Analysis of Molecular Characteristics of Mycobacterium Tuberculosis and Factors Associated with Transmission in Yunnan Province
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摘要:
目的 了解云南省结核分枝杆菌基因型分布特征、传播及其相关影响因素，为结核病控制提供政策依据。 方法 收集云南省32耐药监测县（区）于2016年至2019年分离的分枝杆菌菌株，采用Spoligotyping和15个MIRU-VNTR位点技术对结核分枝杆菌进行基因分型。 结果 共收集到846株结核分枝杆菌，539株为北京基因型（63.71%），307株非北京基因型包括T1（20.69%，175/846）、T3（4.49%，38/846）、T2（2.36%，20/846）等共16个基因型以及42株（4.96%）新发现或未定义菌株。846株结核分枝杆菌的成簇率为25.89%，其中北京基因型的成簇率为29.68%，非北京基因型成簇率为19.22%，两者差异有统计学意义（χ2 = 15.14，P < 0.001）；北京基因型和非北京基因型结核分枝杆菌与耐药无关；Logistic回归分析显示北京基因型成簇风险是非北京基因型的1.861倍（P < 0.05，95% CI 1.376～2.516），而INH敏感菌株是耐药菌株的1.869倍（P < 0.05，95% CI 1.129～3.094）。 结论 云南省结核分枝杆菌基因型呈高度多态性，但北京基因型仍是主要流行株，云南省存在结核病的近期传播，北京基因型和INH敏感是近期传播的影响因素。 Abstract:Objective To understand the distribution characteristics, transmission, and related influencing factors of Mycobacterium tuberculosis genotypes in Yunnan Province, and to provide policy basis for tuberculosis control. Methods Mycobacterium tuberculosis strains isolated from 32 drug-resistant monitoring counties districts in Yunnan Province from 2016 to 2019 were collected, and Spoligotyping and 15 MIRU-VNTR loci were used for genetic typing of Mycobacterium tuberculosis. Results A total of 846 Mycobacterium tuberculosis strains were collected, of which 539 strains were Beijing genotype （63.71%）, 307 strains were non-Beijing genotype, including 16 genotypes such as T1 （20.69%, 175/846）, T3 （4.49%, 38/846）, T2 （2.36%, 20/846）, and 42 strains （4.96%） were newly discovered or undefined strains. The clustering rate of 846 Mycobacterium tuberculosis strains was 25.89%, of which the clustering rate of Beijing genotype was 29.68%, and the clustering rate of non-Beijing genotype was 19.22%. There was a significant difference between the two （χ2 = 15.14, P < 0.001）. Beijing genotype and non-Beijing genotype Mycobacterium tuberculosis were not related to drug resistance. Logistic regression analysis showed that the clustering risk of Beijing genotype was 1.861 times that of non-Beijing genotype （P < 0.05, 95% CI 1.376-2.516）, and the risk of INH-sensitive strains was 1.869 times that of drug-resistant strains （P < 0.05, 95% CI 1.129-3.094）. Conclusion The Mycobacterium tuberculosis genotypes in Yunnan province are highly polymorphic, but the Beijing genotype is still the main epidemic strain. There is recent prevalence of tuberculosis in Yunnan Province, and Beijing genotype and INH sensitivity are influencing factors for recent transmission. -
Key words:
- Tuberculosis /
- Mycobacterium tuberculosis /
- Genotype /
- Molecular epidemiology /
- Recent prevalence
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图 1 846株结核分枝杆菌的15 MIRU-VNTR位点聚类分析图
Figure 1. Dendrogram of 15 MIRU-VNTR loci in 846 strains of Mycobacterium tuberculosis
表 1 846株结核分枝杆菌的州市分布情况
Table 1. Distributions of 846 Mycobacterium tuberculosis by prefecture
州、市 n 构成比（%） 昆明 62 7.33 昭通 125 14.78 曲靖 101 11.94 楚雄 80 9.46 玉溪 27 3.19 红河 68 8.04 文山 36 4.26 普洱 73 8.63 西双版纳 51 6.03 大理 42 4.96 保山 43 5.08 德宏 35 4.14 丽江 20 2.36 怒江 21 2.48 迪庆 23 2.72 临沧 39 4.61 合计 846 100.00 
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表 2 846株结核分枝杆菌Spoligotyping分型结果
Table 2. Spoligotype of 846 Mycobacterium tuberculosis Strains
序号 基因家族 菌株数（株） 构成比（%） 序号 基因家族 菌株数（株） 构成比（%） 1 Beijing 539 63.71 10 LAM3 and S /convergent 1 0.12 2 T1 175 20.69 11 LAM4 1 0.12 3 T1-T2 2 0.24 12 LAM9 1 0.12 4 T2 20 2.36 13 LAM-RUS1 1 0.12 5 T2-T3 5 0.59 14 X1 2 0.12 6 T3 38 4.49 15 CAS1_DELHI 1 0.12 7 T5 4 0.47 16 EAI3-IND 1 0.12 8 H3 7 0.83 17 U 2 0.24 9 MANU2 4 0.47 18 新发现或未定义 42 5.08
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表 3 结核分枝杆菌成簇影响的单因素分析
Table 3. Univariate Analysis of Clustering of Mycobacterium Tuberculosis
变量 菌株数（株） 成簇数（株） 成簇比例（%） χ2 P 性别 男 622 242 38.91 1.74 0.187 女 224 76 33.93 年龄（岁） < 20 51 25 49.02 3.764 0.288 20～39 314 120 38.22 40～59 306 113 36.93 ≥60 175 60 34.29 民族 汉族 513 191 37.23 0.071 0.79 其他 333 127 38.14 职业 农民 762 279 36.61 3.106 0.078 其他 84 39 46.43 文化程度 小学及以下 489 179 36.61 3.479 0.682 初中 280 107 38.21 高中及以上以上 77 32 41.56 婚姻状况 已婚 677 245 36.19 0.766 0.176 未婚 149 66 44.3 其它 20 7 35 病例来源 滇中 169 75 44.38 4.966 0.174 滇东北 226 83 36.73 滇南 267 99 37.08 滇西 184 61 33.15 基因型 Non-Beijing 307 89 28.99 15.186 0.000* Beijing 539 229 42.49 INH 敏感 760 295 38.82 4.799 0.028* 耐药 86 23 26.74 RFP 敏感 792 298 37.63 0.007 0.931 耐药 54 20 37.04 SM 敏感 769 286 37.19 0.569 0.451 耐药 77 32 41.56 EMB 敏感 832 313 37.62 0.021 0.884 耐药 14 5 35.71 OFX 敏感 827 311 37.61 0.005 0.946 耐药 19 7 36.84 KM 敏感 825 310 37.58 0.002 0.961 耐药 21 8 38.10 耐多药 否 814 307 37.71 0.146 0.702 是 32 11 34.38 任一耐药 否 671 258 38.45 1.026 0.311 是 175 60 34.29 治疗史 初治 749 274 36.58 2.821 0.093 复治 97 44 45.36 *P < 0.05。
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表 4 结核分枝杆菌成簇影响的多因素分析
Table 4. Multifactorial Analysis of Clustering of Mycobacterium Tuberculosis
变量 菌株数（株） 成簇数（株） 成簇百分比（%） OR 95%CI P 基因型 Beijing 539 229 42.49 1.861 1.376～2.516 0.000* Non-Beijing 307 89 28.99 1.0 − − INH 敏感 760 295 38.82 1.869 1.129～3.094 0.015* 耐药 86 23 26.74 1.0 − − *P < 0.05。
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