德国肠出血性大肠杆菌O104:H4暴发疫情带来的思考

2011年4月以来,德国多个地方肠出血性大肠杆菌(EHEC)O104:H4感染和溶血性尿毒综合征(HUS)疫情暴发。本文概述本次疫情的概况以及德国政府采取的应对措施,并从机构协作、信息公开、流行病学发挥的作用、症状监测重要性四个方面讨论对我国口岸卫生检疫工作的启示。     

“超级细菌”与国境卫生检疫

携带NDM-1耐药基因的"超级细菌"最早在印度、巴基斯坦等南亚国家出现,并已蔓延到英国、法国、日本、巴西等国家,全球数以百计的患者确诊感染,多名病例死亡,对目前已知的绝大多数抗生素药物耐药,导致感染者几乎无药可医,其大规模蔓延的潜在危险给全球公共卫生事业和我国国境卫生检疫工作带来了巨大的威胁和挑战。如何正确的看待此次"超级细菌"带来的挑战,加强预警,防范于未然,进一步完善国境卫生检疫工作的手段,提高科技含量,满足《国际卫生条例(2005)》对卫生检疫核心能力建设提出的要求,力争做到对输入性病例包括"超级细菌"在内的新发传染病早发现、早处置、早治疗、早隔离,保障国内人民身体健康,是值得每一个检疫工作者思考的问题。     

肠出血性大肠杆菌O104:H4病原学及其检测方法研究进展

2011年5月以来,德国暴发了由肠出血性大肠杆菌O104:H4感染引起的疫情,世界多个国家相继报告有此类病例发生,这是首次报告由肠出血性大肠杆菌O104:H4感染引起疾病的暴发流行。截至2011年6月24日,已造成3920例感染和48例死亡[1]。该病患者以血水样腹泻、呕吐起病,部分病例并发溶血性尿毒综合征,导致多器官受损,甚至死亡。疫情发生后,世界各国相关学者立即开展其病原学特性研究,同时迅速研制出实验室检测方法和试剂,为该病的及时诊断、治疗和疫情控制发挥了很大作用。本文介绍了肠出血性大肠杆菌O104:H4病原学及其检测方法的研究进展。     

2011年德国肠出血性大肠杆菌O104：H4疫情流行病学调查及启示

2011年5-7月德国发生一起肠出血性大肠杆菌(EHEC)O104(:)H4感染引起的暴发疫情,并波及欧盟其他13个国家及美国、加拿大等地,报告EHEC感染和溶血性尿毒综合征(HUS)病例4400余例[1].自发现疫情以来,德国联邦公共卫生机构罗伯特·科赫研究所(Robert Koch Institute,RKI)联合联邦及有关州卫生部门及医疗、研究机构开展了一系列流行病学调查,掌握了疫情特征,逐步查明病因,为采取控制措施提供了重要依据[1-3].     

对付新型大肠杆菌,难不难？

2011年4月以来，德国发生了新型“肠出血性大肠杆菌O104：H4”感染暴发疫情，波及部分欧洲其他国家及美国、加拿大等16个国家，累计病例数千例，死亡几十例。流行病学调查结果初步确认了本次疫情的传播媒介为芽苗菜，但疑问仍然不少。     

肠出血性大肠杆菌感染的流行病学及临床医学资料概述

大肠杆菌在自然界广泛分布,其中,肠出血性大肠杆菌(EHEC)是引起出血性肠炎最常见的致病菌之一.2011年5月以来,德国由食用“毒蔬菜”引发的出血性肠炎暴发疫情波及了欧州许多国家,美国、加拿大也分别有确诊病例.为此,为了给防治出血性肠炎的暴发流行提供参考依据,从流行病学角度概述了肠出血性大肠杆菌感染的病原学、传染源、传...     

分子分型方法在肠出血性大肠杆菌检测中的应用

自1982年首次发现肠出血性大肠杆菌O157：H7在北美引起出血性肠炎以来,与肠出血性大肠杆菌O157：H7病原菌相关疾病的发生率逐年上升,尤以发达国家病例为多,这可能与其饮食习惯和监测报告系统完善有关。大多数O157：H7肠出血性大肠杆菌的感染是食用了被牛粪污染的食物和饮水引起的,临床症状主要表现为腹部痉挛性疼痛和出血性结肠炎。近些年已经报道过多起由肠出血性大肠杆菌O157：H7引起的暴发流行,因儿童和老年人患者有时会在腹泻后继发诸如溶血性尿毒综合征等严重的并发症而死亡率较高。O157：H7是肠出血性大肠杆菌的主要血清型别,     

荧光定量PCR快速检测食品中肠出血性大肠杆菌O104

目的建立针对肠出血性大肠杆菌O104的荧光定量PCR快速检测方法。方法针对O104的wzx保守基因,设计特异性引物和探针,采用倍比梯度稀释法检测该体系的灵敏度,以另外34株肠道致病菌评价检测方法的特异性;建立了肠出血性大肠杆菌O104感染食品的检测模型以验证方法的适用性。结果建立了荧光定量PCR快速检测肠出血性大肠杆菌O104的方法。每次检测最低限为12.0copies,特异性为100%。结论该法缩短了检测时间,并有良好的灵敏性和特异性,在疾病防控及食品卫生行业中具有应用前景。     

郑州市肠出血性大肠杆菌O157:H7感染监测

[目的]2005年监测郑州市肠出血性大肠杆菌O157：H7感染状况及病原分布特点,为各级卫生行政部门制订新发传染病防治措施,提供基础疫情资料。[方法]监测标本用免疫磁珠集菌方法（IMS）做病原学分离培养、毒力基因检测用多重PCR方法、药敏试验用（K-B）常规方法。[结果]腹泻病人标本185份,大肠杆菌O157：H7检出阳性4份。外环境标本588份,检出大肠杆菌O157：H7阳性20份。用多重PCR方法做毒力基因检测,有6份家畜家禽阳性标本中检出O157：H7毒力基因（Stx2、eaeA、HIyA）为阳性。药敏试验24株肠出血性大肠杆菌O157：H7对8种抗菌药物敏感率为95%以上,对新生霉素100%耐药,其余7种对抗菌药物敏感程度各有差异。[结论]郑州市有散在的大肠杆菌O157：H7感染的病人及动物疫点。奶牛和波尔山羊是大肠杆菌O157：H7动物宿主。     

上海市由腹泻综合监测系统发现的1例O157∶H7感染性腹泻病例的确认及流行病学调查

目的分析上海市首例由腹泻综合监测系统报告的肠出血性大肠杆菌(E.coli)O157∶H7感染性腹泻病例的发现过程及流行病学特征,为防制O157∶H7感染提供依据。方法收集病例的流行病调查资料及临床病史,结合实验室检查结果和历史监测数据进行描述性分析。结果 2013—2015年上海市腹泻综合监测点累计采样8 441例,未检出肠出血性大肠杆菌。2016年6月首次由腹泻患者粪便标本中,检出肠出血性大肠杆菌O157∶H7产毒株,采集密切接触者共8份粪便标本和环节样本3份,均未检出O157∶H7。结论本起E.coli O157∶H7感染散发疫情由腹泻综合监测系统发现,应强化腹泻综合监测系统的作用,及时发现传染源,有效控制肠道传染病传播风险。     

Enteroaggregative E. coli O104 from an outbreak of HUS in Germany 2011, could it happen again?

Enterohaemorrhagic E. coli (EHEC) particularly O157:H7 (Sequence type 11 complex), is the best documented and most well-known of E. coli that cause diarrhoea. The importance of EHEC lies in the severity of disease. Outbreaks can infect thousands of people causing bloody diarrhoea and haemolytic uremic syndrome (HUS) that in turn can result in protracted illness or even death. The ability of EHEC to colonise the human gut is normally associated with the presence of genes from another group of diarrhoeagenic E. coli, the enteropathogenic E. coli (EPEC), via the locus of enterocyte effacement. However, the massive outbreak in Germany was caused by an EHEC which had acquired virulence genes from yet another group of diarrhoeagenic E. coli, the enteroaggregative E. coli (EAEC). In reality EAEC is probably the most common bacterial cause of diarrhoea but is not identified in most diagnostic laboratories. This outbreak emphasises the importance of being able to detect all diarrhoeagenic E. coli and not to focus on E. coli O157:H7 alone. Routine surveillance systems for EAEC, a once ignored global pathogen, would go a long way to reaching this goal. This review describes methods for identifying non-O157 EHEC and describes the key genetic features of EHEC and EAEC. Our aim is to provide information for laboratories and policy makers which enables them to make informed decisions about the best methods available for detecting newly emergent strains of diarrhoeagenic E. coli.     

Outbreak of Shiga toxin-producing Escherichia coli and haemolytic uraemic syndrome

Enterohaemorrhagic Escherichia coli (EHEC) is a group of pathogenic Shiga toxin-producing E. coli that can cause haemorrhagic colitis and haemolytic uraemic syndrome (HUS). The disease usually occurs sporadically, but sometimes also occurs in large outbreaks such as that which recently occurred in northern Germany. EHEC infection is a zoonosis and its reservoir is in ruminant farm animals (cattle, sheep and goats). EHEC infection should be considered in patients with bloody diarrhoea, but in the course of many severe EHEC infections a picture resembling HUS may also occur. Antibiotic treatment is contraindicated because it does not reduce the duration of the disease and may have negative complications. Patients with EHEC infection may spread the bacteria and their care includes contact isolation measures with their own toilet facilities. The E. coli type O104:H4 that occurred in Germany has a combination of specific virulence characteristics. This outbreak affected many people who developed HUS and neurological symptoms following bloody diarrhoea.     

Infektionen des Menschen durch enterohämorrhagischeEscherichia coli (EHEC) in Deutschland, 1996

Zusammenfassung  1996 wurden von uns insgesamt 96 F?lle von h?molytischur?mischem Syndrom (HUS) durch EHEC Erregernachweis und/oder Nachweis spezifischer Antik?rper gesichert. Hinzu kommen 63 durch EHEC verursachte Enteritisf?lle und 40 Ausscheider. Neben den bereits in den Vorjahren geh?uft nachgewiesenen EHEC O157 (O157:H7, O157:H⁻), O26 (O26:H⁻, O26:H11) und O111 (O111:H⁻, O111:H2) ist 1996 erstmals EHEC O103:H2 als Erreger von HUS- und Enteritisf?llen aufgetreten und wurde zweith?ufigster Erreger von EHEC-Infektionen des Menschen. Insgesamt wurden bei 149 komplett charakterisierten Isolaten 26 verschiedene Serovare und zus?tzlich elf St?mme mit nichttypisierbarem O-Antigen nachgewiesen. Dies unterstreicht einerseits die Notwendigkeit der EHEC-Isolierung auf der Grundlage des Shiga Toxin-(Stx)-Nachweises bzw. der stx-Determinanten, anderersteis eine weitere Subtypisierung der Isolate (u. a. Serotypisierung). Ein interdisziplin?res Agieren auf gesundheitspolitischer, medizinischer, veterin?rmedizinischer und administrativer Ebene ist für Deutschland unbedingt zu fordern, um Gesundheits- und Verbraucherschutz zu optimieren.

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Human infections due to enterohaemorrhagic Escherichia coli (EHEC) in Germany, 1996

Summary  In 1996 we confirmed a total of 96 cases of hemolytic uremic syndrome (HUS) by identification of the enterohemorrhagic E. coli (EHEC) pathogen and/or detection of specific antibodies. In addition there were 63 cases of EHEC-induced enteritis and 40 asymptomatic carriers of the organism. Alongside EHEC O157 (O157:H7, O157:H⁻, O26 (O26:H⁻, O26:H11) and O111 (O111:H⁻, O111:H2), which have already been identified frequently in previous years, in 1996 EHEC O103:H2 appeared for the first time as a causative pathogen of HUS and cases of enteritis and was the second most common pathogen causing EHEC-infections in the human. Out of a total of 149 fully characterised isolated, 26 different serovars were identified along with eleven strains with nontypable O-antigens. These findings underline on the one side the importance of EHEC-isolation by identification of the Shiga toxin- (Stx) or stx determinants, and on the other the need for further subtyping of the isolates (e.g. serotyping). An inter-disciplinary effort involving governmental health authorities, medical and veterinary bodies and administration departments in Germany must be called for in order to optimise health protection and the safety of the consumer.

     

Escherichia coli (STEC) serotype O104 outbreak causing haemolytic syndrome (HUS) in Germany and France

At the beginning of May an outbreak of bloody diarrhoea and haemolytic uraemic syndrome (HUS) began in Germany. During the succeeding months following the initial outbreak in Germany, thousands of infections occurred resulting in 877 cases of haemolytic uraemic syndrome (HUS) with 32 deaths and 3,043 cases of enterohaemorrhagic Escherichia coli (EHEC) with 16 deaths.     

Rolle der Erregersurveillance und -subtypisierung zur Ausbrucherkennung bei lebensmittelbedingten bakteriellen Infektionen

The recognition of infection clusters via determination of clonal relationships between pathogen isolates represents the major aim of pathogen subtyping during outbreaks. In addition, a continuing and comprehensive subtyping of pathogen isolates is a prerequisite for early recognition of changes within pathogen populations, especially of new pathogen types and variants. Here, in an exemplary manner, we outline the current practice in Germany for three important agents of food-borne infections, Salmonella enterica, Listeria monocytogenes and enterohemorrhagic Escherichia coli (EHEC). Pathogen subtyping is mostly performed in specialized laboratories. Collection of representative pathogen isolates is therefore critical for comprehensive pathogen surveillance. Salmonella and L. monocytogenes are usually isolated by sample culturing in primary diagnostic laboratories and a considerable number are sent to the respective reference laboratories for further subtyping. However, the current situation in terms of EHEC is problematic. As the detection of shiga toxin (or gene) is sufficient for diagnosis and case reporting, primary diagnostic laboratories actually rarely isolate EHEC; therefore, a concept for appropriate retrieval of isolates is needed to ensure effective EHEC surveillance in Germany.     

诺如病毒核酸检测及病毒基因序列分析

〔目的〕通过对国境口岸输入性感染性腹泻暴发病例的快速检测、排查和病原基因序列分析,为病人的诊断、治疗和口岸突发疫情的处置提供依据,保障国境口岸的卫生安全。〔方法〕利用分子生物学技术,通过粪便样本的核酸(RNA)提取、聚合酶链反应(RT-PCR)、凝胶电泳分析以及基因序列测定、基因序列分析等过程,对造成群体腹泻的病原种类进行确认。〔结果〕9份送检的腹泻病人粪便样本中均检测到诺如病毒特异性核酸片段。经基因序列分析,确认检测到的诺如病毒基因型属基因组Ⅰ(GⅠ)。确认造成马耳他籍船舶"蓝海探索"号暴发腹泻病例的病原为诺如病毒。〔结论〕通过核酸检测等技术手段,可快速确认传染病病原种类,为疫情控制、保障国境口岸的卫生安全提供技术支持。     

Timeliness of surveillance during outbreak of Shiga Toxin-producing Escherichia coli infection, Germany, 2011

In the context of a large outbreak of Shiga toxin-producing Escherichia coli O104:H4 in Germany, we quantified the timeliness of the German surveillance system for hemolytic uremic syndrome and Shiga toxin-producing E. coli notifiable diseases during 2003-2011. Although reporting occurred faster than required by law, potential for improvement exists at all levels of the information chain.     

济南市1起输入性甲型H1N1流感暴发调查

[目的]调查1起甲型H1N1流感暴发的原因,为控制类似疫情提供经验。[方法]2009年7月对济南市1起输入性甲型H1N1病例进行个案调查,用描述性流行病学调查方法进行分析。[结果]本起疫情共报告10例病例,其中境外感染8例,二代病例2例。9例出现发热,最高体温39.7℃,8例体温≥38.0℃,占88.9%。[结论]此起疫情为境外输入甲型H1N1流感暴发疫情。暴发原因不排除境外的同源暴露感染,二代病例为未采取防护的密切接触感染发病。此阶段加强入境人员的健康教育,强化对病例和密接的管理,是控制疫情的关键措施。