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委内瑞拉首次全国抗结核药物耐药性调查中结核分枝杆菌分离株的分子特征分析

Molecular characterisation of Mycobacterium tuberculosis isolates in the First National Survey of Anti-tuberculosis Drug Resistance from Venezuela.

作者信息

Aristimuño Liselotte, Armengol Raimond, Cebollada Alberto, España Mercedes, Guilarte Alexis, Lafoz Carmen, Lezcano María A, Revillo María J, Martín Carlos, Ramírez Carmen, Rastogi Nalin, Rojas Janet, de Salas Albina Vázques, Sola Christophe, Samper Sofía

机构信息

Escuela de Medicina, Universidad Centroccidental Lisandro Alvarado, Venezuela.

出版信息

BMC Microbiol. 2006 Oct 10;6:90. doi: 10.1186/1471-2180-6-90.

Abstract

BACKGROUND

Molecular typing of Mycobacterium tuberculosis strains has become a valuable tool in the epidemiology of tuberculosis (TB) by allowing detection of outbreaks, tracking of epidemics, identification of genotypes and transmission events among patients who would have remained undetected by conventional contact investigation. This is the first genetic biodiversity study of M. tuberculosis in Venezuela. Thus, we investigated the genetic patterns of strains isolated in the first survey of anti-tuberculosis drug-resistance realised as part of the Global Project of Anti-tuberculosis Drug Resistance Surveillance (WHO/IUATLD).

RESULTS

Clinical isolates (670/873) were genotyped by spoligotyping. The results were compared with the international spoligotyping database (SpolDB4). Multidrug resistant (MDR) strains (14/18) were also analysed by IS6110-RFLP assays, and resistance to isoniazid and rifampicin was characterised. Spoligotyping grouped 82% (548/670) of the strains into 59 clusters. Twenty new spoligotypes (SITs) specific to Venezuela were identified. Eight new inter-regional clusters were created. The Beijing genotype was not found. The genetic network shows that the Latin American and Mediterranean family constitutes the backbone of the genetic TB population-structure in Venezuela, responsible of >60% of total TB cases studied. MDR was 0.5% in never treated patients and 13.5% in previously treated patients. Mutations in rpoB gene and katG genes were detected in 64% and 43% of the MDR strains, respectively. Two clusters were found to be identical by the four different analysis methods, presumably representing cases of recent transmission of MDR tuberculosis.

CONCLUSION

This study gives a first overview of the M. tuberculosis strains circulating in Venezuela during the first survey of anti-tuberculosis drug-resistance. It may aid in the creation of a national database that will be a valuable support for further studies.

摘要

背景

结核分枝杆菌菌株的分子分型已成为结核病流行病学中的一项重要工具,它能够检测疫情暴发、追踪流行趋势、识别基因型以及发现常规接触调查无法察觉的患者之间的传播事件。这是委内瑞拉首次开展的结核分枝杆菌遗传多样性研究。因此,我们调查了作为全球抗结核药物耐药性监测项目(世界卫生组织/国际防痨和肺部疾病联盟)一部分的首次抗结核药物耐药性调查中分离出的菌株的遗传模式。

结果

通过间隔寡核苷酸分型技术(spoligotyping)对670株临床分离株(共873株)进行基因分型。将结果与国际间隔寡核苷酸分型数据库(SpolDB4)进行比较。还通过IS6110 - 限制性片段长度多态性分析(IS6110 - RFLP)对耐多药(MDR)菌株(14株/18株)进行分析,并对异烟肼和利福平耐药性进行了特征描述。间隔寡核苷酸分型技术将82%(548/670)的菌株分为59个簇。鉴定出20种委内瑞拉特有的新间隔寡核苷酸型(SITs)。创建了8个新的区域间簇。未发现北京基因型。遗传网络显示,拉丁美洲和地中海家族构成了委内瑞拉结核分枝杆菌遗传群体结构的主干,在所研究的结核病病例总数中占比超过60%。从未接受过治疗的患者中耐多药率为0.5%,既往接受过治疗的患者中耐多药率为13.5%。分别在64%和43%的耐多药菌株中检测到rpoB基因和katG基因的突变。通过四种不同分析方法发现有两个簇完全相同,推测代表耐多药结核病近期传播的病例。

结论

本研究首次概述了首次抗结核药物耐药性调查期间委内瑞拉流行的结核分枝杆菌菌株情况。它可能有助于建立一个国家数据库,这将为进一步研究提供宝贵支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c938/1621067/6aa1bf8c305e/1471-2180-6-90-1.jpg

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