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[基于线性探针分析获得的单倍型的秘鲁耐药结核分枝杆菌菌株的遗传结构]

[Genetic structure of drug-resistant Mycobacterium tuberculosis strains in Peru based on haplotypes obtained from a line probe assay].

作者信息

Santos-Lazaro David, Puyen Zully M, Gavilan Ronnie G

机构信息

Instituto Nacional de Salud, Lima, Perú.

Universidad Peruana de Ciencias Aplicadas, Lima, Perú.

出版信息

Rev Peru Med Exp Salud Publica. 2021 Oct-Dec;38(4):577-586. doi: 10.17843/rpmesp.2021.384.7834. Epub 2022 Apr 1.

DOI:10.17843/rpmesp.2021.384.7834
PMID:35385010
Abstract

OBJECTIVE.: To determine the genetic structure of drug-resistant strains of Mycobacterium tuberculosis that circulated throughout Peru during the years 2011-2015, by using haplotypes obtained from a line probe assay.

MATERIALS AND METHODS.: A total of 6589 samples that were admitted to the Instituto Nacional de Salud for routine diagnosis using the GenoType® MTBDRplus v2 assay were analyzed during the study period. Resistant haplotypes were created by concatenating 21 polymorphic sites of the evaluated genes using the line probe assay; and the association analysis was carried out with phenotypes obtained by the 7H10 agar ratio method.

RESULTS.: The most frequent mutations were: rpoB S531L (55.4%) and rpoB D516V (18.5%) for rifampicin resistance, and katG S315T (59.5%) and inhA c-15t (25.7%) for isoniazid resistance. We obtained 13 representative haplotypes (87.8% of analyzed samples), 6 corresponded to the multidrug-resistant genotype, 4 to the isoniazid mono-resistant genotype and 3 to the rifampicin mono-resistant genotype. Eighteen regions and the province of Callao showed high haplotype diversity; four showed moderate diversity and two showed low diversity.

CONCLUSIONS.: Most regions showed high haplotype diversity; in addition, most drug-resistant strains of Mycobacterium tuberculosis were concentrated in the cities of Lima and Callao. Likewise, drug-resistant Mycobacterium tuberculosis strains circulating in Peru mainly contain the genetic markers with the highest prevalence worldwide, which are associated with resistance to rifampicin and isoniazid.

摘要

目的

通过使用线性探针分析获得的单倍型,确定2011 - 2015年期间在秘鲁各地传播的结核分枝杆菌耐药菌株的基因结构。

材料与方法

在研究期间,对总共6589份使用GenoType® MTBDRplus v2分析方法送往国家卫生研究院进行常规诊断的样本进行了分析。通过线性探针分析将评估基因的21个多态性位点串联起来创建耐药单倍型;并与通过7H10琼脂比例法获得的表型进行关联分析。

结果

最常见的突变是:利福平耐药的rpoB S531L(55.4%)和rpoB D516V(18.5%),以及异烟肼耐药的katG S315T(59.5%)和inhA c-15t(25.7%)。我们获得了13种代表性单倍型(占分析样本的87.8%),6种对应多药耐药基因型,4种对应异烟肼单耐药基因型,3种对应利福平单耐药基因型。18个地区和卡亚俄省表现出高单倍型多样性;4个地区表现出中等多样性,2个地区表现出低多样性。

结论

大多数地区表现出高单倍型多样性;此外,大多数结核分枝杆菌耐药菌株集中在利马和卡亚俄市。同样,在秘鲁传播的结核分枝杆菌耐药菌株主要含有全球患病率最高的与利福平和异烟肼耐药相关的基因标记。

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