埃博拉出血热防控技术培训：2-病例诊断与疫情报告

埃博拉出血热（EVD）

病例诊断与疫情报告中国疾病预防控制中心2014年12月培训目的掌握埃博拉出血热病例分类与定义掌握埃博拉出血热病例诊断、报告以及疫情报告流程培训内容埃博拉出血热病例的分类与定义，以及与美国CDC、欧盟CDC及WHO病例定义的比较埃博拉出血热病例诊断的程序及其病原学依据埃博拉出血热病例报告以及疫情报告的流程一、病例分类、定义病例定义必须严格按照国家卫计委的最新诊疗方案标准诊断我国病例定义分为三类：留观病例、疑似病例和确诊病例中国的病例定义更新过程旧版（2014.8.14）诊疗方案埃博拉出血热相关病例诊断和处置路径新版（2014.10.20）埃博拉出血热诊疗方案（2014年第1版）中国的病例定义（2014.8.14）诊断依据内容流行病学史来自疫区或21天内有疫区旅行史21天内接触过来自或曾到过疫区的发热者21天内接触过患者及其血液、体液、分泌物、排泄物或尸体等接触过被感染的动物临床表现早期：急性起病，发热并快速进展至高热，伴乏力、头痛、肌痛、咽痛等，并可出现恶心、呕吐、腹痛、腹泻、皮疹等极期：多在病程3-4天后出现。持续高热，感染中毒症状及消化道症状加重，出现不同程度的出血，包括皮肤粘膜出血、呕血、咯血、便血、血尿等；严重者可出现意识障碍、休克及多脏器受累，多在发病后2周内死于出血、多脏器功能障碍等实验室检查见国家卫生计生委发布的《埃博拉出血热诊疗方案》中实验室检查部分 中国的病例定义（2014.8.14）诊断依据内容留观病例

具备上述流行病学史中任何一项的发热（体温＞37.3℃）患者疑似病例具备上述流行病学史中任何一项，且符合以下三种情形之一者：体温≥38.6℃，出现严重头痛、肌肉痛、呕吐、腹泻、腹痛发热伴不明原因出血不明原因猝死确诊病例留观或疑似病例经实验室检测符合下列情形之一者：核酸检测阳性：患者血液等标本用RT-PCR等核酸扩增方法检测，结果阳性。若核酸检测阴性，但病程不足72小时，应在达72小时后再次检测病毒抗原检测阳性：采集患者血液等标本，用ELISA等方法检测病毒抗原分离到病毒：采集患者血液等标本，用Vero、Hela等细胞进行病毒分离血清特异性IgM抗体检测阳性；双份血清特异性IgG抗体阳转或恢复期较急性期4倍及以上升高组织中病原学检测阳性中国的病例定义（2014.10.20）发病前21天内有在埃博拉传播活跃地区居住或旅行史发病前21天内，在没有恰当个人防护的情况下，接触过埃博拉患者的血液、体液、分泌物、排泄物或尸体等发病前21天内，在没有恰当个人防护的情况下，接触或处理过来自疫区的蝙蝠或非人类灵长类动物流行病学史中国的病例定义（2014.10.20）留观病例疑似病例确诊病例具备上述流行病学史中第2、3项中任何一项，并且体温＞37.3℃者具备上述流行病学史中第1项，并且体温≥38.6℃者具备上述流行病学史中符合流行病学史第2、3中任何一项，并且符合以下三种情形之一者：

体温≥38.6℃，出现严重头痛、肌肉痛、呕吐、腹泻、腹痛发热伴不明原因出血不明原因猝死留观或疑似病例经实验室检测符合下列情形之一者：

核酸检测阳性病毒抗原检测阳性分离到病毒血清特异性IgM抗体检测阳性组织中病原学检测阳性《埃博拉出血热诊疗方案》（2014年第1版）中国的病例定义新旧病例定义比较：病例类别不变：留观病例、疑似病例和确诊病例流行病学史进行了调整强调了最长潜伏期（21天）

强调了没有采取恰当个人防护留观病例的病例定义改变（根据流行病学史的不同，体温分两类）流行病学史and>37.3℃流行病学史and≥38.6℃流行病学史>37.3℃≥38.6℃≥38.6℃且出现相关症状不明原因出血不明原因猝死旅行史、居住史留观病例留观病例患者接触史留观病例留观病例疑似病例疑似病例疑似病例动物接触史留观病例留观病例疑似病例疑似病例疑似病例USCDC的病例定义更新过程旧版（2014.8.7）PUI，Probable，ConfirmedcaseHigh，Low，Noknownexposure修订版（2014.10.27,11.16）PUI，ConfirmedcaseHigh，Some，Low（notzero），Noidentifiablerisk

exposureUSCDC的病例定义（2014.8.7）CaseDefinitionPersonUnderInvestigation(PUI)Apersonwhohasbothconsistentsymptomsandriskfactorsasfollows:Clinicalcriteria,whichincludesfeverofgreaterthan38.6degreesCelsiusor101.5degreesFahrenheit,andadditionalsymptomssuchassevereheadache,musclepain,vomiting,diarrhea,abdominalpain,orunexplainedhemorrhage;ANDepidemiologicriskfactorswithinthepast21daysbeforetheonsetofsymptoms,suchascontactwithbloodorotherbodyfluidsorhumanremainsofapatientknowntohaveorsuspectedtohaveEVD;residencein—ortravelto—anareawhereEVDtransmissionisactive*;ordirecthandlingofbatsornon-humanprimatesfromdisease-endemicareas.ProbableCaseAPUIwhoseepidemiologicriskfactorsincludehighorlowriskexposure(s)ConfirmedCase

Acasewithlaboratory-confirmeddiagnosticevidenceofEbolavirusinfection

USCDC的病例定义（2014.8.7）RiskLevelExposureHighriskexposuresPercutaneous(e.g.,needlestick)ormucousmembraneexposuretobloodorbodyfluidsofEVDpatientDirectskincontactwith,orexposuretobloodorbodyfluidsof,anEVDpatientwithoutappropriatepersonalprotectiveequipment(PPE)ProcessingbloodorbodyfluidsofaconfirmedEVDpatientwithoutappropriatePPEorstandardbiosafetyprecautionsDirectcontactwithadeadbodywithoutappropriatePPEinacountrywhereanEVDoutbreakisoccurringLow

riskexposuresHouseholdcontactwithanEVDpatientOtherclosecontactwithEVDpatientsinhealthcarefacilitiesorcommunitysettings.Closecontactisdefinedasbeingwithinapproximately3feet(1meter)ofanEVDpatientorwithinthepatient’sroomorcareareaforaprolongedperiodoftime(e.g.,healthcarepersonnel,householdmembers)whilenotwearingrecommendedpersonalprotectiveequipment(i.e.,standard,droplet,andcontactprecautions;see

InfectionPreventionandControlRecommendations)havingdirectbriefcontact(e.g.,shakinghands)withanEVDpatientwhilenotwearingrecommendedpersonalprotectiveequipment.Briefinteractions,suchaswalkingbyapersonormovingthroughahospital,donotconstituteclosecontactNoknownexposureHavingbeeninacountryinwhichanEVDoutbreakoccurredwithinthepast21daysandhavinghadnohighorlowriskexposure

USCDC的病例定义（2014.11.16）CaseDefinitionPersonUnderInvestigation(PUI)Apersonwhohasbothconsistentsignsorsymptomsandriskfactorsasfollows:Elevatedbodytemperatureorsubjectivefever(subjectiveor>100.4°For38.0°C)orsymptoms,includingsevereheadache,fatigue,musclepain,vomiting,diarrhea,abdominalpain,orunexplainedhemorrhage;ANDAnepidemiologicriskfactorwithinthe21daysbeforetheonsetofsymptoms.ConfirmedCase

Laboratory-confirmeddiagnosticevidenceofEbolavirusinfection.EarlyrecognitioniscriticaltocontrollingthespreadofEbolavirus.Healthcareprovidersshouldevaluatethepatient’sepidemiologicrisk,includingahistoryoftraveltoacountrywithwidespreadEbolavirustransmissionorcontactwithinthepreceding21dayswithapersonwithEbolawhilethepersonwassymptomatic.ClickhereforanevaluationalgorithmtodetermineiftestingforEbolaisindicated.IfadiagnosisofEbolaisbeingconsidered,thepatientshouldbeisolatedinasingleroom(withaprivatebathroom),andhealthcarepersonnelshouldfollowstandard,contact,anddropletprecautions,includingtheuseofappropriatePPE.Infectioncontrolpersonnelshouldbecontactedimmediately.IfEbolaissuspected,thelocalorstatehealthdepartmentshouldbeimmediatelycontactedforconsultationandtoassesswhethertestingisindicatedandtheneedforinitiatingidentificationofcontacts.

RiskLevelExposureHighriskexposuresPercutaneous(e.g.,needlestick)ormucousmembraneexposuretobloodorbodyfluidsofapersonwithEbolawhilethepersonwassymptomaticExposuretothebloodorbodyfluids(includingbutnotlimitedtofeces,saliva,sweat,urine,vomit,andsemenofapersonwithEbolawhilethepersonwassymptomaticwithoutappropriatePPEProcessingbloodorbodyfluidsofapersonwithEbolawhilethepersonwassymptomaticwithoutappropriatePPEorstandardbiosafetyprecautions,DirectcontactwithadeadbodywithoutappropriatePPEinacountrywithwidespreadEbolavirustransmission,HavinglivedintheimmediatehouseholdandprovideddirectcaretoapersonwithEbolawhilethepersonwassymptomaticSomeriskIn

countrieswithwidespreadtransmissionorcasesinurbanareaswithuncertaincontrolmeasures:directcontactwhileusingappropriatePPEwithapersonwithEbolawhilethepersonwassymptomaticorwiththeperson'sbodyfluidsanydirectpatientcareinotherhealthcaresettingsClosecontactinhouseholds,healthcarefacilities,orcommunitysettingswithapersonwithEbolawhilethepersonwassymptomaticClosecontactisdefinedasbeingforaprolongedperiodoftimewhilenotwearingappropriatePPEwithinapproximately3feet(1meter)ofapersonwithEbolawhilethepersonwassymptomaticLow(butnotzero)riskHavingbeeninacountrywithwidespreadEbolavirustransmissionwithinthepast21daysandhavinghadnoknownexposuresHavingbriefdirectcontact(e.g.,shakinghands)whilenotwearingappropriatePPE,withapersonwithEbolawhilethepersonwasintheearlystageofdiseaseBriefproximity,suchasbeinginthesameroomforabriefperiodoftime,withapersonwithEbolawhilethepersonwassymptomaticIncountrieswithoutwidespreadEbolavirustransmission:directcontactwhileusingappropriatePPEwithapersonwithEbolawhilethepersonwassymptomaticTraveledonanaircraftwithapersonwithEbolawhilethepersonwassymptomatic.NoidentifiableriskContactwithanasymptomaticpersonwhohadcontactwithpersonwithEbolaContactwithapersonwithEbolabeforethepersondevelopedsymptomsHavingbeenmorethan21dayspreviouslyinacountrywithwidespreadEbolavirustransmissionHavingbeeninacountrywithEbolacases,butwithoutwidespreadtransmissionorcasesinurbansettingswithuncertaincontrolmeasures,andnothavinganyotherexposuresasdefinedaboveHavingremainedonorintheimmediatevicinityofanaircraftorshipduringtheentiretimethattheconveyancewaspresentina

countrywithwidespreadtransmissionorcasesinurbanareaswithuncertaincontrolmeasures,andhavinghadnodirectcontactwithanyonefromthecommunity.USCDC病例定义新旧病例定义比较：病例类别改变：3种变2种，调查病例（PUI）和确诊病例PUI病例定义改变（提高敏感性）：体温从≥38.6℃降至>38℃发热或自觉发热或出现相关症状等3种情形中，只要满足其中一种暴露风险等级改变：由三级暴露风险（高风险、低风险和无已知风险）改为四级暴露风险（高风险、有一定风险、低风险和无明确暴露风险）各级暴露风险的判定标准改变（见下）USCDC病例定义高风险暴露（HighRisk）中：强调暴露于出现症状的患者或其血液/体液暴露者不再区分实验室、就诊和护理工作人员增加了曾共同居住并直接照顾过出现症状患者的暴露者低风险暴露（LowbutnotzeroRisk）中：增加了过去21天内到过埃博拉病毒流行的国家，且无明确暴露增加了未采取PPE情况下，与患者发病早期的短暂直接接触增加了与出现症状的患者同乘一架飞机删除了未与患者发生高风险暴露接触的人无已知风险（NoIdentifiableRisk）中增加了以下四种情况：接触患者的无症状的密接者接触潜伏期的病人21天前去过埃博拉病毒流行的国家乘坐飞机或轮船到达有埃博拉广泛传播的地区或者未采取明确控制措施的有病例的城市地区后，一直在其附近停留，并且与该社区的人没有任何直接接触有一定风险（SomeRisk）是新增加的分级：在埃博拉病毒广泛流行的国家，直接接触出现症状的患者的人旧版中低风险暴露中的第二种情形（Closecontactinhouseholds,healthcarefacilities,orcommunitysettingswithapersonwithEbolawhilethepersonwassymptomatic）在埃博拉病毒广泛流行的国家，于其他医疗机构中直接护理病例ECDC的病例定义更新过程第一版（2014.9.10）Possible，Probable，ConfirmedcaseClinical，Laboratory，Epidemiological，HighriskexposurecriteriaECDC的病例定义（2014.9.10）CaseDefinitionPossiblecaseNotApplicableProbablecaseApersonmeetingtheclinicalandhigh-riskexposurecriteriaConfirmedcaseApersonmeetingthelaboratorycriteriaECDC的病例定义CriteriaContentsClinicalcriteriaAnypersoncurrentlypresentingorhavingpresentedbeforedeath:Fever≥38.6°C

AND

anyofthefollowing:SevereheadacheVomiting,diarrhoea,abdominalpainUnexplainedhaemorrhagicmanifestationsinvariousformsMulti-organfailure

OR

apersonwhodiedsuddenlyandinexplicablyLaboratorycriteriaAnyofthefollowing:DetectionofEbolavirusnucleicacidinaclinicalspecimenandconfirmationbysequencingorasecondassayondifferentgenomictargets.IsolationofEbolavirusfromaclinicalspecimen.EpidemiologicalcriteriaInthe21daysbeforetheonsetofsymptoms:havingbeeninan

affectedarea;OR

havinghadcontactwithaprobableorconfirmedEVDcase.High-riskexposurecriteriaAnyofthefollowing:closeface-to-facecontact(e.g.withinonemetre)withoutappropriatepersonalprotectiveequipment(includingeyeprotection)withaprobableorconfirmedcasewhowascoughing,vomiting,bleeding,orwhohaddiarrhoea;

orhadunprotectedsexualcontactwitha

caseuptothreemonthsafterrecovery;directcontactwithanymaterialsoiledbybodilyfluidsfromaprobableorconfirmedcase;percutaneousinjury(e.g.withneedle)ormucosalexposuretobodilyfluids,tissuesorlaboratoryspecimensofaprobableorconfirmedcase;participationinfuneralriteswithdirectexposuretohumanremainsinorfromanaffectedareawithoutappropriatepersonalprotectiveequipment;directcontactwithbats,rodents,

primates,livingordead,inorfromaffectedareas,orbushmeat.ECDC与USCDC（2014.8.7版）的病例定义临床标准表述相似（例如≥38.6°C），增加了多器官衰竭和突然或不明原因死亡实验室标准与USCDC一致流行病学标准没有动物接触史高风险暴露标准中，增加了下列四种情况：无恰当PPE情况下，与有咳嗽、呕吐、出血或腹泻症状的可能或确诊病例有过1米内的面对面的接触（在美国当时的风险分级中属于低风险）与恢复期3月内的病人发生无保护的性接触直接接触任何被可能或确诊病例的体液污染的材料直接接触来自疫区的蝙蝠、啮齿类动物、灵长类动物或丛林肉（美国定义中的流行病学史）WHO的病例定义（2014.4.9）RoutinesurveillanceStandardcasedefinitionrecommendedbyWHO-AFROforthenotificationofEbolaorMarburgcases:

SuspectedEbolaorMarburgcasesforroutinesurveillance:Illnesswithonsetoffeverandnoresponsetotreatmentforusualcausesoffeverinthearea,andatleastoneofthefollowingsigns:bloodydiarrhoea,bleedingfromgums,bleedingintoskin(purpura),bleedingintoeyesandurine.

ConfirmedEbolaorMarburgcasesforroutinesurveillance:Asuspectedcasewithlaboratoryconfirmation(positiveIgMantibody,positivePCRorviralisolation)WHO的病例定义Community-basedsurveillanceStandardcasedefinitionAlertcaseforusebythecommunityorcommunity-basedvolunteers.Itmaybeusedforcommunity-basedsurveillanceduringthepre-epidemicphaseandduringtheoutbreak.——Illnesswithonsetoffeverandnoresponsetotreatmentofusualcausesoffeverinthearea,ORatleastoneofthefollowingsigns:bleeding,bloodydiarrhoea,bleedingintourineORanysuddendeathIfanalertcase(livingordead)isidentified:ReportthecasetoasurveillanceteamortotheclosesthealthcentreInstructionsWHO的病例定义DuringanEbolaorMarburgoutbreak（usedforsurveillance）a.CasedefinitiontobeusedbymobileteamsorhealthstationsandhealthcentresSUSPECTEDCASEAnyperson,aliveordead,sufferingorhavingsufferedfromasuddenonsetofhighfeverandhavinghadcontactwith:-asuspected,probableorconfirmedEbolaorMarburgcase;-adeadorsickanimal(forEbola)-amine(forMarburg)OR:anypersonwithsuddenonsetofhighfeverandatleastthreeofthefollowingsymptoms:•headaches•vomiting•anorexia/lossofappetite•diarrhoea•lethargy•stomachpain•achingmusclesorjoints•difficultyswallowing•breathingdifficulties•hiccupOR:anysudden,inexplicabledeath.①OR:anypersonwithinexplicablebleeding②③④WHO的病例定义b.CasedefinitionforexclusiveusebyhospitalsandsurveillanceteamsPROBABLECASEAnysuspectedcaseevaluatedbyaclinicianOR:Anydeceasedsuspectedcase(whereithasnotbeenpossibletocollectspecimensforlaboratoryconfirmation)havinganepidemiologicallinkwithaconfirmedcaseLABORATORYCONFIRMEDCASEAnysuspectedorprobablycaseswithapositivelaboratoryresult.Laboratoryconfirmedcasesmusttestpositiveforthevirusantigen,eitherbydetectionofvirusRNAbyreversetranscriptase-polymerasechainreaction(RT-PCR),orbydetectionofIgMantibodiesdirectedagainstMarburgorEbola.NON-CASE

Anysuspectedorprobablecasewithanegativelaboratoryresult.“Non-case”showednospecificantibodies,RNAorspecificdetectableantigens.①②③Alwaysaskaccompanyingfamilymembersabouthistoryofexposure/contactwhenpatientgiveunclearinformationoristooilltoanswer.NegativehistoryofexposureorsymptomsdoesnotexcludeEbola.Astheoutbreakevolvesandstigmaandfearofbeingputinisolationincrease,patients(andfamilymembers)mightnotsaythetruthaboutsymptomsandhistoryofexposure.Keepyoursuspicionhigh.Sickpeopletravelingfromcountrieswithoutbreakmaynotinitiallytelltruthaftercrossingclosedborder;whenarrivingbyplane.WHO的病例定义-AFewConsiderations二、病例诊断程序及病原学依据1.埃博拉出血热病例诊断程序（1）全国首例埃博拉出血热病例由国家卫生计生委组织国家级专家组，根据病例的流行病学史、临床症状和体征、中国疾病预防控制中心实验室检测和相关实验室平行检测结果等进行诊断

我国首例埃博拉出血热病例的确诊须由两家具有检测资质的实验室平行检测(其中一家必须为中国疾病预防控制中心病毒病所实