Natural Outbreaks and Bioterrorism: How to Deal with the Two Sides Of

Home , Bioterrorism, Pandemic

www.jogh.org 5 4 3 2 1 Laurent Guillier Lionel Koch JoGH ©2020ISGH © 2020TheAuthor(s) the twosidesofsamecoin? bioterrorism: Howtodealwith Natural outbreaksand CBRNEJointDefenseCenter(CIANRBC),Saumur, France PediatricEmergency Department,AP-HP, RobertDebreHospital,Paris,SorbonneUniversity,France BacteriologyUnit,FrenchArmedForcesBiomedicalResearchInstitute(IRBA),BretignysurOrge, France France (ANSES), Maisons-Alfort,France Department ofMicrobiologyandInfectiousDiseases,FrenchArmedForcesBiomedicalResearchInstitute(IRBA),Bretignysur Orge, Risk Assessment Department, University of Paris-Est, French Agency for Food, Environmental and Occupational Health & Safety the outbreakorigin. specific measures,whatever tion andtheestablishmentof tion, theaccuratecharacterisa safety remains theearlydetec The realchallengeforglobal • doi: 10.7189/jogh.10.020317 regarded asaglobal concern[ other strategies.Thus,outbreaks cannolongerbeconsideredasalocalanddistantissue butshouldbe going lockdownofbillions peopleduringtheCOVID-19willhavetobeevaluated andcomparedto pandemic (COVID-19)caused bythenewhumancoronavirusSARS-CoV-2. Theeffectivenessof theon and theUnitedStates[ naturally emerged in alarge spreadhassubsequently impactedEurope newarea,anditsoverwhelming digm oftheissuescausedbyemerging infectious diseasesnowadays:thisextremelydeadlypathogenhas sures to contain the disease [ The globalisationofinternationalexchangescontributes to theinefficiencyofcommonquarantinemea In thelastthirtyyears,paceofemerging infectious diseaseoutbreakshassignificantlyincreased[ monitoring newthreatsandabletoworkwiththesesystems willstayatthecentreofstage. will be to complementandenhance human capabilities butcannot substitute them. Thehumanexperts age it,especiallyinthephasesofpreparednessandresponse effectiveness.Thistechnologylargest impact common effort. Innovative Artificial Intelligence is becoming unavoidable to detect the crisis and to man plans organising theactionofallentities(civilians, militaries,governmentalandnon-governmental)ina velopment ofearlydetectionandpreparationmeasuressuch asthedevelopmentofglobalcontingency 1 , Anne-AurelieLopes 4 , Jean-NicolasTournier

- - 3 ]. This observation was confirmed and emphasised by the coronavirus disease wasconfirmed andemphasisedbythecoronavirusdisease ]. Thisobservation on thetimelinessofresponse:effortshouldthusratherfocusde outbreak, theeffectivenessofresponsetoanoutbreakiscloselydependent scientific investigations.Furthermore,andasdemonstratedbytheCOVID-19 dence, differentiate them is a delicate task requiring complex, long and rigorous nature tobeconsideredseparatelyandhence,intheabsenceofanyattackevi breaks. However, naturaloutbreaksandbiologicalattackshaveatoointertwined F 2 4 ]. The last Ebola outbreak in 2014 in West Africa was regarded as a para ]. 2 health authorities concern is to identify which ones are bioterrorist out and becamemorecomplextoprevent,predictcontain.Nowadays, or thelastthreedecades,outbreakeventshaveconstantlyincreased , AvelinaMaiguy 5 , FabriceBiot 1

3 , SophieGuillier 1 December 2020•Vol. 10 No. 2•020317 1 ,

1 ]. ]. ------

VIEWPOINTS VIEWPOINTS December 2020•Vol. 10 No. 2•020317 Koch’s collection,used withpermission). Photo: Two sidesof thesamecoin(fromLionel gence. oping collaborative intelli and assisteachotherbydevel to learnhowworktogether Both expertsandAIwillhave The use of some spontaneously rare agents could denote a criminal origin, as it has been the case with The useofsomespontaneouslyrareagentscoulddenoteacriminalorigin,asithasbeenthecasewith The agentspecificity the arguments shouldbecarefullyanalysedbeforebeingattributedtoabiologicalattack. [ algorithms todetermine,duringcrisisorshortlyafter, ifthebiologicaleventhadnaturalorinducedcauses [ However, multiplenestedeventssuchasglobalwarming[ then, theidentification of abiological attack isa major international political and judiciary issue [ The BiologicalWeaponsConventionsignedin1972outlawstheuseofbiologicalweapons[ NATURAL ORINDUCEDOUTBREAK:HOWTODISTINGUISHTHEM? unpredictable attackwilloptimisetheeffectivenessofresponse. er preparationmeasuresandresponsetoolsagainstboththeemergence ofanunknownpathogenand share thesameconsequencesandhenceshouldhaveasharedmanagement.Accordingly,grouptogeth Thus, thisreviewwillshowthattherearenoeasywaystodistinguishonefromeachotherbutthey Even theSARS-CoV-2 didnotescapethesuspiciontohavebeenlaboratory-engineered[ outbreak [ Nowadays, whenanoutbreakoccurs,oneofthefirstconcernauthoritiesistoseparateanatural or hybridwarsandbioterroristattacks[ These biologicalattackscouldbeperpetratedbystateornon-stategroupsinthecontextoflowintensity threat isconsideredmorefocusedonactionsagainstthepopulationorvitalinterestpointsofnations. ural orinducedbiohazard.Forexample,theRajneeshsectusedaquitecommon the use of agents can be modified by humans to increase their transmission, lethality or drug resistance capabilities agents canbemodifiedbyhumanstoincreasetheirtransmission, lethalityordrugresistancecapabilities entiate bothevents.Indeed,evenifthereisnoevidence ofusingsuchagentsthroughhistory,natural car in2017[ like EbolavirusinWestAfrica2014-2015[ cause oftheirhighprevalence[ to perpetrateattacks,andsomebacterialtoxinsareconsideredasapotentialwarfareagentpreciselybe Aum ShinrikyosectinJapan1993[ 17 14 - ] andconflicts[ 19 ]. Except for some criteria, like evidence of a release explicitly referring to attacks, the great part of ]. Except for some criteria, like evidence of a release explicitly referring to attacks, the great part of 7 Bacillus anthracis ] fromanintentionalactinvolvingabiothreatagent[ 24 ]. Eventheemergence ofapeculiarnewstraincannotbestand-alonecriteriontodiffer 15 - - ] affectnaturaloutbreaksinanunpredictableway[

man activitycould bethecause[ break appearsduringaseason notcompatiblewiththepathogentime-life,hu other clueforbiologicalattacks couldbetheseasonality,arguing thatifanout in apartofthecontinentrecognised asfreeofthediseaseuntilthen[ Coast ofthe USA [ Amerithrax crisisin2001when aTexan can constituteahintforbiologicalattacksuspicion.It wasthecasewith If apathogenisdetectedinlocationwhereithasneverbeen detectedbefore,it The spatialandtemporaldistribution of severeacuterespiratorysyndromecases[ in 2003thenewhumancoronavirus(SARS-CoV)identified withsurpriseinfront quired andcombinedunusualvirulencefactordrugresistance genes[ pathogens likethe [ 5 ]. At the same time, some natural outbreaks were caused by naturally altered ]. Atthesametime,somenaturaloutbreakswerecaused bynaturallyaltered narios of massive biological attacks against military troops. Since 2001, the a periodofextensiveindustrialbiologicalweaponprogramsstartedwithsce icans population[ lish settlersprobablycausedthedeadlysmallpoxoutbreaksinNativeAmer century, thedistributionofinfectedblanketsfromasmallpoxhospitalEng died fromplagueoverthecitywallsofCaffa[ exploited thesecondplaguepandemicbycatapultingbodiesofsoldiers cal attacks,evenlongbeforethediscoveryofmicrobiology.In1346,Mongols Of course,inHistory,someoutbreakshavebeenthestartingpointofbiologi during the Amerithrax crisis in 2001 [ 23 ]. In sharp contrast, recent natural outbreaks involved top select agents ]. Insharpcontrast,recentnaturaloutbreaksinvolvedtopselectagents 21 6 ]. However, theagentisnotasufficientcriteriontoidentifynat ]. 20 2 Escherichia coli

5 ]. However, the biggest outbreak ofthe Ebola virus occurred ]. In the 20th century, after the discovery of microbiology, ]. Inthe20thcentury,afterdiscoveryofmicrobiology, 3 ] or Yersinia pestis 5 O104:H4inEurope2011,astrainthatac 12 ]. Here too, some natural outbreaks disrupted ]. Heretoo,some naturaloutbreaksdisrupted ], naturalcatastrophes[ causingpulmonaryplagueinMadagas B. anthracis 5 ] in order to adapt their management. ] inordertoadapttheirmanagement. 20 26 ], and, to a lesser extent, with the ], and, to a lesser extent, with the ]. 5 www.jogh.org ]. In the same lines, in the 18th ]. Inthesamelines,in18th 16 strain was found on the East strainwasfoundontheEast ]. Several authors proposed ]. Severalauthorsproposed • Salmonella enteric doi: 10.7189/jogh.10.020317 13 ], human actions ], humanactions 8 , 9 ]. 10 27 ]. Since ]. Since ]. One ]. One 25 [ 11 ] or ] or 22 ]. ]. ------] www.jogh.org • doi: 10.7189/jogh.10.020317 gious pathogen and hence reliable epidemiological data for the intentional use of a contagious disease do gious pathogenandhencereliableepidemiologicaldatafortheintentionaluseofacontagiousdiseasedo affected couldbeevidenceforabiologicalattackisdisputable:recentterroristactionsusednon-conta cases [ in atensedgeopoliticalcontext[ trast, thenaturaltularaemiaoutbreakinKosovo1999-2000reachedseveraldistrictssimultaneously where oneuniquesetofpastrieshasbeendeliberatelycontaminatedbyalaboratorystrain[ can alsooccurinasingleplace,likethe“ ing Multiple startingpointsare commonly considered asignofbiologicalattacklikethefiveletterscontain The originsanddynamics lowed byauniqueglobalspread[ with twoepidemiological spikes [ all rules like the Influenza virus H1N1 pandemic in 2009, which appeared in April in North America not exist[ nomena haveintertwinednature.Moreover, duringanaturaloutbreak,dependingontheknowledge fectiveness onaprospectivebasis[ of thesealgorithmshasbeenreviewedinthelightnewinfectiouseventsbuthavenotyetprovenitsef weightings havebeendeterminedretrospectivelybasedonpastoutbreaksandbioterroristattacks.One the originofanongoingeventbecausealackreliability().Itshouldbenotedthatallcriteriaand items isbeneficialtoprocessdataandimproveawarenessbutshouldnotbesolelyuseddistinguish contextual elementsandtechnicalbiasestoavoidanymisunderstanding[ ough epidemiologicalinvestigations.Resultshavetobeinterpretedverycarefullybytakingintoaccount Thus, to characterise an infectious phenomenon, we should merge the most advanced technics with thor Is thereanyinteresttoidentifyonefromtheother? Africa, travelledacrossthePacificOceantofinallytriggerapandemicinSouthAmerica[ html). Inthesamevein,lastZikavirusnaturaloutbreakshowedanunusualspread,asitemerged in after thefirstalert,185countriesdeclared at leastonecaseofinfection(https://coronavirus.jhu.edu/map. website tovisualiseandtrackthereportedcasesinreal-time[ Systems ScienceandEngineering(CSSE)ofJohnsHopkins University (Baltimore,MD,USA) created a one and30countriesin5monthsforthesecond.ForcurrentCOVID-19pandemic,Centre propagated veryfastallaroundtheworldwithmorethan200countriesaffectedinoneyearforfirst ‡Natural cause. †Induced cause. *Consensual criteria. presence ortheabsenceofcriteria Table 1. Unusual spreading Multiple startingpoints Unusual distribution Emergence oralteredpathogen Selected agent C riteria B. anthracis * 24 Published consensual criteria to assess an unusual outbreak and infectious events in function of the Published consensualcriteriatoassessanunusualoutbreakandinfectiouseventsinfunctionofthe ]. Even the assumption that an unusual swift spread or a large share of the population rapidly 5 ]. Bycontrast,theinfluenzavirus[ spores[

20 ] aswelltheseveralrestaurantstargeted bytheRajneeshcult[ 31 Zika virus(Worldwide)‡ Coronavirus (Worldwide)‡ H1N1 Influenza(Worldwide)‡ Yersinia pestis Francisella tularensis Rajneesh attack(USA)† Amerithrax (USA)† H1N1 Influenza(Worldwide)‡ Ebola outbreak(WestAfrica)‡ Amerithrax (USA)† SARS-CoV (Worldwide)‡ E coli Yersinia pestis Ebola virus(WestAfrica)‡ Neurotoxin botuliniumA(Worldwide)‡ Aum Shinrikyoattack(Japan)† Amerithrax (USA)† P resent 28 29 36 ] and, in 2017, the plague outbreak in Madagascar had multiple index ] and,in2017,theplagueoutbreakMadagascarhadmultipleindex ]. It unusually emerged frominfected pig populations andwasfol ]. O104:H4(Europe)‡ ]. Theconfusionsurroundingthesecriteriaconfirmsthatbothphe Shigella dysenteriae 3 (Madagascar)‡ (Madagascar)‡

28 ], the2003SARS-CoV[ (Kosovo)‡ poisoning” in a laboratory in 1996 in the US, poisoning”inalaboratory1996theUS, 33 ]. In April 2020, less than five months ]. InApril2020,lessthanfivemonths December 2020•Vol. 10 No. 2•020317 All biologicalattacks† Aum Shinrikyoattack(Japan)† Shigella dysenteriae All biologicalattacks† Shigella dysenteriae Common bacterialtoxins† Rajneesh attack(USA)† A 35 26 bsent ]. The list of common-sense ]. Thelistofcommon-sense ] andtheSARS-CoV-2 [ 34 (USA)† (USA)† 22 ]. 30 ]. An attack ]. Anattack ]. Incon 32 ------]

VIEWPOINTS VIEWPOINTS December 2020•Vol. 10 No. 2•020317 ments indelimitedspacesorduringalarge gatheringofpeopleshouldbetheprioritytoimprove technological barriersandcostchallenges.Expertsinbiodefensesuggestedthatmoretargeted measure On the other hand, systematic environmentmonitoringfor all diseasesis, for now, impossibledueto hence morespecificformsofthediseasebutwillhaveabelatedusehealthcare[ also culturalorsocio-economicfactors:themost-disadvantagedindividualswilldevelopmoresevereand netic factors[ For thesameexposition,symptomscandifferaccordingtoindividualvariableslikehealthstatusorge Most ofthetime,highvolatilitylyingininfectiousprocesscomplicatesrecordcases. inanoutbreakcontext,liketheEbolavirusduringlast inWestAfrica[ surveillance and contactreductions[ tion andisolationofcaseswouldhavebeenmoreefficienttopreventinfectionsthantravelrestrictions ever theoutbreakorigin[ mains theearlydetection,accuratecharacterisationandestablishmentofspecificmeasures,what aiming to maximise damagesto the emergency infrastructure [ deed, evenifthesubstantialremainingriskincaseofanattackispossibilitysecondaryactions from health workers and do not consider the public health issues of quick detection and response. In tionally spreadtheSARS-CoV-2 asterrorists[ agent, likeitisnowthecasewithUSdepartmentofjusticecurrentlyconsideringpeoplewhointen about itshazardousnessandtransmission,theinfectiousagentcanbesecondarilyregardedasabiothreat biases andshould becarefullyinterpreted.Indeed, thesimpleactofonline documentationisjustanindi dium tocommunicatesanitary messagesoralerts[ ulatory barriers,socialnetworks appearto be a powerful data collection tool and canalso be usedas a me China toreconstructtheprogression oftheSARS-CoV-2 outbreak[ tion orpeoplewhoarenotusing thehealthcaresystem[ approach.The results areimmediateandallowaccesstoapaucisymptomatic popula tional surveillance systemsofferalogisticallyandeconomically appealingextensiontothistradi Internet-based surveillance To aconnectedage for epidemiologicalstudiesortriggeranalert[ Currently, data management tools can aggregate several inputs and are already used sisted surveillance. [ ciency ofsurveillance forts have been made on informationtechnologiesandelectronicqueryof a data setto improve theeffi stakeholders ofthehealthcaresystemuseinformaticstools intheirdailypractice.Yet,considerableef technologies leavesroomforimprovementintheoutbreak detectionprocess[ eases programsinordertopromoteunusualeventawareness [ giousness. Given the importance of early detection, training has to be a building block in infectious dis ber ofcases)andshouldbeabletoalertpublichealthofficials[ Thus, forthemoment,healthworkerswouldfirstnoticeanunusualevent(diseaseornum idemiological investigationstoavoidanymisinterpretationoftheresults[ of SARS-CoV-2 inthecommunity[ reducing the cost [ sensitivity andspecificityoftheearlydetectionabiologicalattackbut,alsofornaturaloutbreak,while triggered byapermafrostmelting[ [ nonspecific symptoms,thecasedefinitionandoutbreakdeclarationthresholdaresubjecttodebate vated withacertaindelay.However, when itcomestoanewdiseaseorpathologieswithpolymorphic numerous drawbacks as it requires an expensive and complex publichealthnetworkandis often acti cases exceedswhathasbeenexpected[ such well-knowndiseases,thecasedefinitionisclearandanoutbreakdeclaredwhennumberof Some diseases like influenza are internationally monitored [ The challengeofanearlydetection HOW TOEARLYDETECTTHEUNEXPECTED? 45 ]. The source of the infection can be as unpredictable as the local outbreak of anthrax in reindeers ]. Thesourceoftheinfectioncanbeasunpredictablelocaloutbreakanthraxinreindeers 48 ] ortocollectivevariablesinvolved,forexample,inthechainoftransmission[ 51 ]. For example, the analysis of wastewater could be a good way to monitor the spread ]. For example, the analysis of wastewater could be a good way to monitor the spread

55 41 39 ]. It'sanimperativeprerequisitefortheimplementationof anelectronicallyas ]. , 40 ]. DuringtheCOVID-19crisis,ithadbeenestimatedthatearlydetec 46 52 ] orthedetectionofvariolavirusinancientmummies[ ]. However, thesemeasurementsshouldalwaysbepairedwithep 44 ]. This classic and passive way of detection is efficient but has ]. Thisclassicandpassivewayofdetectionisefficientbuthas 4

37 56 ]. However, thesepoliticalconsiderationsarefaraway ]. 59 ]. However, hereagain,thesedataare subject tomany 57 ]. This methodology has been used in 2020 in ]. Thismethodologyhasbeen usedin2020 42 38 44 ] while some others are subject to active ] while some others are subject to active 53 ], therealchallenge for globalsafetyre ] asprotectingthemselvesfromconta ]. The implementation of information ]. Theimplementationofinformation 58 ]. Despiteethicalconcernsand reg www.jogh.org 51 ]. • 54 doi: 10.7189/jogh.10.020317 50 ] as more and more ] asmoreand ]. 43 49 47 ]. For ]. For ] but ] but ]. ------the outbreakthrough communicationandspecific actions. stakeholders ofthecrisispreparation andmanagement.Ingreen:theresponseto the populationanddetection resourcesforinfectiousevents.Inred:the Figure 1. www.jogh.org Possible future detection and management system for outbreaks. In blue: Possible futuredetectionandmanagement systemforoutbreaks.Inblue: • doi: 10.7189/jogh.10.020317 gregate spatial,temporal,epidemiologicalandgenomicdata[ New toolsmayincludeonlinedataprocessing[ origin ofanoutbreakandalsotoexplainthedispersionpathogenthroughitslocalevolution[ tion ofepidemicsinthegenomicera.Thewhole-genomesequencingalreadycanhelptodetermine Pending theadventofAItools,manyinitiativeshavebeenrecentlyproposedtofacilitateinvestiga rent COVID-19pandemic[ rights abusesinnon-democraticcountries[ securing ofthetransmissionandstoragesensitivemedicaldata,nottomentionpossiblehuman sues andshouldbecarefullyconsidered.Theprivacypolicyhastoexaminedaswellthe sions [ action logandvideofootagehadbeenusedtomonitorthepatient’scontactavoidfurthertransmis source oftheinfection.InKorea,duringCOVID-19crisis,GPSfromcellularphone,creditcardtrans ly detectioncouldguidefurtherspecificactionsofscreeningtoidentifypotentialpatientsandeventhe diagnostic couldbeusedtohelpearlydetectionofaninfectiousphenomenoninapopulation.Thisear systemscombinedwithmachinelearningcapabilitiesinpredictionand data obtainedfromsurveillance tious diseaseattheprodromalphasewithpotentialhighestefficiencythanthermicportals.Thecrossing diseases [ epidemiology asthedetectioninreal-timeofrestaurantswithahigherrisktobesourcesfoodborne (AI) isnomorefictionalinLosAngeles[ its citizensanddetectincivilities[ systemstofollow ment ofprojectslikesmartcities.Nowadays,Chinaisalreadyusingvideosurveillance be only the beginning of IoT possibilities as the future could be even more connected with the develop ment more rapidly appropriate measures and focus on a possible source of contamination. This seems to tracking solutions,couldalertcompetentauthoritiesonanongoinginfectionandhelpthemtoimple temperature orheartrate.Thecapabilityofcrossingthesetypesinformationwith,forexample,geo- search [ bution oftheinternetthings(IoT)alreadyusedtofollowchronicillness[ Taken toitslogicalextreme,thenextstepofthisepidemiologicwatchwouldprobablyallowcontri blockbuster movieincreases the anxiety of population or a massivehacking produces millions of requests. rect marker of disease, and such detection system could trigger an alert just becauseaworldwide released through the facial expressions and head gesture in a video [ 66 61 ]. However, systemsisnotwithoutlegalandethical theimplementationofsuchsurveillance 64 ]. A smartphone or a smartwatch is now able to detect modifications of vital parameters like ]. A smartphone orasmartwatchisnowabletodetectmodificationsofvitalparameterslike ]. In the medical field, computers start to help clinicians in the diagnostic of mental illness ]. Inthemedicalfield,computersstarttohelpcliniciansindiagnosticofmentalillness

68 ] butthereisstillnointernationalconsensusontheuseofpersonaldata. 62 ]. Likewise, criminality hot spots prediction by artificial intelligence ]. Likewise,criminalityhotspotspredictionbyartificialintelligence 63 5 67 ]. These new technologies already have some applications in ]. Thesenewtechnologiesalreadyhavesomeapplicationsin

]. Theseconcernshavealreadybeenraisedduringthecur 70 ] uptothedevelopmentoforiginalalgorithmsag 65 ] but could also be used to detect an infec 71 with thecrisisareunavailable. Beingpre detection isuselessiftheresources todeal the crucialsteptorespond an outbreak, Even if the epidemiological monitoring is reaction Early detectionforanearly CRISIS MANAGEMENT regardless oftheircauses(). mon objective to early detect outbreaks, ities and societal choices, withthecom capacities, technicaldevelopment capabil societies willprobablyrelyoneconomic epidemiological monitoringsystemofour idemics [ approaches inthecontextofspreadingep perfectly illustrates the potential of such SARS-CoV-2 (https://nextstrain.org/ncov) Nextstrain tool[ data-sharing practices[ the conditiontocontinueimprove described classiconearealsopossibleat systemwiththepreviously surveillance ]. The interactions of this technological ]. Theinteractionsofthistechnological December 2020•Vol. 10 No. 2•020317 74 ]. Intheyearstocome, 60 ] andforbiomedicalre 73 ] inthecontextof 72 ]. The use of the ]. Theuseofthe 69 ]. ]. ------

VIEWPOINTS VIEWPOINTS December 2020•Vol. 10 No. 2•020317 tem [ for theuserresponsibleofsituationassessment[ tion [ also beimprovedbytheuseofAIintermsnetworkstructuration[ design realistic plans [ previous crises[ preparation phaseofthecrisiscanalsobenefitfromAItoolsbyorderingreuseinformation possible to generate predictions to improve the resilience of a system and to mitigate the risk [ crisis managementtotheauthorities.ByusingclassicriskanalysisdocumentationwithAItools,itisnow Developments ofAIdonotonlyhelpforearlydetection,butmakeavailableafullsetpossibilitiesin Preparedness technologies possible futuresanitarycrisis[ saved lotsofpatients.Inthemeantime,otherconsortiumslikeGRACEmayalsohelpustoprepare among countries, but cooperation helped relieve overloaded Intensive Care Units in some regions and built newhospitalsinWuhanatightschedule.InEurope,crisismanagementstrategiesweredifferent PARE [ capacity thatcanbereleasedthroughthecoordinatedactionofacademicandpubliclaboratorieslikePRE ent deploymentonavalidateddiagnosticworkflowforSARS-CoV-2 [ ternational andEuropeanresearchnetworksmanagedtoimprovethespeedeffectivenessofpres national agenciescalledforbetterinternationalpreparationtorespondfutureoutbreaks[ health response[ to getineachother’s way.Bylearninghowtoworktogether, synergies couldbedevelopedtoimprove would occur, inthemostdevelopedcountries, thereisarisk,evenforthehighlytrainedfirstaidservice tion [ between naturaloutbreakorbioterroristattackdedicatedsometimespreventanaccurateglobalapprecia compartmentalisation betweendifferentgovernmentalbranchesandthe nebulous labellingofthemeans or militaries,governmentalnon-governmentalentities)alreadyhavesomecontingencyplansbutthe vealed thatthelackofsimplePPEputallhealthsystemathighrisk[ Equipment (PPE),intensivecaredevicesandtreatmentshavetobestockpiled.TheCOVID-19crisisre with them. Dedicatedinfrastructureshaveto be prepared and ready for activation and Personal Protective thorities: quickandreliableequipmenthas to beavailableandhealthworkers have to be used towork pared includesbutisnotlimitedtohealthworkersbeingtraineddetect,reactandalerttheau implemented were economicallyprofitable in theUSAduring2009Influenza pandemic[ context wherecitizensaremore andmoreconcernedbypublicexpenses.Indeed,if the vaccinepolicy search intensityshowedthat diseases withagreaterimpactarestillunderfunded[ are first and foremost causing natural outbreaks [ cost-efficient and seems absurd as dangerous pathogens to human can be used for biological attacks but eral levelwithclearsafety,ethical andpracticalguidelines[ a panelofUSAexpertsrecommendedreinforcingthebiological threatcharacterisationresearchatafed such aninvestmentwasunderlinedforalongtime(evenbefore theAmerithraxcrisis)[ Inevitably, to develop an anticipation-centred view required investment. The economic justification of Economic impact DIMENSIONING THEGLOBALPREPAREDNESS simulations, hadtomakedecisionscontrolthespread of avirusstilllittleknown. complex problems().Thiswasexperiencedduringthe COVID-19 crisisinwhichexperts,assistedby together andassisteachotherbydevelopingcollaborativeintelligence,whichwillbethebestwaytosolve creativity arepartoftheproblem-solvingprocess[ of practiceisdescribedasmorerealisticthanpureanalyticalthinking[ of thedecision-makingprocess[ erase the role of human experts [ agement duringinfectiousdiseaseoutbreaks[ years, epidemiologicalandmathematicalmodellingdatawereessentialforriskcharacterisationman trices hadbeenusedtoprojectthebenefitmaintainsocialdistancingmeasures[ 90 76 88 80 ] todesignthebestcrisisresponse.Forexample,duringCOVID-19crisis,socialcontactma ]. As it is, and as unfortunately still demonstrated during the COVID-19 pandemic, if an outbreak ]. Asitis,andasunfortunatelystilldemonstratedduringtheCOVID-19pandemic,ifanoutbreak ]. Duringthecrisis,AIcanalsosortinformationfrommanysensors,merge itandmakerelevant ]. In 2020, in China, coordination by the central authority allowed to deploy medical staff and ]. In2020,inChina,coordinationbythecentralauthorityallowedtodeploymedicalstaffand 83 77 ], improvingthestockholders’trainingwithaseriousgameapproach[ ]. AfterthefailureincontroloflastEbolavirusoutbreakbyWHO,inter 85

] oreven boosting the discovery ofnewdrugs[ 81 94 93 ]. ]. During crisis management, expert intuition developed through years ]. Duringcrisismanagement,expertintuitiondevelopedthroughyears ]. Indeed, intuition and emotions are known for a long time to be part ]. Indeed, intuition and emotions are known for a long time to be part 6

92 ] but ironically, the rising power of AI systems will not ] butironically,therisingpowerofAIsystemswillnot 96 99 89 ]. Both experts and AI will have to learn how to work ]. BothexpertsandAIwillhavetolearnhowwork ]. However, studies about the burden-adjusted re ], whichwillbehelpedbyadecision-supportsys 98 ]. Splitting outbreaks into two causes is not ]. Splittingoutbreaksintotwo causesisnot 79 87 ]. This demonstrating the response ]. Thisdemonstratingtheresponse 95 ] aswellforthemean’salloca 75 86 www.jogh.org ]. Moreover, bothintuitionand ]. Several authorities (civilians ]. Severalauthorities(civilians ]. Resources management can ]. Resources management can • 100 91 doi: 10.7189/jogh.10.020317 ]. Over the past ten ]. Overthepastten ] in an economical ] inaneconomical 97 ], and recently, ], andrecently, 84 78 ], helping to ], helpingto 101 ]. Thus,in 82 ], asim ]. The ]. The ------www.jogh.org • doi: 10.7189/jogh.10.020317 at itthroughfresheyes. evaluation ofpublicpoliciestocontroloutbreakswiththeopportunitythatopinionwilllook the numerousdeathsofCOVID-19andlockdownbillionspeoplewillprobablytriggeranew in thepreparationofresponsetoaninfectiouseventwithepidemicpotential.Thecrisisgeneratedby ically interestingtoconsiderthenaturalbiologicalriskandpossibilityofanattackasasinglethreat that helpstostrengthenpreparednessfornaturaloutbreaks,andviceversa[ globally thesamechallenge.Moreover, preparednessforbiologicalattackshasasignificantaddedvalue For ahealthcaresystem,thepreparationforbiologicalattack[ ical threatsbutwithsubstantialpotentialconsequenceforhumanity[ tingency plans, especially on catastrophic biological risks, which represent a small portion of the biolog as duringthe2014Ebolaoutbreak[ mension their actions appropriately, even though a delayed response is severely judged by public opinion ilar strategy caused substantial wastage in Australia [ sistant bacteriaduetotheimproperantibioticuse[ al programs.Itleadstosociety-bornthreatswithnotablythegrowingemergence ofhighlyantibiotic-re Due to all these miscalculations and misguidances, society lost confidence in the authorities and nation of cropsinafield[ been imaginedwithageneticallymodifiedvirusinfectingmosquitoesabletoperformgenemodification iting technologieslikeCRISPR-Cas9seemstobelimitless[ new bacteriumhasbeencreateddenovoina laboratory [ gene synthesis:a adays, these widely used technics appear to be almost obsolete in comparison with the newcapacities of tion of highly-resistant the immunesystem[ expected resultsasatestfornew modify organisms specificallyleadingtothereconstitutionofSpanishInfluenzavirus[ project of spreading some modified mosquitoes to fight against malaria [ such asthedeploymentofapeacekeepingforceandcholeraoutbreakinHaiti2010[ the waytocontestationofexpertise[ Indeed, theuncertaintyassociatedwithscientificknowledgeoftenchallengesdecisionmakingandopens Misguidances andconsequences plex wastes[ even ifapplicationsofsomethesemodifiedorganisms maybehighlybeneficial,astherecyclingcom agent abletoselectivelykillapartofthepopulationcouldnowbeterrifyingtechnicalpossibility.Thus, publication mustalsobeplacedatthecentreofresearchers' concerns. jor communicationactionsareneededtoovercomethe public reluctance.Ethicsinresearchanddata encouraging research,technologiesandtheirapplicationmust becontrolledtoavoidanymisuseandma have adualnatureandshouldbeconsideredcarefullybefore beingimplemented().Thatiswhy,while breaks’ history,leadtobettercomprehensionandcooperation ofpeople[ VID-19 pandemic,thetransparencyaboutitsprogressreportedinreal-time,forfirsttimeout management oftheCOVID-19pandemicandlockdowndecision[ the samewayithappenedwithEbolaoutbreakin2014[ confidence extendstocrisismanagementprogramsandcancompromiseoutbreakmeasures gens linked to the mistrust in public health programs like vaccination programs [ AI –artificialintelligence Table 2. Increased communications Use ofAI systems Improved surveillance Open data Internet screening Science progress T ype

change

Duality ofdecisionsininfectiousphenomenonmanagement. 117

], theyareswampedinthemiddleofwanderingsreportedbymedia[ horsepox virus 115 109 B. anthracis ]. TheSouthAfrican«coast»project[ ] or, duringresearchexperimentsmimickingnaturalphenomenon,thegenera hasbeenreconstructedusingonlyinternet-boughtsequences[ Better acceptancefromthepopulation Collection andfusiondata Early detectionandcharacterisation Sharing oftheknowledge Weak signaldetection Better understandingofinfectiousprocess P ositive spores[ poxvirus 78

effect ]. Hence,authoritiesandexpertsshouldimprovetheglobalcon 92 vaccine resulted with an ultra-virulent strain able to neutralise vaccineresultedwithanultra-virulentstrainabletoneutralise ]. Sometimes,thebestintentionscanresultinahealthdisaster, 110 7

] and virusesacquiringairbornetransmission[ 119 102 ] orthere-emergence ofnearlyforgotten patho ]. Thus, authorities have to beverycareful to di 113 114 121 ]. Currently,thepossibilitiesofgenomeed 116 ]. Some malicious scenarios have already ]. Somemaliciousscenarioshavealready ] or currently, with the beginning of the ] orcurrently,withthebeginningof 6,104 December 2020•Vol. 10 No. 2•020317 ] that aimed at developing a bacterial ] thataimedatdevelopingabacterial 103 ] oranaturaloutbreak[ 122 Fake news Lose ofhumanexpertise Privacy andhumanrightviolation Misuses ofthedata Data manipulation Creation ofnewthreats N ew 123 107 ].

risk 104 ]. However, duringtheCO ]. Thus, every decision can ]. Thus,everydecisioncan ]. Technology allows us to ]. Technology allows us to ]. Itisthereforeeconom 120 ]. This lack of 108 111 106 112 118 ] ortoun 78,105 ]. Now ] or the ] orthe ], and a ], anda ]. ] is ] is ------

VIEWPOINTS VIEWPOINTS December 2020•Vol. 10 No. 2•020317 REFERENCES 2 1 8 5 4 3 10 9 7 6 Poletto J RSocInterface.2014;11:20140950. Smith KF, Goldberg M,RosenthalS,CarlsonL,ChenJ,C,etal.Globalriseinhumaninfectiousdisease outbreaks. Hao Emerg MicrobesInfect Liu Allen 7915.2012.00340.x Casadevall line:24894605 Barras 343 Tatem 6736(15)60858-3 from thewestAfricanEbolavirusdiseaseepidemic. Heymann doi:10.2807/1560-7917.ES2014.19.42.20936 ternational spread of the 2014 West African Ebola epidemic. emerging zoonoticdiseases. 38279 laboratory recombination. rst.36.2.2679 Feakes

from thecorrespondingauthor),anddeclarenoconflictsofinterest. Competing interests: proved thefinalversion. the manuscript. AM, SG, LG and JNT supplied technical expertise and revised the manuscript. All authors ap uscript. FBhelpeddesigntheReviewandrevisedmanuscript.AALassistedinliteraturesearch Authorship contributions: ported bytheFrenchMinistryofDefense(grantNo.PDH-2-NRBC-4-B-4109). Funding: is independentandimpartial. Acknowledgements: from thiscrisiswhilepreparingthenextone. day. However, SARS-CoV-2 isprobablynotthedeadliestviruswewilleverhavetofight.Wemustlearn first pandemictobenefitfromsomuchadvancedresearchandseveralmajorarticlesarepublishedevery authorities andthepopulation and to avoid false information spreading. Current COVID-19 crisisisthe of thefuturestrategiestopromoteacceptancefinancialandsocietalinvestmentbybothpublic justments in the strategies to optimise the public health response. Communication will also be akey point preparedness. Theevolutionofthreatsaswelltechnologiesdevelopmentswillrequirepermanentad more impactoncrisismanagement,andexpertswillhavetobetterworkwiththesetoolsimprovetheir be abletounderstandtheimplicationsoftheirowndecisionsfully.NewtechnologiesandAIwillhave and itisnolongerenoughtobeaspecialistincrisismanagement,infectiousdiseaseorepidemiology immediately applicable solutions in crisis. The biological crisis is becoming a field of expertise by itself, volved to monitor the evolution of threats and update existing proceduresby developing concrete and ing at local, regional and global levels. Stakeholders from a broader range of backgrounds must be in keeps beingthekeyconcepttoanticipatethem[ events arereferredas“Blackswanevents”anddespiteourinabilitytoforeseetheiroccurrence,knowledge forming continuousscientificandepidemiologicalmonitoring.Still,themostseriousunpredictable rately. To create an efficient way to detect and contain them, the first step is to anticipate them by per The intricatenature of natural outbreaks and biological attacks is too important toconsiderthemsepa CONCLUSION . S-L

P Medline:16647974

, T

Zhong

, AJ V D , C , Murray Saif . , , The BiologicalWeaponsConvention. Greub

DL Gomes Rogers A

. LJ Theauthorsreceivednofinancialsupportfortheauthorshipofthisarticle.publicationwassup

The futureofbiologicalwarfare. , W

, Chen doi:10.1111/1469-0691.12706

, Weiss

KA Song G

DJ MFC . ,

History ofbiologicalwarfareandbioterrorism. Zambrana-Torrelio , L

Hay

, S . SR , , Takemi 2020

Piontti The authors ensure the quality and integrity of their research and declare that their research The authors ensure thequalityandintegrityoftheirresearchdeclarethat their research Fan doi:10.1016/S0065-308X(05)62009-X The authors completed the ICMJE Unified Competing Interest form (available upon request TheauthorscompletedtheICMJEUnified Competing Interestform(availableuponrequest ,

Su Emerg MicrobesInfect SI

Nat Commun

. ; S

9 L Global Transport NetworksandInfectiousDiseaseSpread. , : LKdesignedtheReview, didtheliteraturesearchandwrotefirstdraftofman

505 Li AP K No credibleevidence supporting claimsofthelaboratoryengineeringSARS-CoV-2.

, X , Fidler - Rossi . 7 Is SARS-CoV-2 originatedfromlaboratory?Arebuttal totheclaimofformationvia .

Medline:25401184 Medline:32102621

L DP , . , Morse 2017 Bioglio ,

Microb Biotechnol Tappero

Rev -OffIntEpizoot ;

8 .

SS Lancet 8 : 2020

1124 L

, , Rondinini

Chao JW ; . 9 124 .

Medline:29066781 2015 :

doi:10.1098/rsif.2014.0950 545 doi:10.1080/22221751.2020.1733440 Thomas

DL ]. Thus,weneedtocontinueandintensifynetwork - ; . 7 ,

385 C 2012

. et al

Euro Surveill , Medline:32148173

Di Marco . : MJ 1884 2017 .

; Clin MicrobiolInfect 5 Assessing theimpactoftravelrestrictionsonin , : et al 584 - ; 901 36 - .

7 :

M 621 Global health security: the wider lessons Global healthsecurity:thewiderlessons doi:10.1038/s41467-017-00923-8 . .

Medline:22432943 , Medline:25987157 . et al 2014 - 8 www.jogh.org .

. Medline:30152458

Global hotspots and correlates of Global hotspotsandcorrelatesof doi:10.1080/22221751.2020.17 ; 19

: Adv Parasitol 20936 . • 2014 doi: 10.7189/jogh.10.020317 .

doi:10.1111/j.1751- doi:10.1016/S0140- Medline:25358040 ; 20 : 497 .

doi:10.20506/ 2006 - 502 ; 62 .

Med : 293 ------www.jogh.org REFERENCES • 15 14 13 12 11 31 37 36 35 34 33 32 30 20 19 18 17 16 29 28 27 26 25 23 22 21 24 doi: 10.7189/jogh.10.020317 tives. case controlandenvironmentalstudies. Reintjes jama.1997.03550050058034 oratory workersduetointentionalfoodcontamination. Dembek doi:10.1136/bmjgh-2017-000647 plex humanitarianemergencies: aqualitativesystematicreview. Hammer doi:10.1177/0141076815603234 Bowles ol Lindahl and controlmeasures. Kouadio doi:10.15171/ijoem.2017.963 Rossati line:30152457 Fooks rensics, andtheClinic.ClinChem. 2019;65:383-92. Minogue TD,KoehlerJW, StefanCP, ConradTA.Next-Generation SequencingforBiodefense:BiothreatDetection,Fo Medline:26888897 Waggoner JJ,PinskyBA.ZikaVirus:DiagnosticsforanEmerging PandemicThreat.JClinMicrobiol.2016;54:860-7. 2020;20:533-4. Dong E,DuH,GardnerL.Aninteractiveweb-baseddashboard totrackCOVID-19inrealtime.LancetInfectDis. Li Kolavic Rasko natural anddeliberateepidemics. Radosavljevic Infect natural outbreaks of disease: its use in analyzing the tularemia outbreak in Kosovo in 1999 and 2000. Grunow miol Infect 2020. https://www.cnn.com/2020/03/25/politics/coronavirus-terrorism-justice-department/index.html. Accessed: 24 June CNN PL.Peopleintentionallyspreading coronaviruscouldbecharged withterrorism,DOJsays.CNN.2020.Available: Detecting UnnaturalEpidemics. RiskAnal.2019;39:1465-75. Chen X,ChughtaiAA,MacIntyre CR.RecalibrationoftheGrunow-FinkeAssessmentTooltoImprove Performancein influenza pandemicinswineMexico. Mena enza A(H1N1)intheUnitedStates. Jhung pntd.0003652 Emergence ofEbolainWestAfrica? Alexander science.1236434 Nuttall emmm.201201662 European EscherichiacoliO104:H4outbreak. Karch idemic modelling. Nguyen line:26184960 Fries jama.1997.03550050051033 caused byintentionalcontaminationofrestaurantsaladbars. Török 4567.2001 release inKameido,Japan. Keim doi:10.1073/pnas.1016657108 analysis in support of the Amerithrax investigation. .

H 2015 ,

Liu . Int JAntimicrobAgents BC P

I H MA DA AR TJ ,

2002 ,

SA Smith A Nelson JF

, ;

, VK

, ,

5 ZF R IK S-M CC Denamur , . Dye , , , Tauxe

, : Varshney , , , Holmstrom KA . 30048 Grace Worsham Dedushaj , Global WarmingandItsHealthImpact. Swerdlow , , Butler Finke Kimura 2007 ; Kortpeter , Aljunid 8 Parra-Rojas

, Brainard : V C KL 510

Yu , Sanderson

doi:10.20506/rst.36.2.2680 Medline:32087114 MI .

Belojevic RV

; . ,

Epidemiology. TheSARSwake-upcall. D

135 X-H

E-J - Medline:26615822 Keys Epidemics ,

. , 21

E doi:10.1128/JCM.00279-16

A Quezada-Monroy

The consequencesofhumanactionsonrisksforinfectiousdiseases:areview. Wise

AK S

I . , , PL : D

, , Dobrindt ,

353 Morisetti

Expert RevAntiInfectTher A procedure for differentiating between the intentional release of biological warfare agents and A procedurefordifferentiatingbetweentheintentionalreleaseofbiologicalwarfareagentsand Simons L J Medline:12197873 Kamigaki Gjini

Tang , . , C

. , C Olsen Hunter United NationsSecretary-General’sMechanism. Bacterial Toxins—StaphylococcalEnterotoxinB.

Abshire

, G RP , - CE , Takahashi 71 Hernandez-Vargas Pavlin .

, J ClinMicrobiol S-L A . Unusual epidemic events: a new method of early orientation and differentiation between Unusual epidemicevents:anewmethodofearlyorientationanddifferentiationbetween , . Livengood .

2018

2020 Marathe SL Medline:16893485

N Jorgensen U ,

, , Public Health T . Tang , TG

JA Slutsker Jernigan Climate change,conflictandhealth. , Finlay

; . ; Hammad

doi:10.1016/S1473-3099(20)30120-1

25 55 Clin InfectDis . , PLoS NeglTrop Dis Risk factorsandriskfactorcascadesforcommunicablediseaseoutbreaksincom

Discernment betweendeliberateandnaturalinfectiousdiseaseoutbreaks.

Stanley F Emerg Infect Dis doi:10.3402/iee.v5.30048

, : C-K 20 , M 105951

Dutta eLife Kurata JR

, BB - TR

5 Lewis , doi:10.1046/j.1469-0691.2002.00524.x L . D . Sokolow , , Coronavirus disease2019(COVID-19):currentstatusandfuture perspec

, , .

Medline:29866421 Barth Hengge

. ST Biggerstaff EA Cotter 2016 J . , ,

. 2001 2012 T

, Cortes-Fernández

Oshitani

Medline:32234466 , . BL EMBO MolMed Bannan .

The 2017plagueoutbreakinMadagascar:Datadescriptionsandep Kaufmann doi:10.1017/S0950268806007011 9

. 2012

S ; , Proc Natl Acad Sci U SA 5

2011 Medline:30352865

, ;

;

Rivers B : 39 R R 126

Haley e16777 . , Int JOccupEnvironMed , , 2002 Lieftucht : Mauvais ; Johannes

. 4566 10

Science ; : JD H 2015 52 77

JAMA : .

95 CE , Kamimoto ; JAMA : Infectious diseases following natural disasters: prevention Infectious diseasesfollowingnaturaldisasters:prevention -

8 S13 Wilson Medline:30582887 A . 81 -

- 69 Medline:27350259 BMJ GlobHealth 7 . . ; 104 , 9 . Molecular investigation of the Aum Shinrikyo anthrax Molecular investigationoftheAumShinrikyoanthrax . An outbreakofShigelladysenteriaetype2amonglab

Shaman

S doi:10.1016/j.epidem.2018.05.001 - : . A - Medline:22136700

e0003652 Medline:11724885 26 L 2013 73

, . . R 1997 , , . et al 1997

et al 2012 , doi:10.1016/j.ijantimicag.2020.105951 . et al

Medline:22149618 .

J RSocMed Lara-Puente Medline:21342884 Medline:11749751

; L . 339 ;

. , , 278 doi:10.1373/clinchem.2016.266536 A large community outbreak of salmonellosis ;

Rev -OffIntEpizoot 278 ; J Tularemia outbreak investigation in Kosovo: Tularemia outbreakinvestigationinKosovo: The enemy within us: lessons from the 2011 The enemywithinus:lessonsfromthe2011 et al et al 4 ,

December 2020•Vol. 10 No. 2•020317 : et al : . Microbiol Spectr 841 1287

: . Medline:26042592 : 396 . . 389 2011 Epidemiology of2009pandemicinflu Bacillus anthracis comparative genome Bacillus anthraciscomparativegenome . . - . 2018 8 What Factors Might Have Led to the What FactorsMightHaveLedtothe

- - doi:10.1111/risa.13255 - 2015

. JH 8 . 8 doi:10.7554/eLife.16777 95

2017 ; . . Medline:22927122 108

, doi:10.1016/j.puhe.2011.11.006 Medline:23493705 Medline:9244331 .

et al ; doi:10.1128/JCM.39.12.4566- Medline:9244330 3 ; 108

: : doi:10.1586/eri.11.155

e000647 5027

doi:10.3201/eid0801.010131 ; doi:10.1093/cid/ciq008 8 . : Origins of the 2009 H1N1 Origins ofthe2009H1N1 : 7 390 - . . 20 - 2013 2017 32 -

. 5

doi:10.1371/journal.

. Infect EcolEpidemi . .

Medline:28051192

Medline:30002920 Medline:21383169 Medline:26432813 ;36: ; 1 : 10.1128

Clin Microbiol Clin Microbiol 629

doi:10.1001/ doi:10.1002/ doi:10.1126/ doi:10.1001/ - 37

. Epide .

Med Med ------

VIEWPOINTS VIEWPOINTS December 2020•Vol. 10 No. 2•020317 REFERENCES 65 64 63 62 61 60 59 58 57 56 55 54 53 52 51 50 49 48 47 46 45 44 43 42 41 40 39 38 diseases. LancetInfectDis.2014;14:160-8. Milinovich GJ,WilliamsGM,ClementsACA,HuW. systemsformonitoringemerging Internet-basedsurveillance infectious Bowers KJ,JohnsonSD,PeaseK. ProspectiveHot-SpottingTheFutureofCrimeMapping?BrJ Criminol. 2004;44:641- Infrastructure.PolicyInternet.2018;10:415-53. Surveillance Liang F, DasV, KostyukN,HussainMM.ConstructingaData-DrivenSociety:China’sSocialCredit SystemasaState therap.2017.11.005 tributeurs. Usingconnectedobjectsinclinicalresearch.Therapie. 2018;73:53-62. Dhainaut J-F, HuotL,PomarVB,DubrayC.participantsofRoundTable«Healthtechnologies» ofGiensXXXIII,con line:27525156 Dimitrov DV. MedicalInternetofThingsandBigDatainHealthcare.HealthcInformRes.2016;22:156-63. Medline:29971516 Kostkova P. datasharingforpublichealth:thenextethicalfrontiers.LifeSciSocPolicy.2018;14:16. Diseasesurveillance S2589-7500(20)30026-1 sourced data: apopulation-level study. Lancet Digit observational Health. 2020;2:e201-8. Sun K,ChenJ,ViboudC.Earlyepidemiologicalanalysisofthe coronavirusdisease2019outbreakbasedoncrowd tunities, familiarchallenges.ClinEpidemiol.2017;9:245-50. Ehrenstein V, NielsenH,PedersenAB,JohnsenSP, PedersenL.Clinicalepidemiologyintheeraofbigdata:newoppor ES.2020.25.2.1900321 associated infections: a systematic review. 2020;25:1900321. Euro Surveill. Streefkerk HRA, Verkooijen RP, systems of healthcare- Bramer WM, Verbrugh HA. Electronically assisted surveillance line:31104603 ence forinformingtheresponsetoemerging pathogens.PhilosTrans RSocLondBBiolSci.2019;374:20180276. Polonsky JA,BaidjoeA,KamvarZN,CoriDurskiK,EdmundsWJ,etal.Outbreakanalytics:adevelopingdatasci eid2109.150443 through theEmerging InfectionsProgramSites.Emerg InfectDis.2015;21:1516-9. Vugia DJ,MeekJI,DanilaRN,JonesTF, SchaffnerW, Baumbach J,etal.Training inInfectiousDiseaseEpidemiology doi:10.1038/d41586-020-00973-x Mallapaty S.Howsewagecouldrevealtruescaleofcoronavirusoutbreak.Nature.2020;580:176-7. review ofthemedicalliterature.CritCare.2014;18:521. Thompson J,RehnM,LossiusHM,LockeyD.Riskstoemergency medicalrespondersatterroristincidents:anarrative ternational Conference onSystems,ManandCybernetics. 2004. Kaliouby RE,RobinsonP. Mindreadingmachines:automatedinferenceofcognitive mentalstatesfromvideo.IEEEIn tion offoodborneillnessatscale. DigitalMedicine.2018;1:36. Sadilek A,CatyS,DiPreteL,Mansour R,SchenkT, Bergtholdt M,etal.Machine-learnedepidemiology: real-timedetec 58. Reingold AL.Outbreakinvestigations–aperspective.Emerg InfectDis.1998;4:21-7. doi:10.15585/mmwr.su6503a4 tion of the Spread of Ebola in High-Risk African Countries. MMWR Suppl. 2016;65:21-7. Breakwell L,GerberAR,GreinerAL,HastingsDL,MirkovicK,PaczkowskiMM,etal.EarlyIdentificationandPreven fluenza OtherRespirViruses.2018;12:551-7. Hay AJ,McCauleyJW. andresponsesystem(GISRS)—A futureperspective.In TheWHOglobalinfluenzasurveillance 0029843v3. Accessed:24June2020. taining theCOVID-19outbreakinChina.medRxiv. Available:https://www.medrxiv.org/content/10.1101/2020.03.03.2 Lai S,RuktanonchaiNW, ZhouL,ProsperO,LuoW, forcon FloydJR,etal.Effectofnon-pharmaceuticalinterventions nostics? LancetInfectDis.2019;19:e172-8. Peeling RW, Murtagh M,Olliaro PL. Epidemic preparedness: why is there a need to accelerate thedevelopmentofdiag tious diseaseoutbreaks.Lancet.2017;390:2211-4. Perkins MD,DyeC,BalasegaramM,BréchotMombouliJ-V, RøttingenJ-A,etal.Diagnosticpreparednessforinfec toring ofBiothreats.FrontBioengBiotechnol.2018;6:147. Dunbar J,PillaiS,WunschelD,DickensM,Morse SA, FranzD,etal.Perspective on ImprovingEnvironmentalMoni osecur Bioterror. 2014;12:263-73. Quinn SC, Kumar S. Health Inequalities and Infectious Disease Epidemics: A Challenge for Global Health Security. Bi 2016;2016:85-94. Jensen PM, De FineLichtHH.Predictingglobalvariation in infectiousdiseaseseverity.Evol Med PublicHealth. PLoS Pathog.2013;9:e1003424. Ko DC,UrbanTJ.UnderstandinghumanvariationininfectiousdiseasesusceptibilitythroughclinicalandcellularGWAS. N EnglJMed.2012;367:2057-9. Biagini P, Thèves C, Balaresque P, Géraut A, Cannet C, Keyser C, et al. Variola virus in a 300-year-old Siberian mummy. Can VetJ.2018;59:185-7. Gainer RS.Sporeconcentrationandmodifiedhostresistanceascauseofanthraxoutbreaks:Apractitioner’s perspective. simulation-based study.PLoSOne.2017;12:e0181227. Bédubourg G,LeStratY.Evaluationandcomparisonofstatisticalmethodsforearlytemporaldetectionoutbreaks:A eid0401.980104 doi:10.1093/bjc/azh036

doi:10.4258/hir.2016.22.3.156 doi:10.1098/rstb.2018.0276 Medline:26884415

doi:10.1186/s40504-018-0078-x Medline:29386683

Medline:23935492 Medline:23171117 Medline:25254915

doi:10.1093/emph/eow005 Medline:24290841 Medline:30551872 Medline:29722140 10 Medline:28577861

doi:10.1371/journal.ppat.1003424

doi:10.1056/NEJMc1208124

doi:10.1089/bsp.2014.0032 Medline:28715489 Medline:25323086 Medline:30406093 Medline:28490904

doi:10.1002/poi3.183 doi:10.1016/S1473-3099(13)70244-5 Medline:31304318

doi:10.1016/S1473-3099(18)30594-2

doi:10.1111/irv.12565

doi:10.1016/S0140-6736(17)31224-2 Medline:31964462

doi:10.1371/journal.pone.0181227

doi:10.1186/s13054-014-0521-1

doi:10.3389/fbioe.2018.00147

doi:10.2147/CLEP.S129779

doi:10.1038/s41746-018-0045-1 www.jogh.org Medline:29478706 Medline:26291924 Medline:9452395 Medline:32309796 •

doi:10.2807/1560-7917. doi: 10.7189/jogh.10.020317 Medline:27389301 Medline:32246117

doi:10.1016/j.

doi:10.3201/ doi:10.3201/ doi:10.1016/ Med Med ------

www.jogh.org REFERENCES • 77 76 75 74 73 72 71 70 69 68 67 66 93 92 91 90 89 88 87 86 85 84 83 82 81 80 79 78 doi: 10.7189/jogh.10.020317 and disasterresponse.Lancet.2019;393:276-86. Michaud J,MossK,LicinaD,WaldmanR,Kamradt-ScottA,BarteeM,etal.Militariesandglobalhealth:peace,conflict, experienced bykeystakeholders.PLoSOne.2018;13:e0195885. over microorganisms affectinfectiousdiseasecontrolandinnovation:Aroot-causeanalysisofbarrierstodatasharingas Ribeiro CD,vanRoodeMY,HaringhuizenGB,KoopmansMP, ClaassenE,vandeBurgwal LHM.Howownershiprights Epidemic Data.Trends Parasitol.2019;35:369-79. Cauchemez S,HozeN,CousienA,NikolayB,TenBoschQ.HowModellingCanEnhancetheAnalysisofImperfect mgen.0.000093 genomic epidemiologyandphylogeography.Microb Genom. 2016;2:e000093. Argimón S,AbudahabK,GoaterRJE,FedosejevA,BhaiJ,GlasnerC,etal.Microreact:visualizingandsharingdatafor break inaPersistentlyColonizedHotel.FrontMicrobiol.2016;6:1556. Sánchez-Busó L,GuiralS,CrespiMoyaV, CamaróML,OlmosMP, etal.GenomicInvestigationofaLegionellosisOut Medline:32284619 Ienca M,VayenaE.OntheresponsibleuseofdigitaldatatotackleCOVID-19pandemic.NatMed.2020;26:463-4. line:28336794 Kitchin R.Theethicsofsmartcitiesandurbanscience.PhilosTrans AMathPhysEngSci.2016;374:20160115. Health ResPerspect.2020;11:60-3. Contact Transmission ofCOVID-19inSouthKorea:NovelInvestigationTechniquesforTracing Contacts.OsongPublic effects inOperationalRiskManagement.EngApplArtifIntell.2015;46:289-302. Ramirez de la Huerga M, Bañuls Silvera VA, Turoff M. A CIA–ISM scenario approach for analyzing complex cascading al. Lancet.2013;382:1175-82. otic prescribingratesforacuterespiratory-tractinfections:amultinational,cluster, randomised,factorial,controlledtri Little P, Stuart B, Francis N, Douglas E,Tonkin-Crine S, Anthierens S, et al. Effects of internet-based trainingon antibi 2018 during infectiousdiseaseepidemics.ERJOpenRes.2019;5:00227-2018. Gobat N,AmuasiJ,YazdanpanahY,SigfidL,DaviesH,ByrneJ-P, etal.Advancingpreparednessforclinicalresearch ES.2020.25.3.2000045 nCoV) byreal-timeRT-PCR. 2020;25:2000045. EuroSurveill. Corman VM,LandtO,KaiserM,MolenkampR,MeijerA,ChuDK,etal.Detectionof2019novelcoronavirus(2019- doi:10.3390/v7072797 Kekulé AS.LearningfromEbolaVirus:HowtoPreventFutureEpidemics.Viruses.2015;7:3789-97. line:28146366 Redd SC,FriedenTR.CDC’sEvolvingApproachtoEmergency Response.HealthSecur. 2017;15:41-52. line:32234713 Iacobucci G.Covid-19:Doctorsstillat“considerablerisk”fromlackofPPE,BMAwarns.BMJ.2020;368:m1316. doi:10.3390/v12020135 Gralinski LE,MenacheryVD.ReturnoftheCoronavirus:2019-nCoV. Viruses.2020;12:135. lution. Bioinformatics.2018;34:4121-3. Hadfield J, Megill C, Bell SM, Huddleston J, Potter B, Callender C, et al. Nextstrain: real-time tracking of pathogen evo Wilson HJ, Daugherty PR. Collaborative Intelligence: Humans and AI Are Joining Forces. Harv Bus Rev.Wilson HJ,Daugherty PR.CollaborativeIntelligence: HumansandAIAreJoining Forces.Harv 2018. outbreaks? Ascopingliterature review. Evid Policy. 2020; Epubaheadofprint. Salajan A, Tsolova S, Ciotti M, Suk JE. To what extent does evidence support decision making during infectious disease 70. ing onoutcomesoftheCOVID-19 epidemicinWuhan,China:amodellingstudy.LancetPublic Health.2020;5:e261- Prem K,LiuY,RussellTW, KucharskiAJ,Eggo RM,DaviesN,etal.Theeffectofcontrolstrategiestoreduce socialmix Eng ApplArtifIntell.2015;46:346-53. Slam N,WangW, XueG,WangP. Aframeworkwithreasoning capabilitiesforcrisisresponsedecision–supportsystems. national Publishing;2016. editors. FusionMethodologiesinCrisisManagement:HigherLevel FusionandDecisionMaking.Cham:SpringerInter Snidaro L,VisentiniI.NetworkMethodsandPlanRecognition for FusioninCrisisManagement.In:RogovaG,ScottP, pai.2015.06.023 sources for a hypothetical two-site major incident. Eng Appl Artif Intell. 2015;46:336-45. Hawe GI,CoatesG,WilsonDT, Crouch RS.Agent-basedsimulationofemergency responsetoplantheallocationofre Eng ApplArtifIntell.2015;46:326-35. Vargas FlorezJ,LaurasM,Okongwu U,DupontL.Adecisionsupportsystemforrobusthumanitarianfacilitylocation. col Sci.2019;40:592-604. Chan HCS,ShanH,DahounT, Vogel H,YuanS.AdvancingDrugDiscoveryviaArtificialIntelligence.Trends Pharma State-of-the-art andFutureChallenges.KnowledgeEngineeringforPlanningScheduling.2013. Shah MMS,ChrpaL,JimohF, KitchinD,McCluskeyTL,ParkinsonS,etal.KnowledgeEngineeringToolsinPlanning: setup anduserexperience.EngApplArtifIntell.2015;46:312-25. Radianti J, Lazreg MB, Granmo O-C. Fire simulation-based adaptation of SmartRescue App for serious game: Design, remediation management.EngApplArtifIntell.2015;46:303-11. Moehrle S,RaskobW. Structuringandreusingknowledgefromhistoricalevents forsupportingnuclearemergency and Medline:32220655

doi:10.1089/hs.2017.0006 doi:10.1136/bmj.m1316 doi:10.1098/rsta.2016.0115

doi:10.1038/s41591-020-0832-5

doi:10.1016/S2468-2667(20)30073-6 Medline:31320117 Medline:23915885 Medline:32149043 doi:10.1016/j.engappai.2015.06.017 doi:10.1016/j.engappai.2015.06.020 Medline:29790939

doi:10.1016/j.tips.2019.06.004 Medline:30663597 Medline:30738632

doi:10.1016/S0140-6736(13)60994-0 11

doi:10.24171/j.phrp.2020.11.1.09

doi:10.1093/bioinformatics/bty407 Medline:29718947 doi:10.1016/j.engappai.2015.07.010 doi:10.1016/j.engappai.2015.06.012

doi:10.1016/S0140-6736(18)32838-1 Medline:26834713 Medline:31123684 Medline:31992387

doi:10.1016/j.pt.2019.01.009 doi:10.1332/174426420X15808913064302 December 2020•Vol. 10 No. 2•020317 doi:10.1016/j.engappai.2015.07.016

doi:10.1371/journal.pone.0195885 Medline:28348833

doi:10.3389/fmicb.2015.01556

doi:10.1183/23120541.00227-

doi:10.2807/1560-7917. doi:10.1016/j.engap Medline:31991541 Medline:26184283

doi:10.1099/ Med Med Med ------

VIEWPOINTS VIEWPOINTS December 2020•Vol. 10 No. 2•020317 REFERENCES 105 104 103 102 101 100 99 108 107 106 98 97 96 95 94 110 109 119 118 117 116 115 114 112 111 113 Schoch-Spana Toward aWorkingDefinition. Pétervári J,OsmanM,BhattacharyaJ.TheRoleofIntuitionintheGenerationandEvaluationStagesCreativ Pétervári 2018;56:1122-34. Okoli J,WattJ.Crisisdecision-making:theoverlapbetweenintuitiveandanalyticalstrategies.ManageDecis. 64. Simon HA.MakingManagementDecisions:TheRoleofIntuitionandEmotion.AcadManageExec.1987;1:57- doi:10.1016/j.cmi.2016.10.024 Raoult Watson eid0302.970201 programsjustifiable? tack intervention Kaufmann ity. FrontPsychol.2016;7:1420. U.S. Government:ADelphiStudy. enza A(H1N1)VaccinationintheUnitedStates.PLoSOne. Orata construction andDevelopment/TheWorldBank; Priorities: ImprovingHealthandReducingPoverty.3rded.Washington(DC):TheInternationalBankforRe igation. In:JamisonDT, GelbandH,HortonS,JhaP, LaxminarayanR,MockCN,etal.,editors.DiseaseControl Madhav fensive strategies. Green al practice. Turnour Prosser pnas.1814484116 es areneglectedbyresearchers. Furuse Tumpey line:26809567 McLean Pathog line:30409683 combined. Airborne Transmission of A/H5N1 Virus in Mammals Cause Substantial Attenuation inChickens only when Richard doi:10.1007/s00203-007-0295-9 prepared under various environmental conditions. Baweja mousepox. a recombinantectromeliavirussuppressescytolyticlymphocyteresponsesandovercomesgeneticresistanceto Jackson ence.1119392 ed 1918Spanishinfluenzapandemicvirus. Economic Areain2015:apopulation-level modellinganalysis. disability-adjusted life-yearscaused byinfectionswithantibiotic-resistantbacteriaintheEUand theEuropean Cassini jme.2007.020578 Wolpert 2019 Kwok doi:10.1016/j.endeavour.2008.01.005 Singh Science Reeves doi:10.1038/s41467-018-04252-2 Adli ence.1173759 that havebeenclonedandengineeredinyeast. thesized DNAfragments. Noyce Lartigue doi:10.5465/ame.1987.4275905

M ;

116

MS . .

R RS

RG RB . Y D

The CRISPRtoolkitforgenomeeditingandbeyond. 2014

CR RJ

M KJ N

2018 C . TM . CE , . , , : L , Analysis ofresearchintensityoninfectiousdiseasebyburdenrevealswhichdiseas Inner Workings:Howbacteriacouldhelprecycleelectronic waste. , 711 , ,

, Keim , , Project Coast:eugenicsinapartheidSouthAfrica.

Högberg , Lederman AF

The risk of bioterrorism re-analysed. . , Sci Rep Zaman LeDuc Med JAust Vashee Oppenheim J Virol Voeneky Ramsay Herfst Lavelle , Jacobs-Lorena Watson , Is cellsciencedangerous? ; , Conaty Basler

; 10 - M 362 Meltzer

3 doi:10.1016/j.pt.2016.01.002 doi:10.1016/S1473-3099(18)30605-4

, PS . :

e1003967

Cicero Medline:30647118

Lancet InfectDis

: J

MS . S

, doi:10.1108/MD-04-2017-0333 35 S 2001 ,

, 2017 AJ

Boucher CF

LD ,

MC Cohen S

SJ van denBrand Algire - S ,

, , , . 7 , MI , Mattoo , , Caetano-Anollés Christensen

Fiore 2010 Aguilar .

B Evans ,

Cretikos ; Plachouras PLoS One Medline:30287653 75 ; Ackerman , , 7 ,

Schmid Gallivan M : Adalja

7187 :

D MA 1205

Medline:24699938

; Y .

AE 192 ,

Health Secur . Genetic ControlOfMalariaMosquitoes. AR DH

Franz

The 2010CholeraOutbreakinHaiti:HowScienceSolvedaControversy. PV , Proc NatlAcadSciUSA , Medline:27703439

Chuang .

MA , :

- Bridges A , 541 Medline:28775271 .

10 . .

Sharma GP

Zeng Risk Anal ,

M Construction ofaninfectioushorsepoxvirusvaccinefromchemicallysyn

2018

2019

CD G D Gronvall JMA

. . . doi:10.1073/pnas.1820329116 DR ,

, . , Medline:11152493 An auditofpandemic(H1N1)2009influenzavaccinewastageingener The economic impact of a bioterrorist attack: are prevention and postat

Mulembakani Gronvall Medline:20438435 , Quattrocchi

D Beaton H . ;

; ,

R-Y 13 19 Emerg InfectDis CB J MedEthics Confronting thethreatofbioterrorism:realities,challenges,andde ,

12 , de Meulder . K Beck Solórzano 2017 : ,

: e0188453 , .

doi:10.1126/science.aat7664

e2 ,

Tripathi G Science

Reed 2017 Benders Science , -

13 GK doi:10.1371/journal.ppat.1003967 Kirk Sell F ; , 15 ,

Hall Boëte . 2017

Clin Microbiol Infect ;

C . 37 Medline:30340981 : A

323

Expert Views on Biological Threat Characterization for the Expert ViewsonBiologicalThreatCharacterizationforthe doi:10.3389/fpsyg.2016.01420

P , .

V , .

, doi:10.1038/s41598-017-07000-6

A Jain :

. D , GA 2005 Arch Microbiol 2009 2389 DF

Rubin Hoxha Medline:29351298 , Aggarwal . .

, - C

Swayne . 8 T

, 2007 Lexmond , doi:10.1128/JVI.75.3.1205-1210.2001 2019

, . Ramshaw S doi:10.5694/j.1326-5377.2010.tb03624.x

Ma . Agricultural research,oranewbioweaponsystem? Meyer 2011 Medline:28745924 ; , ; - 310

325 404 1997

et al. Nat Commun E

A L ; , ; Endeavour 33 116 , , Wolfe

: : ;6e22308.

. DE 77 et al 1693 A Simonsen

Cost-Effectivenessof2009PandemicInflu Medline:28314075 D : ;

345 3 Lancet InfectDis P : - , et al ,

: 478 , 80 IA et al 83 et al . Bestebroer

- Creating bacterial strains from genomes Creating bacterialstrainsfromgenomes N .

Trends Parasitol - . 6 . doi:10.1016/S1473-3099(18)30298-6 - .

8 - Expression of mouse interleukin-4 by Expression ofmouseinterleukin-4by . 2008 . Pandemics:Risks,Impacts,andMit 94 Medline:16210530 . Properties of Bacillus anthracis spores Properties ofBacillusanthracisspores 83

. . . Medline:19696314

Global Catastrophic Biological Risks: Global CatastrophicBiologicalRisks: . www.jogh.org Characterization ofthereconstruct doi:10.1371/journal.pone.0188453 2017 Medline:17526685 .

. . 2008

2018 Medline:9204289 Medline:30598444 ;

189 doi:10.1089/hs.2017.0038 , ; et al

23 TM ; ; Proc NatlAcadSciUSA 32 9 : 71 : : • 1911 351 : , . 5

. doi:10.1111/risa.12787 et al - Attributable deaths and Attributable deathsand doi: 10.7189/jogh.10.020317 - . 9 2019 9 2016 . . .

. Medline:17713759

Medline:27810468 . Medline:18316125 Medline:29765029 Mutations Driving Mutations Driving

;

doi:10.1126/sci 19 ; doi:10.1126/sci 32

doi:10.1136/ doi:10.3201/ : 56 doi:10.1073/ 174 - 66 - 6 . .

Med Med PLoS PLoS ------.

www.jogh.org REFERENCES • 124 123 122 121 120 doi: 10.7189/jogh.10.020317 Reliab EngSystSaf Flage S0140-6736(20)30379-2 The Lancet line:32296266 mitigation measurestakenduringthecombattingofCOVID-19pandemic. Bruinen deBruin 2015. perceptions andexperiencesduring periods of lowbutongoing transmission of Ebola virus disease inSierra Leone, Nuriddin jama.2016.1353 eases in the United States: A Review of Measles and Pertussis. Phadke

R BMJ GlobHealth

, VK Aven

A , . , Bednarczyk COVID-19: fightingpanicwithinformation. Jalloh

doi:10.1016/j.ssci.2020.104773 .

Emerging risk – Conceptual definition and a relation to black swan type of events – ScienceDirect. Y

. , MF

2015 Lequarre , . Meyer

RA 2018 ; 144 , Salmon

A-S

: ; 61 E 3 : , e000410 - Bunnell , 7 McCourt .

doi:10.1016/j.ress.2015.07.008 DA , Omer

. R

Medline:29629189 ,

J Bio , Clevestig

FA 13 . Association BetweenVaccineRefusalandVaccine-PreventableDis ,

Jalloh

P , Pigazzani

JAMA

MB Lancet

doi:10.1136/bmjgh-2017-000410 , et al . 2016 . [email protected] France 91220 BretignysurOrge Unite deBacteriologie Infectieuses Departement deMicrobiologieetMaladies Institut deRechercheBiomedicaledesArmees Lionel KOCHMD,PhD Correspondence to:

2020 F . , Trust, fear, stigmaanddisruptions:community Zare Jeddi ; 315 ; 395

December 2020•Vol. 10 No. 2•020317 : 1149 : 537

- M 58 .

, Saf Sci Medline:32087777 et al .

Medline:26978210 .

Initial impacts of global risk Initial impactsofglobalrisk .

2020

; 128 : 104773

doi:10.1016/

doi:10.1001/ .

Med

- -

VIEWPOINTS