摘要目的 探讨MTB北京基因型在人群中的分布及其耐药类型和相关分子特征.方法 江苏省灌云县和浙江省德清县1年内登记确诊的结核病患者399例,分离出MTB菌株者351例,其中男237例,女114例;年龄18～82岁,平均(46±35)岁.采用比例法确定分离株对一线抗结核药物的耐药类型,用直接基因测序识别耐药相关的基因突变,用间隔区寡核苷酸分型技术识别MTB北京基因型,以IS6110限制性内切酶片段长度的多态性(IS6110 IS6110-RFLP)技术确定MTB基因型及其成簇性和惟一性.结果 在分离得到的351株MTB菌株中北京基因型243株,北京基因型患者中耐多药、耐异烟肼和耐利福平分别占18.5%(45/243)、43.2%(105/243)和22.2%(54/243),明显高于非北京基因型[7.4%(8/108)、24.1%(26/108)和12.0%(13/108)];北京基因型菌株中rpoB和katG基因的联合突变率较高,分别为13.2%(32/243)和 4.6%(5/108),OR=2.553,95%CI为1.031～6.324;北京基因型菌株的成簇率[41.2%(100/243)]明显高于非北京基因型[11.1%(12/108)],OR=5.503,95%CI为2.851～10.622.结论 在我国东部农村地区,感染北京基因型菌株的结核病患者发生耐异烟肼、耐利福平和耐多药结核病的危险性较大,其发病有可能由于近期传播所致.

abstractsObjective To investigate the distribution of Mycobacterium tuberculosis (MTB) Beijing genotype, which was isolated from tuberculosis (TB) patients registered in local TB dispensaries in Deqing and Guanyun county respectively within 1 year, as well as its drug-resistant phenotypic and genotypic profiles and genotyping features. Methods A total of 399 TB patients were enrolled from 2 counties. Of the 351 TB patients with MTB isolates available, 237 were male, and 114 were female; aged from 18-82 (46±35) years . The proportion method and DNA sequencing were used to define the susceptibility of the isolates to 4 first line anti-TB drugs and the related mutation. Beijing genotype MTB strains were identified by Spoligotyping, while the "cluster" strains and the "unique" strains were defined by IS6110 restriction fragment length polymorphism (RFLP). Results Beijing genotype MTB strains were identified in 243 of the 351 strains isolated, and the proportion of multi-drug resistance, mono-resistance to rifampin and isoniazid among Beijing genotype MTB was 18.5% (45/243), 43.2% (105/243) and 22.2% (54/243) respectively, all being significantly higher than the non-Beijing genotype MTB, 7.4% (8/108), 24.1% (26/108) and 12.0% (13/108) respectively. katG and rpoB mutations were observed more common among Beijing genotype MTB than among non-Beijing genotype MTB, 13.2% (32/243) and 4.6% (5/108) respectively, OR=2.553, 95%CI: 1.031-6.324. The Beijing genotype MTB was more likely to be clustered than non-Beijing genotype MTB, 41.2% (100/243) and 11.1% (12/108) respectively, OR=5.503, 95%CI: 2.851-10.622. Conclusions In eastern rural China, TB patients infected with the Beijing genotype MTB may have a higher risk to develop isoniazid-or rifampin-resistance and multi-drug resistance. The disease is more likely due to recent transmission.