Vaccination Policy�

GeertLeroux‐Roels

CenterforVaccinology

GhentUniversityandHospital

Summer School on Influenza, Siena (Italy), 1-5 August 2011

  Everyyear5‐15%oftheglobalpopulaBonisaffectedwithupperrespiratorytractinfecBons

  TheWHOglobalesBmates1  3to5millionseverecasesannually

  withannualmortalitybetween250,000‐500,00  Duringseasonalepidemics,largenumbersofinfecBons

occurinallagegroups2  Theratesofinfluenza‐relatedhospitalizaBonsvaryby

ageandriskgroup2  TheburdenofinfluenzainchildrenisunderesBmated3

Seasonal influenza�

1 WHO:FactsheetNo211(hUp://www.who.int/mediacentre/factsheets/fs211/index.html)2 BridgesBetal.In:PlotkinSA,OrensteinWA(eds).Vaccines5thediBon.Philadelphia:Saunders2008:259‐903 TeoSSetal.ArchDisChild,2005;90:532‐536

Evolution of circulating influenza strains�1977 2009 2010Today

InfluenzaAH1N1 anBgenicdrib H1N12009

H3N2 anBgenicdrib

InfluenzaBVictoria lessanBgenicdrib

Yamagata lessanBgenicdrib

Since 1977, H1N1 subtype viruses have continued to co-circulate with influenza A (H3N2) viruses which had first emerged in the 1968 pandemic.

Two antigenically and genetically distinct lineages of influenza B viruses, represented by the reference strains B/Victoria/2/87 (B/Vic) and B/Yamagata/16/88 (B/YM) have co-circulated in humans since at least 1983.

Xu et al. Virus Research 103 (2004) 55–60

  VeryinfecBousrespiratorytractinfecBon  Transmissionroutes:

1.  InhalaBonofaerosol(droplets)generatedbyaninfectedpersonduringtalking,coughing,sneezing

2.  Directcontactwithaninfectedperson3.  Contactwithcontaminatedobjects(toys,doorknob,..)

  Contagiousness:‐  24upriortostartofsymptoms‐  5‐7days(14days)

‐  children>>>adults

Disease transmission�

Systemic symptoms Respiratory symptoms

Sudden onset (high) fever (oral temperature > 37.5°C) stuffy/runny nose – nasal congestion

headache sore throat

fatigue (new or worsening) cough

muscle aches - myalgia (new or worsening) sputum production

Feverishness - chills (new or worsening) dyspnea

(new or worsening) wheezing

Influenza: signs and symptoms�

Influenza like illness (ILI) is defined as the simultaneous occurrence of at least one respiratory and one systemic symptom OR as fever (>37.8°C) and a cough and/or a sore throat in the absence of a known cause other than influenza

Percentage of visits for ILI reported by the US Outpatient Influenza-like Illness Surveillance Network (ILINet)�

Weekly National Summary, September 30, 2007 – July 16, 2011�

CDC – FluView http://www.cdc.gov/flu/weekly/

Respiratory admission rates (England and Wales) and influenza epidemic periods 1994-2000 by age�

Cumulative rates of hospitalization during three influenza seasons by age group (United States 2007-2010) �

CDC - MMWR 2010;59:No. RR-8

✝ rate per 10,000 population

Influenza in children�Influenza-like illness or RTI •  fever (≥ 38°C), feeling feverish/chills •  cough •  sore throat •  runny or stuffy nose •  muscle or body aches •  headaches •  fatigue (very tired)

•  vomiting and diarrhea

In infants influenza is often unrecognized •  Signs and symptoms are not

specific and may suggest a bacterial infection

•  Symptoms include lethargy, poor feeding, and poor circulation

Complications of Pediatric Influenza Infection�

•  ViralandBacterialpneumonia•  BronchioliBs/Croup/TracheobronchiBs•  ExacerbaBonofasthma•  AcuteoBBsmedia

•  GastrointesBnalsymptoms•  MyosiBs/MyocardiBs/PericardiBs

•  Febrileseizures/EncephaliBs/Encephalopathy•  Guillain‐Barrésyndrome/TransversemyeliBs•  Death(3.8/100,000childreninfected)

Pediatrics 2002;110:1246-52; MMWR 2003;(RR-8):1-34

Health Burden of Influenza in Children�

•  AUackratesofinfluenzaare15%to42%inpreschoolandschool‐agedchildren

•  Inasingleinfluenzaseason,upto12%ofchildren<5yearsseekmedicalcare

•  10%to30%increaseinanBmicrobialcoursesprescribedtochildrenduringinfluenzaseason

•  About1childin1000isadmiUedinthehospital

Pediatrics 2002;110:1246-52; MMWR 2003;52 (RR-8):1-34; CDC – 2010 - http://www.cdc.gov/mmwr/pdf/rr/rr5908.pdf

Illness among school children during influenza season�

Resultsofa1‐yearprospecBvestudyoftheeffectofinfluenza

seasononacohortofchildrenenrolledinalargeelementaryschoolinSeaUle(Dec4,2000–April13,2001)

•  Forevery100childrenfollowedupforthisinfluenzaseasonanexcessof28illnessepisodesand63missedschooldays

occurred.

•  Forevery100childrenfollowedup,influenzaaccountedforanesBmated20daysofworkmissedbytheparentsand22

secondaryillnessepisodesamongfamilymembers.

Neuzil et al. Arch Pediatr Adolesc Med 2002;156:986

Visits to medical offices and emergency departments among children < 5 years with acute respiratory illness

or fever caused by laboratory-confirmed influenza�

•  TheaverageannualrateofhospitalizaJonassociatedwithinfluenzais0.9per1000children(80%inchildren<24months)

•  Fewchildrenwithlab‐confirmedinfluenzaweregiventhediagnosisofinfluenzabythetreaBngphysician–  28%intheinpaBentand17%intheoutpaBentsejng

Poehling et al. N Engl J Med 2006;355:31-40 CDC - MMWR 2010;59:No. RR-8

%ofvisits Rateofvisits(#/1000children)

Officevisits 10‐19 50–95

EDVisits 6‐29 6‐27

Annual number of influenza-associated deaths with underlying pneumonia and influenza causes�

•  H3N2waspredominantstrainin22of31influenzaseasons

•  Averagemortalitywas2.7BmeshigherinH3N2‐predominantseasons

Thompson et al. MMWR 2010;59:1057-1062

Period1976‐2007 <19yrs 19‐64yrs <65yrs

Average 97(65‐201) 666(555‐949) 5546(5182‐6373)

Minimum 41(18‐123) 173(112‐402) 673(510‐1327)

Maximum 234(171‐488) 1459(1269‐1781) 13245(12777‐14422)

ProporBonsofaveragedeathoverall

1,5% 10,6% 87,9%

Number of influenza-associated pediatric deaths �by week of death: 2007-2008 season to present�

From FluView CDC

Influenza-associated deaths in children�

Influenza‐associateddeathsareuncommonamongchildren.

Laboratory‐confirmedinfluenzadeathsinUSresidentsyoungerthan18yearsofageduringthe2003/4influenzaseason•  153influenza‐associateddeaths

•  meanagewas3yearsand63%wereyoungerthan5years

•  Mortalityratewashighestamongchildren<6monthsofage

•  29%diedwithin3daysaberonsetofillness

•  BacterialcoinfecBonsidenBfiedin24%

•  67%didnothaveacondiBonthatwasanindicaBonforvaccinaBon

Bhat et al. N Engl J Med 2005;353:2559-67

Influenza in young healthy adults (19-49 years)�

•  Illnessisnotsevere•  hospitalizaBonisrarelyneeded•  Thismaybedifferentduringpandemicinfluenzaoutbreaks

•  AUackratesvaryfrom2‐20%annually•  Influenzacausesabsenteism(0.6–2.5day/illness)

•  Riskfactorsforinfluenza‐relatedcomplicaBons–  (morbid)obesity(BMI≥40)

–  Pregnancyandpost‐partumperiod

–  Raceandethnicity(AmericanIndians/AlaskannaBves,indigenous..)•  HigherprevalenceofunderlyingmedicalcondiBons

•  Accesstomedicalcare

CDC - MMWR 2010;59:No. RR-8

Immunosenescence and influenza�

- Dual challenge: Immunosenescence contributes to two related but independent challenges in older age :

Targonski et al Vaccine 2007;25(16):3066-9; Pawelec Mech Ageing Dev 1999;108:1-7

increased susceptibility to infection and disease

decreased response to vaccination

lower titers and shorter duration

AND

'a decline in the ability to fight infection or mount novel immune responses'

–  What is immunosenescence?

Young Elderly

Immunosenescence and cellular immune response�

Immunosenescence Decline in humoral and cellular immunity N

r of c

ytok

ine

+ C

D4

T ce

lls p

er 1

06 C

D4

cells

From: Denis M. The Lancet Asia Medical Forum, Singapore, May 2006

•  Foreachdeathduetoinfluenza,thereareapproximately8hospitalisaBons1

•  DatafromstudyperformedinEnglandandWalesduring12consecuBveinfluenzaseasons(1989‐2001)illustratehowtheelderlyareatincreasedriskofhospitalisaBon2:

Excess admissions

Influenza in the elderly: frequent hospitalisation�

1Monto et al. Vaccine 2009; 27: 5043-53. 2Fleming et al. Commun Dis Public Health 2003; 6: 231-7.

15-19 20-24

Num

ber o

f ex

cess

adm

issi

ons

2000

1000

0

Age (years)

3000

4000

5000 Excess bed days

Num

ber o

f ex

cess

bed

day

s

2000

1000

0

3000

4000

5000

25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 ≥85

McElhaney.Vaccine 2005;23S1;S1/10-S1/25

Bed rest and permanent disability�

Prolonged periods of bed rest and inactivity related to influenza illness may lead to deconditioning that cannot be reversed and results in permanent disability

Mortality and morbidity linked to influenza �

Deaths/yr (1000s)

Age group

3,000

33,000

0

5

10

15

20

25

30

35

0 ̶ 49 50 ̶ 64 ≥ 65

From 1990-1999, deaths due to influenza in the USA average ± 36,000 and 90% are associated with H3N2

Elderly above 65 account for 90% of all influenza-related

deaths

But also impact on: Cardiovascular function

Functional status

Nichol et al. N Engl J Med 2003; 348:1322-32. McElhaney.Vaccine 2005;23S1;S1/10-S1/25

http://www.cdc.gov/flu/keyfacts.htm; Thompson et al., JAMA 289 (2003), pp. 179–186.

Influenza during pregnancy�

•  AllinfluenzaAinfecJons–  Increaseriskforpretermlaboranddelivery–  Increaseriskforpneumonia,ARDS,shock,fetalehypoxia,death

–  VaccinaBonisrecommended!

•  H1N1vinfecJe:risks+++–  IncreasedhospitalisaBonrate(13%)– MorecomplicaBonsandfatalcases(x6)

–  CDC(USA):700infecBes100IZ28 (4%)

•  Riskfactors:3rdtrimester,obesity,smoking,lowsocio‐economicstatus

CDC 2009; Zaman et al. NEJM 2008; 359: 1555-64 ; Jamieson et al. Lancet 2009 Jul 28 [Epub ahead of print]

Saleeby et al. Obstet Gyn 2009; 114: 885-91

Influenza and pregnancy �During pregnancy (2nd and 3rd trimester) a woman is more susceptible to influenza infection and at higher risk for influenza-related complications

Anatomic and physiologic factors •  elevation of the diaphragm •  less adequate ventilation •  increased breathing rate

Immunologic factors •  pregnancy induces tolerance

Age •  a young person is more susceptible to infection with a pandemic virus (H1N1 2009)

•  Low expression of HLA antigens on syncytiotrophoblast

•  Fetal tissues express molecules that trigger apoptosis of activated lymphocytes

•  Progesteron induces a shift of Th1/Th2 balance towards Th2 and a weaker inflammatory response

•  Placental macrophages produce predominantly anti-inflammatory cytokines, such as IL-10.

•  The number of regulatory T cells increases during pregnancy.

Maternal immune system is tolerized�against paternal antigens�

Pregnancy increases the risk for seasonal influenza complications�

Neuzil et al. Am J Epidemiol 1998;148:1094-1102

Pregnant women are hospitalized more frequently for cardio-pulmonary problems than a post-partum control group.

OddsraJo 95%CI

Week1‐7 1.06 0.68–1.67

Week21‐26 2.52 1.74–3.65

Week37–42 4.62 3.42–6.39

•  Nonpharmacological interventions –  Hand washing

–  Respiratory hygiene

–  Strategies at the community level (closing schools, ..)

•  Pharmacological interventions –  Antiviral medications (adamantanes, NA-inhibitors)

–  Vaccine

Options for controlling influenza �

The most effective strategy for preventing influenza is annual vaccination.

ModifiedfromMarie‐PauleKieny.UpdateofthedevelopmentofA(H1N1)pandemicinfluenzavaccines.November9,2009

Whole virus Split virus Subunit (surface antigen)

Live attenuated

•  Baxter (Austria) •  Omnivest (Hungary)

•  8 manufacturers in China •  CSL (Australia)

•  Sanofi Pasteur (France) •  Green Cross (Korea)

•  GSK Biologicals (Belgium) •  Baxter (Austria)

•  Novartis (US) [adjuvanted and unadjuvanted]

•  MedImmune (US) •  Microgen (Russia)

Seasonal influenza vaccines�

Influenza vaccines�

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr58e724a1.htm

LAIV TIV Route of administration Intranasal IM injection Type of vaccine Live virus Inactivated No. of included strains A (2), B (1) A (2), B (1) Strains updated Annually Annually

Frequency of administration Annually Annually Approved age 2 – 49 years ≥ 6 months Can be given to No risk* All Interval between 2 doses for children aged ≥6 mo to 9 yrs

4 weeks 4 weeks

Composition of the 2011-2012 TIV�

•  A/California/7/2009(H1N1)•  A/Perth/16/2009(H3N2)•  B/Brisbane/16/2008

•  Serologic parameters – antibody production –  Haemagglutination inhibition titer of ≥1:40

Based on a study in which healthy volunteers were challenged with influenza virus. A HI titer of 1:36 corresponded with 50% reduction of the infection rate. (Hobson et al. J Hyg (London) 1972;70:767-77)

–  Single radial haemolysis (SRH) of ≥ 25 mm2

–  Neutralization titers of 1:32 or 1:40

•  Cell mediated immune response

Corrrelates of protection after vaccination �

Annual renewal clinical trial to re-confirm immunogenicity

Regulatory licensing criteria �Immunogenicitycriteria

AnB‐hemaggluBninanBbodytestonserumsampletoquanBfyimmuneresponsetoeachofthestrains3weeksabervaccinaBon(ascomparedtopre‐vaccinaBon)

FDA (US) EMEA (EU) 18-64y > 64y 18-60y > 60y

Seroconversion factor (SCF1) / / ≥ 2.5 ≥ 2.0 Seroconversion rate (SCR2) LL ≥ 40% LL ≥ 30% ≥ 40% ≥ 30% Seroprotection rate (SPR3) LL ≥ 70% LL ≥ 60% ≥ 70% ≥ 60%

1GMT increase ratio

2% subjects w HI x 4 3% subjects w HI >1:40

From Immunogenicity to Clinical Endpoints�

•  ImmunogencitydatafromaRCT

•  EfficacydatafromaRCT–  EfficacyagainstLCI,againstcultureconfirmedinfluenza,againstPCRconfirmedinfluenza

•  EffecJvenessdatafromasurvey– HospitalizaBonanddeatharemostreliablebutsensiBvityandspecficitydependsondefiniBonofclinicalillnessandtheperiodofobservaBon

Incr

easi

ng im

port

ance

for p

ublic

hea

lth

RCT : randomised controlled trial, LCI : Lab Confirmed Influenza, PCR : polymerase chain reaction

Vaccine efficacy (VE, %) Good match Suboptimal match

> 65 years 17-53 18-64 years 70-90* 50-77*

Children 6 mo -15 years (6 mo – 9 yr: 2 doses)

77-91* 51°

*against lab confirmed influenza °against medically-attended, clinically diagnosed pneumonia and influenza

•  Match between vaccine strain and circulating viruses (A/B) •  Immune competence of the subject •  Waning immunity over time •  Intensity and chance of exposure (closed population, herd immunity)

•  Outcome measure (lab-confirmed influenza, hospitalization, MAARI, ..)

Efficacy of seasonal flu vaccines�

Goodwin et al. Vaccine 2006; 24: 1159-69

Ritzwoller et al. Pediatrics 2005; 116: 153-9

Shuler et al. Pediatrics 2007; 119: e587-95

Why vaccinate children against influenza?�

•  Influenzaiscommoninyoungchildren

•  PaediatricinfluenzainfecBonsareobencomplicated

•  PaediatricinfluenzainfecBonsobenrequirehospitalizaBon

•  YoungchildrenarekeytransmiUersofinfluenza

•  Burdenofparentalcareforsickchildrenincreasessocietalimpact

Estimates of vaccine effectiveness in children�

StudyPeriod Studydesign Agegroup Endpoint EffecBveness(%) Ref

1985‐1990 RCT 1‐15yrs LCI‐InflA 77‐91 1

1999‐20002000‐2001

RCT 6‐24mo LCI 1999‐2000662000‐2001none

2

2003‐2004 Casecontrol 6‐59mo LCI 49 3

2003‐20042004‐2005

ObservaBon 6‐59mo LCI 2003‐2004442004‐200557

4

SystemaJcreview

6‐24mo≥24mo

6‐24mo:moreevidence≥24mo:59

5

1.  Neuzil et al. Pediatr Inf Dis J 2001;20:733-740 2.  Hoberman et al. JAMA 2003;290:1608-16 3.  Shuler et al. Pediatrics 2007;119:e587-95

4.  Eisenberg et al. Pediatrics 2008;122:911-9 5.  Jefferson et al. Cochrane Database Syst Rev 2008:CD004879

2003-04 suboptimal match

Heinonen et al. Lancet Infect Dis 2011;11:23-29

Baseline characteristics

Vaccine 2007/2008 •  A/Solomon Islands/3/2006 (H1N1) •  A/Wisconsin 67/2005 (H3N2) •  B/Malaysia/2506/2004 (B/Victoria)

Circulating strains 2007/2008 •  A/Solomon Islands/3/2006 (H1N1) •  A/Wisconsin 67/2005 (H3N2) •  B/Yamagata-like

33 38 Total 71

Weekly numbers of children with laboratory-confirmed Influenza A and B infections in the follow-up cohort

Heinonen et al. Lancet Infect Dis 2011;11:23-29

The effectiveness of the vaccine was high against the well-matched influenza A strains. No significant effectiveness was noted against the mismatched B viruses. TIV was effective in preventing influenza in young children, including those younger than 2 years.

The Benefits of Herd Immunity�

•  HighervaccinaBonratesinapopulaBonprotectbothvaccinatedandunvaccinatedindividuals

•  ReducBonofrespiratoryillnessesamongcontactsofvaccinatedchildrenofallages(Tecumseh,Michigan)

•  AhighproporBonofvaccinerecipientsreduces:•  Riskforbecominginfected

•  Severityofsymptomsifinfected

•  Riskofexposureforunvaccinatedindividuals

De Jong MCM, Bouma A. Vaccine. 2001;19:2722-28, and Monto AS et al. J Infect Dis 1970

•  From 1962 to 1987: Schoolchildren vaccination policy in Japan •  Comparison of monthly rates of death due to pneumonia and influenza in USA

and Japan form 1949 through 1998

Vacc

ine

Dos

es (p

er 1

000

pop.

)

Exc

ess

Dea

th A

ttrib

uted

to P

&I (

per 1

00,0

00 p

op.) •  USA: Rates nearly constant

•  Japan: Rates divided by 3 to 4 when schoolchildren vaccination policy initiated

RESULTS

•  37,000 to 49,000 death prevented per year

•  420 vaccinated child to prevent 1 death

CONCLUSION

Vaccinating schoolchildren provides protection and reduces mortality from influenza among older persons

Reichert TA et al. The Japanese Experience With Vaccinating Schoolchildren Against Influenza, N Engl J Med 2001, 344(12):889-96

Impact on transmission

Impact of school children vaccination: the Japanese experience �

Vaccination of children�•  Childrenaged6monthsto8years

–  Shouldreceive2vaccinedosesseparatedby≥4weeks–  Vaccinedosecontains7.5µgHAofeachinfluenzastrain–  TIVcanbegivenatallages,LAIVonlyatage≥2years

•  Childrenaged9to18years–  Shouldreceive1vaccinedose(TIVorLAIV)–  Vaccinedosecontains15µgHAofeachinfluenzastrain

Safety of Influenza Vaccines in Children�•  TrivalentInacJvatedInfluenzaVaccine(TIV)

– Well‐toleratedinallstudies,includingyoungchildren–  4%to16%withmildfeverorsystemicreacBons

–  3%to6%withinjecBon‐sitereacBons–  Neurologiceventsrare;causalityunclear

•  Live‐AcenuatedInfluenzaVaccine(LAIV)–  Generallywell‐toleratedinchildren–  IncreasedincidenceofrhinorrheaornasalcongesBon,mildfever,GIcomplaints,muscleachesanddecreasedacBvity

–  Increasedincidenceofasthma/wheezinginchildrenyoungerthan5yearsofage

Neuzil KM, Edwards KM. Sem Pediatr Infect Dis. 2002;13:174-81;Neuzil KM, et al. Pediatr Infect Dis J 2001;20:733-40

Countries with recommendations to vaccinate healthy children �

Country AgerangeNorthAmerica

Canada 6‐23months

USA 6months–18years

EuropeAustria ≥6months

Estonia ≥6months

Finland 1‐3years

Latvia 6months–2years

Romania 6months–2years

Slovakia 6months–5years

Slovenia 6months–2years

Vaccine coverage rate in children by country in 10 European countries during seasons 2006/7 and 2007/8�

Blank et al. J Infect 2009;58:446-458

Country Season2006/7 2007/8

UK 6,1 6,1

Germany 14,1 19,3

Italy 11,0 15,0

Spain 10,3 12,4

Austria* 8,3 8,2

CzechRepublic 6,6 7,6

Finland* 2,1 10,4

Ireland 2,9 4,2

Poland 9,9 9,2

Portugal 15,4 15,9

Vaccination of elderly�•  VaccinaBonaimsatreducing:

–  InfecBon•  ILI•  Labconfirmedinfluenza

–  ComplicaBonsleadingtohospitalizaBon•  Pneumonia•  Cardiovasculardisease•  Cerebrovasculardisease•  PersisBngdisability

–  Mortality

SelecBonofprimaryendpoint(s)isimportantforoutcomeandsuccesofaclinicalstudy.

Efficacy of traditional influenza vaccines in the elderly population�

StandardTrivalentInacBvatedVaccines(TIV)donotconveythesamehighlevelofprotecBonintheageingpopulaBonthanintheyounghealthyadults

a) WHO, Weekly epidemiological record 75:281-288, 2000, available at http://www.who.int/vaccine_research/diseases/influenza/Weekly_epidemiological_record_7535.pdf accessed 19/11/2009 b) Adapted from Govaert et al, JAMA 272:1661-5, 1994.

adults 18-64 (a)

0%

20%

40%

60%

80%

100%

1

vacc

ine

effic

acy

0%

20%

40%

60%

80%

100%

elderly 60-69y(b)

elderly >70y(b)

Vacc

ine

effic

acy

Estimates of vaccine effectiveness in elderly�

StudyPeriod #ofsubjects Endpoint EffecBveness(%) Ref

1964‐1966 ReBrementcommunity

T°‐URTIhospitalis

38‐5550‐70

1

1968‐1969 ReBrementcommunity

ILI 50‐70ReducBoninseverityand

duraBonofdisease

2

1968‐1969 354 LCI 62 3

1991‐1992 1838 LCI 58 4

1.  Stuart et al. 1969 2.  Schoenbaum et al. 1969

3.  Edmonson et al. 1971 4.  Govaert et al. 1994

The studies above are (Randomized) Controlled Trials

RCTs are scarce and can no longer be performed since influenza vaccination is recommended for elderly people.

•  10 seasons, 713,872 person seasons of observation •  Avoiding season-to-season variability and misleading, incomplete picture

•  Estimate effectiveness of vaccine for the prevention of •  Hospitalization for pneumonia or influenza •  Death

Effectiveness of the influenza vaccine in reducing the risk of hospitalization for pneumonia or influenza (A) and death (B)�

The estimates of vaccine effectiveness were calculated as (1 – adjusted odds ratio) x 100. The bars indicate the 95% confidence intervals.

HP denotes Health Partners, OX Oxford Health Plans, and KP Kaiser Permanente.

In seasons 1992-1993 and 1997-1998 the antigenic match was suboptimal.

VE: 27%; OR: 0.73 (95 CI 0.68-0.77)

VE: 48%; OR: 0.52 (95 CI 0.50-0.55)

Nichol et al. NEJM 2007;357:1373-81

“… significant reduction in the risk of hospitalization for pneumonia or influenza, and risk for death among community dwelling elderly persons.”

Editorial conclusions accompanying Nichol 2007 study�

•  Overallconclusionsofthestudyaresound•  Supportsthestrategytovaccinateelderlyadultsinthecommunity

•  BeUervaccinesareneeded•  BeUeruptakeofvaccinesisneededinthosewhocareforthevulnerableelderly

Treanor. NEJM 2007;357:1439-411

Influenza vaccination of pregnant women�

•  DespiterecommendaBonofvaccinaBonforpregnantwomenbyACIP*andACOG*,thevaccinaBoncoveragerateofpregnantwomenisthelowestofallgroupsofadultsforwhomvaccinaBonisrecommended;e.g.14.4%in2004)

*ACIP:USAdvisoryCommiUeeonImmunizaBonPracBces*ACOG:AmericanCollegeofObstetriciansandGynecologists

LuPetal.InfluenzavaccinaBonofrecommendedadultpopulaBons,US,1989‐2005.Vaccine2008;26:1786‐1793.

Why is the influenza vaccine coverage rate in pregnant women low?�

•  Pregnantwomen,midwives,doctorsarenotadequatelyinformedabouttheincreasedrisksofinfluenzainfecBonsduringpregnancy.

•  InfluenzaisgenerallyconsideredasabenigninfecBon

•  ConcernaboutsafetyofvaccinesingeneralandinfluenzavaccinesinparBcular

•  AjtudetoavoidvaccinaBonduringpregnancy

Zaman et al. New Engl J Med 2008;359:1555-64

Influenza vaccination is beneficial for mother and infant�

Cumulative cases of laboratory-proven influenza in infants whose mothers received influenza vaccine (vs control)�

Zaman et al. New Engl J Med 2008;359:1555-64

When to vaccinate?�

•  InfluenzaacBvityisvariableandlargelyunpredictable•  Surveillancedatacanestablishcountry‐specificnorms•  YearlyinfluenzavaccinaBonshouldbegininOctober•  AimtoachievemaincoveragebyMid‐November,•  ButconBnuetovaccinatethroughoutthefluseason

Influenza-like illness (ILI) data collected by GP sentinel network in Belgium during 5 consecutive seasons showing the variation in time of start and peak.

The flu outbreak in season 2010-2011 lasted from Christmas 2010 (week 51) to the beginning of March 2011 (week 9). The intensity of the epidemic was moderate. The incidence rate was the highest among children.

Influenza vaccination recommendations�

Allpersonsaged≥6months ✓

Personsaged6to59months ✓*

Personsaged≥50years ✓* ✓ (65+)

Personswithchronicpulmonary,cardiovascular,renal,hepaBc,neurologic,hematologic,metabolicdisorders(diabetesmellitus)

✓* ✓

Personswhoareimmunosuppressed ✓* ✓

Personswhoareorwillbecomepregnantduringinfluenzaseason ✓* ✓

Aged6‐18monthsreceivingL‐Taspirintherapy ✓* ✓

ResidentsofnursinghomesorotherchronicfaciliBes ✓*

Morbidlyobesepersons(BMI≥40) ✓*

Healthcarepersonnel ✓* ✓(±)

Householdcontactsandcaregiversofchildren<5years(children<6months!!)

✓*

Householdcontactsandcaregiversofpersonsatrisk ✓*

* When vaccine supply is limited

Age‐based

•  Everybodyaboveadefinedagelimit•  Generallyallpersonsaged≥65years

Risk‐based

•  Everyoneundertheage‐definedlimitsufferingfromunderlying/chronicillnessess

•  PaBentswithcardiovascular,respiratory,renal,metabolicdiseaseorimmunocompromised

•  Pregnacy(morerecently)

Healthandsocialcareworkers•  RecommendedinseveralEUcountries

Recommendations in Europe�

WorldHealthOrganizaJon(resoluJon56.19ofMarch28,2003)

•  75%vaccinaBoncoverageby2010fortheelderly(≥65yearsofage)

EuropeanParliamentsupportedthiscall

•  EuropeanParliamentresoluBon[P6_TA(2005)0406]onthestrategyagainstaninfluenzapandemic,October26,2005.

WHO Vaccination objectives�

Influenza vaccine distribution in 56 countries,1997 and 2003 �

The Macroepidemiology of Influenza Vaccination (MIV) Study Group in Vaccine 2005;23:5133

Vaccination coverage rates in eleven European countries during two consecutive influenza seasons�

BlankP,SchwenkglenksM,SzucsT.

JournalofInfecBon2009;58:446‐58 �

Figure1.VaccinaBoncoverageratesingeneralpopulaBon

Figure2.VaccinaBoncoverageratesin

a)persons≥65ofagewithoutchroniccondiBons

b)persons<65ofagewithchroniccondiBons

c)persons≥65ofagewithchroniccondiBons

d)non‐targetgroupmembers

Figure3.VaccinaBoncoverageratesinchildren

Vaccine coverage rates in the general population�

Blank et al. J Inf 2009;58:446-458

Vaccine coverage rates in at-risk populations�

Blank et al. J Inf 2009;58:446-458

Vaccine coverage rates in children – by country�

Blank et al. J Inf 2009;58:446-458

Vaccine coverage rates in children – by age groups�

Blank et al. J Inf 2009;58:446-458

Summary of findings of the Blank et al. study�

•  Influenzacoverageratesrangedfrom9.5%to28.7%inthegeneralpopulaBon

•  YearonyearincreasesweresmallexceptforUKandFinland

•  Individualsaged≥65yearsshowedhighercoverageratesthatthegeneralpopulaBon

•  Rangingfrom13.9%inCzechRepublicto70.2inUK

•  CVRinelderlyadultsneedtoincreasetomeetWHOobjecBve

•  Coverageofat‐riskunder65isconsiderablylowerthanintheelderlyandneedstobeimproved

Summary of findings of the Blank et al. study�

•  VaccinaBoninchildrenshoweddifferencesbetweenseasonsandbetweencountries

•  LowestVCRofchildreninIreland(4.2%)vsGermany(19.2%)

•  MoredataonvaccinaBonofchildrenisneededtoincreaseinformaBonavailabletoHCP

•  HCPshouldproacBvelyrecommendvaccinaBontoat‐riskpopulaBons

•  BroadcommunicaBoncampaignstoeducatepubliconinfluenzaandthevaccine.

The first three reasons for and against vaccination in the general population (season 2007-2008)�

Blank et al. J Inf 2009;58:446-458

Most common reasons for receiving influenza vaccine (in order of importance)�

•  Doctor/nurseotherHCPrecommendedit

•  FluisaseriousillnessthatIdonotwanttoget•  WanttoavoidinfecBngmyfamily/friends

•  Becauseofmyage

•  BecauseIamnotingoodhealth

•  NaBonalrecommendaBonandreimbursement

•  TopreventmefrominterrupBngmyprofessionalacBvity

Common reasons for not receiving influenza vaccine �

•  IdonotthinkIamverylikelytocatchtheflu

•  Iamtooyoungtobevaccinated

•  Ihaveneverconsidereditbefore•  Myfamilydoctorneverrecommendedittome

•  Influenzaisnotaseriousenoughillness•  Iamconcernedaboutthepossiblesideeffects

How to improve vaccine uptake?�•  Increaseawarenessof

–  Severityofinfluenza(insomepopulaBons)–  BenefitsofvaccinaBon–  Safetyofvaccines–  Cost‐benefitraBo

•  InformaBoncampaignsfor–  Physicians,nurses,otherHCW–  Policymakers–  Generalpublic

•  Lowerthresholds–  Reimbursement–  EaseofaccessandadministraBon

Recommended Reading�

•  PrevenBonandcontrolofinfluenzawithvaccines–RecommendaBonsoftheAdvisoryCommiUeeonImmunizaBonPracBcesACIP),2010.MMWR2010;59–No.RR‐8

•  BridgesC.etal.InacBvatedinfluenzavaccines.In:Vaccines5thEd.Eds.Plotkin,Orenstein,Offit.Saunders‐Elsevier2008,pages259‐290

•  EffecBvenessofinfluenzavaccineinthecommunity‐dwellingelderly.Nicholetal.NEJM2007;357:1373‐81

•  VaccinaBoncoverageratesinelevenEuropeancountriesduringtwoconsecuBveinfluenzaseasons.BlankP,etal.JInf2009;59:446‐58.

•  ThemacroepidemiologyofinfluenzavaccinaBonin56countries,1997‐2003.ThemacroepidemiologyofinfluenzavaccinaBon(MIV)studygroup.Vaccine2005;23:5133‐43.