BACKGROUND: Patients with meningoencephalitis often present to emergency departments and receive a lumbar puncture as part of their diagnostic evaluation. Many of these patients have abnormal cerebrospinal fluid (CSF) but no specific infectious agent is identified. We describe a study using both routine methods (e.g., culture) and newer advanced molecular diagnostic laboratory tests to identify the range and proportion of infectious agents in CSF among persons with suspected meningitis or encephalitis or other indication for lumbar puncture.
METHODS: This is a multicenter, prospective, observational study by the Centers for Disease Control and Prevention, Olive View-UCLA Medical Center, and EMERGEncy ID NET, a network of 11 geographically diverse university-affiliated urban emergency departments. Pediatric and adult patients for whom lumbar puncture was performed in the emergency departments were invited to participate in the study. Demographic and clinical data were collected using standardized data entry forms. The advanced molecular testing will consist of multiple techniques in three phases. In the pilot phase; ten samples will be tested in which a probable infectious agent was identified by routine hospital testing done at the time of admission and ten in which no infectious agents were identified. Each of the 20 will be tested with a multiplex PCR assay, a target-directed next generation sequencing assay, and a high-density microarray. In the second phase, the best performing assay in the pilot study will be used to test a large number of samples from patients with undetermined etiology. In the final phase, a subset of samples in which no infectious agent was identified will be analyzed by deep metagenomic next gen sequencing.
RESULTS: As of November, 2015, 856 of an anticipated 1,000 subjects were enrolled in the study. Among the 621 participants with complete data, 38% were Hispanic/Latino, 29% were non-Hispanic white, and 27% were non-Hispanic black. Participant age ranged from 26-51 years, with a median of 38 years. Examples of relevant past medical history among participants include HIV/AIDS, sepsis, leukemia, and heroin abuse. Hospital laboratory findings included Cryptococcus, Mycobacteria, Herpes simplex, Enterovirus, West Nile Virus, Staphylococcus aureus (MRSA), and S. pneumoniae. Findings from advanced molecular diagnostic laboratory tests are pending.
CONCLUSIONS: For a large proportion of patients with meningoencephalitis, no specific infectious agent is identified. Advanced molecular diagnostic laboratory tests may provide additional insights into these diagnoses.