib/DTaP/IPVHib/DTaP/IPV sanofi pasteursanofi pasteur 7/25/057/25/05 2,4,6, and 15 2,4,6, and 15 to 18 mos.to 18 mos.

To be To be reviewedreviewed

Pending Pending licensurelicensure

TdapTdap

Scott A. Halperin, MDScott A. Halperin, MD

From the 39th National Immunization Conference – Washington, D.C. (March 2005)

TdapTdap

• Adolescent/adult formulation of tetanus Adolescent/adult formulation of tetanus and diphtheria toxoids plus acellular and diphtheria toxoids plus acellular pertussis vaccinepertussis vaccine– Reduced content of diphtheria toxoidReduced content of diphtheria toxoid– Reduced content of acellular pertussis Reduced content of acellular pertussis

antigensantigens

How frequent is pertussis in How frequent is pertussis in adolescents and adults?adolescents and adults?

• We still don’t know.

• Prospective population-based data– 3.7-4.5 cases/1000 person years

• Ward et al, APERT study

~800,000-1,000,000 cases annually in the United States

Clinical and Laboratory Course of Clinical and Laboratory Course of PertussisPertussis

ClinicalClinical picture picture

CultureCulture

Lympho-Lympho-cytosiscytosis

IncInc CatarrCatarr ParoxysmalParoxysmal ConvalescConvalesc

NoneNone CommonCommoncoldcold

Coughing Coughing paroxysms paroxysms followed by followed by vomiting, vomiting,

cyanosis, or cyanosis, or whoopwhoop

Gradual Gradual decrease in decrease in

frequency and frequency and severity of severity of coughing coughing episodesepisodes

Weeks after exposureWeeks after exposure00 11 22 33 44 55 66

- - - -- - - - ++++++++++++++++++ ++++++++++ - - - - - - - - - - - - - - - - - - - - - - - -

Stage Stage

Transmission of PertussisTransmission of Pertussis

• Adolescents get pertussis from community and Adolescents get pertussis from community and household contactshousehold contacts

• Adults get pertussis from their school age Adults get pertussis from their school age childrenchildren

• The disease ranges from asymptomatic to severeThe disease ranges from asymptomatic to severe• Adult and adolescent parents give pertussis to Adult and adolescent parents give pertussis to

their young infantstheir young infants• Young infants are at high risk of morbidity and Young infants are at high risk of morbidity and

even mortalityeven mortality

Extending Pertussis Immunizationto Adolescents and Adults

• Is there a disease of sufficient frequency to be prevented?

• Is the disease of sufficient severity to warrant prevention?

• Are there any other reasons to immunize?

• Is there a safe and effective vaccine?• Can the program be implemented?• Would immunization be cost effective?

• Yes

• Yes

• Yes/maybe• Yes• Yes• Yes

Options for implementationOptions for implementation

• Universal adolescentUniversal adolescent• Universal adolescent and adultUniversal adolescent and adult

– Young adultsYoung adults– Every 10 yearsEvery 10 years

• Targeted immunizationTargeted immunization– Cocoon strategy (infant households)Cocoon strategy (infant households)– Teachers, health care workers, child care Teachers, health care workers, child care

workersworkers– Pregnant womenPregnant women

Recommendations from June 2005Recommendations from June 2005

• ACIP recommended universal adolescent (11 ACIP recommended universal adolescent (11 – 18 years of age) use of Tdap in place of Td – 18 years of age) use of Tdap in place of Td in June 2005in June 2005

• Became CDC policy when published in Became CDC policy when published in MMWRMMWR

• Use in adults?Use in adults?– Deferred to a Oct 2005 meeting to give ACIP Deferred to a Oct 2005 meeting to give ACIP

members time to review data. Need better adult members time to review data. Need better adult burden of disease data.burden of disease data.

Latest on Tdap (11/9/05)Latest on Tdap (11/9/05)ADVISORY COMMITTEE ON IMMUNIZATION PRACTICE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICE RECOMMENDS ADULT VACCINATION WITH NEW TETANUS, RECOMMENDS ADULT VACCINATION WITH NEW TETANUS, DIPHTHERIA, AND PERTUSSIS VACCINE (Tdap)DIPHTHERIA, AND PERTUSSIS VACCINE (Tdap)

The Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices (ACIP) at its recent meeting (October 26 and 27) in Atlanta, voted to recommend that adults from 19 to 64 years of age be vaccinated with a newly licensed adult booster tetanus, diphtheria, and pertussis (whooping cough) vaccine (Tdap).

Under the ACIP recommendation, the Tdap vaccine would replace the currently recommended tetanus-diphtheria vaccine that is used as the adult booster vaccine.

Latest on Tdap (11/9/05)Latest on Tdap (11/9/05)ADVISORY COMMITTEE ON IMMUNIZATION PRACTICE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICE RECOMMENDS ADULT VACCINATION WITH NEW TETANUS, RECOMMENDS ADULT VACCINATION WITH NEW TETANUS, DIPHTHERIA, AND PERTUSSIS VACCINE (Tdap)DIPHTHERIA, AND PERTUSSIS VACCINE (Tdap)

The Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices (ACIP) at its recent meeting (October 26 and 27) in Atlanta, voted to recommend that adults from 19 to 64 years of age be vaccinated with a newly licensed adult booster tetanus, diphtheria, and pertussis (whooping cough) vaccine (Tdap).

Under the ACIP recommendation, the Tdap vaccine would replace the currently recommended tetanus-diphtheria vaccine that is used as the adult booster vaccine.

Tdap pearlTdap pearl

• Will eventually replace TdWill eventually replace Td

• Doubles the cost of previous strategy Doubles the cost of previous strategy that focused only on Tdthat focused only on Td

• Real beneficiary will be very young Real beneficiary will be very young infantsinfants

InfluenzaInfluenza

Influenza pearlsInfluenza pearls• Incrementalism in immunization policyIncrementalism in immunization policy• Rapid change in plans – both good and badRapid change in plans – both good and bad• Order vaccine early (as in April)Order vaccine early (as in April)• Pay attention to surveillancePay attention to surveillance

There are some people who should not be vaccinated without first consulting a physician. These include:

•severe allergy to chicken eggs. •severe reaction to TIV vaccination in the past. •developed Guillain-Barré syndrome (GBS) within 6 weeks of getting TIV vaccine previously. •TIV vaccine is not approved for use in children less than 6 months of age. •People who have a moderate or severe illness with a fever should wait to get vaccinated until their symptoms lessen

INFLUENZA - INFLUENZA - Who Should Who Should NotNot Be Vaccinated ? Be Vaccinated ?

Live Attenuated Influenza VaccineLive Attenuated Influenza Vaccine

• Important new tool for prevention of influenza in Important new tool for prevention of influenza in healthy persons 5-49 years healthy persons 5-49 years

• Administered by nasal spray, no preservativeAdministered by nasal spray, no preservative

• Efficacy in children 5-17 years (lab confirmed Efficacy in children 5-17 years (lab confirmed influenza)influenza)

– 87-93% (seasons with good vaccine match and 87-93% (seasons with good vaccine match and antigenically drifted circulating influenza strains) antigenically drifted circulating influenza strains)

• 1 dose 89% and 2 doses 94%1 dose 89% and 2 doses 94%

Belshe R et al NEJM 1998, Belshe et al CID 2004

Live Attenuated Influenza Vaccine Live Attenuated Influenza Vaccine (continued)(continued)

• Studies pending on comparative effectiveness of Studies pending on comparative effectiveness of live, attenuated versus inactivated influenza live, attenuated versus inactivated influenza vaccinesvaccines

• Additional safety data being collected for Additional safety data being collected for licensure among children 1-4 yearslicensure among children 1-4 years

• CAIV-T supplement to BLA early 2006?CAIV-T supplement to BLA early 2006?

Most promising intervention?Most promising intervention?

Jane Seward, M.B.B.S., M.P.H. Jane Seward, M.B.B.S., M.P.H.

Centers for Disease Control and PreventionCenters for Disease Control and Prevention

New Viral VaccinesNew Viral Vaccines

From the 39th National Immunization Conference – Washington, D.C. (March 2005)

MMRV VaccineMMRV Vaccine

• Merck and Co., Inc, licensing application filed Merck and Co., Inc, licensing application filed 2004. Licensed Sept 2005. ACIP 2004. Licensed Sept 2005. ACIP recommended Oct 2005 (to be posted)recommended Oct 2005 (to be posted)

• Lyophilized, frozen formulationLyophilized, frozen formulation• Immunological equivalency with MMR and V Immunological equivalency with MMR and V

vaccinesvaccines• Some increase in fever post vaccination Some increase in fever post vaccination

versus MMR aloneversus MMR alone• Potential to decrease number of injections in Potential to decrease number of injections in

childhood schedule and to increase varicella childhood schedule and to increase varicella vaccine coverage to equal MMR coveragevaccine coverage to equal MMR coverage

HAVHAV• Two versions with supplement to Two versions with supplement to

original license approved in late 2005original license approved in late 2005

• Recommended by ACIP Oct 2005 – to Recommended by ACIP Oct 2005 – to be postedbe posted

• Minimum age now 12 moMinimum age now 12 mo

• Universal – not just high risk statesUniversal – not just high risk states

IOM Report , (Viral) Vaccines for the IOM Report , (Viral) Vaccines for the 2121stst Century, United States Century, United States

Level 1Level 1

• CytomegalovirusCytomegalovirus

• Influenza (universal)Influenza (universal)

Level 2Level 2

• Hepatitis CHepatitis C

• Herpes simplex virusHerpes simplex virus

• Human papillomavirusHuman papillomavirus

• Respiratory syncytial virus (infants, elderly)Respiratory syncytial virus (infants, elderly)

Level 3Level 3

• Parainfluenza virusParainfluenza virus

• RotavirusRotavirus

Level 4Level 4

• Epstein-Barr virusEpstein-Barr virus

IOM Report, 2000, Vaccines for the 21st Century: tool for decision making

PreventivePreventive Viral Vaccines on the Horizon Viral Vaccines on the Horizon

• Live, attenuated influenza (1-4 years)Live, attenuated influenza (1-4 years)

• HPV (cervical dysplasia and cancer, HPV (cervical dysplasia and cancer, anogenital warts)anogenital warts)

• Rotavirus (RV diarrhea)Rotavirus (RV diarrhea)

• Zoster (shingles and post herpetic neuralgia)Zoster (shingles and post herpetic neuralgia)

New Vaccines for New Vaccines for Meningococcal DiseaseMeningococcal Disease

Nancy Rosenstein, MDNancy Rosenstein, MDMeningitis and Special Pathogens BranchMeningitis and Special Pathogens Branch

Division of Bacterial and Mycotic DiseasesDivision of Bacterial and Mycotic Diseases

39th National Immunization Conference – Washington, D.C.

March 2005

Rates of Meningococcal Disease by Age Group Rates of Meningococcal Disease by Age Group and Burden of Disease, U.S., 1991-2002*and Burden of Disease, U.S., 1991-2002*

0

5

10

15

20

25

<1 1 2-4 5-9 10-13 14-17 18-24 25-64 >=65

Burden of disease (%)

0

1

2

3

4

5

6

7

8

9

10

Rates per 100,000

Burden of Disease Rate per 100,000

*ABCs data

Rates of Meningococcal Disease by Age Rates of Meningococcal Disease by Age Group and Serogroup, U.S., 1992-2001*Group and Serogroup, U.S., 1992-2001*

0

1

2

<5 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 >=85

Rates per 100,000

B C Y W-135

*ABCs data

Changing Serogroup Changing Serogroup Distribution in the U.S.*Distribution in the U.S.*

1990-1992

B 43%

C 40%

Y 9%

W135 3%

1997-2001

B 25%

C 31% Y 37%

W135 2%

*ABCs

MCV4 (A/C/Y/W-135)MCV4 (A/C/Y/W-135)

• Licensed January 2005 for 11 – 55 yoaLicensed January 2005 for 11 – 55 yoa• BLA supplement to original filed March BLA supplement to original filed March

2005 for ages 2 – 10 years2005 for ages 2 – 10 years• 11 – 55 years recommended by ACIP and 11 – 55 years recommended by ACIP and

posted in 2005posted in 2005• Younger age pending licensureYounger age pending licensure• G-B Syndrome and shortage G-B Syndrome and shortage

ACIP Recommendations for ACIP Recommendations for Use of MCV4 and MPSV4Use of MCV4 and MPSV4

• Vaccination recommended forVaccination recommended for• Preadolescent visit and high school entryPreadolescent visit and high school entry• College freshmen living in dormitoriesCollege freshmen living in dormitories• Other groups at high riskOther groups at high risk

• Catch-up campaigns not recommendedCatch-up campaigns not recommended• Other individuals can chose to be Other individuals can chose to be

vaccinatedvaccinated• In 11-55 yo, MCV4 preferred, MPSV4 In 11-55 yo, MCV4 preferred, MPSV4

acceptableacceptable

Duration of Protection, Duration of Protection, MCV4MCV4

• MPSV4 in adults MPSV4 in adults >> 3-5 years protection 3-5 years protection• Conjugate vaccines induce memory and Conjugate vaccines induce memory and

higher antibody levels which should higher antibody levels which should provide longer protectionprovide longer protection

• UK studies =90% VE at 3 yrs in 11-18 yoUK studies =90% VE at 3 yrs in 11-18 yo• Therefore, we assume MCV4 will provide Therefore, we assume MCV4 will provide

protection of >8 yrs protection of >8 yrs

Routine Vaccination of Adolescents Routine Vaccination of Adolescents with MCV4with MCV4

• Goal is routine vaccination of young adolescents Goal is routine vaccination of young adolescents at pre-adolescent visit (11-12 year old)at pre-adolescent visit (11-12 year old)

• For adolescents who have not already received For adolescents who have not already received vaccine, vaccination at high school entry (15 vaccine, vaccination at high school entry (15 years old) is recommended as an effective years old) is recommended as an effective strategy to reduce meningococcal disease strategy to reduce meningococcal disease incidence in adolescents and young adults. incidence in adolescents and young adults.

• ACIP recognizes that supply may be an issue for ACIP recognizes that supply may be an issue for the first few yearsthe first few years

Routine Vaccination of AdolescentsRoutine Vaccination of Adolescents

• Other adolescent who wish to decrease their Other adolescent who wish to decrease their risk of meningococcal disease may elect to risk of meningococcal disease may elect to receive MCV4receive MCV4

• All 11-18 yo covered by VFCAll 11-18 yo covered by VFC

Last thoughts on immunizationLast thoughts on immunization

• The Immunization Action Coalition The Immunization Action Coalition www.immunize.orgwww.immunize.org

• ““The Pink Book”The Pink Book”• MMWR by e-mailMMWR by e-mail• Immunization registriesImmunization registries• Modify guidelines to suit your own practiceModify guidelines to suit your own practice• Educate your staff (see “The Pink Book”)Educate your staff (see “The Pink Book”)

Guideline for ChildrenGuideline for Children

Thank you and “Go Cowboys!”Thank you and “Go Cowboys!”

Well Visits By AgeWell Visits By Age

0

20

40

60

80

100

0 2 4 6 8 10 12 14 16 18 20 22 24

Age (years)

PercentAnnual Well

Visits

IMS National Disease and Therapeutic Index (NDTI) Projected-Total DiagnosisVisits - Calendar 2003 (000)NDTI.

US Census Bureau National Population Projections - Last Revised Date: January 19, 2001.