Influenza Vaccination

AnswertheFF:
1. What is within the pharmacist's scope of practice related to influenza immunization with
respect to assessing patient eligibility, risk and vaccine administration?
2. What are the different types of influenza vaccines available, how are they used, and what are their risks and
benefits? (e.g. intramuscular, intradermal, intranasal, live vs inactivated, etc.)
AppendixA:CharacteristicsofinfluenzavaccinesavailableforuseinCanada,20152016*
BGP
Manufacture
Pharma
rand
ULC
Product
(Abbott)
name
Influvac
GSK
Fluviral
Novartis
Agriflu
Novartis
Fluad
PediatricT
M
and
Fluad
AstraZeneca
Sanofi
Sanofi
FluMist
Pasteur Pasteur
Quadrivalen
Vaxigrip Fluzone
t
Vaccine
preparations
TIV
Vaccinetype
Inactivated
Inactivated Inactivated Inactivate Inactivate
surface Inactivated
Live
d
d
antigen
splitvirus
attenuated
subunit
subunit
splitvirus splitvirus
subunit
Routeof
IM
administration
Authorized
agesforuse
18years
TIV
IM
6months
TIV
IM
TIV
IM
Pediatric:
623
months
(lessthan
6months
2y)
TIV
IM
TIV
IM
LAIV
Intranasal
spray
6months 6months 259years
GSK
Flulaval
Tetra
Sanofi
Pasteur
Fluzone
Quadrivalen
t
QIV
QIV
Inactivated
splitvirus
Inactivated
splitvirus
IM
IM
6months
6months
Adult:
65years
106.57.5FFU
oflive
attenuated
15gHA 15gHA
reassortants 15gHA
15gHA
/0.5mL /0.5mL
/0.2mLdose /0.5mLdose /0.5mLdose
dose
dose
givenas0.1
mLineach
nostril
Antigen
15gHA
content(each /0.5mL
ofstrains)
dose
15gHA
/0.5mL
dose
15gHA
/0.5mL
dose
Pediatric:
7gHA
/0.25mL
dose
Adult:
15gHA
/0.5mL
dose
Adjuvant
No
No
MF59(oil
inwater
No
emulsion)
5mL
multidose
vial
5mL
multi
dosevial,
5mL
single
multidose
Singledose dose
vial,single
prefilled ampoule,
dosepre
syringes
single
filled
withouta dosepre
syringes
needle
filled
withouta
syringes
needle
withor
withouta
needle
Formats
available
No
Single
dosepre
filled
syringes
withluer
tip
No
No
No
5mL
multi
dosevial,
single
dose
Prefilled
5mL
ampoule,
singleuse
multidose
single
glasssprayer vial
dosepre
filled
syringes
withouta
needle
No
5mLmulti
dosevial,
singledose
vials,single
dosepre
filled
syringes
without
attached
needle
AppendixA:CharacteristicsofinfluenzavaccinesavailableforuseinCanada,20152016*
Manufacture
rand
Product
name
BGP
Pharma
ULC
(Abbott)
Influvac
Postpuncture
shelflifefor
n/a
mutlidose
vials
GSK
Fluviral
Novartis
Agriflu
Novartis
Fluad
PediatricT
M
and
Fluad
28days
28days
n/a
Yes
Yes
multidose No
vialsonly
AstraZeneca
Sanofi
Sanofi
FluMist
Pasteur Pasteur
Quadrivalen
Vaxigrip Fluzone
t
7days
28days
n/a
Yes
multi
dosevials
only
Yes
multi
No
dosevials
only
GSK
Flulaval
Tetra
28days
Uptoexpiry
dateindicated
onviallabel
Yes
Yesmulti
dosevials
only
None
None
Thime
rosal
No
Antibiotics
(traces)
Gentamici
None
n
Kanamyci
Kanamycin
n
Neomycin None
Neomycin
Neomycin
Other
clinically
relevantnon
medicinal
ingredients*
Eggprotein
atocopheryl
Egg
hydrogen
protein
succinate
Chicken
Polysorbate
protein
80
Formalde Formalde
hyde
hyde
CTAB
Ethanol
Polysorbat Sodium
e80
deoxycholat
e
Sucrose
Eggprotein
atocopheryl
Egg
hydrogen
Egg
Egg
Eggprotein
Egg
protein
succinate
protein
protein
Gelatin
protein
Formalde
Polysorbate
Formalde Formalde
hydrosylate
Formalde hyde
80
hyde
hyde
Sucrose
hyde
TritonX
Formaldehyd
Polysorbat Polysorbat
Arginine
TritonX 100
e
e80
e80
Monosodium
100
Gelatin
Ethanol
CTAB
CTAB
glutamate
Sucrose
Sodium
deoxycholate
Sucrose
Gentamicin
Sanofi
Pasteur
Fluzone
Quadrivalen
t
Eggprotein
Formaldehyd
e
TritonX100
Sucrose
VaccinePreparationsAvailableforUseinCanada
InactivatedInfluenzavaccines
TrivalentInactivatedInfluenzaVaccines:Unadjuvanted:IMadministered(TIV)
Vaccinescurrentlyavailableforuse
Agriflu(Novartis)
Fluviral(GlaxoSmithKline)
Fluzone(SanofiPasteur)
Influvac(BGPPharmaULC,Note:productsmaystillbelabeledAbbott)
Vaxigrip(SanofiPasteur)
EfficacyandEffectiveness
Multiplestudieshaveshownthatinfluenzavaccineisefficaciouswithhigherefficacydemonstratedagainstlaboratoryconfirmed
influenzathanclinicallydefinedoutcomesFootnote79.Inhealthychildren(equaltooryoungerthan16or18yearsold,dependingonthe
study),asystematicreviewandmetaanalysesshowedthattheefficacyofinfluenzavaccineagainstlaboratoryconfirmedinfluenza
rangedfrom59%to82%;similarly,a2013literaturereviewlookingatinfluenzavaccineeffectiveness,immunogenicityandsafetyin
healthy518yearoldsfoundthatvaccineefficacyagainstlaboratoryconfirmedinfluenzawasvariablebutmostfrequentlybetween65
85%Footnote80,Footnote81,Footnote82,Footnote83,Footnote84,Footnote85,Footnote86,Footnote87,Footnote88,Footnote89,Footnote90,Footnote91,Footnote92,Footnote93,Footnote94,Footnote95,Footnote96,
Footnote97 Footnote98
,
.Efficacyagainstserologicallyconfirmedinfluenzarangedfrom54%to63%andefficacyagainstclinicalillnessranged
between33%and36%Footnote99,Footnote100,Footnote101.Vaccineefficacyagainstinfluenzalikeillnesswasgenerallynotwelldemonstratedin
thestudiesincludedinthe2013literaturereviewinhealthychildren,althoughoneofthesixstudiesassessingthissuggestedvaccine
efficacyof6885%againstthisoutcomeFootnote81,Footnote82,Footnote84,Footnote88,Footnote92,Footnote102.
Inasystematicreviewofhealthyadults,inactivatedinfluenzavaccineefficacyagainstlaboratoryconfirmedinfluenzawasestimatedto
be80%(95%CI[56%,91%])andvaccineeffectivenessagainstinfluenzalikeillnesswasestimatedat30%(95%CI[17%,41%])when
thevaccinestrainmatchedthecirculatingstrainsandcirculationwashighFootnote99.Twootherstudiesfoundsomewhatlowervaccine
efficacyat55%(95%CI[41%,65%])inthe200607seasonFootnote103and68%(95%CI[46%,81%])inthe200708seasonFootnote104.
Vaccineefficacyof50%inhealthyadults(95%CI[27%,65%])hasbeenidentifiedduringselectseasonsofvaccinemismatch,although
mismatchisarelativetermandtheamountofcrossprotectionisexpectedtovary Footnote105,Footnote106,Footnote107.
Intheelderly,vaccineeffectivenessisabouthalfofthatinhealthyadultsandvariesdependingontheoutcomemeasuresandthestudy
populationFootnote108,Footnote109.Systematicreviewshavedemonstratedthattheinfluenzavaccinedecreasestheincidenceofpneumonia,
hospitaladmissionsanddeathsintheelderlyFootnote108andreducesexacerbationsinpersonswithchronicobstructivepulmonary
diseaseFootnote110.
Inobservationalstudies,immunizationhasbeenshowntoreducethenumberofphysicianvisits,hospitalizationsanddeathsinhighrisk
persons18to64yearsofageFootnote111,hospitalizationsforcardiacdiseaseandstrokeintheelderly Footnote112,andhospitalizationanddeaths
inpersonswithdiabetesmellitus18yearsofageandolderFootnote113.Observationalstudiesthatusenonspecificclinicaloutcomesandthat
donottakeintoaccountdifferencesinfunctionalstatusorhealthrelatedbehavioursshouldbeinterpretedwithcaution Footnote114,Footnote115,
Footnote116 Footnote117 Footnote118
,
,
.
Vaccineefficacymaybelowerincertainpopulations(e.g.,personswithimmunecompromisingconditions,elderlypersons)thanin
healthyadults.However,thepossibilityoflowerefficacyshouldnotprecludeimmunizationinthoseathighriskofinfluenzaassociated
morbidity,sincevaccinatedindividualsarestillmorelikelytobeprotectedcomparedtothosewhoareunvaccinated.
Ina2012systematicreviewandmetaanalysisconductedbyOsterholmetal.oninfluenzavaccineefficacyandeffectiveness,efficacyof
TIVinadultswasfoundtobelowerthanwasfoundinotherliteratureFootnote119.Theincludedstudiesin1864yearoldscoverednine
influenzaseasonsandhadarandomeffectspooledvaccineefficacyof59%(95%CI[51,67]).Theauthorsfoundnopapersthatmettheir
inclusioncriteriaforTIVefficacyinchildrenorinolderadults.Theseauthorsfoundvaccineeffectivenesswasvariableforseasonal
influenzawithsixof17analysesinninestudiesshowingsignificantprotectionagainstmedicallyattendedinfluenzaintheoutpatientor
inpatientsetting.Theauthorsconclusionsinthisreviewmaybesubjecttointerpretationbecauseoftherestrictiveinclusioncriteriathat
wereusedtoselectevidenceforthisreview.TheNACImethodologyusesbroaderinclusioncriteriaforavailableevidence,andthus,
interpretationofevidencemayvaryfromotherreviews.
NACIcontinuestoencouragehighqualityresearchoninfluenzavaccineefficacyandeffectivenessasitconstitutescriticalinformationto
makeinfluenzaimmunizationrecommendationsanddataarestilllackingonseveraltopicsofrelevance.
Immunogenicity
IntramuscularadministrationofTIVresultsintheproductionofcirculatingIgGantibodiestotheviralhaemagglutininandneuraminidase
proteins,aswellasamorelimitedcytotoxicTlymphocyteresponse.Bothhumoralandcellmediatedresponsesarethoughttoplayarole
inimmunitytoinfluenza.
Whilehumoralimmunityisthoughttoplayaprimaryroleinprotectionagainstinfection,cellmediatedimmunity,notablycytotoxicT
lymphocyteresponsestointernalviralcomponents,isincreasinglyinvokedasimportantinprotectingagainstsevereoutcomesof
influenza,particularlythoseassociatedwithsubtypeHAvariations(shiftanddrift)Footnote120.Repeatedannualadministrationofinfluenza
vaccinehasnotbeendemonstratedtoimpairtheimmuneresponseoftherecipienttoinfluenzavirus.
Considerationsrelatedtoimmunogenicitystudiesinthepaediatricpopulation
Somestudieshaveshowntheremaybeimmunogenicitydifferencesbetweeninfluenzavaccineproductsinyoungchildren Footnote71,Footnote
121 Footnote122 Footnote123
,
,
.However,theuseofa0.5mLvaccinedosegeneratedamorecomparableimmuneresponsethana0.25mLdosein
children<24monthsandinunprimedchildren.
Overall,theclinicalimplicationsofthesefindingsareunclearasvaccineeffectivenesswasnotstudiedandcouldbeunaffectedeven
whereimmunogenicityislower.Aswell,therearenoestablishedlicensingcriteriaforimmunogenicityinyoungchildrenasthereis
generallyinsufficientinformationonimmunityinthisagegroup.Allfourstudiesthatwerereviewedwithrespecttodiffering
immunologicresponsesbetweenproductsusedlicensingcriteriaforadults,whichhavenotsimilarlybeenproventocorrelatewith50%
efficacyinchildren.ItisimportanttonotethatNACIrecommendstheuseofa0.5mLdoseforallrecipientsoftheunadjuvanted
inactivatedinfluenzavaccine,includingyoungchildren,whichisthoughttomitigatethereducedimmuneresponseobservedinthe
studieswiththe0.25mLdose.Duetoinsufficientinformation,thereisnochangeinproductrecommendationsatthistimeandall
productsauthorizedforuseinthepaediatricpopulationcanbeusedforinfluenzaimmunizationofchildren.
Considerationsrelatedtotheelderlyandthosewithimmunecompromisingconditions
Althoughtheinitialantibodyresponseinelderlyrecipientsmaybelowertosomeinfluenzavaccinecomponentswhencomparedtothose
inotheragegroups,aliteraturereviewidentifiednoevidenceforasubsequentantibodydeclinethatwasanymorerapidintheelderly
thaninyoungeragegroupsFootnote124.
Influenzavaccinationcaninduceprotectiveantibodylevelsinasubstantialproportionofadultsandchildrenwithimmunecompromising
conditions,includingtransplantrecipients,thosewithproliferativediseasesofthehaematopoieticandlymphaticsystems,andHIV
infectedpatientsFootnote125,Footnote126,Footnote127,Footnote128.
Moststudieshaveshownthatadministrationofaseconddoseofinfluenzavaccineinthesameseasontoelderlyindividualsorother
individualswhomayhaveanalteredimmuneresponsedoesnotresultinaclinicallysignificantantibodyboost Footnote128,Footnote129,Footnote130,
,
.
Safety
HealthyadultsreceivingTIVshownoincreaseinthefrequencyoffeverorothersystemicsymptomscomparedwiththosereceiving
placebo.TIVissafeandwelltoleratedinhealthychildren.Mildinjectionsitereactions,primarilysorenessatthevaccinationsite,occur
in7%orlessofhealthychildrenwhoarelessthan3yearsofage.Postvaccinationfevermaybeobservedin12%orlessofimmunized
children1to5yearsofage.
QuadrivalentInactivatedInfluenzaVaccines:Unadjuvanted:IMadministered(QIV)
VaccinesCurrentlyAvailableforuse
FlulavalTetra(GlaxoSmithKline)
FluzoneQuadrivalent(SanofiPasteur)
InaLiteratureReviewonQuadrivalentInfluenzaVaccines
conductedbyNACI,todate,onlyonestudyhasmeasuredQIV
efficacy.Inthatstudy,vaccineeffectivenesswasestimatedat59%inchildren37yearsofage,incomparisontochildrenwhoreceived
hepatitisAvaccineFootnote133.Noliteraturewasfoundonheadtoheadefficacyoreffectivenessstudiesdirectlycomparingtrivalentand
quadrivalentformulations,foreitherinactivatedorliveattenuatedformulations.
Immunogenicity
Inthissamereviewoftheliterature,NACIreviewedtheimmunogenicitydataforQIVproducedbymanufacturerswhosupplied
influenzavaccineinCanadaatthetimeoftheliteraturereview:GlaxoSmithKline,AstraZenecaandSanofiPasteur.TheresultsofPhase
IIandIIItrialsthatcomparedtrivalentformulationstoquadrivalentformulationsgenerallyshowednoninferiorityofthequadrivalent
productsfortheH3N2,H1N1andBstraincontainedinthetrivalentformulations.Asexpected,thesestudiesshowedthattheimmune
responsetotheBstrainthatwasnotinthetrivalentformulationwasbetterinsubjectswhoreceivedthequadrivalentvaccine,which
containedit.Thesefindingswereconsistentacrossagegroupsanddifferenttypesoftrivalentvaccines(inactivatedandLAIV).
InsomeoftheunpublisheddatafrommanufacturersthatweresubmittedtoNACI,theH3N2orH1N1immuneresponseinQIV
recipientswasdifferentcomparedtoTIVrecipients.Forexample,inastudyin635montholdsbyonemanufacturer,theseroconversion
andseroprotectionratesforH1N1andH3N2weremuchhigherinQIVrecipientscomparedtoTIVrecipients.Ofnote,theQIVandTIV
productsinthisstudyweremanufacturedbydifferentprocesses.Inanotherstudy,byadifferentmanufacturer,inadults65yearsand
older,theH1N1seroconversionratewasstatisticallyinferiorinQIVrecipientscomparedtoTIVrecipients.TheH1N1GMTswere
slightlylowerintheQIVrecipientscomparedtotheTIVrecipients;howeverthisresultwasstatisticallynoninferior.Theseresultswere
notfurtherexplainedbytheinvestigators.Thenumberofpatientsinthesestudiesisrelativelysmallandtheclinicalsignificanceofthese
resultsisunknown.Aspreviouslymentioned,comparativevaccineefficacyandeffectivenessdataofTIVandQIVarenotavailable.
InthePhaseIIItrials,recipientsofthetrivalentformulationsshowed,toalesserdegree,someimmuneresponsetotheBstrainnot
containedinthetrivalentformulation.Inonestudyofadults,boththetrivalentandquadrivalentvaccinesmetallthecriteriaintheCHMPand
CBERguidelines,includingthoseforthestrainnotinthetrivalentvaccine.Inallotherstudies,thetrivalentvaccinefailedatleastoneofthe
criteriaforseroprotectionorseroconversionforthemissingBstrain.Ithasbeenhypothesizedthatthereissomelevelofcrossreactivitybetween
Bstrains.Thiscrossprotectionagainstinfectionwithonelineageprovidedbyimmunizationagainsttheotherlineageisuncertain,however,and
tisexpectedtobelowFootnote134.
Safety
TheQIVPhaseIIItrialsgenerallyshowedsimilarandexpectedratesofadverseeventsbetweenthetrivalentandquadrivalent
formulations.Mostofthesestudiesincludedalimitednumberofpatients.Asthequadrivalentformulationshaveahigherantigenic
contentthanthetrivalentvaccine,PhaseIVtrialsandpostmarketingsurveillancewillneedtomonitorwhetherincreasedreactogenicity
willbeaconcernforthequadrivalentvaccine.
TrivalentInactivatedInfluenzaVaccine:Adjuvanted:IMadministered(adjuvantedTIV)
Fluad(Novartis)
FluadPediatricTM(Novartis)
Fluad(Novartis)
AphaseIII,randomized,observerblindedstudycomparingthesafetyandimmunogenicityofaMF59adjuvantedinfluenzavaccinewith
unadjuvantedinfluenzavaccineinadults65yearsofagenotednosignificantdifferenceintheclinicaleffectivenessbetweenadjuvanted
andunadjuvantedTIVintermsofILIFootnote135.However,thisstudywasnotdesignedtoestimatevaccineeffectivenessagainstlaboratory
confirmedoutcomes.
AfewobservationalstudiessuggestthatFluadmaybeeffectiveatreducingtheriskofhospitalizationforinfluenzaanditscomplications
intheelderly,comparedtounvaccinatedindividualsandthosewhoreceivedunadjuvantedtrivalentinactivatedsubunitvaccine.
However,thesestudieshavesignificantmethodologicallimitationsthatmaketheirinterpretationdifficult Footnote65,Footnote136,Footnote137,Footnote
,
,
.
ACanadianobservationalstudyperformedinBritishColumbiabyVanBuynderetal.evaluatedthecomparativeeffectivenessofFluad
toTIVinreducinglaboratoryconfirmedinfluenzaintheelderlyFootnote141.Inthefirstyearofthestudy(20112012season),elderlypeople
inthreehealthauthoritieswereincludedinacommunitybasedcasecontrolstudy.Participantswereincludediftheywere65orolder,
hadILIandwereswabbedandtestedforinfluenza.Theparticipantsincludedelderlyinlongtermcare,aswellasindividualsinthe
community.Influenzatestingwascarriedoutaspartofroutineclinicalcare.Caseshadapositivetestforinfluenza,whereascontrolshad
negativetests.Thechoiceofproductwasdeterminedbyexternalfactorssuchasgeographiclocationandvaccineavailability,andthese
factorswerenotcontrolled.Therewereatotalof84casesand198controls,whichtheauthorsacknowledgedwasaverysmallsample
sizeandwasattributabletothelowlevelofinfluenzaactivityinthecommunitythatyear.Theresultsshowedthatinavarietyof
multivariateanalyses,Fluadeffectivenesswas58%(95%CI:582)andTIVeffectivenesswas24%(95%CI:129%to75%)(personal
communication,PVanBuynder,December2013).Thestudydidnotevaluateprotectionagainsthospitalization.Asthisstudycontinued
forasecondyear,furtherresultswillbediscussedoncepublished.Themethodologicallimitationsofthisstudyshouldbetakeninto
considerationwheninterpretingtheresults.
Immunogenicity
ThemechanismofactionofMF59isnotfullydeterminedandhasprimarilybeenstudiedusinginvitroandmousemodels.Fromthese
studies,itappearsthatMF59mayactdifferentlyfromaluminumbasedadjuvants.ThesestudiesshowthatMF59actsinthemusclefibres
tocreatealocalimmunestimulatoryenvironmentattheinjectionsiteFootnote142.MF59allowsforanincreasedinfluxofphagocytes(e.g.,
macrophagesandmonocytes)tothesiteofinjection.TherecruitedphagocytesarefurtherstimulatedbyMF59,therebyincreasingthe
productionofchemokinestoattractmoreinnateimmunecellsandinducingdifferentiationofmonocytesintodendriticcells Footnote143,Footnote
144
.MF59furtherfacilitatestheinternalizationofantigenbythesedendriticcells Footnote144,Footnote145.Theoverallhighernumberofcells
availablelocallyincreasesthelikelihoodofinteractionbetweenanantigenpresentingcellandtheantigen,leadingtomoreefficient
transportofantigentothelymphnodes,withresultingimprovedTcellprimingFootnote144.
ThereisevidencefromrandomizedcontrolledtrialsthatFluadinduceshigherimmunogenicityandbroadercrossreactivityinadults65
yearsofageandolderascomparedtotheunadjuvantedsubunitvaccines.IntherecentFreyetal(2014)study,adjuvantedsubunitTIV
elicitedasignificantlyhigherantibodyresponsethanunadjuvantedsubunitTIV,especiallyagainstA/H3N2,althoughsuperioritybypre
definedcriteriawasnotformallymetFootnote135.Similarbutlessconsistentresultshavebeenshownintermsofimprovementinantibody
responserelativetosplitvirusvaccine,whichisthetypeofinfluenzavaccineusedmostofteninCanada.Thestudieswhichcompare
FluadtosplitvirusvaccinegenerallycomparedittoavaccinecalledMutagrip ,whichisnotavailableinCanada.Theonestudythat
comparedFluadtoVaxigripfoundsimilarseroprotectionandseroconversionratesforH3N2andahigherimmuneresponseforH1N1
andBforFluadrecipients<75yearsofageFootnote146.Forthose75yearsofageandolder,higherseroprotectionandseroconversionrates
werenotedforallthreestrainsinthosereceivingFluad.InarandomizedclinicaltrialcomparingIntanza(intradermalTIV)toFluadin
participantsaged65yearsandolder,noninferiorityoftheintradermalvaccinecomparedwiththeadjuvantedvaccinewasdemonstrated
fortheA/H1N1andBstrainswiththehaemagglutinationinhibitionassay(HAI)methodandforallthreestrainswiththesingleradial
haemolysis(SRH)methodFootnote147.
ACanadianstudyconductedbythePublicHealthAgencyofCanada/CIHRInfluenzaResearchNetwork(PCIRN)lookedatthe
immunogenicityofFluad(AdjuvantedTrivalentInactivatedVaccine:ATIV),Intanza15(TIVID)andAgriflu(subunitTIV)in
ambulatoryseniors(65years)livinginthecommunityFootnote143.Thisrandomizedcontrolledstudycomprised911participants.FortheB
strain(Brisbane),thebaselineantibodytitresweretoohighformeaningfulresponseassessmentspostimmunization.ForH1N1,
seroprotectionratesweresignificantlyhigherafterATIVthanaftertheothervaccineswhenmeasuredbyHAI,butnotbySRH.For
H3N2,seroprotectionratesweresignificantlyhigherafterATIVthanafterothervaccinesbybothHAIandSRH,whileratesdidnot
differsignificantlybetweenTIVIDandthesubunitTIV.Inthemicroneutralization(MN)assay,titers40toH3N2wereachievedmore
frequentlyafterATIVthanaftertheothervaccines.GMTswerehighestafterATIVforbothAviruses.Whenimmuneresponseswere
comparedusingcriteriaforlicensinginfluenzavaccinesinseniors,all3vaccinesmettheseroprotectioncriterionforeachvirus(both
HAIandSRHassays).ByHAI,ATIVandTIVIDmettheseroconversionandGMfoldincreasecriteriafortheAviruses.TIVdidnot
meettheseroconversioncriterionforH3N2.BySRHassay,theGMfoldincreasecriterionwasnotmetforanyvirusafterTIVIDorTIV
butitwasmetfortheAvirusesafterATIV.Whilestatisticallysignificant,thedifferencesinseroprotectionratesandGMTratiosafter
ATIVorTIVwereofmodestmagnitude.Whetherthiswouldresultingreaterprotectionagainstinfectionisnotyetcertain.
Sixmonthsaftervaccination,residualseroprotectionratestotheAvirusesdidnotdiffersignificantlyamongthe3groups,butonlyATIV
recipientshadratesover60%foreachvirus,meetinginternationalimmunogenicitycriteria.
Theimplicationoftheseimmunogenicityfindingswithregardtoclinicalefficacyisunknownandrequiresfurtherstudy.
Safety
MF59adjuvantedTIVproducesinjectionsitereactions(pain,erythemaandinduration)significantlymorefrequentlythanunadjuvanted
vaccines,buttheyareclassifiedasmildandtransient.Systemicreactions(myalgia,headache,fatigueandmalaise)arecomparableor
morefrequentwithFluadcomparedtounadjuvantedvaccinesandareratedasmildtomoderateandtransient.
FluadPediatricTM(Novartis)
InaLiteratureReviewonPediatricFluadInfluenzaVaccineUseinChildren672MonthsofAgeconductedbyNACI,onlyasingle
efficacytrialofATIVinchildrenaged6to<72monthswasidentifiedFootnote148.However,therewereseveralconsiderationsregardingthe
applicabilityofthistrial.Firstly,theEuropeanMedicinesAgencyidentifiedanumberofcriticalissuesrelatedtotrialmanagement,
qualityofdata,anddatahandlingforthisstudyatsomeofthetrialsitesduringaGoodClinicalPracticeinspectionconductedaspartof
theauthorizationprocessinEuropeFootnote149.Asevidencedintheproductmonograph,efficacydatafromtheefficacytrial,although
available,werenotconsideredingrantingproductauthorizationinCanada.
Secondly,theunadjuvantedTIVcomparatorinthistrialwasshown,inanunrelatedstudy,togeneratealowerimmuneresponse
comparedtoanotherunadjuvantedTIVproductduringthe2006/07seasonFootnote122,Footnote150.Itisnotclearwhatimplicationthishason
clinicalprotection.Finally,thestudyadministered0.25mLdosesofthecomparatorvaccineforchildren<36months,whichislowerthan
thedoseof0.5mLofunadjuvantedinfluenzavaccinethatisrecommendedforthisagegroupinCanada.
Areanalysiswasconductedexcludingtheaffectedtrialsites,andtherewasnonotablechangefromtheoriginalfindings Footnote151.After
reviewingthisinformation,NACIcontinuestobelievethattheconcernswiththetrialidentifiedaboveshouldbetakenintoaccountwhen
assessingtheresultsofthestudy.
Immunogenicity
Inchildren,thereislimitedbutconsistentevidencethatATIVismoreimmunogenicthancomparableunadjuvantedTIVsagainst
influenzaAtypesFootnote148,Footnote152,Footnote153,Footnote154,Footnote155,Footnote156.Inparticular,asingledoseofATIVismoreimmunogenicthana
singledoseofunadjuvantedTIV.However,twodosesofATIVarestillnecessarytoachieveasatisfactoryimmuneresponseagainst
influenzaB.
AlmostallofthestudiesincludedinLiteratureReviewonPediatricFluadInfluenzaVaccineUseinChildren672MonthsofAgeused
vaccineformulationsof0.25mLinchildren635monthsofage,bothfortheadjuvantedvaccineandthecomparatorunadjuvanted
influenzavaccine.OnestudyemployedadoserangingfactorialdesigncomparingadjuvantedandunadjuvantedversionsofseasonalTIV
andQIVadministeredtochildren636monthsoldFootnote154.Immunogenicitydatawaspresentedfor0.25mLATIV(n=27)and0.5mL
unadjuvantedTIVorQIV,reportedjointlyasasinglegroup(n=50).The0.25mLATIVgeneratedabetterimmuneresponseafterthe
firstandseconddosewhencomparedtothefirstandseconddoseofunadjuvanted0.5mLTIV/QIV.Additionaldataprovidedbythe
authorsseparatingunadjuvantedTIV(n=22)andQIV(n=28),showedasimilarorbetterimmuneresponseforQIVcomparedtoTIV.It
shouldbenotedthatparticipantsreceivingATIVwere,onaverage,olderthanthoseintheunadjuvantedTIVandQIVgroups(whichmay
leadtoanenhancedimmuneresponse)andthefindingsarebasedonsmallsamplesizes.
NACIrecommends0.5mLdosageofunadjuvantedTIVorQIVinallagegroups.WhilethereissomeindicationofhowATIVat0.25
mLdosewouldcomparetounadjuvantedTIVorQIVat0.5mLdoseimmunologicallyinthe6to<24monthagegroup,itisunclear
whetherthestrongerhumoralimmuneresponseinducedbyATIVinonetrialwithaverylimitednumberofparticipantstranslatesintoan
appreciableadvantageintermsofpreventinginfluenzaoritscomplications.
Safety
ThesafetydatainchildrenareconsistentwithwhatisknownaboutATIVssafetyprofileinadults.Inthepaediatrictrials,ATIVwas
morereactogenicthanunadjuvantedTIV,withrecipientsexperiencing1015%moresolicitedlocalandsystemicreactions Footnote157.
However,mostreactionsweremildandresolvedquickly.
Therearecurrentlynodataontheeffectsoflongtermorrepeatedadministrationofadjuvantedinfluenzavaccinesinchildren.Themost
significantexperiencewithanadjuvantedinfluenzavaccineinchildrenwastheAS03adjuvantedH1N1pandemicthathasbeen
associatedwithanincreasedriskofnarcolepsy.AstudypublishedinDecember2014comparingtwoadjuvantedH1N1vaccineproducts
hassuggestedthattheunderlyingimmunemediatedmechanismmaynotbeinitiatedbytheadjuvant,butbyanothercomponentofthe
vaccine,specificallytheH1N1viralantigenFootnote158.However,thepandemicvaccinewasasinglestrainadjuvantedvaccineadministered
onlyduringoneseason,anditisunknownwhateffectsamultistrainadjuvantedvaccineoranadjuvantedvaccineadministeredformore
thanoneseasonmayhaveinyoungchildren.
OnestudyemployedadoserangingfactorialdesignandincludedbothadjuvantedandunadjuvantedversionsofseasonalTIVandQIV
administeredtochildren636monthsoldFootnote154.Overall,therewasnoindicationofanincreasingriskofadverseeventsassociatedwith
increasingMF59dose,antigendose,ortheadditionofasecondBstrain.However,reactogenicityof15gformulationswereslightly
higherforbothadjuvantedandunadjuvantedvaccinescomparedtothe7.5gformulations.
LiveAttenuatedInfluenzaVaccine(LAIV)
FlumistQuadrivalent(AstraZeneca)liveattenuatedvaccine
Note:Thestatementhasbeenupdatedtoreflectthattheevidencesupportingtheuseofliveattenuatedinfluenzavaccineswasbasedon
thetrivalentformulation.Basedonexpertopinion,thecomparativeefficacydatawhichsupportedthepreferentialrecommendationsfor
thetrivalentformulationofLAIVarealsoapplicabletothequadrivalentformulationofLAIVbecausethemanufacturingprocessesand
immunologicmechanismofthequadrivalentLAIVandthetrivalentLAIVproductsarethesame.Thisexpertopinionissupportedbythe
resultsofthenoninferioritystudiescomparingtrivalentandquadrivalentformulationsofLAIV,whichwererequiredbyregulatory
bodiestoauthorizetheuseoftheQLAIVformulation.ComparativevaccineefficacyandeffectivenessdataofTIVorQIV,andthe
quadrivalentformulationofLAIVarenotavailable.
Anumberofstudies(LAIVversusplaceboandLAIVversusTIV)havebeenconductedinchildrenandadults.Twostudieshavedirectly
comparedtheefficacyofLAIVandTIVinyoungerchildren(uptoage5and6)andonestudyhascomparedtheefficacyofLAIVin
asthmaticchildren6to17yearsofageFootnote74,Footnote75,Footnote76.NACIrecognizesthattherearedifferencesinlevelsofevidencefor
youngerandolderchildren.ThereismoreevidencethatdirectlycomparesTIVandLAIVefficacyandthatshowssuperiorefficacyof
LAIVinchildrenyoungerthan6yearsofagethaninolderchildren.Also,forchildrenunder6yearsofage,theevidenceforthe
superiorityofLAIVisofhigherqualityandtheestimateofefficacyishighercomparedtothestudyperformedonchildren6to17years
old.Incontrasttochildren,mostcomparativestudiesinpersons18to59yearsofagehavefoundthatLAIVandTIVhadsimilarefficacy
orthatTIVwasmoreefficaciousFootnote64.FurtherdetailsregardingtherecommendationrationaleforLAIVarefoundinsectionIV.
ComparativevaccineefficacyandeffectivenessdataofTIVorQIV,andthequadrivalentformulationofLAIVarenotavailable.
ReducedeffectivenessofLAIV(quadrivalentformulation)inchildren,overallandcomparedtoinactivatedvaccines,wasreportedduring
the201314influenzaseasonintheUSagainstinfluenzaA(H1N1).Investigationsbythemanufacturerhavedeterminedthatthisreduced
effectivenessismostlikelyattributabletoreducedstabilityofthehemagglutininstalksequencefortheA/CaliforniaH1N1vaccinestrain.
Thermalstabilitytestshaveshownthatthereducedstabilitylikelyresultedinstraindegradationwhenexperiencingdeviationsin
temperatureduringstorageortransport.ThemanufacturerhasindicatedthattheA/CaliforniaH1N1strainusedinthisLAIVformulation
willbereplacedinthe2015/16influenzaseasonwithamorethermalstablestrain.Undocumenteddeviationsintemperatureduring
storageortransportfromthemanufacturertotheprovincialandterritorialdepotsareunlikelytooccurinCanadaas,bycontract,the
contractor,(i.e.,manufacturer)isrequiredtomaintaintherequiredtemperaturesthroughouttransportfromthecontractortotheidentified
users(i.e.,provincialandterritorialdepots)andprovideevidencetothateffectfromthedataanalysisofthetemperaturemonitoring
deviceorcarrierlogs,asapplicable.
BasedoninformationfromtheCanadianSentinelInfluenzaVaccineEffectivenessSurveillanceNetwork,asimilarproblemwasnotseen
inCanadawiththetrivalentLAIV,butthisobservationmustbeinterpretedwithcautionduetothesmallnumberofLAIVrecipients
availableforanalysis.ThisissuecontinuestobemonitoredbyNACI.
NACIhasreviewedtheavailableinformationonthisissue,includingCanadiandata,andcontinuestorecommendpreferentialuseof
LAIVinchildren(seeSectionIV.ChoiceofProduct).LAIVwillcontinuetobemonitoredtoassesswhethertheissueswithlowvaccine
effectivenesshavebeenfullyaddressedwiththeproposedchangetothevaccinestrain.
Immunogenicity
LAIV(FluMistQuadrivalent),whichisadministeredbytheintranasalroute,isthoughttoresultinanimmuneresponsethatmimicsthat
inducedbynaturalinfectionwithwildtypeviruses,withthedevelopmentofbothmucosalandsystemicimmunity.Localmucosal
antibodiesprotecttheupperrespiratorytractandmaybemoreimportantforprotectionthanserumantibody.
StudieshavedemonstratedthatthepresenceofanHAIantibodyresponseaftertheadministrationoftrivalentLAIVispredictiveof
protection.However,efficacystudieshaveshownprotectionintheabsenceofasignificantantibodyresponseFootnote64.Inthesestudies,
LAIVhasgenerallybeenshowntobeequally,ifnotmoreimmunogenic,thanTIVforallthreestrainsinchildren,whereasTIVwas
typicallymoreimmunogenicinadultsthanLAIV.GreaterratesofseroconversiontoLAIVoccurredinbaselineseronegativeindividuals
comparedtobaselineseropositiveindividualsinbothchildandadultpopulations,becausepreexistingimmunitymayinterferewith
responsetoalivevaccine.ForfurtherdetailsconsulttherationalebelowandtheNACIsupplementalstatementforFluMist
.
ThequadrivalentformulationofLAIVhasshownnoninferioritycomparedtothetrivalentformulationinbothchildrenandadults.The
immuneresponsetotheBstrainfoundonlyinthequadrivalentformulationwasbetterinchildrenwhoreceivedthequadrivalent
vaccineFootnote159,Footnote160,Footnote161.
Safety
ThemostcommonadverseeventsexperiencedbyrecipientsoftrivalentLAIVarenasalcongestionandrunnynose,whicharealso
expectedforquadrivalentformulation.Inalargeefficacytrial,wheezingoccurredinrecipientsoftrivalentLAIVvaccineatratesabove
thoseinTIVrecipientsonlyinchildren<24monthsofageFootnote64.Thisisexpectedtobethesameforrecipientsofthequadrivalent
LAIV.
StudiesonthetrivalentformulationofFluMisthaveshownthatvaccineviruscanberecoveredbynasalswabinchildrenandadults
followingvaccination(i.e.,shedding).Thefrequencyofsheddingdecreaseswithincreasingageandtimesincevaccination.Sheddingis
generallybelowthelevelsneededtotransmitinfection,althoughinrareinstances,shedvaccinevirusescanbetransmittedfromvaccine
recipientstounvaccinatedpersons.FormoredetailedinformationonLAIVandviralshedding,consulttheNACIsupplementalstatement
forFluMist.
3. Which patients should receive influenza vaccination, how effective is vaccination, and what are the benefits of
vaccination?
RecommendationsforUse
RecommendedRecipientsofInfluenzaVaccine
Influenzavaccineisrecommendedforeveryone6monthsofageandolderwithoutcontraindications.Toreducethemorbidityand
mortalityassociatedwithinfluenza,immunizationprogramsshouldfocusonthoseathighriskofinfluenzarelatedcomplications,
includingallpregnantwomen,thosecapableoftransmittinginfluenzatoindividualsathighriskofcomplicationsandothersasidentified
inList1.AdditionaldetailregardingtherecipientsidentifiedinList1,includingpregnantwomen,canbefoundinSectionIIIofthe
statement.
List1:Influenzavaccinationisparticularlyrecommendedforthefollowinggroups:
Peopleathighriskofinfluenzarelatedcomplicationsorhospitalization
Adults,includingpregnantwomen,andchildrenwiththefollowingchronichealthconditions:
o cardiacorpulmonarydisorders(includingbronchopulmonarydysplasia,cysticfibrosisandasthma);
o diabetesmellitusandothermetabolicdiseases;
o cancer,immunecompromisingconditions(duetounderlyingdisease,therapyorboth);
o renaldisease;
o anemiaorhemoglobinopathy;
o conditionsthatcompromisethemanagementofrespiratorysecretionsandareassociatedwithanincreasedriskof
aspiration;
o morbidobesity(BMI40);
o Childrenandadolescents(age6monthsto18years)withthefollowingconditions:
neurologicorneurodevelopmentconditions(includingseizuredisorders,febrileseizuresandisolated
developmentaldelay);
undergoingtreatmentforlongperiodswithacetylsalicylicacid,becauseofthepotentialincreaseofReyes
syndromeassociatedwithinfluenza.
Peopleofanyagewhoareresidentsofnursinghomesandotherchroniccarefacilities.
People65yearsofage.
Allchildren6to59monthsofage.
Healthypregnantwomen(theriskofinfluenzarelatedhospitalizationincreaseswithlengthofgestation,i.e.,itishigherinthe
thirdthaninthesecondtrimester).
AboriginalPeoples.
Peoplecapableoftransmittinginfluenzatothoseathighrisk
Healthcareandothercareprovidersinfacilitiesandcommunitysettingswho,throughtheiractivities,arecapableof
transmittinginfluenzatothoseathighriskofinfluenzacomplications.
Householdcontacts(adultsandchildren)ofindividualsathighriskofinfluenzarelatedcomplications(whetherornotthe
individualathighriskhasbeenimmunized):
o householdcontactsofindividualsathighrisk,aslistedinthesectionabove;
o householdcontactsofinfants<6monthsofageastheseinfantsareathighriskofcomplicationsfrominfluenzabut
cannotreceiveinfluenzavaccine;
o membersofahouseholdexpectinganewbornduringtheinfluenzaseason.
Thoseprovidingregularchildcaretochildren59monthsofage,whetherinoroutofthehome.
Thosewhoprovideserviceswithinclosedorrelativelyclosedsettingstopersonsathighrisk(e.g.,crewonaship).
Others:
Peoplewhoprovideessentialcommunityservices.
Peopleindirectcontactduringcullingoperationswithpoultryinfectedwithavianinfluenza.
InadditiontotherecipientsidentifiedinList1,influenzavaccineisalsorecommendedfor:
HealthyIndividualsages564yearsofage
RecentliteraturereviewsconductedbyNACIhaveshownthathealthyindividualsaged5to64yearsbenefitfrominfluenzavaccination.
DetailedinformationregardingthesereviewscanbefoundintheStatementonSeasonalInfluenzaVaccinefor20142015andineachof
therelevantliteraturereviews,availableviatheNACIwebsite.
Travellers
Influenzaoccursyearroundinthetropics.Intemperatenorthernandsoutherncountries,influenzaactivitypeaksgenerallyduringthe
winterseason(NovembertoMarchintheNorthernHemisphereandApriltoOctoberintheSouthernHemisphere).Influenzavaccination
isrecommendedforallindividuals,includingtravellers,aged6monthsandolder,withparticularfocusonpeopleathighriskof
influenzarelatedcomplicationsorhospitalization,peoplecapableoftransmittinginfluenzatothoseathighrisk,andothersasindicatedin
List1.
VaccinespreparedspecificallyforuseintheSouthernHemispherearenotavailableinCanada,andtheextenttowhichrecommended
vaccinecomponentsfortheSouthernHemispheremayoverlapwiththoseinavailableCanadianformulationswillvary.Adecisionforor
againstrevaccination(i.e.,boosting)oftravellerstotheSouthernHemispherebetweenAprilandOctober,iftheyhadalreadybeen
vaccinatedintheprecedingfallorwinterwiththeNorthernHemispheresvaccine,dependsonindividualriskassessment,thesimilarity
ordifferencesbetweentheNorthernandSouthernhemispheresvaccines,andtheavailabilityofareliableandsafevaccineatthe
traveller'sdestination.RefertoImmunizationofTravellersintheCanadianImmunizationGuideforadditionalgeneralinformation.
4. Who should not receive influenza immunization, and what are the contraindications to
vaccination/for the different formulations? Is having a "sensitivity" to eggs a
contraindication to influenza immunization?
E.g. can the flu shot cause the flu?
AdditionalVaccineSafetyConsiderations
Influenzavaccineissafeandwelltolerated.Contraindications,precautionsandcommonadverseeventsaredescribedinSectionII.
AdditionalinformationregardingeggallergicindividualsandGBSisprovidedbelow.
EggAllergicIndividuals
Regardingadministrationofinfluenzavaccinetoeggallergicpersons,aftercarefulreview,NACIhasconcludedthateggallergic
individualsmaybevaccinatedagainstinfluenzausingTIVwithoutpriorinfluenzavaccineskintestandwiththefulldose,irrespectiveof
apastseverereactiontoeggandwithoutanyparticularconsideration,includingimmunizationsetting.Basedonexpertopinion,informed
bytheunderstandingthatQIVmanufacturingprocessesaresimilartothoseofTIVandbyinformationregardingtheeggalbumincontent
ofthecurrentvaccines,similarrecommendationshavebeenmadeforQIV.Waitingperiodpostimmunizationwouldbeasrecommended
intheCanadianImmunizationGuide.Aswithallvaccineadministration,immunizersshouldhavethenecessaryequipmentandbe
preparedtorespondtoavaccineemergencyatalltimes.
SupportingthischangeinrecommendationisworkdonebyDesRochesetal.(2012)Footnote167andGreenhawtetal.(2012)Footnote168.
DesRochesetal.conductedtwostudies,aprospectivecohortstudy(2010/2011and2011/2012fluseasons)in5Canadianhospitals,anda
retrospectivecohortstudy(2007/2008,2008/2009and2009/2010fluseasons)basedoutofoneCanadianhospital.Recruitmentincluded
patientswitheggallergy,includingsevereallergydefinedastheoccurrenceofanaphylaxisorcardiorespiratorysymptomsuponegg
ingestion.Forbothstudies,patientswereexaminedimmediatelybeforevaccinationwithFluviral andremainedunderobservationfor60
minutespostvaccinationbeforebeingreexamined.Overthe5influenzaseasons,457dosesoftheseasonalTIVwereadministeredto
367patients,amongwhom132(153doses)hadahistoryofsevereeggallergy.Fourpatientsreportedmildallergiclikesymptomsafter
previousinfluenzavaccination(1urticaria,2vomiting,and1eczema),butnoneexperiencedanadverseeventwhengiventhecurrent
vaccine.While13patientsdevelopedmildallergiclikesymptomsinthe24hoursfollowingvaccination,noneofthe367patients
developedanaphylaxis.
DesRochesetal.alsoconductedaliteraturereviewoneggallergicpatientswhohadbeenvaccinated.Atotalof26studieswerefound,
representing4729dosesofinfluenzavaccineadministeredto4172patientswitheggallergy,ofwhich513patientshadbeenidentifiedas
havingsevereeggallergy.Noneofthe4172patientsexperiencedanaphylaxispostinfluenzaimmunization.Forthe597doses
administeredtothe513patientswithahistoryofsevereallergicreactiontoegg,the95%CIoftheriskofanaphylaxiswas0%to
0.62%Footnote167.Greenhawtetal.(2012),usinginclusioncriteriaofahistoryofaseverereaction,includinganaphylaxis,totheingestionof
eggandapositiveskintestresultorevidenceofserumspecificIgEantibodytoegg,conducteda2phasemulticentrestudyinwhich
phase1consistedofarandomized,prospective,doubleblind,placebocontroltrialofTIVtoeggallergicchildren,usinga2step
approachinwhichgroupAreceived0.1mLofinfluenzavaccine,followedin30minutesiftherewasnoreaction,withtheremainderof
anageappropriatedose.GroupB,bycontrast,receivedaninjectionofnormalsalinefollowedin30minutesiftherewasnoreactionwith
thefull100%oftheageappropriatedose.PhaseIIwasaretrospectiveanalysisofsingledoseversusdivideddosesadministrationofTIV
ineligiblestudyparticipantswhodeclinedparticipationintheRCT.AllparticipantsinbothphasesreceivedTIVwithoutdevelopingan
allergicreactionFootnote168.
DataarenotcurrentlyavailabletosupportthisrecommendationforLAIV
5. What are the risks of influenza immunization? Be prepared to explain common and rare side effects and safety
concerns/myths.
VaccineSafetyandAdverseEvents
DatafrompostmarketingsurveillanceofinfluenzavaccinesinCanada(CAEFISS)haveshownseasonalinfluenzavaccinestohavea
safeandstableAdverseEventsFollowingImmunization(AEFI)profilewithnounexpectedevents.
AllinfluenzavaccinescurrentlyauthorizedforuseinCanadaareconsideredsafeforuseinpersonswithlatexallergies.Themultidose
formulationsofinactivatedinfluenzavaccinethatareauthorizedforuseinCanadacontainminutequantitiesofthimerosal,whichisused
asapreservativeFootnote18,Footnote19.Largecohortstudiesofhealthdatabaseshavedemonstratedthatthereisnoassociationbetween
childhoodvaccinationwiththimerosalcontainingvaccinesandneurodevelopmentaloutcomes,includingautisticspectrumdisorders Footnote
20
.Despitetheabsenceofdataindicatinganyassociatedrisk,influenzavaccinemanufacturersinCanadaarecurrentlyworkingtowards
productionandmarketingofthimerosalfreeinfluenzavaccines.AllsingledoseformulationsofinactivatedvaccineandLAIVare
thimerosalfree.RefertoVaccineSafetyPart2oftheCanadianImmunizationGuideforadditionalinformation.
CommonAdverseEvents
WithIMadministeredinfluenzavaccines,injectionsitereactionsarecommonbutaregenerallyclassifiedasmildandtransient.
AdjuvantedTIVtendstoproducemoreextensiveinjectionsitereactionsthannonadjuvantedTIV,butthesereactionsarealsogenerally
mildandresolvespontaneouslywithinafewdays.ThemostcommonadverseeventsexperiencedbyrecipientsoftrivalentLAIVare
nasalcongestionandrunnynose,whicharealsoexpectedforthequadrivalentformulation.Additionalinformationcanbefoundinthe
relevantsubsectionsofSectionVoftheStatement.
LessCommonandSeriousorSevereAdverseEvents
Seriousadverseeventsarerarefollowingimmunizationandinmostcases,dataareinsufficienttodetermineacausalassociation.Allergic
responsestoinfluenzavaccinearearareconsequenceofhypersensitivitytosomevaccinecomponents.RefertoContraindicationsand
Precautionsbelowforadditionalinformation.
OtherReportedAdverseEventsandConditions
GuillainBarrSyndrome(GBS)
RecentstudiessuggestthattheabsoluteriskofGBSintheperiodfollowingseasonalandA(H1N1)pdm09influenzavaccinationisabout
oneexcesscaseper1millionvaccinesandthattheriskofGBSassociatedwithinfluenzainfectionislargerthanthatassociatedwith
influenzavaccination.AdditionalinformationregardingGBSisfoundinSectionV.
Oculorespiratorysyndrome(ORS)
Oculorespiratorysyndrome(ORS),whichisdefinedasthepresenceofbilateralredeyesplusoneormorerespiratorysymptoms(cough,
wheeze,chesttightness,difficultybreathing,difficultyswallowing,hoarsenessorsorethroat)thatstartswithin24hoursofvaccination,
withorwithoutfacialoedema,wasfoundduringthe20002001influenzaseason;fewcaseshavebeenreportedsincethen.ORSisnot
consideredtobeanallergicresponse.
PersonswhohavearecurrenceofORSuponrevaccinationdonotnecessarilyexperiencefurtherepisodeswithfuturevaccinations.Data
onclinicallysignificantadverseeventsdonotsupportthepreferenceofonevaccineproductoveranotherwhenrevaccinatingthosewho
havepreviouslyexperiencedORS.RefertoContraindicationsandPrecautionsbelowforadditionalinformation.
GuidanceonReportingAdverseEventsFollowingImmunization(AEFI)
ToensuretheongoingsafetyofinfluenzavaccinesinCanada,reportingofAEFIsbyvaccineprovidersandothercliniciansiscritical,and
insomejurisdictions,reportingismandatoryunderthelaw.
Vaccineprovidersareaskedtoreportthroughlocalpublichealthofficialsanyseriousorunexpectedadverseeventfelttobetemporally
relatedtovaccination.AnunexpectedAEFIisaneventthatisnotlistedinavailableproductinformationbutmaybeduetothe
immunization,orachangeinthefrequencyofaknownAEFI.ThefollowingAEFIsareofparticularinterest:
ORS
GBSwithin6weeksfollowingimmunization
RefertoVaccineSafetyinPart2oftheCanadianImmunizationGuide,thenationalAdverseEventsFollowingImmunizationReport
FormandtheUserGuidetotheCompletionandSubmissionoftheAEFIReportsforadditionalinformationaboutAEFIreporting.
ContraindicationsandPrecautions
Contraindications
Influenzavaccineshouldnotbegivento:
peoplewhohavehadananaphylacticreactiontoapreviousdose;or
peoplewhohavehadananaphylacticreactiontoanyofthevaccinecomponents,withtheexceptionofegg(RefertoSectionV
Additionalvaccinesafetyconsiderations).
RefertoContentsofImmunizingAgentsAvailableforUseinCanadainPart1oftheCanadianImmunizationGuideforalistofall
vaccinesauthorizedforuseinCanadaandtheircontentsandtoVaccineSafetyinPart2oftheCanadianImmunizationGuidefor
informationregardingthemanagementofadverseevents,includinganaphylaxis.
AdditionalLAIVSpecificcontraindicationsandprecautions
LAIViscontraindicatedfor:
Childrenlessthan24monthsofage,duetoincreasedriskofwheezing.
Individualswithsevereasthma,asdefinedascurrentlyonoralorhighdoseinhaledglucocorticosteriodsoractivewheezing,or
thosewithmedicallyattendedwheezinginthe7dayspriortovaccination.
Childrenandadolescents,2to17yearsofagecurrentlyreceivingaspirinoraspirincontainingtherapybecauseofthe
associationofReyessyndromewithaspirinandwildtypeinfluenzainfection.Itisrecommendedthataspirincontaining
productsinchildrenlessthan18yearsofagebedelayedforfourweeksafterreceiptofLAIV.
Pregnantwomen,becauseitisaliveattenuatedvaccineandthereisalackofsafetydataatthistime.However,itisnot
contraindicatedinbreastfeedingmothers.
Personswithimmunecompromisingconditions,duetounderlyingdisease,therapy,orboth,asthevaccinecontainslive
attenuatedvirus.
Asaprecautionarymeasure,LAIVrecipientsshouldavoidcloseassociationwithpersonswithsevereimmunecompromisingconditions
(e.g.,bonemarrowtransplantrecipientsrequiringisolation)foratleasttwoweeksfollowingvaccination,becauseofthetheoreticalrisk
fortransmittingavaccinevirusandcausinginfection.
Precautions
Allergicreactionstopreviousvaccinedoses
Expertreviewoftherisksandbenefitsofvaccinationshouldbesoughtforthosewhohavepreviouslyexperiencedseverelower
respiratorysymptoms(wheeze,chesttightness,difficultybreathing)within24hoursofinfluenzavaccination,anapparentsignificant
allergicreactiontothevaccineoranyothersymptomswhichcouldindicateasignificantallergicreaction(e.g.,throatconstriction,
difficultyswallowing)thatraiseconcernregardingthesafetyofreimmunization.Thisadvicemaybeobtainedfromlocalmedical
officersofhealthorotherexpertsininfectiousdisease,allergyandimmunologyorpublichealth.
Inviewoftheconsiderablemorbidityandmortalityassociatedwithinfluenza,adiagnosisofinfluenzavaccineallergyshouldnotbe
madewithoutconfirmation,whichmayinvolveskintesting,fromanallergyorimmunologyexpert.Individualswhohaveanallergyto
substancesthatarenotcomponentsoftheinfluenzavaccinearenotatincreasedriskofallergytoinfluenzavaccine.
Oculorespiratorysyndrome(ORS)
IndividualswhohaveexperiencedORSwithoutlowerrespiratorytractsymptomsmaybesafelyreimmunizedwithinfluenzavaccine.
PersonswhoexperiencedORSwithlowerrespiratorytractsymptomsshouldhaveanexpertreview.Healthcareproviderswhoareunsure
whetheranindividualpreviouslyexperiencedORSversusanIgEmediatedhypersensitivityimmuneresponseshouldseekadvice.
GuillainBarrsyndrome(GBS)
AlthoughtheevidenceconsideringinfluenzavaccinationandGBSisinadequatetoacceptorrejectacausalrelationbetweenGBSin
adultsandseasonalinfluenzavaccination,avoidingsubsequentinfluenzavaccinationofpersons
knowntohavehadGBSwithinsixweeksofapreviousinfluenzavaccinationappearsprudentatthistime.However,thepotentialriskof
GBSrecurrenceassociatedwithinfluenzavaccinationmustbebalancedagainsttheriskofGBSassociatedwithinfluenzainfectionitself.
Severeacuteillnesswithorwithoutfever
Administrationofseasonalinfluenzavaccineshouldusuallybepostponedinpersonswithseriousacuteillnessuntiltheirsymptomshave
abated.Immunizationshouldnotbedelayedbecauseofminoracuteillness,withorwithoutfever.Ifsignificantnasalcongestionis
presentthatmightimpededeliveryofLAIVtothenasopharyngealmucosa,inactivatedvaccinescanbeadministeredorLAIVmaybe
deferreduntilresolutionoftheillness.
Administrationofinfluenzavaccinetoeggallergicpersons
AllinfluenzavaccineproductsauthorizedforuseinCanadaaremanufacturedbyaprocessinvolvingchickeneggs,whichmayresultin
thevaccine`scontainingtraceamountsofresidualeggprotein.Eggallergicindividualsmaybevaccinatedagainstinfluenzausing
inactivatedTIVorQIV,withoutpriorinfluenzavaccineskintestandwiththefulldose,irrespectiveofapastseverereactiontoegg,and
withoutanyparticularconsiderationincludingimmunizationsetting.Formoreinformationregardingvaccinationofeggallergic
individuals,pleaseseeSectionVofthisstatement.Dataarenotcurrentlyavailabletosupportvaccinationofeggallergicindividualswith
LAIV.
Druginteractions
Althoughinfluenzavaccinecaninhibittheclearanceofwarfarinandtheophylline,clinicalstudieshavenotshownanyadverseeffects
attributabletothesedrugsinpeoplereceivinginfluenzavaccine.ItisrecommendedthatLAIVnotbeadministereduntil48hoursafter
antiviralagentsactiveagainstinfluenza(oseltamivirandzanamivir)arestopped,andthatantiviralagents,unlessmedicallyindicated,not
beadministereduntiltwoweeksafterreceiptofLAIVsothattheantiviralagentsdonotkillthereplicatingvirus.Ifantiviralagentsare
administeredwithinthistimeframe(i.e.,from48hoursbeforetotwoweeksafterLAIVisgiven),revaccinationshouldtakeplaceatleast
48hoursaftertheantiviralsarestopped.
ThisconcludesthesummaryofrelevantinfluenzavaccineinformationtypicallyfoundintheCanadianImmunizationGuide.Themore
detailedtechnicalinformationrelatedtoseasonalinfluenzavaccinecanbefoundintheremainderofthisstatement.
6. What is Guillain Barre syndrome? How common is this in patients who receive influenza vaccination? When
would it occur in relationship to the administration of influenza vaccination? Would certain patients be more
susceptible to developing this?
7. Which influenza vaccine formulations do and do not contain the mercurybased preservative thimerosal? What is the evidence that mercury/thimerosal may be linked to autism or other
neurodevelopmental disorders?
8. What needs might be unique to special patient populations when considering the risks and benefits of influenza
vaccination -e.g. geriatrics, pediatrics, pregnancy, lactation,etc.?
9.If a patient does develop an adverse vaccine reaction after receiving influenza vaccination at a pharmacy, how
should the pharmacist manage this situation? Can a pharmacist administer epinephrine for hypersensitivity
reactions if warranted?
Managementofanaphylaxis
Anaphylaxisisamedicalemergencyandrapidrecognitionandmanagementcanbelifesaving.Everyvaccineprovidershouldbefamiliar
withthesignsandsymptomsofanaphylaxisandbepreparedtoactquickly.
Protocols
Advancepreparationforemergencymanagementofanaphylaxisisessential.Itisrecommendedthatvaccineprovidersdevelop,post,and
regularlyrehearseawrittenanaphylaxisemergencymanagementprotocol.Protocolsshouldspecifythenecessaryemergencyequipment,
drugsanddosages,andmedicalpersonnelnecessarytosafelyandeffectivelymanageanaphylaxis.RefertoStepsforbasicmanagement
ofanaphylaxisforasummaryofthebasicmanagementofanaphylaxisinanonhospitalsetting.
Steps for basic management of anaphylaxis in a non-hospital setting
(Steps1,2,3shouldbedonepromptlyandsimultaneously)
1. Assess circulation, airway, breathing, mental status, skin, and body weight (mass). Secure an oral
airway if necessary. Direct someone to call 911(where available) or emergency medical services.
2. Position the vaccine recipient on their back or in a position of comfort if there is respiratory distress;
elevate the lower extremities. Place the vaccinee on their side if vomiting or unconscious. Pregnant
anaphylactic vaccinees should be placed semi-recumbent on their left side with their legs elevated.
3. Inject epinephrine intramuscularly in the mid-anterolateral aspect of the thigh: 0.01 mg/kg
body weight of 1:1000 (1 mg/mL) solution
o ADOLESCENT or ADULT: maximum - 0.5 mg
o CHILD: maximum - 0.3 mg
Record the time of the dose.
Repeat every 5 to 15 minutes as needed, for a maximum of three doses.
4. Stabilize vaccinee; perform cardiopulmonary resuscitation if necessary, give oxygen and establish
intravenous access if available and give adjunctive treatment (i.e. diphenhydramine hydrochloride or
Benadryl) if indicated.
5. Monitor vaccinees blood pressure, cardiac rate and function, and respiratory status.
6. Transfer to hospital for observation.
AdaptedfromSimonsFE,ArudussoLR,BiloMBetal.WorldAllergyOrganizationguidelinesfortheassessmentandmanagementof
anaphylaxis.JAllergyClinImmunol2011;127(3):593e122.
Rapidassessmentandpositioning
Rapidinterventionisofparamountimportance.Assessairway,breathingandcirculation;establishanairwayifneeded.Whenassessing
theairway,lookspecificallyatthelips,tongueandthroatforsignsofswelling.Positionthepersonflatontheback,unlesshe/sheis
vomitingorunconscious(thenplaceontheside)orinrespiratorydistress(mayneedtoelevateheadandchestforcomfort).Legsshould
beelevatedtohelpmaintainbloodpressure.Directsomeonetocall911oremergencymedicalservicesfortransportationtohospital.
Epinephrine
Promptadministrationofepinephrineisthepriorityandshouldnotbedelayed.Epinephrineisthetreatmentofchoicefor
managementofanaphylaxisincommunityandhealthcaresettingsasitpreventsandrelievesupperairwayswelling,hypotensionand
shock.Inaddition,itcausesincreasedheartrate,increasedforceofcardiaccontractions,increasedbronchodilation,anddecreasedrelease
ofhistamineandothermediatorsofinflammation.Epinephrinereachespeakplasmaandtissueconcentrationsrapidly.
Failuretoadministerepinephrinepromptlymayresultingreaterriskstotheanaphylacticvaccineethanusingepinephrineimproperly.If
uncertain,erronthesideoftreatment;therearenocontraindicationstotheuseofepinephrine.Iftimeislostearlyinthetreatmentofan
acuteanaphylacticepisode,subsequentmanagementcanbecomemoredifficult.
Epinephrine0.01mg/kgbodyweightofa1:1000(1mg/mL)solutionshouldbeadministeredintothemidanterolateralaspectofthe
thigh;thedeltoidmuscleofthearmisnotaseffectiveasthethighinabsorbingepinephrine.Scissorsmaybeneededtocutclothingto
establishaccess.Ifscissorsarenotreadilyavailable,epinephrinemaybeadministeredthroughclothing.Althoughthereisaslightly
increasedriskofinfection,timelyadministrationofepinephrineisthepriority.Theriskofinfectioncanbeaddressedoncethepersonhas
stabilized.RefertoTable1forepinephrinedosingguidelines.Forinfantslessthan7monthsofage,thedoseofepinephrineshouldbe
determinedbyweight,ifpossible.Forexample,aninfantweighing4kg(8.8lb)shouldreceive0.04mgofepinephrinein0.04mLof
1:1000(1mg/mL)solution.
Table 1: Dose of epinephrine (1:1000, 1 mg/mL solution), by age or weight
Age
WeightTable 1 - Footnote 1
Dose by injection
Dose by autoinjector
Adapted from Immunization Action Coalition. Medical Management of Vaccine Reactions in Children and
Teens (PDF document) . Accessed June 2012.
Table 1 - Footnote 1
Rounded weight at the 50th percentile for each age range
Maximum dose for children 12 years of age and younger
Maximum dose for adolescents
0 6 months
Up to 9 kg (20
pounds)
7 - 36 months
9 - 14.5 kg (20 - 32 lb) 0.1 - 0.2 mg
37 - 59 months
15 - 17.5 kg (33 39
lb)
5 - 7 years
0.01 mg/kg body weight Not applicable
0.15 - 0.3 mgTable 1 - Footnote
Not applicable
Junior dose of 0.15 mg
18 - 25.5 kg (40 56
lb)
0.2 - 0.3 mgTable 1 - Footnote 2
Junior dose of 0.15 mg
8 - 12 years
26 - 45 kg (57 99 lb)
0.3 mgTable 1 - Footnote 2
If , less than 30 kg (66 lbs) give Junior

dose
If 30 kg or more: Give standard dose
13 years and
older
46 + kg (100 + lb)
0.5 mgTable 1 - Footnote 3
Give standard dose of 0.3mg
Anepinephrineautoinjector(Allerject,Anapen,EpiPenorTwinject)maybeusedifthepersonwhoadministersitis
knowledgeableaboutproperuseandthecorrectdoseofepinephrineforageorbodyweightisavailableintheautoinjector.Thejunior
doseisintendedforchildrenwhoweigh1530kg.Thejuniororpediatricpreparationscontain0.15mg(0.3mL)ofepinephrine1:2000
perdose(EpiPenJr.;AnapenJr.150)or0.15mg(0.15mL)ofepinephrine1:1000perdose(Twinject0.15mg).Thestandarddoseis
intendedforchildrenandadultsweighing30kgormore.Thestandardpreparationscontain0.3mg(0.3mL)ofepinephrine1:1000per
dose.
Mildandtransienteffectssuchaspallor,tremor,anxiety,palpitations,headacheanddizzinessoccurwithinminutesafterinjectionofa
recommendeddoseofepinephrine.Theseeffectsconfirmthatatherapeuticdosehasbeengiven.
Ensurethepersonliesdown.Fatalitycanoccurwithinsecondsifthevaccineestandsorsitssuddenlyafterepinephrine.Peopleshould
remaininarecumbentpositionfollowingreceiptofanepinephrineinjectionandbemonitoredclosely.
Adjunctivetreatment
Asanoptionaladjuncttoepinephrine,adoseofdiphenhydraminehydrochloride(e.g.,Benadryl)maybegiventorelieveitching,
flushing,urticaria,andnasalandeyesymptoms.Generallytheinjectableformatisusedalthoughoraltabletsorliquidelixirmayalsobe
used;inallformatsthedosingisthesame.RefertoTable2fordiphenhydraminehydrochloridedosingguidelines.Diphenhydramineis
generallynotrecommendedforinfantsunder12monthsofage,andshouldbeusedwithcautionbetween1223monthsbecauseitmay
causedrowsinessorparadoxicalexcitement.Whengiventochildren,dosageshouldbedeterminedbyweight(1mg/kg).
Table 2: Dose of diphenhydramine hydrochloride, by age

Age
Weight (pounds)
Dose of diphenhydramine hydrochloride
Use with caution in children 12 - 23 months due to risk of sedation or paradoxical excitement.
12-23 monthsTable 2 - Footnote 1
7-12 kg (15-25 lbs)
6.25 - 12.5 mg
2 to 4 years
12-25 kg (25-55 lbs)
12.5 - 25 mg
5 to 11 years
25-45 kg (55-99 lbs)
25 - 50 mg
12 years and older
45 kg + (99 lbs or more)
50 mg
Whenindicated,givehighflowsupplementaloxygen(6to8L/minute)byfacemaskororopharyngealairway(ifavailable)topeople
withcyanosis,dyspneaoranyotherseverereactionrequiringrepeateddosesofepinephrine.
Peopleonbetablockersmaybemoreresistanttoepinephrine.
Transfertohospital
Allvaccineesreceivingemergencyepinephrinemustbetransportedtohospitalimmediatelyforevaluationandobservation.Sincethe
symptomsofananaphylacticreactioncanreoccuraftertheinitialreaction(biphasicanaphylaxis)inupto23%ofadultsandupto11%of
children,hospitalizationisrecommendedformonitoring.Generally,patientsarehospitalizedovernightormonitoredforatleast12hours.
Abiphasiccourseofanaphylaxisismorelikelytooccuriftheadministrationofepinephrineisdelayed.
10.What documentation must the pharmacist complete when providing Ministry-funded

influenza vaccination services?
Liveattenuatedinfluenzavaccine:
Onlythequadrivalentformulationoftheliveattenuatedinfluenzavaccine(LAIV)[FluMist Quadrivalent(AstraZeneca)]willbe
availableinCanadainthe201516season.Thestatementhasbeenupdatedtoreflectthattheevidencesupportingtheuseoflive
attenuatedinfluenzavaccineswasbasedonthetrivalentformulationofLAIV.Basedonexpertopinion,thecomparativeefficacydata
whichsupportedthepreferentialrecommendationsforthetrivalentformulationofLAIVarealsoapplicabletothequadrivalent
formulationofLAIVbecausethemanufacturingprocessesandimmunologicmechanismofthequadrivalentLAIVandthetrivalent
LAIVproductsarethesame.Thisexpertopinionissupportedbytheresultsofthenoninferioritystudiescomparingtrivalentand
quadrivalentformulationsofLAIV,whichwererequiredbyregulatorybodiestoauthorizetheuseoftheQLAIVformulation.
ComparativevaccineefficacyandeffectivenessdataofTIVorQIV,andthequadrivalentformulationofLAIVarenotavailable.
DecreasedeffectivenessofquadrivalentLAIVwasobservedintheUnitedStatesofAmericawiththeinfluenzaA(H1N1)strainin
childrenduringthe201314influenzaseason.Investigationsbythemanufacturerhavedeterminedthatthisreducedeffectivenessismost
likelyattributabletoreducedstabilityintheA/CaliforniaH1N1vaccinestrainwhenexposedtotemperaturefluctuations.NACIhas
reviewedtheavailableinformationonthisissue,includingCanadiandata,andconcludesthatthiseventisunlikelytooccurinCanada
becausebycontract,thecontractor,(i.e.,manufacturer)isrequiredtomaintaintherequiredtemperaturesthroughouttransportfromthe
contractortotheidentifiedusers(i.e.,provincialandterritorialdepots)andprovideevidencetothateffectfromthedataanalysisofthe
temperaturemonitoringdeviceorcarrierlogs,asapplicable.NACIthereforecontinuestorecommendpreferentialuseofLAIVin
children.NACIwillcontinuetomonitorthisissueandwillreviewadditionalinformationasitarises.
Choiceofvaccineproductforchildren623months(seesectionIV):
FluadPediatricTMwillbeavailableontheCanadianmarketstartinginthe201516influenzaseasonforuseinchildren6to<24months.
FluadPediatricTMisanadjuvantedtrivalentinfluenzavaccineadministeredasa0.25mLdosebyintramuscularinjection(referto
AppendixAforproductcharacteristics).
NACIhasreviewedtheavailableevidenceonFluadPediatricTMandhasconcludedthatFluadPediatricTMmaybeusedinchildren6to
<24monthsofage(NACIRecommendationGradeB).
Forchildren623months,NACIrecommendsthat,giventheburdenofinfluenzaBdisease,QIVshouldbeused.IfQIVisnotavailable,
eitherunadjuvantedoradjuvantedTIVshouldbeused.
Choiceofvaccineproductforchildren217years(seeSectionIV):
NACIrecommendsLAIVuseforhealthychildrenandadolescents2to17yearsofagewhodonothavecontraindicationstothisvaccine.
ThereisevidenceforthepreferentialuseofLAIVinyoungchildren(youngerthan6yearsofage)basedonsuperiorefficacyoftrivalent
LAIVcomparedtotrivalentinactivatedinfluenzavaccine(TIV)(GradeA),withweakerevidenceofsuperiorefficacyinolderchildren
(GradeI).ItisanticipatedthatthesuperiorefficacyforLAIVoverTIVextendsbeyondage6years,buttheevidencedoesnotindicateat
whichspecificagetheefficaciesofLAIVandTIVbecomeequivalent.GiventheburdenofinfluenzaBdiseaseinchildren,ifLAIVis
notavailableforthoseforwhomitisconsideredsuperior,quadrivalentinactivatedinfluenzavaccine(QIV)shouldbeused.IfQIVisnot
available,TIVshouldbeused.
ForchildrenwithunderlyingconditionsorcontraindicationsthatprecludetheuseofLAIV,NACIrecommendsthat,giventheburdenof
influenzaBdisease,QIVshouldbeused.IfQIVisnotavailable,TIVshouldbeused.Morespecifically,for:
Healthychildren:IfLAIVisnotavailableforthoseforwhomitisconsideredsuperior,NACIrecommendsthatQIVshouldbe
usedinthisagegroup.IfQIVisnotavailable,TIVshouldbeused.
Childrenwithimmunecompromisingconditions,whichareacontraindicationtoLAIV:GiventheburdenofinfluenzaBdisease
inchildren,QIVshouldbeused.IfQIVisnotavailable,TIVshouldbeused.
Childrenwithsevereasthma(asdefinedinSectionIIunderContraindicationsandPrecautions)ormedicallyattendedwheezing
intheprevioussevendays:GiventheburdenofinfluenzaBdiseaseinchildren,QIVshouldbeused.IfQIVisnotavailable,
TIVshouldbeused.
Childrenwithotherchronichealthconditions:LAIVcanbeusedinthisgroup.Ifinactivatedvaccineisbeingused,giventhe
burdenofinfluenzaBdiseaseinchildren,QIVshouldbeused.IfQIVisnotavailable,TIVshouldbeused.
NACIrecommendsthatchildrenwithcysticfibrosismayreceiveLAIViftheindividualisnotbeingtreatedwith
immunosuppressivedrugs,suchasprolongedsystemiccorticosteroids,andmeetstheothercriteriaforLAIVadministration.
Childrenandadolescentswithneurologicorneurodevelopmentconditions:
FollowingarecentpublicationbytheCanadianImmunizationMonitoringProgramActive(IMPACT),NACInowincludeschildrenand
adolescentswithneurologicorneurodevelopmentconditions,includingseizuredisorders,febrileseizuresandisolateddevelopmental
delay,amongthegroupsforwhominfluenzavaccinationisparticularlyrecommended.
Oculorespiratorysyndrome:
Thedefinitionforoculorespiratorysyndrome(seesectionII)hasbeenupdatedtobeconsistentwiththeuserguideforreportingof
adverseeventsfollowingimmunization.
Intanza:
SanofiPasteurhasconfirmedthatIntanzawillnolongerbeavailableontheCanadianmarket.Consequently,informationrelatedto
Intanzahasnotbeenincludedinthe20152016statement.
CoadministrationofLAIVwithothervaccines:
NACIrecommendsthatLAIVbegiventogetherwith,oratanytimebeforeoraftertheadministrationofanyotherliveattenuatedor
inactivatedvaccine.NACIrecognizesthatsomevaccineprovidersmaychoosetogiveLAIVandotherlivevaccinessimultaneouslyor
separatedbyatleast4weekstoavoidanypossibilityofimmuneinterference.Alternatively,aninactivatedinfluenzavaccine(TIVor
QIV)maybegiven.
Background
TheWorldHealthOrganizations(WHO)recommendationsonthecompositionofinfluenzavirusvaccines aretypicallyavailablein
Februaryofeachyearfortheupcomingseason.TheWHOrecommendsthat,whereavailable,seasonalquadrivalentinfluenzavaccines
containtherecommendedthreevirusesforthetrivalentvaccineaswellastheinfluenzaBviruslineagethatisnotincludedinthetrivalent
vaccine.
AnnualinfluenzavaccinerecommendationsforuseinCanadaaredevelopedbytheInfluenzaWorkingGroup(IWG)forconsiderationby
NACI.Recommendationdevelopmentincludesreviewofavarietyofissues,including:theburdenofinfluenzaillnessandthetarget
populationsforvaccination;safety,immunogenicity,efficacy,andeffectivenessofinfluenzavaccines;vaccineschedules;andother
aspectsofinfluenzaimmunization.DetailsregardingNACIsevidencebasedprocessfordevelopingastatementareoutlinedin
EvidenceBasedRecommendationsforImmunization:MethodsoftheNACI,January2009,CCDR.
HealthcareprovidersinCanadamayoffertheseasonalvaccinewhenitbecomesavailable,sinceseasonalinfluenzaactivitymaystartas
earlyasNovemberinthenorthernhemisphere.Decisionsregardingtheprecisetimingofvaccinationinagivensettingorgeographicarea
shouldbemadeaccordingtolocalepidemiologicfactors(influenzaactivity,timingandintensity),opportunemomentsforvaccination,as
wellasprogrammaticconsiderations.Furtheradviceregardingthetimingofinfluenzavaccinationprogramsmaybeobtainedthrough
consultationwithlocalpublichealthagencies.
Althoughvaccinationbeforetheonsetoftheinfluenzaseasonisstronglypreferred,vaccinemaystillbeadministeredupuntiltheendof
theseason,althoughitsutilitymaybecompromisedifexposuretoinfluenzaalreadyhasoccurred.Vaccineprovidersshoulduseevery
opportunitytogiveinfluenzavaccinetoindividualsatriskwhohavenotbeenimmunizedduringthecurrentseason,evenafterinfluenza
activityhasbeendocumentedinthecommunity.
Thedecisiontoincludespecificinfluenzavaccinesaspartofpubliclyfundedprovincialandterritorialprogramsdependsonmultiple
factors,suchascostbenefitevaluationandotherprogrammaticandoperationalfactors,forexampleshelflifeandimplementation
strategies.Notallproductswillbemadeavailableinalljurisdictionsandavailabilityofsomeproductsmaybelimited;therefore,
individualprovincesandterritoriesmustbeconsultedregardingtheproductsavailableinindividualjurisdictions.
II.ClinicalInformationforVaccineProviders(CanadianImmunizationGuide)
TheCanadianImmunizationGuide,whichiswrittenprimarilyforhealthcareproviders(frontlineclinicians,publichealthpractitioners)
butisalsousedbypolicymakers,programplannersandthegeneralpublic,hasbeenatrusted,readerfriendlysummaryofthevaccine
statementsprovidedbyNationalAdvisoryCommitteeonImmunizationforover40years.
AsnotedintheIntroduction,theinformationinthissection,ClinicalInformationforVaccineProviders,replacestheinfluenzachapterof
theCanadianImmunizationGuideandisadaptedforinclusionintherevisedNACIStatementonSeasonalInfluenzaVaccine.Witha
newNACIStatementonSeasonalInfluenzarequiredeachyear,therationaleforthisformatchangeistoallowtheusertohavequick
accesstotheinformationthatheorsherequireswithinonedocument,whetheritistherelevantinfluenzavaccineinformationthatis
writtenprimarilyforthefrontlinevaccineprovidersasisfoundinthissection,orthemoredetailedtechnicalinformationthatisfoundin
therestofthisStatement,commencinginSectionIII.
KeyInformation
What
InfluenzaisarespiratoryinfectioncausedprimarilybyinfluenzaAandBviruses.InCanada,influenzagenerallyoccurseachyearinthe
latefallandwintermonths.Symptomstypicallyincludethesuddenonsetofhighfever,chills,sorethroat,coughandmyalgia.Other
commonsymptomsincludeheadache,lossofappetite,fatigue,andcoryza.Nausea,vomitinganddiarrhoeamayalsooccur,especiallyin
children.Mostpeoplewillrecoverwithinaweekortendays,butsomeareatgreaterriskofmoreseverecomplications,suchas
pneumonia.
BothinactivatedandliveattenuatedinfluenzavaccinesareauthorizedforuseinCanada;somearetrivalentformulationsandsomeare
quadrivalentformulations.
Influenzavaccineissafeandwelltolerated.Influenzavaccinecannotcauseinfluenzaillnessbecausetheinactivatedinfluenzavaccines
donotcontainlivevirusandthevirusesinliveattenuatedinfluenzavaccinesareweakenedsothattheycannotcauseinfluenza.
Who
Influenzavaccinationisrecommendedforallindividualsaged6monthsandolder(notingproductspecificageindicationsand
contraindications),withparticularfocuson:peopleathighriskofinfluenzarelatedcomplicationsorhospitalization,includingall
pregnantwomen,peoplecapableoftransmittinginfluenzatothoseathighrisk,andotherslistedinList1.
How
Risksandbenefitsofinfluenzavaccineshouldbediscussedpriortovaccination,aswellastherisksofnotbeingimmunized.
Doseandschedule
Childrenwhohavebeenpreviouslyimmunizedwithseasonalinfluenzavaccineandadultsshouldreceiveonedoseofinfluenzavaccine
eachyear.Children6monthstolessthan9yearsofagereceivingseasonalinfluenzavaccineforthefirsttimeintheirlifeshouldbegiven
twodoses,withaminimumintervaloffourweeksbetweendoses.Therouteofadministrationanddosagevariesbyproduct(referto
Table3).WiththeexceptionofadjuvantedTIVforchildren,(i.e.,FluadPediatricTM),thedoseforintramuscular(IM)inactivated
vaccinesis0.5mLforallagegroups.ForFluadPediatricTM,availableforchildren6to<24monthsofage,thedoseis0.25mL.
ContraindicationsandPrecautions
Personswhohavedevelopedananaphylacticreactiontoapreviousdoseofinfluenzavaccineortoanyofthevaccinecomponents,with
theexceptionofegg,orwhohavedevelopedGuillainBarrSyndrome(GBS)withinsixweeksofinfluenzavaccination,shouldnot
receiveafurtherdose.
NACIhasconcludedthateggallergicindividualsmaybevaccinatedagainstinfluenzausinginactivatedTIVandQIVwithoutaprior
influenzavaccineskintestandwiththefulldose.LAIVshouldnotbegiventoeggallergicindividuals,aseggallergyhasnotyetbeen
studiedforLAIV.
Administrationoftheseasonalinfluenzavaccineshouldusuallybepostponedinpersonswithseriousacuteillnessesuntiltheirsymptoms
haveabated.Immunizationshouldnotbedelayedbecauseofminoracuteillness,withorwithoutfever.Ifsignificantnasalcongestionis
presentthatmightimpededeliveryofLAIVtothenasopharyngealmucosa,inactivatedvaccinescanbeadministeredorLAIVcanbe
deferreduntilresolutionoftheillness.
Why
Annualvaccinationisrequiredbecausethebodysimmuneresponsefromvaccinationdiminisheswithinayear.Also,becauseinfluenza
viruseschangeoften,thevaccineisreviewedeachyearandupdatedasnecessarytokeepupwiththechangingviruses.
Epidemiology
DiseaseDescription
Itisestimatedthatbetween1020%ofthepopulationbecomesinfectedwithinfluenzaeachyear Footnote1.Ratesofinfluenzainfectionare
highestinchildrenaged59years,butratesofseriousillnessanddeatharehighestinchildrenaged<2years,olderpersons(>65years),
andpersonswithunderlyingmedicalconditionsFootnote2.Influenzainfectionnotonlycausesprimaryillnessbutalsocanleadtosevere
secondarymedicalcomplications,includingviralpneumonia,secondarybacterialpneumoniaandworseningofunderlyingmedical
conditions.
InfectiousAgent
InfluenzaAvirusesareclassifiedintosubtypesonthebasisoftwosurfaceproteins:haemagglutinin(HA)andneuraminidase(NA).
Threesubtypesofhaemagglutinin(H1,H2andH3)andtwosubtypesofneuraminidase(N1andN2)arerecognizedamonginfluenzaA
virusesashavingcausedwidespreadhumandiseaseoverthedecades.ImmunitytotheHAandNAproteinsreducesthelikelihoodof
infectionandtogetherwithimmunitytotheinternalviralproteins,lessenstheseverityofdiseaseifinfectionoccurs.
InfluenzaBviruseshaveevolvedintotwoantigenicallydistinctlineagessincethemid1980s,representedbyB/Yamagata/16/88likeand
B/Victoria/2/87likeviruses.VirusesfromboththeB/YamagataandB/Victorialineagescontributevariablytoinfluenzaillnesseachyear.
Overtime,antigenicvariation(antigenicdrift)ofstrainsoccurswithinaninfluenzaAsubtypeoraBlineage.Antigenicdrift,whichmay
occurinoneormoreinfluenzavirusstrains,usuallyrequiresseasonalinfluenzavaccinestobereformulatedannually.
Transmission
Influenzaisprimarilytransmittedbydropletsspreadthroughcoughingorsneezingandmayalsobetransmittedthroughdirectorindirect
contactwithcontaminatedrespiratorysecretions.Theincubationperiodofseasonalinfluenzaisusuallytwodaysbutcanrangefromone
tofourdays.Adultsmaybeabletospreadinfluenzatoothersfromonedaybeforesymptomonsettoapproximatelyfivedaysafter
symptomsstart.Childrenandpeoplewithweakenedimmunesystemsmaybeinfectiousforlonger.
RiskFactors
Thepeopleatgreatestriskofinfluenzarelatedcomplicationsareadultsandchildrenwithunderlyinghealthconditions(seeList1);
residentsofnursinghomesandotherchroniccarefacilities;people65yearsofageandolder;children6to59monthsofage;pregnant
women;andAboriginalPeoples.
SeasonalandTemporalPatterns
InCanada,influenzagenerallyoccurseachyearinthelatefallandwintermonths.
SpectrumofClinicalIllness
Symptomstypicallyincludethesuddenonsetofhighfever,coughandmuscleaches.Othercommonsymptomsincludeheadache,chills,
lossofappetite,fatigueandsorethroat.Nausea,vomitinganddiarrheamayalsooccur,especiallyinchildren.Mostpeoplewillrecover
withinaweekortendays,butsomeincludingthose65yearsofageandolder,youngchildren,andadultsandchildrenwithchronic
conditionsareatgreaterriskofmoreseverecomplications,suchaspneumonia.
DiseaseDistribution:Incidence
Global
Worldwide,annualepidemicsresultinanapproximatelyonebillioncasesofinfluenza,aboutthreetofivemillioncasesofsevereillness,
andabout250,000to500,000deaths.Forcurrentinternationalinfluenzaactivityinformation,refertoWHOsFluNetwebsite .
National
Influenzaisrankedamongthetop10infectiousdiseasesaffectingtheCanadianpopulationFootnote3.Currentinfluenzaactivityinformation
canbefoundontheAgencysFluWatchwebsite.TheFluWatchprogramcollectsdataandinformationfromvarioussourcestoprovidea
nationalpictureofinfluenzaactivity.
InfluenzaactivityinCanadausuallyislowinthespringandsummer,beginstoriseoverthefallandpeaksinthewintermonths.
Dependingontheyear,thepeakmayoccurasearlyaslatefalloraslateasearlyspring.Itisestimatedthat,inagivenyear,anaverageof
12,200hospitalizationsrelatedtoinfluenzaFootnote4,Footnote5,Footnote6andapproximately3,500deathsattributabletoinfluenzaoccurFootnote7.
However,itshouldbenotedthatinfluenzatestingisoftennotconductedtoconfirmaninfluenzadiagnosis,andthatpatientsmaypresent
tohospitalwithcomplicationsofinfluenzaafterviralsheddinghasbeenstopped.Forthisreason,theoverallincidenceofinfluenzamay
beunderestimatedandthusisbestdeterminedbyperiodiccohortstudies.Therateofhospitalizationanddeathduetoinfluenzaisbest
estimatedbymodellingofexcessdeathsandhospitalizationsduetocardiorespiratoryconditionsduringinfluenzaseason Footnote8.
PreparationsAvailableforUseinCanada
ThissectiondescribestheinfluenzavaccinepreparationsthatarecurrentlyavailableforuseinCanada.Allinfluenzavaccinesavailable
foruseinCanadahavebeenauthorizedforusebyHealthCanada.However,notallpreparationsauthorizedforusearenecessarily
availableinthemarketplace.Thevaccinemanufacturersdeterminewhethertheywillmakeanyoralloftheirproductsavailableina
givenmarket.
Theantigeniccharacteristicsofcurrentandemerginginfluenzavirusstrainsprovidethebasisforselectingthestrainsincludedineach
year'svaccine.AllmanufacturersthatdistributeinfluenzavaccineproductsinCanadaconfirmtoHealthCanadathatthevaccinestobe
marketedinCanadafortheupcominginfluenzaseasoncontaintheWHOrecommendedantigenicstrainsfortheNorthernHemisphere.
Vaccineproducersmayuseantigenicallyequivalentstrainsbecauseoftheirgrowthproperties.
LAIVcontainsstandardizedquantitiesoffluorescentfocusunits(FFU)ofliveattenuatedinfluenzavirusreassortants.Inactivated
seasonalinfluenzavaccinescontainstandardizedamountsoftheHAproteinfromrepresentativeseedstrainsofthetwohumaninfluenza
Asubtypes(H3N2andH1N1)andeitherone(fortrivalentvaccines)orboth(forquadrivalentvaccines)ofthetwoinfluenzaBlineages
(YamagataorVictoria).TheamountofNAinthevaccinesisnotstandardized.HAbasedserumantibodyproducedtooneinfluenzaA
subtypeisanticipatedtoprovidelittleornoprotectionagainststrainsbelongingtotheothersubtype.Thepotentialfortrivalentvaccineto
stimulateantibodyprotectionacrossBlineagesrequiresfurtherevaluationandmaybedependentuponfactorssuchasageandprior
antigenicexperiencewiththetwoBlineagesFootnote9,Footnote10,Footnote11,Footnote12,Footnote13,Footnote14.
AsummaryofthecharacteristicsofinfluenzavaccinesavailableinCanadacanbefoundinAppendixA.Forcompleteprescribing
information,readersshouldconsulttheproductleafletorinformationcontainedwithintheHealthCanadasauthorizedproduct
monographsavailablethroughHealthCanadasDrugProductDatabase.
InactivatedInfluenzaVaccines
TheinactivatedinfluenzavaccinescurrentlyauthorizedforuseinCanadaareamixofsplitvirusandsubunitvaccines.Insplitvirus
vaccines,thevirushasbeendisruptedbyadetergent.Insubunitvaccines,HAandNAhavebeenfurtherpurifiedbyremovalofother
viralcomponents.RefertoBasicImmunologyandVaccinologyinPart1oftheCanadianImmunizationGuideformoreinformation
aboutinactivatedvaccines.
BothtrivalentandquadrivalentinactivatedinfluenzavaccinesareauthorizedforuseinCanada.
Adjuvanted,InactivatedInfluenzaVaccines
Twoofthetrivalentproducts,FluadandFluadPediatricTM,containtheadjuvantMF59,whichisanoilinwateremulsioncomposedof
squaleneastheoilphase,stabilizedwiththesurfactantspolysorbate80andsorbitantriolateincitratebuffer.Theotherinactivated
productsdonotcontainanadjuvant.
LiveAttenuatedInfluenzaVaccine(LAIV)
FluMistQuadrivalentisaliveattenuatedinfluenzavaccineforadministrationbyintranasalsprayandauthorizedforuseforpersons259
yearsofage.TheinfluenzastrainsinFluMistQuadrivalentarecoldadaptedandtemperaturesensitive,sotheyreplicateinthenasal
mucosaratherthanthelowerrespiratorytract.
Efficacy,EffectivenessandImmunogenicity
Influenzavaccinehasbeenshowntobeefficacious,withhigherefficacydemonstratedagainstlaboratoryconfirmedinfluenzathan
clinicallydefinedoutcomes.
Immunizationhasbeenshowntoreducethenumberofphysicianvisits,hospitalizationsanddeathsinhighriskadults.
Inyoungchildren,uptosixyearsofage,thereisevidencethattrivalentLAIVprotectsbetterthanTIV,withlessevidenceinolder
children.Basedonexpertopinion,thecomparativeefficacydatawhichsupportedthepreferentialrecommendationsforthetrivalent
formulationofLAIVarealsoapplicabletothequadrivalentformulationofLAIVbecausethemanufacturingprocessesandimmunologic
mechanismofthequadrivalentLAIVandthetrivalentLAIVproductsarethesame.Thisexpertopinionissupportedbytheresultsofthe
noninferioritystudiescomparingtrivalentandquadrivalentformulationsofLAIV,whichwererequiredbyregulatorybodiestoauthorize
theuseoftheQLAIVformulation.ComparativevaccineefficacyandeffectivenessdataofTIVorQIV,andthequadrivalentformulation
ofLAIVarenotavailable.
ReducedeffectivenessofquadrivalentLAIVinchildren,overallandcomparedtoinactivatedvaccines,hasbeenreportedduringthe
201314influenzaseasonintheUSagainstinfluenzaA(H1N1).Investigationsbythemanufacturerhavedeterminedthatthisreduced
effectivenessismostlikelyattributabletoreducedstabilityintheA/CaliforniaH1N1vaccinestrainwhenexposedtotemperature
fluctuations.NACIhasreviewedtheavailableinformationonthisissue,includingCanadiandata,andconcludesthatthiseventis
unlikelytooccurinCanadabecausebycontract,thecontractor,(i.e.,manufacturer)isrequiredtomaintaintherequiredtemperatures
throughouttransportfromthecontractortotheidentifiedusers(i.e.,provincialandterritorialdepots)andprovideevidencetothateffect
fromthedataanalysisofthetemperaturemonitoringdeviceorcarrierlogs,asapplicable.NACIthereforecontinuestorecommend
preferentialuseofLAIVinchildren.(seeSectionIV.ChoiceofProduct).NACIwillcontinuetomonitorthisissueandwillreview
additionalinformationasitarises.
ForasummaryofefficacystudiesrefertoSectionVofthisstatement.
Immunogenicity
Theantibodyresponseaftervaccinationdependsonseveralfactors,includingtheageoftherecipient,priorandsubsequentexposureto
antigensandthepresenceofimmunecompromisingconditions.Humoralantibodylevels,whichcorrelatewithvaccineprotection,are
generallyachievedbytwoweeksafterimmunization;however,theremaybesomeprotectionaffordedbeforethattime.
RecommendationsforUse
RecommendedRecipientsofInfluenzaVaccine
Influenzavaccineisrecommendedforeveryone6monthsofageandolderwithoutcontraindications.Toreducethemorbidityand
mortalityassociatedwithinfluenza,immunizationprogramsshouldfocusonthoseathighriskofinfluenzarelatedcomplications,
includingallpregnantwomen,thosecapableoftransmittinginfluenzatoindividualsathighriskofcomplicationsandothersasidentified
inList1.AdditionaldetailregardingtherecipientsidentifiedinList1,includingpregnantwomen,canbefoundinSectionIIIofthe
statement.
List1:Influenzavaccinationisparticularlyrecommendedforthefollowinggroups:
Peopleathighriskofinfluenzarelatedcomplicationsorhospitalization
Adults,includingpregnantwomen,andchildrenwiththefollowingchronichealthconditions:
o cardiacorpulmonarydisorders(includingbronchopulmonarydysplasia,cysticfibrosisandasthma);
o diabetesmellitusandothermetabolicdiseases;
o cancer,immunecompromisingconditions(duetounderlyingdisease,therapyorboth);
o renaldisease;
o anemiaorhemoglobinopathy;
o conditionsthatcompromisethemanagementofrespiratorysecretionsandareassociatedwithanincreasedriskof
aspiration;
o morbidobesity(BMI40);
o Childrenandadolescents(age6monthsto18years)withthefollowingconditions:
neurologicorneurodevelopmentconditions(includingseizuredisorders,febrileseizuresandisolated
developmentaldelay);
undergoingtreatmentforlongperiodswithacetylsalicylicacid,becauseofthepotentialincreaseofReyes
syndromeassociatedwithinfluenza.
Peopleofanyagewhoareresidentsofnursinghomesandotherchroniccarefacilities.
People65yearsofage.
Allchildren6to59monthsofage.
Healthypregnantwomen(theriskofinfluenzarelatedhospitalizationincreaseswithlengthofgestation,i.e.,itishigherinthe
thirdthaninthesecondtrimester).
AboriginalPeoples.
Peoplecapableoftransmittinginfluenzatothoseathighrisk
Healthcareandothercareprovidersinfacilitiesandcommunitysettingswho,throughtheiractivities,arecapableof
transmittinginfluenzatothoseathighriskofinfluenzacomplications.
Householdcontacts(adultsandchildren)ofindividualsathighriskofinfluenzarelatedcomplications(whetherornotthe
individualathighriskhasbeenimmunized):
householdcontactsofindividualsathighrisk,aslistedinthesectionabove;
householdcontactsofinfants<6monthsofageastheseinfantsareathighriskofcomplicationsfrominfluenzabut
cannotreceiveinfluenzavaccine;
o membersofahouseholdexpectinganewbornduringtheinfluenzaseason.
Thoseprovidingregularchildcaretochildren59monthsofage,whetherinoroutofthehome.
Thosewhoprovideserviceswithinclosedorrelativelyclosedsettingstopersonsathighrisk(e.g.,crewonaship).
o
o
Others:
Peoplewhoprovideessentialcommunityservices.
Peopleindirectcontactduringcullingoperationswithpoultryinfectedwithavianinfluenza.
InadditiontotherecipientsidentifiedinList1,influenzavaccineisalsorecommendedfor:
HealthyIndividualsages564yearsofage
RecentliteraturereviewsconductedbyNACIhaveshownthathealthyindividualsaged5to64yearsbenefitfrominfluenzavaccination.
DetailedinformationregardingthesereviewscanbefoundintheStatementonSeasonalInfluenzaVaccinefor20142015andineachof
therelevantliteraturereviews,availableviatheNACIwebsite.
Travellers
Influenzaoccursyearroundinthetropics.Intemperatenorthernandsoutherncountries,influenzaactivitypeaksgenerallyduringthe
winterseason(NovembertoMarchintheNorthernHemisphereandApriltoOctoberintheSouthernHemisphere).Influenzavaccination
isrecommendedforallindividuals,includingtravellers,aged6monthsandolder,withparticularfocusonpeopleathighriskof
influenzarelatedcomplicationsorhospitalization,peoplecapableoftransmittinginfluenzatothoseathighrisk,andothersasindicatedin
List1.
VaccinespreparedspecificallyforuseintheSouthernHemispherearenotavailableinCanada,andtheextenttowhichrecommended
vaccinecomponentsfortheSouthernHemispheremayoverlapwiththoseinavailableCanadianformulationswillvary.Adecisionforor
againstrevaccination(i.e.,boosting)oftravellerstotheSouthernHemispherebetweenAprilandOctober,iftheyhadalreadybeen
vaccinatedintheprecedingfallorwinterwiththeNorthernHemispheresvaccine,dependsonindividualriskassessment,thesimilarity
ordifferencesbetweentheNorthernandSouthernhemispheresvaccines,andtheavailabilityofareliableandsafevaccineatthe
traveller'sdestination.RefertoImmunizationofTravellersintheCanadianImmunizationGuideforadditionalgeneralinformation.
ChoiceofSeasonalInfluenzaVaccine
Table1summarizescurrentrecommendationsbyspecificageandriskgroupsforthechoice(s)ofinfluenzavaccinecurrentlyavailable
foruseinCanada.
Table1:Choiceofinfluenzavaccineforselectedageandriskgroups(forpersonswithoutacontraindicationtothevaccine)
Recipientby
agegroup
Vaccinetypes
availablefor
use
Comments
TIV=trivalentinactivatedinfluenzavaccine(forIMadministration);QIV=Quadrivalentinactivatedinfluenzavaccine;LAIV=live
attenuatedinfluenzavaccine
**
LAIV:NACIrecommendsLAIVforhealthychildrenandadolescents2to17yearsofagewhodonothavecontraindicationstothis
vaccine.ThereisevidenceforthepreferentialuseofLAIVinyoungchildren(youngerthan6yearsofage)basedonsuperiorefficacy
oftrivalentLAIVcomparedtoTIV(GradeA),withweakerevidenceofsuperiorefficacyinolderchildren(GradeI).Itisanticipated
thatthesuperiorefficacyforLAIVoverTIVextendsbeyondage6years,buttheevidencedoesnotindicateatwhichspecificagethe
efficaciesofLAIVandTIVbecomeequivalent.GiventheburdenofinfluenzaBdiseaseinchildren,ifLAIVisnotavailableforthose
forwhomitisconsideredsuperior,QIVshouldbeused.IfQIVisnotavailable,TIVshouldbeused.
TIV,QIVandadjuvantedTIVareauthorizedforthisagegroup.
TIV
Children623
QIV
monthsofage
Forchildren623months,NACIrecommendsthat,giventheburdenofinfluenzaBdisease,QIV
AdjuvantedTIV
shouldbeused.IfQIVisnotavailable,eitherunadjuvantedoradjuvantedTIVshouldbeused.
**
TIV
Children217
QIV
yearsofage
LAIV
ForrecommendationsregardinguseofLAIVinhealthychildrenandadolescents2to17yearsof
agewhodonothavecontraindicationstothisvaccine,seethenotebelowthistable.
LAIVisnotrecommendedforchildrenwithimmunecompromisingconditions,seebelow.LAIV,
TIVorQIVcanbeusedinchildrenwithchronichealthconditions,includingasthmathatisnot
severe,andcysticfibrosiswithoutimmunesuppression(seeContraindicationsandPrecautions
sectionbelowfordefinitionregardingsevereasthma).
Adults1859
yearsofage
TIV
QIV
LAIV
TIVandQIVarethepreferredproductsforadultswithchronichealthconditions.
LAIVisnotrecommendedforadultswithimmunecompromisingconditions.
Adults6064
TIV
Table1:Choiceofinfluenzavaccineforselectedageandriskgroups(forpersonswithoutacontraindicationtothevaccine)
Recipientby
agegroup
Vaccinetypes
availablefor
use
Comments
yearsofage
QIV
Adults65+
yearsofage
TIV
QIV
AdjuvantedTIV
Pregnant
women
TIV
QIV
LAIVisnotrecommendedbecauseofthetheoreticalrisktothefetusfromadministeringalivevirus
vaccine.
VaccineAdministration
Dose,RouteofAdministrationandSchedule
WiththevarietyofinfluenzavaccinesavailableforuseinCanada,itisimportantforpractitionerstonotethespecificdifferencesinage
indications,routeofadministration,dosageandschedulefortheproductsthattheywillbeusing(Table2).
VaccineadministrationpracticesarediscussedintheCanadianImmunizationGuide.Forinfluenzavaccinesgivenbytheintramuscular
route,thedeltoidmuscleistherecommendedsiteinadultsandchildren12monthsofageandtheanterolateralthighistherecommended
siteininfantsbetween6and12monthsofage.
Table2:Influenzavaccine:Recommendeddosageandroute,byage,forthe20152016season
Agegroup
LAIV
(FluMist)
Quadrivalent)
IN
MF59adjuvantedTIV(Fluad
PediatricTMorFluad)
IM
TIVwithoutadjuvantor
QIVIM
Numberofdoses
required
TIV=Trivalentinactivatedinfluenzavaccine,QIV=Quadrivalentinactivatedinfluenzavaccine,LAIV=Liveattenuatedinfluenza
vaccine,IM=Intramuscular,IN=intranasal
Influvac18years,Fluviral6months,Agriflu6months,Vaxigrip6months,Fluzone6months,FlulavalTetra6monthsand
FluzoneQuadrivalent6months.
*
Thisinformationdiffersfromtheproductmonograph.Asnotedinthepreambleofthisstatement,recommendationsforuseandother
informationinthisstatementmaydifferfromthatsetoutintheproductmonographs/leafletsoftheCanadianmanufacturers.
**
Children6monthstolessthan9yearsofagewhohaveneverreceivedtheseasonalinfluenzavaccinerequiretwodosesofinfluenza
vaccine,withaminimumintervaloffourweeksbetweendoses.Eligiblechildren<9yearsofagewhohaveproperlyreceivedoneor
moredosesofseasonalinfluenzavaccineinthepastshouldreceiveonedoseperinfluenzavaccinationseasonthereafter.
623months 0.5mL*
0.25mL
1or2**
28years
0.5mL
0.2mL(0.1mLper
nostril)
1or2**
917years
0.5mL
0.2mL(0.1mLper
nostril)
1859years
0.5mL
0.2mL(0.1mLper
nostril)
6064years
0.5mL
65years
0.5mL
0.5mL
BoosterDosesandReImmunization
Boosterdosesarenotrequiredwithinthesameinfluenzaseason.
SerologicalTesting
Serologictestingisnotnecessarybeforeorafterreceivingseasonalinfluenzavaccine.
StorageRequirements
Influenzavaccineshouldbestoredat+2Cto+8Candshouldnotbefrozen.Refertotheindividualproductmonographsforfurther
details.RefertoStorageandHandlingofImmunizingAgentsinPart1oftheCanadianImmunizationGuideforadditionalinformation.
CoadministrationwithotherVaccines
Intheory,theadministrationoftwolivevaccinessequentiallywithinlessthan4weekscouldreducetheefficacyofthesecondvaccine.
StudieshavebeendoneshowingnointerferencewhenadministeringtrivalentLAIVconcomitantlywithmeasles,mumps,rubella
(MMR),measles,mumps,rubella,varicella(MMRV)ororalpoliolivevaccines Footnote15,Footnote16,Footnote17.Nostudieshavebeendoneto
assessthepossibilityofinterferencebetweenLAIVandotherlivevaccines,oronLAIVgivenbeforeorafterotherlivevaccines.Given
thelackofdataforimmuneinterference,basedonexpertopinion,NACIrecommendsthatLAIVcanbegiventogetherwithoratany
timebeforeoraftertheadministrationofanyotherliveattenuatedorinactivatedvaccine.NACIrecognizesthatsomevaccineproviders
maychoosetogiveLAIVandotherlivevaccinessimultaneouslyorseparatedbyatleast4weekstoavoidanypossibilityofimmune
interference.Alternatively,aninactivatedinfluenzavaccine(TIVorQIV)maybegiven.
Notethatthetimingrulesrelatedtotwoparenterallivevaccines(e.g.MMRandvaricellavaccines)stillapply.Formoreinformation
regardingvaccinationadministrationtimingrules,pleaserefertotheCanadianImmunizationGuide.
Whenmultipleinjectionsaregivenatoneclinicvisit,itispreferabletoadministerthemindifferentlimbs.Ifitisnotpossibletodoso,
injectionsgiveninonelimbshouldbeseparatedbyadistanceofatleast2cm.Aseparateneedleandsyringeshouldbeusedforeach
injection.
Thetargetgroupsforinfluenzaandpneumococcalpolysaccharidevaccinesoverlapconsiderably.Healthcareprovidersshouldtakethe
opportunitytovaccinateeligiblepersonsagainstpneumococcaldiseasewheninfluenzavaccineisgiven.
III.SpecificallyRecommendedRecipients:AdditionalInformation
List1insectionIIliststhegroupsforwhichinfluenzavaccinationisparticularlyrecommended.Additionalinformationregardingthese
specificallyrecommendedrecipientsisprovidedbelow.
PeopleatHighRiskofInfluenzaRelatedComplicationsorHospitalization
Adults(includingpregnantwomen)andchildrenwithchronichealthconditionsasnotedinList1.
Anumberofchronichealthconditions,asnotedList1,areassociatedwithincreasedriskofinfluenzarelatedcomplicationsand
influenzacanleadtoexacerbationofthechronicdisease.Influenzavaccinationcaninduceprotectiveantibodylevelsinasubstantial
proportionofadultsandchildrenwithimmunecompromisingconditions,includingtransplantrecipients,thosewithproliferativediseases
ofthehematopoieticandlymphaticsystems,andHIVinfectedpersons.Vaccineefficacymaybelowerinpersonswithimmune
compromisingconditionsthaninhealthyadults.
Asof201516,childrenandadolescentswithneurologicorneurodevelopmentconditions(includingseizuredisorders,febrileseizures
andisolateddevelopmentaldelay)havebeenincludedinthishighriskgroup.ArecentpublicationbytheCanadianImmunization
MonitoringProgramActive(IMPACT)hasdocumentedthattheburdenofinfluenzainfectioninhospitalizedchildrenwithneurological
andneurodevelopmentconditions,eventhosewhoseconditionsdonotobviouslycompromiserespiratoryfunction,issignificant Footnote21.
Overfiveyears(20042009)ofseasonalinfluenzasurveillance,1991childrenwerehospitalizedwithinfluenza,293ofwhomhad
neurologicorneurodevelopmentconditions.These293caseswerefurtheranalyzedtodetermineiftheywouldhavebeenconsideredhigh
riskforinfluenzabasedonanyothervaccineindication.Onehundredandfifteendidnothaveairwaycompromiseoranothervaccine
indication.Thislattergrouppresentedwithseizuresmorefrequentlythanthosewithneurologicandneurodevelopmentconditionsanda
vaccineindication(41.7%vs.26.4%;P=0.006)andrequiredintensivecareunitadmission(20.9%vs.11.8%;P=0.02)andmechanical
ventilation(14.8%vs.4.5%;P<0.001)moreoftenthanchildrenwithoutneurologicorneurodevelopmentconditionbutwithavaccine
indication.Thepreexistingneurologicandneurodevelopmentconditionsincludedthosewithisolatedseizuredisordersincludingfebrile
seizuresandisolateddevelopmentaldelay.Childrenwithneurologicandneurodevelopmentconditionshavethereforebeenaddedtothe
listofconditionsathighriskofinfluenzarelatedcomplicationsorhospitalizationforwhomvaccineisparticularlyrecommended.Inlight
ofthesefindingsinthepaediatricpopulation,NACIwillbefurtherassessingtheinformationavailableforadultswithneurological
conditions.However,itisimportanttonotethatNACIalreadyrecommendsinfluenzavaccineforeveryone6monthsofageandolder
withoutcontraindications.
Peopleofanyagewhoareresidentsofnursinghomesandotherchroniccarefacilities
Suchresidentsoftenhaveoneormorechronicmedicalconditionsandliveininstitutionalenvironmentsthatmayfacilitatethespreadof
influenza.
People65yearsofage
Admissionsattributabletoinfluenzainthisagegroupareestimatedat125to228per100000healthypersons Footnote22,andmortalityrates
increasewithincreasedageFootnote8.
AllChildren6to59monthsofage
Onthebasisofexistingdata,NACIrecommendstheinclusionofallchildren6to59monthsofageamongthespecificallyrecommended
recipientsofinfluenzavaccine.Foradditionaldetailsonchildren2459months,pleaseseetheStatementonSeasonalInfluenzaVaccine
for20122013andforchildren6to23monthspleaseseetheStatementonSeasonalInfluenzaVaccinefor20112012.
PregnantWomen
NACIrecommendstheinclusionofallpregnantwomen,atanystageofpregnancy,amongthespecificallyrecommendedrecipientsof
inactivatedinfluenzavaccineduetotheriskofinfluenzaassociatedmorbidityinpregnantwomen Footnote23,Footnote24,Footnote25,Footnote26,Footnote27,
evidenceofadverseneonataloutcomesassociatedwithmaternalrespiratoryhospitalizationorinfluenzaduringpregnancy Footnote28,Footnote29,
,
,evidencethatvaccinationofpregnantwomenprotectstheirnewbornsfrominfluenzaandinfluenzarelated
hospitalizationFootnote32,Footnote33,Footnote34,Footnote35,andevidencethatinfantsbornduringinfluenzaseasontovaccinatedwomenarelesslikely
tobepremature,smallforgestationalage,andlowbirthweight Footnote36,Footnote37,Footnote38,Footnote39.
ThesafetyofinactivatedinfluenzavaccineduringpregnancyhasbeenreviewedFootnote40.Activestudiesofinfluenzavaccinationduring
pregnancyhavenotshownevidenceofharmtothemotherorfetusassociatedwithinfluenzaimmunization Footnote41.Althoughthe
cumulativesamplesizeofactivestudiesofinfluenzavaccinationinpregnantwomenisrelativelysmall,particularlyinthefirsttrimester,
passivesurveillancehasnotraisedanysafetyconcernsdespitewidespreaduseofinactivatedinfluenzavaccineinpregnancyoverseveral
decadesFootnote23,Footnote24,Footnote40,Footnote42.SurveillancefollowingtheuseofbothadjuvantedandunadjuvantedpH1N1vaccinein>100,000
pregnantwomeninCanadaand>488,000pregnantwomeninEuropehasnotrevealedanysafetyconcernsFootnote43,Footnote44.
Forfurtherdetailsoninfluenzaimmunizationinpregnancyandotherevidencereviewedtoinformthisrecommendation,seethe
StatementonSeasonalInfluenzaVaccinefor20112012andtheStatementonSeasonalInfluenzaVaccinefor20122013.
AboriginalPeoples
BasedonthebodyofevidenceindicatingahigherrateofinfluenzaassociatedhospitalizationanddeathamongAboriginalPeoples,
NACIrecommendstheinclusionofAboriginalPeoplesamongspecificallyrecommendedrecipientsofinfluenzavaccine.
IthasbeenproposedthattheincreasedriskofsevereinfluenzaoutcomesintheAboriginalpopulationsisaconsequenceofmultiple
factors,includinghighprevalenceofchronichealthconditions(e.g.,diabetes,chroniclungdisease,endstagekidneydisease) Footnote45,
obesity,delayedaccesstohealthcareandincreasedsusceptibilitytodiseasebecauseofpoorhousingandovercrowding Footnote46,Footnote47,
Footnote48
.Forfurtherdetailsontheevidencereviewedtoinformthisrecommendation,seetheStatementonSeasonalInfluenzaVaccinefor
20112012.
PeopleCapableofTransmittingInfluenzatoThoseatHighRiskofInfluenzaRelatedComplicationsorHospitalization
Peoplewhoarepotentiallycapableoftransmittinginfluenzatothoseathighriskshouldreceiveannualvaccination,regardlessofwhether
thehighriskpersonhasbeenimmunized.Immunizationofcareprovidersdecreasestheirownriskofillness,aswellastheriskofdeath
andotherseriousoutcomesamongthepatientsforwhomtheyprovidecareFootnote49,Footnote50,Footnote51,Footnote52,Footnote53,Footnote54,Footnote55.
ImmunizationofcareprovidersandresidentsisassociatedwithdecreasedriskofILIoutbreaks Footnote56.Individualswhoaremorelikelyto
transmitinfluenzatothoseatriskofmedicalcomplicationsorhospitalizationduetoinfluenzaincludethefollowinggroups:
HealthCareandotherProvidersinFacilitiesandCommunitySettings
Thisgroupincludeshealthcareworkers(HCWs),regularvisitors,emergencyresponseworkers,thosewhohavecontactwithresidentsof
continuingcareorlongtermcarefacilitiesorresidences,thosewhoprovidehomecareforpersonsinhighriskgroupsandstudentsof
relatedhealthcareservices.
Forthepurposesofthisstatement,HCWsincludeanyperson,paidorunpaid,whoprovidesservices,works,volunteersortrainsina
healthcaresetting.
InfluenzavaccinationprovidesbenefitstoHCWsandtothepatientsforwhomtheycare.NACIconsiderstheprovisionofinfluenza
vaccinationtobeanessentialcomponentofthestandardofcareforallHCWsfortheprotectionoftheirpatients.Thisstandardappliesto
anyperson,paidorunpaid,whoprovidesservices,works,volunteersortrainsinahealthcaresetting.
TransmissionofinfluenzabetweeninfectedHCWsandtheirvulnerablepatientsresultsinsignificantmorbidityandmortality.
RandomizedcontrolledtrialsconductedingeriatriclongtermcaresettingshavedemonstratedthatvaccinationofHCWsisassociated
withsubstantialdecreasesinmorbidityFootnote50,Footnote53,Footnote57andmortalityFootnote49,Footnote50,Footnote52,Footnote53,Footnote57intheresidents.
Therefore,HCWsshouldconsiderittheirresponsibilitytoprovidethehigheststandardofcare,whichincludesannualinfluenza
vaccination.Intheabsenceofcontraindications,refusalofHCWstobeimmunizedagainstinfluenzaimpliesfailureintheirdutyofcare
topatients.
NACIrecommendsthatTIVorQIV,insteadofLAIV,shouldbeusedforHCWsprovidingcaretoindividualswithimmune
compromisingconditions,unlesstheHCWwillonlyacceptLAIV.IfaHCWorotherpersonreceivesLAIVandisprovidingcareto
individualswithsevereimmunecompromisingconditions(definedashospitalizedandrequiringcareinaprotectedenvironment),they
shouldwaittwoweeksfollowingreceiptofLAIVbeforecontinuingtoprovidecaretosuchindividuals.
Toprotectvulnerablepatientsduringinfluenzaoutbreaks,HCWswithconfirmedorpresumedinfluenzaandunvaccinatedHCWswho
arenotreceivingantiviralprophylaxisshouldbeexcludedfromdirectpatientcontact.Healthcareorganizationsshouldhavepoliciesin
placetodealwiththisissue.
Householdcontacts,bothadultsandchildren,ofindividualsathighriskofinfluenzacomplications,whetherornottheindividual
athighriskhasbeenimmunized
Theseindividualsincludehouseholdcontactsofindividualsathighriskofinfluenzarelatedcomplicationsorhospitalization,aslisted
earlier,includinghouseholdcontactsofthose59monthsofage,andhouseholdcontactsofinfants<6monthsofage(whoareathigh
riskofcomplicationsfrominfluenzabutforwhominfluenzavaccineisnotauthorized);andmembersofahouseholdexpectinga
newbornduringtheinfluenzaseason.
Theyalsoincludethoseprovidingregularchildcaretochildren59monthsofage,whetherinoroutofthehome,andthosewhoprovide
serviceswithinclosedorrelativelyclosedsettingstopersonsathighrisk(e.g.,crewsonships).
Others
Peoplewhoprovideessentialcommunityservices
Vaccinationfortheseindividualsshouldbeencouragedtominimizethedisruptionofservicesandroutineactivitiesduringannual
epidemics.Employersandtheiremployees,includinghealthyworkingadults,shouldconsideryearlyinfluenzaimmunization,asthis
interventionhasbeenshowntodecreaseworkabsenteeismduetorespiratoryandrelatedillnesses.
Peopleindirectcontactduringcullingoperationsinvolvingpoultryinfectedwithavianinfluenzaorswineworkers
NACIrecommendsimmunizationagainstseasonalinfluenzaforpeopleindirectcontactwithpoultryinfectedwithanavianinfluenza
duringcullingoperationsastheseindividualsmaybeatincreasedriskofavianinfluenzainfectionbecauseofexposureduringtheculling
operation(seebelow)Footnote58,Footnote59,Footnote60,Footnote61.However,NACIhasconcludedthatthereisinsufficientevidenceatthistimeto
specificallyrecommendroutineinfluenzaimmunizationforswineworkers.Informationinformingthisrecommendationcanbefoundin
theStatementonSeasonalInfluenzaVaccinefor20132014.
Althoughseasonalinfluenzaimmunizationwillnotpreventavianinfluenzainfection,somecountries Footnote62andprovinces,have
recommendedinfluenzaimmunizationonayearlybasisfortheseworkersbasedontherationalethatpreventinginfectionwithhuman
influenzastrainsmayreducethetheoreticalpotentialforhumanavianreassortmentofgenesshouldsuchworkersbecomecoinfected
withhumanandavianinfluenzavirusesFootnote63.Itshouldbenotedthatvaccinationwithseasonalinfluenzavaccinewillnotproduce
protectiveantibodiesagainstthehumanvaccinestrainsforapproximately14days.
Directinvolvementmaybedefinedassufficientcontactwithinfectedpoultrytoallowtransmissionofanavianvirustotheexposed
person.Therelevantindividualsincludethoseperformingthecull,aswellasotherswhomaybedirectlyexposedtotheavianvirus,such
assupervisingveterinariansandinspectors.Itisessentialthatbiosecuritymeasuressuchaspersonalprotectiveequipmentandantivirals
beused.Forfurtherinformationregardingrecommendationsduringadomesticavianinfluenzaoutbreak,seetheAgencyguidanceat
http://www.phacaspc.gc.ca/publicat/daioenia/pdf/nataiguide2006_e.pdf.
IV.ChoiceofProduct
Withtherecentavailabilityofanumberofnewvaccines,someofwhicharedesignedtoenhanceimmunogenicityinspecificagegroups,
thechoiceofproductisnolongerstraightforward.Table2insectionIIsummarizesNACIscurrentrecommendationsforthechoice(s)of
currentlyavailableinfluenzavaccinesinspecificageandriskgroups.Moredetailsalongwithbriefsupportingrationaleareoutlinedhere.
FurtherdetailforthetrivalentformulationofFluMist,andFluadcanbefoundinsupplementaryNACIstatementsforeachproductFootnote
64 Footnote65
,
.FurtherdetailregardingquadrivalentinfluenzavaccinescanbefoundintheStatementonSeasonalInfluenzaVaccinefor
20142015andintheliteraturereviewregardingquadrivalentinfluenzavaccines,availableviatheNACIwebsite.
PaediatricConsiderations
Thefirsttimethatchildren<9yearsofagereceiveseasonalinfluenzaimmunization,atwodosescheduleisrequiredtoachieve
protectionFootnote66,Footnote67,Footnote68.Severalstudieshavelookedatwhetherthesetwoinitialdosesneedtobegiveninthesameseason Footnote
,
,
.Englundetal.reportedsimilarimmunogenicityinchildren623monthsofagewhethertwodosesweregiveninthe
sameorseparateseasonswhentherewasnochange,oronlyminorvaccinestrainchange,invaccineformulationbetweenseasons Footnote11,
Footnote12
.However,seroprotectionratestotheBcomponentwereconsiderablyreducedinthesubsequentseasonwhentherewasamajorB
lineagechange,suggestingthatthemajorchangeinBviruslineagereducedtheprimingbenefitofpreviousvaccination Footnote10,Footnote12.
IssuesrelatedtoeffectiveprimeboostwhenthereisamajorchangeininfluenzaBlineageacrosssequentialseasonsrequiresfurther
evaluationFootnote70.Becausechildren623monthsofagearelesslikelytohavehadpriorprimingexposuretoaninfluenzavirus,special
effortiswarrantedtoensurethatatwodosescheduleisfollowedforpreviouslyunvaccinatedchildreninthisagegroup.
Publishedandunpublishedevidencesuggestmoderateimprovementinantibodyresponseininfants,withoutanincreasein
reactogenicity,withtheuseoffullvaccinedoses(0.5mL)forunadjuvantedinactivatedinfluenzavaccines Footnote71,Footnote72.Thismoderate
improvementinantibodyresponsewithoutanincreaseinreactogenicityisthebasisforthefulldoserecommendationforunadjuvanted
inactivatedvaccineforallages.Formoreinformation,refertoStatementonSeasonalInfluenzaVaccinefor20112012.
Inchoosingavaccineproductforthepaediatricagegroup,itisimportanttoconsiderthefollowing:
theburdenofinfluenzaBdiseaseinthepaediatricpopulationbeingcaredfor;
thepotentialformismatchbetweenthepredominantcirculatingstrainofinfluenzaBandthevaccinestraingivenhistorical
trends;and
theefficacy,immunogenicityandsafetyprofileofthevaccine.
WiththeavailabilityofQIV,itisimportanttoevaluatetheburdenofinfluenzaBtoconsidertheimpactofprotectionfromhavingbothB
lineagestrainsinthevaccine.Canadiansurveillancedatafrom200102to201213hasshownthatinfluenzaBstrainsaccountedfor17%
oflaboratoryconfirmedtestsforinfluenza.Previously,inanticipationofQIVsentrancetotheCanadianmarket,NACIhadassessedthat
theburdenofinfluenzaBishighestinpeoplelessthan20yearsofage.Children<24monthsofagemakeupapproximately2%ofthe
CanadianpopulationFootnote73.Usingcasebasedlaboratorydatafrom2001to2012,children023monthsofageaveraged(excluding2009)
10.8%ofreportedinfluenzaBcases(range8.3%to13.7%).Withrespecttosevereoutcomes(e.g.,hospitalization,ICUadmissionand
death),influenzaBwasconfirmedin15.1%to58.2%ofpaediatricinfluenzaassociatedhospitalizations(children16yearsofage)
reportedbyIMPACTbetween2004/05and2012/13(excludingthe20092010pandemicseason).Theproportionofhospitalizationsdue
toinfluenzaBrelativetoallinfluenzahospitalizationshasbeengenerallysimilartotheproportionofinfluenzaBdetectionsinthe
generalpopulationduringthesametimeperiod.AdditionalinformationcanbefoundintheStatementonSeasonalInfluenzaVaccinefor
20142015.
IntheNACILiteratureReviewonQuadrivalentInfluenzaVaccines,areviewofBlineageantigensincludedintheCanadianinfluenza
vaccinesandthecirculatingstrainseachseasonindicatesamatchin5ofthe12seasonsfrom20012002throughto20122013,a
moderatematch(about50%fromeachlineage)in1season,andamismatchinremaining6influenzaseasons(70%ofthecharacterized
Bstrainswereoftheoppositelineagetotheantigeninthatseasonsvaccine).
Children6to23monthsofage
Therearethreetypesofvaccineauthorizedforuseinthisagegroup:TIV,QIVandadjuvantedTIV(ATIV).
Choiceofvaccineproductforchildren6to23monthsofage
ATIVhasrecentlybeenmadeavailableforuseinchildren623months.ThereiscurrentlyinsufficientefficacydataonATIVcompared
tounadjuvantedTIVorQIVtodeterminetherelativeclinicalbenefitofATIV.ThereislimitedbutconsistentevidencethatATIVis
moreimmunogenicthanunadjuvantedTIVagainstinfluenzaAtypes.Inparticular,asingledoseofATIVismoreimmunogenicthana
singledoseofunadjuvantedTIV.However,twodosesofATIVarestillnecessarytoachieveasatisfactoryimmuneresponseagainst
influenzaB.SafetydatashowedATIVwasmorereactogenicthanunadjuvantedTIV,withrecipientsexperiencing1015%moresolicited
localandsystemicreactions.However,mostreactionsweremildandresolvedquickly.(SeeSectionV.Vaccinepreparationsavailablefor
useinCanadaformoreinformationonATIV.)
Forchildren623months,NACIrecommendsthatgiventheburdenofinfluenzaBdisease,QIVshouldbeused.IfQIVisnotavailable,
eitherunadjuvantedoradjuvantedTIVshouldbeused.
Children2to17yearsofage
Therearethreetypesofvaccineauthorizedforuseinthisagegroup:TIV,QIVandLAIV.
Choiceofvaccineproductforchildren2to17years
NACIrecommendsLAIVuseforhealthychildrenandadolescents2to17yearsofagewhodonothavecontraindicationstothisvaccine.
ThereisevidenceforthepreferentialuseofLAIVinyoungchildren(youngerthan6yearsofage)basedonsuperiorefficacyoftrivalent
LAIVcomparedtoTIV(GradeA),withweakerevidenceofsuperiorefficacyinolderchildren(GradeI).
Basedonexpertopinion,thecomparativeefficacydatawhichsupportedthepreferentialrecommendationsforthetrivalentformulationof
LAIVarealsoapplicabletothequadrivalentformulationofLAIVbecausethemanufacturingprocessesandimmunologicmechanismof
thequadrivalentLAIVandthetrivalentLAIVproductsarethesame.Thisexpertopinionissupportedbytheresultsofthenoninferiority
studiescomparingtrivalentandquadrivalentformulationsofLAIV,whichwererequiredbyregulatorybodiestoauthorizetheuseofthe
QLAIVformulation.ComparativevaccineefficacyandeffectivenessdataofTIVorQIV,andthequadrivalentformulationofLAIVare
notavailable.ItisanticipatedthatthesuperiorefficacyforLAIVoverTIVextendsbeyondage6years,buttheevidencedoesnot
indicateatwhichspecificagetheefficaciesofLAIVandTIVbecomeequivalent.GiventheburdenofinfluenzaBdiseaseinchildren,if
LAIVisnotavailableforthoseforwhomitisconsideredsuperior,QIVshouldbeused.IfQIVisnotavailable,TIVshouldbeused.
ForchildrenwithunderlyingconditionsorcontraindicationsthatprecludetheuseofLAIV,NACIalsorecommendsthat,giventhe
burdenofinfluenzaBdisease,QIVshouldbeused.IfQIVisnotavailable,TIVshouldbeused.Morespecifically,for:
Healthychildren:ifLAIVisnotavailableforthoseforwhomitisconsideredsuperior,NACInowrecommendsthatQIVshould
beusedinthisagegroup.IfQIVisnotavailable,TIVshouldbeused.
Childrenwithimmunecompromisingconditions,whichareacontraindicationtoLAIV:GiventheburdenofinfluenzaBdisease
inchildren,QIVshouldbeused.IfQIVisnotavailable,TIVshouldbeused.
Childrenwithsevereasthma(asdefinedinSectionIIunderContraindicationsandPrecautions)ormedicallyattendedwheezing
intheprevioussevendays:GiventheburdenofinfluenzaBdiseaseinchildren,QIVshouldbeused.IfQIVisnotavailable,
TIVshouldbeused.
Childrenwithotherchronichealthconditions:LAIVcanbeusedinthisgroup.Ifinactivatedvaccineisbeingused,giventhe
Healthychildrenandadolescents217yearsofage
Withrespecttotheliveattenuatedinfluenzavaccine,NACIrecommendsitsuseforhealthychildrenandadolescents2to17yearsofage
whodonothavecontraindicationstothisvaccine.
Aspreviouslynoted,thereisevidenceforthepreferentialuseofLAIVinyoungchildren(youngerthan6yearsofage)basedonsuperior
efficacyoftrivalentLAIVcomparedtoTIV(GradeA),withweakerevidenceofsuperiorefficacyinolderchildren(GradeI).Itis
anticipatedthatthesuperiorefficacyofLAIVoverTIVextendsbeyondage6years,buttheevidencedoesnotindicateatwhichspecific
agetheefficaciesofLAIVandTIVbecomeequivalent.Basedonexpertopinion,thisisexpectedtoapplytoquadrivalentLAIVaswell.
GiventheburdenofinfluenzaBdiseaseinchildren,ifLAIVisnotavailableforthoseforwhomitisconsideredsuperior,QIVshouldbe
used.IfQIVisnotavailable,TIVshouldbeused.
TwostudieshavedirectlycomparedtheefficacyofLAIVandTIVinyoungerchildren(uptoage5and6)andonestudyhascompared
theefficacyofLAIVandTIVinasthmaticchildren6to17yearsofageFootnote74,Footnote75,Footnote76.NACIrecognizesthatthereare
differencesinlevelsofevidenceforyoungerandolderchildren.ThereismoreevidencethatdirectlycomparesTIVandLAIVefficacy
andthatshowssuperiorefficacyofLAIVinchildrenyoungerthan6yearsofagethaninolderchildren.Also,forchildrenunder6years
ofage,theevidenceforthesuperiorityofLAIVisofhigherqualityandtheestimateofefficacyishigher,comparedtotheonestudy
performedonchildren6to17yearsold.
ThestudybyFlemingetal.(2006)lookingat2229asthmaticchildren617yearsofage(meanage11)showedsuperiorefficacyofLAIV
overTIVinthisagegroupFootnote74.TheseresultsseemtohavebeenmostlydrivenbyinfluenzaBandwerenotsignificantfortheH3N2
strain.Althoughthestudyhaslimitations,suchasthefactthatthestudypopulationwasasthmaticandsomaynotbegeneralizabletoall
children,itsstrengthsincludearandomizeddesignandcultureconfirmedoutcome.
Itishypothesizedthataschildrengetolder,theyaremorelikelytohavehadpreviousinfluenzainfection,whichmightinterferewiththe
immuneresponseelicitedtoLAIV.ItisnotknownatwhatageLAIVefficacyisnolongersuperiortoTIVinchildren,andmayvary
frompersontoperson,dependingontheirexperiencewithvariousinfluenzaviruses.Inadults,comparativeefficacytrialsofLAIVand
TIVhaveshowneithernodifferenceorsuperiorefficacyofTIV.Moreevidenceisneededthatdirectlycomparestheefficacyand
effectivenessofLAIVandTIVorQIV,especiallyinchildrenover6yearsoldandNACIconsidersthisaresearchpriority.
NACIalsoacknowledgesthatLAIVoffersotheradvantagestochildren,includingneedlefreeadministration.Also,asalive,replicating
wholevirusformulationadministratedintranasally,itelicitsmucosalimmunitywhichmaymorecloselymimicnaturalinfectionand
contributetothesuperiorefficacycomparedtoTIV.
Childrenwithimmunecompromisingconditions
NACIrecommendsagainstLAIVforindividualswithimmunecompromisingconditions.(NACIRecommendationGradeD).Giventhe
Livevaccinesaregenerallycontraindicatedinpeoplewithimmunecompromisingconditions,withsomeexceptions.NACIconcludes
thatthereisinsufficientevidencesupportingtheuseofLAIVinthosewithimmunecompromisingconditions,intermsofbothsafetyand
effectiveness.ThetrivalentformulationofLAIVhasbeenadministeredtoapproximately170childrenandadultswithmildtomoderate
immunesuppressionduetoHIVinfectionsand10childrenwithmildtomoderateimmunesuppressionduetocancer.Althoughthese
smallstudiesdemonstratedasimilarsafetyprofiletohealthyindividuals,basedonexpertopinion,NACIconcludesthattheuseofLAIV
inthispopulationiscontraindicated.
Childrenwithasthma
NACIrecommendsthatLAIVcanbeusedinchildren24monthsandolderwithstable,nonsevereasthma.(NACIRecommendation
GradeB).
LAIVshouldnotbeusedinthosewithsevereasthma(asdefinedascurrentlyonoralorhighdoseinhaledglucocorticosteriodsoractive
wheezing)andthosewithmedicallyattendedwheezinginthe7dayspriortovaccination.
AstudyoftrivalentLAIVfoundincreasedratesofwheezinginchildren623monthsofagewhencomparedtoTIV Footnote77.Children2
yearsofageandolderandadolescentswithasthmawhoreceivedLAIVinclinicaltrialsshowedthattherewasnosignificantdifference
betweenLAIVandTIVintheexacerbationofasthmapostvaccination.SeveralstudiesdemonstratedthatthetrivalentLAIViswell
toleratedinasthmatics,andithasbeendemonstratedtohaveahigherrelativeefficacycomparedtoTIVwithmatchedandmismatched
strainsFootnote74.NACI'sreviewofcurrentevidenceontheuseofLAIVinchildren2yearsofageandoverwithasthmaandwheezing
supportstheuseofLAIVinstable,nonsevereasthmatics;however,NACIrecommendsagainstLAIVinthosewithsevereasthmaor
medicallyattendedwheezingintheprevioussevendays.GiventheburdenofinfluenzaBdiseaseinchildren,QIVshouldbeused.IfQIV
isnotavailable,TIVshouldbeused.
Childrenwithotherchronichealthconditions
NACIrecommendsthatLAIVcanbeusedinchildrenwithchronichealthconditions(excludingthosewithimmunecompromising
conditionsandsevereasthma,asdefinedabove).(NACIRecommendationGradeB).
Alimitednumberofimmunogenicityandefficacystudieshavebeenconductedinthispopulation.Basedonexpertreview,itisexpected
thatLAIVshouldbeasimmunogenicandefficaciousinimmunecompetentchildrenwithchronichealthconditionsasitisinhealthy
children.
Atthistime,thereisinsufficientevidencetorecommendLAIVpreferentiallyoverinactivatedvaccinesinchildrenwithchronichealth
conditions.Ifinactivatedvaccineisbeingused,giventheburdenofinfluenzaBdiseaseinchildren,QIVshouldbeused.IfQIVisnot
available,TIVshouldbeused.
ACanadianstudyconductedbyBoikosetal.(2014)duringthe201213seasonfollowedacohortof168participants,218yearsofage
withcysticfibrosisfor56daysfollowingadministrationoftrivalentLAIVtoevaluatethesafetyofLAIVinthispopulation(see
AppendixBforevidencetable)Footnote78.Individualswereexcludediftheywereusingsystemiccorticosteroids,considered
immunosuppressed,orhadnasalpolypsorrhinorrheaconsideredsignificantenough(byvaccinator)topreventLAIVfromreachingthe
nasalmucosa.Overall,LAIVwasfoundtobewelltoleratedbythestudyparticipants.Whencomparingtheatriskperiod(028dayspost
receiptofLAIV)tothenonatriskperiod(2956dayspostLAIV),therewasnosignificantincreaseintherateofincidentrespiratory
deteriorations[incidentrateratio(IRR):0.72(95%CI:0.11,4.27)]orallcausehospitalizationswasobserved[IRR:1.16(95%CI:0.30,
4.81)].Atleastonesolicitedadverseeventwasreportedinthefirstweekfollowingvaccinationby64%ofparticipants.Themostfrequent
symptomsreportedincludedfever,runnynose,nasalcongestion,headaches,andtiredness.Thirteencasesofwheezingwerereported
[RR:4.33(95%CI:1.26,14.93)],withthegreatestincidenceoccurringduringthedayofvaccination.Of15participantswhoreported
rednessinbotheyes,13werereportedduringthefirstthreedayspostvaccination,andallreportsoffacialswelling(n=10)alsooccurred
duringthesametimeperiod.Mostofthesesymptomsoccurredwithin24hoursofvaccinationandwerecompatiblewithoculo
respiratorysyndrome.
Cysticfibrosisisaconsideredahyperinflammatorydisorder,andunlesstreatedwithimmunosuppressivedrugs,suchasprolonged
systemiccorticosteroids,childrenwithcysticfibrosisarenotconsideredimmunosuppressed,andmayreceiveLAIV.Thefindingsinthe
studybyBoikosetal.(2014)providereassurancethatLAIVissafeforuseinthispopulation.
NACIrecommendsthatchildrenwithcysticfibrosismayreceiveLAIViftheindividualisnotbeingtreatedwithimmunosuppressive
drugs,suchasprolongedsystemiccorticosteroids,andmeetstheothercriteriaforLAIVadministration.
Adults
Adults1859yearsofage
Therearethreetypesofvaccineavailableforuseinadults1859yearsofage:TIV,QIVandLAIV.Forhealthyadultsinthisagegroup,
NACIconsidersallthreetypesofvaccinetobeacceptablechoices(unlesscontraindicated).
Foradultsinthisagegroupwithchronichealthconditions,TIVorQIVmaybeused.
AdditionalinformationcanbefoundintheNACIstatement:Recommendationsontheuseoflive,attenuatedinfluenzavaccine
(FluMist):SupplementalStatementonSeasonalInfluenzaVaccinefor20112012.
Adults6064yearsofage
Thevaccinesavailableforuseinadults6064yearsofage,withorwithoutchronichealthconditions,areTIVandQIV.
Adults65yearsofage
Threetypesofvaccineareavailableforuseinadults65yearsofage:TIV,QIVandMF59adjuvantedTIV.
Pregnantwomen
TIVandQIVareavailableforuseinpregnantwomen.Duetoalackofsafetydataatthistime,LAIV,whichisaliveattenuatedvaccine,
shouldnotbeadministeredtopregnantwomen,butitcanbeadministeredtobreastfeedingwomen.
Coadministrationwithothervaccines
NACIhasreviewedthepotentialforimmuneinterferencewhenlivevaccinesareadministeredsequentiallywithinashorttimeperiod
(lessthan4weeks).Ingeneral,NACIrecommendsthattwoliveparenteralvaccinesbeadministeredeitheronthesamedayoratleast
fourweeksapartFootnote162.Intheory,theadministrationoftwolivevaccinessequentiallywithinlessthan4weekscouldreducethe
efficacyofthesecondvaccine.Possibleimmunemechanismsinclude(i)theinhibitoryandimmunomodulatoryeffectsofsystemicand
locallyproducedcytokinesonBandonviralreplicationandTcellresponse(ii)immunosuppressioninducedbycertainviruses(suchas
measles);and(iii)directviralinterferenceasaresultofcompetitionforacommonniche.Mucosalvaccinesmayhavelessimpactona
parenteralvaccineandviceversa.Theimmuneresponsewithamucosalvaccinemaybecompartmentalizedtothemucosawhilethattoa
parenteralvaccineissystemic.Itislikelythatthereissomeinteractionbetweenthesystemicandmucosalcompartments;however,the
extenttowhichthisinteractionoccursisnotknown.
Giventhelackofdataforimmuneinterference,basedonexpertopinion,NACIrecommendsthatLAIVcanbegiventogetherwithorat
anytimebeforeoraftertheadministrationofanyotherliveattenuatedorinactivatedvaccine.NACIrecognizesthatsomevaccine
providersmaychoosetogiveLAIVandotherlivevaccinessimultaneouslyorseparatedbyatleast4weekstoavoidanypossibilityof
immuneinterference.Alternatively,aninactivatedinfluenzavaccine(TIVorQIV)maybegiven.

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6months 6months 259years

9 - 14.5 kg (20 - 32 lb) 0.1 - 0.2 mg

0.01 mg/kg body weight Not applicable

0.15 - 0.3 mgTable 1 - Footnote

Junior dose of 0.15 mg

0.2 - 0.3 mgTable 1 - Footnote 2

Junior dose of 0.15 mg

0.3 mgTable 1 - Footnote 2

If , less than 30 kg (66 lbs) give Junior

0.5 mgTable 1 - Footnote 3

Give standard dose of 0.3mg

Table 2: Dose of diphenhydramine hydrochloride, by age

Dose of diphenhydramine hydrochloride

7-12 kg (15-25 lbs)

12-25 kg (25-55 lbs)

25-45 kg (55-99 lbs)

12 years and older

45 kg + (99 lbs or more)

10.What documentation must the pharmacist complete when providing Ministry-funded

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