我国5岁以下儿童小肠结肠炎耶尔森菌病流行特征与致病性耶尔森菌比较基因组学初步研究

发布时间：2018-04-25 00:27

本文选题：小肠结肠炎耶尔森菌 + 儿童　；参考：《中国疾病预防控制中心》2017年硕士论文

【摘要】：目的:掌握致病性小肠结肠炎耶尔森菌在我国5岁以下儿童的流行特征,确定优势流行型别。了解我国5岁以下儿童感染致病性小肠结肠炎耶尔森菌的三间分布与临床特征,为小肠结肠炎耶尔森菌的临床诊断与防控策略提供科学依据。方法:分为基于病原学诊断的总体调查和专项调查。总体调查在全国10个省份的哨点医院开展小肠结肠炎耶尔森菌的病原学监测,采集因急性腹泻就诊的病例粪便,进行小肠结肠炎耶尔森菌的检测分离与分子分型。专项调查重点通过一家儿童哨点医院开展深入调查,在总体调查的基础上开展病例个案信息调查,分析小肠结肠炎耶尔森菌感染病例的三间分布与临床特征,同时纳入一家成人腹泻病例哨点医院形成比较研究。,结果:1.总体调查2010—2015年全国10省共计纳入5岁以下儿童腹泻病例7304例,经病原学确诊共43例病例粪便分离到致病性小肠结肠炎耶尔森菌,平均感染率为0.59%,3/0:3型小肠结肠炎耶尔森菌为主要流行型别(41/43)。男性约占全部感染病例2/3(27/43),2岁以下约占全部病例70%(30/43)。85.19%(23/27)参加便常规检查的感染病例检出粪便白细胞。存在三例长期慢性排菌病例,排菌时间最长可达3个月。腹泻儿童分离到的致病性小肠结肠炎耶尔森菌多数(36/43)与猪只或农家犬分离菌株具有相同的PFGE带型,少数未在动物菌株中发现一致带型。与猪或犬菌株具有相同带型的儿童菌株中,多数(30/36)与同一省份的猪或犬菌株带型相同,少数(6/36)与其他省份的猪菌株带型一致。我国罕见的4/0:3型菌株与我国流行的3/0:3型菌株PFGE带型不存在交叉。2.专项调查2011—2015年共计纳入5岁以下儿童腹泻病例2127例,成人腹泻病例1904例,经病原学确诊共有13例儿童与2例成人病例分离到致病性小肠结肠炎耶尔森菌,儿童腹泻病例的感染率(0.61%,13/2127)高于成人(0.11%,2/1904),儿童与成人各有1例2/0:9型感染病例,余为3/0:3型感染。腹泻儿童与腹泻成人感染致病性小肠结肠炎耶尔森菌均不存在年龄、性别或季节差异。检出粪便白细胞的腹泻儿童致病性小肠结肠炎耶尔森菌感染率(1.79%)高于未检出粪便白细胞的腹泻儿童(0.00%);伴有发热的腹泻儿童感染率(2.07%)高于不伴有发热的腹泻儿童(0.42%);感染致病性小肠结肠炎耶尔森菌的腹泻儿童比一般腹泻儿童具有更高的发热与粪便白细胞阳性率。成人感染致病性小肠结肠炎耶尔森菌与发热或粪便白细胞无关。生物1A型小肠结肠炎耶尔森菌在腹泻成人的分离率(1.52%)高于5岁以下腹泻儿童(0.28%),多数成人(20/29)与全部儿童(6/6)腹泻病例分离的生物1A型菌株携带ystB基因。2岁以上腹泻儿童的分离率高于2岁以下,5岁以下儿童的夏季分离率高于秋季,儿童腹泻病例的分离率不存在性别差异;成人腹泻病例的分离率与年龄、性别或季节无关。腹泻儿童与成人生物1A型菌株的分离率与是否发热、粪便是否检出白细胞无关。结论:我国5岁以下儿童致病性小肠结肠炎耶尔森菌的感染率不亚于发达国家,流行型别为生物血清型3/0:3型。发热与粪便白细胞是腹泻儿童感染致病性小肠结肠炎耶尔森菌的临床特征。屠宰猪和农家犬与5岁以下腹泻儿童感染致病性小肠结肠炎耶尔森菌密切相关。目的:初步确认我国致病性耶尔森菌中具有差异性和代表性的小肠结肠炎耶尔森菌、假结核耶尔森菌在目前完成图测序菌株中的系统发育关系,尤其是兼具典型的致病性与非致病性小肠结肠炎耶尔森菌毒力基因表型的aill+ystB+小肠结肠炎耶尔森菌在三种致病性耶尔森菌中的系统发育地位。方法:选取具有差异性和代表性的小肠结肠炎耶尔森菌、假结核耶尔森菌进行三代完成图测序、数据组装、全基因组组分分析、功能注释与比较基因组分析,包括基于核心基因组的系统发育分析与基于SNP的系统发育分析。结果:1.基于核心基因组的系统发育分析a.在基于核心基因组(1419个单拷贝核心基因的氨基酸序列)的系统发育树中,小肠结肠炎耶尔森菌、鼠疫耶尔森菌、假结核耶尔森菌之间无交叉。本研究测序的假结核耶尔森菌与鼠疫耶尔森菌位于同一支,相对于其他假结核耶尔森菌距离鼠疫耶尔森菌的系统发育关系更近。b.小肠结肠炎耶尔森菌内,典型的致病性小肠结肠炎耶尔森菌内部存在血清型聚集性。c.小肠结肠炎耶尔森菌内,非致病性小肠结肠炎耶尔森菌与兼具致病性与非致病小肠结肠炎耶尔森菌毒力基因表型的非典型菌株分为两支。2.基于SNP的系统发育分析与基于核心基因组的系统发育分树相比,区别在于:a.本研究测序的假结核耶尔森菌与鼠疫耶尔森菌分属两支,并与NCBI的假结核耶尔森菌测序株聚为一支。b.典型的致病性小肠结肠炎耶尔森菌分支内,0:9血清型菌株QH2011-2-63B位于所有0:3和0:9血清型致病性小肠结肠炎耶尔森菌的外侧。c.非致病性小肠结肠炎耶尔森菌聚在非典型菌株分离地菌株的内部。结论:1.小肠结肠炎耶尔森菌内部在既有典型致病性小肠结肠炎耶尔森菌分支、非致病性小肠结肠炎耶尔森菌分支的基础上,新增一支兼具致病性与非致病小肠结肠炎耶尔森菌毒力基因表型的非典型小肠结肠炎耶尔森菌分支,该分支与非致病性小肠结肠炎耶尔森菌的系统发育关系更近。2.本研究组测序的假结核耶尔森菌较其他国家完成图测序的假结核耶尔森菌距离鼠疫耶尔森菌的系统发育关系更近。
[Abstract]:Objective: to understand the epidemic characteristics of the pathogenic Jerson bacteria under 5 years old in China and determine the dominant epidemic types. To understand the three distribution and clinical characteristics of the pathogenic Jerson bacteria infected with pathogenic small enterocolitis under 5 years of age in China, and provide a scientific basis for the clinical diagnosis and prevention and control strategy of Jerson bacteria enterocolitis. Methods: the general survey and special investigation were conducted on the basis of etiological diagnosis. The overall survey was conducted in the sentinel Hospital of 10 provinces in China to carry out the etiological monitoring of Yersinia enterocolitica, collect the cases of the cases of acute diarrhoea and carry out the detection and separation of yerssinia enterocolitica and the molecular classification. The children's sentinel hospital carried out an in-depth investigation and carried out case case information survey on the basis of the overall survey to analyze the three distribution and clinical features of the cases of Jerson infection of enterocolitis, and to make a comparative study of a sentinel hospital for adult diarrhoea cases. Results: 1. overall survey from 2010 to 2015 in 10 provinces in the whole country included 5 7304 cases of children with diarrhea under the age of age were diagnosed as pathogenic enterocolitis of 43 cases of Jerson bacteria, the average infection rate was 0.59%, and the main epidemic type (41/43) of type 3/0:3 enterocolitis was 41/43. The male accounted for all cases of 2/3 (27 /43), and the total cases were 70% (30/43).85.19% (23/27) under the age of 2. Three cases of chronic chronic bacteria exclusion were found in three cases of chronic chronic bacterial infection, and the longest time for bacteria exclusion was up to 3 months. Most of the pathogenic enterocolitis (36/43) isolated from diarrhoea children (36/43) had the same PFGE band as that of pig or farm dog isolates, and a few were unfound in the animal strains. The majority (30/36) is the same as the pig or dog strain in the same province, and a few (6/36) is the same as the pig strains in other provinces. The rare 4/0:3 strain of our country and the PFGE band of the popular 3/0:3 strain of our country do not have a cross.2. special investigation 2011 to 2015. There were 2127 cases of diarrhea in children under 5 years of age and 1904 cases of adult diarrhea. A total of 13 cases of children and 2 cases of adult cases were isolated to the pathogenic Jerson bacteria. The infection rate of children with diarrhea (0.61%, 13/2127) was higher than that of adults (0.11%, 2/1904). There were 1 cases of 2/0:9 infection in children and adults, and the other was 3/0:3 type. Infection. There was no age, sex or seasonal difference in the prevalence of pathogenic enterocolitis in diarrhoea children and adults with diarrhoea. The incidence of Jerson bacteria infection in diarrhoea children with diarrhoea in fecal leukocytes (1.79%) was higher than that of diarrhoea children who had not detected fecal white blood cells (0%), and the infection rate of diarrhoea children with fever (2.07). %) was higher than non fever diarrhea children (0.42%); the diarrhea children infected with Jerson bacteria of pathogenic enterocolitis had higher fever and fecal leukocyte positive rate than those with general diarrhea. The adult infected Jerson bacteria of the pathogenic enterocolitis were not related to the fever or fecal white cells. The biological 1A type enterocolitis was in the abdomen. The separation rate of diarrhoea (1.52%) was higher than that of children under 5 years of age (0.28%). Most adults (20/29) and all children (6/6) isolated from diarrhoea cases had higher separation rate than 2 years old, and the separation rate of children under the age of.2 was higher than that of 2 years old. The separation rate of children under 5 years old was higher than that in autumn, and the separation rate of children with diarrhea was not present. The separation rate of adult diarrhea cases was independent of age, sex or season. The separation rate of 1A type strains in diarrhoea children and adult organisms was not related to fever and whether the detection of white blood cells in feces. Conclusion: the infection rate of pathogenic Yersinia enterocolitica in children under 5 years of age in our country is no less than that in developed countries, and the epidemic type is the biological sera. Type 3/0:3 type. Fever and fecal leukocytes are the clinical features of Jerson bacteria infected with pathogenic enterocolitis in diarrhoea children. Slaughtered pigs and farm dogs are closely related to the infection of Jerson in children under 5 years of age. Objective: to preliminarily identify the differential and representative small intestinal knot in the pathogenic Jerson bacteria in China. The phylogenetic relationship of the strains of Jerson, Jerson, and Jerson, especially the typical pathogenicity and non pathogenic Jerson's virulence gene phenotype, in the phylogenetic status of Jerson bacteria of aill+ystB+ enterocolitis in three pathogenic yelson bacteria. The difference and representative Jerson bacteria of the enterocolitis and the three generation of Jerson bacterium tuberculosis were sequenced, data assembly, whole genome component analysis, functional annotation and comparative genome analysis, including phylogenetic analysis based on core genome and SNP based phylogenetic analysis. Results 1. the system based on the core genome Phylogenetic analysis A., in the phylogenetic tree based on the amino acid sequences of the core genome (1419 single copy core genes), does not cross between Jerson, Yersinia pestis, and Jerson bacteria. The sequence of this study is the same branch of the sequenced Mycobacterium tuberculosis and the Yersinia pestis, relative to other pseudo tuberculosis. The phylogenetic relationship between ersinia pestis and Yersinia pestis is closer to.B. in the.C. bacteria of.B. enterocolitis. The typical pathogenic enterocolitis of Jerson has a seroaggregated.C. enterocolitis, the non pathogenic Jerson and the non pathogenic and non pathogenic small intestinal colitis. The atypical strains of virulent gene phenotypes were divided into two.2. based SNP based phylogenetic analysis and the phylogenetic tree based on the core genome. The difference was that the A. of Yersinia pestis and Yersinia pestis were divided into two branches, and the sequence of Yersinia pestis from NCBI was a typical pathogenicity of.B.. In the branch of Jerson bacteria of enterocolitis, the 0:9 serotype QH2011-2-63B is located within all 0:3 and 0:9 serotype QH2011-2-63B pathogenic Jerson non pathogenic Jerson bacteria in the atypical isolates. Conclusion: the internal of Jerson bacteria of 1. enterocolitis is typical pathogenicity On the basis of the branching of the Jerson bacteria of enterocolitis and the branch of the non pathogenic enterocolitis, a new branch of atypical enterocolitis, which has both pathogenicity and non pathogenic Jerson's virulence gene phenotypes, is added to the branch of the atypical enterocolitis, which is closely related to the phylogenetic relationship of the non pathogenic Jerson of the enterocolitis, which is more close to.2. In this study, the sequence of the false tuberculosis Jerson bacteria is closer than that of other countries in the phylogenetic relationship between the false tuberculosis Jerson strain and the bacterium Jerson.

【学位授予单位】：中国疾病预防控制中心
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R725.1;R181.3

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