The Role and Benefits of

Influenza Vaccination in Elderly

Kuntjoro Harimurti
Division of Geriatric Medicine, Dept. of Internal Medicine
Faculty of Medicine UI, Cipto Mangunkusumo Hospital
Jakarta
Influenza in the elderly
• 5-15% population affected by influenza infection
each year, higher rates during epidemics
resulting from antigenic drift
• Considerable human suffering and economic
burden
• Vulnerable populations: older adults, children,
and those with chronic diseases
• Among older adults, increasing age correlate
with increased risk hospitalization and all-cause
mortality

Falsey et al. Clin Infect Dis. 2006;42:518-24

Harper et al. Clin Infect Dis. 2009;48:1003-32
https://gis.cdc.gov/GRASP/Fluview/FluHospRates.html
Rates of influenza-associated hospitalization by influenza season and age group—
U.S Influenza Hospitalization Surveillance Network (FluSurv-NET)

Czaja CA, et al. Open Forum Infect Dis. 2019;6:ofz225

 Effect of aging on the immune response
NK cell
Reduction in number
Macrophage of cells in weakened
health type Dendritic cell
Lower expression of
TLR ↓ in antigen capture
Lower production ↓ in migration
levels of IL-6, TNF-a, ↓ in T-cell activation
IL-12, IFN-a capacity

B cell T cell
↓ in high affinity antibodies production ↓ in diversity of the T-cell receptor
↓ in diversity of antibody reaction ↓ in production of granzyme B in
↓ ability of bone marrow cells to CD*+ T cells
support survival of antibody- ↓ in the production of IFN-g in
producing plasma B cells CD*+ T cells

Bahadoran A, et al. Front. Microbiol. 7:1841.

Influenza immunity and aging:
innate immunity
• ↓ expression of TLRs on macrophages
• ↓ proinflammatory cytokines produced upon antigenic
stimulation
• ↓ plasmacytoid dendritic cells, and
• ↓ produce less interferon-a to stimulate downstream
innate and adaptive immune mechanisms

• Milder initial clinical presentation of disease, ↓ prevalence

of fever in elderly patients, ↓ vaccine responsiveness
Influenza immunity and aging:
adaptive immunity
• Humoral immunity
• ↓ ability to mount effective humoral responses to new
antigens
• ↓ Antibody titers in response to influenza vaccines
• Cellular immunity
• Age-related thymic involution and changes in thymus-
independent cell-level

• Longer duration of illness, vulnerable to the effects of

influenza, ↓ protective response to influenza
immunizations
Immune response to influenza vaccination:
young vs. old age
 Post-vaccine response (unadjusted)
in young vs. elderly, by influenza sub-type

Goodwin K, et al. Vaccine 2006;24(8):1159-1169

Clinical benefits influenza vaccination in the
elderly
• The exact magnitude of the benefit immunization strategy
among older adults is debatable
• The protective effect of influenza vaccine is diminished in
elderly compare to younger adults due to change in
immune response
• Evidences of influenza vaccination efficacy and
effectiveness in elderly mostly gathered from
observational studies which can lead to bias esp. selection
or healthy user bias
• Furthermore, the use of endpoints in evaluating flu
vaccine efficacy and effectiveness may come to different
results
Trucchi C. J Prev Med Hyg 2015; 56: e37-e43
 Cochrane review:
Vaccines for preventing influenza in the elderly
No of Study/
Outcome Study Design, setting Results
Participants
Influenza RCT 3/2217 RR 0.42 (0.27;0.46)
Cohort, nursing homes 8/1941 RR 0.65 (0.32;1.29)
Cohort, community 2/18249 RR 0.19 (0.02;2.01)
dwelling
Influenza-like illness RCT 4/6894 RR 0.59 (0.47;0.73)
Cohort, nursing homes 26/12388 RR 0.76 (0.66;0.88)
Cohort, community 4/9613 RR 0.75 (0.42;1.33)
dwelling
Pneumonia Cohort, nursing homes 17/10274 RR 0.53 (0.43;0.66)
Cohort, community 2/18090 RR 0.88 (0.64;1.20)
dwelling
Hospitalisation for ILI Cohort, nursing homes 12/28032 RR 0.51 (0.32;0.81)
or pneumonia Cohort, community 9/784643 RR 0.73 (0.62;0.85)
dwelling
Death from flu or Cohort,
añolnursinganç
homes 27/32179 ภาษาไทย
ortuguês RR 0.46 (0.33;0.63)
pneumonia Cohort, community 1/163391 RR 0.87 (0.70;1.09)
dwelling

Demicheli V. Cochrane Database of Systematic Review. 01 February 2018

Influenza vaccine efficacy and effectiveness against lab-
confirmed influenza in adults >50 y.o.
Adjusted standard dose inactivated influenza vaccine
effectiveness (VE) by influenza type and subtype

Russel K, et al Vaccine. 2018;36(10):1272–1278.

Benefits of influenza vaccination beyond
prevention of acute infection
• There is compelling evidence for the association between
influenza infection and acute myocardial infarction (AMI)
• There is a peak of both influenza and cardiac deaths in
winter
• Influenza epidemics are associated with increased
hospitalisation rates for AMI and other cardiovascular-
related condition
Influenza associated complications/
other manifestations

• Primary viral pneumonia

• Secondary bacterial
• pneumonia
• Encephalitis, Guillain-Barré syndrome
(GBS), myelitis, seizures, psychosis, neuritis
• Reye’s syndrome
• Myocarditis, pericarditis, heart failure, AMI
• GI, myositis, shock

Ghebrehewet et al. BMJ 2016; 355: i6258

Time Series of Daily Cardiovascular Disease (CVD)
Mortality by Age Group in New York City, 2006-2012

Nguyen JL, et al. JAMA Cardiol. 2016 Jun 1; 1(3): 274–281.

Seasonal Excess Cardiovascular Disease (CVD) Mortality
With Seasonal Average Emergency Department Visits for
Influenza-Like Illness (ILI) in New York City, 2006 to 2012

Nguyen JL, et al. JAMA Cardiol. 2016 Jun 1; 1(3): 274–281.

 Major Adverse Cardiovascular Events
Comparing Influenza Vaccine vs Control

Udell JA, et al. JAMA. 2013;310(16):1711-1720.

Cardiovascular Mortality Comparing
Influenza Vaccine vs Control

Udell JA, et al. JAMA. 2013;310(16):1711-1720.

 Cochrane review:
Influenza vaccines for preventing cardiovascular disease

• Eight trials of influenza vaccination compared with

placebo or no vaccination, with 12,029 participants
• Cardiovascular mortality was significantly reduced
by influenza vaccination overall (RR 0.45, 95%CI
0.26 to 0.76)
• In studies of patients with coronary heart disease,
composite outcomes of cardiovascular events
tended to be decreased with influenza vaccination
compared with placebo
• Generally no significant difference was found
between comparison groups regarding individual
añol anç ภาษาไทย
ortuguêsoutcomes such as myocardial infarction

Clar C, et al. Cochrane Database Syst Rev. 2015 May 5;(5):CD005050

 Cumulative incidences of cardiovascular outcomes among
elderly participants with histories of myocardial infarction

(a) All-cause death. (b) Recurrent myocardial infarction or (c) Hospitalization due to
cardiovascular death. heart failure.

Wu HH, et al. PLOS ONE 2019;14(7): e0219172.

Influenza vaccination also can reduce the risk of deaths

The University of Sydney

Wang et al. Vaccine 2007; 25: 1196-1203

Cumulative hospitalization rates for ACS in elderly patients with
CKD according to influenza vaccination status and number of
vaccinations

Chen C-I, et al. Medicine. 2016;95(5):e2588

Effect of Influenza Vaccination on Risk of Stroke:
A Systematic Review and Meta-Analysis

Lee KR, et al. Neuroepidemiology 2017;48:103–110

Mechanisms by which influenza infection may
precipitate acute myocardial infarction

MacIntyre CR, et al. Heart 2016;102:1953-1956

Guideline Recommendations of the International Cardiology Societies
on Anti-influenza and Antipneumococcal Vaccination
in the Heart Failure Population
Report Society Recommendation and level of evidence
2010 comprehensive Heart Failure Society “Pneumococcal vaccine and annual influenza
heart failure Practice of America vaccination are recommended in all patients with
guideline HF in the absence of known contraindications”
Level of evidence: B
2013 ACCF/AHA ACCF/AHA “Secondary prevention interventions (eg, lipids,
guidelines for the smoking cessation, influenza and pneumococcal
management of heart vaccines)”
failure Level of evidence: recommended plan of care for
patients with chronic HF
2016 European ESC “Annual influenza vaccination may be considered in
guidelines on patients with established cardiovascular disease”
cardiovascular disease Level of evidence: IIb, C
prevention in clinical
practice
2016 ESC guidelines for ESC “Receive immunization against influenza and
the diagnosis and pneumococcal disease”
treatment of acute and Level of evidence: key topics and self-care skills to
chronic heart failure include in patient education
Kadoglou NPE. Rev Esp Cardiol. 2019;72:51510.1016
 Efficacy of accepted coronary interventions and influenza
vaccine in the prevention of myocardial infarction

Intervention
Coronary intervention Prevention efficacy/effectiveness against
acute myocardial infarction

Smoking cessation Secondary 32–43%

Statins Secondary 19–30%

Antihypertensive drugs Secondary 17–25%

Influenza vaccine Secondary 15–45%

MacIntyre CR, et al. Heart 2016;102:1953-1956

Take Home Massages
• Older adults are at high risk for having infection, including
influenza due to diminished response immune in aging
• Despite immune senescence during aging, influenza
vaccine have role to increase seroprotection and
seroconversion among vaccinated elderly
• The benefits of influenza vaccine not limited in prevening
acute infection but also covering prevention from serebro-
cardiovascular diseases
• To conclude, influenza vaccination is highly recommended
– both in healthy and high-risk elderly