1. Vaccination of Adolescents Andrew Kroger National Center for Immunization and Respiratory Diseases National Assembly on School- based Health Care (NASBHC)

2. 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

3. Adolescent Vaccination

4. The 11-12 Year Old Visit The recommended age for certain vaccines An opportunity to catch- up on lapsed vaccinations

5. Adolescent Vaccines Recommended 1.Tdap or Td 2.Meningococcal Conjugate 3.Human Papillomavirus Catch-up 1.Hepatitis B 2.MMR 3.Varicella 4.Polio Risk Groups 1.Pneumococcal Polysaccharide 2.Influenza 3.Hepatitis A 4.Meningococcal Polysaccharide

6. Tetanus,reduced-diphtheria, acellular pertussis vaccine

8. Pertussis

9. 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

10. 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

11. Adolescent Pertussis Vaccination Objectives Primary –Protect vaccinated adolescents Secondary –Reduce B. pertussis reservoir –Potentially reduce incidence of pertussis in other age groups

12. Tdap Vaccines Adacel TM (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

13. General Principles for Use of Tdap 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

14. 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

15. 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 Vaccines *if the person has completed the recommended childhood DTaP vaccination series

16. 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

17. Tdap For Persons Without A History 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 recommendation

18. 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

19. 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

20. Conditions NOT Precautions for Tdap Following a dose of DTaP/DTP: –Temperature 105 o F (40.5 o 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

21. DTaP and Tdap Administration Errors Error DTaP 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 Error DTaP 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

22. Meningococcal Conjugate Vaccine

25. 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)

26. 18-23 years old1.4 / 100,000 18-23 years old not college student1.4 / 100,000 Freshmen 1.9 / 100,000 Freshmen in dorm5.1 / 100,000 Meningococcal Disease Among Young Adults, United States, 1998-1999 Bruce et al, JAMA 2001;286;688-93

27. 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

28. Meningococcal Belt

29. Meningococcal Vaccine Recommended for certain high-risk persons: –complement component deficiency –functional or anatomic asplenia –HIV infection (“should be considered”)

30. Conjugate vaccine - MCV

31. 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

32. Meningococcal Conjugate Vaccine Contraindications and Precautions Contraindications Severe allergic reaction to vaccine component or following prior dose Precautions Moderate or severe acute illness Menactra: prior history of Guillain-Barré if not extremely high risk for meningococcal disease

33. MCV: Extremely High Risk Microbiologists routinely exposed to isolates of Neisseria meningitidis

34. Human Papillomavirus

35. 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)

36. Human Papillomavirus Vaccine

38. 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 infection 74% 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

39. Human Papillomavirus >100 types Cutaneous (~60 types) “Common” warts ( hands/feet) Mucosal (~40types) (~40 types) “high-risk” types(16,18) “low-risk” types (6,11) (6,11) low grade cervical abnormalities high grade abnormalities/ high grade abnormalities/ cancer precursors cancer precursors anogenital cancers anogenital cancers low grade cervical abnormalities genital warts genital warts respiratory papillomas respiratory papillomas

40. Skin Warts and Tags

41. 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%

42. Cervical Cancer Mortality Rates U.S., 1946-1984 Source: Program for Improving Clinical Pap Smear Programs and Management, Office of Population Affairs, DHHS, 1987.

43. Efficacy for Prevention of Clinical HPV Disease Due to HPV 6/11/16/18* Endpoint Vaccine N Cases Placebo N Cases Efficacy(95% CI) HPV 16/18 related CIN2/3 or AIS 8487 08460 53 100(93,100) HPV 6/11/16/18 related CIN 7858 47861 83 95(87, 99) HPV 6/11/16/18 related Genital warts 7897 17899 91 99(94,100) *Integrated dataset; results in the Per-Protocol Populations

44. Immunogenicity Bridge Antibody Titers by Age at Enrollment Anti-HPV 6 GMTs (Quadrivalent HPV vaccine) 91011121314151617181920212223 Age at Enrollment (Years) 500 700 900 1100 1300 1500 1600 Serum GMT with 95% CI, mMU/mL Efficacy Program Merck, unpublished data, ACIP presentation by Eliav Barr, February 2006

45. 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

46. Pediatricians ’ Intention to Recommend HPV Vaccine for Female and Male Patients, by Age Kahn J et al. Journal of Adolescent Health 2005

47. Additional Visits Needed for Females, 1 st HPV Vaccine at Well Visit vs. Any Visit 24 mo window to vaccinate Type of visit 1 st vaccine *Adapted from Dr. Cynthia Rand, Univ Rochester

48. 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

49. Recommendations Routine vaccination Catch-up vaccination Special situations Precautions and contraindications

50. 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

51. 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

52. 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

53. 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

54. Special Situations Equivocal or abnormal Pap test Positive HPV test Genital warts

55. 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

56. Cervical Cancer Screening Recommendations USPSTF 2003 ACS 2002 ACOG 2003 Age to startAge 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 Force ACS – American Cancer Society ACOG – American College of Obstetricians and Gynecologists Conv – Conventional Cervical Cytology LBC – Liquid-based Cytology

57. 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

58. 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

60. Questions?