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