Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2019
Do Intracerebral Cytokine Responses Explain the Harmful Effects of Dexamethasone in Human Immunodeficiency Virus-associated Cryptococcal Meningitis?
Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda.PLoS neglected tropical diseases · 2020Trial
- Assessing Statistical Methods for Estimating the Cerebrospinal Fluid Early Fungicidal Activity as an Endpoint for Cryptococcal Meningitis Clinical Trials: A Systematic Review and Simulation Study.Open forum infectious diseases · 2026Article
- Predictive value of inflammatory factors on the efficacy of adjuvant Dexamethasone in the treatment of refractory purulent meningitis among pediatric patients.Journal of medical biochemistry · 2024Article
- Clinical treatment of cryptococcal meningitis: an evidence-based review on the emerging clinical data.Journal of neurology · 2024Review
- Molecular Diagnostics ofDiseases (Basel, Switzerland) · 2024Review
- Complex Decisions in HIV-Related Cryptococcosis: Addressing Second Episodes of Cryptococcal Meningitis.Current HIV/AIDS reports · 2024Review
- Systemic and cerebrospinal fluid biomarkers for tuberculous meningitis identification and treatment monitoring.Microbiology spectrum · 2024Article
- Cryptococcal meningitis.Nature reviews. Disease primers · 2023Review
- MUC5AC Genetic Variation Is Associated With Tuberculous Meningitis Cerebral Spinal Fluid Cytokine Responses and Mortality.The Journal of infectious diseases · 2023Article
- Lenalidomide Improves Cognitive Function and Reduces Immune Reconstitution Inflammatory Syndrome in HIV-1-Related Cryptococcal Meningitis.Journal of inflammation research · 2022Article
- Harnessing the Potential of Multiomics Studies for Precision Medicine in Infectious Disease.Open forum infectious diseases · 2021Review
- Immune reconstitution inflammatory syndrome in non-HIV cryptococcal meningitis: Cross-talk between pathogen and host.Mycoses · 2021Observational
- Cryptococcal Immune Reconstitution Inflammatory Syndrome: From Blood and Cerebrospinal Fluid Biomarkers to Treatment Approaches.Life (Basel, Switzerland) · 2021Review
- Antimicrobial Therapy in the Context of the Damage-Response Framework: the Prospect of Optimizing Therapy by Reducing Host Damage.Antimicrobial agents and chemotherapy · 2020Review
- Central Nervous System Cryptococcal Infections in Non-HIV Infected Patients.Journal of fungi (Basel, Switzerland) · 2019Review
- A Diagnostic Formula for Discrimination of Tuberculous and Bacterial Meningitis Using Clinical and Laboratory Features.Frontiers in cellular and infection microbiology · 2019Article
- Recent advances in managing HIV-associated cryptococcal meningitis.F1000Research · 2019Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundThe CryptoDex trial showed that dexamethasone caused poorer clinical outcomes and slowed fungal clearance in human immunodeficiency virus-associated cryptococcal meningitis. We analyzed cerebrospinal fluid (CSF) cytokine concentrations from participants over the first week of treatment to investigate mechanisms of harm and test 2 hypotheses: (1) dexamethasone reduced proinflammatory cytokine concentrations, leading to poorer outcomes and (2) leukotriene A4 hydrolase (LTA4H) genotype influenced the clinical impact of dexamethasone, as observed in tuberculous meningitis.
methodsWe included participants from Vietnam, Thailand, and Uganda. Using the Luminex system, we measured CSF concentrations of the following: interferon γ, tumor necrosis factor (TNF) α, granulocyte-macrophage colony-stimulating factor, monocyte chemoattractant 1, macrophage inflammatory protein 1α, and interleukin 6, 12p70, 8, 4, 10, and 17. We determined the LTA4H genotype based on the promoter region single-nucleotide polymorphism rs17525495. We assessed the impact of dexamethasone on cytokine concentration dynamics and the association between cytokine concentration dynamics and fungal clearance with mixed effect models. We measured the influence of LTA4H genotype on outcomes with Cox regression models.
resultsDexamethasone increased the rate TNF-α concentration's decline in (-0.13 log2pg/mL/d (95% confidence interval, -.22 to -.06 log2pg/mL/d; P = .03), which was associated with slower fungal clearance (correlation, -0.62; 95% confidence interval, -.83 to -.26). LTA4H genotype had no statistically significant impact on outcome or response to dexamethasone therapy. Better clinical outcomes were associated with higher baseline concentrations of interferon γ.
conclusionsDexamethasone may slow fungal clearance and worsen outcomes by increasing TNF-α concentration's rate of decline.
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