Metagenomic detection of central nervous system infections missedby conventional testing

Community-acquired infectious meningoencephalitis is associated with high rates of mortality and morbidity, compounded by limited access to diagnostic resources. The current study assessed acute central nervous system (CNS) infections in patients with meningoencephalitis enrolled in a hospital-based diagnostic surveillance study in São Paulo, Brazil. Cerebrospinal fluid (CSF) was collected from 600 patients between March 2018 and November 2019 and initially screened for a broad range of pathogens according to a local diagnostic algorithm. Standard microbiological and molecular diagnostic methods were applied. Metagenomic sequencing was used as a complementary approach to investigating etiology in instances where no pathogen was initially identified. Standard testing identified infectious etiologies in 292 patients (48.6%), with 227 (77.7%) confirmed as viral infections, predominantly caused by enteroviruses (n = 144) and herpesviruses (n = 40). Nonviral agents were identified in 65 patients (22.3%). Metagenomic sequencing (mNGS) of 277 of 308 undiagnosed patients revealed several additional potential etiologies, including Parvovirus B19, Toxoplasma gondii, Picobirnavirus, other enterovirus species and Vesivirus, the latter being associated with CNS infection for the first time. These findings underscore the complexity of CNS infections and highlight the potential of metagenomics to improve diagnostic accuracy, inform treatment strategies, and support efforts to address future pandemics.