喀什地区结核分枝杆菌基因型分布及其与肺结核患者临床特征的关联

Distribution of Mycobacterium tuberculosis genotypes in Kashgar region and their association with clinical characteristics of pulmonary tuberculosis patients

目的:了解喀什地区结核分枝杆菌(Mycobacterium tuberculosis,MTB)基因型分布情况,以及基因分型与肺结核患者临床特征之间的关联。方法:收集2020年喀什地区结核病定点医院临床分离的MTB菌株,将其中有完整病例信息的810例肺结核患者和其对应的810株MTB临床分离株纳入研究。肺结核患者的个案信息从“结核病管理信息系统”中调取,包括患者的姓名、性别、年龄、职业等基本信息和临床症状、影像学表现、治疗史、治疗方案、治疗结局等。采用Illuminate HiSeq二代测序平台对MTB菌株进行基因分型,并鉴定谱系。结果:810株MTB中Lineage2谱系292株(36.0%)、Lineage3谱系321株(39.6%)、Lineage4谱系197株(24.4%)。喀什市、疏附县、疏勒县等县、市的MTB的谱系分布不均;有效测得的572株亚谱系中Lineage2.2.1亚谱系占44.6%(255/572)、Lineage2.2.2亚谱系占6.8%(39/572);Lineage3.1.3亚谱系占14.9%(85/572);Lineage4谱系分化较广,即Lineage4.1~4.9,其中Lineage4.5亚谱系占29.9%(171/572)。菌株谱系与患者临床症状之间差异不明显;相较其他谱系,Lineage3谱系菌株感染者痰涂片阳性比例更低(27.7%,89/321),但明确治愈者的比例更高(37.1%,119/321),差异均有统计学意义(χ^(2)值分别为6.192和24.558,P值均<0.05)。结论:喀什地区MTB谱系、亚谱系分布呈基因多态性,Lineage3谱系感染患者涂片阳性率较低,临床治愈率较高。

Objective:To investigate the distribution of Mycobacterium tuberculosis(MTB)genotypes in the Kashgar region and to analyze the correlation between these genotypes and the clinical characteristics of pulmonary tuberculosis patients.Methods:MTB strains were collected from tuberculosis-designated hospitals in Kashgar in 2020.The study included 810 tuberculosis patients with complete case information and their corresponding 810 MTB clinical isolates.Case information for the pulmonary tuberculosis patients was retrieved from the“Tuberculosis Management Information System”encompassing the patient’s name,gender,age,occupation,clinical symptoms,imaging findings,treatment history,treatment plan,and treatment outcome.MTB strains were genotyped and their lineages identified using the Illumina HiSeq second-generation sequencing platform.Results:Among the 810 MTB strains,292 strains(36.0%)belonged to Lineage2,321 strains(39.6%)belonged to Lineage3,and 197 strains(24.4%)belonged to Lineage4.The distribution of MTB lineages varied across different counties and cities,including Kashgar,Shufu County,and Shule County.Among the 572 effectively measured sublineages,Lineage 2.2.1 accounted for 44.6%(255/572)and Lineage2.2.2 accounted for 6.8%(39/572);the Lineage3.1.3 sublineage accounted for 14.9%(85/572).Lineage4 showed a wide differentiation into sublineages,namely Lineage4.1 to Lineage4.9,with the Lineage4.5 sublineage comprising 29.9%(171/572).There was no significant difference between the strain lineage and the clinical symptoms of the patients.However,compared with other lineages,individuals infected with Lineage3 strains had a lower proportion of sputum smear positivity(27.7%,89/321)and a higher proportion of clear cure(37.1%,119/321).These differences were statistically significant(χ^(2) values were 6.192 and 24.558,respectively,with P values<0.05).Conclusion:The distribution of MTB lineages and sublineages in the Kashgar region demonstrates genetic polymorphism.Lineage3 infections are associated with a low sputum smear positivity rate and a high clinical cure rate.