IL BURDEN DELL'INFLUENZA E L'IMPATTO DEL VACCINO SULL'ANZIANO - Stefania Maggi CNR-Invecchiamento Padova
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IL BURDEN DELL’INFLUENZA E L’IMPATTO DEL
VACCINO SULL’ANZIANO
Stefania Maggi
CNR-Invecchiamento
Padova
DISCLOSURE Grant di ricerca da: • TAKEDA, MSD, GSK, PFIZER
Outline • Il burden dell’Influenza: un problema complesso • Il valore della vaccinazione: ben oltre la prevenzione dell’influenza
Casi di Influenza in Italia 2018-19
• Circa il 15% della popolazione
• Oltre 8 Milioni di casi sintomatici
• Ospedalizzazione e mortalità più frequenti nella popolazione anziana
(oltre il 90% delle morti)
Copertura vaccinale in Italia: circa 50%
(target minimo 75%, target ottimale 95%)
https://www.epicentro.iss.it/influenza/aggiornamenti
Disabilità e influenza
Catastrophic Disability:
Defined as a loss of independence in ≥3 basic activities of daily living2
• 14.6% of older adults hospitalized with influenza experience catastrophic disability3
• Dysregulated immune response is the ‘sleeping giant’ of chronic diseases. Flu wakes the giant, increasing
the risk of catastrophic disability with:
– Stroke, heart failure
– Pneumonia4
– Ischemic heart disease
– hip fracture
1.McEthaney JE Front Immunol 2016; 7:41, 2.Ferrucci et al. JAMA1997; 277:728. 3.Andrewes MK.
Canadian Immunization Conference 12/7/2016. 4.Barker Arch Int Med 1998; 158:645. 5.Falsev
NEJM 2005; 352:1749 From Greember. ESWI Riga 2017,
Globally, most leading causes of death are
non-communicable diseases1
Deaths (millions)
0 2 4 6 8 10
Ischaemic heart disease
Stroke
COPD
Lower respiratory
tract infections
Dementia
1. WHO. The top 10 causes of death. 2018. https://www.who.int/en/news-room/fact-sheets/detail/the-top-10-causes-of-death [last accessed 29-Jul 2019].Globally, most leading causes of death are
non-communicable diseases1
… but vaccine preventable diseases may play a role
Deaths (millions) VPDs associated wth triggering or exacerbation of
0 2 4 6 8 10 this condition
Ischaemic heart disease Influenza2, Pneumococcus3, Varicella/zoster4
Stroke Varicella/zoster4, Influenza5
COPD Influenza6, Pneumococcus6
Lower respiratory
tract infections
Dementia Varicella/zoster7
1. WHO. The top 10 causes of death. 2018. https://www.who.int/en/news-room/fact-sheets/detail/the-top-10-causes-of-death [last accessed 29-Jul 2019]; 2. Fischer WA 2nd et al. Glob Heart 2014;9:325–36; 3. Corrales-Medina VF et al. PLoS Med 2011;8:e1001048;
4. Zhang Y et al. J Stroke Cerebrovasc Dis 2017;26:1807–16; 5. Lee KR et al. Neuroepidemiology 2017;48:103–10;
6. Froes F et al. Int J Chron Obstruct Pulmon Dis 2017;12:3457–68. 7. Chen VC et al. J Clin Psychiatry 2018;79:pii:16m11312.Effetti dell’infezione del virus influenzale
nella malattia cardiovascolare
Esacerbazione di CVD Effetti diretti
pre-esistenti
L’influenza può portare ad
un’alterazione dell’omeostasi
L’infiammazione sistemica porta ad L’infezione virale può portare a
una rottura delle placche miocardite o miopericarditi
aterosclerotiche
Infarto del Insufficienza
Stroke
miocardio cardiaca cronica
Udell J. Expert Rev Cardiovasc Ther, 2015Infarto Acuto del Miocardio
dopo malattia influenzale (2009-2014)
● Studio caso-controllo in Canada (2009-2014) su 148,307 casi di influenza per valutare l’associazione tra malattia
influenzale confermata da laboratorio e ospedalizzazione per AMI in adulti (364 casi, età mediana: 77 a)
● INCIDENZA DI RICOVERO PER INFARTO ACUTO DEL MIOCARDIO:
6 VOLTE maggiore durante i 7 giorni successivi all’influenza
Kwong JC, et al. N Engl J Med. 2018;378(4):345-353
Kwong JC, Schwartz KL, Campitelli MA. N Engl J Med. 2018;378(26):2540-2541Time-series: Association between influenza-like illness
and hospitalization for heart failure. The ARIC Study
• ILI was temporally
associated with increase in
HF hospitalizations.
• A 5% increase in ILI was
associated a 24% increase in
HF hospitalizations rates
Kytömaa S, JAMA Cardiol 2019Influenza and Hip Fracture
- Retrospective cohort: 9,237 incident hip fractures
Nursing Home (NH) residents, 2000 - 2009
Results:
ILI hospitalizations are associated with a 13% average
increase in hip fracture hospitalization
Significant Temporal association
McConeghy KW,. J Gerontol A Biol Sci Med Sci. 2017
Variation from 1 to 6 Hip Fracture/100 person-years in
American NH, Cohort study ( Medicare) Could Flu be one
Result : < 15% variability explained by NH or resident
characteristics
of the causes?
Zullo AR. J Am Geriatr Ass 2018Influenza Increases Disability
residents in 2351 Nursing home in the USA
ADL Decline (>3 points in the 0-28 ADL scale)
Influenza Mortality
William H. Barker Arch Intern Med 1998 Gozalo PL JAGS 2013
influenza mortality was strongly associated
Nearly 2 fold increase Disability rates with flu episodes
with high (≥4 points) ADL declineOutline • Il burden dell’Influenza: un problema complesso • Il valore della vaccinazione: ben oltre la prevenzione dell’influenza
EVOLUZIONE DEI VACCINI ANTINFLUENZALI
DOMANI
-Vaccino ad alto dosaggio [60
mg/ceppo]
USA dal 2009 TIV HD
OGGI
Dal 2019 QIV HD
QIV In fase di approvazione Europea
ADIUVATO MF59 TIV -Vaccino Ricombinante RIV QIV
IERI LAIV non in ITALIA già autorizzato USA
Trivalente classico TIV Sottomessa registrazione in
Europa ottobre 2019Vaccino antinfluenzale ad alto dosaggio- HIGH DOSE • Attualmente utilizzato in US e Canada • Procedura di registrazione avviata anche in Italia • 60 mcg of HA per ceppo 4x quantità di antigene di HA in confronto ai vaccini tradizionali (15mcg) • Indicato per i soggetti dai 65 anni di età • Novembre 2019 Approvazione FDA vaccino alto dosaggio formulazione quadrivalente con indicazione dai 65 anni di età • Registrazione in corso in Europa già sottomessa a European Medicine Agency (EMA)
Influenza vaccination reduces the incidence of ACS events in older
adults with chronic disease
Taiwan Longitudinal Health Insurance database 1996-2008
Relative risk of hospitalization with Acute Coronary Relative risk of hospitalization with ACS in Chronic
Syndrome (ACS) in COPD patients (n=7,722)1 Kidney Disease (CKD) patients (n=4,406) 2
1 1
0,8 0,8
0,6 0,6
0,4 0,4
0,2 0,2
0 0
1 vaccination 2-3 vaccinations ≥4 vaccinations 1 vaccination 2-3 vaccinations ≥4 vaccinations
Significantly fewer ACS first events in vaccinated vs Significantly fewer ACS first events in vaccinated vs
unvaccinated COPD patients in all seasons (PInfluenza Vaccination was Associated with a Lower Risk of Major CV
Events in a Meta-Analysis of Small RCTs
Influenza Placebo/ MACE*: CV Death, MI, Stroke, HF
Vaccine Control UA, or Urgent Coronary Angioplasty
Study Events Total Events Total RR (95% CI)
Reproduced with permission from JAMA. 2013;310(16):1711-1720.
Copyright©2013 American Medical Association. All rights reserved.
Govaert 7 927 5 911 1.38 (0.44 – 4.32)
FLUVACS 32 145 54 147 0.60 (0.41 – 0.87)
FLUCAD 16 325 30 333 0.55 (0.30 – 0.98)
De Villiers 20 1620 20 1622 1.00 (0.54 – 1.85)
Phrommintikul 20 221 42 218 0.47 (0.29 – 0.77)
Total 95 3238 151 3231 0.64 (0.48 – 0.86)
2.93% 4.67%
0.2 0.5 1 2 5
Absolute Risk Difference: 1.7%
Influenza Vaccine Better Placebo/Control Better
Number Needed to Treat: 58
* major adverse cardiovascular events
Udell JA, et al. JAMA. 2013;310(16):1711-1720.Danish nationwide study on Influenza
vaccination and Heart Failure
To determine whether influenza vaccination is associated
with improved long-term survival in patients with newly
diagnosed HF.
To determine whether the frequency of vaccinations and
the cumulative number of vaccinations is associated with
improved long-term survival
Modin D et al. Circulation. 2019 Jan;139(5):575-586.Data: study subjects
Danish National
Patient Registry
All first diagnosis of heart failure
(ICD-10 I50, I130, I132)
1st Jan 2003– 1st June 2015
N=151,328
Exclusion:
-569 < 18 years old
-16 711 died 30 days
Final study population
N= 134,048
Modin D et al. Circulation. 2019 Jan;139(5):575-586.Results (Median follow-up about 3.7 years, mean age: 73 years)
Vaccination parameters and age
were entered as time-varying
covariates in a time-dependent Cox
regressions model adjusted for all
variables displayed in Table 1 with
the addition of inclusion year.
Modin D et al. Circulation. 2019 Jan;139(5):575-586.Results: Causation
Vaccination parameters and age were entered as time-varying covariates in a time-dependent Cox regressions model adjusted for all variables displayed in Table
1 with the addition of inclusion year.
Modin D et al. Circulation. 2019 Jan;139(5):575-586.Possibile meccanismo cardioprotettivo della
vaccinazione antinfluenzale
● Prevenire l’infezione evita
un’alterazione dell’omeostasi
● La risposta immunitaria a seguito
della vaccinazione può di per sé
avere un effetto benefico:
● Gli anticorpi indotti dalla
vaccinazione potrebbero
promuovere la stabilizzazione
della placca attraverso
l'attivazione del recettore della
bradichinina 2
Bhatt et al. JACC Heart Fail. 2017 Mar;5(3):194-203
23Vaccinazione antinfluenzale come intervento per
la prevenzione dell'infarto miocardico
● La vaccinazione antinfluenzale offre potenzialmente rendimenti maggiori rispetto
alla maggior parte degli altri interventi in prevenzione secondaria dell'infarto del
miocardio:
Intervento Efficacia (%)
Smettere di fumare 32–43
Statine 19–30
Farmaci anti ipertensivi 17–25
Vaccino anti influenzale 15–45
● Le stime sull'efficacia dei vaccini anti influenzali nella prevenzione dell'infarto
miocardico si mantengono in un intervallo di efficacia simile rispetto alla
normale misura di terapia coronarica di routine come lo smettere di fumare o
l’uso delle statine o della terapia ipertensiva
MacIntyre CR, et al. Heart 2016, 102(24):1953Influenza and Hip Fracture
Impact of flu vaccine on hip fracture ( Cohort study) (n=4344)
2001 and 2013
Increase risk was 1.26 (1.1-1.51) ONLY in Unvaccinated Cohort
2 weeks following a week with high infection burden
Daily fracture rates were significantly higher in winter (1.1
fractures/day) compared to summer, fall, and spring.
Fraenkel M,. Osteopor Int . 2017Economic benefits from vaccinations
• Generally, economic evaluations of vaccinations in older adults show a favourable cost-
effectiveness ratio and cost is lower than for other preventive actions1
• Influenza vaccination coverage of 75% among individuals >65 years in Europe would
result in €153–219 million saved in healthcare cost1,2
BUT ALSO
• Intangible economic benefits due to:
– attenuated severity of disease3
– reduction in complications (influenza and pneumococcal vaccinations may reduce the incidence of MI
by up to 50%) and comorbidities1,3
– decreased polypharmacy and antibiotics use4
1. Doherty TM et al. Eur Geriatr Med 2018;9:289–300; 2. Preaud E et al. BMC Public Health 2014;14:[Epub]; 3. Bonanni P et al. J Mark Access Health Policy 2015;3:[Epub]; 4. Kwong JC et al.
Clin Infect Dis 2009;49:750–756...................To Summarize
Self-amplifying cycle between Influenza and comorbidities leading to decline in physiological function
etc. (and unknown), frustrated homeostasis, more likely & sooner
immune dysregulation, chronic inflammation more severe
CO-MORBIDITIES Influenza
immediate step loss lung injury, bacteremia, acute stress etc.
accelerated chronic decline (and unknown)
(Respiratory, Cardiovascular,
Influenza
Influenza
Systems Function
dysfunction (symptomatic)
Influenza
etc.)
failure (life-threatening)
death
adolescence Age geriatrics
Modified from Quinton LJ et al. Physiol Rev. 2018;98(3):1417-1464.Infections in Elderly Adults
• Clinical features
Traditional • Changes in laboratory
values
parameters • Clinical response
• Microbiological response
• Cause-specific mortality
Physical and Cognitive
Geriatric functions
parameters Complications
Health care aspectsGeriatric Parameters
Does the patient return to the same level of physical function?
Physical &
Cognitive Did the cognitive function of the patient change during and after the infection?
functions Has depression become clinically apparent and has it affected the recovery of function?
What are the infectious and not infectious complications?
Complications
Do they differ from those seen in the younger patients with the same infection?
Is the length of hospitalization and the cost care higher for older than for younger patients
Healthcare with the same infectious disease?
aspects Is the discharge to a place other than home required?You can also read
