New Vaccines and Recommendations William Atkinson, MD, MPH* Boise Immunization Summit September 30, 2013 *Representing the Immunization Action Coalition, Saint Paul, MN

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 MCV4 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

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/

What’s New in Immunization 2013 Schedules Influenza vaccines Tdap in pregnancy Measles redux Meningococcal vaccines HPV vaccines

2012-2013 Influenza Season Week 15 ending April 13, 2013 2012-2013 Influenza Season Week 15 ending April 13, 2013. Ten influenza-associated pediatric deaths were reported to CDC during week 15. One death was associated with an influenza A (H3) virus and occurred during week 11 (week ending March 16, 2013), one death was associated with 2009 H1N1 virus an occurred during week 13 (week ending March 30, 2013), and one death was associated with an influenza A virus for which the subtype was not determined and occurred during week 12 (week ending March 23, 2013). Seven deaths were associated with influenza B viruses and occurred during weeks 8, 11, 12, 14, and 15 (weeks ending February 23, March 16, March 23, April 6, and April 13, 2013). A total of 126 influenza-associated pediatric deaths have been reported during the 2012-2013 season from Chicago [1], New York City [4] and 37 states (AL [1], AR [4], AZ [3], CA [4], CO [5], FL [8], GA [2], HI [1], IA [1], IL [1], IN [4], KS [2], KY [1], LA [1], MA [4], MD [3], ME [1], MI [6], MN [4], MS [1], NE [1], NH [3], NJ [7], NM [3], NV [1], NY [8], OH [4], OK [1], PA [1], SC [4], SD [3], TN [3], TX [16], UT [3], VA [1], WA [1], and WI [4]).

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 MMWR 2013;62(RR-7)

Influenza Vaccine Abbreviations RIV refers to recombinant HA influenza vaccine trivalent (RIV3) for 2013-14; LAIV refers to Live Attenuated Influenza Vaccine quadrivalent (LAIV4), for 2013-14 MMWR 2013;62(RR-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) MMWR 2013;62(RR-7)

Recently-approved Influenza Vaccines Quadrivalent influenza vaccine, live attenuated (LAIV4 - Flumist Quadrivalent, MedImmune) Quadrivalent influenza vaccines, inactivated (IIV4 - Fluarix Quadrivalent, GSK; Fluzone Quadrivalent, sanofi); Flulaval Quadrivalent, IDB/GSK) Cell culture-based influenza vaccine (ccIIV3-Flucelvax, Novartis) Recombinant hemagglutinin vaccine (RIV3 – FluBlok, Protein Sciences) MMWR 2013;62(RR-7)

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 MMWR 2013;62(RR-7)

Quadrivalent Influenza Vaccines Rationale Predominant lineage is difficult to predict in advance of the season Quadrivalent vaccines contain one virus from each B lineage MMWR 2013;62(RR-7)

Influenza Vaccine Preference ACIP has not stated a preference for any influenza vaccine presentation (live or inactivated, quadrivalent or trivalent) in any age or risk group All influenza vaccines should be used only in the age group and indication approved by the Food and Drug Administration MMWR 2013;62(RR-7)

Influenza Vaccine Administration Errors Clinicians should not administer Influenza vaccine (IIV and LAIV) to persons outside the licensed age range for the vaccine they are using If LAIV or IIV* is given outside the licensed age ranges it is not necessary to repeat the dose unless a 0.25 mL dose was administered to a person 3 years or older *except Fluzone Intradermal in some circumstances

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 ages 2-49 years Similarly immunogenic to LAIV3 MMWR 2013;62(RR-7)

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 MMWR 2013;62(RR-7)

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 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 MMWR 2013;62(RR-7)

Flulaval Quadrivalent (IIV4) (ID Biomedical/ GSK) Approved for persons aged 3 years and older Available in 5 mL multidose vial for IM injection Both Flulaval (IIV3) and Flulaval Quadrivalent (IIV4) available likely more IIV3 available than IIV4 during 2013-14 Similarly immunogenic to trivalent MMWR 2013;62(RR-7)

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) MMWR 2013;62(RR-7)

Flucelvax (ccIIV3) (Novartis) Approved for persons 18 yrs and older Available in 0.5mL single dose vials for IM injection Vaccine viruses for ccIIV3 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 MMWR 2013;62(RR-7)

FluBlok (RIV3) (Protein Sciences) Approved for persons 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 MMWR 2013;62(RR-7)

Other Vaccines Available for 2013-14 Standard dose IIVs (multiple brands) for persons 6 months and older, BUT age indications differ by brand Intradermal IIV (Fluzone Intradermal)—18 through 64 years High dose IIV (Fluzone High Dose)—65 years and older MMWR 2013;62(RR-7)

Fluzone Intradermal Injection Device

Fluzone Intradermal Licensed by U.S. FDA in May 2011 Approved only for persons 18 through 64 years of age Dose is 0.1 mL administered in the deltoid area by a specially designed microneedle and injector system Formulated to contain more HA (27 mcg) than a 0.1 mL dose of regular Fluzone formulation (9 mcg) MMWR 2011;60(33):1128-32

TIV Intradermal Administration Error Persons older than 65 years or much younger than 18 years are more likely to have skin that is too thin for proper intradermal administration Persons younger than 9 years and 65 and older: Fluzone ID is invalid. Re- immunize appropriately Persons 9 through 17 years: if the HCP is certain that the dose was given intradermally, the dose may be counted and does not need to be repeated

Fluzone High-Dose Contains 4 X amount of influenza antigen than regular Fluzone Approved only for persons 65 years and older Produced higher antibody levels; slightly higher local reactions Studies underway to assess clinical effectiveness MMWR 2011;60(33):1128-32 27

Influenza Vaccination for Persons with Egg Allergy Most IIV and all LAIV contain residual egg protein Most people with “egg allergy” can receive influenza vaccine Persons age 18 through 49 years with severe egg allergy should receive Flublok (Protein Sciences) which is completely egg-free If Flublok is not available or the person is age <18 or >49 then refer to an allergist MMWR 2013;62(RR-7)

One Dose or Two? Influenza Vaccine for Children 6 Months Through 8 Years Children 6 months through 8 years require 2 doses in first season they are vaccinated One dose if previously vaccinated and have received at least 1 dose of 2009 (H1N1)-containing vaccine (2009 monovalent, or 2010-11, 2011-12, or 2012-13 seasonal vaccines) MMWR 2013;62(RR-7)

Health Care Personnel and Influenza Vaccination, U.S., 2012 Influenza Vaccination Rates (internet panel, Nov 2012) Occupation Rate Pharmacists 89% Physicians 84% Nurses 82% Other 77% 2020 Healthy People Goal is 90% Lowest among assistants/ aides (43%) and administrative/non-clinical support staff (55%) www.cdc.gov/flu/pdf/fluvaxview/hcp-ips-nov2012.pdf

2012-2013 Influenza Season Week 15 ending April 13, 2013 2012-2013 Influenza Season Week 15 ending April 13, 2013. Ten influenza-associated pediatric deaths were reported to CDC during week 15. One death was associated with an influenza A (H3) virus and occurred during week 11 (week ending March 16, 2013), one death was associated with 2009 H1N1 virus an occurred during week 13 (week ending March 30, 2013), and one death was associated with an influenza A virus for which the subtype was not determined and occurred during week 12 (week ending March 23, 2013). Seven deaths were associated with influenza B viruses and occurred during weeks 8, 11, 12, 14, and 15 (weeks ending February 23, March 16, March 23, April 6, and April 13, 2013). A total of 126 influenza-associated pediatric deaths have been reported during the 2012-2013 season from Chicago [1], New York City [4] and 37 states (AL [1], AR [4], AZ [3], CA [4], CO [5], FL [8], GA [2], HI [1], IA [1], IL [1], IN [4], KS [2], KY [1], LA [1], MA [4], MD [3], ME [1], MI [6], MN [4], MS [1], NE [1], NH [3], NJ [7], NM [3], NV [1], NY [8], OH [4], OK [1], PA [1], SC [4], SD [3], TN [3], TX [16], UT [3], VA [1], WA [1], and WI [4]).

Pertussis

September 11, 2013

Pertussis in the U.S. 2012 48,277 reported cases Highest annual total since 1951 More than twice as many cases as in 2011 (2011=18,719) 17 deaths reported (14 among infants less than 3 months of age) 2010: 27,550 cases with 27 deaths (25 of these in children under a year old). Also increase in cases in 7-10 year olds. Compared to 2010, fewer pertussis cases were reported in 2011. Sporadic outbreaks occurred in several states. During the first half of 2012, increased pertussis activity or outbreaks have been reported in a majority of states, and Washington declared a pertussis epidemic in April. As of July 5, 2012, 37 states have reported increases in disease compared with the same time period in 2011. Provisional counts from our surveillance system indicate that more than 17,000 cases of pertussis were reported to CDC through July 12, 2012. 10 pertussis-related deaths have been reported during that same time period. The majority of deaths continue to occur among infants younger than 3 months of age. The incidence rate of pertussis among infants exceeds that of all other age groups. The second highest rates of disease are observed among children 7 through 10 years old. Rates are also increased in adolescents 13 and 14 years of age. Recent Outbreak Activity Localized outbreaks of pertussis are not uncommon and occur throughout the year. Some examples of pertussis activity in the US include: A pertussis epidemic was declared in Washington on April 3, 2012. There have been 3,014 cases reported statewide through July 14, 2012, compared to 219 reported cases in 2011 during the same time period. There were 965 cases reported statewide in 2011 compared to 608 reported cases in 2010. Visit the Washington State Department of Health for the most recent information. Minnesota is experiencing high rates of pertussis in 2012. As of June 20, 2012, 1,241 cases have been reported statewide. Visit the Minnesota Department of Health for the most recent information. High rates of pertussis are being reported in Wisconsin. As of July 2, 2012, 2,815 cases have been reported. During the same time period in 2011, only 197 confirmed plus probable cases were reported. Visit the Wisconsin Department of Health Services for the most recent information. States with incidence of pertussis the same or higher than the national incidence (as of July 5, 2012), which is 5.24/100,000 persons Wisconsin 50.7 Utah 14.2 New York 7.3 Washington 39.2 Maine 14.1 Illinois 6.7 Montana 32.7 Oregon 13.4 Pennsylvania 6.3 Vermont 23.7 New Mexico 11.7 Missouri 5.8 Minnesota 23.4 Arizona 8.3 Idaho 5.7 Iowa 21.0 Colorado 8.2 Alaska 5.2 CDC unpublished data. www.cdc.gov/pertussis/outbreaks.html

Tdap Recommendations Routinely recommended at 11 or 12 years of age Catch up 13 through 18 years who have not been vaccinated with Tdap Administer Tdap to ALL unvaccinated adults 19 years and older including adults over 65 years of age* *Off-label recommendation. MMWR 2011; 60 (No. 1):13-5 M04d12 Tdap010

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 (such as for wound management) Protect the infant- pass antibodies on. *Off-label recommendation. MMWR 2013:62( (No.7): 131-135

Tdap Revaccination Revaccination with Tdap applies ONLY to pregnant women Does NOT apply to family members or other contacts ACIP considering revaccination for certain high-risk populations (such as healthcare personnel) Protect the infant- pass antibodies on. MMWR 2013:62( (No.7): 131-135

Measles – United States, 2013* 159 cases reported to CDC from 16 states and NYC 157 (99%) cases are import- associated 23 imports were U.S. residents 146 (92%) unvaccinated or undocumented vaccination status (92 PBE, 15 too young) 8 outbreaks accounting for 77% of cases *as of August 24. MMWR 2013;62:741-43

Measles Keep Your Guard Up Any patient with fever and rash should be assumed to have measles until proven otherwise immediate isolation Be highly suspect of patients with fever and coryza and/or conjunctivitis, particularly if unvaccinated or international travel Be certain of your measles immunity status MMWR 2013;62(RR-4)

MMR Vaccine First dose at 12-15 month, second dose routinely at 4-6 years of age Minimum interval between doses is 4 weeks Infants as young as 6 months should receive MMR before international travel Adults with unknown or undocumented MMR vaccination history should receive 1 or 2 doses MMWR 2013;62(RR-4)

Appropriate vaccination against measles, mumps, and rubella Evidence of Measles, Mumps, and Rubella Immunity for Healthcare Personnel (HCP) Appropriate vaccination against measles, mumps, and rubella 2 doses of measles and mumps vaccine at least 1 dose of rubella vaccine, or Laboratory evidence of immunity, or Laboratory confirmation of disease Physician-diagnosed disease no longer recommended as evidence of measles or mumps immunity MMWR 2013;62(RR-4)

Meningococcal Vaccine Meningococcal disease is bad. In fact it’s downright scary. It can kill you within 24 hours or destroy limbs. Meningococcal Vaccine

Meningococcal Disease Incidence, United States, 1970-2011 Historically, meningococcal disease has been cyclical with peaks in disease incidence every 8-10 years. Rates of disease have cycled around 1 case/100,000 population, but have been declining for the last 10-15 years, and we have remained at a nadir of disease incidence for the last 5-6 years. The reasons for this sustained low in disease incidence are unknown, but there is no indication, even looking at preliminary 2010 and 2011 data, that rates are increasing. 1970-1996 NNDSS data, 1997-2011 ABCs data estimated to U.S. population with 18% correction for under reporting

Meningococcal Vaccines Vaccine Type Age Menomune PS 2 yrs and older Menactra Conj 9 mos – 55 yrs Menveo Conj 2 mos* – 55 yrs MenHibrix Conj 6 wks – 18 mos *as of August 1, 2013

Meningococcal Vaccine Recommendations Routine vaccination of all persons 11 through 18 years of age routine vaccination at 11 or 12 years with booster dose* at 16 years vaccination of previously unvaccinated adolescents at age 13 to 15 years with booster dose* at 16 to 18 years Minimum interval between doses is 8 weeks *off-label recommendation. MMWR 2013;62(RR-2)

Meningococcal Vaccine Recommendations 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 microbiologists exposed to N. meningiditis persons 2 months and older who travel or live in endemic areas MMWR 2013;62 (RR-2):1-27

Meningococcal Vaccine Recommendations Not routinely recommended for person age 19 years or older who are not at increased risk Recommended for persons age 19 through 21 who are first-year college students AND living in a resident hall 1 dose if previously unvaccinated booster dose if previous dose given at age younger than 16 years MMWR 2013;62(RR-2)

HibMenCY (MenHibrix) 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

MCV4-CRM (Menveo) (Novartis) Approved by FDA in February 2010 as a single dose in persons 2 through 55 years License modification approved in August 2013 to include children 2 through 23 months of age Approved schedule for children age 2 through 7 months doses at 2, 4, 6 and 12-15 months of age

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 MenHibrix or Menveo* or Menactra (9 mos or older) persistent complement pathway deficiencies anatomic or functional asplenia including sickle cell disease Infants traveling to sub-Sahara Africa or the Hajj should receive Menveo, not MenHibrix* *ACIP has not yet made a recommendation on the use of Menveo in infants MMWR 2013;62 (RR-2):1-27

Menveo Vaccine Administration Errors Liquid C-Y-W135 component administered without using it to reconstitute the lyophilized A component Revaccination may not be needed serogroup A disease is rare in the U.S. so revaccination not needed if the person does not plan to travel outside the U.S. revaccinate (no minimum interval) if international travel anticipated especially to Africa

MCV4 and Pneumococcal Conjugate Vaccine (PCV) In clinical trials Menactra brand MCV4 appeared to reduce the response to PCV administered at the same visit Menveo brand MCV4 did not affect the immunogenicity of PCV Menactra should not be administered until at least 4 weeks after completion of the PCV series Menveo can be administered at any time before, simultaneous with or after PCV MMWR 2013;62(RR-2):18.

Asplenia Asplenic persons are at increased risk of invasive disease caused by S. pneumoniae and N. meningiditis Asplenic persons should receive PCV13, PPSV and MCV4 Menactra brand MCV4 should not be administered until at least 4 weeks after completion of the PCV13 series* Menveo can be administered at any time before, simultaneous with or after PCV *applies to persons of all ages. MMWR 2013;62(RR-2)

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 Lets take a moment to review- there are 2 products available. Bot are a 3 dose series and the ACIP has harmonized the schedule MMWR 2007;56 (RR-2)

HPV-Associated Cancers in the United States 33,369 HPV-associated cancers diagnosed annually (2004-2008) 12,080 men 21,290 women Site Total Cancers Attributable to HPV Cervix 12,170 96% Anus 6230 93% Vagina 2680 64% Oropharynx 27,480 63% Vulva 4490 51% Penis 1570 36% American Cancer Society. www.cancer.org/acs/groups/. Gillison ML, et al. Cancer. 2008;113(10 Suppl) 3036-3046; MMWR 2012;61:258-261

HPV Immunization Rates*, NIS-Teen, 2011 Females13-17 Years of Age HPV Vaccine U.S. ID 1 or more doses 53.0% 45.5% 3 dose series completion ** 70.7% 73.3% Significant number of girls who began the HPV series do not receive all three doses. Related factors include: parents often lack awareness of the importance of vaccinating preteen girls  not receiving a strong recommendation for HPV vaccination from healthcare providers *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

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)

Pediatrics 2013;131:645–651

HPV Vaccines 2 products HPV2 (Cervarix) – females only HPV4 (Gardasil) – females and males Both products are a 3 dose series over 6 months Lets take a moment to review- there are 2 products available. Bot are a 3 dose series and the ACIP has harmonized the schedule MMWR 2010; (59)20; 626-632

ACIP HPV Vaccination Recommendations 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 Females Routine: 11 or 12 years Catch-up: 13 through 26 years Administer HPV4 or HPV2 Immunization recommendations are different based on gender.

Strategies for Increasing HPV Vaccination Rates in Clinical Practices 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

The Future Revaccination with Tdap among nonpregnant persons Meningococcal serogroup B vaccine HPV vaccines with additional oncogenic types More vaccine safety concerns

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