不明原因疾病的流行病学调查方法.ppt

1不明原因疾病的流行病学调查方法The Epidemiologic Approach to Disease of Unknown Cause.2调查调查+控制控制+调查调查+控制控制+未知未知调查调查+控制控制+调查调查+控制控制+已知已知未知未知已知已知传染源或传播模式传染源或传播模式病原体病原体3疾病聚集报告增多原因健康知识的传播健康知识的传播电影：电影：“Erin Brockovich”（布罗克维奇（布罗克维奇/永不妥协永不妥协/伊人当自强）伊人当自强）互联网：互联网：信息渠道信息渠道分享信息分享信息传播谣言、怀疑、恐慌传播谣言、怀疑、恐慌4“A little knowledge is a dangerous thing.”“一知半解，更加危险一知半解，更加危险”（英谚）5疾病聚集报告增多原因健康知识的传播健康知识的传播对政府的不信任对政府的不信任（美国）政府刻意掩盖（美国）政府刻意掩盖个别流氓科学家的作为个别流氓科学家的作为Tuskegee（Alabama）事件（事件（1943-1973）一粒老鼠屎害了一锅粥一粒老鼠屎害了一锅粥6疾病聚集报告增多原因健康知识的传播健康知识的传播对政府的不信任对政府的不信任非传染病发病率增加非传染病发病率增加传染病的减少传染病的减少人均寿命增加人均寿命增加疾病监测的加强疾病监测的加强环境污染、行为危险因素环境污染、行为危险因素报告能力和发现意识报告能力和发现意识7种种类ClassificationTotalPercent胃胃肠道道Gastrointestinal12523肿瘤瘤Cancers8015命名的命名的综合症合症Named syndromes7514神神经Neurological5510其他其他Other509呼吸道呼吸道Respiratory458出生缺陷出生缺陷Birth defects407不明原因死亡不明原因死亡Unexplained death204医医疗反反应Medical reactions204实验室人室人为错误Laboratory artifacts153群体反群体反应Mass sociogenic reactions102皮疹皮疹Rashes102所有不明原因所有不明原因All unknown cause545100美国CDC调查的不明原因疾病Investigations of diseases of unknown etiology,US CDC 1946-19998不明原因综合症Syndromes of unknown cause identified in sampleKawasaki Disease,Brainerd diarrhea,传染性单核细胞增多综合症Infectious mononucleosis格林巴例综合症Guillian-Barre Syndrome系统性红斑狼疮Systemic Lupus erythematosis雷氏综合症Reyes syndrome溶血性尿毒综合症Hemolytic-Uremic Syndrome海湾战争综合症Gulf War Syndrome9不明原因死亡调查Unexplained death investigations婴幼儿突然死亡综合症Sudden infant death syndrome(SIDS)夜间突然死亡Sudden unexplained nocturnal death家族性肾上腺脑白质营养不良聚集性Familial clusters医疗错误Medical malpractice 10现场流行病学（暴发疫情）调查步骤组织准备核实诊断确定暴发或流行的存在建立病例定义核实病例并计算病例数 描述性分析（三间分布）建立并检验假设迅速采取控制措施 完善现场调查报告交流反馈一般是一般是10个步骤个步骤1112131415美国四个州的无痛性甲状腺炎调查南达科他南达科他 明明尼尼苏苏达达 艾奥瓦艾奥瓦内布拉斯加内布拉斯加 16内布拉斯加 Nebraska 198442 个病例Elevated T4 and symptoms（焦虑、呼吸短促、心悸、心跳加快、体重减轻）6 CountiesCase control study forDietary iodineCold and cough medicines“viral illness”53%vs 32%p=0.05Viral cultures,HLA typing,Urinary Iodine17南达科他南达科他 明尼苏达明尼苏达 18June 1985 a specialist reports 8 cases from a neighboring state Onset Max.24 hr.Age Sex Residencedate T4*RAIU(%)53MValley Springs,S.D.3 84 20 0.634FValley Springs,S.D.5 85 18 17.057MBeaver Creek,S.D.5 85 22 1.041FValley Springs,S.D.5 85 18 2.676FValley Springs,S.D.6 85 14 7.8?MLuverne,Minn.6 85 high 1.029MValley Springs,S.D.?27 2.2?MLuverne,Minn.?high low*normal range=5 12.RAIU 甲状腺低放射性碘甲状腺低放射性碘摄入入;normal range=10%35%.19Initial stepsVerify the diagnosisIs this a laboratory error?Will other specialists confirm the diagnosis?Interview PatientsNotify adjacent statesFind more hyperthyroisism2021Symptoms of 28 patients with elevated T4 Symptom PercentFatigue 92Weakness 83Tachycardia or palpitations79Shortness of breath 68Weight loss 66Tremor 62Nervousness 60Sleeplessness 51Headaches 45Heat intolerance 38Excessive sweating 34Diarrhea 1622Widened Case FindinglSurvey of patient records from medical clinics(4 states)for past 18 monthslTelephone survey of doctors in arealLetters to all doctors in arealDescribe the outbreaklRequest reporting23Case definition applied to all reportsT4,free T4 or T3 25%higher than upper limit of normal for the laboratory 2 of the following:Sleeplessness,nervousness,headache,increased heart rate,palpitations,short of breath,fatigue,sweating,tremor,diarrhea,heat intolerance,weight loss.Excluded Graves disease,T4 replacement24Case finding identified 121 cases that fit the definition.Age group M F Total (years)#(%)0 9 112(2)10 19 358(7)20 29 7815(12)30 39 151429(24)40 49 81018(15)50 59 16622(18)60 69 9514(12)70+31013(11)Total 6259 121(100)25Thyrotoxicosis by month 26Incidence of thyrotoxicosis per 10,000 by county27New informationExperts opinionViral causeIodine-induced hyperthyroidismInformation from new casesFamily of 54 cases ate meat1 non-case a vegetarianFood from one store all national except local“beef trimmings”Was beef contaminated with iodine?28The second case control study showed a very specific association29调查暴发的10个步骤 10 steps of an outbreak investigation准备现场工作准备现场工作 Prepare for field work证实暴发存在证实暴发存在 Establish existence of an outbreakTimeVerify the diagnosis 验证诊断验证诊断Define,count,and interview cases 定义，计数，采访病例定义，计数，采访病例确定人、地点和时间特征确定人、地点和时间特征 Characterize person,place and timeDevelop a hypothesis 提出假设提出假设Develop analytic study to test hypothesis 通过分析研究验证假说通过分析研究验证假说Reconsider,refine,retest hypothesis 再推敲，修正和再检验假说再推敲，修正和再检验假说实施控制措施实施控制措施 Implement Control将调查结果进行交流将调查结果进行交流 Communicate Findings30知道病原体有很大的优势，比如：伤寒Knowing the etiology is a major advantage.E.g.Typhoid食物或者水源传播Transmission by food or water人是唯一宿主Human reservoir only人传人罕见Person to person transmission very rare70%病例是隐形感染70%infections asymptomatic潜伏期8-24天8-24 day incubation period治疗方法明确Treatment well defined病例定义和确诊方法Case definitions and confirmatory tests31受关注的程度不一样：领导关注度l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32Unexplained respiratory disease and death in four states Other individual persons with similar illness in same large area.May 14 1993,two members of the same family die within 5 daysFever,myalgias,headache,and cough,Rapid development of respiratory failure.Tests for plague and other respiratory pathogens yielded no cause.333435363738新浪、雅虎、腾讯对阜阳的报道39调查暴发的10个步骤 10 steps of an outbreak investigation准备现场工作准备现场工作 Prepare for field work证实暴发存在证实暴发存在 Establish existence of an outbreakTimeVerify the diagnosis 验证诊断验证诊断Define,count,and interview cases 定义，计数，采访病例定义，计数，采访病例确定人、地点和时间特征确定人、地点和时间特征 Characterize person,place and timeDevelop a hypothesis 提出假设提出假设Develop analytic study to test hypothesis 通过分析研究验证假说通过分析研究验证假说Reconsider,refine,retest hypothesis 再推敲，修正和再检验假说再推敲，修正和再检验假说实施控制措施实施控制措施 Implement Control将调查结果进行交流将调查结果进行交流 Communicate Findings40要重点考查实验室检测已经做过什么检测？What diagnostic tests have been done什么应该做的检测还没有做呢？What diagnostic tests have not been done41什么检测做了？什么检测没有做？What tests were done or not done?检测检测Test ResultTiming痰涂片痰涂片Sputum smearND血培养血培养Blood CultureND鼠疫鼠疫F1抗体抗体Plague F-1 antibody-earlySARS PCR-OKAI PCR-OK兔拉热免疫荧光兔拉热免疫荧光Tularemia CF-early鹦鹉热免疫荧光鹦鹉热免疫荧光Psittacosis CFND呼吸道合呼吸道合 胞病毒胞病毒IgM RSV IgM+-early426期的麻疹阜阳的第一份流调报告43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；44要注意假疫情癔病空姐的皮疹小孩身上的沥青45调查暴发的10个步骤 10 steps of an outbreak investigation准备现场工作准备现场工作 Prepare for field work证实暴发存在证实暴发存在 Establish existence of an outbreakTimeVerify the diagnosis 验证诊断验证诊断Define,count,and interview cases 定义，计数，采访病例定义，计数，采访病例确定人、地点和时间特征确定人、地点和时间特征 Characterize person,place and timeDevelop a hypothesis 提出假设提出假设Develop analytic study to test hypothesis 通过分析研究验证假说通过分析研究验证假说Reconsider,refine,retest hypothesis 再推敲，修正和再检验假说再推敲，修正和再检验假说实施控制措施实施控制措施 Implement Control将调查结果进行交流将调查结果进行交流 Communicate Findings46疾病的标识符：Disease Identifiers:症状Symptomatology体征（物理检查）Signs(Physical examination)临床评价（肌电图，脑电图，等）Clinical evaluations(EKG,EEG,etc.)不符合其他疾病Lack of compatibility with other diseases对治疗的反应Response to treatment实验室检测（病毒分离、血糖等）Laboratory tests(virus isolation,blood sugar,etc.)47使用能够包括多数病例或者所有病例的一个症状Use one characteristic that will include most or all cases腹泻Diarrhea发烧Fever皮疹Rash皮疹+发烧 Rash+fever黄疸Jaundice咳嗽+发烧 Cough+fever48使用一些更特异的症状Use a number of more specific characteristics 草莓舌Strawberry tongue柯氏斑Koplicks spots脑脊液Spinal fluid WBCs 50/ml冠状动脉瘤Coronary artery aneurisms49与其他疾病不符Lack of compatibility with other diseases不是其他已知病因的皮疹Rash not known to be due to another etiology 没有那些能明确引起嗜酸性粒细胞增多的原因的记录No record of any known cause of eosinophilia 尸检不能发现死亡原因Postmortem examination fails to demonstrate an adequate cause of death 50Epidemiologic criteria流行病学标准时间Time地点Place人Person宿主因素（基础疾病）Host factors(underlying illness)与其他病例的关系Linkages to other cases与危险因素的关系Associations with risk factors51避免包括怀疑的暴露Avoid including suspected exposure吃过A牌爆米花后72小时出现腹泻或者呕吐diarrhea or vomiting occurring up to 72 hours after eating Brand A popcorn.52暴发期间，特异度增加During outbreaks specificity improves90%Specificity50%Specificity53在封闭人群中的病例定义Case definition in a closed group真正的病例真正的病例True Case类似的病例类似的病例Similar disease54在开放人群中的病例定义Case definition in an open groupTrue CaseSimilar disease55调查暴发的10个步骤 10 steps of an outbreak investigation准备现场工作准备现场工作 Prepare for field work证实暴发存在证实暴发存在 Establish existence of an outbreakTimeVerify the diagnosis 验证诊断验证诊断Define,count,and interview cases 定义，计数，采访病例定义，计数，采访病例确定人、地点和时间特征确定人、地点和时间特征 Characterize person,place and timeDevelop a hypothesis 提出假设提出假设Develop analytic study to test hypothesis 通过分析研究验证假说通过分析研究验证假说Reconsider,refine,retest hypothesis 再推敲，修正和再检验假说再推敲，修正和再检验假说实施控制措施实施控制措施 Implement Control将调查结果进行交流将调查结果进行交流 Communicate Findings5631例重症病例年龄分组年龄分组死亡年龄死亡年龄3岁以内岁以内平均平均1.5岁岁5718例死亡病例发病到死亡发病到死亡1-11天天 平均平均3天天58Person to person transmissionTimePlace5935%did know the person with whom they had contactTimePlace6035%did know the person with whom they had contactTimePlace6110%are pneumonia and 90%Upper respiratory infectionTimePlace6290%of infections are asymptomatic(e.g.polio)TimePlace63Without identification of asymptomatic infection you see thisTimePlace64A zoonosis 10%of animal infections transmit to man.TimePlace65Without knowledge of the animal disease it will look like thisTimePlace66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6768l阜阳市2008年14月份手足口病发病情况l而且不少病例有手足口皮疹症状（50%）691983-1985 1983-1985 马里兰州各季度马里兰州各季度PGH重症监护病房心跳停止病人重症监护病房心跳停止病人Cardiac arrests,by quarter and year,PGH ICU,Maryland,1983-1985198319841985Number of Cardiac Arrests季度和年度季度和年度 Quarter and Year020304010心跳停止病例数心跳停止病例数701983198419850151052520季度和年度季度和年度 Quarter and YearNumber of Cardiac Arrests1983-1985 马里兰州各季度各班次马里兰州各季度各班次PGH重症监护病房心跳停止病人数重症监护病房心跳停止病人数Cardiac arrests,by shift,PGH ICU,Maryland,1983-1985夜班Night shift晚班Evening shift白班Day shift心跳停止病例数心跳停止病例数7100-0304-0708-1112-1516-1920-23020406080每日各时段每日各时段（军队时间）（军队时间）Hour of Day(Military time)Number of Cardiac Arrests1983-1985 马里兰州每日各时段马里兰州每日各时段PGH重症监护病房心跳停止病重症监护病房心跳停止病人数人数 Cardiac arrests,by time and period,PGH ICU,Maryland,1983-1985流行前Pre-epidemic流行中 Epidemic流行后 Post-epidemic心跳停止病例数心跳停止病例数72不同护士管理病人的心跳骤停的危险Relative risk of cardiac arrest by nurse护士护士Nurse1983-85EpidemicEpidemic PM143.95.011.2131.91.62.41961.40.75.01061.31.72.81181.00.65.0300.70.40.71290.70.91.773心跳骤停的重复发生Recurrent cardiac arrests病人病人Pt日期日期Date护士护士Nur病人病人Pt日期日期Date护士护士NurA1983/07/1026D1984/05/17 14A1983/08/04118D1084/06/05 14B1984/01/0214E09/01113B1984/01/0214E09/0314B1984/01/0514F10/0214C1995/03/15154F10/1114C1995/03/1933F10/121474同一个病例的心跳骤停：发生多次心跳骤停的病例Arrests on same patient:patients with multiple arrests同一个病例的心跳骤停次数同一个病例的心跳骤停次数Arrests on护士护士NursesOne patient140thers111323034075不同因素和不同护士护理发生心跳骤停的危险Risk of cardiac arrest by factor and nurse危险因素危险因素Risk factorNurse 140thers术后术后Post operative50%(24)3.8%(314)非术后非术后Not Post Operative35%(37)10%(475)年龄年龄Age6950%(12)14%(153)76其他关键因素的联系Other key associations与下列因素无关系No association with 基础疾病underlying illness用药或者治疗medication or treatment与一个床位有关联Association with one bed与工作时间无关系No association with hours worked死亡的时间和病人的状况无特征可循Deaths unexpected by timing and patients condition死亡与高钾有关联Deaths associated with hyperkalemia771983198419850151052520季度和年度季度和年度 Quarter and YearNumber of Cardiac Arrests1983-1985 马里兰州各季度各班次马里兰州各季度各班次PGH重症监护病房心跳停止病人数重症监护病房心跳停止病人数Cardiac arrests,by shift,PGH ICU,Maryland,1983-1985夜班Night shift晚班Evening shift白班Day shift心跳停止病例数心跳停止病例数78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。79“凳子”模型80专专家家诊诊断断意意见见81Simple case definitions Be aware ofMass sociogenic reactionsPublicityMultiple diseasesLaboratory errorsExtend case findingConsider mild and asymptomaticLook for exposures not causesDo not quit ask for help82l要有扎实的理论基础和专业技能l要有内外两支工作团队l要有良好的体魄l要有必胜的信心l要有无功而返的心理准备l要善于思考，善于总结l要有应对媒体（）的思想准备