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感染性腹泻预防控制对策与实验室监测的研究

【作者】 王勇

【导师】 马静; 黄留玉;

【作者基本信息】 中国人民解放军军事医学科学院 , 军事预防医学, 2007, 博士

【摘要】 有效的监测体系是感染性腹泻预防与控制的基础,实验室监测是有效控制感染性腹泻流行的主要环节,目前国外对于感染性腹泻的监测主要从食源性和水源性疾病等病因的角度来预防和控制感染性腹泻,如食源性疾病监测网(Foodborne Disease ActiveSurveillance Network,FoodNet)和水源性疾病监测系统(Waterborne Disease OutbreakSurveillance System,WBDOSS)等监测系统,不仅有效地控制了感染性腹泻的暴发流行,还可做出及时的预警。因此,本研究按照国际实验室监测的理念和方法,将分布于城市内、城乡结合部和郊区的三个等级的医疗机构作为感染性腹泻监测哨点,与疾病预防控制机构的中心实验室构建一个感染性腹泻实验室监测网络(平台),以探索传染性疾病实验室监测的模式和方法,同时对感染性腹泻预防控制对策进行系统研究,为感染性腹泻的预防控制提供系统完整的理论基础和技术依据。本研究构建了可用于公共卫生监测系统中的实验室监测平台,组织了以三个监测点和一个中心实验室为基础结构的监测体系,主要包括监测哨点、中心实验室、实验室人员、实验室设备与试剂、标本的采集、运送和保存以及实验室的安全和管理等部分。感染性腹泻实验室监测网络按照统一的诊断标准、统一的标本采集方法、统一的调查方法、统一的实验室方法,开展感染性腹泻实验室监测,并针对各个环节进行严格质量控制。中心实验室将收集的各种资料信息建立数据库,定期进行汇总,分析各监测点感染性腹泻病例的基本情况和特征、病原体检出的种类、构成及耐药状况和影响因素,并将结果及时反馈至监测哨点,以开展对监测哨点的技术培训和临床指导。本实验室监测平台,在较小的经费投入情况下试运行两年,形成了感染性腹泻实验室实验室监测工作模式,并在监测工作中获得了以下结果:一是获得了北京部分地区感染性腹泻流行规律,以夏秋季为主,患者年龄段主要集中在20岁~49岁,两年的比例分别为49.3%和44.2%。二是明确了北京部分地区感染性腹泻的病原谱和变化趋势,两年的监测结果显示,2005年监测点收集腹泻标本480份,检出率为54.79%,其中致病菌47.1%,条件致病菌25.9%,A组轮状病毒22.1%,混合感染4.9%。主要病原菌为致泻性大肠杆菌和痢疾杆菌,痢疾杆菌不仅所占比例下降,而且构成也发生了变化,主要以福氏志贺菌F4c为主,占所有福氏志贺菌的56.8%。条件致病菌所占比例也较高,并呈上升趋势。轮状病毒性腹泻不仅发生于儿童,而且在成人中也占较高比例。2006年采集到450份标本,除检出率(28.89%)有所降低外,在病原菌的构成和变化趋势上与2005年一致。三是检查确认了北京部分地区主要病原菌的耐药模式,两年检测到的肠道致病菌对青霉素类、氨基糖甙类、第三代头孢类、糖肽类耐药比较严重,而对碳青霉烯类、单环β-内酰胺类比较敏感。四是通过对感染性腹泻标本阳性分离与患者主要临床症状的回顾性研究发现,患者就诊时的最高体温、腹痛持续时间、腹泻次数和需要静脉注射治疗等特征可以作为感染性腹泻病原培养的指标,提出了血样便和腹泻持续时间并不能够作为从标本中分离出致病菌的临床指征。五是通过感染性腹泻危险因素1∶1配对的病例对照研究和暴发疫情调查,确认了饭前、便后洗手是感染性腹泻发生的保护因素,而瓜果食前不清洗、生吃海鲜、饭前和便后不洗手和食品加工不规范是危险因素。最后,根据本感染性腹泻实验室监测的运行情况、监测结果以及调查研究结果,提出了以加强感染性腹泻实验室监测的建设,提高基层医疗机构的监测和报告意识,加强技术人员的专业培训,积极开展以病原分型技术为主的科研工作,同时在公众中间开展广泛的宣传教育,提高公众的自身防病意识和社会卫生意识为主的五项对策和五项建议。本研究依据感染性腹泻防治的国际先进理念,构建了以哨点医院和中心实验室为主要组成的感染性腹泻实验室监测平台,并按照设计方案有效开展监测工作。运行两年来的监测数据,反映了监测点感染性腹泻的发病和流行基本规律,而且临床分析和细菌类病原体检测结果,以及开展的危险因素的研究和暴发调查,为临床治疗提供了病原学依据,提出的对策和建议能为预防控制其流行提供有益的基本模式和方法。

【Abstract】 Effective surveillance system is the base of infectious diarrhea prevention and control, and laboratory surveillance is critical part of controlling infectious diarrhea epidemic or outbreak. Many countries, such as USA, they prevent and control infectious diarrhea through FoodNet, WBDOSS and other lab surveillance systems. So a infectious diarrhea laboratory surveillance network was created according to the international standard theories and experiences of surveillance lab system in this study, in order to find some ways and pattern of laboratory surveillance for preventing and controlling infectious diarrhea, even for other infectious diseases in the future.The frameworks of this infectious diarrhea surveillance network based on one centre lab and three different grades hospitals and clinics as sentinel loci, and which were located in different area, such as city, countryside and suburb. The surveillance network was composed by surveillance locus, centre lab, technicians and doctors, equipments and reagents, samples collecting, carrying and saving, and safety management of lab. The surveillance lab system uniformed diagnosis standard, methods of sample collection, investigation ways, detection methods, then each critical point was done quality control. The centre lab collected the infectious diarrhea patients information, the diarrhea pathogens, percents and antibiotics resistances and risk factors analysis, then all information were feed back to each surveillance loci, so as to educate and direct. The lab surveillance network has run two years under lesser funds supporting, formed the infectious diarrhea laboratory surveillance pattern, and acquired some results.The first result was the epidemic of infectious diarrhea in some areas in Beijing, the epidemic seasons were summer and autumn, the populations from 20 to 49 years which was the mainly populations.The second result was the infectious diarrhea pathogens and variational trends. In 2005, 480 feces samples were collected, the total positive rate was 54.79%, include pathogens bacteria were 47.1%, condition pathogens bacteria was 25.9%, and rotavirus positive samples were 22.1%, and mixed infection was 4.9%. Shigella had different types and serotypes, the B serotype of Shigella flexneri, especial F4 serotype was high positive rate than other Shigella types. The proportion of conditioned pathogens was ascended, and the rotavirus infection happened not only in children, also the proportion of adults infection was more than before data .The surveillance results of 2006 which collected about 450 feces samples, the component pathogens were similar to those results of 2005, but the positive rate only 28.89%.The third result was the antibiotics resistant pattern of the infectious diarrhea main pathogens bacteria. Twenty-four specific antibiotics were selected for determining the susceptibility of bacterial pathogens isolated from feces samples. The results showed that all most bacterial isolates were susceptible to meropenem, fosfomycin, cefotaxime- clavulanic acid, ceftazidime and aztreonam, but resistant to teicoplanin, vancomycin, rifampin, erythromycin, tetracycline, ampicillin and trimethoprin.The forth result was a retrospective study, which found some independent variables associated with positive stool culture were: fever, duration of abdominal pain, and requirement of IV fluid therapy. Neither bloody diarrhea nor persistent diarrhea was associated with positive stool culture.The fifth result was an case-control (1:1) study and an accident of food poisoning happened in the period of surveillance process, some risk factors of infectious diarrhea were found, the conditional logistic analysis results showed that the protective factor were washing hands in time with soap, and having dinner in some restaurants and eating fresh seafood were risk factors, another risk factor which food processing without heating will induce infectious diarrhea.Based on some results and experiences of this surveillance system, some strategies and suggestions were advanced, the strategies included developing infectious diarrhea lab surveillance network, strengthening diarrhea patients surveillance and report, educating the technicians who work in clinic and clinic department in community, disseminating knowledge about preventing diarrhea, and typing pathogens bacteria of diarrhea with new and standard method, such as PFGE. At the same time, some suggestions were advanced from lab surveillance, included improving consciousness and management in clinic department, developing some new researches about infectious diarrhea prevention, control, and improving society sanitation habits and conception.According to the projects, the surveillance lab composes by different grades clinic lab can develop surveillance effectively. After two years development, the surveillance results suggested the infectious diarrhea epidemic in Beijing area, and the clinical analysis and lab results also offer theories, technology bases and basic laboratory surveillance pattern for prevention and control infectious diarrhea and other infectious diseases in the future.

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