1、2003年埃及伤寒：年埃及伤寒：疾病负担和危险因素疾病负担和危险因素Typhoid Fever in Egypt,2003:Burden of disease and risk factors for infectionMichael Lynch MD,MPHFoodborne and Diarrheal Diseases BranchNational Center for Infectious Diseases概述概述Overview 伤寒的流行特点和临床特征伤寒的流行特点和临床特征 Background on typhoid fever 伤寒发病率伤寒发病率 Incidence of ty
2、phoid fever 伤寒危险因素伤寒危险因素 Risk factors for typhoid fever 控制策略控制策略 Control strategies威廉威廉.巴德巴德William BuddMoorhead R.JRSM,95(11)p.562伤寒伤寒Typhoid fever 临床特征临床特征 Clinical features 较长潜伏期（较长潜伏期（1014天）天）Long incubation period(10-14 days)无特异性症状无特异性症状 Symptoms non-specific 高死亡率（高死亡率（520）High mortality(5-20%)
3、诊断诊断 Diagnosis 血液、骨髓培养分离到伤寒杆菌血液、骨髓培养分离到伤寒杆菌 Blood or bone marrow culture 血清学检验通常不可靠血清学检验通常不可靠 Serologic assays unreliable伤寒是由沙门氏菌属的细菌引起的有生命危险的急性发热性伤寒是由沙门氏菌属的细菌引起的有生命危险的急性发热性疾病疾病Life-threatening acute febrile illness caused by Salmonella serotype Typhi(S.Typhi)疾病负担疾病负担Burden of typhoid fever全球每年全球每年2
4、1，000，000人罹患伤寒，人罹患伤寒，200，000人因此死亡人因此死亡 21 million illnesses and 200,000 deaths worldwide有伤寒疫情的国家缺乏疾病负担的确切数据有伤寒疫情的国家缺乏疾病负担的确切数据 Burden ill-defined in endemic countries多重抗药性多重抗药性 Multidrug-resistant typhoid fever疾病传播疾病传播Transmission of S.Typhi 人类是传染源和宿主人类是传染源和宿主 Humans are reservoir 粪口途径传播粪口途径传播 Sprea
5、d through fecal oral route 两种主要的传播模式两种主要的传播模式 Two major modes of transmission 水水 Water 食物食物 Food(milk,shellfish,produce)美国美国1912-1994年伤寒年发病率年伤寒年发病率Typhoid Fever:Annual Incidence,United States,1912-1994Water 美国美国1912-1994年伤寒年发病率年伤寒年发病率Typhoid Fever:Annual Incidence,United States,1912-1994WaterFood 美国
6、美国1912-1994年伤寒年发病率年伤寒年发病率Typhoid Fever:Annual Incidence,United States,1912-1994WaterFood地方性伤寒危险因素地方性伤寒危险因素Risk factors for endemic typhoid fever 印度尼西亚印度尼西亚 1998 水水 Indonesia 1998=Water 巴基斯坦巴基斯坦 1995 食物和水食物和水 Pakistan 1995=Food and water 智利智利 1981 食物食物 Chile 1981=Sharing food at lunch 伤寒的控制伤寒的控制Contr
7、ol of typhoid fever 提高水源质量提高水源质量 Improving water quality 加强食品安全加强食品安全 Improving food safety 预防接种预防接种 Vaccination匹兹堡匹兹堡1900-1910年伤寒死亡率和引用安全水源的人口比例年伤寒死亡率和引用安全水源的人口比例Death rate for typhoid fever,and proportion of population with treated water,Pittsburgh PA,1900-1910 020406080100120140160190001020304050
8、60708091910020406080100First water treatment plant opened,1907Typhoid fever death rate per 100,000 populationPercent ofpopulationwith treatedwaterRosenau MJ.Preventive Medicine and Hygiene,5th ed,1927,p 111食品安全策略（智利：圣地亚哥）食品安全策略（智利：圣地亚哥）Food safety measures:Typhoid fever in Santiago,Chile 从霍乱中吸取教训从霍乱
9、中吸取教训 Response to cholera 减少污水污染食品的策略减少污水污染食品的策略 Measures to decrease sewage contamination of food 禁用污水灌溉禁用污水灌溉 Ban on contaminated water for irrigation 禁止餐馆出售不安全食品禁止餐馆出售不安全食品 Banned restaurants from selling items at risk 对群众进行肠道传染病传播途径的宣传教育对群众进行肠道传染病传播途径的宣传教育 Educated consumers about enteric pathog
10、ens 智利，圣地亚哥南部大城市智利，圣地亚哥南部大城市1984-1991年年公共医疗系统伤寒报告病例公共医疗系统伤寒报告病例Reported cases of typhoid fever,South Metropolitan Health Service,Santiago,Chile,1984-1991Alcayaga et al.Rev Chile Infect 1993;1:5-10Cholera Prevention Program伤寒的预防接种伤寒的预防接种Vaccines for typhoid fever 接种接种 Vaccines 口服减毒活疫苗口服减毒活疫苗 Live att
11、enuated oral(Ty21a)注射多聚糖抗原注射多聚糖抗原 Vi polysaccharide parenteral(Vi)新疫苗新疫苗 New Vi conjugate(Vi-rEPA)为什么不作为常规控制策略为什么不作为常规控制策略 Challenges as control strategy 昂贵昂贵 Expensive 保护期较短保护期较短 Limited duration伤寒控制面临的挑战伤寒控制面临的挑战Challenges 伤寒多发在发病率难以估计，危险因素难以评估的地伤寒多发在发病率难以估计，危险因素难以评估的地区区 Typhoid fever occurs in pl
12、aces where:Incidence is difficult to measure Risk factors are difficult to assess 需要相关信息，以使卫生资源分配最优化需要相关信息，以使卫生资源分配最优化 Need information to allocate limited resources 快速评估方法快速评估方法 Develop method for rapid assessment埃及伤寒现况埃及伤寒现况Typhoid fever in Egypt 国家被动监测国家被动监测 National syndrome-based surveillance 年
13、发病率年发病率15/100,000 15/100,000/year 不到不到1%的病例经培养确诊的病例经培养确诊 1 year of age 就诊时体温大于等于就诊时体温大于等于38.0C Temperature 38.0C at visit 不明原因发热不明原因发热3天或天或3天以上天以上 Fever 3 days without any identified cause 伤寒伤寒 Typhoid fever 从血液中分离出沙门氏菌属细菌从血液中分离出沙门氏菌属细菌 Salmonella Typhi isolated from blood抽样抽样Sampling政府发热医院政府发热医院(n=
14、1)Fayoum Fever hospital(n=1)发热医师发热医师(n=15)Fever specialists(n=15)主要的医疗服务提供者主要的医疗服务提供者20%Primary care providers 20%地区医院地区医院(n=6)District hospitals(n=6)农村医疗机构农村医疗机构20%Rural health units 20%实验室方法实验室方法Laboratory methods 血培养血培养 Single blood culture 相关实验室相关实验室 Fayoum Fever Hospital,General Common,and NAMR
15、U labs 多重抗药性多重抗药性 Multidrug-resistant 氨比西林氨比西林 ampicillin 氯霉素氯霉素 chloramphenicol 甲氧苄氨嘧啶甲氧苄氨嘧啶-磺胺类磺胺类 trimethoprim-sulfamethoxazole结果结果Results 监测到监测到2655例病例例病例 2655 patients met inclusion criteria 6的病人确诊为伤寒的病人确诊为伤寒 Typhoid fever confirmed in 166(6%)patients 9血样污染血样污染 Contaminants(9%)血培养结果校正血培养结果校正Blo
16、od culture adjustments 单血培养的敏感度为单血培养的敏感度为50 Single blood culture 50%sensitive 阳性结果数乘以阳性结果数乘以2 Multiplied number positive cultures by 2 污染血样污染血样 Contaminated blood cultures 假设阳性率与未污染血样相同假设阳性率与未污染血样相同 Similar to untested specimens抽样校正抽样校正Sampling adjustmentProvider levelCases of typhoidParticipating p
17、roviders加权加权MultiplierFever Hospital311/11District Hospital126/61Fever Specialist4714/151.1Rural Health Unit2426/1345.2Primary Care Provider5234/1845.4研究时间期限校正（使用研究时间期限校正（使用Fayoum 2002年年发热医院数据）发热医院数据）Using 2002 Fayoum Fever Hospital data to adjust for study time frameNumber casesStudy time frame35/1
18、08=32%病例和发病率计算校正病例和发病率计算校正Adjustment of case count and incidence calculation全部病例全部病例Total cases(Blood culture and missed)培养敏感度培养敏感度Sensitivityof culture抽样因素抽样因素Sampling factor时间期限时间期限Time frame=调整病例数调整病例数 Adjusted case count调整病例数调整病例数 Adjusted case count =发病率发病率 Incidence 人口数人口数 populationxxx发病率计算发病
19、率计算Incidence calculationsProviderTyphoid cases*SamplingBlood CultureTimeFrameAdjusted cases Percent TotalFever Hospital321231916%District Hospital13123782%Specialist491.12331510%Rural Health Unit275.62383425%Primary Care585.023188957%FAYOUM1793307100%*adjusted for contamination rateFayoum 伤寒发病率伤寒发病率
20、Typhoid fever incidence in Fayoum基于全人口基于全人口Population based148/100,000/year基于发热医院基于发热医院Fever hospital based 9/100,000/year年龄分布年龄分布Age distribution of cases Age Cases(%)Percent Incidence n=165 population 1-14 118(72)39 272/100,000/yr15+47(28)61 68/100,000/yr伤寒的多重抗药性伤寒的多重抗药性Multidrug-resistant typhoid
21、 共实验共实验165例例 165 S.Typhi isolates tested 51例（例（31）有抗药性）有抗药性 Multidrug-resistance in 51(31%)为发现抗为发现抗Ciprofloxacin No Ciprofloxacin resistance局限性局限性Limitations 未作以下校正未作以下校正 No adjustment made for:未就医的病人未就医的病人 Patients who do not seek any medical care 曾采取抗菌治疗的病人曾采取抗菌治疗的病人 Patients who have used prior a
22、ntibiotic therapy 加权系数的不确定性加权系数的不确定性 Uncertainty in multipliers 血培养的敏感度血培养的敏感度 Sensitivity of blood culture 季节效应季节效应 Effect of seasonality摘要摘要Summary of incidence 基于全人口的疾病负担快速评估基于全人口的疾病负担快速评估 Population-based rapid burden assessment established:Fayoum 的伤寒发病率高的伤寒发病率高 Incidence of typhoid fever in Fay
23、oum high 大多数伤寒患者是在初级诊疗单位诊治大多数伤寒患者是在初级诊疗单位诊治 Highest proportion of typhoid fever patients evaluated at primary care level 多重抗药性的高流行率多重抗药性的高流行率 High prevalence of multidrug-resistant typhoid fever危险因素危险因素Risk Factors病例对照研究病例对照研究Case-control study 目的目的 Objective:证实埃及证实埃及Fayoum Governorate 伤寒发病的危险因伤寒发病的
24、危险因素素 To identify risk factors for typhoid fever in Fayoum Governorate,Egypt 在在2003年年6月到月到9月开展研究月开展研究 Conducted June-September,2003方法方法Case-control study methods 监测病例监测病例 Cases from ongoing surveillance 血培养发现沙门氏菌血培养发现沙门氏菌 S.Typhi in blood 大于大于1岁岁 1 year of age 发热超过发热超过3天（包括天（包括3天）天）Febrile illness 3
25、 days 对照对照 Controls clinic based 和病例在同一医疗单位就诊的人和病例在同一医疗单位就诊的人 Seen at healthcare facility following case 年龄组匹配年龄组匹配 Matched by age group(1-4,5-14,15-50,50+)排除疑似伤寒和肠道疾病排除疑似伤寒和肠道疾病 Suspected typhoid or enteric disease excluded 1：2配对配对 2 controls per case方法方法Case-control study methods 埃及卫生部工作人员担任入户调查工作
26、埃及卫生部工作人员担任入户调查工作 In home interviews by trained MOH personnel 询问发病前询问发病前14天内有关食品和水的暴露天内有关食品和水的暴露 Food and water exposures in 14 days before illness 家庭用水抽样家庭用水抽样 Sample of household water 方法方法Case-control study methods 主要方法主要方法 Primary measure of association 匹配的匹配的OR值值 matched odds ratio(MOR)特异危险度计算特
27、异危险度计算 Attributable risk calculation*P(OR 1)P(OR 1)+1*Gregg,M.Field Epidemiology,2002,p.146Where P=percent controls exposed病例和对照的一般特征病例和对照的一般特征Case-control subject characteristicsCharacteristic 病例病例Cases 对照对照Controls (n=97)(n=200)年龄中位数年龄中位数Median age in years 10 12女性比例女性比例Percent female 50 45家庭人口数家庭
28、人口数Number people in house 9.1 8.9农民比例农民比例Percent farmers 47 41家中有电视的比例家中有电视的比例Percent houses with TV 74 79单因素分析：食品因素单因素分析：食品因素Bivariate analysis:Food itemsExposure%Cases%Controls MOR 95%CI (n=97)(n=200)带叶蔬菜带叶蔬菜Leafy vegetables 47 49 0.9 0.4-1.9瓜类瓜类Melons 81 79 1.1 0.4-3.6牛奶牛奶Milk 57 62 0.8 0.4-1.4冰淇
29、淋冰淇淋Ice cream 68 68 1.0 0.5-1.9 街头小吃街头小吃Street vendor 23 17 1.8 0.8-4.4 单因素分析：水的因素单因素分析：水的因素Bivariate analysis:WaterExposure%Cases%Controls MOR 95%CI (n=97)(n=200)家庭管道输水家庭管道输水Piped water 79 90 0.4 0.2-0.9to home家庭储备用水家庭储备用水Store water 90 79 4.3 1.5-14.8at home食用冰食用冰Consume ice 40 28 2.2 1.0-4.7在水渠清洗
30、用具在水渠清洗用具Wash utensils 15 5 3.7 1.4-12.9In canal 在家中用肥皂清洗在家中用肥皂清洗Soap at home 59 70 0.4 0.2-0.9 多因素分析多因素分析Multivariate analysisExposure Conditional OR*95%CI Attributable risk 家庭储备用水家庭储备用水Store water 3.5 1.2-9.866%at home在水渠清洗器具在水渠清洗器具Wash utensils 4.0 1.3-12.113%in canal *controlling for other signi
31、ficant exposures不同年龄组多因素分析不同年龄组多因素分析Conditional odds ratio by age group for storing water at home and washing utensils in canal 饮用水处理饮用水处理Drinking water handling 只有只有2的居民每天可获得的居民每天可获得 流动饮用水流动饮用水 Only 2%of residents have source of drinking water available everyday 在使用储藏水的居民中，在使用储藏水的居民中，85用容器或手舀水用容器或手
32、舀水 Among those who store water,85%get water by scooping饮用水检测结果饮用水检测结果Results:Drinking water testingExposure%Cases%Controls MOR*95%CI (n=97)(n=192)大肠杆菌培养大肠杆菌培养Coliform growth 30 21 1.6 0.9-2.8结论结论Conclusions大多数大多数Fayoum居民罹患伤寒与家庭储备用水有关居民罹患伤寒与家庭储备用水有关 Large proportion of typhoid fever in Fayoum is asso
33、ciated with storing water in the home小部分病例的患病与开放式水渠有关小部分病例的患病与开放式水渠有关 Small proportion associated with open canal改善水质降低伤寒发病率改善水质降低伤寒发病率 Improved water quality could decrease incidence of typhoid in Fayoum局限性局限性Limitations 食品因素尚未定论食品因素尚未定论 Food exposures not adequately defined 从病人中选取对照的影响从病人中选取对照的影响
34、Ill controls may decrease study power 社会经济学情况的估计社会经济学情况的估计 Measures of socioeconomic status启示启示Where does this lead us?由调查结果引发的讨论由调查结果引发的讨论 Several questions follow from these results:改善水质的干预措施应采取什么形式？改善水质的干预措施应采取什么形式？What form should intervention to improve water quality take?水质干预是否可行？水质干预是否可行？Is w
35、ater quality intervention feasible?如果不可行，是否还有其他策略？如果不可行，是否还有其他策略？If not,are there viable alternative strategies?改善水质改善水质Improving water quality Canal水处理装置水处理装置Water treatment facility家庭家庭Home管道管道Pipes-增加数量增加数量 build more-改善现有装置改善现有装置 improve existing operations-煮沸煮沸 boiling-使用点使用点 point-of-use安全用水系统
36、安全用水系统Safe Water System家庭水处理家庭水处理 Household level water treatment使腹泻类疾病发病率降低使腹泻类疾病发病率降低40 Shown to decrease diarrheal disease 40%尚未评估其对伤寒的效果尚未评估其对伤寒的效果Not evaluated for typhoid 摘要摘要Summary 疾病负担快速评估疾病负担快速评估 Rapid burden assessment 基于全人口的发病率估计基于全人口的发病率估计 Population based incidence estimate (148/100,00
37、0)选取有代表性的病例进行病例对照研究选取有代表性的病例进行病例对照研究 Representative cases for case-control study 病例对照研究病例对照研究 Case-control study 证实危险因素（储藏水，在沟渠中洗涤）证实危险因素（储藏水，在沟渠中洗涤）Identified risk factors (stored water,washing in canal)可能的干预策略可能的干预策略 Potential intervention strategies 方法的可变更性方法的可变更性 Method potentially transferable感
38、谢感谢AcknowledgementsEgyptian Ministry of Health Dr.Said el OunFayoum Governorate Dr.El Rafee Dr.Mahmoud Dr.MohamedFayoum Fever Hospital LabFayoum General Common LabFayoum governorate cliniciansNAMRU-3Dr.Fouad YoussefDr.Ken EarhartDr.Frank MahoneyDr.Rana HajjehDr.Greg JenningsDr.Momtaz WasfyMohamed Ab
39、delmaksoudMoustafa Abdel FadeelWaleed WilliamMuhamed ElmoftyCDCDr.Steve LubyDr.Eric MintzDr.Padmini SrikantiahDr.John Crump年龄的影响年龄的影响Effect of age Exposure Cases(%)Controls(%)Conditional 95%CI n=97 n=200 OR家用储藏用水家用储藏用水Store water 87/97(90)158/200(79)3.5 1.2-9.8in homeAge 1-14 64/69(91)108/140(77)6.4 1.4-29.6Age 15+23/27(85)50/60(83)1.3 0.1-11.2 年龄的影响年龄的影响Effect of age Exposure Cases(%)Controls(%)Conditional 95%CI n=97 n=200 OR沟渠中洗涤沟渠中洗涤Wash utensils 14/96(15)10/200(5)4.0 1.3-12.1in canalAge 1-14 5/68(7)5/140(4)0.9 0.2-4.5Age 15+9/27(33)5/60(8)12.9 1.4-118.4
