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基于纳米孔靶向测序的颅内结核诊断:一种有前景且可靠的方法。

Nanopore-targeted sequencing (NTS) for intracranial tuberculosis: a promising and reliable approach.

机构信息

Department of Tuberculosis, The School of Public Health of Nanjing Medical University, The Second Hospital of Nanjing, Nanjing, 211166, China.

Department of Tuberculosis, The Second Hospital of Nanjing, Nanjing, 211100, China.

出版信息

Ann Clin Microbiol Antimicrob. 2024 Oct 9;23(1):89. doi: 10.1186/s12941-024-00751-x.

DOI:10.1186/s12941-024-00751-x
PMID:39385187
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11466032/
Abstract

BACKGROUND

The World Health Organization predicted 10.6 million new tuberculosis cases and 1.5 million deaths in 2022. Tuberculous meningitis, affecting 1% of active TB cases, is challenging to diagnose due to sudden onset, vague symptoms, and limited laboratory tests. Nanopore-targeted sequencing (NTS) is an emerging third-generation sequencing technology known for its sequencing capabilities. We compared its detection efficiency with Xpert, MTB culture, PCR, and AFB smear in cerebrospinal fluid samples to highlight the substantial potential of NTS in detecting intracranial tuberculosis.

METHODS

This study included 122 patients suspected of having intracranial tuberculosis at the Second Hospital of Nanjing in Jiangsu Province, China, between January 2021 and January 2024. The Univariate logistic regression and random forest regression identified risk factors and clinical markers. A chi-square test evaluated diagnostic accuracy for different image types of intracranial tuberculosis.

RESULTS

The research involved 100 patients with intracranial tuberculosis. Among them, 41 had tuberculous meningitis, 27 had cerebral parenchymal tuberculosis, and 32 had mixed intracranial tuberculosis. Besides, 22 patients were diagnosed with other brain conditions. In diagnosing intracranial tuberculosis, NTS demonstrated a sensitivity of 60.0% (95% CI: 49.7-69.5%) and a specificity of 95.5% (95% CI:75.1-99.8%), with an AUC value of 0.78 (95% CI: 0.71 to 0.84), whose overall performance was significantly better than other detection methods. There was no notable difference (P > 0.05) in diagnostic accuracy between NTS and the final diagnosis for intracranial tuberculosis patients with varying imaging types. Furthermore, patients who tested positive had a 31.500 (95% CI: 6.205-575.913) times higher risk of having intracranial tuberculosis compared to those with negative results.

CONCLUSION

Due to its convenience, efficiency, quick turnaround time, and real-time sequencing analysis, NTS might become a promising and reliable method for providing microbiological diagnoses for patients with intracranial tuberculosis and for screening populations at risk.

摘要

背景

世界卫生组织预测 2022 年将有 1060 万例新的结核病病例和 150 万人死亡。结核性脑膜炎影响活动性结核病病例的 1%,由于发病突然、症状模糊和实验室检测有限,诊断具有挑战性。纳米孔靶向测序(NTS)是一种新兴的第三代测序技术,以其测序能力而闻名。我们将其与 Xpert、MTB 培养、PCR 和 AFB 涂片在脑脊液样本中的检测效率进行了比较,以突出 NTS 在检测颅内结核方面的巨大潜力。

方法

本研究纳入了 2021 年 1 月至 2024 年 1 月期间在中国江苏省南京第二医院疑似颅内结核的 122 例患者。单变量逻辑回归和随机森林回归确定了风险因素和临床标志物。卡方检验评估了不同颅内结核影像学类型的诊断准确性。

结果

本研究涉及 100 例颅内结核患者。其中,41 例患有结核性脑膜炎,27 例患有脑实质结核,32 例患有混合性颅内结核。此外,22 例患者被诊断为其他脑部疾病。在诊断颅内结核方面,NTS 的敏感性为 60.0%(95%CI:49.7-69.5%),特异性为 95.5%(95%CI:75.1-99.8%),AUC 值为 0.78(95%CI:0.71 至 0.84),其整体性能明显优于其他检测方法。对于不同影像学类型的颅内结核患者,NTS 与最终诊断的诊断准确性无显著差异(P>0.05)。此外,与检测结果为阴性的患者相比,检测结果为阳性的患者发生颅内结核的风险高 31.500 倍(95%CI:6.205-575.913)。

结论

由于其方便、高效、快速周转时间和实时测序分析,NTS 可能成为一种有前途和可靠的方法,为颅内结核患者提供微生物学诊断,并为高危人群进行筛查。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e2/11466032/af40f78623a3/12941_2024_751_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e2/11466032/d3cfffc25125/12941_2024_751_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e2/11466032/90a5668c2bb8/12941_2024_751_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e2/11466032/f301bb6ed5f3/12941_2024_751_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e2/11466032/af40f78623a3/12941_2024_751_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e2/11466032/d3cfffc25125/12941_2024_751_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e2/11466032/90a5668c2bb8/12941_2024_751_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e2/11466032/f301bb6ed5f3/12941_2024_751_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e2/11466032/af40f78623a3/12941_2024_751_Fig4_HTML.jpg

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