Abstract
Coccidioidal meningitis (CM) is a rare but life-threatening complication of disseminated coccidioidomycosis, occurring in ~16% of cases, particularly among children in endemic regions such as the southwestern US and northern Mexico. Without timely diagnosis and antifungal therapy, pediatric CM is almost universally fatal within the first year. Hydrocephalus develops in up to 50% of cases. In 2000, Galgiani et al. established fluconazole as first-line therapy for CM. Subsequent guidelines refined management but did not specifically address pediatric patients (>1 month-≤19 years). No studies in the fluconazole era have systematically evaluated risk factors for complications in this population. We therefore conducted a systematic review and proportional synthesis of pediatric CM cases, focusing on CNS complications and outcomes. PubMed/MEDLINE, Embase (Ovid), and Web of Science were systematically searched (2000-2025). PROSPERO registration ID (1130290). Inclusion criteria encompassed epidemiological studies, case series, and case reports that described at least one pediatric case of CM or CNS involvement, confirmed by diagnostic methods. Cases in adults, neonates (<1 month), congenital infections, teratogenicity studies, reviews, or incomplete reports were excluded. Only cases with complete individual data (n = 48) were included. Methodological rigor was ensured using JBI Critical Appraisal Tools. Of 1089 studies, 31 met the inclusion criteria, representing 3874 pediatric cases. CM/CNS involvement was confirmed in 165 cases (4.25%; 95% CI: 3.6-4.9%), with hydrocephalus in 62 (37.5%). Among 48 case reports with complete data, fluconazole was first-line therapy in 65%. Serum CF titers ≥ 1:16 were associated with hydrocephalus plus stroke (p = 0.027) and independently predicted adverse outcomes (relapse/death; OR = 4.5, p = 0.037), whereas lifelong azole therapy was associated with improved outcomes (overall survival mean, 82 vs. 32 months; p = 0.002). Pediatric CM remains highly lethal, with hydrocephalus a frequent and severe complication. High serum CF titers (≥1:16) predict poor outcomes, emphasizing the urgent need for standardized, pediatric-specific diagnosis and management guidelines.