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坦桑尼亚结核分枝杆菌 rpoB 基因突变模式及 GeneXpert MTB/RIF 检测中利福平耐药的预测因素。

The pattern of rpoB gene mutation of Mycobacterium tuberculosis and predictors of rifampicin resistance detected by GeneXpert MTB/RIF assay in Tanzania.

机构信息

Muhimbili University of Health and Allied Sciences, School of Public Health and Social Sciences, Dar es Salaam, Tanzania.

Tanzania Field Epidemiology and Laboratory Training Program, Dar es Salaam, Tanzania.

出版信息

PLoS One. 2024 Aug 26;19(8):e0296563. doi: 10.1371/journal.pone.0296563. eCollection 2024.

DOI:10.1371/journal.pone.0296563
PMID:39186753
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11346956/
Abstract

INTRODUCTION

Antimicrobial resistance in Mycobacterium tuberculosis (MTB) poses a significant challenge to tuberculosis (TB) management worldwide. Rifampicin resistance (RR) has been associated with the rpoB gene mutation. No study was conducted in Tanzania to determine the commonest mutation. The inconsistent findings from various studies support the need to determine whether reported mutation patterns are applicable in our setting. We determined the frequency of rpoB gene mutation and factors associated with RR, which were detected using GeneXpert MTB/RIF assay.

METHODS

We conducted a retrospective cross-sectional study involving data from the National Tuberculosis and Leprosy Program database from 2020 to 2022 for cases investigated using GeneXpert MTB/RIF assay. Descriptive analysis was performed to determine the frequency of categorical variables. The chi-square test and logistic regression analysis assessed the relationship between the independent variables and outcome. The 95% confidence interval and a significance level of p<0.05 were used to assess the strength of association.

RESULTS

A total of 56,004 participants had a status of MTB and RR, where 38,705/56,004 (69.11%) were males. Probe E mutation (codon 529-533), 89/219 (40.64%) was predominant. Human immunodeficiency virus (HIV)-positive patients had a higher gene mutation, 134/10601 (1.26%) than HIV-negative, 306/45016 (0.68%) (p<0.001). Patients with both pulmonary and extra-pulmonary TB had about four times greater odds of developing rifampicin resistance (AOR 3.88, 95%CI: 1.80-8.32). RR was nearly nine times higher in previously treated patients than new patients (AOR 8.66, 95% CI: 6.97-10.76). HIV-positive individuals had nearly twice the odds of developing RR than HIV-negative individuals (AOR 1.91, 95%CI: 1.51-2.42).

CONCLUSION

The rate of RR was lower compared to other studies in Tanzania, with probe E mutations the most prevalent. Patients with disseminated TB, HIV co-infection and those with prior exposure to anti-TB had more risk of RR. The findings highlight the need to strengthen surveillance of multidrug-resistant TB among high risk patients.

摘要

简介

结核分枝杆菌(MTB)的耐药性对全球的结核病(TB)管理构成了重大挑战。利福平耐药(RR)与 rpoB 基因突变有关。坦桑尼亚尚未进行研究来确定最常见的突变。来自不同研究的不一致发现支持需要确定报告的突变模式是否适用于我们的环境。我们使用 GeneXpert MTB/RIF 检测确定了 rpoB 基因突变的频率以及 RR 相关的因素。

方法

我们进行了一项回顾性的横断面研究,涉及 2020 年至 2022 年期间国家结核病和麻风病规划数据库中的数据,这些数据是通过 GeneXpert MTB/RIF 检测进行调查的。使用描述性分析来确定分类变量的频率。卡方检验和逻辑回归分析评估了独立变量与结果之间的关系。95%置信区间和 p<0.05 的显著性水平用于评估关联的强度。

结果

共有 56004 名参与者的 MTB 和 RR 状态,其中 38705/56004(69.11%)为男性。探针 E 突变(密码子 529-533),89/219(40.64%)占优势。与 HIV 阴性患者相比,HIV 阳性患者的基因突变率更高,134/10601(1.26%)比 HIV 阴性患者的 306/45016(0.68%)更高(p<0.001)。同时患有肺内和肺外结核病的患者比仅患有肺内结核病的患者发生利福平耐药的几率高四倍(优势比 3.88,95%CI:1.80-8.32)。与新患者相比,既往治疗患者发生 RR 的风险几乎高九倍(优势比 8.66,95%CI:6.97-10.76)。与 HIV 阴性个体相比,HIV 阳性个体发生 RR 的几率高近两倍(优势比 1.91,95%CI:1.51-2.42)。

结论

RR 率低于坦桑尼亚的其他研究,探针 E 突变是最常见的。播散性结核病、HIV 合并感染和既往接触抗结核药物的患者发生 RR 的风险更高。这些发现强调需要加强对高危患者的耐多药结核病的监测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95c3/11346956/775c1b495b71/pone.0296563.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95c3/11346956/0477a8c5aa22/pone.0296563.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95c3/11346956/775c1b495b71/pone.0296563.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95c3/11346956/0477a8c5aa22/pone.0296563.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95c3/11346956/775c1b495b71/pone.0296563.g002.jpg

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