546. Resolution of a Cluster of Travel-Associated Leptospira santarosai Infection in Four Adolescents by Plasma Microbial Cell-Free DNA Detection with the Karius Test®

Abstract

Abstract Background Leptospira can cause severe infections but their diagnosis can be challenging. Diagnosis is limited by nonspecific, protean clinical symptoms; the fastidious nature of Leptospira; and poor specificity, sensitivity, and long turnaround times of serologic testing. Given these limitations, identifying epidemiological clusters of leptospirosis can be challenging. Rapid, non-invasive diagnosis of leptospirosis by microbial cell-free DNA (mcfDNA) next-generation sequencing (NGS) of plasma offers a means to overcome these limitations in individual diagnosis and public health epidemiological surveillance. Methods The Karius Test® (KT) detects and quantifies mcfDNA in molecules/µL (MPM) in plasma from a curated genomic database of >20,000 organisms reporting on >1000 pathogens through the Karius CLIA certified/CAP accredited lab (Redwood City, CA). Four KT detections of Leptospira santarosai were identified April - August 2021 across four independent United States institutions. Clinical review was performed by pediatric infectious diseases consultants. Results KT detected L. santarosai in four adolescents with travel to Costa Rica or Belize (Table). A broad work-up was performed in all patients. McfDNA NGS was the first test to identify L. santarosai as the diagnosis in all cases with an average time to diagnosis of 2.5+/- 0.58 days from sample collection, enabling narrowed, targeted antibiotic treatment. L. santarosai mcfDNA was positive in three patients despite pretreatment; average L. santarosai mcfDNA concentration was 173.5+/- 186.1 MPM. Leptospira serologies were confirmatory in three patients, potential epidemiological exposures were identified in all patients, and all recovered. Conclusion KT enabled rapid, non-invasive diagnosis of diverse manifestations of L. santarosai against a competing broad differential in four adolescent travelers returning from Costa Rica or Belize. The resolution of the etiology of this cluster of patients with leptospirosis demonstrates the potential utility of mcfDNA to quickly diagnose and support case definitions of reportable diseases and the potential importance of plasma mcfDNA NGS in public health and epidemiological surveillance. Disclosures Asim A. Ahmed, MD, Karius: Employee|Karius: Stocks/Bonds Sara Saporta-Keating, MS, MD, Pfizer: Co-investigator in investigator-driven study sponsored by Pfizer.