BACKGROUND
Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test.
METHODS
In a 1-year, multicenter, prospective study, we investigated the usefulness of metagenomic NGS of CSF for the diagnosis of infectious meningitis and encephalitis in hospitalized patients. All positive tests for pathogens on metagenomic NGS were confirmed by orthogonal laboratory testing. Physician feedback was elicited by teleconferences with a clinical microbial sequencing board and by surveys. Clinical effect was evaluated by retrospective chart review.
RESULTS
We enrolled 204 pediatric and adult patients at eight hospitals. Patients were severely ill: 48.5% had been admitted to the intensive care unit, and the 30-day mortality among all study patients was 11.3%. A total of 58 infections of the nervous system were diagnosed in 57 patients (27.9%). Among these 58 infections, metagenomic NGS identified 13 (22%) that were not identified by clinical testing at the source hospital. Among the remaining 45 infections (78%), metagenomic NGS made concurrent diagnoses in 19. Of the 26 infections not identified by metagenomic NGS, 11 were diagnosed by serologic testing only, 7 were diagnosed from tissue samples other than CSF, and 8 were negative on metagenomic NGS owing to low titers of pathogens in CSF. A total of 8 of 13 diagnoses made solely by metagenomic NGS had a likely clinical effect, with 7 of 13 guiding treatment.
CONCLUSIONS
Routine microbiologic testing is often insufficient to detect all neuroinvasive pathogens. In this study, metagenomic NGS of CSF obtained from patients with meningitis or encephalitis improved diagnosis of neurologic infections and provided actionable information in some cases. (Funded by the National Institutes of Health and others; PDAID ClinicalTrials.gov number, .)
We used unbiased metagenomic next-generation sequencing to diagnose a fatal case of meningoencephalitis caused by St. Louis encephalitis virus in a patient from California in September 2016. This case is associated with the recent 2015–2016 reemergence of this virus in the southwestern United States.
Hepatitis E virus (HEV) infection uncommonly causes chronic hepatitis and neurologic disease. We describe a case of genotype 3a HEV meningoencephalitis diagnosed by metagenomic next-generation sequencing, illustrating the power of an unbiased molecular approach to microbial testing and the first reported case of HEV infection presumably acquired through lung transplantation.
Background: Commercial sex venues (CSV), bathhouses and sex clubs, have a long history of serving a high-risk population. In those facilities, patrons engage in multiple sexual encounters and often in highrisk sexual behaviors. Designing prevention interventions specifically for CSVs could be an effective way to increase testing and control HIV transmission. Methods: In collaboration with the AIDS Healthcare Foundation (AHF), our team distributed free HIV self-test kits using vending machines located at two CSVs in Los Angeles, California. Test kit dispensing rate was monitored remotely. Patrons receiving a test kit were surveyed regarding their testing experience, test result and follow up. Linkage to care was offered to participants. Results: During 18 months, 1,398 kits were dispensed. The survey was completed by 110 patrons (response rate =7.9%). Among those who reported that they used the test kit (n=96), 17 (17.7%) participants reported a first-time reactive HIV result. At the time of the survey, six participants with reactive results reported seeking confirmatory testing and linkage to care and four had initiated treatment. Two participants requested linkage-to-care assistance. Participants reported valuing the privacy and convenience of the vending machine but were skeptical on the accuracy of their result. The startup cost, including the purchase of two vending machines, was $10,000 and the recurring cost (monitoring, test kits, personnel) was $33.81 per kit vended. Conclusions: While survey response was low, our results demonstrate that an intervention using vending machines and HIV self-test kits in CSVs was acceptable, feasible, used by the CSV patrons and can help identify new HIV cases.
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