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结核分枝杆菌 3 谱系在坎帕拉-乌干达的遗传变异性及其后果。

Genetic variability and consequence of Mycobacterium tuberculosis lineage 3 in Kampala-Uganda.

机构信息

Department of Medical Microbiology, College of Health Sciences, Makerere University, Kampala, Uganda.

Department of Veterinary Medicine, Clinical and Comparative medicine, College of Veterinary Medicine, Animal Resources and Bio Security, Makerere University, Kampala, Uganda.

出版信息

PLoS One. 2019 Sep 9;14(9):e0221644. doi: 10.1371/journal.pone.0221644. eCollection 2019.

DOI:10.1371/journal.pone.0221644
PMID:31498808
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6733460/
Abstract

BACKGROUND

Limited data existed exclusively describing Mycobacterium tuberculosis lineage 3 (MTB-L3), sub-lineages, and clinical manifestations in Kampala, Uganda. This study sought to elucidate the circulating MTB-L3 sub-lineages and their corresponding clinical phenotypes.

METHOD

A total of 141 M. tuberculosis isolates were identified as M. tuberculosis lineage 3 using Single nucleotide polymorphism (SNP) marker analysis method. To ascertain the sub-lineages/sub-strains within the M. tuberculosis lineage 3, the direct repeat (DR) loci for all the isolates was examined for sub-lineage specific signatures as described in the SITVIT2 database. The infecting sub-strains were matched with patients' clinical and demographic characteristics to identify any possible association.

RESULT

The data showed 3 sub-lineages circulating with CAS 1 Delhi accounting for 55% (77/141), followed by CAS 1-Kili 16% (22/141) and CAS 2/CAS 8% (12/141). Remaining isolates 21% (30/141) were unclassifiable. To explore whether the sub-lineages differ in their ability to cause increased severe disease, we used extent of lung involvement as a proxy for severe disease. Multivariable analysis showed no association between M. tuberculosis lineage 3 sub-lineages with severe disease. The risk factors associated with severe disease include having a positive smear (OR = 9.384; CI 95% = 2.603-33.835), HIV (OR = 0.316; CI 95% = 0.114-0.876), lymphadenitis (OR = 0. 171; CI 95% = 0.034-0.856) and a BCG scar (OR = 0.295; CI 95% = 0.102-0.854).

CONCLUSION

In Kampala, Uganda, there are three sub-lineages of M. tuberculosis lineage 3 that cause disease of comparable severity with CAS-Dehli as the most prevalent. Having HIV, lymphadenitis, a BCG scar and a smear negative status is associated with reduced severe disease.

摘要

背景

在乌干达坎帕拉,仅有少量数据专门描述结核分枝杆菌谱系 3(MTB-L3)、亚谱系和临床表现。本研究旨在阐明循环的 MTB-L3 亚谱系及其相应的临床表型。

方法

采用单核苷酸多态性(SNP)标记分析方法,鉴定了 141 株结核分枝杆菌分离株为结核分枝杆菌谱系 3。为确定结核分枝杆菌谱系 3 内的亚谱系/亚株,根据 SITVIT2 数据库中描述的直接重复(DR)位点,检查所有分离株的亚谱系特异性特征。将感染的亚株与患者的临床和人口统计学特征相匹配,以确定任何可能的关联。

结果

数据显示,有 3 个亚谱系循环,CAS1 德里占 55%(77/141),其次是 CAS1-Kili 16%(22/141)和 CAS2/CAS8%(12/141)。其余 21%(30/141)无法分类。为了探讨亚谱系在引起严重疾病的能力上是否存在差异,我们使用肺受累程度作为严重疾病的替代指标。多变量分析显示,结核分枝杆菌谱系 3 亚谱系与严重疾病之间没有关联。与严重疾病相关的危险因素包括痰涂片阳性(OR=9.384;95%CI=2.603-33.835)、HIV(OR=0.316;95%CI=0.114-0.876)、淋巴结炎(OR=0.171;95%CI=0.034-0.856)和卡介苗疤痕(OR=0.295;95%CI=0.102-0.854)。

结论

在乌干达坎帕拉,有 3 个结核分枝杆菌谱系 3 亚谱系引起的疾病严重程度相当,其中以 CAS-Dehli 最为普遍。HIV、淋巴结炎、卡介苗疤痕和痰涂片阴性与严重疾病减少有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a401/6733460/2bfed7037c9b/pone.0221644.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a401/6733460/2bfed7037c9b/pone.0221644.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a401/6733460/2bfed7037c9b/pone.0221644.g001.jpg

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