2017

Early risk assessment:What to expect of the 2017/18 influenza season in Norway

REPORT

Earlyriskassessment:

Whattoexpectofthe2017/18influenzaseasoninNorway

DepartmentofInfluenza

What to expect of the 2017/18 influenza season in Norway • Norwegian Institute of Public Health

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PublishedbyNorwegianInstituteofPublicHealthDivisionofInfectionControlandEnvironmentalHealthDepartmentofInfluenzaDecember2017

Title:Earlyriskassessment:Whattoexpectofthe2017/18influenzaseasoninNorway

Author(s):DepartmentofInfluenza

Thereportcanbedownloadedaspdfatwww.fhi.no/en/publ/

Graphicdesigntemplate:PerKristianSvendsenandGreteSøimer

Graphicdesigncover:FeteTyper

MeSH:influenza,publichealthsurveillance,influenzaseason2017-18,riskassessment,influenzavaccine

Citation:DepartmentofInfluenza.Earlyriskassessment:Whattoexpectofthe2017/18influenzaseasoninNorway.Report2017.Oslo:NorwegianInstituteofPublicHealth,2017.

What to expect of the 2017/18 influenza season in Norway • Norwegian Institute of Public Health

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What to expect of the 2017/18 influenza season in Norway • Norwegian Institute of Public Health

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Tableofcontents

Scope_____________________________________________________________________________ 5

Summaryprospectsforthe2017/18season _____________________________________________ 6

Summaryoftheprevious2016/2017season_____________________________________________ 7

The2017/18seasonthisfar __________________________________________________________ 8Influenza-likeillnessinprimaryhealthcare 8Severeinfluenza 8Laboratoryconfirmedinfluenza 9Geneticcharacterizationsofthevirusesincirculation 12Antiviralsusceptibility 14Vaccine 14

Vaccinematch 14Vaccinedistributionandcoverage 15

Infectioncontrolmeasures 15Pre-seasonpopulationimmunitytoinfluenza,August2017 16

TheNationalSeroepidemiologicalInfluenzaProgramme 16Summaryofoutcomes 16HighseroprevalencestoinfluenzaAvirusesinAugust2017 16LowtomoderateseroprevalencestoinfluenzaBvirusesinAugust2017 18ImmunityagainstanewinfluenzaB/Victoria-lineagehemagglutinindoubledeletionvariant 18

Acknowledgements________________________________________________________________ 19

References _______________________________________________________________________ 20

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Scope

ThisreportpresentstheassessmentbytheNorwegianInstituteofPublicHealth(NIPH)ontheinfluenzasituationearlyinthe2017/2018season,andpossiblecharacteristicsoftheupcominginfluenzaoutbreakinNorway.Thereportisbasedondatafromalate-summerserosurvey,early-seasonsurveillancedata,vaccinesalesandexperiencefrompreviousinfluenzaseasons.Thereportismeanttosupportcapacityplanninginthehealthservices,providebackgroundinformationtoinfectioncontrolandotherhealth-careandpublichealthpersonnel,aswellastoprovidein-depthinformationoninfluenzaoutbreaksingeneral.Atthispoint,asthe2017-2018outbreakisbeginningtounfold,itisofparticularinteresttoassessthedifferentcirculatinginfluenzaviruses,theireventualspread,andhowthiswillinfluencetheextentofillness,severeillnessandmortalityinvariousriskandagegroups.ThereportisthisyearwritteninEnglish,sincewepresumethatthepre-seasonimmunityandearlysurveillancedataanalysismaybeofinterestbeyondNorway.

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Summaryprospectsforthe2017/18season

• Influenzaactivityiscurrentlyverylow.Virusdetectionshavestartedtoincreaseearly,butisnotescalatingasfastaslastyear.NoticeableoutbreakactivitybyChristmas/NewYearislikelybutthemainoutbreakmaypeaklater.

• UptonowinfluenzaA(H3N2)detectionshavebeeninmajoritybutB/Yamagatalineagevirusesatpresentappeartobeincreasingmore.InfluenzaA(H1N1)pdm09andB/Victoria-lineagevirusesappeartoplayaminorrolesofar.

• IncreasedpopulationimmunitymeasuredinantibodiesagainstinfluenzaA(H1N1)pdm09andA(H3N2)inbloodsamplescollectedinAugust2017,particularlyinagegroupsimportantforvirusspread,mightlimitcirculationofthesevirusescomparedtothelasttwowinters.AlowerproportionhasantibodiesagainsttheinfluenzaBviruses.

• Theeventualmagnitudeoftheoutbreakcannotbeforecasted.• InfluenzaA(H3N2)andinfluenzaB/Yamagatalineageviruses,ofvariantssimilar

tovirusescirculatinglastwinter,arethemostlikelycandidatesforpredomination.BoththerecentincreaseininfluenzaBandthehighprevalenceofantibodiesagainstA(H3N2)virusesspeakinfavouroftheB/Yamagatavirus.However,itisstilltooearlytotellwhichofthetwowillbeinmajority,andthismayalsocometovarybyregion.

• BoththeA(H3N2)andB/Yamagatalineagevirusestendedtoinfecttheelderlylastwinterbutincurrent-seasonearlydatatheelderlyarenotequallyprominentamongtheinfected.However,earlydataonhospitalisedinfluenzacasesindicatethattheseviruseswillmostlikelycausemostdiseaseandsevereoutcomesamongtheelderly.

• ThevaccineeffectagainstthecirculatingH3viruseswillprobablybelowtomoderate.ThevaccineeffectagainstB/Yamagatawillalsoprobablybelowtomoderate,sincethisvirusstrainisnotincludedinthevaccine.However,somecrossprotectionbetweenB/Victoria,whichisincludedinthevaccine,andthecirculatingB/Yamagataisexpected.

• Vaccinationisthebestmeasuretopreventsevereinfluenzainhigh-riskgroups.Sincetheeffectofinfluenzavaccinesvary,useofantiviralsshouldalsobeconsidered,bothforvaccinatedandunvaccinatedpeopleandinparticularforriskgroups.

Influenzaoutbreaksareintheirverynatureunpredictable.TheNIPHmonitorsthesituationcloselyandmayaddupdatestotheassessmentasneeded.Influenzasurveillancedataarepublishedweeklyonwww.fhi.no/influensa.

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Summaryoftheprevious2016/2017season

In2016/2017,theinfluenzaepidemicstartedunusuallyearly.ThemainoutbreakpeakedaroundChristmas/NewYear(Fig.1)andwasdominatedbyinfluenzaA(H3N2),geneticgroup3C.2a.InfluenzaB/Yamagata-lineagevirusesculminatedverylatewithaminorpeakinmid-May,butthetotalnumberofdetectionswaslow.FortheNorwegianpopulationasawhole,lastseason’sinfluenzaepidemicwasofmediumintensity(Fig.1).However,forpeople65yearsorolder,theepidemicwasofextraordinaryintensity.Ahighproportionofelderlyvisitedgeneralpractitionersoremergencyclinicsandseveraloutbreaksinnursinghomeswerereported.Theincidenceofelderlythatwashospitalisedduetoinfluenzawashighercomparedtotheprevioustwoseasons.Theinfluenzaepidemicwasestimatedtohavecausedabout1700excessdeathsattributabletoinfluenza,withmostdeathsoccurringintheelderly.

Lastseasontheapproximatenumberofvaccinedosesusedwas533000doses,ofwhichthemajoritywasusedforpeopleover65years.Thevaccineeffectwasdeemedasmoderateagainstthecirculatingstrains.

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The2017/18seasonthisfar

Influenza-likeillnessinprimaryhealthcare

Sinceweek40/2017,theoccurrenceofinfluenza-likeillness(ILI)inNorwayhasbeenverylow(Fig.1).TheproportionofpatientsdiagnosedwithILIatgeneralpractitionersandemergencyclinicshasslowlyincreasedfrom0.3%inweek43/2017to0.5%inweek48/2017.Todeterminethestartofthisseason’sinfluenzaoutbreak,thresholdvalueshasbeencalculated,usingtheMovingEpidemicMethod(MEM)(1).Thisyear’soutbreakisdefinedtostartwhentheILI%reaches0.80%.Thismeansthataccordingtothismeasure,inweek48/2017,thisseason’sinfluenzaoutbreakhadnotyetstarted.AlmostallcountiesinNorwayhadverylowinfluenzaactivityinweek48,buttheILI%variedbetweenthecounties.Twocounties,OsloandFinnmarkhadbothcrossedtheoutbreakthreshold,withILIproportionsof0.9%,whichindicateslowinfluenzaactivity.

Figure1.Theproportionofpatientsdiagnosedwithinfluenza-likeillness(ILI)atgeneralpractitionersandemergencyclinicsinNorway2012-2017.

DespiteofverylowILIactivitysofar,fromweek40/2017toweek48/2017,twoconfirmedoutbreaksofinfluenzaA-viruswerereportedfromnursinghomes,whichisearlyandindicateslocalinfluenzaviruscirculation.Overall,thesurveillanceresultsfromprimaryhealthcaresuggeststhattheoccurrenceofILIwillcrossthenationaloutbreakthresholdwithinthenextthreetofourweeks.However,thereisstilluncertaintiesabouthowfasttheinfluenzaactivitywillincreaseandwhenthepeakoftheoutbreakisreached.ThepeaknormallyculminateseitheraroundNewYearoraftermid-February(Fig.1).

Severeinfluenza

Fromweek40/2017throughweek48/2017influenzavirushasbeendetectedin84(1.4%)ofthe5924hospitalisedpatientsthathavebeentested.Ofthese,47personshavebeen60yearsorolder.InfluenzaAvirushasbeendetectedin66hospitalisedpatients,whereasinfluenzaBvirushasbeendetectedin18hospitalisedpatients.Eventhoughthe

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numberofhospitalisedpatientsisstilllowerthisseasonwhencomparedwiththenumberofhospitalisationsatthesametimelastseason,theseresultssuggestthatthisyear’sinfluenzaoutbreakmayalsocausemostseverediseaseinpeopleaged60yearsorolder.InfluenzaA(H3N2)andinfluenzaB-Yamagatavirusesarebothknowntocausemostseverediseaseinthisagegroup.Thismeansthathospitalisationsandinfluenzarelatedexcessdeathsareexpectedinthisagegroup,buttheextentdependsonhowwidespreadA(H3N2)becomesanditmaybelimitedbypre-existingimmunity(seesectionaboutpre-seasonpopulationimmunitytoinfluenza,August2017)inthispartofthepopulationsinceaverysimilarH3viruscirculatedwidelyinthisagegroupduringtheoutbreaklastseason.

ThereportingfromtheNorwegianIntensiveCareRegistryofinfluenzapatientsinICUstartedinweek46/2017.Sinceweek46,twoconfirmed(usingICD-10diagnosticcodeJ10)andninesuspected(J11)influenzacasesinICUwerereported.NodeathsofinfluenzapatientsinICUhasbeenreportedsofar.

Sinceweek40/2017throughweek47/2017,noexcessall-causemortalityhasbeenobserved.

Laboratoryconfirmedinfluenza

Theextentoftestingforrespiratorypathogenshasbeenincreasingyearbyyear(Fig.2),andinfluenzatestingistypicallyperformedaspartofabroadertestingscheme.Duringthe2016/17season,outcomesofmorethan160000influenzatestswerereportedtoNIPH.

Figure2.Weeklynumberofspecimenstestedforinfluenzavirus,thisseasonandthepreviousthreeseasons.

BasedondatafromanumberofotherlaboratoriesinNorway,themostfrequentlydetectedpathogenthisautumnhasbeenrhinoviruswithMycoplasmapneumoniaealsobeingwidespreadandotherpathogens,includinginfluenzavirus,beingconsiderablylesscommon.

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Nevertheless,duetotheextentoftesting,thereweresporadicdetectionsofinfluenzavirusesduringeveryweekthroughthesummer,ashasalsobeenthecaseinallrecentyears.AnincreaseofinfluenzaAvirusdetectionsbeganinmid-October(week43)andhascontinuedthroughweek48,butwithaslightdropbothinnumberofpositivesandproportionpositiveinweek47.InfluenzaBvirusdetectionsdidnotincreasemuchuntilitmorethandoubledinweek46,andbyweek48ithasalmostcaughtupwiththeweeklynumberofinfluenzaAdetections.

Figure3.Laboratorydetections,Norway,startof2017-2018season,comparedwithprecedingseasons.Theleft-handpanelshowstheweeklynumberofinfluenzavirusdetections,theright-handpanelshowstheweeklyproportionofinfluenzaviruspositivesamongthosetested.Whereasthetestsensitivityprobablyhasnotchangedduringtheyearscoveredbythegraph,thenumberofspecimenstestedhasrisengradually.

Whencomparingpositivityrateswithpreviousseasons(Fig.3,right-handpanel),thecoursesofarisalignedwithseasonsthatpeakedwellafterNewYear.Therefore,althoughthenumberofinfluenzacasesarealreadyincreasingandhigherthanmostpreviousseasonsatthistimeofyear,itcannotbeconcludedthatactivityisheadingtowardanearlymainpeak.Agradualrisewithaslow-downoverChristmas/NewYearandthenaresumedincreasetowardalatermainpeak,similartoe.g.the2015/2016season,seemsjustaslikely.

Thelaboratorydetectionsdataavailableatthisstagegivenoinformationregardingtheeventualmagnitudeoftheoutbreak.

WhereastherehasbeentwiceasmanyinfluenzaAdetectionsasinfluenzaBsincethestartoftheseason,influenzaBdetectionshaverecentlybeenincreasingmoreandthetypeAdominancehasgraduallybeenlostduringthelastthreeweeks(Fig.4,leftpanel).Ifthistrendcontinues,theinfluenzaBvirusesmaytakepredominanceinthebuild-uptothemainoutbreak.

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Figure4.Weeklyproportionsofinfluenzatype(leftpanel)andinfluenzaAsubtype(rightpanel),startof2017-2018season,Norway.

AmongthesubtypedinfluenzaAviruses(n=181),thestrongpredominanceofA(H3N2)overA(H1N1)appearstobemaintained,andmostoftheA(H1N1)detectionsareconcentratedinsouthwesternNorway.AmongtheinfluenzaBvirusesforwardedtotheNationalInfluenzaCentre(NIC)inNIPHandfurtheridentified,48(96%)havebelongedtotheB/Yamagata/16/1988lineageandonly2totheB/Victoria/2/1987lineage.

Figure5.Laboratorydetections,Norway,startof2017-2018season.Weeklynumberofthedifferentinfluenzavirusesisdisplayedasstackedbars,andinfluenzaviruspositivityratesofsentinelspecimens(two-weekaverages)andalllabtesting,respectively,areshownaslinegraphs.

Basedonthecurrentdata,influenzaA(H3N2)andB/Yamagata-lineagevirusesarethetwothataremost likelytopredominate,withA(H1N1)pdm09andB/Victoria-lineageviruseslikelytoplayalesserroleinNorwaythiswinter.

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Toelucidateageprofilesforthedifferentviruses,thenumberofdetectionsperagegroupwasdividedbythepopulationsizeoftheagegroup,thusproducingseasonalincidencesofdetections(Fig.6).

Figure6.Agegroup-specificcumulativeseasonalincidenceofvirusdetections,forinfluenzaA(H1N1)pdm09,A(H3N2),andB/Yamagata-lineage.OnlytwoB/Victoria-lineageviruseshavebeendetectedatthisstage,bothinthe25-59yearsagegroup.Thecumulativenumberofdetectionsrecordedineachagegroupisdividedbytheagegrouppopulationsize,toachievebettercomparabilitybetweenagegroups.Theincidencescannotbecomparedbetweenthedifferentviruses,sincetheextentoftestingforsubtypeandlineagevarieswidely.

Althoughnumbersaresmall,influenzaA(H1N1)casesareskewedmoretowardinfantsthanobservedfortheotherinfluenzaviruses.

TheageprofileforinfluenzaA(H3N2)virusesassumesaW-shapelikelastseason,butlastwintertheincidencefortheelderlywasmuchhigherthanalltheotheragegroupsandthisisnotseennow,atleastnotyet.Thehigherincidenceinelderlylastwinterwasevidentalreadybyweek45/2016,whenthecumulativenumberofH3caseswaslowerthanthepresentdatacollectedthroughweek48/2017.

Similarly,lastwintertheelderlyweremorethantwiceaslikelyaspeopleinotheragegroupstobediagnosedwithinfluenzaB/Yamagata-lineageviruses,andthisisnotapparentsofarthisseason.

Theearly-seasonageprofilesthusmaygivesomehopethattheupcomingseasonmightnotselectivelyaffecttheelderlyinthesamewayasthepreceding2016/2017season.Theagepatternsmaychangeastheoutbreakprogresses.

Geneticcharacterizationsofthevirusesincirculation

Asofweek46,43%(57viruses)ofallinfluenzavirusesreceivedatNICNorwayhavebeenfurthercharacterisedgenetically.AselectionofsequencesisavailableinGISAID(www.gisaid.org).

Asthepreviousseason,theinfluenzaA(H3N2)virusesarepredominatingthestartofthe2017/18season(Fig.7:ClusteranalysisofH3).BothH3N2group3C.2aand3C.2a1virusesarecirculating;however,the3C.2amaingroupofviruseshassofaroutnumberedthe3C.2a1virusesandseemtobemorewidespread.Thesame3C.2aviruseswerealsodominatingthepreviousseasoninNorway,incontrastto3C.2a1virusesinmostofEurope.TheH3N2vaccinecomponentalsobelongstothe3C.2agroupofvirus,butseveral

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3C.2asubcladeshaveemerged,makingthegeneticpictureforH3virusesverycomplex(Fig.7:ClusteranalysisofH3).

Figure7.MaximumparsimonyclusteranalysisoftheHAgeneofNorwegianinfluenzaH3viruswithnorthern3C.2a(2017/18)andsouthern3C.2a1(2018)hemispherevaccineH3virusesasreferences(whitecircles).Virusesarecolour-codedbydefinedgeneticsubgroups.HAaminoacidsubstitutionsdefiningthedifferentgeneticgroupsaregiven(withreferencetoA/Texas/50/2012).

TheNAgeneofthe3C.2avirusesgroupgeneticallytogetherwiththeNAgenesoftheothergroupofH3viruses,the3C.2a1(notshown).Theeffectofthisreassortmentiscurrentlyunknown.

TheinfluenzaB/YamagatavirusesaresimilartothevirusesfromthepreviousseasoninNorwayandgroupgeneticallywithclade3B/Yamagata-lineageviruses(Fig.8).TwosinglerecentvirusesfromdifferentpartsofNorwaystandoutfromtheotherB/Yamagatathisandpreviousseason,possessingtwoaminoacidsubstitutionsinHAcomparedtothevaccinestrain,namelypositionsQ122KandT181A.TheincreaseinB/Yamagatacasesthelastweekscannotbeexplainedbythegeneticanalysisofthecirculatingviruses.

OnlytwoinfluenzaB/Victoriaviruseshavesofarbeendetected,thesehavenotyetbeengeneticallycharacterised.

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Figure8.MaximumparsimonyclusteranalysisoftheHAgeneofNorwegianinfluenzaB/YamagataviruswithnorthernhemispherevaccineB/Yamagatavirus(redcircle)asreference.Virusesarecolour-codedbyvirusesfromthe2017/18season(green)andfromprevious2016/17season(white).KeyHAaminoacidsubstitutionsaregiven.

TheH1N1virusesareallclade6B.1andthelargestgeneticgrouppossessesthefollowingsubstitutions:T72S,S74R,D97N,P137S,S162N,S164T,K163Q,I216TandI295V.

Antiviralsusceptibility

Noresistancetowardsneuraminidaseinhibitorslikeoseltamivirandzanamivirhassofarbeendetectedoutof8H3viruses,9H1virusesand1influenzaBvirusanalysed.

Vaccine

VaccinematchAsthepredominantH3influenzastraininNorwaybelongstothesamegroupofH3virusesastheH3vaccinecomponent,thevaccinewillinducesomeprotectiontowardstheH3viruses.WeexpectvaryinglevelsofprotectionasseveraldifferentsubgroupsofH3virusesareincirculation(2).TheWHOCollaboratingCentrelaboratoryinLondonestimatesthatabout70-80%ofthe3C.2aH3virusescirculatingduringthelastseasonandthesummermonthswillbewellcoveredbythevaccine,and60%ofthe3C.2a1H3viruses(3).TheH1virusesmatchtheH1vaccinecomponent.However,theB/VictoriavirusinthevaccineisnotagoodmatchtowardstheB/YamagatavirusescurrentlycirculatinginNorway,stillsomecross-protectionisexpected.

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TheinfluenzavaccinefortheNorthernhemisphere2017/18containsthreedifferentviruscomponents:

• A/Michigan/45/2015(H1N1)pdm096B.1-likevirus• A/HongKong/4801/2014(H3N23C.2a)-likevirus• B/Brisbane/60/2008-(B/Victoria)-likevirus

VaccinedistributionandcoverageAvailablevaccinesforthevaccinationoftargetsgroups(riskgroupsandhealthcareworkers)(4)aresplitvaccineVaxigrip®2017/18fromSanofiPasteur,andsub-unitvaccineInfluvac®2017/18fromBGPProducts.Bothvaccinesareavailablefortheprivatemarket,inadditiontonasalvaccineFluenzTetrafromAstraZeneca.

AsofseventhofDecemberNIPHhasdistributedover525000vaccinedosesforthetargetgroups.InadditionNIPHandotherwholesalershavedistributednearly113000dosesfortheprivatemarket.Totalvolume:almost638000vaccinesdoses.Thisisanincreaseof90000dosescomparedtolastyear.

AsofsixthofDecember337091personshavebeenregisteredinthenationalvaccineregistrySYSVAKasvaccinatedwiththisseason’svaccine.Themajorityofthem–229952-areover65yearsofage.Thereisacertainlagtimeintheregistrationofsomevaccinations,sotherealnumberofvaccinatedisprobablymuchhigher.

TheinfluenzavaccinecoverageinNorwayremainslow.Nevertheless,ithasincreasedthelastcoupleofyears,especiallyintheelderlyandamonghealthcareworkers.Lastseasonthevaccinecoverageinthegeneralpublicwas10%.Thecoveragewas38%amongtheelderlyand17%inhealthcareworkers.Consideringtheincreaseinvaccinesalesthisseason,itseemsthatthevaccinecoverageingeneralwillbeatleastashighaslastyear’s.Thiswillhopefullycontributetofewerhospitaladmissionsanddeathsduetoinfluenzaamongtheriskgroupsthecomingseason,sinceitwilladdtothepriorimmunityalreadypresentinthepopulation.

Infectioncontrolmeasures

Vaccinationisthemosteffectivepreventivemeasureagainstinfluenza.Sincetheeffectofinfluenzavaccinesvary,useof antivirals shouldbe considered forpatients experiencinginfluenzaillness,particularlyforthosebelongingtoriskgroups.Antiviraltreatmentshouldbeinitiatedasearlyaspossibleafteronsetofsymptoms(preferablywithin48hours),bothfor vaccinated and unvaccinated patients. For patients with severe influenza requiringhospitalisation,treatmentwithantiviralsshouldalsobeconsideredlaterinthecourseofthedisease.

Topreventtransmissionofinfluenza,itisalsoimportanttopracticegoodhandandrespiratoryhygiene.

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Pre-seasonpopulationimmunitytoinfluenza,August2017

TheNationalSeroepidemiologicalInfluenzaProgramme

TheNationalSeroepidemiologicalInfluenzaProgrammeannuallycollectsinAugustabout2000 serum samples during theweeks 31-35 from clinical/microbiological laboratoriescoveringthe19countiesofNorway.Theseanonymisedconvenienceseraareaimedtoberepresentativeof theNorwegianpopulationgeographicallyandbyagecomposition.Thesera are tested by the hemagglutination-inhibition (HI) test to determine the antibodyimmunity to relevant circulating influenzaviruses.HI titres³40against the influenzaAstrainsand³80againstether-treatedinfluenzaBstrainsareconsideredasprotectivelevelsandrecordedasseropositiveintheanalysis.

The2017serumpanelwastestedbyHIagainsttheNorthernhemisphere2017/18seasonalinfluenza vaccine strains (trivalent/quadrivalent). In addition, two recent viruses wereanalysedinHI:A/California/07/2009(H1N1pdm09/X179A),thepreviousH1N1vaccinevirus,andA/Norway/3806/2016,arecentH3N23C.2a.1variant-likevirusbelongingtothesame group of viruses as A/Singapore/MIFIMH-16-0019/2016, the new H3 vaccinecomponentofthe2018influenzavaccinefortheSouthernhemisphere(Table1).

The results are shown in Fig. 9 and Table 1. HI testing is still ongoing and the presentpreliminaryanalysishasbeencarriedoutonasubsetrepresentingapproximately¾ofthecomplete annual panel. Protective immunity from subsequent seasonal vaccination willcomeinaddition.

SummaryofoutcomesTheseroprevalencetobothinfluenzaAvirusesisrelativelyhigh,indicatinggoodprotectiveimmunityagainstthetwoinfluenzaAvaccine-likeviruses.However,newH3N2HAvariantswithmajorantigenicdriftmaygivelessprotectioninthepopulation.Historically,H3N2viruseshavehigherfrequencyofmutationsinHAandmaythushaveahigherpotentialfornewvariantsascomparedtotheH1N1pdm09viruses,whichhaveundergonelittleantigenicchangesincethepandemicin2009.TheseroprevalencetoinfluenzaBvirusesislowtomoderate,asithasbeenthelastfewyears.Thismayindicateapopulationvulnerabilitythathasnotbeenexploitedduringthelastseasons,forreasonsnotwellunderstood.Inaddition,althoughitremainsrarelydetectedandthatapreliminaryanalysissuggestcross-immunityfromrelatedviruses,thenewinfluenzaB/VictoriaHAdeletionvariantmaybereasonforsomeconcern.

HighseroprevalencestoinfluenzaAvirusesinAugust2017TheseroprevalencesagainstbothinfluenzaA(H1N1)-andA(H3N2)-virusesareunusuallyhighinAugust2017andhadincreasedsignificantlyfromAugust2016(Fig9).Thehighestincreaseinprotectiveantibodyimmunity,by22percentagepoints,isseenagainstA(H3N2)withall-agesseroprevalencealmostdoubled.ThisreflectsthedominantcirculationofH3N2vaccine-likevirusestheprecedingseason.Surprisingly,anincreaseinseroprevalencetoA(H1N1)by9percentagepoints(18%relativeincrease)isseeneventhoughveryfewH1N1virusesweredetectedtheprecedingseason.

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ThehighestantibodyseroprevalencestobothH1N1andH3N2virusesareseenin5-14and15-24yearolds(Table1).ThisholdsforboththeH1N1virusestested,A/California/07/2009andA/Michigan/45/2015(clade6B.1),thepreviousseasonandthecurrentseasonH1vaccinevirus,withabout75to80%seropositiveinthesetwoagegroups,i.e.increasesby8and10percentagepointsfrompreviousyear.Additionally,theseroprevalencestoH1N1intheagegroups25-59and60+yearoldsarehigherthanseentheyearbeforewithabout8to10percentagepointsincrease,whileforthe0-4yearoldsthereisadecreaseof8percentagepoints.

ThehighestseroprevalencesagainsttheH3N2vaccinevirusA/HongKong/4801/2014(anH3N23C.2avariant)arealsointhosebetween5-14and15-24yearsoldwith80%and67%.Thisisanincreasefromthepreviousyearby20and33percentagepoints,respectively.TheseroprevalencesfortheotheragegroupsagainstH3N2havealsoincreasedsubstantiallybybetween15to19percentagepointsfromAugust2016.Interestingly,theseroprevalencesinvariousagegroupsagainstarecentnewH3N23C.2a.1-groupvirus,A/Norway/3806/2016,aresimilartotheprevalencestoA/HongKong/4801/2014-likevirus.AnH33C.2a.1-variantvirus(A/Singapore/INFIMH-16-0019/2016)wasrecentlyselectedastheH3N2vaccinecomponentfortheSouthernhemisphere2018season.

Figure9.InfluenzaseroprevalenceinAugust2017.All-agespercentageofserawithprotectiveHI-titreagainsttheH1N1,H3N2,B-VictoriaandB-Yamagataviruscomponentsofthe2017/2018Northernhemispheretrivalent/quadrivalentinfluenzavaccine(Bluecolumns,preliminarydata).Forcomparison,thecorrespondingseroprevalenceinAugust2016isalsoshown(Orangecolumns).

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Table1.Agegroupseroprevalencestothe2017/2018influenzavaccinecomponentsandtworecentcirculatingvariants(H1N1pdm09andH3N23C.2a.1)ofseracollectedinAugust2017.

Virus

Agegroup(yrs)

0-4 5-14 15-24 25-59 60-99

A(H1N1)pdm09A/Cal/07/2009(X179A) 24%* 78% 81% 52% 46%A(H1N1)A/Michigan/45/2015(6B.1)(V) 24% 74% 81% 49% 41%A(H3N2)A/HongKong/5738/2014(3C.2a)**(V) 33% 80% 67% 35% 42%A(H3N2)A/Norway/3806/2016(3C.2a.1) 31% 80% 74% 40% 46%B(Vic)B/Brisbane/60/2008(V) 8% 30% 22% 12% 22%B(Yam)B/Phuket/3073/2013(V4) 4% 24% 34% 21% 17%

*Percentage of sera with HI titre ≥40 for influenza A virus and ≥80 for influenza B virus. The results arepreliminarydatafromabt.2/3ofthe2017serumpanel.Numberofsamples(n)ineachagegroupare:113,199,222,503,and276.(V):TrivalentvaccinevirusesoftheNorthernhemisphere2017/2018vaccine;(V4):thefourthcomponentin4-valentvaccine.**A/HongKong/5738/2014isanA/HongKong/4801/2014-likevirus

LowtomoderateseroprevalencestoinfluenzaBvirusesinAugust2017LesschangesfromAugust2016inseroprevalencesareseenagainstthetwoinfluenzaBlineagesB/VictoriaandB/Yamagata,bothfor‘Allages’andinthevariousagegroups(Fig8).Formostagegroupschangesinseroprevalencesarelessthan+/-5percentagepoints,exceptforthose60yearsandoldertotheB/Victoria-lineagevaccinecomponentB/Brisbane/60/08withanincreaseof11percentagepoints.

ImmunityagainstanewinfluenzaB/Victoria-lineagehemagglutinindoubledeletionvariantDuringlastseason,aB/Brisbane/60/08(B/Victoria-lineage)hemagglutinin(HA)doubledeletionvariantwasidentifiedintheUSandNorwayaswellassomeothercountries,causingseriousconcernforlackofimmunitytothisnewB/Victoria-lineagevariantvirusinthehumanpopulationasindicatedbyantigeniccharacterizationusingmonospecificferretantisera.However,preliminaryHIanalysisusingpre-2016/17humanserafromourannualserumcollectionmayindicatethatthereissomelevelofcross-reactiveantibodiesinthepopulationtothisnewvariant(datanotshown).Furthermore,thisvarianthasnotbeenseeninincreasednumbersduringthe2017SouthernHemisphereseasonandthus,theriskformajorspreadofthisvirusvariantinitscurrentformmaybelowerthaninitiallyfeared.However,influenzaBvirusestendtocirculatelaterinseasonandifadditionalmutationsintheHAtakeplace,theexistingcross-immunityinthehumanpopulationmaygivelessprotection.

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Acknowledgements

TheNIPHwouldliketoexpressourgratitudetoallmedicaldoctorsandotherstaffattheregulargeneralpractitioneroffices,emergencyclinicsandmicrobiologicallaboratoriesthathavecontributedtothesurveillancebysendingsamplesanddata.WearealsoverygratefulforthecontributionofdatafromtheNorwegianIntensiveCareRegistry,andtothehospitalsandnursinghomesfornotifyingoutbreaksinVESUV.

WewouldalsoliketothankallthehealthcareworkersthathaveorganisedthetargetgroupvaccinationandcontributedtotheregistrationofinfluenzavaccinationsinSYSVAK.

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References

1. VegaTetal.InfluenzasurveillanceinEurope:establishingepidemicthresholdsbythemovingepidemicmethod.Influenzaandotherrespiratoryviruses2012;7(4):546-58

2. Sullivan,S.G.,etal.,Lowinteriminfluenzavaccineeffectiveness,Australia,1Mayto24September2017.EuroSurveill,2017.22(43).

3. WORLDWIDEINFLUENZACENTRE-WHOCCforReference&ResearchonInfluenza,TheFrancisCrickInstitute:ReportpreparedfortheWHOannualconsultationonthecompositionofinfluenzavaccinefortheSouthernHemisphere2018.https://www.crick.ac.uk/media/393884/crick_sh2017_vcm_report_to_post.pdf

4. Recommendedriskgroupsforinfluenzavaccinationseason2017-2018.https://www.fhi.no/sv/influensa/influensavaksine/influensavaksine-risikogrupper/

Published by The Norwegian Institute of Public Health December 2017P.O.Box 4404 NydalenNO-0403 OsloTel: + 47-21 07 70 00

The report can be downloaded as pdf at www.fhi.no/en/publ/