ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2014
Neutrophil-associated central nervous system inflammation in tuberculous meningitis immune reconstitution inflammatory syndrome.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03092817 (A Randomized Double Blind Placebo Controlled Trial of Adjunctive Dexamethasone for the Treatment of HIV-infected Adults With Tuberculous Meningitis), which is not on this map. Cited by 56 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized Double Blind Placebo Controlled Trial of Adjunctive Dexamethasone for the Treatment of HIV-infected Adults With Tuberculous Meningitis
Who cites it
56 citing papers in PubMed, 80 citations in OpenAlex.
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- Towards host-directed therapy: The role of matrix metalloproteinases in the immunopathogenesis of tuberculosis.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2026Review
- Host-directed treatments for tuberculous meningitis: A multi-platform approach across mouse and human models.Research square · 2026Article
- Miliary Tuberculosis: A Comprehensive Review of Epidemiology, Clinical Manifestations, Diagnosis, Treatment, and Complications.Infection and drug resistance · 2026Review
- The progress of tuberculous meningitis medical management in adults.Surgical neurology international · 2026Review
- Inflammatory biomarkers as predictors of paradoxical reaction in tubercular meningitis: a prospective observational study.BMJ neurology open · 2026Article
- MMPs and NETs are detrimental in CNS-tuberculosis with MMP Inhibition in CNS-tuberculosis mice improving survival.Journal of neuroinflammation · 2025Article
- Tuberculous Meningitis Across the Lifespan.The Journal of infectious diseases · 2025Review
- Inflammatory markers in the cerebrospinal fluid linked to mortality in tuberculous meningitis.Brain communications · 2025Article
- Tuberculous ventriculitis as a devastating neurological manifestation of immune reconstitution inflammatory syndrome: A case report in immunocompetent patient.International journal of surgery case reports · 2024Article
- Infliximab for Intractable Paradoxical Reaction in Culture-Negative Tuberculosis Meningitis.Journal of clinical neurology (Seoul, Korea) · 2024Article
- Paradoxical Deterioration During Treatment of Tuberculous Meningitis Responded to Infliximab But Not to Steroids.European journal of case reports in internal medicine · 2024Article
- Interactions between CNS and immune cells in tuberculous meningitis.Frontiers in immunology · 2024Review
- Perplexing paradoxical reactions: navigating the complexity of protracted tuberculosis meningitis-a case report.Frontiers in immunology · 2024Article
- Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome-An Extempore Game of Misfiring with Defense Arsenals.Pathogens (Basel, Switzerland) · 2023Review
- Recent advances in understanding the human host immune response in tuberculous meningitis.Frontiers in immunology · 2023Review
- Influence of Strongyloides stercoralis Coinfection on the Presentation, Pathogenesis, and Outcome of Tuberculous Meningitis.The Journal of infectious diseases · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
backgroundThe immunopathogenesis of tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS) remains incompletely understood, and we know of only 1 disease site-specific study of the underlying immunology; we recently showed that Mycobacterium tuberculosis culture positivity and increased neutrophils in the cerebrospinal fluid (CSF) of patients with tuberculous meningitis (TBM) are associated with TBM-IRIS. In this study we investigated inflammatory mediators at the disease site in patients with TBM-IRIS.
methodsWe performed lumbar puncture at 3-5 time points in human immunodeficiency virus (HIV)-infected patients with TBM (n = 34), including at TBM diagnosis, at initiation of antiretroviral therapy (ART) (day 14), 14 days after ART initiation, at presentation of TBM-IRIS, and 14 days thereafter. We determined the concentrations of 40 mediators in CSF (33 paired with blood) with Luminex or enzyme-linked immunosorbent assays. Findings were compared between patients who developed TBM-IRIS (n = 16) and those who did not (TBM-non-IRIS; n = 18).
resultsAt TBM diagnosis and 2 weeks after ART initiation, TBM-IRIS was associated with severe, compartmentalized inflammation in the CSF, with elevated concentrations of cytokines, chemokines, neutrophil-associated mediators, and matrix metalloproteinases, compared with TBM-non-IRIS. Patients with TBM-non-IRIS whose CSF cultures were positive for M. tuberculosis at TBM diagnosis (n = 6) showed inflammatory responses similar to those seen in patients with TBM-IRIS at both time points. However, at 2 weeks after ART initiation, S100A8/A9 was significantly increased in patients with TBM-IRIS, compared with patients with TBM-non-IRIS whose cultures were positive at baseline.
conclusionsA high baseline M. tuberculosis antigen load drives an inflammatory response that manifests clinically as TBM-IRIS in most, but not all, patients with TBM. Neutrophils and their mediators, especially S100A8/A9, are closely associated with the central nervous system inflammation that characterizes TBM-IRIS.
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