Immunization Update: 2018

Transcription

1 Immunization Update: 2018 Stephan Foster, Pharm.D. FAPhA CAPT (Ret) USPHS Professor, University of Tennessee College of Pharmacy Liaison for APhA, Advisory Committee on Immunization Practices (ACIP) Jeff Goad, Pharm.D., MPH, FAPhA Professor and Chair, Department of Pharmacy Practice Chapman University School of Pharmacy

2 Target Audience: Pharmacists and Pharmacy Technicians ACPE#: L06-P/T Activity Type: Application-based

3 This activity is supported by an independent educational grant from Sanofi Pasteur U.S. and Merck & Co., Inc.

4 Disclosures Stephan Foster, Pharm.D. is on advisory boards with Pfizer, Seqirus, and Sanofi- Pasteur and on speakers bureaus with Pfizer, Merck, Seqirus, and Sanofi-Pasteur Jeff Goad, Pharm.D. is on advisory boards with Merck, GSK and Sanofi-Pasteur and on the speakers bureau for Merck The American Pharmacists Association is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

5 Learning Objectives 1. Identify important recent changes to the immunization schedules for adults and children in the United States and apply them to representative patient cases. 2. Describe specific immunization recommendations for special populations, including patients considered high risk, children and adolescents, and older adults. 3. Discuss the epidemiology of outbreaks of vaccine-preventable diseases in the United States. 4. Summarize information about the efficacy and possible adverse effects of recently licensed vaccines. 5. List promising new vaccines in the development pipeline.

6 1. The Most common cause of Shoulder Injuries Related to Vaccine Administration (SIRVA) is : A. Both Patient and Provider are standing B. The Vaccination is given too high on the shoulder C. The needle used in the vaccination is too short D. The patient moved during the injection

7 2. The proper administration site and dosing interval of RZV (Shingrix ) is: A. 0.5 ml Intramuscularly now and 1 month later B ml subcutaneously as a single dose C ml intramuscularly now and 6 months later D. 0.5 ml intramuscularly now and 2 to 6 months later

8 3. Pneumococcal Vaccination of adults 65 years and older with PCV13 is under reevaluation by the ACIP because: A. Enough adults 65 years and older will be vaccinated that herd immunity may no longer require the need for vaccination B. Carriage rates remain high so vaccination may need to be continued C. There is no need to re-evaluate the use of PCV13 in adults over 65 years of age D. Concern of a decrease in pneumococcal disease due to herd effects secondary to infant immunization with PCV13 may make vaccination of adults 65 years and older unnecessary

9 4. The Vaccine Effectiveness (VE) of the l influenza vaccine A. was 25% against A/H3N3 and higher than seen in Australia B. was the same for all 4 serotypes (A/H1N1, A/H3N2, B/Yamagata and B/Victoria) C. was lower due to serotype drift in the B/Yamagata strain D. was so low that vaccination was not useful

10 5. Which is the only vaccine on the adult schedule with a preferential recommendation? A. Flumist B. Shingrix C. Heplisav-B D. Pneumovax

11 Essential Strategies to Increase Immunization Levels Recordkeeping Accurate Current Immunization Information Systems (IIS) Reminder and recall to patients Computer generated telephone calls Mailers Reminder and recall to providers Computer generated lists Reduce barriers and missed opportunities Standing orders

12 Immunization Schedules

13 Mumps outbreak 2018 Adult Schedule 2 dose: <15 yrs

14 2018 Pediatric Schedule Still no LAIV 3 rd dose mumps outbreak MenHibrix D/C d

15 2018 Adult Schedule Not Contraindicated

16 2018 Adult Schedule

17 Vaccine Administration

18 Anatomy of the upper arm Shoulder Injury Related to Vaccine Administration (SIRVA) Image by Alissa Eckert, CDC Division of Communication Services 18

19 Number of shoulder dysfunction reports Shoulder dysfunction reports following IIV, N (% among all IIV reports) by influenza season, (1.5%) 149 (2.0%) 148 (1.8%) 184 (2.0%) 223 (2.4%) 174 (2.0%) Influenza season 1 Shimabukuro T (CDC); VAERS reports vaccinated and received July 1, 2010 through June 30,

20 Place of IIV vaccination for adults (%): National flu survey vs. VAERS reports of shoulder dysfunction following IIV in adults Doctors office, Hospital Pharmacy/Store Workplace Health Department School/University Nursing Home/Senior facility Mobile clinics Other Unknown % of reports National Internet flu Survey % of adults early VAERS reports of SDFI % of reports in adults Data for national flu survey for the influenza season from July through November 52

21 Place of vaccination in shoulder dysfunction reports following IIV, July 2010-June 2016 Doctor's office/hospital 319 (32%) Pharmacy/Store 399 (40%) Workplace Health department 50 (5%) 121 (12%) 72% School/University 26 (3%) Nursing home/senior facility 5 (<1%) Mobile clinics 6 (<1%) Other 18 (2%) Unknown 62 (6%) Number of shoulder dysfunction reports Shimabukuro T (CDC); VAERS reports vaccinated and received July 1, 2010 through June 30,

22 Methods: definition of shoulder dysfunction following IIV 1 Shoulder pain and restricted range of motion following injection of IIV into the upper arm Affected shoulder must be of same arm in which IIV was administered alone Onset <48 hours after IIV vaccination Symptoms last longer than one week (to differentiate from injection site reactions) 2 1 Adapted from the Vaccine Injury Compensation Program (VICP) definition for shoulder injury following vaccine administration (SIRVA) with modification 2 Modified from VICP requirement of >6 months of residual effects due to limitations on follow-up in VAERS 22

23 Characteristics of shoulder dysfunction reports following IIV, July 2010-June 2016 * Not mutually exclusive Most commonly reported shoulder dysfunction-related adverse events * (N=1,006 total reports) n (%) Shoulder pain 442 (44) Injected limb mobility decreased 407 (41) Joint range of motion decreased 191 (19) Drug administered at inappropriate site 156 (16) Bursitis 94 (9) Arthralgia 92 (9) Rotator cuff syndrome 90 (9) Frozen shoulder 57 (6) Shimabukuro T (CDC); VAERS reports vaccinated and received July 1, 2010 through June 30, 2016 Shoulder bursitis 30 (3) 32

24 Shoulder dysfunction reports following IIV where a contributing factor was described (222 of 1,006 reports), July 2010-June 2016 Contributing factors * described in narrative (N=222 total reports) n Vaccination given too high on arm 177 Improper/poor administration technique 35 Uneven position between vaccinator and patient (vaccinator 5 standing and patient sitting) Other (needle too long, past history of shoulder pain, etc.) 22 * Not mutually exclusive Shimabukuro T (CDC); VAERS reports vaccinated and received July 1, 2010 through June 30,

25 Duration 1 of unresolved shoulder dysfunction in reports following IIV, June 2010-July 2016 n (%) Total reports days 299 (35) days 234 (27) days 99 (12) (13) days 365+ days 105 (12) Missing 12 (1) 1 Duration is calculated by date of report date of adverse event onset, if date of report was missing, receive date was used 25

26 Reporter type among shoulder dysfunction reports following IIV compared to non-shoulder dysfunction reports, July June Percent of reports Patient Vaccine provider Manufacturer Other/Unknown Shoulder dysfunction % of reports Non-shoulder dysfunction % of reports Shimabukuro T (CDC); VAERS reports vaccinated and received July 1, 2010 through June 30,

27

28 Herpes Zoster

29 MMWR. May 15, 2008 / 57(Early Release);1-30

30 Epidemiology of Herpes Zoster (HZ) and Postherpetic Neuralgia (PHN) Approximately 1 million cases annually. 1,2 4 cases per 1000 HZ incidence increases with age 2,3 <1 case per 1000 children >15 cases per 1000 adults 80 years and older For adults 50 years and older with HZ, 10-18% go on to develop PHN Jumaan et al., JID, 2005, 191: Yawn et al., Mayo Clin Proc. 2007; 82: Insigna et al., J Gen Intern Med. 2005, 20: Images: Public Health Image Library, Centers for Disease Control and Prevention, retrieved from

31 Comparison of Zostavax (ZVL) and Shingrix (RZV) Zostavax (ZVL) Shingrix (RZV) Type of vaccine Live Inactivated Adjuvant None AS01 B Storage Frozen Refrigerate * Regimen 1 dose 2 doses (2 months apart) Efficacy against disease 51.3% (varies by age) 97.2% 50 years Duration 7-8 years 3.2 years (model predicts 19 yrs to zero) SAE/ADR 1.9% / 48.3% 1.1% / 84.4% (17% Grade 3) * Discard 6 hours after reconstitution if not administered Lal H. et al. N Engl J Med. 2015;372:

32 Shingles Vaccines Efficacy Comparison Percent Vaccine Efficacy yrs yrs yrs >= 80 yrs 0 ZVL 1,2 3, 4 Vaccine RZV 1 Oxman M. NEJM. 2005;352: ; 2 Schmader KE. Clin Infect Dis. 2012;54: ; 3 Lal et al., NEJM 2015;372(22): (ZOE-50); 4 Cunningham AL. NEJM. 2016;375: (ZOE-70)

33 ZVL vs RZV Against Post-Herpetic Neuralgia ZVL VE against PHN (95% CI) y Not studied y 65.7% ( ) % ( ) OVERALL 66.5% ( ) RZV VE * against PHN (95% CI) y 100.0% (40.8% %) y 100.0% (-442.9% %) y 93.0% (72.4% %) 80 y 71.2% (-51.6% %) OVERALL ( 70 y) 88.8% (68.7% %) * - Assumes two dose completion 1. Harpaz et al. MMWR 2008;57(RR5) 2. Cunningham et al., NEJM 2016;375(11): (Pooled ZOE-50 and ZOE-70).

34 100% Vaccine Efficacy Persistence Against HZ ZVL, Short-Term Persistence Study and Kaiser Permanente Southern California 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 ZVL - KPSC ZVL STPS 1. Oxman et al., NEJM 2005, 352: Schmader et al., Clin Infect Dis 2012, 55(10): Tseng et al., J Infect Dis 2016, 123(12):

35 100.0% RZV and ZVL Efficacy Persistence Against HZ (Various Studies) 90.0% 80.0% 70.0% 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% 0.0% Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 Cunningham et al., NEJM 2016;375(11): Oxman et al., NEJM 2005, 352: Schmader et al., Clin Infect Dis 2012, 55(10): Tseng et al., J Infect Dis 2016, 123(12): RZV ZVL - KPSC ZVL STPS

36 Shingrix PI, 2018

37 Shingrix Vaccine Diluent is the adjuvant suspension Use same syringe to reconstitute and then administer Discard vaccine after reconstitution if not given within 6 hours Shingrix FDA Package Insert:

38 ACIP Zoster Vaccination Recommendation 2018 Recombinant zoster vaccine (RZV) is preferred over ZVL for the prevention of herpes zoster and related complications. RZV is recommended for the prevention of herpes zoster and related complications for immunocompetent adults aged 50 years. RZV is recommended for the prevention of herpes zoster and related complications for immunocompetent adults who previously received zoster vaccine live (ZVL). Dooling KL. Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines. MMWR Morb Mortal Wkly Rep 2018;67:

39 RZV GRADE - Considerations Population Immunocompetent adults aged 50 years or older Intervention 2 doses of RZV administered IM at 0, 2 months Comparison Placebo or no vaccine (no head-to-head ZVL to RZV) Outcomes (meet Type 1 GRADE Evidence for the following): Herpes zoster (HZ) Post herpetic neuralgia (PHN) Duration of protection against HZ Severe adverse events Reactogenicity (Grade 3 reactions)

40 ZVL Vaccination Rates National Health Interview Survey, Have you ever received a shingles vaccine? Race/Ethnicity Sample Size % (95% CI) Difference from 2014 Total 10, ( ) 2.7 * White 7, ( ) 2.7 * Black 1, ( )** 2.0 Hispanic or Latino 1, ( )** 1.3 Asian ( )** 9.5 * Other ( ) 11.8 * p<0.05 when compared to ** p<0.05 when compared to White. 1. Williams et al., MMWR 2017;66(No. SS-11):1 28.

41 Need to Improve Vaccine Recall System RZV requires 60 day follow-up for second dose Reminder and recall systems Align with medication synchronization Electronic health records Prescription dispensing software Immunization information systems 1 dose uptake of ZVL 2007: National immunization Survey (Lu et al, Vaccine 27:882-7); : NHIS (Am J Prev Med 40:e1-6 & MMWR February 5, 2016 / 65(1);1 36), 2016 CDC, unpublished

42 Questions What if you ve already had an ZVL vaccine, can you get RZV? How long do you have to wait? Can you give it if patient had HZ in the past? What if they have an active infection, should RZV be given? Can you give RZV if no history of VZV? How much protection do you get with only 1 dose of RZV? Is there any population where ZVL is recommended over RZV? What is the route of administration? How do you keep records to make certain patient is recalled?

43 Mumps

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45

46 Third Dose of MMR Vaccine? 61-88% 3 MMRs vaccine effectiveness 1,2,3 Studies had high percentage of patients with MMR2 Three studies ages 9 years through college age No serious adverse effects reported after 3 MMR 2,3,4 3 MMRs appears to provide short-term boost in antibodies and seroconverts most seronegative persons 1. Cardemil CV et al., NEJM 2017, 377(10): Nelson GE et al., Pediatr Infect Dis J 2013, 32(4): Ogbuanu IU et al., Pediatrics 2012, 130(6):e Albertson JP et al., MMWR 2016, 65(26):731-4.

47 ACIP Mumps Recommendation Persons previously vaccinated with two doses of a mumps-containing vaccine who are identified by public health as at increased risk for mumps because of an outbreak should receive a third dose of a mumpscontaining vaccine to improve protection against mumps disease and its complications

48 Pneumococcal

49

50 Source: ACIP Meeting, October 2016

51 PCV 13 (Prevnar) in Persons 65 years and older Background Pneumococcal conjugate vaccines have dramatically reduced IPD in adults through indirect effects PCV13 effective against IPD including pneumonia with bacteremia PCV13 demonstrated 45% efficacy (95% CI 14 65%) against vaccine-type nonbacteremic pneumococcal pneumonia (NBPP) - CAPITA ACIP recommended routine use of 13-valent pneumococcal conjugate vaccine (PCV13) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) for adults aged 65 years in 2014 Herd effects may limit the continued use Uncertainty around the burden of vaccine preventable non-bacteremic pneumonia 2018: Re-evaluation for need and revision of recommendation for routine PCV13 use among adults 65 years and older ACIP,

52 Terms of Reference (Review plan) Data on efficacy, effectiveness, immunogenicity, cost-effectiveness Is PCV13 reducing disease among adults 65 years and older Is there a benefit to continuing PCV13 in adults Review current recommendations using up-to-date evidence Disease and vaccine impact Indirect vs direct effects Carriage

53 IPD rates among adults 65 years, ACIP, October 2017

54 ACIP, October 2017

55 6-59 Months of age 30% Carriage all serotypes ACIP, October 2017

56 Carriage in Adults 65 years and older Colonization precedes disease 1 multicenter study of 3000 patients ( ) 47% vaccinated with PCV % vaccinated with PPSV Nasal Swabs Results Vaccinated N=1353 Non-Vaccinated N=1464 Pneumococcal Carriage 1.8% 1.6% PCV 13 VT-Pneumococcal Carriage 0.2% 0.1% Conclusion Carriage is rare in adults 65 years and older Difficult to distinguish direct vs indirect effect Presentation by Dr. Almea Mataanock, CDC, ACIP Meeting February 2018

57 PCV13 Evidence Presented to Date Pneumococcal carriage among adults 65 years old very low (1.8%) PCV13-type carriage 0.2% in PCV13 coverage 65 years old ~ 40% Invasive pneumococcal disease (IPD) PCV13-type IPD declined among all age groups IPD incidence in adults 65 years old plateaued in Modeled direct and indirect effects project relatively few cases prevented Serotype 3 IPD does not follow the same pattern as other PCV13-types Presentation by Dr. Almea Mataanock, CDC, ACIP Meeting February 2018

58 Evidence Presented to Date Vaccine effectiveness (VE) against PCV13-type* IPD Study Population VE (95% Confidence Interval) CAPiTA Randomized control trial Dutch adults 65 years old 75% (41 91) CDC Traditional Methods IPD cases identified through ABCs matched with population-based controls 65% (19 85) CDC CMS Medicare part B IPD cases matched with controls 47% (4 71) * CDC Traditional Methods and CDC CMS VE includes serotype 6C VE against PCV13-type pneumococcal pneumonia Study Population VE (95% Confidence Interval) CAPiTA Randomized control trial Dutch adults 65 years old 45% (14 65) Louisville Pneumonia Study Test negative design in a cohort U.S. adults 65 years old 73% (13 92) Presentation by Dr. Almea Mataanock, CDC, ACIP Meeting February 2018

59 Pneumococcal Disease Conclusions Invasive pneumococcal disease among adults and children have plateaued in Reductions driven by types 19A and 7F No observed evidence of serotype replacement in children or general adult population Continue monitoring changes in serotype distribution to inform future vaccine policy Upcoming ACIP discussions PCV13 impact on pneumonia Public health impact Cost-effectiveness Possible Decisions PCV13 or No PCV13 for adults 65 years old Expanding indications for adults <65 years old Presentation by Dr. Almea Mataanock, CDC, ACIP Meeting February 2018

60 Influenza

61 Severity Of Past Influenza Seasons Alicia Fry, CDC, Immunization Summit Very High High Moderate Mild Alicia Fry (CDC), 12/2017

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71 24.3% in 16-17

72 VE estimates from other countries Northern Hemisphere ( ) Final estimates UK: all viruses: VE=39.8% (23, 53); H3N2 VE=32% (10, 48) Europe hospital network/older adults (65yrs+): H3N2 VE=17% (1, 31) Interim estimates Canada: All viruses: H3N2 VE=42% (18, 59) Europe (IMOVE): H3N2 VE=38% (21, 51) Southern Hemisphere (2017) Interim estimates: Australia: All viruses: VE=33% (17, 46) ; H3N2 VE=10% (-16, 31) Alicia Fry (CDC), 12/2017 Sullivan, Eurosurveillance; Pebody, Eurosurveillance; Rondy,EurosurveillanceSkowronski Eurosurveillance; KisslingEurosurveillance

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74 Tammy Santibanez (CDC), December 2107

75

76 Interim adjusted vaccine effectiveness against medically attended influenza by age group, Vaccine Effectiveness Influenza positive Influenza negative Unadjusted Adjusted* Any influenza A or B virus N vaccinated /Total (%) N vaccinated /Total (%) VE % 95% CI VE % 95% CI Overall 741/1712 (43) 1518/2850 (53) 33% (24 to 41) 36% (27 to 44) Age group (yrs) 6 mos 8 127/359 (35) 408/739 (55) 56% (42 to 66) 59% (44 to 69) /288 (35) 104/300 (35) 0% (-41 to 29) 5% (-38 to 34) /561 (35) 444/989 (45) 33% (17 to 46) 33% (16 to 47) /288 (55) 277/454 (61) 21% (-6 to 42) 17% (-15 to 40) /216 (73) 285/368 (78) 23% (-14 to 47) 18% (-25 to 47) * Multivariate logistic regression models adjusted for site, age, sex, race/ethnicity, self-rated general health status, interval from onset to enrollment, and calendar time. MMWR. Weekly / February 16, 2018 / 67(6);

77 Interim adjusted vaccine effectiveness against medically attended influenza A(H3N2) by age group, Vaccine Effectiveness Influenza positive Influenza negative Unadjusted Adjusted* N vaccinated /Total (%) N vaccinated /Total (%) VE % 95% CI VE % 95% CI Influenza A/H3N2 Overall 530/1143 (46) 1518/2850 (53) 24% (13 to 34) 25% (13 to 36) Age group (yrs) 6 mos 8 79/200 (40) 408/739 (55) 47% (27 to 61) 51% (29 to 66) /203 (37) 104/300 (35) -10% (-60 to 24) -8% (-62 to 29) /395 (39) 444/989 (45) 21% (-1 to 37) 20% (-4 to 38) /198 (58) 277/454 (61) 11% (-24 to 37) 12% (-26 to 39) /147 (72) 285/368 (78) 25% (-16 to 51) 17% (-35 to 49) * Multivariate logistic regression models adjusted for site, age, sex, race/ethnicity, self-rated general health status, interval from onset to enrollment, and calendar time. MMWR. Weekly / February 16, 2018 / 67(6);

78 Interim adjusted vaccine effectiveness against medically attended influenza A(H1N1)pdm09 and B by age group, Vaccine Effectiveness Influenza positive Influenza negative Unadjusted Adjusted* N vaccinated /Total (%) N vaccinated /Total (%) VE % 95% CI VE % 95% CI Influenza A/H1N1pdm09 Overall 60/208 (29) 1518/2850 (53) 64 (52 to 74) 67% (54 to 76) Age group (yrs) 6 mos 17 22/105 (21) 512/1039 (49) 73 (56 to 83) 78 (63 to 87) /84 (31) 721/1443 (50) 55 (28 to 72) 51 (20 to 70) 65 12/19 (63) 285/368 (78) 50 (-31 to 81) 34 (-96 to 78) Influenza B Overall 132/323 (41) 1518/2850 (53) 39 (23 to 52) 42% (25 to 56) Age group (yrs) 6 mos 17 46/127 (36) 512/1039 (49) 42 (14 to 60) 36 (1 to 58) /151 (35) 721/1443 (50) 46 (23 to 62) 50 (28 to 66) 65 33/45 (73) 285/368 (78) 20 (-62 to 60) 25 (-62 to 66) * Multivariate logistic regression models adjusted for site, age, sex, race/ethnicity, self-rated general health status, interval from onset to enrollment, and calendar time. MMWR. Weekly / February 16, 2018 / 67(6);

79 Antigenic Characterization of U.S. Influenza A Viruses October 1, 2017 to Present A (H1N1)pdm09: all are A/Michigan/45/2015-like (vaccine component) A(H3N2): 291 of 297 (98.0%) inhibited by ferret antisera raised against A/Michigan/15/2014, a cell propagated A/Hong Kong/4801/2014-like reference virus representing the H3N2 component of the vaccine 64.4% of viruses tested were well-inhibited by ferret antiserum raised against the egg-propagated A/Hong Kong/4801/2014 reference virus B/Victoria linage: 45.1% reacted poorly with ferret antisera raised against cell propagated B/Brisbane/60/2008 reference virus, representing a B component in both quadrivalent and trivalent influenza B/Yamagata lineage: All similar to cell propagated B/Phuket/3073/2013, representing B component in the quadrivalent influenza

80 Summary Influenza Vaccine Effectiveness Interim results for season (through February 3, 2018) indicate vaccination reduced influenza medically attended illness by 36% 25% (13 to 36) VE against A(H3N2) for all ages 51% (29 to 66) in children aged 6m 8 years No other age groups had statistically significant VE estimates 67% (54 to 76) VE against A(H1N1)pdm09 42% (25 to 56) VE against B (mostly B/Yamagata, not in IIV3) Final VE results at end of season will be used to calculate averted burden (cases, hospitalizations, deaths) Vaccination averts thousands of hospitalizations each year during , 47,000 (11, ,000) influenza hospitalizations averted Antiviral Resistance Budd AP. Update: Influenza Activity United States, October 1, 2017 February 3, MMWR Morb Mortal Wkly Rep 2018;67: H3N2 H1N1 B Oseltamivir S R 1.0% S Zanamivir S S S Peramivir S R 1.0% S

81 Vaccine Virus Selection for February 22, 2018: W.H.O. recommended Composition of Influenza Virus Vaccines for Use in the Northern Hemisphere Influenza Season March 1, 2018: Vaccines and Related Biological Products Committee Meeting Agreed A/Michigan/45/2015 (H1N1)pdm09-like virus A/Singapore/INFIMH /2016 (H3N2)-like virus - Change a B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage) - Change a B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage). Quad 2 nd strain

82 Live Attenuated Influenza Vaccine (LAIV4) Past and Future 2003 LAIV3 Licensed 2-49 years 2012 LAIV4 licensed Replace LAIV3 following season 2014 LAIV Preferred 2-8 yrs 2015 LAIV Preference Removed LAIV4 Not LAIV4 Not 2016 Recommended 2017 Recommended 2018 LAIV4 Recommended 2-49 years No Preference

83 Variability in LAIV Effectiveness Estimates Higher effectiveness in studies conducted outside the U.S. e.g., Canada, United Kingdom, Germany, Finland (which have continued to use LAIV) Reasons not completely understood; possibilities include Differences in use of trivalent as compared with quadrivalent LAIV Small sample size and imprecision of estimates in most individual studies Differences in prevalence of prior vaccination among children in different countries and populations Previous exposure to LAIV Variation in Influenza Viruses / Different Seasons There may be difference among IIV not evaluated

84 LAIV A(H1N1) Vaccine Strain A/Bolivia LAIV strain replicated less well A/Slovenia strain to replace A/Bolivia Shedding demonstrating through Day 7, after Dose 1 of the vaccine demonstrates replication Higher percentage of shedding seen in seronegative subjects More immunogenic Similar conversion rates to pre-pandemic H1N1 strain New assays used in selection process of LAIV strains 84

85 Issues discussed by ACIP Influenza important cause of morbidity and mortality in children New formulation not clinically tested Comparable to IIV against H3N2 Good effectiveness against B No safety concerns Unknown if effective against H1N1 Lack of LAIV is a problem in some programs (local, schools) Decrease coverage in 5-12 year-olds by 2% National coverage unchanged (no increase or decrease) Consumer confidence important Cause of previous lack of effectiveness plausible LAIV still licensed by FDA Not holding all manufacturers to same standards

86 VOTE Passed For the season, immunization providers may choose to administer any licensed, age appropriate influenza vaccine, (including LAIV, IIV, and RIV). LAIV4 is as an option for influenza vaccination for persons for whom it is otherwise appropriate.

87 Different Pediatric Doses >6 Months

88 Hepatitis B

89 Heplisav-B (Dynavax) In the U.S.: 850, million with chronic HBV since 2014 likely due to heroin and opioid epidemic 5,000 people die from HBV per year from chronic liver disease Hepatitis B Vaccine (Recombinant), Adjuvanted Heplisav-B FDA licensed November 9, 2017 for 18 years and older Series of 2 doses, separated by 1 month Adjuvant stimulates TLR9, combined with HBsAg elicits anti-hbsag Ab Seroprotection 90.0%-100.0% 70.5%-90.2% with existing Hepatitis B vaccines Better response in diabetes, kidney disease than current HepB vaccines Non-responders very small Local & systemic AEs similar to other Hep B vaccines Signal with CV disease will monitor in post-marketing studies

90 ACIP Workgroup Considerations 2 dose; minimum interval 4 weeks When a vaccine series initiated with one dose of a vaccine from a different manufacturer must be completed with HEPLISAV-B, 3 total Hepatitis B vaccine doses should be administered Fewer doses may mean better compliance with series completion and earlier protection ACIP to review more safety data and economic analysis in future ACIP Vote: Non-preferential HEPLISAV-B a hepatitis B vaccine that may be used to vaccinate persons aged 18 years and older against infection caused by all known subtypes of HBV.

91 Quick Shots Hepatitis A PEP changes Decrease in antigen amount in the Immune Globulin supply IGIM dose now 5x the amount: ml/kg (70 kg= 7-14 ml) HPV consider harmonization of male and female schedule Oropharyngeal cancer rates increasing in males and vaccination may prevent Meningococcal Challenges in getting students vaccinated in outbreaks Still low number of cases

92 Vaccination Scenarios Not Indicated Contraindicated Not Indicated Not contraindicated Give? Indicated Not contraindicated Indicated Contraindicated

93 Case Scenarios Zoster 60 year old, immunocompromised Give shingles vaccine? If so, which one? Mumps 20 year college student lives on campus when mumps breaks out IZ history: 2 doses of MMR at 1 year and 5 years of age Serology positive for mumps antibodies at 18 years of age Give a 3 rd dose of MMR?

94 WHO, Vaccines in the Pipeline Pathogen Month of most recent update Updating Partner Study Status Vaccine HIV June 2017 HVTN, IAVI, MHRP Phase I/II Malaria November 2017 University of Washington Phase III RTS,S/AS01 TB November 2017 Aeras Phase I/II Non-BCG recombinant Dengue November 2017 WHO Secretariat Phase IV Dengvaxia (19 countries) RSV November 2017 PATH Phase I/II Rotavirus November 2017 PATH Other enterics November 2017 PATH Phase I/II Shigella and ETEC Zika January 2018 WHO Secretariat Phase I/II Lassa, MERS-CoV, Nipah November 2017 CEPI Ebola/Marburg November 2017 Oxford Phase I-III Pneumococcal infections November 2017 MSF Epicentre Phase 1-IV new combos, new valency

95 1. The Most common cause of Shoulder Injuries Related to Vaccine Administration (SIRVA) is : A. Both Patient and Provider are standing B. The Vaccination is given too high on the shoulder C. The needle used in the vaccination is too short D. The patient moved during the injection

96 2. The proper administration site and dosing interval of RZV (Shingrix ) is: A. 0.5 ml Intramuscularly now and 1 month later B ml subcutaneously as a single dose C ml intramuscularly now and 6 months later D. 0.5 ml intramuscularly now and 2 to 6 months later

97 3. Pneumococcal Vaccination of adults 65 years and older with PCV13 is under reevaluation by the ACIP because: A. Enough adults 65 years and older will be vaccinated that herd immunity may no longer require the need for vaccination B. Carriage rates remain high so vaccination may need to be continued C. There is no need to re-evaluate the use of PCV13 in adults over 65 years of age D. Concern of a decrease in pneumococcal disease due to herd effects secondary to infant immunization with PCV13 may make vaccination of adults 65 years and older unnecessary

98 4. The Vaccine Effectiveness (VE) of the l influenza vaccine A. was 25% against A/H3N3 and higher than seen in Australia B. was the same for all 4 serotypes (A/H1N1, A/H3N2, B/Yamagata and B/Victoria) C. was lower due to serotype drift in the B/Yamagata strain D. was so low that vaccination was not useful

99 5. Which is the only vaccine on the adult schedule with a preferential recommendation? A. Flumist B. Shingrix C. Heplisav-B D. Pneumovax