7th AnnualDell Children’s Medical Center

Pediatric Conference

Current and Future Vaccine Recommendations from the ACIP

Larry K. Pickering, MD, FAAP

April 11, 2014

Austin, TX

Faculty Disclosure Information:

In the past 12 months, I have had no relevant financial relationships with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services discussed in this CME activity.

I do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation.

OBJECTIVES

• Describe recent changes to the pediatric and adult immunization schedules

• Lessons learned from vaccine surveillance systems

• Highlight major vaccine issues and updates

• Discuss future directions

1994 schedule from Red Book paper

The Fine Print

Vaccines Recommended

Number of ACIP Vaccine Recommendations, by Year, Since 1995*

* This chart takes into account General Recommendations on Immunization, recommendations for health care professionals, the annual recommended routine childhood immunization schedule (1995-present), the annual recommended routine adult immunization schedule, and recommendations pertaining to vaccines such as those for rabies, yellow fever, smallpox, and Japanese encephalitis that are not part of any routine immunization schedule in the United States.

Changes to the 2014 Immunization Schedules

• Infant meningococcal vaccination (January 2013)• Tdap in pregnant women (February 2013)• Meningococcal disease: Prevention and Control: RR (March

2013)• Interim influenza recommendations (May 2013)• MMR and congenital rubella syndrome: RR

(June 2013)• PCV13 and PPSV23 vaccines for 6-18 year olds with

immunocompromising conditions (July 2013)• Update on use of VariZIG (July 2013)• Influenza vaccines (2013/14 season): RR (September 2013)• Japanese encephalitis vaccine for children: (November 2013)• Haemophilus influenzae RR: (February 2014)

http://www.cdc.gov/vaccines/hcp/acip-recs/recs-by-date.html

Incidence Declines in All Age Groups

ABCs cases from 1993-2011 estimated to the 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

14

Incidence in All Serogroups, United States, 1993-2012*

*Source: ABCs cases from 1993-2012 estimated to the U.S. population with 18% correction for under reporting

Meningococcal VaccineRecommendations

Vaccine FDA Routine High Risk

MenACWY-D(Menactra)

9 mo.-55 yr.

11-21 yr. 9 mo.-55 yr.

MenACWY-CRM (Menveo)

2 mo.-55 yr.

11-21 yr. 2 mo.-55 yr.

HibMenCY-TT (MenHibrix)

*not for travelers

6 wk.-18 mo.

Hib 6 wk.-18 mo.*

MMWR 2014; 63:148-54

MMWR 2014; 63:148-54

56%

61%

43%

40% 34%

Influenza Deaths by Age Group122 Cities Mortality Reporting System,

Number of Influenza Deaths by Age Group and Year

*

**Data as of week 6, 2014

**

*Data from week 15, 2009 – week 39, 2010

MMWR 2013; 62:997

Flu vaccination during 2012-13 season

resulted in 79,260 fewer hospitalizations

and 6.6 million fewer cases of influenza

National Estimated Vaccination Coverage Levels among Adolescents 13-17 Years,

National Immunization Survey-Teen, 2006-2012

Tdap: tetanus, diphtheria, acellular pertussis vaccine.MCV4: meningococcal conjugate vaccineHPV: human papillomavirus vaccine

Strength of HPV Vaccine Recommendation for Female Patients, Pediatricians and

Family Physicians (N=609)

Allison et al. https://cdc.confex.com/cdc/nic2011/webprogram/Paper25181.html

IID-9: Children 19-35 Months Who Received No Vaccinations, 2008-2012, U.S.

Source: National Immunization Survey

Tracking Measure- Program goal to sustain percentage of <1%

MMWR 2013; 62(30): 607-612

Vaccination coverage among children in kindergarten- US, 2012-2013. MMWR 2013;62:607.

“I’m pregnant. I was told that

vaccines are now

recommended for pregnant

women but I don’t know ...”

Estimated Influenza Vaccination (trivalent) Coverage, Pregnant

Women*

* Behavioral Risk Factor Surveillance (BRFSS) data from December-February interviews only, for women 18-44 years pregnant or not pregnant when interviewed; sample sizes for pregnant women per season ranged from 400-800. Differences in influenza vaccination coverage between pregnant and not pregnant women were statistically significant (p<0.05) for 2005-06 and 2008-09 through 2012-13 seasons (age adjusted), p<0.05). Other estimates for pregnant women from PRAMS (MMWR February 24, 2012 / 61(07);113-118); NHFS (Ding et al. Am. J. Obstetrics & Gynecology, June 2011 Supplement); and internet panel survey (MMWR August 19, 2011 / 60(32);1078-1082, MMWR September 28, 2012 / 61(38 ):758 – 763, MMWR September 27, 2013 / 62(38): 787-792)

Vaccination coverage by provider recommendation and/or offer

*Women who didn't visit a provider since August 2012 (n=27) or women who didn't know whether they received provider recommendation or offer (n=55) were excluded from this analysis.

AAP 2013 Tdap Recommendations

Tdap vaccine is recommended for every pregnancy administered from week 27 to 36 of gestation

“Cocooning“ is still important since Tdap effectiveness is only 65-81% and ineffective in small premature infants

Tdap-induced pertussis antibodies transferred to newborn in high concentrations and persist for 2 months

Safe for mother and infant

Recommended to protect pregnant women and theirinfants

Optimal timing is important Influenza (any trimester) Pertussis (every pregnancy from week 27-36) Only potential strategy to prevent young infant deaths and hospitalizations

Maternal Immunization: Benefits

Clin Obstet Gynecol. 2012;55:474-86

33

Conclusions

No new unexpected vaccine safety concerns noted among pregnant women who received Tdap (or their infants)

Limited number of pregnancy reports with repeat Tdap doses received by VAERS

CDC will continue to monitor the safety of Tdap vaccine during pregnancy, with special emphasis on repeated doses of Tdap

ACIP meeting: February 26-27, 2014

Human Papillomavirus:Types and Disease Association

Skin warts (hands and feet)

Mucosal/genital(~40 types)

High-risk: types16, 18, 31, 45(and others)

Low-risk:types 6, 11

(and others)

Low-grade cervical abnormalitiesCancer precursorsAnogenital cancers

Low-grade cervical abnormalitiesGenital wartsLaryngeal papillomas

Non-mucosal/cutaneous(~60 types)

Muñoz N et al. N Engl J Med 2003;348:518-527.

Type Attribution by Cancer Site

Cervical In Situ Cervical Vulvar Vaginal Anal Penile Oropharyngeal0

10

20

30

40

50

60

70

80

90

100

66

60

49

55

79

48

60

15

21

1418

8 96

10

18

62 3

64

9

1

31

25

9

37

30

HPV 16/18

HPV 31/33/45/52/58

Other HPV

HPV Negative

Cancer Site

Perc

ent

Saraiya et al, presented at AACR Health Disparities in Cancer, 2013

Revised Estimated Percentages of Cancers Attributed to HPV in the

U.S. Cancer HPV attributabl

e% (95% CI)

HPV 16/18attributable% (95% CI)

HPV 31/33/45/52/58

attributable % (95% CI)

Cervical 91 (88-92) 66 (63-69) 15 (12-17)

Vaginal 75 (63-84) 55 (43-67) 18 (11-30)

Vulvar 69 (62-75) 49 (41-56) 14 (10-20)

Anal Male Female

89 (77-95)92 (85-96)

79 (66-88)80 (70-87)

4 (1-13)11 (6-19)

Penile 63 (52-73) 48 (37-59) 9 (4-17)

Oropharyngeal Male Female

72 (68-76)63 (55-71)

63 (59-68)51 (43-59)

4 (3-7)9 (6-15)

Oropharynx

Average Number of New HPV-Associated Cancers by Sex, in the United States, 2005-2009

n=3039 n=2317

n=3084

n=11279n=9312

n=1687

n=1003

Jemal A et al. J Natl Cancer Inst 2013;105:175-201

n=694

HPV VaccinesQuadrivalent

(Gardasil)Bivalent

(Cervarix)

Manufacturer Merck GlaxoSmithKline

VLP types 6, 11, 16, 18 16, 18

Producer cells Saccharomyces cerevisiae (yeast)

Baculovirus infected Trichoplusia in insect cell

line

Schedule (IM) 3 dose series 3 dose series

Estimated to Protect (%)

Genital Warts 90% --

Cervical and other cancers

70% 70%

VLP – virus like particle; IM - Intramuscular

Evolution of recommendations for HPV vaccination in the United States

40

Quadrivalent Routine, females 11 or 12 yrs*and 13-26 yrs not previously vaccinated

Quadrivalent or Bivalent Routine, females 11 or 12 yrs*and 13-26 yrs not previously vaccinated

Quadrivalent May be given, males 9-26 yrs*

Quadrivalent (HPV 6,11,16,18) vaccine; Bivalent (HPV 16,18) vaccine

* Can be given starting at 9 years of age; ** For MSM and immunocompromised males, quadrivalent HPV vaccine through 26 years of age

June October

Quadrivalent Routine, males 11 or 12 yrs* and 13-21 yrs not previously vaccinated

May be given, 22-26 yrs**

October

Disease Associations with Most Frequent Types of HPV

Diseases HPV type

Cutaneous warts 1, 2, 3, 4, 10, others

Cancer (cervical, anal, penile, oropharyngeal)

16, 18, 31, 33, 45, 52, 58

Condyloma acuminata (anogenital warts)

6, 11

Recurrent respiratory papillomatosis

6, 11

Burd. Clin Microbiol Rev 2003; 16:1-17

Oropharyngeal Cancer

• HPV 16 causes head and neck cancers• Molecular, epidemiologic, and clinical evidence

suggest these tumors are distinct from HPV-negative oropharyngeal cancers

• Risk factors for HPV-positive and HPV-negative oropharyngeal cancers differ: HPV-positive cancers: tobacco, sexual

behaviors (typically younger victims)

HPV-negative cancers: tobacco, alcohol (typically older victims)

44

Comparison of 9vHPV Vaccine and qHPV VaccineComparison of 9vHPV Vaccine and qHPV Vaccine

AAHS225μg

AAHS500μg

620μg

1140μg

ADJUVANTqHPV vaccine

9vHPV vaccine

1640μg

1820μg

630μg

1140μg

1660μg

1840μg

3120μg

3320μg

4520μg

5220μg

5820μg

AAHS =Amorphous aluminum hydroxyphosphate sulfate

Why Parents Say “No” to HPV Vaccine

* Not mutually exclusive.

** Did not know much about HPV or HPV vaccine. 2011 NIS-Teen available at http://www.cdc.gov/vaccines/stats-surv/nis/nis-2011-released.htm#nisteen

Parents who do not intend to vaccinate daughter in next 12 months, NIS-Teen 2008-2009

Actual and Achievable Vaccination Coverage if Missed Opportunities Were Eliminated: Adolescents 13-17 Years, NIS-Teen 2012

54

93

0

20

40

60

80

100

HPV-1 (girls)

Per

cen

t V

acci

nat

ed

Vaccine

Actual

Achievable

Missed opportunity: Healthcare encounter when some, but not all ACIP-recommended vaccines are given.HPV-1: Receipt of at least one dose of HPV.

Among girls unvaccinated for HPV, 84% had a

missed opportunity

HPV Vaccine Communications During the Healthcare Encounter

• HPV vaccine is often presented as ‘optional’ whereas other adolescent vaccines are recommended

• Some expressed mixed or negative opinions about the vaccine: ‘new vaccine’; concerns over safety/efficacy

• When parents expressed reluctance, providers were hesitant to engage in discussion

• Some providers shared parent’s views that teen was not at risk for HPV and could delay vaccination until older

Goff et al. Vaccine (2011). doi:10.1016/i.vaccine.2011.07.082 Hughes et al. BMC Pediatrics. 2011;11:74. www.biomedcentral.com/1471-2431/11/74

HPV Vaccine Safety Summary

• Six years of post-marketing safety surveillance in females demonstrating safety of Gardasil

• Syncope has been reported after HPV vaccine

• Ongoing safety studies for males and bivalent vaccine

• CDC and FDA are continuing to monitor HPV vaccine safety

HPV vaccine safety concerns

• Safety questions for any new vaccine More due to high visibility of HPV vaccine

• Anecdotes in press due to events temporally related to vaccination

• Anti-vaccine websites

• Goal 1: Reduce missed clinical opportunities to recommend and administer HPV vaccines

• Goal 2: Increase parents’, caregivers’, and adolescents’ acceptance of HPV vaccines

• Goal 3: Maximize access to HPV vaccination services

• Goal 4: Promote global HPV vaccination uptake

Accelerating HPV Vaccine Uptake in the United States: Goals

IOM Report - 2011

• Evaluated a list of adverse events and their association with 8 different vaccines covered by the National Vaccine Injury Compensation Program (VICP)

• Benefits or effectiveness were not assessed• Based on scientific evidence, the committee

developed 158 causality conclusions and assigned each to one of four categories

MMWR 2013; 62:591-95

Predicted numbers of coincident, temporally associated events after a single dose of a hypothetical vaccine,

based upon background incidence ratesNumber of coincident events

since a vaccine doseBaseline rate used for estimate

Within 1 day

Within 7 days

Within 6

weeks

GBS (per 10 million vaccinated people)

0.51 3.58 21.50 1.87 per 100,000 person-years (all ages: UK Health Protection Agency data)

Optic neuritis (per 10 million female vaccinees

2.05 14.40 86.30 7.5 per 100,000 person-years in US females

Spontaneous abortions (per 1 million vaccinated pregnant women)

397 2780 16,684 Based on date from the UK (12% of pregnancies)

Sudden death within 1 h of onset of any symptoms (per 10 million vaccinated)

0.14 0.98 5.75 Based upon UK background rate of 0.5 per 100,000 person-years

Lancet 2009; 374:2115-22

Comparison of 20th Century Annual Morbidity and Current Morbidity: Vaccine-Preventable Diseases

Disease20th Century

Annual Morbidity†2013

Reported Cases † †Percent Decrease

Smallpox 29,005 0 100%

Diphtheria 21,053 0 100%

Measles 530,217 184 > 99%

Mumps 162,344 438 > 99%

Pertussis 200,752 24,231 88%

Polio (paralytic) 16,316 0 100%

Rubella 47,745 9 > 99%

Congenital Rubella Syndrome 152 0 100%

Tetanus 580 19 97%

Haemophilus influenzae 20,000 18* > 99%

† JAMA. 2007;298(18):2155-2163† † CDC. MMWR January 3, 2014;62(52);ND-719-ND-732. (MMWR week 52 provisional data) * Haemophilus influenzae type b (Hib) < 5 years of age. An additional 13 cases of Hib are estimated to have occurred among the 212 reports of Hi (< 5 years of age) with unknown serotype.

Figure 1. Estimated incidence of invasive Hib infection in <5 year olds, United States, 1980-2011* Bacterial Core Surveillance (ABCs) data; 2010-2011

**Among those with known vaccination status (n=241/288)

FIGURE 3. Percentage of children aged <5 years with cases of invasive Haemophilus influenzae type b (Hib) disease,* by vaccine status — United

States 2002–2012

3 infants with CRS born in the U.S. All mothers

exposed to rubella in Africa. All infants

had severe defects.

MMWR 2013;62(12): 226-229

MMWR 2013;62(12): 226-229

MMWR 2010; 59:1305-1308

http://www.cdc.gov/vaccines/hcp/patient-ed/conversations/index.html

Conclusions• Routine immunizations provide a tremendous

benefit to infants, children, adolescents, adults and to society

• Immunization is a shared public / private responsibility

• During visits, vaccines and other evidence-based preventive services should be provided

• Continue monitoring adolescent vaccination coverage among different groups to assess coverage by race/ethnicity and other sociodemographic factors to identify barriers

• Every day, 11,000 births occur in the U.S.

Future Considerations• Duration of protection of Tdap• Tdap repeat doses in pregnancy• Use of PCV13 in adults and integration with PPSV13• PCV13 dose reduction in children• Use of zoster vaccine in adults beginning at 50 years of

age, and duration of protection• HPV vaccine: integration of HPV9 and number of doses• Meningococcal B-containing vaccines• Several influenza vaccine preparations• Vaccine hesitancy and pseudoscience