1. Vaccine Update 2017 Shireesha Dhanireddy, MD
Associate Professor, Department of Medicine
Division of Infectious Diseases, University of Washington
September 2017

2. Financial Disclosures
NONE **But, as an infectious diseases provider, I AM PRO-VACCINE

3. Objectives
Summarize techniques that can be useful when dealing with patients who are skeptical of vaccines
Discuss the factors that played a role in the California measles outbreak
Describe the current state of vaccine recommendations and guidelines

4. Our competition …

5. Resistance to Vaccination
Mom brings her 12-month old healthy child to clinic for routine visit. Mom does not want child vaccinated due to concern of possible link between MMR vaccine and autism. What do you advise?

6. Original publication linking MMR to autism
Small case series (eight children) with no controls published in reported on children who developed autism within one month of measles vaccine.
Proposed that measles vaccine travels to intestine, damages intestine, and brain-damaging proteins enter bloodstream.
Over ensuing decade, epidemiological studies consistently found no evidence of a link between MMR vaccine and autism. (Madsen et al., NEJM 2002; 347: 1477)
Paper retracted 12 years later.

7. MMR and Autism
Strong scientific evidence that MMR vaccine does not cause autism (Danish cohort study, > 2,000,000 person-years, Madsen et al., NEJM 2002; 347: 1477)
Timing of vaccination in relation to timing of the occurrence of the event
MMR: True vaccine risk — encephalitis or severe allergic reaction 1 in 1,000,000

8. Misconceptions about vaccines
Many reasons for fear or opposition to vaccination:
religious/philosophical objections
government interference
safety/efficacy concerns
not concerned about the disease itself
As a practitioner, listen and try to understand concerns, fears, beliefs
Provide accurate information to our patients and their parents

9. Rates of Non-vaccination for non-medical reasons
Colorado, Kansas, Indiana, DC have the highest rates

10. Worldwide: 20 million cases annually
Concern: “Vaccine-preventable diseases have been virtually eliminated in the United States, so there is no need for my child to be vaccinated.”
Worldwide: 20 million cases annually
440 deaths per day, 17 deaths per hour
Declared eliminated from the US in 2000
Most subsequent cases imported or linked
In 1997 to 2000, most measles cases in the United States were associated with international visitors or US residents who were exposed to the measles virus while traveling abroad
More than 90 percent of people who are not immunized will get measles if they are exposed to the virus
This last statement is very important- herd immunity, risk to vulnerable populations

11. California Outbreak
Started in late December 2014 with majority cases linked to Disneyland in California
January 2015: 104 cases in 14 states
January 23, 2015: CDC issued a Health Advisory
Most unvaccinated

12. Minnesota Measles 2017 Outbreak
From 1997 through 2016, total of 56 cases of measles
2017  79 cases to date
Why?

13. Minnesota Measles 2017 Outbreak

14. Measles Immunization and Efficacy
Licensed in 1963
Inactivated vaccination from  live attenuated
Revaccinate those who received inactivated (killed) vaccine
Usually administered as MMR or MMRV
One dose of MMR: approximately 93% effective
Two doses of MMR: approximately 97% effective
Two doses recommended since 1989

15. Impact of Vaccine
Sspe =- subacute sclerosing panencephalitis

16. Measles Adverse reaction Natural infection per 100,000
Vaccine-related per 100,000
Encephalitis
50-400
0.1
Pneumonia
3,800-7,300
None
Convulsions
500-1,000
Death
10-10,000
What is measles - aka rubeola, resp contact spread, very infectious, cough, runny nose, conjunctivitis
Subacute sclerosing panencephalitis
Controversy about autism; groups even around here don’t vaccinate for this reason

18. Question: Pneumococcal Vaccine
A 65 year old man presents to the clinic for routine care. He has not been vaccinated against for pneumonia. Which of the following is most accurate?
He does not need vaccination unless he has other risk factors
He needs a PCV13 alone
He needs a PCV13 followed 1 year later by a PPSV23
He needs a PPSV23 alone

19. Pneumococcal Disease 4 million cases/year in US
445,000 hospitalizations/year
22,000 deaths/year
Cox CM. CDC Manual for the Surveillance of Vaccine Preventable Diseases

20. Pneumococcal Disease Age Disease Incidence Cases/100,00 (# of cases)
Death Rate Deaths/100,000
(# of deaths)
<1
31.4 (142)
0.22 (1) 1
24.6 (112)
2-4
12.6 (171)
0.15 (2)
5-17
2.2 (111)
0.02 (1)
18-34
3.7 (261)
0.26 (18)
35-49
10.3 (670)
0.65 (42)
50-64
19.5 (1,068)
1.86 (102)
> 65
37.0 (1,291)
5.61 (196)
Total
12.9 (3,828)
1.22 (363)
Cox CM. CDC Manual for the Surveillance of Vaccine Preventable Diseases

21. Pneumococcal Vaccine in Adults: Who need it?
Persons > 65 years of age
Persons age with:
Chronic lung disease (asthma or COPD)
Chronic heart disease (except HTN)
Chronic liver disease
CSF leak
Smokers
Diabetes
Alcoholism
Functional or anatomic asplenia
Immunocompromising conditions
Basically anyone who is at risk for invasive pneumococcal disease

22. Pneumococcal Vaccine Efficacy
Direct effects of PPSV23 vaccination in the elderly controversial
Cochrane Review
Strong evidence for PPSV23 efficacy against invasive disease
Inconclusive efficacy for pneumonia
In patients with COPD, decreased likelihood of exacerbations
Not associated with significant decrease in mortality
? Less efficacious in adults with chronic illness
Cochrane Review. 2013, 2017

23. Clin Infect Dis. 2013;56:e59-e67

24. Pneumococcal Vaccine (PPSV23): Revaccination
Not recommended for most persons
Who should be revaccinated?
Persons aged with
Functional or anatomic asplenia
Immunocompromising conditions
Multiple vaccinations not recommended
MMWR (34);

25. PPSV23 vs PCV13 PCV13 recommended for some immunocompromised adults
PPSV23 – contains polysaccharide antigens
PCV13 – contains immunogenic proteins conjugated to pneumococcal polysaccharides
PCV13 recommended for some immunocompromised adults
PCV13 recommended for persons > 65 if not received already in adulthood
MMWR. 2015;64(34):944-7

26. Question: Pneumococcal Vaccine
A 65 year old man presents to the clinic for routine care. He has not been vaccinated against for pneumonia. Which of the following is most accurate?
He does not need vaccination unless he has other risk factors
He needs a PCV13 alone
He needs a PCV13 followed 1 year later by a PPSV23
He needs a PPSV23 alone

28. Question: Zoster Vaccine
A 64 year old woman with a self-reported history of shingles 2 years ago and type II diabetes presents to clinic. What do you recommend regarding the zoster vaccine?
Vaccine is contraindicated given her history of diabetes
Vaccine not indicated given her history of zoster
Check VZV titer to confirm history. If negative, proceed with vaccination
Recommend zoster vaccine

29. Herpes Zoster
Develops in 30% of people over a lifetime (1million + cases a year in US)
Incidence increases with age
8-10x more likely in people > 60
May lead to postherpetic neuralgia (PHN)
“pain that persists more than 30 days after the onset of rash or after cutaneous healing”
Kimberlin DW, Whitley RJ. NEJM 2007;356:
Gann JW, Whitley RJ. NEJM 2002;347:340-6

30. Zoster Vaccine (Zostavax)
Study Design
N = 38,546
Adults > 60
Randomized, double-blind
Followed for mean 3.1 yrs
Single dose vaccine vs placebo
Vaccine is same strain as varicella (merck-oka strain) but 14 x more potent
Decreased Herpes Zoster by 51.3%
Decreased PHN by 66.5%
Oxman MN et al. NEJM 2005;352:

31. Zoster Vaccine: 2008 ACIP Recommendations
Age Specific Recommendations:
All persons > 60 years*
Excludes those with contraindications to live vaccine
Includes those with history of zoster or have chronic medical conditions
Dose:
Single dose
Vaccine has FDA approval for pts over 50 years of ago
MMWR 2008;57(RR-5):1-40

32. Update on Herpes Zoster Vaccine (HZV)
October 2008: the ACIP recommended a dose of HZV for all adults >60 years unless they have contraindications
March 2011: FDA approved use of Zostavax in adults aged years
Should we be administering HZV at ages years?

33. ACIP HZ Working Group Conclusion
Affirms existing recommendation for routine vaccination of persons 60 years of age and older
Burden of HZ disease in increases with age
HZ vaccine administration should be timed to achieve the greatest reduction in burden of HZ and its complications
There is insufficient evidence for long term protection offered by the HZ vaccine
Providers should counsel persons who are vaccinated at years of age that the duration of protection offered by the vaccine is uncertain; therefore they may not be protected when the incidence of HZ and its complications are highest.

34. Question: Zoster Vaccine
A 64 year old woman with a self-reported history of shingles 2 years ago and type II diabetes presents to clinic. What do you recommend regarding the zoster vaccine?
Vaccine is contraindicated given her history of diabetes
Vaccine not indicated given her history of zoster
Check VZV titer to confirm history. If negative, proceed with vaccination
Recommend zoster vaccine

35. Question 2: Zoster Vaccine
A 64 year old woman with rheumatoid arthritis on steroids and a biologic asks if she may receive the zoster vaccine. What do you recommend?
Vaccine is contraindicated given she is immunosuppressed
Recommend zoster vaccine
Wait for something else?

36. Zoster Vaccines Varicella-Zoster Virus
VZV
VZV
Zostavax Live Attenuated Vaccine 1

37. Zoster Vaccines + Varicella-Zoster Virus Live Attenuated Vaccine
VZV
Glycoprotein E
AS01 Adjuvant System
VZV +
Live Attenuated Vaccine
Subunit Vaccine (Hz/su)
Investigational 1

38. Investigational
HZ/su Vaccine Efficacy Against First Episode of Zoster in Immunocompetent Patients
Background - Randomized, Controlled, Phase 3 trial Multicenter, International; n = 15, Adults aged > Safety and efficacy of herpes zoster subunit (HZ/su) vaccine - Excluded those with prior h/o zoster or immunosuppressed Excluded if previously vaccinated against varicella or zoster - Median follow-up 3.2 years
Study Arms (two doses one month apart) - Zoster Subunit Vaccine (n = 7,698) - Placebo (n = 7,713)
Source: Lal H, et al. N Eng J Med. 2015;372: 1

39. Investigational
HZ/su Vaccine Efficacy Against First Episode of Zoster in Immunocompetent Patients ≥50
Source: Lal H, et al. N Eng J Med. 2015;372: 1

40. Investigational
HZ/su Vaccine Safety and Efficacy Against First Episode of Zoster in Immunocompetent Adults ≥70
Source: Cunningham AL, et al. N Eng J Med. 2016;375: 1

42. Meningococcal Vaccine Question
A 11 year old otherwise healthy child presents for routine vaccinations. Which of the following is the most accurate regarding meningococcal vaccination?
Not needed at this age
Give meningococcal conjugate vaccine (MCV4)
Give meningococcal polysaccharide vaccine (MPSV4)
Give meningococcal B vaccine only
Give both MCV4 and meningococcal B vaccines 1

43. Meningococcal Quadrivalent Vaccines Serogroups Included in Vaccine: A, C, Y, W-135
x B
 C
 Y
 W-135 1

44. Meningococcal Quadrivalent Vaccine Serogroups Included in Vaccine: A, C, Y, W-135
Menactra (MCV4) - Conjugate vaccine - FDA-Approved in Approved for ages 9 months to 55 years
Menveo (MCV4) - Conjugate vaccine - FDA-Approved in Approved for ages 2 months to 55 years
Menomune (MPSV4) - Polysaccharide vaccine - FDA-Approved in Approved for persons >2 years of age 1

45. Meningococcal B VaccinesY
W-135 1

46. Meningococcal Group B Vaccine Serogroups Included in Vaccine: B
MenB-4C (Bexsero) - Recombinant vaccine - FDA-Approved in 2015 for ages 10 to 25 years - 2 dose series ≥1 month apart
MenB-FHbp (Trumenba) - Recombinant vaccine - FDA approved in 2014 for ages 10 to 25 years - Healthy adolescents and young adults: 2 doses at 0, 6 months - Adults at risk for meningococcal disease: 3 doses at 0, 1-2, 6 months - Vaccinated during serogroup B meningococcal disease outbreaks: 3 doses at 0, 1-2, 6 months 1

47. ACIP Meningococcal B Vaccine Recommendation Adolescents and Young Adults
Recommended for people years of age at increased risk, preferred age 16-18:
Meningococcal B outbreak
Asplenia
Complement deficiency
On eculizumab (Soliris)
Microbiologist with potential exposure to Neisseria meningitidis
Same vaccine should be used for all doses
Source: CDC. MMWR. 2015;64: 1

48. Investigational
Meningococcal Pentavalent Vaccine Serogroups Included in Vaccine: A, B, C, Y, W-135 A B C Y
W-135 1

49. Meningococcal Vaccine Question
A 11 year old otherwise healthy child presents for routine vaccinations. Which of the following is the most accurate regarding meningococcal vaccination?
Not needed at this age
Give meningococcal conjugate vaccine (MCV4)
Give meningococcal polysaccharide vaccine (MPSV4)
Give meningococcal B vaccine only
Give both MCV4 and meningococcal B vaccines 1

51. Question: Influenza Vaccine
67 year old man with moderate COPD presents for his routine visit in the fall.
Which of the following is most appropriate regarding immunization against influenza?
Live attenuated vaccine should be given as it has been found to be more effective than the inactivated vaccine.
High-dose, trivalent, inactivated vaccine should be administered.
Standard-dose, trivalent, inactivated vaccine should be administered
ACIP recommendations 8/8/2008

52. Influenza > 30,000 deaths in US per year
Never too late to vaccinate
Greatest mortality risk in elderly, immunosuppressed, obese, pregnant
Everyone age >6 months old should be vaccinated!!

53. Influenza 2017-2018 Vaccines will be covering: Vaccines available:
A/Michigan/45/2015 (H1N1)-like virus
A/Hong Kong/4801/2014 (H3N2)-like virus
B/Brisbane/60/2008-like virus
+/- B/Phuket/3073/2013-like virus
Vaccines available:
Inactivated Quadrivalent,
Inactivated Trivalent
Recombinant

54. No LAIV recommended for 2016-2017 season
LAIV previously recommended for 2-8 year old children
Reports of poor protection against H3N2
Most recent data show no protection against H1N1

55. Prevention High Dose Trivalent Influenza Vaccine
Sponsored by manufacturer
Double the cost
24% relative decrease in incidence
1.4% incidence vs 1.9% incidence
Diaz Granados CA et al. N Engl J Med 2014;371:635

56. Fluzone High Dose Vaccine Efficacy Study
Randomized, blinded study in US, Canada (N = 32,000)
(mild) & (moderately severe) seasons
Lab confirmed influenza: 1.43% HD vs. 1.89% SD
Relative efficacy 24.2% (9.7, 36.5)
OR:
4-5 fewer cases/1000 vaccinated
217 vaccinations to prevent one additional case
Cost
HD: ~$25 VS. SD: ~$12
Safety: AE comparable for HD and SD

57. Recombinant Influenza Vaccine
Dunkle LM et al. N Engl J Med 2017

58. Recombinant Influenza Vaccine
Phase 3-4 randomized, blinded study in US (N = ~9000)
season
Recombinant quadrivalent (RIV4) vs standard inactivated quadrivalent (IIV4)
Lab confirmed influenza: 2.2% (96 cases) RIV4 vs. 3.2% (138 cases) IIV4
~30% reduction
Dunkle LM et al. N Engl J Med 2017

59. Influenza & Parotitis
– several 100 cases of confirmed influenza with parotitis
Mostly in school-aged children and men
More likely with influenza A (H3N2)
CDC recommends clinicians to evaluate patients with acute parotitis (not associated with mumps outbreak) to consider influenza

60. Influenza 2017 and beyond
New treatment option – Peramivir 600mg IV qday
Available IV only
FDA approved for treatment of acute, uncomplicated influenza
Cost: ~$1000
De Jong M et al. Clin Infect Dis 2014;59(12):172

61. Question: Influenza Vaccine
67 year old man with moderate COPD presents for his routine visit in the fall.
Which of the following is most appropriate regarding immunization against influenza?
Live attenuated vaccine should be given as it has been found to be more effective than the inactivated vaccine.
High-dose, trivalent, inactivated vaccine should be administered.
Standard-dose, trivalent, inactivated vaccine should be administered
ACIP recommendations 8/8/2008

62. Objectives
Summarize techniques that can be useful when dealing with patients who are skeptical of vaccines
Discuss the factors that played a role in the California measles outbreak
Describe the current state of vaccine recommendations and guidelines

63. Take Home Points Counsel patients regarding importance of vaccination
Provide evidence, discuss protection of others in community
New subunit (non-live) zoster vaccine will be available soon and may be an option for patients with contraindication to live vaccine
Consider indications for giving meningococcal B vaccination
Live influenza vaccine currently not recommended