Association between Vitamin D and Tumor Necrosis Factor-α Levels with the Severity and Outcomes of Tuberculous Meningitis: An Analytical Observational Study in a Referral Hospital in Indonesia

Abstract

Tuberculous meningitis (TBM) is the most severe extrapulmonary tuberculosis associated with high morbidity and high mortality. Host immune responses—particularly involving vitamin D and tumor necrosis factor-alpha (TNF-α)—play key roles in TBM pathogenesis, severity, and outcomes. This analytical observational study aimed to assess the relationship between serum levels of vitamin D and TNF-α with TBM severity and clinical outcomes. The study was conducted at a referral hospital in Indonesia. The Serum 25(OH)D and TNF-α levels in TBM patients were measured. The severity was graded using the modified British Medical Research Council (BMRC) scale, and the outcomes were evaluated using the Glasgow Outcome Scale (GOS). The mean 25(OH)D level was 14.7 ± 6.3 ng/mL, with 67.5% of patients being vitamin D deficient (<20 ng/mL); among them, 85.2% had severe TBM (Grade III). The mean TNF-α level was 35.4 ± 11.2 pg/mL, with 62.5% of patients with Grade III TBM showing elevated TNF-α (>30 pg/mL). Poor outcomes (GOS 1–3) occurred in 78.9% of patients with high TNF-α and in 71.4% of those with both low vitamin D and high TNF-α. Statistically significant associations (p < 0.05) were observed between both biomarkers and TBM severity and outcomes. These findings suggest that vitamin D deficiency and elevated TNF-α levels are linked to increased TBM severity and worse prognosis. Monitoring and potentially modulating these biomarkers may offer value in improving TBM management and outcomes.