Novel Treatment of Cryptococcal Meningitis via Neurapheresis Therapy.

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 significant improvement in survival compared with uniform mortality without treatment, this drug paradigm has not led to a consistent cure. Neurapheresis therapy, extracorporeal filtration of yeasts from cerebrospinal fluid (CSF) in infected hosts, is presented here as a novel, one-time therapy for CM. In vitro filtration 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. This is the first 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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1093/infdis/jiy286

Publication Info

Smilnak, Gordon J, Lefko T Charalambous, Drew Cutshaw, Alykhan M Premji, Charles D Giamberardino, Christi G Ballard, Andrew P Bartuska, Tiffany U Ejikeme, et al. (2018). Novel Treatment of Cryptococcal Meningitis via Neurapheresis Therapy. The Journal of infectious diseases, 218(7). pp. 1147–1154. 10.1093/infdis/jiy286 Retrieved from https://hdl.handle.net/10161/23249.

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Scholars@Duke

Sheng

Huaxin Sheng

Associate Professor in Anesthesiology

We have successfully developed various rodent models of brain and spinal cord injuries in our lab, such as focal cerebral ischemia, global cerebral ischemia, head trauma, subarachnoid hemorrhage, intracerebral hemorrhage, spinal cord ischemia and compression injury. We also established cardiac arrest and hemorrhagic shock models for studying multiple organ dysfunction.  Our current studies focus on two projects. One is to examine the efficacy of catalytic antioxidant in treating cerebral ischemia and the other is to examine the efficacy of post-conditioning on outcome of subarachnoid hemorrhage induced cognitive dysfunction.

Perfect

John Robert Perfect

James B. Duke Distinguished Professor of Medicine

Research in my laboratory focuses around several aspects of medical mycology. We are investigating antifungal agents (new and old) in animal models of candida and cryptococcal infections. We have examined clinical correlation of in vitro antifungal susceptibility testing and with in vivo outcome. Our basic science project examines the molecular pathogenesis of cryptococcal infections. We have developed a molecular foundation for C. neoformans, including transformation systems, gene disruptions, differential gene expression screens, and cloning pathogenesis genes. The goal of this work is to use C. neoformans as a model yeast system to identify molecular targets for antifungal drug development. There are a series of clinical trials in fungal infections which are being coordinated through this laboratory and my work also includes a series of antibiotic trials in various aspects of infections. Finally, we have now been awarded a NIH sponsored Mycology Unit for 5 years with 6 senior investigators which is focused on C. neoformans as a pathogenic model system, but will include multiple areas of medical mycology from diagnosis to treatment.

Lad

Shivanand Lad

Professor of Neurosurgery

Dr. Nandan Lad is a neurosurgeon, scientist, and entrepreneur and Professor and Vice Chair of Innovation for Duke Neurosurgery. He is Director of the Functional & Restorative Neuromodulation Program and the Duke NeuroInnovations Program, a systematic approach to innovation to large unmet clinical needs.

He completed his MD and PhD in Biochemistry at Chicago Medical School and his neurosurgical residency training at Stanford with fellowships in both Surgical Innovation and Functional Neurosurgery.  

Neuromodulation; Neurorestoration; Bioengineering; Medical Device Design; Clinical Trials; Data Science; Health Outcomes.


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