CIDRAP statement on NIH study into CWD species barrier

Center for Infectious Disease Research and Policy

CIDRAP statement on NIH study into CWD species barrier*

A recently published National Institutes of Health (NIH) study provides laboratory evidence of a strong species barrier that may prevent a chronic wasting disease (CWD) spillover from cervids such as deer to humans.

While this is good news, the study authors noted that the finding doesn't preclude the possibility of a spillover, which remains a significant concern and a focus of our work. The need to prepare for such an event—and its serious consequences for human and animal health—has not changed.

CWD and prion experts agree that significant knowledge gaps remain that require ongoing research and vigilance, including the need to:

• Better characterize CWD strains and the factors driving their emergence. Because different prion strains can have distinct properties—including unique host ranges—it is important to consider all CWD strains. While the NIH study used multiple sources of CWD-positive material, it is unclear which prion strains were represented. Consequently, different CWD strains with heightened ability to cross species barriers may not have been included. Likewise, the emergence of novel CWD strains with different spillover potential is also possible, as was mentioned in the study.
• Identify and consider the implications of all host factors that can affect CWD transmission. Relatively little is known about how even recognized factors (eg, host genetics, route of exposure, involved tissue types) work together. Interspecies transmission of prion disease (eg, CWD spread to non-cervid species) often entails a long incubation period, which can also be shaped by host factors. Thus, the duration of an experimental transmission study is important. The NIH's study endpoint was 180 days, which provides insight but may have been insufficient. 
• Understand the possible role of intermediate hosts and how it might alter transmission dynamics. CWD spillover risk is already difficult to assess from lab experiments alone, and accounting for intermediate hosts—which could make spillover more likely—is another complicating factor. 
• Continue surveillance for the emergence of an atypical human prion disease. For instance, an increased incidence of prion disease in humans—particularly in young people with known exposure to, or high-risk interaction with, CWD-infected animals—could indicate a spillover.
• Advance prion diagnostic testing for non-cervid species and, ideally, develop lab tests that can differentiate human prions from those derived from cervids or other animals.
• Include comparisons of CWD prions used in experimental transmission studies to those with known zoonotic potential (eg, classical bovine spongiform encephalopathy ["mad cow disease"]) and those not considered a human health risk (eg, scrapie, a prion disease of sheep and goats). 

While organoid models such as those used in the NIH study are very useful, they are a complement to rather than a substitute for epidemiologic research that continues to highlight the risk of a CWD spillover to humans.

*This statement reflects the input and review of the Working Group Co-chairs of the CIDRAP Chronic Wasting Disease Contingency Planning Project.