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Perplexing paradoxical reactions: navigating the complexity of protracted tuberculosis meningitis-a case report.

Authors :
Gooding MS
Hammoud DA
Epling B
Rocco J
Laidlaw E
Kuriakose S
Chaturvedi M
Galindo F
Ma SV
Mystakelis H
Poole A
Russo K
Shah M
Malone JL
Rupert AW
Sereti I
Manion M
Source :
Frontiers in immunology [Front Immunol] 2024 Oct 31; Vol. 15, pp. 1441945. Date of Electronic Publication: 2024 Oct 31 (Print Publication: 2024).
Publication Year :
2024

Abstract

Tuberculous meningitis (TBM) has considerable mortality and morbidity, and it often presents therapeutic challenges when complicated by paradoxical reactions (PRs). Here, the clinical course of four cases of TBM patients complicated by PRs in a longitudinal TB cohort is described while also providing insights from the larger clinical cohort. Research flow cytometry, biomarker analysis, and drug concentrations were performed on available samples. All participants were initiated on standard antituberculosis therapy (ATT) and enrolled at the onset of PRs (PR group) or 2-4 months after the start of ATT (controls). The four TBM participants highlighted here presented with fevers, headaches, neurological deficits, and fatigue at the initial presentation. Upon diagnosis, all were initiated on rifampin, isoniazid, pyrazinamide, and ethambutol (RHZE) at standard doses and on corticosteroids. The median time to first PR was 37 days with recrudescence of initial TBM signs and symptoms at the time of PR. At the time of referral, all participants had low drug concentrations requiring dose optimization and regimen intensification as well as recrudescent flares upon corticosteroid taper, with one individual developing enlargement of tuberculoma 1 year following completion of ATT. Based on biomarkers and flow cytometry, PRs are characterized by elevated interferon-gamma and ferritin levels in the plasma compared to controls. In the TBM participants, T-cell activation with elevated levels of inflammatory biomarkers in the cerebrospinal fluid (CSF) was seen at the time of PR. These unique and highly detailed TBM cases provide insights into the pathogenesis of PRs, which may assist with future diagnostics and treatment.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2024 Gooding, Hammoud, Epling, Rocco, Laidlaw, Kuriakose, Chaturvedi, Galindo, Ma, Mystakelis, Poole, Russo, Shah, Malone, Rupert, Sereti and Manion.)

Details

Language :
English
ISSN :
1664-3224
Volume :
15
Database :
MEDLINE
Journal :
Frontiers in immunology
Publication Type :
Academic Journal
Accession number :
39559357
Full Text :
https://doi.org/10.3389/fimmu.2024.1441945