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

Chen Yang, Tianzhen Wang, Yicheng Guo, Yi Zeng, Weiwei Gao
Author Information
  1. Chen Yang: Department of Tuberculosis, The School of Public Health of Nanjing Medical University, The Second Hospital of Nanjing, Nanjing, 211166, China.
  2. Tianzhen Wang: Department of Tuberculosis, The Second Hospital of Nanjing, Nanjing, 211100, China.
  3. Yicheng Guo: Department of Tuberculosis, The School of Public Health of Nanjing Medical University, The Second Hospital of Nanjing, Nanjing, 211166, China.
  4. Yi Zeng: Department of Tuberculosis, The School of Public Health of Nanjing Medical University, The Second Hospital of Nanjing, Nanjing, 211166, China. 960559051@qq.com.
  5. Weiwei Gao: Department of Tuberculosis, The Second Hospital of Nanjing, Nanjing, 211100, China. weiweigao1106@163.com.

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.

Keywords

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Grants

  1. M2021073/the Nanjing Health Science and Technology Development Special Fund
  2. HBRCYL08/Reserve Talent Program of Nanjing Second Hospital

MeSH Term

Humans
Female
Male
Adult
Tuberculosis, Meningeal
Middle Aged
Mycobacterium tuberculosis
Sensitivity and Specificity
China
Young Adult
Aged
Nanopore Sequencing
High-Throughput Nucleotide Sequencing
Adolescent

Word Cloud

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