1、肠出血性大肠杆菌0104：H4发现过程及防控策略,0104：H4电镜图片,EHEC bacteria, O104:H4 outbreak strain. Scanning electron microscopy. Bar: 1 m.Source: Holland, Laue (Robert Koch Institute),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aa
2、tA 、aggR和aap阳性,O104:H4,产志贺毒素O104：H4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因而产生的变种德国疫情特点感染病例中HUS重症病例比例达25%HUS成人患者约占89%，且多数是女性血清型为O104型潜伏期平均为8天，以往为3至4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呕吐,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，则两种疗法同时使用抗生
3、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0104:H4信息流向图,德国应对0104:H4策略,Routine surveillance systemReports to the European Union and the World Health OrganizationEnhanced surveillance systemCentralising the epidemiological information exchange Accelerating the data flow to
4、the national level Implementing a syndromic surveillance system for bloody diarrhoea in emergency departmentsAssessing the capacities for HUS-treatment in Germany Initiating active laboratory surveillance,受影响的国家,Source: Germany Robort Koch Instiitute,德国EHEC/HUS病例时间分布（按发病时间统计，截至6月23日）,Robert Koch Ins
5、titute (RKI),德国HUS病例年龄别及性别发病率-截至5月31日,Source: Germany Robort Koch Instiitute,年龄组,发病率,HUS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 cases with travel history the area of residence at the time of infect
6、ion),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, EHEC/HUS outbreak, Germany, May-June 2011 (n=1,021),Source: Germany Robort Koc
7、h Instiitute,Estimated 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 is based on 98 cases: The median between the onset of diarrhoea and
8、 the onset of HUS is 5 days.,Back projection from the daily onsets of disease to the exposure period,up to 90% of HUS cases probably falls within the period between 5 May and 24 May,Source: Germany Robort Koch Instiitute,HUS cases presented chronologically: Onset of disease, date of hospitalization,
9、 of diagnosis, of notification to health authorities, and of receipt of notification at the RKI (reporting),Source: Germany Robort Koch Instiitute,Results of the univariate and multivariate analysis of risk factors for the development of bloody diarrhoea in two canteens in Frankfurt am Main,Source:
10、Germany Robort Koch Instiitute,Recipe-Based 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. A total of 31 (18%) persons from the groups c
11、ontracted bloody diarrhea or EHEC/HUS.,Fruit and vegetable exposures associated with the incidence of HUS (p-value 0.1) in the univariate analysis of the raw vegetable case-control study,A 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
12、 years, 45 years or older), gender and residence,Source: Germany Robort Koch Instiitute,豆芽溯源,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 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,As of July,
13、 25th 2011; 10.00am During the outbreak period a total of 4,321 cases were reported to the RKI including 3,469 EHEC cases and 852 HUS casesIn 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 Contr
14、ol 76 EHEC including 1 patient who died 49 HUS cases were reported across other countries of the European Union,Press 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 EHEC-infection/H
15、US related to the 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
16、period takes into account 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 Instiitute,O104: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RKI、ECDC、WHO 消息跟踪媒体
17、报道，为公众沟通提供技术支持 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CDC)实验室储备标准血清建立检测毒力基因方法合成特异性PCR检测引物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防控指导根据部应急办指示，起草防控方案协助临床专家修改临床救治指南 7日下午召开（各省市区、19个口岸城市CDC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,O104:H4风险评估卫生部应急办/国家CDC,暴发菌株通过食品传入我国风险低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我国从欧洲进口的生鲜蔬菜和其他食品数
18、量有限可能出现赴德旅行或归国人员在德感染病例，但输入性病例因粪-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应机制HUS病死率高须关注病例救治指导各地医疗机构做好病例的发现、报告、检测和病例管理,O104:H4应对建议,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、风险评估和救治经验等信息随时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CD
19、C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,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O157H7感染性腹泻应急处理预案,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
20、病例疑似病例或其他腹泻病患者，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O157：H7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O157：H7，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O157H7感染性腹泻应急处理预案,暴发疫情在1个县(区)或相毗邻的县(区)境内，2周内发现
21、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； 发现不少于3例的确诊病例。,肠出血性大肠杆菌O104:H4感染防控方案中疾控疾发2011270号,病例定义疑似病例发病前10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EHECO104:H4病原者；有微血管病性溶血性贫血（外周血涂片破碎红细胞2）、血小板减少、肾脏受累（血尿、蛋白尿、急性肾损伤）等HUS临床表现者。,肠出血性大肠杆菌O104:H4感染防控方案中疾控疾发2011270号,病
22、例定义实验室确诊病例：疑似病例，符合下列二项之一者从粪便标本中分离到EHEC O104:H4菌株, stx1和/或stx2基因检测阳性从粪便标本中检测到stx1和/或stx2基因阳性，同时aggR、wzy（O104)和fliC (H4)基因检测全部阳性临床诊断病例：在同一起暴发疫情中与实验室确诊病例流行病学密切相关，并排除其他疾病的疑似病例,病例的报告与处置,病例报告（医疗机构）大疫情报告：感染性腹泻，备注标注菌株血清型属地疾控中心采集标本病例处置（疾控机构）核实病例报告辖区卫生行政部门及上级疾控机构检测、或上送各市首例由省CDC复核,预防控制措施-散发个案,医疗机构疑似病例住院治疗转诊时做好个人防护和运输工具的消毒处理按肠道传染病做好院内感染控制工作社区卫生机构定期随访轻症病例和/或密切接触者疾控机构开展个案调查、标本检测指导病家做好排泄物和被污染物品的消毒处理对患者及其密切接触者开展健康教育,预防控制措施-出现暴发疫情,建立多部门联合机制做好疾病监测、报告、流行病学调查落实“三管一灭”各项措施疫情控制效果评估做好健康教育及风险沟通,
