1、不明原因疾病的流行病學調(diào)查方法不明原因疾病的流行病學調(diào)查方法The Epidemiologic Approach to Disease of Unknown Cause.2調(diào)查調(diào)查+控制控制+調(diào)查調(diào)查+控制控制+未知未知調(diào)查調(diào)查+控制控制+調(diào)查調(diào)查 +控制控制+已知已知未知未知已知已知傳染源或傳播模式傳染源或傳播模式病原體病原體3疾病聚集疾病聚集報告增多原因報告增多原因 健康知識的傳播健康知識的傳播 電影：電影：“Erin Brockovich”（布羅克維奇（布羅克維奇/ 永不妥協(xié)永不妥協(xié)/ 伊人當自強）伊人當自強） 互聯(lián)網(wǎng)：互聯(lián)網(wǎng)： 信息渠道信息渠道 分享信息分享信息 傳播謠言、懷疑、恐慌傳

2、播謠言、懷疑、恐慌4“A little knowledge is a dangerous thing.” “一知半解，更加危險一知半解，更加危險”（英諺）5疾病聚集疾病聚集報告增多原因報告增多原因 健康知識的傳播健康知識的傳播 對政府的不信任對政府的不信任 （美國）政府刻意掩蓋（美國）政府刻意掩蓋 個別流氓科學家的作為個別流氓科學家的作為 Tuskegee（Alabama） 事件（事件（1943-1973） 一粒老鼠屎害了一鍋粥一粒老鼠屎害了一鍋粥6疾病聚集疾病聚集報告增多原因報告增多原因 健康知識的傳播健康知識的傳播 對政府的不信任對政府的不信任 非傳染病發(fā)病率增加非傳染病發(fā)病率增加 傳染病

3、的減少傳染病的減少 人均壽命增加人均壽命增加 疾病監(jiān)測的加強疾病監(jiān)測的加強 環(huán)境污染、行為危險因素環(huán)境污染、行為危險因素 報告能力和發(fā)現(xiàn)意識報告能力和發(fā)現(xiàn)意識7種類種類ClassificationTotalPercent胃腸道胃腸道Gastrointestinal12523腫瘤腫瘤Cancers8015命名的綜合癥命名的綜合癥Named syndromes7514神經(jīng)神經(jīng)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醫(yī)療反應醫(yī)療反應M

4、edical reactions204實驗室人為錯誤實驗室人為錯誤Laboratory artifacts153群體反應群體反應Mass sociogenic reactions102皮疹皮疹Rashes102所有不明原因所有不明原因All unknown cause545100美國美國CDC調(diào)查的不明原因疾病調(diào)查的不明原因疾病Investigations of diseases of unknown etiology, US CDC 1946-19998不明原因綜合癥不明原因綜合癥Syndromes of unknown cause identified in sample Kawasaki

5、 Disease, Brainerd diarrhea, 傳染性單核細胞增多綜合癥傳染性單核細胞增多綜合癥Infectious mononucleosis 格林巴例綜合癥格林巴例綜合癥Guillian-Barre Syndrome 系統(tǒng)性紅斑狼瘡系統(tǒng)性紅斑狼瘡Systemic Lupus erythematosis 雷氏綜合癥雷氏綜合癥Reyes syndrome 溶血性尿毒綜合癥溶血性尿毒綜合癥Hemolytic-Uremic Syndrome 海灣戰(zhàn)爭綜合癥海灣戰(zhàn)爭綜合癥Gulf War Syndrome9不明原因死亡調(diào)查不明原因死亡調(diào)查Unexplained death investig

6、ationsUnexplained death investigations 嬰幼兒突然死亡綜合癥嬰幼兒突然死亡綜合癥Sudden infant death syndrome (SIDS) 夜間突然死亡夜間突然死亡Sudden unexplained nocturnal death 家族性腎上腺腦白質(zhì)營養(yǎng)不良聚集性家族性腎上腺腦白質(zhì)營養(yǎng)不良聚集性Familial clusters 醫(yī)療錯誤醫(yī)療錯誤Medical malpractice 10現(xiàn)場流行病學現(xiàn)場流行病學（暴發(fā)疫情）（暴發(fā)疫情）調(diào)查步驟調(diào)查步驟 組織準備 核實診斷 確定暴發(fā)或流行的存在 建立病例定義 核實病例并計算病例數(shù) 描述性分析（

7、三間分布） 建立并檢驗假設 迅速采取控制措施 完善現(xiàn)場調(diào)查 報告交流反饋一般是一般是10個步驟個步驟1112131415美國四個州的無痛性甲狀腺炎調(diào)查美國四個州的無痛性甲狀腺炎調(diào)查南達科他南達科他 明尼蘇達明尼蘇達 艾奧瓦艾奧瓦內(nèi)布拉斯加內(nèi)布拉斯加 16內(nèi)布拉斯加內(nèi)布拉斯加 Nebraska 1984Nebraska 1984 42 個病例個病例 Elevated T4 and symptoms（焦慮、呼吸短促、（焦慮、呼吸短促、心悸、心跳加快、體重減輕）心悸、心跳加快、體重減輕） 6 Counties Case control study for Dietary iodine Cold an

8、d cough medicines “viral illness” 53% vs 32% p=0.05 Viral cultures, HLA typing, Urinary Iodine17南達科他南達科他 明尼蘇達明尼蘇達 18June 1985 a specialist reports 8 cases June 1985 a specialist reports 8 cases from a neighboring statefrom a neighboring state Onset Max. 24 hr. Age Sex Residencedate T4* RAIU (%)53MVa

9、lley 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 甲狀腺低放射性碘攝入甲狀腺低放射性碘

10、攝入; normal range = 10% 35%.19Initial stepsInitial steps Verify the diagnosis Is this a laboratory error? Will other specialists confirm the diagnosis? Interview Patients Notify adjacent states Find more hyperthyroisism2021Symptoms of 28 patients with elevated Symptoms of 28 patients with elevated T4

11、T4 Symptom PercentFatigue 92Weakness 83Tachycardia or palpitations79Shortness of breath 68Weight loss 66Tremor 62Nervousness 60Sleeplessness 51Headaches 45Heat intolerance 38Excessive sweating 34Diarrhea 1622Widened Case FindingWidened Case Findingl Survey of patient records from medical clinics (4

12、states) for past 18 monthsl Telephone survey of doctors in areal Letters to all doctors in arealDescribe the outbreaklRequest reporting23Case definition applied to all reportsCase definition applied to all reports T4, free T4 or T3 25% higher than upper limit of normal for the laboratory 2 of the fo

13、llowing: 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 Case finding identified 121 cases that fit the defin

14、ition.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)25ThyrotoxicosisThyrotoxicosis by month by month 26Incidence of Incidence of thyrotoxicosisthyrotoxicosis per 1

15、0,000 per 10,000 by countyby county27New informationNew information Experts opinion Viral cause Iodine-induced hyperthyroidism Information from new cases Family of 5 4 cases ate meat 1 non-case a vegetarian Food from one store all national except local “beef trimmings” Was beef contaminated with iod

16、ine? 28The second case control study showed a The second case control study showed a very specific associationvery specific association調(diào)查暴發(fā)的調(diào)查暴發(fā)的1010個步驟個步驟 10 steps of an outbreak investigation準備現(xiàn)場工作準備現(xiàn)場工作 Prepare for field work證實暴發(fā)存在證實暴發(fā)存在 Establish existence of an outbreakTimeVerify the diagnosis

17、驗證診斷驗證診斷Define, count, and interview cases 定義，計數(shù)，采訪病例定義，計數(shù)，采訪病例確定人、地點和時間特征確定人、地點和時間特征 Characterize person, place and timeDevelop a hypothesis 提出假設提出假設Develop analytic study to test hypothesis 通過分析研究驗證假說通過分析研究驗證假說Reconsider, refine, retest hypothesis 再推敲，修正和再檢驗假說再推敲，修正和再檢驗假說實施控制措施實施控制措施 Implement Con

18、trol將調(diào)查結(jié)果進行交流將調(diào)查結(jié)果進行交流 Communicate Findings30知道病原體有很大的優(yōu)勢，比如：傷寒知道病原體有很大的優(yōu)勢，比如：傷寒Knowing the etiology is a major advantage. E.g. TyphoidKnowing the etiology is a major advantage. E.g. Typhoid 食物或者水源傳播食物或者水源傳播Transmission by food or water 人是唯一宿主人是唯一宿主Human reservoir only 人傳人罕見人傳人罕見Person to person tran

19、smission very rare 70%病例是隱形感染病例是隱形感染70% infections asymptomatic 潛伏期潛伏期8-24天天8-24 day incubation period 治療方法明確治療方法明確Treatment well defined 病例定義和確診方法病例定義和確診方法Case definitions and confirmatory tests31受關(guān)注的程度不一樣：領導關(guān)注度受關(guān)注的程度不一樣：領導關(guān)注度l 截至截至5月月19日第日第362人次人次 國家類專家：國家共派國家類專家：國家共派49批批170人次，人次， 國家臨床國家臨床29批，批，12

20、2人次人次 流行病等專家流行病等專家20批，批，48人次。人次。 省級類專家：總共派省級類專家：總共派43批批105人人 臨床專家臨床專家30批批75人人 流行病學等專家流行病學等專家13批批30人。人。 行政領導和司機行政領導和司機87人（列表）人（列表） 花名冊，文件、簡訊、工作報告花名冊，文件、簡訊、工作報告 流調(diào)信息組、臨床救治組、宣傳教育組、樣本采集運流調(diào)信息組、臨床救治組、宣傳教育組、樣本采集運輸組、綜合組輸組、綜合組32Unexplained respiratory disease and death in four states Other individual persons

21、 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、騰訊對阜陽的報道新浪、雅虎、騰訊對阜陽的報道調(diào)查暴發(fā)的調(diào)查暴發(fā)的10

22、10個步驟個步驟 10 steps of an outbreak investigation準備現(xiàn)場工作準備現(xiàn)場工作 Prepare for field work證實暴發(fā)存在證實暴發(fā)存在 Establish existence of an outbreakTimeVerify the diagnosis 驗證診斷驗證診斷Define, count, and interview cases 定義，計數(shù)，采訪病例定義，計數(shù)，采訪病例確定人、地點和時間特征確定人、地點和時間特征 Characterize person, place and timeDevelop a hypothesis 提出假設提

23、出假設Develop analytic study to test hypothesis 通過分析研究驗證假說通過分析研究驗證假說Reconsider, refine, retest hypothesis 再推敲，修正和再檢驗假說再推敲，修正和再檢驗假說實施控制措施實施控制措施 Implement Control將調(diào)查結(jié)果進行交流將調(diào)查結(jié)果進行交流 Communicate Findings要重點考查實驗室檢測要重點考查實驗室檢測 已經(jīng)做過什么檢測？已經(jīng)做過什么檢測？What diagnostic tests have been done 什么應該做的檢測還沒有做呢？什么應該做的檢測還沒有做呢？

24、What diagnostic tests have not been done什么檢測做了？什么檢測沒有做？什么檢測做了？什么檢測沒有做？What tests were done or not done?What tests were done or not done?檢測檢測Test ResultTiming痰涂片痰涂片Sputum smearND血培養(yǎng)血培養(yǎng)Blood CultureND鼠疫鼠疫F1抗體抗體Plague F-1 antibody-earlySARS PCR-OKAI PCR-OK兔拉熱免疫熒光兔拉熱免疫熒光Tularemia CF-early鸚鵡熱免疫熒光鸚鵡熱免疫熒光P

25、sittacosis CFND呼吸道合呼吸道合 胞病毒胞病毒IgM RSV IgM+-early426期的麻疹期的麻疹阜陽的第一份流調(diào)報告阜陽的第一份流調(diào)報告43要敢于懷疑他們的同質(zhì)性癌癥村2002年9月14日南京湯山中毒事件42人死亡，最終確診為毒鼠強和氟乙酰胺聯(lián)合中毒；44要注意假疫情癔病空姐的皮疹小孩身上的瀝青調(diào)查暴發(fā)的調(diào)查暴發(fā)的1010個步驟個步驟 10 steps of an outbreak investigation準備現(xiàn)場工作準備現(xiàn)場工作 Prepare for field work證實暴發(fā)存在證實暴發(fā)存在 Establish existence of an outbreakT

26、imeVerify the diagnosis 驗證診斷驗證診斷Define, count, and interview cases 定義，計數(shù)，采訪病例定義，計數(shù)，采訪病例確定人、地點和時間特征確定人、地點和時間特征 Characterize person, place and timeDevelop a hypothesis 提出假設提出假設Develop analytic study to test hypothesis 通過分析研究驗證假說通過分析研究驗證假說Reconsider, refine, retest hypothesis 再推敲，修正和再檢驗假說再推敲，修正和再檢驗假說實施

27、控制措施實施控制措施 Implement Control將調(diào)查結(jié)果進行交流將調(diào)查結(jié)果進行交流 Communicate Findings疾病的標識符：疾病的標識符： Disease Identifiers:Disease Identifiers: 癥狀癥狀Symptomatology 體征（物理檢查）體征（物理檢查） Signs (Physical examination) 臨床評價（肌電圖，腦電圖，等）臨床評價（肌電圖，腦電圖，等）Clinical evaluations (EKG, EEG, etc.) 不符合其他疾病不符合其他疾病Lack of compatibility with oth

28、er diseases 對治療的反應對治療的反應Response to treatment 實驗室檢測（病毒分離、血糖等）實驗室檢測（病毒分離、血糖等） Laboratory tests (virus isolation, blood sugar, etc.)使用能使用能夠夠包括多數(shù)病例或者所有病例的一個癥狀包括多數(shù)病例或者所有病例的一個癥狀Use one characteristic that will include most or all cases 腹瀉腹瀉Diarrhea 發(fā)燒發(fā)燒Fever 皮疹皮疹Rash 皮疹皮疹+發(fā)燒發(fā)燒 Rash+fever 黃疸黃疸Jaundice 咳嗽咳

29、嗽+發(fā)燒發(fā)燒 Cough + fever使用一些更特異的癥狀使用一些更特異的癥狀Use a number of more specific characteristics 草莓舌草莓舌Strawberry tongue 柯氏斑柯氏斑Koplicks spots 腦脊液腦脊液Spinal fluid WBCs 50/ml 冠狀動脈瘤冠狀動脈瘤Coronary artery aneurisms與其他疾病不符與其他疾病不符Lack of compatibility with other diseasesLack of compatibility with other diseases 不是其他已知病

30、因的皮疹不是其他已知病因的皮疹Rash not known to be due to another etiology 沒有那些能明確引起嗜酸性粒細胞增多的原因的沒有那些能明確引起嗜酸性粒細胞增多的原因的記錄記錄No record of any known cause of eosinophilia 尸檢不能發(fā)現(xiàn)死亡原因尸檢不能發(fā)現(xiàn)死亡原因Postmortem examination fails to demonstrate an adequate cause of death Epidemiologic criteriaEpidemiologic criteria流行病學標準流行病學標準 時

31、間時間Time 地點地點Place 人人Person 宿主因素（基礎疾?。┧拗饕蛩兀ɑA疾?。?Host factors (underlying illness) 與其他病例的關(guān)系與其他病例的關(guān)系Linkages to other cases 與危險因素的關(guān)系與危險因素的關(guān)系Associations with risk factors避免包括懷疑的暴露避免包括懷疑的暴露Avoid including suspected exposureAvoid including suspected exposure 吃過吃過A牌爆米花后牌爆米花后72小時出現(xiàn)腹瀉或者嘔吐小時出現(xiàn)腹瀉或者嘔吐 diarrhe

32、a or vomiting occurring up to 72 hours after eating Brand A popcorn. 暴發(fā)期間，特異度增加暴發(fā)期間，特異度增加During outbreaks specificity improves90% Specificity50% Specificity在封閉人群中的病例定義在封閉人群中的病例定義Case definition in a closed groupCase definition in a closed group真正的病例真正的病例True Case類似的病例類似的病例Similar disease在開放人群中的病例定義在

33、開放人群中的病例定義Case definition in an open groupCase definition in an open groupTrue CaseSimilar disease調(diào)查暴發(fā)的調(diào)查暴發(fā)的1010個步驟個步驟 10 steps of an outbreak investigation準備現(xiàn)場工作準備現(xiàn)場工作 Prepare for field work證實暴發(fā)存在證實暴發(fā)存在 Establish existence of an outbreakTimeVerify the diagnosis 驗證診斷驗證診斷Define, count, and interview

34、cases 定義，計數(shù)，采訪病例定義，計數(shù)，采訪病例確定人、地點和時間特征確定人、地點和時間特征 Characterize person, place and timeDevelop a hypothesis 提出假設提出假設Develop analytic study to test hypothesis 通過分析研究驗證假說通過分析研究驗證假說Reconsider, refine, retest hypothesis 再推敲，修正和再檢驗假說再推敲，修正和再檢驗假說實施控制措施實施控制措施 Implement Control將調(diào)查結(jié)果進行交流將調(diào)查結(jié)果進行交流 Communicate Fi

35、ndings5631例重癥病例年齡分組年齡分組死亡年齡死亡年齡3歲以內(nèi)歲以內(nèi)平均平均1.5歲歲5718例死亡病例發(fā)病到死亡發(fā)病到死亡1-11天天 平均平均3天天58Person to person transmissionPerson to person transmissionTimePlace5935% did know the person with whom they 35% did know the person with whom they had contacthad contactTimePlace6035% did know the person with whom they

36、 35% did know the person with whom they had contacthad contactTimePlace6110% are pneumonia and 90% Upper 10% are pneumonia and 90% Upper respiratory infectionrespiratory infectionTimePlace6290% of infections are asymptomatic (e.g. 90% of infections are asymptomatic (e.g. polio)polio)TimePlace63Witho

37、ut identification of asymptomatic Without identification of asymptomatic infection you see thisinfection you see thisTimePlace64A A zoonosiszoonosis 10% of animal infections 10% of animal infections transmit to man.transmit to man.TimePlace65Without knowledge of the animal disease Without knowledge

38、of the animal disease it will look like thisit will look like thisTimePlace66在阜陽手足口病中差點發(fā)揮更大的作在阜陽手足口病中差點發(fā)揮更大的作用（或可能發(fā)揮了重大的作用）用（或可能發(fā)揮了重大的作用）補補阜陽日記阜陽日記6768l 阜阜陽市陽市2008年年14月份手足口病發(fā)病情況月份手足口病發(fā)病情況l 而且不少病例有手足口皮疹癥狀（而且不少病例有手足口皮疹癥狀（50%） 1983-1985 1983-1985 馬里蘭州各季度馬里蘭州各季度PGH重癥監(jiān)護病房心跳停止病人重癥監(jiān)護病房心跳停止病人Cardiac arrests

39、, 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心跳停止病例數(shù)心跳停止病例數(shù)1983198419850151052520季度和年度季度和年度 Quarter and YearNumber of Cardiac Arrests1983-1985 馬里蘭州各季度各班次馬里蘭州各季度各班次PGH重癥監(jiān)護病房心跳停止病人數(shù)重癥監(jiān)護病房心跳停止病人數(shù)Cardiac arrests, by shift, PG

40、H ICU, Maryland, 1983-1985夜班Night shift晚班Evening shift白班Day shift心跳停止病例數(shù)心跳停止病例數(shù)00-0304-0708-1112-1516-1920-23020406080每日各時段每日各時段 （軍隊時間）（軍隊時間）Hour of Day (Military time)Number of Cardiac Arrests1983-1985 馬里蘭州每日各時段馬里蘭州每日各時段PGH重癥監(jiān)護病房心跳停止病重癥監(jiān)護病房心跳停止病人數(shù)人數(shù) Cardiac arrests, by time and period, PGH ICU, Mar

41、yland, 1983-1985流行前Pre-epidemic流行中 Epidemic流行后 Post-epidemic心跳停止病例數(shù)心跳停止病例數(shù)不同護士管理病人的心跳驟停的危險不同護士管理病人的心跳驟停的危險Relative risk of cardiac arrest by nurse護士護士Nurse1983-85EpidemicEpidemic PM143.95.011.2131.91.62.41961.40.75.01061.31.72.81181.00.65.0300.70.40.71290.70.91.7心跳驟停的重復發(fā)生心跳驟停的重復發(fā)生Recurrent cardiac a

42、rrests病人病人Pt日期日期Date護士護士Nur病人病人Pt日期日期Date護士護士NurA1983/07/1026D1984/05/17 14A1983/08/04118D1084/06/05 14B1984/01/0214E09/01113B1984/01/0214E09/0314B1984/01/0514F10/0214C1995/03/15154F10/1114C1995/03/1933F10/1214同一個病例的心跳驟停：發(fā)生多次心跳驟停的病例同一個病例的心跳驟停：發(fā)生多次心跳驟停的病例Arrests on same patient: patients with multipl