immunosenescence and vaccine failure
DESCRIPTION
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. Burden of preventable infectious diseases (PIDs) - PowerPoint PPT PresentationTRANSCRIPT
IMMUNOSENESCENCEand
VACCINE FAILURE
Jean-Pierre MICHEL et
Pierre Olivier LANGGeneva Medical University & Hospitals
DISCLOSUREI 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
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
20% of
chronic cough
in old adults
are
linked to an
unrecognized
Pertussis
infection
WHO position paper.
Wkly Epidemiol Rec 2005;80:31-9
50% of the 8’000 Diphtheria cases
notified in Europe between
1999 and 2008concerned people
over 45 y.
WHO – CISID – htpp:/data.euro.who.int/cisid
Two thirds of the 2,000 Tetanus cases
notified in Europe between 1999 and 2008occur in people aged over 65 years
ECDC http://ecdc.europa.eu/en/publications/Publications/0910
BURDEN ofINFECTIOUSDISEASES in
the OLD ADULTS (1)
In the EU, the number of excess deaths associated with influenza
is estimated between 40’000 and 220’000,
depending of the seasonal variationTILLETT HE et al Lancet 1980; 1: 793-5
Streptococcus
pneumoniae is
the cause of
30%
of community-
acquired
pneumonia
http://www.who.int/vaccine_
research/diseases/ari/en/index3.html
Most influenza-related
andpneumococcal
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
Lower respiratory infections4th cause of death
in developed countries LIANG SY et al Clin Geriatr Med 2007; 23: 441-56
BURDEN ofINFECTIOUSDISEASES in
the OLD ADULTS (2)
In the US,
approximately
1’000 to 3’000 children
die each year of
vaccine preventable
diseases
Each year,approximately
50’000 to 70’000 US adults
die ofvaccine preventable
diseases
To summarize the problem
BURDEN ofINFECTIOUSDISEASES in
the OLD ADULTS (3)
POLAND GA, Vaccine 2010, in Press
European Centre for Disease Prevention and Control, 2008
Importance of herd immunity
In the US,
approximately
1’000 to 3’000 children
die each year of
vaccine preventable
diseases
Each year,approximately
50’000 to 70’000 US adults
die ofvaccine preventable
diseases
To summarize the problem
BURDEN ofINFECTIOUSDISEASES in
the OLD ADULTS (3)
This imbalance is strikingand reflecting of a number of underlying
structural, economic, cultural and political issues
POLAND GA, Vaccine 2010, in Press
Avoid mortality linked to preventable infectious diseasesE.g. Influenza vaccine all-cause mortality by 48–50% in community-dwelling older persons
Reduce complications and hospitalisationE.g. Hospitalisations for influenza or pneumonia were by 27% in community dwelling older influenza vaccinees
Decrease antibiotic useE.g. Antibiotic prescriptions were by 64% following influenza vaccination in a Canadian study
Decrease antibiotic-resistant infectionsE.g. Pneumococcal conjugate vaccine nasopharyngeal carriage of penicillin-resistant Streptococcus pneumoniae
Cost effectivenessE.g. Herpes zoster vaccine quality-adjusted life years compared with no
vaccination in older persons
Expected benefits of vaccinationin the ageing population
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
Avoid mortality linked to preventable infectious diseasesE.g. Influenza vaccine all-cause mortality by 48–50% in community-dwelling older persons
Reduce complications and hospitalisationE.g. Hospitalisations for influenza or pneumonia were by 27% in community dwelling older influenza vaccinees
Decrease antibiotic useE.g. Antibiotic prescriptions were by 64% following influenza vaccination in a Canadian study
Decrease antibiotic-resistant infectionsE.g. Pneumococcal conjugate vaccine nasopharyngeal carriage of penicillin-resistant Streptococcus pneumoniae
Cost effectivenessE.g. Herpes zoster vaccine quality-adjusted life years compared with no
vaccination in older persons
Expected benefits of vaccinationin the ageing population
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
Why vaccine coverage rate
of old adults so low ?
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
ImmunosenescenceDefinition
Adapted from Beatrix GRUBECK-LOEBENSTEIN et al Aging Clin Exp Res 2009; 21: 1-9
A constellation of age-related changes
to the immune system,
resulting mainly in
1) greater susceptibility to infections
2) reduced response to vaccination
Innate Adaptive
NeutrophilsNb = but functions
Macrophages Nb = but functions
Natural Killer cells or
Dendritic cells
The innate and adaptive immune responses
IMMUNE RESPONSESCapture of Ag
Ag Presentation to T cells
DCs= Nb functions
IL6, IL1, TNF-α
Cellular immunity (T cells)
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
Adapted from GRUBECK-LOEBENSTEIN B Adv Immunol 2002; 80: 243-84
Child Young adult Aged adult
senescent T cells Memory CD45 RA- CD8 CD28 + Effector CD45 RA+ CD8 CD28 -
Ageing T-Cells Thymic involution
( of central production of naive T-cells + shinkring of the peripheral T-cells pool)
Memory Ratio of ------------------------- for Cytotoxic and Helper T cells
Naives
1. Reductionof the repertoire of
the naive T cells receptors (TCR)
PFISTER G et al Ann N Y Acad Sci. 2006;1067:152-7
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
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 ------------------------- for Cytotoxic and Helper T cells
Naives
2. Loss of expressionof
CD28 cell surfacemarker
EFFROS RB et al Exp Gerontol 1994; 29: 601-9
1. Decrease of the telomerase activity
at each replication
resistance to apoptosis
VALENZUELA HF et alClin Immunol 2002; 105: 117-25
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
Changes in cytokines production throughout life
GRUBECK-LOEBENSTEIN B Adv Immunol 2002; 80: 243-84
Child Young adult Aged adult
IL-2
IL-4
TFN- IL15
CHIU WK et al J Immunol 2006; 177: 7802-10
Innate Adaptive
NeutrophilsNb = but functions
Macrophages Nb = but functions
Natural Killer cells or
Dendritic cells
The innate and adaptive immune responses
IMMUNE RESPONSESCapture of Ag
Ag Presentation to T cells
DCsNb functions
IL6, IL1, TNF-α
Cellular immunity (T cells)
Humoral immunity (B cells)
Antibody production
Adapted from Beatrix GRUBECK-LOEBENSTEIN et al Aging Clin Exp Res 2009; 21: 1-9
19
B-cell responses and ageing
Adapted from SIEGRIST CA and ASPINALL R. Nat Rev Immunol 2009;9:185-94
Most bones contain haemotopoeitic bone marrow, rich in B-cell progenitors
Large number of naive B-Cells (diverse specificity)
Small number of memory B-
cell clones
Production of naive B-cells
Accumulation of
memory B-cells(limited specificity)
Decreased haematopoietic bone
marrow with fat depsosits
and decreased B-cell progenitors
20
B-cell responses and ageing
Adapted from SIEGRIST CA and ASPINALL R. Nat Rev Immunol 2009;9:185-94
Most bones contain haemotopoeitic bone marrow,
rich in B-cell progenitors
Large number of naive B-Cells (diverse specificity)
Small number of memory B-
cell clones
Production of naive B-cells
Accumulation of
memory B-cells(limited specificity)
Decreased haematopoietic bone
marrow with fat depositsand decreased
B-cell progenitors
ImmunosenescenceIn 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 functionsDefects 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: 299-304LESSOURD 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 failurein the old population
IgG anti-CMV carrier
P TRZONKOWSKI et al Vaccine 2003; 21: 3826-36
Pre-vaccination chronic proinflammatory activity
exacerbated by the vaccine
1) High cytokines profile: IL10 IL6 TNFα
2) Low immunosupressive cortisol level
?
Impaired immune response
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
Altered cellular functions
Post vaccination antibody
concentration
Impaired elimination
of pathogens
Persistance of antibody
concentrations
Chronic inflammatoryprocess
Susceptibility to infections
Osteoporosis
AtherosclerosisSarcopenia
Mortality due to infectious diseases
and cardio-vx diseases Adapted from
B GRUBECK- LOEBENSTEINAging 2009; 21: 1-9
Post FLU vaccine response inyoung (N = 913) and old adults (N = 4492)
0
20
40
60
80
H1N1 H3N2 B
0
20
40
60
80
H1N1 H3N2 B
Seroconversion(% of subjects with 4-fold AB increase)
Seroprotection(% 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)
0
20
40
60
80
H1N1 H3N2 B
0
20
40
60
80
H1N1 H3N2 B
Seroconversion(% of subjects with 4-fold AB increase)
Seroprotection(% of subjects with AB titres > 40)
Meta-analysis of 50 surveys performed since 1986 GOODWIN K et al Vaccine 2006; 24: 1159-69
**
**
**
** ****
% %
RUBINS JB et al Inf Immunity 1999: 67: 5979-84
Antibody responses of old adults to all 23 capsular polysaccharides after
Pneumococcal vaccine
N = 53, m.a = 71 y.
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.
RUBINS JB et al Inf Immunity 1999: 67: 5979-84
3.7%
48%
80%
Age-related antibody responses after Pneumococcal vaccination
0
5
10
15
20
25
6B 14 19F 23F
22-46 y.o. 63-79 y.o. 80-89 y.o. > 90 y.o
Eli
sa I
gG
GM
C (g
/ml)
ROMERO-STEINER S Clin Inf Dis 1999; 29: 281-8
Immune Response to 23-v PnPS
HAINZ U et al Vaccine 2005; 23 : 2232-5
Age-dependant persistence of antibody after tetanus vaccine
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
TIME
Vaccine programs
for a better life
Acceptance: +/-
Previous exposures to pathogens
Immunosenescence
Individual variations !!
The target: old adults
How to improve it ?
How good is their health?
Scientificknowledge
Pregnancy
ChildrenHow to improve their growth ?
Are they healthy ?
Scientificknowledge
Very effective
Precise guidelines
Well accepted
Herd immunity
Infant immunity may indirectly protect the elderly
Rate of VT- IPD before and after introduction of PCV7 USA 1998-2003
MMWR, Sept 16, 2005 / 54(36);893-897
Reduced incidence of Invasive Pneumococcal Disease (IPD-VT) in the elderly after introduction
of PCV7 in infants
REICHERT TA et al N Engl J Med 2001; 344: 889-96
Exc
ess
De
ath
s F
rom
Pn
eu
mo
nia
an
d I
nflu
en
za
(pe
r 1
00
,00
0 P
op
ula
tion
)
0
2
4
6
8
10
12
14
1950
1954
1958
1962
1966
1970
1974
1978
1982
1986
1990
1994
1998
P&I* Mortality Rate
1962: Program to vaccinate school children with inactivated influenza vaccine begins
1987: Parents allowed to refuse vaccination
1994: Program discontinued
Japanese school vaccination program with TIV reduced mortality in the
CommunityP&I = Pneumonia & Influenza mortality rate
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
TIME
Vaccine programs
for a better life
Clinicalrecommendationsfor the ageing and
aged adults
Part ofPREVENTIVEMEDICINE !
The target: old adults
How to improve it ?
How good is their health?
Scientificknowledge
Continuity ofthe vaccine program !!
HEALTHY AGEING How to improve it ?Midlife adults
How good is their health ?
Scientificknowledge
Pregnancy
ChildrenHow to improve their growth ?
Are they healthy ?
Scientificknowledge
Very effective
Precise guidelines
Well accepted
?
Influenza vaccination andrisk 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
SISCOVICK DS et al Am J Epidemiol 2000; 152: 674-7
Influenza vaccination seemed to be associated with
a reduced risk ofprimary cardiac arrestOR = 0.51 [0.33- 0.79]
Coronary Artery Disease (CAD) and
Influenza vaccineRandomized, 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 assecondary prevention of
Cardio Vascular Diseases (CVD)
The American Heart Association and American College of Cardiology
recommendInfluenza vaccine
(TIV intra muscular)
as part of « secondary » preventionin 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
71% 70%68%
66%63%
53% 53%51%
37%
30%
25%
0% 0%0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
A B C D E F G H I J K
2006
/7 V
acci
natio
n C
over
age
Rat
e (%
)
≥65 years < 65 years at risk Healthcare Workers* Source: TNS survey 2006/7Data in file
2014 WHO goal = 75%
2006 WHO goal = 50%
2006/2007
Flu Vaccine coverage rate in the population < 65 at risk
71% 70%68%
66%63%
53% 53%51%
37%
30%
25%28%
17%
24%
14%
0%
37%37%
56%
35%39%
34%
17%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
A B C D E F G H I J K
2006
/7 V
acci
natio
n C
over
age
Rat
e (%
)
≥65 years < 65 years at risk Healthcare Workers* Source: TNS survey 2006/7Data in file
2014 WHO goal = 75%
2006 WHO goal = 50%
Flu Vaccine coverage rate in the health care workers (HCWs)
71% 70%68%
66%63%
53% 53%51%
37%
30%
25%28%
17%
24%
14%
22%
17%
34%
39%35%
56%
37% 37%
24% 24%
17%13%
22%25%
22%
16%
25%
20%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
A B C D E F G H I J K
2006
/7 V
acci
natio
n Co
vera
ge R
ate
(%)
≥65 years < 65 years at risk Healthcare Workers* Source: TNS survey 2006/7Data in file
HERD IMMUNITY !
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
0
20
40
60
80
100
Day 0 Day 30 Day 90
With nutritional supplements
Without nutritional supplements
Responses to TT vaccine with and without ready to use canned food
LESSOURD B Nature Rev 1995; 53: S86-94
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. 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 virus-like 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 immunosenescencePossible 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
Part ofpreventivemedicine !
Developing aconsensual
vaccineprogramme
The target: old adults
How to improve it ?
How good is their health?
Scientificknowledge
Pregnancy
ChildrenHow to improve their growth ?
Are they healthy ?
Scientificknowledge
Very effective
Precise guidelines
Well accepted
TIME
!
How to improve it ?Midlife adults
How good is their health ?
Scientificknowledge
Continuity of the vaccine programHEALTHY AGEING
BURDEN of PREVENTABLE INFECTIOUS DISEASES
in the ELDERLY
European Union + European Economic Area + European Free Trade Associaion
European Union Geriatric Medicine Society
Proposed EUGMS and IAGG-ERvaccine 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
- Influenza vaccine
New medical/injury event(after assessment of the vaccine status)
Multiple hospital stays(after assessment of the vaccine status)
- Td or TT vaccine - Pneumococcal vaccine
- TdaP or Td or TT vaccine- Influenza vaccine
- Pneumococcal vaccine- Herpes Zoster vaccine*
Each year after the retirement age (after assessment of the vaccine status)
By the 9 th decade of age / Nursing Home admission
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
« A transitional state »
ROBUSTNESS
FRAILTY
ADLDEPENDENCE
FRAILTY life long processtime
DEATHPhysiological reserves
Total
Used
AVAILABLE
Age, Gender, Lifestyle, Socio-economic status,
Co-morbidities, Affective, Cognitive and Sensory
Impairments (…)
Adapted from FRIED LP et al Sci Aging Knowl Environ 2005; 31: pp 24 (sageke.sciencemag.org)
Sarcopenia Total energyexpenditure
CYCLEof
FRAILTY
Chronic undernutrition. Age. Malnutrition. Disease(s). Environment
Dysregulations. Hormones. Immunologic. Inflammation. Coagulation
Resting metabolic rate
Immobilisation Impaired balance Falls / trauma Infections Drugs use
Hospital admissions Disabilty Dependence Institutionalisation Death
Relationship between frailty and vaccines ?