VaccineDeliveryResearchDigest,STARTCenter–June2016

VACCINEDELIVERYRESEARCHDIGEST

UNIVERSITY OF WASHINGTONSTRATEGIC ANALYSIS , RESEARCH, & TRAINING (START) CENTER

REPORTTO THEBILL & MELINDAGATES FOUNDATION

AUGUST 15 , 2016

PRODUCEDBY:LEVINE , GA ; ROWHANI-RAHBAR, A .

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TABLEOFCONTENTS1. INTERVENTIONSFORIMPROVINGCOVERAGEOFCHILDHOODIMMUNISATIONINLOW-ANDMIDDLE-

INCOMECOUNTRIES. 3o Asystematicreviewof14clusterandindividualRCTsofinterventionstoimprovevaccinationcoverage

inchildrenbirthtofouryears.2. THEECONOMICANDOPERATIONALVALUEOFUSINGDRONESTOTRANSPORTVACCINES. 4

o Aneconomicanalysisoftheimpactonvaccineavailabilityandcostsofusingunmannedaerialvehicles(UAVs)forvaccinedistribution,comparedwith“traditional”landdistributionmethods.

3. EXPERIENCEOFINTEGRATINGVITAMINASUPPLEMENTATIONINTOPOLIOCAMPAIGNSINTHEAFRICANREGION. 5o Adescriptiveanalysis and reviewof the relationshipbetweenpolio campaigns inAngola,Chad,Cote

d’IvoireandTogoandvitaminAsupplementationcoverage.4. CONTRIBUTIONOFPOLIOERADICATIONINITIATIVETOSTRENGTHENINGROUTINEIMMUNIZATION:

LESSONSLEARNTINTHEWHOAFRICANREGION. 6o AnarrativesummaryanddescriptiveanalysisofimmunizationcoverageofBCG,DTP3andfirstdoseof

MCV1usingavailableWHO/UNICEFdata from late1990-2014, relatingcoverage topolioeradicationactivities.

5. CONTRIBUTIONOFPOLIOERADICATIONINITIATIVETOEFFECTIVENEWVACCINEINTRODUCTIONINAFRICA,2010-2015. 7o AdescriptiveanalysisandreviewoftherelationshipbetweenpolioeradicationactivitiesinAfricaand

introductionofothervaccines.6. FRAMEWORKFOROPTIMALGLOBALVACCINESTOCKPILEDESIGNFORVACCINE-PREVENTABLE

DISEASES:APPLICATIONTOMEASLESANDCHOLERAVACCINESASCONTRASTINGEXAMPLES. 8o A review presentation of an analytic framework for and approach to developing a vaccine stockpile

“optimizationframework”thatconsidersthe“dynamicsofglobalvaccinesupplyanddemand.”7. BEYONDVERTICALANDHORIZONTALPROGRAMS:ADIAGONALAPPROACHTOBUILDINGNATIONAL

IMMUNIZATIONPROGRAMSTHROUGHMEASLESELIMINATION. 9o Anexpertreviewthatproposesa“diagonalapproach”tomeasleselimination(versusavertical

approach)thatcouldcontributetostrengtheningthelargerhealthsysteminfrastructure.8. FEASIBILITYANDLIMITATIONSOFVACCINETWO-DIMENSIONALBARCODINGUSINGMOBILEDEVICES.

10o Ananalysisoftheperformanceofanewbarcodescanningapplicationformobiledevices(Androidand

iOS),whichtestedthescansuccessrate,accuracyandtimetoscan,underdifferentconditionsofbarcodesize,curvature,fadingandlightingconditions.

9. THEECONOMICVALUEOFINCREASINGGEOSPATIALACCESSTOTETANUSTOXOIDIMMUNIZATIONINMOZAMBIQUE. 11o Amodelinganalysis.Authorsdevelopedandappliedageo-temporalmappingapplicationtodetermine

thenumberofpregnantwomeninMozambiquereachablebyexistingtetanustoxoidimmunizationstations,andtoestimatetheburdenofdiseaseandcostsassociatedwithlackofaccess.

10. INTERVENTIONSTOIMPROVEHPVVACCINEUPTAKE:ASYSTEMATICREVIEW. 12O AsystematicreviewofexperimentalandobservationalstudiesofinterventionstoimproveHPVvaccine

whichincluded51studiesfrombothhigh-incomecountriesandlow-middle-incomecountries.APPENDIX 13

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1. INTERVENTIONSFORIMPROVINGCOVERAGEOFCHILDHOODIMMUNISATIONINLOW-AND

MIDDLE-INCOMECOUNTRIES.Oyo-ItaA,WiysongeCS,OringanjeC,NwachukwuCE,OduwoleO,etal.CochraneDatabaseSystRev.2016Jul10;7:CD008145.[Epubaheadofprint]PMID:27394698

ABSTRACT(ABRIDGED)BACKGROUND:Immunisationisapowerfulpublichealthstrategyforimprovingchildsurvival,notonlybydirectlycombatingkeydiseasesthatkillchildrenbutalsobyprovidingaplatformforotherhealthservices.However,eachyearmillionsofchildrenworldwide,mostlyfromlow-andmiddle-incomecountries(LMICs),donotreceivethefullseriesofvaccinesontheirnationalroutineimmunisationschedule.ThisisanupdateoftheCochranereviewpublishedin2011andfocusesoninterventionsforimprovingchildhoodimmunisationcoverageinLMICs.SEARCHMETHODS:WesearchedtheCochraneCentralRegisterofControlledTrials2016,;MEDLINEIn-ProcessandOtherNon-IndexedCitations,MEDLINEDailyandMEDLINE,OvidSP;CINAHL,EbscoHost;Embase,OvidSP;LILACS,VHL;SociologicalAbstracts,ProQuest.WedidacitationsearchforallincludedstudiesinScienceCitationIndexandSocialSciencesCitationIndex;EmergingSourcesCitationIndex,ISIWebofScience.WealsosearchedthetwoTrialsRegistries:ICTRPandClinicalTrials.gov.SELECTIONCRITERIA:Eligiblestudieswererandomisedcontrolledtrials(RCT),non-RCTs,controlledbefore-afterstudies,andinterruptedtimeseriesconductedinLMICsinvolvingchildrenagedfrombirthtofouryears,caregivers,andhealthcareproviders.DATACOLLECTIONANDANALYSIS:Weindependentlyscreenedthesearchoutput,reviewedfulltextsofpotentiallyeligiblearticles,assessedriskofbias,andextracteddata.Wethenconductedrandom-effectsmeta-analysesandusedGRADEtoassessthecertaintyofevidence.MAINRESULTS:Fourteenstudiesmetourinclusioncriteria.ThesewereconductedinGeorgia,Ghana,Honduras,India,Mali,Mexico,Nicaragua,Nepal,Pakistan,andZimbabwe.Onestudyhadanunclearriskofbias,and13hadhighriskofbias.Theinterventionsevaluatedinthestudiesincludedcommunity-basedhealtheducation,facility-basedhealtheducation,householdincentives,regularimmunisationoutreachsessions,homevisits,supportivesupervision,informationcampaigns,andintegrationofimmunisationserviceswithintermittentpreventivetreatmentofmalaria.Wefoundmoderate-certaintyevidencethathealtheducationatvillagemeetingsorathomeprobablyimprovescoveragewiththreedosesofdiphtheria-tetanus-pertussisvaccines(DTP3).Wealsofoundlow-certaintyevidencethatfacility-basedhealtheducationplusredesignedvaccinationremindercardsmayimproveDTP3coverage.Householdmonetaryincentivesmayhavelittleornoeffectonfullimmunisationcoverage.Regularimmunisationoutreachmayimprovefullimmunisationcoveragewhichmaysubstantiallyimproveifcombinedwithhouseholdincentives.Homevisitstoidentifynon-vaccinatedchildrenandreferthemtohealthclinicsmayimproveuptakeofthreedosesoforalpoliovaccine.Therewaslow-certaintyevidencethatintegrationofimmunisationwithotherservicesmayimproveDTP3coverage.AUTHORS'CONCLUSIONS:Providingparentsandothercommunitymemberswithinformationonimmunisation,healtheducationatfacilitiesincombinationwithredesignedimmunisationremindercards,regularimmunisationoutreachwithandwithouthouseholdincentives,homevisits,andintegrationofimmunisationwithotherservicesmayimprovechildhoodimmunisationcoverageinLMIC.Mostoftheevidencewasoflowcertainty,whichimpliesahighlikelihoodthatthetrueeffectoftheinterventionswillbesubstantiallydifferent.WEB:http://www.dx.doi.org/10.1002/14651858.CD008145.pub3IMPACTFACTOR:6.22CITEDHALF-LIFE:4.80UWEDITORIALCOMMENT:IAuthorsnotethattheinterventionsevaluatedwereextremelyheterogeneous,andvariedinhowdeliveryintensity,andpointoutthatextrapolatingresultstodifferentsettingsordifferentpopulationswouldbeinappropriate,andthusgeneralizabilityislimited.Alimitednumberofstudiesareavailable,thusquestionsremainaboutthefeasibilityandoptimaldeliveryandimplementationstrategies.Authorsalsocautionthatlong-termfollow-upwasn’tconducted,andthussustainabilityisn’twellunderstood.

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2. THEECONOMICANDOPERATIONALVALUEOFUSINGDRONESTOTRANSPORTVACCINES.

HaidariLA,BrownST,FergusonM,BancroftE,SpikerM,etal.Vaccine.2016Jul25;34(34):4062-7.Epub2016Jun20.PMID:27340098

ABSTRACTBACKGROUND:Immunizationprogramsinlowandmiddleincomecountries(LMICs)facenumerouschallengesingettinglife-savingvaccinestothepeoplewhoneedthem.Asunmannedaerialvehicle(UAV)technologyhasprogressedinrecentyears,potentialusecasesforUAVshaveproliferatedduetotheirabilitytotraversedifficultterrains,reducelabor,andreplacefleetsofvehiclesthatrequirecostlymaintenance.METHODS:UsingaHERMES-generatedsimulationmodel,weperformedsensitivityanalysestoassesstheimpactofusinganunmannedaerialsystem(UAS)forroutinevaccinedistributionunderarangeofcircumstancesreflectingvariationsingeography,population,roadconditions,andvaccineschedules.WealsoidentifiedtheUAVpayloadandUAScostsnecessaryforaUAStobefavorableoveratraditionalmulti-tieredlandtransportsystem(TMLTS).RESULTS:ImplementingtheUASinthebaselinescenarioimprovedvaccineavailability(96%versus94%)andproducedlogisticscostsavingsof$0.08perdoseadministeredascomparedtotheTMLTS.TheUASmaintainedcostsavingsinallsensitivityanalyses,rangingfrom$0.05to$0.21perdoseadministered.TheminimumUAVpayloadsnecessarytoachievecostsavingsovertheTMLTS,forthevariousvaccineschedulesandUAScostsandlifetimestested,weresubstantiallysmaller(upto0.40L)thanthecurrentlyassumedUAVpayloadof1.5L.Similarly,themaximumUAScoststhatcouldachievesavingsovertheTMLTSweregreaterthanthecurrentlyassumedcostsunderrealisticflightconditions.CONCLUSION:ImplementingaUAScouldincreasevaccineavailabilityanddecreasecostsinawiderangeofsettingsandcircumstancesifthedronesareusedfrequentlyenoughtoovercomethecapitalcostsofinstallingandmaintainingthesystem.OurcomputationalmodelshowedthatmajordriversofcostssavingsfromusingUASareroadspeedoftraditionallandvehicles,thenumberofpeopleneedingtobevaccinated,andthedistancethatneedstobetraveled.WEB:http://dx.doi.org/10.1016/j.vaccine.2016.06.022IMPACTFACTOR:3.62CITEDHALF-LIFE:5.50UWEDITORIALCOMMENT:theHERMESsimulationsrepresentedeveryvaccinefial,facility,storageequipment,transportdevice,routeandpersonnelinthesupplychain.AuthorsmodeledascenarioinwhichprovincialstoresdelivervaccinesmonthlytoUAVs,whichsupplythehealthcenterintheregion,usingongoingUAVshipmentsbasedonlocaldemand,withassumptionsaboutUAVcapacityanddistancebasedoncurrentlyavailableUAVsonthemarket.Vaccineavailabilitywasbasedonnumberofpeoplereceivingvaccinesdividedbynumberofpeopleseekingvaccinesathealthcenters,notthetotalpopulationofvaccine-eligibleindividuals.Figure1isavisualdepictionofthedifferentmodelschemesforarangeofdifferentdeliveryscenarios(roaddistance;numberandlocationofhubs,districtandprovincialstoresandhealthcenters;integrationwithTMLTS)byUASandTMLSinoneprovinceinMozambique.Sensitivityanalysisvariedthepopulationservedbythehealthcenter,populationdistributioninurbancentersorthroughoutthedistrict,roadspeedandroaddistancetraveledforTMLTSroutes,seasonalityinfluencesonaccessibilityofhealthcenters,andintroductionofadditionalvaccinestotheEPIschedule.Figure2depictsthecost-savingsestimatedundereachoftheseconditions.Assumingvariousflightdelays,a4-weekdelaypost-vaccinationintroductionwasthefirstscenariounderwhichtheUASwasn’tabletoachievecostsavings(Figure3).Authorsreportthatthecostsavingswereprimarilyattributabletoroadspeed,sizeofpopulationdemandingvaccine,andthetraveldistancecapacity,comparedwithtraditionallandtravelvehicles.

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3. EXPERIENCEOFINTEGRATINGVITAMINASUPPLEMENTATIONINTOPOLIOCAMPAIGNSINTHEAFRICANREGION.ChehabET,AnyaBM,OnyangoAW,Tevi-BenissanMC,OkeibunorJ,etal.Vaccine.2016Jun27.[Epubaheadofprint]PMID:27364094

ABSTRACTINTRODUCTION:VitaminAdeficiencyisapublichealthproblemthataffectschildrenacrosstheWHOAfricanRegion.CountrieshaveintegratedvitaminAsupplementationindifferentchildhealthinterventions,mostnotablywithpoliocampaigns.TheintegrationofvitaminAinpoliocampaignswasdocumentedasabestpracticeinAngola,Chad,Coted'Ivoire,Tanzania,andTogo.TherearepotentialriskstovitaminAsupplementationassociatedwiththepolioendgameandcertificationintheAfricanRegion.METHODS:WereviewedthefindingsfromthedocumentationofbestpracticesassessmentthatwasconductedbytheWHORegionalOfficeforAfricain2014and2015inthefivecountriesthatnotedintegrationofvitaminAwithpolioasabestpractice.Inaddition,wereviewedthecoverageratesfororalpoliovirusvaccineandvitaminAsupplementationinAngola,Chad,Coted'Ivoire,Tanzania,andTogoin2014and2015.RESULTS:VitaminAdeficiencyin2004rangedfrom35%inTogotoashighas55%inAngola.AllfivecountriesintegratedvitaminAsupplementationinatleastonecampaignin2013-2014andallachievedover80%coverageforvitaminAsupplementationwhenitwasintegratedwithpolio.DISCUSSION:Giventheprogressofthepolioprogram,anddecreasingcampaigns,thereisariskthatfewerchildrenwillbereachedeachyearwithvitaminAsupplementation.WerecommendthatforcountriesstrengthentheintegrationofvitaminAsupplementationwithroutineimmunizationservices.WEB:http://dx.doi.org/10.1016/j.vaccine.2016.05.056IMPACTFACTOR:3.62CITEDHALF-LIFE:5.50UWEDITORIALCOMMENT:IntegrationofvitaminAincludedintegrationinthecampaignplanning,implementationandpost-campaignactivities.Authorsdescribethefollowing“lessonslearnt”regardingintegrationofvitaminAsupplementationwithOPVintheCoted’Ivoirecontext:importanceofgrassrootsmicroplanning,goodlocalcoordination,involvementofallstakeholdersatthedistrictandnationallevelsinthecampaignaswellasinsocialmobilization,involvementoflocalauthoritiesincludingcivilsociety,religiousleaders,military,andinvolvementoflocalradiostations.ChallengesintheCoted’Ivoirecontextincluded“slowingdownofvaccinationteamsastheyhadtoadministerthetwointerventions,theadditionalresourcesfromthenutritionprogramnotalwaysarrivingontime,theroundsbeingveryclosetogether,andthelowdailyallowancespaidtovaccinators.”Authorscautionthatwiththe“windingdown”ofpolioeradicationefforts,coveragedataandreportingofVitaminAsupplementationmaysuffer,sincereportingisoftenlinkedcurrently.FourofthefivecountriesevaluatedusepolioeradicationactivitiestodeliverVitaminA,andthusauthorscautionthataseradicationisreachedandpolioactivitiesarerolledback,thecoverageofVitaminAsupplementationandqualityandconsistencyofcoveragedataonsupplementationmaysuffer.AuthorsrecommendlinkingVitaminAsupplementationwithotherhealthdeliveryplatformstoimprovesustainabilityandmaintaincoverage,andrecommendcountriesfurtherintegratevitaminAsupplementationintotheirEPIschedules,toavoidinterruptionsincoveragefollowingplannederadicationin2019.*Thisarticle(aswellasarticles4&5)ispartofaspecialsectioninthepublicationthismonthfeaturingmultiplearticlesabouttheinfluenceofpoliooneliminationactivitiesinsub-SaharanAfricaondifferentaspectsofthehealthsystem.

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4. CONTRIBUTIONOFPOLIOERADICATIONINITIATIVETOSTRENGTHENINGROUTINEIMMUNIZATION:LESSONSLEARNTINTHEWHOAFRICANREGION.AnyaBM,MoturiE,AschalewT,CaroleTevi-BenissanM,AkanmoriBD,etal.Vaccine.2016Jul7.[Epubaheadofprint]PMID:27396492

ABSTRACTBACKGROUND:Importantinvestmentsweremadeincountriesforthepolioeradicationinitiative.On25September2015,amajormilestonewasachievedwhenNigeriawasremovedfromthelistofpolio-endemiccountries.RoutineImmunization,beingakeypillarofpolioeradicationinitiativeneedstobestrengthenedtosustainthegainsmadeincountries.Forthis,thereisahugepotentialonbuildingontheuseofpolioinfrastructuretocontributetoRIstrengthening.METHODS:WereviewedestimatesofimmunizationcoverageasreportedbythecountriestoWHOandUNICEFforthreevaccines:BCG,DTP3(thirddoseofdiphtheria-tetanustoxoid-pertussis),andthefirstdoseofmeasles-containingvaccine(MCV1).Weconductedasystematicreviewofbestpracticesdocumentsfromeightcountrieswhichhadsignificantpolioeradicationactivities.RESULTS:ImmunizationprogrammeshaveimprovedsignificantlyintheAfricanRegion.RegionalcoverageforDTP3vaccineincreasedfrom51%in1996to77%in2014.DTP3coverageincreased>3foldsinDRC(18-80%)andNigeriafrom21%to66%;and>2foldsinAngola(41-87%),Chad(24-46%),andTogo(42-87%).CoverageforBCGandMCV1increasedinallcountries.Ofthe47countriesintheregion,18(38%)achievedanationalcoverageforDTP3⩾90%for2yearsmeetingtheGlobalVaccineAction(GVAP)target.AdecreasewasnotedintheEbola-affectedcountriesi.e.,Guinea,LiberiaandSierraLeone.CONCLUSIONS:PEIhasbeenassociatedwithincreasedspendingonimmunizationandtherelatedimprovements,especiallyintheareasofmicroplanning,servicedelivery,programmanagementandcapacitybuilding.Continuedeffortsareneededtomobilizeinternationalanddomesticsupporttostrengthenandsustainhigh-qualityimmunizationservicesinAfricancountries.StrengtheningRIwillinturnsustainthegainsmadetoeradicatepoliovirusintheregion.WEB:http://dx.doi.org/10.1016/j.vaccine.2016.05.062.IMPACTFACTOR:3.62CITEDHALF-LIFE:5.50UWEDITORIALCOMMENT:Bestpracticesweregroupedintothefollowingcategories:microplanning,implementationandservicedelivery,capacitybuildingandprogrammanagement.Whilethecountriesassessedarediverse,bestpracticesinthesesettingsmaynotbecompletelyrepresentativeofallsettings,andcountrieswerenotrandomlyselectedforthisreview..Notethatwhileimmunizationcoveragetrendsinthefocuscountriesovertimeareinformative,coverageislikelyinfluencedbyarangeoffactorsinadditiontotheinfluenceofpolioeradicationactivities,andtrendsovertimeshouldnotbeassumedtobecausedexclusivelybysupportandinfrastructureofpolioeradicationactivities,butmayalsobeinfluencedbyotherfactors,suchasotherhealthsystemstrengtheningactivities,targetedEPIactivities,andeconomicchangesinthecountry.Withoutcomparisontosimilarcountrieswithoutpolioeradicationinitiativesduringthesametimeperiod,itisnotpossibletoattributechangesexclusivelytopolioeradicationinitiatives.

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5. CONTRIBUTIONOFPOLIOERADICATIONINITIATIVETOEFFECTIVENEWVACCINEINTRODUCTIONINAFRICA,2010-2015.CaroleTevi-BenissanM,MoturiE,AnyaBM,AschalewT,DickyAB,etal.Vaccine.2016Jul5.[Epubaheadofprint]PMID:27396517

ABSTRACTBACKGROUND:SignificantprogresshasbeenmadetoincreaseaccesstovaccinesinAfricasincethe1974launchoftheExpandedProgrammeonImmunization(EPI).Successesincludetheintroductionofseveralnewvaccinesacrossthecontinentandlikelyeradicationofpolio.Weexaminedthecontributionofpolioeradicationactivities(PEI)onnewvaccineintroductioninthecountriesoftheAfricanRegion.METHODS:WereviewedcountryspecificPEIreportstoidentifybestpracticesrelevanttonewvaccineintroduction(NVI),andanalyzedtrendsinvaccinecoverageduring2010-2015fromimmunizationestimatesprovidedbyWHO/UNICEF.RESULTS:Ofthe47countriesinAfricanRegion35(74%)haveintroducedPCV,27(57%)haveintroducedrotavirus,and14(30%)haveintroducedIPV.NationalintroductionsforHPVvaccinehavebeendonein5countries,while15countrieshavehelddemonstrationandpilotprojects.In2014,theregionalcoverageforthethirddoseofPCV(PCV3)androtavirusvaccineswas50%and30%respectively.Byendof2015,allcountrieswithinthemeningitisbeltwillhaveintroducedMenAfriVac™vaccine.CONCLUSIONS:PEIactivitieshadapositiveeffectinstrengtheningtheprocessofnewvaccineintroductionintheAfricanRegion.Themajorcontributionwasinavailingimmunizationfundingandprovidingtrainedandexperiencedtechnicalstafftointroducevaccines.Moreinvestmentisneededtoadvocateandsustainfundinglevelstomaintainthemomentumgainedinintroducingnewvaccinesintheregion.WEB:http://dx.doi.org/10.1016/j.vaccine.2016.05.063IMPACTFACTOR:3.62CITEDHALF-LIFE:5.50UWEDITORIALCOMMENT:Authorsdescribearangeofimportantcontributionsofthepolioeradicationinitiativetosystemsthatsupportedsuccessfulintroductionofothervaccinesandprogramstoimprovecoverage.However,itisimportanttonotethatthatwhilethesuccessfulnationalintroductionofmultiplenewvaccinationprogramsintheAfricaregionhaveoccurredsincepolioeradicationinitiativeswerescaledupintheregion,introductionwasalsolikelyinfluencedbyarangeofotherfactorsinadditiontopolioeradicationactivities,andsuccessfulintroductionshouldnotbeassumedtobecausedexclusivelybysupportandinfrastructurefromthepolioeradicationactivities.Otherfactorsthatchangedovertime,suchasotherhealthsystemstrengtheningactivitiesandinfrastructuresupport,andeconomicchangesinthecountriesandtheregionalllikelyinfluenceddecisionstointroduceothervaccinesandsupportedsuccessfulintroductionandscale-up.Withoutcomparisontosimilarcountrieswithoutpolioeradicationinitiativesduringthesametimeperiod,itisnotpossibletoattributechangesexclusivelytotheinfluenceofpolioeradicationinitiatives.

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6. FRAMEWORKFOROPTIMALGLOBALVACCINESTOCKPILEDESIGNFORVACCINE-PREVENTABLE

DISEASES:APPLICATIONTOMEASLESANDCHOLERAVACCINESASCONTRASTINGEXAMPLES.ThompsonKM,DuintjerTebbensRJ.RiskAnal.2016Jul;36(7):1487-509.Epub2014Aug11.PMID:25109229

ABSTRACTManagingthedynamicsofvaccinesupplyanddemandrepresentsasignificantchallengewithveryhighstakes.Insufficientvaccinesuppliescannecessitaterationing,leadtopreventableadversehealthoutcomes,delaytheachievementsofeliminationoreradicationgoals,and/orposereputationrisksforpublichealthauthoritiesand/ormanufacturers.Thisarticleexploresthedynamicsofglobalvaccinesupplyanddemandtoconsidertheopportunitiestodevelopandmaintainoptimalglobalvaccinestockpilesforuniversalvaccines,characterizedbylargeglobaldemand(forwhichweusemeaslesvaccinesasanexample),andnonuniversal(includingnewandniche)vaccines(forwhichweuseoralcholeravaccineasanexample).WecontrastourapproachwithothervaccinestockpileoptimizationframeworkspreviouslydevelopedfortheUnitedStatespediatricvaccinestockpiletoaddressdisruptionsinsupplyandglobalemergencyresponsevaccinestockpilestoprovideon-demandvaccinesforuseinoutbreaks.Formeaslesvaccine,weexplorethecomplexitythatarisesduetodifferentformulationsandpresentationsofvaccines,considerationofrubella,andthecontextofregionaleliminationgoals.Weconcludethatglobalhealthpolicyleadersandstakeholdersshouldprocureandmaintainappropriateglobalvaccinerotatingstocksformeaslesandrubellavaccinenowtosupportcurrentregionaleliminationgoals,andshouldprobablyalsodosoforothervaccinestohelppreventandcontrolendemicorepidemicdiseases.Thisworksuggeststheneedtobettermodelglobalvaccinesuppliestoimproveefficiencyinthevaccinesupplychain,ensureadequatesuppliestosupporteliminationanderadicationinitiatives,andsupportprogresstowardthegoalsoftheGlobalVaccineActionPlan.WEB:http://dx.doi.org/10.1111/risa.12265.IMPACTFACTOR:2.50CITEDHALF-LIFE:9.40UWEDITORIALCOMMENT:Figure1isasimpleschematicofthemaincomponentsofvaccinesupplymanagementforaglobalstockpile,whichconsiderscomponentsoftheglobaldiseasemanagementstrategy,potentialstockpiledemand,vaccinesupplyoptimizationcomponents,andtheassociatedfinancialcostsandhealthandeconomicbenefits.

Figure2isaconceptualmodelofthe“stocks(currentamountsorlevelsofvaccineinthesupplychain)andflows(incomingandoutcoming)”forvaccineproduction,filling,storageprocessesofaglobalvaccinestockpileovertime.The7stocksincludevaccineinproduction,bulkvaccine,bulkstockpile,othervaccinebulk(forcombinedformulations),vaccineinfilling,filledvaccineandfilledstockpile.Authorsdescribedynamicoptimizationofastockpileastheprocessbywhichthedifferencebetweenpublichealthbenefitsandtotalfinancialcostsismaximized.Figure3isasimilarconceptualmodelofthestocksandflowstosupportoptimizationoftotalsocialcosts,accountingforthebalancebetweencasesofillnessaverted/publichealthbenefits,andtotalfinancialcosts,assumingfinancialconstraintsexists.Thissupportsa“dynamictransmissionmodel”thataccountsforthediseaseincidenceinapopulationandconsiderationoftheincidencewithandwithoutvaccination,whichisbothinfluencedbyandinfluencesthedecisionprocessforstockpiledistribution.

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7. BEYONDVERTICALANDHORIZONTALPROGRAMS:ADIAGONALAPPROACHTOBUILDINGNATIONALIMMUNIZATIONPROGRAMSTHROUGHMEASLESELIMINATION.OrensteinWA,SeibK.ExpertRevVaccines.2016Jul;15(7):791-3.Epub2016Mar28.PMID:26967373

ABSTRACTPlansforreducingandeventuallyeradicatingmeaslesgloballyincludeachievingandmaintaininghighvaccinationcoveragewithtwodosesofmeaslescontainingvaccines(viaroutineandmassvaccination),monitoringdisease,respondingtooutbreaks,buildinggoodcommunications,andimplementingresearchanddevelopmenttoimproveoverallprograms(e.g.healthsystemsstrengthening).Globalprogressonmeaslesvaccinationhassavedmillionsoflives–anestimated17.1millionbetween2000and2014–andhasthepotentialtosavemanymore,especiallyifcountriesbeginusingmeasleseliminationtobuilduptheiroverallnationalimmunizationprograms.WEB:http://dx.doi.org/10.1586/14760584.2016.1165614IMPACTFACTOR:3.46CITEDHALF-LIFE:4.60UWEDITORIALCOMMENT:A“diagonalapproach”referstotheapplicationofdisease-specificortargeted“vertical”resourcestobuilduptheplatformsforthedeliveryofcomprehensivepreventionandtreatmentservices,viaamore“horizontal”approach.Useofsuchresourcestobuildanddevelopmorecomprehensivehealthcareservicesorintegratedapproachestostrengthenthehealthsystemisa“verticalapproach.”Authorsdescribehowmeasleseliminationcanbeaddressedusingadiagonalapproachthatalsostrengthensthesystemfordeliveringotherkeyinterventions.Authorsexplainthatmeaslesisanidealcandidateforadiagonalapproachbecauseofitshighlyinfectiousnature(andthusthehighcoveragenecessarytopreventoutcomes),it’scyclicaloutbreaknature,andtheeasewithwhichitisclinicallyidentified.Forthesereasons,coverageisapriorityandgapsincoverageandinthedeliverysystemoverallareeasilyandquicklyidentified,whichcanbeusedtoinformneedsandopportunitiesforleveragingresourcestoaddresssuchgaps.Theimportanceofmonitoringandsurveillancesothatoutbreakscanbeidentifiedearlyandinterventiontargetedtopreventlargeroutbreakshasalsoledtothedevelopmentofasurveillancesystemthatcanbeleveragedtobuildamorecomprehensivesurveillanceinfrastructurefortrackingotherincidentillnessregionallyandovertime.

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8. FEASIBILITYANDLIMITATIONSOFVACCINETWO-DIMENSIONALBARCODINGUSINGMOBILEDEVICES.BellC,GuerinetJ,AtkinsonKM,WilsonK.JMedInternetRes.2016Jun23;18(6):e143.PMID:27339043

ABSTRACTBACKGROUND:Two-dimensional(2D)barcodinghasthepotentialtoenhancedocumentationofvaccineencountersatthepointofcare.However,thisiscurrentlylimitedtoenvironmentsequippedwithdedicatedbarcodescannersandcompatiblerecordsystems.Mobiledevicesmaypresentacost-effectivealternativetoleverage2Dvaccinevialbarcodesandimprovevaccineproduct-specificinformationresidingindigitalhealthrecords.OBJECTIVE:Mobiledeviceshavethepotentialtocaptureproduct-specificinformationfrom2Dvaccinevialbarcodes.Wesoughttoexaminethefeasibility,performance,andpotentiallimitationsofscanning2Dbarcodesonvaccinevialsusing4differentmobilephones.METHODS:AuniquebarcodescanningappwasdevelopedforAndroidandiOSoperatingsystems.Theimpactof4variablesonthescansuccessrate,dataaccuracy,andtimetoscanwereexamined:barcodesize,curvature,fading,andambientlightingconditions.Twoexperimentersperformed4trials10timeseach,amountingtoatotalof2160barcodescanattempts.RESULTS:Ofthe1832successfulscansperformedinthisevaluation,zeroproducedincorrectdata.Five-millimeterbarcodesweretheslowesttoscan,althoughonlyby0.5secondsonaverage.Barcodeswithupto50%fadinghada100%successrate,butsuccessratedeterioratedbeyond60%fading.Curvedbarcodestooklongertoscancomparedwithflat,butsuccessratedeteriorationwasonlyobservedatavialdiameterof10mm.Lightconditionsdidnotaffectsuccessrateorscantimebetween500luxand20lux.Conditionsbelow20luximpededthedevice'sabilitytoscansuccessfully.Variabilityinscantimewasobservedacrossdevicesinalltrialsperformed.CONCLUSIONS:2Dvaccinebarcodingispossibleusingmobiledevicesandissuccessfulunderthemajorityofconditionsexamined.Manufacturersutilizing2Dbarcodesshouldtakeintoconsiderationtheimpactoffactorsthatlimitscansuccessrates.Futurestudiesshouldevaluatetheeffectofmobilebarcodingonworkflowandvaccineadministratoracceptance.WEB:http://dx.doi.org/10.2196/jmir.5591IMPACTFACTOR:5.82CITEDHALF-LIFE:3.80UWEDITORIALCOMMENT:TAble2showsthetotalnumberandpercentofsuccessfulscansforeachvariableconditionofsize,fading%,curvature,andillumination,bymobiledevice.Teststhatcombineddifferentvariableconditions(eg.highfadingandlowlight)weren’tconducted,thuswhetherthereareadditiveormultiplicativeimplicationsofthesefactorsisn’tclear.Thesetestswereconductedassumingbarcodeswereprinted“ideally”andmobilephoneswere“modern,”butitwouldbeimportanttoassesshowolder/lessmoderndevicesperformandtheinfluenceofaless-than-perfectly-printedbarcodeonaccuracy,sothattheconstraintsunderwhichtheseapplicationsperformarewell-informed.Authorsnotethatbarcodesareincreasinglyusedformedicationandmedicaldevicesalready,thoughnotnecessarilyinlow-resourcesettings.Anotherpotentialuseofbarcodesisforeasilytrackingexpirationdates.Theyalsopointoutthatapplicationsthatallowbarcodestobereadcouldbeusednotonlybyhealthcareproviders,butbypatientsthemselves.

Authorsrecommendausabilitystudytoevaluatethetrainingrequirements,astoevaluatehowbesttointegratescanningintoproviderworkflow.

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9. THEECONOMICVALUEOFINCREASINGGEOSPATIALACCESSTOTETANUSTOXOIDIMMUNIZATION

INMOZAMBIQUE.HaidariLA,BrownST,ConstenlaD,ZenkovE,FergusonM,etal.Vaccine.2016Jul29;34(35):4161-5.Epub2016Jun29.PMID:27340098

ABSTRACTBACKGROUND:Withtetanusbeingaleadingcauseofmaternalandneonatalmorbidityandmortalityinlowandmiddleincomecountries,ensuringthatpregnantwomenhavegeographicaccesstotetanustoxoid(TT)immunizationcanbeimportant.However,immunizationlocationsinmanysystemsmaynotbeplacedtooptimizeaccessacrossthepopulation.IssuesofaccessmustbeaddressedforvaccinessuchasTTtoreachtheirfullpotential.METHODS:ToassesshowTTimmunizationlocationsmeetpopulationdemandinMozambique,ourteamdevelopedandutilizedSIGMA(StrategicIntegratedGeo-temporalMappingApplication)toquantifyhowmanypregnantwomenarereachablebyexistingTTimmunizationlocations,howmanycannotaccesstheselocations,andthepotentialcostsanddiseaseburdenofnotcoveringgeographicallyharder-to-reachpopulations.Sensitivityanalysescoveredarangeofcatchmentareasizestoincluderealistictraveldistancesandtodeterminetheareasomelocationswouldneedtocoverinorderfortheexistingsystemtoreachatleast99%ofthetargetpopulation.RESULTS:For99%ofthepopulationtoreachhealthcenters,peoplewouldberequiredtotravelupto35km.Limitingthisdistanceto15kmwouldresultin5450(3033-7108)annualcasesofneonataltetanusthatcouldbepreventedbyTT,144,240(79,878-192,866)DALYs,and$110,691,979($56,180,326-$159,516,629)intreatmentcostsandproductivitylosses.Acatchmentarearadiusof5kmwouldleadto17,841(9929-23,271)annualcasesofneonataltetanusthatcouldbepreventedbyTT,resultingin472,234(261,517-631,432)DALYsand$362,399,320($183,931,229-$522,248,480)intreatmentcostsandproductivitylosses.CONCLUSION:TTimmunizationlocationsarenotgeographicallyaccessiblebyasignificantproportionofpregnantwomen,resultinginsubstantialhealthcareandproductivitycoststhatcouldpotentiallybeavertedbyaddingorreconfiguringTTimmunizationlocations.Theresultingcostsavingsofcoveringthesehardertoreachpopulationscouldhelppayforestablishingadditionalimmunizationlocations.WEB:http://dx.doi.org/10.1016/j.vaccine.2016.06.065IMPACTFACTOR:3.62CITEDHALF-LIFE:5.50UWEDITORIALCOMMENT:Therelationshipbetweenthesizeofthecatchmentarearadiusforahealthcenterandtherateofincreaseinthesizeofpopulationcoveredwasnon-linear;thesizeoftheadditionalpopulationcoveredincreasedatanincreasingrateforlargercoverageradiusesupto4km,butafterthatthesizeoftheadditionalpopulationcoveragegainedforlargerradiuscatchmentareasdeclines(Figure1).Authorssuggestthatthesubstantialrateofchangeincoverageforslightlylargerradiiisduetoreachingadditionalpeopleinurbancenterswithonlyslightlylargercatchmentareas,andexplainthatatacertaindistance,lessadditionalpeoplearereachedwithlargercatchmentareasbecausetheareaswillincludelessdenselypopulatedruralareas,wherecoverageislessefficientlygained.Authorsnotethatevenusinglargercatchmentareas,ruralpopulationsaremoredifficulttoreachandlessefficientlyaccessed,whichisdisplayedvisuallyinFigure2.Likewise,thereare“diminishingreturn”intermsoftheeconomicimpactofcoveringthese“hardtoreach”populationsatlargergeographicradii,inthatdifferencesincases,case-relatedcostsandDALYSlostarelesspronouncedasthesizeofradiusincreasesatlargerradii.Authorsrecommendthatconductingoutreachfromexistingfixedcenters,providingtransportationorreimbursementfortravelmayeffectivemethodstoincreasereachandcoverage,inadditiontoaddingadditionalsitesorchanginglocationsofsitestoreachalargerpopulation.

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10. INTERVENTIONSTOIMPROVEHPVVACCINEUPTAKE:ASYSTEMATICREVIEW.WallingEB,BenzoniN,DornfeldJ,BhandariR,SiskBA,etal.Pediatrics.2016Jul;138(1).Epub2016Jun13.PMID:27296865

ABSTRACTCONTEXT:Thehumanpapillomavirus(HPV)vaccineisasafe,effectivecancerpreventionmethodthatisunderutilizedintheUnitedStates.Despiteincreasedunderstandingofbarrierstovaccination,ratesremainlow.Globally,developedanddevelopingnationshaveachievedhighratesofvaccination.OBJECTIVE:IdentificationofeffectivestrategiesisnecessarytooptimizeuptakeoftheHPVvaccine.WesystematicallyreviewedtheliteraturefornationalandinternationalinterventionsthathavesuccessfullyincreasedHPVvaccineuptake.DATASOURCES:WeusedastandardizedprotocoltosearchforarticlespublishedbetweenJanuary1,2006,andApril30,2015,in3electronicdatabases:PubMed,Scopus,andEmbase.STUDYSELECTION:WeidentifiedinterventionsdesignedtoincreaseHPVvaccineuptakeamongadolescentsandyoungadultsaged11to26years.Allstudydesignswereacceptable.Onlyarticlesthatincludedpostinterventionvaccinationrateswereincluded.DATAEXTRACTION:Twoauthorsindependentlyreviewedeacharticlefordataextractionandqualityassessment.InterventionswereclassifiedaccordingtotheCommunityPreventiveServiceTaskForceguide.RESULTS:ResultswerereportedaccordingtotheRE-AIM(Reach,Effectiveness,Adoption,Implementation,Maintenance)framework.Fifty-onearticlesmeteligibilitycriteria:2informationalinterventions,18behavioralinterventions,and31environmentalinterventions.FactorsassociatedwithHPVvaccineuptakewereincreasedvaccineavailability,decreasedfinancialbarriers,andinterventionstargetingbothprovidersandpatients.LIMITATIONS:LackofconsistentRE-AIMmetricreporting,limitingourabilitytoassessinterventionvalidityandquality.CONCLUSIONS:Population-basedvaccinationstrategiesthatincreasedvaccineavailabilityreachedthegreatestnumberofadolescentsandweremostsuccessfulinachievinghighratesofvaccination.WEB:http://dx.doi.org/10.1542/peds.2015-3863IMPACTFACTOR:5.80CITEDHALF-LIFE:8.30UWEDITORIALCOMMENT:TheRE-AIMevaluationcriteriaagainstwhichinterventionswereassessedisexplainedinTable4..StudiesassessinginformationalandbehavioralinterventionswereexclusivelyconductedintheUSorotherhigh-incomecountries.

Environmentalinterventionsaimedto“changethesocialenvironmenttofacilitatevaccination,eg.decreasedfinancialbarriers,novelvaccinationlocations”andincludedinterventionsatthe“small(organizationalguidelines,nogovernmentinvolvement)”,and“largepolicylevels(formallaws,rulesorregulations,nationalorlocalgovernmentinvolvement).”Environmentinterventionswereconductedinbothhigh-andlow-resourcesettings.Schoolandclinic-basedvaccinationprogramsweretheprimaryinterventionapproachesusedinlow-resourcesettings.Authorspointoutthattheabilitytoreachlarge,diversepopulationsregardlessofthehealthaccessoftheindividuals,andtheincreasedaccesstotheHPVvaccinewereimportantcontributingfactorstosuccessoftheseprograms.Authorsnotethatschool-basedprogramswerewidelyacceptedbykeystake-holders.Onelimitationwasthatschool-basedprogramsprimarilytargetedyoungadolescents,andvaccinationcoveragewasimpededbypoorschoolattendance.

VaccineDeliveryResearchDigest,STARTCenter–June2016

APPENDIX:PUBMEDSEARCHTERMS

(((((vaccine[tiab]ORvaccines[tiab]ORvaccination[tiab]ORimmunization[tiab]ORimmunisation[tiab]ORvaccine[mesh]ORimmunization[mesh])AND(logistics[tiab]ORsupply[tiab]OR"supplychain"[tiab]ORimplementation[tiab]ORexpenditures[tiab]ORfinancing[tiab]OReconomics[tiab]OR"Costeffectiveness"[tiab]ORcoverage[tiab]ORattitudes[tiab]ORbelief[tiab]ORbeliefs[tiab]ORrefusal[tiab]OR"Procurement"[tiab]ORtimeliness[tiab]ORsystems[tiab]))OR("vaccinedelivery"[tiab]))NOT("invitro"[tiab]OR"immuneresponse"[tiab]ORgene[tiab]ORchemistry[tiab]ORgenotox*[tiab]ORsequencing[tiab]ORnanoparticle*[tiab]ORbacteriophage[tiab]ORexome[tiab]ORexogenous[tiab]ORelectropor*[tiab]OR"systemsbiology"[tiab]OR"animalmodel"[tiab]ORcattle[tiab]ORsheep[tiab]ORgoat[tiab]ORrat[tiab]ORpig[tiab]ORmice[tiab]ORmouse[tiab]ORmurine[tiab]ORporcine[tiab]ORovine[tiab]ORrodent[tiab]ORfish[tiab]))AND(English[LA])AND("2016/6/15"[PDAT]:"2016/07/14"[PDAT]))

*On July28,2016, this searchofEnglish languagearticlespublishedbetween June15,2016andJuly 14, 2016 and indexed by the US National Library of Medicine resulted in 207 uniquemanuscripts.