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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1535447
This article is part of the Research Topic Big Data and Precision Medicine: Diagnosis and Treatment, Drug Discovery, and Integration of Multiple Omics View all 14 articles

The Role of Isoniazid Dosage and NAT2 Gene Polymorphism in the Treatment of Tuberculous Meningitis

Provisionally accepted
Yi Jian Yi Jian 1Yuhang Bao Yuhang Bao 2*Fashuang Yang Fashuang Yang 1*Mei Zhu Mei Zhu 3*
  • 1 People's Hospital of Jinsha County, Bijie, Guizhou, Bijie, China
  • 2 Zhijin County People's Hospital, Zhijin, China
  • 3 Zhejiang Provincial People's Hospital Bijie Hospital, Bijie, China

The final, formatted version of the article will be published soon.

    Background: Tuberculous meningitis (TBM) is a non-purulent inflammatory condition affecting the meninges and spinal membranes, caused by Mycobacterium tuberculosis (MTB) infection. This study seeks to explore the impact of varying INH dosages and NAT2 gene polymorphisms on TBM treatment, contributing new insights to improve clinical management and patient prognosis. Methods: Patients with TBM hospitalized between July 2020 and December 2022 were categorized into two groups based on INH dosage: the standard-dose group (300 mg/day) and the high-dose group (600 mg/day). General and baseline data were collected, and NAT2 genotypes were identified using real-time fluorescent PCR with melting curve analysis. The clinical characteristics and outcomes of patients with TBM under varying INH dosages were analyzed.Results: This study enrolled 119 patients with TBM, including 32 (26.9%) in the standard-dose group and 87 (73.1%) in the high-dose group. The NAT2 genotypes were distributed as follows: 34 (28.6%) fast acetylators (FA), 73 (61.3%) intermediate acetylators (IA), and 12 (10.1%) slow acetylators (SA). By month 12, 25 patients (21.0%) experienced disability or death, with 22 cases (18.5%) occurring by the end of the 3rd month. Disability and mortality rates differed significantly between the standard-dose and high-dose groups for IA-type TBM patients (P = 0.014). Univariate analysis showed significant differences between groups in baseline focal neurological impairment and disability or mortality by the 3rd and 12th months. Multivariate logistic regression identified INH dosage, cranial nerve palsy, age, and headache as key prognostic factors for TBM.High-dose INH treatment was associated with a reduced incidence of disability or death compared to the standard-dose regimen, indicating better efficacy and prognosis. In patients with IAtype TBM, the high-dose group showed a significantly lower rate of disability or mortality, suggesting that higher INH dosages may reduce the risk of adverse outcomes.

    Keywords: tuberculous meningitis, NAT2, Isoniazid, Treatment, prognosis

    Received: 27 Nov 2024; Accepted: 30 Dec 2024.

    Copyright: © 2024 Jian, Bao, Yang and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yuhang Bao, Zhijin County People's Hospital, Zhijin, 552100, China
    Fashuang Yang, People's Hospital of Jinsha County, Bijie, Guizhou, Bijie, China
    Mei Zhu, Zhejiang Provincial People's Hospital Bijie Hospital, Bijie, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.