Clinical Parameters, Routine Inflammatory Markers, and LTA4H Genotype as Predictors of Mortality Among 608 Patients With Tuberculous Meningitis in Indonesia
| Autor: | Michelle S M A Damen, Jessi Annisa, Tri Hanggono Achmad, Bachti Alisjahbana, Ela Hayati, Lidya Chaidir, Rovina Ruslami, Arjan van Laarhoven, Sofiati Dian, Mihai G. Netea, Reinout van Crevel, Ahmad Rizal Ganiem, Carolien Ruesen |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Tuberculosis Genotype Neutrophils 030106 microbiology lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] HIV Infections Kaplan-Meier Estimate Disease Gastroenterology Tuberculous meningitis Leukocyte Count Young Adult 03 medical and health sciences Cerebrospinal fluid Internal medicine Humans Immunology and Allergy Medicine Prospective Studies Promoter Regions Genetic Cerebrospinal Fluid Proportional Hazards Models Randomized Controlled Trials as Topic Epoxide Hydrolases Inflammation business.industry Hazard ratio Mycobacterium tuberculosis medicine.disease Neutrophilia lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] Infectious Diseases Indonesia Tuberculosis Meningeal Multivariate Analysis Cohort Immunology Female medicine.symptom business Cohort study |
| Zdroj: | The Journal of Infectious Diseases, 215, 7, pp. 1029-1039 The Journal of Infectious Diseases, 215, 1029-1039 |
| ISSN: | 0022-1899 |
| DOI: | 10.1093/infdis/jix051 |
| Popis: | Contains fulltext : 174715.pdf (Publisher’s version ) (Closed access) Background: Damaging inflammation is thought to contribute to the high morbidity and mortality of tuberculous meningitis (TBM), but the link between inflammation and outcome remains unclear. Methods: We performed prospective clinical and routine laboratory analyses of a cohort of adult patients with TBM in Indonesia. We also examined the LTA4H promoter polymorphism, which predicted cerebrospinal fluid (CSF) leukocyte count and survival of Vietnamese patients with TBM. Patients were followed for >1 year. Results: We included 608 patients with TBM, of whom 67.1% had bacteriological confirmation of disease and 88.2% had severe (ie, grade II or III) disease. One-year mortality was 43.7% and strongly associated with decreased consciousness, fever, and focal neurological signs. Human immunodeficiency virus (HIV) infection, present in 15.3% of patients, was associated with higher mortality and different CSF characteristics, compared with absence of HIV infection. Among HIV-uninfected patients, mortality was associated with higher CSF neutrophil counts (hazard ratio [HR], 1.10 per 10% increase; 95% confidence interval [CI], 1.04-1.16), low CSF to blood glucose ratio (HR, 1.16 per 0.10 decrease; 95% CI, 1.04-1.30), CSF culture positivity (HR, 1.37; 95% CI, 1.02-1.84), and blood neutrophilia (HR, 1.06 per 109 neutrophils/L increase; 95% CI, 1.03-1.10). The LTA4H promoter polymorphism correlated with CSF mononuclear cell count but not with mortality (P = .915). Conclusions: A strong neutrophil response and fever may contribute to or be a result of (immuno)pathology in TBM. Aggressive fever control might improve outcome, and more-precise characterization of CSF leukocytes could guide possible host-directed therapeutic strategies in TBM. |
| Databáze: | OpenAIRE |
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