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Six Years of Food Virology Research:
The NoroCORE Project Dr. Lee-Ann Jaykus, Ph.D.
Scientific Director, USDA NIFA Food Virology Collaborative Presentation to FDA Southeast Regional Meeting
October 17, 2017
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� LongTermGoal:Toreducetheburdenoffoodbornediseaseassociatedwithviruses,par5cularlynoroviruses
� Approach:Mul5-disciplinaryteamworkinginanintegratedmannertodevelopimprovedtools,skills,andcapacitytounderstandandcontrolfoodbornevirusrisks
� Objec5ves(Cores):MolecularvirologyDetec5onEpidemiologyandRiskAnalysisPreven5onandControlExtensionandOutreachEduca5onandCapacityBuilding
The USDA-NIFA Food Virology Collaborative
Ext
ensi
on &
Outr
each
Educa
tion
Detection
Epidemiology & Risk Analysis
Molecular Virology
Control Strategies
� MolecularVirology:Developimprovedmethodstofacilitatethestudyoffoodbornevirusesandtofurtherelucidatethesignificanceofviralfoodbornedisease
� Detec5on:Developandvalidatesensi5ve,rapid,andprac5calmethodstodetectandgenotypehumannorovirusinrelevantsamplematrices
� EpidemiologyandRiskAnalysis:Collectandanalyzepopula:ondataontheburdenofvirus-associateddisease,includingepidemiologicala=ribu:onandcharacteriza:onofriskandcosts
� Preven5onandControl:Improveunderstandingtheoccurrenceandbehaviorofhumannorovirusinthefoodsafetycon:nuumsoastoinformdevelopmentofscien:ficallyjus:fiablecontrolmeasures
Research Activities
� ExtensionandOutreach:Translateanddisseminatenewknowledgeaboutfoodbornevirusesintoprac:cesthatreachtargetaudiencesinrelevantworkenvironmentsandacrossawidearrayofstakeholdergroups
� CapacityBuilding:Buildscien:ficandhumancapacitytosupportincreasedandsustainedeffortsinfoodvirologybyfosteringinforma:onandexchange,expandingprofessionalcapacitythroughformalstudenteduca:onandtrainingini:a:ves
Extension, Outreach, & Education Activities
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Partners (Collaborators)
Stakeholders
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Core 1: Molecular Virology
§ Humannorovirusesaretheleadingcauseofacutegastroenteri5sinU.S.,probablyworldwide
§ Responsiblefor21millioncases;70,000hospitaliza5ons;and800deathsannually(CDCes5mates)
§ $2billionannuallyinhealthcareandlostproduc5vitycosts§ Responsiblefor>5millioncasesoffoodbornediseaseannually
§ Aroundfood-related15,000hospitaliza5onsannually[26%,2ndinrank]§ Around150food-relateddeathsannually[11%,4thinrank]
§ Causeoffoodbornediseaseofunknowne5ology?
Disease Burden
Core #3: Epidemiology and Risk Analysis
Foodborne15%
Person-to-person78%
Waterborne
Environmental0.2%
Other/Unknown7%
<0.1%--Fecal matter vs. vomitus --Low infectious dose --High degree of shedding --Virus persistence and resistance --Important venues
Foodborne Transmission
Infected food workers cause about 70% of reported norovirus outbreaks from contaminated food.
Foods Implicated* in Norovirus Outbreaks Reported to CDC by Commodity and Point of
Contamination (2001-2008)
0
20
40
60
80
100
120
140
No.ofO
utbreaks Produc5on&Processing
Prepara5on&ServiceUnknown**
*Limitedtooutbreakswithasimplefood(consis5ngofasinglecommodity)implicated**Insufficientorconflic5nginforma5onprovidedinoutbreakreport
Hall et al. 2012. Emerg. Infect. Dis. 18(10):1566-1573.
Vomit Splatter
Tung et al., in preparation
Risk Modeling
� NorOPTIMAL(NorovirusOn-linePredic5veTooltoInves5gateMi5ga5onALterna5ves)isasimula5onmodeldesignedtocompareefficacyofdifferentinterven5onstrategiesinmicroenvironmentsbasedonhealthriskandcost
� KeyfeaturesofNorOPTIMAL� “Agent”basedmodel� Probabilis5csimula5on� Inputsinformedbyresearchfromthecollabora5ve(e.g.,
transferrates)andpublishedliterature� Producesriskmetricsincludeinfec5onprobability,disease
progression,andoutbreaksize
Agents interact according to spatial layout and schedule of activities
� Purpose:Improveunderstandingtheoccurrenceandbehaviorofhumannorovirusinthefoodsafetycon5nuumsoastoinformdevelopmentofscien5ficallyjus5fiablecontrolmeasures.• Ac5vity4.1:Evaluateandmonitorvirusoccurrencepre-andpost-
harvest,includingalterna5vemicrobiologicalindicators
• Ac5vity4.2:Develop/evaluatenovelan5viralagentsforhandandsurfacedisinfec5onincollabora5onwithindustrialpartners
• Ac5vity4.3:Testefficacyofcandidatetechnologiestoremoveand/orinac5vatevirusesandtheirsurrogatesinfoods(pilotscale)
• Ac5vity4.4:Movepromisingprocessingtechnologiestowardcommercializa5onusingstage-gateapproach
Core # 4: Prevention & Control
§ Surfaces § Room temperature: Days/ weeks
§ Foods and water § Refrigeration: Weeks/months/ years § Freezing: Months/ years
§ Also depends on surface/food and virus, RH § Transferability
§ Variable (0.1%->90%) § Depends on moisture, surfaces, pressure, virus § Sequential (10X)
§ Environmental contamination § Outbreaks § Endemic
§ Virus concentrations
§ Persistence and concentration on hands § Airborne? § Relative importance (attribution)
Virus Persistence
§ Product relevance?
§ Methods § Refrigeration and freezing
§ Drying and aw § Conventional preservatives
§ What about heat? § Surrogates differ in heat resistance
§ Norovirus and hepatitis A generally more resistant
Inactivation: ‘Traditional’ Methods in Food Processing
§ Formulation matters § Efficacy impacted by concentration and contact time § Active compounds (ingredients)
§ Chlorine, 1,000-5,000 ppm (+) § Benzalkonium chloride chloride (-) § Phenols § Hypochorous acid, up to 250 ppm § Silver dihydrogen citrate § Activated hydrogen peroxide § Emerging technologies
§ Surface coatings (e.g., light activated fluorinated TiO2) § Copper (>70%) § Nanoparticle technology
§ Soft surfaces? § Potential drawbacks
Prevention: Surface Disinfection, Direct Contact
CopperasaSelfSani5zingSurface
� Used as antimicrobial since ~2500 BC
� Copper touch surfaces reduce hospital acquired infection rates
� Broadly antimicrobial � Efficacy against variety of
viruses and bacteria � Data lacking for human
noroivirus
Department of Food, Bioprocessing and Nutrition Sciences
Salgado et al., 2013
Hypothesis:Coppersurfacesmaybeusefultoreduceenvironmentallymediatedhumannorovirustransmission
Electron Microscopy Results
What Doesn’t Work
§ Broad spatial coverage § Potential drawbacks § Application approach and
concentration matter § Active ingredients
§ Hydrogen peroxide § ClO2
§ Others? § Application to clean-up after
vomiting event or reservoir locations like restrooms?
§ Soft surfaces?
Prevention: Surface Disinfection, Indirect Contact (Fogging)
§ Product type [actives] § Alcohol [60-90%, ethanol, isopropanol, n-propanol] (-) § Povidone-iodine (+/-) § Benzalkonium chloride chloride (-) § Triclosan (-) § Chlorhexidine (-) § “Sanitwice”? § Emerging actives
§ Copper § Bismuth subsalicylate § Others?
§ Formulation matters § Product application (volume and time) § Validation/methodological issues § Regulatory/licensing/use issues
Hand Sanitizers
ASTM E-1838-02 (Fingerpad Method)
Norovirus Strain-Specific Ethanol Sensitivity
Core #5: Extension and Outreach
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Prevention: Extension and Outreach
§ Audiences § Fresh produce § Shellfish § Retail (food handlers) § Consumers § Public health officials
§ Methods § Curricula § Training programs § Written materials
§ Issues § Resources § Evaluation § Compliance § Sustained behavior change
� FreshProduceIndustry� Contribu5onstona5onalGAPstrainingcurriculum
� MolluscanShellfishIndustry(ISSC)� Contribu5onstona5onalharvester/dealertrainingcurriculum� Educa5onalvideo� Recrea5onalboaters
� FoodService/GroceryIndustries� Environmentalsampling� Vomit/fecalmaqerclean-upguidelines
� Sanita5onandHygieneIndustry(includingCLIA)� Tes5ngcandidatetechnologies
Core 5: Extension and Outreach
� Website
� Comprehensivereagent/protocolexchange� VLPs,glycans,reversegene5cssystems� CDC“Pla5numPanel”
� Literaturedatabase� Freelyaccessiblepaperstocollaborators(n>3,000)� FreelyaccessibleabstractsonWeb
� Discre5onaryfunding
� Studenttraining� Undergrad:11(NCSU,Clemson,BCM,Emory,UGA,OSU,IIT)� Grad:12(BCM,Emory,OSU,Rutgers,Clemson,U-DE,NCCU,
GSU,UGA,NCSU)
Core 6: Capacity Building
Educational Visuals
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Hand-Washing
Summary of Achievements � Cellculturemodel!� Comprehensivesurrogatecomparison,Tulaneprobably
mostrelevant� Detec5on
� Lotsofligandswithbroaderreac5vity� Microarraysforgenotyping� Beqerunderstandingofinfec5vitydilemma
� Keyepidemiologicalfindings� Improvedunderstandingofdiseaseburden� Roleoffreshproduceand“complex”foods� Importanceoffoodhandler� Children/elderly
� Aerosoliza5onofvirusduringvomi5ng� Prototyperiskmodel
Summary of Achievements � Foodprocessing
� Resistancetomostcommonlyusedfoodprocesses� Perhapsmoreheatresistantthanpreviouslythought� Novelprocessesofpromise� Whatdoesnotwork� Hurdleapproach?
� Sani5zersanddisinfectants� Noneresultincompleteinac5va5onatnormaluse
recommenda5ons� Highconcentra5onsandlongcontact5mesnecessary,
par5cularlyonsurfaces� Coppermaybepromising
� Crossdisciplinary,holis5capproach� Sharethewealth� Team-buildingiscri5cal
� Timecommitmentbyleadership
� Budgetforsupportstaff� Moneymakesthingshappen!
� Inevitableadministra5vehurdles
� Listentostakeholders� Evalua5onisachallenge!� Others…..
Lessons Learned
Follow our progress…
http://norocore.ncsu.edu
www.facebook.com/norocore
@ NoroCORE H h
� TheENTIREteam
� ALLourstakeholders� Thegraduatestudentsandstaff� NCSUadministrators
� USDANIFAstaff� USDANIFA,award#2011-68003-30395
Acknowledgements
Students and Staff Laboratory
� Dr. Rebecca Goulter
� Dr. Blanca Escudero-Abarca
� Dr. Jennifer Shields
� Dr. Naim Montezeri
� Dr. Caleb Suh
� Dr. Chip Manuel
� Dr. Matthew Moore
� Dr. Erin Almand
� Mr. Jon Baugher
� Mr. Eric Moorman
� Ms. Katie Overbey
� Ms. Janie Outlaw
Administration
� Dr. Lynette Johnston
� Dr. Christina Moore
� Dr. Elizabeth Bradshaw
� Dr. O.D. “Chip” Simmons
� Ms. Katie Gensel
� Mr. Malakai Erskine