NIH researchers never said there is no risk of CWD spillover to humans

Two mule deer in field

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Some news stories on a recent study finding a strong chronic wasting disease (CWD) species barrier between cervids such as deer and humans have concluded that there is no risk of a zoonotic spillover of the fatal prion disease.

But the study authors and other leading CWD and prion experts don't share that conviction.

"We think there's a low risk," senior study author Cathryn Haigh, PhD, Chief of the Prion Cell Biology Unit at the National Institutes of Health (NIH)'s Rocky Mountain Laboratories in Hamilton, Montana, told CIDRAP News. "We can't say no risk."

The research was published in Emerging Infectious Diseases in mid-May.

[The finding] is encouraging in that it emphasizes that at least with current CWD strains, there is a high species barrier, but it certainly doesn't mean that it [spillover] isn't possible or that the threshold of the species barrier might not change in the future when CWD strains evolve.

Brian Appleby, MD

Brian Appleby, MD, director of the National Prion Disease Pathology Surveillance Center at Case Western Reserve University, said the study's conclusions are congruent with those from previous research but aren't the final answer to whether it can transmit to humans.

"They weren’t able to transmit chronic wasting disease to these human cerebral organoids, but that's not a human," he said. "And there are so many other factors that go into transmission outside of such experimental spaces. It is encouraging in that it emphasizes that at least with current CWD strains, there is a high species barrier, but it certainly doesn't mean that [spillover] isn't possible or that the threshold of the species barrier might not change in the future when CWD strains evolve."

Appleby is a cochair of a working group that is part of the CWD Contingency Planning Project at the University of Minnesota's Center for Infectious Disease Research and Policy (CIDRAP), publisher of CIDRAP News. CIDRAP has issued a statement saying that the study results haven't changed the urgent need for continued disease surveillance and preparation for a potential species jump.

Research used lab-grown tissues

Haigh believes the study was the first human organoid (lab-grown tissues that function similar to simplified versions of organs) CWD work, whereas previous research has used other models such as mice. "Organoids aren't manipulated to change the protein expression of the prion protein, and a lot of the mice proteins are deliberately manipulated to do that, so it's closer to a human brain environment than anything that's been done before."

To assess the ability of CWD prions to infect human brain tissue, Haigh and colleagues exposed human brain organoids to high concentrations of mixed brain tissues from CWD-infected white-tailed deer, mule deer, and elk for 1 week. The team then periodically tested the organoids for signs of infection for 180 days.

At the end of the experiment, there was no evidence of CWD replication or protein deposits from human prions. "Overall, the unsuccessful propagation of CWD in cerebral organoids supports a strong species barrier to transmission of CWD prions to humans," the authors concluded.

The CIDRAP statement on the study pointed out that, depending on host factors, interspecies CWD transmission often takes longer than 180 days. Haigh said that that endpoint was chosen based on her team's previous work on human prion infection. "We can detect it [human prion infection] pretty readily at 60 days, it's much stronger at 90, and then by 180, it's pretty strong," she said. "We don't really see it get much stronger after that but we haven't followed them a lot further out."

The organoids were made up of two of three known human prion genetic backgrounds, one of which was previously tied to susceptibility to animal-to-human prion disease. "The two genotypes we tested make up about 80 to 90% of the population," Haigh said, adding that they are now testing the third genotype. "We can't confirm that that one wouldn't take up infection yet."

Need for continued human, animal CWD surveillance, research

Appleby called for research looking at the transmission of CWD into farm animals and using models such as transgenic animals to see how it could alter the risk for humans. "Prion disease is not the same across all animals," he said. "It not only causes concern for cervids but also for other animals, production animals, for example, that could get into our food supply. Could they develop the disease and that might alter the species barrier to humans?"

Haigh said examining the structure of CWD prions and then modeling them to simulate their similarities and differences with the human prion protein could lead to a better understanding of their potential interactions.

Surveillance needs to remain really vigilant.

Cathryn Haigh, PhD

CIDRAP's statement recommends more research into prion diagnostic testing for non-cervid (eg, human) species and lab tests that could differentiate human prions from those from cervids or other animals. Comparisons of CWD prions used in experimental transmission studies to those with known zoonotic potential (eg, bovine spongiform encephalopathy [BSE], or "mad cow disease") and those not considered a human health risk (eg, scrapie, a prion disease of sheep and goats) are also warranted.

All agree that continued animal and human surveillance is critical. "If a new strain emerges that has a better capacity to convert to human prions, we would need to know where it is," Haigh said. "Surveillance needs to remain really vigilant."

Appleby said that continued preparation for a potential spillover is "absolutely" necessary, pointing to the United Kingdom's BSE epidemic in the 1990s. A variant of Creutzfeldt-Jakob disease (CJD) related to BSE began affecting people in the UK who ate the contaminated beef in 1996, with human cases peaking from 1999 to 2004. 

"The consensus, including many of the top-rated scientists of the time, was that there wasn't any risk of human transmission," he said. "We don't want to repeat that."

What is CWD?

CWD, a neurologic disease caused by misfolded proteins called prions, affects cervids such as deer, elk, moose, and reindeer. The disease poses an ongoing threat to cervids, because it can spread from animal to animal and through environmental contamination. CWD cases have been identified in 34 US states, 5 Canadian provinces, Norway, Finland, Sweden, and South Korea.

Signs of the disease include weight loss, uncoordinated movement, listlessness, excessive thirst or urination, drooling, drooping ears, and behavioral changes.

While CWD isn't known to infect people, the World Health Organization and the US Centers for Disease Control and Prevention recommend against eating meat from infected animals and urge taking precautions when field-dressing or butchering cervids. 

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