【作者】 吕华坤；

【导师】 王蓓； 汪华；

【作者基本信息】 东南大学 ， 流行病与卫生统计学， 2005， 硕士

【摘要】 目的:探索江苏省农村居民结核病发生的危险因素,了解江苏省结核菌株耐药情况以及结核分支杆菌可变数目串联重复序列(variable numbers tandem repeats,VNTR)多态性分布,为控制我省结核病疫情提供依据。方法:(1)按1﹕1配对的病例对照研究设计,多级随机抽样抽取新发结核病例及其相应对照各318例。采用条件logistic回归分析方法,分析讨论结核病的多种危险因素。(2)收集江苏省结核病人菌株304株,采用间接比例法检测各结核菌株对利福平、异烟肼、链霉素、乙胺丁醇四种一线抗结核药的药物敏感性,分析各类病人耐药情况。(3)采用多位点重复串联序列(Muti-locus VNTR assay,MLVA)分型方法,提取67株结核菌DNA,对VNTR位点进行PCR扩增、2%琼脂糖电泳,用BioNumerics软件进行VNTR多态性分析和聚类分析。结果:(1)在单因素分析中,人均收入高、住房楼房、人均住居面积大、膳食营养(鸡蛋、肉类)好、劳动疲乏、经济负担重、有负性事件、有结核相关疾病史、吸烟、有TB接触史等因素的OR值分别为0.726、0.649、0.823、0.913、0.906、1.849、2.027、3.867、2.355、1.389、3.599,P值均小于0.05。在多因素分析中,人均收入高、家庭经济负担重、劳动疲劳、有结核相关疾病史、有负性事件、有TB接触史是影响农村结核发病的主要因素。(2)收集病人结核菌株304株,其中非结核分支杆菌22株,占7.2%;牛型结核分支杆菌36株,占11.8%。非结核分支杆菌的耐药率为90.3%。结核分支杆菌耐药率62.1%,其中初治病人耐药率59.6%,复治病人耐药率为68.1%,各类地区、男女病人以及城乡结核杆菌耐药率差异无显著性,不规则治疗的结核病人的结核菌耐药危险性较高。(3)选择了15个VNTR位点,67株结核杆菌呈现明显的多态性,共可分8个基因型,其中较多的一型为VII型,占32.6%,其他型别菌株数量较接近,没有特别明显的优势型别。结论:(1)人均收入低、家庭经济负担重、劳动疲劳、有结核相关疾病史、有负性事件、有TB接触史是影响农村结核发病发生的主要因素。政府大力发展农村经济,提高农民收入;农民合理安排农活,调节情绪,提高自身生活质量;卫生部门加强对结核病人的治疗和管理等,将有利于对农村结核病的防制。(2)结核菌总耐药率、初治组耐药率以及复治组耐药率均较高;非结核菌占一定比例,其耐药率也较高。加强菌株菌型检测和药敏检测,根据药敏检测结果,采取个体化治疗方案,对结核病控制有重要意义。(3)江苏省结核分支杆菌VNTR具有明显的多态性,可分为8个基因型,且各基因型别在不同类型的地区间存在一定的差异。MLVA分型技术具有稳定、简单、可重复的优点,可用于结核分支杆菌的流行病学调查。更多还原

【Abstract】 Observe: To explore the risk factors of pulmonary tuberculosis among rural dweller in jiangsu province, to determine the status of drug resistance and study the character of genetic diversity of jiangsu’s mycobacterium tuberculosis (M.tb) strains based on variable numbers of tandem repeats (VNTR).Methods:(1)Using paired-matched case-control study, 318cases and 318 controls were interviewed ,data were analyzed by conditional logistic regression model. (2) 304 strains were isolated and identified. Drug resistence was tested with indirect proportion method. In which four first line anti-tuberculosis drugs (rifamycins, isoniaizid, streptomycin, ethambutol) were performed. (3) Using muti-loci VNTR assay (MLVA) to analyze for the polymorphism and clustering of VNTR among 67 strains by PCR, 2% agarose electrophoresis and the BioNumerics (version3.0) software.Results (1) Single-variable analysis showed that capita-income, type of house, housing area per member, nourishment(meat, egg), fatigue after working, heavy economic burden, negative events, catching relevant disease, smoking, prior exposure to PTB were associated with incidence of PTB, with ORs of 0.726、0.649、0.823、0.913、0.906、1.849、2.027、3.867、2.355、1.389、3.599,all P<0.05,but all factors except for smoking, type of house, housing area per member entered into multiple regression model. (2) 90.3% drug-resistant strains were determined in non-mycobacterium tuberculosis which account for 7.2%. 62.1% M.tb resisted at least one of four drugs, 59.6% drug-resistant strains were showed in new cases, 68.1% in retreatment cases. The rate of drugs resistance was no statistical significant difference among the three areas, so did it between female and male cases, between city and rural cases. Non-regularly treated case showed much risk in drug-resistance than regularly-treated cases. (3) 15 VNTR-locus form the genome of M.tb were selected,The distribution of 67 strains showed definite polymorphism, 8 different genotypes were finally classified in which 32.6% strains were clustered to one genotype, the others were scattered.Conclusion It is suggest that the epidemic situation of PTB would be controlled with well-managed PTB and measures against other risk factors. Cases were cured with drugs selected by drug-resistance examination. The VNTR loci in M.tb isolated from Jiangsu showed marked polymorphism, the MLVA is an available one for epidemiological survey.更多还原