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CASE REPORT article

Front. Immunol.
Sec. Microbial Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1441945
This article is part of the Research Topic Tuberculous Meningitis Associated Paradoxical Reaction – The Dark Side of the Immune Response View all articles

Perplexing Paradoxical Reactions: Navigating the Complexity of Protracted Tuberculosis Meningitis-A Case Series

Provisionally accepted
Megan S. Gooding Megan S. Gooding 1*Dima A. Hammoud Dima A. Hammoud 2Brian Epling Brian Epling 3Joseph Rocoo Joseph Rocoo 3Elizabeth Laidlaw Elizabeth Laidlaw 3Safia Kuriakose Safia Kuriakose 1Mansi Chaturvedi Mansi Chaturvedi 4,5Frances Galindo Frances Galindo 3Stella V. Ma Stella V. Ma 3Harry Mystakelis Harry Mystakelis 3April Poole April Poole 3Kelly Russo Kelly Russo 6Maunank Shah Maunank Shah 6Joseph Malone Joseph Malone 7Adam W. Rupert Adam W. Rupert 8Irini Sereti Irini Sereti 3Maura Manion Maura Manion 3*
  • 1 Frederick National Laboratory for Cancer Research, National Cancer Institute at Frederick (NIH), Frederick, Maryland, United States
  • 2 Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center (NIH), Bethesda, Maryland, United States
  • 3 National Institute of Allergy and Infectious Diseases (NIH), Bethesda, Maryland, United States
  • 4 National Heart, Lung, and Blood Institute (NIH), Bethesda, Maryland, United States
  • 5 Division of Pulmonary and Critical Care, University of Maryland Medical Center, Baltimore, Maryland, United States
  • 6 Baltimore County Department of Health, Baltimore, Maryland, United States
  • 7 Montgomery Count Department of Health and Human Services, Rockville, Maryland, United States
  • 8 AIDS Monitoring Laboratory, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States

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

    Tuberculosis meningitis (TBM) has considerable mortality and morbidity, and it presents with therapeutic challenges including often being complicated by paradoxical reactions (PR). Here we describe the clinical course of four cases of TBM patients complicated by PR in a longitudinal TB cohort, 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 onset of PR (PR group) or 2-4 months after ATT start (controls). The four TBM participants highlighted here presented with fevers, headaches, neurological deficits, and fatigue at initial presentation. Upon diagnosis, all were initiated on RHZE at standard doses and 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 one 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. Within the TBM participants, T cell activation with elevated levels of inflammatory biomarkers in the CSF were seen at the time of PR. These unique and highly detailed TBM cases provide insights into the pathogenesis of PR that may assist with future diagnostics and treatment.

    Keywords: tuberculosis meningitis, paradoxical reaction, case series, Immunocompetent, Therapeutic drug monitoring

    Received: 31 May 2024; Accepted: 23 Sep 2024.

    Copyright: © 2024 Gooding, Hammoud, Epling, Rocoo, Laidlaw, Kuriakose, Chaturvedi, Galindo, Ma, Mystakelis, Poole, Russo, Shah, Malone, Rupert, Sereti and Manion. 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:
    Megan S. Gooding, Frederick National Laboratory for Cancer Research, National Cancer Institute at Frederick (NIH), Frederick, 21702-1201, Maryland, United States
    Maura Manion, National Institute of Allergy and Infectious Diseases (NIH), Bethesda, MD 20892-9807, Maryland, United States

    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.