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不明原因疾病的流行病学调查方法TheEpidemiologicApproachtoDiseaseofUnknownCause.1 调查+++控制+调查+++控制+++未知调查+++控制+调查+控制+++已知未知已知传染源或传播模式病原体2 疾病聚集报告增多原因健康知识的传播电影：“ErinBrockovich”（布罗克维奇/永不妥协/伊人当自强）互联网：信息渠道分享信息传播谣言、怀疑、恐慌3 “Alittleknowledgeisadangerousthing.”“一知半解，更加危险”（英谚）4 疾病聚集报告增多原因健康知识的传播对政府的不信任（美国）政府刻意掩盖个别流氓科学家的作为Tuskegee（Alabama）事件（1943-1973）一粒老鼠屎害了一锅粥5 疾病聚集报告增多原因健康知识的传播对政府的不信任非传染病发病率增加传染病的减少人均寿命增加疾病监测的加强环境污染、行为危险因素报告能力和发现意识6 种类ClassificationTotalPercent胃肠道Gastrointestinal12523肿瘤Cancers8015命名的综合症Namedsyndromes7514神经Neurological5510其他Other509呼吸道Respiratory458出生缺陷Birthdefects407不明原因死亡Unexplaineddeath204医疗反应Medicalreactions204实验室人为错误Laboratoryartifacts153群体反应Masssociogenicreactions102皮疹Rashes102所有不明原因Allunknowncause545100美国CDC调查的不明原因疾病Investigationsofdiseasesofunknownetiology,USCDC1946-19997 不明原因综合症SyndromesofunknowncauseidentifiedinsampleKawasakiDisease,Brainerddiarrhea,传染性单核细胞增多综合症Infectiousmononucleosis格林巴例综合症Guillian-BarreSyndrome系统性红斑狼疮SystemicLupuserythematosis雷氏综合症Reye’ssyndrome溶血性尿毒综合症Hemolytic-UremicSyndrome海湾战争综合症GulfWarSyndrome8 不明原因死亡调查Unexplaineddeathinvestigations婴幼儿突然死亡综合症Suddeninfantdeathsyndrome(SIDS)夜间突然死亡Suddenunexplainednocturnaldeath家族性肾上腺脑白质营养不良聚集性Familialclusters医疗错误Medicalmalpractice9 美国四个州的无痛性甲状腺炎调查南达科他明尼苏达艾奥瓦内布拉斯加10 内布拉斯加Nebraska198442个病例ElevatedT4andsymptoms（焦虑、呼吸短促、心悸、心跳加快、体重减轻）6CountiesCasecontrolstudyforDietaryiodineColdandcoughmedicines“viralillness”53%vs32%p=0.05Viralcultures,HLAtyping,UrinaryIodine11 南达科他明尼苏达12 June1985aspecialistreports8casesfromaneighboringstateOnsetMax.24‑hr.AgeSexResidencedateT4*RAIU(%)53MValleySprings,S.D.3‑84>200.634FValleySprings,S.D.5‑851817.057MBeaverCreek,S.D.5‑85221.041FValleySprings,S.D.5‑85182.676FValleySprings,S.D.6‑85147.8?MLuverne,Minn.6‑85"high"1.029MValleySprings,S.D.?272.2?MLuverne,Minn.?"high""low"*normalrange=5‑12.RAIU‑甲状腺低放射性碘摄入;normalrange=10%‑35%.13 InitialstepsVerifythediagnosisIsthisalaboratoryerror?Willotherspecialistsconfirmthediagnosis?InterviewPatientsNotifyadjacentstatesFindmorehyperthyroisism14 15 Symptomsof28patientswithelevatedT4SymptomPercentFatigue92Weakness83Tachycardiaorpalpitations79Shortnessofbreath68Weightloss66Tremor62Nervousness60Sleeplessness51Headaches45Heatintolerance38Excessivesweating34Diarrhea1616 WidenedCaseFindingSurveyofpatientrecordsfrommedicalclinics(4states)forpast18monthsTelephonesurveyofdoctorsinareaLetterstoalldoctorsinareaDescribetheoutbreakRequestreporting17 CasedefinitionappliedtoallreportsT4,freeT4orT3>25%higherthanupperlimitofnormalforthelaboratory≥2ofthefollowing:Sleeplessness,nervousness,headache,increasedheartrate,palpitations,shortofbreath,fatigue,sweating,tremor,diarrhea,heatintolerance,weightloss.ExcludedGrave’sdisease,T4replacement18 Casefindingidentified121casesthatfitthedefinition.AgegroupMFTotal(years)#(%)0‑9112(2)10‑19358(7)20‑297815(12)30‑39151429(24)40‑4981018(15)50‑5916622(18)60‑699514(12)70+31013(11)Total6259121(100)19 Thyrotoxicosisbymonth20 Incidenceofthyrotoxicosisper10,000bycounty21 NewinformationExpertsopinionViralcauseIodine-inducedhyperthyroidismInformationfromnewcasesFamilyof54casesatemeat1non-caseavegetarianFoodfromonestoreallnationalexceptlocal“beeftrimmings”Wasbeefcontaminatedwithiodine?22 Thesecondcasecontrolstudyshowedaveryspecificassociation23 调查暴发的10个步骤10stepsofanoutbreakinvestigation准备现场工作Prepareforfieldwork证实暴发存在EstablishexistenceofanoutbreakTimeVerifythediagnosis验证诊断Define,count,andinterviewcases定义，计数，采访病例确定人、地点和时间特征Characterizeperson,placeandtimeDevelopahypothesis提出假设Developanalyticstudytotesthypothesis通过分析研究验证假说Reconsider,refine,retesthypothesis再推敲，修正和再检验假说实施控制措施ImplementControl将调查结果进行交流CommunicateFindings24 知道病原体有很大的优势，比如：伤寒Knowingtheetiologyisamajoradvantage.E.g.Typhoid食物或者水源传播Transmissionbyfoodorwater人是唯一宿主Humanreservoironly人传人罕见Persontopersontransmissionveryrare70%病例是隐形感染70%infectionsasymptomatic潜伏期8-24天8-24dayincubationperiod治疗方法明确Treatmentwelldefined病例定义和确诊方法Casedefinitionsandconfirmatorytests25 受关注的程度不一样：领导关注度截至5月19日第362人次国家类专家：国家共派49批170人次，国家临床29批，122人次流行病等专家20批，48人次。省级类专家：总共派43批105人临床专家30批75人流行病学等专家13批30人。行政领导和司机87人（列表）花名册，文件、简讯、工作报告流调信息组、临床救治组、宣传教育组、样本采集运输组、综合组26 UnexplainedrespiratorydiseaseanddeathinfourstatesOtherindividualpersonswithsimilarillnessinsamelargearea.May141993,twomembersofthesamefamilydiewithin5daysFever,myalgias,headache,andcough,Rapiddevelopmentofrespiratoryfailure.Testsforplagueandotherrespiratorypathogensyieldednocause.27 28 29 30 31 32 新浪、雅虎、腾讯对阜阳的报道33 调查暴发的10个步骤10stepsofanoutbreakinvestigation准备现场工作Prepareforfieldwork证实暴发存在EstablishexistenceofanoutbreakTimeVerifythediagnosis验证诊断Define,count,andinterviewcases定义，计数，采访病例确定人、地点和时间特征Characterizeperson,placeandtimeDevelopahypothesis提出假设Developanalyticstudytotesthypothesis通过分析研究验证假说Reconsider,refine,retesthypothesis再推敲，修正和再检验假说实施控制措施ImplementControl将调查结果进行交流CommunicateFindings34 要重点考查实验室检测已经做过什么检测？Whatdiagnostictestshavebeendone什么应该做的检测还没有做呢？Whatdiagnostictestshavenotbeendone35 什么检测做了？什么检测没有做？Whattestsweredoneornotdone?检测TestResultTiming痰涂片SputumsmearND血培养BloodCultureND鼠疫F1抗体PlagueF-1antibody-earlySARSPCR-OKAIPCR-OK兔拉热免疫荧光TularemiaCF-early鹦鹉热免疫荧光PsittacosisCFND呼吸道合胞病毒IgMRSVIgM+-early36 6期的麻疹阜阳的第一份流调报告37 要敢于怀疑他们的同质性癌症村2002年9月14日南京汤山中毒事件42人死亡，最终确诊为毒鼠强和氟乙酰胺联合中毒；38 要注意假疫情癔病空姐的皮疹小孩身上的沥青39 调查暴发的10个步骤10stepsofanoutbreakinvestigation准备现场工作Prepareforfieldwork证实暴发存在EstablishexistenceofanoutbreakTimeVerifythediagnosis验证诊断Define,count,andinterviewcases定义，计数，采访病例确定人、地点和时间特征Characterizeperson,placeandtimeDevelopahypothesis提出假设Developanalyticstudytotesthypothesis通过分析研究验证假说Reconsider,refine,retesthypothesis再推敲，修正和再检验假说实施控制措施ImplementControl将调查结果进行交流CommunicateFindings40 疾病的标识符：DiseaseIdentifiers:症状Symptomatology体征（物理检查）Signs(Physicalexamination)临床评价（肌电图，脑电图，等）Clinicalevaluations(EKG,EEG,etc.)不符合其他疾病Lackofcompatibilitywithotherdiseases对治疗的反应Responsetotreatment实验室检测（病毒分离、血糖等）Laboratorytests(virusisolation,bloodsugar,etc.)41 使用能够包括多数病例或者所有病例的一个症状Useonecharacteristicthatwillincludemostorallcases腹泻Diarrhea发烧Fever皮疹Rash皮疹+发烧Rash+fever黄疸Jaundice咳嗽+发烧Cough+fever42 使用一些更特异的症状Useanumberofmorespecificcharacteristics草莓舌Strawberrytongue柯氏斑Koplick’sspots脑脊液SpinalfluidWBC’s>50/ml冠状动脉瘤Coronaryarteryaneurisms43 与其他疾病不符Lackofcompatibilitywithotherdiseases不是其他已知病因的皮疹Rashnotknowntobeduetoanotheretiology没有那些能明确引起嗜酸性粒细胞增多的原因的记录Norecordofanyknowncauseofeosinophilia尸检不能发现死亡原因Postmortemexaminationfailstodemonstrateanadequatecauseofdeath44 Epidemiologiccriteria流行病学标准时间Time地点Place人Person宿主因素（基础疾病）Hostfactors(underlyingillness)与其他病例的关系Linkagestoothercases与危险因素的关系Associationswithriskfactors45 避免包括怀疑的暴露Avoidincludingsuspectedexposure吃过A牌爆米花后72小时出现腹泻或者呕吐diarrheaorvomitingoccurringupto72hoursaftereatingBrandApopcorn.46 暴发期间，特异度增加Duringoutbreaksspecificityimproves90%Specificity50%Specificity47 在封闭人群中的病例定义Casedefinitioninaclosedgroup真正的病例TrueCase类似的病例Similardisease48 在开放人群中的病例定义CasedefinitioninanopengroupTrueCaseSimilardisease49 调查暴发的10个步骤10stepsofanoutbreakinvestigation准备现场工作Prepareforfieldwork证实暴发存在EstablishexistenceofanoutbreakTimeVerifythediagnosis验证诊断Define,count,andinterviewcases定义，计数，采访病例确定人、地点和时间特征Characterizeperson,placeandtimeDevelopahypothesis提出假设Developanalyticstudytotesthypothesis通过分析研究验证假说Reconsider,refine,retesthypothesis再推敲，修正和再检验假说实施控制措施ImplementControl将调查结果进行交流CommunicateFindings50 31例重症病例年龄分组死亡年龄3岁以内平均1.5岁51 18例死亡病例发病到死亡1-11天平均3天52 PersontopersontransmissionTimePlace53 35%didknowthepersonwithwhomtheyhadcontactTimePlace54 35%didknowthepersonwithwhomtheyhadcontactTimePlace55 10%arepneumoniaand90%UpperrespiratoryinfectionTimePlace56 90%ofinfectionsareasymptomatic(e.g.polio)TimePlace57 WithoutidentificationofasymptomaticinfectionyouseethisTimePlace58 Azoonosis10%ofanimalinfectionstransmittoman.TimePlace59 WithoutknowledgeoftheanimaldiseaseitwilllooklikethisTimePlace60 在阜阳手足口病中差点发挥更大的作用（或可能发挥了重大的作用）补阜阳日记61 62 阜阳市2008年1～4月份手足口病发病情况而且不少病例有手足口皮疹症状（50%）63 1983-1985马里兰州各季度PGH重症监护病房心跳停止病人Cardiacarrests,byquarterandyear,PGHICU,Maryland,1983-1985198319841985NumberofCardiacArrests季度和年度QuarterandYear020304010心跳停止病例数64 1983198419850151052520季度和年度QuarterandYearNumberofCardiacArrests1983-1985马里兰州各季度各班次PGH重症监护病房心跳停止病人数Cardiacarrests,byshift,PGHICU,Maryland,1983-1985夜班Nightshift晚班Eveningshift白班Dayshift心跳停止病例数65 00-0304-0708-1112-1516-1920-23020406080每日各时段（军队时间）HourofDay(Militarytime)NumberofCardiacArrests1983-1985马里兰州每日各时段PGH重症监护病房心跳停止病人数Cardiacarrests,bytimeandperiod,PGHICU,Maryland,1983-1985流行前Pre-epidemic流行中Epidemic流行后Post-epidemic心跳停止病例数66 不同护士管理病人的心跳骤停的危险Relativeriskofcardiacarrestbynurse护士Nurse1983-85EpidemicEpidemicPM143.95.011.2131.91.62.41961.40.75.01061.31.72.81181.00.65.0300.70.40.71290.70.91.767 心跳骤停的重复发生Recurrentcardiacarrests病人Pt日期Date护士Nur病人Pt日期Date护士NurA1983/07/1026D1984/05/1714A1983/08/04118D1084/06/0514B1984/01/0214E09/01113B1984/01/0214E09/0314B1984/01/0514F10/0214C1995/03/15154F10/1114C1995/03/1933F10/121468 同一个病例的心跳骤停：发生多次心跳骤停的病例Arrestsonsamepatient:patientswithmultiplearrests同一个病例的心跳骤停次数Arrestson护士NursesOnepatient140thers111323034069 不同因素和不同护士护理发生心跳骤停的危险Riskofcardiacarrestbyfactorandnurse危险因素RiskfactorNurse140thers术后Postoperative50%(24)3.8%(314)非术后NotPostOperative35%(37)10%(475)年龄Age<30years41%(17)4.4%(182)30-4944%(16)4.2%(167)50-6931%(16)8.0%(287)>6950%(12)14%(153)70 其他关键因素的联系Otherkeyassociations与下列因素无关系Noassociationwith基础疾病underlyingillness用药或者治疗medicationortreatment与一个床位有关联Associationwithonebed与工作时间无关系Noassociationwithhoursworked死亡的时间和病人的状况无特征可循Deathsunexpectedbytimingandpatient’scondition死亡与高钾有关联Deathsassociatedwithhyperkalemia71 1983198419850151052520季度和年度QuarterandYearNumberofCardiacArrests1983-1985马里兰州各季度各班次PGH重症监护病房心跳停止病人数Cardiacarrests,byshift,PGHICU,Maryland,1983-1985夜班Nightshift晚班Eveningshift白班Dayshift心跳停止病例数72 病因确定环节研究可以从一个点开始，从三个方面收集证据；证据的积累强化假说的强度，无需所有证据或证据簇均为阳性结果；重视不支持假设病因证据的意义；相似特征事件的类比（经验）引导研究的重要方法。73 “凳子”模型74 专家诊断意见75 SimplecasedefinitionsBeawareofMasssociogenicreactionsPublicityMultiplediseasesLaboratoryerrorsExtendcasefindingConsidermildandasymptomaticLookforexposures–notcausesDonotquit–askforhelp76 要有扎实的理论基础和专业技能要有内外两支工作团队要有良好的体魄要有必胜的信心要有无功而返的心理准备要善于思考，善于总结要有应对媒体（）的思想准备77
