early risk assessment - fhi.no · the report can be downloaded as pdf at graphic design template:...

2019EARLY RISK ASSESSMENT:

What to expect of the 2018/19 influenza season in Norway

Karoline Bragstad Kristian Waalen Trine Hessevik Paulsen Torstein Aune Brigitte KlüwerKjersti Rydland Olav Hungnes

REPORT

Early risk assessment

What to expect of the 2018/19 influenza season in Norway

Division of Infection Control and Environmental Health;

Department of Influenza

Early risk assessment for the 2018/19 influenza season in Norway • NIPH

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Published by Norwegian Institute of Public Health Division of Infection Control and Environmental Health Department of Influenza December 2018

Title: Early risk assessment: What to expect of the 2018/19 influenza season in Norway

Authors: Karoline Bragstad Kristian Waalen Trine Hessevik Paulsen Torstein Aune Birgitte Klüwer Kjersti Rydland Olav Hungnes

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

Graphic design template: Per Kristian Svendsen

Graphic design cover: Fete Typer ISBN digital 978-82-8082-988-7. Citation: Bragstad K, Waalen K, Paulsen TH, Aune T, Klüwer B, Rydland KM, Hungnes O. " Early risk assessment: What to expect from the 2018/19 influenza season in Norway". [Utsikter for influensasesongen 2018/2019] Report 2018. Oslo: Norwegian Institute of Public Health, 2018.

http://www.fhi.no/en/publ/


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Content

Scope _____________________________________________________________________________ 4

Summary early observations and prospects for the 2017/18 season __________________________ 5

The 2018/19 season thus far __________________________________________________________ 6 Influenza-like illness (ILI) in primary health care 6 Severe influenza: laboratory confirmed hospitalised cases 6 Laboratory confirmed influenza 7 Age distribution of the different viruses 10 Genetic characterizations of the viruses in circulation 11 Antiviral susceptibility 11

Vaccine __________________________________________________________________________ 12 Vaccine match 12 Vaccine distribution and coverage 12

Population immunity against recent influenza viruses, August 2018 _________________________ 13 Phylogeny 15

References ________________________________________________________________________ 17

Acknowledgements. ________________________________________________________________ 17

Appendices _______________________________________________________________________ 18 18 18 18 18

Methods

Influenza-like illness

Virological surveillance.

Surveillance of laboratory-confirmed influenza in hospitalised

patients Influenza seroepidemiology 18


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Scope

ThisbriefreportpresentstheassessmentbytheNorwegianInstituteofPublicHealth(NIPH)ontheinfluenzasituationearlyinthe2018/2019season,andpossiblecharacteristicsoftheupcominginfluenzaoutbreakinNorway.Thereportisbasedondatafromalate-summerserosurvey,early-seasonsurveillancedata,andvaccinedistributiondata.Thereportismeanttosupportcapacityplanninginthehealthservices,providebackgroundinformationtoinfectioncontrolandotherhealth-careandpublichealthpersonnel,aswellastoprovideearlyin-depthinformationontheinfluenzaoutbreakingeneral.Atthispoint,asthe2018-2019outbreakisbeginningtounfold,itisofparticularinteresttoassessthedifferentcirculatinginfluenzaviruses,theireventualspread,andhowthiswillinfluencetheextentofillness,severeillnessandmortalityinvariousriskandagegroups.

Whattoexpectfromthe2018/19influenzaseasoninNorway

Early risk assessment


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Summary early observations and prospects for the 2017/18 season

• InfluenzavirusesareontheincreaseinNorway,butstillatalowlevelastheChristmas/NewYearholidaysareapproaching.

• Comparingwithhistoricaldata,theweeklydevelopmentsofclinicalandlaboratoryverifiedinfluenzaisfollowingacoursethatinpreviousyearshaveledtooutbreakspeakinginlateFebruaryorMarch.

• InfluenzaA(H1N1)virusesarebecomingincreasinglypredominant.InfluenzaBvirusesareunusuallyrare.

• SeroepidemiologydatafromAugust2018indicatethatimmunityinNorwayagainstcirculatinginfluenzaA(H1N1)andA(H3N2)virusesisquitestrong.AlsofortheB/Yamagata-lineagevirusthatcausedlastwinter’sinfluenzaoutbreak,therewasamarkedincreaseinpeoplewithantibodyatprotectivelevels.

• Addedtothiscomestheimmunityduetothesubsequentinfluenzavaccinationcampaignintheautumn.Ratesofvaccinationwereraisedconsiderablythisyear.

• TheA(H1N1)virusesareclade6B.1A/Michigan/45/2015andgrouptogetherwiththeA/Switzerland/3330/2017referencestrain,butwiththeadditionalsubstitutionsN129D,S185IandN260DinthehaemagglutininHA1subunit.

• WehaveatthispointnoindicationthatthesechangesintheHA1causesignificantantigenicdriftfromthevaccinestrainandrecentlycirculatingA(H1N1)viruses1.

• Providedthatthereisnosignificantantigenicdrift,andgiventhatimmunityagainsttheA(H1N1)virusisstrong,thereisagoodpossibilitythatpopulationimmunitywilllimittheextentofthedevelopinginfluenzaoutbreak.

• Nonetheless,experiencefrompreviousseasonsindicatethatoutbreakswithA(H1N1)virusesthatemergedwiththe2009pandemicinsomeinstancescauseseverediseasethatrequiresintensivecareamongthenon-elderly.Whilethegreatmajorityofcasesaremild,andtheupcomingoutbreakmaypossiblybeoflimitedextent,suchseverecasesmustbeexpectedalsothisseason.

• Noresistantviruseshavebeenfoundamongthe74influenzaviruseshithertotestedforsusceptibilitytoantiviraldrugs.


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The 2018/19 season thus far

Influenza-like illness (ILI) in primary health care

TheILI-rateshavebeenatbaselinelevelsfromweek40throughoutweek50.TheILIproportionhasbeenstableat0.3%fromweek41to46beforerisingto0.5%inweek48and49,stillnotexceedingtheepidemicthreshold.Comparedwithhistoricaldata(Figure1),seasonswithasimilardevelopmenthavehadinfluenzaoutbreaksthatculminatedinlateFebruaryorMarch.

Figure 1: Weekly incidence of ILI, Norway 2018-2019 season. The graph shows the proportion of patients in general practice and emergency clinics presenting with ILI, by calendar week. A selection of previous seasons is also shown.

Severe influenza: laboratory confirmed hospitalised cases

Thenumberoflaboratoryconfirmedinfluenzacasesamonghospitalisedpatientswaslowduringthestartoftheseason,buttheincreaseinthenumberofcasespickedupspeedintheweeks49and50,particularlyinthe60+agegroup.AllofthecaseshavebeenInfluenzaA.Thenumberofcasesarelowerthantheywereatthesametimeduringthetwoprecedingseasons.

Inweek44,higherthanexpectedall-causemortalitywasobservedinpeople65yearsorolder.


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Figure 2: Left hand panel: The number of influenza virus detections in hospitalised patients per week during influenza season 2018/2019, age-distributed, in the nine participating medical microbiology laboratories. Right hand panel: The number of hospitalised patients with confirmed influenza per week compared to the previous four influenza seasons. To be able to compare the seasons, week 1/2016 is the average of the number of patients hospitalised with influenza in week 53/2015 and week 1/2016.

Laboratory confirmed influenza

TherehasbeenagradualincreaseinthedetectionsofinfluenzavirusesinNorwaysincethebeginningofOctober,withamoremarkedincreaseinweeks49and50.Theweeklytotalandtheproportionofpositivesisstillcomparablylow(Figure3).Historically,seasonswithacorrespondingdevelopmentofproportionpositiveshavehadoutbreakspeakinginlateFebruaryorMarch(e.g.,2011/2012;2014/2015;2015/2016).

Duringthefirstfewweeks,therewasaslightmajorityofA(H3N2)viruses.Thishas,however,increasinglyshiftedtowardA(H1N1)predominanceinmostpartsofthecountry.Interestingly,inthewesternNorwaycountyofSogn&Fjordane,amarkedincreaseininfluenzaAdetectionsduringthelasttwoweeksappeartobecausedbyA(H3N2)viruses.Thismaypossiblybeduetoalocal“foundereffect”.


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Figure 3: Laboratory detections, Norway 2018-2019. Upper left-hand panel: Weekly proportion of influenza virus positive specimens, with previous season proportions shown for comparison. Upper right-hand panel: Weekly number of influenza virus detections, with previous season numbers shown for comparison.

Lower panel: Weekly number of the different influenza viruses is displayed as stacked bars, while influenza virus positivity rates of sentinel specimens (“fyrtårn”, 2-wk average) and all lab testing, respectively, are shown as line graphs.

Altogether,46476patientshavebeentestedforinfluenzaduringweeks40-50,resultingin870detectionsofinfluenzaAand27detectionsofinfluenzaB.AmongtheinfluenzaAvirusdetections,thereisaclearandincreasingpredominanceofsubtypeH1(Figure3,4).


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Figure 4. Proportions of 2018/19 season influenza virus subtypes and lineages among viruses analysed in Norway, by 19th December 2018. All-laboratories proportions of A/B type, A subtypes and B lineages are shown in the first four diagrams. The subtype and lineage frequencies are superimposed on type distributions in the lower middle panel, for comparison with the distribution among sentinel specimen data (lower right panel).

To limit the subtype testing bias in the all-laboratories data (nearly three times more viruses have been tested for H1 than for H3), only H1 positives that have also been tested for H3 are counted in the top-middle diagram. A similar proportion is obtained through an alternative approach that uses data from a higher number of laboratories that test all A positives for H1 but not H3, shown in the top-right diagram, where A positives testing negative for H1 serve as a proxy for H3. The sentinel data are not subtype biased in this way but the numbers are very limited at this point.

If the predominance of A(H1N1) indeed remains through this winter’s main outbreak, this will represent a continuation of a pattern of H1N1 predominance every third season since the virus emerged with the 2009 pandemic (figure 5). This subtype also predominated during the 2013-14 season but that was a very small outbreak.


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Figure 5: Predominance of influenza viruses in Norway, 2009-2018.

Age distribution of the different viruses

PreliminaryageprofilesfortheA(H1N1)andA(H3N2)virusesindicatethattheagepatternsthisseasondonotdifferfromrecentseasons(Figure6).InfantsarestronglyrepresentedamongcaseswithA(H1N1)infection,andpersons60yearsandolderarestronglyrepresentedamongcaseswithA(H3N2)infection.AgeprofilesforinfluenzaB/YamagataandB/Victoriaarenotavailableduetotheverylownumberofvirusesanalysed.

Figure 6. Cumulative incidence per 10 000 population of subtype/lineage detections by age group, based on viruses analysed in the Norwegian National Influenza Centre early in the 2018/19 influenza season.


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Genetic characterizations of the viruses in circulation

TheanalysedH1N1virusesareallcharacterisedasclade6B.1A/Michigan/45/2015virusesandthemajorgroupofH1virusescurrentlypossessesthefollowingsubstitutions:S74R,N129D,S183P,S185I,R223QandN260DandgroupphylogeneticallytogetherwiththeA/Switzerland/3330/2017,orevenclosertotheA/Ukraine/7993/2018referencestrain(seephylogenetictreeattheendofthereport).ThereisalsoasmallergroupofH1virusescirculatingpossessingthekeysubstitutionsI404MandN496S,groupingtogetherwithcladeA/Paris/1289/2017referencestrain.

TheN1geneoftheA/Switzerland/330/2017-likevirusespossessedthekeyaminoacidsubstitutions:Q50K,V67I,F74SandS95NforthesamephylogeneticclusteringastheHAgenes.TheclosestrelativeistheA/Ukraine/7992/2018referencestrain.

ThecharacterisedH3N2virusesareall3C.2a1bA/Alsace/1746/2018viruses,howeverthesedivideintotwoequallyprevalentsubgroups;thecladeA/Iceland/78/2018subgroupwiththeA106VandT131KkeysubstitutionsandthecladeA/LaRioja/2202/2018subgroupwiththeI48R,T128A,T135K(seephylogenetictreeattheendofthereport).

TheN2geneoftheA/Iceland/78/2018-likevirusespossessedthekeyaminoacidsubstitutions:P136LandS315R.

InfluenzaB-Yamagatavirusescharacterisedthisfarseemtobethesameaspreviousseason,allclade3viruses.

Antiviral susceptibility

Noresistancetowardsneuraminidaseinhibitorslikeoseltamivirandzanamivirhassofarbeendetected,outof23H3viruses,50H1virusesand1influenzaBvirusanalysed.


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Vaccine

Vaccine match

TheH1virusescirculatingisofthesamegeneticgroup6.B1astheH1componentinthevaccine.Althoughsomefewmutationshavebeenfoundthatcouldinfluenceonthevaccine-match,itisexpectedthatthevaccinetoasatisfactorydegreewillcovertheH1viruses,asitdidlastseason.BothN129DandS85IsubstitutionscharacterisingthemostprevalentH1groupofvirusesinNorwayatpresentarepositionedinantibodyrecognitionsitesAandE,respectively.Inaddition,allNorwegianvirusespossesstheR223Qsubstitutionthatisassociatedwithantigenicdrift.ThissubstitutionwashoweveralsopresentintheH1virusesfromlastseasonandstillthevaccineshowedsatisfactoryeffectiveness.Sofar,wehavereceived19samplesfromvaccinatedpersonsandnonehadlabconfirmedinfluenza.Atthesametimelastseasonwehadreceived16samplesfromvaccinatedpersonsandfourwereinfluenzapositives(1H1,2H3,1B/Yamagata).ForinfluenzaAH3N2virusesweexpectthesamepoorvaccineeffectivenessaspreviousseason.ItisexpectedthatthevaccineswillinducegoodprotectionagainstinfluenzaBviruses.ThetrivalentvaccinecontainstheinfluenzaB-Victoriadeletionvariant,butsomecrossprotectionagainstB-Yamagataviruses,aswellasnon-deletionB-Victoriaviruses,isalsoanticipated.

Vaccine distribution and coverage Atotalof870000influenzavaccinedoseshavebeendistributedsofarthisseason;712000ofthesewerespecificallymeantforpersonsinmedicalriskgroupsandhealthcarepersonnelinvolvedindirectpatientcare.Thesenumbersrepresentanincreaseindistributeddosesof55-60%overthelasttwoyears(Figure7).

Figure 7: Influenza vaccine doses (seasonal) distributed in Norway, 2008 through 2018 as per 19th December. HCW = Health Care Workers.

EstimatesofvaccinecoverageinthevariousriskgroupsinthecurrentseasonwillnotbeavailableuntilOctober/November2019.


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Population immunity against recent influenza viruses, August 2018

TheNationalInfluenzaSeroepidemiologyProgrammeannuallyinAugustcollectsabout2000anonymisedconvenienceserafromclinical/microbiologicallaboratoriesacrossNorway.Thesera,aimedtoberepresentativeoftheNorwegianpopulationgeographicallyandbyagecomposition,aretestedbythehaemagglutination-inhibition(HI)testtodeterminetheantibodyimmunityagainstrelevantcirculatinginfluenzaviruses.Asanausteritymeasure,onlyasubsetof1178serawereanalysedthisyear.

Fig 8. Seroprevalence in August 2018 to current influenza A and B reference and vaccine strains for ‘All ages’ (0-99+) and in various age groups. For comparison, seroprevalences to some virus strains in August 2017 are also shown. X179A= A/California/07/2009 (H1N1)pdm09; Michigan= A/Michigan/45/2015 (H1N1)pdm09 clade 6B.1; Hong Kong = A/Hong Kong/5738/2014 (H3N2) clade 3C.2a; Singapore= A/Singapore/INFIMH-16-0019/2016 (H3N2) clade 3C.2a1 ; Switzerland= A/Switzerland/8060/2017 (H3N2) clade 3C.2a2; B/Brisbane= B/Brisbane/60/2008 (Victoria lineage); B/Norway= B/Norway/2409/2017 (Victoria lineage, amino acid 162-163 deletion variant); B/Phuket= B/Phuket/3073/2013 (Yamagata lineage).

Themainfindingsareshowninfigure8andsummarisedasfollows:

ForA(H1N1)viruses,thecomparativelystrongpopulationimmunitythathasbeenaccumulatedinrecentyearshadbeenmaintainedinmostagegroups,eventhoughcirculationofthisviruswaslimitedduringthepreviousseason.

Similarly,forA(H3N2)viruses,thecomparativelystrongpopulationimmunityobservedlastyear,stemmingfrompreviousoutbreaksandvaccination,wasessentiallymaintained.Theproportionofpeoplewithprotectiveantibodylevels(seroprevalence)maybesomewhatloweragainstsomemorerecentgeneticvariants,particularlyinthe15-24yearsagegroup.


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TheseroprevalenceagainstB/Victoria-lineagevirusesremainedlowwithoverallseroprevalenceof20%againstthepreviousB/VictoriavaccinecomponentB/Brisbane/60/2008.

Interestingly,theseroprevalenceagainstanewlyemerged“doubledeletion”variant,representedbyB/Norway/2409/2017inouranalysis,showsadifferentandreducedpatternforthosebelow25yearsold,andparticularlythoseyoungerthan15years.Forthose25yearsandoldertheseroprevalenceagainstthetwovirusvariantswassimilar.Thedeletionvariantvirusisnowforthefirsttimeincludedinthecurrentinfluenzavaccine.

B/Yamagata-lineagevirusespredominatedlastwinter,andtheseroprevalenceagainstthecurrentvariantB/Phuket/3070/2013increasedsince2017inallagegroups.Thelargestincreaseoccurredinpeopleyoungerthan25years,withmoremodestincreasesinotheragegroups.


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Phylogeny


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References

1 EuropeanCentreforDiseasePreventionandControl(ECDC):Influenzaviruscharacterisation,SummaryEurope,November2018https://ecdc.europa.eu/en/publications-data/influenza-virus-characterisation-summary-europe-november-2018

Acknowledgements.

Theworkpresentedreliesheavilyontheessentialcontributionsbythesentinelphysicians,Norwegianmedicalmicrobiologylaboratories,otherparticipantsinNorwegianinfluenzasurveillance,aswellastheWHOCollaboratingCentreforInfluenzaReferenceandResearchattheFrancisCrickInstitute,London,UKandotherpartnersintheWHOGlobalInfluenzaSurveillanceandResponseSystemandtheEuropeanInfluenzaSurveillanceNetwork.Dataontheincidenceofinfluenza-likeillnessareprovidedbytheDepartmentofInfectiousDiseaseEpidemiologyandModelling,NorwegianInstituteofPublicHealth,whichalsoassistedwithmortalitymonitoring.

AnumberofsequenceswereaccessedintheGISAIDdatabaseEpiFluandwegratefullyacknowledgethecontributionsofallthepeopleandinstitutionsthathavebeendevelopingandmaintainingthissharingmechanism,aswellastheauthors,originatingandsubmittinglaboratoriesofthesequencedatathatwehaveused.

WefurthermoregratefullyacknowledgetheexcellenttechnicalworkperformedbyValentinaM.Johansen,AnneMariaLund,MariePaulsenMadsen,RemilynRamos-OcaoandMarianneMorken.

Withbestregards,

KarolineBragstad,KristianWaalen,TrineHessevikPaulsen,TorsteinAune,BirgitteKlüwer,KjerstiRydland,andOlavHungnes

NationalInfluenzaCentre/DepartmentofInfluenza,DivisionforInfectionControlandEnvironmentalHealth,NorwegianInstituteofPublicHealth,Oslo,Norway

28December2018

https://ecdc.europa.eu/en/publications-data/influenza-virus-characterisation-summary-europe-november-2018

https://ecdc.europa.eu/en/publications-data/influenza-virus-characterisation-summary-europe-november-2018


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Appendices

Methods

Influenza-like illness Influenza-likeillness(ILI)inNorwayismonitoredthroughTheNorwegianSyndromicSurveillanceSystem(NorSSS).NorSSSisapopulation-basedautomatedelectronicsystemthatdailyprovidesdatafromallGPsandemergencyclinicsinprimaryhealthcareinNorway.TheDepartmentofInfluenzaattheNorwegianInstituteofPublicHealth(NIPH)receivesdatafromtheNorwegianHealthEconomicsAdministration(HELFO).NorSSShasbeeninoperationsince2014andissupportedbyretrospectivedatafromthe2006-07seasonandonwards.

Virological surveillance. AnetworkofvolunteersentinelphysiciansthroughoutthecountrycollectsspecimensfrompatientswithILIforanalysisattheNationalInfluenzaCentre.Inaddition,medicalmicrobiologylaboratoriesthatperforminfluenzadiagnosticsweeklyreportthenumberofpositivesandthenumberofspecimenstested,accordingtovirustype/subtype,detectionmethodandpatientagegroup.TheselaboratoriesalsocontributeinfluenzapositivespecimenstotheNICforfurthercharacterisation.Eventhoughmostoftheselaboratoriesareaffiliatedtohospitals,alargeproportionofspecimenstestedforinfluenzavirusarefromoutpatientsvisitinggeneralpractitioners.

Surveillance of laboratory-confirmed influenza in hospitalised patients Asanextensiontothebasicweeklyreportingofinfluenzadiagnostictestingoutcomes,ninemedicalmicrobiologylaboratoriesstratifytheirreportintohospitalisedpatientsandoutpatients.Together,theselaboratoriescoverapproximately60%oftheNorwegianpopulation,andreporteachweekthenumberofinfluenzavirusdetectionsinhospitalisedpatients(allwards)aswellasoutpatientsaccordingtoinfluenzatype(A,B)andagegroup.Thisextendedreportingconstitutesthebasisforthesurveillanceoflaboratoryconfirmedinfluenzainhospitalisedpatients.Thisisthefifthyearthissurveillancesystemisinoperation.

Influenza seroepidemiology TheNationalInfluenzaSeroepidemiologyProgrammeannuallyinAugustsolicitsabout2000serumsamplescollectedduringtheweeks31-35fromclinical/microbiologicallaboratoriescoveringthe19countiesofNorway.TheseanonymisedconvenienceseraareaimedtoberepresentativeoftheNorwegianpopulationgeographicallyandbyagecomposition.Theseraaretestedbythehaemagglutination-inhibition(HI)testtodeterminetheantibodyimmunitytorelevantcirculatinginfluenzaviruses.HItitres≥40againsttheinfluenzaAstrainsand≥80againstether-treatedinfluenzaBstrainsareconsideredasprotectivelevelsandrecordedasseropositiveintheanalysis.

Published by the Norwegian Institute of Public Health January 2019P.O.Box 222- SkøyenNO-0213 OsloTel: + 47-21 07 70 00The report can be downloaded as pdf at www.fhi.no/en/publ/

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