1、肠出血性大肠杆菌H调查过程及防控策略O104:H4 罕见血清型，此前未见暴发报道 有个案报告（2006年韩国29岁女性HUS）菌株毒力基因 志贺样毒素2基因阳性（stx2+）志贺样毒素1基因阴性（stx1）粘附基因阴性（eae）溶血素基因阴性（hly）肠集聚性大肠杆菌质粒（EaggEC）毒力基因aatA、aggR和aap阳性O104:H4 产志贺毒素产志贺毒素O104H4O104H4型大肠杆菌型大肠杆菌 肠聚集性大肠杆菌通过噬菌体获得一种产志贺毒素编码基肠聚集性大肠杆菌通过噬菌体获得一种产志贺毒素编码基因而产生的变种因而产生的变种 德国疫情特点德国疫情特点 感染病例中感染病例中HUSHUS重症
2、病例比例达重症病例比例达25%25%HUSHUS成人患者约占成人患者约占89%89%，且多数是女性，且多数是女性 血清型为血清型为O104O104型型 潜伏期平均为潜伏期平均为8 8天，以往为天，以往为3 3至至4 4天天 成人多为出血性腹泻伴腹部痉挛，而儿童患者则经常出现成人多为出血性腹泻伴腹部痉挛，而儿童患者则经常出现呕吐呕吐临床救治临床救治 血液透析/血浆置换 帮助排除病菌在患者体内释放的毒素，对部分患者无效 单克隆抗体Eculizumab(Soliris,依库珠单抗）德国海德堡大学治疗3名年幼HUS成功，但仍需评估 如果血液透析无效，就注射Soliris 如果仍无好转，则两种疗法同时使
3、用 抗生素 因抗生素可增加细菌毒素释放，不推荐使用 但德国传染病学会近日建议可考虑在某些条件下使用碳青霉烯类抗生素、利福平和大环内酯类抗生素德国应对德国应对0104:H40104:H4信息流向图信息流向图德国应对德国应对0104:H40104:H4策略策略Routine surveillance systemReports to the European Union and the World Health OrganizationEnhanced surveillance systemCentralising the epidemiological information exchange
4、Accelerating the data flow to the national level Implementing a syndromic surveillance system for bloody diarrhoea in emergency departmentsAssessing the capacities for HUStreatment in Germany Initiating active laboratory surveillance受影响的国家Source:Germany Robort Koch Instiitute德国德国EHEC/HUS病例时间分布病例时间分布
5、（按发病时间统计，截至（按发病时间统计，截至6月月23日）日）Robert Koch Institute(RKI)德国德国HUS病例年龄别及性别发病率病例年龄别及性别发病率-截至截至5 5月月3131日日Source:Germany Robort Koch Instiitute年龄组年龄组发病率发病率HUSHUS地区分布地区分布Figure 2:Incidence of HUS during the outbreak according to district,in which the infection has probably taken place(home district or in
6、 cases with travel history the area of residence at the time of infection)潜伏期平均为8天，以往为3至4天志贺样毒素1基因阴性（stx1）我国从欧洲进口的生鲜蔬菜和其他食品数量有限合成特异性PCR检测引物Results of the univariate and multivariate analysis of risk factors for the development of bloody diarrhoea in two canteens in Frankfurt am MainO104:H4应对建议单克隆抗体E
7、culizumab(Soliris,依库珠单抗）Accelerating the data flow to the national level随时针对该疫情影响进行风险评估感染病例中HUS重症病例比例达25%Assessing the capacities for HUStreatment in Germany可进行菌株血清分型、分子生物学检测和溯源比对等德国EHEC/HUS病例时间分布（按发病时间统计，截至6月23日）Figure 2:Incidence of HUS during the outbreak according to district,in which the infect
8、ion has probably taken place但德国传染病学会近日建议可考虑在某些条件下使用碳青霉烯类抗生素、利福平和大环内酯类抗生素O104:H4应对建议Proportions of patients with bloody diarrhea among all patients visiting emergency departments,by age and sex as well as number of participating emergency departments in areas more affected by the EHEC/HUS outbreak,EH
9、EC/HUS outbreak,Germany,MayJune 2011(n=1,021)Source:Germany Robort Koch InstiituteEstimated probability function of the incubation period(based on 73 individuals)with corresponding point-by-point 95%confidence intervals.The median incubation period is 8 days，based on 73 individuals.The calculation i
10、s based on 98 cases:The median between the onset of diarrhoea and the onset of HUS is 5 days.Back projection from the daily onsets of disease to the exposure periodup to 90%of HUS cases probably falls within the period between 5 May and 24 MaySource:Germany Robort Koch InstiituteHUS cases presented
11、chronologically:Onset of disease,date of hospitalization,of diagnosis,of notification to health authorities,and of receipt of notification at the RKI(reporting)Source:Germany Robort Koch InstiituteResults of the univariate and multivariate analysis of risk factors for the development of bloody diarr
12、hoea in two canteens in Frankfurt am Main Source:Germany Robort Koch InstiituteRecipeBased Restaurant Cohort Study 10 groups with a total of 176 participants could be identified,who dined in the same restaurant during the period from 12 to 16 May 2011 There were 168 persons included in the analysis.
13、A total of 31(18%)persons from the groups contracted bloody diarrhea or EHEC/HUS.溶血素基因阴性（hly）Accelerating the data flow to the national levelEnhanced surveillance systemO104:H4应对建议Results of the univariate and multivariate analysis of risk factors for the development of bloody diarrhoea in two cante
14、ens in Frankfurt am Main我国从欧洲进口的生鲜蔬菜和其他食品数量有限According to the European Centre for Disease Prevention and Control发现不少于10例的具有显著的流行病学联系，且无其它原因可解释的疑似病例；HUS cases presented chronologically:Onset of disease,date of hospitalization,of diagnosis,of notification to health authorities,and of receipt of notifi
15、cation at the RKI(reporting)HUS cases presented chronologically:Onset of disease,date of hospitalization,of diagnosis,of notification to health authorities,and of receipt of notification at the RKI(reporting)The three weeks time period takes into account the incubation period,the diagnostics period
16、as well as the period for reporting of a case.溶血素基因阴性（hly）输入性病例因粪口途径导致该病国内广泛传播可能性小肠出血性大肠杆菌H调查过程及防控策略合成特异性PCR检测引物因抗生素可增加细菌毒素释放，不推荐使用标本检测能力（菌培养、PCR检测），阳性菌株及时上送国家CDC进一步分析鉴定Source:Germany Robort Koch InstiituteSource:Germany Robort Koch InstiituteFruit and vegetable exposures associated with the inciden
17、ce of HUS(pvalue 0.1)in the univariate analysis of the raw vegetable casecontrol studyA total of 26 cases(9 men,17 women)and 81 controls with a target ratio of 1:3 by age group(18-34 years,35-44 years,45 years or older),gender and residence Source:Germany Robort Koch Instiitute豆芽溯源豆芽溯源 下萨克森州比嫩比尔特的一家
18、农场生产的芽苗菜是这次疫下萨克森州比嫩比尔特的一家农场生产的芽苗菜是这次疫情传染源头情传染源头 调查人员还没有从任何食物样本中找到病原体调查人员还没有从任何食物样本中找到病原体肠出血肠出血性大肠杆菌性大肠杆菌0104:H40104:H4，包括在这家农场以及饭馆、患者家，包括在这家农场以及饭馆、患者家的厨房获取的样本的厨房获取的样本 在德国确认埃及一家公司的葫芦巴种子是EHEC源头 欧盟方面已于7月初宣布，到今年10月底，暂停从埃及进口葫芦巴、豆芽和油料三种作物种子 2009年至2011年期间从埃及进口的所有葫芦巴种子必须即刻从商场下架 病例数病例数As of July,25th 2011;10
19、.00am During the outbreak period a total of 4,321 cases were reported to the RKI including 3,469 EHEC cases and 852 HUS cases In total 50 patients died,including 18 EHEC patients and 32 HUS patients As of July,22nd 2011 According to the European Centre for Disease Prevention and Control 76 EHEC incl
20、uding 1 patient who died 49 HUS cases were reported across other countries of the European UnionPress Release of Robert Koch-Institute The outbreak is considered to be over July,26th 2011 In the past several weeks the Robert Koch Institute reported sporadic cases of EHECinfection/HUS related to the
21、current outbreak.The last onset of disease to be attributed to the outbreak was reported on 4 July 2011.Since that date no new cases of the disease related to the outbreak have been notified to the RKI and therefore the RKI considers the outbreak to be over.The three weeks time period takes into acc
22、ount the incubation period,the diagnostics period as well as the period for reporting of a case.This means that the largest EHEC outbreak in Germany is over Source:Germany Robort Koch InstiituteO104:H4应对准备 开展风险评估 组织内部专家，分析疫情进展，评估其危害和影响 密切跟踪疫情动态，提供风险评估依据 关注RKIRKI、ECDCECDC、WHO WHO 消息 跟踪媒体报道，为公众沟通提供技术支
23、持 了解报道动向，评估舆论报道发展趋势O104:H4应对准备 做好技术准备（国家做好技术准备（国家CDC)CDC)实验室实验室 储备标准血清储备标准血清 建立检测毒力基因方法建立检测毒力基因方法 合成特异性合成特异性PCRPCR检测引物检测引物 起草并在网站发布实验室检测方案起草并在网站发布实验室检测方案 可进行菌株血清分型、分子生物学检测和溯源比对等可进行菌株血清分型、分子生物学检测和溯源比对等防控指导防控指导 根据部应急办指示，起草防控方案根据部应急办指示，起草防控方案 协助临床专家修改临床救治指南协助临床专家修改临床救治指南 7 7日下午召开（各省市区、日下午召开（各省市区、1919个口
24、岸城市个口岸城市CDCCDC及重大专项网络实验室）视频会及重大专项网络实验室）视频会议，通报疫情进展，指导监测和实验室检测议，通报疫情进展，指导监测和实验室检测O104:H4O104:H4风险评估风险评估卫生部应急办卫生部应急办/国家国家CDCCDC 暴发菌株通过食品传入我国风险低暴发菌株通过食品传入我国风险低 暴发为食源性传播暴发为食源性传播 未发现人与人之间接触所致广泛传播证据未发现人与人之间接触所致广泛传播证据 我国从欧洲进口的生鲜蔬菜和其他食品数量有限我国从欧洲进口的生鲜蔬菜和其他食品数量有限 可能出现赴德旅行或归国人员在德感染病例，但可能出现赴德旅行或归国人员在德感染病例，但 输入性
25、病例因粪口途径导致该病国内广泛传播可能性小输入性病例因粪口途径导致该病国内广泛传播可能性小 如我国发现少量输入性病例，亦不必启动高级别应急反如我国发现少量输入性病例，亦不必启动高级别应急反应机制应机制 HUSHUS病死率高病死率高 须关注病例救治须关注病例救治 指导各地医疗机构做好病例的发现、报告、检测和病例指导各地医疗机构做好病例的发现、报告、检测和病例管理管理O104:H4O104:H4应对建议应对建议 及时获取德国、欧盟（及时获取德国、欧盟（ECDC）、）、WHO等有关疫情及感染来源、传播途径调查、等有关疫情及感染来源、传播途径调查、风险评估和救治经验等信息风险评估和救治经验等信息 随时
26、针对该疫情影响进行风险评估 根据风险评估意见，随时调整应对响应级别和措施根据风险评估意见，随时调整应对响应级别和措施 指导临床机构提高病例发现意识和能力，指导临床机构指导临床机构提高病例发现意识和能力，指导临床机构HUSHUS救治技术能力准备救治技术能力准备 公布病例定义 可疑病例采样、送检、菌培养方法 HUS治疗 发现病例后，医院感染控制（肠道防护）指导各级指导各级CDC 病例调查 标本检测能力（菌培养、PCR检测），阳性菌株及时上送国家CDC进一步分析鉴定 病例污染环境处理 发挥专业机构优势，做好公众风险沟通，引导公众理性对待疫情发挥专业机构优势，做好公众风险沟通，引导公众理性对待疫情及时
27、获取德国、欧盟（ECDC）、WHO等有关疫情及感染来源、传播途径调查、风险评估和救治经验等信息HUS cases presented chronologically:Onset of disease,date of hospitalization,of diagnosis,of notification to health authorities,and of receipt of notification at the RKI(reporting)德国EHEC/HUS病例时间分布（按发病时间统计，截至6月23日）密切跟踪疫情动态，提供风险评估依据发病前10天内有肠出血性大肠杆菌感染流行地区的
28、旅行或居住史，或者发病前10天内与临床诊断/实验室确诊病例有密切接触，且符合下列条件之一者O104:H4应对准备合成特异性PCR检测引物Back projection from the daily onsets of disease to the exposure periodThe outbreak is considered to be over July,26th 2011根据风险评估意见，随时调整应对响应级别和措施Source:Germany Robort Koch Instiitute产志贺毒素O104H4型大肠杆菌在流行区内，经省级专家组确认，与确诊病例流行病学密切相关，并排除其它
29、疾病的疑似病例在流行区内，经省级专家组确认，与确诊病例流行病学密切相关，并排除其它疾病的疑似病例帮助排除病菌在患者体内释放的毒素，对部分患者无效Reports to the European Union and the World Health OrganizationFruit and vegetable exposures associated with the incidence of HUS(pvalue 0.帮助排除病菌在患者体内释放的毒素，对部分患者无效Source:Germany Robort Koch InstiituteAssessing the capacities for
30、 HUStreatment in Germany罕见血清型，此前未见暴发报道肠出血性大肠杆菌防控策略 疾病监测 腹泻病人（必要时增加肾脏科病人）食品 宿主动物 预防控制 预防措施 健康教育及风险沟通 风险评估 疫情控制措施全国肠出血性大肠杆菌全国肠出血性大肠杆菌O157H7O157H7感染性腹泻感染性腹泻应急处理预案应急处理预案疑似病例有鲜血便、低烧或不发烧、痉挛性腹痛的腹泻病例腹泻若干天后继发少尿或无尿等表现的急性肾功能衰竭病例腹泻病人粪便标本O157抗原免疫胶体金方法检测阳性者符合以上条件之一者，即为疑似病例全国肠出血性大肠杆菌O157H7感染性腹泻应急处理预案确诊病例疑似病例或其他腹泻病
31、患者，具有以下条件之一者即为确诊病例从粪便标本中检出产生志贺毒素的肠出血性大肠杆菌O157H7或恢复期血清O157脂多糖(LPS)IgG抗体呈4倍升高或经蛋白印记试验证实血清标本有与O157LPS、或肠出血性大肠杆菌溶血素、或志贺毒素分子量一致的特异性抗体腹泻病例的粪便中分离出不产生志贺毒素1或志贺毒素2及其变种的肠出血性大肠杆菌O157H7，亦为确诊病例(不产毒)临床病例在流行区内，经省级专家组确认，与确诊病例流行病学密切相关，并排除其它疾病的疑似病例全国肠出血性大肠杆菌全国肠出血性大肠杆菌O157H7O157H7感染性腹泻感染性腹泻应急处理预案应急处理预案 暴发疫情暴发疫情在在1 1个县个
32、县(区区)或相毗邻的县或相毗邻的县(区区)境内，境内，2 2周内周内发现不少于发现不少于1010例的具有显著的流行病学联系，且无其例的具有显著的流行病学联系，且无其它原因可解释的疑似病例；它原因可解释的疑似病例；发现不少于发现不少于3 3例的确诊病例。例的确诊病例。HUS cases presented chronologically:Onset of disease,date of hospitalization,of diagnosis,of notification to health authorities,and of receipt of notification at the R
33、KI(reporting)如果仍无好转，则两种疗法同时使用潜伏期平均为8天，以往为3至4天德国HUS病例年龄别及性别发病率在1个县(区)或相毗邻的县(区)境内，2周内未发现人与人之间接触所致广泛传播证据未发现人与人之间接触所致广泛传播证据有鲜血便、低烧或不发烧、痉挛性腹痛的腹泻病例发现不少于3例的确诊病例。Results of the univariate and multivariate analysis of risk factors for the development of bloody diarrhoea in two canteens in Frankfurt am Main发现
34、不少于10例的具有显著的流行病学联系，且无其它原因可解释的疑似病例；Results of the univariate and multivariate analysis of risk factors for the development of bloody diarrhoea in two canteens in Frankfurt am Main随时针对该疫情影响进行风险评估暴发菌株通过食品传入我国风险低Since that date no new cases of the disease related to the outbreak have been notified to th
35、e RKI and therefore the RKI considers the outbreak to be over.起草并在网站发布实验室检测方案跟踪媒体报道，为公众沟通提供技术支持指导临床机构提高病例发现意识和能力，指导临床机构HUS救治技术能力准备帮助排除病菌在患者体内释放的毒素，对部分患者无效Implementing a syndromic surveillance system for bloody diarrhoea in emergency departments罕见血清型，此前未见暴发报道但德国传染病学会近日建议可考虑在某些条件下使用碳青霉烯类抗生素、利福平和大环内酯类抗
36、生素帮助排除病菌在患者体内释放的毒素，对部分患者无效根据部应急办指示，起草防控方案O104:H4应对准备未发现人与人之间接触所致广泛传播证据全国肠出血性大肠杆菌O157 H7感染性腹泻应急处理预案Results of the univariate and multivariate analysis of risk factors for the development of bloody diarrhoea in two canteens in Frankfurt am Main符合以上条件之一者，即为疑似病例76 EHEC including 1 patient who diedThe me
37、dian between the onset of diarrhoea and the onset of HUS is 5 days.Implementing a syndromic surveillance system for bloody diarrhoea in emergency departments调查人员还没有从任何食物样本中找到病原体肠出血性大肠杆菌0104:H4，包括在这家农场以及饭馆、患者家的厨房获取的样本如果血液透析无效，就注射SolirisA total of 26 cases(9 men,17 women)and 81 controls with a target
38、ratio关注RKI、ECDC、WHO 消息在流行区内，经省级专家组确认，与确诊病例流行病学密切相关，并排除其它疾病的疑似病例Source:Germany Robort Koch Instiitute10 groups with a total of 176 participants could be identified,who dined in the same restaurant during the period from 12 to 16 May 2011During the outbreak period a total of 4,321 cases were reported
39、to the RKI合成特异性PCR检测引物志贺样毒素2基因阳性（stx2+）欧盟方面已于7月初宣布，到今年10月底，暂停从埃及进口葫芦巴、豆芽和油料三种作物种子of 1:3 by age group(18-34 years,35-44 years,45 years or older),gender and residenceFruit and vegetable exposures associated with the incidence of HUS(pvalue 0.起草并在网站发布实验室检测方案Results of the univariate and multivariate an
40、alysis of risk factors for the development of bloody diarrhoea in two canteens in Frankfurt am Main输入性病例因粪口途径导致该病国内广泛传播可能性小合成特异性PCR检测引物如我国发现少量输入性病例，亦不必启动高级别应急反应机制In total 50 patients died,including 18 EHEC patients and 32 HUS patients符合以上条件之一者，即为疑似病例如果仍无好转，则两种疗法同时使用10 groups with a total of 176 part
41、icipants could be identified,who dined in the same restaurant during the period from 12 to 16 May 2011组织内部专家，分析疫情进展，评估其危害和影响49 HUS cases were reported across other countries of the European UnionInitiating active laboratory surveillanceA total of 26 cases(9 men,17 women)and 81 controls with a target
42、 ratioEnhanced surveillance systemO104:H4风险评估卫生部应急办/国家CDC肠出血性大肠杆菌肠出血性大肠杆菌O104:H4O104:H4感染防控方案感染防控方案中疾控疾发中疾控疾发20112702011270号号 病例定义病例定义疑似病例疑似病例 发病前发病前1010天内有肠出血性大肠杆菌感染流行地区的旅天内有肠出血性大肠杆菌感染流行地区的旅行或居住史，或者发病前行或居住史，或者发病前1010天内与临床诊断天内与临床诊断/实验室确实验室确诊病例有密切接触，且符合下列条件之一者诊病例有密切接触，且符合下列条件之一者有血性腹泻或腹部痉挛性疼痛等症状，无实验室证有血性腹泻或腹部痉挛性疼痛等症状，无实验室证据诊断为其他非据诊断为其他非EHECO104:H4EHECO104:H4病原者；病原者；有微血管病性溶血性贫血（外周血涂片破碎红细胞有微血管病性溶血性贫血（外周血涂片破碎红细胞22）、血小板减少、肾脏受累（血尿、蛋白尿、）、血小板减少、肾脏受累（血尿、蛋白尿、急性肾损伤）等急性肾损伤）等HUSHUS临床表现者。临床表现者。
