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.
Conclusion: 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 IA-type 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.
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http://dx.doi.org/10.3389/fimmu.2024.1535447 | DOI Listing |
Vet Res Commun
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Laboratory of Clinical Veterinary Medicine for Large Animals, Kitasato University School of Veterinary Medicine, 35-1 Higashi-23bancho, Towada, 034-8628, Aomori, Japan.
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View Article and Find Full Text PDFRev Inst Med Trop Sao Paulo
March 2025
Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Dermatologia, Ambulatório de Imunodeficiências Secundárias, São Paulo, São Paulo, Brazil.
Tuberculosis (TB) is the most common comorbidity in people living with HIV/AIDS (PLWH), including those under antiretroviral treatment. PLWH are 28 times more likely to develop TB in Brazil, the leading cause of HIV-related deaths globally, with approximately 161,000 reported deaths worldwide in 2023. Early diagnosis of latent tuberculosis infection (LTBI) and prophylactic therapy can reduce TB cases, prevent disease progression, and decrease transmission in high-risk populations.
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March 2025
Division of Global HIV and Tuberculosis, US Centers for Disease Control and Prevention, Atlanta, GA, USA.
BMC Infect Dis
March 2025
Postgraduate Program in Collective Health, Laboratory of Epidemiology, Universidade Federal Do Espírito Santo, Vitória, Espírito Santo, Brazil.
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View Article and Find Full Text PDFInt J Pharm
March 2025
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Kolkata 700054 India. Electronic address:
Pulmonary delivery of combination anti-tubercular drugs can prevent emergence of drug resistance and improve therapeutic efficacy. However, several drugs in anti-Tuberculosis combinations possess contrasting physicochemical properties that necessitate precise particle engineering with meticulous design for successful co-delivery. High dose requirements further constrain addition of excipients in the formulation.
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