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合肥市2023—2024年结核分枝杆菌北京基因型主导传播的分子流行病学特征
张超, 李方磊, 吴金菊, 杨庆生, 周婷婷, 张文艳
安徽预防医学杂志 ›› 2025, Vol. 31 ›› Issue (4) : 292-295.
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合肥市2023—2024年结核分枝杆菌北京基因型主导传播的分子流行病学特征
Molecular epidemiological characteristics of dominant transmission of Beijing genotype of Mycobacterium tuberculosis in Hefei from 2023 to 2024
目的 揭示2023—2024年合肥市结核分枝杆菌的基因型分布特征及传播动态,评估北京基因型菌株的传播优势与耐药关联。方法 依据《中国结核病防治工作技术指南》,收集合肥市5所县级定点医院(庐江县人民医院、肥东县人民医院、长丰县中医院、肥西县人民医院、安徽医科大学附属巢湖医院)442株结核分枝杆菌临床分离株。采用间隔区寡核苷酸分型(Spoligotyping)技术进行基因分型,通过SITVITWEB数据库确定国际型别编号(SIT),利用MIRU-VNTRplus平台进行聚类分析。采用比例法检测异烟肼与利福平耐药性,运用χ2检验/Fisher确切概率法分析不同基因型耐药的差别。结果 合肥市结核分枝杆菌基因型分布以北京基因型为主(占85.07%,376/442),其中SIT1型占比最高(占78.73%,348/442);非北京基因型以T基因家族为主(占11.08%,49/442)。成簇率高达92.99%(411/442),且北京基因型成簇率(99.20%,373/376)显著高于非北京基因型(57.58%,38/66)(χ2=149.230,P<0.001)。北京基因型在性别(男83.87%,女89.11%)、年龄(≤45岁90.00%,>45岁84.14%)、治疗史(初治84.09%,复治93.48%)亚组中分布均匀(P>0.05)。北京基因型与非北京基因型的MDR-TB检出率分别为3.19%(12/376)和3.03%(2/66),差异无统计学意义(PFisher=1.000)。结论 合肥市结核病流行由高度同源的北京基因型菌株主导,呈现近期传播活跃特征,但其与MDR-TB无固有遗传关联。需加强基于分子分型的传播簇监测,实施精准干预以阻断传播链。
Objective To reveal the genotype distribution characteristics and transmission dynamics of Mycobacterium tuberculosis in Hefei from 2023 to 2024,and to evaluate the transmission advantage and drug resistance association of Beijing genotype strains. Methods According to the Technical Guidelines for Tuberculosis Prevention and Control in China,442 clinical isolates of Mycobacterium tuberculosis were collected from five designated county-level hospitals in Hefei (Lujiang County People's Hospital,Feidong County People's Hospital,Changfeng County Hospital of Traditional Chinese Medicine,Feixi County People's Hospital,and Chaohu Hospital Affiliated to Anhui Medical University).Spacer oligonucleotide typing (spoligotyping) was used for genotyping,and the international SIT number was determined through the SITVITWEB database.The MIRU-VNTRplus platform was utilized for cluster analysis.Drug resistance testing for isoniazid and rifampicin was conducted by the proportional method.The chi-square test or Fisher's exact probability method was used to analyze the differences in drug resistance among different genotypes. Results The genotypic distribwtion of Mycobaterium tuberculosis in Hefei City is predominantly the Beijing gerotype (85.07%,376/442),and SIT1 was the most common type (78.73%,348/442).Non-Beijing genotypes were mainly from the T gene family (11.08%,49/442).The clustering rate was remarkably high (92.99%,411/442),and the clustering rate of Beijing genotype (99.20%,373/376) was significantly higher than that of non-Beijing genotype (57.58%,38/66) (χ2=149.230,P<0.001).The Beijing genotype was evenly distributed across gender (83.87% in males,89.11% in females),age (90.00% in ≤45 years old,84.14% in >45 years old),and treatment history (84.09% in initial treatment,93.48% in retreatment) subgroups (P>0.05).The incidence rates of MDR-TB for the Beijing genotype and non-Beijing genotype were 3.19% (12/376) and 3.03% (2/66),respectively,with no statistically significant difference (PFisher=1.000). Conclusion The epidemic of tuberculosis in Hefei is dominated by highly homologous Beijing genotype strains,showing active recent transmission characteristics,but it has no inherent genetic association with MDR-TB.It is necessary to strengthen the monitoring of transmission clusters based on molecular typing,and implement precise interventions to block the transmission chain.
Mycobacterium tuberculosis / Spoligotyping / Beijing genotype
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Mycobacterial interspersed repetitive unit (MIRU) typing has been found to allow rapid, reliable, high-throughput genotyping of Mycobacterium tuberculosis, and may represent a feasible approach to study M. tuberculosis molecular epidemiology. To evaluate the use of MIRU typing in discriminating M. tuberculosis strains, isolates from 105 patients in Wuhan City, China, were genotyped by this method as compared to spoligotyping. MIRU typing identified 55 types that defined 21 clusters and 34 unique isolates. The discriminatory power was high [Hunter–Gaston discriminatory index (HGDI), 0.97]. Spoligotyping showed that 86 (81.9 %) of 105 isolates belonged to the Beijing family genotype. For Beijing family and non-Beijing strains, the discriminatory power of MIRU was high (HGDI, 0.95 and 0.98, respectively). Among the alleles of the MIRU loci for the Beijing family, only locus 26 was highly discriminative, but for non-Beijing strains, loci 10, 16 and 26 were highly discriminative. MIRU typing is a simple and fast method which may be used for preliminary screening of M. tuberculosis isolates in China.
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\n Sixty rifampin (RIF)-resistant and 75 RIF-susceptible\n Mycobacterium tuberculosis\n isolates from Shandong Province, China, were analyzed for\n rpoB\n gene mutations and genotyped. Mycobacterial interspersed repetitive unit (MIRU) genotype 223325173533 was overrepresented among RIF-resistant isolates. MIRU combined with IS\n 6110\n restriction fragment length polymorphism analysis as the second-line genotyping method may reflect epidemiologic links more reliably than each method alone.\n
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Information on the genetic variability of drug resistant isolates of Mycobacterium tuberculosis is of paramount importance to understand transmission dynamics of disease and to improve TB control strategies. Despite of largest number of multidrug-resistant (MDR) tuberculosis cases (1, 30,000; 27% of the global burden), strains responsible for the expansion or development of drug-resistant Mycobacterium tuberculosis infections have been poorly characterized in India. Present study was aimed to investigate the genetic diversity in MDR isolates of Mycobacterium tuberculosis in North India.Spacer oligonucleotide typing (spoligotyping) was performed on 293 clinical MDR isolates of Mycobacterium tuberculosis recovered from cases of pulmonary tuberculosis from North India. Spoligotyping identified 74 distinct spoligotype patterns. Comparison with an international spoligotype database (spoldb4 database) showed that 240 (81.91%) and 32 (10.92%) strains displayed known and shared type patterns, while 21 (7.16%) strains displayed unique spoligotype patterns. Among the phylogeographic lineages, lineage 3 (East African-Indian) was found most predominant lineage (n = 159, 66.25%), followed by lineage 2 (East Asian; n = 34, 14.16%), lineage 1 (Indo-Oceanic; n = 30, 12.50%) and lineage 4 (Euro American; n = 17, 7.08%). Overall, CAS1_DEL (60.41%; SITs 2585, 26, 2694, 309, 381, 428, 1401, 141, 25, 1327) was found most pre-dominant spoligotype pattern followed by Beijing (14.16%; SITs255, 260, 1941, 269) and EAI3_IND (5.00%; SITs 298, 338, 11). The demographic and clinical characteristics were not found significantly associated with genotypic lineages of MDR-M.tuberculosis isolates recovered from pulmonary TB patients of North India.Present study reveals high genetic diversity among the Mycobacterium tuberculosis isolates and highlights that SIT141/CAS1_Del followed by SIT26/ Beijing lineage is the most common spoligotype responsible for the development and transmission of MDR-TB in North India. The high presence of shared type and unique spoligotype patterns of MDR strains indicates epidemiological significance of locally evolved strains in ongoing transmission of MDR-TB within this community which needs to be further monitored using robust molecular tools with high discriminatory power.
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\n To determine the prevalence and molecular characteristics of drug-resistant tuberculosis in Hunan province, drug susceptibility testing and spoligotyping methods were performed among 171\n M. tuberculosis\n isolates. In addition, the mutated characteristics of 12 loci, including\n katG\n,\n inhA\n,\n rpoB\n,\n rpsL\n, nucleotides 388 to 1084 of the\n rrs\n gene [\n rrs\n (388–1084)],\n embB\n,\n pncA\n,\n tlyA\n,\n eis\n, nucleotides 1158 to 1674 of the\n rrs\n gene [\n rrs\n (1158–1674)],\n gyrA\n, and\n gyrB\n, among drug-resistant isolates were also analyzed by DNA sequencing. Our results indicated that the prevalences of isoniazid (INH), rifampin (RIF), streptomycin (SM), ethambutol (EMB), pyrazinamide (PZA), capreomycin (CAP), kanamycin (KAN), amikacin (AKM), and ofloxacin (OFX) resistance in Hunan province were 35.7%, 26.9%, 20.5%, 9.9% 15.2%, 2.3%, 1.8%, 1.2%, and 10.5%, respectively. The previously treated patients presented significantly increased risks for developing drug resistance. The majority of\n M. tuberculosis\n isolates belonged to the Beijing family. Almost all the drug resistance results demonstrated no association with genotype. The most frequent mutations of drug-resistant isolates were\n katG\n codon 315 (\n katG\n 315\n ),\n inhA15\n,\n rpoB\n 531\n,\n rpoB\n 526\n,\n rpoB\n 516\n,\n rpsL\n 43\n,\n rrs\n 514\n,\n embB\n 306\n,\n pncA\n 96\n,\n rrs\n 1401\n,\n gyrA\n 94\n, and\n gyrA\n 90\n. These results contribute to the knowledge of the prevalence of drug resistance in Hunan province and also expand the molecular characteristics of drug resistance in China.\n
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