Transcript Influenza vaccine

IMMUNOSENESCENCE
and
VACCINE FAILURE
Jean-Pierre MICHEL
et
Pierre Olivier LANG
Geneva Medical University & Hospitals
DISCLOSURE
I am NOT
An immunologist
A vaccine specialist
A public health specialist
I am simply
A geriatrician
1. Burden of
preventable
infectious diseases (PIDs)
2. Immunosenescence
3. Roles of
the homeostatic milieu
4. Consequences of
the age related changes in
immune responses
5. Strategy to address
immunosenescence
6. Take home messages
Two thirds of the 2,000
Tetanus cases
notified in Europe between 1999 and 2008
occur in people aged over 65 years
ECDC http://ecdc.europa.eu/en/publications/Publications/0910
20% of
chronic cough
in old adults
are
linked to an
unrecognized
Pertussis
infection
BURDEN of
INFECTIOUS
DISEASES in
the OLD ADULTS
(1)
50% of the 8’000
Diphtheria cases
notified
in Europe
between
1999 and 2008
concerned people
over 45 y.
WHO – CISID –
htpp:/data.euro.who.int/cisid
WHO position paper.
Wkly Epidemiol Rec 2005;80:31-9
The incidence of postherpetic neuralgia
increases with advancing age,
reaching more than 50% in older patients with
Herpes zoster
SCHMADER K Clin Infect Dis 2001;32:1481-6
Lower respiratory infections
4th cause of death
in developed countries
LIANG SY et al Clin Geriatr Med 2007; 23: 441-56
Streptococcus
pneumoniae is
the cause of
30%
of communityacquired
pneumonia
BURDEN of
INFECTIOUS
DISEASES in
the OLD ADULTS
(2)
Most
influenza-related
and
pneumococcal
disease
deaths
occur in people
aged 65 y.o.
THOMPSON WW et al
Jama 2003; 289: 179-86
WHO
Wkly Epidemiol Rec 2007;82:93-104
http://www.who.int/vaccine_
research/diseases/ari/en/index3.html
In the EU, the number of excess deaths
associated with influenza
is estimated between
40’000 and 220’000,
depending of the seasonal variation
TILLETT HE et al Lancet 1980; 1: 793-5
To summarize the problem
In the US,
approximately
1’000 to 3’000 children
die each year of
vaccine preventable
diseases
BURDEN of
INFECTIOUS
DISEASES in
the OLD ADULTS
(3)
Each year,
approximately
50’000 to 70’000
US adults
die of
vaccine preventable
diseases
POLAND GA, Vaccine 2010, in Press
Importance of herd immunity
European Centre for Disease Prevention and Control, 2008
To summarize the problem
In the US,
approximately
1’000 to 3’000 children
die each year of
vaccine preventable
diseases
BURDEN of
INFECTIOUS
DISEASES in
the OLD ADULTS
(3)
Each year,
approximately
50’000 to 70’000
US adults
die of
vaccine preventable
diseases
This imbalance is striking
and reflecting of a number of underlying
structural, economic, cultural and political
issues
POLAND GA, Vaccine 2010, in Press
Expected benefits of vaccination
in the ageing population
Avoid mortality linked to preventable infectious diseases
E.g. Influenza vaccine  all-cause mortality by 48–50% in community-dwelling
older persons
Reduce complications and hospitalisation
E.g. Hospitalisations for influenza or pneumonia were  by 27% in community
dwelling older influenza vaccinees
Decrease antibiotic use
E.g. Antibiotic prescriptions were  by 64% following influenza vaccination in a
Canadian study
Decrease antibiotic-resistant infections
E.g. Pneumococcal conjugate vaccine  nasopharyngeal carriage of penicillinresistant Streptococcus pneumoniae
Cost effectiveness
E.g. Herpes zoster vaccine  quality-adjusted life years compared with no
vaccination in older persons
NICHOL KL et al N Engl J Med 2007;357:1373-81; KWONG J et al Clin Infect Dis 2009;49:750-6;
DAGAN R Clin Microb Infect 2009;15(Suppl 3):16-20, HORNBERGER J et al Ann Intern Med 2006;145:317-35
Expected benefits of vaccination
in the ageing population
Avoid mortality linked to preventable infectious diseases
E.g. Influenza vaccine  all-cause mortality by 48–50% in community-dwelling
older persons
Reduce complications and hospitalisation
Why
vaccine
coverage rate
Decrease antibiotic
use
E.g. Antibiotic prescriptions were  by 64% following influenza vaccination in a
Canadian study
of
Decrease antibiotic-resistant
infections
old
adults
so low ?
E.g. Pneumococcal conjugate vaccine  nasopharyngeal carriage of penicillinE.g. Hospitalisations for influenza or pneumonia were  by 27% in community
dwelling older influenza vaccinees
resistant Streptococcus pneumoniae
Cost effectiveness
E.g. Herpes zoster vaccine  quality-adjusted life years compared with no
vaccination in older persons
NICHOL KL et al N Engl J Med 2007;357:1373-81; KWONG J et al Clin Infect Dis 2009;49:750-6;
DAGAN R Clin Microb Infect 2009;15(Suppl 3):16-20, HORNBERGER J et al Ann Intern Med 2006;145:317-35
1. Burden of
preventable
infectious diseases (PIDs)
2. Immunosenescence
3. Roles of
the homeostatic milieu
4. Consequences of
the age related changes in
immune responses
5. Strategy to address
immunosenescence
6. Take home messages
Immunosenescence
Definition
A constellation of age-related changes
to the immune system,
resulting mainly in
1) greater susceptibility to infections
2) reduced response to vaccination
Adapted from Beatrix GRUBECK-LOEBENSTEIN et al Aging Clin Exp Res 2009; 21: 1-9
The innate and adaptive
immune responses
Capture of Ag
IMMUNE RESPONSES
Ag Presentation
to T cells
Dendritic cells
Innate
Neutrophils
Nb = but  functions
Adaptive
DCs
=  Nb  functions
Cellular immunity
(T cells)
Macrophages
Nb = but  functions
Natural Killer cells
 or 
 IL6,  IL1,
 TNF-α
Adapted from Beatrix GRUBECK-LOEBENSTEIN et al Aging Clin Exp Res 2009; 21: 1-9
Ageing T-Cells
Thymic involution
( of central production of T-cells)
Memory 
 Ratio of ----------------Naives 
Child
Young adult
Aged adult
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




 senescent T cells
 Memory CD45 RA- CD8 CD28 +
 Effector CD45 RA+ CD8 CD28 Adapted from GRUBECK-LOEBENSTEIN B Adv Immunol 2002; 80: 243-84
Ageing T-Cells
Thymic involution
( of central production of naive T-cells + shinkring of the peripheral T-cells pool)
Memory 
 Ratio of ------------------------Naives 
1. Reduction
of the repertoire of
the naive T cells
receptors (TCR)
for Cytotoxic and Helper T cells
2. Significant
shortening
of telomeres length
of the naive T Cells
 resistance to apoptosis
PFISTER G et al Ann N Y Acad Sci.
2006;1067:152-7
PFISTER G et al Ann N Y Acad Sci.
2006;1067:152-7
Based on TARGONSKI PV et al Vaccine 2007; 25: 3066-9
Ageing T-Cells
Thymic involution (
of central production of T-cells)
Memory 
 Ratio of ------------------------Naives 
for Cytotoxic and Helper T cells
2. Loss of expression
of
CD28 cell surface
marker
EFFROS RB et al
Exp Gerontol 1994; 29: 601-9
153 community dwelling persons (65-98 y.o.)
10% with CD28 AB production by 24%
GORONZY JJ et al J Virol 2001; 75: 12182-7
1. Decrease of
the telomerase activity
at each replication
 resistance to apoptosis
VALENZUELA HF et al
Clin Immunol 2002; 105: 117-25
Changes in cytokines production
throughout life
Child
Young adult
Aged adult
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


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
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








IL-2
TFN- IL15
IL-4
GRUBECK-LOEBENSTEIN B Adv Immunol 2002; 80: 243-84
CHIU WK et al J Immunol 2006; 177: 7802-10
The innate and adaptive
immune responses
Capture of Ag
IMMUNE RESPONSES
Ag Presentation
to T cells
Dendritic cells
Innate
Neutrophils
Nb = but  functions
Adaptive
DCs
Nb  functions
Cellular immunity
(T cells)
Macrophages
Nb = but  functions
Natural Killer cells
 or 
 IL6,  IL1,
 TNF-α
Humoral immunity
(B cells)
Antibody production
Adapted from Beatrix GRUBECK-LOEBENSTEIN et al Aging Clin Exp Res 2009; 21: 1-9
B-cell responses and ageing
Most bones contain
haemotopoeitic
bone marrow,
rich in B-cell
progenitors
Decreased
haematopoietic bone
marrow with fat
depsosits
and decreased B-cell
progenitors
Large number
of naive B-Cells
(diverse specificity)
Small number
of memory Bcell clones
 Production
of naive B-cells
Accumulation
of
memory B-cells
(limited specificity)
19 R.
Adapted from SIEGRIST CA and ASPINALL
Nat Rev Immunol 2009;9:185-94
B-cell responses and ageing
Most bones contain
haemotopoeitic
bone marrow,
rich in
B-cell progenitors
Decreased
haematopoietic bone
marrow with fat
deposits
and decreased
B-cell progenitors
Large number
of naive B-Cells
(diverse specificity)
Small number
of memory Bcell clones
 Production
of naive B-cells
Accumulation
of
memory B-cells
(limited specificity)
20 R.
Adapted from SIEGRIST CA and ASPINALL
Nat Rev Immunol 2009;9:185-94
Immunosenescence
In summary
Ageing

Changes in T and B cell populations
 number of naive cells
 number of effector T and memory B and T cells

 Repertoire of immune functions
Defects in cooperation between T and B cells

Impaired immune responses in the old adults
Beatrix GRUBECK-LOEBENSTEIN et al Aging Clin Exp Res 2009; 21: 1-9
However large longitudinal studies
showed that
at the same age,
old adults ARE NOT ALL
immunosenescent
STRANDHALL J Exp Gerontol 2007; 42: 753-61 & WIKBY A et al Biogerontol 2008; 9: 299-308
1. Burden of
preventable
infectious diseases (PIDs)
2. Immunosenescence
3. Roles of
the homeostatic milieu
4. Consequences of
the age related changes in
immune responses
5. Strategy to address
immunosenescence
6. Take home messages
Malnutrition and immunity
Protein energy
malnutrition

Alteration of
T cell responses

 Delayed-type hypersensibility
 IL2 production
 T cell proliferation
 Antibody response
Micronutriment
deficits
 Vitamin E
 Vitamin D
 Vitamin B12
 Selenium
 Zinc

Immunodeficiency
FATA FT et al Ann Int Med 1996; 124: 299-304
LESSOURD B Am J Clin Nutr 1997; 66: 478S-84S
FULOP T et al Clin Infect Dis 2009;48:443-8
Chronic diseases and Immunity
High burden of chronic diseases
Impaired immunity

Inadequate antibody response
to
vaccine
FULOP T et al Clin Infect Dis 2009;48:443-8
Other causes of vaccine failure
in the old population
?
IgG anti-CMV carrier
Pre-vaccination chronic
proinflammatory activity
exacerbated by the vaccine
1) High cytokines profile:
 IL10
 IL6
 TNFα
2) Low immunosupressive
cortisol level
Impaired
immune response
P TRZONKOWSKI et al Vaccine 2003; 21: 3826-36
1. Burden of
preventable
infectious diseases (PIDs)
2. Immunosenescence
3. Roles of
the homeostatic milieu
4. Consequences of
the age related changes in
immune responses
5. Strategy to address
immunosenescence
6. Take home messages
Consequences of age related
immune system changes
Age related changes
INNATE
Age related changes
INNATE +
ADAPTATIVE
Age related changes
ADAPTATIVE

 Post vaccination
antibody
concentration
Impaired elimination
of pathogens
 Persistance of
antibody
concentrations
Altered cellular functions

Chronic inflammatory
process
 Susceptibility to
infections


Osteoporosis
Atherosclerosis
Sarcopenia
 Mortality due to
infectious diseases
and cardio-vx diseases
Adapted from
B GRUBECK- LOEBENSTEIN
Aging 2009; 21: 1-9
Post FLU vaccine response in
young
and old adults
(N = 913)
%
%
80
80
60
(N = 4492)
*
*
60
**
**
**
40
40
20
20
0
0
H1N1
H3N2
B
H1N1
H3N2
B
Seroconversion
Seroprotection
(% of subjects with 4-fold AB increase)
(% of subjects with AB titres > 40)
Meta-analysis of 50 surveys performed since 1986
GOODWIN K et al Vaccine 2006; 24: 1159-69
FLU vaccine response in elders
< 75 y. (N = 1945) and > 75 y. (N= 2492)
%
%
80
80
**
60
**
**
60
**
40
40
**
**
20
20
0
0
H1N1
H3N2
B
H1N1
H3N2
B
Seroconversion
Seroprotection
(% of subjects with 4-fold AB increase)
(% of subjects with AB titres > 40)
Meta-analysis of 50 surveys performed since 1986
GOODWIN K et al Vaccine 2006; 24: 1159-69
Antibody responses of old adults
to all 23 capsular polysaccharides after
Pneumococcal vaccine
N = 53, m.a = 71 y.
RUBINS JB et al Inf Immunity 1999: 67: 5979-84
Cumulative immune responses of old adults
to 23 polysaccharides pneumococcal vaccine
( at least two fold increase in polysscharide – specific IgG)
N = 53, m.a = 71 y.
80%
48%
3.7%
RUBINS JB et al Inf Immunity 1999: 67: 5979-84
Age-related antibody responses
after Pneumococcal vaccination
Immune Response to 23-v PnPS
25
20
15
10
5
0
14
6B
22-46 y.o.
63-79 y.o.
23F
19F
80-89 y.o.
> 90 y.o
ROMERO-STEINER S Clin Inf Dis 1999; 29: 281-8
Age-dependant persistence of antibody
after tetanus vaccine
HAINZ U et al Vaccine 2005; 23 : 2232-5
1. Burden of
preventable
infectious diseases (PIDs)
2. Immunosenescence
3. Roles of
the homeostatic milieu
4. Consequences of
the age related changes in
immune responses
5. Strategy to address
immunosenescence and
vaccine failure
6. Take home messages
Strategy to address
immunosenescence
1. Promoting life long vaccine programmes
2. Filling the adult vaccine gap
3. Reminding vaccine boosters
4. Improving macro- and micro- nutritional status
5. Developing new vaccines designed for old
population
6. Reversing immunosenescence
7. Establishing vaccine recommendations for the
ageing population
Vaccine
programs
for a better life
Scientific
knowledge
Very effective
Pregnancy
Precise guidelines
How to improve their
Well accepted
growth ?
Children
Are they healthy ?
Herd immunity
Scientific
knowledge
Acceptance: +/Previous exposures
to pathogens
Immunosenescence
Individual
variations !!
The target: old adults
How to improve it ?
How good
is their health?
Infant immunity may indirectly protect the elderly
Rate of VT- IPD before and after introduction of PCV7
USA 1998-2003
Reduced incidence of Invasive
Pneumococcal Disease (IPD-VT)
in the elderly after introduction
of PCV7 in infants
MMWR, Sept 16, 2005 / 54(36);893-897
Excess Deaths From Pneumonia and Influenza
(per 100,000 Population)
Japanese school vaccination
program with TIV reduced
mortality in the Community
14
P&I*&Mortality
Rate mortality rate
P&I = Pneumonia
Influenza
12
10
8
6
1987: Parents
allowed to refuse
vaccination
4
2
1994: Program
discontinued
1962: Program to vaccinate
school children with inactivated
influenza vaccine begins
0
REICHERT TA et al N Engl J Med 2001; 344: 889-96
Strategy to address
immunosenescence
1. Promoting life long vaccine programs
2. Filling the adult vaccine gap
3. Reminding vaccine boosters
4. Improving macro- and micro- nutritional status
5. Developing new vaccines designed for old
population
6. Reversing immunosenescence
7. Establishing vaccine recommendations for the
ageing population
Vaccine
programs
for a better life
Scientific
knowledge
Very effective
Pregnancy
Precise guidelines
How to improve their
Well accepted
growth ?
Scientific
knowledge
Continuity of
the vaccine program !!
HEALTHY AGEING
Children
Are they healthy ?
Midlife adults
How to improve it ?
How good is their health ?
Scientific
knowledge
Clinical
recommendations
for the ageing and
aged adults
Part of
PREVENTIVE
MEDICINE !
The target: old adults
How to improve it ?
How good
is their health?
?
Influenza vaccination and
risk of primary cardiac arrest
Population-based case-control study
342 cases of Primary cardiac arrest
(registered from 1988 to 1994 in the Washington area)
Demographically similar controls (N = 549)
Spouses of subjects were interviewed
Influenza vaccination
seemed to be associated with
a reduced risk of
primary cardiac arrest
OR = 0.51 [0.33- 0.79]
SISCOVICK DS et al Am J Epidemiol 2000; 152: 674-7
Coronary Artery Disease (CAD)
and Influenza vaccine
Randomized, controlled trial
301 patients hospitalized for CAD
(myocardial infarction or planned angiography/stenting)

After one year
RR of cardiovascular mortality = 0.25 [0.07-0.86]
in vaccinated compared with NOT vaccinated

After two years
Same tendency
(but samples were too small to show any significant difference)
GURFINKEL EP et al Tex Heart Inst 2004; 25: 25-31 and
GURFINKEL EP et al Tex Heart Inst 2004; 31: 28-32
Coronary Artery Disease (CAD)
and Influenza vaccine
Randomized. double blind, placebo controlled study with a 12 month-follow-up
658 optimally treated CAD patients
(72% of men; mean age = 59.9  10.3 y.)

3 end points in 2 population groups (Vaccinated vs. Non Vaccinated)
-
-

Cardiovascular death + myocardial infarction + coronary revascularization:
HR: 0.54 [0.24-1.21] (P =0.13)
Coronary ischemic event:
HR: 0.54 [0.29-0.99] (P =0.047)
Does Influenza vaccine significantly improve
the clinical course of CAD patients?
CISZEWSKI A et al Eur Heart J 2008; 29: 1350-8
Influenza vaccination as
secondary prevention of
Cardio Vascular Diseases (CVD)
The American Heart Association and
American College of Cardiology
recommend
Influenza vaccine
(TIV intra muscular)
as part of « secondary » prevention
in persons with coronary and
other atherosclerotic diseases
DAVIS MM et al JACC 2006; 48: 1498-502
INFLUENZA
(Seasonal Flu)
Flu Vaccine coverage rate
in the 65+ population
100%
2006/2007
2006/7 Vaccination Coverage Rate (%)
90%
2014 WHO goal = 75%
80%
71%
70%
68%
70%
66%
63%
2006 WHO goal = 50%
60%
53%
53%
51%
50%
37%
40%
30%
30%
25%
20%
10%
0% 0%
0%
A
* Source: TNS survey 2006/7
Data in file
B
C
D
≥65 years
E
F
< 65 years at risk
G
H
Healthcare Workers
I
J
K
Flu Vaccine coverage rate
in the population < 65 at risk
100%
2014 WHO goal = 75%
2006/7 Vaccination Coverage Rate (%)
90%
80%
71%
70%
68%
70%
66%
63%
60%
56%
53%
53%
2006 WHO goal = 50%
51%
50%
40%
37%
35%
37%
39%
37%
34%
30%
28%
30%
25%
24%
17%
20%
17%
14%
10%
0%
0%
A
* Source: TNS survey 2006/7
Data in file
B
C
D
≥65 years
E
F
< 65 years at risk
G
H
Healthcare Workers
I
J
K
Flu Vaccine coverage rate
in the health care workers (HCWs)
100%
HERD IMMUNITY !
2006/7 Vaccination Coverage Rate (%)
90%
80%
71%
70%
68%
70%
66%
63%
60%
56%
53%
53%
51%
50%
40%
37%
39%
37%
35%
37%
34%
30%
28%
30%
25%
24%
25%
22%
20%
20%
17%
17%
16%
24% 25%
24%
22%
22%
17%
14%
13%
10%
0%
A
B
* Source: TNS survey 2006/7
Data in file
C
D
≥65 years
E
F
< 65 years at risk
G
H
Healthcare Workers
I
J
K
Strategy to address
immunosenescence
1. Promoting life long vaccine programmes
2. Filling the adult vaccine gap
3. Reminding vaccine boosters
4. Improving macro- and micro- nutritional status
5. Developing new vaccines designed for old
population
6. Reversing immunosenescence
7. Establishing vaccine recommendations for the
ageing population
Correlation between
pre- and post- vaccination
antibody concentrations
KAML M et al Vaccine 2006; 24: 6808-11
Strategy to address
immunosenescence
1. Promoting life long vaccine programmes
2. Filling the adult vaccine gap
3. Reminding vaccine boosters
4. Improving macro- and micro- nutritional status
5. Developing new vaccines designed for old
population
6. Reversing immunosenescence
7. Establishing vaccine recommendations for the
ageing population
Responses to TT vaccine with and
without ready to use canned food
100
80
60
40
20
0
Day 0
Day 30
Day 90
With nutritional supplements
Without nutritional supplements
LESSOURD B Nature Rev 1995; 53: S86-94
Strategy to address
immunosenescence
1.
2.
3.
4.
5.
Promoting life long vaccine programmes
Filling the adult vaccine gap
Reminding vaccine boosters
Improving macro- and micro- nutritional status
Developing new vaccines designed for old
population
6. Understanding the links between frailty and
immunosenescence
7. Establishing vaccine recommendations for the
ageing population
Improving immune response
in old adults
• Increasing of the dosage of antigens in the
vaccine
• Developing novel vaccines based on viruslike particles
• Including more powerful adjuvants in the
vaccine composition
• Combining vaccination with simultaneous
immuno-stimulant patches (although chronic or
repeated immuno-stimulation is deleterious in ageing)
• Exploring new routes of administration
BRIGHT RA et al Vaccine 2007; 10; 3871-8; GUEBRE-XABIER M et al J Virol 2004; 78:7610-8
FRECH SA et al Vaccine 2005; 4:946-50; GLENN GM et al Immunol 2006;304:247-68
Strategy to address
immunosenescence
1. Promoting life long vaccine programmes
2. Filling the adult vaccine gap
3. Reminding vaccine boosters
4. Improving macro- and micro- nutritional status
5. Developing new vaccines designed for old
population
6. Reversing immunosenescence
7. Establishing vaccine recommendations for the
ageing population
Reversing immunosenescence
Possible therapeutical targets
• Major detrimental role of thymic atrophy
– Treatment with recombinant IL-7 reverses thymic
atrophy and increases thymic output
• Negative effect of senescent CD8+CD28– Physical removal from the circulation
– Inducing apoptosis of these cells
• Adverse impact of chronic CMV infection
– CMV vaccine to be administrated during childhood
But !!!!!!!!
Pierre Olivier LANG Personal communication 2010
Strategy to address
immunosenescence
1. Promoting life long vaccine programmes
2. Filling the adult vaccine gap
3. Reminding vaccine boosters
4. Improving macro- and micro- nutritional status
5. Developing new vaccines designed for old
population
6. Reversing immunosenescence
7. Establishing vaccine recommendations for the
ageing population
Vaccine
programs
for a better life
Scientific
knowledge
Very effective
Pregnancy
Precise guidelines
How to improve their
Well accepted
growth ?
Scientific
knowledge
Continuity of
the vaccine program
HEALTHY AGEING
Children
Are they healthy ?
Midlife adults
How to improve it ?
How good is their health ?
Part of
preventive
medicine !
Developing a
consensual
vaccine
programme
Scientific
knowledge
The target: old adults
How to improve it ?
How good
is their health?
!
European Union + European Economic Area + European Free Trade Associaion
BURDEN of PREVENTABLE
INFECTIOUS DISEASES
in the ELDERLY
European Union Geriatric Medicine Society
Proposed EUGMS and IAGG-ER
vaccine programme for the old adults
By the 7th decade /Retirement age
(after a clinical assessment of the vaccine status)
- TdaP or Td vaccine
- Influenza vaccine
- Pneumococcal vaccine
- Herpes Zoster vaccine
Each year after the retirement age (after assessment of the vaccine status)
- Influenza vaccine
New medical/injury event
Multiple hospital stays
(after assessment of the vaccine status)
(after assessment of the vaccine status)
- Td or TT vaccine
- Pneumococcal vaccine
By the 9 th decade of age / Nursing Home admission
- TdaP or Td or TT vaccine
- Influenza vaccine
- Pneumococcal vaccine
- Herpes Zoster vaccine*
MICHEL JP et al Rejuvenation Research 2009; 19: 127-35
1. Burden of
preventable
infectious diseases (PIDs)
2. Immunosenescence
3. Roles of
the homeostatic milieu
4. Consequences of
the age related changes in
immune responses
5. Strategy to address
immunosenescence
6. Take home messages
Preventable infectious diseases
are
forgotten, but not gone!
LIFE COURSE VACCINE
PROGRAMME
GUSMANO M & MICHEL JP AGING 2009; 21: 258-63
Mrs Quality of Life
and
I
thank you
for
your attention
FRAILTY  life long process
time
« A transitional state »
Age, Gender, Lifestyle,
Socio-economic status,
Co-morbidities, Affective,
Cognitive and Sensory
Impairments (…)
ROBUSTNESS
Total
FRAILTY
AVAILABLE
Used
ADL
DEPENDENCE
Physiological reserves
DEATH
. Age
. Malnutrition
. Disease(s)
. Environment
Dysregulations
. Hormones
. Immunologic
. Inflammation
. Coagulation
Chronic undernutrition
CYCLE
 Total
energy
expenditure
of
FRAILTY
Sarcopenia
 Resting metabolic rate
Immobilisation
Impaired balance
Infections
 Hospital admissions
Disabilty
Institutionalisation
Falls / trauma
 Drugs use
Dependence
Death
Relationship between frailty and vaccines ?
Adapted from FRIED LP et al Sci Aging Knowl Environ 2005; 31: pp 24 (sageke.sciencemag.org)