Revisiting the use of adenosine deaminase in cerebrospinal fluid analysis for infectious meningoencephalitis

Abstract Adenosine deaminase (ADA) levels in the cerebrospinal fluid have neither been validated as a reliable diagnostic marker nor sufficiently studied in patients with tropical diseases and human immunodeficiency virus (HIV) infection. To investigate cerebrospinal fluid (CSF)ADA levels in different central nervous system (CNS) infections, define a cutoff value, and assess correlations between CSF-ADA and other laboratory parameters. In 206 patients whose CSF-ADA levels were measured, we analyzed data on baseline characteristics, diagnoses, CSF-ADA levels, and additional laboratory parameters. These CSF-ADA levels were compared according to microbiological diagnosis, and correlations with other CSF and blood parameters were analyzed. Compared with the non-CNS infectious control group (n = 40), 2 subgroups showed significantly higher CSF-ADA levels: Mycobacterium tuberculosis (n = 45, p < 0.0001) and Neisseria meningitidis (n = 11, p = 0.0400). The identified cutoff values were 5.5 and 7.3 IU/L for M. tuberculosis and CNS coinfections, respectively. For M. tuberculosis, sensitivity was 61.2% and specificity was 72.4%, whereas coinfections demonstrated 50% of sensitivity and 82.8% of specificity. The CSF-ADA levels correlated positively with CSF protein (Spearman rank correlation coefficient [rs] = 0.3009, p < 0.0003) and weakly correlated negatively with CSF glucose (rs = -0.1895, p < 0.0254). Patients with M. tuberculosis infection exhibited significantly higher CSF-ADA levels, as reflected by the mean, median, and standard deviation, than those with other infectious etiologies combined (n = 121) and those with bacterial and viral infections analyzed separately (p < 0.05). When stratified according to HIV status, a significant difference in CSF-ADA levels was observed only among patients with varicella-zoster virus infection (p = 0.0428). The CSF-ADA levels were elevated in tuberculous and meningococcal meningitis. Higher cutoff values may occur in CNS coinfections. Therefore, CSF-ADA may serve as a supportive diagnostic tool in cases of suspected TBM, meningococcal meningitis, and CNS coinfections.