Advances in molecular diagnostic testing for central nervous system infections.

Central nervous system (CNS) infections present an ongoing diagnostic challenge for clinicians, with an aetiological agent remaining unidentified in the majority of cases even in high-income settings. This review summarizes developments in a range of diagnostic methods published in the past 18 months. Several commercial assays exist for the detection of viral, bacterial and fungal pathogens using single multiplex PCR. Multicentre validation of the Biofire FilmArray panel illustrated high sensitivity for bacterial and fungal pathogens, but poor results for Cryptococcus species detection. The development of microarray cards for bacterial CNS pathogens shows promise but requires further validation. Few developments have been made in proteomics and transcriptomics, contrasted with significant increase in the use of metagenomic (or unbiased) sequencing. Novel viruses causing CNS infection have been described using this technique but contamination, cost, expertise and turnaround time requirements remain restrictive. Finally, the development of Gene Xpert and Ultra has revolutionized tuberculosis meningitis diagnostics with newly released recommendations for their use from the WHO. Progress has been made in the clinical validation and international recommendation of PCR-based tests for CNS infections. Sequencing techniques present the most dynamic field, although significant ongoing challenges persist.