Download Adult Vaccines: Update 2015

Adult Vaccines:
Update 2015
Thomas M File, Jr MD MSc MACP FIDSA FCCP
Chair, Infectious Disease Division
Summa Health System
Akron, Ohio;
Professor of Internal Medicine,
Chair ID Section
Northeast Ohio Medical University
Rootstown, Ohio
Objectives
Review new developments in
adult vaccines
 Focus on Influenza and pneumococcal
vaccines
 Additional comments: Zoster, Tdap
Burden of Vaccine-Adult Preventable
Disease in the US
Disease
Annual Burden of Disease, United States
Influenza
200,000 hospitalizations; 36,000 deaths (> 90% in older
adults)
Invasive
pneumococcal
disease
44,000 cases, 4500 deaths (higher rates of both in older
adults and persons with comorbidities)
Hepatitis B
51,000 infections (95% adults); 2000-3000 deaths;
1.25 million with chronic HBV infection
Human
papillomavirus
6.2 million new infections (>4000 women die in US
annually; ? Male deaths)
Pertussis
10,454 cases reported in 2007 (3152 adults)
Severe illness in infants; often transmitted by older child or
adult
Zoster
1 million cases; risk for shingles and postherpetic neuralgia
increases with age
4
Immunizations: Return on Investment
 Vaccine preventable infections represent
significant Economic Burden
 Vaccine ROI:
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
For each birth cohort vaccinated:
42,000 lives saved
20 million cases of disease prevented
13.6 billion dollars saved in direct costs
69 billion dollars saved total (with indirect cost)
For each dollar spent, $10.20 saved
Zhou et al. Arch Ped Adolesc Med. 2005
2013 Adult Immunization
Coverage, US
**Influenza Estimates 2013-14.
MMWR. Feb 6, 2015. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6404a6.htm#Tab2
Healthy People 2020 Objectives on Immunization and Infectious Disease. www.Healthypeople.gov/2020/.
Consequences of lapses of
immunization: Outbreaks
•California (2010)
•9,143 cases of pertussis (including ten infant deaths)
were reported throughout California. Most cases reported
in 63 years.
•Measles outbreak source
•Ohio (2010-2014)
–In 2010, there were 964 cases of pertussis reported by
Columbus and Franklin Counties. Most cases reported in
25 years.
–In 2014, there have been 377 cases of measles (10
hospitalized) since March.
–In 2014, there have been 460 cases of mumps (many
Vaccine-Preventable Diseases
Issues with Adult Vaccination

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Busy Practice
Costly Inventory
Storage and Handling Concerns
Frequently Changing Practice Guidelines
Lack of System-wide Documentation
Inconsistent Reimbursement
Patient Objections/Myths
Physician-Patient Miscommunication
National Foundation for Infecgious Diseases. Surveys of consumers and physicians
2010
The Communications Breakdown
Recommendation
“You
need to
get this
vaccine.”
OR
“I want
you to
get this
vaccine.”
VaccineMotivated
Patient
Not a Recommendation
“Do you
want this
vaccine?”
OR
“Think
about
getting the
vaccine.”
VaccineAmbivalent
Patient
Vaccines: Very high benefit/risk ratio
 All vaccines have possible side effects,
most mild, rarely severe
 The risk of disease far outweighs the risk
of vaccine
 MESSAGE:
 Vaccines Effective
 Need Clear, Unambiguous message
 Safe
 Need to recommend
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Recommended Adult Immunization: 2015
13
2015-2016 U.S. Influenza
Vaccine Composition
 A/California/7/2009 (H1N1)
• Unchanged
 A/Switzerland/9715293/2013 (H3N2)
• Change
 B/Phuket/3073/2013-like virus.
• Similar to last year
 B/Brisbane/60/2008-like virus (in
quadrivalent)
15
INFLUENZA VACCINE-Importance
 Influenza may lead to many complications in adults
• secondary pneumonia
• exacerbation of underlying disease(i.e., chronic lung or heart
disease)
 Influenza virus changes antigens over time;
patients may therefore, not be immune because of
prior exposure
 Efficacy
• Depends on: 1. Immunogenicity; 2. Serotype match
• Recently varied 20-60% pending patient type
 Can be given at SAME time as pneumococcal
vaccine
US Influenza Vaccines
Prepared from embryonated chicken eggs inoculated with
specific strains of virus
 IIV: ‘Killed’, injectable “All comers” 6 months and
older--Both Trivalent (TIV) and Quadrivalent)
 IIV Intradermal
 Approved May 2011 for 18-64 years [smaller needle]
 All Quadrivalent
 LAIV: Live-attenuated, cold-adapted nasal (CANNOT
replicate at body temperature)-nasal spray
 very minimal viral shedding; OK to give to nurses unless taking
care of severely immunocompromised patients (e.g. Stem cell
transplant)
 Indicated only for healthy people 2-50 years; All Quadrivalent
TIV, trivalent inactivated vaccine
*Falsey AR et.al. J Infect Dis. 2009;200:172-180.
INFLUENZA VACCINE
High Dose
 Fluzone High-Dose
 Contains 60 mcg each of the 3 Influenza antigens
(compared to 15 each for regular TIV)
 Slightly higher rate of MILD reactions
 Indications: Patients > 65 years.
 Costs
 In large clinical trial had shown high-dose vaccine
was 24.2% more effective in preventing influenza
in adults > 65 than the standard vaccine.
 N Engl J Med 2014;371:635-45
Newer Influenza Vaccines
(Cell culture)
 Flucelvax 
 In place of chicken eggs, uses animal cells (Canine Kidney) as
host(reference strain obtained form virus originally grown in
eggs)
 Approved ≥ age 18
 Flublok 
 Recombinant vaccine (RIV) — egg-free hemagglutinin influenza
vaccine produced by recombinant DNA technology using a
baculovirus (a virus that infects insects) that produces virus-like
particles, hemaglutinin (vaccine of choice for true egg allergy)
 Approved ages >18; Only 16 week shelf life
 Adverse events similar to other inactive vaccines
INFLUENZA VACCINE
Reduction in Hospitalizations for Cardiac disease and Strokes (Nichols
et a. NEJM 348, April 3, 2003)
 Observational studies of large cohorts (140,000;
146,000), ’98-’99 AND ’99-’00, 3 HMOs,  age
65
 Vaccination against influenza associated with
reduction in hospitalization for :
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Cardiac disease (19% both seasons)
Cerebrovascular disease (16%; 23%)
Pneumonia and Influenza (32%; 29%)
All cause Death (48%; 50%)
 Possible mechanisms: infection cause alterations
in clotting factors, platelet aggregation, amount
of inflammatory- response cytokines which
enhance thrombosis
 Similar findings of more recent study (JAMA.
2013;310(16):1711-1720)
Adults who get Flu Vaccine
help Protect elderly
 People > 65 years were less likely to have serious
influenza-illness when 1/3 of younger adults
within their communities were immunized.
 Cases of influenza-related illness in the elderly
could have been prevented if more non-elderly
adults had received the flu vaccine.
Taksler et al Clin Infect Dis 2015; doi:10.1093/cid/civ630
Influenza ‘Nuts and Bolts’1
 Vaccination season: Soon as available to
~April
 Influenza season unpredictable-can start Oct
 Immunity will last for almost all patients (no concern for
waning immunity for most))
 Late season vaccination important and underutilized
 LAIV can be safely used in MOST healthcare settings as
alternative to TIV2
 Egg allergy NO LONGER contraindication3
 Anaphylaxis is EXCEEDINGLY rare [<10 documented cases]
 Flublok if concern
 OK to give egg-based if not history of severe anaphylaxis
• If vaccinated, should be observed ~30 minutes in office
1.
2.
Centers for Disease Control and Prevention. Inactivated Influenza Vaccine 2011-12. Available at: http://www.cdc.gov/vaccines/pubs/vis/downloads/vis-flu.pdf
Talbot TR, et al. Infect Control Hosp Epidemiol. 2010;31:987-995.
Influenza Vaccine and Egg Allergy: ACIP 2013
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Which vaccine for each patient?
 Patient
 Pregnant women
 67 y/o diabetic
 Prior hives with
eggs
 48 y/o smoker
 58 y/o COPD
 18 month child
 Vaccine
 Trivalent inactive(> 6 months)
 Trivalent ‘High dose’ inactive
(65 +)
 Nasal ‘live’ vaccine (2-50)
 Intradermal vaccine (18-64)
 Quadrivalent inactive (>6 mo)
 Cell Culture; Recombinant
(Flublok) (>18)
 Cell Culture (canine cell;
Flucelvax  ) (> 18)
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Influenza and Pregnancy
 Pregnant woman at high risk for severe
complications and death
 Cellular immune response diminished
 Maternal influenza associated with
increased (Zaman et al. NEJM 2008)
 Maternal hospitalization
 Fetal malformation
 Other illnesses
 Prevention is best approach
 Newborns are at high risk for severe
complications
 Several reports of 2nd MRSA infection
 No approved vaccine for infants < 6 months
of age
 All care givers need to be free from possible
transmission to this vulnerable population
Benefits/Obligations of Influenza vaccine for
Healthcare providers
 As HCW we all have an obligation to protect our
patients
 Transmission may occur without illness
• May be asymptomatic carriers
• Infectious prior to onset of symptoms
 Studies show reduced transmission after vaccination
 Protection form acute illness
 For H1N1 greatest morbidity and mortality is in ‘healthy’
individuals aged 20-50.
 Protection of family members (especially if very
young or with medical conditions)
 Mandatory immunization of all HCW being
implemented at SUMMA
77% of Influenza ‘asymptomatic’
 Flu Watch Study1
 Course of influenza over 5 cohorts (2006-11)
 Serology; PCR; Weekly assessment for RTI
 Findings
 77 % appeared to asymptomatic
 Only 17% of PCR-confrimed infection sought medical attention
 “A large number of well individuals in the
community make a substantial contribution to
transmission.”2
1. Hayward et al. Lancet Resp Med. 2014; 2: 445-54;
2. 2. Horby Lancet Resp Med. 2014; 2: 430
Centers for Disease Control and Prevention. 2010. Active Bacterial Core Surveillance Report,
Emerging Infections Program Network, Streptococcus pneumoniae, 2009.
http://www.cdc.gov/abcs/reports-findings/survreports/spneu09.pdf. Accessed February 3, 2011.
Pneumococcal Diseases causes more deaths per
year in US than Breast Cancer or Prostate Cancer
Xu. Et al. Deaths: Prelimanary data for 2007. Natl Vital Stat Rep. 2009; 58: 1-51
Pneumococcal Vaccines-adults
 90 known serotypes of S. pneumoniae
 Pneumococcal polysaccharide vaccine (PPSV23)
 Inactive vaccine; contains 23 serotypes which account for majority (75-80%)
of clinical disease.
 Approved for use in adults of any age; ? Efficacy for pneumonia
 Pneumococcal conjugate vaccine (PCV13)
approved for use in adults age 50 and older
 Inactive vaccine, conjugated with diptheria CRM 197 protein); 13 serotypes
which account for approx 45-50% of invasive disease
 Approval from FDA announced December 30, 2011 for adults 50 years and
older
 Previously approved and recommended for use in children
 CDC’s Advisory Committee on Immunization Practices (ACIP)
recommends use for patients who are immunocompromised
PNEUMOCOCCAL VACCINE
13 valent conjugated vaccine study for adults
CAPITA Study (Community Acquired Pneumonia
Immunization Trial in Adults)
 RCT trial in Netherlands
 Design
 13 valent conjugate vaccine (same as pediatric vaccine)
 Placebo controlled (1:1); approx 85,000 subjects, > 65 years of age,
community dwelling
 Endpoints:
• Primary-prevention of CAP (serotype specific)
• Secondary-all cause CAP, colonization (2000 subjects), mortality,
bacteremia
 RESULTS:
 45% reduction in vaccine typed non-bacteremic
pneumonia
 75% reduction in vaccine type IPD;
Bonten MJM et al. N Engl J Med 2015; 372: 1114–1125.
Strategies for sequential use of Conjugate
and Polysaccharide vaccine use in adults
 Conjugate vaccine more immunogenicity (higher
antibody levels) and can have booster effect
 13 serogroups (accounts for approx 50% of invasive cases of
pneumococcal disease
 Polysaccharide vaccine less immunogenecity and NO
booster effect (may have hyporesponsiveness)
 But has 23 serogroups (accounts for approx 89% of invasive cases)
 Give Conjugate first followed by polysaccharide for
potentially optimal effect
 If polysaccharide given initially wait one year to
administer the conjugate vaccine (reduce ?
Hyporesponsiveness)
32
33
Source: Designed by National Foundation for Infectious Disease based on CDC recommendations; 2012
Newer CDC Recommendations 2015 for aged > 65
Patient Scenarios
24 year with asthma has not previously
received any pneumococcal vaccine
28 year old woman with HIV infection
received one dose PPSV23 a year ago.
Patient Scenarios
24 year with asthma has not previously
received any pneumococcal vaccine
PPSV23 now; PCV age 65 followed by PPSV 6-12
months later
28 year old woman with HIV infection
received one dose PPSV23 a year ago.
Patient Scenarios
24 year with asthma has not previously
received any pneumococcal vaccine
PPSV23 now; PCV age 65 followed by PPSV 6-12
months later
28 year old woman with HIV infection
received one dose PPSV23 a year ago.
One dose PCV now (> one year since PPSV);
2nd
dose PPSV23 age 32 (> 5 years since
PCV);
3rd
dose PPSV age 65
Patient Scenarios
 42 year old male cochlear implants, no
prior vaccines
 66 year old male, CHF, received PPSV23
age 55
Patient Scenarios
 42 year old male cocjhlear implants, no
prior vaccines
One dose PCV now; one dose PPSV23 >
8 weeks later; 2nd dose PPSV23 age 65
 68 year old male received PPSV23 age 66
Patient Scenarios
 42 year old male cochlear implants, no
prior vaccines
One dose PCV now; one dose PPSV23
> 8 weeks later; 2nd dose PPSV23 age 65
 68 year old male received PPSV23 age 66
One dose PCV13 now
Pertussis Vaccine: Adults
 DTaP (Pediatric vaccine)
 Daptacel™, Infanrix™, Tripedia™
 Contains higher concentration of diptheria toxoid and
acellular pertussis
 Tdap = Tetanus and Diptheria Toxoid, and
Acellular Pertussis
 Adacel™ (Sanofi Pasteur); Boostrix™ (GSK)
 Single dose for persons 11-18 years of age who have completed
the childhood series
 Single dose for adults aged 19 years and older (Including adults
65+ [esp. those with infant contact)
 Tdap should be administered regardless of interval since the last
tetanus-containing vaccine, especially if the patient will have
contact with children <12 months of age
ACIP Tdap Recommendations
Specific Priority Groups
 Pregnant women at 27-36 weeks'
gestation
 AT EACH PREGNANCY!
 Adults, regardless of age, who are in
close contact with infants younger than
age 12 months (e.g., parents,
grandparents, or child-care providers)
 Healthcare Providers
Repeat Tdap in Pregnancy
Retrospective chohort 29,155 pregnant women;
ages 14-49; 2007-2013
Sukumaran L et al. JAMA 2015; 314:1581-87
Zoster Vaccine (Zostavax ™)
 Live vaccine
• Not for pregnancy, immunocompromised
 Approved for the prevention of herpes zoster
(shingles) in persons aged 50 years and older.
(CDC ≥ 60)
 Single SC injection within 30 minutes of
reconstitution
• In 38,000 patient study, reduced the incidence of
shingles by 51% in persons aged 60 years and older
(less effective in older patients)
• Incidence of postherpetic neuralgia less by 39%.
Zoster Vaccine (Zostavax ™)
Most common questions
 What if no history of chicken pox?
• OK to give
 What if past zoster?
• Give after resolution of past episode; no specific
time interval recommended
 Is it covered by Medicare
• Covered by Part D not Part B. Insurance
payment varies by plan.
• To be covered by ACA
 Should I receive if around pregnant or
immunosuppressed persons?
• YES--not transmitted
The wars of the world: Saving lives
through vaccination
 Without the safe and effective vaccines that we
too often take for granted now, more than 300
million who lived full and rewarding lives during
the 20th century would have died prematurely of
a vaccine-preventable disease. Compare this
with the 160 million estimated to have been
killed in all wars combined during the same
century. Stated another way, vaccines saved
twice as many lives as were lost in war during
the most destructive 100 years in human history.
DW Kimberlin Inf Dis News. Aug 1, 2011
Summary
 New Influenza vaccines
 Chose based on age, allergy, preference
 Adult Conjugate pneumococcal vaccine
 Now wirh specific CDC recommendations
 Sequential administration with polysaccharide (give
conjugate first)
 CMS will pay for 2 vaccines
 Tdap
 For every pregnancy
 Zoster
 Will be covered by ACA