结核分枝杆菌
肺结核
全基因组关联研究
医学
抗药性
广泛耐药结核
逻辑回归
内科学
流行病学
基因型
生物
单核苷酸多态性
遗传学
基因
病理
作者
Yiwang Chen,Qi Jiang,Peierdun Mijiti,Howard Takiff,Qian Gao
出处
期刊:eLife
[eLife Sciences Publications, Ltd.]
日期:2023-05-03
卷期号:12
被引量:3
摘要
Drug resistance is a known risk factor for poor tuberculosis (TB) treatment outcomes, but the contribution of other bacterial factors to poor outcomes in drug-susceptible TB is less well understood. Here, we generate a population-based dataset of drug-susceptible Mycobacterium tuberculosis (MTB) isolates from China to identify factors associated with poor treatment outcomes. We analyzed whole-genome sequencing (WGS) data of MTB strains from 3196 patients, including 3105 patients with good and 91 patients with poor treatment outcomes, and linked genomes to patient epidemiological data. A genome-wide association study (GWAS) was performed to identify bacterial genomic variants associated with poor outcomes. Risk factors identified by logistic regression analysis were used in clinical models to predict treatment outcomes. GWAS identified fourteen MTB fixed mutations associated with poor treatment outcomes, but only 24.2% (22/91) of strains from patients with poor outcomes carried at least one of these mutations. Isolates from patients with poor outcomes showed a higher ratio of reactive oxygen species (ROS)-associated mutations compared to isolates from patients with good outcomes (26.3% vs 22.9%, t-test, p=0.027). Patient age, sex, and duration of diagnostic delay were also independently associated with poor outcomes. Bacterial factors alone had poor power to predict poor outcomes with an AUC of 0.58. The AUC with host factors alone was 0.70, but increased significantly to 0.74 (DeLong’s test, p=0.01) when bacterial factors were also included. In conclusion, although we identified MTB genomic mutations that are significantly associated with poor treatment outcomes in drug-susceptible TB cases, their effects appear to be limited.
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