Advancing the Use of RT-QuIC for Applications in CWD Management

What is the issue 

Chronic wasting disease (CWD) is an emerging infectious disease that is fatal to free-ranging and captive animals in Cervidae, the deer family.  

Traditional tools for detecting CWD are limited and do not permit the use of non-invasive sampling approaches or an assessment of environmental contamination by prions. These limitations are now being overcome with a new high throughput, CWD prion detection tool, the real-time quaking induced conversion (RT-QuIC) assay. RT-QuIC enables the detection of prions from tissue sources below 1ppm. This level of sensitivity has the theoretical capability to measure prions from ante-mortem tissues and environmental samples. The development and deployment of the real-time quaking-induced conversion (RT-QuIC) assay has the potential to transform our understanding of CWD and provide new opportunities for improved surveillance and management.  

The widespread application of RT-QuIC has been hampered by the lack of well-characterized reference reagents that ensure proper assay functioning and performance, and a lack of preparation methods that minimize false positives and negatives for multiple sample types. Rigorous approaches for RT-QuIC data analysis and interpretation are also lacking. 

What is our approach 

In collaboration with the Universities of Wisconsin, Minnesota, Texas Health Science Center at Houston, Cornell University, the USGS Montana and Wisconsin Cooperative Wildlife Research Units, the Northern Rocky Mountain Science Center, the US Fish and Wildlife Service National Elk Refuge, the Wyoming Game and Fish Department, the Wisconsin Department of Natural Resources, and the Maine Department of Inland Fisheries and Wildlife, the USGS National Wildlife Health Center (NWHC) is working to address gaps that hinder the widespread application of RT-QuIC for improved CWD management. 

We are using RT-QuIC to fully characterize a range of biological tissues, body fluids, and excreta that are CWD-positive and CWD-not detected and comparing those results between standard diagnostic detection approaches and gold standard animal bioassays (a transgenic mouse bioassay). We are developing quality control metrics for RT-QuIC reagents. We are testing and deploying new extraction and sampling approaches that enable the specific and sensitive detection of CWD prions using RT-QuIC with deer tissues, with CWD-exposed soils, and with cervid feces. We are devising and deploying new analytical approaches for RT-QuIC data.  

What are the benefits   

Better CWD prion detection using RT-QuIC could improve diagnostics for CWD by increasing sensitivity and decreasing selectivity. Greater sensitivity may enable less-invasive ante-mortem surveillance tools for captive herds and wildlife populations.  The capability to detect CWD prions in the environment may increase our understanding of the role of environmental transmission in CWD and could be used to drive science-based management practices for the reduction of environmental transmission risk.