seasonal influenza immunization - mdbriefcase...
TRANSCRIPT
Seasonal Influenza
Immunization Strategies for Older Adults
Planning Committee
Program Leads
• Shelly McNeil, MD, FRCPC
• Paul Van Buynder, MBBS, MPH, FAFPHM
Expert Reviewers
• John Axler, MD, FCFP, CCFP
• Phyllis Bedder, MD
• Sol Stern, MD, MSc, BSc, MCFP
• William Schaffner, MD
Learning Objectives
After successful completion of the program, the participant will be
able to:
• Describe burden of influenza in adults aged 65 and older.
• List the vaccine options available for seasonal influenza
immunization of adults aged 65 and older.
• Differentiate vaccine products approved for seasonal influenza in
adults aged 65 and older.
• Effectively counsel older adult patients about the importance of
seasonal influenza vaccination.
Vaccine abbreviations used in this program
• TIV = trivalent inactivated virus vaccine
• aTIV = MF59-adjuvanted TIV
• hdTIV = high-dose TIV
• QIV = quadrivalent influenza virus vaccine
Influenza Immunization for Adults 65+ Years
• burden of influenza-related illness
• age-related changes in immunity
• current opportunities for stimulating influenza immunity
• importance of immunization
Influenza Virus
• 3 types: A,B,C (A and B cause seasonal influenza epidemics)
• Influenza A subtypes: based hemagglutinin (H) and neuraminidase (N), e.g., H1N1 or H3N2
• Influenza B strains: B/Yamagata and B/Victoria
In Canada:1
• Influenza and pneumonia = a top 10 cause of death
• 23,000 cases/year
• 2,200 hospitalizations
• 3,500 deaths
• … but under-reported!
The World Health Organization (WHO) Naming
Convention
• The antigenic type (e.g., A, B, C)
• The host of origin (e.g., swine, equine, chicken, etc. For human-origin
viruses, no host of origin designation is given.)
• Geographical origin (e.g., Denver, Taiwan, etc.)
• Strain number (e.g., 15, 7, etc.)
• Year of isolation (e.g., 57, 2009, etc.)
• For influenza A viruses, the hemagglutinin and neuraminidase
antigen description in parentheses (e.g., (H1N1), (H5N1))
Seasonal Epidemics Caused by:
• Influenza A: including subtypes (H1 or
H3) + (N1 or N2)
• Influenza B: including lineages
B/Yamagata- and B/Victoria-like viruses
Strain Effects
Influenza A
• associated with the most significant burden of illness; vast majority of hospitalizations and deaths
• A(H3N2) - impact on the older adult population + comorbidity
• level of circulation linked to seasonal surges in all-cause mortality and hospitalizations
• Influenza-attributable pneumonia and influenza hospitalizations, as well as respiratory and circulatory hospitalizations, are greatest in influenza A (H3N2) predominant seasons
Influenza B
• usually affects younger population, but worse outcomes in older adults
Practice Tip
• Remind older adult patients that the flu virus changes from year to
year, so it is important to get your shot every year
Atypical Presentation in Older Adults
• Fever?
• Lower respiratory tract symptoms
• Atypical complaints e.g., anorexia,
mental status changes, and
unexplained fever
• Worsening respiratory status in COPD
and heart failure
• Pneumonia
• Gastrointestinal symptoms
Burden in Older Adults
In adults aged 65 and older in Canada:
• Influenza-related hospital admissions occur in 125 to 228 per
100,000 healthy individuals. 1
• Mortality rates increase with increased age.1
• Can trigger myocardial infarction or strokes9,10
Burden in Older Adults
Age-related decline in immune function impairs both the ability to resist
influenza infection and to respond to influenza vaccination6
• Majority of influenza-related deaths; also excess mortality from
cardiovascular diseases, strokes, diabetes, and pneumonia
• Loss of independence in the activities of daily living and diminished
quality of life
• Serious disability: influenza, pneumonia, and cardiovascular
complications
• Expected rise in permanent disability for aging population due to
influenza-related illness
The Unmet Need
• Goal of 80% unmet
• In the 2015-2016 season, coverage was only 65
• Influenza immunization decreases the incidence of pneumonia,
hospitalization, death
• Immunosenescence: standard influenza vaccines (TIV or QIV)
produce a weaker response in older adults; enhanced vaccines
designed to address this need
• High burden of A(H3N2) - need to improve immunogenic vaccine
effectiveness14
Unique needs of older patients, newer vaccine options
Madeline
• 72 years of age
• good overall health; mild hypertension
• recently re-married, likes to travel
• 5 grandchildren
• Currently October; will be travelling and
visiting grandchildren
• due for seasonal influenza
immunisation
Case Challenge
• “I am not old! I’m quite young and
strong still. And I never get sick.”
Case Challenge
“I am not old! I’m quite young and strong still. And I never get sick.”
What age group is identified as especially recommended for influenza
immunization due to age-related decline in immunity?
a) Adults age 50 and older
b) Adults age 65 and older
c) Adults age 70 and older
d) Adults age 75 and older
Counselling
• As people are living longer than ever before, some might disregard
the increasing importance of getting their ‘flu shot’ after age 65 simply
because they still feel young and strong.
• A recommended approach to providing vaccination is to make a
short, affirmative statement (e.g., “It is time for your flu shot.”)
Important Counselling Messages
• Get your flu shot. The shot is the best
way to prevent the flu.
• The flu can be serious.
• The shot is especially important for
people age 65 and older.
• There are 2 types of vaccines especially
made for people 65 and older. One is a
high-dose vaccine and the other is
called an adjuvanted vaccine.
Additional Protection
• Take care of your overall health.
• Practice preventive habits.
• See your doctor right away if you think
you might have the flu.
• Stay up to date on all recommended
shots.
Case Challenge
Which of the following types of vaccine
are options for Madeline?
a) TIV, standard dose
b) TIV, MF59-adjuvanted
c) TIV, high dose
d) QIV
e) LAIV
f) a, b, or c
g) a, b, c, or d
h) All of the above
LAIV = live attenuated influenza vaccine; TIV = trivalent influenza vaccine; QIV = quadrivalent influenza vaccine
Influenza Vaccines
• SOS Network: pooled effectiveness
data from 3 seasons was 41.7%, and
39.3% in adults aged 65 and older17
• Vaccines are reformulated annually to
account for drift
• TIV contains 3 virus (2A + 1B); QIV
contains 2A + 2B
See Table 3 of the Canadian Immunization Guide Chapter on
Influenza and Statement on Seasonal Influenza Vaccine for 2017–
2018 too view vaccines indicated in adults age 65 and older in
Canada for the 2017-2018 season
Vaccine Products
Product Type
(abbreviation)
Product Type Route of
Administration
TIV trivalent inactivated
vaccine
IM
QIV quadrivalent influenza
vaccine
IM
aTIV MF59-adjuvanted trivalent
vaccine
IM
hdTIV
trivalent inactivated
vaccine, quadruple dose
IM
IM = intramuscular injection
Immunosenescence
• Innate immunity declines with age.
• Immunosenescence makes vaccine immunogenicity a challenge in
older adults.
• Vaccination in this group is a high priority since influenza infection
carries the highest risk of serious outcomes in this group.
Cross-Protection
• Heterotypic antibody protection (cross-protection) occurs when
vaccine effectiveness against one strain confers a cross-strain
effectiveness against another strain
• Efficacy of influenza vaccines depends on the degree of similarity to
strains in circulation, as well as the age and immunocompetence of
the vaccine recipient
• Vaccines have variable ability to provide cross-protection
• High heterogeneity of circulating influenza viruses makes cross-
protection desirable
• Example = H3N2
Enhanced Vaccines
Enhanced influenza vaccines were developed to address challenges in
the aging population, specifically:
• immunosenescence
• the burden illness, particularly associated with A(H3N2
• to bridge the antigenic gap between circulating and vaccine strains
• Two vaccine formulation strategies have been introduced, which aim
to improve immunogenicity over standard TIV:
adjuvanted TIV (aTIV)
high-dose TIV (hdTIV)
Adjuvanted Trivalent Influenza Vaccine
The MF59 adjuvant contained in aTIV is an oil-in-water emulsion
composed of squalene as the oil phase, stabilized with the surfactants
polysorbate 80 and sorbitan trioleate, in citrate buffer
O’Hagan DT, et al. Vaccine. 2012;30(29):4341–8.
aTIV Mechanism of Action
More antibodies target the ‘head’ of the hemagglutinin antigen
aTIV Safety and Efficacy
• higher immunogenicity of aTIV over TIV across strains, particularly
against A/H3N2
• longer duration of enhanced immune response over the influenza
season
• greater breadth of the immune response, with aTIV showing higher
immunogenicity against heterotypic strains
• local reactions at injection site
aTIV Successes in Older Adults
Adjuvanting increases vaccine immunogenicity, resulting in
comparatively higher levels of haemagglutination inhibition antibodies,
and greater protection against all influenza.
• Canadian study: efficacy of 63% in adults 75+ years; no efficacy was
seen with standard TIV.52
• Northern Italy, the LIVE Study: increased efficacy of aTIV of 25%
versus standard TIV against pneumonia-related or influenza-related
hospitalisation, despite use in frail elderly.53
• Systematic review and meta-analysis suggested that aTIV, compared
with a conventional non-adjuvanted TIV, is effective in reducing
influenza-related outcomes in older adults, particularly
hospitalisations.54
High Dose TIV
• 4X dose
• 60 µg of haemagglutinin (HA) per strain, compared to 15 µg HA per
strain in a standard dose, administered as a single 0.5 mL dose by
intramuscular injection
• The hdTIV for older adults was designed to provide superior
protection26
TIV 15 µg HA per strain X4
hdTIV Efficacy and Safety
• Phase III trials: higher antibody response and reduced laboratory-
confirmed influenza versus standard TIV55,56
• Enhanced protection against serious, life-threatening pneumonia
associated with influenza.57
• The safety profile of high-dose TIV is similar to that of standard TIV55
hdTIV Success in Older Adults
• Phase 2 and 3 studies: antibody response was significantly higher
than that induced by standard TIV vaccine
• Retrospective cohort study of over 2 million people in the US:
significantly more effective than standard-dose vaccine in prevention
of influenza-related hospital admissions
• 22% more effective than the standard TIV
• 22% more effective for prevention of influenza hospital admissions
• Real world studies: significantly more effective than standard TIV in
the prevention of influenza-related medical encounters,
hospitalizations, and death
Case Challenge 3
Which of the following types of vaccine
are expected to provide greatest
immunogenicity for Madeline?
a) TIV or QIV, standard dose
b) TIV, high dose
c) TIV, MF59-adjuvanted
d) b or c
Population-Based Protection
• Vaccination of healthcare practitioners has a protective effect on
residents of long-term care facilities, including reduced mortality
among patients
• Influenza vaccination of healthcare personnel is currently
recommended in over 40 countries
• Vaccination of all individuals over 6 months of age helps to establish
community protection (herd-immunity) against influenza. Since
children play an important role in the transmission of influenza, they
are an important group for vaccination, even beyond their own
protection.
• Vaccination of all older adults also contributes to herd immunity
Conclusion
• Annual influenza immunization of people age 65 and older is the best
protection available against influenza. Influenza vaccines are among
the safest vaccines in the world, and influenza immunization is cost-
effective in this group
• Annual influenza vaccination of the older adult population is the
primary strategy for disease prevention and control.27
• Enhanced vaccines provide superior protection versus standard TIV
in this group and should be selected wherever possible
• Additional measures to limit transmission include vaccinating those in
proximity to the patient, including children, as well as preventive
behaviours such as hand-washing
Key Points
• Older adults have higher burden of influenza-related illness,
hospitalization, and death from influenza due to immunosenescence
and suboptimal response to standard influenza vaccines, especially
to A(H3N2).
• Influenza vaccination reduces complications and long-term risks.
• Immunosenescence in people age 65 and older contributes to loss of
both existing influenza immunity and impaired immune response to
vaccination.
• Enhanced vaccines (aTIV, hdTIV) confer greater benefits for
overcoming the problem of immunosenescence after age 65 than
standard TIV.
Key Points
• The MF59 adjuvant in aTIV was designed to both enhance and
broaden the immune response to influenza compared to standard
TIV. The use of aTIV can confer improved immunity, including
heterotypic immunity for those age 65 and older.
• The hdTIV vaccine provides quadruple the dose of standard TIV, for
an enhanced vaccine response compared to standard-dose TIV.
• When vaccinating older adults, identify people who are high-priority
for influenza vaccination including family members and others who
are near to them.
Resources
Canadian Immunization Guide Chapter on Influenza and Statement on
Seasonal Influenza Vaccine for 2017–2018
Public Health Agency of Canada (PHAC) - Immunization and Vaccines
National Advisory Committee on Immunization (NACI)
Immunize Canada
Frequently asked Questions (video with Dr Paul Van Buynder)
FluWatch (Flu surveillance)
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