Actionable Diagnosis of Neuroleptospirosis by Next-Generation Sequencing

A 14-year-old boy with severe combined immunodeficiency presented 3 times to a medical facility over 4 months with fever and headache that progressed to hydrocephalus and status epilepticus necessitating a medically-induced coma after starting empiric steroids for a suspected autoimmune condition. An exhaustive diagnostic workup including brain biopsy was unrevealing. In collaboration with Dr. Charles Chiu’s lab (UCSF Department of Laboratory Medicine), unbiased next-generation sequencing of the patient’s cerebrospinal fluid and computational analysis of the results using an ultra-rapid bioinformatics pipeline for comprehensive pathogen detection identified 475 sequence reads out of 3,063,784 (0.016%) corresponding to Leptospira spp. This result was obtained within 48 hours of sample receipt. The patient responded dramatically when treated with appropriate antimicrobials and discontinuation of steroids, and was discharged home 24 days later near his premorbid baseline.

[ Read the Article in the New York Times ][ Press Release ]