Early Epidemiological Assessment of the Virulence of Emerging Infectious Diseases A Case Study of an Influenza Pandemic 英文参考文献.docVIP

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Early Epidemiological Assessment of the Virulence of Emerging Infectious Diseases A Case Study of an Influenza Pandemic 英文参考文献.doc

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Early Epidemiological Assessment of the Virulence of Emerging Infectious Diseases A Case Study of an Influenza Pandemic 英文参考文献

EarlyEpidemiologicalAssessmentoftheVirulenceof EmergingInfectiousDiseases:ACaseStudyofan InfluenzaPandemic HiroshiNishiura1*,DonKlinkenberg1,MickRoberts2,JohanA.P.Heesterbeek1 1Theoretical Epidemiology, University of Utrecht, Utrecht, The Netherlands, 2Centre for Mathematical Biology, Institute of Information and Mathematical Sciences, MasseyUniversity,Auckland,NewZealand Abstract Background:Thecasefatalityratio(CFR),theratioofdeathsfromaninfectiousdiseasetothenumberofcases,providesan assessment of virulence. Calculation of the ratio of the cumulative number of deaths to cases during the course of an epidemictendstoresultinabiasedCFR.Thepresentstudydevelopsasimplemethodtoobtainanunbiasedestimateof confirmedCFR(cCFR),usingonlytheconfirmedcasesasthedenominator,atanearlystageofepidemic,evenwhenthere havebeenonlyafewdeaths. Methodology/PrincipalFindings:OurmethodadjuststhebiasedcCFRbyafactorofunderestimationwhichisinformedby thetimefromsymptomonsettodeath.Wefirstexaminetheapproachbyanalyzinganoutbreakofsevereacuterespiratory syndrome in Hong Kong (2003) with known unbiased cCFR estimate, and then investigate published epidemiological datasetsofnovelswine-origininfluenzaA(H1N1)virusinfectionintheUSAandCanada(2009).Becauseobservationofa fewdeathsalonedoesnotpermitestimatingthedistributionofthetimefromonsettodeath,theuncertaintyisaddressed bymeansofsensitivityanalysis.ThemaximumlikelihoodestimateoftheunbiasedcCFRforinfluenzamaylieintherangeof 0.16–4.48%withintheassumedparameterspaceforafactorofunderestimation.Theestimatesforinfluenzasuggestthat the virulence is comparable to the early estimate in Mexico. Even when there have been no deaths, our model permits estimatingaconservativeupperboundofthecCFR. Conclusions:AlthoughonehastokeepinmindthatthecCFRforanentirepopulationisvulnerabletoitsvariationsamong sub-populationsandunderdiagnosis,ourmethodisusefulforassessingvirulenceattheearlystageofanepidemicandfor informingpolicymakersandthepublic. Citation:NishiuraH,KlinkenbergD