【作者】 鞠长燕；

【导师】 刘衡川；

【作者基本信息】 四川大学 ， 营养与食品卫生， 2007， 硕士

【摘要】 目的研究深圳市健康人群对流脑的易感性，为预防控制流脑提供依据；分析深圳市健康人群中脑膜炎奈瑟菌(以下简称Nm)的带菌率及性别、年龄分布，确定人群中Nm的感染情况；研究Nm的菌群结构和遗传关系，对流脑的流行趋势作出预测，分析Nm的耐药性，指导临床和预防用药。方法采集健康人群血清样本800份，依据GB16884-1997的酶联免疫法(ELISA)，分别定量血清中A、C、Y和W135群Nm抗体的含量；采集1225份健康人的咽拭子，分离鉴定Nm，用血清学诊断和PCR法分群；用脉冲场凝胶电泳(PFGE)和多位点测序(MLST)进行分子分型；并用2006 CLSI／NCCLS推荐的纸片扩散法测定Nm的抗生素敏感性。结果A、C、Y、W135群流脑抗体含量中位数分别是4.07，2.31，1.35，1.75μg／mL，健康人群C群和Y群流脑抗体水平的性别差异无统计学意义，A群和W135群流脑抗体水平有性别差异，各年龄组抗体水平的差异均有统计学意义；Nm带菌率为4.4％(55／1255)，其中B群49株(3.9％)，C群4株(0.3％)，29E 2株(0.2％)。在两次流脑疫情中各分离到1株B群Nm；用PFGE对57株Nm进行分型，可以得到52个PFGE型，按照85％相似度可以分为11个群(complex)，每群含有2～4株菌；对39株Nm进行MLST，发现36个不同的ST型和9个新的等位基因，58.3％(21／36)的ST型是首次发现，75.0％(27／36)的ST型是中国独有的；氨苄西林，头孢曲松，头孢噻肟，美洛培南，米诺环素，氯霉素，利福平敏感；所有菌株均对复方新诺明耐药，部分Nm对环丙沙星，萘啶酸耐药，有多重耐药现象。结论45岁以上人群的A群和C群流脑抗体含量低，是流脑流行期的高危人群；人群中Y群和W135群流脑抗体水平较低，人群可能普遍易感；人群中主要携带B群Nm，PFGE显示菌株基因高度多态化，无优势菌株，B群Nm引起暴发的机会不大；MLST结果显示Nm基因的变化可能来自不同菌株间基因的水平传递，来自外源基因的可能性较小；Nm菌株对多数抗生素敏感，对磺胺类药物耐药情况严重。更多还原

【Abstract】 Objective To learn the immune level of healthy people to N. meningitidis(Nm) in Shenzhen, China, to learn the population structure and genetic relationship among carried meningococci, in order to facilitate the prevention and control of meningococcal disease.Methods ELISA was applied to measure the antibody against meningococcal serogroupA, C, Y, and W135(MenA, C, Y, and MenW135). Nm were isolated and identified from throat swabs culture according to GB16884-1997. The isolates were characterized by pulse field gel electrophoresis(PFGE) and multilocus sequence typing(MLST). The antibiotic susceptibility of Nm was tested by K-B assay.Results The median concentration of anti-MenA, C, Y, and W135 were 4.07, 2.31, 1.35, 1.75μg/mL, respectively, there were statistical difference between different age groups. Nm were isolated from 55 swabs, giving an overall carriage rate of 4.4%, in which 34(3.9%) isolates were Group B, 4(0.3%) isolates were Group C, 2(0.2%) isolates were Group 29E. Moreover, 2 strains were isolated from patients and close contact. 52 PFGE patterns were obtained, which designated to 11 complexes according to 85% relateness(tolerance was 1.5%,optimization was 1.5%). 36 different STs were obtained by MLST, and 9 new allele number were assigned. 58.3%(21/36) STs were found for the first time, 75.0% (27/36) STs were unique to China. All isolates were sensitive to penicillin, ampicilin, ceftriaxone, cefotaxime, meropenem, minocycline, chloramphenicol succinate, rifampicin, while all isolates were resistant to compound sulfamethoxazole.Conclusion People seniored to 35 years old were the high risk population who need more attention in meningococcal disease. The result demonstrated diversity of MenB, without a dominant PFGE type, which means a little chance to breakout. It was speculated that Nm isolates in Shenzhen comprised heterogeneous clones, which mostly derive from clones identified in local area.更多还原