1、2003年埃及伤寒：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Overview 伤寒的流行特点和临床特征 Background on typhoid fever 伤寒发病率 Incidence of typhoid fever 伤寒危险因素 Risk factors
2、for typhoid fever 控制策略 Control strategies威廉. 巴德William BuddMoorhead R. JRSM, 95 (11) p.562伤寒Typhoid fever 临床特征 Clinical features 较长潜伏期（1014天） Long incubation period (10-14 days) 无特异性症状 Symptoms non-specific 高死亡率（520） High mortality (5-20%) 诊断 Diagnosis 血液、骨髓培养分离到伤寒杆菌 Blood or bone marrow culture 血清学
3、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疾病Life-threatening acute febrile illness caused by Salmonella serotype Typhi (S. Typhi)疾病负担Burden of typhoid fever全球每年21，000，000人罹患伤寒，200，000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 Burden ill-defined in e
4、ndemic countries多重抗药性 Multidrug-resistant typhoid fever疾病传播Transmission of S. Typhi 人类是传染源和宿主 Humans are reservoir 粪口途径传播 Spread through fecal oral route 两种主要的传播模式 Two major modes of transmission 水 Water 食物 Food (milk, shellfish, produce) 美国1912-1994年伤寒年发病率Typhoid Fever: Annual Incidence, United Sta
5、tes, 1912 -1994Water 美国1912-1994年伤寒年发病率Typhoid Fever: Annual Incidence, United States, 1912 -1994WaterFood 美国1912-1994年伤寒年发病率Typhoid Fever: Annual Incidence, United States, 1912 -1994WaterFood地方性伤寒危险因素Risk factors for endemic typhoid fever 印度尼西亚 1998 水 Indonesia 1998 = Water 巴基斯坦 1995 食物和水 Pakistan
6、1995 = Food and water 智利 1981 食物 Chile 1981 = Sharing food at lunch 伤寒的控制Control of typhoid fever 提高水源质量 Improving water quality 加强食品安全 Improving food safety 预防接种 Vaccination匹兹堡1900-1910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, 19
7、00-1910 First 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）Food safety measures: Typhoid fever in Santiago, Chile 从霍乱中吸取教训 Response to cholera 减少污水污
8、染食品的策略 Measures to decrease sewage contamination of food 禁用污水灌溉 Ban on contaminated water for irrigation 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 Educated consumers about enteric pathogens 智利，圣地亚哥南部大城市1984-1991年公共医疗系统伤寒报告病例Reported cases of typhoid fever, South M
9、etropolitan Health Service, Santiago, Chile, 1984-1991Alcayaga et al. Rev Chile Infect 1993;1:5-10Cholera Prevention Program伤寒的预防接种Vaccines for typhoid fever 接种 Vaccines 口服减毒活疫苗 Live attenuated oral (Ty21a) 注射多聚糖抗原 Vi polysaccharide parenteral (Vi) 新疫苗 New Vi conjugate (Vi-rEPA) 为什么不作为常规控制策略 Challen
10、ges as control strategy 昂贵 Expensive 保护期较短 Limited duration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区 Typhoid fever occurs in places 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 Need information to allocate limited resources 快速评估方法 Develop method
11、 for rapid assessment埃及伤寒现况Typhoid fever in Egypt 国家被动监测 National syndrome-based surveillance 年发病率15/100,000 15/100,000/year 不到1% 的病例经培养确诊 1 year of age 就诊时体温大于等于38.0C Temperature 38.0C at visit 不明原因发热3天或3天以上 Fever 3 days without any identified cause 伤寒 Typhoid fever 从血液中分离出沙门氏菌属细菌 Salmonella Typhi
12、isolated from blood抽样Sampling政府发热医院(n=1)Fayoum Fever hospital (n=1)发热医师(n=15) Fever specialists (n=15)主要的医疗服务提供者20% Primary care providers 20% 地区医院(n=6) District hospitals (n=6)农村医疗机构20%Rural health units 20%实验室方法Laboratory methods 血培养 Single blood culture 相关实验室 Fayoum Fever Hospital,General Common,
13、 and NAMRU labs 多重抗药性 Multidrug-resistant 氨比西林 ampicillin 氯霉素 chloramphenicol 甲氧苄氨嘧啶-磺胺类 trimethoprim-sulfamethoxazole结果Results 监测到2655例病例 2655 patients met inclusion criteria 6的病人确诊为伤寒 Typhoid fever confirmed in 166 (6%) patients 9血样污染 Contaminants (9%) 血培养结果校正Blood culture adjustments 单血培养的敏感度为50
14、Single blood culture 50% sensitive 阳性结果数乘以2 Multiplied number positive cultures by 2 污染血样 Contaminated blood cultures 假设阳性率与未污染血样相同 Similar to untested specimens抽样校正Sampling adjustmentProvider levelCases of typhoidParticipating providers加权MultiplierFever Hospital311/11District Hospital126/61Fever Sp
15、ecialist4714/151.1Rural Health Unit2426/1345.2Primary Care Provider5234/1845.4研究时间期限校正（使用Fayoum 2002年发热医院数据）Using 2002 Fayoum Fever Hospital data to adjust for study time frameNumber casesStudy time frame35 / 108 = 32%病例和发病率计算校正Adjustment of case count and incidence calculation全部病例Total cases(Blood
16、culture and missed)培养敏感度Sensitivityof culture抽样因素Sampling factor时间期限Time frame= 调整病例数 Adjusted case count调整病例数 Adjusted case count =发病率 Incidence 人口数 populationxxx发病率计算Incidence calculationsProviderTyphoid cases*SamplingBlood CultureTimeFrameAdjusted cases Percent TotalFever Hospital321231916%Distri
17、ct Hospital13123782%Specialist491.12331510%Rural Health Unit275.62383425%Primary Care585.023188957%FAYOUM1793307100%*adjusted for contamination rateFayoum 伤寒发病率Typhoid fever incidence in Fayoum基于全人口Population based148 / 100,000/year基于发热医院Fever hospital based 9 / 100,000/year年龄分布Age distribution of c
18、ases 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Multidrug-resistant typhoid 共实验165例 165 S. Typhi isolates tested 51例（31）有抗药性 Multidrug-resistance in 51 (31%) 为发现抗Ciprofloxacin No Ciprofloxacin resistance局限性Limitations 未作以下校
19、正 No adjustment made for: 未就医的病人 Patients who do not seek any medical care 曾采取抗菌治疗的病人 Patients who have used prior antibiotic therapy 加权系数的不确定性 Uncertainty in multipliers 血培养的敏感度 Sensitivity of blood culture 季节效应 Effect of seasonality 摘要Summary of incidence 基于全人口的疾病负担快速评估 Population-based rapid burd
20、en assessment established: Fayoum 的伤寒发病率高 Incidence of typhoid fever in Fayoum high 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 High prevalence of multidrug-resistant typhoid fever危险因素Risk Factors病例对照研究Case-control study 目的 Objective: 证实埃
21、及Fayoum Governorate 伤寒发病的危险因素 To identify risk factors for typhoid fever in Fayoum Governorate, Egypt 在2003年6月到9月开展研究 Conducted June-September, 2003方法Case-control study methods 监测病例 Cases from ongoing surveillance 血培养发现沙门氏菌 S. Typhi in blood 大于1岁 1 year of age 发热超过3天（包括3天） Febrile illness 3 days 对照
22、Controls clinic based 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 Matched by age group (1-4, 5-14, 15-50, 50+) 排除疑似伤寒和肠道疾病 Suspected typhoid or enteric disease excluded 1：2配对 2 controls per case方法Case-control study methods 埃及卫生部工作人员担任入户调查工作 In home interviews by trained MOH perso
23、nnel 询问发病前14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 Sample of household water 方法Case-control study methods 主要方法 Primary measure of association 匹配的OR值 matched odds ratio (MOR) 特异危险度计算 Attributable risk calculation* P(OR 1)P (OR 1) + 1*Gregg, M. Field Epidemiology, 2002,
24、p. 146Where P = percent controls exposed病例和对照的一般特征Case-control subject characteristicsCharacteristic 病例Cases 对照Controls (n=97) (n=200)年龄中位数Median age in years 10 12女性比例Percent female 50 45家庭人口数Number people in house 9.1 8.9农民比例Percent farmers 47 41家中有电视的比例Percent houses with TV 74 79单因素分析：食品因素Bivari
25、ate analysis: Food itemsExposure % Cases % Controls MOR 95% CI (n=97) (n=200) 带叶蔬菜Leafy vegetables 47 49 0.9 0.4-1.9瓜类Melons 81 79 1.1 0.4-3.6牛奶Milk 57 62 0.8 0.4-1.4冰淇淋Ice cream 68 68 1.0 0.5-1.9 街头小吃Street vendor 23 17 1.8 0.8-4.4 单因素分析：水的因素Bivariate analysis: WaterExposure % Cases % Controls MOR
26、95% CI (n=97) (n=200) 家庭管道输水Piped water 79 90 0.4 0.2-0.9to home家庭储备用水Store water 90 79 4.3 1.5-14.8at home食用冰Consume ice 40 28 2.2 1.0-4.7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Soap at home 59 70 0.4 0.2-0.9 多因素分析Multivariate analysisExposure Conditional OR* 95% CI Attributable risk
27、 家庭储备用水Store water 3.5 1.2-9.866%at home在水渠清洗器具Wash utensils 4.0 1.3-12.113%in canal *controlling for other significant exposures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Drinking water handling 只有2的居民每天可获得 流动饮用水 Only 2% of residents h
28、ave source of drinking water available everyday 在使用储藏水的居民中， 85用容器或手舀水 Among those who store water, 85% get water by scooping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Coliform growth 30 21 1.6 0.9-2.8结论Conclusions大多数Fayoum居民罹患伤寒与家庭储备用水有关 Large p
29、roportion of typhoid fever in Fayoum is associated with storing water in the home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 Improved water quality could decrease incidence of typhoid in Fayoum局限性Limitations 食品因素尚未定论 Food exposures not adequately defined 从病人中选取对照的影响 Ill c
30、ontrols may decrease study power 社会经济学情况的估计 Measures of socioeconomic status启示Where does this lead us? 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？ What form should intervention to improve water quality take? 水质干预是否可行？ Is water quality intervention feasible? 如果不可行，是否还有其他
31、策略？ If not, are there viable alternative strategies?改善水质Improving water quality Canal水处理装置Water treatment facility家庭Home管道Pipes- 增加数量 build more- 改善现有装置 improve existing operations- 煮沸 boiling- 使用点 point-of-use安全用水系统Safe Water System家庭水处理 Household level water treatment使腹泻类疾病发病率降低40 Shown to decreas
32、e diarrheal disease 40%尚未评估其对伤寒的效果Not evaluated for typhoid 摘要Summary 疾病负担快速评估 Rapid burden assessment 基于全人口的发病率估计 Population based incidence estimate (148 / 100,000) 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 Case-control study 证实危险因素（储藏水，在沟渠中洗涤） Identified risk factors (s
33、tored water, washing in canal) 可能的干预策略 Potential intervention strategies 方法的可变更性 Method potentially transferable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 cli
34、niciansNAMRU-3Dr. Fouad YoussefDr. Ken EarhartDr. Frank MahoneyDr. Rana HajjehDr. Greg JenningsDr. Momtaz WasfyMohamed AbdelmaksoudMoustafa Abdel FadeelWaleed WilliamMuhamed ElmoftyCDCDr. Steve LubyDr. Eric MintzDr. Padmini SrikantiahDr. John Crump年龄的影响Effect of age Exposure Cases (%) Controls (%) C
35、onditional 95% CI n=97 n=200 OR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 1.4-29.6 Age 15+ 23/27 (85) 50/60 (83) 1.3 0.1-11.2 年龄的影响Effect of age Exposure Cases (%) Controls (%) Conditional 95% CI n=97 n=200 OR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 0.2-4.5 Age 15+ 9/27 (33) 5/60 (8) 12.9 1.4-118.4
