不明原因疾病的流行病学调查方法.ppt
不明原因疾病的流行病学调查方法The Epidemiologic Approach to Disease of Unknown Cause.,2,3,疾病聚集报告增多原因,健康知识的传播电影:“Erin Brockovich”(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,4,“A little knowledge is a dangerous thing.”“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,6,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,7,美国CDC调查的不明原因疾病Investigations of diseases of unknown etiology,US CDC 1946-1999,8,不明原因综合症Syndromes of unknown cause identified in sample,Kawasaki 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 Syndrome,9,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10个步骤,11,12,13,14,15,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,16,内布拉斯加 Nebraska 1984,42 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 Iodine,17,南达科他,明尼苏达,18,June 1985 a specialist reports 8 cases from a neighboring state,19,Initial steps,Verify the diagnosisIs this a laboratory error?Will other specialists confirm the diagnosis?Interview PatientsNotify adjacent statesFind more hyperthyroisism,20,21,Symptoms of 28 patients with elevated T4,22,Widened Case Finding,Survey of patient records from medical clinics(4 states)for past 18 monthsTelephone survey of doctors in areaLetters to all doctors in areaDescribe the outbreakRequest reporting,23,Case definition applied to all reports,T4,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 replacement,24,Case finding identified 121 cases that fit the definition.,25,Thyrotoxicosis by month,26,Incidence of thyrotoxicosis per 10,000 by county,27,New information,Experts 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?,28,The second case control study showed a very specific association,调查暴发的10个步骤 10 steps of an outbreak investigation,准备现场工作 Prepare for field work,证实暴发存在 Establish existence of an outbreak,Time,Verify the diagnosis 验证诊断,Define,count,and interview cases 定义,计数,采访病例,确定人、地点和时间特征 Characterize person,place and time,Develop a hypothesis 提出假设,Develop analytic study to test hypothesis 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,实施控制措施 Implement Control,将调查结果进行交流 Communicate Findings,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 tests,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,Unexplained 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 days,Fever,myalgias,headache,and cough,Rapid development of respiratory failure.,Tests for plague and other respiratory pathogens yielded no cause.,新浪、雅虎、腾讯对阜阳的报道,调查暴发的10个步骤 10 steps of an outbreak investigation,准备现场工作 Prepare for field work,证实暴发存在 Establish existence of an outbreak,Time,Verify the diagnosis 验证诊断,Define,count,and interview cases 定义,计数,采访病例,确定人、地点和时间特征 Characterize person,place and time,Develop a hypothesis 提出假设,Develop analytic study to test hypothesis 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,实施控制措施 Implement Control,将调查结果进行交流 Communicate Findings,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 done,什么检测做了?什么检测没有做?What tests were done or not done?,6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,调查暴发的10个步骤 10 steps of an outbreak investigation,准备现场工作 Prepare for field work,证实暴发存在 Establish existence of an outbreak,Time,Verify the diagnosis 验证诊断,Define,count,and interview cases 定义,计数,采访病例,确定人、地点和时间特征 Characterize person,place and time,Develop a hypothesis 提出假设,Develop analytic study to test hypothesis 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,实施控制措施 Implement Control,将调查结果进行交流 Communicate Findings,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.),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+fever,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 aneurisms,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,Epidemiologic 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 factors,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.,暴发期间,特异度增加During outbreaks specificity improves,90%Specificity,50%Specificity,在封闭人群中的病例定义Case definition in a closed group,真正的病例True Case,类似的病例Similar disease,在开放人群中的病例定义Case definition in an open group,True Case,Similar disease,调查暴发的10个步骤 10 steps of an outbreak investigation,准备现场工作 Prepare for field work,证实暴发存在 Establish existence of an outbreak,Time,Verify the diagnosis 验证诊断,Define,count,and interview cases 定义,计数,采访病例,确定人、地点和时间特征 Characterize person,place and time,Develop a hypothesis 提出假设,Develop analytic study to test hypothesis 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,实施控制措施 Implement Control,将调查结果进行交流 Communicate Findings,31例重症病例,年龄分组,死亡年龄3岁以内平均1.5岁,18例死亡病例,发病到死亡1-11天 平均3天,Person to person transmission,35%did know the person with whom they had contact,35%did know the person with whom they had contact,10%are pneumonia and 90%Upper respiratory infection,90%of infections are asymptomatic(e.g.polio),Without identification of asymptomatic infection you see this,A zoonosis 10%of animal infections transmit to man.,Without knowledge of the animal disease it will look like this,66,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,阜阳市2008年14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%),1983-1985 马里兰州各季度PGH重症监护病房心跳停止病人Cardiac arrests,by quarter and year,PGH ICU,Maryland,1983-1985,1983,1984,1985,Number of Cardiac Arrests,季度和年度 Quarter and Year,0,20,30,40,10,心跳停止病例数,季度和年度 Quarter and Year,Number of Cardiac Arrests,1983-1985 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,每日各时段(军队时间)Hour of Day(Military time),Number of Cardiac Arrests,1983-1985 马里兰州每日各时段PGH重症监护病房心跳停止病人数 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,不同护士管理病人的心跳骤停的危险Relative risk of cardiac arrest by nurse,心跳骤停的重复发生Recurrent cardiac arrests,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,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,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 hyperkalemia,季度和年度 Quarter and Year,Number of Cardiac Arrests,1983-1985 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,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,专家诊断意见,Simple case definitions Be aware ofMass sociogenic reactionsPublicityMultiple diseasesLaboratory errorsExtend case findingConsider mild and asymptomaticLook for exposures not causesDo not quit ask for help,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,