Vaccination of Adolescents

Andrew KrogerNational Center for Immunization and

Respiratory Diseases

National Assembly on School-based Health Care (NASBHC)

Disclosure

The speaker is a U.S. government employee and has no conflict or interest with any manufacturer of products

The speaker will discuss the use of Tdap in a manner that varies from the package insert

Adolescent Vaccination

The 11-12 Year Old Visit

•The recommended age for certain vaccines

•An opportunity to catch-up on lapsed vaccinations

Adolescent VaccinesRecommended1. Tdap or Td2. Meningococcal Conjugate3. Human Papillomavirus

Catch-up1. Hepatitis B2. MMR3. Varicella4. Polio

Risk Groups1. Pneumococcal Polysaccharide2. Influenza 3. Hepatitis A 4. Meningococcal Polysaccharide

Tetanus,reduced-diphtheria, acellular pertussis vaccine

Tetanus,reduced-diphtheria, acellular pertussis vaccine

Pertussis

Pertussis Clinical Features

Stages– Incubation period – 5-10 days (21 days

rare)

– Catarrhal Stage – 1-2 weeks

– Paroxysmal Stage – 1-6 weeks (10 days rare)

– Convalescent stage – 2-3 weeks

Pertussis Clinical Features

Complications – Secondary bacterial infection pneumonia

• More often in infants < 6 months

– Seizures, otitis media, anorexia, dehydration

– Complications from actual coughing: choking, epistaxis, subdural hematoma, hernia, rib fractures, rectal prolapse

Adolescent Pertussis Vaccination Objectives

Primary– Protect vaccinated adolescents

Secondary– Reduce B. pertussis reservoir– Potentially reduce incidence of pertussis in

other age groups

Tdap Vaccines

AdacelTM (sanofi pasteur)– Licensed June, 2005– Approved for persons 11-64 years of age

Boostrix® (GlaxoSmithKline)– Licensed May, 2005– Approved for persons 10-18 years of age

General Principles for Use ofTdap and Td Among Adolescents

• Tdap products are interchangeable

• Tdap preferred to Td to provide protection against pertussis

• Licensed only for a single dose at this time

• Tdap not approved or recommended for children 7-9 years of age

ACIP Recommendations for Tdap Vaccines

• Adolescents 11-12 years of age should receive a single dose of Tdap instead of Td*

• Adolescents 13-18 years who have not received Tdap should receive a single dose of Tdap as their catch-up booster instead of Td*

*if the person has completed the recommended childhood DTaP vaccination series, and has not yet received a Td booster

*if the person has completed the recommended childhood DTaP vaccination series, and has not yet received a Td booster

• ACIP encourages adolescents who received a Td booster to receive a single dose of Tdap to provide protection against pertussis*

• A 5-year interval between the Td and Tdap is encouraged to reduce the chance of a local reaction

ACIP Recommendations for Tdap VaccinesACIP Recommendations for Tdap Vaccines

*if the person has completed the recommended childhood DTaP vaccination series*if the person has completed the recommended childhood DTaP vaccination series

Minimum Interval Between Td and Tdap

• ACIP did not define an absolute minimum interval between Td and Tdap

• Provider will need to decide based on whether the benefit of pertussis immunity outweighs the risk of a local adverse reaction

Tdap For Persons Without AHistory of DTaP

• All adolescents should have documentation of having received a series of DTAP, DTP, DT, or Td

• Persons without documentation should receive a series of 3 vaccinations

• Preferred schedule:– Single dose of Tdap*– Td at least 4 weeks after the Tdap dose– Second dose of Td at least 6 months after the Td dose

**off-label recommendationoff-label recommendation**off-label recommendationoff-label recommendation

Tdap Contraindications

• Severe allergic reaction to a vaccine component or following a prior dose

• Encephalopathy within 7 days of administration of a pertussis vaccine that is not attributable to another identifiable cause

Tdap Precautions

• History of an Arthus-type reaction following a previous dose of tetanus- or diphtheria-containing vaccine

• Progressive neurological disorder, uncontrolled epilepsy, or progressive encephalopathy

• History of Guillain-Barré syndrome (GBS) within 6 weeks after a previous dose of tetanus toxoid-containing vaccine

• Moderate or severe acute illness

Conditions NOT Precautionsfor Tdap

Following a dose of DTaP/DTP:– Temperature 105o F (40.5o C) or higher– Collapse or shock-like state– Persistent crying lasting 3 hours or longer– Convulsions with or without fever– History of an extensive limb swelling reaction

DTaP and Tdap Administration Errors

ErrorDTaP given to person >7 years

Tdap given to child <7 years as DTaP #1, 2, or 3

Tdap given to child <7 years as DTaP #4 or 5

ErrorDTaP given to person >7 years

Tdap given to child <7 years as DTaP #1, 2, or 3

Tdap given to child <7 years as DTaP #4 or 5

Action

Count dose as valid

Do not count dose; give DTaP now

Count dose as valid

Action

Count dose as valid

Do not count dose; give DTaP now

Count dose as valid

Meningococcal Conjugate Vaccine

Meningococcal Conjugate Vaccine

Meningococcal Vaccine

Recommended for:– all persons at the preadolescent visit (ages 11-

12 years)– persons about to enter high school (age 15

years)– college freshmen living in a dormitory– other adolescents who wish to reduce their risk

for meningococcal disease

MMWR 2005;54(RR-7)MMWR 2005;54(RR-7)

18-23 years old 1.4 / 100,000

18-23 years old not college student 1.4 / 100,000

Freshmen 1.9 / 100,000

Freshmen in dorm 5.1 / 100,000

Meningococcal Disease Meningococcal Disease Among Young Adults, United Among Young Adults, United

States, 1998-1999States, 1998-1999

Bruce et al, JAMA 2001;286;688-93

Meningococcal Vaccine

Recommended for certain high-risk persons:

– military recruits– certain research and laboratory personnel– travelers to and U.S. citizens residing in

countries in which N. meningitidis is hyperendemic or epidemic

Meningococcal Belt

Meningococcal Vaccine

Recommended for certain high-risk persons:

– complement component deficiency– functional or anatomic asplenia– HIV infection (“should be considered”)

Conjugate Conjugate vaccine - MCVvaccine - MCV

Meningococcal Vaccines

Menomune – ‘old’

4 types – A,C,Y,W-135

Approved for >2 yrs of age

1 dose, selective revaccination

Subcutaneous injection

Menactra – new

4 types– A,C,Y,W-135

Approved for 11-55 years of age

1 dose, (currently) no revaccination

Intramuscular injection

Meningococcal Conjugate VaccineContraindications and Precautions

Contraindications

Severe allergic reaction to vaccine component or following prior dose

Precautions

Moderate or severe acute illnessMenactra: prior history of Guillain-Barré if not extremely high risk for

meningococcal disease

MCV: Extremely High Risk

•Microbiologists routinely exposed to isolates of Neisseria meningitidis

Human Papillomavirus

Human Papillomavirus (HPV) Vaccine

A vaccine to prevent cervical cancer

Licensed for 9-26 year olds as:

Gardasil™– Merck- Quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP Vaccine

Cervarix™- GlaxoSmithKline (GSK) pending licensure (Types 16 and 18)

Human Papillomavirus Vaccine

Human Papillomavirus Vaccine

HPV Prevalence: Population Estimates, U.S.

20 million people are infected 6.2 million new infections each year> 50% of sexually active men & women acquire

genital HPV infection74% of new infections occur in persons 15 – 24

years of age

W. Cates, STD April 1999, Weinstock, Perspectives on Sexual and Reproductive Health 2004, Koutsky Am J Med 1997

Human PapillomavirusHuman Papillomavirus>100 types>100 types

CutaneousCutaneous(~60 types)(~60 types)

““CommonCommon””wartswarts

((hands/hands/feet)feet)

MucosalMucosal(~(~4040 types)types)

““high-risk”high-risk”typestypes

(16,18)(16,18)

““low-risk”low-risk”typestypes (6,11)(6,11)

• low grade cervical low grade cervical abnormalitiesabnormalities

• high grade abnormalities/high grade abnormalities/ cancer precursors cancer precursors • anogenital cancersanogenital cancers

• low grade cervical low grade cervical abnormalitiesabnormalities

• genital wartsgenital warts• respiratory papillomasrespiratory papillomas

Skin Warts and Tags

Background: HPV-associated Conditions HPV types 16,

18, 6, 11

Clifford GM, BJ Ca 2003, Munoz Int J Cancer 2004; Brown J Clin Micro 1993; Carter Cancer Res 2001;Clifford Cancer Epi Biomarkers Prev 2005; Gissman Proc Natl Acad Science 1983;Kreimer Cancer Epidemiol Biomarkers Prev. 2005* All oncogenic types

HPV types 16, 18

Cervical cancer 70%

High/low grade cervical abnormalities 40%

Anal, vulvar, vaginal, penile 70%*

Head and neck cancers 10%

HPV 6, 11

Low grade cervical abnormalities 10%

Genital warts 90%

RRP 90%

Cervical Cancer Mortality Rates U.S., 1946-1984

0

2

4

6

8

10

1246 48 50 52 54 56 58 60 62 64 66 68 70 72 74 76 78 80 82 84

Year

Mo

rtal

ity

Rat

e (p

er 1

00,0

00)

Source: Program for Improving Clinical Pap Smear Programs and Management, Office of Population Affairs, DHHS, 1987.

Source: Program for Improving Clinical Pap Smear Programs and Management, Office of Population Affairs, DHHS, 1987.

Efficacy for Prevention of Clinical HPV Disease Due to HPV

6/11/16/18*

EndpointVaccine

N CasesPlacebo

N Cases Efficacy (95% CI)

HPV 16/18related CIN2/3 or AIS

8487 0 8460 53 100 (93,100)

HPV 6/11/16/18related CIN

7858 4 7861 83 95 (87, 99)

HPV 6/11/16/18related Genital warts

7897 1 7899 91 99 (94,100)

*Integrated dataset; results in the Per-Protocol Populations

Immunogenicity Bridge

Antibody Titers by Age at Enrollment Anti-HPV 6 GMTs (Quadrivalent HPV vaccine)

9 10 11 12 13 14 15 16 17 18 19 20 21 22 23Age at Enrollment (Years)

500

700

900

1100

1300

15001600

Ser

um

GM

T w

ith

95%

CI,

mM

U/m

L

Efficacy Program

Merck, unpublished data, ACIP presentation by Eliav Barr, February 2006

Potential Unintended Consequences of HPV

Vaccine– Research shows generally low levels of HPV knowledge

– Multiple influences on adolescent sexual behavior

– Fear of STD not apparent major motivation for abstinence

Increase in sexual risk unlikely

Pediatricians’ Intention to Recommend HPV Vaccine for Female and Male Patients, by

Age

0

10

20

30

40

50

60

70

80

90

100

11 year olds 14 year olds 17 year olds

% s

om

ew

hat

or

extr

em

ely

lik

ely

female

male

Kahn J et al. Journal of Adolescent Health 2005

Quadrivalent HPV Vaccine

Summary

High efficacy in 16 to 26 year-old females who are naïve to the HPV vaccine type– HPV 16,18 related CIN 2/3 – HPV 6,11,16,18 related CIN – HPV 6,11,16,18 related external genital lesions

No evidence of efficacy against disease in persons already infected with relevant type

Efficacy data available through 5; duration of protection and need for booster unknown

Safe; side effects mainly local reactions

Recommendations

Routine vaccination Catch-up vaccination Special situations Precautions and contraindications

Routine Vaccination Recommendation

ACIP recommends routine vaccination of females 11-12 years of age with three doses of quadrivalent HPV vaccine

The vaccination series can be started as young as 9 years of age

Rationale: Routine Vaccination Females at 11-12 Years

Routine– Prevalent infection, targeting ‘high risk’ groups not possible

– Modeling shows greater impact

11-12 years– Vaccination prior to sexual debut

– Implementation advantages; consistent with young adolescent health care visit

– High antibody titers after vaccination at this age

– Data through 5 years show no evidence of waning immunity; ongoing studies will monitor duration of protection

Females 13-26 Years Recommendation

Vaccination is recommended for females 13-26 years of age who have not been previously vaccinated

Ideally vaccine should be administered before onset of sexual activity, but females who are sexually active should still be vaccinated

Rationale: Vaccination of Females 13-26 Years

Females not yet sexually active can be expected to have the full benefit of vaccination

Sexually active females may not have full benefit of vaccine because they may have been infected with vaccine HPV types,

however:

– Only a small percentage are likely to have been infected with all four vaccine HPV types

– For those already infected with >1 vaccine HPV types, vaccine would provide protection against disease caused by the other vaccine HPV types

– Therefore, although overall vaccine effectiveness would be lower, most females will still derive benefit from

vaccination

Special Situations

Equivocal or abnormal Pap test

Positive HPV testGenital warts

Cervical Cancer Screening

Cervical cancer screening – no change

– 30% of cervical cancers caused by HPV types not in the quadrivalent HPV vaccine

– Vaccinated females could subsequently be infected with non-vaccine HPV types

– Sexually active females could have been infected prior to vaccination

Decision to vaccinate should not be based on Pap testing, HPV DNA testing or HPV serologic testing

Providers should education women about the importance of cervical cancer screening

Cervical Cancer Screening Recommendations

USPSTF2003

ACS2002

ACOG2003

Age to start Age 21 or within 3 yrs of sexual activity

Age 21 or within 3 yrs of sexual activity

Age 21 or within 3 yrs of sexual

activity

Interval <30 yr

≥ 30 yr

Conv: at least every 3 yrs

Conv: 1 yr LBC: 2 yr

2-3 yrs

1 yr

2-3 yrs

USPSTF – U.S. Preventive Services Task ForceACS – American Cancer SocietyACOG – American College of Obstetricians and GynecologistsConv – Conventional Cervical CytologyLBC – Liquid-based Cytology

USPSTF – U.S. Preventive Services Task ForceACS – American Cancer SocietyACOG – American College of Obstetricians and GynecologistsConv – Conventional Cervical CytologyLBC – Liquid-based Cytology

Precautions and Contraindications

Contraindication: History of immediate hypersensitivity or severe allergic reaction to yeast or to any vaccine component

Precaution: Moderate or severe acute illnesses: should be deferred until after the illness improves

Vaccination during Pregnancy:Recommendation

Initiation of the vaccine series should be delayed until after completion of the pregnancy

If a woman is found to be pregnant after initiating the vaccination series, completion should be

delayed until after the pregnancy  

If a vaccine dose has been administered during pregnancy, there is no indication for intervention

Questions?