ModernToolsetsforDefeatingBothEpidemicandEndemic
InfectiousDiseasesPROF ES S OR AN TON I N O Z I C H I C H I , P R E S I DEN T
P H I L I P . E C K H O F F@ C O M C A S T . N E T
A P R ES ENTAT IO N TO THE 4 9 TH S ES S IO N O F THE INTERNAT IO NAL S EM INAR S O N P LANETAR Y EMERGENC I ES , MAJO RANA C ENTR E , ER I C E , S I C I LY, I TALY
P R O F E S S O R AN TON I N O Z I C H I C H I , P R E S I DEN T
A UGU S T 2 0 - 2 3 , 2 0 1 6
P H I L I P A E C K H O F F AN D L OW EL L L W OOD
P H I L I P . E C K H O F F@ C O M C A S T . N E TOpinions expressedhereinarethoseoftheauthorsonly
ThePathogensResponsibleForInfectiousDiseasesareaGlobalThreat-- TheirActionsConstituteanOngoingPlanetaryEmergencyofFirstMagnitude§MostpathogensareAncient Enemiesofhumanity– often“atleastasoldasWeare”
§ Haveimposed titanic burdens ofmorbidity-&-morta lity§ Mostallofour~100,000,000,000ancestorsdiedofpathogenicdiseasesormalnutrition– not fromthenow-standarddegenerativediseasesoftheDevelopedWorld
§ Havebecome ever-more-threatening ashuman population densities havesoared,speeds-&-scales oftransportation haveclimbed,....§ The1918-20‘influenza’pandemickilled~108 people–wellover5%ofallhumansthenalive§ Beforeitsglobaleradicationin1977– culminatingaWHO-sponsoredcampaignledbyDAHenderson-- smallpoxhadkilled~100,000,000peopleinthe20th centuryalone
§Overallburden§ Over11Mdeaths everyyearfrominfectious diseases, nutritional disorders, andmaternal mortality§ Over7Mofthese annual avoidable deaths occur in children <5yearsold
§Currently-endemic diseases§ Malaria,TBand HIV§ Pneumonia and other respiratoryinfections; enteric infections
§Pathogeneradicationasapathwaytodefinitivelyaddressingendemics– andobviatingepidemics/pandemics§ Resistance isalways anissue fordrugsand vectorcontrol: ”Ourwits against theirgenes!” -- Lederberg§ Intense disease control – anovel ‘feature’ofmodern times -- isvulnerable to reversalsoffunding, political failures andcollapses of social order
§Zoonosesandother pathogenic sourcesofepidemics/pandemics ofemerginginfectiousdiseases,e.g.,§ Ebola, Zika,...§ Antigenically-novel and/or hypervirulent aeroviral strains: influenza, SARS/MERS,...
§ToolsetsforEradicationend-gameareusefulforpandemicsuppression asEradicationandpandemiccontrol aredualproblems
§MostpathogensareAncient Enemiesofhumanity– often“atleastasoldasWeare”§ Haveimposed titanic burdens ofmorbidity-&-morta lity
§ Mostallofour~100,000,000,000ancestorsdiedofpathogenicdiseasesormalnutrition– not fromthenow-standarddegenerativediseasesoftheDevelopedWorld§ Havebecome ever-more-threatening ashuman population densities havesoared,speeds-&-scales oftransportation haveclimbed,....
§ The1918-20‘influenza’pandemickilled~108 people–wellover5%ofallhumansthenalive§ Beforeitsglobaleradicationin1977– culminatingaWHO-sponsoredcampaignledbyDAHenderson-- smallpoxhadkilled~100,000,000peopleinthe20th centuryalone
§Overallburden§ Over11Mdeaths everyyearfrominfectious diseases, nutritional disorders, andmaternal mortality§ Over7Mofthese annual avoidable deaths occur in children <5yearsold
§Currently-endemic diseases§ Malaria,TBand HIV§ Pneumonia and other respiratoryinfections; enteric infections
§Pathogeneradicationasapathwaytodefinitivelyaddressingendemics– andobviatingepidemics/pandemics§ Resistance isalways anissue fordrugsand vectorcontrol: ”Ourwits against theirgenes!” -- Lederberg§ Intense disease control – anovel ‘feature’ofmodern times -- isvulnerable to reversalsoffunding, political failures andcollapses of social order
§Zoonosesandother pathogenic sourcesofepidemics/pandemics ofemerginginfectiousdiseases,e.g.,§ Ebola, Zika,...§ Antigenically-novel and/or hypervirulent aeroviral strains: influenza, SARS/MERS,...
§ToolsetsforEradicationend-gameareusefulforpandemicsuppression asEradicationandpandemiccontrol aredualproblems
GlobalDiseaseEradicationEfforts§GlobalEradicationofsmallpox(Variola major)wasadefiningtriumphofOurspecies§ Thepurposeful exterminationofaruinoushumanpathogen
§Keylessonsoftheanti-smallpoxcampaign§ Timely(!)casedetection§ Vaccinationcoverageand(eventual)logisticssufficiency§ Adaptivetactics§ Roleofmid-Campaigntechnical-&-programmaticinnovations
§Rinderpestwasthe2nd GlobalEradicationtriumph§ Recapitulatedlessonsofthesmallpoxeradicationcampaign
§Earlyattemptsagainstotherdiseasesfailed§ Yellowfever§ Malaria
§OtherEradicationCampaignsarenow inlatestages,nearingsuccess§ Polio§ GuineaWorm
§NewefforttoGloballyEradicatemalariaannounced in2007
MalariaEpidemiologyandBurdenhasChangedTremendouslySince2000§Decreaseindeathsfrom839,000in2000to438,000in2015§Source:WMR 2015
§ScaleupofLLINs,IRS,andART§Increaseinfinancing§Changeinproportionofpeoplelivingindifferentlevelsofmalarialendemicity inAfrica
Bhattetal,Nature 2015
TheAfricanMalariaLandscapeHasShifted
Bhattetal,Nature 2015
VectorControlHasPlayedAMajorRole§Just2%ofsub-SaharanAfricanpopulationsleptunderinsecticide-treatednetin2000§≥halfofthispopulationwas‘covered’in2015
§Source:WMR 2015
§ITNsandIRSwereresponsibleformuchofthedeclineinendemicity,accordingtoarecentanalysis
Bhattetal,Nature 2015
EnabledByEver-HigherLevelsofFunding
WorldMalaria Report2015
…ButProgressIsFragile§Riseofpyrethroid resistance(andinsecticide resistancemoregenerally)§Needtoreplacebednetsfrequently,maintaininghighpopulationcoverage§Shiftsinvectorspeciescompositionandfeedingbehaviors§ ObservedchangeinAn.farauti bitingbehaviorinSolomonIslandsfrom1972to2007§ 1972datafromTaylor1975§ 2007datacourtesyTanyaRussell,MTC
§ Couldmakeindoortargeting(netsandspraying)lesseffective
§Fundingcontinuityandsocialorderissues§ RecentexampleofVenezuela
MalariaEradicationIsABig,Long-TermGoal§GlobalMalariaEradicationwasattemptedbefore(~’58- ~’70)§ Itisnoteasytocomplete
§ArenewedeffortwaslaunchedattheMalariaForumin2007§Ideal:theburdenofmalariaisstablyatzeroforever,robusttoanykindofreversal§Pesticideanddrugresistance,economiccrisis,fatigue,etc…
§Givennumbers,time,andpressure,Evolution– “..theirgenes”-- willwinotherwise
§MalariaEradicationisdifficult§Extensiveheterogeneities§Baselinetransmissionintensity§Multiplelocalvectorspecies§Populationdensities§Typesofhousing§Baselinehealthcare§Resistancestatuses§ Immunestatus
§Manylogistic-challenging areas
BasicAnalyticalFrameworkforEradication§Partitionintoregionaleliminationeffortsandprioritize§Reducetransmission§ Vectorcontrol§ Prophylaxis§ Vaccines?
§Clearinfections§ Diagnostics§ Drugs§ Campaigns
§Preventreintroduction§ Casemanagement§ Surveillance§ Aidedby“stickiness”?(DLSmith)
§Availabletools(present+10yrs)§ Drugs§ Single-encounter,radical-cure§ Prophylaxis
§ Diagnostics§ Vaccines?§ Vectorcontrol§ Nets§ IRS§ Larvalcontrol,sourcemanagement§ Newapproaches(e.g.,geneticgambits)
§ Fieldlogisticssupport§ Polioexample
§Modelingandquantitativeanalysis§ Datasystemsandmonitoring
DataAnalysisandMathematicalModelsAidUnderstandingofLocalEpidemiology
2013Round-1 Household PrevalenceGwembe, Southern, Zambia
MalariaSeasonalityinZambia
GWEMBE DISTRICT
RDT-confirmed clinical cases
Lakefron
t
HotDrySeason
UsingMalariaGenomicstoDetectChangesinTransmissioninSenegal
Daniels et al. PNAS 2015
WhatDoesitTaketoCompletetheGlobalEradicationofWildPoliovirus?
§Progressoverpasttwoyears— comparedtoa12-monthwindowfromJune2014
§Needtoclearlastpockets-of-contagion inNigeria,Pakistan,andAfghanistan
PolioRiskMapsforTargetingVaccination
Upfill-Brownetal.,BMCMedicine2014
MoreWasNeededforPolioinNigeria§BetterPopulation Maps§ Remotesensingandfeatureextractiontomapwherepeoplelive
§ Developmentofnewmicroplans
§VaccinatorTracking§ Super-resolutionphotogrammetry- andGPS-enabled§ Real-timecoverageestimation§ Targetingofun-reachedneighborhoods,evenhouses
§Investment inColdChaintechnologies§ Storage§ Outreach§ Situationalawareness
§Accessandsecurityforvaccinators
VaccinatorTrackingwithImprovedPopulationMapsAllowsReal-timeCoverageEstimates
PolioInvestmentsHelpedInterruptEbolainNigeria!
ButWeareNotReadyforNextEpidemic
InnovationisNeededforEndemicDiseaseEradicationandSuppressionofPandemics§AreasforInnovation§ Innovation inVaccine ColdChainsupport§ Innovation inVaccines§ Innovation inDrugsandDrugDelivery§ Innovation inNovelVector Control§ Innovation inImmunological Tools
§DeliveryandLogisticsarekey!§ Innovation thatfacilitates thisareverydesirable§ Informationsystems
§Internationalenablingenvironment§ Rapid,extensively-rehearsed set-of-responses§ Pre-authorization andfunding-in-the-bank
InnovationinVaccineColdChainSupport§Newcost-efficientvaccinerefrigeratorsforchallenging(e.g., low-qualitypower)conditions§ E.g.,MetaFridge
§New-technologyvaccineoutreachsupport§ Evaporatescoldwater/ice atlowpressure toprovideshelf-stable, weight-efficient thermal battery
§ Aimedtosupplantpresent ice-filled carriers
UnprecedentedLogisticsSupportEnabledVia‘BoilingIce’
Device initially turnedon(Charged inSeattle)
Ambient temperature measured onoutsideofcarrier. Variations causedbymovement of
device, exposure tosunetc.
Lidopeningsofdevice, vaccinator retrievingvaccines fromunit.
Day1 Day2 Day3 Day4 Day5
InnovationinDrugs§Gastricretentiondevicesthatreleasedrugsoverdaystoweeksaftersingle-occasionoralingestion
§Extendpharmacokineticsfar beyondtraditionaltimeconstants
§Improveseaseofdelivery,achievablecoverageandadherence, anddurationofbiomedicalaction
§BobLangerandGioTraversoatMIThavedemonstratedworkingprototypesforivermectin
InnovationinVaccines
comprehensiveandenduringimmunizationatbirth§ Reliable protection againstall vaccination-preventable pathogenic diseases
§Timed-release packagingforimmunogens
§Receive entirecourseofatimedpulsatile-release vaccinationseriesinasingleinjection§ Technology demonstrated forIPVbyBobLangerandAnaJaklenec atMIT
§ Alsosupports single injection administration ofpreviously-incompatible vaccines
§Nowfirmlyonthepathtocomprehensiveandenduringimmunizationatbirth§ Reliable protection againstall vaccination-preventable pathogenic diseases
InnovationinModifiedMosquitoes—GeneDriveforIndividualAnophelesSpecies
8Years AfterReleasePopulation EliminatedConstruct AtFixationMixofWildtype andGene DriveLossofConstruct
Burt,PhilTransRoySoc B2014 Eckhoffetal,under review
Available drive techniques Effectofgermline homing
InnovationinImmunologicalTools
ThePathwayForwardThePathwayForwardMajorPlanetaryEmergency§Infectious DiseasesareaMajorPlanetaryEmergency
§ Theongoing annualdeathtollisnotablysevere§ We’verecentlyseen ≤10%ofthehumanracepathogen-slaughtered in2years
§ Pandemicrisksfromemergingpathogensthreateneveryone,everywhere,continually§ EbolainHouston&Lagos; ZikainMiami&New York;SARSinBeijing&Toronto
§ Especially‘ifanythingreally goeswrong’inamajorpopulation-pool
§Innovation — guided byscientificstudy, computation, andstrategy— isurgentlyneeded to informenhanceactions§ Extantmeansaredubiouslysufficient– andarebeingcontinually‘outgrown,’aswellasover-matched
§International partnerships— withestablished, pre-staffed/equipped/exercised, pre-funded responsecapacities— arecorecomponents ofwhatarerequired
§ThesamecapabilitiescanbeexercisedtocompletediseaseregionaleliminationandEradicationefforts— whilekeeping thesefullypreparedtoaddresshyper-epidemics