Next-generation sequencing of cerebrospinal fluid for the diagnosis of unexplained central nervous system infections

Abstract Background Central nervous system (CNS) infections cause significant morbidity and mortality in pediatric patients. However, in approximately half of clinical cases, the aetiology is unidentified. As an unbiased molecular diagnostic technology, next generation sequencing (NGS) is gradually being applied to investigate CNS infections. This narrative review summarizes and critiques the literature on this new technology for aetiologic identification of unexplained CNS infections in pediatric patients and discusses the future development prospects of this technology in the field of pediatrics. Methods A comprehensive PubMed search was conducted of articles published from 1 January 2008 to 26 June 2020 to retrieve all available studies on this topic. Other relevant articles were identified from recent reviews and the bibliographies of the retrieved full-text articles. Results Among the 441 studies retrieved, 26 pediatric studies, comprising 15 case reports and 11 case series, used NGS as a diagnostic tool. In these 26 studies, NGS was performed on cerebrospinal fluid samples from 529 pediatric patients, and potential causal pathogens were identified in 22.1% of cases. Conclusion There is increasing evidence that NGS can play a role in identifying the causes of unexplained encephalitis, meningoencephalitis, and meningitis in pediatric patients, although the diagnostic value of NGS is difficult to quantify. There is an increasing need for close collaboration between laboratory scientists and clinicians. We believe that further clinical studies should be performed to evaluate the performance of NGS for individual targets, and in high-risk populations.