Novel treatment of cryptococcal meningitis via neurapheresis terapy

Abstract

Cryptococcal meningitis (CM) has emerged as the most common life-threatening fungal meningitis worldwide. Current management involves a sequential, longitudinal regimen of antifungals; despite a signifcant improvement in survival compared with uniform mortality without treatment, this drug paradigm has not led to a consistent cure. Neurapheresis therapy, extracorporeal fltration of yeasts from cerebrospinal fluid (CSF) in infected hosts, is presented here as a novel, one-time therapy for CM. In vitro fltration of CSF through this platform yielded a 5-log reduction in concentration of the yeast and a 1-log reduction in its polysaccharide antigen over 24 hours. Additionally, an analogous closed-loop system achieved 97% clearance of yeasts from the subarachnoid space in a rabbit model over 4-6 hours. Tis is the frst publication demonstrating the direct ability to rapidly clear, both in vitro and in vivo, the otherwise slowly removed fungal pathogen that directly contributes to the morbidity and mortality seen in CM.