William Atkinson, MD, MPH*Idaho Immunization Conference

Boise, IdahoSeptember 30 2013

Vaccine Update

*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 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

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 vaccine• Tdap in pregnancy• Meningococcal vaccines• HPV vaccines• Vaccine hesitancy

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/

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).

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)

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

Quadrivalent Influenza VaccinesRationale

• 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

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

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

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

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

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

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

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

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

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

Yes

No

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

Yes

No

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

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 consideredMMWR 2012; 61(32):613-618.

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

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.

Health Care Personnel and Influenza Vaccination

Source: www.cdc.gov/flu/pdf/fluvaxview/hcp-ips-nov2012.pdf

Influenza Vaccination Rates(internet panel, Nov 2012)

Occupation Rate Pharmacists 88.7%Physicians 83.8%Nurses 81.5%Other 76.7%

2020 Healthy People Goal

is 90%

Lowest among assistants/ aides (43.4%) and administrative/non-clinical support staff (54.5%)

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

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.htmlMMWR 61 (37) ND-516

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

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

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

Adult Tdap Recommendations

• Administer Tdap to unvaccinated adults 19 years and older including adults 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

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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

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

Meningococcal Disease Incidence, United States, 1970-2011

1970

1972

1974

1976

1978

1980

1982

1984

1986

1988

1990

1992

1994

1996

1998

2000

2002

2004

2006

2008

*201

00

0.5

1

1.5

2

Year

Rate

per

100

,000

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

Meningococcal Vaccines

Vaccine Type Age• Menomune PS 2 yrs and older

• Menactra Conj 9 mos – 55 yrs

• Menveo Conj 2 mos* – 55 years

• MenHibrix Conj 6 wks – 18 mos

*as of August 1, 2013

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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

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

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

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

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

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%

HPV Immunization Rates*, NIS-Teen, 2011Females13-17 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 Vaccine U.S. ID1 or more doses 53.0% 45.5%

3 dose series completion **

70.7% 73.3%

Actual and Potentially Achievable Vaccination Coverage if Missed Opportunities Were

Eliminated: NIS-Teen, 2011

Td/Tdap MenACWY HPV-10

20

40

60

80

100

85.370.5

53

91.5 90.9 89.5 ActualPotentially Achievable

Vaccine

Perc

ent

Vacc

inat

ed 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

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

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

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

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

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

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

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)

CDC Vaccines and ImmunizationContact 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/