1. William Atkinson, MD, MPH* Idaho Immunization Conference Boise, Idaho September 30 2013 Vaccine Update *Representing the Immunization Action Coalition, Saint Paul, MN

2. Disclosures William Atkinson has no financial conflict or interest with the manufacturer of any product named during this presentation The speaker will discuss the use of Tdap and HPV vaccines in a manner not approved by the Food and Drug Administration (FDA) but recommended by ACIP The speaker will not discuss vaccines not licensed by the FDA

3. Disclosures The recommendations to be discussed are primarily those of the Advisory Committee on Immunization Practices (ACIP)  composed of 15 experts in clinical medicine and public health who are not government employees  provides guidance on the use of vaccines and other biologic products to the Department of Health and Human Resources, CDC, and the U.S. Public Health Service www.cdc.gov/vaccines/recs/acip /

4. What’s New in Immunization 2013 schedules Influenza vaccine Tdap in pregnancy Meningococcal vaccines HPV vaccines Vaccine hesitancy

5. 2013 Immunization Schedules Published in MMWR on February 1, 2013 Childhood, adolescent and adult schedules published together for the first time Childhood and adolescent schedules merged (separate schedules since 2007) Footnotes consolidated Download schedules from CDC website www.cdc.gov/vaccines/schedules/

6. Influenza Vaccine Abbreviations TIV (Trivalent Inactivated Influenza Vaccine) replaced with IIV (Inactivated Influenza Vaccine):  IIV refers to inactivated vaccines (egg and cell- culture based)  Includes trivalent (IIV3) and quadrivalent (IIV4) vaccines;  Where necessary, cell-culture-based IIV is referred to as ccIIV/ccIIV3; RIV refers to recombinant HA influenza vaccine  Trivalent (RIV3) for 2013-14; LAIV refers to Live Attenuated Influenza Vaccine  Quadrivalent (LAIV4), for 2013-14).

7. Influenza Vaccine Virus Strains for 2013-14 Trivalent vaccines will contain:  An A/California/7/2009 (H1N1)-like virus,  An H3N2 virus antigenically like the cell- propagated prototype virus A/Victoria/361/2011, and  A B/Massachusetts/2/2012-like virus (Yamagata lineage) Quadrivalent vaccines, will contain, in addition:  A B/Brisbane/60/2008-like virus (Victoria lineage)

8. Recently-approved Influenza Vaccines Quadrivalent influenza vaccine, live attenuated (LAIV4):  Flumist Quadrivalent (MedImmune) Quadrivalent influenza vaccines, inactivated (IIV4):  Fluarix Quadrivalent (GSK)  Fluzone Quadrivalent (Sanofi Pasteur) Cell culture-based influenza vaccine (ccIIV3):  Flucelvax (Novartis) Recombinant hemagglutinin (HA) vaccine (RIV3):  FluBlok (Protein Sciences) www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm093830.htm

9. 9 Quadrivalent Influenza Vaccines Rationale Two lineages of influenza B viruses: Victoria and Yamagata  Immunization against virus from one lineage provides only limited cross- protection against viruses in the other Trivalent vaccines contain only one B vaccine virus  Only one B lineage is represented Predominant lineage is difficult to predict in advance of the season Quadrivalent vaccines contain one virus from each B lineage

10. 10 Flumist Quadrivalent (LAIV4) (MedImmune) Will replace trivalent LAIV starting 2013-14  Same presentation (intranasal sprayer) and administration Recommendations same as those for trivalent LAIV  Healthy, non-pregnant persons aged 2-49 years Similarly immunogenic to LAIV3 No preferential recommendation for LAIV vs. IIV where either is otherwise appropriate Acceptable alternative to other licensed products used within indications and recommendations

11. 11 Fluarix Quadrivalent (IIV4) (GSK) Approved for persons aged 3 years and older Available in 0.5mL prefilled syringes for IM injection Both Fluarix (IIV3) and Fluarix Quadrivalent (IIV4) available  Likely more IIV3 available than IIV4 during 2013-14 Similarly immunogenic to trivalent Acceptable alternative to other licensed products used within indications and recommendations

12. 12 Fluzone Quadrivalent (IIV4) (sanofi) Approved for persons aged 6 months and older  Three different presentations, all for IM injection 0.25 mL prefilled syringes for 6 through 35 months Also in 0.5mL syringes and 0.5 mL vials Both Fluzone (IIV3) and Fluzone® Quadrivalent (IIV4) will be available  Likely more IIV3 available than IIV4 in 2013-14 Similarly immunogenic to trivalent Acceptable alternative to other licensed products used within indications and recommendations

13. 13 Influenza Vaccine Preference ACIP has not stated a preference for quadrivalent or trivalent influenza vaccine in any age or risk group All influenza vaccines should be used only in the age group approved by the Food and Drug Administration

14. 14 Vaccines Produced via Non-Egg- Based Technologies May permit more rapid scale up of vaccine production (e.g., as might be needed during a pandemic) Two vaccines this season, both trivalent:  Cell culture-based  Recombinant hemagglutinin (HA)

15. 15 Flucelvax (ccIIV3) (Novartis) Approved for persons aged 18 and older Vaccine virus propagated in Madin Darby Canine Kidney cells Available in 0.5mL single dose vials for IM injection Vaccine viruses for ccIIV are not propagated in eggs; however, initial reference strains have been passaged in eggs  cannot be considered egg-free, though expected to contain less egg protein than other IIVs Acceptable alternative to other licensed products used within indications and recommendations

16. 16 FluBlok (RIV3) (Protein Sciences) Approved for persons aged 18 through 49 years Vaccine contains recombinant influenza virus hemagglutinin  Protein is produced in insect cell line  No eggs or influenza viruses used in production Available in 0.5mL single-dose vials for IM injection Egg-free Acceptable alternative to other licensed products used within indications and recommendations

17. 17 Other Vaccines Available for 2013-14 Standard dose IIVs (multiple brands)  For persons age 6 months and older, BUT age indications differ by brand High dose IIV (Fluzone High Dose)—65 yrs. and over Intradermal IIV (Fluzone Intradermal)— 18 through 64 yrs. ACIP currently expresses no preferences

18. 18 Influenza Vaccination for Persons with Egg Allergies—2011-12 and 2012-13 Can the individual eat lightly cooked egg (e.g., scrambled egg) without reaction?*† After eating eggs or egg-containing foods, does the individual experience ONLY hives? After eating eggs or egg-containing foods, does the individual experience other symptoms such as:  Cardiovascular changes (e.g., hypotension)  Respiratory distress (e.g., wheezing)  Gastrointestinal (e.g., nausea/vomiting)  Reaction requiring epinephrine  Reaction requiring emergency medical attention Administer vaccine per usual protocol Yes Administer IIV Observe for reaction for at least 30 minutes following vaccination No Refer to a physician with expertise in management of allergic conditions for further evaluation Yes No

19. 19 Influenza Vaccination for Persons with Egg Allergies—2013-14: First Modification Can the individual eat lightly cooked egg (e.g., scrambled egg) without reaction?*† After eating eggs or egg-containing foods, does the individual experience ONLY hives? After eating eggs or egg-containing foods, does the individual experience other symptoms such as:  Cardiovascular changes (e.g., hypotension)  Respiratory distress (e.g., wheezing)  Gastrointestinal (e.g., nausea/vomiting)  Reaction requiring epinephrine  Reaction requiring emergency medical attention Administer vaccine per usual protocol Yes Administer RIV3, if patient aged 18 through 49 yrs.; OR Administer IIV Observe for reaction for at least 30 minutes following vaccination No Administer RIV3, if patient aged 18 through 49 yrs.; OR Refer to a physician with expertise in management of allergic conditions for further evaluation Yes No

20. 20 Influenza Vaccination for Persons with Egg Allergies—2013-14: Second Modification Addition of the following: For individuals with no known history of exposure to egg, but who are suspected of being egg-allergic on the basis of previously performed allergy testing:  Consultation with a physician with expertise in the management of allergic conditions should be obtained prior to vaccination  Alternatively, RIV3 may be administered if the recipient is aged 18 through 49 years

21. 21 One Dose or Two? Vaccine for Children 6 Months Through 8 Years Children aged 6 months through 8 years require 2 doses in first season they are vaccinated If previously vaccinated, need to have received 2009(H1N1)-containing vaccine (2009 monovalent, or 2010-11, 2011-12, or 2012-13 seasonal vaccines) This season (as the last), there are two acceptable approaches for determining the number of doses These differ in whether or not vaccination history prior to the 2010-2011 season is considered MMWR 2012; 61(32):613-618.

22. 22 Dose algorithm for 6mo through 8yr olds, 2013-14 season—First approach MMWR 2012; 61(32):613-618. * Doses should be administered a minimum of 4 weeks apart.

23. 23 Dose algorithm for 6mo through 8yr olds, 2013-2014 season—Alternative approach If vaccination history before 2010–11 is available If child received  ≥2 seasonal influenza vaccines during any previous season,  And ≥1 dose of a 2009(H1N1)-containing vaccine (monovalent 2009(H1N1) or 2010-11, 2011-12 or 2012-13 seasonal vaccine),  Then the child needs only 1 dose in 2013–14.  Children 6mos—8yrs for whom this is not the case need 2 doses Need only 1 dose of vaccine in 2013–14 if :  ≥2 doses of seasonal influenza vaccine since July 1, 2010; or  ≥2 of seasonal influenza vaccine before July 1, 2010, and ≥1 dose of monovalent 2009(H1N1) vaccine; or  ≥1 dose of seasonal influenza vaccine before July 1, 2010, and ≥1 dose of seasonal influenza vaccine since July 1, 2010. MMWR 2012; 61(32):613-618.

24. Health Care Personnel and Influenza Vaccination Source: www.cdc.gov/flu/pdf/fluvaxview/hcp-ips-nov2012.pdf Influenza Vaccination Rates (internet panel, Nov 2012) OccupationRate Pharmacists88.7% Physicians83.8% Nurses81.5% Other76.7% 2020 Healthy People Goal is 90% Lowest among assistants/ aides (43.4%) and administrative/non-clinical support staff (54.5%)

25. 25 H7N9 Avian Influenza First human infections - 132 cases and 37 deaths* most from Shanghai and all from China Most cases believed to have had contact with birds No evidence of sustained person-to- person transmission Aggressive control measures since April 2013 *as of May 30, 2013

26. 26 Pertussis in the U.S. – 2012 Nationwide – provisional 2012  41,880 reported cases More than twice as many cases as in 2011 year (2011=18,719) Several outbreaks or increased activity in several states in 2012 17 deaths reported (14 among infants less than 3 months of age) 12,424 cases reported in 2013 (as of August 4) CDC unpublished data, www.cdc.gov/pertussis/outbreaks.html MMWR 61 (37) ND-516

27. 27 Pertussis-Containing Vaccines DTaP (pediatric)  Approved for ages 6 weeks through 6 years  3 doses needed for protection Tdap (adolescents and adults)  Boostrix (GlaxoSmithKline) - approved for persons 10 years of age and older  Adacel (sanofi pasteur) - approved for persons ages 11 through 64 years  Neither approved by FDA for persons 7 through 9 years of age  Both approved as a single booster dose

28. 28 Pertussis Vaccine Effectiveness DTaP  Very good short-term protection  Effectiveness wanes over time  Even modest waning, with high exposure, can result in Infection of vaccinated children Increase rates of disease in communities Tdap  Despite high adolescent vaccination rates, a lot of disease in this age group  Effectiveness and duration of protection being evaluated

29. 29 Adolescent Tdap Recommendations Routinely recommended at 11 - 12 years of age Catch up 13 through 18 years who have not been vaccinated with Tdap Children 7 through 10 years who are not “fully vaccinated against pertussis”*  “fully vaccinated against pertussis” is 5 doses of DTaP, or 4 doses of DTaP if the fourth dose was administered on or after the fourth birthday *Off-label recommendation. MMWR 2011; 60 (No. 1):13-5

30. 30 Adult Tdap Recommendations Administer Tdap to unvaccinated adults 19 years and older including a dults over 65 years of age* Tdap should be administered as soon as feasible to unvaccinated  healthcare personnel with direct patient contact  close contacts of infants younger than 12 months of age, including unvaccinated postpartum women *Off-label recommendation for Adacel. MMWR 2011; 60 (No.41):1);1424-1426

31. 31 Tdap - Additional Information There is no minimum interval between the last dose of tetanus toxoid- containing vaccine and a dose of Tdap If possible, Boostrix should be used for adults 65 years of age and older  Administer Adacel* if Boostrix is not available *Off-label recommendation. MMWR 2011; 60 (No.1):13-5

32. 32 Tdap and Pregnant Women Administer a dose of Tdap vaccine to during each pregnancy irrespective of the woman’s prior history of receiving Tdap* To maximize passive transfer of antibody to the fetus optimum timing of Tdap is between 27 and 36 weeks gestation Tdap may be administered earlier in pregnancy if necessary (e.g. wound management) *Off-label recommendation. MMWR 2013:62( (No.7): 131-135

33. Meningococcal Disease Incidence, United States, 1970-2011 1970-1996 NNDSS data, 1997-2011 ABCs data estimated to U.S. population with 18% correction for under reporting *In 2010, estimated case counts from ABCs were lower than cases reported to NNDSS and may not be representative

34. 34 Meningococcal Vaccines VaccineTypeAge MenomunePS2 yrs and older MenactraConj9 mos – 55 yrs MenveoConj2 mos* – 55 years MenHibrixConj6 wks – 18 mos *as of August 1, 2013

35. 35 Meningococcal Vaccine Recommendations Routine vaccination of adolescents at 11-12 years with booster dose at 16 years Routine vaccination persons 2 months and older at increased risk of meningococcal disease  Medical conditions (asplenia, complement deficiency)  Previously unvaccinated first-year college students living in a resident hall <22 years of age  Military recruits  Microbiologists  Persons 9 months and older who travel or live in endemic areas

36. 36 HibMenCY (MenHibrix) (GSK) Approved by FDA in June 2012 Contains Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y polysaccharides conjugated to tetanus toxoid Approved for 4 doses among children 6 weeks through 18 months of age Approved schedule is doses at 2, 4, 6 and 12 through 15 months of age

37. 37 Meningococcal Vaccine Recommendations ACIP does not recommend routine meningococcal vaccination of infants Infants at increased risk for meningococcal disease should be vaccinated with 4 doses of HibMenCY (or Menveo?*)  persistent complement pathway deficiencies  anatomic or functional asplenia including sickle cell disease HibMenCY (or Menveo?*) can be used in infants ages 2 through 18 months who are in communities with meningococcal disease outbreaks *ACIP has not made a recommendation on the use of Menveo in children

38. 38 Human Papillomavirus (HPV) 20 million currently infected  Half of infections are among persons 15 through 24 years of age Infection occurs soon after sexual debut Most sexually active adults become infected at some point in their life Most severe disease occurs from persistent infection

39. HPV-Associated Cancers in the United States 33,369 HPV-associated cancers diagnosed annually (2004-2008)  12,080 men  21,290 women American Cancer Society. www.cancer.org/acs/groups/. Gillison ML, et al. Cancer. 2008;113(10 Suppl) 3036-3046; MMWR 2012;61:268-261 SiteTotal Cancers Attributable to HPV Cervix12,17096% Anus623093% Vagina268064% Oropharynx27,48063% Vulva449051% Penis157036%

40. HPV Immunization Rates*, NIS-Teen, 2011 Females13-17 Years of Age *Percentages 1 or more human papillomavirus vaccine doses, either HPV4 or HPV2 reported among females only (n=9,220) ** Percentage of females who received 3 doses among those who had at least 1 HPV dose and at least 24 weeks between the first dose and interview date MMWR 2012; 61 (No. 34): 671- 677 HPV VaccineU.S.ID 1 or more doses53.0%45.5% 3 dose series completion ** 70.7%73.3%

41. Actual and Potentially Achievable Vaccination Coverage if Missed Opportunities Were Eliminated: NIS-Teen, 2011 Healthy People 2020 Objectives HPV-1 coverage is among females only. Source: NIS Teen 2011; Slide courtesy Shannon Stokley (CDC/NCIRD/ISD)

42. Pediatrics 2013;131:645–651

43. 43 ACIP HPV Vaccine Recommendations 2 products: HPV2 (Cervarix) and HPV4 (Gardasil)  Approved for ages: 9 through 26 years* Both products are a 3 dose series Schedule*:  Administer the 2nd dose 1-2 months after dose 1  Administer the 3rd dose 6 months (24 weeks) after dose 1 and at least 12 weeks after dose 2 *Off-label recommendation. Cervarix FDA approved 9 – 25 yrs. MMWR; (59)20; 626-629

44. ACIP HPV Vaccination Recommendations Females Routine: 11 or 12 years Catch-up: 13 through 26 years Administer HPV4 or HPV2 Males Routine: 11 or 12 years Catch-up: 13 through 21 yrs All 22 through 26 years Immunocompromised HIV infected MSM Healthy men: 22 -26 years may be vaccinated Administer HPV4 only MMWR 2011;60(No. 50):1705-8.

45. 45 Strategies for Increasing HPV Vaccination Rates in Clinical Practice Recommend HPV vaccine!  Include HPV vaccine when discussing other needed vaccines Integrate standard procedures supporting vaccination  Assess for needed vaccines at every clinical encounter  Immunize at every opportunity  Standing orders Reminder and recall Tools for improving uptake of HPV: www.cdc.gov/vaccines/teens

46. 46 Causes of Parent/Guardian Vaccine Hesitancy “Lifestyle” issues Political issues Fear of side effects  No vaccine has ever been shown to cause autism, SIDS, or any other chronic condition

47. 47 Children With Personal Belief Exemption 9-fold higher risk of varicella (Colorado, 1998-2008) 23-fold higher risk of pertussis (Colorado, 1996-2007) Introduce vaccine-preventable diseases (particularly measles) into school settings Expose children with medical exemptions to infection

48. 48 Personal Belief Exemptions Permitting personal belief exemptions and easily granting exemptions are associated with higher and increasing nonmedical U.S. exemption rates State policies granting personal belief exemptions and states that easily grant exemptions are associated with increased pertussis incidence JAMA. 2006;296:1757-1763

49. 49 Reducing Vaccine Hesitancy and Personal Belief Exemptions Engage the parent and answer their questions if possible Be sure the parent understands that unvaccinated students will be excluded from school in the event of an outbreak Provide the parent with information Suggest reliable websites for further information (some are listed on IAC “What If” fact sheet)

50. CDC Vaccines and Immunization Contact Information Telephone 800.CDC.INFO (for patients and parents) Email nipinfo@cdc.gov (for providers) Website ww.cdc.gov/vaccines/ Vaccine Safety www.cdc.gov/vaccinesafety/